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By

Dr Shikha Dhal

Oral cavity

Read pages 891-898 perez,Subsites

1. Lip

2. Buccal mucosa

3. Lower alveolus

4. Retromolar trigone

5. Oral tongue

6. Floor of mouth

7. Upper alveolus

8. Hard palate

Management

Diagnosis

Treatment

Surgery

Surgery preferred over

radiotherapy as a single

modality

Assessment of

Unresectability

1. Lesions involving or close to bone: to prevent radionecrosis.

2. Site where surgery is not functionally & cosmetically morbid.

3. Young patients: p/o a subsequent second primary.

4. Presence of SMF

1. Gross extension to skull base:Erosion of pterygoidplates, sphenoid bone, widening of foramen ovale.

2. Encasement if ICA> 270 degrees and clinically fixed nodes.

3. Involvement of mediastinalstructures, prevertebralfascia or cervical vertebrae.

Principles of resection1. Enbloc resection of primary tumor whenever possible.

2. In continuity neck dissection when direct extension of primary into neck.

3. Third dimension ( the base) is taken carefully into account before excision, because, as the thickness increases so does the risk of regional metastases & the need for adjuvant elective neck dissection in oral cavity cancers.

4. Adequate margin to obtain clear FS & permanent margin:1.5-2 cm ,clear margin:> 0.5 cm,closemargin:< 0.5 cm

5. FS confirmation for margins may be done if facilitiy is available: LVI cannot be assessed on FS.

6. If perineural invasion is suspected ,the nerve should be dissected both proximally and distally & resected to obtain clearance of disease.

7. C/L neck can be addressed : when p/o B/L ( palate,tongue) C/L metastases is high, tumor crossing midline( ant .tongue & FOM)/midline tumors.

8. Elective neck treatment is often used for management of the clinically node negative patient with oral cancer, and therapeutic neck dissections are performed for patients with clinically apparent nodal disease .Because of the high occult metastatic rate for many cancers, elective neck treatment is encouraged in all but the earliest stages of primary site disease.

N0: Selective neck dissection: for oral cavity:SOHND, I-III

N1-N2a-c:selective or comprehensive neck dissection.

N3: comprehensive neck dissection.

Contd..

Surgical approaches to cancers of the oral cavity may: transoral, transcervical (pull-through), or alternatively, via mandibulectomy, which is sometimes necessary to obtain the exposure required to achieve adequate margins.

In cases where the mental or alveolar nerve is involved with tumor, the nerve should be proximally resected and analyzed microscopically.

A tracheotomy is often necessary to maintain a patent airway because of the large amount of oral edema resulting from extensive resection and placement of myocutaneous flaps in the oral cavity.

Contd..

Tumors that approximate the gingiva should be resected with the gingiva and periosteum as an additional deep margin, while those that appear to involve the periosteum should be resected with an additional deep margin of bone. This last procedure is termed a marginal mandibulectomy.

Depending on the extent of tumor involvement, this may involve resection of a bicortical rim of bone at the upper aspect of the alveolus (rim mandibulectomy), or alternatively selective removal of the inner cortex using a vertical or oblique resection (sagittalmandibulectomy). It is commonly recommended to leave at least a 1-cm thick segment of bone inferiorly following a rim mandibulectomy to reduce the risk of pathologic fracture.

Those lesions that directly invade bone should be resected with a segment of bone. This often requires soft-tissue or osseous reconstruction of the resected bone segment.

Reconstruction 1. Mucosal defects: small defects :primary closure/local flap/SSG;

large defects : primary closure, skin graft, local flap (intraoral defects reconstruction with palatal, tongue, and buccal mucosa flaps but usually at the cost of decreased function), regional flap(pectoralis major flap, trapezius flap, and latissimus dorsiflap) /or free tissue transfer ( the radial forearm flap,theanterolateral thigh flap, the rectus abdominis flap, and the fibula flap) from different sites.

2. Soft tissue loss:( pedicled flaps eg. PMMC) or free tissue transfer

3. Skeletal defects +/- soft tissue & skin loss: free fibula/deep circumflex iliac artery, regional osteomyocutaneous flaps, plate, PMMC.

4. Skin defects: local flaps/ forehead flaps, deltopectoral flaps/ PMMC, free flaps.

Total glossectomy defects are well suited for free flap

reconstruction. Reconstruction of the mandible often

requires free flaps that contain bone and soft tissue such as

the fibula flap, the iliac crest flap, and the scapular flap.

Compared to reconstruction plates free flaps also allow the

potential for a sensate flap through neural anastomosis. A

sensate flap may result in improved swallowing and speech

function, but few studies have unequivocally demonstrated an

improvement in these functional outcomes.

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Radiotherapy is preferred over surgery as a single modality

Severe impairment of function & cosmesis with surgery.

Comorbidity

For early ( T1, few T2) lip, oral tongue, and floor of the

mouth tumors, radiation therapy is an effective means of

securing tumor control. Acceptable control rates have been

achieved with brachytherapy alone or with a combination of

brachytherapy and external beam radiation. Early work

indicates that the success rate of radiotherapy is higher if

some or all of the treatment is administered with

brachytherapy .

Radiation therapy in advanced oral cavity cancers ( stage

T3 &T4) can be delivered preoperatively or postoperatively.

Disadvantages of

preoperative radiation

therapy

Advantages Postoperative

radiation treatment

a delay in definitive

surgical treatment.

limits the dose of radiation

that can be delivered due

to the risk of wound

complications after

surgery.

no dose limitation.

no delay in the

implementation of surgical

resection.

Gives a complete

pathologic staging of the

tumor.

Indications

Postoperative Radiotherapy Brachytherapy

1. Primary:

large primary:T3/T4

positive or close margins

deep infitrative tumor

high grade tumor

LVI & PNI

suspicion of mandibular cortical

involvement.

2. Lymph node:

bulky nodal disease:N2/N3

Extranodal extension

Multiple level involvement

Multiple nodes

1. Accessible lesions.

2. Small ( preferably <3 cm) tumors.

3. Lesions away from bone.

4. N0 nodal status.

5. Superficial lesions.

6. Favourable histology

7. Proliferative or ulcerative lesions.

EORTC 22931:( Bernier et al. 2004): 334 pts with operable stage III/IV oral cavity, oropharynx, larynx & hypopharynx randomized to postop RT( 2/66Gy) vs postop CRT (2/66G y & cisplatin 100 mg/m2 on days 1,22,43).All pts received 54 Gy to the low risk neck. Eligible stages: pT3-4N0/+,T1-2N2-3 & T1-2N0-1 with ECE, positive margins, or PNI.

This study demonstrated a benefit in locoregional control and disease-free survival for the chemoradiation arm, but no overall survival benefit was appreciated.

ARM 5Y PFS (%) 5Y OS (%) LRR (%) GrIII

toxicity

(%)

Sx→RT 36 40 31 21

Sx→ CTRT 47 (p=0.04) 53 (p=0.02) 18 (p=0.007) 41 (p=0.001)

RTOG 95 01(Cooper et al. 2004): 459 pts with operable oral cavity,

oropharynx, larynx or hypopharynx who had ≥2 involved odes. ECE

or a positive margin to postop RT(2/66Gy) vs postop chemoRT

(2/66Gy & cisplatin 100 mg/m2 three wkly).

ChemoRT.Postoperative concurrent administration of high-dose

cisplatin with radiotherapy is more efficacious than radiotherapy alone

in patients with locally advanced head and neck cancer and does not

cause an undue number of late complications.

Combined analysis(Bernier 2005):chemoRT improved OS, DFS, LRC

for ECE, &/or positive margin in stage III/IV,PNI,LVI, & / or

enlarged LN in levels IV-V for oral cavity & oropharynx tumors.

Patients with ≥2 LN without ECE did not benefit from chemo.

ARM LRC (%) DFS(%) OS(%) Ac. Toxicity

Gr III (%)

Sx→ RT 72 43 57 34

Sx→ CTRT 82

(p=Significan

t)

54

(p=0.04)

63

(p=NS)

77 (P<0.001)

The landmark studies of the Radiation Therapy Oncology Group (RTOG)

9501 and the European Organisation for Research and Treatment of Cancer

(EORTC) 22931, followed by the comparative analysis of Bernier and

colleagues, demonstrated that all patients with resected head and neck

cancer receiving standard fractionated postoperative radiation who are

found to have positive margins or extranodal extension should be assigned

to a combined chemoradiation approach using concurrent cisplatin (100

mg/m2 on days 1, 22, and 43).

More recently, the German Cancer Society 95-06 trial demonstrated that

even with hyperfractionated accelerated treatment regimens, patients that

received concurrent 5-FU and mitomycin experienced an improvement in

locoregional control and overall survival.

Finally, a study by Garden and colleagues examined patients with stage III

and IV disease who received a concomitant boost treatment regimen and

cisplatin on days 1 and 22, and found that 4-year locoregional progression-

free survival was 74% and that 4-year overall survival was 54%.Clearly, the

ideal chemotherapeutic regimen in the postoperative setting has not yet

been fully elucidated.

Chemotherapy and Radiation

The application of chemotherapy to the treatment of head and neck cancer dates back to the 1960s. There are a number of studies that demonstrate a benefit of concurrent chemotherapy administration in the definitive treatment of head and neck cancer with radiation. Although these trials vary with respect to radiation dose, fractionation schedule, and chemotherapy regimen, they have in common a randomized comparison between radiotherapy and radiotherapy plus chemotherapy. The advantage of concurrent chemotherapy with radiation has been further examined in the context of several meta-analyses. These meta-analyses generally identify a small overall survival benefit for the use of chemotherapy on the order of 1% to 8%. Summary analyses suggest no significant survival benefit for the use of neoadjuvantand adjuvant chemotherapy, but do suggest a clear benefit for the use of concurrent chemoradiation.

Posner et al. (NEJM 2007): randomized 501 pts with unresectable stage II-IV head & neck cancers( 14% oral cavity) to TPF ( docetaxol/cisplatin/5FU) vs PF (cisplatin/5FU) induction chemo f/b carboplatin chemoRT(70-74 Gy).Induction TPF improved LRC & 3 yr OS ( 48% to 62 % ),but DM.

Rose F. et al ( Asian Pacific J. cancer prevention): alternate schedule is as effective as standard three weekly schedule with respect to OS,LRC, time to local & systemic relapse rate.

Ho et al. demonstrated that 3 weekly schedule was less well tolerated than weekly schedule.

Several recent studies have focused on the use of chemoradiation in patients with high-risk pathologic features following initial surgery.

Cooper et al. reported the results of a randomized study in North America comparing radiation alone (60 to 66 Gy) to chemoradiation (same radiation dose plus three cycles of 100 mg/m2 cisplatin) in patients with head and neck carcinoma demonstrating high-risk features after gross total resection. High-risk disease was defined as any or all of the following: two or more involved lymph nodes, extracapsular extension of nodal disease, and microscopically involved resection margins. This study demonstrated a benefit in locoregional control and disease-free survival for the chemoradiation arm, but no overall survival benefit was appreciated.

A parallel study in Europe by Bernier et al. randomized patients to essentially equivalent treatment arms following head and neck cancer surgery. Eligibility criteria included patients with pathologic T3 or T4 disease (except T3/N0), or patients with any T-stage disease with two or more involved lymph nodes, or patients with T1-2 and N0-1 disease with unfavorable pathologic findings (extranodal spread, positive margins, perineural involvement, or vascular embolism). Local control, progression-free survival, and overall survival were superior for patients on the chemoradiation arm. These studies suggest that the addition of chemoradiation following surgery may be beneficial in selected patients with high-risk head and neck cancer, although with increased toxicity profiles.

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Trials of Adjuvant Radiation

Although surgery has emerged as the preferred initial treatment approach for the majority of patients with tumors of the oral cavity, adjuvant radiation is commonly recommended to enhance the likelihood of locoregional tumor control.

Robertson et al. conducted a phase III study in the United Kingdom of 350 patients with T2-4/N0-2 oral cavity or oropharyngeal cancers comparing surgery and postoperative radiation versus radiation alone. Because a difference in survival was identified, the study was closed early. The authors found that after 23 months, overall survival, cause-specific survival, and local control were all improved on the surgery plus radiation arm.

In regards to buccal mucosa cancers, Mishra et al. conducted a prospective randomized trial of surgery with or without adjuvant radiation 6 weeks after surgery. They reported a 30% absolute improvement in disease-free survival, although there was no difference in overall survival with the use of adjuvant radiation therapy.

Radiation Techniques

Carcinoma of the oral cavity has traditionally been treated with opposed lateral fields, using either two-dimensional or three-dimensional CT-based techniques.

During simulation and treatment patients are commonly immobilized with a thermoplastic mask. Patients are placed in supine position with a bite block (for oral tongue and floor of mouth cases) to depress the tongue away from the palate (Fig. 41.14); some institutions use a cork and tongue blade for this purpose. Reasons for tongue depressor or cork use:

To spare upper teeth, upper gingiva and soft palate and to stabilize the tongue in floor

of mouth, lower lip, retromolar trigone and tongue tumors. Tongue stabilization in other oral cavity tumors.

The involved lymph nodes, commissures of the lips, and any scars in postoperative patients are outlined with thin solder wires.

For patients with a short neck, the shoulders are depressed by having the patient pull on a tensioning device looped beneath the feet. Generally, the oral cavity tumor bed and upper echelon lymph nodes are included within the initial lateral fields (Fig. 41.15).

If a three-dimensional (3-D) plan is to be generated,

orthogonal films for the superior (oral cavity) volume are

taken and the supraclavicular-neck field is simulated. CT

scans are then taken in the treatment position with the mask

in place. If a 3-D plan is not used, opposing portals are

simulated. A 3-D plan should be used for all except simple

opposed-lateral fields.

Borders: The upper border of the field is positioned to provide a 1.5- to 2-cm border on

the tumor bed in an attempt to partially spare parotid glands and hard palate if

possible without compromising coverage of the tumor bed and regional

lymphatics.

The inferior border of the field resides at approximately the thyroid notch, just

above the true vocal cords.

.Anterior: 2 cm in front of primary tumor (usually in front of mandible).

The posterior border is set at the mid-vertebral body /Back of vertebral

corpuses level if level V nodal coverage is not required. The nodal volume

should include level Ia-Ib, II, and III. For patients with more advanced neck

disease or neck risk or positive level V lymph nodes, where the posterior chain

requires radiation, the initial fields should be set behind the C1 vertebral body

spinous process

Lymph node (+): back of vertebral spinous processes.

Lymph node (+): neck and supraclavicular field is also treated.

The portals are then reduced at approximately 45 Gy to spare high dose to the spinal cord.

If patients harbor cervical lymph node metastases, or high-risk disease, then the lower neck will also be treated. In this case, a single half-beam-blocked anteroposterior field is matched to the inferior border of the opposed lateral fields at the level of the thyroid notch. An anterior larynx block is used, which protects not only the central larynx from unnecessary radiation dose, but also protects against spinal cord overdose due to three-field overlap.

Conformal RT Fields :

CTV1: GTV + 1 cm

CTV2: level Ib, II, III lymphatics

PTV: CTV + 0.5–1 cm

Megavoltage beams with an energy range between 4 and 6 MV are most suitable for treatment of cancers involving the oral cavity. ( dmax:a maximum dose at about 1 to 1.5 cm below the skin surface).

Cobalt-60 (similar average energy to that from 4 MV linear accelerators) remains a very acceptable radiation delivery unit for cancers in this region owing to the small lateral separation distances in the head and neck area.

When higher energy beams are used, bolus material may be necessary to bring dose to the surface as required for tumors that extend to the skin. This is particularly important in patients with large volume nodal disease or extracapsular extension where adequate dosing of superficial tissues is required.

Tissue compensating filters should be used with opposed lateral fields when the variation of the separation is >3 cm. All fields should be treated daily and at least 5 treatment days per week.

Normal tissues that are in the field but need not be irradiated are shielded with either mounted lead blocks or multileaf collimators.

In recent years, there has been increasing use of intensity-modulated radiation therapy (IMRT) for the treatment of head and neck region tumors. With regard to oral cavity cancer, IMRT offers the opportunity to diminish normal tissue toxicities, including damage to major salivary glands (xerostomia) and to the mandible (osteoradionecrosis). Dosimetric analysis of radiation dose to the parotid glands with evaluation of resultant salivary function suggests that limiting mean parotid dose to <26 Gy is associated with improved postradiation salivary function.

Ideal candidates for IMRT include patients with T1-3 primary lesions with ≤ N2b neck disease.

IGRT has provided an opportunity to enhance daily treatment precision for IMRT delivery. Tomotherapy, which involves the helical delivery of intensity modulated radiation, enables a high degree of target conformality coupled with the capacity for diagnostic CT scanning, thereby allowing image guidance for adaptive radiotherapy and daily setup verification .

IMRT volumes:

GTV: clinical/ radiographic gross disease.

CTV 1: postop bed ,including 0.5-2cm margin on primary &/or nodal GTV.

CTV2: elective neck.

Individualized PTV’s are used for GTV,CTV1,CTV2 with margin

Simultaneous Integrated Boost Technique (“Dose painting”):

GTV: 70Gy/2.12 Gy/fx(definitive),

CTV1:postop bed/high risk areas 60-66 Gy/2Gy/fx

CTV2:54-59.4 Gy at 1.8 Gy/fx.

60 Gy in 2-Gy fractions to the uninvolved but high-risk regions, and 54 Gy in 1.8-Gy fractions to the low-risk region

Definitive RT

Conventional fractionation: 66- 74(nccn) ya70(book) Gy/2 Gy in 6-7 weeks.

Altered fractionation:

1. 6 fraction/ week acclerated; 66-74Gy to gross disease, 44-64 Gy to subclinical disease.

2. Concomittant boost acclerated RT: 72 Gy/6 weeks ( 1.8 Gy /fraction , large field; 1.5 Gy boost as second daily fraction during the last 12 treatment days.)

3. Hyperfractionation: 81.6 Gy/7 weeks (1.2 Gy/fraction, twice daily)

Concurrent chemoradiation:

Conventional fractionation: primary and gross adenopathy: 70 Gy ( 2 Gy/fraction) & uninvolved nodal station: 44-64(nccn) ya 45-50 Gy.

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Postoperative RT Preferred interval b/w resection & postoperative RT < 6 weeks.

Can be started as soon as wound healing is complete, usually within 2 to 3 weeks after surgery.

Primary: 60-66 Gy(2 Gy/fraction)

However, for close or positive microscopic margins or extracapsularnodal extension, a 4- to 6-Gy localized boost should be considered. If there is gross residual disease, either further surgical resection or focal boosting up to 70 Gy is advisable.

Neck: involved nodal station:60-66 Gy ( 2Gy/ fraction)

uninvolved nodal station: 44-64 Gy( nccn) ( 1.6-2Gy/fraction) ya50-54(perez)

Postoperative chemoradiation: concurrent single agent Cisplatin i.v. at 30 (check chemo book) mg/m2 weekly or 100 mg/m2 three weekly.

Altered Fractionation

It is well appreciated that head and neck tumors are rapidly proliferating. Intensified radiation fractionation schedules to counter rapid tumor cell repopulation as a means of improving outcome as hyperfractionation or accelerated fractionation should be considered for patients being treated with radiation alone, as this approach has been demonstrated to improve the likelihood of locoregional tumor control .

The Radiation Therapy Oncology Group's (RTOG 90-03) altered fractionation randomized trial comparing conventional fractionation to hyperfractionation, split-course, and concomitant boost technique demonstrated a significant improvement in disease-free survival for the hyperfractionation and concomitant boost arms . These altered fractionation regimens were associated with higher incidence of grade 3 or worse acute mucosal toxicity, but no significant difference in overall toxicity at 2 years following completion of treatment. However, oral cavity carcinoma constituted a minority of cases enrolled in these studies.

Tumors suitable for brachytherapy

T1-2N0: Radical BRT: 65-75(book) ya 60-70 ebm Gy low dose rate Ir192 or equivalent doses with fractionated high dose rate.

When definitive radiation is used for oral cavity cancer, boosting the primary tumor with either interstitial implantation, submental, or intraoral cone therapy can result in increased tumor control and decreased complications, particularly osteoradionecrosis .

T1-3 N0-1: EBRT:56-60 Gy/28-30 fraction/6 week

Boost BRT: LDR Ir192:15-20 Gy or HDR: 14Gy in fractions over 2 days(4-3-3-4Gy)

Brachytherapy

Brachytherapy has been used to boost the primary site in the oral cavity before or following external beam radiation (Fig. 41.18).

When brachytherapy is used as a sole treatment modality, doses of 65 to 75 Gy are commonly prescribed over 6 to 7 days for oral tongue , FOM & buccal mucosa. Traditionally, radiation has been delivered using low-dose rates of 0.4 to 0.6 Gy per hour to the target volume. However, there has been recent interest in high-dose rate and pulsed-dose rate techniques , although there is no compelling evidence that these techniques are superior to traditional low-dose rate radiation in the treatment of head and neck cancer. Many techniques for brachytherapy in the oral cavity have been described. Brachytherapy can be accomplished with either rigid cesium needles or with iridium-192 (192Ir) sources afterloaded into angiocaths. The most common technique is afterloading with 192Ir. Guide needles can be inserted either free-hand or with the aid of a custom template to help maintain optimal source spacing.

Radioactive isotopes that have been used in the past in interstitial radiotherapy of oral carcinomas include radium-226, cesium-137, gold-198, and tantalum-182. Iridium-192 used in the form of pins (epingles), wires, or seeds preloaded in a plastic ribbon have the advantage of being suitable for afterloading techniques, and thus is used commonly for temporary implants. Iodine-125 may be substituted and is the isotope of choice for permanent implants. The use of remote afterloading of iridium sources with high-dose rate (HDR) is replacing the use of hand-loaded seeds in ribbons in most institutions.

For oral tongue lesions, if a combination of external-beam radiotherapy and interstitial implant is considered, several series have reported on the importance of adequate interstitial implant dose. The total implant dose is correlated with local control. Those patients who received an external-beam dose less than 40 Gy along with a higher brachytherapy dose achieved higher local control rates than those who received a lower brachytherapy dose. If the patients have neck disease, surgery with or without postoperative radiotherapy is recommended over radiotherapy alone.

Depending on the size of the lesion a single plane, double plane, or volume implant can be used to cover the tumor with a 1-cm margin.

For tumors <1 cm in thickness, single plane implants are adequate.

Surface mold radiation can also be considered for small tumors <1 cm depth or superficial lesions of the lip, hard palate, lower gingiva, and floor of the mouth.

However, when lesions exceed 2.5 cm, it is difficult to avoid significant cold spots in the implant volume. For this reason, it is recommended that for lesions larger than 2.5 cm part of the treatment be given with external beam radiation to supplement the dose to the cold spots. In this setting, a combined treatment plan typically gives 50 Gy over 5 weeks with external beam radiation followed by 30 Gy with a brachytherapy implant.

As tumors get too close to the mandible or are large in volume, the risk of osteoradionecrosis increases.

Surface mold radiotherapy can be used as a primary

treatment for select initial or recurrent superficial lesions of

the hard palate, lower gingiva, and floor of the mouth. An

impression is usually made of the surface to be irradiated and

a mold in the form of a partial dental plate is made of dental

plaster. After distribution of radioactive isotopes has been

outlined, iridium seeds, wires, or tubes for HDR treatment

can be inserted into the predrilled holes or grooves in the

mold and sealed with dental plaster. Treatment can be carried

out on an outpatient basis with the patient wearing the

surface mold several hours a day, or the patient can be

admitted into the hospital and wear the surface mold for

most of the day except during mealtimes. HDR remote

afterloading with fractionated delivery may be used with

surface mold.

Trials of brachytherapy

Decroix and Ghossein reported outcomes in 602 patients

with cancer of the oral tongue treated with radium

implantation or implantation plus external beam radiation. In

this series, recurrence at the primary site or at the primary

site and neck was 14% and 22% for T1 and T2 lesions,

respectively.

The Royal Marsden Hospital reported local control rates of

90% at 5 years for T1 and T2 tumors treated with interstitial

radiation with or without external beam radiation

Pernot et al. reported local control rates of 96% for T1, 85%

for T2, and 64% for T3 lesions of the oral cavity treated with

brachytherapy and neck dissection. In this series, local

regional control rates were 83%, 70%, and 44%,

respectively. Retrospective studies suggest that control rates

at the primary site of early oral cavity lesions treated with

brachytherapy alone or a combination of brachytherapy plus

external beam radiation range from approximately 70% to

>95%. Involvement of the mandible is a contraindication to

definitive radiotherapy because it compromises control and

increases the risk of osteoradionecrosis.

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5

Intraoral Cone The intraoral cone is another delivery tool to enable boosting of

radiation dose to sites within the oral cavity while avoiding direct dose to the mandible (Fig. 41.20). This technique is generally best suited for anterior oral cavity lesions in edentulous patients. However, palatal arch sites can be targeted with the intraoral cone as well. Treatment with intraoral cone involves either 100 to 250 kilovolt (peak) (kvp) x-rays or electron beams in the 6 to 12 MeVrange.

Lesions up to 3 cm are amenable to treatment with intraoral cone as long as they are accessible. Intraoral cone therapy requires careful daily positioning and verification by the physician. For this purpose the device is equipped with a periscope to visualize the lesion. The cone abuts the mucosa and is centered directly over the lesion. Intraoral cone treatment should take place prior to external beam radiation so that the lesion can be adequately visualized. A major advantage of cone therapy is that it is highly focal to the tumor bed but noninvasive. Hence, when available, for suitable lesions, it may be preferred over brachytherapy.

Intraoral cone, like interstitial brachytherapy, is a localized

radiation therapy technique that has been used to boost the

dose to the primary tumor in the oral cavity. Institutions with

significant experience with this technique have reported

results that rival those obtained by interstitial brachytherapy .

Either technique for boosting the primary tumor has resulted

in improved outcomes compared to high-dose radiation

therapy alone . In general, external beam radiation therapy

followed by either technique is preferable over radiation

therapy alone.

The advantages of peroral radiotherapy over interstitial radiotherapy or external-beam radiotherapy in properly selected patients are as follows: (1) only a small volume is irradiated and salivary gland function is therefore preserved and late dental problems avoided, (2) no hospitalization or anesthetics are necessary, and (3) the risk of bone necrosis is minimal.

Peroral radiotherapy can also be used in combination with external-beam radiotherapy to deliver a boost dose to lesions that are marginally encompassed by an intraoral cone. The boost should be given before the external-beam treatment and is usually 21 to 27 Gy in 3-Gy fractions.

Dental Care

Prior to the initiation of head and neck radiation a careful oral and dental evaluation, including a panoramic radiograph, should be performed.

Dentition in poor condition should be identified and considered for extraction to minimize the subsequent risk of osteoradionecrosis.

Specifically, those teeth that will reside within the high-dose radiation volume that demonstrate significant periodontal disease, advanced caries, abscess formation, or are otherwise in a state of disrepair should be extracted.

In addition, impacted teeth, unopposed teeth, and teeth that could potentially oppose a segment of a resected jawbone should be considered for extraction if they are anticipated to reside within the high-dose radiation treatment volume.

Extraction of marginal teeth should also be considered in patients who are deemed unable to maintain adequate oral hygiene.

A gap of 2 wks b/w extraction & initiation of RT should be there to provide for healing.

Routine extraction of all teeth included in the irradiated volume is

not recommended. The only teeth removed are those that are

unsalvageable, likely to require extraction shortly after irradiation,

or potentially damaging to the surrounding tissues.

When tooth extraction is done before or after irradiation, the

underlying alveolar bone must be smoothed to allow primary

closure of the gingival tissues.

Antibiotics are used routinely as a prophylaxis against infection.

All patients are given dental prophylaxis with cleansing of their

teeth and instructed on oral hygiene.

Mouth irrigation with 1% sodium fluoride solution is started

during radiotherapy and continued permanently after radiotherapy

to minimize radiation caries.

Radiation can induce several chronic effects in the oral cavity that warrant routine surveillance. Radiation can impair bone healing and diminish the capacity for successful recovery following trauma or oral surgery. For this reason, elective oral surgical procedures including extractions must be very carefully considered after radiation. Escalation of dental caries deriving from xerostomia following radiation is well recognized (Fig. 41.21).

Radiation of the major salivary glands changes the nature of salivary secretions , which can increase the accumulation of plaque and debris, reduce salivary pH, and reduce the buffering ability of saliva. This creates an environment in the oral cavity, which predisposes patients to caries.

During a course of radiation to the oral cavity, simple techniques such as the use of custom molds to absorb electron backscatter can diminish hot-spot mucositis from dental fillings and improve treatment tolerance (Fig. 41.22). Attention to oral hygiene with frequent dental follow-up examinations and cleanings, daily fluoride therapy (Fig. 41.23), flossing, and brushing should be an integral component of the education and postradiation care of patients.

Prognostic and Predictive Factors

The most significant prognostic factor for outcome in oral cavity carcinoma is the presence of cervical metastases. In patients with positive cervical metastases the 5-year survival is reduced by approximately 50% from that in the absence of metastases . The prognosis diminishes further when patients harbor multiple levels of nodal involvement or extracapsularextension (ECE).

In a retrospective review, Myers et al. found that 5-year disease-specific and overall survival rates for pathologically N0 patients were 88% and 75%, respectively; these decreased to 65% and 50%, respectively, if patients were node positive but without evidence of ECE. Patients who were node positive with evidence of ECE had 5-year disease-specific and overall survival rates of 48% and 30%, respectively.

Tumor infiltration, depth of invasion, grade, location,

number & size of nodes, ECE, PNI, microvascular invasion

Oral cavity Lip

Stage 5 Yr. Relative

survival

I 69.5-73.5%

II 55.5-60.4%

III 41.8-47.3%

IV 40.3-33.6%

Stage 5 Yr. Relative

survival

I 86.5-92.7%

II 75.5-91.5%

III 39.8-69.8%

IV 34.2-60.1%

Several histopathologic factors in the primary lesion are

associated with adverse prognosis. Tumor thickness and depth

of invasion have been shown to confer a higher risk of

regional metastases . Perineural invasion has been correlated

with cervical lymph node metastases, extracapsular

extension, and diminished survival . Microvascular invasion

has also been correlated significantly with cervical lymph

node metastases . However, lymphatic invasion has not been

correlated significantly with cervical lymph node invasion.

The prognostic significance of grade has also been evaluated .

Because of the wide variation in pathologic interpretation, it

is difficult to discern the independent value of histologic

grading as a prognostic or predictive value .

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6

Clinically detected nodal metastasis by T stageN0 % N1% N2-3%

Oral cavity

T1 86 10 4

T2 70 19 11

T3 52 16 31

T4 24 10 66

Floor Of Mouth

T1 89 9 2

T2 71 18 10

T3 66 20 24

T4 46 10 43

RMT

T1 88 2 9

T2 62 18 20

T3 46 21 33

T4 32 18 50

Over the past few years, two proposals—the so-called Brussels guidelines from Gre´goire et al., and the Rotterdam guidelines from Nowak et al.—emerged from the literature for the delineation of the neck node levels.

Recommendations:

1. The entire operative bed should be covered, especially in case of ECE, as tumor cells might have spilled during surgery.

2. In case of pathological involvement of level II, it is recommended to extend the upper border of level II to include the undissectedretrostyloid space upto the base of skull.

3. In case of pathological involvement of level IV & Vb, it is recommended to include the SCF in the CTV.

4. When pathological LN abuts or invades a muscle (paraspinal/subhyoid muscle) routinely not removed in RND/MND should be included in the CTV,at least for entire invaded level.

5. When pathological LN is located at the boundary with a level which has not been dissected, it is recommended to extend the CTV to include in the adjacent level.

The clinically & radiologically node negative neck should be treated

where the risk of nodal metastasis is thought to be >20 %

When tumor is found in lymph nodes from a neck dissection, adjuvant

radiotherapy is recommended unless there is only a solitary positive

node 3 cm in diameter without extracapsular spread.

If radiotherapy is delayed to more than 3 months after surgery because

of surgical complications, the potential risks of EBRT may outweigh

the benefits.

recommend growing GTV isotropically by 10 mm to produce a

CTV70.

The CTV70 is then copied to form the CTV44 which is expanded to

include other nodal levels at lower risk of occult nodal metastases.

Overall CTV-PTV margins should be 3–5 mm in each direction.

Hot-spots of 107 per cent within the mandible should be avoided.

When only one side of the neck is treated, an arrangement of

three coplanar beams can usually provide good tumour

coverage while sparing the contralateral mucosa and parotid

gland. At least one of the beams must have no exit dose through

the spinal cord for this organ to remain within tolerance.In

practice this means the angle of the posterior oblique beam is

chosen to provide best coverage of the PTV while avoiding the

cord (Fig. 10.4). A matched anterior neck beam is often

required to treat low neck nodes.

Where treatment is unilateral, anterior and posterior oblique

wedged fields arechosen, with a lateral field sometimes used to

improve homogeneity medially in the target volume. An

ipsilateral anterior neck field is matched to treat inferior neck

nodes if required.

Subsite-Specific Treatment and Results

Carcinoma of the Lip

Lymph node metastasis from carcinoma of the lower lip most

frequently involves the ipsilateral prevascular submandibular

nodes. Carcinoma arising near the midline of the lower lip

usually metastasizes to the submental lymph nodes.

Carcinoma at or near the commissure may rarely metastasize

to the facial nodes within the substance of the cheek.

Carcinoma of the upper lip may metastasize directly to the

upper cervical, preauricular, or submandibular nodes.

However, contralateral metastases are infrequent.

.

7

Lip

Early stage carcinoma of the lip can be managed with surgery or

radiation therapy. However, surgery is generally preferred for

small tumors (<2 cm). Although the local control of T1 and T2

squamous cancers of the lip is excellent with surgical resection,

disruption of the oral sphincter provided by the orbicularis muscle

can lead to oral incompetence if not properly reconstructed.

Therefore, a number of reconstructive methods have been

developed to help preserve oral sphincteric function even

following large excisions for T3 and T4 lesions. For these larger

lesions, surgery( W/E with marginal/segmental hemimandible

resection) followed by radiotherapy/ chemoradiotherapy remains

a standard therapy.

RadiotherapySurgery

Usually indicated for upper lip

moderately large (>3 cm) infiltrative

lesions that would otherwise require a

complicated plastic surgery with less

satisfactory cosmetic and functional

results.

Tumors involving the commissure

because surgical excision of the

commissure, would not yield

satisfactory cosmetic and functional

results.

Elderly patients who are at a high risk

for complications from general

anesthesia or who have persistent or

recurrent disease after surgery.

Postoperatively when the surgical

margin is inadequate, there is invasion

of the soft tissues of the neck caused by

cervical lymph node metastasis, and in

combination with surgery for advanced

resectable disease.

preferred for majority of lower lip small lesion up to 2 cm in diameter that do not involve the commissure,

young patients,

very advanced disease with bone invasion,

cervical lymph node metastases,

recurrent disease after radiotherapy.

Advanced lesions with bone, nerve, or node involvement frequently require a combined modality approach.

Surgical treatment for early lesions (0.5–1.5 cm) uses a V- or

W-shaped excision, depending on the size of the defect,

which facilitates cosmetic primary closure. If the vermilion is

diffusely involved with little or no involvement of the

muscle, a vermilionectomy may be performed and the

mucosa from the labial vestibule of the oral cavity advanced

to cover the defect.

Mohs and Snow, reported the results for 1,448 patients

treated with microscopically controlled surgery for SCCs of

the lower lip between 1936 and 1976. Eighty-three percent

had cancers less than 3 cm in diameter, with a 5-year cure

rate of 96.6%. For 192 patients with cancers that measured 2

cm or more, the cure rate dropped to 60%. For patients with

grade 1 or 2 SCC, the 5-year cure rate was 96%, as

contrasted with 67% for 81 patients with grade 3 or 4 SCC

Radiotherapy modalities commonly used for carcinoma of the lip include external-beam radiotherapy with orthovoltagex-rays or electrons & interstitial implants with radium or iridium.

The treatment volume should include the lesion with adequate margins. Leukoplakic changes on the lip adjacent to the lesion should also be included in the treatment volume.

For small superficial tumors, a single field with 100- to 150-kV x-rays is sufficient. For deeper, more advanced tumors, 200- to 250-kV x-rays or electrons are usually used.

The optimal dose-fractionation schedule depends on the volume of irradiation. For small lesions (<2 cm in diameter), a dose of 45 Gy to 50 Gy in 15 fractions over 3 weeks is usually adequate, with good cosmetic results. For larger lesions, more protracted treatments with 50 to 70 Gy in 4 to 7 weeks are often used.

When primary radiotherapy is used to treat lip cancer, the target volume should include the primary tumor plus a 1.5- to 2-cm margin for orthovoltage or a 2-2.5 cm margin for electron. For early stage lesions, photons in the orthovoltage range (100 to 250 keV) or electrons may be used. The electron energy should be chosen based on the thickness of the lesion (commonly 6 to 9 MeV).

Effort should be made to shield the underlying gum, dentition, and mandible as appropriate. This can be accomplished with the use of oral shields or cerrobendstents. The recommended dose is 50 Gy in 4.5 to 5 weeks for smaller lesions and 60 Gy in 5 to 6 weeks for larger lesions. Some institutions have used an approach where external beam radiation is given to approximately 40 to 50 Gy followed by a brachytherapy boost, or smaller lesions are treated by primary brachytherapy alone.

An important consideration in managing lip cancer is the risk of regional metastatic disease. Generally, the risk of regional lymph node metastatic disease for T1 and T2 cancers of the lip is lower than for stage-matched tumors of other oral cavity sites. Thus, elective neck dissection is recommended for patients with T3 and T4 carcinomas of the lip; however, it may not be warranted for all T1 and T2 lesions. T3/4 tumors are treated with opposed lateral fields with inferior border is at the thyroid notch and the posterior border is at the posterior aspect of the spinousprocess. When regional nodes are positive,a low neck field is matched to the inferior border of the opposed lateral fields.

Some institutions have used as moustache field for elective irradiation of the perifacial lymphatics (approximately 50 Gy) for more advanced upper lip lesions. Sentinel lymph node biopsy may prove to be useful in the management of patients of node-negative lip cancers, but further clinical investigation in this area is needed.

dobbs Most tumors are treated with electrons or superficial X-rays.

The PTV should be by the 90 per cent isodose of the electron or superficial X-ray beam. Once the PTV has been defined and marked as above, isodose charts are used to select the required energy to give 90 per cent coverage from the surface to the deep margin.

Tissue equivalent bolus is used as required either to increase the surface dose or to reduce unwanted deep penetration.

The applicator size can then be calculated. If electrons are used, the 90 per cent isodose in the lateral plane is 3–5 mm inside the edge of the applicator, which represents the 50 per cent dose. Electrons bow inwards at depth at higher energies, so if a high energy is chosen the applicator size will need to be correspondingly larger to avoid underdosing the deep lateral margin.

A 3–4 mm thick lead mask is then constructed with a cut-out area over the target volume. An intraoral lead shield is used to protect the gums and teeth from the exit beam. It is lined with wax to absorb secondary electrons.

.

8

IMRT is not indicated except for the occasional patient with

advanced neck disease and/or clinical PNI, when it is

necessary to extend the dose distribution to the skull base

and reduce the dose to the contralated parotid. For more

advanced lesions, combining chemotherapy with EBRT is

appropriately considered.

Definitive RT Brachytherapy

1. T1N0: 2/50 Gy f/b boost to 56-60 Gy.

Alternately 45Gy/3 Gyfraction.

2. T2N0: 2/50 Gy f/b boost to 60-66 Gy

3. T3N0: 2/50 Gy f/b boost to 60-70Gy & level I & II are treated.

4. T4 or LN+: 2/50 Gy f/b boost to 66-70Gy & level I & IV are treated.

1. BRT alone : for T1-2

lesion, LDR dose : 60-70

Gy at 0.8-1 Gy/hr.

2. As boost 2-4 wks after

EBRT(50-54 Gy) : LDR

dose15-30 Gy.

Indications:T1-2N0 Lesions

T.V.:

Dose: 50-70Gy in 5-7 days LDR

Technique:

Rigid afterloading needles maintained in place by Template

Classical plastic tubes

Spacers to decrease dose to gingiva, teeth & other lip

lip The clinical target volume includes all visible and palpable tumour

extensions with a safety margin of 5 - 10 mm according to the different directions. Because there is little movement of interstitial implanted sources when adequately fixed with templates or plastic tubes, the PTV usually corresponds very closely to the CTV.

Technique:

It is nowadays classically performed with Iridium192, applied in small source carriers. These are usually hypodermic needles but also guideneedles, classic nylon tubes, silk threads, small vascular catheters, guide gutters, or a combination of more of these afterloading techniques in the same patient. Whenever possible a custom made protection device should be prepared to shield the upper lip and the lower gum (fig 8.1). The protector consists of a 2mm lead shield placed between both lips and the mandible, contained in an acrylic mouthpiece.

Brachytherapy

Source carriers like: hypodermic needles , guide needles, classic nylon

tubes, silk threads, small vascular catheters, guide gutters, or a combination

of more of these afterloading techniques in the same patient are used.

Whenever possible a custom made protection device should be prepared to

shield the upper lip and the lower gum.

Target volume: All visible & palpable tumor with 5-10 mm margin.

8.1A: Acrylic custom made protection Fig 8.1B: X-Ray of implant with protector.

device containing a 2mm lead plate for shielding

upper lip and lower gum during brachytherapy

Typical hypodermic needle implant of the lip in an

equilateral triangular configuration with

protection device in place. Needles have been afterloaded

with Iridium 192 wires (2A). X-Ray control

(2B).

These are hollow, bevelled needles with small outer

diameter (0.8mm) and variable length (4 to 8cm),

open at both ends. The rigid fixed steel and template

system avoids collapse of the sources.

Used in lip tumors of less than 3cm in largest

diameter, not involving the lateral commissurae. The

inner diameter is 0.5 mm and can be afterloaded

with 0.3mm iridium192 wires.

Hypodermic needles

These are hollow, bevelled needles with small outer diameter (0.8mm) and variable length (4 to 8cm), open at both ends. They cause little trauma and can be directly inserted in the tissues. This technique is the optimal technique for lip carcinoma (Fig 8.2). The rigid fixed steel and template system avoids collapse of the sources due to the elasticity of the soft tissues.

Templates with predrilled holes (0.6 mm) in a triangular configuration and with spacing of 10 to 15mm should be available in the department.

Hypodermic needles can be used in lip tumours of less than 3cm in largest diameter, not involvingthe lateral commissurae. The inner diameter is 0.5 mm and can be afterloaded with 0.3mm iridium192 wires.

Classis nylon tubes They have a larger diameter than hypodermic needles. They are

more flexible, allowing a better adaptation to round surfaces.

However it is more difficult to keep good parallelism between

tubes over the whole length of the treated volume.

Large plastic tubes are therefore indicated for larger masses, or

when the lateral commissurae or cheek are involved.

Interstitial implant in three planes :

the deep and middle plane with plastic

tubes,

the superficial with hypodermic needles

They have a diameter which is larger (1.6 to 1.9mm) than hypodermic needles. They are more

flexible, allowing a better adaptation to round surfaces (Fig 8.3). However it is more difficult to keep

good parallelism between tubes over the whole length of the treated volume Large plastic tubes are

therefore indicated for larger masses, or when the lateral commissurae or cheek are involved.

Their loading has sometimes to be delayed as long as necessary for regression of the post

brachytherapy trauma and oedema.

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9

Silk threads

They are seldom used for the brachytherapy of lip cancer, unless it

is a very small lesion preferentially in the upper lip. They can be

used in the completion of a plastic-tube implant, or in

combination with hypodermic needles. For example when a part

of the tumor bulges out of the implanted area and a sub-optimal

dosage is achieved, this can be corrected by an additional silk

thread that can “warm up” the under-treated area.

Basal cell cancer of the uppr lip implanted with the silk thread technique (4A)

and cosmetic result two years later (4B).

Small vascular catheters

Their indications for lip cancer are similar to the indications

for silk thread and small plastic tubes.

Guide gutters

Guide gutters are only exceptionally used. They are reserved

to treat lesion with limited lateral

commissura involvement.

Treatment Outcome

Results of radiotherapy in select series of patients treated with radiotherapy for carcinoma of the lip are shown in Table 29-2. Control of the primary lesion can be achieved with external-beam irradiation or interstitial implants in the majority of patients. Those with recurrent disease after radiotherapy or cervical lymph node metastasis are usually treated surgically. The local control rate by interstitial implant is comparable to that achieved with external irradiation, although for larger lesions, better cosmetic results are obtained with protracted external-beam radiotherapy.

Complications of Treatment

Oral competence, which permits patients to control oral secretions and effectively suck, speak, and swallow, requires the sphincteric function of an intact orbicularis oris muscle. Hence, disruption of the sphincteric function resulting from division of the orbicularis oris should be restored. Microstomia and drooling secondary to oral incompetence may occur after a large flap reconstruction. If the oral opening is too small, the patient may not be able to inset a denture.

There will be some atrophy of the irradiated tissues; this progresses with time. Soft tissue necrosis may occur; this problem is reduced by schemes that prolong the treatment.

MSKCC

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10

Carcinoma of the Oral Tongue Routes of Spread Carcinoma of the oral tongue usually

spreads by direct invasion into the floor of the mouth, anterior tonsillar pillar, base of tongue, and mandible. Approximately 30% to 40% of the patients have cervical lymph node metastasis on presentation. The thickness as well as the T stage of the tongue lesion is directly correlated with the incidence of lymph nodal involvement.The subdigastric(level II) nodes are most frequently involved. The submandibular and midjugular lymph nodes are less commonly involved, and the submental, lower jugular, and posterior cervical nodes are rarely involved. The distribution of lymph nodes reported by Lindberg is shown in Fig. 29-12.

Oral Tongue

Selection of Treatment Modality

Both surgery and RT result in cure rates that are similar for similar stages. The disadvantages of surgery include removal of part of the tongue and the decision of whether or not to do a neck dissection for the N0 neck. The disadvantage of RT is the risk of necrosis.

Excisional Biopsy (TX)

Excisional biopsy of a small lesion may show inadequate or equivocal margins. An interstitial implant or re-excision will produce a high rate of local control.

Early Lesions (T1 or T2)

A partial glossectomy with primary closure or a skin graft may be done transorally and is usually the preferred therapy. Depending on the depth of invasion, an elective neck dissection may be indicated. Postoperative radiation therapy is recommended for patients with large primary tumors (T3, T4), close or positive surgical margins, evidence of perineural spread, multiple positive nodes, or extracapsular extension, invasive pattern. In regard to an invasive pattern, multiple studies have demonstrated that the risk of cervical lymph node metastases is much greater for tumors with a depth of invasion of 5 mm or greater.

In patients with positive margins or extranodal extension, a postoperative chemoradiation approach has been shown to be superior to radiation alone in the analysis of pooled RTOG and EORTC data by Bernier and colleagues, and now is the standard of care, albeit with increased toxicity.

Primary radiotherapy techniques can be used for patients who refuse or are unable to tolerate surgery.

Moderately Advanced Lesions (T2 or T3)

The preferred treatment for the majority of these patients is partial glossectomy, neck dissection, and postoperative RT/ CRT based treatment as previously described.

Advanced Lesions (T4)

Total glossectomy and sometimes a laryngectomy combined with postoperative RT or chemoRT. Some patients are best treated with palliative intent.

Surgery Combined

Surgery is indicated for small lesions (<1 cm) located on the dorsum, the tip, or the lateral border of the tongue that can be excised without resulting in dysfunction, especially in young patients.

Surgery is also preferred in elderly patients who tolerate partial glossectomy better than radiotherapy and in whom preservation of speech is not important.

Certain carcinomas of the tongue arising from syphilitic glossitis, lesions that are edematous and deeply infiltrative, lesions that have invaded the mandible, lesions that have invaded the glossopalatine sulcus, and advanced lesions with multiple lymph node metastases are best managed with combined surgery and radiation with or without chemotherapy.

Surgical approaches to oral tongue cancers : transoral, transcervical,

or alternatively via mandibulectomy to obtain the exposure necessary

to achieve adequate margins.

Partial glossectomy is the most common procedure performed for

oral tongue cancers, and the extent of resection depends on the size

and growth pattern of the tumor.

The tongue is essentially comprised of skeletal muscle; wide margins

are encouraged to avoid retraction of muscle fibers with microscopic

tumor cells that serve as a source of local recurrence.

Total glossectomy may be indicated for extensive tumors or those that

involve the intrinsic tongue musculature. It can result in difficulty

with deglutition, maintenance of an adequate airway & aspiration .

Thus laryngectomy may be necessary in some cases. However,

properly selected patients with adequate postoperative rehabilitation

(laryngeal suspension and palatal augmentation) can be treated with

total glossectomy without laryngectomy.

Tumor size and depth of invasion are currently the most reliable indicators for predicting cervical metastases in patients with oral tongue squamous-cell carcinoma.

Because of the high risk of nodal metastases the neck should be addressed either with surgery or radiation in all but the earliest tumors of the oral tongue.

Patients with small oral tongue cancers should be considered for neck therapy, particularly if the primary tumor exhibits extension onto the floor of mouth or there is increased tumor thickness. Treatment of the clinically negative neck is most often accomplished by supraomohyoid neck dissection. Elective neck dissection appears to result in better overall cancer outcome than observation.

Potential pitfalls of observation include a salvage rate of only one-third for patients who do not undergo elective neck dissection along with resection of the oral cavity primary.

For patients with a clinically and radiographically N0 neck, with well-lateralized disease, or those who do not undergo neck dissection, 50 to 54 Gy should be considered to the ipsilateral neck as elective nodal irradiation (Fig. 41.16).

Patients with advanced lesions and high-risk disease (particularly with multiple positive nodes) should receive radiation treatment to the bilateral neck.

.

11

Recurrence in the primary lesion after radiotherapy is

difficult to salvage by surgery, with one study quoting 5-year

actuarial survival rates of 39%, and 27% for locoregional

recurrence. Local recurrence after treatment with

glossectomy alone has a similarly dismal prognosis, with

some studies reporting less than 10% of patients being

successfully salvaged at 4 years after being diagnosed with

recurrent disease. Metastatic cervical lymph node metastases

that develop after the primary lesion has been controlled can

be successfully salvaged, although survival after neck

recurrence has been documented to be as low as 18 months.

Opposing lateral fields are used to encompass the tongue and upper neck bilaterally, and this volume should be treated to 50 to 54 Gy(see Fig. 41.12A and Table 41.1).

In patients with unilateral lymph node metastasis, the rate of contralateral occult node metastases has been found to be high in OCC, up to 35% to 40%.Therefore, contralateral nodal treatment in all patients with carcinoma of the oral tongue is advocated because of its aggressive behavior and because it is not a well-lateralized structure such as the buccal mucosa.

With opposed laterals, the superior border is 1-1.5 cm above the dorsum of the tongue or 2 cm above tumor, inferior border is at the thyroid notch, posterior border is placed at the posterior aspect of the spinous process, the anterior border is 2 cm anterior to the tumor. When LN+, a low neck field is matched to the inferior border of the opposed lateral fields.

3DCRT & IMRT are preferred approaches

Superficial T1 lesions can be treated with brachytherapy alone. Commonly, 192Ir temporary implants are used to deliver 50 to 60 Gywith dose rates of 40 to 60 cGy per hour. Although the primary lesion may shrink after the external irradiation, the treatment volume for the interstitial implant is usually determined before any treatment is initiated.

For infiltrating T1 or T2 lesions, a combined approach using external beam and a brachytherapy or intraoral cone boost should be considered. As a boost before or after EBRT ( 45 Gy), interstitial brachytherapy 25-30 Gy or intraoral cone 15-24 G Gy may be used.

Definitive RT for advanced lesions, without chemotherapy:> 72 Gy ( 1.8-2 Gy/ fx), (altered fractionation is recommended)

Definitive chemoradiation: 70 Gy/2Gy per fx.

Postop EBRT:50-54 Gy/ 1.8-2 Gy per fraction followed by boost to 60-66 Gy to high risk areas including primary surgical bed, close margins, extranodal extension, nodal involvement, LVSI or PNI. Postoperative treatment should include the site of primary tumor, dissected neck, and draining lymphatics. The lymph node areas are treated from 54 Gy, for uninvolved lymph nodes being treated electively, to 60 Gy.

Oral tongue & Floor of mouth Brachytherapy Interstitial implant is an integral part of radiotherapy for carcinoma of

the oral tongue if definitive radiotherapy is the primary treatment approach.

The implant dose is directly correlated with local control. External radiotherapy alone is not recommended, as it is rarely successful.

Early superficial lesions can be controlled with a single-plane interstitial implant or peroral radiotherapy alone. For lesions greater than 1 cm in thickness, double-plane or volume implants in combination with external irradiation are usually used.

Brachytherapy has also been used in the postoperative setting for T1-2-N0

squamous cell carcinomas of the oral tongue and the floor of mouth with close or positive margins. The recommended dose is 60 Gy. High rates of locoregional control, close to 90%, with low risk of chronic sequelae have been reported.

The most important step in treatment planning for interstitial implants is the determination of the treatment volume. Sometimes the true extent of the tumor cannot be adequately determined without anesthesia because of pain. With the patient under general anesthesia, it is not uncommon to find a tumor more extensive than anticipated.

For interstitial implants of carcinoma of the tongue and floor of the mouth, dose rates in the range of 30 to 100 cGy per hour for the minimum tumor dose have been commonly used when low-dose rate (LDR) brachytherapy is the treatment approach. Although some authors recommend adjustments of the total dose according to the dose rate; Mazeron and coworkers suggest that for dose rates between 30 and 100 cGy per hour, no adjustment of total dose is indicated. Overcorrection of dose for reduced overall treatment time may lead to a high incidence of local recurrence.

Localization films of the implant are usually taken on the day of the procedure.

Computer dosimetry provides detailed information on the dose distribution within the implant volume. The dose distribution in several parallel planes intersecting the tumor volume should be obtained. An isodose curve that encompasses the entire tumor volume on all the planes that intersect the volume should be used to calculate the minimum tumor dose.

Sometimes part of the implant may be removed during the course of treatment when there is a volume of overdosage within the implant.

The optimal minimum tumor doses for local control vary with the size of the primary lesions. For T1 and select small T2 lesions, the implant alone is used with a dose of 60 to 70 Gy. For larger T2 lesions, a total dose between 75 to 80 Gy is delivered by using both intestitialimplant and external-beam radiotherapy, with 30 to 40 Gy being a typical dose delivered by external-beam radiation.

The incidence of soft-tissue and bone necrosis depends on the total dose as well as on tumor volume, but is independent of the dose rate. It is important to separate the ribbons from the mandible by the use of dental rolls sutured in place.

HDR fractionated interstitial brachytherapy is the preferred

treatment nowadays. A phase III trial of high- and low-dose

interstitial radiotherapy for early oral tongue cancer showed that

HDR can be an alternative to LDR, with similar rates of local

control and the advantage of eliminating exposure to the medical

staff.

If not using HDR, an afterloading technique using iridium seeds

is preferable because of the reduced radiation exposure to the

medical and paramedical personnel. The afterloading technique

also allows more time for optimal placement of needles, because

no radiation exposure occurs during the procedure. The dosing

regimen for HDR brachytherapy is typically 54 to 60 Gy in 9 to

10 fractions.

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12

Oral Tongue:

Indications: T1 N0, T2 N0 < 3cm lesion

T.V.: GTV + 5 mm margin

Dose: Alone:60-65 Gy LDR

Boost 20-25 Gy after EBRT dose of 45-50 Gy

Techniques: Guide-gutter technique

Tongue The aim should be to treat the gross tumour volume which is

usually palpable plus a margin of at least 5mm all around it. It should be remembered that the lower end of hairpin and loop implants have no crossing sources as they do at the top and the length of the limbs need therefore to be long enough to ensure the volume is adequately covered.

7 Technique

7.1 Pre-planning:

Before going ahead with the implant it is necessary to measure the tumor carefully and plan the exact number of radiation sources to be used with their length and separation. This will allow a provisional dosimetry to be performed so that a source activity can be chosen to deliver a dose rate of 40 to 50cGy/h during the implant.

1.Guide-gutter technique: Iridium wire hairpins are prepared with a fixed separation of

12 mms. This limits the width of volume which can be treated to approximately 15 mm and the technique can therefore only be used for smaller tumors (no more than 30 mm in length).

The implant can be performed with the patient sitting upright under LA and sedation or rarely under GA.

The number and length of hairpins to be used is prehandedlydecided from the provisional dosimetry. The aim is for the sources to be equidistant, parallel and straight and to cover the target volume. The first phase of the implant is performed with inactive guide gutters (inactive device). These are introduced into the tongue with the help of fluoroscopy which ensures that they are parallel and equidistant.

For tumors that are near the tip of the tongue the anterior

needle will be reflected backwards by the mandible. This

should be accounted for before beginning the implant so that

there is no divergence orconvergence of the needles at depth.

(Fig 9.1) The guide gutter is first inserted angled towards the

mid line of the tongue but once within the muscle it is

straightened out so that the lateral limb of the hairpin runs 3

to 4 mms below the mucosa of the lateral border of tongue

(Fig 9.2).

The separation between the hairpin guides should be 10 to 15

mm.

Once fluoroscopy has confirmed that the hairpin guides are

parallel and equidistant, a black silk suture is run under the

bridge of each one (Fig 9.3).

Local Anesthesia

Fig 9.2 : Implantation of the guide gutter, starting with the

posterior, followed by the anterior with the third

implanted in between

When the guide gutters are in position, the radioactive hairpins

can be cut to the desired length; it is usual to use 4 to 5 cm for

implantation of the lateral border of tongue. The active hairpin is

introduced into the guide gutter starting with the most posterior

and slotted down the stainless steel guide. Once in position the

hairpin is held in position in the tongue with a Reverdin needle

and the inactive stainless steel guide withdrawn from the tongue.

The preprepared suture is then tied over the bridge of the hairpin

to secure it within the tongue.

Implantation of the guide gutter, starting with

the posterior, followed by the anterior with the

third implanted in between

Insertion of the silk suture. And Loading of the iridium hairpin inside the gutter.

Replacement of the guide gutter by the iridium hairpin. and End of the implantation : the three

hairpins are implanted and sutured.

After the implant is completed, AP and lateral radiographs

are taken, which will be used for computerized dosimetry

AP X-ray Lateral X-ray

Computerized dosimetry : sagittal planeComputerized dosimetry :

reference volume (PTV).

The “classical” guide-gutter technique as modified by

J.P. Gerard and his team [15] is shown in figures

Bleeding can sometimes occur on insertion or

removal of a guide gutter; this nearly always stops

after 3

to 4 minutes of pressure.

Fork

Applicator in situ

X-ray : lateral view

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13

2. Plastic loop technique

Implantation of the two posterior steel needles After Nylon cordlet introduction inside the Needles, the needles

are removed and replaced by the plastic tube, pulled with the

cordlet.

Plastic loop Technique: The loop technique allows a wider separation between the sources than the

fixed 12 mm separation of a hairpin. It therefore can be used to treat larger volumes. It also has the advantage that iridium wire can be inserted into the plastic tubes with a remote afterloading machine that reduces the risk of exposure; in case of local oedema inducing the risk of displacement of the plastic tubes, it offers the advantage that one can wait for an acceptable local status before loading the iridium wire.As for the guide-gutter technique, the number of loops, their separation and length should have been planned before performing the implant following the rules of the Paris system. Loop techniques are performed under general anaesthesia. It is helpful before starting to outline on the skin of the under surface of the jaw the projection of the tumor to be implanted and the position of the mandible.

The implant is performed by creating a loop of plastic tubing which goes from the skin up over the tongue and down through the skin again. The loop is formed by passing a hollow stainless steel needle through the skin into the tongue (Fig. 9.18). A parallel stainless steel needle forms the other limb of the loop. A nylon cord is passed up the stainless steel needle where it exits into the oral cavity and is then passed down the other needle to form a loop. The stainless steel needles are then removed. A length of plastic tubing with a 1.6 mm outer diameter is threaded over the nylon cord and clamped over the cord at its end. The plastic tube is then pulled into the mouth by the nylon cord so that it reforms a loop passing from the skin over the tongue and back out of the skin (Fig 9.19).

Three or four loops are inserted into the tongue depending on the volume to be treated with a separation between each loop which should ideally be between 15 to 18 mm. To respect the rules of the Paris system and to assure a better homogeneity of dose distribution, the distance between the “legs” of eachloop is the same as the distance between the different loops.

An inert marker wire is passed up the loop so that the position can be identified on radiographs for dosimetry. The plastic rubes are rinsed with a heparin solution (Fig 9.21). A nylon ball and lead washer are passed over the ends of the plastic tube in preparation for fixing the implant once it is loaded.

Two shielding devices are systematically used in oral-cavity cancers: the first one is a radiotransparent device for radiograph control (Fig 9.22), the second one, identical to the previous one, is made of lead (Fig 9.23) in order to decrease the dose to the critical organs.

Plastic tubes are cleaned with a tubes with metallic

heparin solution. B)Fixation of the. buttons.

A, B : Shielding system, tailored for each patient (must be

evaluated according to the GTV, to

the brachytherapy procedure, and to the patient tolerance).

After check radiographs have confirmed that the

loops are equidistant and parallel the implant can be

Two shielding devices are systematically used in oral-cavity cancers:

the first one is a radiotransparent device for radiograph control (Fig

9.22), the second one, identical to the previous one, is made of lead

(Fig 9.23) in order to decrease the dose to the critical organs. After check radiographs have confirmed that the loops are

equidistant and parallel the implant can be loaded by passing

a pre-encapsulated iridium wire up the pre-implanted plastic

tube to form a loop of iridium wire over the tongue (Fig

9.24, 25). The radioactive wire is maintained in place by

clamping the inert ends of the plastic inner tubing to the

hollow plastic tube loop to fix their position.

Remote Afterloading:

It is difficult for a remote afterloading device to negotiate the radioactive source around the tight curve of a plastic tube loop. The implant therefore has to be done with straight line (27) sources. Care needs to be taken to avoid a cold spot at the top of the implant at the surface of the tongue where retraction of the isodoses can result in a cold spot at the tongue surface which may be involved by tumour. This is achieved by allowing the plastic tube to protrude 4 to 5 mms above the tongue surface where it is maintained in place with one or two plastic buttons. (27) The afterloading machine also must be programmed to double the dwell time at the top three source positions in order to achieve a source distribution similar to the old Manchester Indian Club needle with increased activity at the uncrossed top end. Brachytherapy may also be indicated as postoperative treatment; in this case only the plastic-tube

technique should be used.

During the implant Although patients are usually able to speak and swallow with the

implant in place, it is good practice to maintain adequate hydration

with intravenous fluids & start on ryles tube feeding.

Antibiotics cover during the implants and for 1 week after the

implant.

Patients are also encouraged to irrigate the mouth with salt and

baking soda solutions or half-strength peroxide solutions during

and after the implant period.

Analgesics are prescribed whenever necessary. The peak reaction

of mucous membranes usually does not occur until several days to

1 week after the implant.

Complication

Because interstitial radiotherapy is an integral part of radiotherapy in patients receiving radiotherapy alone for carcinoma of the oral tongue, a small area of the mandible usually receives a dose in excess of 75 Gy. The incidence of osteonecrosiswas 19% in the series reported by Delclos and coworkers. Most of the necrosis healed with conservative management, although only 35% of the bone necrosis in that series required surgical treatment, for a total of 6% of patients requiring surgical management. Another series reported a 38% complication rate, such as erosive ulcerations and bone exposure, in patients who received brachytherapy for stage I and II disease.

The patients who also received external-beam radiotherapy in addition to brachytherapy had higher rates of complications than those treated with brachytherapy alone, but the incidence of neck metastases occurred in 31% to 51% of patients in whom the neck was not electively irradiated.

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14

Treatment outcome There have been multiple studies on the outcomes of patients

treated with surgery in carcinoma of the oral tongue. One recent retrospective study from Japan demonstrated a superiority of surgery over brachytherapy in stage I and II tumors, with 5-year overall survival rates for the LDR, HDR, and surgery groups of 84.0%, 72.9%, and 95.4%, respectively.

Another study by Aksu and colleagues compared definitive radiation with surgery and postoperative radiation in 80 patients with stages I through IVA disease.The patients that received surgery and postoperative radiation therapy had a 5-year overall survival advantage versus those treated with definitive radiation alone (49% versus 16%, respectively). Studies such as these confirm that when feasible, surgery should be performed as the definitive treatment modality in patients with oral tongue cancer.

Definitive radiotherapy results for carcinoma of the oral

tongue are given in Table 29-4. Most of the patients in the

series reported by Wendt and associates[75] and Mazeron and

associates did not have cervical lymph node metastasis at the

time of treatment, whereas 50% of the patients in the series

reported by Fletcher presented with cervical lymph node

metastasis. As noted previously, the incidence of occult

metastasis in early-stage squamous cell carcinoma of the oral

tongue is between 20% and 48%.

Survival Long-term survival in carcinoma of the oral tongue is directly

related to the stage of disease. In a series of 204 patients treated between 1940 and 1971, reported by Fu and associates, the overall 5-year actuarial survival was 32% and determinate survival was 47% for all stages. The prognosis for patients who had cervical lymph node metastasis on presentation and persistent or recurrent disease at 3 months after treatment was significantly poorer than the prognosis for patients who had no cervical lymph node metastasis on presentation and those who were free of disease at 3 months after treatment.

A recent series of 370 stage T1 and T2 cases reported by Shibuya and associates showed that the 5-year primary tumor control was 85% for superficial lesions, 70% for exophytic lesions, and 45% for infiltrative lesions. The 5-year overall survivals for stages T1, T2a, and T2b were 84%, 78%, and 72%, respectively.[80]

Carcinoma of the Floor of the Mouth

Carcinomas of the floor of the mouth usually spread by direct

invasion into the tongue, the lower alveolar ridge, the mandible,

and the submandibular glands.

Approximately 30% of the patients have cervical lymph node

metastasis on presentation. The submandibular lymph nodes are

most frequently involved. Metastasis to subdigastric nodes,

midjugular nodes, and submental nodes are less frequent.

The incidence of lymph node metastasis is directly proportional to

the stage of the primary lesion; 9% for T1 lesions, 25% for T2

lesions, and 68% for T3 and T4 lesions (Fig. 29-15).

Similarly, 20% of the patients without initial lymph node

metastasis subsequently develop cervical lymph node metastasis.

Early stage floor of the mouth cancer can be treated effectively by radiation therapy or surgery. However, surgery is usually preferred in patients who are medically operable because proximity of the tumor to the mandible confers a significant risk of radiation-induced ulceration and osteoradionecrosis. Small lesions of the floor of the mouth are most commonly resected transorally. The surgical defect can be left to heal by granulation or reconstructed with a split thickness skin graft or local flap.

Advanced stage floor of the mouth cancers are usually managed by a combination of surgery and radiation or chemoradiation, especially when there is invasion of the mandible and the presence of large or multiple cervical lymph node metastases or extensive involvement of the musculature of the tongue.

For medically inoperable patients, or unresectable stage T4b disease, a combination of chemotherapy and radiotherapy should be considered.

Surgery is used in the treatment of recurrent disease after radiotherapy.

Small (T1 and T2) lesions may be treated with a combination of

external beam radiation and boost with interstitial implant or

intraoral cone. Superficial or exophytic T1 cancers are treated

with either brachytherapy or intraoral cone RT to

approximately 65 Gy and the neck is observed. Lesions that are

suitable for intraoral cone RT may be boosted with this

technique prior to EBRT of the primary lesion and upper neck.

Use of EBRT alone results in suboptimal cure rates and is

discouraged

For lesions that are very close to the mandible, brachytherapy is

contraindicated .Infiltrative lesions that are tethered to the

mandible and advanced lesions following surgical resection

should receive postoperative radiation.

In the surgical management of floor of the mouth cancer, special attention should be paid to mandibular invasion. A cancer that appears to involve only the periosteum or that only superficially invades the mandible can be removed via a transoral or transcervical approach in which a marginal mandibulectomy is performed.

Segmental mandibulectomy may be necessary for patients with a limited mandibular height when there is no direct bone invasion, because marginal mandibulectomy may leave these patients with insufficient bone, placing them at high risk for radionecrosis or pathologic fracture. A full thickness segmental resection may be necessary if there is frank bone invasion.

For advanced cancers, resection of the anterior arch of the mandible may be necessary. Defects of the anterior segment of the mandible require reconstruction with bone, usually with a free fibular or iliac crest graft.

Management of the neck is similar to that for other tumors of the oral cavity. Patients with lesions <2-mm thick with no adverse pathologic factors and a clinically and radiographicallynegative neck may be observed after primary resection. Otherwise most N0 patients should receive either selective neck dissection or radiation therapy. Patients with advanced lesions and high-risk disease (particularly with multiple positive nodes) should receive radiation treatment to bilateral necks.

Combined Treatment Policies

Postoperative RT is preferred, because the risk of bone complications and fistulae is higher with preoperative RT. Concurrent chemotherapy may be necessary based on pathologic findings. Preoperative RT may be used if the patient has a large fixed node.

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15

With opposed laterals, the superior border is 1-1.5 cm above

the dorsum of the tongue ( 2 cm above the tumor).

A cork should be used b/w the teeth to exclude palate & if

possible , tip of tongue , from field.

Level I nodes are always treated & level II is included for depth

of invasion>1.5 mm ( with posterior border at the posterior

aspect of the spinous process).

The inferior border is at the thyroid notch.

The lower lip is excluded when possible.

When LN+ , a low neck field is matched to the inferior border

of the opposed lateral field.

Opposing lateral fields encompass the oral cavity tumor bed

and upper neck bilaterally, and this volume is commonly

treated to 50 to 54 Gy. High-risk areas (primary surgical bed,

positive/close margins, extracapsular extension, perineural

spread) may receive additional boost treatment up to 60 to

66 Gy.

The entire width of the mandibular arch is included and the

superior border is shaped to spare part of the parotid gland.

If the neck is clinically positive, the portals are enlarged to

include all of the upper neck nodes, and en face low neck

field is added. N0 Floor of the mouth

(Tongue extension −)N0 Floor of the mouth

(Tongue extension +)

If definitive radiation therapy is used with non-IMRT techniques, for most carcinomas of the floor of mouth without bone invasion, we recommend external-beam irradiation with 50 to 54 Gy delivered at 2 Gy per fraction, five fractions per week, to the primary lesion with adequate margins and the upper neck, including the submandibularand subdigastric nodes, followed by a boost to the primary lesion with 10 to 20 Gy using interstitial implant, peroralcone irradiation, or external-beam irradiation. The boost portion of treatment encompasses any visible tumor plus a margin, and we prefer using 3-D conformal radiotherapy (Fig. 29-16).

If IMRT is used as definitive treatment alone, the entire region can be treated using a dose-painting technique, delivering 70 Gy to the primary tumor and involved lymph nodes, 59.4 to 63 Gy in 1.8-Gy fractions or 60 Gy in 2-Gy fractions to the uninvolved but high-risk regions, and 54 Gy in 1.8-Gy fractions to the low-risk region. The lower neck is routinely irradiated when cervical lymph node metastases are present.

Similar to carcinoma of the oral tongue, the floor of the mouth is not a well-lateralized structure and thus the bilateral neck is generally treated in all cases. If a LAN field is used, the standard dose is 50 Gy in 2-Gy fractions or 50.4 Gy in 1.8-Gy fractions.

For advanced, unresectable lesions not amenable to implantation, patients can be treated with external-beam radiotherapy using accelerated hyperfractionation with a concomitant boost technique.

Brachytherapy Similar interstitial radiotherapy techniques for carcinoma of the oral

tongue are used for carcinoma for the floor of the mouth, as shown in Fig. 29-10.

Interstitial Irradiation

Implantation of T1–T2 lesions confined to the floor of the mouth with minimal extension to the mucosa of the tongue can be accomplished with iridium using the plastic tube technique.

The iridium seeds in nylon ribbons are afterloaded into nylon tubes extending from the skin of the submental region to the floor of the mouth. The nylon tubes are pulled in behind stainless steel needles, which are then removed.

For large lesions, the catheters are usually placed with the use of needles inserted through the submental skin to the dorsum of the tongue, to deliver an adequate dose throughout the tumor volume. If the tubes terminate in the floor of the mouth, the iridium ribbons must protrude at least 1 cm or have double-strength seeds at the tip. Alternately, longer dwell times can be used with HDR. The recommended LDR dose is 60-70 Gy & intraoral cone dose is 3Gy/fx to 45 Gy over 3 wks.

FOM brachytherapy In defining the CTV, a safety margin is chosen, which is at least 5

mm in all directions, except towards the mandible, which formsPlesiobrachytherapy:

Moulds can be used only for very superficial lesions (up to 5-mm target depth). The applicator must be adapted to the topography of the tumor. This is achieved by an appropriate choice of moulds, either standard or customised. Fixation and immobilisation are crucial.

7.2 Interstitial Brachytherapy:

Both guide-gutter and plastic-tube techniques are applicable (8,17,23). Specific guidelines for floor of-mouth cancer include the following: in order to decrease the dose to the mandible and consequently the risk of osteoradionecrosis, the contact of radioactive lines with the mandible should be minimised. Moreover, the radioactive lines must be inclined or bent according to the internal surface of the mandible, reducing even more the dose to the bone. a natural barrier.

Guide gutters as well as plastic tubes are therefore implanted

parallel to each other (Fig 10.1-7). To determine the distance

between the lines and the length of the radioactive lines,

three parameters must be considered: the target volume , the

situation of the tumor in relation to the mandible, and the

rules of the Paris system. Too large intersource spacing

should be avoided, to limit the dose delivered to the

mandible. With the guide-gutter technique, the distance

between the two parallel lines is fixed by the dimensions of

guide gutters: 12 mm. Ideal separation between the double

pins is consequently 12 mm. When it is not achievable, this

spacing should be kept, as far as possible, between 8 and 14

mm. (25) With the plastic tube technique, there is of course

more flexibility, but again intersource spacing should not

exceed 14 mm.

7.2.1 Guide-gutter technique

Local anaesthesia

Fig 10.2: Implantation of the guide gutter and

insertion of the silk suture

Fig 10.3:

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16

Loading of the iridium hairpin Removal of the guide gutter replaced

by the iridium hairpin

X-ray control: AP and lateral view

Shielding System

Plastic-tube technique

Tumors of the pelvilingual sulcus are implanted with two or three loops perpendicular to the mandible, according to a technique similar to that described for mobile tongue cancers (Fig 10.9,10). The external branches of the loops are as far as possible angled away from the inner table of the mandible so that just the apex of the loop is close to the bone, reducing the dose to this critical organ. If the tumor does not involve the ventral surface of the tongue, it is not necessary to load the bridge of the loop with radioactive wires, and two parallel wires then replace the loop.

Tumors superficially extending to the gingival mucosa, when not suitable for surgery because of age or poor health status, are implanted using the plastic tube technique (see figure) or with the crossing technique used for post operative implants. (13,23)

Postoperative implants, with or without external beam radiation therapy, may be indicated when surgical margins are positive or close to tumor. Large tumors of the floor of mouth that do not reach the gingiva but infiltrate the sulcus and the ventral surface of the tongue are often treated by wide resection using a myocutaneous flap. In this case, the implantation is not performed in the flap, but in the residual disease. (13,23)

The length of the radioactive lines is crucial. There is a clear relationship between this length and the risk of osteoradionecrosis and, while the target volume should be adequately covered (including the 5 mm safety margin), it is advised to avoid too long radioactive lines, particularly in contact with the internal surface of the mandible. With the guide-gutter technique, 2 to 3 cm long hairpins are often chosen. (8,11,17)

Tumors situated on or close to the midline are often implanted with five radioactive sources, two anterior, and three posterior (see figure), forming a trapezium, which can easily be divided into three equilateral triangles, thus respecting the rules of the Paris system. (8)

Anterolateral or posterior tumors are in most cases implanted with two or three guide gutters or two or three plastic loops, in a plane perpendicular to the mandible.

The plastic tubes are then implanted along the insertion of the flap; the anterior branch can also be implanted at a few millimetres from the suture, with the posterior branch in the flap. Tumors adhering to the gingiva are more difficult to treat, especially when the surgeon has resected the superior part (rim) of the mandible arch, leaving the inferior rim.

In this case, the mucosa of the tongue is used for covering the rim, and is sutured to the lip and/or the cheek. This mucosa is furthermore at high risk of local recurrence, and the plastic loops have to bridge the rim. To achieve this, the spacing of the external branches of the loops has to be greater than that of the internal branches, with regard to the mandible, and optimisation is consequently highly recommended. (23) A shielding system is always employed in order to decrease the dose to the teeth and the mandible and also to maintain the sources in good position throughout irradiation (Fig 10.8). This shielding system must be tested during the implantation procedure and may need modification according to the geometry of the implant and the tolerance of the patient. (9,16,17,20)

Plastic tubes are implanted by three

sagittal loops; the distance between the different

tubes is checked

Fig 10.10: X-ray control: AP view

Intraoral Cone Irradiation

Intraoral orthovoltage or electron cone RT requires daily

positioning by the physician and is preferable to interstitial

RT because there is little or no irradiation of the

mandible. An intraoral cone can be used for well-

circumscribed anterior superficial lesions and is easiest to

perform in the edentulous patient.

Management of Recurrence

Local recurrence after RT or surgery is heralded by

ulceration, pain, or increased induration. Recurrences have a

slightly elevated or rolled border, whereas necroses do not.

Biopsy should be done as soon as ulceration appears, if it is

within the original tumor site. Ulcers that appear on adjacent

normal tissues are likely due to RT and not cancer.

RT failure is managed by surgery. Surgical failure occasionally

is salvaged by re-resection and postoperative RT-based

treatment. Recurrence in the soft tissues of the neck is rarely

eradicated by any procedure.

Nodes appearing in a previously untreated neck are managed

by neck dissection with or without postoperative RT;

chemoRT is indicated if ECE is present.

Treatment Outcome

The results of definitive radiotherapy of carcinoma of the

floor of the mouth, as reported in several recent series, are

given in Table 29-5. Most patients were treated with a

combination of external irradiation and interstitial implants.

The control of the primary lesion is directly proportionate to

the stage of the disease. Control of the cervical lymph node

metastasis is also related to the N staging. Approximately two

thirds of cases of N1 disease (lesion < 3 cm in diameter) can

be controlled with radiation alone or in combination with

surgery.

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17

Results of Treatment

The local control rates for 170 patients treated with RT alone versus surgery alone or with RT between 1964 and 1990 at the University of Florida were T1, 79% versus 76% (P = .76); T2, 72% versus 76% (P = .86); T3, 45% versus 82% (P = .03); and T4, 0% versus 67% (P = .08).Local control rates for T1 or T2 cancers are comparable after RT versus surgery; patients with T3 or T4 lesions have improved local control if surgery is part of the treatment. The differences in 5-year survival between the two treatment groups were not statistically significant.

The results of brachytherapy alone or combined with EBRT for 448 patients treated at the Centre Alexis Vautin were reported by Pernot et al. and revealed the following 5-year local control and survival rates: T1, 93% and 69%; T2, 65% and 41%; and T3, 49% and 25%, respectively. Shorter time intervals between brachytherapy and EBRT were associated with significantly improved local control and survival for those who received both modalities.

Following treatment, the most common site of failure is the site of

the primary lesion, with or without simultaneous failure in the

cervical lymph nodes. Approximately 80% of the recurrences

appear within 2 years following treatment. Failure in the cervical

lymph nodes alone or in distant metastasis alone is rare.

A relatively large series of 160 patients from France showed that

brachytherapy alone offers excellent local control of 89% for T1

and T2 lesions with a 5-year survival of 76%. In spite of the good

local control rate of carcinoma of the floor of the mouth, actuarial

survival of these patients is poor, owing to a significant number of

deaths from intercurrent disease or a second primary cancer.

Follow-Up

There are two major difficulties in follow-up after RT: soft tissue ulcers and enlarged submandibular glands. An ulcer in the floor of the mouth within 2 years of treatment can be either recurrence or necrosis. If the lesion appears to be soft tissue necrosis, a trial of conservative therapy is adequate. Failure to stabilize or resolve is an indication for biopsy. A negative biopsy does not rule out recurrence, and repeat deep biopsies may be necessary. An enlarged submandibular gland(s) may be a sequel to obstruction of the submandibular duct; contrast-enhanced CT is useful to distinguish between an enlarged submandibular gland and tumor in a lymph node.

Follow-up of surgical cases may be difficult if skin grafts or flaps have been used because of the associated induration and thickness of the flaps. If the submandibular ducts have been reimplanted, stenosis may occur with subsequent enlargement of the submandibular glands.

Complications

Radiation Therapy

FOM has lower RT tolerance d/t increased risk of soft tissue injury & ORN. A small soft-tissue necrosis (approximately 10% to 21% of the patients, usually within 2 years of treatment) may develop, usually in the site of the original lesion where the dose is highest. These are moderately painful and respond to local anesthetics, antibiotics, & analgesics. Treatment with pentoxifylline 400 mg three times daily may be beneficial.

If the ulceration develops on the adjacent gingiva, the underlying mandible is exposed. These areas are mildly painful. They are managed by discontinuing dentures, local anesthetics, antibiotics, and smoothing of the bone by filing if needed. These small bone exposures do not often progress to osteoradionecrosis (ORN) and either sequestrate a small piece of bone or are simply recovered by mucous membrane. Severe ORN may require daily hyperbaric oxygen treatments for 4 to 6 weeks, either alone or in conjunction with surgical intervention (hemimandibulectomy).

Surgical

These include bone exposure, orocutaneous fistula, and failure of osteomyocutaneous flaps. Salvage procedures after RT are associated with an increased risk of complications. Damage to the lingual nerve or the hypoglossal nerve, although rare, is associated with difficulty in swallowing and/or speaking.

Radiation-Induced Bone Disease

The edentulous person is less likely to develop serious RT-induced mandibular damage than a person with teeth. The most frequent problem involving the mandible is a bone exposure. The gingivadisappears, exposing the underlying bone. If the exposed area is small, the patient is often unaware of the problem. If the patient has dentures, those dentures should be discontinued or altered to relieve the pressure over the exposed bone. If sharp bony edges appear, they are filed and the bone edge lowered to speed healing. Healing may require months or even years.

If ORN develops, hyperbaric oxygen has been used with some success. Conservative measures should be given a fair trial, but if unsuccessful, segmental mandibulectomy and an osteomyocutaneous flap reconstruction is performed.

Buccal Mucosa

Verrucous carcinoma accounts for <5% of all oral cavity

carcinomas, occurs most often in the buccal mucosa, has a

more favorable prognosis, and is considered a low-grade

malignancy. Surgical resection remains the preferred mode of

treatment for primary lesions of the buccal mucosa. Adjuvant

radiation treatment is usually not indicated. Since verrucous

carcinomas rarely metastasize, elective neck dissection is

often not indicated for patients with this disease.

Routes of spread

Squamous-cell carcinoma of the buccal mucosa can extend to

involve the pterygoid muscles, and superiorly, they can grow

to involve the alveolar ridge, palate, GBS, maxillary sinus,

mandible. The majority of patients have cancer that extends

beyond the buccal mucosa. Metastasis to the cervical lymph

nodes most commonly affects the submandibular nodes.

Lymph node metastasis occurs in approximately 9% to 31%

of the patients during the course of the disease. Involvement

of the upper cervical and the parotid lymph nodes is less

common.

Treatment

Selection of Treatment Modality

Small lesions (≤1 cm) may be excised with primary closure;small

lesions that involve the lip commissure or in the mid-cheek

without sulcus invasion are treated by RT. Lesions 2 to 3 cm in size

can be treated with surgery or by RT, usually the former. Transoral

resection is preferred and is most convenient for small lesions.

Larger lesions are usually treated with surgery (composite

resection of buccal mucosa with mandible or upper alveolus or

overlying skin) and postoperative RT or chemoRT. A recent

report stated that T classification and negative margins are not

adequate predictors of local control, and even early buccal tumors

could benefit from adjuvant therapy to enhance local control. In

another series, local recurrence occurred in all patients with stage

I and II disease treated with wide local.

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18

Surgery Tumors approximating the gingiva should be resected with the

gingiva and periosteum as an additional deep margin, while those that involve the periosteum should be resected with an additional deep margin of bone. Cancers that directly invade bone should be resected with a segment of bone.Repair may require a maxillary prosthesis. A myocutaneous flap repairs full-thickness removal of the cheek.

A radical neck dissection is recommended in all patients with a node-positive neck, whereas a supraomohyoid neck dissection can be considered in the node-negative neck.

Surgery is also considered in patients who recur after radiotherapy as salvage. One series reported a 5-year actuarial disease-free survival after surgical salvage of 59.7%.

Irradiation Technique

As in other sites of the oral cavity, adjuvant treatment with chemotherapy and radiation is recommended in patients with positive margins or extranodal extension. In cases that are inoperable, radiotherapy in combination with chemotherapy can be used.

Buccal mucosa lesions are suited for treatment with electrons, intraoral cone, and interstitial techniques to spare the contralateral normal tissues. When tumors extend into one of the gingivobuccal gutters or onto bone, treatment must be entirely by EBRT.

Intraoral device can be placed to displace & shield the tongue.

An ipsilateral mixed photon/electron beam ( or wedged photon pair) & a boost is given with brachytherapy or intraoral seeds.

Field borders: 2cm anterior & superior to the lesion ; posteriorlyat the posterior aspect of the spinous processes if nodes are to be irradiated; inferiorly at the thyroid notch.

The oral commissures & lips should be excluded or shielded if possible.

Postop volume include the tumor bed, scars, & ipsilateral IB & II nodes.

Patients with positive nodes receive B/L neck RT to the upper & lower neck.

Buccal Mucosa:

Indications:

Brachytherapy alone indicated for small (<4cm), well-defined

lesions in anterior 2/3rd

As boost after EBRT for larger lesions

T.V.: GTV + margins

Dose: Alone 65-70 Gy

Boost 25-30 Gy

Technique: Guide Gutter Technique: Lesion < 2cm

Plastic tube technique: For other lesions

Either 3-D conformal therapy or IMRT should be used to

spare the contralateral parotid gland. Because buccal mucosa

lesions are lateralized, treatment of the contralateral buccal

mucosa is not necessary in T1 and T2 lesions. Postoperative

dosing regimens for buccal mucosa cancer are similar to

other regions of the oral cavity.

doses of 66 Gy in 2-Gy fractions for positive margins, 60 Gy

in 2-Gy fractions or 59.4 to 63 Gy in 1.8-Gy fractions to

high-risk regions, and 54 Gy in 1.8-Gy fractions for low-risk

regions. An LAN is often used, treated to either 50 Gy in 2-

Gy fractions or 50.4 Gy in 1.8-Gy fractions.

Results of Treatment

Diaz et al. recently reported the M. D. Anderson experience for 119 patients treated with surgery alone (84 patients) or combined with adjuvant RT (35 patients) between 1974 and 1993. Tumor recurrence developed in 54 patients (45%): local recurrence in 27 patients (23%); regional recurrence in 13 patients (11%); local and regional recurrence in 11 patients (9%); and distant metastases in 3 patients (3%). The 5-year survival rates versus stage were stage I, 78%; stage II, 66%; stage III, 62%; stage IV, 50%; and overall, 63%.

A study by Lin and colleagues examined 121 patients with M0 disease treated with either surgery alone, radiotherapy alone, or surgery plus postoperative radiation. The rate of local recurrence in patients with T1-

2-N0 disease who received surgery alone was 40%, and for locally advanced disease both locoregional control and overall survival were improved in those patients receiving a combined-modality approach.[

Nair et al. reported the definitive RT results for 234 cases of buccalmucosa cancer treated in southern India during the 1982 calendar year. The 3-year disease-free survival rates were stage I, 85%; stage II, 63%; stage III, 41%; and stage IV, 15%. Thirty-two patients had verrucouscarcinoma; the 3-year disease-free survival rate was 47%, similar to that for other grades of SCC.

Complications of Treatment

The buccal mucosa is tolerant of high-dose RT, and

complications are uncommon. Bone exposure may appear on

the mandible or maxilla. Trismus may develop if the muscles

of mastication receive high doses.

Surgical injury of Stensen’s duct may cause obstruction and

parotitis. Injury to branches of the VII nerve may occur. Split-

thickness skin grafts may shrink and produce partial trismus.

Resection of the lip commissure may produce oral

incompetence.

Treatment Outcome

Reports of the select retrospective studies of carcinoma of

the buccal mucosa can be found in Table 29-6.A prospective,

randomized trial from India examined the role of

postoperative radiotherapy in stages III and IV carcinoma of

the buccal mucosa. The 3-year actuarial disease-free survival

was 68% versus 38%, with and without postoperative

radiotherapy. The 3-year actuarial overall survival was 94%

versus 84%, respectively.

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19

Hard Palate and Upper Alveolar Ridge

Initial growth tends to be superficial, although these tumors

can extend through the periosteum of bone into regions

adjacent to the oral cavity, such as the paranasal sinuses and

floor of the nose. Lymph node spread is present in less than

10% of patients.

Although radiation can be used to treat carcinomas of this

site, surgery is preferred. Postoperative radiation therapy

should be delivered when there are adverse features; that is,

close/positive margins, perineural extension, vascular

invasion, high-grade histology, multiple positive nodes, or

extracapsular extension.

Surgery

Maxillary antrum not involved: partial maxillectomy or RT in select T1-2 lesions.

Maxillary antrum involved: orbital floor preserving total maxillectomy with reconstruction.

A defect in the maxilla results in lack of oral/nasal separation that can impair the ability to speak and swallow effectively. An obturator ( synthetic polymer) with or without a skin graft is the most common method used to restore oral/nasal separation.

Regional pedicled flaps and free-tissue transfers may provide alternatives to obturation. However, their use is somewhat controversial for reconstruction of palatal defects since these nonremovable flaps may mask local recurrences that can be more readily identified in patients whose defects are obturated.

Elective treatment of the neck is controversial for hard palate

region tumors. Although some series have shown lower rates of

occult metastases for palatal tumors when compared to other oral

cavity sites, preoperative imaging should be performed to evaluate

for the presence of metastases to the retropharyngeal nodes since

these are difficult to evaluate on clinical examination and are at

some risk for spread from primary palatal tumors.

Ameloblastoma

The treatment for ameloblastoma is surgery; however, local

recurrence is a problem.

Limited experience with RT suggests that it may reduce the

probability of progression and result in long-term local control in

the occasional patient with incompletely resectable disease.

Very superficial lesions of the hard palate can be treated

definitively with surface molds. If definitive external-beam

radiation therapy is used with conventional techniques, the patient

is treated with opposed-lateral fields or wedge pairs to 66 to 74

Gy in 2-Gy fractions.

When IMRT techniques are used, a dose of 70 Gy is used for gross

tumor, 59.4 to 63 Gy for high-risk regions, and 54 Gy for low-risk

regions.

In the postoperative setting, doses of 60 to 66 Gy using 1.8 to 2

Gy per fraction are administered, with a dose of 66 Gy being

reserved for patients with positive margins. Postoperative

radiotherapy usually begins 2 to 3 weeks after surgery.

A prosthesis (i.e., obturator) can be placed over the postsurgical

defect during radiotherapy. Alternatively, a balloon filled with

water can be used to compensate for postsurgical tissue defects.

The radiation field

should encompass

the entire surgical

bed. In most cases it

is necessary to treat

with opposed lateral

fields to cover the

volume at risk.

However, for well-

lateralized lesions of

the upper alveolar

ridge, ipsilateral

radiation with a

wedge pair may be

adequate.

Treatment Outcome

Owing to the rarity of this disease, limited information is available.

Evans and Shah reported their 15-year experience from the Memorial

Sloan-Kettering Cancer Center. For stage I squamous cell carcinoma of

the hard palate, the 5-year disease-free survival rate was 75% (6/8); all

patients were treated with surgery alone. For stage II disease, 46%

(6/13) were disease free at 5 years; postoperative radiotherapy was

added in one patient. In stage III disease, the 5-year disease-free survival

rate was 40% (4/10); one patient in the group received postoperative

radiotherapy. In stage IV patients, 8% (1/12) of patients treated with

surgery alone, 25% (1/4) of those treated with radiotherapy alone, and

none (0/2) of those treated with the combined modality were disease-

free at 5 years. In another series of patients with squamous cell

carcinoma of the hard palate, from the University of Virginia, select

early-stage lesions were equally effectively treated by radiotherapy as

surgery during the supervoltage era. Patients with a clear margin after

surgical resection had improved local control. See Table 29-9 for select

results of definitive radiation therapy of the hard palate.

Carcinoma of the Upper Gingiva Routes of Spread Carcinomas of the upper gingiva usually

spread by direct invasion into the maxillary sinus or the upper gingivobuccal sulcus. Lymph node metastasis most frequently involves the submandibular lymph nodes. The subdigastric and upper cervical nodes are less frequently involved. At diagnosis, 18% to 52% of patients have positive lymph nodes.

Treatment Approach Because of early bone involvement and the risk of bone exposure after the tumor is irradiated, surgery is the treatment of choice for carcinomas of the upper gingiva. Except for early superficial lesions, most tumors of the hard palate and upper gingiva are treated with surgery. Postoperative radiotherapy is added in high-risk patients.

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20

For gingival lesions, if PNI is present, the entire hemimandible from mental foramen to the TMJ is treated

Fields cover the primary with 2 cm margins and the upper neck nodes. The low neck is treated for T3/4 or LN+.

Definitive RT for T1:60-66 Gy, T2: 66-70 Gy,T3-4:> 72 Gywithout chemotherapy & 70 Gy with chemotherapy.

Postop EBRT: 1.8-2 Gy/fx to 50-54 Gy f/b boost to 60 -66 Gy to high risk ares.

A balloon filled with water can be used to compensate for postsurgical tissue defects. Postoperative radiotherapy usually begins 2 to 3 weeks after surgery.

Treatment Outcome In the review of the Memorial Sloan-Kettering Cancer Center experience of 61 patients with upper gingival tumor treated mostly with surgery, the 5-year survival rate was 51% (31/61). Clinical stage was the only predicator of survival.In another series of 82 patients from Japan, the 5-year local control rate was 61% with a 5-year actuarial survival of 45%. A third more recent series from India examined the results of 110 patients with tumors of the superior gingival-buccal complex treated with either surgery alone, radiation alone, or a combined modality approach. Five-year progression-free survival was 49% for patients treated surgically and 0% with a nonsurgical approach. T stage and extracapsular spread were predictors of disease progression.

Carcinoma of the Lower Gingiva

Routes of Spread

Tumor spreads mainly through the occlusal ridge alone or in combination with penetration of the buccal or lingual plates in edentulous patients. Lymph node metastasis is present in 13% to 24% of patients with carcinoma of the lower gingiva. The submandibular lymph nodes are most frequently involved. Involvement of the subdigastric and upper cervical nodes is less common. Direct invasion of the mandible may be present in 50% of the patients on initial examination. The actual extent of bone involvement may exceed that shown on radiographs. Therefore, additional imaging is essential to accurate preoperative assessment.

Treatment Approach

Because of frequent bone involvement and lymph node

metastasis, surgery has been the primary treatment modality

in the management of carcinoma of the lower gingiva.

Early superficial lesions can be expeditiously treated by a

simple excision or marginal resection with skin graft.

Patients with advanced T stage, radiologic or histologic

evidence of mandibular invasion, tumors involving the

symphyseal region, and decreased tumor differentiation have

high propensity for regional metastases. Therefore, elective

treatment of the neck should be considered.

Mandible uninvolved or

minimally involved:

Mandible grossly involved

W/E with marginal mandibulectomy ( avoided in RMT disease, edentulous mandible, paramandibulardisease, post RT)

Indications of MM: tumor close to the mandible to achieve adequate margins ( 5-10 mm), limited superficial bony erosion, limited periosteal invasion.

W/E with segmental/ hemimandibulectomy with postoperative CT-RT

Indications of Segmental Mandibulectomy:gross tumor invadind the mandible, prior RT, edentulous mandible, gross paramandibular disease, whenever inferior soft tissue & bony margin of 1 cm is not possible( RMT, gross perioteal invasion)

Irradiation

In patients with more advanced disease, postoperative radiotherapy can reduce the incidence of local recurrence.

Early superficial lesions, less than 2 cm in diameter, can be adequately treated with 60 Gy using electrons in 3 to 4 weeks using a peroral cone.

Carcinomas that involve a large surface area with little or no bone invasion may be treated by EBRT. T1–T2 carcinomas are treated with altered fractionation; larger tumors are treated with combined EBRT and concomitant chemotherapy.

Orthovoltage energies should not be used over bone.

For more advanced unresectable disease, a definitive external-beam irradiation technique, preferrably with IMRT, should be used to a dose of 70 Gy.

If IMRT is not available and conventional techniques are being used, oblique- or right-angle, wedged-pair field arrangements can be used to spare the contralateral salivary glands.

Treatment Outcome

Local control of carcinomas of the lower gingiva treated with radiotherapy alone was achieved in 71.5% (5/7) of T1 lesions, 70% (7/10) of T2 lesions, 59% (10/17) of T3 lesions, and 29% (4/14) of T4 lesions in the series reported by MacComb.[92] The 5-year survival rate of 108 patients treated between 1947 and 1960 at the MD Anderson Cancer Center was 46%.[92] Most series report excellent local control with surgery followed by postoperative radiotherapy when indicated. Results from select series are shown in Table 29-7.[110],[113] In the aforementioned study at MD Anderson Cancer Center[112] examining prognostic factors of the disease, the authors found that advanced T stage, positive surgical margins, mandibular invasion, and cervical metastases were all associated with a worse overall survival.

Results of Treatment

Mandibular Gingiva

Overholt et al. reported 155 patients with SCCs of the lower alveolar ridge treated at M. D. Anderson between 1970 and 1990. Surgery alone was used for 131 patients and the remainder received surgery and RT. Five-year survival for patients with T1 and T2 cancers were 85% and 84%, respectively, compared with 66% and 64%, respectively, for those with T3 and T4 malignancies. Local control at 2 years was impacted by tumor size (P = .021) and margin status (P = .027), whereas 5-year cause-specific survival was influenced by tumor size (P = .001), margin status (P = .011), mandibular invasion (P <.05), and the presence of lymph node metastases (P <.001).

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21

Retromolar Trigone

Byers et al. reported the M. D. Anderson results for 110 previously untreated patients with SCC of the retromolar trigone treated between 1965 and 1977, with a minimum 5-year follow-up. Surgery was often selected for patients with leukoplakia, poor teeth, mandible invasion, large neck nodes, or trismus. RT was selected for poorly differentiated tumors, for mainly exophytic lesions, and lesions involving the faucial arch or soft palate, or lesions having ill-defined borders, and for patients who had poor surgical risk. The local control rates were as follows: T1, 12 of 13 (92%); T2, 50 of 57 (88%); T3, 18 of 20 (90%); and T4, 15 of 20 (75%). Local control was similar after surgery and/or RT. The absolute 5-year survival rate was 26%.

Mendenhall et al. reported on 99 patients with retromolar trigone SCCs treated between 1966 and 2003 with RT alone (35 patients) or combined with surgery (64 patients). The 5-year locoregional control rates after RT versus surgery and RT were stages I–III, 51% and 87%; stage IV, 42% and 62%; and overall, 48% and 71%, respectively. The 5-year cause-specific survival rates after RT versus surgery and RT were stages I–III, 56% and 83%; stage IV, 50% and 61%; and overall, 52% and 69%, respectively. Multivariate analysis revealed that the likelihood of cure was better after surgery and RT compared with definitive RT

Hard Palate

Shibuya et al.reported the results for 38 cases of carcinoma of the hard palate and 82 cases of carcinoma of the upper alveolar ridge treated between 1953 and 1982 in Japan. Sixty-six patients were managed initially by RT alone to the primary lesion, and 54 patients were managed by RT and surgery. The 5-year actuarial survival rate by stage was the following: stage I, 56%; stage II, 41%; stage III, 32%; and stage IV, 12%. There was no difference in survival when comparing hard palate versus upper alveolar ridge, SCC versus minor salivary gland tumors, or RT alone versus RT plus surgery as the initial therapy. The overall risk for metastatic lymph nodes was 47% for hard palate and 49% for the upper alveolar ridge. Thirty patients were recorded as having “slight bone invasion” and no metastases and had a 5-year survival rate of 75% when treated by RT.

Complications of Treatment

Surgical complications include orocutaneous fistula, bone

exposure, extrusion of a metal tray, and loss of graft or flap.

Following hemimandibulectomy, the edentulous patient

usually cannot wear dentures.

The complications of RT include soft tissue necrosis, bone

exposure, and ORN. The risk is greatest for patients with

advanced lesions of the lower gum and retromolar trigone.

Huang et al. reported the following rates of grade 3 bone and

soft tissue complications in 65 patients treated for retromolar

trigone carcinomas: preoperative RT, 0 of 10 patients (0%);

surgery and postoperative RT, 5 of 39 patients (13%); and RT

alone, 2 of 16 patients (13%).

Retromolar Trigone

Cancers of the retromolar trigone may be advanced at

presentation because only a thin layer of soft tissue overlies

the bone in this region and invasion of the underlying bone

may occur early. In addition, there are multiple pathways for

spread from this site including the buccal mucosa, tonsillar

fossa, glossopharyngeal sulcus, floor of the mouth, base of the

tongue, hard and soft palate, masticator space, and maxillary

tuberosity.

Frequently metastasize to the subdigastric lymph nodes. The

submandibular and upper cervical lymph nodes are affected

less often. The incidence on diagnosis is approximately 30%.

Early stage T1 and T2 cancers can be treated equally effectively with surgery or radiation with primary control rates for T1 and T2 tumors of 92% and 88%, respectively.

For more extensive superficial lesions that extend to involve the soft palate or tonsillar complex but do not invade bone, radiotherapy may be a better treatment option, since broad resection of the palate can result in poor speech and swallow outcomes.

Well-lateralized lesions of the retromolar trigone can be treated by ipsilateral mixed beam techniques or angled wedge techniques.

Stage III and IV lesions commonly require combined surgery and radiation. A limiting factor for the achievement of adequate surgical resection margins for tumors in this area includes extension of tumor posterosuperiorly into the pterygopalatinefossa and into the base of skull.

When external-beam irradiation is used alone with conventional methods, a technique using mixed electrons and photons with single lateral fields or parallel opposing fields with 2 : 1 weighting favoring the side of the disease can be used. Usually a dose of 66 to 74 Gy in 2-Gy fractions is administered.

IMRT can be used when available, using a dose of 70 Gy for gross disease, 59.4 to 63 Gy for high-risk disease, and 54 Gy for low-risk disease.

Prophylactic treatment of the neck is essential as lesions located in the retromolar trigone have a high propensity for metastases in the neck. We generally treat the contralateral lymph node levels I through V electively in patients with T3, T4, or node-positive disease, whether in definitive treatment or in the postoperative setting.

(Fig. 29-19).

T4N0

Retromolar Trigone

(Postoperative)

Treatment Outcome MD Anderson Cancer Center reported results of 159 patients

with squamous cell carcinoma of the anterior faucial pillar and retromolar trigone region treated with radiation.[114] Local control with radiation alone for T1 lesions was 71% (12/17); for T2lesions, 70% (51/81); for T3 lesions, 76% (19/25); and three of five T4 lesions were controlled. Most of the failures were treated with surgery, and the ultimate control rate was 100% for T1, 94% for T2, and 92% for T3. The overall N0 neck failure rate was 11%. The authors recommend elective treatment of subdigastric and upper jugular nodes to the level of the hyoid. The 5-year determinate survival rate in the series was 83%. A more recent study at the Notre-Dame Hospital in Quebec demonstrated 5-year regional control rates of 88% after definitive radiation and 67% after salvage surgery.[115] See Table 29-8 for select results of treatment for carcinoma of the retro molar trigone.[115-117]

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22

Management of Recurrent Disease The appropriate management of recurrent oral cavity cancer

depends largely on the extent of disease, the prior therapy administered, and whether the recurrences are local, regional, or both. Obviously, if there is distant disease recurrence, systemic therapy approaches will likely assume primary importance. In the case of small recurrences at the primary site for patients treated with primary excision only, further excision with or without postoperative radiotherapy is often recommended. For larger recurrences in patients who received radiation as part of their initial management, the rate of surgical salvage is quite low. In some cases, further resection may be considered for palliation or curative treatment attempt, particularly in the setting of a clinical trial. Systemic therapy, reirradiation, and palliative care are other options for this group of patients, and the risks and benefits of each should be discussed with the individual patient.

Critical Normal Tissues

Acute and Late Effects Acute changes occur in the oral mucosa, the

salivary glands, and the taste buds during irradiation. Unless the

parotid glands are blocked or constrained, xerostomia occurs after a

few weeks.

With 3-D conformal treatment or IMRT, the restoration of at least

partial salivary function can be effectively accomplished with

appropriate limits. Dosimetric sparing of the parotid glands during

IMRT in head and neck cancer, defined by a mean parotid dose, less

than or equal to 26.5 Gy, is feasible when the parotid–planning target

volume overlap is less than 20%.

Acute mucositis cannot be avoided. For the definitive treatment of

lesions with radiotherapy, the goal is to achieve mucositis that is either

patchy (grade 2) or confluent (grade 3).

Xerostomia✓ Radiation > 3000 cGy

✓ Starts after 1 wk of treatment

✓ Dose related

✓ Saliva flow reaches ‘zero’ with 6000 cGy

✓ Serous acini affected more than mucous acini

✓ May resolve within 6 months

✓ If persisted for more than 1 yr, permanent damage

Management

Sialogogues

Pilocarpine

Bethanecol

Prophylactic

- Pilocarpine, Amifostine ( not used)

MucositisWith common fractions of 180 to 220 cGy per day, mucositis with erythema is

noted in 1 to 2 weeks and increases throughout the course of therapy -to a maximum in 4 weeks- with persistence until healing occurs 2 or more weeks after the completion of therapy.

Management

-Systemic

(1) Pain management

- Analgesics: WHO ladder

- Adjuncts: Relaxation, imagery, biofeedback, hypnosis and transcutaneous electrical nerve stimulation

- b carotene

(2) Radioprotectors

- Amifostine: Scavenge free radicals

(3) Biologic Response Modifiers

- G-CSF, GM-CSF, Keratinocyte Growth Factor

Topical Diluting agents

Saline, bicarbonate rinses, frequent water rinses, dilute hydrogen peroxide rinses

Coating agents

Kaolin-pectin, aluminum chloride, aluminum hydroxide, magnesium hydroxide, hydroxypropyl cellulose, sucralfate

Lip Lubricants

Water-based lubricants, lanolin

Topical anesthetics

Dyclonine HCl, xylocaine HCl, benzocaine HCl, diphenhydramine HCl

Analgesic agents

Benzydamine HCl

Late effects are seen as bone necrosis in the mandible and the maxilla, which occurs after breakdown of the mucosa and exposure of the bone with ensuing osteomyelitis.Teeth in poor condition should be extracted prior to radiation therapy. The teeth must be maintained in good condition to avoid extractions, which can lead to infection. Soft-tissue necrosis is frequently seen after both brachytherapy and peroral cone treatment. It is painful, but usually heals without surgery. A necrotic mandible often must be resected.

With the advent of IMRT, there appears to be a reduction in the toxicity associated with treatment of the oral cavity. A study from the University of Michigan demonstrated no cases of osteoradionecrosis in 176 patients treated with head and neck cancer from 1996 to 2005 with at least 6 months of follow-up.Of these patients, 75% received greater than or equal to 65 Gy to at least 1% of the mandibular volume, and 50% had received at least 70 Gy to this volume. However, the authors found a high level of falloff across the mandible, with the average gradient being 11 Gy.

Dental and Oral Care After radiotherapy, there is increased

susceptibility to infection and development of dental caries. This is

due to the decreased amount and pH of the saliva, diminished

vascular supply, reduced number of osteoblasts and osteoclasts,

altered normal metabolism of bone, and impaired ability to heal in

response to physical, chemical, and biologic injuries after head and

neck irradiation. As a result, osteoradionecrosis develops in

patients following head and neck irradiation, especially if proper

preradiotherapy dental care was not done. The mandible is most

commonly involved and the maxilla is rarely affected. The risk of

osteonecrosis is directly related to the radiation dose to the bone.

The incidence and severity of dental decay and osteonecrosis can

be minimized with proper dental care and hygiene before, during,

and after head and neck irradiation.

During radiotherapy, patients are encouraged to irrigate the

mouth with a salt and baking soda solution (1/2 to 1 teaspoon of

salt and 1/2 to 1 teaspoon of baking soda in 1 quart of warm

water) three to four times daily. Moniliasis is a common

complication during irradiation of the head and neck. This can be

effectively controlled with systemic antifungal agents. Once the

patient has been placed on an agent, it is important to maintain its

use until the completion of radiotherapy. Otherwise, moniliasis

usually recurs if treatment is discontinued during the course of

radiotherapy.

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23

After radiotherapy, the patients are continued on a good oral hygiene program and topical fluoride applications (mouth rinses) as well as a fluoride-containing dentifrice. Caries are filled and there are no unusual contraindications for endodontic procedures. Extractions are performed whenever necessary and antibiotics are routinely used to minimize the risk of infection. When osteonecrosis develops, it is usually managed conservatively with topical or systemic antibiotics and analgesics initially. Good oral hygiene is imperative. Loose spicules of bone above the gingival crest are gently removed. Healing may take place over a period of several months. Partial mandibulectomy is performed only if conservative management fails and the patient continues to have persistent pain, infection, or trismus.

Dietary supplements such as instant breakfast, Sustagen, Ensure, or other homemade substitutes are soothing to the mucosa and easy to swallow, and provide a substantial amount of calories as well as essential vitamins.

In patients with severe pain and dysphagia or problems of mastication or excessive weight loss, tube feeding may be necessary. The aim of a dietary program during head and neck irradiation is to provide adequate nutrition and prevent weight loss. Percutaneous gastrostomy tube placement may be required for patients who lose more than 10% of their body weight. Multiple studies have shown that prophylactic gastrostomy tubes are safe and may limit weight loss in patients receiving radiation for head and neck cancer, and we strongly consider their placement, particularly in patients receiving chemotherapy in conjunction with radiation.

Follow up History and physical exam :

Year 1, every 1–3 mo

Year 2, every 2–4 mo

Years 3–5, every 4–6 mo

> 5 years, every 6–12 mo

Post-treatment baseline imaging of primary (and neck if treated) recommended within 6 mo of treatment (category 2B)

Further reimaging as indicated based on signs/symptoms; not routinely recommended for asymptomatic patients

Chest imaging as clinically indicated

Thyroid-stimulating hormone (TSH) every 6-12 mo if neck irradiated

Speech/hearing and swallowing evaluation and rehabilitation as clinically indicated

Smoking cessation and alcohol counseling as clinically indicated

Dental evaluation