Cyber knife in urological malignancies

Radiosurgery in urological malignancies

Debnarayan Dutta, MDConsultant Radiation Oncologist

Apollo Speciality Hospital, Chennai

INDIA

duttadeb07@gmail.com

Apollo Speciality Hospital, Chennai

Cancer management Facilities- Medical, surgical & radiation oncology unit

- 320 slice CT scan

- MRI scan with ‘time of flight’ technology

- Bone marrow transplant unit

- Two LA with 3DCRT, IMRT & IGRT

- HDR brachytherapy

- BrainLAB system

- CyberKnife

- Tumour board

- Multi-disiplinary support system

- 17 yrs experience in radiation therapy

- 8 yrs experience in IMRT

- 10 yrs experience in BrainLAB

‘The Week’ magazine ranking 2010

3rd rank in oncology

(after TMH & AIIMS)

Cyberknife

Accuray Confidential

Linear

Accelerator

Manipulator

Image

Detectors

X-ray Sources

IMAGING

SYSTEM

ROBOTIC

DELIVERY

SYSTEM

TARGETING SOFTWARE

Robotic Radiosurgery

Highly precise RT delivery system

- Respiratory tracking

- Fiducial based tracking system

- Intra-fraction motion correction

- Uncomparable dose distribution

- X-ray based image verification

Hypofractionated RT

- High dose short course RT

- Higher BED delivered to target

Ideal for moving targets

Unique features of Cyberknife:

‘Frameless’ treatment of intra & extra cranial disease

Both intra & extra-ceanial

tumours can be treated

Unique features of Cyberknife:

– Relies on intra-fraction imaging to continually assess target movement

– Stated total clinical accuracy of .50mm

Chang et al.Neurosurgery, 2003

Murphy MJ et al. Int J Radiat Oncol Biol Phys. 2003

Sub-millimeter accuracy

CyberKnifeNovalis / Trilogy

Unique features of Cyberknife:

Unmatched dose distribution

Higher low dose spillage with Novalis.

Better dose conformity with Cyberknife

DRR

LIVE

Unique features of Cyberknife:

‘6-D tracking system’

Unique features of Cyberknife:

‘Fiducial tracking’

Fiducial tracking is the most effective method of tumour tracking

Unique features of Cyberknife:

Non-coplanar field arrangement

Unique features of Cyberknife:

‘Dose painting’ technique

– Highly conformal dose delivery

– Both isocentrically and non-isocentrically

– Non-coplanar beam arrangement

– Flexible fractionation schedule

– Flexible treatment delivery

Synchrony respiratory tracking system: Cyberknife

Synchrony respiratory tracking system• Continuously tracks tumor motion during treatment

– Synchrony RespiratoryTracking System

• Continual tracking of motion throughout treatment

• Continuously adapts to variations in breathing patterns in 3D

– Model updated throughout treatment based on both internal & external motion

• Beam automatically corrects for target movement

0.75mm targeting accuracy

Unique features of Cyberknife:

Shorter overall treatment time

Site Schedule Days

Lung cancer 60 Gy/3# 3 days

45 Gy/3# 3 days

Prostate 36.25 Gy/5# 5 days

Brain tumours 20-30 Gy/3-5 # 3-5 days

AVMs 12-25 Gy/1# 1 day

Single fraction Rx 12-25 Gy/1# 1 day

Cyberknife IMRT

36.25 Gy/5# 70 Gy/35#

~3 hours ~10 hours

Daily treatment

Cyberknife: 45 min

IMRT: 15 min

With Cyberknife both total duration (min) &

treatment days are short

Total treatment duration in hrs

• Highest level of comfort

• Pain-free / No anesthesia

• No invasive head or body frame

• No breath-holding during treatment

• Significantly reduces treatment time

• Treats only affected areas

• Minimizes acute side effects

• Treats tumors anywhere in the body

• Sub-millimeter accuracy

• Dynamic (Inter-fraction) motion tracking

Cyberknife : Advantages

Radiosurgery in urological malignancies

- Prostate cancer

- Renal cell cancer

- Urinary bladder cancer

• Most prevalent malignancy in males in western community

• 2nd MC cause of mortality in the west

• Uncommon in Asians, probably shorter lifespan

• In TMH, constitutes 2.4% of all registered pts in 2000

• In recent years, more early prostate cancer patients are diagnosed

with prostate cancer

• Prostate cancer is slow growing tumour, risk of bone metastasis is

high in ‘high risk’ group patient

Prostate cancer

Risk stratification

RISK STRATIFICATION

LOW RISK INTERMEDIATE HIGH

T1,2a, PSA < 10 ng/ml,

GS</=6

T2b,

GS=7

T3,4,PSA>20ng/ml,

GS>7

Wait & watch

Surgery

Radiation therapy

HT

Radiosurgery

Combination

Surgery

Radiation therapy

HT

Radiosurgery

Combination

Surgery

Radiation therapy

HT

Radiosurgery

Combination

Radiotherapy

Radiation techniques:

2D Planning

Conformal Radiation therapy

- 3D-CRT

- IMRT

- SBRT

Target volume:

CTV – prostate with capsule + SV

T1 & small T2 with less PSA less GS only prostate is sufficient.

PTV – 1 cm margin.

Inclusion of pelvic lymph nodes still controversial.

Ca prostate Incidence of pelvic LN metastasis at diagnosis

Study T1a,b T1c T2a T2b,c T3

Pisansky 12/457

(2.6%)

15/456

(3.3%)

130/1206

(10.8%)

81/320

(25%)

-

Petros &

Catalona

2/61

(3.3%)

33/425

(7.8%)

0

Sands 6/127 (5%) 41/243

(16.9%)

95/199

(47.7%)

Van

Poppel

2/40(5%) 18/199

(9%)

25/46

(54%)

Hanks 1/21(5%) 38/135(28%) 48/95(50%)

Radiotherapy Radiation therapy schedules

Conventional fractionation:

- 70Gy/ 35# / 7 wk

- 2Gy/#

- Acute rectal & bladder toxicity

Hypofractionation schedule:

- High dose per fraction, short course treatment

- Equivalent loco-regional control

Ultra-hypofractionation schedule:

- Very short course, high dose per fraction

- Usual treatment duration 5 to 7 days

Conformal Radiation therapy

reduces toxicity

• RCT

• Royal Marsden Tait et al.Gr 2 or more 5 Vs 15%.

• Rotterdam trial Koper et al.

Grade 2 GI toxicity (32% vs. 19%, p = 0.02).

• M.D. Anderson Storey et al.

No dif but Dose 78 vs 70.

• Nonrandomized trials

• 15/27 improvement

• Most pronounced when dose escalation was not used.

• When dose escalation was used, no increased toxicity was demonstrated, except when the dose to the rectum >75 Gy.

• No article suggested increased toxicity with 3D-CRT for similar doses delivered compared with

conventional RT.

WPRT VS PORT:RTOG trial 9413

1323 patients with localized disease andrisk of LN involvement >15% & PSA <100

WP RT+ NCHT

PFS 60%

PO RT+ NCHT

44%

WP RT+ AHT

49%

PO RT+ AHT

50%

• WP RT NCHT improves PFS compared with PO RT and NCHT or PO RT and AHT, and

compared with WPRT + AHT in patients with a risk of LN involvement of 15%.

•Median follow-up : 59.5 mnths

• No OS advantage JCO 2003

Subset analysis of RTOG 9413

Subset of 694 patients studied

325 patients WP RT N&CHT

Median PFS 5.2yrs

324 patients PO RT N&CHT.

FS ≥10 × 11 but <11 × 11

cm)

MP FS<10x11cm

•Median PFS was 5.2, 3.7, and 2.9 years ( p 0.02).

•7-year PFS was 40%, 35%, and 27%

•RT field size has a major impact on PFS, and it is advised that

nodal treatment should be done in patients with a risk of LN inv >15% .

Roach IJROBP 2006

Dose escalation: improve LC

Author Study type Patient criteria Study details Results

Kurban et al Prospective

multi-

institutional

N= 4839

1986-95

T1-2 low risk

prostate cancer

No neo-adj HT

RT dose 60-78 Gy

3DCRT planming

Median FU 6.3 yrs

8-year PSA control rates were 72

to 93%. Dose >72 Gy had lower

PSA relapse rate.

Zietman MDACC

Randomized

N= 393

T1-2 disease

PSA < 105ng/dl

Arm 1: Conv RT 70.2 Gy

Arm 2: Conv RT 79.2 Gy

Median FU: 5.5 yrs

5-yr PSA rFS higher with dose

escalation (61% vs 80%). 49%

risk reduction in biochemical

failure.

Pollack et al MDACC

Randomized

N=301

Low risk prostate

cancer

Arm 1 (n=150): Conv RT 70

Gy

Arm 2 (151): 3DCRT 78 Gy

PSA rFS higher with dose

escalation (70% versus 64%;

p=0.03)

Peeters et al Randomized

Netherland

N=669

T1-4

Arm 1 (n=150): Conv RT 68

Gy

Arm 2 (151): Conv RT 78 Gy

Median FU: 51 months

5-yr PSA relapse-free survival

superior with high dose (64% vs.

54%; p = .02).

Zelefsky et al Randomized

MSKCC

N=1100

1988-98

RT dose systematically

increased from 64.8 to 86.4

Gy by increments of 5.4 Gy

in consecutive groups of pts.

5-yr PSA rFS was higher with

dose escalation in favorable,

intermediate and unfavourable

groups.

Zelefsky et al Single arm N=561

1996-2000

RT dose: 81 Gy to PTV 8-yr PSA rFS for favorable-,

intermediate-, and unfavorable-

risk groups were 85%, 76%, 72%

Prostate Cancer: Dose escalation studies

Intensity modulated radiation therapy

76- 81 Gy at 2 Gy/# dose delivered

Dose to target higher

Rectal & Bladder dose is high

High acute reactions

Dose escalation methods

IMRT/ 3DCRT

Dose escalation methods

Brachytherapy

Dose escalation methods

Brachytherapy seed implant

Dose escalation methods

HDR Brachytherapy implant

HDR brachytherapy implant

High dose rate

Invasive procedure

Skill dependent

Toxicities after Radiation therapy

Rectal toxicity

- Telengectasia

- Bleeding

- Bladder toxicity

- Incontinence

- Bleeding

- Thimble bladder

- Urethral stricture

-Erectile dysfunction

- Quality of life

Toxicity depends upon dose

Motion during treatment is a problem in Prostate Cancer

Cyberknife is the only technology which corrects movement between each field treatment

Author Study Patient criteria Study details Results

Martin Prospect

ive

PMH

N= 92

June 2001- Mar

2004

60 Gy /20 fr/ 4 wks

IMRT, FU: 38 mo

3 yr PSA relapse free was 76%.

RTOG Gr ≥3 GI toxicity in 1 patient

Kupelian Clevelan

d Clinic

N= 770

1998-2005

70 Gy; 2.5-Gy/fr/ 5

wks.

FU: 45 mo

5 yr PSA relapse free of low,

intermediate and high-risk disease was

95%, 85%, and 68%, respectively.

Livsey Retrosp

ective

Manche

ster

N= 705 men

T1-T4 disease

1995 -1998

Conformal RT (50

Gy/16fr/ 22 days)

Median FU: 48

months

Favourable, intermediate, poor

prognostic groups biochemical control

was 82%, 56%, and 39%. RTOG Gr ≥2

GI and bowel toxicity was 5% and 9%.

Lukka Randomi

zed

NCI

Canada

N= 936

Mar 1995-

Dec1998

Long arm: 66 Gy/33

fr 45 days

Short arm: 52.5

Gy/20 fr 28 days

5 yrs, PSA relapse free survival was

52.95% in long and 59.95% in short arm.

GI toxicity higher with short arm (11% vs

7%)

Tsuji Chiba

Japan

N=201

June 1995-Feb

2004

Three clinical trials RTOG Gr ≥2 GI toxicity. 5-yr PSA

relapse-free survival 83.2% without any

local recurrence.

Prostate Cancer: Hypofractionation studies

Author Study Patient criteria Study details Results

King Prospective N=41

Stanford

SBRT (CyberKnife)

36.25 Gy/ 5 fr/ 1 week

Median FU: 33 months

Biochemical control 100%

At 12 months, 78% achieved PSA nadir

RTOG Gr ≥3 rectal toxicity 4.8%

Friedland Prospective N=112

Naples

Feb2005-Dec

2006

SBRT (CyberKnife)

RT dose: 35-36 Gy/5 fr

Median FU: 24 months

3 patients had failure (two local and one

distant failure). 82% no erectile

dysfunction

Brachytherapy

Galalae Three centre

data

N=611

Localized

prostate cancer

HDR brachytherapy

combined with EBRT

5-yr PSA relapse-free survival were 96%,

88%, and 69% for favorable-,

intermediate-, and unfavorable-risk

patients

Prostate Cancer: Ultra-hypofractionation studies

Fullar et al, IJROBP 2008

Radiosurgery mimicking brachytherapy

Fullar et al, IJROBP 2008

Radiosurgery mimicking brachytherapy

Fullar et al, IJROBP 2008

Radiosurgery vs brachytherapy: Dosimetry

Radiosurgery vs brachytherapy: Dosimetry

Fullar et al, IJROBP 2008

Hossain et al, IJROBP 2010

SBRT vs IMRT : Dosimetry

Hossain et al, IJROBP 2010

SBRT vs IMRT : Dose distribution

Hossain et al, IJROBP 2010

Hossain et al, IJROBP 2010

Hossain et al, IJROBP 2010

SBRT: Early outcome of Ph II study (n=45)

SBRT: Early outcome of Ph II study (n=45)

SBRT: Clinical outcome (n=112)

Frieland et al, IJROBP 2009

Probability of maintaining erectile function

Robinson et al IJROBP 2002

King et al. IJROBP 2010

QOL: Sexual function domains

5 yr FU data with biochemical control & QOL function

QOL: Sexual function domains

King et al. IJROBP 2010

Aluwin J of Endourology 2010

Experiences from new centres

Aluwin J of Endourology 2010

Experiences from new centres

Stage Grade Treatment Treatment of recurrence

/ residual disease

Ta G1 TURBT + Immediate single

chemotherapy instillation with in

24 hrs of TURBT

Repeat TURBT

If sign of muscle

invasion consider

cystectomyG2-3

TURBT + Intravesicle therapyTcis G1-3

T1 G1-3

Superficial urinary Bladder

Author Study type Study details Results Remarks

van der

Werf-

Messing

Randomized

( n= 174)

Arm1: pre-OP RT

(30 Gy/15 fr) +

Nephrectomy

Arm 2:

Nephrectomy only

5 yr Survival:

50%

No difference between

Surgery alone and Pre-

OP RT + Surgery arm;

Increased resectability

in T3 disease

Juusela Randomized

(n=88)

Arm 1:

Nephrectomy alone

Arm 2: Pre OP RT

(33Gy; 2.2 Gy/Fr) +

Nephrectomy

5 yr Survival:

Arm 1: 63%

Arm 2: 47%

(p-value= NS)

No difference in

survival

Renal cell cancer: Pre-OP RT

Renal cell cancer: Post-OP RTAuthor Study type Study details Results Remarks

Kao GD Retrospective

(n=12)

Loco-regionally

advanced RCC

RT dose: 41.4- 63 Gy;

1.8-2 Gy/Fr

5 yr local control

rate 100%

High precision RT was used.

Acceptable toxicity profile.

Rabinovitch RA Prospective

Non-randomized

n=172;

year1978-88

Early (T1-2) localized

RCC

Treated with surgery

alone

7 yr actuarial loco-

regional failure 5%

30 pts had distant

metastasis

Adjuvant treatment may not

be useful in early RCCs

without nodal involvement.

Fugitt RB Randomized New Castle, United

Kingdom,

RT dose 55 Gy in 2.04

Gy/Fr

No survival

advantage with

PORT

4 patients died due to RT

induced hepatotoxicity

Kjaer M Randomized Copenhagen Renal

Cancer Study Group

Stage II/III RCC

RT dose 50Gy/20

fractions

No Survival

advantage with

PORT

44% had significant GI

complication

19% died due to RT induced

complications.

Sub-optimal radiation

therapy delivered

Author Study type Study details Results

Walsh L Prospective

n=12

Nude mice were injected

subcutaneously with A498 human

RCC cells.

RT dose: 48 Gy/3 fr(one per

week)

At 7 wks post-RT,

30% reduction in

volume

Beitler JJ Prospective

n=9

Medically inoperable RCC

SBRT

40 Gy/5 fr/1 week

Median FU 26.7 months

OS: 46% (4/9)

Loco-regional failure:

11% (1/9)

Wersall PJ Prospective

n=8

Medically inoperable RCC

SBRT

40 Gy/5 fr/1 week

Median FU 26.7 months

median OS: 58

months

loco-regional control

87%

Renal cell cancer: SBRT

Urological malignancies: Role of SBRT

Conclusion

- Hypofractionated RT / SBRT is an option in low risk carcinoma prostate

- Short course RT is equally effective compared with conv RT

- Short course RT is well tolerated and have similar gr 3/4 toxicities.

- Biochemical control is impressive in short term follow up data

-Need long term follow up data

- Radiosurgery is an interesting option in RCC & metastatic disease.

Indications of Cyberknife: Intracranial lesions

• Benign intracranial tumours

- Acustic neuromas

- Schwannomas

- Small meningiomas

- Chordomas

- Residual low grade gliomas

- Atriovenous malformation (AVMs)

• High grade gliomas after recurrence / post RT residual disease.

Indications of Cyberknife:

Extra-cranial lesions

• Small (T1) primary lung cancer

• Localized prostate cancer.

• Inoperable pancreatic cancer.

• Localized gall bladder cancer.

• Recurrent head and neck cancer in primary site or node.

• Residual disease/ boost treatment in nasopharynx/PNS region.

Indications of Cyberknife: Metastatic disease

• Solitary (or Oligo) brain metastasis.

• Solitary (or Oligo) lung metastasis.

• Solitary (or Oligo) liver metastasis.

• Isolated bone metastasis.

Thank you

+91-9884234290

duttadeb07@gmail.com