Post Treatment SurveillanceIFHNOS New York 2014

Michiel van den Brekel• Head and Neck Service• Netherlands Cancer Institute,

Amsterdam

William Carroll• George W Barber, Jr. Professor of

Surgery• Section Head and Neck Oncology,

University Alabama Birmingham

Surveillance

• Different Perspectives– Patient– Doctor– Society– Oncologic

• Current Protocols, future perspectives

Patient perspective• Attention, security / being taken care

– Feels safer (oncologic perspective)• Rehabilitation

– Physical Condition– Functional Sequellae

• WHO core set disability– Psychological distress / acceptance

• Builds personal relationship with doctor

HN Rehabilitation Program of the Netherlands Cancer Institute

Goal• The curatively treated HN cancer patient regains his/her

place in society, using his/her own abilities• Prevention and treatment of treatment sequels

A multidisciplinary team approach with clear goals for each patient

• HN Surgeon and Radiotherapist• Specialist in physical medicine and rehabilitation• SLP• Physiotherapist• Dietician• Social worker• Etc.

Stepped Care Model Targeting Anxiety and Depression

Step 1: Step 2: Step 3: Step 4: Watchful waiting Self-help Counselling Psychologist/

Internet / book nurse antidepressants

Example of numberof patients in: 100 70 35

15 (recovered) out: 30 35

20

Week 0 2 7 12

Krebber et al. BMC Cancer 2012;12:173

Doctor perspective• Care of patient

– Early detection of recurrence / 2nd primaries– Rehabilitation– Smoking / Alcohol Cessation !– Thyroid function (every 6 months)*

• Scientific reasons– outcome, toxicity

• Quality control– Audit, complications, QOL, feedback learning

• Financial incentives versus workload

Society Perspective• Cost – benefit

– chances to increase survival– influence on QALY ?– Rehabilitation has impact on return to society ?

• How long• Who should do it ?

– NP/PA/residents– treating physician– general practitionar

Oncologic Perspective

• Chance to develop a recurrence• Chance to find recurrence before symptoms• Curability when detected• Screening second primaries

– 33% of deaths due to alcohol and tobacco related 2nd primaries

– Incidentalomas found…• Curability versus morbidity

– Prognostic significance of screening• US National Lung Screening Trial• Dutch-Belgian lung cancer screening trial (NELSON):

Time Window Surveillance

Undetectable tumor detectable Symptoms

ResidualTumor

death

Surveillance

Incurable• How often, for how long• Find before symptoms occur

• Fast growing recurrences: more symptoms, less curability• Slow growing recurrences: less symptoms, early detection less

important• Imaging: when, which modality• Future

• blood tests, sputum, brush, breath analysis (e-nose)

Ritoe, Cancer 2004402 patients with laryngeal cancer

• 4639 routine visits• in 2% of visits an asymptomatic recurrence was found• 224 events

• 83 local recurrence• 37 regional recurrences• 55 lung metastases / 2nd primaries (50% of DM are in fact 2nd primaries: Geurts et

al)• 27 HNSCC 2nd primaries

• In case of recurrences: still 35% survival !!

How Recurrences are Detected

No Difference in Survival

How Long ?• Ritoe (Larynx): 78% recurrences / 2nd primaries in first 3 years• Boysen (all sites): 76% of recurrences in first 2 years• De Visscher (all sites): 76% of recurrences and 2nd primaries in first 3 years• Lester: 95% of all evens in first

• 2.7 years for oropharynx• 2.3 years for hypopharynx• 4.7 years for larynx

Second Primaries in Netherlands

• 1989-2008: 16.937 oral + oropharyngeal cancers– 3177 2nd primaries (19%)

• 837(26 %) synchronous (< 6 months)– 397 (47%) HNSCC– 79 (9%) esophagus– 197 (24%) lung

• 2340 (74%) metachronous– 708 (30%) HNSCC– 205 (9%) esophagus– 656 (28%) lung

– 1/3 of mortality is because of 2nd primaries– Smoking and drinking is major cause of death (also

cardiovascular)

How Often

Undetectable tumor detectable Symptoms

ResidualTumor

death

Lead timeMostly 3-6 weeks

Per

cent

age

dete

ctio

n as

ympt

omat

ic

month

(months)

Ritoe, Cancer 2007: Markov Model Comparing

prognosis with different schemesAge 50 Age 70

Life expectancy (general population) 27.7 11.6Current follow-up 22.2 10.5No follow-up 21,4 10.2Perfect follow-up 24.7 11.0

Disease Specific Mortality for men (%)Current follow-up 33.6 14.7No follow-up 38.5 17.5Perfect follow-up 18.4 7.3

Published Guidelines

BAHNO NCCN ASHNS SHNS DHNS

Year 1 4–6 w 1–3 m 1–3 m 1–3 m 2 m

Year 2 4–6 w 2–4 m 2–4 m 2–4 m 3 m

Year 3 3 m 4–6 m 3–6 m 3–6 m 4 m

Year 4 6 m 4–6 m 4–6 m 4–6 m 6 m

Year 5 6 m 4–6 m 4–6 m 4–6 m 6 m

>Year 6 1 yr 6–12 m 1 yr 1 yr None

By courtesy of Prof. Remco de Bree

By courtesy of Prof. Remco de Bree

2004

By courtesy of Prof. Remco de Bree

By courtesy of Prof. Remco de Bree

NCCH Guidelines 2014

NCCH Guidelines 2014

2nd Primary Lung Cancer Screening

• 5-10% of surviving HNSCC develop pulmonary cancer

• US National Lung Screening Trial (NLST): 20% reduction in lung cancer mortality in high-risk cohort

• Dutch-Belgian lung cancer screening trial (NELSON):

– 7582 participants: 3 CT scans in 5.5 years » 458 (6%) positive screen results» 200 (2.6%) were diagnosed with lung cancer. » Positive screenings had a predictive value of 40.6%

(1.2% false-positive)» Survival benefit awaiting

Individualizing Surveillance• Length and intensity

– Between 3-5 year is optimal for HNSCC– Shorter than 3 months interval is not effective– Risk of locoregional recurrences versus

chances to effectively treat them• Smoking / alcohol / HPV• Tumor and treatment dependent

• In case effective options available and high risk recurrence: more frequent and vice versa.

Conclusions• Little evidence, possibly some survival advantage • Interval: less than 3 months very inefficient

– How long: 3-5 years– Modality: dependent on salvage/treatment

possibilities / consequences• Lung 2nd primaries: annual CT defendable

– Who: trained physician / NP / PA• More emphasis on:

– Train symptom awareness of patient !!– Stop smoking / alcohol– Rehabilitation

Surveillance of the N0 Neck

Options for the N0 Neck• Observation

– Based on an estimated low risk of occult metastases: T1 larynx

• Staging– CT / MRI / PET– Ultrasound (guided FNAC)– Sentinel node biopsy

• Treatment– Elective ND– Elective Radiotherapy

The N0 Neck – Considerations

• Risk of occult disease• Modality of treatment for

primary• Will the neck be entered?• Prognostic impact of W&S

policy– Follow-Up reliability

• Morbidity of neck treatment• Patient and doctor

preferences

Benefits of Elective ND

• Provides pathological information• Facilitates microvascular surgery• Early treatment

– Avoids delayed presentation– may improve overall outcome ? – Helps avoid radiotherapy

• In about 10% patient ? • Limited morbidity if unilateral

Disadvantages Elective Neck Treatment

• Overtreatment for 50-70%– costs, OR time

• morbidity• Change in patterns of

metastasis – recurrences– second primaries in 30%

Regional recurrence after (s)elective neck dissection cN0 neck

Author Year Primary RTx Neck recurrence

Percentagefailure

McGuirt 1995 FOM None 1/26 3.8%

Spiro 1996 Oral cavity None 6/152 5%

Hosal 2000 All None 6/127 4%

Chow 1989 Oral cavity None 5/63 8%

Carvalho 2000 Oral/Oropharynx 44% 7/154 4.5 %

Yuen 1997 Tongue Some 3/33 9%

BHNCSG 1998 Oral cavity Some 6/72 8%

D’Cruz 2008 Tongue 35% 9/159 5.7%

Sensitivity US-FNAC N0 Neck

Author Tumor N0 Neck Sides Sens SpecvdBrekel (1993)

HNSCC 43 73 100

Righi (1997) HNSCC 33 50 100Takes (1998) HNSCC 64 48 100Nieuwenhuis (2002)

Oral SCC (T3-4) 23 71 100

Nieuwenhuis (2002)

Oral SCC (T1-2) 37 25 100

Hodder (2000) Oral SCC (T1-4) 33 58 100Borgemeester (2009)

Oral SCC (T1-2) 37 18 100

Borgemeester (2009)

HNSCC (T3-4) 128 39 100

US-FNAC vs conventional imaging meta-analysis

De Bondt et al. Eur. J. Radiol. 2007

Sensitivity versus radiologist

Radiologist

Neck sides examined HP positive Sensitivity (%)

1 39 11 9

2 29 14 29

3 31 11 45

4 43 17 53

Prognostic Impact Wait & See

• Depends on salvage rate of neck metastases– treatment delay– metastatic rate of the lymph node

metastases

• Study: decrease treatment delay by regular USFNAC follow-up after transoral excision

Wait & See and Prognosis

Kligerman 33 33% 27%Ho 28 36% 30%Fakih 40 57% 30%Cunningham 43 42% 50%McGuirt 103 36% 59%Vandenbrouck

36 47% 82%

TOTAL 283 41% 50%

van den Brekel 77 18% 71%Nieuwenhuis 161 21% 79%

Pts N+ salvagedPalpation

USFNAC

Survival NKI• 5-year survival in W&S oral cavity (T1-2) is 79%. • 5-year survival in END oral cavity(T2) is 75%.

years from diagnosis

Surv

ival

Pro

babi

lity

0 1 2 3 4 5 6 7

0.0

0.2

0.4

0.6

0.8

1.0

36 34 29 24 19 14 8 5 Mondholte W&S40 31 23 15 14 10 7 4 Mondholte electief ND

Mondholte W&S

Mondholte electief ND

Survival

p = 0.48356 (logrank, two-sided)

Follow-up in months6050403020100

Dis

ease

Spe

cific

Sur

viva

l1,0

0,8

0,6

0,4

0,2

0,0

W&S delayed-censoredEND N+-censoredEND N0-censoredW&S N0-censoredW&S delayedEND N+END N0W&S N0

5-year DSS

Wait and scan

Flach et al. Oral Oncol 2013;49:165-168

• 1990-2004 VUmc• 234 patients• T1 / T2 oral SCC

Conclusions• No difference in survival between W&S and END if follow-up

is very strict

• The incidence of occult LNM is very high in oral cancer, even T1

• US-FNAC to select for a W&S policy remains disputable…..– ND spared in 70%– 90% of eventual ND patients needed Radiotherapy

• SN biopsy might be more accurate than imaging but less than END, role unclear