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(1)

두경부암의 치료발전과정과 새로운 치료전략

울산의대 서울아산병원 종양내과

김 성 배

(2)

1.재발성 또는 전이성 두경부 편평상피암 환자 를 대상으로 한 EXTREME trial(cetuximab+5- FU+CDDP vs 5-FU+ CDDP)에서 primary end point는?

1) Duration of response

2) Progression-free survival time 3) Overall survival

4) Time to treatment failure

5) Response rate

(3)

2. 다음 중 두경부암과 human papilloma virus (HPV)의 관계를 옳게 묘사한 것은?

1)

HPV는 두경부암 발생과 상관이 있고,

HPV+ HNSCC는 HPV-HNSCC에 비해 생존기간이 길다.

2) HPV는 두경부암 발생과 상관이 있고,

HPV+ HNSCC는 HPV-HNSCC에 비해 생존기간이 짧다.

3) HPV는 두경부암 발생과 상관이 있으나, HPV 감염과 두경부암 생존과는 무관하다.

4) HPV와 두경부암 발생과는 무관하다.

5) None of above

(4)

3. Human papilloma virus (HPV)와 관련된 두경부암이 호발하는 부위는 ?

1) Larynx

2) Oral cavity

3) Hypopharynx

4) Oropharynx

5) Maxillary sinus

(5)

Contents

• Epidemiology

• Advances in surgery, RT, and chemotherapy

• Re-exploration of induction treatment

Anti-EGFR Therapy in SCCHN

HPV and oropharyngeal cancer

Palliative care for HNSCC

(6)

Epidemiology

around 500,000 new cases / year

World USA/EU Korea

8 16/18 6?

Annual

incidence rate per 100,000

inhabitants

Parkin DM, et al. Cancer Incidence in Five Continents. Vol. VIII. IARC. 2002.

(7)

Cancers of upper aerodigestive tract (UADT) in Korea (2001)

Primary site Male Female Total

Larynx 459(51.6%) 29(16.8%) 488(45.9%)

Oral cavity 112(12.6%) 63(36.4%) 175(16.5%)

Oropharynx 87 (9.8%) 19(11.0%) 106(10.0%)

Hypopharynx 99 (11.1%) 2 (1.2%) 101( 9.5%) Nasopharynx 53 ( 6.0%) 21(12.1%) 74 (7.0%) Paranasal

sinuses 33 ( 3.7%) 13 (7.5%) 46 (4.3%)

Nasal cavity 18 (2.0%) 10 (5.8%) 28 (2.6%) Unknown

Primary

18 (2.0%) 4 (2.3%) 22 (2.1%)

Lymphoma 8 (0.9%) 12 (6.9%) 20 (1.9%)

Trachea 2 (0.2%) 0 (0%) 2 (0.2%)

Esophagus 1 (0.1%) 0 (0%) 1 (0.1%)

Total 890(83.7%) 173(16.3%) 1,063(100%)

Kim KM et al. J Kor Med Sci 18:80, 2003

(8)

Advances in surgery

• Less extensive surgery

-Total laryngectomy  supracricoid laryngecotomy -Hemimandibulectomy  mandibular swing

• More reliable reconstructive surgery

-Myocutaneous flaps

(in particular major pectoralis flap)

-Free flap

(9)

Advances in radiation therapy

• Hyperfractionated RT

(to increase the total dose)

• Accelerated RT(to reduce overall

treatment time and cell repopulation)

• Radiosensitizer

• IMRT

(10)

Advances in chemotherapy

• HNSCC are chemosensitive tumors

- Platinum based chemotherapy - Taxane based chemotherapy

• Combining chemotherapy with radiation is better than alone in locally advanced HNSCC

- Induction chemotherapy followed by RT - Concurrent chemoradiotherapy

- Sequential induction  CCRT - Adjuvant CCRT

• Molecular target therapy

- EGFR pathway is important

(11)

Contents

• Epidemiology

• Advances in surgery, RT, and chemotherapy

• Re-exploration of induction treatment

Anti-EGFR Therapy in SCCHN

HPV and oropharyngeal cancer

Palliative care for HNSCC

(12)

STRATIFY Site

Stage

RA ND OM ZI E

Induction Chemotherapy

(2 cycles)

Responder (1 cycle)

Radiation Therapy

Complete Response Residual

Disease Non-

Responder Surgery

Radiation Therapy

Surgery

Radiation Therapy

Schema of VA Laryngeal Cancer Study

•332 patients, previously untreated stage Ⅲ or Ⅳ

VALCSG. N Eng J Med 324: 1685, 1991 Surgery

(13)

OS DFS

CT→ RT

S → RT

• Median follow-up : 33 months

• 2 yr Sur: 68% (p=0.9846)

CT→ RT

S → RT

Shorter DFS, but not significant (p=0.1195)

VALCSG. N Eng J Med 324: 1685, 1991

(14)

Patterns of Tumor Recurrence

S→RT CT→RT

SITE OF RECURRENCE (N=166) (N=166)

No. of patients (%)

Primary* 4(2) 20(12) =0.042

Regional 9(5) 14(8)

Distant 29(17) 18(11) =0.001

All 42(25) 52(31)

*Includes recurrences with either positive or negative nodes.

VALCSG. N Eng J Med 324: 1685, 1991

(15)

Investiga tors

N of patients

Induction

chemotherapy

Local therapy

Comments

VA 1991

332 PF×3 S/XRT

vs. XRT

64% larynx preservation with chemotherapy; fewer distant metastases

EORTC 1996

194 PF×3 S/XRT

vs. XRT

42% larynx preservation with chemotherapy

Pacca -gnella (Studio) 1994

237 PF×4 S/XRT

vs. XRT

Survival advantage for

chemotherapy in subgroup analysis

Domenge (GEETEC) 2000

174 PF×3 S/XRT

vs XRT

Survival advantage for chemotherapy

Abbreviations: S = surgery; XRT = radiation therapy

Selected studies of PF induction

chemotherapy

(16)

Debates on Induction Chemotherapy

• Pros

• Hight RR→Survival

• Feasible in multiple trials

• Not enhance RT toxicity

• Organ preservation

• Systemic control

• Testing of new agents

• Evaluation of targeted therapies

• Cons

• No improvement in local- regional control or overall

survival in randomized study

• Delay of definitive local therapy

• Accelerated repopulation

• Loss of curative option if PD

• Added toxicities (regimen specific)

• Additional small decrease in distant mets= survival

benefit

(17)

Meta-Analysis of Locoregional Treatment With and Without Chemotherapy: Effect on Survival

Trial

Category

Hazard

Ratio(95% CI)

Chemo therapy Effect(p)

Hetero geneity (p)

Absolute benefit

2Yr 5Yr

Adjuvant 0.98

(0.85-1.19)

0.74 0.35 1% 1%

Neoadjuvant 0.95

(0.88-1.01)

0.10 0.38 2% 2%

Concomitant 0.81

(0.76-0.88)

<0.0001 <0.0001 7% 8%

Total 0.90

(0.85-0.94)

<0.0001 <0.0001 4% 4%

Pignon et al, Lancet 355: 949, 2000

(18)

MACH-NC: Effect of Chemotherapy on 5-Yr Survival

Trial Category No of Trials

No of Patients

Difference (%)

P value

All trials 65 10850 +4 <0.0001

Adjuvant 8 1854 +1 0.74

Induction 31 5269 +2 0.10

PF 15 2487 +5 0.01

Other chemoTx 16 2782 0 0.91

Concomitant 26 3727 +8 <0.0001

Monnerat, et al. Annals of Oncology, 13995-1006,2002

(19)

CCRT for Organ Preservation in

Advanced Laryngeal Cancer (RTOG 91-11)

547 III/IV resectable laryngeal cancer Study enrollment: 1992.8.-2000.5.

Major end point: organ preservation Median FU: 3.8 yr

Forastiere et al, N Eng J Med 349:2091, 2003

Tx Arm Larynx

Preservation Rate at 2 Yr

Rate of LRC

Rate Of DM

2yr Sur

Induction

FP x 3  RT 70Gy

75% 61% 9% 76%

Concurrent

CDDP (D1, 22, 43) + RT 70Gy

88% 78% 8% 74%

RT alone, 2Gy/Fx 70Gy/ 7wk

70% 56% 16% 75%

(20)

Induction ChemoTx plus RT does not improve organ preservation vs RT alone in patients with locally advanced laryngeal cancer (RTOG91-11, Med FU 6.9 yr)

Tx Arm Larynx

Preservation Rate at 5 Yr

Rate of LRC at 5yr

Rate of DM at 5yr

5 yr Sur G3,4/5 toxicity

Induction FP x 3  RT 70Gy

70% 45% 14% 59% 49.6/0.6

CCRT

CDDP (D1, 22, 43) + RT 70Gy

84% 47% 13% 55% 76.4/3.5

RT alone, 2Gy/Fx 70Gy/ 7wk

66% 34% 22% 54% 46.7/1.8

Forastiere et al, PASCO abst #5517, 2006

(21)

Phase Ⅲ Trials: Taxane Induction Therapy

Study Induction Therapy

Local Therapy

n ORR

(%)

CR (%)

Med PFS (Mo)

Med OS (Mo) Hitt CDDP, FU

Paclitaxel CDDP, FU

70 Gy + CDDP 70 Gy +

CDDP

193 189

69 80

14 33

12 20

37 43 Vermor

-ken CDDP, FU Docetaxel, CDDP, FU

66-70Gy 66-70Gy

181 177

54 68

7 9

8.4 12.7

14.2 18.6

Hitt et al. J Clin Oncol 23: 8636, 2005

Vermorken et al. J Clin Oncol 24(18S): 5516, 2006

(22)

TAX324 Phase Ⅲ Study

Statification Stage Ⅲ, IV Unresectable

Organ preservation RA ND OM ZI AT OI N

T P

EUA

P F

F

Carboplatin weekly

Radiotherapy

3 Cycles of chemotherapy

3-yr OS : 62% for TPF & 48% for PF ( HR: 0.70; P = .0058) 3-yr PFS: 49% for TPF & 37% for PF (HR: 0.71; P = .004)

PASCO 2006

(23)

.

TPF vs PF

1, 2 cycle TPF vs PF 3 cycle

Concomitant Chemo/RT

종양평가 종양평가

R A N D OM I Z A T I O N

Follow up

종양평가

Study Schema

Primary end point: clinical response rate

Seconday end point: pathologic response rate, overall survival,

progression survival

(24)

.

Inclusion Criteria

조직학적 또는 세포학적으로 입증된, 국소적으로 진행된 두경부암 (적합한 원발종양부위: 구강, 구강인두, 하인두, 후두, 부비강, 비인두)

최소 한 개 이상의 양측 또는 단측 계측 가능한 병변

원격전이의 증거가 없는 Stage III 또는 Stage IV

수술불가능한 종양

1) 기술적 절제불능: 종양 고정 (Tumor Fixation), 두개저부 또는 경추침범, 비인두침범, 림프절 고정

2) 연구자 판단 – 수술후 기대되는 치료효과 저하 – 다음에 해당하는 환자 -모든 T3-4

-모든 N2-3 단계 (T1N2 제외) -장기 보존을 위한 환자

(25)

KCSG –HN (7개 기관)

ORR 1yDFR 2yDFS 1yOS 2yOS

TPF (n=43)

84.9% 75.9% 70.0% 88.5% 79.2%

PF (N=43)

81.0% 65.7% 55.1% 75.3% 67.8%

(26)

A Randomized Phase II Study of CCRT +/- Neoadjuvant Docetaxel, Cisplatin in Advanced Nasopharyngeal Ca

C T

C

T P P P P P P P P

RT

Week 1 2 3 4 5 6 7 8 9 10 11 12 13 14

C = cisplatin 75 mg/m2 T = taxotere 75 mg/m2 P = cisplatin 40 mg/m2

Chan AT, PASCO abst #5544, 2005

(27)

Response Rate by Treatment Arm

(NP: nasopharygeal tumor, LN: neck lymph nodes)

Response Rate Neoadjuvant arm

(n=28)

Control arm (n=25) (a) after neoadjuvant TC NP LN*

CR 6(22%) 10(50%) PR 18(64%) 6(30%)

SD 4(14%) 4(20%) PD 0(0%) 0(0%)

(b) after cisplatin-RT NP LN* NP LN*

CR 27(96%) 16(80%) 21(84%) 15(65%) PR 1(4%) 3(15%) 4(16%) 8(35%)

SD 0(0%) 1(5%) 0(0%) 0(0%) PD 0(0%) 0(0%) 0(0%) 0(0%)

* Pts with LN(-) at baseline were excluded for calculation of LN response

(28)

Gr 3/4 toxicities during cisplatin-RT

Toxicity during cisp-RT

Neoadjuvant arm (n=28)

G3 G4

Control arm (n=25)

G3 G4

P-value Hematological

Anemia 3(10%) 0 5(20%) 0 0.3133 Thrombocytopenia 1(4%) 1(4%) 0 1(4%) 0.1090 Neutropenia 6(21%) 22(79%) 3(12%) 1(4%) <0.0001 Febrile neutropenia 0 0 1(4%) 0 0.2853 Non-hematological

Anorexia/nausea/vomiting 3(10%) 0 3(12%) 0 0.3556 Dehydration/renal 5(18%) 0 7(28%) 0 0.5820 Fatigue 2(7%) 0 2(8%) 0 0.9061 Electrolytes 4(14%) 0 0 0 0.0699 Mucositis/odynophagia 10(36%) 1(4%) 11(44%) 1(4%) 0.2387 Transfusion 4(14%) 0 4(16%) 0 0.8618

(29)

Renewed interest in a re-exploration of induction treatment

• There is the recognition that more effective induction regimens may well exist.

• A reversal in the pattern of failure previously seen in this disease.

• Chemotherapy responsiveness may be a kind of biomarker, which might prove useful in

identifying those patients who might be best

treated nonoperatively.

(30)

Paradigm Shift in the Treatment of Head and Neck Cancer

Induction Chemotherapy

(Surgery) Chemoradiotherapy RT  Chemotherapy Surgery

Posner M, et al, Oncol Spectrumns, 2001

(31)

Locally Advanced SCCHN

R A N D O M I Z E

Chemotherapy

Radiation plus chemotherapy

Radiation plus chemotherapy

Future Randomized Trials of Induction Chemotherapy

What chemoradiotherapy combination to use?

In which population is this strategy most likely beneficial?

(32)

Contents

• Epidemiology

• Advances in surgery, RT, and chemotherapy

• Re-exploration of induction treatment

Anti-EGFR Therapy in SCCHN

HPV and oropharyngeal cancer

Palliative care for HNSCC

(33)

Type of tumor

Tumors with EGFR expression Head and neck 90–100%

Colon 75–89%

Pancreas Up to 95%

Breast Up to 91%

Renal Up to 90%

NSCLC Up to 80%

Ovary Up to 77%

Bladder Up to 72%

Glioma Up to 63%

EGFR Expression in Human Tumors

Lung (NSCLC)

Colorectal Head and neck

(34)

Ang K, et al. Cancer Res 2002;62:7350–7356

Tumor EGFR expression as a prognostic factor

High EGFR expression in SCCHN is linked to lower survival and increased risk of locoregional relapse

(35)

EGFR-targeted monoclonal antibody

therapy has

demonstrated additive or synergistic

antitumor activity in a variety of animal models in vitro and in

vivo when administered in combination with

chemotherapy or radiation therapy

Courtesy of José Baselga (modified)

Cetuximab:

Mechanisms of action

(36)

Comparison of EGFR Mabs & TKIs

MAb TKI

examples Cetuximab,

Panitumumab

Gefitinib,Erlotinib, Lapatinib

Mechanism of action

Bind to

extracellular ligand binding domain

Bind to

intracellular TK domain

Route of

administration

Intravenous Oral

Schedule Every 1-3 weeks Daily

Common AE Rash,

hypersensitivity reactions

Rash, diarrhea, nausea

Cost per month 13000 USD (cetuximab)

2500 USD (erlotinib) Availability Cetuximab is FDA

approved (CRC, SCCHN)

Erlotinib is FDA approved (NSCLC), gefitinib in Japan (NSCLC)

(37)

Ph III RT ± Cetuximab in LA HNSCC:

Study Design

RT

+ cetuximab

RT

Locally advanced HNSCC

Stratification

KPS

90-100 vs 60-80 Tumor stage

T1-3 vs T4 N0 vs N1

RT fractionation Once daily Twice daily

Concomitant boost

*Absence of locoregional disease progression at scheduled follow-up visits (assessed by an independent review committee)

n=211

n=213

Bonner JA, et al. N Engl J Med. 2006;354:567-578.

Primary:

locoregional control*

Secondary:

OS, PFS, ORR,

QOL, Safety

(38)

Efficacy results for phase III study

RT (n = 213) Cetuximab + RT (n = 211)

Hazard ratio [CI]/ p value

Median survival 29.3 months 49.0 months

0.74 [0.57–

0.97]

p = 0.03

3-year rate 45% 55% p = 0.05

Median

locoregional control

14.9 months 24.4 months

0.68 [0.52–

0.89]

p = 0.005

3-year rate 34% 47% p < 0.01

Median

progression-free survival

12.4 months 17.1 months

0.70 [0.54–

0.90]

p = 0.006

3-year rate 31% 42% p = 0.04

(39)

Adverse event RT (n=212)

Cetuximab + RT (n=208)

p valuea

Mucositis/stomatitis 52% 56% 0.44

Dysphagia 30% 26% 0.45

Radiation dermatitis 18% 23% 0.27

Xerostomia 3% 5% 0.32

Fatigue/malaise 5% 4% 0.64

Acne-like rash 1% 17% <0.001

Infusion-related reactionsb 0% 3% 0.01

aFisher’s exact test

bListed for its relationship to Erbitux

Cetuximab + RT:

Relevant grade 3–5 adverse events

Bonner J, et al. N Engl J Med 2006;354:567–578

(40)

51/M, Tonsil ca, Before

After RT+weekly Erbitux

(41)

Survival advantage with Cetuximab + RT compared to CRT vs RT

1 Bonner JA, et al. N Engl J Med 2006; 2Huguenin P, et al. J Clin Oncol 2004; 3Calais G, et al. J Natl Cancer Inst 1999;

4Semrau R, et al. Int J Radiat Oncol Biol Phys 2006; 5Budach V, et al. J Clin Oncol 2005

7 7

14

18

20

0 5 10 15 20

Median survival advantage (months) Carboplatin + 5-FU

+ conventional RT3 Cisplatin + hyperfractionated RT2

Cetuximab + RT1

Carboplatin + 5-FU + hyperfractionated RT (CB)4

Mitomycin C + 5-FU + hyperfractionated RT5

CB, concomitant boost

p=0.15 (not significant)

p=0.02

p=0.02

p=0.02 p=0.03

(42)

RTOG 0522: Phase III CRT ± Cetuximab in Locally Advanced HNSCC (Ongoing)

RT

+ cisplatin + cetuximab

RT

+ cisplatin

Locally advanced HNSCC

Stratification

Primary site

Larynx vs non-larynx Zubrod status

0 vs 1 Nodal status

N0 vs N1, N2a, N2b vs N2c, N3

Use of IMRT No vs Yes

Pretreatment PET/CT No vs Yes

Required enrollment: 720 patients

Primary:

DFS

Secondary:

OS,

locoregional

control, safety

(43)

Recurrent/Metastatic SCCHN

• 1

st

line setting

(Cisplatin/Carbo+ 5-FU/or Taxane) -30% RR

-3~4 Mo PFS -6~8 Mo OS

• 2

nd

line setting

- 3~4 Mo OS

(44)

Year Patients Regimen OS OR G3-4 toxicity 1992 Forastiere AA,

et al.1

277 cisplatin + 5-FU carboplatin + 5-FU

methotrexate

NS 32%

21%

10%

neutropenia mucositis

1992 Jacobs C, et al.2

249 cisplatin + 5-FU 5-FU

cisplatin

NS 32%

13%

17%

vomiting mucositis

1994 Clavel M, et al.3

382 CABO

cisplatin + 5-FU cisplatin

NS 34%

31%

15%

vomiting

2005 Gibson MK, et al.4

218 cisplatin + 5-FU cisplatin + paclitaxel

NS 27%

26%

reduced for ci splatin + pacli

taxel

Recurrent and/or metastatic SCCHN:

phase III chemotherapy results in first line

No improvement in overall survival in recent decades

CABO=cisplatin, methotrexate, bleomycin and vincristine; NS=not significant; OR=overall response 1. Forastiere AA, et al. J Clin Oncol 1992;10:1245–1251; 2. Jacobs C, et al. J Clin Oncol 1992;10:257–263;

3. Clavel M, et al. Ann Oncol 1994;5:521–526; 4. Gibson MK, et al. J Clin Oncol 2005;23:3562–3567

(45)

EXTREME: Phase III Platinum/5-FU

± Cetuximab in 1 st Line RM HNSCC

Platinum/5FU + cetuximab

Platinum/5FU

Treatment-naïve refractory and/or metastatic HNSCC*

Stratification

Prior chemotherapy KPS <80 vs ≥80

EITHER carboplatin (AUC 5, d1) OR cisplatin (100

mg/m2 IV, d1) + 5-FU (1000 mg/m2 IV, d1-4) q3w for a maximum of 6 cycles

Cetuximab 400 mg/m2 initial dose then 250 mg/m2 weekly until progression or unacceptable toxicity

n=222

n=220

Vermorken JB, et al. Presented at: American Society of Clinical Oncology Annual Meeting 2007. June 1-5, 2007. Abstract 6013.

Primary:

OS

Secondary:

ORR, duration of response,

TTP, QOL,

Safety

(46)

Patients at risk PFS time (months)

CT only CT + Cetuximab

220 103 29 8 3 1

222 138 72 29 12 7

HR [95%CI]: 0.538 [0.431–0.672]

Strat. log-rank test: <.0001

EXTREME: Progression-free Survival (PFS)

CT only

CT + Cetuximab

Progression free (%)

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0 3 6 9 12 15

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5.6 months 3.3 months

Vermorken JB, et al. ECCO 2007 (Abstract No. O#5501; updated information presented)

(47)

10.1 months 7.4 months

Patients at risk Survival time (months)

CT only CT + Erbitux

220 173 127 83 65 47 19 8 1

222 184 153 118 82 57 30 15 3

HR [95%CI]: 0.797 [0.644–0.986]

Strat. log-rank test: 0.0362

EXTREME: Overall Survival

CT only

CT + Cetuximab

Survival probability

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0

0 3 6 9 12 15 18 21 24

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Vermorken JB, et al. ECCO 2007 (Abstract No. O#5501; updated information presented)

(48)

EGFR-inhibitor are associated with related skin reactions

• Mechanism-based toxicity

-EGFR is expressed in skin

• Sterile, acneiform follicular or perifollicular dermatitis

-affects face, trunk, neck

• Typically develops within first 3 weeks of therapy

• Similar rash rate

-cetuximab ≥80%

-panitunimab 90-95%

-erlotinib 61.7%

-gefitinib 45-67%(dose-related)

(49)

EGFR signaling

(50)

Contents

• Epidemiology

• Advances in surgery, RT, and chemotherapy

• Re-exploration of induction treatment

Anti-EGFR Therapy in SCCHN

HPV and oropharyngeal cancer

Palliative care for HNSCC

(51)

Improved Survival of Patients With Human

Papillomavirus--Positive Head and Neck Squamous Cell Carcinoma in a Prospective Clinical Trial

• Nonsmoker, nondrinker

• Younger age

• Similar sex ratio

• Low level of p53 and pRB protein

• P16 upregulated

• Favorable prognosis -absence of field

cancerization,

-immune surveillance to viral- specific tumor antigens

- an intact apoptotic response to radiation

OS DFS

J Natl Cancer Inst. 2008;100(4):261-269

(52)

Symptom Treatment Notes

Mucositis Allopurinol mouthwash

GM-CSF gargle

Human placental extract

Weak supporting evidence

Dysphagia Hydration and nutrition Speech & language pathologist

Transient or permanent or severe

Dependent on types of treatment

Xerostomia Frequent intake of water, icechips

Artificial saliva Pilocarpine

Evidence is weak

Change in speech Adaptive

devices(amplifiers)

May not return to baseline level Decreased QOL Supportive treatments,

psychotherapy

Return to baseline level over the long term

Depression Emotional support

antidepressant

Transient or prolonged

Anxiety Emotional support

anxiolytics

Anxiolytics can induce fatigue or delirium

Goldstein NE et al, JAMA 299:1818-1825, 2008

(53)

Follow up

• Local and/or regional and/or distant failure

• Second primary cancer

• Treatment side effects

• Comorbid illness

• Pain and/or denutrition

• Need for functional rehabilitation and/or social reinsertion

(54)

Summary

• There are better induction regimens than others

• Although CCRT is considered as the standard

treatment in LA HNSCC, sequential regimens are promising.

• EGFR is an important pathway

• We could reduce the intensity of the therapy for those likely to have the best outcomes (e.g. HPV+

HNSCC)

• Importance of interdisciplinary team in the care of

HNSCC better outcome and QOL

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