Management of carcinoma hypopharynx

By- Dr. Isha JaiswalModerator- Dr. Shantanu Sapru

Date: 10th December 2014

Topics to be covered:

• Pre-treatment evaluation• Staging• Treatment overview

• Evidence based treatment• NCCN guidelines

Surgery Radiotherapy Chemotherapy Biological therapy

Evaluation of patients with suspected hypopharyngeal cancer

Clinical Exanimation of head & neckFiber optic laryngopharyngoscopy & biopsy of primary tumorContrast enhanced CT scan face and neckContrast enhanced MRI face & neckChest X RayBlood investigations

Optional investigationsCECT chestPET ScanBarium swallow

Fiber-optic direct laryngoscopy• used routinely to complement the laryngeal mirror examination. • assessment of extent of primary tumor & mobility of vocal cords.• critical in assessing the superficial spread of neoplasm• superior to any imaging modality in detecting mucosal spread• can be attached to a photographic device• biopsy of the tumor is done for histopathological confirmation.

Typical findings of hypopharyngeal cancer on endoscopy:Ulceroproliferative/infiltrative growth.mucosal ulceration.pooling of the saliva in the pyriform fossa.oedema of the arytenoids. fixation of the cricoarytenoid joint, or true vocal cords or both.

CECT Scan Face & Neck• Timing: should be done before biopsy of to avoid post biopsy oedema.• Advantages: aids in staging by detection of:

Limitations

invasion into larynx. extra laryngeal/extra pharyngeal spread. paraglottic space spread. spread to retropharyngeal space. clinically occult metastatic lymphadenopathy.

Failure to detect small superficial tumours & early laryngeal cartilage involvement. Underestimating ulcerative and infiltrative lesions overestimating tumor extent due to inflammation/ oedema & distortion of adjacent normal

structures

MRI Face & Neck• Compared to CECT shows better soft tissue contrast & less artifact from

dental fillings.• An important adjunct study in three situations:

• Disadvantages :

Determining cartilage invasion :shown by increase T2 signal & post contrast enhancement.

Determining extent of extralaryngeal/paraglottic space involvement Determining oesophageal involvement shown by increased T2 signal, wall thickening

and effaced fat planes

motion artefacts. overestimating tumour extent :inflammation/ oedema /distortion

In detection of unknown /small primary tumorIn evaluating clinically occult nodal involvementIn follow up to differentiate between treatment sequelae & tumor

recurrence/residual

Role Of 18FDG PET-CT

Impact Of FDG-PET On Staging &Management of H&N SCC*

A multicenter study of 233 H&N SCC patients (including 46 hypopharyngeal cancer)

TNM staging and therapeutic decisions were first determined based on conventional workup & then FDG-PET data was used to restage the patients & reanalyse their management.

PET and conventional workup revealed discordant TNM staging in 100 patients (43%).

PET was deemed significantly more accurate than conventional staging & improved the staging in 20% of patients.

Incorporation of PET data ultimately impacted management in 32 patients (13.7%).

*Lonneux M, Hamoir M, Reychler H, et al. Positron emission tomography with [18F]fluorodeoxyglucose improves staging and patient management in patients with head and neck squamous cell carcinoma: a multicenter prospective study. J Clin Oncol 2010;28:1190–1195.

CONCLUSIONS: FDG-PET is a reliable imaging procedure in the detection of clinically occult primary tumor/node and recurrent/residual carcinomas localized in the head and neck.

it cannot as yet replace other diagnostic procedures in pretreatment planning but does contribute valuable complementary diagnostic information.

TNM STAGING- AJCC 7TH edition (2010)*T1: Tumour limited to one subsite of hypopharynx and ≤ 2 cm in greatest dimension.

T2: Tumour invades more than one subsite or adjacent site or measures >2cm but ≤ 4 cm without fixation of hemilarynx.

T3: Tumours > 4 cm or with fixation of hemilarynx or extension into esophagus

T4a: Tumor invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, central compartment of soft tissue.T4b: Tumor invades prevertebral fascia, encases the carotid artery or involves mediastinal structures.

*Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging handbook, 7th ed. New York: Springer, 2010.*

TNM STAGING- AJCC 7TH edition (2010)*

• N0: No regional LN• N1: Single ipsilateral LN ≤ 3cm• N2a: Single ipsilateral LN 3-6cm b: Multiple ipsilateral LNs ≤ 6cm c: Bilateral or contralateral LNs ≤ 6cm• N3: Any LN more than 6cm

• M stage: • Mx- cannot be assessed, • M0- no distant metastasis, • M1- distant metastasis

Stage groupingStage 0 Tis N0 M0

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage III T1, T2T3T3

N1N0N1

M0M0M0

Stage IV A T1,T2,T3T4a

N2N0,N1,N2

M0M0

Stage IV B Any TT4b

N3Any N

M0M0

Stage IV C Any T Any N M1

Treatment options Surgery Types IndicationsEvidence

Targeted therapyTypes IndicationsEvidence

ChemotherapyTypes IndicationsEvidence

Radiotherapy TypesIndicationEvidence

Multi modality treatment

General Treatment Recommendations Based On Hypopharynx Tumor Stage*

*Perez & Brady's Principles and Practice of RadiationOncology

Single Modality:• – Surgery or RT

Choice depends on• – Tumor: site, extension• – Patient: preference, comorbidities• – Expertise of the multidisciplinary team, available resources Equally effective: however no randomised trials for surgery vs. RT.

Each modality can salvage the other if local recurrence.

EARLY STAGE (I-II)(T1-T2, N0)

ADVANCED STAGE:(III/IV)T1-2, N1-3 / T3-4, N0-N+

Multi Modality: • Radiotherapy with altered fractionation schedules • Radiotherapy with chemotherapy• Radiotherapy with biological therapy• Neoadjuvant chemotherapy f/b surgery• Surgery f/b RT/CT-RT

Choice depends on• Tumor: site, extension• Patient: preference, comorbidities• Expertise of the multidisciplinary team, available resources

Treatment options

Surgery ± neoadjuvant/adjuvant

chemo/radiotherapy

Voice preserving

surgeryRadical surgery

RadiotherapyConventional/altered #

± chemotherapy

± biological

therapy± salvage

surgery

RADIATION THERAPY

Definitive RT• conventional fractionation• hyper fractionation • accelerated radiotherapy

Preop-RTPost-op RT

Benefits of RT over surgery• Probability of functional morbidity or cosmetic defects is reduced.• Risk of a major postoperative complication is avoided• Elective neck RT can be included with little added morbidity.• Surgical salvage of RT failure is supposed to have better outcome than the RT salvage

of a surgical failure.

Indications for primary radiotherapy• small sized tumor• larynx/voice preservation• those who refuse surgery

 CAUSE-SPECIFIC AND OVERALL SURVIVAL FOR CARCINOMA OF THE PYRIFORM SINUS TREATED WITH RADIATION ALONE

2001

As stage increases 5 years survival with RT alone

decreases

Radiation treatment intensification

2. Addition of chemotherapy to RT

1. Altered fractionation RT

3.Chemotherapy +Altered fractionation RT

4. Addition of biological therapy to RT

*2Horiot JC. Controlled clinical trials of hyperfractionated and accelerated radiotherapy in otorhinolaryngologic cancers [in French].Bull Acad Natl Med 1998;182(6)*#Cummings B, O’Sullivan B, Keane T. 5-year results of a 4 week/twice daily radiation schedule: the Toronto Trial. Radiother Oncol2000

*2

*3

TRIALS OF HYPERFRACTIONATION

1992 EORTC 22791

TRIALS OF PURE ACCELERATED FRACTIONATION

*!Jackson et al. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer.Radiother Oncol 1997*2Skladowski Ket al. 7-day-continuous accelerated irradiation (CAIR) of head and neck cancer—. Radiother Oncol 2000;55*3Overgaard J,. The DAHANCA 6 and 7 trial: a study of 5 versus 6 fractions per week of conventional radiotherapy of (SCC) of the head and neck. Radiother Onco *4Hliniak AZ.. Radiother Oncol 2000;56:S5.

*1

*2

*3

*4

Aim: to find whether shortening of treatment time by use of six instead of five radiotherapy fractions per week improves the tumour response in squamous-cell carcinoma.

Lancet. 2003

randomised trial between January, 1992, and December, 1999,

1485 patients treated with primary radiotherapy alone,1476 eligible patients were randomly assigned five (n=726) or six (n=750) fractions per week at the same total dose and fraction number (66-68 Gy in 33-34 fractions)

TWO SUBPROTOCOLS: DAHANCA 6, which included all glottic carcinomas, and DAHANCA 7, included tumours of the supraglottic larynx,pharynx, and oralcavity

The only difference in the two subprotocols was that DAHANCA 6 dealt only with the fractionation effect,whereas the DAHANCA 7 also included treatment with the hypoxic radiosensitiser nimorazole.

More than 97% of the patients received the planned total dose. Median overall treatment times were 39 days (six-fraction group) and 46 days (five-fraction group).

Primary locoregional tumour control as function of number of fractions per week

Overall 5-year locoregional control rates were 70% and 60% for the six-fraction and five-fraction groups, respectively (p=0.0005).

primary tumour control (76 vs 64% for six and five fractions, p=0.0001), but was non-significant for neck-node control

Disease specific survival Overall survival

Disease-specific survival improved (73 vs 66%) for six and five fractions but not overall survival

Early and late radiation-related morbidity Acute morbidity was significantly more frequent with six than with five fractions, but was transient.

CONCLUSIONAccelerated radiotherapy applied to squamous-cell carcinoma of the head and neck yields better locoregional control than does a conventional schedule with identical dose and fractionation.

2010 IAEA-ACC

*1 Dische, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radiother Oncol 1997; *2 Poulsen, et al. A randomised trial of accelerated and conventional radiotherapy for stage III and IV SCCHN: aTTROG Radiother Oncol 2001; *3 Bourhis, et al. Preliminary results of the GORTEC 96–01 randomized trial, comparing very accelerated radiotherapy versus concomitant radio-chemotherapy for locally inoperable HNSCC. Int J Radiat Oncol Biol Phys 2001;

*1

*2

*3

1997

2010

.

• Patients with stage III or IV SCC (n=1076) were randomized to 4 treatment arms:

2000

(1) Standard fractionation

70 Gy/35 daily fractions/7 weeks

(2) Hyper fractionation

81.6 Gy/68 twice-daily fractions/7 weeks

(3) Accelerated fractionation with split

67.2Gy(1.6bid)/42 fractions/6 weeks

with a 2-week rest after 38.4 Gy

(4) Accelerated fractionation with concomitant boost 72 Gy/42 fractions/6 weeks.(1.8Gy/f with 1.5 Gy /f boost on last 12 fractions)

RTO 90-03 Results: at 2years• LRC:• significant improvement in 2 yr locoregional control for

the hyper fractionation and concomitant boost arms .• DFS:• trend toward improved disease-free survival (p = 0.067

and p = 0.054 respectively for the hyper fractionation and concomitant boost arms

• OS: difference in overall survival was not significant.

• TOXICITY:• 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.

2006GORTEC 9402

CHEMOTHERAPY

• NEOADJUVANT• CONCURRENT• ADJUVANT

1996EORTC 24891

EORTC trial 24891 compared PF (cisplatin and 5-FU) induction chemotherapy followed by radiation therapy (RT) versus total laryngectomy, radical neck dissection, and postoperative RT in patients with hypopharyngeal cancer 

Role of NACT for larynx preservationNACT-RT Vs Surgery-RT

Survival Disease free survival

Metastasis free survival Larynx preservation

• Treatment failures occurred at approximately the same frequencies in both arms.

• Fewer failures at distant sites in the induction-chemotherapy arm

• The median duration of survival was 25 months in the immediate-surgery arm and 44 months in the induction-chemotherapy arm

• The 3- and 5-year estimates of retaining a functional larynx in patients treated in the induction chemotherapy arm were 42% and 35% respectively.

CONCLUSION OF EORTC 24891

Choice of chemotherapy regimen:2 drug vs.3 drug regimen

2007: TAX323/EORTC 24971

PATIENT CHRACTERISTICS:

29%pts of ca hypopharynx

Aim :compare TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease.

Primary end point :PFS

358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group

ARM A (N=177) ARM B(N=181) TOTAL P value

CONCLUSION OF TAX 323

At a median follow-up of 32.5 months, the median PFS was 11.0 months in the TPF group and 8.2 months in the PF group .

There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group.

2007: TAX 324

15% patients of ca hypopharynx

Aim: compare induction chemotherapy with docetaxel plus cisplatin and fluorouracil(TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy for treatment of SCCH& N

Results of TAX 324more patients survived in the TPF group than in the PF group

estimates of overall survival at 3 years were 62% in theTPF group and 48% in the PF group,

median overall survival was 71 months and 30 months, respectively (P = 0.006).

better locoregional control in the TPF group than in the PF group (P = 0.04)

incidence of distant metastases in the two groups did not differ significantly (P = 0.14)

Rates of neutropenia and febrile neutropenia were higher in the TPF group;

chemotherapy was more frequently delayed because of hematologic adverse events in the PF group

2009 GORTEC 2000-01

CONCURRENT CHEMORADIOTHERAPY

An Intergroup Phase III Comparison of Standard Radiation Therapy and Two Schedules of Concurrent Chemoradiotherapy in Patients With Unresectable

Squamous Cell Head and Neck Cancer.

J Clin David J. Adelstein Oncol 21:92-98. 20032003CTRT VS RT ALONE

which one is better in unresectable HNSCC?

ARM C

CTRT of 2 Gy/d, was split between the first CT course (30 Gy) & third CT course (30 to 40 Gy).

A total dose of 60 to 70 Gy was given

The radiation therapy break was planned to allow for the possibility of surgical resection in those patients rendered resectable after the first two courses of chemotherapy and the first30 Gy of radiation.

Patients who had achieved a complete response after this induction or who remained unresectable proceeded, without surgery, tocomplete chemoradiotherapy.

2003, 2006,2012Forastiere et al

•RT Vs. CTRT Vs. NACT-RT which one is better?

J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 2

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Vol 24, No 18S (June 20 Supplement), 2006: 5517

2012 Radiotherapy Alone Vs. Concurrent CTRT Vs. Sequential NACT-RT

J Clin Oncol. 2013 Mar 1;31(7):845-52. doi: 10.1200/JCO.2012.43.6097. Epub 2012 Nov 2

Loco regional control Overall survival

Larynx preservation

2012 UPDATE

No Published Phase 3 Trial Study Have Tested

Induction Chemotherapy f/b chemoradiotherapy

Vs Upfront Chemoradiotherapy

ALTERED FRACTIONATION± CHEMO-RADIOTHERAPY

Lancet Oncol. 2012 Feb;13(2):145-53. doi: 10.1016/S1470-2045(11)70346-1. Epub 2012 Jan 18

2012

aimed to assess the efficacy and safety of a combination of approaches.

STAGE III/IV, M0 HNSCC

n=840

RANDOMIZED

Arm AConventional

chemo radiotherapy

RT – 70Gy/6w 1st 40Gy 2Gy/#/d, 5#/w

Next 30Gy (off the spinal cord) 1.5Gy/#/BD

CT – 2 cycles of 5days each, 4w apart.

Carboplatin 70mg/sqm/d + 5FU 600mg/sqm/d

RT – 70Gy/35#/7w at 2Gy/#, 5#/w

CT – 3 cycles of 4days each, 3w apart.

Carboplatin 70mg/sqm/d + 5FU 600mg/sqm/d

RT – 64.8Gy/3.5w at 1.8Gy/#/BD,

5#/w

Arm AConventional

chemoradiotherapy

Arm BAccelerated RT with

concomitant CT

Arm CVery

Accelerated RT

. Median follow-up was 5·2 years

 Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy or very accelerated radiotherapy

conventional chemoradiotherapy improved PFS compared with very accelerated chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy.

More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001).

(60%) of patients in the conventional chemoradiotherapy group, (64%) of patients in the accelerated radiotherapy-chemotherapy group, and (70%) of patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045).

Results of GORTEC 9902

CONCLUSION OF GORTEC 9902

1. Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy.

• 2. Acceleration of radiotherapy cannot compensate for the absence of chemotherapy.

• 3. Acceleration of radiotherapy is probably not beneficial in concomitant chemo-radiotherapy schedules.

2000Lancet. 2000 Mar 18;355(9208):949-552007Radiother Oncol. 2007 Oct;85(1):156-70. Epub 2007 May 4.2009Radiother Oncol. 2009 Jul;92(1):4-14. doi: 10.1016/j.radonc.2009.04.014. Epub 2009 May 142011Radiother Oncol. 2011 Jul;100(1):33-40. doi: 10.1016/j.radonc.2011.05.036. Epub 2011 Jun 16

ABSOLUTE BENEFITS- oral cavity-8.9% oropharynx-8.1% larynx-5.4% hypopharynx-4%

2011 update

platinum based regimen more effective.no significant difference efficacy between mono and multi drug platinum regimens

• LEVEL 1 EVIDENCE OF ADDITION OF CT IN TERMS OF OVER ALL SURVIVAL.• ADDITION OF CT-ABSOLUTE BENEFIT IN SURVIVAL-5%IN 5 YRS.• INDUCTION/ADJUVANT-2% SUVIVAL BENEFIT• CONCURRENT CTRT 8% 5YR SURVIVAL BENEFIT• BENEFIT MORE IN CONCURRENT CTRT• BENEFIT DECREASES WITH INCREASING AGE.• ABSOLUTE BENEFITS-oral cavity 8.9% oropharynx-8.1% larynx-5.4%

hypopharynx-4%

MACH- NC-CONCLUSIONS

MARCH META-ANALYSIS

20062010

The Lancet, Volume 368, Issue 9538, Pages 843 - 854, 2 September 2006

15 Randomized Trials of Varied Fractionation (1970-1998)

PATIENT CHARACTERISTICS7073 patientsTumours sites: mostly oropharynx and larynx 74% patients had stage III—IV disease

hyper fractionated

accelerated

accelerated with total dose reduction

Overall survival was the main endpoint

median follow up:6 yr

benefit Conventional vs Altered Hyper fractionation vs Accelerated fractionation

Locoregional control

Loco regional control 6.4 %times higher

benefit was higher with hyper fractionated radiotherapy

( OS 8% at 5 years) than with accelerated radiotherapy

(2% with accelerated fractionation without total dose reduction and 1·7% with total

dose reduction at 5 years, p=0·02)

Survival benefit absolute benefit of 3·4% at 5 years with altered

fractionated radiotherapy,

RESULTS OF MARCH META-ANALYSIS:There was a significant survival benefit in altered fractionation.(3.4%at 5 years)There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6·4% at 5 years; p<0·0001The benefit was significantly higher in the youngest patients

InterpretationAltered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit

Role of biological therapy

• Cetuximab with RT• Bonner et al- • 424 patients• Locally advanced SCCHN• 15% pt : Ca hypopharynx

Bonner et al, 2006

Drawback: in control arm RT alone given (not a standard treatment for stage III and IV HNSCC)

• LOCOREGIONAL CONTROL • OVERALL SURVIVAL

Bonner et al 2010 update: 5 years follow up

subgroups analysis demonstrated effect of cetuximab was pronounced in patients with

oropharyngeal carcinoma, T1-T3 disease,concomitant boost radiation, N1-N3,KPS 90-100 ,male patients, EGFR expression ≤ 50%, ≤65 years.

Surgical options in operable Ca hypopharynxVoice preservation surgeryin early hypopharynx cancer

Supraglottic laryngectemyHemilaryngectomyPartial laryngopharyngectomy

Radical Laryngectomy in advanced stages

Total laryngectomyTotal laryngopharyngectomy

Primary Surgery• T1 and T2 Tumors: voice

conservation surgery• INDICATIONS

• CONTRAINDICATIONS

voice conservation approaches possible refuse radiation

vocal fold fixation, cartilage invasion, postcricoid invasion, deep pyriform sinus invasion, extension beyond the larynx

• T3 / T4 Tumors• INDICATIONS

dysfunctional larynxpt. with bulky destructive tumor that

severely compromise airway or destroy cartilage, bone, soft tissue undergo immediate laryngopharyngectomy and post op radiation

operation indication parts removed contraindication

hemilaryngectomyhorizontal partial

supraglottic laryngectomy(SGL)

T1/T2 pyriform sinus tumor

voice preservation for early supraglottic extension

epiglottis aryepiglottic fold false cords upper 1/3-1/2 of

thyroid cartilage ±hyoid bone

preserves one or both arytenoids & true vc

thyroid,cricoid cartilage invasion

arytenoid involvement vocal fold fixation postcricoid invasion deep pyriform sinus invasion extension beyond the larynx fixed neck nodes inadequate pulmonary

function

extended supraglottic laryngectomy

supraglottic lesion with<1cm base of tongue invasion

same as SGL with removal of i/l bot upto circumvallete papillae

operation indications removes contraindication

partial laryngopharyngectomy

used for small medial and anterior pyriform sinus lesion

false vocal cord epiglottis aryepiglottic fold pyriform sinus,

tvc are preserved

transglottic extension, cartilage invasion vocal cord paralysis, pyriform apex invasion, postcricoid invasion extralaryngeal spread poor pulmonary reserve

total laryngectomy

Advanced pyriform sinus lesion

cartilage invasion

removes hyoid, thyroid, cricoid cartilage, epiglottis strap muscle. Patient left with a permanent tracheostoma and pharynx reconstruction

total laryngopharyngectomy

for more advanced hypopharyngeal lesion

total laryngectomy plus removal of varying

amount of pharyngeal wall

Advances in surgery

• In recent years, advancements in organ preservation surgery have included the use of

• Transoral laser microsurgery • Transoral robotic surgery. • AdvantageLess morbidityavoiding tracheostomy and the use of feeding tubes

Transoral Laser Surgery: Inclusion Criteria *

Complete endoscopic visualization of the growthTumor extension to the contralateral VC < 3mmAbsence of arytenoid involvement (except vocal process)Subglottic extension < 5mmSupraglottic extension no further than lateral extension of ventricleMobile vocal foldsNo cartilage involvement

*Motamed M, et. al. Salvage conservation laryngeal surgery after irradiation failure for early laryngeal cancer. Laryngoscope 2006; 116:451-455

ADJUVANT RADIOTHERAPY IN

OPERATED HNSCC

Preoperative RT Vs postoperative RT: RTOG 73-03

Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries

duration of follow-up was 9-15 years, Loco-regional control& absolute survival was estimated & compared

1987

N=277 patients.Operable stage T2-T4 /N± oral cavity(14%) Oropharynx(17%) Supraglottic larynx(26%) Hypopharynx(43%)

Postoperative stage III or IV SCCHN

R

ANDOMIZE Arm 2:Post-op RT 60 Gy.

n= 141

Arm 1: Pre-op RT 50 Gyn=136

Long-term Follow-up Of RTOG Study 73-03

*(Tupchong L et al. Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):21-8.)

outcome preopRT postopRT

LRC 58% 70%

LRF within 2 years 59% 58%

LRF after 2years 27% 8%

Overall survival similar

toxicity similar

• Post op RT is better than preop RT for LRC

1991

Indications for post operative radiotherapy

Primary: Large primary - T4 or T3 with soft tissue

infiltration Close or positive margins of excision Deep infiltrative tumour High grade tumour Lympho-vascular and perineural invasion

Lymph nodes: Bulky nodal disease N2 / N3 Extra nodal extension Multiple level involvement

POSTOPERATIVE RADIOTHERAPYIs PO CTRT better than PORT alone?

RANDOMIZE Cisplatin

100 mg/m2 d 1, 22, 43

XRT

XRT

Cooper et al, 2004; Bernier et al, 2004.

SURGERY

RTOG 95-01459 patients

EORTC 22931 334 patients

EORTC (66 Gy over 6 ½ wks)RTOG (60–66 Gy over 6-6 ½ wks)

Postoperative Chemoradiotherapy

•  RESULTS OF POSTOP CHEMORADIATION TRIAL

EORTC 22931 only

Bernier et alN=334

EORTC 22931 and RTOG 9501

RTOG 9501 only

Cooper et al.2004N=459

stage III/IV disease

margin+ ≥2positive l.n

ECE+ ECE + ECE +

margin +margin+

PNI+embolism

NCCN GUIDELINES