Three clinical trials comparing different treatments for oropharynx and larynx cancer were summarized: 1. RTOG 9003 found that hyperfractionated RT showed significantly improved OS and LRC compared to standard fractionation for advanced cancers. Acute toxicities were similar between arms. 2. GORTEC 9902 and the study by Brizel et al. found CCRT with altered fractionation like hyperfractionation or accelerated fractionation improved outcomes over RT alone. 3. RTOG 9501 and EORTC 22931 showed that for cancers with high-risk features, adjuvant chemoRT with cisplatin improved locoregional control and DFS compared to RT alone, with

1. TRAILS AND 2D
OROPHARYNX CANCER
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2. TRIALS - TOPICS
COMPARISON RESULT TRAIL NAME
HFX VS conv RT HFX EORTC 22791
ACC RT vs Conv aCC RT DAHANCA 6 & 7
ACC vs HYP vs SPLIT HYP RTOG 90- 03
CCRT vs ACC CCRT vs V.ACC
RT
ACC. CCRT GORTEC 99-02
IMRT SIB benefits in HPV + RTOG 00-22
CCRT vs RT CCRT GORTEC 9401
CCRT ,IC ,AC,AGENTS CCRT , single agent high dose CDDP,
>70yrs
MACH - NC
RT vs CCRT vs Split course 3weekly CDDP + RT E1392
weekly cddp in ccrt beckman et al
HFX in CCRT vs RT hyp CCRT brizel et al
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3. Comparison Result Trial Name
adj.rt VS adj.chemo rt adj.chemo RT RTOG 9501
EORTC 22931
induction chemo ,ccrt VS
CCRT
CCRT paradigm
IC - TPF vs PF TPF tax 324
benefitc of docetaxel + DECIDE
cetuximab RT vs CDDP RT,
low risk HPV
CDDP + RT De ESCALaTE
INT. risk HPV RTOG 1016
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6. • HFX RT VS RT
• ACC RT VS RT
• RT vs HFX vs ACC vs split course
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7. EORTC 22791
• patients - 356
• done - 1980 - 1987
• final report - 1990
• comparison CF vs HF
• in oropharynx carcinoma - T2,T3,N0,N1 < 3cm
• Conventional Fractionation - 70Gy/35-40 # / 2Gy or
1.8Gy/# - 5days /week
• Hyperfractionation - 80.5 Gy/1.5Gy/# BD - 7weeks
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8. • 5yr LRC -
• the superiority is mostly seen in the T3 N0 ,T3N1
• acute toxicities in HF arm
• no difference in late toxicities
• the OS p value =0.08 , set a trend to improved survival
CF HF p value
5yr LRC 40% 59% 0.02
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11. RTOG 9003
• Official Title:
• Phase III Randomized Comparison of Radiotherapy
Fractionation in Advanced Squamous Cell Carcinoma of
the Head and Neck: Twice-Daily Hyperfractionation vs
Split-Course Accelerated Hyperfractionation vs
Accelerated Fractionation With Concomitant Boost vs
Standard Fractionation
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12. objectives
• Determine whether hyperfractionation and/or
accelerated fractionation (split-course or with a
concomitant boost) improves the locoregional control
rate over standard fractionation radiotherapy in
patients with advanced squamous cell carcinomas of
the head and neck.
• Determine the disease-free survival and overall survival
of these patients treated with different radiotherapy
fractionation schemes.
• Determine the acute and late toxicities of each
fractionation schedule.
• Compare the quality of life on the two regimens.
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16. • at 5 years - only the hyperfractionate RT shows significant OS p -0.05
• LRC was observed only in hyperfractionated arm p-0.05
• DFS was also observed in all arms, but not statitically significant
• grade 3 toxicities were similar in all arms
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17. CCRT > RT
• altered fractionation in concurrent chemo radiotherapy
• GORTEC 9902- RT > acc RT
• brizel et al -Hyperfractionation RT > RT
• coventional fractionationation in CCRT
• gortec 9401 - carbo + 5fu 3weekly
• INTERPHASE E1392 - 3weekly cisplatin > cis + 5fu
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23. FIRST AND FINAL REPORT
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24. • Stage IV, hemoglobin level lower than 125 g/L, and standard treatment were independent
prognostic factors of short survival and locoregional failure by univariate and multivariate
analysis.
• One or more grade 3 to 4 complications occurred in 56% of the patients in arm B, compared
with 30% in arm A (P was not significant).
• conclusion: Concomitant radiochemotherapy improved overall survival and locoregional
control rates and does not statistically increase severe late morbidity.
• Anemia was the most important prognostic factor for survival in both arms.
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25. • We did a multicentre, double-blind, randomised, placebo-controlled trial in 351
patients (haemoglobin <120 g/L in women or <130 g/L in men) with carcinoma of
the oral cavity, oropharynx, hypopharynx, or larynx.
• Patients received curative radiotherapy post operatively or definitive RT were studied
• All patients were assigned to subcutaneous placebo (n=171) or epoetin beta 300
IU/kg (n=180) three times weekly, from 10-14 days before and continuing
throughout radiotherapy.
• The primary endpoint was locoregional progression-free survival. We assessed also
time to locoregional progression and survival.
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26. • 148 (82%) patients given epoetin beta achieved haemoglobin
concentrations higher than 140 g/L (women) or 150 g/L (men)
compared with 26 (15%) given placebo.
• However, locoregional progression-free survival was poorer
with epoetin beta than with placebo p=0.0008. For
locoregional progression p=0.007
• and for survival was, p=0.02.
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27. • Epoetin beta corrects anaemia but does not improve cancer
control or survival.
• Disease control might even be impaired.
• WE SHOULD NOT PROPHYLACTICALLY GIVE EPO -BETA
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29. • cispaltin is beneficial than cisplatin + 5fu
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30. WEEKLY CISPLATIN
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31. • The purpose-
• to determine the feasibility and efficacy of hyperfractionated accelerated
radiotherapy (HFRCB) combined with simultaneous chemotherapy with weekly
cisplatin (CDDP) in locally advanced inoperable head and neck cancer.
• From August 1999 to December 2002,
• 37 patients (median age, 59 years)
• with stage III (n = 2) and stage IV (n = 35) squamous cell cancer of the oropharynx
and hypopharynx were treated with,.
• Concomitant boost radiotherapy (1.8 Gy, days 1-38 and 1.5 Gy boost, days 22-38,
twice daily with at least a 6-hour interval; total dose 69.9 Gy) and
• simultaneous cisplatin, 40 mg/m2 weekly, were given.
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32. • . Toxicity was manageable, with neutropenia , thrombocytopenia and mucositis grade III/ IV
in Chemotherapy was restricted to four weekly applications in 29 patients mainly because of
mucosal toxicity with a median dose intensity of 160 mg/m2 (0-200) of cisplatin in 5.5
weeks.
• With a median follow-up of 28 months for living patients, the 2-year overall survival rate was
67%.
• The median overall and relapse-free survival times were 36 and 31 months, respectively.
• HFRCB in combination with weekly cisplatin achieves a high rate of locoregional control and
survival.
• Four weekly cycles of 40 mg/m2 cisplatin seem to be the dose limit for most patients.
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33. INDUCTION CHEMO
• PARADIGM - Ic= CRT < CRT
• TAX 323 - IC + RT ,TPF>PF
• TAX324 - IC + CRT, if at al given GIVEN TPF > PF
• DECIDE - benefits of docetaxel
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35. More patients had febrile neutropenia in the IC group (16 patients)
than in the chemoradiotherapy alone group (1 patient).
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37. PF TPF
MEDIAN OS 14.5
months
18.8
months
MEDIAN PFS 8.2 months 11 months
3 YR OS 26 % 37 %
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41. DECIDE - DocEtaxel based Chemotherapy
plus or minus Induction chemotheapy to
Decrease Events in HNC
• phase 3, randomized
• open-label trial, 280 patients
• persons with pathologically confirmed SCCHN; N2/N3 disease without metastases;
• CRT alone (CRT arm)
• [5 days of D (25 mg/m2), F (600 mg/m2), hydroxyurea (500 mg BID), and RT (150 cGy BID) followed by a 9
day break] or
• (IC arm)
• 2 cycles of IC [D (75 mg/m2), P (75 mg/m2), F (750 mg/m2 day 1-5)] followed by the same CRT .
• Primary endpoint was OS.
• Secondary endpoints included DF free survival, failure pattern, and recurrence-free survival
(RFS).
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42. • here they have taken out
platinum and instead
used hydroxyurea, and
looked for any adverse
events decrease, better
tolerability, and survival
benefits
• the toxicites leukopenia,
neutropenia were higher
in IC arm , p-0.003, p-0.02
• no OS benefit. p-0.70
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43. MACH - NC

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49. • Results: 24 new trials, most of them of concomitant chemotherapy,
were included with a total of 87 trials and 16,485 patients.
• Both direct (6 trials) and indirect comparisons showed a more
pronounced benefit of the concomitant chemotherapy as compared
to induction chemotherapy.
• For the 50 concomitant trials, the hazard ratio was 0.81 (p<0.0001) and
the absolute benefit 6.5% at 5 years.
• There was a decreasing effect of chemotherapy with age (p=0.003, test
for trend).
• Conclusion: The benefit of concomitant chemotherapy was confirmed
and was greater than the benefit of induction chemotherapy.
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51. 2021 UPDATE
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52. MACH NC UPDATE -2021
1. CCRT superior to RT Alone
2. Use of radiotherapy with concurrent
chemotherapy resulted in 19 % reduction in deaths
3. 6.5 % improvement in 5 yr survival and 13.5 %
improvement in locoregional control,p<0.0001
4. 2.9 % reduction in risk of distant metastasis which
was not significant
5. Maximum benefit of chemo in young patients.
6. absolute decrease in benefits age > 70 years
7. Single agent is equivalent to combination
chemotherapy
8. Cisplatin is better than other agents
9. Induction chemo shows NO OS benefit
10. CCRT> RT
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53. ADJUVANT CHEMO RT
• RTOG 9501
• EORTC 22931
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58. EORTC 22931
• Risk features- positive margins,
ECE, PNI, vascular tumor
embolism, involvement of level 4,5
nodes
• High dose cisplatin chemotherapy
administered concomitantly on
days 1,22 and 43 with EBRT- 60 to
66 gy in postop setting
RTOG 9501
• Pathological risk factors- positive
margins, ECE, >/= 2 Nodes involved
• RT alone vs High dose cisplatin
chemotherapy administered
concomitantly on days 1,22 and 43
with EBRT- 60 to 66 gy in postop
setting
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60. • RTOG 9501
• Randomised HNC cases to post op chemo RT ( 3 weekly chemo ) vs post op RT alone
○ Benefit in locoregional control and disease free survival in chemo RT arm
○ OS comparable
• EORTC 22931
○ Similar study design as RTOG 9501
○ Local control, PFS, and OS were superior in the chemo RT arm
COMPARATIVE ANALYSIS FROM BOTH STUDIES SHOWED ENE AND MICROSCOPICALLY
INVOLVED MARGINS WERE THE RISK FACTORS THAT BENEFITED MOST FROM CHEMO RT
But patients with two or more involved nodes without ENE did not appear to get any benefit from
addition of chemotherapy
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61. 2D - planning
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62. 2D - oropharynx
• Position
• Supine position with neck extension
• Left lateral position
• IMMOBILISATION
• Head rest
• Shoulder strap
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63. TARGET VOLUME
Entire oropharynx includes base of tongue , tonsil ,
pharyngeal walls and
B/L - level IB - V
Portals
Opposing laterals
Opposing laterals with single anterior field
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64. BORDERS B/L FIELD
• Superior border : Zygoma
• Inferior border: clavicle
• Anterior border : Anterior border of masseter muscle
• Posterior border : 2 cm behind mastoid tip
• off cord after 40Gy - posterior border moved to mastoid tip
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65. PRESCRIPTION
● Midline depth
● 66 Gy in 33 fractions over 6.3 weeks
off cord at. 40 Gy
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66. THREE FIELD
• upper field borders
• Superior border : Zygoma
• Inferior border: clavicle
• Anterior border : Anterior border of masseter
muscle
• Posterior border : 2 cm behind mastoid tip
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67. LAN FIELD BORDERS
• upper border - 0.5cm below the cricothyroid groove
• or cricothyroid groove and use half beam block
technique, to avoid junction hotspot.
• lower border- clavicle
• lateral border - junction of medial 2/3 and lateral 1/3 of
clavicle
• with midline layrngeal shielding
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69. PRESCRIPTION
• Portals
• upper - opposing lateral
• LAN - single AP
• 2 PHASE
• Ist phase- 40Gy /20# /2Gy /# - 4weeks
• 2nd phase - post border of lateral fileds moved anterior
to mastoid tip, and proceed upto 66Gy
• 26Gy/13#/ 2Gy/# over 2.3 weeks
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70. • 3phase technique
• Ist phase- 40Gy /20# /2Gy /# - 4weeks
• 2nd phase - off cord and proceed upto 60 Gy
• 3rd phase - 6Gy only to gross diease - mostly used in
case of N0,N1 .
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71. REFRENCE
• PUBMED
• LANCET
• RED JOURNAL
• NCCN
• DOBBS 3RD EDITION
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72. Acknowledgement
• Asst Prof - Dr.Durga prasad MD RT
• Prof - Dr. Jeeva MD RT
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73. THANK YOU