Important Studies Flashcards
Concurrent CRT vs. RT alone
GORTEC 94-01University of Queensland: Denis et al, IJROBP, 2003. 226 Stage III/IV oropharynx”→70 Gy with carbo/5-FU x3
vs. RT alone.
CRT improved 5-yr LC 48% vs. 25%
5-yr DFS 27% vs. 15%
5-yr OS 22% vs. 16%
increased acute but not late toxicity
The addition of concurrent chemo improves LC and OS without increase in late toxicity in oropharynx.
Coventional vs. Altered fx
GORTEC 99-02: Bourhis et al, Lancet, 2012. 559 Stage III or IV SCC. Randomized to:
1) RT 70 Gy/7 weeks with carbo/5FU
2) Acc RT 70 Gy/6 weeks (2 Gy daily for 40 Gy then 1.5 BID) with carbo/5FU/
3) Very Acc RT 64.8 Gy/3.5 weeks, no chemo
Slight improvements with conventional RT
3-yr PFS 38% Conv vs. 34% Acc vs. 32% Very Acc
3-yr OS 43% Conv vs. 39% vs. 37%
3-yr LFR 42% vs. 45% vs. 50%
3-yr DM 25% vs. 34% vs. 28% (NS)
G3-4 mucosal toxicity 69% vs. 76% vs. 84% p=0.0001
Feeding tube 60% vs. 64% vs. 70%, p=0.045
Conventional fractionation with chemo results in superior OS and lower toxicity compared to accelerated RT.
Defined HPV stratification/ Standard CCRT vs. AFX CRT
RTOG 0129: “Ang et al, NEJM, 2010. 323 Stage III-IV SCC or oral cavity, oropharynx, hypopharyx, or larynx”→Standard RT 70 Gy with cisplatin
vs. accelerated fractionation with concominant boost (AFX-CB) 72 Gy in 6 weeks concurrent cis.
HPV positive vs. negative has different prognosis.
3-yr OS by RPA group (see commentary for classes):
Low risk: 93%
Int risk: 71%
High risk: 46%
3-yr OS HPV+/HPV-: 82% vs. 57%
3-yr DM HPV+/HPV-: 9% vs. 15%
3-yr LRC HPV+/HPV-: 86% vs. 65%
There is no difference in LRF, PFS, OS, DM, and toxicity in AFX-CB vs. standard RT.
TORS vs chemoRT
ORATOR: Nichols et al, Lancet, 2019. 68 Oropharynx T1-2, N0-1 or N2b (up to two nodes ≤3cm) HPV+/-(88% were HPV+). “Phase II TORS and neck dissection [71% had post-op RT] vs. RT with or without chemotherapy.
RT resulted in superior 1-yr dysphagia scores but not to a clinically meaningful degree.
Addition of cetuximab to cisplatin and RT
RTOG 0522: Ang et al, JCO, 2014. 891 oropharynx Stage III or IV randomized to “concurrent cisplatin+/-cetuximab.
No diff in 3 yr OS (76% vs. 73%) or PFS (59% vs. 61%). With cetuximab, mucositis and skin reactions worse
Adding cetuximab to RT and cisplatin did not improve outcomes.
Ipsilateral Tonsil RT
Princess Margaret Hospital: O’Sullivan et al, IJROBP, 2001. 228 Ipsilateral tonsil, no surgery. Retrospective. RT only to ipsilateral side, no chemo
Contralateral failure:
T1 0%, T2 1.5%, T3 10%, T4 0%, N0 0%, N1 9%, N2/3 0%.
Sig risk for failure if involving medial one third of palate, BOT
No difference in LC or RC for HPV+ vs. HPV-
Ispilateral neck radiation in tonsil cancer T1-T2N1-N2b results in excellent control. no difference per HPV status
Nomogram for recurrence with HPV
Princess Margaret Hospital: O’Sullivan et al, JCO, 2013. 505 Oropharynx H&N cancer, HPV positive and negative treated with CRT
HPV+ T1-3N0-2c have a low DM risk. N2c have worse DM with RT alone
Cisplatin vs cetuximab
RTOG 1016: Gillison et al, Lancet, 2019. 849 HPV+ locally advanced oropharynx p16+ “→RT 70 Gy in 6 weeks (DAHANCA) SIB 56 & 52.5 Gy with concurrent
cisplatin vs. cetuximab.
5-yr OS 85% vs. 78% 5-yr PFS 78% vs. 67% 5-yr LRF 10% vs. 17% 5-yr DM 9% vs. 12% Severe and acute toxicity similar
Cetuximab with RT resulted in inferior OS and PFS compared to cisplatin in HPV+ oropharynx. Toxicity is not reduced with cetuximab
De-Escalate: Mehanna et al, ESMO, 2018. 304 Stage III-IV (T3N0, T4N0, T1N1-T2N3) HPV+ oropharynx cancer →70 Gy in 6 weeks with cisplatin vs. cetuximab.
2-yr OS 98% vs. 89%
2-yr any recurrence 16% vs. 6%
Severe and any grade toxicity similar
Cetuximab with RT resulted in inferior OS and LC compared to cisplatin in HPV+ oropharynx. Toxicity is not reduced with cetuximab.
HPV+ chemoRT vs. RT alone
NRG HN002: Yom et al, ASTRO, 2019. 296 Oropharynx HPV+ “Phase II→60 Gy IMRT with weekly cis vs. 60 Gy alone
IMRT+cis: 2-yr PFS 91%, p=0.035
IMRT: 2-yr PFS 88%, p=0.088%, CI extends below 85%
Dsyphagia scores acceptable in both arms
60 Gy IMRT+cisplatin met the pre-determined criteria for further study. Cisplatin should not be removed.
HPV+ Ongoing chemoRT vs. RT immuno
NRG HN005 (ongoing): 532 Oropharynx HPV+ T1-3, N1, and <10 PY (AJCC 8)”→70 Gy in 6 weeks (DAHANCA) + cisplatin vs. 60 Gy/ 30 fx + cisplatin vs. 60 Gy/ 30 fx + nivolumab
HPV+ PORT de-escalation in intermediate risk
EGOC 3311: Ferris et al, ASCO, 2020. 377 Resectable oropharynx cancer stage III-IV, p16+, who undergo TORS
TORS →
• Low risk (negative margins, no ECE, 0-1 nodes): observed
• Intermediate risk (close margins, <5 nodes, ENE ≤1 mm): 50 Gy vs. 60 Gy
• High risk (>1 mm ENE, positive margins, or ≥5 nodes):
66 Gy RT weekly cisplatin
2-yr PFS
Low risk: 94%
Int risk (50 Gy vs. 60 Gy): 95% vs. 96%
High risk: 91%
“All approaches led to favorable outcomes in HPV+ oropharynx.
TORS and adjuvant 50 Gy RT for intermediate risk warrants comparison to chemoRT in a phase III trial.
HPV+ Ongoing PORT de-escalation
PATHOS (ongoing): 242 Oropharynx cancer stage II-III (T1-T3, N0-2b, <10 PY), p16+, who undergo TORS
Intermediate risk: 50 Gy IMRT vs. 60 Gy
High risk: 60 Gy IMRT vs. 60 Gy with weekly cisplatin”
Ongoing TORS vs. chemoRT
EORTC 1420-HNCG-ROG “Best of” (ongoing): 160 Oropharynx Stage I/II HPV+/-. “TORS and neck dissection vs. RT.
ORATOR2 (ongoing): Lawson. 140 T1-2, N0-2, p16 +/- “TORS and neck dissection vs. RT with or without chemotherapy”
