Important Studies Flashcards
Post-op RT dose
MDACC: “Peters et al, IJROBP, 1993. Stage III or IV oral cavity, oropharynx, hypopharynx, larynx who underwent surgery who required post-op RT. Low risk: →52.2 Gy or 57.6 (dose changed to 57.6 after excess failures seen with 52.2)
vs. 63 Gy. High risk: →63 Gy vs. 68.4 Gy. “At 2-yr follow-up, ECE benefits from dose escalation to ≥63 Gy.
At 5 to 20-yr f/u there is no benefit in LRC with dose escalation from 63 Gy –> 68.4 Gy in the high risk group or 57.6 –> 63 Gy in the low risk group. Chemo was not used in this study.
Low risk RT dose
University of Leuven, Belgium: “Nevens et al, Radiother Oncol, 2017. Previously untreated head and neck cancer. →50 Gy to elective nodes vs. 40 Gy to elective nodes.
Reduction of salivary toxicity with 40 Gy
2-yr LF 3.9% in 40 Gy arm, similar to 50 Gy
5-yr RR 8% vs. 14%, p=0.10
5-yr DM 24% vs. 13%, p=0.07
5-yr OS ~50-55%, not different
At 5 year follow-up, there is no difference RR. Low recurrences in the low dose PTV in both arms suggests 40 Gy may be adequate. There is a possibility the study is underpowered.
Altered fractionation meta-analysis
MARCH - HN: “Baujat et al, Cochrane Database Syst Rev, 2010. “Meta-analysis of 15 trials evaluating the benefit of altered fractionation (defined as either hyperfx, accelerated, or accel with dose reduction) compared to conventional fx. Update: Meta-analysis of 33 trials
5-yr OS benefit of +3.4% with altered fractionation (best benefit with hyperfx, +8%)
5-yr LC benefit of +6.4%
Long term f/u:
• Compared to primary or post-op conv fx, altered fx benefit in OS: 5-yr +3.1% and 10-yr +1.2%
• OS benefit only in hyperfx group: 5-yr OS +8.1% and 10-yr OS +3.9%
• Compared to conv fx chemo RT, OS worse with hyperfx RT alone, 5-yr OS -5.8% and 10-yr OS -5.1%
Altered fractionation
RTOG 9003: Stage III-IV (or II for BOT/hypopharynx), previously untreated, to have primary RT
1) Conventional 70/35 fx in 2Gy
2) Hyperfx 81.6/68 fx in 7 wks in 1.2Gy BID
3) Accel Split: 67.2/42 fx in 6 wks at 1.6Gy BID with 2-wk break at 38.4Gy
4) Accel-con boost: 72Gy/42 fx in 6 wks at 1.8Gy and 1.5Gy
IMRT not allowed
Hyperfrac and accelerated concominant boost result im improved outcomes and lower toxicity than standard fractionation
IAEA-ACC: glottic, supraglottic pharynx, oral cavity not receiving chemo, eligible for curative RT→5 fx per week vs. 6 fx per week. 66-70 Gy/ 33-35 fx, no chemo [no nimorazole as in DAHANCA 6/7].
5-yr LRC 42% 6 f vs. 30% 5 fx
5-yr OS 35% vs. 28%, p=0.07
5-yr DSS 50% vs. 40%
DAHANCA 6 & 7: glottic, supraglottic pharynx, oral cavity not receiving chemo, treated with primary RT”→5 fx per week vs. 6 fx per week. 66-68 Gy/ 33-34 fx, no chemo. Nimorazole for all except for glottic. 5-yr LRC 70% 6 fx vs. 60% 5 fx
DAHANCA 6 14.5-yr LRF 22% vs. 29%
Larynx preservation 80% vs. 68%
5-yr DSS 73% vs. 66%
No change in OS
Acute morbidity more frequent with 6 fx but was transient
Hyperfx with chemo
DAHANCA 28: HPV negative Stage III-IV H&N cancer. Hyperfx accel RT 76 Gy/ 56 fx BID with cisplatin + nimorazole. 3-yr LRF 21%
3-yr OS 74%. Acute severe dysphagia in 67%. Acute severe mucositis in 61%.
Hyperfx accel RT wih cisplatin and nimorazole is feasible. Although acute toxicity was high, late toxicity seems acceptable.
Post-op H&N Altered fractionation
MDACC: Ang et al, IJROBP, 2001; Post-op H&N defined as:
Low risk: 0 factors
int risk: 1 factor, no ECE
high risk: ECE or >=2 factors
Low risk - no PORT
Intermediate risk - 57.6 Gy
High risk : →63 Gy/5 wks accel vs. 63 Gy/7 wks conv + 2 wks CCB.
Low Risk: 90% LRC, 83% OS
Int risk: 94% LRC, 66% OS
High Risk: 68% LRC, 42% OS
Low risk is unlikely to benefit from adjuvant RT.
Int risk benefits from mod dose adjuvant RT.
In high risk there is still opportunity for improvement in LRC.
Addition of chemo to post-op RT
EORTC 22931 (Bernier et al, NEJM, 2004):
T3-4, T1-2N2-3, T1-2N0 with ENE +M PNI or LVI, OC or OPX with level IV or V nodes. →Post-op RT 66 Gy (54 Gy to low risk)
vs. same RT + cisplatin x3. 5-yr OS 40% vs. 53%
3-yr OS 49% vs. 65%
5-yr LRC 69% vs. 82%.
RTOG 9501 (Cooper et al, NEJM, 2004 Cooper et al, IJROBP, 2012": operable H+N with ≥2 N+, ENE, or + margin. "→Post-op RT 60 Gy ± 6 Gy boost vs. same RT + cisplatin x3. The addition of chemo to adjuvant RT improves OS and LRC in post-op H&N tumors with risk factors.
Pooled EORTC 22931 RTOG 9501: The addition of chemo to adjuvant RT improves OS in post-op H&N tumors with ECE or positive margins.
Addition of chemo to post-op RT, altered fx
OTAC: locally advanced, resected oral cavity tumors with ECE, positive margin, Stage III/IV, >2 nodes, PNI with N+, LVI with N+, major reconstruction required.
→56-60 Gy/ 28-30 fx, 5 fx per wk vs. same RT & concurrent weekly cisplatin vs. 56-60 Gy, 6 fx per wk, no chemo.
No difference in 5-yr LRC or OS, even with high risk features including T stage, N stage, and ECE
Concurrent chemo
MACH-NC: Meta-analysis of 93 trials. Chemo (all forms of sequencing) had an absolute 5-yr OS benefit of +4.5%. If concurrent chemo, 5-yr OS benefit is +8%.
Addition of concurrent cetuximab to RT
Bonner et al, NEJM, 2006: Stage III or IV nonmetastatic SCC of oropharynx, hypopharynx, or larynx →RT with concurrent cetuximab
vs. RT alone.
Median LC 24 vs. 15 mos
2-yr LC 50% vs 41%
median OS 49 vs. 29 mos
3-yr OS 55% vs 45%. Acneiform rash and infusion reactions more common, but otherwise not more toxic.
OS for grade 2-4 acneiform rash 69 mos vs 25 without
Addition of chemo to hyperfx RT
Duke: T3-4 cancers or T2N0 BOT. “→75 Gy hyperfx, 1.2 Gy BID vs. concurrent cis/5FU (split 1 wk RT break at 40 Gy) → adj cis/5FU.
CRT improved 3-yr LC from 44% to 70%
3-yr OS 34% vs. 55%, p=0.07
Definitive CRT vs. RT, split course
INT: Adelstein et al, JCO, 2003:
Unresectable oral cavity, oropharynx, larynx, or hypopharynx→70 Gy alone
vs. 70 Gy + concurrent cisplatin x 3 vs. split-course 70 Gy + cis/5-FU. Continuous CRT improved 3-yr OS (37% vs. RT 23% vs. split-course plus chemo 27%) and DFS, but increased Gr 3-4 toxicity
Induction chemo
GSTTC Italian Study Group: locally advanced, Stage III-IV unresectable. →induction TPF vs. no induction, →conc cis/5FU vs. conc cetuximab, 2x2 randomization. Induction chemo improved OS, PFS, LRC, and CR. Median OS induction 55 vs. 32 mos
3-yr OS 58% vs. 47%.
DeCIDE: N2 or N3 SCC of H&N. →Induction TPF, RT + conc THF vs. RT + conc THF. No benefit in 30-mos OS, RFS, or DMFS
PARADIGM: unresectable, low surgical curability T3/T4, N2/3 (but not T1N2), or organ preservation→Induction TP, RT + conc carbo or docetaxol
vs. RT + conc cis.
No benefit to induction TPF. Trial terminated early. Toxicity is increased.
Hospital Universitario 12 de Octubre, Madrid:
unresectable, Stage III-IV
→Induction TPF, RT + conc cis
vs. induction PF, RT + conc cis
vs. RT + conc cis. No benefit to induction chemotherapy. Toxicity is increased.
Planned neck dissection
PET-NECK: N2 or N3 SCC of H&N→chemoRT then PET in 3 mos then neck dissection only if incomplete or equivocal response
vs. planned neck dissection. OS is noninferior with neck dissection guided by PET vs. planned dissection in all.
Post-op RT field
DAHANCA: Kjems et al, IJROBP, 2016:
H&N cancer treated with primary radiation. Retrospective. 77% IMRT. RP nodes only included for posterior pharyngeal wall involvement. Level IB only included in oral cavity tumors. Recurrences in RP and level I after radiation are rare and should be limited to posterior pharyngeal wall or oral cavity involvement.
