Table 5.
Radiation Deintensification Trials: Upfront Radiation Dose Reduction
| Study | Treatment Arms | Outcomes | Toxicities |
|---|---|---|---|
| NRG-HN002 17 | Reduced dose def CRT | Null hypothesis 2 yr PFS ≤85%: | Higher acute toxicity with CRT. |
| (Phase II, randomized) | (60Gy IMRT + LD cis 40 mg/m2 × 6c, n=157): | - CRT 90.5% [84.5–94.7], p=0.0350, rejecting null hypothesis | Acute Grade 3–4 (p<0.001): 79.6% vs. 52.4% |
| p16+ OPC. | VS. | - AFRT 87.6% [81.1–92.5], p=NS, failing to reject null hypothesis | Late Grade 3–4 toxicit (p=NS): 21.3% vs. 18.1% |
| AJCC7 T1–2 N1–2b, T3 N0–2b. | AFRT alone (60Gy/5 wks IMRT, n=149): | 2 yr LRF (p=0.02): 3.3% vs. 9.5%, HR 2.56 [1.11–5.88] | |
| <10 PYSH. | 19.9% Unilateral RT. 80.1% Bilateral RT. | 2 yr DM (p=0.58): 4.0% vs. 2.1%, HR 0.70 [0.20–2.50] | |
| Median FU = 2.6 years | 2 yr OS (p=0.93): 96.7% vs. 97.3%, HR 1.05 [0.34–3.23] | ||
| UNC/UF 82–83 | Reduced def CRT for all (n=114): | 2 yr PFS: 86% [77.5–91.3] | Acute ≥ Grade 3 toxicity: |
| (Phase II) | 60Gy RT + LD cis 30 mg/m2 wkly | 2 yr LRC: 95% [88.6–97.9] | - 2% xerostomia |
| p16+ OPC. | No chemo for T0-T2 N0–1. | 2 yr DMFS: 91% [83.9–95.4] | - 34% mucositis |
| AJCC7 T0–3 N0–2C and ≤10 PYSH | 2 yr OS: 95% [89.3–98.1] | - 21% dysphagia | |
| or > 5 yrs smoking abstinence. | Median FU = 31.8 months | - 4 local failures, half in T2N0–1 treated without chemo. | - 38/113 (33%) patients required peg |
| LCCC1612 84 | Reduced def CRT for all | 1 yr PFS was comparable: 92% IMPT, 93% IMRT | More short-term pegs with IMRT: 8% vs. 39% |
| (Phase II). | 60Gy RT + LD cis 30 mg/m2 wkly | ||
| p16+ OPC. | IMPT (n=25) vs. IMRT (n=46) | IMPT patients had better patient-report QOL and swallowing symptom scores than IMRT. | |
| AJCC7 T0–3 N0–2C and ≤10 PYSH | No chemo for T0–2 N0–1. | ||
| or > 5 yrs smoking abstinence. | Median FU = not reported | ||
| If ≥10 PYSH: only wild-type p53 eligible. | |||
| PacCIS 85 | SOC def CRT 70.6Gy + cis/5FU | p16+ OPC subset analysis: | Grade ≥3 acute dysphagia: |
| (Phase III) | (n= 105 total; 19 p16+ OPC) | 3yr PFS (p=0.653): 83.9% SOC VS. 84.6% 63Gy | 77.1% SOC, 81.1% 63Gy |
| AJCC7 Stg III/IV HNC. | VS. | ||
| Reduced def CRT 63Gy + cis/pacl | 3yr OS (p=0.76): 83.5% SOC VS. 92.3% 63Gy | Grade ≥3 acute functional mucositis: | |
| (n= 111 total; 13 p16+ OPC) | 64.2% SOC, 59.4% 63Gy | ||
| Median FU = 3.7 yrs | |||
| NRG-HN005 | SOC def CRT (70Gy+HD cis × 2c) | Ongoing, not reported | Ongoing, not reported |
| (Phase II/III) | VS. | ||
| p16+ OPC. | Reduced def CRT (60Gy+HD cis × 2c) | ||
| AJCC7 T1–2 N1–2B, T3 N0–2B. | VS. | ||
| <10 PYSH. | Reduced dose def RT + IO (60Gy+nivolumab) | ||
| PROTEcT / NCT04104945 | Reduced def CRT 60Gy + chemo | Ongoing, not reported | Ongoing, not reported |
| p16+ OPC. | Chemo options: HD cis, LD cis 40 mg/m2, cetux | ||
| AJCC8 T1–3 N1–2. | Omission of IB from ENI volume. |
5FU=5-fluorouracil, AFRT= altered fractionation radiation therapy, AJCC7=American Joint Committee on Cancer 7th Edition, AJCC8=American Joint Committee on Cancer 8th Edition, c=cycle, cetux=cetuximab, chemo=chemotherapy, cis=cisplatin, CRT=chemoradiation therapy, def=definitive, DM=distant metastasis, DMFS=distant-metastasis free survival, FU=follow-up, fxs= fractions, Gy=gray, HD=high-dose, HNC=head and neck cancer, HR=hazard ratio, IMPT=intensity-modulated proton therapy, IMRT=intensity-modulated radiation therapy, IO=immunotherapy, LD=low-dose, LRF= locoregional failure, NS=not significant, OPC= oropharyngeal cancer, OS=overall survival, peg=percutaneous endoscopic gastrostomy, PFS=progression-free survival, PYSH=pack-year smoking history, QOL=quality of life, RT=radiation therapy, SOC=standard of care, wk=week, wkly=weekly, yr=year.