Table 4.
Radiation Deintensification Trials: Elective Radiation Dose or Volume Reduction
| Study | Treatment Arms | Outcomes | Toxicities |
|---|---|---|---|
| RAVD 76 | IND cis/pacl/cetux x2c ± everolimus (n=89) → | HPV+ OPC (n=59): | Acute pegs (p=0.040): |
| (Phase I/II) | GR ≥50% shrinkage (n=37) → | 2yr PFS (p=0.10): 93.1% GR vs. 74.0% NR | 50.0% GR vs. 73.5% NR |
| AJCC7 IVA-IVB HNSCC. | No ENI. 75Gy to gross disease (BID every other wk). | 2yr OS: 92.1% GR vs. 95.2% NR | Peg dependence at 6 months (p = 0.005): |
| Oral cavity, OPC, Larynx, | NR <50% shrinkage (n=52) → | 5.7% GR vs. 32.6% NR | |
| Hypopharynx, Unknown Primary | 45Gy ENI (to next LN station) + 75Gy to gross disease. | >90% of LRFs developed in the highest risk/dose RT volume. | |
| cancers all included. | Mean FU = 24 months | ||
| Montreal 77 | IMRT + concurrent carbo/5FU (n=29). | 2 yr PFS : not reported | Acute grade 3 mucositis: 52% |
| (Phase II) | 2 yr LRC: 100% | ||
| p16+ OPC | SOC def CRT 70Gy to HR volume, 59.4Gy IR volume | 2 yr OS: 100% | All patient-reported QOL outcomes (except dry mouth) |
| AJCC7 III/IV | Reduced ENI dose: 43.2 Gy/24 fxs | returned to baseline within 10 months of treatment end. | |
| T1-4N0–2b and N3 with primary not extending beyond midline and ipsilateral nodes only; smokers permitted. | Reduced ENI volume: no contralateral RP or level IV LNs. | ||
| Median FU = 44 months | |||
| EVADER / NCT03822897 | SOC def RT 70Gy | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | SOC def CRT 70Gy + HD cis x3c | ||
| HPV+ OPC. | |||
| AJCC8 T1–3 N0–1. | ENI volumes reduced. | ||
| SAVER / NCT04609280 | ENI volumes reduced. Omission of contralateral LNs. | Ongoing, not reported | Ongoing, not reported |
| (Phase II) | Treat only ipsilateral level II and III LN levels. | ||
| p16+ OPC. | If PORT: 54 Gy SOC | ||
| AJCC8 T1–4 and N0, N1, or N3. | If def RT: 69.96Gy SOC |
5FU=5-fluorouracil, AFRT= altered fractionation radiation therapy, AJCC7=American Joint Committee on Cancer 7th Edition, AJCC8=American Joint Committee on Cancer 8th Edition, BID=bidaily, c=cycle, carbo=carboplatin, cetux=cetuximab, cis=cisplatin, CRT=chemoradiation therapy, def=definitive, ENI=elective nodal irradiation, FU=follow-up, fxs= fractions, GR=good response, Gy=gray, HD=high-dose, HNSCC=head and neck squamous cell carcinoma, IMRT=intensity-modulated radiation therapy, IND=induction, LN=lymph node, LRF= locoregional failure, NR=no response, OPC= oropharyngeal cancer, OS=overall survival, pacl=paclitaxel, PFS=progression-free survival, PORT=postoperative radiation therapy, QOL=quality of life, RP=retropharyngeal, RT=radiation therapy, SOC=standard of care, yr=year.