Head & Neck
Randomised TOS vs DO-IMRT in early oropharynx/supraglottis/hypopharynx: swallowing function comparable, toxicity profiles differ.
EORTC 1420 Best-of NCT02984410
ForT1-T2 N0-1 OPSCC/SGSCC or T1 N0 HPSCC, fit for TOS or RT
+3.9 points
90%CI -2.7 to +10.5; p=0.326, not met
TL;DR12-mo MDADI adjusted difference +3.9 points (90%CI -2.7 to +10.5; p=0.326), TOS vs DO-IMRT; no swallowing difference, more mucosal toxicity with DO-IMRT.
The RT cost is mucosal, not swallowing: DO-IMRT carried mucositis 39% vs 10%, dry mouth 49% vs 14% and dysgeusia 46% vs 17%, against TOS hemorrhage 5% and fistula 2%, with G≥3 TRAEs 21% each. DO-IMRT dose, fractionation and target volume are not reported in source, so dysphagia-sparing constraints cannot be benchmarked.
In T1/T2 N0-1 oropharyngeal or supraglottic, or T1 N0 hypopharyngeal carcinoma fit for either modality, this supports choosing TOS or DO-IMRT on toxicity profile and preference rather than expected 12-month swallowing; it does not address T3-T4 or N2+ disease. The longer read
DO-IMRT's cost is mucosal: mucositis 39% vs 10%, dry mouth 49% vs 14%, dysgeusia 46% vs 17%, with G≥3 TRAEs 21% each. Dose and constraints are not reported in source, and 7/44 declined RT, so the arm's swallowing estimate rests on 64% evaluable.
All TOS pts were operated, with hemorrhage 5% and fistula 2%. Numerically higher 6-mo CR (98% vs 82%) and 2y EFS (84% vs 72%, HR=1.64, 95%CI 0.77-3.50) are not significant, so oncologic superiority of TOS is not established.
10 details 1 trial watching
Phase III, randomised 1:1, 25 centres in 9 countries, accrual 2018-2024. Powered (80%, alpha 10% two-sided) for a 10-point MDADI difference; 54 evaluable needed, 84 planned for 35% attrition, 86 randomised.
T1/T2 N0-1 OPSCC/SGSCC or T1 N0 HPSCC suitable for either TOS or DO-IMRT. Median age 64, 86% OPSCC, 49% HPV-positive; arms balanced.
Dysphagia-optimized IMRT (DO-IMRT). Dose, fractionation and target volumes not reported in source. 7/44 (16%) allocated to DO-IMRT declined treatment.
Primary: MDADI total score at 12 months (ANCOVA). Secondary: MDADI at 4.5, 6 and 9 months, PSS-HN, oncological outcomes, toxicity.
12-mo MDADI adjusted difference +3.9 points (90%CI -2.7 to +10.5; p=0.326), consistent across sensitivity analyses. Arm-level secondary outcomes are in the table.
| Endpoint | TOS | DO-IMRT | Effect |
|---|---|---|---|
| Unrestricted diet (PSS-HN) at 12 mo | 87% | 83% | n/a |
| Feeding tube at 12 mo | None | None | n/a |
| Complete response at 6 mo | 98% | 82% | n/a |
| 2y EFS | 84% | 72% | HR=1.64 (95%CI 0.77-3.50), p=0.200 |
| OS | 97% | 100% | n/a |
| G≥3 treatment-related AEs | 21% | 21% | n/a |
| AE | TOS | DO-IMRT |
|---|---|---|
| Mucositis | 10% | 39% |
| Dry mouth | 14% | 49% |
| Dysgeusia | 17% | 46% |
| Hemorrhage | 5% | n/a |
| Fistula | 2% | n/a |
G≥3 treatment-related AEs 21% in each arm. TOS: hemorrhage 5%, fistula 2%. DO-IMRT vs TOS: mucositis 39% vs 10%, dry mouth 49% vs 14%, dysgeusia 46% vs 17%.
ORATOR randomised TORS against RT in OPSCC and also found comparable function with different toxicity profiles. Best-of extends the comparison to supraglottic and hypopharyngeal primaries and to a phase III frame, but still with a small N.
The EFS HR CI (0.77-3.50) is wide and follow-up reaches only 2 years. A 49% HPV-positive mix limits transfer to HPV-positive de-escalation. RT technique is unreported, so the DO-IMRT arm cannot be audited.
With swallowing function apparently similar, toxicity profile and patient preference become the deciding factors. The numerically lower CR and EFS in the DO-IMRT arm (98% vs 82%; 84% vs 72%) are not significant and may partly reflect pts who declined RT, so they need longer follow-up before they carry weight.
CONSORT flow
Phase III, but differential 12-mo MDADI evaluability (86% vs 64%) and 16% refusal of DO-IMRT; CI does not exclude the 10-point margin, so equivalence is not shown.
- Does the EFS gap persist with longer follow-up?
- Swallowing function beyond 12 months n=150 · primary completion 2031-06 · MDADI at 2y, transoral resection vs IMRT, T1-T2 OPSCC
- Does HPV status modify the TOS vs RT comparison?