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.
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?
📚 Sources · 📄 1 paper
Abstract
The longer read
Best-of is the first phase III to randomise transoral surgery against dysphagia-optimized IMRT in early oropharyngeal, supraglottic and hypopharyngeal carcinoma with swallowing as the primary question. It ends roughly where ORATOR, the earlier randomised oropharyngeal comparison, left the field: no functional reason at 12 months to prefer one modality. The size of what was actually excluded matters, though. The adjusted MDADI difference of +3.9 points has a 90% CI of -2.7 to +10.5, and that upper bound sits just past the 10-point difference the trial was powered to detect. This is a non-significant superiority test at a lenient two-sided alpha of 10%, not a demonstration of equivalence, and reading it as 'swallowing is the same' claims more than the design supports.
The larger methodological problem is who is missing. Twelve-month MDADI was evaluable in 86% of the TOS arm against 64% of the DO-IMRT arm, and 7 of 44 pts allocated to DO-IMRT declined treatment. Missingness that is unequal and tied to refusing the allocated modality is unlikely to be random. The source does not say what the refusers received or whether they contributed MDADI data, so the DO-IMRT estimate rests on a smaller and possibly selected group. The investigators frame the refusal rate as evidence of how hard equipoise is to hold. For anyone designing the next surgery-versus-RT trial in this space, that may be the most transferable finding.
The oncologic secondaries lean toward TOS in raw terms: CR at 6 months 98% vs 82%, 2-year EFS 84% vs 72% with HR=1.64 and a 95% CI of 0.77-3.50. A trial sized for a functional endpoint has little power here, and the CR gap may partly reflect intention-to-treat accounting of pts who never started RT. Overall survival was 97% with TOS and 100% with DO-IMRT. The honest reading is that nothing oncologic has been shown, but a radiation oncologist should not wave the EFS signal away either. It is the number most worth watching at longer follow-up.
For the RT reader, the toxicity split is the actionable content. DO-IMRT produced the expected mucosal profile, with more mucositis, xerostomia and dysgeusia, while TOS carried hemorrhage and fistula at low rates. Severe treatment-related AEs were 21% in each arm. Because dose, fractionation and constraint details are not reported in the source, it is not possible to judge whether the DO-IMRT arm reflects contemporary constrictor and parotid sparing. The xerostomia and dysgeusia rates therefore cannot be benchmarked against a reader's own practice. The HPV-positive fraction of 49% also places this population between HPV-driven de-escalation cohorts and classic tobacco-related disease, so neither group is cleanly represented.
What the trial changes is the conversation, not the default. For an early-stage pt suitable for either modality, it supports presenting both as functionally comparable at a year, with the choice resting on the type of toxicity the pt would rather risk, tumour characteristics and preference. It does not settle long-term swallowing beyond 12 months, does not establish oncologic equivalence, and says nothing about locally advanced or N2+ disease.