Head & Neck
IMPT vs IMRT at 70 Gy/33 fx with cisplatin: both 12-mo co-primaries (G-tube/weight loss composite, UW-QoL) negative, while LRC and OS stay exploratory.
TORPEdO
ForLocally advanced oropharyngeal SCC, 96% p16+, cisplatin-eligible, no N3
18% vs 7%
adj OR 2.80 (97.5% CI 0.75–10.41), p=0.079, not met; UW-QoL p=0.56
TL;DR18% vs 7% 12-mo G-tube dependence/≥20% weight loss (p=0.079), UW-QoL 78.3 vs 77.1 (p=0.56): IMPT not superior to IMRT, locally advanced oropharyngeal SCC.
Lower OAR doses on IMPT did not become function: 12-mo UW-QoL 78.3 vs 77.1, and ≥20% weight loss ran higher on IMPT (20/110 vs 3/53), persisting at 24 mo in 12 of 95. Dutch NTCP-enriched pts also showed no clear gain (78.2 vs 75.8), undercutting model-based IMPT referral in locally advanced oropharyngeal SCC.
In cisplatin-eligible locally advanced oropharyngeal SCC, mostly p16-positive, planned for 70 Gy in 33 fractions with bilateral neck RT, this does not support IMPT over optimised IMRT for 12-mo swallowing, nutrition or QoL; it does not extend to N3 disease, induction chemo, or post-operative RT.
The RT read: IMPT against IMRT planned to identical 70 Gy/33 fx targets and OAR priorities gave no 12-mo functional gain (UW-QoL 78.3 vs 77.1), while ≥20% weight loss ran 20/110 vs 3/53. Dutch NTCP-enriched pts showed 78.2 vs 75.8, weakening model-based IMPT referral.
11 details 2 trials watching
Phase 3, multicentre, open-label RCT at 20 UK NHS hospitals, 2:1 by minimisation, N=205 (136 IMPT, 69 IMRT). IMPT delivered at two proton centres, IMRT at the local referring centre. Median follow-up 28.3 mo (IQR 26.5 to 39.3).
Newly diagnosed locally advanced oropharyngeal SCC suitable for concurrent CRT including bilateral neck treatment; 197/205 (96%) p16-positive, 99 (48%) T3 or T4. Excluded: N3, upfront neck dissection, induction chemo, prior H&N RT, or a feeding tube needed before treatment.
70 Gy to the therapeutic target and 56 Gy to lower-risk volumes in 33 daily fractions over 6.5 weeks, RBE 1.1 for IMPT, same OAR planning priorities in both arms. IMPT plans checked against 3-mm setup and 3.5% range uncertainty, with daily CBCT and a week-3 repeat planning CT in both arms.
Concurrent cisplatin 100 mg/m² every 3 weeks x2. 138 (69%) of 199 received both cisplatin cycles; 49 (25%) received cisplatin then carboplatin.
Co-primary at 12 mo: gastrostomy-tube dependence or severe (≥20%) weight loss, and UW-QoL physical composite score; either reaching significance counted as success (α=0.025 each). LRC and OS were exploratory.
Neither co-primary met. Composite events were driven by weight loss (20/110 vs 3/53); G-tube dependence was 2% in both arms.
| Endpoint | IMPT | IMRT | Effect |
|---|---|---|---|
| G-tube dependence or ≥20% weight loss, 12 mo (co-primary) | 21/119 (18%) | 4/59 (7%) | adj OR 2.80 (97.5% CI 0.75–10.41), p=0.079 |
| ≥20% weight loss, 12 mo | 20/110 (18%) | 3/53 (6%) | n/a |
| G-tube dependence, 12 mo | 2/119 (2%) | 1/59 (2%) | n/a |
| UW-QoL physical composite, 12 mo (co-primary) | 78.3 | 77.1 | diff 1.3 (97.5% CI –3.7 to 6.2), p=0.56 |
| UW-QoL physical composite, 3 mo | 70.8 | 66.8 | diff 4.0 (99% CI –1.4 to 9.5) |
| UW-QoL physical composite, 24 mo | 81.6 | 79.9 | diff 1.7 (99% CI –3.6 to 7.0) |
| 24-mo freedom from LRR | 94% (99% CI 86–98) | 97% (82–100) | HR 2.6 (99% CI 0.3–20.3), p=0.24 |
| 24-mo OS | 95% (86–98) | 95% (81–99) | HR 1.6 (99% CI 0.3–8.8), p=0.47 |
14 serious AEs in 12 pts, treatment-related in one IMPT vs four IMRT; no treatment-related deaths. Grade 3 weight loss persisted at 24 mo in 12 (13%) of 95 IMPT pts vs none on IMRT.
PARSPORT made parotid-sparing IMRT the photon benchmark. TORPEdO asks whether IMPT adds function over IMRT planned to the same OAR targets; at 12 mo it did not.
Feeding-tube policy was set per centre and prophylactic placement was lower on IMPT (26% vs 38%), confounding tube and weight endpoints. IMPT delivery was more disrupted (replanning 61% vs 30%, cyclotron-driven interruptions), so a mature proton service may perform differently.
The composite leaned against IMPT on weight loss (18% vs 6% at 12 mo), opposite to the dosimetric hypothesis, though p=0.079 does not establish harm. With OAR doses lower on IMPT for most structures and no functional gain, the gap between dosimetric advantage and patient-reported benefit is now the open question.
CONSORT flow
Randomised phase 3, both co-primaries null, source concludes IMRT remains SOC. Open-label, N=205, 2:1 allocation: wide CIs cannot exclude a meaningful difference either way.
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