GI Lower
Dose escalation in LARC, from an accrual window (2013-2015) that predates TNT, RAPIDO and PRODIGE-23.
SIB-CRT vs Standard CRT for LARC (NCT02195141) NCT02195141
ForStage II/III rectal adenocarcinoma, neoadjuvant chemoradiation candidates
15.2% vs 18.4%
P=0.695, primary endpoint not met
TL;DR9yr OS 74.3% vs 48.9% (HR 0.43, P=0.008) with SIB dose escalation to 56Gy PGTV, despite identical pCR.
The primary endpoint (pCR) was flat, so the survival separation cannot be read as a downstaging effect, and LC (87.1% vs 70.1%) and MFS (70.8% vs 47.2%) moved together. That pattern, plus benefit only in chemo-naive pts, frames SIB to 56Gy as a boost worth testing where periop chemo is not deliverable, not a general escalation.
The escalation is modest and deliverable, 56 Gy SIB to PGTV inside a 50 Gy/25 fx pelvis, with acute G3 toxicity no worse (14.5% vs 19.6%). LC 87.1% vs 70.1% (HR 0.40) is the on-target signal; the equally large MFS gain (HR 0.48) is not, and that mismatch is the reason to treat this as hypothesis-generating rather than a reason to boost routinely.
The interaction is the med onc read: SIB benefit was confined to pts who got no perioperative chemotherapy (9yr DFS 70.8%, HR 0.343, P=.014), with none added in those who did. That frames escalated RT as a substitute where systemic therapy cannot be delivered, not an addition on top of a standard chemo backbone.
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Prospective randomized phase 2 trial, 1:1, N=106 (55 SIB-CRT, 51 CRT), accrued August 2013 to February 2015. Median follow-up 116.6 months.
Stage II/III rectal adenocarcinoma planned for neoadjuvant chemoradiotherapy. Radical surgery was planned 6 to 8 weeks after chemoradiation.
Control arm: 50 Gy/25 fx to the pelvis. Experimental arm: same 50 Gy/25 fx pelvis with simultaneous integrated boost to 56 Gy to PGTV and 60 Gy to lateral metastatic nodes when present.
Primary: pCR rate. Secondary: DFS, OS, MFS, local control, cancer-specific survival and toxicity.
Acute grade 3 toxicity 14.5% (SIB-CRT) vs 19.6% (CRT), primarily radiation dermatitis. No late toxicity reported in source.
The primary endpoint was null while every time-to-event secondary was positive, an internally inconsistent pattern for a boost acting through the pelvis. Accrual closed in 2015, before TNT became standard, and the subgroup that drove the benefit was defined by chemotherapy receipt, which was not randomized.
| Endpoint | SIB-CRT | CRT | Effect size |
|---|---|---|---|
| OS | 74.3% | 48.9% | HR 0.43, P=0.008 |
| DFS | 70.8% | 47.4% | HR 0.46, P=0.013 |
| MFS | 70.8% | 47.2% | HR 0.48, P=0.017 |
| LC | 87.1% | 70.1% | HR 0.40, P=0.038 |
| CSS | 77.4% | 57.2% | P=0.027 |
Randomized phase 2, N=106, survival endpoints secondary; benefit driven by a chemo-naive subgroup and unexplained by the null pCR primary.
In stage II/III LARC pts who are not candidates for perioperative chemotherapy, this supports testing an SIB boost to the primary as a long-term-control strategy; it does not extend to pts receiving standard periop chemo, where no added benefit was seen.
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