onc brain

Multicenter, open-label, randomized phase 3 across 17 hospitals in China (NCT06507371). 1:1 allocation, n=77 per arm, stratified by clinical N stage (cN0 vs cN+). Pathologic response read by blinded independent central review.

Rectal adenocarcinoma with lower edge ≤10 cm from the anal verge, cT3-4 N0/+ M0, MSS/pMMR, age 18-75, ECOG PS 0-1. No positive lateral lymph node permitted, which excludes the population where lateral nodal management is itself contested.

Both arms received 5Gy x 5 days. The experimental arm's modification was target volume only: radiation to the tumor bed without tumor-draining lymph nodes, against conventional short-course fields in the control. Dose and fractionation were held constant, so the field is the only RT variable.

Experimental: tislelizumab 200 mg IV d1 plus oxaliplatin 130 mg/m² IV d1 and capecitabine 1000 mg/m² PO d1-14. Control: the same CAPOX backbone without tislelizumab. Both followed by TME, then adjuvant therapy and follow-up.

Primary: pCR rate in the ITT population. Secondary: MPR rate, TRG, organ preservation rate, EFS, OS and AEs. Only pCR and MPR are reported in the source; the time-to-event secondaries are not.

The presentation states the experimental approach reduced the incidence of severe gastrointestinal adverse events, consistent with a smaller irradiated volume, but no grade-specific rates are reported in source.

The control arm's 28.6% pCR sits above what short-course RT with consolidation chemotherapy has historically produced in pMMR disease, so the comparator is not obviously weak. The experimental result approaches the response depth usually reserved for dMMR/MSI-H disease, where checkpoint blockade already produces high complete-response rates; extending that to MSS is the claim being made.

Nodal recurrence is the outcome that decides whether sparing the tumor-draining nodes is safe, and no recurrence, EFS or OS data appear in the source. A pCR advantage at TME cannot answer it, and the cN+ stratum is where a nodal-omission failure would show first.

The trial's mechanistic premise, that irradiating draining nodes depletes the lymphocyte reservoir a PD-1 agent needs, is testable but not tested here: the field change and the checkpoint inhibitor were introduced together. A three-arm design (node-sparing RT + CAPOX, conventional RT + CAPOX + tislelizumab) would be needed to separate them.

Randomised phase 3, 1° EP met by central review, but confounds nodal-target omission with PD-1 addition and reports no recurrence or survival data.

Randomized phase III, 1:1, N=228 (115 TRT vs 113 control). Stratified by liver metastases and brain metastases. Primary: overall survival; key secondary ORR, PFS, toxicity.

Treatment-naive confirmed SCLC, stage IV or stage III ineligible for curative chemoradiation, ECOG PS 0-1, at least one measurable thoracic lesion. Asymptomatic or stable brain metastases allowed.

Both arms: 4 cycles durvalumab 1500 mg + carboplatin AUC=5 + etoposide 100 mg/m2 IV d1 with d2-3 IV or 200 mg/m2 PO d2-4, Q3W, then durvalumab 1500 mg Q4W until progression, toxicity, or patient choice.

30 Gy in 10 fractions starting day 21-28, so delivered concurrently with the later chemoimmunotherapy cycles rather than as post-chemo consolidation. PCI 25-30 Gy to responders and WBRT 20-30 Gy for brain metastases were optional per local routine in both arms. Target volume, technique, and dose constraints not reported in source.

Primary endpoint not met. PFS was likewise flat (5.1 vs 5.0 mo, HR 1.10, p=0.49), and neither landmark subgroup shifted the estimate below 1.0.

CREST (Slotman, Lancet 2015) established the same 30 Gy/10 fx schedule as consolidative TRT after chemotherapy alone and showed a 2-year OS gain. This trial asks the schedule against a durvalumab-containing backbone and finds nothing, which is the relevant question now that chemo-IO is standard first line.

Toxicity was a key secondary but no AE data appear in the source slides, so a harm-versus-local-benefit tradeoff cannot be assessed. No local control or pattern-of-failure endpoint is shown, and permitted PCI plus WBRT in both arms further blurs the RT contrast between arms.

The timing choice matters for how far the null generalizes: day 21-28 puts RT alongside active chemo-IO, not after it, so this tests concurrent thoracic RT rather than the CREST consolidation paradigm. What it does not settle is whether the null reflects absent local benefit or a benefit cancelled by added toxicity.

Randomised phase III, primary OS endpoint, prespecified stratification; result diverges from CREST-era practice of consolidative TRT. Design internally valid for the null claim.