#1
Source: Journal of Clinical Oncology | Authors: Mo S, Zhou C, Ma M, … Ding C, Peng J — Fudan University Shanghai Cancer Center, multicenter (China) | Published: 2026-07-29
Score: 12/20 — Base 8 (JCO) + Phase III RCT (+3) + biomarker-guided / precision surveillance (+1) = 12. No survival bonus applied: the primary endpoint is a process measure (curative-intent treatment rate), and the authors state OS/DFS benefit is pending mature data.
The FIND trial (NCT05904665) randomized 584 patients with resected nonmetastatic colorectal cancer to ctDNA methylation-guided dynamic surveillance versus standard CT-based monitoring; a positive ctDNA triggered immediate imaging, and two consecutive negatives returned the patient to routine intervals. At a median follow-up of 23.3 months recurrence rates were essentially identical (18.0% vs 18.6%, p=.919) — but what happened at recurrence was not. The ctDNA-guided arm reached curative-intent metastasis-directed therapy in 48.1% versus 23.6% of recurrences (relative risk 2.03, p=.008), and detected recurrence a median 3.9 months earlier (time to clinical recurrence 9.5 vs 13.4 months, p<.001). Among recurrences confined to liver and/or lung, curative resection rates were 42.3% versus 18.2% (p=.002), with more favourable hepatic anatomy: ≤3 lesions in 75.0% vs 28.6% (p=.005), ≤3 cm in 90.0% vs 57.1% (p=.033), and unilobar disease in 80.0% vs 28.6% (p=.002). The honest caveat is that this is a resectability endpoint, not a survival endpoint — whether the extra salvage surgery translates into overall survival remains unproven.
Post angle: The trial doesn't find more recurrences — it finds them while they're still resectable. Frame it as the first randomized phase III to show ctDNA surveillance changes what you can DO at relapse, while being clear that OS is still pending. #GIOnc #CRC #ctDNA #PrecisionMedicine
#2
Source: Journal of Clinical Oncology | Authors: Rocha Lima CMSP, Yothers G, George TJ, Hochster HS, … Kopetz S, Wolmark N, Overman MJ — NRG-GI004/SWOG-S1610, NRG Oncology / SWOG, multicenter (US) | Published: 2026-07-29
Score: 13/20 — Base 8 (JCO) + Phase III RCT (+3) + PFS survival benefit (+2) = 13. Placement note: the ASCO GI topline for this trial appeared in the April 10, 2026 edition, so this is the mature full publication rather than a first look; it is presented second behind FIND, which is genuinely new to the digest, consistent with the standing practice of not re-leading an already-covered trial.
COMMIT (NRG-GI004/SWOG-S1610) is now fully published — the mature peer-reviewed paper behind the ASCO GI topline this digest covered on April 10. This three-arm open-label phase III randomized first-line dMMR/MSI-H mCRC patients 1:1:1 to mFOLFOX6/bevacizumab, atezolizumab monotherapy, or the triplet; the chemotherapy-alone arm was closed after 20 patients once KEYNOTE-177 reported, and the trial continued as atezolizumab versus triplet with a revised target of 100 patients. From November 2017 to March 2025, 102 patients enrolled (FFX/bev n=20, atezolizumab n=41, triplet n=41). At a median follow-up of 46 months, PFS favoured the triplet over atezolizumab monotherapy (hazard ratio 0.439, 95% CI 0.23 to 0.84; p=.0103, below the prespecified critical value of 0.0152). Objective response rate was 86.1% versus 46%, and 12-month disease control was 64.7% versus 32.4%. Grade 3 or higher adverse events of any attribution occurred in 52 patients — 18 in the atezolizumab arm and 34 in the combination arm. The rationale was that VEGF inhibition plus chemotherapy might synergize with PD-L1 blockade in the roughly half of dMMR patients who progress within 12 months on single-agent PD-1 therapy.
Post angle: The mature numbers behind April's ASCO GI topline. The interesting question isn't whether the triplet works — it's which dMMR patients actually need it, given that single-agent immunotherapy already cures a substantial fraction and the toxicity nearly doubled. #GIOnc #CRC #MSI #Immunotherapy
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Gastroenterology — 1,608 whole-slide images across three cohorts (Austin, MCO, DYNAMIC); prognostic in all three (HR 4.73 / 2.84 / 2.10) and, critically, still separating outcomes within patients already labelled NCCN high-risk stage II (HRs 2.96–3.50, all p<.05), independent of T stage, MMR status and nodal adequacy.
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EBioMedicine — in 414 randomized phase 3 participants there was a significant treatment-by-TCD interaction for DFS (p=.009) and OS (p=.001): TCD-high tumours gained from irinotecan-CRT (DFS HR 0.57, OS HR 0.50) while TCD-low tumours trended toward worse OS (HR 1.55, p=.07). Hypothesis-generating per the authors.
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Gut — tumour cells internalise NET-DNA via macropinocytosis, activating cGAS–STING–IRF1 to upregulate both CEACAM1 and PD-L1, with tumour-derived CSF2/CSF3 driving NET formation in a feed-forward loop; DNase I plus PD-L1 antibody synergised against peritoneal metastasis in humanised mice, organoid–T cell cocultures and ex-vivo ascites.
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Gut — galectin-14 binds UGP2 to boost UDP-glycosyl donor production and heparan sulphate synthesis, driving contact-dependent CD8 exhaustion partly via FGFR1; high HS modification tracked with worse survival in patients. That the driver is primate-specific is itself the point — mouse-only pipelines could not have surfaced it.
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New England Journal of Medicine (Editorial) — Shivan Sivakumar on what the pan-RAS inhibitor readouts mean for a disease where RAS sat undruggable for four decades.
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Nature Communications — high-fat diet and faecal microbiota from patients with obesity-associated CRC deplete the GABA-producing commensal Bacteroides ovatus; microbial GABA signals through epithelial GABA-B receptors and TPI1 to restrain nuclear YAP, and oral GABA or wild-type B. ovatus recolonisation reduced tumour burden in mice.
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Journal of Hepatology (Editorial) — Stephen Chan, Bruno Sangro and Lorenza Rimassa on where HCC care most needs to move next; a useful short read for framing trial-design priorities.