Top 5 Papers
#1
Source: Journal of Clinical Oncology | Authors: Iveson TJ, Sobrero AF, Yoshino T, Souglakos J, Saunders MP, Iwasa S, et al. (SCOT investigators, international multicenter) | Published: JCO Vol 44 Issue 15 — May 20, 2026 print issue
Score: 14/20 — Base 8 (JCO) + Phase III RCT (+3) + Practice-defining noninferiority with regimen-specific differentiation (+3) = 14
The international SCOT trial randomized high-risk stage II and stage III colorectal cancer patients to 3 vs 6 months of adjuvant CAPOX or FOLFOX. With a median 113-month follow-up and 1,255 OS events, 5-year OS was 82.4% in both arms (HR 0.96, 95% CI 0.8–1.07), establishing noninferiority of 3 months. The benefit was regimen-dependent: noninferiority was confirmed for 3 vs 6 months of CAPOX but NOT for 3 vs 6 months of FOLFOX. Noninferiority also held in the 1,087-patient rectal cancer subgroup. These final long-term OS data — a decade after the original Lancet Oncology DFS report — cement 3 months of CAPOX as a defensible standard for many high-risk stage II/III patients, while reserving 6 months for FOLFOX-based regimens.
Post angle: SCOT FINAL OS at 113 months: 3-month CAPOX = 6-month CAPOX (5-yr OS 82.4% both arms). But 3-month FOLFOX is NOT noninferior. Pick your backbone wisely. Less chemo, same survival — if you're using CAPOX. #CRC #ColorectalCancer #AdjuvantTherapy #GIOnc
#2
Source: Journal of Clinical Oncology | Authors: Kanemitsu Y, Shimizu Y, Mizusawa J, Inaba Y, Hamaguchi T, Shida D, et al. (JCOG Colorectal Cancer Study Group, Japan) | Published: JCO Vol 44 Issue 15 — May 20, 2026 print issue
Score: 13/20 — Base 8 (JCO) + Phase II/III RCT (+3) + Practice-informing negative OS (+2) = 13
JCOG0603 randomized 300 patients with curatively resected colorectal liver metastases to adjuvant mFOLFOX6 (n=151) or hepatectomy alone (n=149). At a median follow-up of 7.7 years, adjuvant chemotherapy improved disease-free survival (5-yr DFS 49.7% vs 40.5%, HR 0.72, p=0.03) but did NOT translate to an overall survival benefit (5-yr OS 73.4% vs 80.1%; 7-yr OS 69.4% vs 72.4%; HR 1.07, 95% CI 0.73–1.57). The DFS–OS disconnect is striking and clinically uncomfortable: post-recurrence salvage therapy appears sufficient to wash out the early DFS gain. These long-term data challenge reflexive use of adjuvant oxaliplatin chemotherapy after CRLM resection and argue for a more biomarker-driven, ctDNA-informed approach to patient selection.
Post angle: JCOG0603 long-term: adjuvant mFOLFOX6 after CRLM resection improves DFS (HR 0.72) but NOT OS (HR 1.07). 7.7-year follow-up, n=300. The DFS-OS disconnect is real. Time to rethink reflexive adjuvant chemo for resectable CRLM? #CRC #LiverMets #GIOnc #ColorectalCancer
#3
Source: Journal of Clinical Oncology | Authors: Sinicrope FA, Shi Q, Smyrk TC, Goldberg RM, Alberts SR, et al. (Alliance for Clinical Trials in Oncology) | Published: JCO Vol 44 Issue 15 — May 20, 2026 print issue (epub January 2026)
Score: 11/20 — Base 8 (JCO) + Phase III retrospective biomarker analysis (+2) + Biomarker-guided precision (+1) = 11
A tissue-free epigenomic ctDNA assay (Guardant) was applied to 2,260 stage III colon cancer patients enrolled in the Alliance N0147 Phase III adjuvant FOLFOX trial. Post-surgery ctDNA positivity rate was 20.4%. ctDNA-positive vs ctDNA-negative patients had dramatically different outcomes: time-to-recurrence HR 5.96, DFS HR 5.03, and OS HR 4.45 (all p<0.0001). Five-year DFS was 27.7% in ctDNA-positive vs 77.1% in ctDNA-negative patients. Tumor fraction and somatic mutation profile (TP53, KRAS) further stratified risk within the ctDNA-positive subgroup. This is one of the largest prospective-retrospective ctDNA datasets in resected colon cancer and supports tissue-free assays as a clinically deployable tool for adjuvant treatment escalation/de-escalation trials.
Post angle: Alliance N0147 ctDNA: tissue-free epigenomic assay applied to 2,260 stage III colon cancers post-surgery. ctDNA+ rate 20.4%. ctDNA+ vs ctDNA-: HR DFS 5.03, HR OS 4.45. 5-yr DFS 27.7% vs 77.1%. The tissue-free era is here. #ctDNA #LiquidBiopsy #CRC #GIOnc #PrecisionOncology
#4
Source: Annals of Oncology | Authors: Martinelli E, Ciardiello D, Napolitano S, Troiani T, Cardone C, et al. (GOIM — Gruppo Oncologico dell'Italia Meridionale) | Published: Annals of Oncology Vol 37 Issue 5 — May 2026 print issue (online Dec 22, 2025)
Score: 10/20 — Base 7 (Annals of Oncology) + Randomized Phase II (+2) + Biomarker-guided liquid biopsy selection (+1) = 10
CAVE-2 GOIM randomized (2:1) 156 patients with RAS/BRAF wild-type pretreated metastatic colorectal cancer to cetuximab + avelumab (Arm A, n=104) or cetuximab monotherapy (Arm B, n=52) as rechallenge therapy after prior anti-EGFR exposure. The addition of avelumab did NOT increase efficacy over cetuximab alone, closing the door on broad anti-EGFR + checkpoint combinations in this setting. However, comprehensive plasma ctDNA-guided genomic profiling identified a molecularly defined subgroup that derived clear benefit from anti-EGFR rechallenge — validating liquid biopsy as the gatekeeper for rechallenge decisions in the mCRC continuum of care. The trial reinforces that the era of unselected anti-EGFR rechallenge is over.
Post angle: CAVE-2 GOIM: avelumab + cetuximab does NOT beat cetuximab alone for anti-EGFR rechallenge in RAS/BRAF WT mCRC. BUT ctDNA-guided liquid biopsy selection identifies the responders. Anti-EGFR rechallenge is now a biomarker-driven decision, not a reflex. #CRC #LiquidBiopsy #cfDNA #GIOnc
#5
Source: Nature Communications | Authors: Pan L, Calderaro J, Ziol M, Nault J-C, Zucman-Rossi J, et al. (Centre de Recherche des Cordeliers / Inserm / multicenter European consortium) | Published: May 19, 2026
Score: 7/20 — Base 6 (Nature Communications) + Biomarker / precision-medicine framework (+1) = 7
An integrative genomic, transcriptomic, epigenomic and proteomic analysis of 529 HCC samples — validated in an external 807-sample cohort — identifies nine robust molecular subtypes. Three driver-defined subtypes dominate: CTNNB1/APC-mutant (25%), TP53-mutant (21%), and AXIN1/IRF2-mutant (11%). A rare but highly aggressive TP53+CTNNB1 double-mutant subtype (6%) was identified, along with a BAP1-mutant subtype (6%) and two immune-related subtypes (17% and 8%) whose drivers remain undefined. The classifier captures oncogenic-pathway interplay and links subtypes to clinical behavior, providing a reproducible, externally validated framework for precision-medicine trials and biomarker-driven systemic therapy in HCC.
Post angle: HCC multiomics — 529 discovery + 807 validation samples → 9 reproducible molecular subtypes. CTNNB1/APC (25%), TP53 (21%), AXIN1/IRF2 (11%), plus a deadly TP53+CTNNB1 double-mutant (6%). Now we have a real precision-medicine framework for HCC trials. #HCC #LiverCancer #PrecisionMedicine #GIOnc
Additional Papers of Interest
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Liver Transplantation (Feb 2026) — multicenter retrospective cohort of 61 TransMet-eligible patients across 7 centers; weighted-cohort 5-yr restricted mean survival 51.0 mo, identical to the TransMet liver-transplant arm — supports the real-world generalizability of TransMet eligibility criteria for highly selected unresectable CRLM.
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Radiology (Mar 2026) — Prospective multimodal ablation-zone assessment enables onsite reablation of 14% of CRLMs with initially insufficient margins; cumulative local tumor progression at 1/2/3 yr was 7%/12%/12% when margin >5 mm — and zero with margin >10 mm. Practical roadmap for technique-driven CRLM ablation.
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Nature Reviews Gastroenterology & Hepatology (May 13, 2026) — Spagnoli et al. propose an integrated, stage-based framework that treats CSPH (clinically significant portal hypertension) as the central stratifier across cirrhosis decompensation and HCC therapy decisions. Useful clinical re-anchoring for hepatocellular carcinoma management in compensated cirrhosis.
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