PURPOSE Adjuvant chemotherapy after hepatectomy is controversial in liver-only metastatic colorectal cancer (CRC). We conducted a randomized controlled trial to examine if adjuvant modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) is superior to hepatectomy alone for liver-only metastasis from CRC. PATIENTS AND METHODS In this phase II or III trial (JCOG0603), patients age 20-75 years with confirmed CRC and an unlimited number of liver metastatic lesions were randomly assigned to hepatectomy alone or 12 courses of adjuvant mFOLFOX6 after hepatectomy. The primary end point of phase III was disease-free survival (DFS) in intention-to-treat analysis. RESULTS Between March 2007 and January 2019, 300 patients were randomly assigned to hepatectomy alone (149 patients) or hepatectomy followed by chemotherapy (151 patients). At the third interim analysis of phase III with median follow-up of 53.6 months, the trial was terminated early according to the protocol because DFS was significantly longer in patients treated with hepatectomy followed by chemotherapy. With median follow-up of 59.2 months, the updated 5-year DFS was 38.7% (95% CI, 30.4 to 46.8) for hepatectomy alone compared with 49.8% (95% CI, 41.0 to 58.0) for chemotherapy (hazard ratio, 0.67; 95% CI, 0.50 to 0.92; one-sided P = .006). However, the updated 5-year overall survival (OS) was 83.1% (95% CI, 74.9 to 88.9) with hepatectomy alone and 71.2% (95% CI, 61.7 to 78.8) with hepatectomy followed by chemotherapy. In the chemotherapy arm, the most common grade 3 or higher severe adverse event was neutropenia (50% of patients), followed by sensory neuropathy (10%) and allergic reaction (4%). One patient died of unknown cause after three courses of mFOLFOX6 administration. CONCLUSION DFS did not correlate with OS for liver-only metastatic CRC. Adjuvant chemotherapy with mFOLFOX6 improves DFS among patients treated with hepatectomy for CRC liver metastasis. It remains unclear whether chemotherapy improves OS.

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INTRODUCTION:The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set.METHODS:The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC.RESULTS:In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [−] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034–0.356], P < 0.001).DISCUSSION:Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.

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Background: It currently remains unclear whether the anatomical pattern of lymph node (LN) spread differs between young (≤ 45 years, Y) and elderly (≥ 80 years, E) patients with stage III colon cancer (CC).Materials and Methods: Two groups of patients (Y and E) with stage III CC who underwent extensive (D3) lymphadenectomy at Japanese centers were retrospectively analyzed. The primary endpoint was the proportion of positive central LN. The planned sample size was at least 210 (Y) based on an expected value of 9.1% and threshold of 5%, and 230 (E) based on an expected value of 2% and threshold of 5%.Results: Two-hundred and ten Y patients and 348 E patients were identified and compared. The total number of LN harvested and the total number of invaded LN were significantly higher in group Y (median of 31.5 (3-151) vs. 21 (3-116), P < 0.001 and median of 3 (1–21) vs. 2 (1–25), P < 0.001, respectively). The proportion of positive central LN was higher in group Y than the prespecified threshold of 5% (9.52% (95% CI: 6.24–14.2%), p = 0.007); however it was similar to the threshold in group E (4.59% (95% CI:2.84–7.31%), p = 0.351). In multivariate models, central LN invasion was identified as a poor prognostic factor in group Y (HR3.66 (95% CI (1.29–8.87)), but not in group E (HR2.02 (0.95–4.27)).Conclusions: Young stage III colon cancer patients have a higher risk of central LN invasion, suggesting a more aggressive disease biology. The presence of central LN invasion is associated with a worse outcome.