PURPOSE The International Union Against Cancer highlighted tumor budding as a tumor-related prognostic factor. International assessment criteria for tumor budding were recently defined by the 2016 International Tumor Budding Consensus Conference (ITBCC2016). This study aimed to clarify the prognostic and predictive values of tumor budding in a randomized controlled trial evaluating the superiority of adjuvant chemotherapy with oral tegafur-uracil over surgery alone for stage II colon cancer (SACURA trial; ClinicalTrials.gov identifier: NCT00392899 ). PATIENTS AND METHODS Between 2006 and 2010, we enrolled 991 patients from 123 institutions with stage II colon cancer. Tumor budding was diagnosed by central review on the basis of the criteria adopted in the ITBCC2016. We prospectively recorded all clinical and pathologic data, including the budding grade, and performed prognostic analyses after 5 years of completing the patients’ registration. RESULTS Of 991 tumors, 376, 331, and 284 were classified as BD1, BD2, and BD3, respectively; the 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < .001), and ranged widely in T4 tumors (86.6% to 53.3%). The budding grade significantly correlated with recurrence in the liver, lungs, lymph nodes, and peritoneum ( P < .001 to .01). Multivariable analysis revealed that budding and T stage exerted an independent impact on RFS, and on the basis of the Harrell concordance index, these two factors substantially contributed to the improvement of the Cox model for predicting RFS. Both the BD2 and BD3 groups demonstrated greater improvement in the 5-year recurrence rate in the adjuvant chemotherapy group than the surgery-alone group by approximately 5%, but the difference was statistically nonsignificant. CONCLUSION Tumor budding grade on the basis of the ITBCC2016 criteria should be routinely evaluated in pathologic practice and could improve the benefit of adjuvant chemotherapy for stage II colon cancer.

This phase III study, ACTS-CC, is the first study in which demonstrated the efficacy of S-1, an oral fluoropyrimidine, as adjuvant chemotherapy for stage III colon cancer by confirming its noninferiority to UFT/LV in terms of disease-free survival. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer.

Background: Efficacy of adjuvant chemotherapy in patients with stage II colon cancer is still controversial. The SACURA trial is a randomised-controlled study evaluating the superiority of 1-year adjuvant treatment with oral tegafureuracil (UFT) to surgery alone for stage II colon cancer. Methods: Patients were randomly assigned to the surgery-alone group or UFT group (UFT at 500e600 mg/day for 5 days, followed by 2-day rest, for 1 year). The primary end-point was disease-free survival (DFS). Target sample size was 2000, determined with one-sided alpha of 0.05, power of 0.9 and assumed hazard ratio (HR) 0.729. Results: A total of 1982 patients (997 in the surgery-alone group and 985 in the UFT group) were analysed. Median follow-up was 69.5 months, median age was 66 years and for stage IIA/ IIB/IIC, the distribution was 84%/13%/3%. The 5-year DFS rate was 78.4% in the surgery-alone group and 80.2% in the UFT group. The HR for DFS was 0.91 (95% confidence interval [CI], 0.75e1.10; p Z 0.31); superiority of UFT was not demonstrated. Approximately 9% of patients experienced second cancers, which consist 40.7% of the DFS events. The 5-year relapse-free and overall survival rates of the surgeryalone and UFT group were 84.6% and 87.2% (HR, 0.82; 95% CI, 0.65e1.04) and 94.3% and 94.5% (HR, 0.93; 95% CI, 0.66e1.31), respectively. Subgroup analysis failed to disclose superiority in prognosis of adding UFT to the patients with risk factors for recurrence. Conclusions: Superiority of 1-year adjuvant UFT over surgery alone was not demonstrated in stage II colon cancer. Patients with risk factors for recurrence did not benefit from UFT. Trial registration: ClinicalTrials. Gov. #NCT00392899.

Background:The Adjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC) is a phase III trial designed to validate the non-inferiority of S-1 to UFT/leucovorin (LV) as postoperative adjuvant chemotherapy for stage III colon cancer. We report the results of a planned safety analysis.Methods:Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive UFT/LV (UFT, 300 mg m−2 per day as tegafur; LV, 75 mg per day on days 1–28, every 35 days, 5 courses) or S-1 (80, 100, or 120 mg per day on days 1–28, every 42 days, 4 courses). Treatment status and safety were evaluated.Results:Of 1535 enrolled patients, a total of 1504 (756 allocated to S-1 and 748 to UFT/LV) were analysed. The completion rate of protocol treatment was 77% in the S-1 group and 73% in the UFT/LV group. The overall incidence of adverse events (AEs) were 80% in S-1 and 74% in UFT/LV. Stomatitis, anorexia, hyperpigmentation, and haematological toxicities were common in S-1, whereas increased alanine aminotransferase and aspartate aminotransferase were common in UFT/LV. The incidences of ⩾grade 3 AEs were 16% and 14%, respectively.Conclusion:Although AE profiles differed between the groups, feasibility of the protocol treatment was good. Both S-1 and UFT/LV could be safely used as adjuvant chemotherapy.

We present a case of low-grade angiosarcoma of the breast. A 26-year old woman presented with a lump in the left breast. An elastic hard and ill-defined tumor, 80 x 50 mm in size, was palpated in the upper region of her left breast. Mammography showed a dense lesion with poorly defined border. Ultrasonography showed a hyper-and hypo-echoic lesion with an unclear border, but no definite tumor. Fine needle aspiration cytology showed no evidence of malignancy. Therefore, she was followed with a diagnosis of mastopathy. Six months later, the lump got enlarged. A contrast-enhanced MRI of the breast was performed. It showed a 100 x 60 mm enhancing vascular mass. Most parts of the tumor enhanced remarkably at the early phase, and prolonged enhancement was recognized at the late phase. Core needle biopsy was performed, and a possible angiosarcoma was diagnosed. It is not easy to diagnose the mammary angiosarcoma. MRI may contribute to the accurate diagnosis and play an important role regarding this entity.