Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302)

BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H₀: 55% and H₁= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.     

关于医学教育专业人才培养方案修订的几点思考

随着“健康中国”战略的实施，需要建立与之相匹配的“新医科”人才培养体系，“基于医疗卫生系统的需求，以职业胜任力为导向”的教育教学改革势在必行。因此修订人才培养方案时要以胜任力为目标驱动重新梳理培养目标和毕业要求；采用“课程矩阵”设计法，反向设计、正向施工的原则优化课程体系；根据课程目标凝炼课程内容、精炼核心课程；充分利用网络开放课程资源，选修课分模块化设置；通过多种形式将创新创业教育贯穿人才培养全过程。     

Referral patterns and outcomes of a highly specialised pelvic exenteration multidisciplinary team meeting: A retrospective cohort study

IntroductionThe purpose of this study was to review recommendations made from a specialist pelvic exenteration (PE) multidisciplinary team (MDT) and to provide insights as to the impact of the MDT on patient selection and clinical decision making.Materials & methodsA retrospective review was conducted at Royal Prince Alfred Hospital's PE MDT between June 2014 and December 2015. Data was collected from the recorded minutes of MDT meetings. Referral information and clinical data was extracted from individual patient files. Additional data including operative dates and surgical resection margins were collected from electronic medical records.ResultsOf the 183 patients considered for PE during the MDT meeting, 104 (57%) were recommended for surgery. Factors that influenced the recommendation in favour of surgery were referral by a surgeon (P = 0.004), referral from a rural location (P = 0.05) and having locally advanced primary cancer (P < 0.001). Patients who were seen by the unit's surgeon prior to the MDT did not impact on the MDT recommendation nor the decision for or against surgery (P = 0.771). The most common reason for recommendation against PE was unresectable distant metastatic disease (43%).ConclusionsThe PE MDT meeting is a critical step in the patient care pathway and facilitates critical decision making. Anatomically-based contraindications to surgery (i.e. involvement of adjacent organs, bone and neurovascular structures) do not appear to influence MDT decision making regarding resectability.