// Young Wan Kim 1 , Eun Hee Choi 2 , Bo Ra Kim 3 , Woo-Ah Ko 4 , Yeong-Mee Do 4 and Ik Yong Kim 1 1 Department of Surgery, Division of Colorectal Surgery, Yonsei University Wonju College of Medicine, Wonju, Korea 2 Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea 3 Department of Internal Medicine, Division of Gastroenterology, Yonsei University Wonju College of Medicine, Wonju, Korea 4 Health Insurance Review & Assessment Service, Seoul, Korea Correspondence to: Young Wan Kim, email: youngwkim@yonsei.ac.kr Keywords: colonic neoplasms, adjuvant chemotherapy, survival, mortality Abbreviations: NCCN: National Comprehensive Cancer Network; ASA: American Society of Anesthesiologists. Received: December 14, 2016     Accepted: April 19, 2017     Published: May 10, 2017 ABSTRACT Background: To examine the impact of chemotherapy delay on survival in patients with stage II or III colon cancer and the factors associated with the delay (≥8 weeks) of adjuvant chemotherapy. Methods: Patients undergoing curative resection and adjuvant chemotherapy in a national population-based cohort were included. Results: Among 5355 patients, 154 (2.9%) received chemotherapy more than 8 weeks after surgery. Based on a multivariate analysis, the risk factors associated with chemotherapy delay ≥8 weeks were older age [65 to 74 years (hazard ratio [HR]=1.48) and ≥75 years (HR=1.69), p=0.0354], medical aid status in the health security system (HR=1.76, p=0.0345), and emergency surgery (HR=2.43, p=0.0002). Using an 8-week cutoff, the 3-year overall survival rate was 89.62% and 80.98% in the <8 weeks and ≥8 weeks groups, respectively (p=0.008). Independent prognostic factors for inferior overall survival included chemotherapy delay ≥8 weeks (HR=1.49, p=0.0365), older age [65 to 74 years (HR=1.94) and ≥75 years (HR=3.41), p<0.0001], TNM stage III (HR=2.46, p<0.0001), emergency surgery (HR=1.89, p<0.0001), American Society of Anesthesiologists score of 3 or higher (HR=1.50, p<0.0001), and higher transfusion amounts (HR=1.09, p=0.0392). Conclusions: This study shows that delayed commencement of adjuvant chemotherapy, defined as ≥ 8 weeks, is associated with inferior overall survival in colon cancer patients with stage II or III disease. The delay to initiation of adjuvant chemotherapy is influenced by several multidimensional factors, including patient factors (older age), insurance status (medical aid), and treatment-related factors (emergency surgery).

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The impact of delayed commencement of adjuvant chemotherapy (eight or more weeks) on survival in stage II and III colon cancer: a national population-based cohort study.

Development and Evaluation of a Navigation-Based, Multilevel Intervention to Improve the Delivery of Timely, Guideline-Adherent Adjuvant Therapy for Patients With Head and Neck Cancer

Background Locally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates. Methods A systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded. Results Of the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%. Conclusion A validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.

Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review.

Purpose This study aimed to use propensity score matching (PSM) to compare the short- and long-term outcomes of laparoscopic surgery for the treatment of rectal cancer in elderly and middle-aged patients. Methods Data were retrospectively obtained from 588 patients aged ≥60 years when they underwent laparoscopic surgery for rectal cancer in our hospital between January 2009 and December 2016. The patients were divided into an elderly group (≥70 years) or a middle-aged group (60-69 years), and were subsequently matched 1:1 using PSM for sex, body mass index, Charlson comorbidity index (CCI), tumor location, clinical stage, and American Society of Anesthesiologists (ASA) score. A total of 115 patients from each group were matched and included in the study, and their short-term and long-term outcomes were compared. Results The elderly group had greater intraoperative blood loss and a higher surgical conversion rate, although the other outcomes were similar between the two groups (surgical time, pathology results, 30-day incidence of complications, and incidence of major complications). No patients died intraoperatively or within 30 days after surgery. There were no significant differences in the two groups' rates of tumor recurrence, 5-year overall survival, and 5-year disease-free survival. Conclusion Although elderly patients had greater intraoperative blood loss and a higher surgical conversion rate, laparoscopic surgery for rectal cancer provided similar short-term and long-term outcomes among middle-aged and elderly patients.

Short- and long-term outcomes of laparoscopic surgery in elderly patients with rectal cancer.

Precise and accurate control of cell cycle progression is required to maintain cell identity and proliferation. Failing to keep it will lead to genome instability and tumorigenesis. Cell Division Cycle 25 (CDC25) phosphatases are the key to regulating the activity of the master cell cycle controller, cyclin-dependent kinases (CDKs). Dysregulation of CDC25 has been shown to associate with several human malignancies. Here, we reported a series of derivatives of the CDC25 inhibitor, NSC663284, bearing quinones as core scaffolds and morpholin alkylamino side chains. Among these derivatives, the cytotoxic activity of the 6-isomer of 5,8-quinolinedione derivatives (6b, 16b, 17b, and 18b) displayed higher potency against colorectal cancer (CRC) cells. Compound 6b possessed the most antiproliferative activity, with IC50 values of 0.59 μM (DLD1) and 0.44 μM (HCT116). The treatment of compound 6b resulted in a remarkable effect on cell cycle progression, blocking S-phase progression in DLD1 cells straight away while slowing S-phase progression and accumulated cells in the G2/M phase in HCT116 cells. Furthermore, we showed that compound 6b inhibited CDK1 dephosphorylation and H4K20 methylation in cells. The treatment with compound 6b induced DNA damage and triggered apoptosis. Our study identifies compound 6b as a potent CDC25 inhibitor that induces genome instability and kills cancer cells through an apoptotic pathway, deserving further investigation to fulfill its candidacy as an anti-CRC agent. 

6-Regioisomeric 5,8-quinolinediones as potent CDC25 inhibitors against colorectal cancers.

Current practices and challenges of adjuvant chemotherapy in patients with colorectal cancer.

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Current practices and challenges of adjuvant chemotherapy in patients with colorectal cancer.