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Anal cancer is a relatively rare, mostly HPV-related cancer. The curative treatment consists of concurrent chemoradiation delivered with modern radiotherapy techniques. The prognosis for most patients with early localized disease is very favourable; however patients with locally advanced disease and/or HPV negative tumours are at higher risk of locoregional and distant treatment failure. Tailored approaches are presently being investigated to determine the most suitable regimen in terms of radiotherapy dose prescription, target volume selection, normal tissue avoidance, and combination therapy. Metastatic anal cancer is treated with chemotherapy aiming at prolonged survival. The role of immune therapy in the clinical setting is being investigated. There is little knowledge on the biology of anal cancer, and an urgent need for more clinical and translational research dedicated to this disease. In this article, the evidence-base for the current treatment is briefly reviewed, and perspectives on future research needs are high-lighted., (Copyright © 2021. Published by Elsevier Inc.)

Background: Gastrointestinal (GI) cancer patients may not be considered for therapy with fluoropyrimidines (FPs) because of previous cardiovascular (CV) toxicity or preexisting risk factors; such patients may benefit from raltitrexed-based therapy., Patients and Methods: Patient, tumor, and treatment characteristics, as well as clinical outcomes of all consecutively treated patients with raltitrexed at the Royal Marsden Hospital between October 1998 and July 2011 were examined. GI cancer patients who developed CV toxicity as a result of FPs and those with significant CV risk factors receiving raltitrexed were included in this analysis., Results: A total of 247 patients (155 and 92 with CV FP-related CV toxicities and significant CV risk factors, respectively) treated with raltitrexed alone or in combination were examined after a median follow-up of 47.1 months. CV toxicity profiles of patients receiving capecitabine (n = 110) and 5-fluorouracil (n = 45) were largely similar. Of raltitrexed-treated patients, 13 (5%) experienced CV toxicities and 1 (< 0.1%) died as a result of myocardial infarction. The median progression-free survival (PFS) and overall survival (OS) were 36.0 months (95% confidence interval [CI], 26.5-48.6) and 44.3 months (95% CI, 33.1-56.8), respectively. The 5-year survival for early stage GI malignancies (n = 140) was 62.0% (95% CI, 50.1-71.9). Median PFS and OS were not reached in this group (interquartile range = 38.4 months to NR); median PFS and OS for advanced GI malignancies (n = 107) were 18.8 (95% CI, 11.9-25.7) and 23.7 months (95% CI, 17.0-26.9), respectively., Conclusion: A raltitrexed-based regimen is well-tolerated therapy with comparable efficacy to FPs in patients with GI malignancies with significant CV toxicities or risk factors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although progress has been made in the molecular stratification of esophagogastric adenocarcinoma, the outlook for advanced disease remains poor. The present evaluation of over 500 patients treated at a single European high-volume tertiary center during a 6-year period gives important information on current and developing "real-world" treatment patterns and outcomes., Results: The overall survival for the whole cohort was 11.5 months, with a range of treatments used in first-, second-, and third-line settings. Treatment with sequential lines of therapy was associated with better outcomes, although only 39% and 14% of patients subsequently received treatment in the second- and third-line setting, respectively. Treatment within a therapeutic clinical trial was associated with significantly improved survival., Conclusion: At present, a substantial proportion of patients with advanced esophagogastric adenocarcinoma will not proceed beyond first-line therapy, and for this group refinement of initial systemic therapies are required to improve outcomes. Although a number of established first- and second-line treatment options are now available, the therapeutic landscape of the disease continues to change, most notably in the application of immunotherapy and increasing interest in establishing evidence-based interventions in the third-line setting and beyond. A small but growing proportion of patients will benefit from sequential treatment approaches incorporating multiple lines of therapy, and improved selection of such patients will be a key challenge for clinicians moving forwards. Data such as these provide an overview of current treatment patterns and outcomes which can be used to inform planning of future research effectively within existing treatment frameworks., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group., Patients and Methods: All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan-Meier method and comparisons made using Cox regression., Results: Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging., Conclusion: In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Childhood poverty is unacceptably common in the US and threatens the health, development, and lifelong well-being of millions of children. Health care providers should be prepared through medical curricula to directly address the health harms of poverty. In this article, authors from The Child Poverty Education Subcommittee (CPES) of the Academic Pediatric Association Task Force on Child Poverty describe the development of the first such child poverty curriculum for teachers and learners across the medical education continuum., Methods: Educators, physicians, trainees, and public health professionals from 25 institutions across the United States and Canada were convened over a 2-year period and addressed 3 goals: 1) define the core competencies of child poverty education, 2) delineate the scope and aims of a child poverty curriculum, and 3) create a child poverty curriculum ready to implement in undergraduate and graduate medical education settings., Results: The CPES identified 4 core domains for the curriculum including the epidemiology of child poverty, poverty-related social determinants of health, pathophysiology of the health effects of poverty, and leadership and action to reduce and prevent poverty's health effects. Workgroups, focused on each domain, developed learning goals and objectives, built interactive learning modules to meet them, and created evaluation and faculty development materials to supplement the core curriculum. An editorial team with representatives from each workgroup coordinated activities and are preparing the final curriculum for national implementation., Conclusions: This comprehensive, standardized child poverty curriculum developed by an international group of educators in pediatrics and experts in the health effects of poverty should prepare medical trainees to address child poverty and improve the health of poor children., (Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDA) has a very poor prognosis. Treatment with FOLFIRINOX has been shown to improve outcomes, but can be associated with significant toxicity., Materials and Methods: A retrospective review was performed of all patients with locally advanced or metastatic PDA treated with FOLFIRINOX at the Royal Marsden between November 2010 and November 2013. Efficacy, tolerability, and potential prognostic factors were evaluated., Results: Twenty-seven patients with metastatic PDA and 22 patients with locally advanced PDA were treated with FOLFIRINOX. Patients received a median of 9 cycles (range, 1-26) of FOLFIRINOX. The overall response rate was 41% (20 patients), and a further 17 patients (35%) had stable disease. Thirty-five patients (71%) received FOLFIRINOX in the first-line setting, with a median progression-free survival and overall survival, respectively, of 12.9 months and 18.4 months for patients with locally advanced disease; and 8.4 months and 12.2 months for patients with metastatic disease. The most frequently occurring Grade 3/4 toxicities were neutropenia (29%), fatigue (18%), febrile neutropenia (14%), thromboembolism (12%), and thrombocytopenia (10%). In a univariate analysis, reduction in CA 19-9 of >50% (P < .001), normalization of CA19-9 (P < .001), surgery after FOLFIRINOX (P = .004), and use of prophylactic pegfilgrastim (P = .005) were prognostic for overall survival., Conclusion: The efficacy and tolerability of FOLFIRINOX for PDA at our institution is similar to that reported in clinical trials. Careful selection of patients and monitoring of response (according to CA19-9) and toxicities can help maximize advantage in this patient population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: The impact of adding bevacizumab to perioperative chemotherapy in patients with colorectal cancer (CRC) undergoing liver resection is yet to be defined. A retrospective review of our patient records showed that the addition of bevacizumab did not increase morbidity or mortality related to liver resection. Pathologic complete response (CR) is associated with prolonged survival., Background: Patients with colorectal cancer (CRC) and liver metastases benefit from perioperative chemotherapy and liver resection. The potential benefit of adding bevacizumab is yet to be defined. The impact of bevacizumab on liver resection complications has been explored in a small number of retrospective studies., Methods: The records of patients with CRC and liver metastases who underwent liver resection and had received perioperative chemotherapy were reviewed. Complications were reported separately for 2 groups (chemotherapy alone vs chemotherapy and bevacizumab). Survival outcomes (progression-free survival [PFS] and overall survival [OS]) for responders and nonresponders were estimated using the Kaplan-Meier method., Results: Fifty-two patients received chemotherapy alone and 42 patients received chemotherapy and bevacizumab. The median time from the end of systemic treatment to liver resection was 59 days (33-181 days) for the chemotherapy group and 62 days (44-127 days) for the chemotherapy and bevacizumab group. Postoperative complications developed in 54% of the chemotherapy group and in 48% of the chemotherapy and bevacizumab group. Severe complications (grade III-V) occurred in only 13% and 12%, respectively (P = .822). Pathologic complete response (CR) was seen in 11/94 patients. Poor performance status (PS) before starting chemotherapy was associated with higher rates of complications (P = .002), and severe complications led to prolonged hospital admission (P = .001). Patients with pathologic CR had longer OS (P = .0275), but there was no difference in OS between responders and nonresponders (P = .778)., Conclusion: The addition of bevacizumab to chemotherapy does not increase liver resection complication rates. Pathologic CR is associated with prolonged survival., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Preoperative chemotherapy has demonstrated a survival benefit for patients with potentially resectable esophageal cancer; however, currently it is not possible to predict the benefit of this treatment for an individual patient. This prospective study was designed to correlate gene expression profiles with clinical outcome in this setting., Patients and Methods: Eligible patients were deemed to have resectable disease after staging by computed tomography, endoscopic ultrasound, and laparoscopy as indicated and following discussion at the multidisciplinary team meeting. All patients received neoadjuvant platinum and fluoropyrimidine-based chemotherapy; and clinical data were entered prospectively onto a study-specific database. Total RNA was isolated from pretreatment tumor biopsies obtained at baseline endoscopy and analyzed using a cDNA array consisting of 22,000 cDNA clones., Results: Of the patients with adequate follow-up accrued between 2002 and 2005, 35 satisfied the quality control measures for the microarray profiling. Median follow-up was 938 days. Supervised hierarchical clustering of normalized data revealed 165 significantly differentially expressed genes based on overall survival (OS; P < .01) with 2 distinct clusters: a poor outcome group: N = 17 (1 year OS 46.2%) and a good outcome group: N = 18 (1 year OS 100%). Genes identified included those previously associated with esophageal cancer and, interestingly, a group of genes encoding proteins involved in the regulation of the TOLL receptor-signaling pathway., Conclusion: This initial study has highlighted groups of tumors with distinct gene expression profiles based on survival and warrants further validation in a larger cohort. This approach may further our understanding of individual tumor biology and thus facilitate the development of tailored treatment.