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The use of genomic testing is rapidly emerging as an important clinical tool both for cancer diagnosis and for guiding treatment decisions in a wide range of malignancies, including gastrointestinal (GI) cancers such as colorectal cancer (CRC). Advances in technologies such as polymerase chain reaction and next‐generation sequencing methods have made it possible to noninvasively screen for CRC through, for example, the use of blood‐ or stool‐based testing, with high specificity. Tests are also available that can provide prognostic information beyond traditional clinicopathologic factors such as tumor size, grade, and nodal status, which can enable clinicians to more accurately risk stratify patients for recurrence. Lastly, in the setting of resected CRC, tests are now available that can detect circulating tumor DNA as a means for noninvasive minimal/molecular residual disease monitoring, thereby potentially guiding the use of adjuvant chemotherapy and/or escalating or de‐escalating therapy. The Gastrointestinal Cancer Therapy Expert Group (GICTEG) recently convened a virtual meeting to discuss current issues related to genomic testing in GI cancer, with the goal of providing guidance on the use of these tests for the practicing community oncologist, for whom GI cancer may be only one of many tumor types encountered. This article provides a summary of the discussion and highlights the key opinions of the GICTEG on this topic. Implications for Practice: The Gastrointestinal Cancer Therapy Expert Group seeks to provide practical guidance and opinion on the treatment of gastrointestinal malignancies, including colorectal cancer (CRC), for the practicing community oncologist in situations for which guidelines from established bodies, such as the National Comprehensive Cancer Network and the American Society of Clinical Oncology, may be less clear. In the present report, clinical guidance on the use of molecular assays for a range of clinical indications in CRC is presented, including the use of circulating tumor DNA to detect minimal/molecular residual disease in patients with successfully resected early‐stage CRC. The Gastrointestinal Cancer Therapy Expert Group (GICTEG) recently convened a virtual meeting to discuss current issues related to genomic testing in gastrointestinal cancer, with the goal of providing guidance on the use of these tests for the practicing community oncologist. This article provides a summary of the discussion and highlights the key opinions of the GICTEG on this topic. [ABSTRACT FROM AUTHOR]

Background: Hand‐foot skin reaction (HFSR) is the most common regorafenib‐induced adverse event and is in need of effective prevention and palliation. Materials and Methods: The Regorafenib Dose Optimization Study (ReDOS), a four‐arm, previously published trial with a 1:1:1:1 randomization scheme, was analyzed in a manner in keeping with the original protocol to assess whether clobetasol 0.05% cream (a corticosteroid) applied to the palms and soles twice per day for 8 weeks was more effective when prescribed preemptively (before the development of HFSR) versus reactively (after the development of HFSR). Patients were assessed during the first two cycles of regorafenib. Results: Sixty‐one patients received preemptive clobetasol, and 55 received reactive clobetasol. Groups were balanced on demographics. Over the first two cycles, no evidence of HFSR occurred in 30% with preemptive clobetasol versus 13% with reactive clobetasol (p =.03). During the first cycle, 54% and 45% of patients had no HFSR with preemptive and reactive clobetasol, respectively (p =.35). During the second cycle, 33% and 15% had no HFSR with preemptive and reactive clobetasol, respectively (p =.02). During the second cycle, rates of grade 1, 2, and 3 HFSR were 30%, 8%, and 3%, respectively, with preemptive clobetasol and 43%, 18%, and 7%, respectively, with reactive clobetasol (p =.12). Patient‐reported outcomes showed HFSR compromised nearly all activities of daily living with worse quality of life in patients who received reactive versus preemptive clobetasol. No clobetasol‐induced adverse events were reported. Conclusion: Preemptive clobetasol might lessen regorafenib‐induced hand‐foot reactions compared with reactive therapy. Further confirmatory studies are needed in a larger patient cohort. Implications for Practice: Regorafenib causes hand‐foot skin reactions. Preemptive clobetasol, a high‐potency topical corticosteroid, appears to lessen the severity of this adverse event. Although further study is needed, the favorable adverse event profile of this intervention might prompt clinicians to discuss this option with their patients. Hand‐foot skin reaction is a common regorafenib‐induced adverse event. This article reports on the use of topical clobetasol and its role when administered preventively, before a skin reaction occurs. [ABSTRACT FROM AUTHOR]

The outbreak of coronavirus disease 2019 (COVID‐19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID‐19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), is characterized by rapid human‐to‐human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS‐CoV‐2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID‐19 infection pandemic will be addressed, with suggestions of some practical approaches. Implications for Practice: The main management strategies for treating cancer patients during the COVID‐19 epidemic include clear communication and education about hand hygiene, infection control measures, high‐risk exposure, and the signs and symptoms of COVID‐19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case‐by‐case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS‐CoV‐2 virology and epidemiology. Cancer patients have an increased risk of contracting COVID‐19. This article addresses the challenges associated with managing cancer patients during the COVID‐19 infection pandemic and suggests some practical approaches. [ABSTRACT FROM AUTHOR]

Background: The incidence of colorectal cancer (CRC), particularly left‐sided tumors (LT), in adolescents and young adults (AYA) is rising. Epigenetic events appear to play an important role in tumorigenesis and cancer progression, especially in younger patients. We compared molecular features of LT to right‐sided tumors (RT) in AYA. Materials and Methods: A total of 246 LT and 56 RT were identified in a cohort of 612 AYA with primary CRC. Tumors were examined by next‐generation sequencing (NGS), protein expression, and gene amplification. Tumor mutational burden (TMB) and microsatellite instability (MSI) were determined based on NGS data. Results: RT showed higher mutation rates compared with LT in several genes including BRAF (10.3% vs. 2.8%), KRAS (64.1% vs. 45.5%), PIK3CA (27% vs. 11.2%), and RNF43 (24.2% vs. 2.9%). Notably, additional mutations in distinct genes involved in histone modification and chromatin remodeling, as well as genes associated with DNA repair and cancer‐predisposing syndromes, were characteristic of RT; most frequently KMT2D (27.8% vs. 3.4%), ARID1A (53.3% vs. 21.4%), MSH6 (11.1% vs. 2.3%), MLH1 (10.5% vs. 2.3%), MSH2 (10.5% vs. 1.2%), POLE (5.9% vs. 0.6%), PTEN (10.8% vs. 2.3%), and BRCA1 (5.4% vs. 0.6%). MSI was seen in 20.8% of RT versus 4.8% of LT. RT had a higher frequency of TMB‐high regardless of MSI status. Conclusion: Molecular profiling of AYA CRC revealed different molecular characteristics in RT versus LT. Epigenetic mechanisms and alteration in DNA repair genes warrant further investigation and may be a promising treatment target for CRC in AYA. Implications for Practice: Colorectal cancer (CRC) in adolescents and young adults (AYA) comprises a distinct entity with different clinicopathologic features and prognosis compared with older patients. Molecular profiling of right‐ and left‐sided tumors in AYA is needed to gain novel insight into CRC biology and to tailor targeted treatment in this age group. This study found that right‐ and left‐sided CRC show distinct molecular features in AYA, overall and in subgroups based on microsatellite instability status. Alterations in DNA double‐strand break repair and homologous recombination repair, as well as epigenetic mechanisms, appear to play a critical role. The present molecular profiling data may support the development of personalized treatment strategies in the AYA population. This article explores the molecular makeup of left‐sided and right‐sided colorectal cancers in populations aged 40 years. [ABSTRACT FROM AUTHOR]

Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Background: Deficiencies in the DNA mismatch repair system cause errors during DNA replication, which in turn give rise to microsatellite instability (MSI). The impact of MSI on survival in metastatic colorectal cancer (mCRC) is unclear. This cohort study aims to investigate the prognostic and predictive value of MSI in mCRC prior to the immune therapy era. Materials and Methods: A total of 75 MSI‐high (MSI‐H) mCRC patients (pts) and 75 matched (age, gender, disease sidedness, metachronous/synchronous) microsatellite‐stable (MSS) mCRC pts were identified from 1,268 mCRC pts who had MSI/mismatch repair test results at Mayo Clinic Rochester between January 1992 and July 2016. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized the Kaplan‐Meier method, log‐rank test, and Cox proportional hazards models. Results: The MSS group was well matched to the MSI‐H group based on age, gender, location, and chronicity of metastatic disease. MSI‐H mCRC pts had earlier disease recurrence (median time from initial diagnosis to metastatic disease diagnosis, MSI‐H group 12.9 vs. MSS group 20.9 months, p = .034). Median overall survival (OS) was 28.1 and 37.4 months for MSI‐H and MSS pts, respectively (p = .99). In total, 94.7% of MSI‐H pts and 98.7% of MSS pts had fluoropyrimidine‐based chemotherapy for metastatic disease, and there was no difference in OS between these two groups (32.3 vs. 37.4 months, p = .91). Forty‐three MSI‐H and thirty‐nine MSS pts had metastasectomy and/or ablation of metastases (p = .51) with longer median OS compared with pts without metastasectomy (MSI‐H: 82.0 vs. 13.9, p < .001; MSS: 69.9 vs. 19.7, p < .001). Age <65 years, BRAF wild type, and metastasectomy were associated with better OS in univariate analysis. Only metastasectomy remained statistically significant in multivariate analysis (p < .001). Conclusion: In mCRC, patients with MSI‐H tumors have similar, but numerically shorter, median overall survival compared with those with MSS tumors. In both groups, metastasectomy and ablation of metastatic disease should be considered to optimize OS. Implications for Practice: This study clearly demonstrated the survival benefits that aggressive metastasectomy provides in selected microsatellite instability‐high metastatic colorectal cancer patients. This could be meaningful practice‐changing information that has been long awaited. [ABSTRACT FROM AUTHOR]

Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background. Preclinical and epidemiological data suggest that metformin might have antineoplastic properties against colon cancer (CC). However, the effect of metformin use on patient survival in stage III CC after curative resection is unknown. The survival outcomes were comparable regardless of the duration of metformin use. Patients and Methods. Before randomization to FOLFOX (folinic acid, 5-fluorouracil, oxaliplatin) with or without cetuximab, 1,958 patients with stage III CC enrolled in the N0147 study completed a questionnaire with information on diabetes mellitus (DM) and metformin use. Cox models were used to assess the association between metformin use and disease-free survival (DFS), overall survival (OS), and the time to recurrence (TTR), adjusting for clinical and/or pathological factors. Results. Of the 1,958 patients, 1,691 (86%) reported no history of DM, 115 reported DM with metformin use (6%), and 152 reported DM without metformin use (8%). The adjuvant treatment arms were pooled, because metformin use showed homogeneous effects on outcomes across the two arms. Among the patients with DM (n = 267), DFS (adjusted hazard ratio [aHR], 0.90; 95% confidence interval [CI], 0.59-1.35; p = .60), OS (aHR, 0.99; 95% CI, 0.65-1.49; p = .95), and TTR (aHR, 0.87; 95% CI, 0.56-1.35; p = .53) were not different for the metformin users compared with the nonusers after adjusting for tumor and patient factors. The survival outcomes were comparable regardless of the duration of metformin use (>1,1-5,6-10, ≥11 years) before randomization (ptrend = .64 for DFS, ptrend = .84 for OS, and ptrend = .87 for TTR). No interaction effects were observed between metformin use and KRAS, BRAF mutation status, tumor site,T/N stage, gender, or age. Conclusions. Patients with stage III CC undergoing adjuvant chemotherapy who used metformin before the diagnosis of CC experienced DFS, OS, and TTR similar to those for non-DM patients and DM patients without metformin use. [ABSTRACT FROM AUTHOR]

Introduction. A KRAS mutation represented the first genomic biomarker to predict lack of benefit from anti-epidermal growth factor receptor (EGFR) antibody therapy in advanced colorectal cancer (CRC). Expanded RAS testing has further refined the treatment approach, but understanding of genomic alterations underlying primary and acquired resistance is limited and further study is needed. Materials and Methods. We prospectively analyzed 4,422 clinical samples from patients with advanced CRC, using hybrid- capture based comprehensive genomic profiling (CGP) at the request of the individual treating physicians. Comparison with prior molecular testing results, when available, was performed to assess concordance. Results. We identified a RAS/RAF pathway mutation or amplification in 62% of cases, including samples harboring KRAS mutations outside of the codon 12/13 hotspot region in 6.4% of cases. Among cases with KRAS non-codon 12/13 alterations for which prior test results were available, 79 of 90 (88%) were not identified by focused testing. Of 1,644 RAS/RAF wild-type cases analyzed by CGP, 31% harbored a genomic alteration (GA) associated with resistance to anti- EGFRtherapy in advanced CRC including mutations in PIK3CA, PTEN, EGFR, and ERBB2. We also identified other targetable GA, including novel kinase fusions, receptor tyrosine kinase amplification, activating point mutations, as well as micro-satellite instability. Conclusion. Extended genomic profiling reliably detects alterations associated with lack of benefit to anti-EGFR therapy in advanced CRC, while simultaneously identifying alterations potentially important in guiding treatment. The use of CGP during the course of clinical care allows for the refined selection of appropriate targeted therapies and clinical trials, increasing the chance of clinical benefit and avoiding therapeutic futility. [ABSTRACT FROM AUTHOR]

Regorafenib is an oral multikinase inhibitor that inhibits several kinases relevant to tumor biology in several cancers, including colorectal carcinoma (CRC) and gastrointestinal stromal tumor (GIST). In phase III trials, regorafenib significantly improved overall survival versus placebo in patients with metastatic CRC progressing after all available standard therapies, and significantly prolonged progression-free survival in patients with advanced GIST in whom at least imatinib and sunitinib had failed. Thus, this agent holds promise as a new standard of care for CRC and GIST patients after disease progression following all other approved therapies.The clinical trials reported to date show that this new treatment has a consistent adverse event profile that is quite different from that of traditional cytotoxic chemotherapies. The most common adverse events of regorafenib include dermatologic and mucosal toxicities (especially hand-foot skin reaction, rash, and oral mucositis), constitutional symptoms (e.g., fatigue, nausea, and weight loss), vascular effects (especially hypertension), and gastrointestinal symptoms (e.g., diarrhea). To help health care professionals anticipate and manage the adverse events associated with regorafenib, we describe our experiences in clinical trials and show that such toxicities can be effectively managed with close observation of patients from initiation of dosing, along with prompt appropriate interventions, including dose modifications, if necessary. [ABSTRACT FROM AUTHOR]

Background. The Avastin® Registry: Investigation of Effectiveness and Safety (ARIES) study is a prospective, community-based observational cohort study that evaluated the effectiveness and safety of first-line treatment patterns, assessing the impact of chemotherapy choice and treatment duration. Methods. The ARIES study enrolled patients with metastatic colorectal cancer (mCRC) receiving first-line chemotherapy with bevacizumab and followed them longitudinally. The protocol did not specify treatment regimens or assessments. Analyses included all patients who initiated bevacizumab in combination with either first-line oxaliplatin with infusional 5-fluorouracil and leucovorin (FOLFOX) or irinotecan with infusional 5-fluorouracil and leucovorin (FOLFIRI). Progression-free survival (PFS) and overall survival (OS) times were estimated using Kaplan-Meier methods. Hazard ratios (HRs) were estimated with multivariate Cox regression analysis, adjusting for potential confounding factors. Results. In total, 1,550 patients with first-line mCRC were enrolled (median follow-up, 21 months) and most received FOLFOX--bevacizumab (n = 968) or FOLFIRI-- bevacizumab (n = 243) as first-line therapy. The baseline characteristics and median treatment duration were generally similar between subgroups. There were no significant differences in the median PFS (10.3 months vs. 10.2 months) or OS (23.7 months vs. 25.5 months) time between the FOLFOX--bevacizumab and FOLFIRI--bevacizumab subgroups, respectively, by unadjusted analyses. Multivariate analyses showed FOLFIRI-bevacizumab resulted in a similar PFS (HR, 1.03; 95% confidence interval [CI], 0.88 -1.21) and OS (HR, 0.95; 95% CI, 0.78 -1.16) outcome as with FOLFOX--bevacizumab. The incidence proportions of bevacizumab-associated adverse events were similar for FOLFOX- and FOLFIRI-based therapies. Conclusions. In first-line mCRCpatients, the FOLFOX-- bevacizumab and FOLFIRI--bevacizumab regimens were associated with similar treatment patterns and clinical outcomes. [ABSTRACT FROM AUTHOR]

Background. There is scant evidence to guide the management of patients after hepatic artery embolization (HAE).We examined length of stay (LOS), laboratory patterns, medication usage, morbidity, and mortality of patients hospitalized after HAE for metastatic neuroendocrine tumors. Methods. Data were abstracted retrospectively from electronic medical records on LOS, liver function tests (LFTs), i.v. antibiotics, analgesia, peak temperature, bacteremia, hepatic abscess formation, carcinoid crisis, and metastatic burden on cross-sectional imaging. Results. In 2005-2009, 72 patients underwent 174 HAEs for carcinoid and islet cell tumors. The median LOS was 4 days (range, 1-8 days). There was no correlation between peak LFTs and tumor burden. Declines in LFTs were not uniform before hospital discharge; 25%, 37%, 30%, 53%, and 67% of patients were discharged before their respective aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total and direct bilirubin levels began to decline, with no readmissions for acute hepatic failure. The median i.v. analgesia dose was 60 mg oral morphine equivalents (range, 3-1,961 mg). Pre-HAE i.v. antibiotics were administered in 99% of cases; post-HAE fever occurred in 37% of patients, with no documented bacteremia. One patient developed a hepatic abscess after HAE. There were two carcinoid crises. The single in-hospital death was associated with air in the portal veins. Conclusions. The duration and intensity of in-hospital care following HAE should be managed on an individual basis. A downward trend in LFTs is not required before discharge. Modest use of i.v. analgesia suggests that many patients could exclusively receive oral analgesics. Given the rarity of serious complications, hospital stays could be shortened, thereby reducing costs and nosocomial risks. [ABSTRACT FROM AUTHOR]

Systemic therapy has led to a median survival time for patients with advanced colorectal cancer (CRC) almost fourfold longer than that expected with best supportive care, an outcome achieved through combining chemotherapeutic and targeted biologic agents. Although the latter can include anti-epidermal growth factor receptor antibodies, such as cetuximab and panitumumab, we now have strong evidence that patients whose tumors harbor mutated KRAS will not benefit from this class of agent. Acceptance of the reliability and importance of the KRAS data took several years to evolve, however, for a variety of reasons. The timeline from the presentation and publication of small, retrospective phase II studies to widespread acceptance of the KRAS predictive value and changes in behavior--specifically, modifications of ongoing national trials in advanced/ metastatic CRC, changes in national guidelines and practice patterns, and adjustments to the labeled indications for the monoclonal antibodies--was lengthy. In this commentary, we discuss whether or not the process of data disclosure regarding KRAS status and treatment of advanced CRC patients was effective in permitting timely decisions regarding ongoing publicly funded clinical trials and whether or not such decisions were rational and ethical. The overall goals are to highlight lessons learned regarding early disclosure of clinical trial results, as well as vetting and adoption of new scientific data, and to propose modifications for handling similar situations in the future. [ABSTRACT FROM AUTHOR]

Purpose. We explored the prognostic value of actual tumor measurements (TM) versus World Health Organization (WHO) criteria as three-level (responder, stable, and progression) and two-level (responder and nonresponder) variables at 12 and 24 weeks as predictors of survival in Intergroup Trial N9741, a phase III trial in metastatic colorectal cancer (CRC). Methods. All patients with measurable disease (N = 1,188) were included. The percentage changes in TM from baseline to 12 and 24 weeks were calculated. The prognostic values of TM versus WHO criteria (as three and two-level variables) at 12 and 24 weeks were compared, using Cox models for overall survival (OS) in a landmark analysis, adjusting for baseline tumor size, performance status, and treatment arm. Results. Tumor status at 12 weeks by WHO criteria (three or two levels) or actual TM were all strongly associated with OS. Actual TM provided no meaningful additional benefit compared with the three-level WHO criteria. Tumor status at 24 weeks was also strongly associated with survival, but added no additional prognostic value compared with the 12-week assessment. At 12 weeks, actual TM improved prognostic characterization of patients with WHO status of response, but provided no additional value in patients with stable disease or progression. Conclusions. In N9741, the use of actual TM, or following tumor status beyond 12 weeks, did not improve survival prediction compared with a single three-level response assessment at 12 weeks, suggesting that 12-week tumor status could be an appropriate phase II trial endpoint in metastatic CRC. [ABSTRACT FROM AUTHOR]

Background. The Bevacizumab Regimens' Investigation of Treatment Effects (BRiTE) study is a prospective, observational cohort study designed to elucidate safety and effectiveness outcomes associated with bevacizumab combined with chemotherapy as used in clinical practice for first-line treatment of metastatic colorectal cancer (mCRC). Patients and Methods. Baseline characteristics, prespecified bevacizumab-related adverse events, and effectiveness data were collected from 1,953 mCRC patients who were receiving first-line treatment including bevacizumab at 248 U.S. sites. Results. At database lock, the median follow-up was 20.1 months. At baseline, 46% of patients were aged ≥65 years and 49% had an Eastern Cooperative Oncology Group performance status score ≥1. Fluorouracil, leucovorin, and oxaliplatin was the most common first-line chemotherapy regimen (56%). Overall rates of bevacizumab-related adverse events in the BRiTE study, such as gastrointestinal perforation (1.9%), arterial thromboembolic events (2%), grade 3-4 bleeding (2.2%), and de novo hypertension requiring medication (22%), were consistent with those reported in randomized clinical trials (RCTs) of bevacizumab in first-line mCRC treatment. The median progression-free survival (PFS) and overall survival (OS) times were 9.9 (95% confidence interval [CI], 9.5-10.3) months and 22.9 (95% CI, 21.9 -24.4) months, respectively. Conclusion. The median PFS and OS durations and safety profile of bevacizumab in the BRiTE study were similar to those in RCTs of bevacizumab plus chemotherapy in first-line mCRC patients. The observations from the BRiTE study complement and expand upon RCT data, providing clinical information in a large cohort of bevacizumab-treated patients and subgroups such as the elderly. The Oncologist 2009;14:862-870 [ABSTRACT FROM AUTHOR]

New agents for the treatment of metastatic colorectal cancer have extended median overall survival to more than 20 months, an increase that has changed the view of advanced colorectal cancer from an acute to a chronic condition. This article proposes a shift in treatment strategy from the concept of successive "lines" of therapy, in which chemotherapy is continued until disease progression, to that of a continuum of care, in which the use of chemotherapy is tailored to the clinical setting and includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays," and surgical resection of metastases in selected patients. In this approach, the distinction between lines of therapy is no longer absolute. This represents a paradigm shift in the management of metastatic colorectal cancer to that of a continuum of care approach that includes individualized planning, in which patients are given the opportunity to benefit from exposure to all active agents and modalities while minimizing unnecessary treatment and toxicity, with the ultimate goal of improving survival as well as quality of life. [ABSTRACT FROM AUTHOR]

In this study, whole exome sequencing was conducted on tumor samples and paired germline samples from patients with Sertoli‐Leydig cell tumors to explore not only DICER1 mutations for Chinese populations but also other genetic variations related to pathogenesis and prognosis, which could lay a preliminary foundation for genetic counseling. [ABSTRACT FROM AUTHOR]

This letter to the editor remarks on additional considerations for the management of febrile neutropenia during the COVID‐19 pandemic, in response to the letter by Boutayeb et al. [ABSTRACT FROM AUTHOR]

The article discusses small bowel adenocarcinoma (SBA) which accounts for almost one third of all small intestinal malignancies. It is a rare disease and therefore prospective trials limited to this disease are few and the optimal therapy for SBA is unknown. However, two recent studies have indicated that the combination of a fluoropyrimidine, such as 5-fluorouracil or capecitabine, and oxaliplatin may be reasonable first line chemotherapy for metastatic SBA till larger trials are carried out.

Background: BRAF V600E mutations are present in 8%-10% of patients with metastatic colorectal cancer (mCRC) and portend poor prognosis. This study investigated the impact of metastasectomy for patients with BRAF V600E mCRC., Subjects, Materials, and Methods: Using prospective clinical and molecular data, patients with BRAF V600E mCRC were analyzed for clinical characteristics and survival. Statistical analyses utilized the Kaplan-Meier method, log-rank test, and Cox proportional hazard models., Results: Fifty-two patients were identified between July 1, 2008, and January 4, 2016. Patient characteristics included median age 65 years, 61% female, Eastern Cooperative Oncology Group performance status ≤1, 71% with right-sided tumors, and 28% with liver-limited metastasis. In the first-line setting, 7% (4/52) received fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/bevacizumab (BEV) and 81% were treated with doublet chemotherapy consisting of fluoropyrimidine, oxaliplatin, and BEV. Median overall survival (OS) for all 52 patients was 25 months with median progression-free survival (PFS) of 9.3 months. With median follow-up of 18.3 months, 21 patients underwent metastasectomy with longer OS (29.1 months vs. 22.7 months, hazard ratio [HR] = 0.33; confidence interval [CI], 0.12-0.78; p  = .01) and PFS (13.6 months vs. 6.2 months, HR = 0.53, CI, 0.28-0.97; p  = .03) compared with the non-metastasectomy cohort. In multivariate analysis, metastasectomy remained significant for improved survival outcomes (HR = 0.52; 95% CI, 0.07-1.02; p  = .02). Median disease-free survival after metastasectomy was 9.7 months (95% CI, 5.5-19.5). Two patients remain disease-free at the time of last follow-up, with one patient without relapse for greater than 2 years (28.9 months)., Conclusion: Multimodality therapy incorporating metastasectomy for BRAF V600E mCRC should be considered and might be associated with improved overall survival in select patients., Implications for Practice: BRAF V600E metastatic colorectal cancer (mCRC) represents an extremely difficult molecular subset of colorectal cancer to treat. To date, this subset remains refractory to standard chemotherapies, prompting extensive clinical investigation regarding novel treatment approaches and targeted modalities. While the use of metastasectomy for expanded RAS wild-type and RAS mutated mCRC has resulted in improved overall survival for select patients, utilization of metastasectomy in patients with BRAF V600E mCRC remains controversial. This article explores the authors' experience with BRAF V600E mCRC to ascertain whether a multidisciplinary approach incorporating metastasectomy for well-selected patients improves overall survival., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)