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Simple Summary Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy (AC) is controversial. A novel immune response classifier has previously been validated to refine patient selection, but its impact on oncologist treatment planning had yet to be described. In this survey, all but one oncologist altered clinical practice recommendations, and recommendations for AC prescriptions were reduced by half (among the Immunoscore-high cases (low recurrence risk)). This study revealed that the Immunoscore results could significantly decrease AC use in patients with stage II colon cancer who may not benefit from it, thereby reducing the administration of nonvalue care. Abstract Background: Adjuvant chemotherapy use in stage II colon cancer is controversial. Current prognostic risk factors do not take the tumor immune microenvironment into account. Consideration of the Immunoscore, which measures the host immune response at the tumor site, may assist clinicians in reducing adjuvant chemotherapy use in patients who are unlikely to benefit from it. This study sought to determine the potential clinical utility of the Immunoscore, via its effect on medical oncologists’ recommendations for management of patients with stage II colon cancer. Methods: De-identified vignettes of 10 patients with stage II colon cancer were presented to 25 practicing medical oncologists. Each participant completed surveys indicating recommendations for adjuvant chemotherapy and surveillance strategies. An educational session was subsequently conducted, and the same patient profiles were re-presented but included immunoscore results. Participants were again asked to provide their recommendations. A participant was counted as influenced if their responses were altered after immunoscore test results were provided. Results: All but one participant (96%) altered a management recommendation for ≥1 case. For individual cases, a mean of 55% (range, 40–80%) of participants altered their recommendations for adjuvant chemotherapy and/or surveillance. For the immunoscore-high cases (low-risk of recurrence), recommendations for adjuvant chemotherapy use decreased from 60% to 31%. Conclusions: These results indicate a willingness by oncologists to integrate immunoscore information into clinical practice recommendations. Incorporation of immunoscore data resulted in the reduction of nonvalue care in the simulated population. Confirmation in prospective studies is planned.

SummaryVantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (n = 16).

INTRODUCTION: The prevalence of older patients with metastatic colorectal cancer (mCRC) will continue to increase with our aging population. Treatment of mCRC has changed significantly in the last few decades as we have learned how to personalize the treatment of mCRC to the biology of the tumor, utilizing new treatment approaches. With an ever-changing treatment paradigm, managing the population of older adults becomes paramount. We will review current recommendations for evaluation and treatment, along with challenges associated with the management of older adults diagnosed with metastatic colorectal cancer. AREAS COVERED: This review will highlight the pivotal clinical trials that defined the use of systemic therapy, immunotherapy and targeted therapies for mCRC, and how those are applied to the older patient population. In addition, we will outline the tools for an in-depth assessment of an older adult in regards to treatment planning and management of therapy-related toxicities. EXPERT OPINION: A comprehensive geriatric assessment can assist in the selection of treatment for an older adult with mCRC. While frail older patients can frequently only tolerate single agents or modified regimens, fit older adults remain candidates for a wider range of treatment options. However, since all of these treatments are associated with possible toxicities, each patient’s treatment must be personalized to the patient’s goals and wishes through a shared decision-making process.

Background: Patients with esophageal cancer (EC) have high rates of malnutrition due to tumor location and treatment-related toxicity. Various strategies are used to improve nutritional status in patients with EC including oral and enteral support. Methods: We conducted a retrospective analysis to determine the impact of malnutrition and prophylactic feeding jejunostomy tube (FJT) placement on toxicity and outcomes in patients with localized EC who were treated with neoadjuvant chemoradiation therapy (nCRT) followed by esophagectomy. Results: We identified 125 patients who were treated with nCRT between 2002 and 2014. Weight loss and hypoalbuminemia occurred frequently during nCRT and were associated with multiple adverse toxicity outcomes including hematologic toxicity, nonhematologic toxicity, grade &ge, 3 toxicity, and hospitalizations. After adjusting for relevant covariates including the specific nCRT chemotherapy regimen received and the onset of toxicity, there were no significant associations between hypoalbuminemia, weight loss, or FJT placement and relapse-free survival (RFS) or overall survival (OS). FJT placement was associated with less weight loss during nCRT (p = 0.003) but was not associated with reduced toxicity or improved survival. Conclusions: Weight and albumin loss during nCRT for EC are important factors relating to treatment toxicity but not RFS or OS. While pretreatment FJT placement may reduce weight loss, it may not impact treatment tolerance or survival.

BACKGROUND: Pancreatic adenocarcinoma (PCA) incidence is higher in Black compared to White patients. Beyond race, neighborhood socioeconomic status (nSES) may also inform disparities. However, these effects on metastatic pancreatic adenocarcinoma (mPCA) are not well-studied. The aim of this study was to explore whether nSES influences survival in patients with mPCA. METHODS: nSES measures were derived from U.S. census data at the census tract (CT) level. We correlated medical records of mPCA patients (diagnosed 2010-2016; n=370) to nSES measures retrospectively via a geocode derived from patient address. Multivariable cox proportional hazards models were used to identify patient-level (age, sex, race, marital status, treatment (radiation/chemo/surgery), PCA family history, stage, Jewish ancestry, tobacco use, BMI, diabetes, and statin use) and nSES measures (deprivation, racial concentration, stability, transportation access, immigration) associated with mPCA survival; P values

Given the prevalence and the rising incidence of hepatocellular carcinoma (HCC) in older adults worldwide, there is an urgent need to improve our understanding of the implications of treatment modalities in this population. The care of older patients with HCC is challenging due to the lack of evidence-based recommendations in this population. The current treatment approach for older patients relies on extrapolation of data from clinical trials conducted mostly in younger patients or fit older adults. Further, in the last few years, the arsenal of systemic treatments has increased with currently seven FDA-approved therapies available for patients with advanced HCC. Therefore, understanding how to apply current data to this unique and diverse patient population is necessary. This review will aim to shed light on the approach to older adults with HCC through an assessment of available data in the literature.

Purpose The objectives were to evaluate dosing schedules of labetuzumab govitecan, an antibody-drug conjugate targeting carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) for tumor delivery of 7-ethyl-10-hydroxycamptothecin (SN-38), in an expanded phase II trial of patients with relapsed or refractory metastatic colorectal cancer. Patients and Methods Eligible patients with at least one prior irinotecan-containing therapy received labetuzumab govitecan once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles. End points were safety, response, pharmacokinetics, and immunogenicity. Results Eighty-six patients who had undergone a median of five prior therapies (range, one to 13) were each enrolled into one of the four cohorts. On the basis of Response Evaluation Criteria in Solid Tumors 1.1, 38% of these patients had a tumor as well as plasma carcinoembryonic antigen reduction from baseline after labetuzumab govitecan treatment; one patient achieved a partial response with a sustained response spanning > 2 years, whereas 42 patients had stable disease as the best overall response. Median progression-free survival and overall survival were 3.6 and 6.9 months, respectively. The major toxicities (grade ≥ 3) among all cohorts were neutropenia (16%), leukopenia (11%), anemia (9%), and diarrhea (7%). The antibody-drug conjugate’s mean half-life was 16.5 hours for the four cohorts. Anti-drug/anti-antibody antibodies were not detected. The two once-weekly dose schedules, showing comparable toxicity and efficacy, were chosen for further study. Conclusion Monotherapy with labetuzumab govitecan demonstrated a manageable safety profile and therapeutic activity in heavily pretreated patients with metastatic colorectal cancer, all with prior irinotecan therapy. Further studies of labetuzumab govitecan treatment alone or in combination with other therapies in earlier settings are indicated.

Addressing the needs of older adults with cancer is critical for the delivery of high-quality, patient-centered care. The Association of Community Cancer Centers (ACCC) has identified barriers and best practices for serving this growing patient population in order to help support the multidisciplinary team in understanding and proactively preparing for this large subgroup of patients. A survey was administered to 332 cancer professionals. 95% agreed that their older adult patients would benefit from a comprehensive geriatric assessment, yet only 17% of respondents are performing CGAs. 74% of respondents are not using any screening tool to identify high risk patients. The top three barriers to this were time/personnel and limited familiarity with available, validated tools. 61% are not focused on increasing older adult participation in clinical trials which leads to a disparity in care. Techniques for evaluating fitness, cognitive status, psychological status, comorbidities, and toxicity risk were often informal and not recorded in an EMR. Three in-depth focus groups were completed at programs demonstrating effective, yet different models of care for an older population. City of Hope Cancer Center is running a Senior Adult program under a grant where patients receive care in concordance with a score (CARG toxicity calculator) and a team review with a geriatrician. Sidney Kimmel Cancer Center has a consultative clinic where patients attend a 2-hour appointment to complete a comprehensive geriatric assessment with oncology, geriatrics, and specialists including pharmacy and nutrition. ACCC has recommended resources to address deficits in care, particularly in the community setting.

Although initially approved for metastatic colorectal cancer (mCRC) tumors with epidermal growth factor receptor (EGFR) overexpression, the use of anti-EGFR antibodies is now restricted to wild-type KRAS tumors. Little is known about prescribers' response to new clinical data, practice guidelines, and US Food and Drug Administration (FDA) label change with regard to the use of anti-EGFR antibodies in clinical practice.Commercially insured patients with mCRC who received second-line therapy between 2004 and 2010 were identified by dusing the LifeLink Health Plan Claims Database. We calculated the fraction of patients receiving anti-EGFR antibody in 2-month intervals. χ(2) tests were used to compare treatment rates at four time points: time 1: June 2008, ASCO presentation of clinical data; time 2: February 2009, ASCO guidelines publication; time 3: August 2009, FDA label change; time 4: April 2010 to 8 months after FDA label change.Five thousand eighty-nine patients received second-line therapy; of these, 2,599 patients received an anti-EGFR antibody. Median age was 60 years (range, 20 to 97), with 57% male sex. The majority of patients (59.4%) received an anti-EGFR antibody at time 1, with significant decrease at each of the subsequent time points (time 2: 46.2% [P = .019]; time 3: 35.2% [P.001]; Time 4: 16.2% [P.001]). Multivariable logistic regression did not show any affect of age, sex, comorbidities, or region of the country on this pattern.The use of anti-EGFR antibodies for mCRC decreased after the presentation of clinical trial data, ASCO guidelines publication, and FDA label change. These data suggest that oncologists respond rapidly to new evidence and professional guidelines, and readily incorporate predictive biomarkers into clinical practice.