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Neoadjuvant chemoradiation (nCRT) followed by esophagectomy is the standard treatment for locally advanced esophageal cancer. Older patients are often felt to be poor candidates for nCRT. Limited data is available to guide the use of nCRT in this population. A retrospective review of patients treated at a tertiary cancer center between 2002 and 2014 was conducted grouping patients by age (≥ 65 or < 65) for evaluation of differences in toxicity and outcomes. Evaluation of pre-treatment platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) was also performed. Univariate (UVA) and multivariate analyses (MVA) determined associations between age, toxicities and outcomes. The Kaplan-Meier method (KM) assessed overall survival (OS) and relapse free survival (RFS). 125 patients were identified for this study (67 aging <65, and 58 ≥ 65). In the UVA, advanced age was only associated with increased hematologic toxicity (p =.04). After adjusting for covariates in the MVA, there were no significant differences in toxicity between older and younger patients. There were also no differences between overall survival and relapse free survival between age groups. Increased pre-treatment NLR was strongly correlated with advanced age (p =.01), increased hospitalizations (p =.04), and decreased RFS (p =.002). Older patients who underwent nCRT followed by esophagectomy had similar toxicities and outcomes as younger patients suggesting that nCRT before esophagectomy is safe in select older adults with esophageal cancer. PLR and NLR may serve as prognostic markers of aging, toxicity, and outcomes. Further research is warranted to optimize the therapy of older patients with this disease. [ABSTRACT FROM AUTHOR]

While a number of landmark clinical trials have led to the approval of combination chemotherapy regimens for metastatic pancreatic adenocarcinoma (mPC), older patients are underrepresented in these studies. We evaluated changes in practice patterns in the management of mPC among medical oncologists in the combination chemotherapy era (CCE). A retrospective analysis of patients treated at a tertiary cancer center between 2000 and 2015 was conducted. The cohort was divided into two groups (Pre-CCE, diagnosed with mPC between 2000 and 2009 and Post-CCE, diagnosed between 2010 and 2015). Fisher's exact test was used to compare categorical variables. Univariate (UVA) and multivariate analyses (MVA) were conducted to determine the impact of treatment and prognostic variables on survival. 473 older patients with mPC were identified. Post-CCE, there were statistically significant increases in the use of chemotherapy (p <.005). While usage of gemcitabine was similar between groups, use of fluoropyrimidines, platinum, taxanes, and irinotecan increased Post-CCE. Use of chemotherapy conferred a modest but significant survival benefit (5 months Pre-CCE versus 6 months Post-CCE, p <.005). UVA and MVA showed significantly improved survival when older patients were treated with 2 or more chemotherapeutic agents. Despite the limited data available to guide clinicians on optimal usage of these treatments in older patients, medical oncology practice patterns for mPC have changed at an academic cancer center. Increases in chemotherapy use seems to confer a small survival benefit. Additional prospective data in older patients is necessary to improve our management of older patients with mPC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Older patients make up the majority of patients with pancreatic cancer, with a median age of 71 years at diagnosis. However, older patients are underrepresented in clinical trials in pancreatic cancer. This study investigates trends in age distribution of patients enrolled in clinical trials for advanced pancreatic cancer over time, and examines outcomes and toxicity in older patient subgroups from two studies conducted by Eastern Cooperative Oncology Group and American College of Radiology Imaging Network (ECOG-ACRIN) in this disease. 16,042 patients from 38 phase III clinical trials for locally advanced or metastatic pancreatic adenocarcinoma published between 1997 and 2016 were identified and included in this analysis. Outcomes and toxicity by age were examined in two of the trials, ECOG-ACRIN trials E2297 and E6201, which included a total of 1146 patients. The median age across the trials was 62.7 years; median ages for individual trials ranged from 57 years to 66 years. Weighted linear regression showed no significant change in median age over time. Combined analysis of the two ECOG-ACRIN trials demonstrated higher rates of fatigue, thrombocytopenia, and infection in those ≥75 years compared with those <75 years, but despite this showed no difference in overall survival (OS) or progression-free survival (PFS) (OS: 5.7 vs. 5.6 months and PFS: 2.8 vs 3.5 months). Enrollment of older adults in phase III pancreatic cancer clinical trials has not increased over time, despite increasing number of older patients seen in clinic. Increased efforts are needed to enhance enrollment of older patients in clinical trials, and to promote trials specifically for older patients, in order to improve the evidence base for treating this patient population. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the fourth leading cause of cancer-related death in the US with an increasing incidence in older adults (OA) over age 70. There are currently no treatment guidelines for OA with metastatic pancreatic cancer (mPCA) and selecting a chemotherapy regimen for these patients is subjective, based largely on chronologic age and performance status (PS). Geriatric screening tools provide a more objective and accurate evaluation of a patient's overall health but have not yet been validated in patient selection for mPCA treatment. This study aims to elucidate the optimal chemotherapy treatment of vulnerable OA with mPCA and understand the geriatric factors that affect outcomes in this population. The GIANT (ECOG-ACRIN EA2186) study is multicenter, randomized phase II trial enrolling patients over age 70 with newly diagnosed mPCA. This study utilizes a screening geriatric assessment (GA) which characterizes patients as fit, vulnerable, or frail. Patients with mild abnormalities in functional status and/or cognition, moderate comorbidities, or over age 80 are considered vulnerable. Enrolled patients are randomized to one of two dose-reduced treatment regimens (gemcitabine/nab-paclitaxel every other week, or dose-reduced 5-fluoruracil (5FU)/ liposomal irinotecan (nal-IRI) every other week). GA and quality of life (QoL) evaluations are completed prior to treatment initiation and at each disease evaluation. Overall survival (OS) is the primary endpoint, with secondary endpoints including progression free survival (PFS) and objective response rate (ORR). Enrolled patients will be stratified by age (70–74 vs ≥75) and ECOG PS (0–1 vs 2). Additional endpoints of interest for OA include evaluation of risk factors identified through GA, QoL evaluation, and toxicities of interest for older adults. Correlative studies include assessment of pro-inflammatory biomarkers of aging in the blood (IL-6, CRP) and imaging evaluation of sarcopenia as predictors of treatment tolerance. The GIANT study is the first randomized, prospective national trial evaluating vulnerable OA with mPCA aimed at developing a tailored treatment approach for this patient population. This trial has the potential to establish a new way of objectively selecting vulnerable OA with mPCA for modified treatment and to establish a new standard of care in this growing patient population. Trial Registration: This trial is registered with ClinicalTrial.gov Identifier NCT04233866. [ABSTRACT FROM AUTHOR]

Psychosocial status contributes to overall quality of life (QOL) for patients with cancer as psychosocial distress is commonly seen in this population. We sought to describe the psychosocial needs of older adults with metastatic breast cancer (MBC) treated in the community. We evaluated the correlation between the patient's psychosocial status and the presence of other geriatric abnormalities in this patient population. This is a secondary analysis of a completed study evaluating older adults (≥65 years) with MBC treated at community practices who received a geriatric assessment (GA). This analysis evaluated psychosocial factors collected during GA, including depression assessed by Geriatric Depression Scale (GDS), perceived social support (SS) assessed by Medical Outcomes Study Social Support Survey (MOS), and objective social supportassessed by demographic variables (living situation and marital status). Perceived SS was further subdivided into tangible social support (TSS) and emotional social support (ESS). Kruskal-Wallis tests, Wilcoxon tests, and Spearman's correlations were used to assess the relationship between psychosocial factors, patient characteristics, and geriatric abnormalities. One hundred older patients with MBC were enrolled and completed GA with a median age of 73 years (65–90). Almost half of the participants (47%) were either single, divorced, or widowed and 38% lived alone, demonstrating a significant number of patients with objective social support deficits. Patients with HER2+ or triple negative MBC had lower overall SS scores compared to patients with ER/PR+ or HER2- MBC (p = 0.033). Patients on fourth line of therapy were more likely to screen positive for depression compared to patients on earlier lines of therapy (p = 0.047). About half (51%) of the patients indicated at least one SS deficit on the MOS. A higher GDS and lower MOS score correlated with greater total GA abnormalities (p = 0.016). Evidence of depression correlated with poor functional status, decreased cognition, and a high number of co-morbidities (p < 0.005). Abnormalities in functional status, cognition, and high GDS are associated with lower ESS (p = 0.025,0.031,0.006 respectively). Psychosocial deficits are common among older adults with MBC treated in the community and are associated with the presence of other geriatric abnormalities. These deficits require a thorough evaluation and management to optimize treatment outcomes. [ABSTRACT FROM AUTHOR]

Nutritional issues among older adults with cancer are an understudied area of research despite significant prognostic implications for treatment side effects, cancer-specific mortality, and overall survival. In May of 2015, the National Cancer Institute and the National Institute on Aging co-sponsored a conference focused on future directions in geriatric oncology research. Nutritional research among older adults with cancer was highlighted as a major area of concern as most nutritional cancer research has been conducted among younger adults, with limited evidence to guide the care of nutritional issues among older adults with cancer. Cancer diagnoses among older adults are increasing, and the care of the older adult with cancer is complicated due to multimorbidity, heterogeneous functional status, polypharmacy, deficits in cognitive and mental health, and several other non-cancer factors. Due to this complexity, nutritional needs are dynamic, multifaceted, and dependent on the clinical scenario. This manuscript outlines the proceedings of this conference including knowledge gaps and recommendations for future nutritional research among older adults with cancer. Three common clinical scenarios encountered by oncologists include (1) weight loss during anti-cancer therapy, (2) malnutrition during advanced disease, and (3) obesity during survivorship. In this manuscript, we provide a brief overview of relevant cancer literature within these three areas, knowledge gaps that exist, and recommendations for future research. [ABSTRACT FROM AUTHOR]

Identifying knowledge gaps and research opportunities in cancer and aging research was the focus of a three-part conference series led by the Cancer and Aging Research Group from 2010 to 2015. The third meeting, featured representatives from the NIA, NCI, ACS and PCORI each of whom discussed research priorities and funding opportunities in cancer and aging at their respective agencies. This manuscript reports on the proceedings of that conference with a specific focus on funding priorities for interventions to improve the quality of life and survivorship of older adults with cancer. Helpful tips from each funder regarding writing a scientifically strong research proposal are presented. [ABSTRACT FROM AUTHOR]

Background Older patients with metastatic pancreatic cancer (mPC) are poorly represented in clinical trials. We compared patterns of care and outcomes of patients with mPC < and > 65 yrs (Group 1 and Group 2, respectively) treated at Fox Chase Cancer Center (FCCC) to identify predictors of survival and better understand the treatment approaches. Methods Charts of 579 patients with mPC treated at FCCC from 2000 to 2010 were reviewed. Group 1 and Group 2 were compared with respect to baseline, treatment characteristics, and overall survival (OS) after diagnosis of metastatic disease. Results 299 patients in Group 1 (median age 57) and 280 patients in Group 2 (median age 73) were evaluated. Patients in Group 2 were less likely to receive any chemotherapy for mPC compared to Group 1 (65% vs 75%, p = 0.001) and if treated were less likely to receive more than one agent (37% vs 53%, p < 0.001). Survival was comparable between the two groups ( p = 0.16) and Charlson Co-morbidity Index did not emerge as a prognostic factor. Longer OS was associated with higher number of agents used in both groups ( p < 0.001). Liver metastases conferred worse survival ( p = 0.02) while lung metastases conferred better survival in both groups ( p = 0.002). Conclusions Older mPC patients are less likely to receive chemotherapy and receive fewer agents yet have similar OS compared to younger patients. OS improves with increasing number of agents, supporting the use of combination chemotherapy in healthy older patients. Our findings encourage enrollment of older patients with mPC with good performance status onto clinical trials with stratification by site of metastases. [ABSTRACT FROM AUTHOR]

Purpose Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision. Methods We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥ 65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated. Results Among 500 patients (mean age 73, range 65–91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3–5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses. Conclusion PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements.Methods: In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed.Findings: Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6-21·3). 38 (35·5% [95% CI 26·5-45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related.Interpretation: These data support the therapeutic potential of pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements.Funding: Incyte Corporation. [ABSTRACT FROM AUTHOR]