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Geriatric assessment (GA) has been shown to decrease toxicity from systemic therapy, improve completion of chemotherapy, and reduce hospitalizations in older adults with cancer. Given the aging of the cancer population, this has the potential to have a positive impact on the care of a large swath of patients seen. Despite endorsement by several international societies, including the American Society of Clinical Oncology, uptake of GA has been low. Lack of knowledge, time, and resources has been cited as reasons for this. Although challenges to developing and implementing a cancer and aging program vary depending on the health care context, GA is adaptable to every health care context from low- to high-resource settings, as well as those in which geriatric oncology is a well-established or just emerging field. We provide an approach for clinicians and administrators to develop, implement, and sustain aging and cancer programs in a doable and sustainable way.

Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

Mortality from non-small cell lung cancer (NSCLC) has improved with screening and novel treatments. The substance use epidemic has threatened health outcomes in a variety of diseases, but little is known about how it is associated with NSCLC outcomes.We performed a retrospective cohort study of 211 patients with NSCLC treated at a safety-net hospital. Sociodemographic data and clinical outcomes were extracted via review of electronic medical records. Patients were stratified based on substance use status. Comparative and multivariable analyses were performed to evaluate baseline characteristics and lung cancer outcomes including survival.Among 193 patients (91.5%) with information available on substance use, 24.9% reported substance use; specifically, alcohol, marijuana, and illicit substances. Patients with substance use were more likely to have increased health care utilization and poor social determinants of health, including safe housing, stable employment, and social support. There were no significant differences in treatment adherence. Only 6.3% of patients with substance use did not receive guideline concordant care (GCC) compared to 24.8% of patients without substance use; due to poor performance status, increased comorbidities, or loss to follow up. On univariable analysis, patients with substance use experienced inferior median overall survival (OS) if they had metastatic disease (0.40Substance use is associated with poor social determinants of health and increased health care utilization. On multivariable analysis, substance use was not independently associated with OS once guideline-concordant care was used. Future studies should focus on improving our understanding of these associations, delineating potential mechanisms, and developing evidence-based strategies to reduce health care utilization and overcome challenges related to poor social determinants of health.

Background There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. Methods We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination ICIs between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariable logistic regression analyses. External confirmation was performed on an independent cohort from Massachusetts General Hospital. Results The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1-0.9). These results were also demonstrated in the confirmatory cohort (OR 0.46, 95% CI 0.2-0.9) of 169 patients of whom 49 developed ICI colitis (29%). Pre-treatment neutrophil-to-lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1-0.9) only in the discovery cohort. Conclusions This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and graft-versus-host-disease. This observation should be validated prospectively in future studies.

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.US National Institutes of Health National Cancer Institute Cancer Center.

Background: The prevalence of electronic cigarette (e-cigarette) use and its impact on smoking cessation among cancer survivors in the United States is largely unknown. We sought to estimate the prevalence of e-cigarette use and examine its associations with cigarette smoking and smoking quit attempts among smoking-related cancer survivors in the United States. Methods: We obtained data from the 2014–2017 annual cycles of the National Health Interview Survey for participants with self-reported history of smoking-related cancer(s). We calculated the prevalence of current e-cigarette use and utilized multinomial logistic regression in examining the independent association between e-cigarette use and cigarette smoking. Appropriate survey weights were applied in estimating the prevalence rates, relative risk ratios (RRR), ORs, and confidence intervals (CI). Results: Our sample comprised 3,162 smoking-related cancer survivors. The prevalence of current e-cigarette use was 3.18% (95% CI, 2.40–3.96). Current e-cigarette users were 83 times as likely as never users to be current cigarette smokers (RRR, 82.89; 95% CI, 16.54–415.37). Among those with a history of cigarette smoking, current e-cigarette users were 90% less likely to be former smokers (OR, 0.10; 95% CI, 0.05–0.18). No association was seen between current e-cigarette use and a smoking quit attempt in the prior year. Conclusions: E-cigarette use among cigarette ever smokers was associated with a lower likelihood of being a former smoker/having quit smoking, and e-cigarette use was not associated with smoking quit attempts. Impact: Our findings do not provide evidence that e-cigarette use facilitates smoking cessation among smoking-related cancer survivors.

BackgroundPancreatic cancer (PC) is a challenging target for immunotherapy due to its immune-suppressive microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of tumor-infiltrating lymphocytes (TILs). We hypothesized that the combination of CRT and pembrolizumab can further expand and activate TILs.MethodsPatients with resectable or borderline resectable PC were randomized 2:1 to the investigational treatment (Arm A) of pembrolizumab 200mg IV every 3 weeks concurrently with CRT (capecitabine 825 mg/m2 orally twice daily and radiation 50.4 Gy in 28 fractions over 28 days) or CRT only (Arm B) prior to surgical resection. The primary endpoints were safety and difference in TILs density between Arm A and B assessed using multiplexed immunofluorescence on resected tumor specimens. As a correlate analysis, single cell RNA-sequencing (scRNA-seq) was performed to quantify gene expression in T cells from tumors and peripheral blood, and to track expanded T cell clonotypes in these compartments (n=4 patients Arm A; n=3 patients Arm B). The study was amended after enrollment of 37 patients to allow FOLFIRINOX prior to CRT, given changes in standard of care.Results37 patients were enrolled (24 Arm A, 13 Arm B). After neoadjuvant therapy, 13 patients had unresectable disease (9 on A, 4 on B), and 24 patients underwent surgery and were evaluable for the TILs primary endpoint (17 arm A, 7 arm B). The mean difference (A-B) in CD8+ T cell density was 36 cells/mm2 (95% CI -85 to 157, stdev 130) (p 0.48). Additional analysis did not show significant differences in activated cytotoxic T cells, regulatory T cells, M1- or M2-like polarized macrophages, or granulocytes. The median recurrence free survival (RFS) was 18.2 months on Arm A and 14.1 on Arm B (p 0.41). Overall survival was 27.8 months on Arm A and 24.3 on Arm B (p 0.68) with a median follow up of 2.2 years. The most common grade 3 treatment-related toxicities were lymphopenia reported in 29% on Arm A and 31% on Arm B, respectively followed by diarrhea in 8% on Arm A attributed to CRT. scRNA-seq revealed clonal expansion and expression of co-inhibitory markers among TIL subsets.ConclusionsThe combination of CRT and pembrolizumab is safe. Preliminary analysis shows that the addition of pembrolizumab to CRT has minimal effects on intratumoral densities of TILs and other immune cell populations. Single cell transcriptome analyses enable in-depth characterization of the functional responses of T cells to pembrolizumab in the setting of CRT.AcknowledgementsThis study was funded by MerckTrial RegistrationNCT02305186Ethics ApprovalThe study was conducted at 6 sites: University of Virginia, Dana Farber Cancer Institute, MD Anderson Cancer Center (MDACC), Mayo Clinic, Hartford Healthcare Cancer Center, and University of Miami. Written informed consent was provided by the study participants and the protocol was approved by the relevant local IRBs in each site.

62 Background: The Comprehensive Geriatric Assessment (CGA) improves the outcomes of older patients with cancer, and by identifying of geriatric impairments the CGA can guide the development of supportive interventions. However, the implementation of these interventions in a real-world setting can be burdensome for patients, particularly when additional visits are required in an often frail population. Therefore, our team developed a collaborative model for home-based delivery of CGA-guided interventions. Methods: We performed a retrospective review of community-dwelling patients aged ≥ 70 years with an active cancer diagnosis who were deemed to be frail by a CGA and who received home-based CGA-guided supportive interventions under a collaborative care model established by the geriatric oncology and the palliative home care teams at Hartford HealthCare Cancer Institute between October 2020 and April 2022. The collaboration is based on multidisciplinary discussion of the CGA results / interventions and weekly rounds to discuss patient’s progress and emerging needs. Results: A total of 182 patients received a CGA during the study period, 54% (n = 99) were determined to be frail based on impairment in ≥ 7 geriatric domains. Among all eligible patients, 19 patients (19%) were included in the collaborative model. The median age of enrolled patients was 84 years (74-90), 12/19 (63%) had metastatic cancer, 7/19 (37%) received systemic treatment, and 8/19 (42%) received radiation. The average number of geriatric impairments per patients was 9.5 (7-12). Geriatric impairments addressed at home were skilled nursing (19/19), physical therapy (18/19), occupational therapy (12/19), speech-language-pathology (2/19), nutrition (5/19), or social worker (11/19) support at home. The average number of unplanned hospitalizations was 1.16 per patient (range 0-4), and the average unplanned emergency room visit was 0.89 per person (range 0-4) during study time. Transition to hospice occurred in 8/19 patients (42%), the median time to transition to hospice was 33.5 days (15-167). Conclusions: This study demonstrates the feasibility of a collaborative model for home-based geriatric oncology care in a real-world setting to help reduce the burden of care on patients and ensure patient-centered delivery of CGA-guided interventions. Findings underscore the need for future work to evaluate the impact of this novel geriatric oncology care model on patient outcomes.

Background Older adults (≥65 years) with gastrointestinal (GI) cancers who receive chemotherapy are at increased risk of hospitalization caused by treatment-related toxicity. Geriatric assessment (GA) has been previously shown to predict risk of toxicity in older adults undergoing chemotherapy. However, studies incorporating the GA specifically in older adults with GI cancers have been limited. This study sought to identify GA-based risk factors for chemotherapy toxicity–related hospitalization among older adults with GI cancers. Patients and Methods We performed a secondary post hoc subgroup analysis of two prospective studies used to develop and validate a GA-based chemotherapy toxicity score. The incidence of unplanned hospitalizations during the course of chemotherapy treatment was determined. Results This analysis included 199 patients aged ≥65 years with a diagnosis of GI cancer (85 colorectal, 51 gastric/esophageal, and 63 pancreatic/hepatobiliary). Sixty-five (32.7%) patients had ≥1 hospitalization. Univariate analysis identified sex (female), cardiac comorbidity, stage IV disease, low serum albumin, cancer type (gastric/esophageal), hearing deficits, and polypharmacy as risk factors for hospitalization. Multivariable analyses found that patients who had cardiac comorbidity (OR 2.48, 95% CI 1.13-5.42) were significantly more likely to be hospitalized. Conclusion Cardiac comorbidity may be a risk factor for hospitalization in older adults with GI cancers receiving chemotherapy. Further studies with larger sample sizes are warranted to examine the relationship between GA measures and hospitalization in this vulnerable population.

PURPOSE: Hospitalizations during cancer treatment are costly, can impair quality of life, and negatively affect therapy completion. Our objective was to identify risk factors for unplanned hospitalization among older adults receiving chemotherapy. METHODS: This is a secondary analysis of a multisite cohort study (N = 750) of patients ≥ 65 years of age evaluated with a geriatric assessment (GA) to predict chemotherapy toxicity. The primary outcome of this analysis was unplanned hospitalizations during treatment; the secondary outcome was length of stay (LOS) of the first hospitalization. Independent variables included pretreatment GA measures, laboratory values, cancer type and stage, and treatment intensity characteristics. We used logistic regression to estimate the odds of hospitalization and generalized linear models for LOS in multivariable analyses. RESULTS: The sample median age was 72 years (range, 65-94 years); 59% had stage IV disease. At least one unplanned hospitalization occurred in 193 patients (25.7%) during receipt of chemotherapy. In multivariable analyses controlling for cancer type, the following baseline characteristics were significantly associated with increased odds of hospitalization: needing help bathing or dressing (odds ratio [OR], 1.8; 95% CI, 1.0 to 3.1), polypharmacy (≥ 5 meds) (OR, 1.6; 95% CI, 1.1 to 2.4), more comorbid conditions (OR, 1.1; 95% CI, 1.0 to 1.3), availability of someone to take them to the doctor (OR, 2.0; 95% CI, 1.0 to 4.1), CrCl < 60 mL/min (OR, 1.7; 95% CI, 1.1 to 2.4), and albumin < 3.5 g/dL (OR, 1.8; 95% CI, 1.2 to 2.8). In multivariable analyses, older age, self-reported presence of liver or kidney disease, living alone and depressive symptoms were associated with longer LOS. CONCLUSION: Readily available GA variables and laboratory data, but not age, were associated with unplanned hospitalizations among older adults receiving chemotherapy. If validated, these data can inform prediction models and the design of interventions to decrease unplanned hospitalizations.

When the COVID-19 pandemic began, formal frameworks to collect data about affected patients were lacking. The COVID-19 and Cancer Consortium (CCC19) was formed to collect granular data on patients with cancer and COVID-19 at scale and as rapidly as possible. CCC19 has grown from five initial institutions to 125 institutions with >400 collaborators. More than 5,000 cases with complete baseline data have been accrued. Future directions include increased electronic health record integration for direct data ingestion, expansion to additional domestic and international sites, more intentional patient involvement, and granular analyses of still-unanswered questions related to cancer subtypes and treatments.

646 Background: Limited data guides the management of older adults with cancer, a patient population that continues to be under-represented in clinical trials. Comprehensive Genomic Profiling (CGP) drives the enrollment on biomarker-based trials and may inform treatment selection. This analysis aims to evaluate the use of CGP in older patients with gastrointestinal (GI) malignancies and to compare results of genomic profiling across age groups. Methods: Clinical CGP results derived from Next Generation Sequencing (NGS) of tumor tissue (n=92802) were reviewed for patients with GI malignancies. Genomic alterations (GAs) and complex signatures were identified, based on hybridization-captured, adapter ligation-based sequencing. Association between age group (< 65: n=51652; 65-74: n=28972; 75+: n=12178) and biomarkers of interests was evaluated using Chi-square test, adjusting for multiple testing using Bonferroni correction. Delay-adjusted incidence rates in populations included in the study were acquired from SEER Databases. Results: The majority of patients in the CGP cohort were 99%). An analysis of specific GAs among all the GI cancers analyzed showed an age-associated increase of high tumor mutational burden (≥10 mut/Mb) (TMB-H) (5.6% vs 6.6% vs 10.7% for respective age groups, p

Background Immune checkpoint inhibitors targeting PD-1/PD-L1 pathway demonstrated promising activities in variety of malignancies, however little is known regarding their efficacy in adults aged ≥65 years. Methods We conducted a systematic review and a study-level meta-analysis to explore efficacy of ICIs based on age, younger vs older than 65 years. We included in this analysis randomized controlled phase II or III studies in patients with metastatic solid tumors that compared efficacy of PD-1 or PD-L1 inhibitors to a non-PD-1/PD-L1 inhibitor. Aggregated estimates of overall survival (OS) and progression-free survival (PFS) are based on random/mixed effects (RE) models to allow for heterogeneity between the studies. Results Initial search identified 53 articles, 17 were randomized controlled trials that compared nivolumab, pembrolizumab or atezolizumab to chemotherapy or targeted therapy. Only 9 trials reported hazard ratiios (HR) for OS based on age and were included in this meta-analysis. Out of those studies seven reported HR for PFS but only 4 studies included subgroup-analysis based on age for PFS. The overall estimated random-effects HR for death was 0.64 with 95% CI of 0.54–0.76 in patients ≥65 years vs. 0.68 with 95% CI of 0.61–0.75 in patients

Purpose The purpose of this paper is to investigate and classify the defects on silicon-based power devices under extreme conditions. Design/methodology/approach Electrical characterization was performed on MOS devices to study their interface defects. The devices were subjected to a voltage or a current constraint to induce defects, and then measurements were done to detect the effects of those defects. Measurements include current voltage, capacitance and conductance characterization. The Hill–Coleman method was used to calculate the interface states density in each case. Findings It was found that most of the defects have energies within the upper band gap of the semiconductor. Originality value The method used in this paper allows the determination of any interface defects on a Si/SiO2 structure.

Current research efforts focusing on improving outcomes of older adults with cancer lack the appropriate infrastructure to support this growing need. The Cancer and Aging Group R21/33 National Institute of Health (NIH)/National Institute of Aging (NIA) grant aims to support development of geriatric oncology research through dedicated cores. The mission of the Core on Behavioral, Psychological, and Supportive Care Interventions will be to provide guidance in the field of non-pharmacological interventions. The Core will provide investigators with expertise, advocacy, and support in study design, development, and execution.

The excitement about immunotherapy is justified. Patients with advanced disease and limited life expectancy before immune checkpoint inhibitors are now having prolonged and sometimes complete responses to treatment; however, most patients do not respond to checkpoint inhibitors. The hope for a meaningful response with only a limited risk of high-grade toxicity generated a prognostic dilemma for patients with advanced cancers and their treating oncologists. Older adults with advanced cancers are at the intersection of multiple biologic and clinical factors that can influence the efficacy of immunotherapy. Treating physicians should take all of these elements into account when considering treatment options for an older adult with advanced disease. Oncologists should have an honest conversation with their patients regarding the uncertainty around the clinical profile of checkpoint inhibitors. Early high-quality goals of care discussions can help manage expectations of older adults with advanced cancer treated with immunotherapy. We review in this paper select clinical characteristics that are important to consider when evaluating an older adult for checkpoint inhibitor therapy. In addition, we discuss strategies to optimize goals of care discussion given the increasing complexity of prognostication in the immunotherapy era.

4128 Background: Pancreatic cancer (PC) is a challenging target for immunotherapy due to suppressive immune-microenvironment. Neoadjuvant chemoradiation (CRT) can increase the presence of tumor-infiltrating lymphocytes (TILs). We hypothesized that the combination of CRT and pembrolizumab can lead to further increase in TILs and their activation. Methods: Patients with resectable or borderline resectable PC were randomized 2:1 to the investigational treatment (Arm A) of pembrolizumab 200mg IV every 3 weeks concurrently with CRT (capecitabine 825 mg/m2 orally twice daily and radiation 50.4 Gy in 28 fractions over 28 days) or CRT only (Arm B) prior to surgical resection. The primary endpoints were treatment safety and density of TILs with the objective to estimate differences in TILs density between the investigational and the control arms. Immune cell densities were assessed using multiplexed immunofluorescence on resected tumor specimens. Densities of CD8+TILs were measured in 2-10 representative regions containing residual cancer per case and then averaged to obtain overall densities. The study was amended after enrollment of 37 patients to allow FOLFIRINOX prior to CRT, given changes in standard of care. Results: 37 patients were enrolled (24 Arm A and 13 Arm B). Post-neoadjuvant therapy, 13 patients had unresectable disease (9 on A and 4 on B), and 24 patients underwent surgery and were evaluable for the TILs primary endpoint (17 arm A and 7 arm B). The mean difference (A-B) in CD8+ cell density was 36 cells/mm2 (95% CI -85 to 157, stdev 130) (p 0.48). Additional analysis did not show significant differences in CD8+Ki67+ (activated cytotoxic T-cells), CD4+, and CD4+FOXP3+ (regulatory T cells), M1- or M2-like polarized macrophages, or granulocytes. The median recurrence free survival (RFS) was 18.2 months on Arm A and 14.1 on Arm B (p 0.41) and Overall Survival was 27.8 months on Arm A and 24.3 on Arm B (p 0.68) with a median follow up of 2.2 years. The most common grade 3 treatment-related toxicities were lymphopenia reported in 29% on Arm A and 31% on Arm B followed by diarrhea in 8% on Arm A attributed to CRT. There was only 1 DLT of increased ALT attributed to the combination on Arm A that resolved after holding the treatment and receiving steroids. There were no major surgical complications reported within 30 days post-surgery. Conclusions: The combination of CRT and pembrolizumab is safe. Preliminary analysis shows that the addition of pembrolizumab to CRT has minimal effects on several immune cell populations including CD8+TILs in the PC microenvironment. The study is currently enrolling 25 more patients who receive FOLFIRINOX prior to randomization to CRT+/- Pembrolizumab, which will help to dissect the immune modulatory effect of chemotherapy followed by CRT. Clinical trial information: NCT02305186.

388 Background: Pancreatic cancer is mostly diagnosed in patients (pts) aged ≥ 65 years and the mortality rate is the highest among older adults. As the population ages, it is expected that there will be a significant rise in the number of older pts with mPDAC but guidance regarding their management is limited as these pts are under-represented in clinical trials. The oncological care of older adults in daily practice is challenged by various age-related conditions. Therefore, a better understanding of the real-world population will help in the development of more effective tx strategies. This study describes the proportion of pts with mPDAC who were treated, the types of regimens received, and the associated survival outcomes by age at diagnosis. Methods: Data were extracted for pts diagnosed with mPDAC between Jan 2015 and Mar 2020 from the Flatiron Health database. Pts were stratified into three age groups at diagnosis: 70% of regimens prescribed to pts aged 80y+. The median OS (mOS) for patients treated with GNP, gem-mono, FOLFIRINOX, and liposomal irinotecan-based regimens are presented in the table. Conclusions: This study of treatment patterns among pts with mPDAC found that older pts were more likely to have a decreased performance status and are less likely to receive treatment. However, older adults who received systemic therapy had comparable survival outcomes to younger pts treated with a similar regimen. The results of this large descriptive analysis suggest that the treatment strategy of mPDAC should not be based on age but rather on an overall assessment of the performance/functional status and geriatric profile of older pts. [Table: see text]

e24024 Background: Older adults are at increased risk for postoperative delirium (POD). This risk might be higher in patients with cancer as underlying malignancy and its complications predispose individuals to develop delirium. Therefore, it is important to evaluate the onset of delirium in this patient population especially as POD is associated with increased risk of rehospitalization, decline in cognitive function, morbidity and mortality. Methods: We performed a retrospective review of patients aged ≥ 70 years admitted January 2017 through July 2019 to a tertiary care referral center for a high-risk surgery, defined as associated with a mortality risk greater than 1%. Cancer related surgeries (CRS) were identified through cross matching with Cancer Registry. Patients who had delirium assessment in the postoperative setting using the Confusion Assessment Method (CAM) were included. Chi-square tests of proportion, Wilcoxon Ranked Sum and multivariate logistic regression analyses were conducted. Results: A total of 2340 patients were included in this analysis, 315 of whom had (CRS). Overall, the age (median, IQR) of patients at surgery was 76 years (72-80) and the length of stay (LOS) was 7 (4-11) days. Patients receiving CRS were younger (75, 72-79) than those with non-CRS (76, 72-81) (p = 0.022); had a shorter post-operative LOS (4, 2-7 vs. 5, 3-8; p > 0.001), and were less likely to develop POD (7.6% vs. 16.1%; p < 0.001). Among patients receiving CSR, those who developed POD were older (78 vs. 74; p = 0.008) and had longer post-operative LOS (14.0 vs. 4.0; p < 0.001). Those having experienced radiotherapy (RT) for cancer within the year before the surgery, were more likely to develop POD (40.0% vs. 6.6% p. < 0.001). Chemotherapy in the year prior to surgery did not increase the risk of POD (6.1% vs. 7.8%; p = 0.721). Among those having non-CRS, a cancer diagnosis did not affect POD. A logistic regression predicting POD indicated that the lower likelihood of POD following CRS was independent of age or gender (OR = 0.40; p < .001); RT within one year prior was independent predictor of higher POD (OR = 5.48; p = 0.003). Our data presentation will include further analysis of POD risk factors. Conclusions: Although older adults receiving CRS were significantly less likely to develop delirium than patients with other high-risk surgeries, it is still important to evaluate POD in this population due to its impact of patients’ outcomes. Further understanding of POD risk factors, such as preoperative RT, would allow the development of targeted interventions that might lessen the risk.

89 Background: There is a lack of predictive markers informing on the risk of colitis in patients treated with immune checkpoint inhibitors (ICIs). The aim of this study was to identify potential factors associated with development of ICI colitis. Methods: We performed a retrospective analysis of melanoma patients at Dana-Farber Cancer Institute who received PD-1, CTLA-4, or combination blockade between May 2011 to October 2017. Clinical and laboratory characteristics associated with pathologically confirmed ICI colitis were evaluated using multivariate logistic regression analyses. External validation was performed on an independent cohort from Massachusetts General Hospital. Results: The discovery cohort included 213 patients of whom 37 developed ICI colitis (17%). The odds of colitis were higher in patients treated with ipilimumab either as monotherapy or in combination with nivolumab compared to those treated with pembrolizumab. Vitamin D use was recorded in 66/213 patients (31%) before starting ICIs. In multivariable regression analysis, vitamin D use conferred significantly reduced odds of developing ICI colitis (OR 0.35, 95% CI 0.1–0.9). These results were confirmed in the validation cohort of 169 patients of whom 49 developed ICI colitis (29%). Pretreatment neutrophil/lymphocyte ratio (NLR) ≥5 predicted reduced odds of colitis (OR 0.34, 95% CI 0.1–0.9) only in the discovery cohort. Conclusions: This is the first study to report that among patients treated with ICIs, vitamin D intake is associated with reduced risk for ICI colitis. This finding is consistent with prior reports of prophylactic use of vitamin D in ulcerative colitis and GVHD. This observation should be validated prospectively in future studies. [Table: see text]

The advent of immune checkpoint inhibitors (ICIs) has changed the landscape of cancer treatment. Older adults represent the majority of cancer patients; however, direct data evaluating ICIs in this patient population is lacking. Aging is associated with changes in the immune system known as "immunosenescence" that could impact the efficacy and safety profile of ICIs. In this paper, we review aging-associated changes in the immune system as they may relate to cancer and immunotherapy, with mention of the effect of chronic viral infections and frailty. Furthermore, we summarize the current clinical evidence of ICI effectiveness and toxicity among older adults with cancer.

Non-small cell lung cancer (NSCLC) is mostly a disease of older adults, with its incidence and mortality rates increasing exponentially after the age of 65 years. Immune checkpoint inhibitors (ICIs) have changed the scene of NSCLC treatment after a long and relatively stagnant period of standard treatment regimens. However, little is known about the specific impact of these agents in older adults for whom care is often complicated by a variety of syndromes. This underlines the importance of understanding the dynamics of new cancer treatments in an older patient population. In this paper, we will review ICIs' mechanism of action and data from published clinical trials relevant to older adults. In addition, we will discuss immune aging and treatment-related toxicity as potential challenges facing the use of checkpoint inhibitors in older adults with NSCLC.

Immune checkpoint inhibitors (ICIs) are based on the understanding that there are multilayered checks and balances which can be manipulated to unleash already existing, but paralyzed, immune responses to cancer. These agents are safer and more efficacious than classic cytotoxic drugs making them a very attractive therapeutic option, especially in older adults. Current available data do not suggest significant age-associated differences in the clinical profile of ICIs. It must be noted, however, that there is still relatively little information on the use of ICIs in adults over 75years of age and aging is associated with a decline in the immune system or "immunosenescence" which theoretically can reduce the efficacy of these immune based therapies. In this paper, we review the mechanism of action of ICIs, current clinical data on their use in older adults, and age-associated immune changes that might have a direct impact on their activity in this population. We chose to focus on mainly adaptive cellular immunity, and especially on components of the immune system that are implicated directly in the immune checkpoint process.

Cancer is primarily a disease of older adults. The treatment of advanced stage tumors usually involves the use of systemic agents that may be associated with significant risk of toxicity, especially in older patients. Immune checkpoint inhibitors are newcomers to the oncology world with improved efficacy and better safety profiles when compared to traditional cytotoxic drugs. This makes them an attractive treatment option. While there are no elderly specific trials, this review attempts to look at the current available data from a geriatric oncology perspective. We reviewed data from phase III studies that led to newly approved indications of checkpoint inhibitors in non-small cell lung cancer, melanoma, and renal cell cancer. Data were reviewed with respect to response, survival, and toxicity according to three groups:65 years, 65-75 years, and75 years. Current literature does not allow one to draw definitive conclusions regarding the role of immune checkpoint inhibitors in older adults. However, they may offer a potentially less toxic but equally efficacious treatment option for the senior adult oncology patient.

e19559Background: Patients taking ibrutinib are at increased risk of bleeding and atrial fibrillation / flutter (AFF). Data regarding safety of ibrutinib is mostly based on information from clinica...

10052Background: The prevalence of e-cigarette use, and its impact on smoking cessation, among cancer survivors in the United States is unknown. We sought to estimate the prevalence of e-cigarette ...

125 Background: Immune Checkpoint Inhibitors (ICIs) are used to treat patients with a wide spectrum of malignancies. Individuals enrolled in clinical trials are usually more fit compared to patients seen in everyday practice. Therefore, it is important to evaluate the safety profile of these agents in real-world data. In addition, it is not clear if the safety of these agents is similar across all age groups. Methods: We reviewed the FDA Adverse Event Reporting System (FAERS) for adverse events associated with the use of PD-1 inhibitors (nivolumab and pembrolizumab); PD-L1 inhibitor (atezolizumab); and CTLA-4 inhibitor (ipilimumab). Our analysis was restricted to reports that included only an ICI as a suspect agent. For each agent, we performed a descriptive analysis of hospitalization (HO) and death (DE) outcomes, as well as select adverse events of special interest (AESI). We compared the distribution of each outcome within age groups ( < 65 years; 67-75; > 75) using Mantel-Haenszel chi -quare test for trend. Results: A total of 23,586 safety reports were included in our analysis. 415 for atezolizumab, 10,026 for nivolumab, 4,808 for pembrolizumab, 6,339 for ipilimumab, and 1,988 for the combination nivolumab plus ipilimumab. Increased age was associated with a statistically significant trend of more hospitalizations for all drugs except for the combination nivolumab plus ipilimumab where hospitalization rate was high ( > 80%) but similar across all age groups. Prevalence of any of the AESI was higher as age increased for all drugs (p < 0.0001) except for atezolizumab (p 0.12) and combination nivolumab plus ipilimumab (p 0.488). Proportion of older patients who experienced death was higher for pembrolizumab (p < 0.001), ipilimumab (p 0.002), and combination nivolumab plus ipilimumab (p < 0.001). Conclusions: Our analysis suggests that among patients treated with ICI, older individuals receiving pembrolizumab, Nivolumab or ipilimumab were more likely to develop immune related AEs, and to be hospitalized. An increased rate of death with higher age was seen with the use of pembrolizumab, ipilimumab, and combination nivolumab + ipilimumab. Older patients treated with ICIs should be monitored carefully for treatment-related AEs.

e21544 Background: Immune checkpoint inhibitors (ICIs) have a promising activity in variety of malignancies however little is known regarding their efficacy and toxicity profile in older adults (≥65 yo). Accordingly, we performed a meta-analysis of published trials using anti-PD-1 or PD-L1 to define the activity of these agents in this subset of patients. Methods: We conducted a search using PubMed and Web of Science databases for randomized controlled trials (RCTs) of PD-1 and PD-L1 inhibitors including nivolumab (N), pembrolizumab (P), and atezolizumab (A). We then identified the studies that reported a subgroup analysis of overall survival (OS) based on an age cutoff. Results: We identified a total of 17 RCTs that compared N, P and A to chemotherapy or targeted therapy. Out of those trials only 9 reported hazard ratio (HR) based on age and were included in this meta-analysis. These trials treated a total of 5033 patients including 2315 patient ≥65 yo (46%). The overall estimated, random-effects hazard ratio (HR) for death was 0.69 with 95% CI of 0.63 -0.74 (p < 0.0001) in the general population favoring ICIs. Based on the selected trials, there was evidence of a 31% reduction in the hazard of death with PD1/PDL1 inhibitors compared with chemo/targeted therapy. This OS benefit persisted when the analysis was done based on disease type (NSCLC or others) or the drug target (PD-1 or PD-L1). Analysis based on age cutoff of 65 yo showed that the efficacy of PD-1 and PD-L1 inhibitors did not vary for older or younger patients. The overall estimated random-effects HR was 0.64 with 95% CI of 0.54 -0.76 in patients ≥65 yo vs. 0.68 with 95% CI of 0.61-0.75 in patients < 65 yo. Data regarding toxicity based on age was available only for 3 trials. The rate of grade 3-4 toxicities was comparable between the 2 groups (45-50% in patients ≥ 65 compared to 37.1-50% in patients < 65). Conclusions: PD-1 and PD-L1 inhibitors efficacy using N, P or A is comparable in older and younger adults when using an age cutoff of 65 years. Future ICIs trials should report efficacy and toxicity based on age.

10057Background: Older patients with cancer are at increased risk of hospitalizations during cancer treatment. Our objective was to identify risk factors for unplanned hospitalization among older a...