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Background: Certain populations have been historically underrepresented in clinical trials. Broadening eligibility criteria is one approach to inclusive clinical research and achieving enrollment goals. How broadened trial eligibility criteria affect the diversity of eligible participants is unknown. Methods: Using a nationwide electronic health record-derived deidentified database, we identified a retrospective cohort of patients diagnosed with 22 cancer types between April 1, 2013 and December 31, 2022 who received systemic therapy (N=235,234) for cancer. We evaluated strict versus broadened eligibility criteria using performance status and liver, kidney, and hematologic function around first line of therapy. We performed logistic regression to estimate odds ratios for exclusion by strict criteria and their association with measures of patient diversity, including sex, age, race or ethnicity, and area-level socioeconomic status (SES); estimated the impact of broadening criteria on the number and distribution of eligible patients; and performed Cox regression to estimate hazard ratios for real-world overall survival (rwOS) comparing patients meeting strict versus broadened criteria. Results: When applying common strict cutoffs for eligibility criteria to patients with complete data and weighting each cancer type equally, 48% of patients were eligible for clinical trials. Female (odds ratio, 1.30; 95% confidence interval [CI], 1.25 to 1.35), older (age 75+ vs. 18 to 49-years old: odds ratio, 3.04; 95% CI, 2.85 to 3.24), Latinx (odds ratio, 1.46; 95% CI, 1.39 to 1.54), non-Latinx Black (odds ratio, 1.11; 95% CI, 1.06 to 1.16), and lower-SES patients were more likely to be excluded using strict eligibility criteria. Broadening criteria increased the number of eligible patients by 78%, with the strongest impact for older, female, non-Latinx Black, and lower-SES patients. Patients who met only broadened criteria had worse rwOS versus those with strict criteria (hazard ratio, 1.31; 95% CI, 1.27 to 1.34). Conclusions: Data-driven evaluation of clinical trial eligibility criteria may optimize the eligibility of certain historically underrepresented groups and promote access to more inclusive trials. (Sponsored by Flatiron Health.) [ABSTRACT FROM AUTHOR]

Background: Older women with breast cancer frequently experience toxicity‐related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low‐cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity‐related hospitalization during adjuvant chemotherapy for breast cancer. Methods: In a prospective study of women >65 years old with stage I–III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity‐related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates. Results: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity‐related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity‐related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66–11.54, p =.003). Conclusions: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4‐fold increased risk of toxicity‐related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors. In this study, nearly one in four older women with early breast cancer experienced toxicity‐related hospitalization during chemotherapy. Women who reported more than one fall in the 6 months leading up to chemotherapy had a greater than four times higher odds of experiencing toxicity‐related hospitalization during treatment than women who reported no falls. [ABSTRACT FROM AUTHOR]

This review describes the barriers and challenges faced by older adults of color with cancer and highlights methods to improve their overall care. In the next decade, cancer incidence rates are expected to increase in the United States for people aged ≥65 years. A large proportion will be older adults of color who often have worse outcomes than older White patients. Many issues contribute to racial disparities in older adults, including biological factors and social determinants of health (SDOH) related to healthcare access, socioeconomic concerns, systemic racism, mistrust, and the neighborhood where a person lives. These disparities are exacerbated by age‐related challenges often experienced by older adults, such as decreased functional status, impaired cognition, high rates of comorbidities and polypharmacy, poor nutrition, and limited social support. Additionally, underrepresentation of both patients of color and older adults in cancer clinical research results in a lack of adequate data to guide the management of these patients. Use of geriatric assessments (GA) can aid providers in uncovering age‐related concerns and personalizing interventions for older patients. Research demonstrates the ability of GA‐directed care to result in fewer treatment‐related toxicities and improved quality of life, thus supporting the routine incorporation of validated GA into these patients' care. GA can be enhanced by including evaluation of SDOH, which can help healthcare providers understand and address the needs of older adults of color with cancer who face disparities related to their age and race. [ABSTRACT FROM AUTHOR]

A modified version of the PGDx elioTM Plasma Resolve assay was validated as a laboratory-developed test (LDT) for clinical use in the Molecular Diagnostics Laboratory at Fox Chase Cancer Center. The test detects single nucleotide variants (SNVs) and small insertions and deletions (indels) in 33 target genes using fragmented genomic DNA extracted from plasma. The analytical performance of this assay was assessed with reference standard DNA and 29 samples from cancer patients and detected 66 SNVs and 23 indels. Using 50 ng of input DNA, the sensitivity was 95.5% to detect SNVs at 0.5% allele frequency, and the specificity was 92.3%. The sensitivity to detect indels at 1% allele frequency was 70.4%. A cutoff of 0.25% variant allele frequency (VAF) was set up for diagnostic reporting. An inter-laboratory study of concordance with an orthologous test resulted in a positive percent agreement (PPA) of 91.7%. [ABSTRACT FROM AUTHOR]

The primary aim of this study is to characterize long-term quality of life (QOL) in patients with esophageal and gastroesophageal junction (EGEJ) cancers who underwent curative intent treatment. EGEJ survivors were recruited to participate in a one-time cross-sectional survey study using validated questionnaires assessing QOL. Chart review was conducted for patient demographics and clinical characteristics. Spearman correlation coefficients, Wilcoxon signed-rank test, and Fisher's exact test were used to assess relationships between patient characteristics and long-term outcomes. QOL was relatively high in this sample, as evidenced by high median scores on the functional scales and low median scores in the symptom domains of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, with an overall median global health score of 75.0 (range 66.7-83.3). Patients using opiates at the time of survey reported lower role functioning (P =.004), social functioning (P =.052), and overall global health (P =.041). Younger patients had significantly higher rates of reflux (P =.019), odynophagia (P =.045), choking (P =.005), and cough (P =.007). Patients using opiates or of younger age had lower QOL and higher symptoms in this cohort of long-term EGEJ survivors. [ABSTRACT FROM AUTHOR]

Opinion statement: The need for evidence-based data in the rapidly growing group of older patients is vast and more elderly-specific studies are desperately needed, for which there is clear demand from both patients and providers. Notably, many of the studies discussed in this review included unplanned subset analyses based on age and/or were not originally stratified by age; therefore, these data, particularly overall survival data, need to be interpreted with some caution as they may not be statistically valid based on the initial trial design and statistical plan. As we await data from ongoing elderly-specific trials, our recommendation for managing older patients with CRC should include geriatric screening tools (e.g., CSGA, VES-13, G8, CARG, CRASH) to help guide treatment adjustments for improved tolerability without sacrificing efficacy. For patients with a positive screen for significant geriatric concerns, a full geriatric assessment is recommended to guide treatment approach and supportive care. Prior data support the use of all approved medications for CRC in older adults who are fit; however, treatment breaks and dose attenuation with potential escalation are reasonable options for these patients. Ultimately, management decisions in the care of older adults with mCRC must be made through shared decision-making with the patient with consideration for the patient's functional status, comorbidities, goals of care, social support, as well as potential toxicities and possible effect on QoL. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) carries a high risk of venous thromboembolism (VTE). Several risk assessment models (RAMs) predict benefit of thromboprophylaxis in solid tumors; however, none are verified in metastatic pancreatic cancer (mPC). Methods: A retrospective mPC cohort treated at an academic cancer center from 2010 to 2016 was investigated for VTE incidence (VTEmets). Multivariable regression analysis was used to assess multiple VTE risk factors. Overall survival (OS) was compared between mPC groups with and without VTE. Survival was analyzed using Kaplan–Meier survival plots and Cox proportional hazards regressions. Results: 400 mPC patients (median age 66; 52% males) were included. 87% had performance status of ECOG 0–1; 70% had advanced stage at PC diagnosis. Incidence of VTEmets was 17.5%; median time of occurrence 3.48 months after mPC diagnosis. Survival analysis started at median VTE occurrence. Median OS was 10.5 months in VTEmets vs. 13.4 in non‐VTE group. Only advanced stage (OR 3.7, p =.001) correlated with increased VTE risk. Conclusions: The results suggest mPC carries a significant VTE burden. VTE predicts poor outcomes from the point of median VTE occurrence. Advanced stage disease is the strongest risk factor. Future studies are needed to define risk stratification, survival benefit, and choice of thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Background Despite national guideline recommendations for universal biomarker testing (KRAS , NRAS , BRAF , and mismatch repair and microsatellite instability [MMR/MSI]) in all patients with metastatic colorectal cancer (mCRC), little is known regarding adherence to these recommendations in routine practice. Methods We retrospectively reviewed patients with mCRC diagnosed between January 1, 2013, and December 27, 2018, from a de-identified electronic health record–derived database. We analyzed disparities in KRAS , NRAS , BRAF , and MMR/MSI testing by race, age, sex, and insurance status using χ2 tests and t tests. We evaluated changes in biomarker testing over time with attention to changes around dates of landmark publications and guideline updates using χ2 tests and Cochran-Armitage tests. Results A total of 20 333 patients were identified of which 66.6% had test results for any biomarker. Rates of test results for all 4 biomarkers statistically significantly increased over time (P  < .001). However, as of June 30, 2018, the rate of test results was only 46% for NRAS , 56% for KRAS , and 46% for BRAF. As of December 31, 2017, the rate of MMR/MSI testing was 59%. Higher documented testing rates were associated with younger age, lower Eastern Cooperative Oncology Group performance status, and commercial insurance. There were no clinically meaningful and/or statistically significant differences in documented testing rates by tumor sidedness, race, sex, or initial stage. Conclusions Increased rates of documented testing for NRAS , BRAF , and MMR/MSI in mCRC was seen between 2013 and 2018 reflecting adoption of guideline recommendations. However, the rate of documented testing remains lower than expected and warrants additional research to understand the extent to which this may represent a clinical practice quality concern. [ABSTRACT FROM AUTHOR]

The use of immune checkpoint inhibitors is increasing in clinical practice. While they have provided significant benefit to many patients, a new category of adverse effects, immune-related adverse effects, has emerged with their use. These effects can range from mild to severe and affect nearly every organ system. A man in his 70swith metastatic gastro-oesophageal junction adenocarcinoma who received one cycle of third-line pembrolizumab presented after three episodes of transient left facial paresthesia, the last of which extended to the left extremities and disturbed peripheral vision of the left eye. He was found to have subclinical seizures and cerebrospinal fluid positive for Ma2/Ta paraneoplastic antibodies, consistent with paraneoplastic limbic encephalitis. We describe an unusual presentation of paraneoplastic limbic encephalitis. This case adds to the limited literature describing the association of paraneoplastic limbic encephalitis and treatment with immune checkpoint inhibitors as well as the observed associations with immune-related adverse events and treatment responses. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA) is a component of cell-free DNA (cfDNA) that is shed by malignant tumors into the bloodstream and other bodily fluids. ctDNA can comprise up to 10% of a patient's cfDNA depending on their tumor type and burden. The short half-life of ctDNA ensures that its detection captures tumor burden in real-time and offers a non-invasive method of repeatedly evaluating the genomic profile of a patient's tumor. A challenge in ctDNA detection includes clonal hematopoiesis of indeterminate potential (CHIP), which can be distinguished from tumor variants using a paired whole-blood control. Most assays for ctDNA quantification rely on measurements of somatic variant allele frequency (VAF), which is a mutation-dependent method. Patients with certain types of solid tumors, including colorectal cancer (CRC), can have levels of cfDNA 50 times higher than healthy patients. ctDNA undergoes a precipitous drop shortly after tumor resection and therapy, and rising levels can foreshadow radiologic recurrence on the order of months. The amount of tumor bulk required for ctDNA detection is lower than that for computed tomography (CT) scan detection, with ctDNA detection preceding radiologic recurrence in many cases. cfDNA/ctDNA can be used for tumor molecular profiling to identify resistance mutations when tumor biopsy is not available, to detect minimal residual disease (MRD), to monitor therapy response, and for the detection of tumor relapse. Although ctDNA is not yet implemented in clinical practice, studies are ongoing to define the appropriate way to use it as a tool in the clinic. In this review article, we examine the general aspects of ctDNA, its status as a biomarker, and its role in the management of early (II–III) and late (IV; mCRC) stage colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

Background The COVID-19 pandemic has led to delays in patients seeking care for life-threatening conditions; however, its impact on treatment patterns for patients with metastatic cancer is unknown. We assessed the COVID-19 pandemic's impact on time to treatment initiation (TTI) and treatment selection for patients newly diagnosed with metastatic solid cancer. Methods We used an electronic health record–derived longitudinal database curated via technology-enabled abstraction to identify 14 136 US patients newly diagnosed with de novo or recurrent metastatic solid cancer between January 1 and July 31 in 2019 or 2020. Patients received care at approximately 280 predominantly community-based oncology practices. Controlled interrupted time series analyses assessed the impact of the COVID-19 pandemic period (April-July 2020) on TTI, defined as the number of days from metastatic diagnosis to receipt of first-line systemic therapy, and use of myelosuppressive therapy. Results The adjusted probability of treatment within 30 days of diagnosis was similar across periods (January-March 2019 = 41.7%, 95% confidence interval [CI] = 32.2% to 51.1%; April-July 2019 = 42.6%, 95% CI = 32.4% to 52.7%; January-March 2020 = 44.5%, 95% CI = 30.4% to 58.6%; April-July 2020 = 46.8%, 95% CI= 34.6% to 59.0%; adjusted percentage-point difference-in-differences = 1.4%, 95% CI = −2.7% to 5.5%). Among 5962 patients who received first-line systemic therapy, there was no association between the pandemic period and use of myelosuppressive therapy (adjusted percentage-point difference-in-differences = 1.6%, 95% CI = −2.6% to 5.8%). There was no meaningful effect modification by cancer type, race, or age. Conclusions Despite known pandemic-related delays in surveillance and diagnosis, the COVID-19 pandemic did not affect TTI or treatment selection for patients with metastatic solid cancers. [ABSTRACT FROM AUTHOR]

Background Geriatric assessment (GA) is recommended for evaluating fitness of an older adult with cancer. Our objective was to prospectively evaluate the gaps that exist in the assessment of older adults with metastatic breast cancer (OA-MBC) in community practices (CP). Methods Self-administered GA was compared to provider's assessment (PA) of patients living with MBC aged ≥65 years treated in CP Providers were blinded to the GA results until PA was completed. McNemar's test was used to detect differences between PA and GA. Results One hundred patients were enrolled across 9 CP (median age 73.9). Geriatric assessment detected a total of 356 abnormalities in 96 patients; of which, 223 required interventions. African American and widowed/single patients were more likely to have abnormalities identified by GA. On average, across 100 patients, PA did not detect 25.5% of GA-detected abnormalities, mostly in functional status, social support, nutrition, and cognition. These differences were less pronounced among providers with more clinical experience. Patients with abnormal Timed Up and Go tests more likely had additional abnormalities in other domains, and more abnormalities that were not identified by PA. Providers were "surprised" by GA results in 33% of cases, mainly with cognitive or social support findings, and reported plans for management change for 39% of patients based on GA findings. Conclusions Including a GA in the care of OA-MBC in CP is beneficial for the detection of multiple abnormalities not detected by routine PA. [ABSTRACT FROM AUTHOR]

Opinion statement: Pancreatic cancer is increasing in incidence in the USA. This disease disproportionately affects older adults, and as the percentage of adults > 65 years old increases with the aging of the baby boomers, the prevalence is expected to rise over the coming decade. These patients are often more susceptible to disease-related symptoms and have less ability to withstand both cancer and treatment-related side effects. Therefore, it is imperative that treating physicians thoughtfully consider their recommended treatment approach towards this vulnerable patient population. This review focuses on the current state of research of older adults with pancreatic adenocarcinoma, highlighting deficiencies in the representation of this patient population in clinical trials. It is vital that the treating physicians take a nuanced approach towards therapy of localized and metastatic disease in geriatric patients. A one size fits all treatment algorithm is no longer appropriate in any cancer patient, let alone the elders who are particularly vulnerable to developing treatment-related toxicities. To help guide therapy decisions, it is important to perform a comprehensive geriatric assessment which may uncover unexpected frailty and lead to a change in the recommended treatment approach. In this way, we can support older adults during therapy for this aggressive malignancy and provide optimal care. [ABSTRACT FROM AUTHOR]

Cholangiocarcinomas are rare tumors originating at any point along the biliary tree. These tumors often pose significant challenges for diagnosis and treatment, and often carry a poor prognosis. However, in recent years, studies have identified significant molecular heterogeneity with up to 50% of tumors having detectable mutations, leading to the guideline recommendations for molecular testing as part of the diagnostic workup for these tumors. In addition, better classification of these tumors and understanding of their biology has led to new drugs being approved for treatment of this resistant tumor. This manuscript will provide a comprehensive review of the epidemiology, risk factors, diagnostic approach, molecular classification, and treatment options for patients with advanced cholangiocarcinomas. [ABSTRACT FROM AUTHOR]

Background Gemcitabine and nab-paclitaxel (GA) is a first-line treatment for patients with metastatic pancreatic cancer (mPDAC). The traditional dosing schedule of GA is days 1, 8, and 15 of a 28-day cycle. Frequently, older adults are given a modified dosing schedule using 2 doses per cycle because of toxicity. We retrospectively analyzed treatment patterns and outcomes of older adults with mPDAC given these 2 dosing schedules. Methods Patients 65 years or older with mPDAC treated with GA in a nationwide real-world database between January 1, 2014, and May 31, 2019, were included. Demographic, disease, and treatment information were collected. Patients were grouped by dosing at treatment initiation (traditional vs modified dosing schedules). Endpoints were time on treatment (TOT) and overall survival (OS) in patients receiving at least 2 cycles. All statistical tests were 2-sided. Results 1317 patients were included (traditional dosing schedule: n = 842; modified dosing schedule: n = 475). Median age at diagnosis was 72 and 73 years for traditional and modified dosing schedules, respectively (P <.001), but sex, race, and performance status were not statistically significantly different. The median TOT and OS were better for the traditional vs modified dosing schedule (unadjusted median TOT, first-line = 4.18 vs 3.26 mo, P =.04; OS = 9.44 vs 7.63 mo, P =.003). Conclusion In this real-world cohort, treatment of older mPDAC patients with a modified dosing schedule of GA resulted in shorter TOT and worse OS vs a traditional dosing schedule. With the caveats of potential confounding that exist in a nonrandomized retrospective database, these results suggest that dose intensity may be important, and prospective studies are necessary to ensure we treat our patients most effectively. [ABSTRACT FROM AUTHOR]

Background: Patients with advanced esophageal cancer carry poor prognoses; limited data exist to guide second-line therapy in the metastatic setting. Paclitaxel has been used yet is associated with limited efficacy. There is preclinical evidence of synergy between paclitaxel and cixutumumab, a monoclonal antibody targeting insulin-like growth factor-1 receptor. We conducted a randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) in the second-line for patients with metastatic esophageal or gastroesophageal junction (GEJ) cancers. Methods: The primary endpoint was progression-free survival (PFS); 87 patients (43 in arm A, 44 in arm B) were treated. Results: Median PFS was 2.6 months in arm A [90% CL 1.8-3.5] and 2.3 months in arm B [90% 2.0-3.5], P =.86. Stable disease was observed in 29 (33%) patients. Objective response rates for Arms A and B were 12% [90% CI, 5-23%] and 14% [90% CI, 6-25%]. Median overall survival was 6.7 months [90% CL 4.9-9.5] in arm A and 7.2 months [90% CL 4.9-8.1] in arm B, P = 56. Conclusion: The addition of cixutumumab to paclitaxel in second-line therapy of metastatic esophageal/GEJ cancer was well tolerated but did not improve clinical outcomes relative to standard of care (ClinicalTrials.gov Identifier: NCT01142388). Paclitaxel has been used for second-line treatment of esophageal cancer, with limited efficacy. Considering the preclinical evidence of synergy between paclitaxel and cixutumumab, this randomized phase II trial of paclitaxel (arm A) versus paclitaxel plus cixutumumab (arm B) was conducted. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]