Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Performance Status Restriction in Phase III Cancer Clinical Trials.

BACKGROUND: Patients with good performance status (PS) tend to be favored in randomized clinical trials (RCTs), possibly limiting the generalizability of trial findings. We aimed to characterize trial-related factors associated with the use of PS eligibility criteria and analyze patient accrual breakdown by PS. METHODS: Adult, therapeutic, multiarm phase III cancer-specific RCTs were identified through ClinicalTrials.gov. PS data were extracted from articles. Trials with a PS restriction ECOG score ≤1 were identified. Factors associated with PS restriction were determined, and the use of PS restrictions was analyzed over time. RESULTS: In total, 600 trials were included and 238,213 patients had PS data. Of those trials, 527 studies (87.8%) specified a PS restriction cutoff, with 237 (39.5%) having a strict inclusion criterion (ECOG PS ≤1). Enrollment criteria restrictions based on PS (ECOG PS ≤1) were more common among industry-supported trials (P<.001) and lung cancer trials (P<.001). Nearly half of trials that led to FDA approval included strict PS restrictions. Most patients enrolled across all trials had an ECOG PS of 0 to 1 (96.3%). Even among trials that allowed patients with ECOG PS ≥2, only 8.1% of those enrolled had a poor PS. Trials of lung, breast, gastrointestinal, and genitourinary cancers all included <5% of patients with poor PS. Finally, only 4.7% of patients enrolled in trials that led to subsequent FDA approval had poor PS. CONCLUSIONS: Use of PS restrictions in oncologic RCTs is pervasive, and exceedingly few patients with poor PS are enrolled. The selective accrual of healthier patients has the potential to severely limit and bias trial results. Future trials should consider a wider cancer population with close toxicity monitoring to ensure the generalizability of results while maintaining patient safety.

The utilization and impact of adjuvant therapy following neoadjuvant therapy and resection of pancreatic adenocarcinoma: does more really matter?

BACKGROUND: Although neoadjuvant therapy is increasingly administered to patients with pancreatic ductal adenocarcinoma (PDAC), the impact of additional adjuvant therapy (AT) following resection is not well defined. METHODS: The National Cancer Database (NCDB) was queried for patients who received neoadjuvant therapy followed by R0 or R1 resection for PDAC. Factors influencing survival, including the receipt of AT were evaluated. RESULTS: Of patients receiving neoadjuvant therapy and resection 680 (33.8%) received AT and 1331 (66.2%) did not. For R0 resected patients (n = 1800), lymphovascular invasion (HR 1.24, p = 0.034) and increasing N classification (N1: HR 1.27, p = 0.019; N2: HR 1.51, p = 0.004) were associated with increased risk of death while AT was not associated with improved overall survival (OS) (HR 0.88, p = 0.179). Following R1 resection (n = 211), AT was associated with reduced risk of death (HR 0.57, p = 0.038). Within propensity matched cohorts, median OS for patients receiving and not receiving AT was 32.1 and 30.0 months after R0 resection (p = 0.184), and 23.6 and 20.5 months after R1 resection (p = 0.005). CONCLUSION: This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection.

Definitive Pelvic Radiotherapy and Survival of Patients With Newly Diagnosed Metastatic Anal Cancer.

Background: Chemotherapy with or without pelvic radiotherapy (RT) is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for metastatic anal cancer (MAC), despite limited clinical evidence for RT in this setting. In addition, increasing evidence shows that local therapies, including RT, may increase patient survival for some types of metastatic cancers. The purpose of this study was to evaluate the patterns of care and association between definitive pelvic RT and overall survival (OS) for patients with MAC. Methods: The National Cancer Database was analyzed to evaluate OS of patients with newly diagnosed MAC treated with chemotherapy with or without pelvic RT. Those who did not undergo treatment, treated with surgery, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results: From 2004 through 2015, 437 patients received chemotherapy alone and 1,020 received pelvic chemoradiotherapy (CRT). At a median follow-up of 17.3 months, CRT was associated with improved OS on univariate (P<.001) and multivariate analysis (hazard ratio [HR], 0.70; 95% CI, 0.61-0.81; P<.001). Propensity score-matched analysis demonstrated superior median survival (21.3 vs 15.9 months) and 2-year OS rates (46% vs 34%) with CRT compared with chemotherapy alone (P<.001). Landmark analyses limited to long-term survivors of ≥1, ≥2, and ≥4 years showed improved OS with CRT in all subsets (all P<.05). CRT with therapeutic doses (≥45 Gy) was associated with longer median survival than palliative doses (<45 Gy) and chemotherapy alone (24.9 vs 10.9 vs 15.6 months, respectively; P<.001). The benefit of CRT was present among not only those with distant lymph node metastasis (HR, 0.63; P=.04) but also those with distant organ disease (HR, 0.74; P<.001). Conclusions: In this large hypothesis-generating analysis, patients with newly diagnosed MAC who received definitive pelvic RT with chemotherapy lived significantly longer than those who received chemotherapy alone. Prospective trials evaluating definitive local RT for MAC are warranted.

Real-world treatment patterns among patients with unresected stage III non-small-cell lung cancer.

Aim: Little is known about recent treatment patterns among patients with unresected stage III NSCLC in the real world. This retrospective study used medical records from USA community oncology practices to address this knowledge gap. Materials & methods: Eligible patients were stage III NSCLC adults diagnosed between 1 January 2011 and 1 March 2016 without surgical resection. Treatment patterns were assessed across three progression intervals, from stage III diagnosis through third progression. Results: The most common regimen in interval 1 was platinum doublet chemotherapy + radiation therapy, in interval 2 was chemotherapy only, and in interval 3 was non-platinum chemotherapy monotherapy. Conclusion: Most patients were treated following national guidelines, but important unmet needs remain.

Treatment of muscle invasive bladder cancer in the elderly: navigating the trade-offs of risk and benefit.

PURPOSE: Despite the fact that bladder cancer patients have the highest median age of any type of cancer, older patients with muscle invasion are often under-treated. METHODS: In this review, we report the most up to date literature on the patterns of care and treatment of older patients with muscle invasive bladder cancer. Data on under-treatment, geriatric principles, cystectomy, perioperative chemotherapy, and bladder preservation for older patients are presented and analyzed. CONCLUSION: Chronologic age should not exclude patients from curative-intent therapy. Functional age as determined by geriatric assessments and multidisciplinary evaluation can help clinicians decide on the best course of treatment for individual patients. Cystectomy, perioperative chemotherapy, and curative-intent bladder preservation are reasonable options in healthy older adults. Observation should be limited to patients with extremely poor performance status and very limited life expectancy.

Hypofractionation for breast cancer: lessons learned from our neighbors to the north and across the pond.

Adjuvant whole breast irradiation was established within the standard of care for breast-conserving therapy in the early 1980s, following the results of major randomized trials comparing mastectomy vs breast-conserving surgery and radiation. Since that time, techniques and treatment strategies have evolved, but one major thread that carries forward is the need to balance cost, efficacy, complications, and convenience. Fortunately, data from randomized trials conducted in Canada and Great Britain provide a solid framework for the consideration of hypofractionated radiation in the treatment of breast cancer. In this review we discuss the rationale and underlying radiobiologic concepts for hypofractionation, and review the clinical trials and American Society for Radiation Oncology (ASTRO) guidelines supporting this approach. We also review the practical considerations for treatment planning, including dosimetric criteria and how to approach treatment of the node-positive patient. In the current era of healthcare reform and cost awareness, thoughtful utilization of hypofractionation may offer considerable savings to individual patients and the healthcare system--without compromising clinical outcomes or quality of life.

Extended Follow-Up Outcomes from Pooled Prospective Studies Evaluating Efficacy of Interstitial Alpha Radionuclide Treatment for Skin and Head and Neck Cancers.

The initial favorable efficacy and safety profile for Alpha DaRT have been demonstrated (NCT04377360); however, the longer-term safety and durability of the treatment are unknown. This pooled analysis of four prospective trials evaluated the long-term safety and efficacy of Alpha DaRT for the treatment of head and neck or skin tumors. A total of 81 lesions in 71 patients were treated across six international institutions, with a median follow-up of 14.1 months (range: 2-51 months). Alpha DaRT sources were delivered via a percutaneous interstitial technique and placed to irradiate the tumor volume with the margin. The sources were removed two to three weeks following implantation. A complete response was observed in 89% of treated lesions (n = 72) and a partial response in 10% (n = 8). The two-year actuarial local recurrence-free survival was 77% [95% CI 63-87]. Variables, including recurrent versus non-recurrent lesions, baseline tumor size, or histology, did not impact long-term outcomes. Twenty-seven percent of patients developed related acute grade 2 or higher toxicities, which resolved with conservative measures. No grade 2 or higher late toxicities were observed. These data support the favorable safety profile of Alpha DaRT, which is currently being explored in a pivotal US trial.

Phase 2 study of pre-excision single-dose intraoperative radiation therapy for early-stage breast cancers: six-year update with application of the ASTRO accelerated partial breast irradiation consensus statement criteria.

BACKGROUND: Intraoperative radiation therapy (IORT) allows delivery of high-dose radiation at the time of lumpectomy, potentially sparing adjuvant daily radiation. A phase 2 study of pre-excision IORT was performed for early-stage breast cancer. METHODS: Patients ≥ 48 years of age with invasive ductal carcinoma, ≤ 3 cm, and clinically node-negative were eligible for this study, which was approved by institutional review board. Ultrasound was used to select electron energy and cone size to cover the tumor plus 1.5- to 2.0-cm lateral margins and 1-cm-deep margins (90% isodose). Fifteen Gy was delivered with a Mobetron irradiator, and immediate needle-localized partial mastectomy followed. Local event results were updated using the Kaplan-Meier method. RESULTS: A total of 53 patients received IORT alone. Median age was 63 years, and median tumor size was 1.2 cm. Of these, 81% were positive for estrogen receptor or progesterone receptor, 11% were positive for human epidermal growth factor receptor 2, and 15% were triple-negative. Also, 42%, 49%, and 9% would have fallen into the Suitable, Cautionary, and Unsuitable groups, respectively, of the American Society of Therapeutic Radiation Oncology consensus statement for accelerated partial breast irradiation. Median follow-up was 69 months. Ipsilateral events occurred in 8 of 53 patients. The 6-year actuarial rate of ipsilateral events was 15% (95% confidence interval = 7%-29%). The crude event rate for Suitable and Cautionary groups was 1 of 22 (5%) and 7 of 26 (27%), respectively. Overall survival was 94.4%, and breast cancer-specific survival was 100%. CONCLUSIONS: The rate of local events in this study is a matter of concern, especially in the Cautionary group. On the basis of these findings, pre-excision IORT, as delivered in this study, may not provide adequate local control for less favorable early-stage breast cancers.

Treatment of older patients with head and neck cancer: a review.

The incidence of head and neck cancer (HNC) in the elderly is increasing. The treatment of HNC often includes multimodality therapy that can be quite morbid. Older patients (herein, defined as ≥65 years) with HNC often have significant comorbidity and impaired functional status that may hinder their ability to receive and tolerate combined modality therapy. They have often been excluded from clinical trials that have defined standards of care. Therefore, tailoring cancer therapy for older patients with HNC can be quite challenging. In this paper, we performed a comprehensive literature review to better understand and discuss issues related to therapeutic recommendations that are particular to patients 65 years and older. Evidence suggests that older patients have similar survival outcomes compared with their younger peers; however, they may experience worse toxicity, especially with treatment intensification. Similarly, older patients may require more supportive care throughout the treatment process. Future studies incorporating geriatric tools for predictive and interventional purposes will potentially allow for improved patient selection and tolerance to intensive treatment.

Feasibility and Safety of Diffusing Alpha-Emitter Radiation Therapy for Recurrent or Unresectable Skin Cancers.

Importance: Patients with recurrent or unresectable skin cancers have limited treatment options. Diffusing alpha-emitter radiation therapy (DaRT), a novel solid tumor management strategy using alpha-particle interstitial brachytherapy, may address this challenge. Objective: To evaluate the feasibility and safety of using DaRT to manage recurrent or unresectable skin cancers. Design, Setting, and Participants: This prospective cohort study of patients who received a 2-week to 3-week treatment course and were followed up for 24 weeks after treatment during 2021 and 2022 at 2 sites in the US. Patients with malignant skin tumors or soft tissue tumors were recruited if they had limited treatment options for tumors recurrent after prior surgery or external beam radiotherapy or unresectable tumors. Intervention: Patients underwent DaRT to deliver a physical dose of 10 Gy (equivalent weighted dose of 200 CGE) to the tumor. Main Outcomes and Measures: Feasibility of the DaRT procedure was evaluated based on the ability of investigators to successfully deliver radiation to the tumor. Patients were followed up for adverse events (AEs) for 24 weeks and for tumor response by physicians' physical examination and imaging 12 weeks after device removal. Results: This study included 10 participants with recurrent or unresectable skin cancer (median [IQR] age, 72 [68-75] years; 6 males [60%]; 4 females [40%]). Six patients (60%) had recurrent disease, and 4 (40%) had tumors that were deemed unresectable. Tumors were located on the nose, chin, eyelid, scalp, neck, trunk, and extremities. Median (range) tumor volume before treatment was 2.1 cm3 (0.65-12.65 cm3). The mean (SD) prescription dose coverage of the gross tumor volume was 91% (2.8%) with all tumors having coverage of 85% or more. No device-related grade 3 AEs were noted. Common AEs were grade 1 to 2 erythema, edema, and pruritus. At 12 weeks following treatment, there was a 100% complete response rate. Nine of 10 complete responses (90%) were confirmed by CT imaging. Conclusions and Relevance: This cohort study suggests the feasibility and preliminary safety of DaRT in the management of recurrent or unresectable skin cancers. The favorable safety profile and high response rates are promising. A US trial for marketing approval based on this pilot study is under way. Trial Registration: ClinicalTrials.gov Identifier: NCT04377360.

Predicting future cancer incidence by age, race, ethnicity, and sex.

INTRODUCTION: Cancer remains a substantial burden on society. Our objective was to update projections on the number of new cancer diagnoses in the United States by age, race, ethnicity, and sex through 2040. MATERIALS AND METHODS: Population-based cancer incidence data were obtained using Surveillance, Epidemiology, and End Results (SEER) data. Population estimates were made using the 2010 US Census data population projections to calculate future cancer incidence. Trends in age-adjusted incidence rates for 23 cancer types along with total cancers were calculated and incorporated into a second projection model. RESULTS: If cancer incidence remains stable, annual cancer diagnoses are projected to increase by 29.5% from 1.86 million to 2.4 million between 2020 and 2040. This increase outpaces the projected US population growth of 12.3% over the same period. The population of older adults is projected to represent an increasing proportion of total cancer diagnoses with patients ≥65 years old comprising 69% of all new cancer diagnoses and patients ≥85 years old representing 13% of new diagnoses by 2040. Cancer diagnoses are projected to increase in racial minority groups, with a projected 44% increase in Black Americans (from 222,000 to 320,000 annually), and 86% in Hispanic Americans (from 175,000 to 326,000 annually). DISCUSSION: The landscape of cancer care will continue to change over the next several decades. The burden of disease will remain substantial, and the growing proportion of older and minority patients with cancer remains of particular interest. These projections should help guide future health policy and research priorities.

Radiation Therapy in Older Adults With Cancer: A Critical Modality in Geriatric Oncology.

Radiation therapy (RT) is a commonly used modality in the treatment of older adults with cancer, and RT represents an attractive oncologic treatment option, providing a noninvasive local therapy with limited systemic side effects. The Journal of Clinical Oncology (JCO) recently published a special series on Geriatric Oncology providing a comprehensive overview of multiple treatment modalities available to older adults with cancer. The purpose of this short review is to highlight the importance of RT in the treatment of older adults and encourage multidisciplinary participation in their care.

Disparities in older adult accrual to cancer trials: Analysis from the alliance for clinical trials in oncology (A151736).

BACKGROUND: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance). METHODS: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value <0.20 were included in a multivariable fixed-effects linear model. RESULTS: The median age of 66,708 patients across 237 trials was 60 years (range 18-102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial's expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1-21.3%, p < 0.0001). In multivariable analyses, non-genitourinary (GU) cancer types (p < 0.001), trimodality+ trials (estimate 8.78, 95%CI 2.21-15.34, p = 0.009), and phase 2 trials (estimate 4.43 95% CI -0.06-8.91; p = 0.05) were all associated with larger EDDs. CONCLUSIONS: Disparate enrollment of older adults is not equal across cancer trials. Future strategies to improve older adult inclusion should focus on trial types associated with the highest disparate enrollment.

Association between Prior Malignancy Exclusion Criteria and Age Disparities in Cancer Clinical Trials.

Prior malignancy exclusion criteria (PMEC) are often utilized in cancer clinical trials; however, the incidence of PMEC and the association of PMEC with trial participant age disparities remain poorly understood. This study aimed to identify age disparities in oncologic randomized clinical trials as a result of PMEC. Using a comprehensive collection of modern phase III cancer clinical trials obtained via ClinicalTrials.gov, we assessed the incidence and covariates associated with trials excluding patients with prior cancers within 5+ years from registration (PMEC-5). Using the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database, we further sought to determine the correlation between PMEC-5 and age disparities. PMEC-5 were used in 41% of all trials, with higher PMEC-5 utilization among industry-supported trials as well as trials evaluating a targeted therapy. Comparing trial patient median ages with population-matched median ages by disease site and time-period, we assessed the association between PMEC-5 and age disparities among trial participants. PMEC-5 were independently associated with heightened age disparities, which further worsened with longer exclusionary timeframes. Together, PMEC likely contribute to age disparities, suggesting that eligibility criteria modernization through narrower PMEC timeframes may work toward reducing such disparities in cancer clinical trial enrollment.

Evolution and Current Status of the Multidisciplinary Management of Locally Advanced Rectal Cancer.

The management of locally advanced rectal cancer has grown in both complexity and quality since the first proctectomy. What once was a malignancy with a fairly consistent treatment algorithm for decades, a recent paradigm shift in the care of these patients has led to a more personalized, multidisciplinary approach with variations in timing, sequence, duration, and potential exclusion of multimodality therapies. This review summarizes the most important evidence behind these developing overarching concepts to provide a context for this paradigm shift.

Randomized phase II study of a home-based walking intervention for radiation-related fatigue among older patients with breast cancer.

BACKGROUND: Fatigue is a common side effect of radiation therapy and can dramatically affect the quality of life in older cancer patients. We compared a home-based graduated walking intervention with a fixed walking recommendation.recommendation to exercise to determine the effects of these interventions during adjuvant radiotherapy (RT) on older women with breast cancer. METHODS: A randomized phase 2 trial in women ≥65 years, with stage 0-3 breast cancer. Prior to initiating breast RT, women were randomized to a Home-Based Graduated Walking Program (HBGWP) or a fixed walking recommendation. The primary outcome of fatigue was measured by the Total Disruption Index (TDI) of the Fatigue Symptom Inventory (FSI). Secondary outcomes including a short physical performance battery (SPPB) and questionnaires on exercise, physical function, fatigue (PROMIS Fatigue), and fatigue-related symptoms were collected at 3 time points. The primary goal was to compare the change in TDI between arms at the end of RT. Random coefficients models were used to determine the association between arm, fatigue, and exercise over time. Linear regression models were used to describe the change in outcome variables between visits. RESULTS: Median age of the 54 participants (27 per arm) was 69 years (range 65-84). The baseline characteristics were similar between study arms. The number of minutes walking per week increased in both arms (mean 21 min/wk. baseline to 83 min/wk. end of RT, p < 0.01) and physical function improved over time in both arms (median 10.5 at baseline to 12 at end of RT, p < 0.01).There was no significant difference in change in TDI between arms (2.7 ± 9.9 vs. 1.8 ± 14.0, p = 0.61)between baseline and end of RT. However, in our linear regression model increasing walking over time was associated with statistically significant lower levels of fatigue (-2.44+/- 1.04, p = 0.04), but not in posthoc subgroup analyses. CONCLUSION: The HBGWP did not decrease fatigue more than the fixed recommendation to exercise. Both the graduated intervention and fixed recommendation lead to increased walking which was associated with lower fatigue in this study of older adult breast cancer patients.

Developing an electronic geriatric assessment to improve care of older adults with cancer receiving radiotherapy.

Older adults make up a substantial proportion of patients diagnosed with cancer. Gaps in evidence of care for older adults with cancer leads to treatment heterogeneity and poor outcomes. Medical and Surgical Oncology clinics throughout the world are increasingly using Geriatric Assessment (GA) based approaches to treatment that are beginning to improve care through treatment decision-making communication, health-related quality of life outcomes, and reducing chemotherapy toxicities. Yet, GA based approaches are not often used in radiation oncology clinics. This manuscript aims to describe the ongoing development of an electronic patient-reported GA with real-time data interpretation and recommendation delivery to help increase the use of a personalized GA based approach to the care of older adults within radiation oncology clinics. Future studies demonstrating the utility and benefit of GA based approaches to help older adults undergoing radiotherapy for their cancers are still sorely needed.

Decreasing incidence of upper age restriction enrollment criteria among cancer clinical trials.

BACKGROUND: Age disparities among cancer clinical trial participants are pervasive and worsening over time. Identification of factors associated with age disparities is critical to improve enrollment of older patients on trials. The incidence and impact of trial eligibility criteria that exclude patients on the basis of age remains opaque. METHODS: ClinicalTrials.gov was queried for completed oncologic randomized controlled trials (RCTs). Phase 3 RCTs assessing a therapeutic intervention among adult cancer patients were included. Trial eligibility criteria were assessed using the ClinicalTrials.gov website as well as trial publications and protocol documentation. RESULTS: Seven hundred and forty-two trials met inclusion criteria, with a total combined enrollment of 449,720 patients. Upper age restriction enrollment criteria were identified for 10.1% of RCTs; the median age cutoff for restricted trials was 72 years (interquartile range 70-80 years). Linear regression modeling revealed decreasing incidence of age restriction criteria over time, at a rate of -1.1% annually (p = .03); trials initiating enrollment in 2002-2005, for example, had a 16.1% rate of age-restrictive eligibility criteria, compared with 7.6% for trials initiating enrollment in 2010-2014. CONCLUSION: Use of eligibility criteria that explicitly exclude patients on the basis of age appears to be decreasing with time. Future efforts should aim to better characterize the relationship between eligibility criteria (such as those that exclude patients on the basis of specific organ function) and their association with age disparities among enrolled patients.

Sex-Based Disparities Among Cancer Clinical Trial Participants.

Landmark investigation two decades ago demonstrated sex-based disparities among participants in cancer cooperative group trials. Although federal efforts have aimed to improve representation of female patients in government-sponsored research, less is known about sex disparities in the broader landscape of modern oncologic randomized controlled trials. Using ClinicalTrials.gov, we identified randomized controlled trials related to colorectal or lung cancer (the two most common non-sex-specific disease sites). Among the 147 included trials, the proportion of female patients enrolled on trial was on average 6.8% (95% confidence interval = -8.8% to -4.9%) less than the proportion of female patients in the population by disease site (P < .001). Whereas no statistically significant underrepresentation of women was noted within the 26 cooperative group trials, sex disparities were markedly heightened for the 121 noncooperative-group-sponsored trials. Furthermore, underrepresentation of women did not improve with time. Future efforts should therefore focus on addressing these pervasive sex-based enrollment disparities beyond cooperative group trials alone.