tbuckley/cabot-search huggingface dataset:
Effect of demographic and clinician factors on patients' likelihood of pursuing hereditary cancer genetic testing.
Authors: Liliana Arida-Moody, Erika N. Hanson, Emerson Delacroix, Sarah Austin, Elizabeth A. Rizzo, Erika Koeppe, Jennifer J. Griggs, Ken Resnicow, Elena Martinez Stoffel
Journal: Journal of Clinical Oncology (2024)

e22538 Background: Hereditary cancer genetic testing (GT) is an essential tool for cancer screening and prevention. As indications for GT expand, we may consider whether patients are sufficiently informed and motivated to undergo testing. We surveyed people meeting criteria for GT to assess their likelihood to pursue GT. Methods: Individuals who met modified NCCN guidelines for GT based on self-reported personal/family cancer history were invited to participate in a clinical trial of interventions promoting uptake of GT. Participants completed a baseline survey assessing experiences and attitudes relating to GT. Respondents were asked to rate their perceived importance of GT and their readiness to receive GT (scale of 0-10). These outputs were averaged (Cronbach’s alpha = 0.841) into an index representing their likelihood of pursuing GT. Linear regression was performed to investigate the relationship between several independent variables and the likelihood of pursuing GT. Gender, age, and race were considered, as well as self-reported circumstantial factors including 1) whether the individual had previously heard of GT, 2) whether a biologic relative had previously received GT, 3) qualifying eligibility variable(s) (family vs personal history of cancer), and 4) whether the individual had received a clinical recommendation to undergo GT. Results: 312 participants completed the baseline survey. The mean age of respondents was 61.9 ± 14.47 years, 52% identified as male, and 91% were white. 53% of respondents qualified for the trial based on family history alone and 15% had a clinician recommendation for GT. Younger age was associated with higher likelihood of pursuing GT (p = 0.004) as was receiving a prior recommendation for GT from a clinician (p = 0.01). When clinician recommendation was added to the model, the R-squared value increased from 0.44 to 0.64, indicating that recommendation accounts for a large portion of variance. Gender, race, personal/family cancer history, having previously heard of GT, and a biologic relative having received GT were not statistically significant. Conclusions: Concordant with previous literature, clinician recommendation to undergo GT is a significant contributor to the likelihood of pursuing GT. Older individuals may have lower readiness for GT compared with their younger counterparts, which could have implications for clinicians’ approaches to genetic counseling. Given that indications for GT have expanded, clinicians should remain up to date with current clinical guidelines.
Reduced time to efficacy signals in advanced cancer trials using Chauhan weighted trajectory analysis.
Authors: Utkarsh Chauhan, Daylen Mackey, John Robert Mackey
Journal: Journal of Clinical Oncology (2024)

e23028 Background: As Kaplan-Meier (KM) analyzes single unidirectional endpoints, most advanced cancer randomized clinical trials (RCTs) are powered for a 1 0 endpoint of either progression free survival (PFS) or overall survival (OS). This disregards efficacy information carried by stable disease (SD), partial response (PR), and complete response (CR) that may precede progressive disease (PD) and death. Chauhan Weighted Trajectory Analysis (CWTA), a generalization of KM, permits simultaneous evaluation of multiple rank ordered endpoints. We hypothesized that using CWTA with all efficacy inputs could expedite RCT efficacy signals. Methods: We performed 100-fold simulations of RCTs in advanced cancer and determined the time to first significant efficacy signal (p &lt; 0.05) for KM PFS and OS (logrank test) and CWTA (weighted logrank test). RCTs were stochastically generated at defined sample size (SS) allocated 1:1 to control or intervention and run for 60 months. Rank ordered health statuses were CR = 0, PR = 1, SD = 2, PD = 3, and Death = 4. All patients we assigned SD at time 0 and, each month, were capable of response (PR then CR), maintained SD, or irreversible exacerbation to PD or Death. Event probabilities were modified between groups as defined by a hazard ratio (HR). We modeled a control group CR rate of ~10% and a PR rate of ~50% to reflect first-line advanced cancer RCTs with a dropout rate of 10% over 60 months. At increments of SS and HR, we determined the mean and standard deviation of time-to-efficacy signals. Results: CWTA markedly reduced the time-to-efficacy signals when compared to KM PFS (23% to 67%) and KM OS (43% to 82%) (Table 1). Conclusions: CWTA, by incorporating the entirety of the cancer trajectory including disease response, progression, and death, meaningfully expedites the efficacy signals of cancer treatments compared to KM PFS and OS. We have previously reported CWTA increases trial power and reduces sample size requirements (Chauhan U, Zhao K, Walker J, Mackey JR; 2023. DOI: 10.3390/biomedinformatics3040052). Using CWTA rather than KM reduces trial duration, cost, and numbers of patients needed to evaluate therapies in advanced cancer, while reducing the regulatory risk inherent in powering a trial for a single KM primary endpoint. [Table: see text]
Contribution of mammography to breast cancer detection among pathogenic germline BRCA carriers by age and mutated gene.
Authors: Hadar Goldvaser, Rinat Bernstein-Molho, Rachel Michaelson-Cohen, Lior Moss, David Gekhtman, Miri Sklair-Levy, Rachel Rabinovitch, Ariela Tomer, Yahelli Miller, Pnina Moore, Ephrat Levy-Lahad, Sari Lieberman
Journal: Journal of Clinical Oncology (2024)

10615 Background: Healthy carriers of pathogenic germline BRCA 1/2 (gBRCA) may choose between risk reducing mastectomy and intensive screening surveillance. Current international guidelines recommend both annual breast MRI and annual mammography. The aim of this study was to investigate the added contribution of annual mammography in gBRCA carriers to the annual breast MRI. Methods: A retrospective study from 2 large centers comprising gBRCA carriers who were diagnosed with breast cancer between 2000-2022 and were aware of their gBRCA status prior breast cancer diagnosis. Collected data included age at diagnosis, mutated gene and mode of breast cancer diagnosis (MRI, mammography, ultrasound [US], or other means [including clinical or incidental findings]). Data on pregnancy and breastfeeding at the time of breast cancer diagnosis were also collected. Differences in the mode of diagnosis were analyzed by age (≤40y vs. &gt;40y) and mutated gene (BRCA1 vs. BRCA2). Results: The cohort included 200 gBRCA carries: 134 (67%) BRCA1, 62 (31%) BRCA2 and 4 (2%) with both BRCA1 and BRCA2 mutations. The median age at the time of breast cancer diagnosis was 41 (24-88). Most cancers (68%) were diagnosed by MRI, followed by mammography (14.5%), US (7%) and other means (10.5%). While MRI was the most common diagnosis modality in both age groups, the distribution of mode of diagnosis was significantly different in younger women (≤40y) where breast cancer detection was more commonly by US or following clinical findings, compared to older women, p&lt; 0.001 (see Table). Five women were pregnant and 9 women were breastfeeding at the time of breast cancer diagnosis, all age 40 or younger. Four (80%) of pregnant carriers and 5 (55.6%) of breastfeeding carriers were diagnosed by US. There was no difference in mode of diagnosis between BRCA1 to BRCA2 carriers, p=0.974. There were only 16 women under age 30 that were diagnosed with breast cancer, 2 (12.5%) of whom were diagnosed with mammography. Conclusions: MRI is the most common modality for breast cancer diagnosis in gBRCA carriers who were aware if there gBRCA prior breast cancer diagnosis. Annual mammography also has a meaningful role in this population. We did not identify a subgroup in which it could be omitted. The increased utility of US among younger women is attributed to reduced utilization of MRI/mammography during pregnancy and breastfeeding. This finding strengthens the role of US screening in gBRCA carriers who are not eligible for other methods of imaging. [Table: see text]
Nutritional assessment for 891 patients with common cancer in a cancer hospital of southwest China.
Authors: Huiqing Yu, Mengting Chen, Junhui Zhang
Journal: Journal of Clinical Oncology (2024)

e23280 Background: Malnutrition is a problem affecting tumor patients greatly. To investigate the nutritional status of hospitalized patients with common malignant tumor in a cancer hospital of Southwest China. Methods: From April 2017 to May 2021, we enrolled 891 patients with cancer hospitalized for treatment in Chongqing university Cancer Hospital. These patients were diagnosed with one of the following 16 different types of malignant tumors: lung cancer, gastric cancer, liver cancer, colorectal cancer, breast cancer, esophageal cancer, cervical cancer, endometrial cancer, nasopharyngeal carcinoma, malignant lymphoma, leukemia, pancreatic cancer, ovarian cancer, prostate cancer, bladder cancer and brain tumor. Patient-generated subjective global assessment (PG-SGA), anthropometric measurements, and laboratory examination were used to evaluate the nutritional risk or nutritional status.Cancer pain status were assessed with the Numerical Rating Scale (NRS). We also investigated the nutritional therapy of these cancer patients. Results: According to the PG-SGA score, 48.7% (434/891) of the cancer patients were severe malnutrition (PG-SGA≥9), 31.2% (312/891) were moderate malnutrition (8≥PG-SGA≥4), 14.7% (131/891) were mild malnutrition (PG-SGA 2~3), and only 5.4% (48/891) patients were no malnutrition (PG-SGA 0~1) . The rate of malnutrition for gastrointestinal cancer patients is higher than Nongastrointestinal cancer patients (67.3% vs. 44.6%, χ2 = 31.48, P &lt; 0.001). Multiple linear regression analysis, PG-SGA scores and body mass index (P &lt; 0.001), serum total protein(P &lt; 0.001), hemoglobin serum(P &lt; 0.001), albumin (P &lt; 0.001), prealbumin ( P&lt; 0.001), calf circumference (left side, P = 0.001) were correlated. Age(≥65 years), albumin( &lt; 40g/L), prealbumin ( &lt; 150mg/L) and cancer pain (NRS≥4) are the risk factors of severe malnutrition. However, only 26.8% (200/746) of all the moderately and severely malnourished patients received nutritional therapy. Conclusions: 94.6% of the common malignant tumor patients enrolled in the present study were malnutrition. PG-SGA is an effective tool to assess malnutrition in cancer patients, it is recommended to conduct routine assessment of cancer patients at the beginning of admission. Nutritional therapy of malignant tumor patients with malnutrition is very low. Suggestions for patients with malignant tumor after admission nutritional risk screening, and comprehensive nutritional evaluation, including PG-SGA score, and to give the right nutritional therapy.
Statistical fragility of findings from randomized phase 3 trials in pediatric oncology.
Authors: Hannah Olsen, Pei-Chi Kao, Caleb Richmond, David Stephen Shulman, Wendy B. London, Steven G. DuBois
Journal: Journal of Clinical Oncology (2024)

e23003 Background: The fragility index (FI) and survival-inferred fragility index (SIFI) have been proposed as adjunctive metrics to facilitate interpretation of p-values in clinical trials. FI/SIFI is the number of patients on a positive (p &lt; 0.05) trial’s experimental arm who would need to switch from “responder/non-event” to “non-responder/event” to cause p &gt; 0.05. Fragility indices have been reported previously in medical oncology, with median values &lt; 10 often seen in the literature. This metric has not been studied in pediatric oncology trials. Methods: PubMed was used to identify randomized phase 3 pediatric oncology trials published between 1980-2020. We report trial characteristics and calculate FI for trials with a binary outcome and SIFI for trials with a time-to-event outcome. We also report the fragility quotients (FQ and SFQ) to normalize FI and SIFI relative to trial size. Results: 113 trials included sufficient data for analysis. The median FI for trials with a binary outcome (n = 40) was 4.5 (range: 1-33). The median SIFI for trials with a time-to-event outcome (n = 73) was 13 (range: 0-61). The FI or SIFI was less than the number of patients lost to follow-up in 25% of 36 trials. Median FQ = 0.026 and SFQ = 0.03, indicating that revised outcome in 2.6% or 3% of trial participants would be sufficient to alter the trial conclusion. FQ and SFQ did not significantly vary according to trial characteristics. While sample sizes increased over time (mean 187, 1980s; mean 437, 2010s), FQ and SFQ remained stable between 2-3%. Conclusions: The statistical conclusions of pediatric oncology phase 3 trials hinge on a relatively small number and proportion of patients. Despite sample size limitations of low prevalence diseases, pediatric cancer trials appear similarly or less fragile than adult oncology trials. Fragility was similar for large versus small trials and remained constant over four decades. [Table: see text]
Discharge outcomes in COVID and non-COVID cohorts of hospitalized patients with cancer: A comparative analysis in the first year of the COVID-19 pandemic.
Authors: Bilja Kurian Sajith, Sandra K. Cesario, Anecita P. Fadol, Joseph Nates
Journal: Journal of Clinical Oncology (2024)

e23063 Background: This research aimed to assess and compare the discharge outcomes in two cohorts of hospitalized oncology patients – those with COVID-19 and those without COVID-19 in the initial year of COVID pandemic. Methods: This study compared the length of hospital stay, 30-day readmission, in-hospital mortality, death within 30 days of admission, and death within 90 days of admission between the COVID cohort and the non-COVID cohort, based on prospectively collected hospitalization data from March 2020 to February 2021 at a prominent US cancer center. Results: The study included 4,225 oncology patients, with 551 having COVID-19. Aged on average around 61, both cohorts showed similar gender distribution and were predominantly White or Caucasian, with the most common cancers being hematological. Patients in the COVID cohort experienced a significantly extended hospital stay with a mean length of 12.2 days versus 8.27 days for the non-COVID cohort (p &lt; 0.001). The median stay was also longer for the COVID cohort at 8 days [1, 103] compared to 5 days [1, 141] for the non-COVID cohort. The COVID cohort had a lower 30-day readmission rate post-discharge at 66.6% compared to 71.7% in the non-COVID cohort, with the difference being statistically significant (p = 0.015). Within the COVID cohort, a smaller proportion of patients were readmitted within 30 days of discharge (66.6%), as opposed to the non-COVID cohort (71.7%), with a p-value of 0.015. Although the COVID cohort experienced a higher rate of in-hospital mortality at 11.3% compared to 6.9% in the non-COVID cohort (p &lt; 0.001), there were no significant differences in the rates of death within 30 days of admission (COVID cohort: 25.6% vs. non-COVID cohort: 27.6%, p = 0.349) or within 90 days of admission (COVID cohort: 28.9% vs. non-COVID cohort: 31.7%, p = 0.195) between the two cohorts. Conclusions: Oncology patients with COVID-19 faced longer hospital stays and higher in-hospital mortality rates than those without COVID-19. However, the COVID-19 cohort had a lower rate of readmission within 30 days after discharge. Despite the greater severity of hospitalization for COVID-19 patients, the mortality rates 30 and 90 days post-admission did not significantly differ from those without COVID-19. These findings underscore the need for intensified care and monitoring of hospitalized oncology patients with COVID-19, while also acknowledging the comparable longer-term survival between the cohorts.
Cancer care during a time of crisis: Israel’s experience during wartime.
Authors: Rottenberg Yakir, Adam Rose
Journal: Journal of Clinical Oncology (2024)

e23030 Background: During the last decades, there have been many crises in the world, including COVID-19, the Ukraine-Russia war and major tsunamis and earthquakes. These situations create challenges for providing appropriate care for cancer patients. It remains an important research priority to understand how to improve care delivery for cancer patients under conditions of stress or emergency. Methods: Israel has one of the highest-quality healthcare systems in the world. Strengths of the health system include advanced technology, universal health insurance, and four strong health maintenance organizations. Israel’s health system recently performed relatively well during the COVID-19 pandemic. Here, we report on system efforts to continue providing care despite the massive terrorist attack by Hamas of October 7, 2023, the ongoing rocket fire, and the mobilization of young and middle-aged adults to the army, which led to staff shortages. Our report focuses in particular on efforts to maintain continuity and quality of care for cancer patients. Results: There have been three main pillars of Israel’s efforts to maintain care for cancer patients despite the challenges. 1) We activated strategies learned from previous events, including the COVID-19 pandemic and other wars. This enabled continuing treatment of cancer patients, including those who had been evacuated from border-adjacent areas, in oncology departments that are either missile-proof or adjacent to a protected area. 2) The existence of universal health insurance, together with strong health maintenance organizations, enabled us to fill in gaps in social needs and ensure that no patient is “left behind”. This, in turn, allowed patients and their care teams to continue their cancer care without reimbursement barriers or other interruptions, despite the challenges. 3) There was a massive groundswell of volunteerism and lay-led social service initiatives. Almost half (48.6%) of the Israeli population engaged in some volunteer activity during the first two weeks of the war. This included volunteers who provided transportation for patients to and from treatments, donation of medications aimed at helping evacuees from border areas, and volunteer medical staff, such as recent retirees. These civil initiatives played a critical role in providing the initial response to the urgent needs that were left unaddressed by the government. Conclusions: We identified three main pillars that enabled continuity and high quality of care for cancer patients to continue despite a major crisis. A rapid response due to having similar, previous experiences and ready plans. A high-performance and resilient health delivery system, and lay volunteerism in times of crisis. While Israel’s challenges in the present period are unique, nevertheless lessons can be learned by health systems that wish to become more resilient and able to provide adequate care in times of crisis.
Project Facilitate: An analysis of the increased utilization in the oncology single patient expanded access pathway.
Authors: Mitchell Chan, Cameron Wilson, Jessica Boehmer, Tamy Kim, Richard Pazdur
Journal: Journal of Clinical Oncology (2024)

11029 Background: FDA Oncology Center of Excellence’s (OCE) Project Facilitate (PF) was launched in June 2019 in response to perceived barriers providers face when accessing Expanded Access (EA). PF staff provide step-by-step support to oncology healthcare providers requesting use of investigational drugs to treat their patients with cancer. Since launch, PF has received an increased number of oncology single patient EA applications each calendar year. An analysis of single patient investigational new drug applications (IND) received was performed over each calendar year, starting June 1, 2020. Methods: Data was extracted from PF’s central database between June 1, 2020 and December 31, 2023. Data collected included IND receipt date, granting date, status, application type, indication, drug name, address of requestor, and patient demographics. The starting date of June 1, 2020 was chosen since it was when PF staff officially started performing clinical review of applications. Results: Of the 2791 oncology single patient expanded access applications extracted, there were 681 (24.4%) emergency INDs (eIND) and 2110 (75.6%) non-emergency single patient INDs (SPI). Applications received by calendar year increased since June 1, 2020 to December 31, 2020 (397, 14.2%), 2021 (682, 24.4%), 2022 (822, 29.5%), and 2023 (890, 31.9%). The top-3 disease areas requested include high grade glioma (262, 9.4%), multiple myeloma (213, 7.6%), and melanoma (186, 6.7%). The top-3 disease areas requested in pediatric patients &lt; 17 years of age (568, 20.4%) include AML (88, 15.5%), high grade glioma (85, 15%), and ALL (47, 8.3%). Race and ethnicity information was provided in 32 applications containing white/Caucasian (24, 75%), Black or African American (4, 12.5%), Asian (2, 6.25%), and Hispanic or Latino (2, 6.25%). Applications were received from 46 states and 1 US territory, Puerto Rico. The top 3 states requestors resided in were CA (346, 12.4%), NY (317, 11.4%), and TX (276, 9.9%). Although rare, 22 (0.79%) applications were denied or placed on clinical hold most commonly due to curative or established therapies being available. Conclusions: Project Facilitate saw a 20.4% increase in oncology single patient expanded access requests received from calendar year 2021 compared to 2022 and an 8.3% increase from 2022 to 2023, equaling a 30.4% increase in 2023 compared to 2021. [Table: see text]
Underrepresentation of Asian Americans, Native Hawaiians, and other Pacific Islanders (AA &amp; NHPI) in cancer clinical trials that led to FDA approvals in 2010-2022.
Authors: Ruby Leong, Felice Yang, Jennifer J. Lee, Geetika Srivastava, Suparna B. Wedam, Asma Ali Dilawari, Chaohong Fan, Grace Tran, Sso Lee, Frances Andrada, Clara Lee, Lola A. Fashoyin-Aje, Laleh Amiri-Kordestani, Harpreet Singh, Steven Lemery, Richard Pazdur, Donna Rivera, Jennifer Gao, Tamy Kim
Journal: Journal of Clinical Oncology (2024)

11026 Background: About 6% and 0.3% of the total United States (US) population identify as Asian or NHPI alone, respectively. The most commonly diagnosed cancers among AA &amp; NHPI in the US are breast, prostate, lung, thyroid, and colorectal. Liver, gastric, and head and neck cancers occur in higher rates in AA &amp; NHPI vs. non-Hispanic White. Enrollment of Asian &amp; NHPI patients in multiregional cancer clinical trials may provide additional data regarding intrinsic and extrinsic factors (e.g., diet, infections, environmental exposures) impacting the etiology of cancer. We investigated enrollment trends of NHPI and Asian (within and outside of US) patients in cancer clinical trials that led to an FDA approval from 2010-2022. Methods: We analyzed data from ~98,000 patients in 171 cancer therapeutic clinical trials that led to FDA approvals for breast, prostate, lung, thyroid, colorectal, liver, gastric, and head and neck cancer indications from 2010-2022. Separate race categories of Asian and Native Hawaiian and other Pacific Islander were used. Results: Descriptive statistics of NHPI and Asians within and outside of US enrollment in breast, prostate, lung, thyroid, colorectal, liver, gastric, and head and neck cancer trials that led to an FDA approval from 2010-2022 are summarized in the table. Enrollment of Asian patients in the US was &lt;1% (except for liver cancer) and NHPI patients was &lt;0.2%. Conclusions: Although cancer is the leading cause of death for AA &amp; NHPI, AA &amp; NHPI are under-represented in cancer clinical trials, especially when data are further disaggregated into enrollment of NHPI and Asians within and outside of the US. Cancer etiology may vary in Asians in the US vs. Asia due to different intrinsic/extrinsic risk factors, underscoring the importance of enrolling more AA &amp; NHPI into clinical trials to expand the evidence supporting drug approvals in the US and to advance health equity through clinical trial diversity. [Table: see text]