bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary patterns and the risk of hematological malignancy in the California Teachers study cohort.
Authors: Conic Julijana Zoran , Chen Lily Zhiying , Reske Thomas , Ali Lobna
Published: June 2024

10545

Background: Many studies show a correlation between diet and the risk of developing cancer, but most of these studies pertain to solid tumors and data linking certain diets to hematologic malignancies is scarce. This study aims to elucidate the effect of dietary patterns on the risk of developing hematologic malignancy. This study aims to elucidate dietary patterns and correlation with the risk of developing a hematologic malignancy. Methods: Data from 106,029 women in the California Teachers Study (CTS) cohort was analyzed, 476 participants were diagnosed with lymphocytic, monocytic, or other leukemia, 895 with Hodgkin’s or non-Hodgkin’s lymphoma, and 227 with multiple myeloma between 1995-2020. Results: Five major dietary patterns were identified as: 1) plant-based diet, characterized by a high consumption of fruit and vegetables, 2) high-protein, high-fat diet characterized by a high consumption of animal proteins animal protein (e.g., meat and eggs) and added fats (e.g., butter and mayonnaise), 3) high-carbohydrate diet characterized by a high consumption of convenience foods, pasta, and bread, 4) ethnic diet characterized by a high consumption of legumes, soy-based foods, rick and dark-green leafy vegetables and 5) the salad and wine diet characterized by high consumption of salad and low-fat dressing, fish, wine, coffee and tea, using principal factors analysis (PCFA). Relative risk and confidence intervals were analyzed for each dietary pattern and their correlation to a diagnosis of a hematologic malignancy. Models were adjusted for race-ethnicity/birthplace, living/working half a mile from a chemical plan, living/working half a mile from a powerplant, cigarette use, family history of leukemia and/or lymphoma, BMI (kg/m2), daily caloric intake (kcal/day), socioeconomic status, and moderate physical activity (h/wk). Overall, the high-carbohydrate diet was shown to be protective against hematologic malignancy risk with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.73; 95% CI: 0.59, 0.99, p=0.004). A high-carbohydrate diet was also shown to be associated with a reduction in multiple myeloma risk specifically with the lowest RR in all quintiles, but lowest in the 5th quintile (RR: 0.79; 95% CI: 0.63, 0.98, p=0.03). The ethnic diet was associated with a higher risk of multiple myeloma with the highest RR in all quintiles but highest in the 2nd quintile (RR:1.21; 95% CI 1.06, 1.39, p=0.006). Conclusions: The finding that the high-carbohydrate diet is associated with a reduced risk of a hematologic malignancy warrants further research to characterize the degree of risk reduction, what specific foods, if any, in the category offer protective effects, and if it is a potential approach for prevention.
A pilot study on ultra-sensitive circulating tumor DNA detection with a novel methylation amplifier probe in colorectal cancer.
Authors: Xie Guanyi , Li Yangjunyi , He Xiaowen , Guo Shuang , Zhao Liyuan , Yang Lingjian , Zhang Yalong , Li Min , Sun Xueguang , Lan Ping
Published: June 2024

10547

Background: Liquid biopsy is extensively researched for detecting cancer-related methylation markers. However, detecting ultra-low methylation signals in liquid biopsies is extremely challenging. In early-stage cancer patients, less than 1% of circulating cell-free DNA (cfDNA) is tumor tissue-derived DNA (ctDNA), presenting a low signal-to-noise ratio for effective tumor marker detection. Methods: Here, we introduce Methylation Amplifier Probe for Low-signal Enrichment (MAPLE), a method for designing ultra-short hybrid capture probes (25-55 nt). By reducing the length of the probes, MAPLE enhances their intolerance to DNA base mismatches, thereby significantly improving their ability to specifically bind and enrich the targeted methylation haplotypes. A panel consisting of 13,218 CRC-related methylation haplotypes was constructed for validation. 42 samples from patients with cancer and 43 gender/age matched control samples were processed for the panel validation. All the DNA samples underwent bisulfite conversion, library preparation and parallelly hybridized with two capture panels composed with conventional probes (120 nt) or the MAPLE probes, demonstrating its effectiveness in increasing cancer signal-to-noise ratio in the final NGS data. Results: With MAPLE, in the final NGS data, ratio of CRC-related methylation haplotypes reads (signal) in patient’s plasma samples increased from 7% (conventional) to 28% (MAPLE). At 20M total raw reads (1000x sequencing depth), the MAPLE panel detects over four times the targeted haplotype fragments compared to the conventional panel. For a cohort including 42 patients (I-III:24, IV:18) with CRC and 43 gender/age matched controls, the MAPLE panel aided by a machine-learning classifier detected patients with a sensitivity of 0.83 and a specificity of 0.95. Conclusions: This pilot study highlights the potential of ultra-short probes in capturing cancer-related methylation haplotypes, advancing towards an early detection test for pan-cancer.
Analytical and clinical validation of a circulating tumor DNA–based assay for multicancer early detection.
Authors: Tran Le Son , Nguyen Luu Hong Dang , Nguyen Hanh Thi-Hue , Nguyen Duy Sinh , Tang Hung Sang , Giang Hoa , Nguyen Hoai-Nghia , Phan Minh-Duy
Published: June 2024

10548

Background: The development of multi-cancer early detection (MCED) through a single blood test has emerged as a promising method for improving the efficiency of early cancer detection and benefiting population health. However, the lack of analytical validation and clinical evidence for their utility in diverse populations have prevented their use in clinical practice. To address these challenges, we conducted a comprehensive analytical and clinical validation for an MCED test, SPOT-MAS (Screening for the Presence of Tumor by DNA Methylation and Size). Methods: A prospective cohort study (ClinicalTrials.gov identifier: NCT05227261) was conducted at 13 major hospitals and one research institute in Vietnam. Our study recruited asymptomatic participants aged 40 years or older and followed up for 6 and 12 months. Analytical sensitivity of our assay was assessed by using our healthy and cancer-standard samples with known tumor fraction. The clinical performance was assessed by computing the positive predictive value (PPV), the negative predictive value (NPV) and accuracy in detecting tumor tissue-of-origin (TOO). Results: SPOT-MAS demonstrates the capability to detect at least 50% of cancer samples with a specificity of 98% when the samples have a tumor fraction of 0.049 (95% CI: 0.043-0.059). These results were consistently reproduced in both intra- and inter-batch analyses. Furthermore, our test maintains robustness even in the presence of hemoglobin contamination up to 500 mg/dL and genomic DNA contamination of up to 100%. Our analysis of 10,027 eligible participants demonstrated its ability to detect cancers in asymptomatic individuals with a positive predictive value of 58.14% (95%CI: 43.33- 71.62), an accuracy of 84.00% (95%CI: 65.35-93.60) in predicting tumor location and a negative predictive value of 99.92% (95%CI: 99.83-99.96). Conclusions: To our knowledge, this is the first and largest prospective validation study in Asia supporting the utility of SPOT-MAS as a multi-cancer blood test for early detection in a low- and middle-income country, where a nationwide cancer screening program is urgently needed but currently not available. Clinical trial information: NCT05227261 .
Cervical cancer screening in 48000 females over two decades: Feasibility and success of community-based screening in Kerala, India.
Authors: Pai D. Krishnanadha , Bhat B.V. , Gangadharan Harsha , Panda Pankaj Kumar , V C Ravindran , Das Roy Lopamudra , Mullapally Sujith Kumar
Published: June 2024

10550

Background: Cervical Cancer is still significant cause of mortality and morbidity among females in India. Various methods of cancer screening are currently practiced for cervical cancer prevention including human papilloma virus (HPV) screening, pap smear, visual inspection with Lugol’s iodine (VILI), visual inspection with acetic acid (VIA) etc. The success of any cancer screening method is based on the feasibility of large-scale implementation at community level and the scientific validity of the screening test. VIA/VILI has been proven to prevent mortality in cervical cancer. This study is based on analysis of prospectively maintained database of community based cervical cancer screening using VIA/VILI in northern Kerala from 2002 to 2020. Methods: Retrospective analysis of prospective database of cervical cancer screening from 2002 to 2020 done by Malabar Cancer Care Society in Kerala, a non-governmental organization with support from governmental bodies like ISRO. Data was collected into excel sheets and were rechecked. The data on demography, type of screening, detection of precancerous and cancerous lesions was analyzed. Descriptive statistics were used to analyze the data using SPSS Version 20.0. Results: A total of 48008 individuals were screened over 18 years. 55% were premenopausal. 33% were fully asymptomatic and remaining 66% had white discharge per vaginum (25%), bleeding per vaginum (14%) or combination of symptoms (25%). 18% had abnormal per speculum findings (bleeds on touch, discharge etc.) 86% had unhealthy cervix.26% (12650) had VIA/VILI and 74% (35658) had pap smear. The pap smear findings were normal (41%), atrophic (17%), inflammatory (40%) and 2% had pre-cancerous/ cancerous changes. Of these lesions, 46% were HSIL, 36% were LSIL, 5% ASUS and 13% were squamous cell carcinoma (52 cases). Screen positive rate was 325 (0.005%) out of 48008. Treatment of precancerous lesions was by Cryotherapy (54%), LEEP (10%) and Surgery (36%). Treatment of invasive carcinoma was by surgery (91%) and radiation (85%). Referral to regional cancer center was done in 26% patients. The screen positive rate shows decreasing trend over the last two decades. Conclusions: Cervical Cancer screening in large scale in low resource setting is feasible in India by both pap smear and VIA/VILI with community based interventions led by NGO with support from governmental bodies. This model can be considered ideal for India and other low middle income countries with logistic difficulties for large scale HPV based screening.
Evolving burden of lung cancer attributable to occupational carcinogens in 38 OECD countries: Global, national differences, age dynamics and implications for global health.
Authors: Lakkimsetti Mohit , Vanodia Mihir Paresh , Singh Kushagrita , Goel Shrey , Bathvar Pinank , Patel Dhruval Pinalkumar , Vemparala Priyatha , Patel Juhi , Amin Vishrant , Koyani Himanshu Bharatkumar , Gadhiya Dhruvkumar , Desai Hardik Dineshbhai
Published: June 2024

10576

Background: Lung cancer (LC) remains a predominant cause of global mortality and disability, particularly significant in Organization for Economic Cooperation and Development (OECD) nations. Understanding the evolving burden of LC attributable to occupational carcinogens (OC) is critical due to its prevalence in occupational settings. Methods: Employing a standardized approach from the Global Burden of Disease study, we estimated deaths and disability-adjusted life years (DALYs) caused by lung cancer linked to OC. Our analysis spans age, gender, year, and location across the 38 OECD countries from 1990-2019. Results were presented as absolute counts and age-standardized rates (ASR) per 100,000 person-years, with projections extended to 2040 using regression frameworks. Results: Deaths from LC attributable to OC increased from 120,862 (95%UI: 91,114-148,937) in 1990 to 167,917 (127,888-208,066) in 2019, with DALYs rising from 2.4 million (1.8-3.1) to 2.9 million (2.2-3.6) over the same period. The United States recorded the highest number of deaths (41,075), followed by Japan (20,496) and the United Kingdom (15,223) in 2019. Notably, the Netherlands exhibited the highest age-standardized mortality rate (ASMR) at 12.62 cases per 100,000, with Belgium and the United Kingdom following closely. Asbestos exposure accounted for the highest number of deaths (147,263), followed by silica (15,660), arsenic (3,172), and diesel engine exhaust (2,798). Males bore a significantly higher burden than females over the last three decades, with the 75-79 age group recording the highest number of deaths (32,477) and the 70-74 age group registering the highest DALYs (613,442). Conclusions: The study underscores the escalating burden of LC attributable to occupational carcinogens across OECD countries, highlighting the imperative for robust preventive measures and targeted interventions. Urgent action is warranted to mitigate exposures to known carcinogens in occupational settings, particularly among vulnerable populations, to curb the escalating public health challenge posed by occupational lung cancer.
Barriers to implementing clinical cancer genetics in sub-Saharan Africa: Perspectives of participants of a virtual cancer genetics course.
Authors: Fadelu Temidayo , Manirakiza Achille Van Christ , Uwineza Annette , Uwinkindi Francois , Koeller Diane R. , Rebbeck Timothy
Published: June 2024

10597

Background: While clinical cancer genetics remains underutilized in sub-Saharan Africa (SSA) and many low-middle income countries, there are few empiric studies assessing knowledge gaps and perspectives of healthcare providers. We conducted a survey of participants of a virtual short course ( https://www.africanoncogenetics.org/home ). Methods: The comprehensive survey, partly adapted from other published instruments, included multiple-choice knowledge and practice questions on cancer genetics, Likert-scale questions on perspectives, and open-ended questions on barriers. Cancer genetics experts reviewed the survey to ensure face-content validity. The online course was given between October and November 2021; participants were invited through snowball circulation on global oncology listservs. Data were summarized with descriptive analysis. Results: There were 370 participant responses included in this analysis. Participants represented 40 countries, with largest representation from Nigeria (n=106, 29%), South Africa (n=50, 14%), and Uganda (n=39, 13%). Participants represented various medical specialties and research domains: laboratory medicine (15%), medical genetics (14%), biomedical science (10%), general practice (9%), and oncology (8%) were the most common. Participants also represented a spectrum of practice settings, with the highest proportions from national hospitals (29%) and private hospitals (8%). Most of the participants 223 (71%) had some genetics lectures during medical/nursing school or other training, but only 116 (37%) had attended any continuing medical education (CME) activities in cancer genetics since starting practice. Moreover, the overwhelming majority 95% expressed interest and willingness to attend a future CME course. Many participants, 148 (47.2%) rated their knowledge of cancer genetics as poor or very poor, 150 (48%) as fair, while only 15 (5%) rated as good or very good. Most participants 196 (62%) considered themselves not qualified to interpret results of clinical cancer genetics testing, 100 (32%) were somewhat qualified, and 19 (6%) very qualified. Many participants 93 (30%) noted cancer genetics testing was not available to their patients; another 67 (22%) noted testing was only available outside the country; and only 47 (15%) had testing available within their primary institutions. In aggregate, the most common listed perceived barriers to implementing cancer genetics testing were costs (18%), lack of testing infrastructure (17%), lack of personnel (17%), and lack of provider knowledge (16%). Conclusions: Our survey demonstrates several perceived gaps limiting clinical cancer genetics testing implementation in SSA. A multi-pronged approach that addresses testing costs, testing infrastructure, and patient and provider education is urgently needed.
Second neoplasms in patients with hereditary retinoblastoma.
Authors: Corral Dolores , Escudero Adela , Rodriguez Salas Nuria , San Roman Sonsoles , Peralta Jesus , Izquierdo Elisa , Feliú Jaime , Perez Martinez Antonio
Published: June 2024

10620

Background: Patients with hereditary retinoblastoma have an increased risk of developing second tumors during adolescence and adulthood. The incidence of second malignant neoplasms (SMNs) is a concern, since SMNs are the leading cause of death in these patients. This risk is increased in patients who have received external radiation therapy as part of treatment but is also increased in non-radiated patients. Increased sarcoma and melanoma risks after hereditary retinoblastoma are well established. Methods: We present a cohort of patients with hereditary retinoblastoma assessed in our multidisciplinary pediatric and adult genetic predisposition cancer unit (UPGeCI) from September 2018 to December 2023. During this period, 62 patients with retinoblastoma were attended, all with RB1 gene mutation. Of these, 84% of patients had bilateral retinoblastoma, and 16% had unilateral retinoblastoma. They ranged in age from 6 months to 55 years (median 13 years). 18 patients (29%) were treated with external beam radiation therapy. Clinical follow-up and orbital magnetic resonance imaging were performed every two years. Results: Six cases of SMNs were detected in 5 patients (9.3%), all soft tissue sarcomas. The mortality rate was 60% (3/5 patients). Four patients (80%) had received external radiotherapy as part of the treatment of retinoblastoma. Three patients presented 3 sarcomas in the facial region within the irradiated area, of which one was an osteosarcoma and the other two leiomyosarcomas. Two of them presented in adulthood, and one at 9 years old. One of the patients died, the other two are living disease-free. The fourth patient who had received external radiotherapy presented with osteosarcoma of the femur at 15 years of age. She died of septic shock. The patient who had not received external radiotherapy presented with osteosarcoma of the tibia at 6 years of age and later with osteosarcoma of the contralateral femur at 10 years of age. She died of progression. Conclusions: There is an increased risk of SMNs in patients with hereditary retinoblastoma, mainly soft tissue sarcomas, with high mortality. This risk increases if they have received external radiation therapy. Therefore, screening for SMNs is essential for of follow-up in patients with heritable retinoblastoma.
An AI-assisted navigation approach for patients with radiographic suspicion of new pancreas cancer.
Authors: John Kristen M. , Tenner Joseph , Croocks Rolando , Valente Cristina , Bingham Bernadette , Habowski Amber N , McEvoy Tara , Zavadsky Tiffany , Beyer Kristen , Mercieca Rita , Nadella Sandeep , Carvino Anthony , Barish Matthew , King Daniel
Published: June 2024

11002

Background: The traditional cancer care paradigm relies on passive referral streams, resulting in suboptimal care delivery. Here, we assessed the results of an AI-assisted navigation approach to proactively coordinate specialty cancer care services for patients with radiographically suspected pancreas cancer. Methods: A natural language processing (NLP) classifier was trained to identify radiology reports suspicious for pancreas cancer from imaging reports generated within Northwell Health. The daily workflow consists of the following: the NLP flags reports with suspicion of pancreas cancer, a coordinator validates the finding, a GI oncologist and navigator coordinates specialty oncology and tumor board referral, and a clinical research coordinator pre-screens for research studies. Patients determined to be hospice-bound or with non-PDAC malignancy are excluded. Care delivery metrics were compared by Mann-Whitney U tests. Results: Prior to implementation, patients with new suspicion of pancreas cancer at our institution experienced a mean of 22 days to biopsy, 32 days to oncology visit, and 56 days to treatment initiation from radiology report with 17% referred to pancreatic multidisciplinary clinic (PMDC). Per monthly average, 1.8 patients were approached for biospecimen studies, 1.5 were consented, and 0.9 were enrolled. In the month following implementation of the AI-assisted navigation pilot, reports from 1666 patients were flagged, resulting in 38 patients with new suspicion of pancreas cancer identified (Table). Of these, 53% underwent biopsy, 50% were seen by an outpatient oncologist, 29% were referred to PMDC, and 42% received treatment at our institution. From date of radiology report, these patients underwent biopsy at a mean of 7 days (p<0.01), outpatient oncology visit at 15 days (p=0.285), and treatment initiation at 34 days (p=0.3479). A monthly average of 4 patients were approached for biospecimen studies, 4 were consented, and 3.2 were enrolled. Conclusions: An AI-guided navigation workflow identified patients earlier in the diagnostic timeline; reduced time to biopsy, follow-up, and treatment initiation; increased patient referrals to PMDC; and tripled participation in biospecimen studies at our institution. [Table: see text]
Prescription drug monitoring program mandates and opioid prescriptions received by patients dying of cancer.
Authors: Bao Yuhua , Zhang Hao , Pinheiro Laura C , Hu Allison Ju-Chen , Portenoy Russell K. , Bruera Eduardo , Reid M. Carrington , Tamimi Rulla M. , Zhang Fang , Paice Judith A. , Rosa William E.
Published: June 2024

11003

Background: Strong consensus supports opioid analgesics as first-line pain management for patients with poor prognosis cancer approaching the end of life (EoL). State legislations that mandate prescriber access of Prescription Drug Monitoring Programs (PDMPs) when prescribing opioids intend to mitigate unsafe opioid prescriptions but may have unintended consequences in restricting access to opioids for patients dying from cancer. This study seeks to assess associations between state implementation of comprehensive PDMP mandates –applicable to all prescribers and all clinical settings and not allowing prescriber discretion – with opioid prescriptions received by patients dying of cancer. Methods: We used SEER cancer registry linked with Medicare fee-for-service claims to identify 184,123 Medicare beneficiaries 66 years or older who died of cancer in 2011-2019 in one of 10 SEER states with an operating PDMP by the beginning of 2011. We measured opioid prescriptions dispensed to patients near the EoL, defined as 30 days prior to death or hospice admission. We exploited staggered implementation of comprehensive PDMP mandates and assessed the association of such implementation with opioid prescriptions dispensed to patients near the EoL. We estimated logistic regressions for dichotomous outcomes and Generalized Linear Models for continuous outcomes. Results: Implementation of comprehensive PDMP mandates was associated with a reduction in the rate of 1 or more opioid days near the EoL from 47.2% to 45.2% (difference, 0.02 [95% CI, -0.027, -0.012]), a reduction in the rate of 1 or more long-acting opioid days from 15.8% to 14.7% (difference, 0.011 [95% CI, -0.016, -0.006]), and a reduction of 130.8 (95% CI, -161.5, -100.2) in total morphine milligram equivalents (MMEs) and of 135.6 (95% CI, -215.1, -56.1) in MMEs from long-acting opioids among patients who received 1 or more days of opioids/long-acting opioids. Conclusions: Comprehensive PDMP mandates were associated with 4-9% reduction in opioid prescriptions dispensed to patients at the EOL. Specific strategies are needed to effectively exempt patients with active cancer from such mandates. [Table: see text]
Payor denial after prior authorization request for long-acting pain medication: Provider and patient perspectives.
Authors: Chino Fumiko , Persaud Sonia , Jinna Sankeerth , Ghazal Lauren Victoria , Salz Talya , Thom Bridgette
Published: June 2024

11004

Background: For patients with cancer, uncontrolled pain can reduce quality of life, lead to treatment breaks, and result in worse cancer outcomes. Guideline-concordant treatment for chronic, severe pain can include long-acting opioid formulations. Pain medications, however, often face prior authorization (PA), which requires providers to obtain payor pre-approval and may result in delayed or denied care. This analysis characterizes PA-related denials for pain medications for patients with cancer. Methods: At an urban comprehensive cancer center, we identified all PA requests for outpatient long-acting opioid (i.e., buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, tapentadol) prescriptions from 2023 and described frequency of PA approvals and denials. For denials, chart review 2 weeks post-PA was conducted of provider notes and patient communications with results summarized qualitatively. Results: 1752 new long-acting opioids prescriptions for 982 unique patients required PA. Of those, 1567 (89.4%) were approved after PA process, 99 (5.6%) were denied, 81 (4.6%) were cancelled after PA initiation, and 6 (0.3%) were unresolved. Most were prescribed by pain specialists including supportive care (n = 699, 40.0%) and anesthesia/pain medicine (n = 444, 25.3%) with most common indication: “Neoplasm related pain (chronic)” (61.1%). Oxycodone was the most common long-acting opioid requiring PA (n = 551, 31.4% of prescriptions), followed by fentanyl (n = 501, 28.6%), hydromorphone (n = 205, 11.7%), and methadone (n = 137, 7.8%). Long-acting morphine was denied most frequently (16.3% of n = 129 PA requests denied), followed by buprenorphine (12.1% of n = 33), and hydromorphone (7.3%). Fentanyl was denied the least (2.8%). The 99 denials affected 62 unique patients, including a patient with 7 denials. Chart review (n = 62) of the 2 weeks post-denial revealed a median of 2 (range 0-8) provider notes mentioning pain or PA barriers and median of 1 (range 0-5) patient calls or messages about the same. 22.6% (n = 14) patients ended up in the ER or admitted to the hospital for pain crisis or failure to thrive. Providers documented poor pain control, weight loss, need to “try and fail” other medications, and noted 11.3% (n = 7) patients ending up paying out of pocket for their medications. Patient messages document uncontrolled pain and unmanageable side effects with some literally begging for relief; one patient spoke of their fear of “dying in pain”. Conclusions: The vast majority of PA requests for long-acting pain medication result in approvals, suggesting that the process -which can delay essential pain management- is largely unnecessary. For the 1 in 20 requests that were denied, provider and patient concerns highlight the negative impact of uncontrolled pain. An improved, transparent PA process is essential for adequately treating chronic, cancer-related pain.
Implementing financial toxicity and health-related social risks screening and referral.
Authors: Thom Bridgette , Aviki Emeline Mariam , Chino Fumiko
Published: June 2024

11006

Background: Financial toxicity (FT), or cancer-related economic hardship, is associated with delayed/skipped care, reduced quality of life, and worse mortality. Screening for FT and health-related social risks (HRSR) as part of assessment for social determinates of health is currently being integrated into clinical care, but there is limited research on outcomes after patients screen positive for FT or HRSR. Methods: We conducted FT and HRSR screening for patients receiving treatment for breast, gynecologic, gastrointestinal, or thoracic cancer at an urban comprehensive cancer center. Screening included the 11-item Comprehensive Score for Financial Toxicity (COST) tool (scored 0-44, lower scores = worse FT) and a HRSR checklist to identify food, housing, medicine, and transportation insecurity. A COST score ≤20 or any endorsed HRSR was considered a positive screen, and financial/assistance counseling referral was offered. Multivariable logistic regression assessed associations of accepting referral, after controlling for demographic and clinical characteristics. Data were collected 09/2022-08/2023. Results: 28,606 patients completed screening, of which 32% (n = 9106) screened positive. Median COST was 16.0. Identified HRSR were: 23% food, 25% housing, 21% medicine, and 24% transportation insecurity. Of positive screens, 51% (n = 4683) requested some form of financial counseling. Associations with accepted referral include: higher FT (β = 1.15, 95% CI: 1.13, 1.16), younger age (β = 1.01, 95% CI: 1.008, 1.02), more essential needs (β = 1.19, 95% CI: 1.13, 1.25), non-White race/ethnicity (β = 1.70, 95% CI: 1.49, 1.93), and stage 3 (β = 1.29, 95% CI: 1.08, 1.53) or stage 4 (β = 1.26, 95% CI: 1.07, 1.49) diagnoses (vs. stage 0/1). Needs of patients who requested counseling included concerns relating to out-of-pocket expenses (68%), non-medical expenses (39%), health insurance coverage (23%), and paying for prescription medication (18%; not mutually exclusive). Of financial counseling sessions with available dispositions (n = 2336/4683, 50%), outcomes (not mutually exclusive) included general counseling (29%), referral to specific assistance programs (e.g., copay assistance, reduced cost care program; 15%), and insurance navigation (15%). One-third of patients requesting counseling did not respond to contact attempts; 21% reported no longer being interested in counseling upon contact. Conclusions: Screening for FT and HRSR was feasible, and one-third of patients were identified as at risk for FT or having an unmet essential need. Patients known to have worse FT outcomes (those with later-stage disease, younger age, higher FT, minoritized groups) were more likely to accept financial counseling; however, only one-half of those at risk accepted help. Future work will focus on improving workflows to ensure assistance meets patient needs, including addressing patient stigma around requesting help.
Early integrated rehabilitation and vocational rehabilitation in 435 patients with breast cancer: A comparison between the intervention group and control group in a prospective study.
Authors: Besic Nikola , Kurir Borovcic Mateja , Mavric Zlatka , Mozetic Anamarija , Zagar Tina , Homar Vesna , Kopcavar Gucek Nena , Skufca Smrdel Andreja Cirila , Kozjek Nada Rotovnik , Hadzic Vedran , Kos Natasa , Pelhan Bojan , Sremec Marko , Rozman Tina , Borstnar Simona
Published: June 2024

11007

Background: Return to work is beneficial both for breast cancer (BC) patients and for society. This study explored the impact of early integrated and vocational rehabilitation on sick leave and disability one year after the start of cancer treatment in BC patients. Methods: The subjects of our prospective study were 435 employed female BC patients (26-65 (mean 52) years of age), who participated in the pilot study on the individualized integrated rehabilitation in 2019-2022 and were followed for at least one year. There were 211 patients in the control group and 224 in the intervention group. The patients completed three questionnaires (EORTC QLQ - C30, B23, and NCCN): before, half and one year after the start of cancer treatment. The control group received the standard rehabilitation programme, offered to all BC patients before the start of the study. The multidisciplinary rehabilitation team reviewed the documentation of the patients from the intervention group before, half and one year after the start of treatment and recommended appropriate interventions according to the patient's needs in compliance with the institute’s new clinical pathway (psychologist, general practitioner, nutritional treatment, physical rehabilitation, kinesiologist-guided online exercises, gynaecologist, analgesia, vocational rehabilitation). Data on the patients’ demographics and needs reported in questionnaires, the extent of the disease and cancer treatment were collected. These data and the frequency of sick leave and disability retirement one year after the start of treatment in both groups of patients were analysed using the chi-square and ANOVA test. Results: The patients from the intervention group had 50 calendar days shorter sick leave compared to the control group (p = 0.002). Patients without metastatic disease from the intervention group had 52 calendar days shorter sick leave compared to the control group (p = 0.002). The intervention group treated with chemotherapy had 43 calendar days shorter sick leave compared to the control group (p = 0.029). The difference in sick leave of the group of patients who did not receive chemotherapy was statistically borderline significant (50 calendar days, p = 0.053). The patients in the intervention group had a better work ability (p < 0.001) and less disability (p < 0.001) than the patients in the control group one year after the start of treatment. Conclusions: One year after the beginning of cancer treatment, patients from the intervention group had shorter sick leave, better work ability, and a lower proportion of disability compared to the control group.
Association of higher baseline stress and pain with clinical outcomes: Secondary analysis from Alliance A011502.
Authors: Gandhi Shipra , Ballman Karla V. , Holmes Michelle D. , Visvanathan Kala , Symington Banu , Carvan Margaret , Matyka Carol , Weiss Anna , Winer Eric P. , Razaq Wajeeha , Carey Lisa A. , Partridge Ann H. , Chen Wendy Y.
Published: June 2024

11016

Background: A011502 is a phase 3 randomized double-blind clinical trial that enrolled high-risk nonmetastatic breast cancer (BC) patients (pts) and randomized pts to aspirin 300 mg daily vs. placebo. There was no significant difference in invasive disease-free survival (iDFS) between the two arms. A secondary objective was to determine the association of inflammation-affiliated factors (stress, depression, poor sleep quality and pain) with iDFS and overall survival (OS). We hypothesized that these baseline factors are associated with worse clinical outcomes. Methods: At baseline, 2735, 2720, 2422 and 2610 pts completed Perceived Stress Scale (PSS), Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI) and Center for Epidemiologic Studies Depression Scale Revised (CESD-R) respectively. Stress was categorized with PSS scores: low (0-13), moderate (14-26) or high stress (27-40). Pain was categorized with BPI scores: none/mild (0-3) or moderate/severe (≥4). Sleep quality was categorized with PSQI scores: good (0-5) or poor ( > 5).Depression was categorized with CESD-R scores: no depression (0-15) or depression (≥16). Associations between the measures of interest and outcomes were performed with multivariable Cox models controlling for age, body mass index, time since diagnosis, race, ethnicity, hormone receptor status and treatment arm. Results: Median follow up was 35 months. The associations from multivariable Cox model are shown in Table 1. Pts who reported high PSS had significantly worse iDFS and (non-significant) worse OS. Moderate/severe average (avg) pain was significantly associated with worse iDFS and OS. Poor sleep quality and depression were associated with worse iDFS and OS but not statistically significant. Conclusions: Pts reporting higher stress and pain at baseline had worse outcomes. We acknowledge that both pain and stress may be related to other non-cancer issues (chronic comorbidities). Our study highlights the need for clinical trials to consider including questionnaires to assess pt-reported outcomes. Future studies are warranted to determine if measures to decrease pain and stress would improve BC outcomes. U10CA180821, U10CA180882, UG1CA233196; https://acknowledgments.alliancefound.org . NCT02927249: Clinical trial information: NCT02927249 . [Table: see text]
Impact of the COVID-19 pandemic mitigation strategies on cancer treatment trials: A meta-analysis of industry and NCI studies.
Authors: Unger Joseph M. , Andrews Hillary , Levit Laura A. , McKelvey Brittany Avin , Stewart Mark , Dressler Emily Van Meter , Flaherty Keith T. , Fredette Peter , Jones Lee , Miller Therica , Onitilo Adedayo A. , Patel Timil , Bruinooge Suanna Steeby , Garrett-Mayer Elizabeth , Schenkel Caroline
Published: June 2024

11021

Background: ASCO and Friends of Cancer Research established a task force to evaluate trial mitigation strategies allowed by US regulators during the COVID-19 pandemic, including the use of telemedicine and remote monitoring. We report the results of a meta-analysis quantifying the impact of these strategies on quality metrics and the recovery time to pre-COVID levels. Methods: We invited 41 sponsors with active US cancer treatment trials from January 2015-May 2022 to contribute deidentified trial-level aggregate data on major protocol deviations (PDs), dropouts, severe or worse toxicity (CTCAE Grade 3-5), and enrollment. We examined outcomes as proportions of participants at-risk during the pre-COVID, initial wave (IW), initial recovery (IR), and secondary recovery (SR) assessment times (Table). Multi-level beta-regression analyses were adjusted for trial phase (“early”, phases I, II, or I/II, vs. “late”, phase III) with study and sponsor as random effects. Indicator variables were used for post-COVID time periods with pre-COVID as the reference. Results: Ten sponsors (9 industry and 1 NCI Cooperative Group) contributed 82 evaluable studies: 63 early and 19 late phase trials. Among the 15,679 participants, enrollment odds decreased 64% in the IW and 45% in the IR but recovered to approximately pre-COVID levels by the SR (Table). Major PDs, dropouts, and severe or worse toxicity all had lower incidence in the IW compared to pre-COVID; these outcomes were also less frequent in IR (p<.05 for each), but not in the SR (p>.05 for each) compared to pre-COVID. Conclusions: Large declines in enrollment rates during the IW rebounded to pre-COVID levels by 2021-2022. We found steep reductions in the rates of reported occurrence of major PDs, dropouts, and severe or worse toxicity during the initial outbreak, which also recovered to pre-COVID levels by 2021-2022. Findings suggest pandemic-related procedural flexibility did not lead to increased reporting of PDs or dropouts and highlight how use of mitigation strategies likely corresponded with the temporary disruption to trial conduct during the pandemic’s peak. Sponsors could consider broader adaptation of trial flexibilities moving forward. [Table: see text]
Project Facilitate: An analysis of the increased utilization in the oncology single patient expanded access pathway.
Authors: Chan Mitchell , Wilson Cameron , Boehmer Jessica , Kim Tamy , Pazdur Richard
Published: June 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 < 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]
Caregivers and legal barriers: Navigating care of a family member diagnosed with cancer.
Authors: Chen Krista Y. , Blackford Amanda L. , Bryant Monica Fawzy , Doran Joanna F. , Hussaini S. M. Qasim
Published: June 2024

11034

Background: Caregivers of patients with cancer are vital for coordinating care, but the extent to which they encounter social and legal barriers is unknown.We performed a nationwide analysis of a legal navigation program to assess caregiver utilization of services. Methods: This is a retrospective analysis of caregivers who used the Triage Cancer Legal & Financial Navigation Program for legal navigation services on behalf of a family member with cancer or for questions regarding caregiver responsibilities. Triage Cancer is a national nonprofit that provides free education on legal and practical issues impacting patients with cancer. We gathered demographic, financial, disease-site, and legal navigation data and implemented Poisson regression models to explore factors associated with each type of primary legal concern that prompted a call for assistance. Results: We examined calls from 553 caregivers between 2021-23 for family members with cancer who were 54% male, 44% aged 40-64y, 51% White, 26% employed, 32% on employer-sponsored insurance, and 42% with income <$50k. Most prevalent cancer types were hematologic (23%), CNS (14%), GI (10%), and breast (9%). A majority of caregivers sought assistance with 1 (51%) or 2 (35%) legal barriers. Most common primary issue was health insurance (34% - including issues related to insurance options, navigation, appeals), followed by financial (22% - financial assistance, housing), disability (15% - insurance applications, claim appeals), other (18% - estate planning, wills, advanced directives; life insurance; family law; education; COVID), and employment (10% - time off, working through treatment, returning to work, job loss, job search, unemployment benefits). Compared to reference groups, caregivers of Black patients (RR 2.2) were more likely to call for financial barriers, patients aged 40-64y (RR 3.4) for disability insurance, uninsured individuals (RR 5.6) for health insurance, and those with income between $50-100k (RR 3.1) or patient age 0-39 (RR 5.2) for employment-related difficulties. Conclusions: This study highlights the social and legal navigation undertaken by caregivers of patients with cancer. It underscores an urgent need for accessible legal navigation that considers the caregiver alongside the patient as one family unit undergoing care. [Table: see text]
Clinical applicability of guideline-recommended molecular targets and genome-targeted cancer therapies.
Authors: Tibau Ariadna , Hwang Thomas J. , Avorn Jerry , Kesselheim Aaron S.
Published: June 2024

11049

Background: Genomic testing has expanded the possibilities of precision medicine, particularly for advanced, treatment-resistant cancer cases. However, the clinical relevance of most genetic alterations remains uncertain, which can lead physicians to overestimate the benefits of tailored therapies. The National Comprehensive Cancer Network (NCCN) guidelines are cancer-specific treatment recommendations that often determine insurance coverage. We assessed the evidence for clinical benefit and actionability of molecular targets for genome-targeted cancer drugs recommended by NCCN. Methods: We identified genome-targeted therapies for solid cancers from the most recent NCCN guidelines. Trial design characteristics were obtained from publications supporting the NCCN recommendations. Genome target actionability was assessed with the European Society for Medical Oncology (ESMO) Scale for Clinical Actionability of molecular Targets (ESCAT). This ranges from genome alternation-therapy combinations that lead to improved outcomes (Tier I) to treatments with potential clinical relevance (Tiers II or III) to those with undetermined relevance (Tiers IV to X). Clinical benefit was evaluated using the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS). Molecular targets at ESCAT Tier I in combination with a given treatment associated with studies demonstrating substantial clinical benefit by ESMO-MCBS (Grades 4-5) were designated as high-benefit, while those linked to studies achieving an ESMO-MCBS Grade of 3 were categorized as promising but unproven. Results: We extracted411 recommendations from NCCN supporting 74 genome-targeted drugs targeting 50 driver alterations. Most recommendations (346/411, 84%) referred to clinical trial data, while one-sixth (65/411, 16%) relied on case reports or preclinical studies. Clinical trials were mostly Phase I or Phase II (271/346, 78%), single arm (262/346, 76%), and evaluated overall response rate as the primary endpoint (271/346, 78%). Over half of target recommendations had Tier I target actionability (246/411, 60%), over one-third were Tier II or III (142/411, 35%), and the rest were undetermined (23/411, 6%). Among 267 scorable trials,12% (32/267) demonstrated substantial clinical benefit (ESMO-MCBS Grades 4-5) and 45% (121/267) were Grade 3. When combining both frameworks,12% (32/267) genomic-based cancer treatments were high-benefit and 33% (88/267) were promising-but-unproven. Conclusions: About one-eighth of genome-targeted cancer therapies recommended in NCCN guidelines received a high benefit rating, while one-third were identified as having a promising but unproven substantial benefit according to the ESCAT and ESMO-MCBS frameworks. Ensuring NCCN recommendations are aligned with well-documented clinical benefits is crucial for promoting informed, evidence-based genomic-guided treatment decisions.