tbuckley/cabot-search huggingface dataset:
Effect of mail-in sperm cryopreservation solution on access to cryopreservation: A national demographic analysis.
Authors: Rachel Passarelli, Stacey A Kenfield, Daniel Nolte, Andre Belarmino, Daniel Civello, James F Smith, Danielle Velez Leitner
Journal: Journal of Clinical Oncology (2024)

e13524 Background: There are many circumstances under which someone may choose to bank their sperm, but forthcoming cancer treatment is among the most common. The advent of services offering mail-in semen analysis and cryopreservation has expanded access to sperm banking, especially for those living in rural areas, far away from traditional andrology labs. This study summarized demographic characteristics and reasons for cryopreservation among those using one such US-based mail-in service, with a focus on patients banking sperm prior to cancer treatment. Methods: Patients &gt;18 years who banked sperm using a mail-in cryopreservation solution developed by Fellow Health, Inc. from March 2021 to January 2024 were included. Test kits sold for research purposes were excluded. To categorize each patient by reason for cryopreservation, we made use of a patient-provided reason, supplied during test kit registration, where available. For the remaining patients, reason was inferred using several data sources including medical history, medications, and clinic and physician information. Patients who could not be reliably classified were omitted from this portion of the analysis. Descriptive statistics of key demographics and reason for cryopreservation were reported under an IRB-approved protocol. Results: 2,154 patients met our inclusion criteria and 725 (33.7%) provided demographic information. Average age was 34.7 (SD=9.2) years and 11.9% identified as a trans female. The majority of the population identified as white (79.5%) and non-Hispanic (84.8%). Over half of the population had a college degree or greater (59.3%), was married/partnered (57.1%), and had private insurance (84.9%). Among the 756 patients whose reason for cryopreservation was discernible, the majority, 450 (59.5%), were doing so in the context of fertility treatment, with only 46 (6.1%) indicating cancer treatment. Other reasons included pre-vasectomy storage (n=137, 18.4%) and gender affirming hormone therapy (n=90, 11.9%). Of the patients who indicated cancer treatment as their reason for cryopreservation, 50.0% lived greater than a 25-mile drive of the nearest National Cancer Institute (NCI)-designated Cancer Center. Conclusions: Surprisingly, few patients utilizing a mail-in service for cryopreservation did so prior to beginning cancer treatment, with most originating from the fertility or pre-vasectomy context. Use was disproportionately high among trans women initiating hormone replacement therapy (HRT), perhaps demonstrating their preference for at-home sample collection to avoid the unique challenges they encounter in a clinical setting. Especially for oncology patients who are admitted to a hospital and cannot leave for fertility preservation, there is an opportunity to further integrate mail-in cryopreservation services within oncology to improve access and reduce time costs.
Barriers to receipt of oncological care at the community level.
Authors: Nithya Ramesh, Shanjeev Kumar Rajeshkumar Chitra, Satya Durugu, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2024)

e13756 Background: Though the field of Oncology is advancing at a rapid pace, there exist several barriers to the receipt of care in cancer patients that are known to affect outcomes. This study aims to describe the social, logistical, and financial barriers to healthcare faced by a diverse group of cancer patients in the community setting. Methods: A total of 40 patients receiving various kinds of oncological care (chemotherapy infusions, radiation therapy, immunotherapy, outpatient follow-up appointments) at a community hospital from 12/2023 to 01/2024 were anonymously surveyed using a standardized questionnaire. Responses were compiled and analyzed. Patients were divided into 2 groups that missed appointments (Group 1) and did not miss appointments (Group 2) during the study period. Results: While there was no difference between ethnic groups, women were less likely to miss their appointments. Patients who were not married, who lived in single-income households with annual income less than $32,048, had less reliable access to transportation and were more likely to miss appointments. Distance from the hospital and having a social worker assigned did not seem to affect compliance with scheduled appointments. Conclusions: Socioeconomic disparities and lack of family support remain significant barriers in the delivery of quality cancer care. These are seen to affect patient compliance and hence treatment outcomes. Hence adequate resources should be allocated to address the holistic needs of our patients and alleviate the above-mentioned barriers. [Table: see text]
Accelerated epigenetic aging and risk of chemotoxicity in older adults with early breast cancer.
Authors: Jingran Ji, Can-Lan Sun, Alexis Ann LeVee, Mina S. Sedrak
Journal: Journal of Clinical Oncology (2024)

1624 Background: Older adults with breast cancer have considerable heterogeneity in their risk of chemotoxicity; two people with the same chronological age have different risks of chemotoxicity. This heterogeneity in chemotoxicity may be due to older adults having variable rates of biological aging. Some older adults age faster biologically compared with their chronological age (i.e., accelerated epigenetic aging [AEA]), while others do not. AEA is a blood biomarker of aging, but its utility as a biomarker of chemotoxicity is unknown. Here, we evaluated the association between AEA and risk of chemotoxicity in older adults with early breast cancer. Methods: In a prospective multicenter study of 397 women age &gt;65 with stage I-III breast cancer treated with neo/adjuvant chemo, we extracted genomic DNA from blood to estimate the participant’s rate of biological aging at baseline (prior to chemotherapy). Using two established epigenetic clocks (AgeAccelGrim and DunedinPACE), we classified individuals as either having AEA or not (dichotomized as a yes/no variable) for each clock. Our primary endpoint was grade 3+ chemotoxicity (yes/no, yes defined as any grade 3+ toxicity attributed to chemo). Using multivariable logistic regression, we examined the association between AEA and grade 3+ chemotoxicity, adjusting for sociodemographic, geriatric, and clinical covariates. Results: The median (range) pretreatment chronological age was 70 (65-85), AgeAccelGrim was -0.88 (-10.4-15.7), and DunedinPACE was 1.03 (0.69-1.45). Of the 397 women, 31 (8%) had AEA per AgeAccelGrim, 63 (16%) had AEA per DunedinPACE, and 184 (46%) experienced grade 3+ chemotoxicity. Women who had evidence of AEA as measured by AgeAccelGrim (≥6.83 years, adjusted OR = 2.73, 95% CI 1.17-6.41, p = 0.02) or DunedinPACE (≥1.17 biological years per chronological year, adjusted OR = 2.20, 95% CI 1.18-4.10, p = 0.01) had greater odds of having grade 3+ chemotoxicity compared to women without AEA (AgeAccelGrim &lt;6.83 or DunedinPACE &lt;1.17, respectively). Conclusions: In this cohort of older women with early breast cancer, those with pre-chemo AEA had increased odds of chemotoxicity compared to women without any evidence of AEA. Future research is needed to examine whether measures of biological age can be translated to the clinical care of older patients with breast cancer. Clinical trial information: NCT01472094 . [Table: see text]
Potentially inappropriate medications and their association with frailty, unplanned hospitalizations, and mortality in patients with cancer treated in the national U.S. Veterans Affairs Healthcare System.
Authors: Jennifer La, Tammy Hshieh, Anahid Hamparsumian, Robert Zwolinski, Jameson Wood, Mayuri Dharne, J. Michael Gaziano, Mary T. Brophy, Nhan Do, Nikhil C. Munshi, Jane A. Driver, Gregory A. Abel, Nathanael Fillmore, Clark DuMontier
Journal: Journal of Clinical Oncology (2024)

1620 Background: We previously operationalized the NCCN list of high-risk medications in older adults into a measurable scale—Geriatric Oncology Potentially Inappropriate Medications (GO-PIMs)—to aid oncology teams in identifying PIMs and understand their impact (1). This scale revealed that PIMs were prevalent and associated with frailty in older patients with blood cancers. The current study aims to evaluate the ability of GO-PIMs to identify high-risk medications and their impact in patients with both solid and liquid tumors managed in a large national healthcare system. Methods: We performed a retrospective cohort study using data from the national Veterans Affairs (VA) Cancer Registry and electronic health record, including all veterans newly diagnosed with a solid or liquid malignancy in the years 2000-2023.The number of GO-PIMs for each patient were measured among outpatient pharmacy prescriptions in the 90 days preceding the initial diagnosis date (the index date). We evaluated the association of PIMs with baseline frailty (the electronic Veterans Affairs-Frailty Index [VA-FI], categorized as nonfrail [0-0.2], mildly frail [&gt;0.2-0.3], and moderate-to-severely frail [&gt;0.3]), time to unplanned hospitalization, and mortality in multivariable models adjusting for age, gender, cancer type and stage, Charlson comorbidity index, and socioeconomic factors (rurality, area deprivation index, and history of homelessness). Results: Among 307,487 newly diagnosed patients (median age 68.5, IQR 62.1-75.8; most common cancers: prostate [20.5%], lung [23.1%], GI [21.3%]), GO-PIMs were prevalent (39% patients with ≥1 GO-PIM). The most common classes of PIMs were SSRIs (12.4%); opioids (10.7%); benzodiazepines (9.5%), and corticosteroids (9.5%). Each additional PIM increased the odds of being mild or moderate-to-severely frail at diagnosis by 65%, controlling for all covariates (ordinal regression adjusted OR [aOR] 1.65, 95% CI 1.63-1.66). Increasing number of PIMs was also associated with a higher hazard of unplanned hospitalization (Cox regression aHR 1.04, 95% CI 1.04-1.05) and death (Cox regression aHR 1.05, 95% CI 1.05-1.06), controlling for frailty and all covariates. Conclusions: Independently of cancer type and stage, comorbidity, and other covariates, increasing PIMs identified by the GO-PIMs scale was associated with an increased risk of frailty at diagnosis, unplanned hospitalization in follow-up, and death. We are implementing the GO-PIMs scale in a clinician-facing application that will automate real-time detection of PIMs and recommendations for oncology teams in routine clinical practice. 1. Hshieh and DuMontier et al., J Natl Compr Canc Netw, 2022.
Incidence of mortality in vulnerable and non-vulnerable older patients with cancer.
Authors: Héctor Alejandro Alejandro Rodriguez Calvillo, David Hernandez Barajas, Omar Alejandro Zayas Villanueva, Estefania Elizabeth Abundis Márquez, Elias Román Urdiales Hidalgo
Journal: Journal of Clinical Oncology (2024)

e13775 Background: Cancer most often affects older adults; 56% of all newly diagnosed cancer patients and 71% of deaths belong to this age group. Frail patients are at increased risk of unfavorable outcomes after Treatment. Methods: This cross-sectional study included adults older than ≥ 65 years who attended the Oncology department were included, with a diagnosis of a solid malignant neoplasm during March 2022-May 2023. Sociodemographic characteristics and characteristics of the disease were evaluated, and the G8 test was applied, a tool that identifies patients at risk of frailty (nutritional status, mobility, age, general health status, neuropsychological status, drugs used); a score ≤14 indicates that they are vulnerable. They were classified into two groups: group 1 (vulnerable) and group 2 (non-vulnerable). Telephone follow-up was performed at 12 and 24 weeks. We evaluated the incidence of mortality in both groups after oncological medical management. Results: Eighty-eight older adults were recruited, the majority were men (77.3%), and the mean age was 74.2 ± 6.71. Forty-seven patients (53.4%) were vulnerable (group 1), and 41 patients (46.6%) were non-vulnerable (group 2). Mortality at 12 weeks was evaluated: vulnerable (29.8%) vs. non-vulnerable (0%), and mortality at 24 weeks: vulnerable (46%) vs. non-vulnerable (4.9%). In both follow-ups, statistically significant results were obtained (&lt;0.001). Conclusions: Vulnerable patients have a higher risk of unfavorable outcomes; their detection is essential to perform a comprehensive geriatric assessment and provide multidisciplinary treatment, improving the prognosis of their disease. [Table: see text]
A window-of-opportunity (WOO) trial of giredestrant +/- LHRHa vs anastrozole+LHRHa in premenopausal women with ER+/HER2- early breast cancer (EBC; IBCSG 67-22; PREcoopERA).
Authors: Elisabetta Munzone, Ruichao Shi, Sherene Loi, Marco Colleoni, Giuseppe Viale, Vesna Bjelic-Radisic, Antonia Perello, Per Karlsson, Balazs Madaras, Roisin M. Connolly, Joana M. Ribeiro, Heidi Roschitzki-Voser, Roswitha Kammler, Barbara Ruepp, Meredith M. Regan, Peter Christian Dubsky
Journal: Journal of Clinical Oncology (2024)

TPS628 Background: Adjuvant endocrine therapy (ET) for premenopausal women with ER+/HER2- EBC often includes ovarian function suppression (OFS) via a GnRH or LHRH agonist (LHRHa) plus an aromatase inhibitor (AI) or tamoxifen. Younger age is associated with lower rates of ET adherence indicating side effects are less acceptable to these women. The development of drug regimens without OFS are clearly an unmet medical need in this setting. New oral selective ER degraders (SERDs) are emerging as potentially useful ETs in the (neo)adjuvant settings. Giredestrant is an efficient and potent SERD and a full antagonist, which translates into better anti-proliferation activity than known SERDs. PREcoopERA is a WOO trial aiming to determine, among premenopausal women with ER+/HER2- EBC: if giredestrant+LHRHa provides greater anti-proliferative activity than anastrozole+LHRHa; and if giredestrant without LHRHa provides similar (non-inferior) anti-proliferative activity to giredestrant+LHRHa. Results would provide rationale for subsequent (neo)adjuvant clinical trials. Methods: PREcoopERA (NCT05896566) is a randomized, open-label, 3-arm, WOO trial evaluating the anti-proliferative activity and safety of the oral SERD giredestrant +/- LHRHa triptorelin, as compared to the AI anastrozole + triptorelin. Eligible are premenopausal women with untreated ER+/HER2- operable stage I-III (excl. T4) EBC, with Ki-67 ≥10%. 220 women will be randomized in 2:2:1 ratio to giredestrant (30 mg/d po for 4 weeks until rebiopsy) + triptorelin (3.75 mg IM on D1); giredestrant alone; or anastrozole (1 mg/d po) + triptorelin. Rebiopsy is planned for D29, either during primary surgery or standalone procedures. The primary endpoint is change in Ki-67 labeling index between pre-treatment diagnostic tumor biopsy and post-treatment rebiopsy, as assessed by the IBCSG Pathology Office. Sample size of 80:80:40 randomized women are planned to test superiority of 4 weeks giredestrant+triptorelin vs anastrozole+triptorelin to reduce Ki-67 (hypothesized percentage changes -80% vs -65%) and to test non-inferiority of 4 weeks giredestrant vs giredesrant+triptorelin (within 10% as non-inferiority margin). The trial was activated on 9 October 2023. The first woman was enrolled on 25 January 2024. Clinical trial information: NCT05896566 .
EGFR mutation testing trends for patients with metastatic, non-squamous non-small cell lung cancer (non-SQ NSCLC) in Queensland, Australia from 2014-2021.
Authors: Zane Yang, Navin Niranjan, Tracey Guan, Robert Mason, Bryan Anthony Chan, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2024)

e13505 Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Epidermal growth factor receptor (EGFR) is the most common actionable mutation in non-small cell lung cancer (NSCLC) with routine testing recommended globally. In late 2013, screening for EGFR mutations was publicly funded in Australia for metastatic non-SQ-NSCLC. However, timely EGFR results are not universally available, often limited by tissue quantity/quality or prolonged turnaround times. This in turn affects access to treatment and thus survival. Methods: We aimed to examine the rates of EGFR testing over time and explore factors impacting results. Cases were identified from the Queensland Oncology Repository, a clinical database consolidating diagnostic, treatment and outcome data for all Queenslanders with cancer through the Queensland Cancer Registry. Cases were included if they had metastatic non-SQ-NSCLC, EGFR testing available via Pathology Queensland, and no other metastatic solid organ cancer within 1 year. Primary outcomes were EGFR mutation testing rates and time from first biopsy to EGFR mutation result, stratified by year of diagnosis and rurality. Results: A total of 3369 cases were included, of which 2871 had EGFR testing. The EGFR mutant (mt) rate was 12.6%, while 16.1% of cases had no EGFR results. Of cases without a conclusive EGFR result, reasons included: 179 transitioned to best supportive care before testing, 208 with insufficient tissue for a conclusive result, and 155 without testing for unclear reasons. The average time from biopsy to EGFR result improved from 29.9 days in 2014 to 21.5 days in 2021, with no significant difference in time to result between major cities, regional or remote areas. Cases with no EGFR results were more prevalent in rural areas. The proportion of patients living in outer regional/remote areas with no EGFR result was 21.1% compared to 15.5% in those living in major cities/inner regional sites. This was a relative increase of 36.2% (95% CI: 10.1% - 68.6%), a significant result (χ2 = 7.7483, p=0.005). Cases with no EGFR results in outer regional and remote sites declined from 30.1% in 2014-2015 to 15.3% in 2020-2021. Conclusions: EGFR mutation testing and result time has improved since 2014. Though time to result was not affected by rurality, significantly more rural patients lacked conclusive EGFR data, highlighting a gap in access to care. The cumulative EGFR no result rate of 16% and result time of 24 days indicates health systems need to more rapidly adapt to new treatment paradigms, particularly in the era of targeted therapies. [Table: see text]
Molecular profiling of serial liquid biopsy specimens utilizing cell free DNA (cfDNA) and circulating tumor cells (CTCs) in TBCRC041: A phase II study of alisertib in endocrine resistant metastatic breast cancer (MBC).
Authors: Karthik Giridhar, Vera Jean Suman, Xiaojia Tang, Hong Ye, Jordan Campbell, Erica L. Mayer, Meghan Sri Karuturi, Aki Morikawa, Gretchen Genevieve Kimmick, Claudine Isaacs, Sun Young Oh, Amy Sanders Clark, Ben Ho Park, Leslie A Bucheit, Jill Tsai, James N. Ingle, Matthew P. Goetz, Antonino Bonaventura D'assoro, Krishna Rani Kalari, Tufia C. Haddad
Journal: Journal of Clinical Oncology (2024)

1037 Background: TBCRC041, a randomized phase 2 trial of alisertib (A) ± fulvestrant (F) in women with HR+/HER2- MBC demonstrated promising clinical activity for alisertib (1). Interrogation of baseline (PreC1) and end of cycle 1 (EOC1) cfDNA and CTCs may identify biomarkers associated with response to A±F. Methods: Plasma cfDNA was sequenced using the Guardant INFINITY platform, which includes genomic and methylated tumor fraction (mTF) analysis. Pathogenic variants were determined using publicly available databases and Mayo Clinic annotation pipelines. CTCs were identified as nucleated, EpCAM+/ cytokeratin+/ CD45- cells and assessed for ER/HER2 staining (RareCyte, Seattle). PFS was defined as the time from randomization to progression or death. EOC1-PFS differs from PFS as time starts at C2D1. Stratified log-rank tests and conditional Cox modeling were used to assess whether PFS or EOC1-PFS differed by mutations in ESR1 or PIK3CA, pre-CTC ≥ 5, or mTF&gt;1%. Results: Of the 91 eligible pts, 84 progressed, and 73 were deceased. In the 86 pts with PreC1-cfDNA results, variants were identified in ESR1 (42; 48.8%), PIK3CA (36; 41.9%), AKT1 (7; 8.1%), PTEN(7; 8.1%), BRCA1 (4; 4.7%), and BRCA2 (7; 8.1%). Pts with a PIK3CAmut had significantly decreased PFS (HR 1.8; 95%CI: 1.1 -2.9, p=0.014) but not by ESR1mut status (p=0.583). PreC1 and EOC1-mTF were determined for 78 and 76 pts, respectively. PreC1-mTF was 0-1% in 21; 1.1-10.0% in 27; and 10.1-100% in 30. mTF levels remained between 0-1% in 17 pts fell to 0-1% in 11 pts, and was 0-1% in 5 pts without a preC1-mTF determination. PFS did not differ with respect to PreC1-mTF (p=0.210), but EOC1-PFS was worse in pts with mTF &gt;1% (HR 3.0; 95%CI: 1.6 -5.2, p&lt;0.001). PreC1 and EOC1-CTC were determined for 78 and 76 pts. 36 (46.2%) pts had a PreC1 CTC count ≥ 5. EOC1-CTC levels remained at (n=17) or increased to (n=1) ≥ 5 and was ≥ 5 in 2 pts without a preC1-CTC determination. EOC1-PFS was not significantly different for EOC1-CTC ≥ 5 (p=0.065), but was significantly decreased in pts with PreC1-CTC≥5 (HR=1.8; 95%CI: 1.1-3.0; p=0.018). Broader cfDNA NGS panel and CTC-derived ER/HER2 staining results will be presented at the meeting. Conclusions: Among patients receiving A±F, PFS varied based on the PIK3CAmutation status. cfDNA and CTC assessment PreC1 and EOC1 provided complementary information. Further validation in larger datasets is needed. 1. JAMA Oncol 2023;9:815. Clinical trial information: NCT02860000 .