bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect and acceptability of jasmine compound essential oil for premenopausal breast cancer survivors suffering from genitourinary syndrome of menopause: A prospective interventional study.
Authors: Zou Mo , Li Xiaorui , Sun Tao
Published: June 2024

1063

Background: Genitourinary syndrome of menopause (GSM) includes dyspareunia, vaginal dryness, vaginal burning, urinary urgency, and recurrent urinary tract infections. Breast cancer survivors (BCSs) exhibit more severe symptoms of GSM than healthy aging women, especially premenopausal BCSs in sexually active lifetime. GSM detrimentally impacts their quality of life and contributes to the premature cessation of endocrine therapy for breast disease. This study aims to explore the efficacy and safety of Jasmine compound essential oil in the treatment of GSM in premenopausal breast cancer women. Methods: Premenopausal sextually-active women with hormone receptor (HR) positive stage I to III BC taking ovarian function suppression (OFS) treatment and endocrine therapy with self-reported vaginal dryness, dyspareunia, or decreased libido were enrolled to the 12 weeks topically applied Jasmine compound essential oil trial. E2 and FSH was measured at baseline and weeks 12. A series of validated sexual quality-of-life questionnaires were completed at baseline, and subsequently at weeks 4, 8, and 12. The primary endpoint is the improvement in sexual pain evaluated based on the Female Sexual Function Index scale (FSFI). Acceptability was measured by patient preference and reported intention to continue using the products. Gynecologic examinations and metagenomic profiling of the vaginal microbiota were conducted at baseline and post-treatment for patients in an exploratory cohort. Results: Overall, 96 BCSs signed consent (mean [range] age, 45 [32-55] years) and 89 completed 12 weeks of treatment. E2 and FSH were maintained within the postmenopausal range without significant fluctuations during the treatment. Topically applied Jasmine compound essential oil resulted in significant improvements in dyspareunia, vaginal dryness, irritation and quality of life over time (all P< 0.001). Both BCSs and their sexual partners reported being satisfied with the essential oil treatment and the adherence rate reached 95% (SD 10). In the 20-patient exploratory cohort, there were improvements in vaginal pH (baseline mean 6.07 compared with 12-week mean 4.68[ P<.001]), and vaginal maturation index (45.3 compared with 52.1[ P<.001]). We also observed a positive influence on the vaginal microbiota after intervention. In patients with elevated baseline abundance of Lactobacillus in the vaginal microbiome, there was a more pronounced improvement in scale scores following essential oil access. Conversely, a high baseline abundance of Escherichia coli may be considered a detrimental factor associated with less benefit from essential oil. Conclusions: Jasmine compound essential oil could relieve vaginal symptoms and improve vaginal health in breast cancer survivors who have experienced menopause after cancer treatment.
Real-world treatment patterns, healthcare resource utilization and costs of care among newly-diagnosed patients with HR+/HER2- metastatic breast cancer.
Authors: Basho Reva K. , Ng Carmen , Dillon Allison , Chen Lu , Cheng Anna , Du Toit Yolande , Abbass Ibrahim M.
Published: June 2024

1073

Background: Current literature on the treatment patterns and economic burden among newly diagnosed patients (pts) with HR+/HER2- metastatic breast cancer (mBC) is outdated and may not adequately capture the rapidly evolving treatment landscape. This study addresses this gap by providing a contemporary and comprehensive summary of real-world treatment patterns, healthcare resource utilization (HRU) and cost of care among HR+/HER2- mBC pts, through their first 3 lines of treatment (LOT) following metastatic diagnosis (met dx). Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2- mBC between 10/01/2016 - 06/30/2022 from the IQVIA PharMetrics Plus database. Pts were required to have≥ 6 months of follow up post met dx. The study classified pts hierarchically into mutually exclusive treatment categories across 3 LOTs following met dx: endocrine therapy only (ET), CDK4/6 inhibitor-based therapy (CDKi), alpelisib-based therapy (ALP), mTOR inhibitor-based therapy (mTOR), PARP inhibitor (PARPi), or chemotherapy (CT). Categories with < 30 pts in each line or those with overlapping targeted treatments were grouped into “Others'' (OTH). Baseline characteristics were assessed in the 12 months prior to met dx. HRU and costs of care (in 2022 USD) were measured during the follow-up period and reported in per patient per month (PPPM). Results: The study included 2,449 pts, with 64.6%, 10.5%, 22.8%, 2.1% pts receiving CDKi, CT, ET and OTH in 1LOT, respectively. In 2LOT (n=1,164), 41% of pts received CDKi, 24% CT, 20% ET, 9% mTOR, 4% ALP and 3% OTH. In 3LOT (n=479), 44% of pts received CT, 21% CDKi, 15% ET, 9% mTOR, 6% ALP and 4% OTH. The median treatment duration in 1LOT was longest for pts receiving CDKi (23.5 months) compared to 17.1 months for ET. The PPPM total costs were $15,396, $16,955 and $17,853 in 1, 2 and 3LOT. In 1LOT, CDKi pts had the highest PPPM costs [Table]. In the 2/3 LOT, ALP-treated pts incurred the highest costs followed by CDKi in 2LOT and mTOR-treated pts in 3LOT (Table). CT and ALP had the highest ER visits in 2 (0.18 and 0.13) and 3 LOT (0.20 and 0.27). Conclusions: The majority of patients received CDKi treatment as their 1LOT with a more fragmented treatment landscape in the 2/3LOTs. The incorporation of agents targeting the PI3K pathway (ALP and mTOR) remained low in the 2/3LOTs. Costs associated with the same targeted treatment increased when used in later lines of therapy. Early optimization of targeted therapy and a focus on adverse event management may be associated with economic benefits. [Table: see text]
Real world outcomes of sequential ADC therapy in metastatic breast cancer: Patients treated with sacituzumab govitecan and trastuzumab deruxtecan.
Authors: Mai Nicholas , Klar Miriam , Ferraro Emanuela , Bromberg Maria , Chen Yuan , Razavi Pedram , Modi Shanu , Chandarlapaty Sarat , Walsh Elaine M. , Drago Joshua Z.
Published: June 2024

1085

Background: Sacituzumab govitecan (SG) and trastuzumab deruxtecan (TDXd) are antibody drug conjugates (ADCs) that are approved for the treatment of HER2 low metastatic breast cancer (MBC). Both carry payloads which inhibit topoisomerase 1, and it is unknown whether these ADCs retain clinical activity when used sequentially to each other. Here we present a retrospective study of patients treated with both SG and TDXd at our institution and report real world progression free survival (PFS), clinical factors associated with longer PFS, and whether ADC sequence impacts outcome. Methods: All patients with MBC treated at MSKCC who had received both SG and TDXd (in any order) were eligible for inclusion. Clinicopathological and demographic data were obtained from retrospective chart review. PFS was determined clinically and calculated using Kaplan-Meier survival analysis. Univariate and multivariate associations of survival were assessed using Cox proportional hazards models. Results: Eighty-five patients met eligibility per the criteria above: 54 with estrogen receptor positive (ER+) MBC and 31 with triple negative breast cancer (TNBC). 33 patients received SG followed by TDXd (14 ER+, 19 TNBC), and 52 received TDXd followed by SG (40 ER+, 12 TNBC). Median age at time of second ADC treatment (ADC2) was 59 among all patients, 62 among SG first, and 58 among TDXd first. This cohort was heavily pre-treated, with median 5 prior therapies at the time of first ADC (ADC1) and 7 at the time of ADC2. Both the SG first and TDXd first cohorts had median 1 line of intervening therapy between ADCs. In the SG first group, median ADC2 (TDXd) PFS was 3.5 months (95%CI 2.7-7.7), and in the TDXd first group median ADC2 (SG) was 2.8 months (95%CI 2.6-3.7). On multivariate analysis, neither ADC sequence (SG first vs. TDXd first, HR 1.30, 95%CI 0.71-2.37, p=0.4) nor ER status (TNBC vs. ER+, HR 1.21, 95%CI 0.63-2.32, p=0.6) showed statistically significant differences in ADC2 PFS between these groups. Instead, later treatment line at the time of ADC2 was significantly associated with shorter ADC2 PFS (continuous, HR 1.11, 95%CI 1.01-1.23, p=0.03). To separately evaluate differences in PFS for each ADC depending upon whether it was first or follow-up therapy, median ADC1 vs. ADC2 PFS is summarized by ADC (Table). Conclusions: In this heavily pre-treated patient cohort, the clinical activity of both SG and TDXd appear modest in the ADC2 setting. Further studies are needed to confirm these findings and to determine whether payload cross-resistance may undermine the benefit of sequential ADC therapy. [Table: see text]
Impact of HER2 low status on genomic signatures in triple negative breast cancer (TNBC).
Authors: Taylor Melissa , Reddy Shilpa , Ashok Kumar Prashanth , Hariri Dana , Sokol Ethan , Sivakumar Smruthy , Quintanilha Julia , Pavlick Dean , Levy Mia Alyce , Ross Jeffrey S. , Lustberg Maryam B.
Published: June 2024

1092

Background: HER2 status has become more important with new treatment regimens subcategorizing HER2 to into low (1+or 2+ FISH-) or absent HER2 expression. Through comprehensive genomic profiling (CGP), we aim to identify distinctive molecular features associated with various immunohistochemistry (IHC) categories of HER2 low tumors. Methods: Retrospective review of pathology specimens submitted to Foundation Medicine were done and 514 TNBC (ER-/PR-/HER20,1+,2+FISH-) and 191 3+/HER2 amplified clinically advanced BC underwent hybrid capture-based CGP to evaluate genomic alterations (GA) in 324 genes, MSI status and tumor mutational burden (TMB, mutations/Mb). PD-L1 expression was determined by IHC (Dako 22C3 TPS). Chi-square test and Mann Whitney U test were used in the statistical comparisons of the 2 groups. Statistical significance was defined as p < 0.05. Results: 53.5% were HER2 IHC 0+, 31.5% were HER2 IHC 1+ and 15.0% were IHC 2+/FISH negative. The HER2 3+/amplified BC were 59% ER+ and 41% ER-. Notable differences in GA frequencies included a significant increase in PIK3CA GA in the HER2 2+ vs the HER 0+ and 1+ groups (p=.0003). A lower frequency in BRCA1 GA in the HER2 2+ (5.2%) vs the HER2 0+ (9.8%) was significant when compared to the 1.0% in the HER2 3+/amplified cases (p<.0001). BRCA2 GA frequencies did not show statistically significant differences among the TNBC HER2 IHC score groups. TP53 and RB1 had the highest frequency in HER2 0+ samples, with decreasing prevalence in the HER2 1+, 2+ and 3+/amplified cases (p<.0001 for both). There was also a trend towards higher frequency of CDH1 GA as the HER2 IHC score increased from 0 to 2+ among TNBC. There were no significant differences in immunotherapy biomarkers (MSI, TMB and PD-L1) based on HER2 status among the TNBC groups. TMB >= 10 mutations/Mb was significantly higher in the HER2 3+/amplified group (p=.004). Conclusions: We found that TNBC HER2 2+ positive FISH show key molecular differences from their HER2 low (1+) or absent (0+) counterparts. The most substantial difference was an increase in GA in PIK3CA. While this is targetable in the hormone positive setting, its potential role as a target in the hormone negative setting is uncertain. Also noted but did not reach significance was a decrease in GA within BRCA1/2 and a positive linear relationship with CDH1 and HER2 IHC expression. These GA differences may indicate potential treatment options for different HER2 subgroups and warrant further investigation. Limitations of our study include the retrospective nature and the lack of clinical data. [Table: see text]
Real-world immune-related adverse events in patients with early triple negative breast cancer who received pembrolizumab.
Authors: Jayan Athira , Sukumar Jasmine S , Fangman Benjamin David , Patel Tejal Amar , Raghavendra Akshara Singareeka , Liu Diane D. , Rauch Ronald , Basen-Engquist Karen , Tripathy Debashish , Barcenas Carlos Hernando
Published: June 2024

1099

Background: The addition of pembrolizumab to chemotherapy (KEYNOTE-522 regimen) in high risk early triple negative breast cancer (TNBC) has improved clinical outcomes. However, this treatment can result in immune-related adverse events (irAEs) involving any organ and in some cases, life-long toxicities or even death. This retrospective study describes real-world patterns of irAEs in patients (pts) with early TNBC who received pembrolizumab at two academic centers. Methods: We evaluated irAEs in pts with stage II-III TNBC from MD Anderson Cancer Center and Lyndon B Johnson diagnosed between January 2018 and May 2023 who received neoadjuvant pembrolizumab plus chemotherapy. We excluded those enrolled on clinical trials. We utilized ASCO irAE and CTCAE v5 guidelines for toxicity grading. Logistic regression assessed the effect of clinical variables on irAEs, adjusting for covariates. Results: We identified 233 pts with a median age of 51 ± 12 years; 62% with stage II and 35% with stage III TNBC; 25% were Hispanic/Latino, 21% non-Hispanic Black and 42% were non-Hispanic White. In total, 80 pts (34%) developed 100 separate irAEs (94 with definite and 6 with possible/probable attribution). The most common irAEs were endocrine (52%) followed by gastrointestinal (23%). Grade ≥ 3 irAE occurred in 26 instances, with the most common being gastrointestinal (13 instances). A fatal irAE occurred in 2 pts where both were colitis. A total of 26 irAEs resulted in hospitalization, 45 required systemic steroids, and 15 required additional immunosuppressive therapy. Most (66) irAEs were unresolved at last follow up, although the majority had improved to grade 1 (37/66) and 32 patients discontinued pembrolizumab early due to irAEs. No clinical factor (race, stage, tumor grade, age, body mass index) was associated with development of an irAE. Conclusions: In this real-world diverse population, we identified a similar rate and severity of irAEs as reported in the KEYNOTE-522 trial. Hospitalizations occurred in 26% of irAEs while most developed persistent immune toxicity. Gastrointestinal irAEs were more common compared to KEYNOTE-522 reported data. Research is needed to better predict and mitigate the burden of irAEs and to improve the long-term survivorship care of pts with early TNBC pts who receive pembrolizumab. [Table: see text]
A single center retrospective cohort study of patients with metastatic breast cancer and leptomeningeal disease: Updated survival data and subgroup analyses by breast cancer subtype.
Authors: Fisch Samantha Catherine , Tsopurashvili Elene , Somepalle Sai Sahitha , Salans Mia , Vasudevan Harish , Chien Amy Jo , Majure Melanie , Rugo Hope S. , Balassanian Ronald , Boreta Lauren , Melisko Michelle E. , Huppert Laura Ann
Published: June 2024

1108

Background: Patients (pts) with metastatic breast cancer (MBC) and leptomeningeal disease (LMD) have a poor prognosis with limited therapies. We previously reported data from our retrospective LMD registry; here we provide an update with additional pts and subgroup analyses highlighting differences in treatment and survival by breast cancer subtype. Methods: In this single center retrospective cohort study, we identified pts with MBC and LMD who received care from 2000-2024 and abstracted key clinical, treatment, and overall survival (OS) data. Results: We identified 111 pts with MBC and LMD, including pts with the following subtypes: HR+/HER2- (n=53, 47.7%), HER2+ (n=30, 27.0%), and triple negative breast cancer (TNBC; n=28, 25.2%). The majority of pts had concurrent brain metastasis (n=82, 73.9%). Median time from diagnosis of MBC to LMD was 16.4 months (mo) (range 0-101.3 mo). Pts received a median of 3 lines of therapy prior to the diagnosis of LMD (range 0-10) and 1 line after the diagnosis of LMD (range 0-4). Most pts received central nervous system-directed (CNS)-directed therapy (n=94, 84.7%), including intrathecal (IT) therapy (n=42, 37.8%) and/or CNS radiation (n=70, 63.1%). Median OS from the diagnosis of LMD to death was 4.1 mo (range 0.1-78.1 mo) and varied by subtype, with pts with HR+/HER2- or HER2+ MBC and LMD living longer than those with TNBC and LMD (4.2 and 6.8 mo respectively vs. 2.0 mo, p<0.01, HR 2.15, 95% CI 1.36-3.39). There was no difference in OS by histology ductal vs. lobular or by presence or absence of concurrent parenchymal brain metastases. Pts who received IT therapy survived longer than those who did not (7.1 vs. 2.7 mo, p=0.01, HR 0.60, 95% CI 0.40-0.90). There was difference in OS by receipt of CNS-directed radiation therapy. Pts diagnosed with LMD from 2015-2024 lived longer than those diagnosed from 2000-2014 (6.4 vs. 2.9 mo, p=0.04, HR 0.67, 95% CI 0.46-0.99). On multivariable analysis, having TNBC was associated with shorter OS from time of LMD to death (p=0.004, HR 2.03, 95% CI 1.25-3.30). Conclusions: This study represents one of the largest case series of pts with MBC and LMD, including the most pts diagnosed after 2015 to our knowledge. Pts with lobular histology, HER2+ BC, TNBC, and those with de novo MBC were over-represented compared to the general MBC population. Pts with HR+/HER2- or HER2+ disease, LMD diagnosed after 2015, and those who received IT therapy survived longer than their respective cohorts. Novel diagnostic and therapeutic strategies for pts with MBC and LMD remains an area of unmet clinical need.
Male breast cancer survival in Mexico between 2007 and 2016: A retrospective cohort.
Authors: Contreras Sergio , Verduzco-Aguirre Haydee Cristina , Huerta-Gutierrez Rodrigo , León-Rodriguez Eucario , Lajous Martin
Published: June 2024

1116

Background: Male breast cancer represents around 1% of all breast cancers worldwide. Due to its rarity, it is more likely to be diagnosed at advanced stages than in women, and survival rates tend to be lower than in female patients. Information about survival in male breast cancer in low- and middle-income countries (LMIC) is scarce. Methods: We conducted a retrospective cohort study cross-linking nationwide reimbursement claims for breast cancer cases between 2007 and 2016 treated within the Seguro Popular health financing scheme to a national mortality registry in Mexico. Age, municipality of residence, clinical stage, and year of treatment initiation were described. Facilities were classified according to location, total breast cancer patient volume, and type of funding. We estimated 5-year overall survival (OS) with 95% confidence intervals (95% CI) through the Kaplan Meier method and used the log-rank test to compare differences between patient groups. Patients with in situ disease and missing data for clinical stage were excluded from survival analyses. Results: We identified 268,703 claims representing 60,846 patients, from which 328 were male (0.53%). Median age was 56 years (IQR 48-67). At treatment initiation, 20.7% of patients had early disease, 46.3% had locally advanced (LA) disease and 15.5% metastatic disease; clinical stage information was missing in 16% of patients Most patients (86.6%) were treated at public facilities, and 40.5% were treated at high volume facilities. With a median follow-up of 4.1 years, five-year OS in the whole cohort was 64.3% (CI 95% 58.1-71.2). In patients with early-stage disease, 5-year OS was 78.7% (95% CI 67.0-92.4), in LA disease 66.3% (95% CI 58.4-75.3) and in metastatic disease 39.7% (95% CI 27.5-57.5) (p <0.001). Patients with LA disease treated at a private facility had improved 5-year OS (88.9%) compared to those who were treated at a public facility (62.8%) (p=0.033). We did not find any other significant differences in survival according to patient or facility characteristics, including patient volume. Conclusions: These results represent the largest cohort to describe survival in men with breast cancer in Latin America. We found a larger proportion of men diagnosed with metastatic disease than described in women in Mexico, and lower than expected survival in patients with early-stage and LA disease.
Patterns and risk factors of immune-related adverse events in a real-world cohort with lung cancer receiving immunotherapy.
Authors: Hu Xiao , Gurinovich Anastasia , Pan Stacey , Salei Yana , Lin Jeffrey , Parsons Susan K.
Published: June 2024

12130

Background: Immune checkpoint inhibitors (ICIs) have emerged as a core pillar of lung cancer (LC) therapy, but ICIs are commonly associated with a spectrum of immune-related adverse effects (irAEs). The real-world patterns and risk factors of irAEs in LC remain uncertain. Methods: Patients with LC newly started on ICIs between 10/01/2018 and 09/30/2021 were retrospectively collected from the Tufts Medical Center cancer registry and pharmacy records. irAEs occurring within 12 months after initiation of ICIs were identified. Univariable logistic regression was used to assess the risk factors of irAEs. Those with p-value<0.20 were included in multivariable logistic regression analysis (MVA), along with clinically relevant factors. Results: Of 125 LC adult patients (median age: 70 years, 68 males), 104 had non-small cell lung cancer (NSCLC), 123 had advanced stages, and 16 had preexisting autoimmune diseases (ADs). Six patients were treated with dual-agent ICIs. Pembrolizumab was the most often used single agent (67.2%). In total 50 irAEs occurred in 39 patients. The most common irAEs were endocrinopathies (34%), pneumonitis (20%), dermatitis (14%), and gastrointestinal toxicity (14%) with the median onset time of 148, 136, 19, and 68 days, respectively. 70% of irAEs were grade 1 or 2. 44% of irAEs were treated with immunosuppression, 38% were referred to specialist care, and 30% required hospitalizations. 56% of irAEs resolved within 12 months and 67.9 % of those were rechallenged with ICIs. In exploratory univariable analyses among all the patients, age, small cell lung cancer (SCLC), PDL1 positivity (TPS≥1%), concurrent NSAIDs use, and radiation therapy had p< 0.2. In MVA, SCLC remained significantly associated with irAEs (OR=4.14, 95% CI [1.50, 12.09], p=0.007). Among NSCLC subset (N=104), age, PDL1 positivity, concurrent NSAIDs, and acetaminophen use had p<0.2. Age (OR=0.94, 95% CI [0.883, 0.990], p=0.026) and PDL1 positivity (OR=3.17, 95% CI [1.12, 9.87], p=0.036) remained significant in MVA (Table). Conclusions: Our study described the real-world patterns of irAEs in LC patients. SCLC was found to be an independent risk factor of irAEs in our cohort. In NSCLC, younger age and PDL1 positivity were associated with irAEs occurrence. Future studies are required to validate these findings in larger samples. [Table: see text]
Quantification of treatment-related time toxicity in patients with advanced stage cancer.
Authors: Zhou Yuhang , Fitzpatrick Madeline Campbell , Hurtado Castillo Marisabel , Sessions William Steele , Aung Kyaw Lwin , Pandey Om Narayan , Goodgame Boone Wilder
Published: June 2024

12137

Background: Treatment-related Time Toxicity (TrTT) in cancer patients is a recently proposed metric to describe the burden of time spent in pursuing medical care, including office/hospital visits, side effect management, lab tests, imaging scans, and travel time. Time toxicity is a valuable concept in patient-centered shared-decision making, especially in the palliative management of end-stage cancer patients with limited life expectancy. Despite tremendous progress in cancer treatment, most of the guideline-recommended treatment options convey short survival benefits of around 3-6 months when compared to supportive care. While medication toxicities are meticulously reviewed with patients, the cumulative burden and impact of time are rarely included in the discussion, partly due to the lack of standardized measurement of TrTT, and the absence of data from clinical trials. Thus, there is a compelling need for the quantification of time toxicity to guide clinical practice and patient preference. Methods: This was an observational analysis of the time toxicity from palliative treatment for patients with incurable solid tumors at a regional safety-net oncology office that focuses on underserved communities. Time toxicity is calculated as the number of days a patient spent with any healthcare-related encounters during a 3-month period from our medical record system. Results: The median age of the total 94 included patients was 57. 54% of the population were Hispanic. The ratios for mild, moderate, and severe time toxicity were 38%, 44%, and 18%, respectively. Immunotherapy was associated with significantly less time toxicity (TrTT = 8.5 days, 95% CI = 6.3-9.7) compared to chemotherapy (26.3 days, 95% CI = 18.3-34.4, P < 0.001), while targeted therapy (13.4, 95% CI = 7.0-19.8, P = 0.01) and hormone therapy (11.9, 95% CI = 4.1-19.7, P < 0.01) also has lower TrTT than chemotherapy. Patients with a worse performance status (ECOG PS 3-4, 30.1 days, 95% CI = 18.3-41.9) experienced higher time toxicity than fitter patients (PS 0-2, 16.7 days, 95% CI = 13.2-20.2, P < 0.05). Among different cancer types, gastrointestinal malignancies were associated with the highest time toxicity with average TrTT of 30.2 days/3 months (95% CI =22.5-37.2). Conclusions: This is the first comprehensive study to quantify real-world Treatment-Related Time Toxicity across multiple cancer and therapy types in an underserved population. We found 18% of patients with incurable solid malignancies experienced severe time toxicity (> 1 in 3 days). Higher TrTT was associated with cytotoxic chemotherapies, GI malignancies, and poor performance status. Time toxicity should be taken into account with other quality-of-life outcomes in treatment pathways and patient-centered oncology care.
Risk assessment of myelosuppression with PARP inhibitors in prostate cancer: Insights from FAERS.
Authors: Jatwani Karan , Sarangdhar Mayur , Kolli Venkatesh , Khosla Atulya Aman , Gopalakrishnan Dharmesh
Published: June 2024

12144

Background: DNA damage repair defects are prevalent in 15% of Prostate cancer. FDA has approved four PARP inhibitors to be used for metastatic castration resistant prostate cancer (mCRPC). Based on the approvals, currently Olaparib, Niraparib, Rucaparib and Talazoparib have been approved alone or in combination with an Androgen receptor pathway inhibitor (ARPI). All these agents have myelosuppressive (MS) events . We aimed to assess the pharmacovigilance (PV), reporting rate, and reaction outcomes of different approved PARP inhibitors in the mCRPC setting reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed MS events in 2,137 patients on PARP inhibitors. MS event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. MS incidences were analyzed within different PARP inhibitors utilized for prostate cancer. Our primary composite endpoint was the PV of MS caused by olaparib, rucaparib, niraparib and talazoparib for the treatment of mCRPC. PARP inhibitors were analyzed as mutually exclusive cohorts. Standard PV metrics were used to determine MS association with PARP inhibitors and two-way ANOVA testing was used to evaluate for statistical significance across the treatment groups. Results: 2,137 prostate cancer patients on PARP inhibitors were identified. MS events (n=677)– olaparib (227/831, 27.32%), rucaparib (n = 171/495, 34.55%), niraparib (63/111, 56.76%), and talazoparib (34/47, 72.34%). MS events were further categorized into five classes – anemia (n = 311, 45.94%), leukopenia (n = 123, 18.17%), thrombocytopenia (n = 107, 15.81%), pancytopenia (n = 102, 15.07%), and myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia (AML, 34, 5.02%). Anemia rates across the four cohorts were identical (table). Leukopenia rates were highest in talazoparib cohort (27.66%). Thrombocytopenia rates were highest in niraparib cohort (24.32%). For pancytopenia, rates were highest in talazoparib 10.64%. MDS/AML rates were Talazoparib (2.13%), Olaparib (1.8%). The relative rates of MS events were significantly different across the PARP inhibitors (p < 0.05, Table). Conclusions: This is the first study specific to prostate cancer analyzing the relative rates of MS events across different PARP inhibitors. Talazoparib exhibited the highest incidence of myelosuppression. This underscores the careful patient selection and vigilant monitoring needed in PARP inhibitors. Prompt recognition of myelosuppression is needed to optimize the safety and efficacy of PARP inhibitor therapies in prostate cancer. [Table: see text]
Ensuring precision medicine for veterans with lung cancer: A randomized clinical trial.
Authors: Thomas Mikalah , Gonzalez Hector , Agrawal Madhuri , Das Millie , Patel Manali I.
Published: June 2024

1501

Background: National guidelines recommend molecular testing for patients with non-small cell lung cancer, yet this is not routinely completed in practice. In prior work, we identified barriers to testing in the Veterans Affairs. First, physicians are unaware if and when testing has occurred. Second, patients are unaware of testing and the implications on treatment and clinical outcomes. In response, in collaboration with a Veteran and Caregiver Advisory Board, we created a multilevel intervention led by a peer volunteer who: 1) provides tailored education of molecular testing for 1 month for Veterans newly diagnosed with lung cancer and, 2) alerts clinicians via secure messaging if tumor samples have not been tested. We conducted this randomized clinical trial to assess whether the intervention improves patient knowledge of molecular testing and patient activation and increases receipt of molecular genomic testing compared with usual care. Methods: All veterans >18 years old with a new diagnosis of any stage non-small cell lung cancer were eligible. Exclusions included inability to consent. All participants completed baseline assessments at randomization and at 1-month follow-up comprised of a 3-question validated precision medicine knowledge questionnaire and a 13-question validated patient activation measure. Genomic testing was assessed by chart review at 6-months followup. We used regression models to assess differences in mean knowledge and activation scores over time between groups and compared rates of genomic testing. Results: 75 Veterans were screened with 46 eligible. All 46 consented to participate, with 23 in each group. All were male (100%), had mean age of 76.3+/-5.54 years; 31 (67.4%) were Latinx; 2 (4.4%) Asian; 11 (23.9%) Black; 1 (2.2%) Native Hawaiian; 32 (69.6%) White; 32 (69.6%) had Stage 4 disease. At 1 month follow-up mean knowledge scores increased over time in the intervention group and remained stable in the control group (mean score 2.30 +/- 0.97 versus 1.16 +/- 1.15, p=0.014). At 1-month follow-up, patient activation increased for the intervention group more than the control group (46.7 +/- 11.3 versus 37.6 +/- 9.26, p=0.002). There were no significant differences in tumor testing between groups (intervention: 95.6% versus control: 86.9%, p=0.62). Conclusions: A volunteer led effort improved patient education regarding precision medicine and patient activation among Veterans as compared with usual care alone. Interventions that include volunteers and other support can enhance care and clinical outcomes among veterans with lung cancer. Clinical trial information: NCT05795959 .
Patterns of screening and access to care in women diagnosed with breast cancer in a safety-net system.
Authors: Kanjwal Shifa , Su Malcolm , Hopson Madeleine , Kashanian Sarah , Ahn Chul , Syed Samira K. , Delgado Ramos Glenda Maria , Unni Nisha , Sadeghi Navid
Published: June 2024

1531

Background: Screening mammography reduces breast cancer specific mortality by allowing diagnosis at an earlier stage. Inconsistent guidelines and limitations in access to primary care are among factors that affect screening uptake. In this study, we reviewed patient characteristics, access to care, and uptake of screening mammogram (SMMG) prior to a breast cancer diagnosis at a safety-net system. Methods: Parkland Health (PH) is the safety-net system for Dallas County and is affiliated with the University of Texas Southwestern Simmons Comprehensive Cancer Center. Electronic medical records of patients with a new invasive breast cancer diagnosis between 2018 and 2019 at PH were reviewed and data on demographics and clinical presentation were collected. Patients were categorized based on SMMG uptake prior to their cancer diagnosis: never-screened, ever-screened (SMMG > 2 years prior to diagnosis) and recent-screened (SMMG within 2 years of diagnosis). Results: A total of 468 new breast cancer cases were identified (48.7% Hispanic; 32.9% Black). Of these, 12.2% were younger than 40 and 27.8% were 40-49. Payer mix included 64.7% uninsured and 34.8% Medicare/Medicaid. Half of the patients (50.6%) never had SMMG. Never-screened rate was higher among younger patients (98.2% in < 40; 53.8% in 40-49; and 39.4% in >50; p < 0.0001). Only 25.2% (118/468) of the patients had a SMMG within 2 years prior to their diagnosis. Among patients aged >40, 44.0% (181/411) were never-screened and 28.7% (118/411) were recent-screened. Screen-detection rate among patients >40 was 40.1% (165/411), of whom 22 (13.3% of screen-detects) were diagnosed with cancer on their first ever SMMG. Race/ethnicity, insurance status, and positive family history of cancer were not significantly different between never, ever, and recent-screened patients. Screening uptake correlated with nodal status, tumor size and stage at diagnosis. Patients who had a prior encounter at Parkland were more likely to have a SMMG. Patients established with Parkland primary care at diagnosis were more likely to have early-stage disease. In patients < 40, 24.6% presented with stage IV disease at diagnosis and 57.9% did not have a primary care provider. A positive family history of breast/ovarian cancer or any cancer was noted in 38.6% and 57.9% of patients < 40, respectively. Conclusions: In the cohort presented here, 27.8% of patients were between age 40-49, reflecting the impact of a gap in the guideline, which is now addressed in the most recent iteration of USPSTF guidelines. Connecting ED users to primary care, identifying higher risk individuals through family history, and increasing SMMG rate in the primary care setting are among strategies to reduce the rate of late-stage diagnosis of breast cancer, particularly among vulnerable patient populations.
The influence of access to care on radiation therapy utilization among older women with breast cancer.
Authors: MeLampy Jane , Chen Mu-Hsun , Mazumdar Madhu , Klein Paula , Marcadis Andrea , Marti Jennifer L
Published: June 2024

1539

Background: In 2004, the Cancer and Leukemia Group B (CALGB) C9343 trial compared outcomes among women aged ≥ 70 who had stage I, estrogen-receptor positive (ER+) breast cancer (BC) who received a lumpectomy and hormonal therapy, treated with and without radiation therapy (RT). While the trial found that overall survival was not different between groups, RT use did not significantly decline after its publication. We investigated regional variation in RT utilization in the United States (US) and its association to access to healthcare among women aged ≥ 70 diagnosed with localized ER+ BC after partial mastectomy (PM) between 2004–2020. We hypothesize that women with greater access to health care will more often receive RT. Methods: To examine regional variation in the use of RT and its association with access to healthcare, we extracted data from the Surveillance, Epidemiology, and End Results 17 registry. From 2004 – 2020, 105,694 women aged ≥ 70 years who received a PM for localized ER+ BC across 199 US counties with a population > 50,000 were identified. Access to healthcare was measured using six socioeconomic (SES) variables: median household income, % with high school education, % of families above poverty line, % with bachelor’s degree, % speaking English, and % employed, measured from 2015-2019. A multivariable linear regression model tested for association between each variable and RT use. A composite SES score was calculated as the sum of z-scores across all six variables and we identified the top 20 and bottom 20 scoring counties. SES score was used as a surrogate for access to healthcare and was correlated to RT use using a linear regression model. Results: The percentage of women aged ≥ 70 receiving RT after PM for localized ER+ BC varied across counties from 19.0% to 84.6%. In 2004, receipt of RT was similar between the top 20 and bottom 20 counties (67.8% vs 65.2%, respectively). This decreased after publication of CALGB C9343; by 2020 receipt of RT was 58.7% for the top 20 and 49.2% for the bottom 20 SES counties (Table). In linear regression analysis, SES was significantly associated with RT use (p<0.0001). In multivariable linear regression analysis, only % above high school education was significantly associated with RT use (p=0.0205). Conclusions: Among women aged ≥ 70 with localized ER+ BC who underwent PM and who were candidates for omission of RT, those who lived in higher SES counties were more likely to receive RT from 2004 – 2020. Since the CALGB C9343 trial in 2004, RT use has declined; however, the decline was less among those with higher SES and therefore likely less among those with greater access to healthcare. These women may experience over treatment, which may result in personal or system wide harms. [Table: see text]
Trend and burden of cancer related hospitalizations in the US: Insights from a National Inpatient Sample Database analysis.
Authors: Singh Rohit , Jatwani Karan , Chitkara Akshit , Batra Akshee , Batra Nitya , Rubens Muni , Ramamoorthy Venkataraghavan , Rabishanker Veda , Saxena Anshul , Khosla Atulya Aman
Published: June 2024

1543

Background: Cancer-related hospitalizations constitute one of the primary drivers of cancer-related healthcare expenses. Understanding the burden and characteristics of these hospitalizations is essential to appropriately direct resources, improve outcomes, and avoid unnecessary hospitalizations. Our study sought to evaluate the national trends, reasons, disposition status, length of stay, and associated costs for cancer-related hospitalizations. Methods: We conducted a retrospective analysis of cancer hospitalizations using the 2008-2019 National Inpatient Sample. Cancer-related hospitalizations were identified using validated Clinical Classification Software (CCS) codes 11 to 45. Trends in hospitalization volume, mortality, length of stay, disposition status, and costs were analyzed overall and by cancer type, adjusted according to the US Consumer Price Index. Results: There were 371 million weighted hospitalizations from 2008 to 2019, of which 15.1% (56 million) were cancer related. The most reported cancer types were breast cancer (11.9%), secondary malignancies (11.2%), and prostate cancer (10.3%). The most common reasons for cancer-related hospitalizations were septicemia (4.8%), pneumonia (4.7%), and complications of surgical procedures or medical care (3.1%). Trend analysis showed that the total number of cancer-related hospitalizationsincreased from 12,963 to 16,500 per 100,000 hospitalizations during the study period (relative increase, 27.3%). Mortality rates decreased from 5.1% to 4.0% (relative decrease, 21.6%), while the length of stay decreased from 3.5 to 3.2 days (relative decrease, 8.6%) during the study period. Disposition to home or short-term facilities decreased (relative decrease, 3.1%), while to long-term facilities increased (relative increase, 20.6%) during the same period. Total hospitalization cost increased from $55.5 billion in 2008 to $76.4 billion in 2019 (a relative increase of 37.7%). Conclusions: Our analysis shows that while cancer-related hospitalizations and associated costs increased substantially, mortality rates, and length of stay decreased. These trends reflect rising cancer burden but improvements in hospital cancer care quality and efficiency. Ongoing efforts to optimize cancer treatment, minimize unnecessary hospitalizations, reduce length of stay, and facilitate safe discharges are needed to improve patient outcomes and control costs further. Continued surveillance and health policies should address the rising demand for high-value cancer care.[Table: see text]
Deep learning vs traditional breast cancer risk assessment models: Are we offering supplemental services to those who benefit the most?
Authors: Lamb Leslie R. , Albasha Heba , Mercaldo Sarah , Carney Andrew , Lehman Constance D
Published: June 2024

1556

Background: Mammography-based deep learning (DL) risk stratification models improve discriminatory accuracy in predicting future breast cancer compared to traditional risk models; however, decisions for and insurance payment of supplemental services such as MRI are driven by traditional scores. The purpose of this study was to compare risk scores and cancer detection rates in patients identified as increased risk by DL vs traditional models in a large screening mammography cohort. Methods: This multisite study included consecutive patients ≥40y undergoing routine bilateral screening mammography from 9/2017 to 1/2022 at five facilities. Tyrer-Cuzick version 8 (TC) and National Cancer Institute Breast Cancer Risk Assessment Tool (BCRAT) 5-year and lifetime models and a DL 5-year model were used to assess risk. The following thresholds were used to define intermediate risk: ≥1.67% for TC and BCRAT 5-year, 2.2 for DL model and high risk: ≥20% for TC and BCRAT lifetime, ≥6.0 for DL model. Patients were included if all risk scores were available. Patient demographics were retrieved from electronic medical records and cancer outcomes through regional tumor registry linkage. The proportion of increased-risk patients and cancer detection rates (CDR [cancers per 1000 women screened]) across models were compared using Pearson’s Chi-square test. Results: 148476 exams in 69464 patients (mean age 58.0y [IQR: 50.0-67.0]) were performed. 81.7% (119386/146075) of exams were in White patients and 18.3% (26689/146075) in races other than White. CDR of those classified as intermediate risk by DL was 7.1 (450/63109) vs 4.7 (320/68545; P<0.001) by TC and 4.2 (300/70831; P<0.001) by BCRAT, and as high risk was 20.6 (305/14772) by DL vs 3.9 (64/16442; P<0.001) by TC and 5.0 (29/5782; P<0.001) by BCRAT. 13.0% (19248/148476) were classified as intermediate risk by DL but not by TC or BCRAT, with a CDR of 6.0 in this cohort. 32.0% (47435/148476) were classified as intermediate risk by TC or BCRAT but not by DL with a CDR of 1.1. 8.5% (12577/148476) were classified as high risk by DL but not by TC or BCRAT with a CDR of 20.8. 11.1% (16451/148476) were classified as high risk by TC or BCRAT but not by DL with a CDR of 1.9. Conclusions: A significant proportion of patients identified as increased risk by DL model are not assessed as increased risk by commonly used risk models, effectively excluding them from accessing potentially life-saving supplemental services. DL scores met the American College of Radiology's acceptable CDR on screening mammography (≥2.5) regardless of traditional scores, however, elevated traditional scores in the absence of elevated DL scores did not meet acceptable standards. Risk assessment guidelines incorporating DL models are necessary to capture patients who benefit the most.
Adaptively learning visual model of surgical resection images via coarse-to-fine–grained strategy for pathological invasiveness prediction in indeterminate stage IA lung adenocarcinoma.
Authors: Yao Lintong , Zhou HaiYu , Cai Linghan , Li Qiaxuan , Xie Daipeng , Lin Hongwei
Published: June 2024

1563

Background: Indeterminate nodules with high risk of malignancy are suggested to receive video-assisted thoracoscopy biopsy. Frozen section assists surgeons to decide surgical strategies for stage IA lung adenocarcinoma (LUAD) intraoperatively, which is time-consuming and may misdiagnosis due to limited sampling and poor tissue quality. Methods: We prospectively enrolled stage IA LUAD patients underwent complete resection between June 2020 and September 2023 in Guangdong Provincial People's Hospital (GDPH), Affiliated Hospital of Guangdong Medical University, Meizhou People's Hospital. All the resected lung nodules were finally diagnosed as pre-invasive lesion (PIL), minimally invasive adenocarcinoma (MIA) or invasive lung adenocarcinoma (IAC) by FFPE pathological diagnosis. Images of the whole section of the lung nodules were taken by smartphones under natural lighting condition in operating theaters without shadowless surgical lights. Patients received preoperative anti-cancer therapy and with low-quality tumor section images were excluded. Images of nodules section, FS reports, FFPE diagnosis and clinical information were prospectively collected. Predictive artificial intelligence (AI) model was developed by a three-step process, which first predict the IAC and non-IAC region at coarse level, and identify fine level features through the high-risk region. The coarse and fine labels were then coordinated through risk ranking loss to reach a final predictive result. Results: We prospectively enrolled 1516 patients with 1638 indetermined lung nodules from preoperative chest CT following the inclusion and exclusion criteria, with 2438 images acquired from intraoperative nodule sections. The included patients have median age of 57 years old and 38.6% male patients. The pathological diagnosis for included lung nodules are 122 PIL nodules, 502 MIA nodules and 1014 stage IA LUAD. A multi-task artificial intelligence based on Coarse-to-Fine-Grained Strategy has been established to classify the indetermined lung nodules during the surgery. For binary classification, AI model reach an AUC of 0.86 in differentiation between IAC or non-IAC. For 3-classification level, AI model reach an AUC of 0.87 in differentiation between PIL, MIA or IAC. We further defined the IAC nodules into G1, G2 and G3 according to IASLC lung adenocarcinoma grading system. For 5-classification level, AI model reach an AUC of 0.86 in differentiation between PIL, MIA, IAC-G1, IAC-G2 and IAC-G3. Conclusions: Our AI models based on images of intraoperative surgical resection could effectively classify indetermined lung nodules, which can assist thoracic surgeons diagnose the nodules rapidly during the surging and decide the following surgical strategies. Clinical trial information: ChiCTR2300075999 .