bluuebunny/crossref_metadata_2025 huggingface dataset:
Utidelone plus bevacizumab for the treatment of HER2-negative breast cancer brain metastases (U-BOMB): A multicenter, single-arm phase II study.
Authors: Yan Min , Lv Huimin , Liu Xinlan , Cuizhi Geng , Wang Shusen , Song Yuhua , Liu Zhenzhen , Niu Limin , Zhang Mengwei , Feng Yajing
Published: June 2024

1081

Background: The primary treatment for brain metastases in patients with HER2-negative advanced breast cancer is predominantly local therapies like radiotherapy, owing to the limited efficacy of systemic therapies. Prior research has demonstrated utidelone's significant permeability across the blood-brain barrier and the preliminary effectiveness of bevacizumab for breast cancer brain metastases. Consequently, this study investigated the efficacy and safety of utidelone combined with bevacizumab in the treatment of advanced breast cancer brain metastases. Methods: This study was a single-arm, multi-center phase II clinical trial (NCT05357417). Eligible patients were aged 18 years or older with either radiotherapy-naive or progressive brain metastases post-radiotherapy, presented with asymptomatic or symptomatic brain metastases associated with HER2-negative breast cancer.Patients received intravenous bevacizumab (15 mg/kg on day 1 of each 3-week cycle) and utidelone (30 mg/m2 on days 1 to 5 of each cycle) until intolerance or disease progression. The primary endpoint was central nervous system objective response rate (CNS-ORR), as assessed according to the Response Evaluation Criteria In Solid Tumors version 1.1. Results: Between May 5, 2022, and October 25, 2023, a total of 46 patients were recruited, with a median age of 52.5 years (range, 33 to 69). Among them, 35 patients had untreated CNS lesions, while 11 had progressive brain metastases after local radiotherapy. The CNS-ORR was 43.5% (95% confidence interval [CI], 28.9%-58.9%). As of January 8, 2024, the median duration of follow-up was 14.6 months, and the median progression-free survival (PFS) was 7.7 months (95% CI: 5.5-10.8) as shown in Table. The 12-month overall survival (OS) rate reached 74.4% (95% CI: 60.0%-92.3%). The most common grade 1-2 adverse events (AEs) were peripheral neuropathy (87.5%), decreased neutrophil count (62.5%), anemia (47.5%), diarrhea (37.5%), and increased alanine aminotransferase (25%). No grade 3 or higher treatment-related AEs occurred. Conclusions: This study preliminarily shows promising efficacy and manageable safety of the combination of utidelone and bevacizumab in the treatment of HER2-negative metastatic breast cancer patients with brain metastases. Clinical trial information: NCT05357417 . [Table: see text]
Efficacy and genomic analysis of HER2-mutant, metastatic triple-negative breast cancer treated with neratinib alone or in combination with trastuzumab in the phase 2 SUMMIT basket trial.
Authors: Jhaveri Komal L. , Hurvitz Sara A. , Brufsky Adam , Bose Ron , de Miguel Maria J. , Evron Ella , Unni Nisha , Reid Sonya A. , Quinn David I. , Mahalingam Devalingam , Saura Cristina , García-Sáenz Jose A. , Martinez-Bueno Alejandro , Guerrero Angel , De La Fouchardiere Christelle , Wildiers Hans , Bischof Georg Friedrich , Bebchuk Judith D. , Eli Lisa DeFazio , Solit David B.
Published: June 2024

1094

Background: Genomic analyses of the SUMMIT metastatic breast cancer (mBC) cohorts suggested that resistance to neratinib (N) occurred primarily via acquisition of additional HER2alterations [Smyth et al. Cancer Discovery 2020]; this finding was independently confirmed in the MutHER clinical trial [Ma et al. Clin Cancer Res 2022]. Addition of trastuzumab (T) to N + fulvestrant (F) in HR+, HER2-negative, HER2-mutant mBC revealed increased efficacy compared to N+F [Jhaveri et al. Ann Oncol 2023]. Here, we report final data from SUMMIT evaluating whether the addition of T to N could improve outcomes in patients (pts) with HER2-mutant, triple-negative mBC (representing up to 3% of triple-negative mBCs) and performed next-generation sequencing (NGS) of serial biopsies to evaluate mechanisms of sensitivity and resistance. Methods: Pts with HER2-mutant triple-negative mBC received N (original SUMMIT cohort) or N+T (in the subsequent cohort): oral N 240 mg/d, i.v. T 8 mg/kg initially followed by 6 mg/kg q3w. Loperamide prophylaxis was mandatory during the first two cycles. Efficacy endpoints: confirmed objective response rate and clinical benefit rate (RECIST v1.1 or modified PERCIST); duration of response; progression-free survival. Retrospective central NGS was performed by MSK-IMPACT (tissue) or MSK-ACCESS (plasma). Results: 10 and 17 pts with triple-negative mBC were enrolled in the N and the N+T cohorts, respectively. Median no. of prior systemic regimens for metastatic disease was 2.5 (range 0–6) for the N and 2 (range 0–7) for the N+T cohort. Efficacy findings are summarized (Table). Diarrhea was the most commonly reported adverse event (N 80% any grade; 20% grade 3; N+T 100% any grade; 18% grade 3; no grade 4/5 or permanent discontinuations in either cohort). Correlation of efficacy to central NGS analysis is ongoing and will be reported. Conclusions: Treatment with either N and/or N+T yielded promising clinical efficacy and has been included in recent NCCN guidelines for HER2-mutant, triple-negative mBC. Molecular mechanisms of intrinsic or acquired sensitivity/resistance per genomic analysis will be reported. Clinical trial information: NCT01953926 . [Table: see text]
Ipatasertib (IPA) combined with non-taxane chemotherapy (CT) for patients (pts) with previously treated advanced triple-negative breast cancer (aTNBC): The PATHFINDER phase IIa trial.
Authors: Lopez-Miranda Elena , Pérez García José Manuel , Gion Maria , Ribelles Nuria , Cortez Patricia , Alonso Romero Jose Luis , Martínez-García María , Gonzalez- Santiago Santiago , Bermejo Begoña , Morales Murillo Serafin , Carañana Vicente , Garrigós Laia , Fernández Melissa , Boix Olga , Alcalá-López Daniel , Cortes Javier , Llombart Antonio
Published: June 2024

1098

Background: New therapies are urgently needed for aTNBC. The PI3K/AKT/mTOR pathway and its link to chemoresistance warrant further investigation in pre-treated TNBC patients. The pan-AKT inhibitor IPA, alone or combined, has shown promise for treating advanced solid tumors. This study assessed the toxicity and efficacy of IPA with non-taxane CT in aTNBC pts. Methods: PATHFINDER (NCT04464174) is a multicenter, open-label, non-comparative, phase IIa trial with a safety run-in phase. Taxane-pretreated aTNBC pts with 1-2 prior CT lines for advanced disease and ECOG 0-1 were eligible. Based on prior treatment and available slots, pts received 21-day cycles of IPA (oral, 400 mg/d for 14 d) either with capecitabine (CA) (oral, 2 g/m2/d for 14 d) (arm A); eribulin (E) (IV, 1.23 mg/m2 on d1 and d8) (arm B); or carboplatin plus gemcitabine (CG) (IV, AUC 5 on d1 and 1000 mg/m2 on d1 and d8, respectively) (arm C) until disease progression (PD) or unacceptable toxicity. Initially, the safety run-in phase included 3 pts/arm to determine phase IIa doses based on the toxicity observed after 2 cycles. The primary endpoint was incidence of adverse events (AEs) as per NCI-CTCAE v.5.0. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Analysis was exploratory with no hypothesis testing. Results: From September 2020 to October 2022, 54 pts were assigned to arms A (n = 22), B (n = 25), and C (n = 7). In arm C, 4 additional pts received a lower dose level of IPA (300 mg/d) in the safety run-in phase. Based on the toxicity profile, this arm did not proceed with the expansion phase. At data cutoff (10th November 2023), median follow-up was 13.8 (2.4-35.5, arm A) and 11.2 (0.2-36.9, arm B) months (mo). All pts discontinued treatment, mainly because of PD (74.1%). Discontinuations due to AEs were 4.5% and 4% in arms A and B, respectively. Incidence of treatment-related (1) any grade (G) TEAEs was 81.8% and 88% and (2) SAEs was 4.5% and 20% for arms A and B, respectively. G≥3 TEAEs occurring in ≥10% of pts are shown (Table). No treatment-related deaths were reported. Median PFS was 2.7 (95%CI, 1.5-4.1) and 3.8 (95%CI, 1.5-9.6) mo; median OS was 15.5 (95%CI, 11.8-19.2) and 11.5 (95%CI, 8.8-25.1) mo; and ORR was 9.1% and 36% for arms A and B, respectively. Conclusions: Combining IPA with CA and E presented an acceptable safety profile. However, adding IPA to CG was not tolerable. E + IPA showed promising efficacy regardless of PI3K/AKT status that merits further evaluation. Clinical trial information: NCT04464174 . [Table: see text]
Identification of HER2 ultra-low based on an artificial intelligence (AI)-powered HER2 subcellular quantification from HER2 immunohistochemistry images.
Authors: Jung Wonkyung , Lee Taebum , SHIN Sangwon , Brattoli Biagio , Mostafavi Mohammad , Park Gahee , Kim Sukjun , Lee Hyunwoo , Cho Yoon Ah , Cho Eun Yoon , Kim So-Woon , Pereira Sergio , Ahn Chang Ho , Ali Siraj Mahamed , Mirsky Douglas E , Ock Chan-Young
Published: June 2024

1115

Background: HER2-targeted antibody-drug conjugates (ADCs) can effectively target tumor cells even in HER2-low breast cancers (1+ and 2+/no amp). We developed an AI-based whole-slide image (WSI) analyzer for immunohistochemistry (IHC)-stained slides, exploring a cutoff differentiating between true HER2 negative versus HER2 ultra-low. Methods: An AI-based IHC WSI analyzer was developed using 6,188 WSIs stained by 19 types of IHC including HER2 and from various cancers, annotated by 153 pathologists. The model predicts cells as tumor cells or non-tumor cells and generates HER2 expression continuous score (HER2ecs, 0-100%), quantifying IHC staining intensity of membrane, nucleus, cytoplasm, and membrane+cytoplasm separately for each cell. A total of 401 HER2 IHC WSIs were acquired from Samsung Medical Center (n=275), Kyung Hee University Hospital (n=78), and Commercial Biobank (n=48), scored as 0 (n=347) and 1+ (n=54) by pathologists. Results: In total, 67,169,114 tumor cells and 119,113,886 non-tumor cells from 401 WSIs were successfully evaluated. Comparing HER2 score 0 versus 1+ by pathologists, mean HER2ecs of nucleus (1.7% vs 4.1%), cytoplasm (6.5% vs 12.9%), and membrane (3.6% vs 8.2%) were comparable. In HER2 score 0 WSIs, membrane HER2ecs of tumor cell was 3.6 ± 7.8% (mean ± standard deviation), while that of non-tumor cell was 0.9 ± 2.9% (p <0.001 vs. tumor cell), suggesting, even in HER2 score 0 cases, tumor cell exhibits HER2 expression beyond non-specific HER2 staining intensity. Based on our internal validation dataset, membrane-specific HER2ecs of 6.0% was the optimal threshold discriminating HER2 no-staining cells versus HER2 incomplete and faint/barely perceptible cells (AI-HER2-weak) per ASCO/CAP guideline. Among HER2 score 0 by pathologists, when applying this cutoff, the proportion of WSIs showing AI-HER2-weak or higher membrane-specific HER2ecs in over 10% of all tumor cells was 23.6% (82/347). Interestingly, that of WSIs among HER2 score 1+ by pathologists was 51.9% (28/54), which is comparable to 52.3%, objective response rate of trastuzumab deruxtecan in HER2-low patients in DESTINY-Breast04. Conclusions: AI-powered subcellular-level analysis enables identification of 23.6% HER2 ultra-low WSIs among HER2 score 0 by pathologist, which is defined by AI-HER2-weak or higher membrane-specific HER2 expression ≥ 10%. Clinical validation of the AI-powered HER2 ultra-low definition is warranted.
The impact of COVID-19 and missed diagnosis of breast cancer.
Authors: Rohatgi Atharva , Liao Cheng-I , Johnson Caitlin Ruth , Kapp Daniel Stuart , Chan John K
Published: June 2024

1118

Background: To evaluate the impact of COVID-19 pandemic on breast cancer diagnosis based on age, race, and regions within the US. Methods: Data on breast cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 were used to calculate estimated and actual incidence rates per 100,000 females. Rates were age-adjusted as appropriate. We compared actual breast cancer incidence rates in the year 2020 to estimated rates based on trends from 2001-2019 with sub-analyses for age, race, and region. Results: From 2001 to 2019, there were 4,005,763 identified cases of breast cancer in the United States. In 2019, prior to the pandemic, the incidence rate of breast cancer was 162.87 per 100,000 in females in the US. Based on the data from 2001 to 2019, breast cancer increased by 1.32% per year (p<0.001). Using these prior trends, it was expected that the incidence of breast cancer to be 165.02 per 100,000 adults (265,206 total cases) in 2020. However, the reported incidence was only 147.77 per 100,000 (237,471). Thus, there were 10.46% (27,735) less breast cancer cases than expected. The missed diagnosis rate was more pronounced in older age groups with 15.89%, 14.75%, and 13.27% cases missed for the age groups 85+, 80-84, and 70-74 respectively. Based on racial and ethnic groups, we found that Hispanic females had the greatest number of missed cases at 13.04% compared to 12.68%, 10.57%, and 8.94% of Non-Hispanic Asians and Pacific Islander (NHAPI), Non-Hispanic White (NHW), and Non-Hispanic Black (NHB) females respectively. The discrepancy between expected and actual number of cases by U.S. region ranged from the highest in the Northeast (11.90%) followed by 11.83%, 10.60%, and 9.49% in the West, South, and Midwest regions respectively. An intersectionality analysis showed that 40–44-year-old Hispanic females residing in the Midwest region had the largest discrepancy at 27.01%. Conclusions: The reported breast cancer cases significantly declined during the pandemic. Older age, Hispanic race and ethnicity, and those residing in the Northeast region had the greatest number of missing cases. As breast cancer is the most common cancer in the United States, more mitigating factors are needed to improve the access to care for patients in these at-risk groups to improve detection of breast cancer and its associated mortality.
Early combination with mycophenolate mofetil for immune-related hepatitis in patients with solid tumors treated with immune checkpoint inhibitors.
Authors: Igawa Yukiko Shimoda , Yoshida Tatsuya , Yoshinami Yuri , Hibino Yukiko , Arima Takamichi , Sato Jun , Maruki Yuta , Shoji Hirokazu , Namikawa Kenjiro , Sudo Kazuki , Honma Yoshitaka , Hashimoto Hironobu , Yamazaki Naoya , Okusaka Takuji , Yonemori Kan , Yamamoto Noboru , Ohe Yuichiro , Kato Ken
Published: June 2024

12133

Background: Hepatitis, as an immune-related adverse event (irAE), occurs in 2%-10% of patients treated with immune checkpoint inhibitors (ICIs). Although guidelines recommend the use of mycophenolate mofetil (MMF) for steroid-refractory and steroid-resistant ir-hepatitis, there has been no evidence on the efficacy of MMF. Methods: We retrospectively reviewed consecutive patients with solid tumors who developed grade 2 or higher ir-hepatitis requiring systemic steroids after ICIs (nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab and ipilimumab) between January 2015 and August 2023. The changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin level, according to the CTCAE version 5.0, were used to assess ir-hepatitis. ALT improvement was calculated as the ratio of the change in ALT values from onset to day 7, normalized by the ALT values at onset. Results: Among 4405 patients treated with ICI during the study period, 130 patients (3%) developed grade 2 or higher ir-hepatitis requiring systemic steroids. The median age was 62 (range: 19-85) years-old, and 122 patients (94%) had an ECOG performance status (PS) 0/1. These patients included 67 (52%) with melanoma, 35 (27%) with lung cancer, 7 (5%) with esophageal cancer, and 21 (16%) with other cancers. Among 123 evaluable patients, 46 patients (46/123, 37%) received MMF including 20 patients experiencing steroid-refractory and 26 steroid-resistant. The median duration from the start of systemic steroids to MMF was 11 days (range: 0-113 days). Improvement of hepatitis to grade 1 with MMF was observed in 40 patients (40/46, 87%) with a median time of 18 (range: 3-176) days. Of the patients evaluated for the impact of the timing of MMF on the improvement of ir-hepatitis (n=38), ALT improvement at day 7 after ir-hepatitis onset in patients who initiated MMF within 3 days of ir-hepatitis onset (early combination group, n=8) was significantly higher compared with the patients who initiated MMF after 3 days of ir-hepatitis onset (late combination group, n=30) (72.3% vs. 41.7%, p=0.02). Additionally, among patients evaluable for systemic steroid dosage (n=45), the total systemic steroid dosage in patients in the early combination group (n=8) was significantly less than in the late combination group (n=37) (median: 2120mg vs 4005 mg, p=0.02). Conclusions: MMF was effective for both steroid-refractory and steroid -resistant ir-hepatitis. Early combination with MMF in addition to systemic steroids can lead to a more rapid improvement of ir-hepatitis compared to late combination with MMF consequently reducing the total systemic steroid dosage. [Table: see text]
Social vulnerability and clinical trial enrollment: The next frontier of health equity.
Authors: Perati Shruthi Reddy , Mohayya Sana M. , Shippey Ernie , Hochster Howard S. , Omene Coral Oghenerukevwe , Pitt Henry A. , Eskander Mariam F.
Published: June 2024

1508

Background: Clinical trials are the basis for novel therapies but may not be representative of disadvantaged groups, particularly low-income individuals. This study assesses how social vulnerability impacts enrollment and explores the interaction between race and social vulnerability among patients with the top five leading causes of cancer death. Methods: The national Vizient Clinical Database was queried for outpatients with lung, breast, prostate, colorectal or pancreas cancer from 2022-2023. This includes data from 98% of academic medical centers and more than 110 cancer hospitals. The exposures of interest were Medicaid insurance and social vulnerability as measured by the Vizient Vulnerability Index (VVI), a novel marker of social drivers of health at the census tract level. Participation in a clinical trial was the primary outcome. A multivariable analysis was performed evaluating the association of social vulnerability quartiles with clinical trial participation. Interaction tests were performed for race and VVI. Results: 2,660,566 patients were identified. Of these, 36,456 (1.4%) enrolled in a clinical trial: 28.6% with breast cancer, 26.3% prostate, 22.8% lung, 12.8% colorectal and 9.5% pancreas. Trial participants were more likely to be young, White, privately insured, have metastatic disease, and live in a less vulnerable census tract.5.3% of trial participants were insured by Medicaid (12.2% of Black participants, 8.5% of Asian participants, and 3.5% of White participants), compared to 6.2% of non-participants (p<0.0001).22.6% of participants lived in highly vulnerable neighborhoods (53.5% of Black participants, 19.7% of White participants, and 5.6% of Asian participants), compared to 25.0% of non-participants (p<0.0001). Living in the most vulnerable VVI quartile was associated with decreased odds of clinical trial enrollment (OR 0.86; 95% CI 0.82-0.91, p=0.0442), as was having Medicaid insurance vs. private insurance (OR 0.76; 95% CI 0.73-0.80, p<0.0001). The highest social vulnerability quartiles in the VVI domains for education, neighborhood resources and transportation were associated with decreased enrollment (Table). High social vulnerability decreased the odds of enrollment for Black patients (OR 0.80; 95% CI 0.68-0.88, p<0.0001) more than White patients (OR 0.88; 95% CI 0.89-0.96, p=0.0028); p=0.0054 for interaction. Conclusions: 1.4% of patients in this contemporary, cross-sectional cohort enrolled in a clinical trial. Patients with Medicaid have a 24% lower odds of enrollment than privately insured patients. Neighborhood social vulnerability is also barrier to enrollment, even more so among Black patients. Interventions to address social determinants of health may increase racial diversity in clinical trials. [Table: see text]
Primary treatment modification strategies among older adults with advanced cancer.
Authors: Mohamed Mostafa Refaat , Rich David , Lund Jennifer Leigh , Seplaki Christopher , Flannery Marie Anne , Loh Kah Poh , Culakova Eva , Tylock Rachael , Magnuson Allison , Dunne Richard Francis , Ramsdale Erika E. , Mohile Supriya Gupta
Published: June 2024

1512

Background: Primary treatment modification (PTM; any change in dose or agents of the planned chemotherapy regimen from the standard guidelines) is a common therapeutic approach among older adults with advanced cancer due to their geriatric vulnerabilities. However, strategies to employ these modifications are understudied. This study compares a PTM strategy based on Geriatric Assessment (PTM-GA) intervention vs. usual care strategy based on oncologist’s impression (PTM-UC) on treatment tolerability in older adults with advanced cancer starting new chemotherapy regimens. Methods: In this subgroup analysis of the GAP 70+ study (NCT02054741; PI: Mohile), we included patients aged ≥ 70 with incurable solid tumors who initiated a chemotherapy course with PTM (n=298). For the first (PTM-GA) group, PTM was guided by GA results and recommendations while for the second (PTM-UC) group, PTM was guided by the treating oncologist's estimate only. Tolerability outcomes were assessed within 3 months of treatment and included: 1) any grade 3-5 clinician-rated toxicity according to National Cancer Institute Common Toxicity Criteria; 2) subsequent dose reduction; 3) Activity of Daily Living (ADL) decline; 4) unplanned hospitalization. We used multivariable, cluster-weighted generalized estimating equations models to examine the association of PTM-GA vs. PTM-UC and outcomes adjusting for confounders. Results: Mean age was 77 years. The most common cancer types were gastrointestinal (37%) followed by lung cancer (26%). PTM-GA versus PTM-UC was associated with reduced risk of grade 3-5 toxicity (relative risk (RR)= 0.77, 95% CI, 0.61- 0.90) and subsequent dose reduction (RR, 0.46; 95% CI, 0.29-0.73). Point estimates suggest that patients with PTM-GA may have a lower risk of unplanned hospitalization but results did not reach statistical significance (RR, 0.69; 95% CI, 0.46–1.02). PTM-GA vs. PTM-UC was not associated with ADL decline (RR, 1.05; 95% CI, 0.74–1.49). Conclusions: Older patients with advanced cancer who had PTM guided by GA recommendations had improved treatment tolerability compared to those who PTM based on oncologist’s estimate only. Integrating GA into treatment dosing decisions may lead to improved outcomes in this vulnerable population.
Human-AI teams to improve accuracy and timeliness of oncology trial prescreening: Preplanned interim analysis of a randomized trial.
Authors: Parikh Ravi Bharat , Guido Matthew , Girard Anthony , Li Yang , Kolla Likhitha , Chen Jinbo , Emanuel Ezekiel J.
Published: June 2024

1524

Background: Identifying eligible patients for oncology clinical trials (“prescreening”) relies on manual chart review by clinical research coordinators (CRCs), which is time-consuming and often inaccurate. Consequently, 70% of patients with cancer who meet trial eligibility criteria are not offered participation. Natural language processing (NLP) may improve the accuracy and timeliness of prescreening. Methods: This was a preplanned interim analysis of a paired-design noninferiority trial, powered to assess timeliness. We adapted NLP algorithms to identify 13 common eligibility criteria related to cancer type/stage, prior systemic therapy, actionable biomarkers, and response criteria. NLP systems performed optical character recognition, entity and relationship extraction, and natural language inference through deep learning and symbolic AI techniques. Deidentified unstructured electronic health records (EHRs) from real-world patients with non-small cell lung (NSCLC) or colorectal (CrCa) cancer were presented to CRCs via a secure platform. Two CRCs were randomized 1:1 to view blocks of 20 charts each with (Human+AI) or without (Human-alone) NLP annotations. In pre-trial assessment, the CRCs had 86% inter-rater agreement. The primary outcome was overall chart-level accuracy, defined as percent of the 13 CRC-coded eligibility items matching a gold standard set, determined by 2-3 clinicians blinded to experimental arms. Paired t-tests compared overall accuracy (noninferiority margin 5%) and criteria-specific accuracy. Significant differences were assessed for superiority using two-sided paired t-tests. Mann-Whitney tests compared the secondary outcome of timeliness (time per chart review). Results: Among 74 (40 NSCLC; 34 CrCa) of a planned 400 patients, overall accuracy for Human+AI was noninferior to Human-alone (78.7% vs. 76.7%, mean difference 2.0%, p<0.001 rejecting inferiority); both were greater than AI-alone (63.5%). Superiority for Human+AI was demonstrated for RECIST response, but not for overall nor other criteria-specific accuracy (Table). Median time per review was lower for Human+AI than Human-alone (34.1 vs 43.9 min, adjusted p=0.05). Conclusions: Human+AI teams can improve timeliness of trial prescreening with noninferior accuracy. This platform is being used for eligibility assessment in an ongoing clinical trial. [Table: see text]
Food for cancer health equity: The impact of a culturally tailored food voucher intervention on food insecurity among Latinx patients with cancer.
Authors: Hanna Maria T. , Wood Emily Hayes , Villicana Gerardo , Lopez Guzman Lesly , Escobar Kasandra , Reynaga Jajaira , Trotter Chardria , Koontz Zachary M. , Seligman Hilary K. , Patel Manali I.
Published: June 2024

1544

Background: Food insecurity disproportionately impacts immigrant, low-income, and racial and ethnic minorities with cancer. In our prior qualitative work, Latinx and multiethnic patients with food insecurity emphasized the importance of culturally tailored food assistance interventions that could minimize stigma and maintain self-efficacy and autonomy. In collaboration with Latinx patients and community partners in Monterey County, California, we co-developed a culturally tailored food voucher intervention. In this study, we conducted a pilot of the intervention among multiethnic and Latinx patients with cancer and tested the impact on food insecurity and health-related quality of life. Methods: We recruited low-income, racial and ethnic minority adults >18 years of age who screened positive for food insecurity using the 2-item Hunger Vital Sign while receiving cancer treatment in a clinic in Monterey County, CA between July 2023 until August 2023. All participants who consented to participate received $40 monthly grocery store gift cards redeemable at a variety of local retailers for 6 months in addition to usual care provided by trained community health workers who assisted with other health-related social needs. We conducted validated surveys at baseline (time of enrollment) and 6-month follow-up (post-intervention) assessing demographics, food behaviors, food insecurity, and health-related quality of life. We compared pre- and post-intervention proportions with food insecurity using McNemar's tests and change in health-related quality of life using paired t-tests. Results: Of the 30 study participants enrolled, 27 (90%) were Latinx; 24 (80%) spoke Spanish as their preferred language; 16 (53%) had advanced (stage 3 or 4) cancer; 12 (40%) were retired or unemployed; 10 (33%) were disabled; 20 (67%) reported a household income <$35,000 USD. Of the 26 (87%) participants who completed post-intervention surveys, the proportion with food insecurity decreased from 100% to 65% (95% CI 0.60-0.77; p=0.01); 100% adhered to recommended treatment; and health-related quality of life scores increased by 8 points from 71.9 +/-16.1 to 79.5+/- 10.5 (p=0.02) from baseline. Conclusions: This culturally tailored food voucher intervention was associated with reductions in food insecurity and improvements in health-related quality of life among low-income Latinx patients with cancer. This intervention may represent an effective approach to overcome food insecurity in Latinx and multiethnic patients with cancer.
Clinical impact and financial feasibility of remote oncology pharmacists' roles in community oncology practices.
Authors: Roman Andrea , Cho Judy , Jovani Juna , Farag Caroline , Carroll Melissa , Conkling Hilary , Greisl Natalie , Hale Brittney , Kendzierski Daniel , Keisler Meredith , Koselke Beth , Hough Shannon
Published: June 2024

1545

Background: The clinical and financial impact of oncology-trained pharmacists in the community oncology setting has not been well documented. The US Oncology Network has introduced a novel remote oncology pharmacist model which provides clinical services to oncology community practices to alleviate the burden on oncologists, enhance patient care, and improve workflows. Methods: Oncology-trained pharmacists remotely reviewed chemotherapy regimens across 12 community oncology practices. Pharmacists identified opportunities to modify therapy based on clinical criteria, waste reduction, and/or financial stewardship. These modifications were discussed with the treatment team or implemented in accordance with practice-approved policies. Clinical and financial metrics were tracked to assess the overall impact of the pharmacist interventions and provider time saved. Results: From January 1, 2023, through December 31, 2023, 27,938 reviews were documented for 19,962 patients. Among these reviews, the majority (14,572, 73%) required modification by the pharmacist, and many (3,005, 21%) were deemed clinically significant by the intervening pharmacist. The most common clinically significant interventions included changes to anticancer drug doses (1155, 38%), modifications to supportive care (742, 25%) and recommendations for additional monitoring (426, 14%). Across 12 practices, 63 drug-related workflow policies were implemented allowing pharmacists to autonomously auto-substitute products, order laboratory tests and adjust chemotherapy doses. These policies saved over 600 hours of physician time. Pharmacist involvement resulted in medication-related margin improvements totaling $9.3M. Practices also experienced a $4.3M reduction in the total cost of care in medication expenses. The cost of the pharmacists during this period was $1.4M, equating to a 560% return on investment compared to margin improvement. Conclusions: Community oncology practices operate within a resource-constrained model with limited access to oncology pharmacists. As invaluable members of the care team, pharmacists identified opportunities to significantly enhance clinical care by focusing on medication safety, dosing, and regimen optimization, while demonstrating a tremendous financial impact on small-scale budgets. Oncology-trained pharmacists play a vital role in alleviating care burden of the clinical team by collaboratively developing practice-approved policies and reviewing clinical orders in a high-risk patient population.
Using an artificial intelligence platform to enhance cancer detection rates in primary care.
Authors: Bakshi Bea , Dadhania Seema , Holloway Peter , Corbett Claire , Payling Miles
Published: June 2024

1560

Background: Patients with cancer who are diagnosed in a primary care setting have the best survival outcomes compared to any other route (e.g. Emergency department, routine referrals, incidental findings etc). This is primarily attributed to detection of cancer at an early stage. In the UK, the Cancer Detection Rate (CDR) metric serves as a measure of this, representing the percentage of cancer diagnoses originating from primary care referral routes. However, detecting cancer presents significant challenges, primarily due to the non-specific nature of cancer presentations, their tendency to overlap with symptoms of other conditions, and their relatively low prevalence. Artificial intelligence (AI) platforms may be able to support this endeavor but are yet to be established. C the Signs is an AI-enabled clinical decision support tool integrated into primary care practices to help clinicians stratify the risk of cancer and advise on which cancer pathway is most appropriate (if at all) for the patient’s presentation and history. Methods: An observational cohort study was undertaken between 1st May 2021 and 31st March 2022 where 35 practices (covering a population of almost 420,000) within the same geographic region in the East of England were offered the use of C the Signs, with the practices opting out as controls. All practices had the same access to referral and cancer diagnostic pathways within the region. The primary end point was to identify if C the Signs had a statistical impact on cancer detection rates in primary care through nationally linked data via Public Health England. Results: In practices utilizing C the Signs the CDR significantly increased from 58.7% in 2020-21 (prior to the implementation of C the Signs) to 66.0% in 2021-22, reflecting a significant increase of 12.3% (p <0.05). In contrast, practices not using C the Signs maintained a stable CDR of 58.4% in both years. There was no statistically significant variance observed in the referral rate between the two groups, indicating no notable increase in diagnostic or referral activities. Conclusions: These findings underscore the importance of integrating cutting-edge technologies into primary care to improve cancer detection rates and facilitate early-stage diagnosis. Implementation of such advancements holds promise for reducing cancer-related mortality rates and enhancing overall patient outcomes.
Effect of a learning-based approach using the echo-signals obtained by a single-unit transducer on detection of breast tumors.
Authors: Moon Hyeong-Gon , Byeon Jinyoung , Lee Yunna , Cheun Jong-Ho , Kim Young-Gon , Kim Kyoung Min
Published: June 2024

1566

Background: Breast cancer mortalities in the less developed countries are predicted to increase over the next decades mainly due to the low utilization rates of breast cancer screening programs. Additionally, studies have shown that the sensitivity and accuracy of breast self-examination in women are suboptimal. Therefore, it is important to develop a novel and affordable technology that can accurately detect small breast tumors in women. We have developed a deep learning-based echo- signal processing system that can detect breast tumors with high sensitivity and accuracy by merely obtaining ego-motion estimated echo-signals generated by a single-unit piezoelectric transducer system. Methods: We have prospectively collected echo-signals using a single-unit piezoelectric transducer system in 200 patients with breast tumors who underwent curative surgery at the Seoul National University Hospital and SMG-SNU Boramae Medical Center between Oct 2022 and Feb 2024. The data from the first 131 cases was used for the training and testing of the deep learning model with the ratio of 8:2, and the subsequent data from 69 cases was used for the external validation. We used ImageNet pre-trained ResNet50 model to train the deep learning model and adopted various data augmentation methods for model robustness. Five nested cross-validation was used to ensure the generalization performance. Results: The median age of the enrolled patients was 55 (IOR, 47-63) and 65 patients (32.5%) had non-palpable breast tumors. Nearly half of the patients (n=93, 46.5%) had tumors smaller than 2.0 cm in the largest dimension. Our deep learning algorithm showed outstanding performance with the area under the curve (AUC) of 0.914±0.022 and 0.964±0.011 for the image- and region-level, respectively, in the training and testing set (n=131). In the external validation set (n=69), the model demonstrated an AUC of 0.846±0.012 and 0.932±0.009 for the image- and region-level, respectively. As shown (Table), the accuracy, sensitivity, and specificity were substantially improved for the region-level analysis when compared with those of the image-level analysis. Conclusions: Using a prospectively collected data from 200 patients, we developed a highly accurate and robust deep learning model to detect breast tumors in women by processing echo-signals obtained by a single-unit piezoelectric transducer system. Our data indicate that deep learning approach based on low-volume echo signal can lead to a novel and affordable breast tumor screening strategy that can improve early breast cancer detection.[Table: see text]
High-dose almonertinib in treatment-naïve EGFR-mutated NSCLC with CNS metastases: Efficacy and biomarker analysis.
Authors: Fan Yun , Li Hui , Xu Yanjun , Huang Zhiyu , Qin Jing , Zhou Rongrong , He Jing-Dong , Zhu Junfei , Yu SZ , Chen Kaiyan , Han Guang , Chen Jun , Tan Wei , Gong Lei , Lou Guangyuan , Ren Biyong , Chen Xiangqi , Zhang Dianbao , Lu Hongyang , Hong Wei
Published: June 2024

2007

Background: Central nervous system (CNS) metastases is inevitable for epidermal growth factor receptor (EGFR)mutant non-small cell lung cancer (NSCLC). The pre-specified analysis of the FLAURA and other phase III studies has unveiled encouraging results in patients with CNS metastasis. Nevertheless, the availability of limited biomarkers poses a challenge for the early prediction of clinical effects. Methods: We launched a prospective, open-label, single-arm clinical trial across multiple centers (ACHIEVE). Participants, all diagnosed with EGFR-mutated NSCLC with CNS metastases, received first line treatment with high dose Almonertinib through once-daily oral administration, with each dose being 165 mg. The primary endpoints focused on progression free survival (PFS). Concurrently, we gathered baseline and end-of-first-cycle plasma samples, subjecting them to a comprehensive 520 gene-based sequencing analysis. Results: A total of 63 patients were selected and enrolled between Jul 6,2021 and Aug 31,2022. The median follow-up time, until Nov 30,2023, was 538 days. The confirmed Overall Response Rate (ORR) was 88.9% (56/63), while 42.9% (27/63) of patients progressed, with a median PFS of 17.71 months (11.96-NE). Moreover, a notable 88.9% (56/63) of intracranial lesions achieved either a Complete Response (CR) in 21 cases (33.3%) or a Partial Response (PR) in 35 cases (55.6%). To guide and enhance clinical strategy selection, we conducted a comprehensive biomarker evaluation using cell-free DNA (cfDNA) sequencing. Of the 60 baseline plasmas that passed quality control, 81.7% (46/60) were identified as having at least one somatic mutation (ctDNA+). No significant differences were observed between ctDNA+ and ctDNA- groups in terms of ORR (p = 0.33), intracranial ORR (p = 0.499), PFS (p = 0.363, HR = 1.75), and intracranial PFS (p = 0.562, HR = 1.56). Furthermore, we developed a novel algorithm named MedSR (Median Short cfDNA fragment Ratio) based on cfDNA fragment distribution patterns to quantify ctDNA amount. Notably, higher baseline MedSR values (above the median) predicted significantly poorer PFS (p = 0.001, HR = 0.22) and intracranial PFS (p = 0.067, HR = 0.35), demonstrating superior efficacy compared to traditional cfDNA biomarkers like maxAF. On Cycle 2, those achieving ctDNA clearance in C2D1, regardless of their ctDNA status on baseline, exhibited significantly improved PFS (p < 0.001, HR = 4.63) and intracranial PFS (p = 0.001, HR = 5.71). Conclusions: High dose Almonertinib exhibited promising efficacy and maintained tolerable safety as a first-line therapy in EGFR-mutated NSCLC with CNS metastases. The novel MedSR score demonstrated potential value in predicting the efficacy of TKI treatment. Clinical trial information: NCT04808752 .
Racial/ethnic disparities in healthcare utilization, post-operative outcomes, and overall survival for IDH-wildtype glioblastoma stratifying by MGMT promoter methylation status.
Authors: Zhu Ping , Chen Clark C
Published: June 2024

2081

Background: Glioblastoma is the most common malignant primary brain tumor and molecular profiles such as IDH1/2 and MGMT promoter methylation status have significant influence on survival outcomes. There is no "real-world" study has investigated the racial/ethnic disparities in healthcare utilization and outcomes for IDH-wildtype glioblastoma patients with MGMT promoter methylation status. Methods: A total of 21971 IDH-wildtype glioblastoma patients ( MGMT promoter-methylated: 41.5%, 9110/21971) were derived from the National Cancer Database (NCDB, 2018-2021). Race/Ethnicity was grouped into Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Asian/Pacific Islander (API), American Indian/Alaska Native (AIAN), Hispanic, and Others. Overall survival (OS) was set as primary outcome. Healthcare utilization and post-operative outcomes are secondary endpoints. Multivariable logistic regression models, Kaplan-Meier methods, and Cox proportional hazards models were performed for post-operative outcomes, healthcare utilization, and overall survival. Results: Compared to NHW, AIAN were 78% more likely to have MGMT promoter methylation after adjusting age and gender (aOR=1.78, p=0.030). API and Hispanic were significantly less likely to undergo GTR over STR comparing to NHW. The odds of receiving chemotherapy and RT for race/ethnicity minorities patients were significantly lower than NHW (Chemotherapy: NHB: aOR=0.79, AIAN: aOR=0.57, Hispanic: aOR=0.83; RT: NHB: aOR=0.88, Hispanic: aOR=0.80). The median OSs by race/ethnicity (NHW, NHB, API, AIAN, Hispanic, and Others, respectively) were: 11.5, 12.3, 14.5, 9.2, 13.6, and 15.6, months ( MGMT promoter-unmethylated, p<0.001), 15.9, 18.8, 23.7, 14.8, 19.6, and 15.5, months ( MGMT promoter-methylated, p<0.001). After adjusting the covariates, NHB, API, and Hispanic experienced significantly lower risk of death comparing to NHW (aHR=0.82, 0.66, and 0.75, all p<0.001). Similar results were validated in stratification analysis by MGMT promoter methylation status, except MGMT promoter-unmethylated AIAN experienced 70% higher risk of death than NHW (aHR=1.70, p=0.021). Conclusions: Our findings suggests that racial/ethnic disparities exist in healthcare utilization, postoperative outcomes, and overall survival in IDH-wildtype glioblastoma population.
Real-world monitoring and treatment patterns in von Hippel-Lindau (VHL) disease-associated central nervous system hemangioblastomas (CNS-Hb).
Authors: Jonasch Eric , Song Yan , Freimark Jonathan , Mohan Manasi , Signorovitch James , Sundaram Murali
Published: June 2024

2086

Background: VHL disease is an inherited tumor syndrome that causes multiple benign and malignant tumors to develop; CNS-Hb is often the first VHL disease manifestation, occurring in 70-80% of patients with VHL. Patients often need many tumor treatments to manage the disease. This study evaluated disease monitoring and treatment patterns among patients with VHL-CNS-Hb. Methods: Using an algorithm based on VHL manifestations, patients with VHL were identified from Optum’s de-identified Clinformatics Data Mart Database. Patients with a CNS-Hb diagnosis were then selected. Treatment patterns were assessed among patients with VHL after their initial diagnosis of CNS-Hb. Incidence rates (IR) of the following treatments for managing CNS-Hb or other VHL-associated tumors were assessed: surgery for removal of VHL-associated tumors, renal ablation, radiotherapy, targeted therapy for RCC, and retinal laser therapy. Rates for tumor treatments were reported as events per 10-person years. Generalized linear models estimated IRs of analgesic use, VHL disease monitoring procedures, and visits to VHL-related medical specialists in the patient and control cohorts, adjusting for age, sex, the number of outpatient visits at baseline, and health plan type. Results: 220 patients with VHL-CNS-Hb were identified. Reflecting the multifaceted nature of VHL disease, the tumor treatments with the highest unadjusted IRs during the study period among these patients were targeted RCC therapies (2.15 per 10-person years), surgical removal of cerebellar and spinal hemangioblastomas (0.52 per 10-person years), and radiotherapy (0.42 per 10-person years). The tablecontains estimated adjusted IRs and IRRs for the use of select analgesics, monitoring procedures, and medical specialist visits for the VHL-CNS-Hb and comparator cohorts. Conclusions: VHL-CNS-Hb presents a multifaceted burden, involving treatments for various VHL-related tumors. Patients with VHL-CNS-Hb use more analgesics, undergo frequent monitoring, and have increased specialist visits compared with the control group. Successful tumor control holds the potential to reduce morbidity and long-term medical management associated with the disease. [Table: see text]
Clinical validation of a novel circulating tumor DNA methylation assay for predicting recurrence of colorectal cancer in patients with curative-intent surgery by monitoring minimal residual disease.
Authors: Kim Jin-Soo , Lee Yun Young , Kim Mi Young , An Joon , Shin Rumi , Park Jin Hyun , Han Jinil , Choi In Sil , Heo Seung Chul , Moon Youngho
Published: June 2024

3620

Background: Circulating tumor DNA (ctDNA)-based liquid biopsy has emerged as a promising tool for early detection and monitoring of cancer. In this study, we developed COLO eDX, a digital-PCR based colorectal cancer (CRC) diagnostic assay using a single CRC-specific methylation biomarker. This study aimed to evaluate the prognostic value as the universal assay for recurrence monitoring in CRC patients with curative-intent surgery. Methods: A total of 116 CRC patients who underwent surgery at Seoul National University Boramae Medical Center were enrolled in the study from Mar 2017 to January 2020. For each patient, postoperative plasma specimens were collected at 7 days and at each regular clinical follow-up visit up to 2 years. The enrolled patients were followed up with radiological and clinical measures for maximally 5 years after surgery. The primary outcome was recurrence-free survival (RFS) according to ctDNA status. Results: The majority of samples collected at 7 days after surgery were ctDNA positive by COLO eDX (65/83, 78.3%) and the ctDNA status was not significantly associated with RFS, suggesting that cancer signatures can still be detected in most cancer patients at least 1 week after surgery. However, ctDNA positivity at 1 month or later was associated significantly worse RFS. In plasma taken between 1- and 9-months after surgery, ctDNA positive group had a significantly higher recurrence rate than ctDNA negative group (hazard ratio [HR], 11.4, 95% confidence interval [CI], 3.8-34.4; P<0.0001). Incorporating serial longitudinal samples, ctDNA status was significantly associated with recurrence (HR, 13.4, 95% CI, 4.3-40.6; P<0.0001). Notably, ctDNA analysis by COLO eDX was a more powerful predictor for predicting recurrence than carcinoembryonic antigen (CEA) assessment (HR, 4.0, 95% CI, 1.4-11.8; P=0.0107 and HR, 1.5, 95% CI, 0.3-8.2; P=0.5949). Conclusions: Postoperative ctDNA monitoring using a CRC-specific epigenetic biomarker-based digital PCR assay is a promising strategy for recurrence prediction and personalized clinical management of CRC through early detection of minimal residual disease (MRD).