tbuckley/cabot-search huggingface dataset:
A retrospective machine learning–based analysis of nationwide cancer comprehensive genomic profiling data to identify features associated with recommendation of mutation-based therapy.
Authors: Hiroaki Ikushima, Kousuke Watanabe, Aya Shinozaki-Ushiku, Katsutoshi Oda, Hidenori Kage
Journal: Journal of Clinical Oncology (2024)

e13510 Background: Comprehensive genomic profiling (CGP) has played key roles in cancer precision medicine through optimization of therapeutic interventions based on genomic alterations in cancer cells. However, the probability of discovering mutation-based treatments through CGP remains low. To enhance the effectiveness and efficiency of cancer precision medicine, it is crucial to identify patients who are likely to benefit from CGP tests. This study aims to identify characteristics of patients in which mutation-based treatments are discovered by CGP tests. Methods: We retrospectively analyzed data from 60,655 patients who underwent CGP tests and were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national data center for cancer CGP in Japan. The C-CAT database covers 99.7% of cancer patients who have undergone CGP tests in Japan. Major cancer types included 10,182 cases of bowel cancer, 8,691 pancreas cancer, 5,062 biliary tract cancer, and 3,777 breast cancer. We developed an eXtreme Gradient Boosting (XGBoost) model using machine learning, and used clinical information as input to predict whether one or more Japanese Pharmaceuticals and Medical Devices Agency (PMDA)-approved drugs are discovered through CGP tests or not. Shapley Additive Explanations (SHAP) was employed to extract significant features that contribute to the model prediction. Results: The prediction model achieved an area under the receiver operating characteristic curve of 0.826 for the overall cancer population. Positive SHAP values were observed for patients with breast (mean SHAP in breast cancer patients: 1.38), lung (1.08), bowel (0.75), and pancreas cancers (0.35), while negative SHAP values were associated with head and neck (-1.75), cervical cancers (-1.54), and brain (-1.33). Positive SHAP values were also associated with presence of liver or lymph node metastasis (0.23, 0.08), shorter intervals between diagnosis and CGP testing or specimen collection and CGP testing, and advanced age. Similar trends were observed in cancer-type-specific prediction models, which also identified their own unique features. In the adolescent and young adult (AYA) age group, primary brain tumors were strongly associated with negative SHAP values (-1.37). Conclusions: Our machine learning-based analysis of nationwide CGP data identified features that predict cases in which mutation-based treatments are discovered by CGP tests, both in the overall cancer population and within specific cancer types and the AYA age group. Expedited CGP testing is recommended for patients who match the identified profile to facilitate early targeted therapy interventions.
Deciphering the global landscape of breast cancer in 38 OECD countries from 1990-2019: A benchmarking global analysis.
Authors: Priyatha Vemparala, Shivani B Sonani, Pinank Bathvar, Gunjan Kochhar, Himanshu Bharatkumar Koyani, Nihar Prafullchandra Vavaliya, Mandeepsinh Vashi, Dhruval Pinalkumar Patel, Mihir Paresh Vanodia, Mohit Lakkimsetti, Juhi Patel, Dhruvkumar Gadhiya, Vishrant Amin, Hardik Dineshbhai Desai
Journal: Journal of Clinical Oncology (2024)

1046 Background: Breast Cancer (BC) stands as the primary contributor to disability and the second leading cause of death among countries belonging to the Organization for Economic Cooperation and Development (OECD). A comprehensive cross-country analysis of BC is crucial to monitor the growing burden. Methods: Employing the global burden of disease framework, we have calculated the incidence, prevalence, mortality, disability-adjusted life years (DALYs), and years of life lost (YLL) attributed to BC, categorized by age, gender, year, and geographical location across the 38 OECD member countries. Results: The total number of BC cases has witnessed a notable increase, rising from 5.5 million (95%UI: 5.1-6) in 1990 to 9 million (8.2-9.8) in 2019. BC-related deaths have also risen from 172,148 (164,284-176,147) in 1990 to 214,458 (195,692-226,347) in 2019, while DALYs have increased from 4.6 (4.5-4.8) in 1990 to 5.1 (4.8-5.5) in 2019. The annual percentage change (APC) in incidence has surged by 59% (44-75%) from 1990 to 2019. The highest APC in age-standardized incidence rates was observed in South Korea at 150% (99-205), while the most substantial decrease was recorded in Switzerland at 3%. Regarding death rates, Japan saw an 11% increase, Costa Rica 10%, Mexico 9%, South Korea 8%, and Turkey 4%, whereas the remaining countries witnessed a decrease from 1990 to 2019. In terms of DALY rates, Mexico and Japan experienced a 10% increase, South Korea 5%, Turkey 3%, with the rest showing a decrease from 1990 to 2019. Males bore a higher burden compared to females, with an APC in total incidence of 109% versus 58%, deaths at 73% versus 24%, and DALYs at 57% versus 10% from 1990 to 2019. The highest overall burden was observed in the 70+ age group, while the &lt;70 and &lt;20 age groups exhibited a decreasing trend. The total number of deaths is projected to continue increasing. Conclusions: In 2019, BC accounted for 6.64% of all cancer-related deaths and 7.9% of DALYs among women. Based on these findings, low-resource countries should consider reallocating funding to combat this burden, and public health policymakers need to prioritize surveillance and early screening efforts.
A phase II trial comparing dalpiciclib in combination with letrozole versus standard chemotherapy as neoadjuvant therapy in patients with high-risk HR- positive HER-2 negative breast cancer: DARLING-02.
Authors: Lina Zhang, Cuizhi Geng, Yueping Liu, Jianjun Han, Meng Han, Ruixue Huang, Xianqiao Li, Ruizhen Luo, Yuntao Li, Jie Ma, Huaihua Qi, Zunyi Wang, Xiaochun Wang, Chao Yang, Jingqiang Yang, Lixian Yang, Jingjing Yu, Yingzhou Zhang, Zhisheng Zhang, Xinping Zhou
Journal: Journal of Clinical Oncology (2024)

TPS626 Background: Dalpiciclib is a CDK4/6 inhibitor that has shown promising efficacy and safety when in combination with endocrine in the treatment of advanced HR+ HER2- breast cancer. Building on preliminary findings from our previous study (Geng, 2023SABCS PO2-02-05), we aim to evaluate the efficacy and safety of dalpiciclib combined with letrozole versus standard chemotherapy as neoadjuvant treatment in patients with high-risk early breast cancer (EBC). Methods: This is a prospective, multicenter, randomized phase II non-inferiority trial. Main eligibility criteria include: female patients ≥18 years, ECOG performance status of 0-1, histologically confirmed invasive breast cancer, clinical stage T1c-T2, cN1–2 or T3-4, cN0-2, ER≥50%, HER2-negative, and Ki67 ≤ 20%. Participants are randomized 1:1 to receive either 24-week experimental intervention (oral dalpiciclib 150mg once daily for 3 weeks on, 1 week off and oral letrozole 2.5 mg/day) or 24-week standard intervention (intravenous epirubicin 100 mg/m² and intravenous cyclophosphamide 500 mg/m² on day 1 for three 3-week cycles, followed by intravenous docetaxel 100 mg/m 2 on day 1 for three 3-week cycles). The primary endpoint is the objective response rate (ORR) assessed by RECIST v1.1. Secondary endpoints include patient-reported outcomes (EORTC QLQ-C30, EORTC QLQ-BR23), residual cancer burden 0–I rate, preoperative endocrine prognostic index score 0 rate, pathological complete response rate , 2-year invasive disease-free survival rate, and safety. Exploratory endpoints include biomarker analysis. The hypothesis is that the experimental group will not be inferior to control group. Assuming an ORR of 70% for both groups, a sample size of 65 patients per group is required to achieve 80% power to detect a non-inferiority margin of up to 20% at a two-sided significance level of 5%. A total of 130 patients are needed (65 per group). Considering a dropout rate of 10% per group, the total sample size is approximately 144 patients. The trial was registered at ClinicalTrials.gov (NCT06107673) and is actively recruiting. Clinical trial information: NCT06107673 .
Diagnostic test use and time to cancer diagnosis in Medicare recipients.
Authors: Karen Chung, Andrew J. Epstein, Michelle K. Kim, Jordan J. Karlitz
Journal: Journal of Clinical Oncology (2024)

1622 Background: In the Medicare-aged population, liver, ovarian and pancreatic cancers have an incidence of 34–73/100,000, are associated with high mortality, can often be associated with no or vague symptoms, and rely on multiple tests for diagnosis (dx). Our objective is to quantitate dx testing and time to a cancer dx in Medicare recipients. Methods: Pts with newly dx’d liver, ovarian or pancreatic cancers were identified in 100% fee-for-service (FFS) Medicare enrollment and claims data from 1 Oct 2017 - 31 Dec 2022. Dx test use was tracked for up to 24 months prior to dx; pts had to have ≥1 dx test within 60 days before the cancer dx date. Inclusion criteria also included ≥24 months of continuous enrollment in FFS Medicare prior to dx and qualification based on age ≥65. Exclusion criteria included prior cancer dx and Medicare Advantage enrollment. The start of dx workup was identified by looking back in time at the sequence of dx tests occurring before the cancer dx date and were separated by ≤60 days between consecutive tests. The earliest test in the sequence was deemed the first dx test. Index date was defined as the latest office visit date before the first dx test or date of the first dx test if no office visit met criteria. Dx tests (ie, biopsies, endoscopies, imaging, lab tests) were identified by billing/CPT codes. Dx workup duration from index to dx date and dx test types received were tracked. Results: Among 59,490 Medicare beneficiaries analyzed, mean age was 77.0 (SD 7.3), 60% were female, and 80% were non-Hispanic White. Median (25 th , 75 th percentile) days from index date to cancer dx was 56 (24, 109) for liver, 47 (20, 91) for ovary, and 43 (16, 89) for pancreas. Dx testing modalities utilized for each cancer type (Table) demonstrate high variability. The percentage of pts who underwent both CT and MRI to help establish a liver, ovarian and pancreatic cancer dx was 38.6%, 14.1% and 32.3%, respectively. While overall imaging use prior to dx was high, PET and PET-CT use was low (&lt;1% PET; 1.7%–2.2% PET-CT). Conclusions: Multiple tests are utilized to establish a cancer dx in Medicare beneficiaries, including use of multiple imaging modalities in the same patient. 25% of pts required more than 89-109 days, depending on cancer type, to establish a dx. There may be opportunities to increase diagnostic efficiency and shorten time to cancer diagnosis in older individuals. [Table: see text]
Predictors of response and surgical approach after neoadjuvant chemotherapy in receptor-positive/HER2-negative stage II-III breast cancer patients treated in two private cancer care centers in Lima, Peru: Real-world data.
Authors: Franklin Aldecoa-Bedoya, Sebastian Aldecoa-Falcon, Silvia Gabriela Falcon
Journal: Journal of Clinical Oncology (2024)

e12659 Background: The role of neoadjuvant chemotherapy (NAC) in hormone receptor-positive HER2-negative breast cancer (BC) is controversial, its main benefit being to improve the surgical outcome in both breast and axilla. The aim of this study was to evaluate the response to NAC, as well as possible predictors and the type surgery performed after primary treatment. Methods: Observational, retrospective study from a database of 1356 consecutive cases of BC between 2016 and 2022 in two private oncology centers in Lima Metropolitana. There were 726 new cases of hormone receptor-positive HER2-negative BC (53.5%), of which those patients with clinical stage II-III who received NAC were considered (n=122, 16.8 % of luminal HER2-negative). Results: The average age of the sample was 46.6 years (range 25-72) with a predominance of luminal B subtype (60.7%) and clinical stage II disease (51.6%), as well as an average delay time to treatment of 33.9 days. Chemotherapy choice was AC every 3 weeks followed by weekly paclitaxel (98.4%). The pathological complete response (pCR) rate was of 16.4% in the breast, 29.1% in the lymph nodes and 13.9% in both. None of the variables studied (age, histologic grade and type, clinical stage, tumor size, number of nodes, hormone receptors, Ki-67 and HER2 low) were predictors of pCR. According to RECIST criteria, tumor shrinking in the breast occurred in the majority of patients (partial and complete response: 86.1%) and eight out of ten patients achieved a tumor size reduction of more than 50%. The rate of mastectomy was 67.2% and radical axillary dissection, 70.5%. Conclusions: In our cohort, we found a pCR rate similar to that reported in the world literature. No predictors of pCR were found. Despite the high proportion of tumor response at breast and node level, the surgical approach was mostly radical. The multidisciplinary BC committee in our setting should be strengthened in order to make better decisions on the surgical approach for patients with hormone receptor-positive HER2-negative stage II-III BC who receive NAC.
Predicting pathological response in early-stage triple-negative breast cancer: Exploring the role of BRCA gene mutations—A retrospective single-institution study.
Authors: Howide Eldib, Kemnasom Nwanwene, Yury Kachynski, Thomas Wright, Mahmoud Abdallah, Love Kumar, Ahmad Mahdi, Leena Alhusari, Mina Shenouda, Maria Tria Tirona
Journal: Journal of Clinical Oncology (2024)

e12656 Background: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer, constituting approximately 15-20% of all breast cancer cases. While less than 10% of all breast cancer patients harbor BRCA1/2 mutations, ~20% of TNBC patients carry these mutations. Notably, at least one-third of BRCA1 carriers develop TNBC. This study aimed to investigate the association between BRCA mutation status and pathological response (PR) in early-stage TNBC patients, specifically, the impact of BRCA positivity on achieving pathological complete response (pCR), and identify other potential predictors of PR. Methods: We conducted a retrospective cohort study of patients with early-stage (Stage I-III) triple-negative breast cancer diagnosed and treated at our institution between January 2012 and June 2022, following Institutional Review Board (IRB) approval. Patients were identified from our Institutional Cancer Registry based on complete data availability (including other inclusion criteria) excluding patients who did not receive neoadjuvant chemotherapy. Data on demographics, tumor characteristics, treatment regimens, and pathological response (assessed according to [specified criteria]) were extracted from the charts. Results: Out of 228 patients diagnosed with early-stage triple-negative breast cancer, 54.6% had no genetic mutations, while 7.9%, 4.9%, and 8.4% harbored BRCA1, BRCA2, and other mutations, respectively. Notably, 23.4% did not receive genetic counseling or testing at our institution. Patients with BRCA2 mutations had a 100% pathological response rate, of which 57.14% had pCR, compared to 85.7% for BRCA1, of which 71.43% had pCR. Furthermore, 93.8% of patients with other genetic mutations had pathological response, of which 56.25% had pCR, as compared to 68.42% in non-mutated cases of which 26.7% had pCR ( P=0.038). Analysis of other variables revealed no significant impact of age, BMI, performance status, or neoadjuvant chemotherapy regimen on pathological response. Conclusions: This retrospective study suggests a trend towards higher complete pathological responses in early-stage triple-negative breast cancer patients with BRCA and other genetic mutations compared to those without. These findings were statistically significant, indicating a potential clinical trend that specific genetic mutations may be associated with improved response to neoadjuvant chemotherapy in early-stage triple-negative breast cancer. Further research is needed to confirm these findings and guide the development of personalized treatment strategies based on a patient's genetic profile. Additionally, our findings highlight the importance of genetic testing for all patients with early-stage triple-negative breast cancer, regardless of age or family history.
Analyzing correlates for cervical cancer awareness in Mauritania, Madagascar, and Benin from the Demographic Health Survey (DHS): 2017-2022.
Authors: Daniel J Olivieri, McKenna Eastment, Noleb Mugume Mugisha, Leeya Fatima Pinder, Manoj Menon
Journal: Journal of Clinical Oncology (2024)

1626 Background: Cervical cancer is the leading cause of cancer-related mortality in low- and middle-income countries (LMICs). Prior studies associate high cervical cancer awareness with reductions in cervical cancer incidence. Herein we utilize nationally representative Demographic and Health Surveys Program (DHS) to analyze correlates of cervical cancer awareness and inform global outreach strategies. Methods: All DHS surveys conducted between 2017-2022 were queried for questions on cervical cancer awareness. Socio-demographic (e.g., age, marital status), socioeconomic (e.g., education, wealth, literacy) and variables pertaining to healthcare decision making, intimate partner violence (IPV), and female genital mutilation/circumcision (FGC/M)) were extracted. Sample weights were applied, and bivariate logistic regressions were performed. Variables with p&lt;0.20 were included in multivariate analysis. Results: Of the DHS surveys, we analyzed data from 25,239 women aged 15-49 years old living in Mauritania, Madagascar, and Benin - the only three countries which met search criteria. Cervical cancer awareness varied from 41% in Mauritania (3,283/7,290), 32% in Madagascar (3,071/9597), and 10% in Benin (783/7,712). After multivariate adjustment, age (OR=1.03 [1.02-1.04]; OR=1.04 [1.03-1.05]; OR=1.03 [1.01-1.05]), education (OR=1.21 [1.06-1.38]; OR=1.68 [1.48-1.91]; OR=1.83 [1.51-2.23]), and wealth index (OR=1.18 [1.07-1.30]; OR=1.24 [1.16-1.32]; OR=1.18 [1.07-1.30]) were associated with increased awareness across Mauritania, Madagascar, and Benin, respectively. Mobile telephone ownership was associated with increased awareness in Mauritania (OR=1.87 [1.48-2.36]) and Benin (OR=1.66 [1.27-2.19]), and internet usage was associated with increased awareness in Madagascar (OR=1.75 [1.46-2.10]) and Benin (OR=1.71 [1.33-2.31]). Women who underwent FCG/M (OR=0.81 [0.67-0.98]) were associated with decreased awareness in Mauritania. Women who experienced IPV were associated with increased awareness (OR=1.39 [1.11-1.73]) in Mauritania. Women who independently make healthcare decisions were associated with decreased awareness in Mauritania (OR=0.88 [0.83-0.95]) but increased awareness in Madagascar (OR=1.07 [1-1.15]). Rurality was associated with decreased awareness in Madagascar (OR=0.71 [0.59-0.84]). Last, less than 1% (200/25,239) of all women were screened for cervical cancer. Conclusions: Age, education, and wealth were associated with increasing awareness, while rurality and FGM/C were associated with decreased awareness in various settings. Given the known association between awareness and screening, targeted efforts to increase awareness among women with lower socioeconomic status has the potential to reduce global cervical cancer disparities.
Geographic disparities in brachytherapy accessibility for cervical cancer.
Authors: Misuk Lee, Hyo Chun Lee
Journal: Journal of Clinical Oncology (2024)

1577 Background: While brachytherapy stands as a crucial component of the treatment for locally advanced cervical cancer, the issue of geographic disparities in brachytherapy accessibility has become a noteworthy public health concern in South Korea. Moreover, the specific factors contributing to these disparities have not been clearly elucidated. In light of this, we conducted a nationwide ecologic study to comprehensively investigate the socioeconomic factors associated with brachytherapy accessibility. Methods: A total of 2,998 patients newly diagnosed with cervical cancer in 2020 were identified through the Korea Central Cancer Registry (KCCR). Across 17 administrative districts in South Korea, 32 brachytherapy facilities were available. To capture unique socioeconomic factors for each region, including the number of Korean Medicaid (K-Medicaid), Medicare (K-Medicare) beneficiaries, marriage immigrants, registered foreigners, and total residents, data were obtained from the Korean Statistical Information Service (KOSIS). Notably, K-Medicaid and K-Medicare represent governmental medical insurance assistance for patients in poverty and those aged over 65, respectively. The brachytherapy accessibility rate (BAR) was defined as the number of brachytherapy procedures divided by new cervical cancer cases. Additionally, each district's socioeconomic factor was normalized by the number of residents. Univariate and multivariate logistic regression analyses were conducted to explore the relationships between BAR and socioeconomic factors. Results: The capital city and its adjoining metropolitan area accounted for 46.9% of the total brachytherapy facilities, with Seoul having 25% (8 out of 32) and Gyeonggi having 21.9% (7 out of 32). Conversely, three non-metropolitan regions had no brachytherapy facilities. In the multivariate logistic regression analysis, the brachytherapy accessibility rate (BAR) demonstrated an inverse association with both the number of K-Medicare beneficiaries and the total immigrant population (Odds ratios of 0.66 and -2.85, respectively). Conclusions: To the best of our knowledge, this is the inaugural study highlighting the robust associations between older age and foreign residency status with reduced accessibility to brachytherapy. The observed inaccessibility to brachytherapy has the potential to impede the delivery of standard care, consequently leading to a poorer prognosis for vulnerable populations. Future research endeavors and targeted social interventions will be imperative to rectify geographic disparities in brachytherapy accessibility and ensure equitable healthcare outcomes.