tbuckley/cabot-search huggingface dataset:
PENTA as a model for advanced integrated cancer management in low-resource settings.
Authors: Luis Eduardo Pino, Andrea Isabel Franco
Journal: Journal of Clinical Oncology (2024)

e13783 Background: Cancer models are reactive, fragmented, and volume-based care, in which the lack of coordination between different layers of care, along with clinical and quality variability, technological pressure, and dominant positions, result in high levels of inefficiency and waste, affecting economic sustainability and hence effective access. This is prohibitive for low-resource settings. Modern healthcare system models in this scenarios should focus on solve this problems. Comprehensive cancer management needs a reorientation towards value- and efficiency-generating architectures.Usual redesigns have focused on direct cost containment through intensified audits or new contracting and payment modalities between stakeholders. However, the real impact of these strategies is marginal, increasing sectoral mistrust and failing to meet the quintuple aim. PENTA is a comprehensive cancer management framework to optimize cancer patient care, with emphasis on clinical governance, data guidance, and clinical-administrative alignment. This is an operational model for stakeholders in low-resource settings. PENTA model has been successfully implemented in health insurance companies in Colombia and in private insurance branch in Peru. Methods: PENTA has been applied since 2020. We employed a work methodology based on the Agile-2 matrix, which allows for fluidity and lower resource consumption. This methodology is hybrid and its execution begins with an initial diagnosis of the process within the partner company. This diagnosis includes prioritizing interventions from each of the axes, but understanding that this is a systemic project that includes 5 fundamental axes. This axes must be worked on simultaneously and interdependently to achieve the greatest value. Axes are: 1. Smart Risk Management, 2. Advanced Clinical Gobernance, 3. Value Audit, 4. Technology Management and 5. Value-based Contracting Focus on managing inefficiencies and waste (optimization model), PENTA can generate early results across various dimensions such as clinical variability and technology costs. Structuring and using a cross-cutting data architecture is fundamental to the model's development into a data control tower. Results: Implementation of a data control tower for cancer cohorts , development of joint clinical pathways (insurer-payer) for prioritized diseases, clinical practice agreements with hierarchical positions on high-cost medications, implementation of mini health technology assessments (HTAs), and generation of new prospective payment modalities based on performance adjustment. The estimated savings generated are $1.5 million for the phase 2 in Colombia and $800,000 for the phase 1 in Peru. Conclusions: PENTA is an agile framework for cancer management that can be sucessfully adapted to low-resource settings.
U.S. FDA analysis of enrollment of Asian patients from India in cancer clinical trials leading to approval from 2010 to 2022.
Authors: Geetika Srivastava, Ruby Leong, Abhilasha Nair, Bindu Kanapuru, Fatima Rizvi, Felice Yang, Jennifer J. Lee, Suparna B. Wedam, Asma Ali Dilawari, Chaohong Fan, Sso Lee, Frances Andrada, Clara Lee, Donna Rivera, Steven Lemery, Jennifer Gao, Tamy Kim, Richard Pazdur
Journal: Journal of Clinical Oncology (2024)

e13779 Background: There are an estimated 4.4 million Indian Americans (Asian Indian), constituting 1.35% of the United States (US) population. Indian Americans enrolled in clinical trials are identified under the broad race category of Asian which includes Asians within the US and outside of US (Ex-US). Although cancer is the leading cause of death for Asians in US, they are under-represented in cancer clinical trials. Enrollment of Asian patients from India (API) in multiregional oncology clinical trials may provide important data regarding intrinsic and extrinsic factors impacting the etiology of cancer as well as response to anti-cancer treatment in Indian Americans. Common cancers reported amongst Asians in US are breast, prostate, colorectal, and lung, and in India are breast, head and neck, cervical and lung. Methods: We analyzed data from ~96,000 patients in 164 cancer therapeutic trials that led to an FDA approval for breast, prostate, colorectal, lung, liver, gastric, head and neck and cervical cancer indications from 2010-2022, and identified country for enrollments for all Asians. Results: Descriptive statistics of Asian patients enrolled within US, Ex-US and from India enrolled in breast, prostate, colorectal, lung, liver, gastric, head and neck, and cervical cancer trials that led to an FDA approval from 2010-2022 are summarized (Table). Enrollment of Asian patients within US was ≤1% (except liver and cervical cancer), from India was ≤2.1% of all Asians enrolled outside of US and ≤0.7% of all enrolled patients. Conclusions: It is difficult to accurately characterize the exact number of Indian Americans enrolled but are likely under-represented in cancer clinical trials leading to FDA approval.Sponsors should collect more granular information regarding enrollment of Asian patients in clinical trials. Enrollment of patients from India is extremely low relative to the population size. Efforts to increase enrollment of Indian Americans as well as patients from India in oncology clinical trials can bolster the evidence that supports FDA drug approval and its applicability to Indian Americans. [Table: see text]
Global perspective of barriers in research among oncologists from low-middle income countries.
Authors: Mel Valerie Cruz Ordinario, Mateus Trinconi Trinconi Cunha, Muhammad Rafiqul Islam, Sonia Mathai, Musliu Adetola Tolani, shamali poojary, Assem Suleimenova, Ichrak Ben Abdallah, Ranjana Karmacharya Badgami, Samvel Bardakhchyan, Gauri Gauraiya Chinchalker, Gustavo Gössling, Fedja Radmilo Djordjevic, Coumba Gueye, Jerry Ndumbalo, Rucha Patil, Ramila Shilpakar, Anju Shrestha, Harold Nathan C. Tan
Journal: Journal of Clinical Oncology (2024)

e13781 Background: Cancer research in low-middle income countries (LMICs) face unique challenges, hindering advancements in patient care. Understanding the practices, barriers and strategic needs encountered by oncologists in LMICs is essential for enhancing research capacities and patient outcomes. This study aimed to assess the barriers and facilitators of research among oncologists in LMICs. Methods: This online cross-sectional survey engaged a diverse group of practicing oncologists from LMICs between December 8, 2023 and February 6, 2024. Respondents include both oncology trainees and consultants primarily from Asia (63%), Africa (18%) and Europe (10%). Using a validated questionnaire (test-retest reliability: 0.98), data analysis was performed using frequency and percentages to detail the survey responses, with 95% confidence intervals calculated to ensure the findings reliability. Results: A total of 276 participants from 29 countries, with a mean age of 38 years, responded to the survey. Fifty three percent (n=146) were male and 46% (n = 126) were female, four participants chose not to disclose. Majority of the respondents were trained in medical oncology and related specialties, 71% (n = 196). Forty one percent (n = 113) of them had less than 5 years’ experience as a cancer physician, while a significant proportion were mid-career oncologists with 5 to 15 years of experience. Regarding individual level barriers; 3% (n = 7) had 60 - 100% protected research time, 3% (n = 8) had local and international mentors, 36% (n = 100) had no biostatistical training, 50% (n = 138) had no clinical trial design training, 11% (n = 29) had utilized qualitative design, 60% (n = 165) had not participated in a population-based study, and 83% (n = 228) had not participated in translational research. In relation to system-level barriers; 30% (n = 84) had inadequate research infrastructure and 43% (n = 120) had no clinical trials unit. Respondents rated the degree of implementation of new research findings into local clinical practice as 3 on a five-point Likert scale. Conclusions: This study highlights the critical gaps in research capacity, resource availability, and infrastructure among oncologists from LMICs. Addressing these barriers through targeted interventions is imperative for advancing cancer research and improving patient outcomes in LMIC settings.
Plasma microRNA signature as a potential early detection biomarker in breast cancer.
Authors: Marina Simian, Paula Lucia Farré, Rocío Duca, Karen Graña, Gaston Magi, Juana Moro, Georgina Scalise, Carla Guscelli, Monica Lis Casalnuovo, Sergio Bayo, Emilio Jose Batagelj, Camila Zaslavsky, Javier Stigliano, Carolina Casimo, Monica Avila, Agustina Benedetti, Graciela Lettieri, Megan Torlaschi, María Inés Diaz Bessone, Adriana De Siervi
Journal: Journal of Clinical Oncology (2024)

e13780 Background: The 5-year survival rate for women with stage I breast cancer (BC) is 99%, falling to 27% if the disease is diagnosed in stage IV. This demonstrates the importance of early detection for the effectiveness of BC treatment. Among the new diagnostic strategies, the use of liquid biopsies is emerging as a promising alternative for early cancer detection and patient follow-up. miRNAs are small non-coding RNA molecules useful as biomarkers, since they can be found in body fluids. Oncoliq’s approach focuses on the relative quantification of a panel of circulating miRNA biomarkers for the early detection of BC using predictive models built with machine learning techniques. Methods: The aim of this work was to identify a highly sensitive miRNA combination based on liquid biopsies together with predictive models, to generate an assay for BC early detection which we named Oncoliq breast. Human plasma samples (n=239) from BC patients and healthy donors (HD) were divided into two cohorts: exploratory (n=66) and validation (n=173). The exploratory cohort was used for the identification of miRNAs using expression microarrays and miRNA-seq. The validation cohort was used for the analytical validation of potential candidates by RT-qPCR. Results: Using ROC curve analysis, 11 miRNAs were identified as potential biomarkers. By RT-qPCR, we validated the expression of the 11 miRNAs. All of them were significantly increased in BC patient samples (n=100) compared to HD (n=73), in accordance with expression microarrays and miRNA-seq results. Using machine learning we established 7 predictive models that combine these miRNAs. After running all the predictive models using logistic regression, the metrics associated with each one were calculated. From these, model 7 showed a sensitivity of 90%, a specificity of 73% and an accuracy of 83%. Conclusions: MiRNAs show satisfactory advantages as biomarkers as they can circulate in body fluids, such as blood and urine. In the presence of diseases such as BC, the level of some specific miRNAs might be altered and this change can be harnessed for detection, diagnosis and prognosis. Here, we generated a panel of 11 miRNAs that showed increased expression in plasma samples from women diagnosed with BC. Oncoliq breast is a promising low cost and highly sensitive novel liquid biopsy test based on circulating miRNAs for BC screening.
Achieving World Health Organization Global Breast Cancer Initiative targets: A situational analysis and action plan in Nigeria.
Authors: Anya Romanoff, Olalekan Olasehinde, Chukwuma Eze Okereke, Olayide S Agodirin, Nuhu Ali, Omorodion Irowa, Abubakar Bala Muhammad, Nneka Sunday Nweke, Funmilola Olanike Wuraola, Israel Adeyemi Owoade, Rivka Kahn, Hannah L Kalvin, Kathleen Lynch, Matteo Di Bernardo, Grace Fitzgerald, Victoria Mango, Rachel Vreeman, Benjamin O. Anderson, T. Peter Kingham, Olusegun Isaac Alatise
Journal: Journal of Clinical Oncology (2024)

e13782 Background: Breast cancer [BC] is the leading cause of cancer incidence and mortality in Nigerian women, with five-year survival of 44% vs. 90% in the US. The World Health Organization [WHO], through the Global Breast Cancer Initiative [GBCI], endorses a 3-pillar program that promotes early-stage detection, timely diagnosis, and expeditious treatment. We performed a situational analysis to understand predictors of achieving WHO targets in Nigeria as a basis for implementing an action plan. Methods: We conducted a cross-sectional study using a prospective multi-institutional BC patient database in Nigeria (funded by ASCO), which was expanded sequentially from a single institution in May 2022 to seven institutions representing all geopolitical zones by May 2023. All newly diagnosed BC patients enrolled in the database from 2022-2024 were included. We analyzed univariate associations with WHO GBCI key performance indicators [KPIs] using logistic regression and global p-values. Results: Five-hundred and seventy-one patients were included. Median age was 48 years (IQR 40,56). Conclusions: The utilization of a multi-institutional BC database inclusive of all geopolitical zones in Nigeria provides vital insight for monitoring progress toward WHO targets. Our findings suggest that breast health clinical encounters (through CBE or mammogram) prior to developing BC are associated with reduced diagnostic delays and early-stage BC diagnosis. For those with BC, multiple touchpoints with the healthcare system are associated with increased delays and late-stage diagnosis, which justifies the need for developing patient navigation programs. [Table: see text]
Impact of radiation dose to the immune cells in stage IV non-small cell lung cancer in the era of immunotherapy.
Authors: Junyi He, Yingxin Liu, Butuo Li, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2024)

e20608 Background: Thoracic radiotherapy now is widely accepted in advanced lung cancer. It is not only been used as palliative therapy but also been involved in Systemic treatments in advanced lung cancer, especially in immune era. However, radiotherapy impairs immune system which can be evaluated by estimated dose of radiation to immune cells (EDRIC). Here, we sought to examine the prognostic impact of the EDRIC in advanced NSCLC in the context of immunotherapy, and to identify the factors influencing EDRIC in this population. Methods: We retrospectively enrolled patients with stage IV NSCLC who had received first-line immunotherapy and thoracic radiation therapy. EDRIC is a specific formulation using a model developed by Jin et al and improved by Ladbury et al, calculated using radiation fraction, mean lung dose (MLD), mean heart dose (MHD), and mean body dose (MBD). Spearman’s rank correlation was used to assess the correlation between variables.Associations between EDRIC [analyzed continuously and categorically (&lt;5.7Gy vs ≥5.7Gy)] and overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier and Cox proportional methods. Results: We conducted a retrospectively analysis of 152 patients with stage IV NSCLC patients. GTV (r = 0.2023, p = 0.0137), PTV (r = 0.4139, p &lt; 0.0001) and N (r = 0.1897, p = 0.0193) stage showed a positive correlation with EDRIC. Negative correlations of lymphocyte nadir with EDRIC (r = -0.3172, p &lt; 0.0001), during/pre lymphocyte nadir with EDRIC (r = -0.2102, p = 0.0093), during/post lymphocyte nadir with EDRIC (r = -0.2750, p = 0.0006) were found. Median PFS was shorter among the EDRIC ≥5.7Gy group (10.2months vs 18.6months; p &lt; 0.0001). Median OS was also shorter among the EDRIC ≥5.7Gy group (19.8 months vs 30.2months; p = 0.024). For ORR (38% vs 46%; p = 0.413) and DCR (84% vs 92%; p = 0.304), there was no statistical significance between EDRIC≥5.7Gy and EDRIC &lt; 5.7Gy. Analyzed as a continuous variable, EDRIC was the only factor associated with worse PFS (HR = 1.001, p = 0.018) and OS (HR = 1.002, p = 0.001) in multivariate analysis. Conclusions: In the era of immunotherapy, EDRIC is an independent predictor for PFS and OS in advanced NSCLC, warranting investigation into techniques to optimize radiation dose to the immune compartment.
Efficacy of systemic treatments in patients with metastatic lung invasive mucinous adenocarcinoma.
Authors: Tarik Demir, Murat Araz, Engin Hendem, Mehmet Zahid Kocak, Mustafa Erman, Onur Bas, Osman Köstek, Nadiye Sever, Esra Zeynelgil, Serdar Karakaya, Carolyn Moloney, Liam IL-Young Chung, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

e20609 Background: Invasive mucinous adenocarcinoma (IMA) is a relatively rare histological subtype of lung adenocarcinomas that differs in its clinical behavior, radiologic features, histopathological, and genomic characteristics than invasive non-mucinous adenocarcinomas (INMA). Methods: We retrospectively investigated medical records of patients diagnosed with lung IMA at four oncology centers in Turkey. Patients who were ≥18 years of age, pathologically diagnosed with lung IMA, and who received at least one course of treatment for metastatic or inoperable disease were included in the study. Results: Forty-one patients were included in the study. The median follow-up was 16.6 months. Among the included patients, 24 (58.5%) were male, 17 (38.5%) were female, and their average age was 62. Six (14.6%) patients had a targetable mutation. Three (7.3%) patients were epidermal growth factor receptor (EGFR), two (4.8%) anaplastic lymphoma kinase (ALK) mutation, and one (2.4%) neurotrophic tyrosine receptor kinase (NTRK2) fusion. Most patients (83.1%) had received platinum-based chemotherapy as a first-line treatment. Of the patients who received cytotoxic chemotherapy, 9 (25.7%) had a partial response, 14 (40%) had a stable response, and 12 (34.3%) had progression. The median PFS was 8.24 months (95% CI: 5.9-10.5 months), and the median OS was 20.4 months (95% CI: 14.4-26.3 months) in all study populations. In those receiving cytotoxic chemotherapy, median PFS and OS were 8.11 months (95% CI: 5.02-11.2) and 17.5 months (95% CI: 11.7-23.3 months), respectively. While the PFS of two EGFR-positive patients were similar at 18.9 months and 20.6 months, the third patient's PFS was quite prolonged (66.5 months). The ALK-positive patients receiving brigatinib and crizotinib PFS were 15.8 months and 2.73 months, respectively. The PFS of the patient receiving entrectinib was only two months. Among the entire patient population, only one patient used oxaliplatin and capecitabine combination (XELOX) as chemotherapy. In this patient, who progressed after four cycles of gemcitabine and platinum first-line treatment, a partial response and 7.23 months PFS were achieved with second line XELOX. Conclusions: Standard-of-care treatments have the same efficacy in IMA and INMA patients. Targetable mutation is less common in IMA patients compared to INMA. 5-FU-based chemotherapies also appear to be effective in lung IMA patients.
Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer
Authors: Ignace Vergote, Antonio González-Martín, Keiichi Fujiwara, Elsa Kalbacher, Andrea Bagaméri, Sharad Ghamande, Jung-Yun Lee, Susana Banerjee, Fernando Cotait Maluf, Domenica Lorusso, Kan Yonemori, Els Van Nieuwenhuysen, Luis Manso, Linn Woelber, Anneke Westermann, Allan Covens, Kosei Hasegawa, Byoung-Gie Kim, Miriam Raimondo, Maria Bjurberg, Felipe Melo Cruz, Antoine Angelergues, David Cibula, Lisa Barraclough, Ana Oaknin, Christine Gennigens, Leo Nicacio, Melinda Siew Leng Teng, Elizabeth Whalley, Ibrahima Soumaoro, Brian M Slomovitz
Journal: New England Journal of Medicine (2024)

Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy.
Spectrum of HER2 alterations in NSCLC: Comparative analysis of tissue and liquid biopsies in lung cancer.
Authors: R. K. Choudhary, Deepak Koppaka, Ashok K Vaid, Shriniwas Subhash Kulkarni, Chirantan Bose, Dr Disha Morzaria, Sachin Apurwa, Poornima Vijayan, Amit Dilip Bhatt, Anantbhushan Ranade, Raymond Page, Darshana Patil, Dadasaheb Akolkar, Sewanti Limaye
Journal: Journal of Clinical Oncology (2024)

e20602 Background: Non-Small Cell Lung Cancer (NSCLC) exhibits a spectrum of molecular alterations that play a crucial role in understanding its heterogeneity and tailoring targeted therapies. Among these alterations, HER2 aberrations have gained significance as potential therapeutic targets. This study aims to explore the diversity of HER2 changes in NSCLC through tissue and liquid biopsies, providing valuable insights into the feasibility and accuracy of either method. Methods: Data from next generation sequencing of 799 tissues and 1380 liquid biopsy specimens was retrospectively analyzed. The study sought to elucidate the prevalence of HER2 alterations with these two methodologies, evaluating their respective strengths and limitations in detecting HER2 changes in NSCLC. Results: HER2 mutations were identified in 2.1% (17/799) of tissue, mirroring the prevalence observed in the TCGA cohort (2%). The liquid biopsy cohort identified Her2 mutations with similar prevalence and was positive for Her2 mutations in 2.2% (30/1380). Within Her2 mutations, HER2 exon 20 insertion mutations emerged as the predominant variant, accounting for all variants in tissue samples and 93.3% (28/30) in liquid biopsies. The most frequent HER2 exon 20 variant was p.Y772_A775dup variant (76.5% in tissue, 71.4% in liquid biopsy), followed by p.E770_A771insAYVM (17.6% in tissue and 7.1% in liquid). Less frequent HER2 mutations included p.G776delinsLC, p.G776delinsVC, p.V777_G778insGSP, p.A775_G776insYVMA. HER2 amplification was detected in 1.4% (5/352) of tissue and 1.3% (8/617) of liquid biopsy samples; concurrent HER2 mutation and Her2 amplification were detected in 3 liquid biopsy samples. 11/60 cases had concurrent targetable alterations in other targetable genes. Most common concurrent alterations were in EGFR followed by KRAS. Concurrent EGFR sensitizing alterations were observed in 7 patients ( 6 EGFR Exon 19 deletion and one EGFR L858R). Only 2/7 patients showed concurrent EGFR/HER2 alterations at baseline, the remaining 5/7 patients had received prior EGFR TKI therapy. Conclusions: Our results demonstrate equivalent Her2 alteration detection rate with liquid biopsy as compared to tissue molecular profiling in NSCLC. Our results support utility of liquid biopsy for Her2 profiling in the primary setting as well as to detect acquired Her2 alterations like in patients post EGFR-TKI therapy. It highlights that HER2mutations coexist with HER2 amplification in subset of advanced NSCLC patients. [Table: see text]