tbuckley/cabot-search huggingface dataset:
Novel screening approach for cancer cachexia using metagenomic gut microbiome profiling in patients with advanced non-small cell lung cancer.
Authors: Taiki Hakozaki, Eder Mendez Salazar, Takayuki Kobayashi, Shota Fukuoka, Shohei Koyama, Hiroyoshi Nishikawa, Daisuke Motooka, Shota Nakamura, Yusuke Okuma, Yukio Hosomi, Haruko Takeyama, Masahito Hosokawa, Bertrand Routy
Journal: Journal of Clinical Oncology (2024)

12090 Background: Cancer cachexia (CC) is a multifactorial syndrome involving immune-metabolic crosstalk across multiple organs and has been associated with a negative clinical impact in patients with non-small cell lung cancer (NSCLC) amenable to immune checkpoint inhibitors (ICIs). In parallel, the gut microbiome (GM) has emerged as a key contributor to ICI response. In this study, we aimed to evaluate the association between CC and GM composition and its metabolic potentials. Methods: We collected fecal samples from 139 patients with advanced NSCLC treated with ICI. In addition to 16S rRNA sequencing for all patients, shotgun metagenomic microbiome profiling was performed for 69 patients to estimate the species-level composition and functional capacity of the GM. Cancer cachexia was diagnosed according to the international consensus based on the body weight changes over the previous six months. Survival time was calculated using the Kaplan-Meier method. GM diversity indices, differential abundance, and functional profiles based on the MetaCyc database were compared between the patients with and without CC. Results: Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group compared to the non-cachexia group [4.5 vs. 11.5 months (p &lt; 0.001) and 10.8 vs. 44.9 months (p &lt; 0.01), respectively]. Both GM profiling techniques revealed a significant difference in beta diversity between both groups (p &lt; 0.01). In addition, metagenomic analyses revealed the distinct characteristics of GM at the species level between the groups. The CC group showed an overrepresentation of the commensal bacteria, such as Escherichia coli, Ruthenibacterium lactatiformans, Hungatella hathewayi,and Eggerthella lenta, whereas the non-CC group showed an enrichment of Parabacteroides distasonis, Eubacterium rectale,and Roseburia inulinivorans. Moreover, functional analysis revealed the significantly different metabolic potentials of GM in the CC group. The CC group showed an enrichment of pathways, such as D-arabinose degradation II, L-lysine degradation, and octan oxidation. Finally, the clustering of patients based on significant metabolic pathways or gene reactions provided a high predictive ability to discriminate between patients with and without CC. Conclusions: The shotgun metagenomic approach allowed for the characterization of the altered gut microbes and their metabolic potentials in patients with CC. Stratification based on the GM profiles may be useful as a novel screening method for CC, which is progressive and may involve more multistage pathology than identified by the conventional approach.
Association of lung cancer-associated cachexia with the metastatic spread to pleura.
Authors: Bartosz Sekula, Pawel Szymanski, Magda Konkel, Alicja Zielińska, Gioia Altobelli, Mikołaj Szewczykowski, Edmund Naczk, Magdalena Dróżka, Witold Rzyman, Rafal Dziadziuszko, Marcin Tomasz Skrzypski
Journal: Journal of Clinical Oncology (2024)

12095 Background: Cancer-associated cachexia (CAC), a major contributor to mortality in patients with non-small cell lung cancer (NSCLC), is characterized by alterations in body composition. Here, we explore the associations between body composition changes and the pattern of lung cancer metastatic spread. Methods: Computer tomography (CT) images from cancer diagnosis and recurrence were used to quantify subcutaneous and visceral adipose tissue (SAT, VAT) and skeletal muscle (SKM) tissue areas at the 3rd lumbar vertebrae level, using an DAFS AI-based software, Voronoi Analytics, in 101 NSCLC pts, who relapsed after surgical treatment of the primary tumor at the Medical University of Gdansk Hospital. The decrease in SKM, SAT and VAT of more than 5% or 10% at cancer relapse was compared with the pattern of cancer recurrence. Results: The median time to recurrence after primary tumor resection was 1.6 years (0.4–6.4 years). There were 38% local or regional recurrences, 59% distant recurrences, and 13% second primary lung cancers. Among the cases with distant recurrence, there were 19% brain recurrences, 22% pleural metastases, 34% lung metastases, 17% bone metastases, and 11% cases of liver relapse. More than one site of distant recurrence occurred in 51 (50%) of patients. Loss of &gt; 5% of SKM, SAT and VAT occurred in 61%, 33% and 41% respectively. Loss of &gt;5% or &gt;10% of SKM was associated with the pleural metastases at the time of cancer recurrence, ( P &lt; 0.001). Median muscle loss was –11.6% for patients with pleural relapse and –5.3 % for patients with other metastatic locations ( P &lt; 0.001). There were no significant associations between other body composition changes and the pattern of recurrences, tumor histology or age. Conclusions: NSCLC relapse to the pleura after surgical treatment of the primary tumor, appears to be associated with a decrease in the skeletal muscle compartment. This finding may inform the design of the future studies aiming to investigate molecular correlates of sarcopenia and cancer-associated cachexia.
Late mortality and chronic health conditions in long-term survivors of nasopharyngeal cancers: The 20-year follow-up of territory-wide Hong Kong Nasopharyngeal Cancer Survivor Study (HKNPCSS).
Authors: Chi Leung Chiang, Ching Lung Cheung, Sik-Kwan Chan, Philip Chun Ming Au, Ka Shun Fong, Chor Wing Sing, Charlene Hoi Lam Wong, James Chung Hang Chow, Ken Ka Man Cheung, Winnie Wing Yan Tin, Edwin Chun Yin Wong, Tracy Tsz Shan Lau, Kenneth Chun Wai Wong, Ann Sum Yin Chan, Victor Ho-Fun Lee, Anne Wing Mui Lee, Wai Tong Ng, Ian Chi Kei Wong
Journal: Journal of Clinical Oncology (2024)

12045 Background: The survival rate of patients with nasopharyngeal cancer (NPC) has significantly improved in the last decade. However, there are only a few studies that have quantified the long-term morbidity and mortality that follow NPC treatment. This study aims to analyze the chronic health conditions, all-cause mortality, and cause-specific mortality among NPC survivors. Methods: The Hong Kong NPC Survivor Study (HKNPCSS) is a retrospective cohort study conducted across all six oncology centers in Hong Kong. It included longitudinal follow-up of 5-year survivors diagnosed with NPC between 1997 to 2015. We compared the standardized mortality ratio (SMRs) of 7893 survivors to a matched population in terms of age, sex, and calendar year. We also calculated the frequencies of chronic conditions of 7893 survivors and 23679 healthy individuals with matched age, sex, and date of cohort entry. Chronic health conditions were classified using the Common Terminology Criteria for Adverse Events. Cox proportional hazard models were used to estimate hazard ratios (HRs) for chronic health conditions. Results: The mean age of NPC survivors was 49.1 years, while healthy individuals had a mean age of 50.5 years. Among the 7893 NPC survivors, the 20-year cumulative all-cause mortality was 34.0% (95% CI, 29.1%-38.9%), with 1668 (59.9%) of 2785 deaths attributed to health-related causes. The SMR for NPC survivors compared to the general population was 3.81 (95% CI, 3.67-3.95), with the highest SMRs observed for pulmonary (SMR: 6.18, 95% CI, 5.73-6.64) and cardiovascular (SMR: 2.12, 95% CI, 1.90-2.36) causes. Among the survivors, 59.2% (n=4674) had severe, life-threatening, or fatal (grade 3-5) health conditions, with a 20-year cumulative incidence of 59.0% (95% CI, 56.4%-61.5%). The adjusted hazard ratio (HR) of grade 3-5 chronic condition in NPC survivors, compared to healthy cohorts, was 7.02 (95% CI, 6.64-7.42). Gastrointestinal (HR: 20.7), hearing, visual, and nasal (HR: 15.4), and neurological (HR: 8.39) conditions had the highest risks. Intensity modulated radiotherapy (IMRT), compared to non-IMRT, was associated with reduced risks of all-cause mortality (HR: 0.83, 95% CI, 0.74-0.91) and a trend towards reduced grade 3-5 chronic health conditions (HR: 0.89, 95% CI, 0.75-1.05). Conclusions: Even 20 years after diagnosis, NPC survivors still face increased risks of late mortality and morbidity. The findings emphasize the need for a comprehensive survivorship program to improve outcomes for NPC survivors.
Retroperitoneal leiomyosarcoma; Demographics, clinicopathological, survival analysis, role of adjuvant radiation and genomic analysis.
Authors: Hafeez Ullah, Abdul Qahar Khan Yasinzai, Bisma Tareen, Naema Daino, Asad Ullah, Saleh Heneidi, Basil Rasool, Nabin R. Karki
Journal: Journal of Clinical Oncology (2024)

e23327 Background: Retroperitoneal leiomyosarcoma (RPL) is an exceedingly rare malignancy and is the second most common subtype of leiomyosarcomas. Most of the information concerning this rare disease is limited to case studies and few literature studies. The study's objectives were to assess the demographics, pathological factors, survival outcomes, genomic landscape and potential for targeted therapy. Methods: Data of retroperitoneal leiomyosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, with cases diagnosed between 2000 and 2020 used for this study and the Cancer Genome Atlas containing sequencing information for 27 cases of RPL. Results: A total of 1406 cases were extracted with mean age of diagnosis of 62.1 years. Of these, RPL had a higher incidence in women (71.5%), more cases affected Whites (58.7%). Histologically, in patients with known grading, most patients’ i.e. 62.35% were grade 3, G3 (poorly differentiated). Nearly all (99.9%) patients presented with a tumor size ≥4.1 cm. Local lymph nodes metastasis were positive in 76.0% of cases when lymph node status was reported. In known cases of distant metastases, the most common site was liver (8.9%). The main treatment modality was surgery only (26.7%, hazard ratio, HR 1.17, p-value &lt; 0.001), followed by the standard of care (surgery and radiation) (18.4%, HR 1.03, p-value &lt; 0.001), and radiation only (18.4%). Five-year overall survival was 40% and 5-year cause-specific survival was 64%. The highest 5-year survival was observed in patients undergoing surgery and radiation (57%), and in combination therapy (chemotherapy, surgery, and radiation) the 5-year survival was 39%. Genetic analysis found the most common mutations included TP53 (51.9%), RB1 (25.9%), and ATRX (14.8%). When accounting for deep deletions and rearrangements, total frequency of the alterations was higher such that TP53 (63.0%), RB1 (51.9%), and ATRX (18.5%). Potentially actionable alterations were rare but included activating alterations in FGFR1, PIK3CA and ESR1, as well as deep deletions of BRCA1. Conclusions: Retroperitoneal leiomyosarcoma is a very rare tumor where surgery and radiation has been the conventional therapy. Our study indicates there are genetic alterations in the majority of retroperitoneal leiomyosarcoma. To further understand the pathogenesis and survival factors, patients with RPL should be enrolled into national and international registries.
Melanoma immunotherapy longitudinal database: A comprehensive approach to capture oncological and toxicity data.
Authors: Reham Abdel-Wahab, Qais Zuri, Waree Rinsurongkawong, Binu Pappachan, Michael Swaim, Priya Master, Calvin Harris, Jeff Lewis, Noha Abdel-Wahab, Adi Diab
Journal: Journal of Clinical Oncology (2024)

e23314 Background: Evaluating immunotherapy approaches is consistently performed in melanoma, a forefront cancer in immunotherapy responsiveness. Although immune checkpoint inhibitors (ICIs) showed the highest significant survival benefits in melanoma, 50% of patients experience recurrence/refractory disease, and ~59% develop grade 3/4 immune-related adverse events (irAEs). Thus, understanding the disease's natural history, exploring biomarkers of response/toxicity, and identifying the efficacy/safety of immunotherapy using real-world data is warranted. Methods: We established a centralized pro-/retrospective database on Research Electronic Data Capture (REDCap), encompassing patients' demographics/comorbidities, disease risk factors, clinicopathological parameters, genomic/immune profiling, treatment modalities, tumor outcomes, irAEs, and patients’ reported outcomes (PROs). Additionally, to streamline data collection and minimize the required time, effort, and cost for manual retrieval, we developed an automated pathway for data capture using MD Anderson Cancer Center (MDACC) electronic data capture (EDC) tools which pull clinical data from EPIC. Data quality will be validated by comparing it to manually retrieved data from an ongoing study of melanoma patients treated with ICIs in the adjuvant setting (NCT04990726). Results: A total of 4074 immunotherapy-treated melanoma patients were identified. We automatically captured demographics and laboratory values at predefined time points from REDCap, along with PROs using validated electronic self-reported questionnaires already built in REDCap. We also automatically captured family history, comorbidities, pathology data, and cancer treatments from the Data Management Initiative (DMI) validated software that automatically captures data from 12 various institutional sources that complement each other, including Radiation Oncology Database, the Biospecimen Information Management System,...etc. Moreover, genomic data were automatically pulled from the Molecular and Clinical Data Integration Platform for 1850 patients. Automated capture of tumor response and irAEs according to the Response Evaluation Criteria in Solid Tumors 1.1. and Common Terminology Criteria for Adverse Events version-5, respectively are currently ongoing and will be presented. Conclusions: Integrating EDC tools demonstrated accurate real-time data capture and minimized the manual retrieval burden. Our immunotherapy-treated melanoma patients’ cohort provides a comprehensive and a valuable resource for exploring the safety signals and efficacy of various immunotherapeutic approaches beyond clinical trials.
Comparison of standard charges for complex proton therapy among Medicare Prospective Payment System (PPS) –exempt and –non-exempt cancer centers.
Authors: Kasey Cargill, Noah Maxwell Feder, Tyler Wilhite, Heath Devin Skinner, Christopher Wilke, Yvonne Marie Mowery
Journal: Journal of Clinical Oncology (2024)

e23039 Background: Proton therapy is one of the most expensive treatment modalities offered to cancer patients, and only 44 proton therapy centers are operational in the U.S. Of those, 5 are Medicare Prospective Payment System (PPS)-exempt and are reimbursed based on their reported costs rather than predetermined prices. These PPS-exempt cancer centers set their adjusted payment rates to reflect the expense required for providing specialized care. We hypothesized that PPS-exempt centers would have higher rates for complex proton therapy delivery compared to non-exempt centers. Methods: We obtained online standard charge files for 44 proton therapy centers in the U.S. We used the CPT code 77525, the per fraction technical charge billed for complex proton treatment delivery, to extract the gross price (base charge for service), de-identified minimum and maximum negotiated price (lowest/highest charge negotiated with third-party payers), and cash price (charge for cash payment of service) per fraction of complex proton therapy. Prices were compared between PPS-exempt and non-exempt proton therapy centers using Wilcoxon/Kruskal Wallis test with a p-value &lt; 0.05 considered significant. Results: Of the 44 proton therapy centers, 39 (88.6%) had publicly available standard charge files, and 5 (11.4%) are private practice not required to provide a standard charge file. Five of the 39 (12.8%) centers are PPS-exempt, and the remaining 34 (87.2%) are PPS non-exempt. Four (80%) PPS-exempt centers had their gross price, minimum and maximum negotiated price, and cash price available in their standard charge file for CPT 77525, while 23 (67.6%) PPS non-exempt centers had their gross price and cash price listed and 19 (55.9%) had the minimum and maximum price available. The median gross charge per fraction for complex proton treatment delivery was $8,035.25 (IQR $7,022.00-$9,427.50) at PPS-exempt versus $6,434.00 (IQR $5,213.00-$12,350.00) at PPS non-exempt centers. The median minimum price was $656.47 (IQR $178.04-$1,353.23) at PPS-exempt versus $1,294.70 (IQR $734.20-$2,267.46) at PPS non-exempt centers. The median maximum price was $8,120.10 (IQR $5,576.40-$11,529.86) at PPS-exempt versus $5,814.00 (IQR $4,830.00-$9,524.70) at PPS non-exempt centers. The median cash price was $5,360.65 (IQR $2,979.51-$6,897.08) at PPS-exempt versus $4,170.40 (IQR $2,828.00-$5,640.00) at PPS non-exempt centers. Conclusions: In summary, 80% of PPS-exempt and 67.6% of PPS non-exempt centers had publicly available standard charge files. Median charges for PPS-exempt centers are higher for gross charge, maximum price, and cash price, however did not meet statistical significance. [Table: see text]
Development and preliminary validation of a platform for systematic, unbiased pre-screening of non-small cell lung cancer (NSCLC) across three community oncology practices.
Authors: Annette Campbell Fontaine, Barbara L. McAneny, Valerie Tucker, Michael Zach Koontz, Chardria Trotter, Joseph Paulson, Christer Svedman, Alexander Pan, Julio Antonio Peguero, Luis T. Campos
Journal: Journal of Clinical Oncology (2024)

e23230 Background: With a rapidly increasing number of candidate drugs and clinical trials in oncology, efficiency in clinical trial execution has become a primary focus area for innovation. Currently, fewer than 5% of oncology patients enroll in clinical trials, and data suggests a lack of diversity in clinical trial patient populations compared to the broader patient demographic. To address these issues, we developed a systematic unbiased pre-screening platform for all patients. This approach holds the promise of hastening clinical trials by enhancing the identification of eligible patients and concurrently promoting diversity among those invited to participate in these trials. Methods: A framework for use of EMR ingested data and standardized abstraction of select 160 variables was developed for patients with NSCLC. An algorithm based on 7 key eligibility criteria was developed to generate an automated assessment of eligibility for a presumed trial. Abstracted data was compared to a medical oncologist’s assessment (gold standard) and the automated tool was validated by comparing eligibility assessment before each visit with that of a medical oncologist. Results: Three community oncology practices in the US participated. Source data-verified values for histology, ECOG PS, treatment history, line of therapy, and current metastatic status were available for &gt; 90% of patients in real-time. Tumor NGS testing rates for actionable alterations exceeded 75%. From Oct 23, 2023 to Jan 14, 2024, 786 NSCLC pts had MD visits. Preliminary validation of the automated tool in 79 patients revealed concordant classification in 76/79 pts (96.2%). Sensitivity, specificity, PPV and NPV were &gt; 90%. Concordance for all variables was 98% between the abstractor and medical oncologist. Conclusions: A platform for systematic, unbiased pre-screening of patients for clinical trials in NSCLC has been developed to support and facilitate oncology sites without imposing financial or resource burdens or affecting routine clinical workflow. Preliminary validation supports high performance. Updated validation data will be presented in the meeting. The high levels of data completeness and quality, including NGS testing rates that are substantially higher than what has previously been reported in community centers, underscore their suitability as clinical trial sites.
Disparities in incidence and mortality of hematologic cancers in Southeast Asia: A 2020 analysis.
Authors: Erin Jay Garbes Feliciano, Urvish Jain, Edward Christopher Christopher Dee, Bhav Jain, Tej A. Patel, Aryan Selokar, Michelle Ann Eala, Frederic Ivan Leong Ting, Gan Gin Gin, Nirmala Bhoo Pathy
Journal: Journal of Clinical Oncology (2024)

e23291 Background: Hematologic cancers (HCs) in Southeast Asia (SEA), a diverse population of over 680 million, are still understudied. Data from the 2020 Global Cancer Observatory (GCO) was used to estimate the incidence and mortality of HCs in the region to provide direction for effective disease control and improve population outcomes. Methods: The International Agency for Research on Cancer’s publicly available GCO data aggregates global cancer incidence and mortality. We report cumulative incidence rate (CIR) and cumulative mortality rate (CMR) defined per 100,000 people, and weighted average age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) in 2020. Data for Hodgkin Lymphoma (HL), Non-Hodgkin's Lymphoma (NHL), Leukemia, and Multiple Myeloma (MM) in the world, in SEA, and in the 11 individual SEA countries are presented. Results: The table presents CIR, ASIR, CMR, and ASMR of hematologic cancers in SEA compared to overall global data. CIR, ASIR, CMR, and ASMR were higher for males than females in SEA. For NHL, CIR was highest in Singapore (18.8), Thailand (10.2), and Brunei (9.6) and lowest in Myanmar &amp; Cambodia (3.6), and Timor-Leste (2.7). ASIR trends were parallel albeit differences were smaller. CMR was highest in Singapore (6.2) and Thailand (5.9) and lowest in Timor-Leste (1.5). ASMR was highest in Brunei (4.5) and lowest in Timor-Leste (2.0). For leukemia, CIR was highest in Singapore (11.1) and lowest in Myanmar (3.1) and Timor-Leste (2.6); ASIR was highest in Singapore (8.9) and lowest in Myanmar (3.2) and Timor-Leste (2.9). CMR was highest in Singapore (5.2) and lowest in Myanmar (2.6) and Timor-Leste (2.3). ASMR was highest in Lao PDR (4.7) and Vietnam (4.5), and lowest in Singapore (3.1) and Timor-Leste (2.9). For MM, CIR was highest in Singapore (4.1), ASIR was highest in Brunei (2.4) and both are lowest in Myanmar (0.4). CMR was highest in Singapore &amp; Thailand (1.8) and lowest in Myanmar (0.35); ASMR rates were similar. For HL, CIR was highest in Brunei Darussalam (1.8) and Singapore (1.4) and lowest in Myanmar (0.2). ASIR trends were similar. CMR was highest in Vietnam (0.26) and lowest in Singapore (0.1) and Myanmar (0.08). ASMR trends were similar. Conclusions: Despite lower regional average incidence and mortality, significant intra-regional variations exist reflecting disparities in the management of HCs. In addition, while data suggests lower disease burden in SEA, mortality rates are still comparable and in some cases worse than the global average. More work is needed to investigate HC epidemiology in SEA to inform cancer control in the region and improve its blood cancer outcomes. [Table: see text]