tbuckley/cabot-search huggingface dataset:
Management outcomes of localized low-risk prostate cancer: A population-based study.
Authors: Shifeng S. Mao, Yue Yin, Rodney E. Wegner, Angela M Sanguino Ramirez, John Lyne, Ralph Miller, Jeffrey Cohen, Arash Samiei
Journal: Journal of Clinical Oncology (2024)

e17096 Background: Optimal management of patients with low-risk prostate cancer (LRPC) remains a topic of debate. While active surveillance (AS) is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study assessed the treatment outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB). Methods: We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local therapy (NLT). Only patients with Charlson-Deyo comorbidity scores of 0 or 1 were included. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups. Results: After a median follow-up of 70.8 months, 24,545 deaths occurred, resulting in an all-cause mortality rate of 13%. Compared to NLT, RP significantly improved overall survival by 47% (1.47, p &lt; .0001), 34% (1.34, p &lt; .0001), 27% (1.27, p &lt; .0001), and 10% (1.10, p = .0002) in the age groups &lt; 60, 60-64, 65-69, and 70-74, respectively. However, the benefit of RP decreased with advancing age, leading to an 11% decrease in survival (0.89, p &lt; .0001) in men aged ≥ 75 years. In contrast, EBRT did not improve overall survival in younger age groups; rather, it decreased survival by 11% (0.89, p = .0020) and 9% (0.91, p = .0111) in patients aged &lt; 60 and 60-64, respectively. However, EBRT significantly improved overall survival in older patients by 6% (1.06, p = .0160) and 27% (1.27, p &lt; .0001) for those aged 70-74 and over 75 years, respectively. Similarly, PSI did not improve overall survival in age groups younger than 64 years but exhibited significant overall survival benefits of 6% (1.06, p = .0242), 11% (1.11, p &lt;.0001), and 34% (1.34, p &lt; .0001) compared to NLT in age groups of 65-69, 70-74, and over 75, respectively. Conclusions: RP improves overall survival in patients with LRPC, especially in younger patients. EBRT and PSI primarily benefit older patients. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. The study is hypothesis-generating and limited by the non-randomized, retrospective, and inherited nature of the NCDB data, which does not provide information regarding patients’ symptoms, sexual function, and disease-specific survival.
Apa-RP: Multicenter phase 2 study of apalutamide (Apa) and androgen deprivation therapy (ADT) for the treatment of high-risk localized prostate cancer (HR LPC) following radical prostatectomy (RP)—Results in Black and non-Black patients (pts).
Authors: Jason Hafron, Daniel Saltzstein, Gordon Brown, Laurence Belkoff, Pankaj Aggarwal, Jennifer Phillips, Amitabha Bhaumik, Tracy McGowan, Neal D. Shore
Journal: Journal of Clinical Oncology (2024)

e17100 Background: Approximately 50% of pts with HR LPC have disease recurrence ≤2 years after RP. Apa-RP (NCT04523207) studied adjuvant Apa + ADT in pts with HR LPC who had undergone RP to determine if the combination improved biochemical recurrence (BCR)-free rate vs historical data from pts who received RP alone. Data are presented for subgroups of Black and non-Black pts. Methods: In this multicenter, open-label, single-arm, phase 2 study conducted at 28 US sites, treatment-naïve pts with HR LPC who had RP received Apa (240 mg; QD) for 12 cycles (28 day cycles) + ADT for 12 months. The study had a diversity goal to enroll ~15% Black pts. The primary endpoint was confirmed BCR-free rate at 24 months, where BCR is defined as two sequential prostate-specific antigen (PSA) levels of &gt;0.2 ng/mL. Secondary endpoints included testosterone recovery (≥150 ng/mL) rate and safety. Modified intention-to-treat analysis set is reported. Results: 108 pts were enrolled (n=15 Black, n=93 non-Black). Black pts were younger than non-Black pts (mean 58.4 vs 66.3 years). Other baseline characteristics were similar, including: median pre-operative PSA 7.6 ng/dL (range 2.2–62.7) and baseline testosterone 340.0 ng/dL (range 43.0–939.0). Confirmed BCR-free rate was 100% (90% CI 93.4, 100.0) (Table); unconfirmed BCR-free rate was 98.4% (90% CI 92.2, 99.7) (Table). Serum testosterone recovery (≥150 ng/dL) event rate at 24 months was 77.4% (95% CI 66.6, 85.1) (Table). Treatment-emergent adverse events were reported in 99.1% (n=107) of pts; 22.2% (n=24) were grade 3–4, 14.8% (n=16) were serious AEs. In total, 13.0% (n=14) and 10.2% (n=11) of pts had treatment dose reductions/interruptions or discontinued due to AEs, respectively. Conclusions: Based on the high BCR-free rate, that persisted for 12 months following treatment, these results suggest that both Black and non-Black pts with HR LPC undergoing RP may benefit from 12 months of treatment intensification with Apa + ADT. Most pts had testosterone recovery. The safety profile of Apa + ADT was consistent with previous reports. Clinical trial information: NCT04523207 . [Table: see text]
Molecular profiling of plasma from matched NCI-MATCH gynecological cancers.
Authors: Amanda Peach, Bao Le, Vishnuprabha Rahul Kannan, Eric Greenbank, Rini Pauly, Li Chen, Ting-Chia Chang, Jennifer S. LoCoco, Lyndsay Harris, Alice P. Chen, Naoko Takebe, Traci L. Pawlowski, Lisa McShane, Peter J. O'Dwyer, James H. Doroshow, P. Mickey Williams, Biswajit Das, Chris Alan Karlovich
Journal: Journal of Clinical Oncology (2024)

5579 Background: During the screening phase of the National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH; NCT02465060) trial, 5954 patients with advanced cancer, approximately 60% of whom had rare or less common cancers, underwent next-generation sequencing of their tumor tissue to determine study eligibility. The majority of the patients could not be assigned to a treatment arm because they did not have a study mutation of interest (MOI). The plasma collected from these patients may provide insight into the genomic landscape of circulating tumor DNA (ctDNA) and inform the potential utility of ctDNA testing for the identification of clinically relevant mutations in these rare histologies. Here we report the molecular profiles of ctDNA from a subset of the NCI-MATCH screened patients with gynecologic cancers. Methods: Cell-free DNA (cfDNA) was extracted and quantitated from plasma collected in Streck blood tubes at study enrollment. Libraries were constructed using the NCI ctDNA v2 assay with a minimum input of 10 ng and were sequenced on the Illumina NovaSeq 6000 with S4 flow cells. Results: Among 200 samples sequenced, four different histologies were represented: uterine endometrioid adenocarcinoma (UEC, n=51), serous endometrial adenocarcinoma (USC, n=35), uterine leiomyosarcoma (ULMS, n=40), and ovarian epithelial (OVT, n=74). Two samples failed, one ULMS due to sequencing error and one OVT due to contamination. The positive percent agreement (PPA) values calculated from clinically relevant MOI derived from OncoKb as both PPA ref_tumor and PPA ref_ctDNA , were 88.6% and 44.1% respectively. The most commonly mutated genes were TP53, KRAS, CTNNB1, and PIK3CA. Additionally, the ctDNA detected mutations not identified in the tumor, including 8 patients (4%) with a PIK3CA mutation. By employing predefined cutoffs of tumor fractions, ctDNA identified 21 out of 25 expected copy number amplifications demonstrating an 84% concordance. Microsatellite instability (MSI) using ctDNA was highest in the UEC (17.6% of patients) followed by USC at 8.6%, OVT at 6.8%, and ULMS at 2.6%. Among the patients with mismatch repair deficiency (MMRd) identified by tumor immunohistochemistry, 50% were identified as MSI-High in plasma. Conclusions: In this cohort of patients with advanced gynecological cancers from the NCI-MATCH trial, clinically relevant mutations detected by ctDNA were 88.6% concordant with data derived from tumor biopsy. In addition, some mutations were identified only in ctDNA, which may be due to tumor heterogenity. The data suggest that liquid biopsy is valuable as a complement to tumor biopsy data and when tissue is unavailable.
Prognostic PSMA-PET PROMISE nomograms for patients with prostate cancer.
Authors: Wolfgang Peter Fendler, Madeleine J. Karpinski, Johannes Hüsing, Kevin Claassen, Lennart Möller, Hiltraud Kajüter, Florian Oesterling, Viktor Grünwald, Lale Umutlu, Helena Lanzafame, Tugce Telli, Anja Merkel-Jens, Anika Hüsing, Claudia Kesch, Ken Herrmann, Andreas Stang, Boris A. Hadaschik
Journal: Journal of Clinical Oncology (2024)

5016 Background: Prostate Specific Membrane Antigen Positron-Emission-Tomography (PSMA-PET) was introduced for prostate cancer staging in 2012. PSMA-PET reported by standardized PROMISE criteria delivers accurate staging with potential prognostic value. Here we assess the prognostic value of PSMA-PET including tumor volume in a large prostate cancer dataset with overall survival follow-up and compare it head-to-head to clinical risk scores. Methods: Prostate cancer patients, who underwent PSMA-PET between October 2014 and December 2019 at the Essen University Hospital, were analyzed retrospectively. We collected PSMA-PET stage using the molecular imaging TNM system (miTNM), tumor volume, SUVmean and overall survival follow-up. The dataset was split into development and validation cohorts (2:1). We created a visual and quantitative nomogram based on Cox regression models with LASSO penalty using the development cohort. Performance of nomograms in the validation cohort were measured using C-index and calibration plots. Head-to-head comparison to clinical risk scores for each staging group was examined using ROC-curves and C-index. Results: The cohort includes 1612 prostate cancer patients across all disease stages with 567 (35.2%) recorded deaths. PSMA-PET based predictors included into the quantitative PSMA-PET nomogram were locoregional lymph node metastases (miN2), distant metastases (miM1a, miM1b pattern, miM1c), tumor volume and tumor SUVmean (Table). The visual nomogram includes distant metastases and total tumor lesion count. Overall C-indices were 0.81 or 0.78 for the quantitative or visual nomogram, respectively. The quantitative PSMA-PET nomogram was superior to STARCAP at initial staging (AUC: 0.72 vs. 0.53; p=0.02), to EAU risk score at BCR (AUC: 0.69 vs. 0.52; p&lt;0.001), and to NCCN groups at any timepoint (AUC: 0.81 vs. 0.73; p&lt;0.001). The visual PSMA-PET nomogram was superior to EAU risk score (AUC: 0.64 vs. 0.52; p&lt;0.001) and NCCN groups (AUC: 0.79 vs. 0.73 p&lt;0.001). Conclusions: Our prognostic PSMA-PET nomograms based on PROMISE criteria were accurate in early and late stages of prostate cancer. Prediction of overall survival was superior when compared to clinical risk tools. Multi-center validation in the PROMISE registry is ongoing. Development cohort (n=1110 patients) univariate regression findings for PROMISE variables included in the quantitative PSMA-PET nomogram for prediction of overall survival.[Table: see text]
Endometrial cancer and obesity trends in the United States in the 21st century.
Authors: Alex Andrea Francoeur, Cheng-I Liao, Jenny Chang, Caitlin Ruth Johnson, Kiran Clair, Krishnansu Sujata Tewari, Daniel Stuart Kapp, John K Chan, Robert E. Bristow
Journal: Journal of Clinical Oncology (2024)

5507 Background: Using two comprehensive national databases, we explore trends in obesity and endometrial cancer rates in the United States. Methods: Data on endometrial adenocarcinoma were obtained from the United States Cancer Statistics (USCS) from 2001-2018 and corrected for hysterectomy and pregnancy using Behavioral Risk Factor Surveillance System data. Data on obesity was collected from the National Health and Nutrition Examination Survey (NHANES) database from 1988-2018. Average annual percentage changes (AAPC) were used to describe trends. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used for statistical analysis. Results: Using USCS data, 615,656 cases of endometrial adenocarcinoma were identified from 2001-2018. The annual increase in endometrial cancer is as follows: Hispanic 1.37% (p&lt;0.0001), Black 1.30% (p&lt;0.0001), and White: -0.17 (p=0.656). Women aged 20-29 have a 4.48% annual increase (p&lt;0.0001) and women aged 30-39 have a 3.00% annual increase (p&lt;0.0001). On intersection analysis, Hispanic women have the largest rate of increase in the 30-39 age group at 4.67% (p&lt;0.0001), followed by Black women, 3.85% (p&lt;0.0001), and White women 2.12% (p=0.02). In the 20-29 age group, rates of endometrial adenocarcinoma are increasing in White women at 4.79% (p&lt;0.0001) and in Hispanic women 4.29% annually (p&lt;0.0001) (Table). Using the NHANES data, the prevalence of obesity in 2018 in adult women is as follows: Black 56.8%, Hispanic 44.1%, and White 40.9%. Rates of obesity for all women are rising 4.6% yearly since 1988 (p&lt;0.05). Class III obesity rates are rising at 9.19% annually (p&lt;0.05). When looking at trends by age, the 20–29 year old women have the highest annual rise in obesity compared to other age groups (AAPC 7.36%, p&lt;0.05). Rates of Class III obesity are increasing at the highest rate in this group as well (AAPC 14.22%, p&lt;0.05). In the 30–39 year old age group, Class III obesity has been increasing 9.48% annually, p&lt;0.05. Conclusions: The current data demonstrate a temporal association between the increasing incidence of endometrial cancer and obesity, and this effect disproportionately impacts younger women and women of color. While additional research is required to confirm a causal relationship, these data warrant targeted health services and public health interventions to stabilize and ultimately reverse the concomitantly rising rates of obesity and endometrial cancer. [Table: see text]
Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity
Authors: Daniel J. Drucker
Journal: Diabetes Care (2024)

The development of glucagon-like peptide 1 receptor agonists (GLP-1RA) for type 2 diabetes and obesity was followed by data establishing the cardiorenal benefits of GLP-1RA in select patient populations. In ongoing trials investigators are interrogating the efficacy of these agents for new indications, including metabolic liver disease, peripheral artery disease, Parkinson disease, and Alzheimer disease. The success of GLP-1–based medicines has spurred the development of new molecular entities and combinations with unique pharmacokinetic and pharmacodynamic profiles, exemplified by tirzepatide, a GIP-GLP-1 receptor coagonist. Simultaneously, investigational molecules such as maritide block the GIP and activate the GLP-1 receptor, whereas retatrutide and survodutide enable simultaneous activation of the glucagon and GLP-1 receptors. Here I highlight evidence establishing the efficacy of GLP-1–based medicines, while discussing data that inform safety, focusing on muscle strength, bone density and fractures, exercise capacity, gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, and the risk of cancer. Rapid progress in development of highly efficacious GLP-1 medicines, and anticipated differentiation of newer agents in subsets of metabolic disorders, will provide greater opportunities for use of personalized medicine approaches to improve the health of people living with cardiometabolic disorders.
Nimotuzumab in combination with radiotherapy for elderly patients with locally advanced cervical squamous cell carcinoma: Results from a prospective, multicenter, open-label, single-arm trial.
Authors: Ang Qu, Jun jie Wang, Yanhong Zhuo, Zi Liu, Hong Zhu, Lichun Wei, Xiaoge Sun, Yuhua Gao, Huijun Cheng, Fengju Zhao, Yipeng Song, QingLian Wen, Xiaohong Zhou, Ping Wang, Jialin Yang, Lijuan Zou, Xiangkun Yuan, Dongyue Wu, Jianli He, Yun Yan Zhang
Journal: Journal of Clinical Oncology (2024)

5527 Background: Locally advanced cervical squamous cell carcinoma (LACSCC) is associated with poor survival, and elderly patients generally have fewer treatment options due to chemotherapy intolerance. Nimotuzumab is a humanized monoclonal antibody that has demonstrated therapeutic activity in many tumors. We conducted a single-arm trial to investigate the efficacy and safety of combining nimotuzumab and radiotherapy for elderly patients with LACSCC. Methods: In this prospective, multicenter, open-label, and single-arm trial, patients with LACSCC were registered (NCT04976478) and enrolled from Nov 2021 to Jan 2023. All patients were ≥ 65 years old, had ECOG of 0-2, histological diagnosis of cervical squamous cell carcinoma, clinical stage IB3-IVA (FIGO 2018), intolerant to chemotherapy, or refused chemotherapy. The regimen was nimotuzumab (200 mg once in a week for 6 weeks) combined with radiotherapy. The radiotherapy scheme contained intensity-modulated radiotherapy (IMRT)/volumetric intensity-modulated arc therapy (VMAT) with pelvic/extended field irradiation (45-50.4Gy, 1.8-2.0Gy/f, 25-28f), and brachytherapy (HR-CTV D90, 80-85Gy), of which brachytherapy plus external beam radiotherapy was completed in 8 weeks. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Other assessed endpoints were objective response rate (ORR), disease control rate (DCR) and complete response rate (CRR). All adverse events were monitored and recorded. Results: As of Jan 2023, 119 elderly patients have been enrolled and all patients were included in the efficacy and safety analysis. The median follow-up was 16.16 months (95% CI: 13.14-17.45). Nimotuzumab combined with radiotherapy resulted in favorable OS (1 year-OS: 96.03%, 95% CI: 89.75-98.50; 2 year-OS: 90.21%, 95% CI: 78.98-95.60), and DFS (1 year-DFS: 85.71%, 95% CI: 76.98-91.31; 2 year-DFS: 78.31%, 95% CI: 66.67-86.29). The ORR was 89.92%, DCR was 93.28%, and CRR was 52.94%. A total of seven patients died, of which three were due to disease progression and two were of unknown causes. The most common Grade 3-5 adverse events (AEs) mainly included leukopenia (3.36%), anemia (2.52%), and neutropenia (1.68%). None of the patients developed severe AEs or deaths. So far, this trial is still ongoing. Conclusions: Among elderly LACSCC patients, adding nimotuzumab to radiotherapy indicated promising efficacy and appeared to have manageable toxicity. Nimotuzumab plus radiotherapy could represent a novel treatment strategy for this population. Clinical trial information: NCT04976478 .
An open label, single arm phase II, multicenter trial of durvalumab and BVAC-C, in patients with HPV 16- or 18-positive cervical cancer and failure of first-line platinum-based chemotherapy (DURBAC).
Authors: Chel Hun Choi, Byoung-Gie Kim, Jeong-Won Lee, Tae-Joong Kim, Yoo-Young Lee, Duck Cho, Byoung-Kwan Hun Park, Sang Yong Song, Dae-Yeon Kim, Kidong Kim, Hee Seung Kim, Jung-Yun Lee, Myong Cheol Lim, Insu Jeon, By-yeong Song, Kwang-Soo Shin, Wuhyun Kim, Chang-Yuil Kang
Journal: Journal of Clinical Oncology (2024)

5513 Background: In the phase I/IIa study of HPV positive recurrent cervical carcinoma, BVAC-C, a pioneering B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant E6/E7 gene of HPV type 16/18, demonstrated favorable tolerability. The ongoing phase 2 clinical trial investigates the potential synergistic effects of combining BVAC-C with durvalumab (MEDI4736), an anti-PD-L1 therapy, to enhance anti-tumor immune responses. Methods: The trial comprises two parts. Part A, utilizing a 3+3 dose-escalation design, assesses BVAC-C combined with 1500 mg durvalumab to establish the maximum tolerated dose (MTD) and recommended dose for Part B. Part B, with an expansion phase involving up to 25 patients, focuses on safety and clinical efficacy, measured by the 6-month progression-free survival (PFS) rate. Part A enrollment commenced in September 2021 across six Korean centers, with 9 participants enrolled and MTD determined by November 2022. 25 patients were enrolled in Part B enrollment was completed with 25 patients by December 2023. Tumor response evaluation follows RECIST 1.1 criteria and iRECIST. The essential eligibility criteria comprise histologically confirmed cervical carcinoma with HPV 16/18 positivity, recurrence following or resistance to a solitary prior first-line platinum-based chemotherapy ± bevacizumab, lack of prior exposure to immune-oncology (IO) drugs, and the presence of measurable disease according to RECIST v1.1. Results: Among 29 patients available for this interim analysis, 6-month PFS-rate was 51% (95% CI 33 – 77). The objective response rate (ORR) was 29.2% (7/24), with 2 complete responses. The disease control rate (DCR) was 66.7% (16/24). With a median follow up of 7 months, the median duration of response (DOR) and PFS were not reached. All evaluated patients exhibited inflammatory cytokine responses (IFN-γ or TNF-α) and robust E6/E7-specific T cell responses following BVAC-C vaccinations. Notably, immune responses correlated with clinical outcomes. The most common treatment-emergent adverse events (TEAEs) were pyrexia and myalgia, mostly grade 1 and manageable. Conclusions: The combination of BVAC-C and durvalumab demonstrates promise as a second-line treatment option with a manageable safety profile for patients with recurrent HPV 16/18 positive cervical cancer. The survival data is scheduled to receive an update during the upcoming ASCO meeting. Further studies are warranted to identify potential biomarkers of treatment response. Clinical trial information: NCT04800978 .