tbuckley/cabot-search huggingface dataset:
Decade of insights: Bleomycin-induced pneumonitis and use of G-CSF in chemotherapy-treated germ cell testicular tumors and Hodgkin lymphoma—Real-world outcomes from an academic cancer center.
Authors: Manan Shah, Amir Mortazavi, Edmund Folefac, Peng Wang, Katharine A. Collier, Lingbin Meng, Kelly Slavens, Meghan Hinkley, Paul Monk, David Alan Bond
Journal: Journal of Clinical Oncology (2024)

e17013 Background: Bleomycin induced pulmonary toxicity (BIP) occurs in 4-10% of treated patients. Preclinical reports suggest G-CSF use may increase BIP risk, due to neutrophil migration to lung tissues. Limited real-world clinical data is available and G-CSF use may reduce risk of treatment related toxicity with curative bleomycin combination treatment. Methods: We conducted a retrospective study of patients with GCT (Germ cell tumor) and HL (Hodgkin’s lymphoma) receiving bleomycin containing chemotherapy and at-least on dose of G-CSF at The James Cancer Center from 2010-2022 using the institutional database. BIP was diagnosed mainly using clinical symptoms complemented by radiological evidence when possible. We reviewed 361 patients, 145 in GCT group and 216 in HL group and clinically relevant information was recorded.Descriptive statistics for the study variables were presented using frequencies and percentages overall. The bivariate associations between G-CSF use and clinical outcomes were assessed using chi-square tests or fisher’s exact tests for the overall sample, and by chemotherapy type. We used SPSS 26.0 for all the statistical analyses, and an alpha level of 0.05 (two-sided) was used for all the tests. Results: Data on 361 patients, including 145 GCT and 216 HL patients treated with at least one dose of bleomycin was available. The median age was 36.3 years in the GCT group and 44.2 years in the HL group.144 patients in the GCT and 50 patients in the HL group received at least 1 dose of G-CSF. BIP occurred in 4.8% in the GCT and 7.4% of patients in the HL group. Only 2 out of 16 patients developing BIP in the HL group received G-CSF. All patients with BIP developed symptomatic disease. On bivariate analysis, no association was noted between BIP and G-CSF in either group (p-value =1.00 in GCT and p-value = 0.32 in HL). Febrile neutropenia (FN) was reported in 4 patients in the GCT group and 29 in the HL group. In the HL subgroup, 28 (28/29) patients developing FN did not receive G-CSF (p-value=0.0008). All patients who developed FN required hospital admission. Conclusions: Use of G-CSF in patients receiving bleomycin was not associated with an increased incidence of BIP. Incidence of FN was higher in patients not receiving G-CSF leading to hospital admissions. [Table: see text]
Xevinapant with radiation and concurrent carboplatin and paclitaxel in patients ineligible for cisplatin with locoregionally advanced squamous cell carcinoma of the head and neck (EXtRaCT study).
Authors: Nabiel Ali Mir, Aditya Juloori, Paul Swiecicki, Rohan Reddy Katipally, Nishant Agrawal, Elizabeth A. Blair, Daniel J. Haraf, Alexander T. Pearson, Everett E. Vokes, Ari Joseph Rosenberg
Journal: Journal of Clinical Oncology (2024)

TPS6126 Background: Locoregionally advanced (LA) head and neck cancer (HNC) patients undergoing chemoradiotherapy (CRT) who are ineligible for cisplatin have comparatively poor outcomes, with only ~40% alive at 5 years. There is an urgent unmet need to improve survival in these vulnerable patients with no standard therapeutic approach. Xevinapant, an oral inhibitor of XIAP and cIAP1/2, sensitizes cancer cells to apoptosis. Randomized phase II results in patients eligible for cisplatin combining xevinapant with CRT showed improved locoregional control, manageable toxicity, and promising survival outcomes. (Sun et al. Lancet Oncol. 2020) The current trial aims to extend these benefits to patients ineligible for cisplatin using xevinapant with carboplatin-paclitaxel-based CRT, hypothesizing safety and tolerability in this high-risk group. Methods: This phase I dose escalation/expansion study investigates xevinapant combined with carboplatin and paclitaxel to treat LA HNC in patients ineligible for cisplatin. Key eligibility includes previously untreated LA HNC and specific cisplatin ineligibility criteria, including &gt;=70yo with moderate to severe comorbidity or vulnerability (Geriatric-8 score ≤ 14 and/or CARG score ≥ 30%) or &lt;70yo with severe comorbidity and/or vulnerability, or &gt;=18yo with an absolute contraindication to cisplatin. The treatment regimen comprises escalating doses of oral xevinapant (50-200 mg daily) on days 1-14 of a 21-day cycle for 3 cycles concurrent with CRT and 3 cycles adjuvant, weekly carboplatin AUC 1.5 IV, and paclitaxel 30 mg/m2 IV for 7 doses, and radiotherapy to 70 Gy in standard 2Gy fractions over 7 weeks with primary endpoint of tolerability and recommended phase 2 dose. A Bayesian-modified toxicity probability interval design will identify the maximum tolerated dose (MTD), targeting a 25% dose-limiting toxicity rate, with a sample size of 24 patients in dose-finding. 18 additional patients will be enrolled in the dose-expansion cohort at the MTD, totaling 42 patients. Secondary objectives include safety, response, progression-free, overall survival, and locoregional and distant control. Exploratory aims: in-clinic geriatric evaluations (Katz ADL, Lawton iADL, MMSE), QoL surveys, symptom tracking via smartphone, and wearable-derived steps and sarcopenia assessment. Recruitment began 02/2024. Clinicaltrials.gov ID: NCT06110195. Clinical trial information: NCT06110195 .
Phase II trial assessing safety, efficacy and immune correlates of heterologous prime-boost with pBI-11 (IM) and TA-HPV (IM) plus pembrolizumab for advanced, PD-L1 CPS≥1, hrHPV+ oropharyngeal cancer.
Authors: Michael K. Gibson, Richard Roden, TC Wu, Ellen Heimann-Nichols
Journal: Journal of Clinical Oncology (2024)

TPS6118 Background: HPV-related OPSCC occurs in younger patients, has a significantly better prognosis, and is most often caused by HPV subtype 16. There is a 90% overall survival for HPV+/p16+ OPSCC (40% for HPV-/p16- OPSCC), which can be cured with multimodality care. For patients with R/M disease, treatment with pembrolizumab (P) +/- chemotherapy is palliative, with a median OS of approximately 12 months for patients with PD-L1 combined positive score (cps) &gt;1 treated with P alone. Heterologous prime boost with DNA priming followed by vaccinia-based boosting against HPV16 viral antigens will be studied using pBI-11 [(DNA vaccine pNGVL4a-SigE7 (detox)/HSP70, HPV16 E7(detox)/ HPV18 E7(detox), HPV16 E6(detox), and HPV18 E6(detox)] followed by TA-HPV (recombinant vaccinia-human papillomavirus (denoted TA-HPV) derived from the Wyeth strain of vaccinia which carries modified E6 and E7 genes from HPV types 16 and 18). This study is approved by the Vanderbilt University IRB and is open accrual (NCT NCT05799144). Methods: Patients with R/M, HPV positive OPSCC without prior therapy for R/M disease, without contraindications to immunotherapy and with a PD-L1 cps &gt; 1 will be screened. There is a 6 patient safety run-in. Treatment with pBI-11 vaccine (2 IM injections on weeks 1 and 4) plus one IM administration of TA-HPV on week 7 will be given in combination with P IV on weeks 1, 4, and 7). Following restaging, all patients will continue (including those with PD) with 3 more cycles of P followed by restaging. The primary clinical outcome is RR to addition of vaccine in the 50% of predicted P non-responders (NR) who proceed to Part II (ie conversion to responders). All responders will continue to receive P until progression. Approximately 54 patients with be enrolled. Two research tumor biopsies and blood draws will be obtained pre- and on treatment (week7-9). Tumor tissue cores will be utilized for immunohistochemical and molecular tests (e.g., expression of immune cell and viral markers, TCR sequencing and total transcripts). Blood with be tested for HPV16/18 E6, E7 antibodies and vaccinia virus neutralizing assays; proliferative responses of peripheral blood lymphocytes to stimulation by HPV16/18 E6 and E7; HPV16/18 E6- and E7-Specific T cells; and HPV DNA in plasma. Data from the 1st four patients enrolled will be presented. Clinical trial information: NCT05799144 .
Treatment analysis of patients diagnosed with intraductal carcinoma of the prostate (IDC-P) in the US from 2000 to 2018.
Authors: Taylor Stamey, Kristen Armel, Andrew W Ju, Shoujun Chen, Musharraf Navaid, Michael Casmer Larkins, Arjun Bhatt
Journal: Journal of Clinical Oncology (2024)

e17011 Background: Intraductal carcinoma of the prostate (IDC-P), considered both a distinct entity (found alone in ~3% of prostate biopsies) and negative prognostic factor of prostatic cancer (identified in ~20% of all patients with prostate cancer). IDC-P represents aggressive disease, and is associated with increased metastasis, recurrence, and prostate cancer-specific death. Given the mortality and rarity of this disease, we analyzed demographic and treatment trends of patients diagnosed with IDC-P in the US. Methods: A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database sponsored by the National Cancer Institute (NCI) was conducted for patients with a diagnosis of IDC-P between 2000 and 2018. Univariate, multivariate, and survival analyses were performed on demographic and treatment characteristics using 95% confidence intervals [CI] and a p-value &lt; 0.05 indicating significance. Results: 1003 patients with complete follow-up and survival data were identified. Patients with local disease that underwent radical prostatectomy without radiotherapy (RT) had increased five-year overall survival (OS) compared those that only received RT (99% vs 75%; p&lt;0.001); those with regional disease did not (p=0.617). No survival benefit was seen among patients that received RT in addition to radical prostatectomy compared to those treated with radical prostatectomy solely (p=0.770 for local disease and 0.909 for regional disease). Lymph node (LN) examination, performed in 33.1% of patients, yielded increased five-year OS compared to absence thereof (99% versus 73%; p&lt;0.001). 45% of patients that had LN examined were found in a single SEER registry (California). The 2.7% of patients that received chemotherapy (CTX) saw no survival benefit in the setting of distant disease (n=14; 0% versus 78%, respectively; p&lt;0.001). No difference was seen in five-year OS with respect to race (p=0.967) though single patients saw decreased OS compared to married ones (hazard ratio (HR)=0.83; p=0.050) and patients younger than 65 years saw increased survival (HR=0.89; p=0.002). On multivariate analysis, the interaction between stage, surgical treatment, and receipt of RT demonstrated a difference in five-year OS (p=0.020). Conclusions: This analysis demonstrates survival benefit with radical prostatectomy solely versus treatment with RT among patients with local IDC-P, and did not find benefit with CTX in patients with distant disease. The survival benefit found with LN examination may be a center- or region-specific outcome. Patient age and marital status may have implications for patient outcomes. Further investigation into specific treatments, socioeconomic factors, and disease surveillance measures for patients with prostate cancer is warranted.
Single-Cell View of Tumor Microenvironment Gradients in Pleural Mesothelioma
Authors: Bruno Giotti, Komal Dolasia, William Zhao, Peiwen Cai, Robert Sweeney, Elliot Merritt, Evgeny Kiner, Grace S. Kim, Atharva Bhagwat, Thinh Nguyen, Samarth Hegde, Bailey G. Fitzgerald, Sanjana Shroff, Travis Dawson, Monica Garcia-Barros, Jamshid Abdul-Ghafar, Rachel Chen, Sacha Gnjatic, Alan Soto, Rachel Brody, Seunghee Kim-Schulze, Zhihong Chen, Kristin G. Beaumont, Miriam Merad, Raja M. Flores, Robert P. Sebra, Amir Horowitz, Thomas U. Marron, Anna Tocheva, Andrea Wolf, Alexander M. Tsankov
Journal: Cancer Discovery (2024)

Abstract Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving the understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA sequencing (scRNA-seq) to de novo identify 54 expression programs and construct a comprehensive cellular catalog of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis. Across cellular compartments, we observe substantial difference in the TME associated with a cancer-intrinsic sarcomatoid signature, including enrichment in fetal-like endothelial cells, CXCL9+ macrophages, and cytotoxic, exhausted, and regulatory T cells, which we validated using imaging and bulk deconvolution analyses on independent cohorts. Finally, we show, both computationally and experimentally, that NKG2A:HLA-E interaction between NK and tumor cells represents an important new therapeutic axis in PM, especially for epithelioid cases. Significance: This manuscript presents the first single-cell RNA sequencing atlas of PM tumor microenvironment. Findings of translational relevance, validated experimentally and using independent bulk cohorts, include identification of gene programs predictive of survival, a fetal-like endothelial cell population, and NKG2A blockade as a promising new immunotherapeutic intervention in PM.
Relugolix prescribing practices and clinical experiences at an urban academic center.
Authors: Maria Jose Fernandez Turizo, Julia Stevens, Guiyu Jessie Xu, Tuyen Yankama, Marc B. Garnick, Morgan R. L. Lichtenstein, Daniel E.C. Fein
Journal: Journal of Clinical Oncology (2024)

e17008 Background: Relugolix is a novel oral GnRH antagonist that is now an alternative option for patients with prostate cancer (PC) who require androgen deprivation therapy (ADT). The potential benefits of relugolix include rapid testosterone decline and recovery, oral administration, and a possible cardiovascular (CV) benefit compared to traditional GnRH agonists. This study examines real-world data on relugolix prescribing practices and clinical experiences at a large, urban academic center. Methods: We conducted a retrospective, single-center cohort study of patients with PC prescribed relugolix from March 2021 through December 2023 at Beth Israel Deaconess Medical Center. We collected patient-related and clinical factors including demographics, comorbidities, CV risk factors, treatment history, reasons for relugolix prescription over GnRH agonists, medication compliance, adverse effects, and treatment outcomes. Descriptive statistics were used to characterize the cohort. Results: Among 267 patients who received a relugolix prescription, median age was 70 years old, 186 patients (69.6%) were Non-Hispanic White, 37 (13.9%) Non-Hispanic Black, 13 (4.9%) Asian, and 6 (2.2%) Hispanic of any race. Across all patients, 228 (85.3%) initiated relugolix with a median therapy duration of 181 days (range: 10 - 807). At the time of prescription, 88 patients (32.9%) were prescribed concurrent androgen receptor signal inhibitors (ARSI) and 186 (69.6%) had localized disease. Median CV risk factors per patient was 2 (range 0 - 7), and 4 patients (1.5%) developed major adverse CV events (MACE), including acute heart failure decompensation, sick sinus syndrome, ventricular tachycardia, and death during treatment. Among physician prescribers, the most common reasons for prescribing relugolix included concern for CV risk (90 prescriptions, 33.3%) and patient preference for oral administration (55 prescriptions, 20.4%). Forty-nine patients (18.3%) were switched from a GnRH agonist, mainly due to physician concern for CV risk (13, 4.9%) or patient preference (17, 6.4%). Conclusions: We describe real-world use of relugolix for PC in a large, diverse single center cohort. The most frequent reasons for choosing relugolix over a GnRH agonist were physician concern for CV risk and patient preference for a tablet over injection. Investigations of treatment initiation and adherence in relation to insurance coverage, adverse effects, and socioeconomic factors require further investigation.
Prognostic nomogram, demographics and comparative analysis of prostate small cell and large cell neuroendocrine carcinoma.
Authors: Nabin R Karki, Abdul Qahar Khan Yasinzai, Asad Ullah, Kue Taylor Lee, Tristin Chaudhury, Hannah Chaudhury, Abdullah Chandasir, Abdul Waheed, Marjan Khan, Aman Goyal, Amir Sohail, Jaydira Del Rivero
Journal: Journal of Clinical Oncology (2024)

e17010 Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences from common types of prostate cancer. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was found to be 71.5 years and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasians (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients of stage 3 tumors, as well as patients who underwent surgery and radiation. The nomogram also indicated a slight increase in mortality with tumors of greater size. Conclusions: Small-cell and large-cell neuroendocrine carcinomas of the prostate are rare; their aggressive nature calls for a deeper understanding and improved prognostic tools. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging arena of oncology.
Ovarian-Adnexal Reporting &amp; Data System (O-RADS) versus modified benign descriptors and IOTA ADNEX (two-step strategy) in classification of ovarian masses.
Authors: Nadiezhda Rodríguez, Sophia Pérez, Juan Nicolás Rodríguez, Nicolás Cantor, Fabian Ardila, Alba Liliana Esquivel, Javier Segovia
Journal: Journal of Clinical Oncology (2024)

e17569 Background: The use of a single and common language in the diagnosis of ovarian tumors is a multidisciplinary effort spanning several decades that has allowed the global adoption of the Ovarian-Adnexal Reporting &amp; Data System (O-RADS) and the International Ovarian Tumor Analysis (IOTA). The objective is to determine the diagnostic accuracy of O-RADS versus modified benign descriptors and IOTA ADNEX in the classification of adnexal masses. Methods: Ambispective diagnostic accuracy study based on ultrasound data collected at a university hospital with a gynecologic oncology unit between 2012 and 2022. Two IOTA-certified level III sonographers classified adnexal masses using modified benign descriptors (MBD). The main outcome was the classification of the masses as benign or malignant for each strategy. Histopathology was used as the diagnostic reference standard. A diagnostic test analysis was performed. Results: 876 patients with 902 adnexal masses were included in the study for both analysis strategies. For the two-step analysis, 573 (64%) met the classification criteria for their evaluation based on MBD (first step) and 329 (36%) were assessed using IOTA ADNEX. 99% (567/573) of the masses classified according to the MBD, were benign by histopathology. The diagnostic performance of IOTA ADNEX (second step) had a sensibility of 93%, specificity of 64%, positive predictive value of 48%, negative predictive value of 96%, AUC (0,880). Regarding the analysis of the O-RADS system to stratify malignancy risk, we observed a prevalence of 58% for O-RADS 2, 22% for O-RADS 3, 11% for O-RADS 4, and 9% for O-RADS 5. Sensibility was 92%, specificity 88%, positive predictive value 48%, negative predictive value del 99%, AUC (0,886). Conclusions: In our experience, the diagnostic accuracy of the two-step strategy or the O-RADS system is similar. However, the ORADS system had a lower proportion of false negatives.
Open-label, phase 2 study of adebrelimab combined with fuzuloparib in the treatment of patients with HRD-positive, recurrent platinum-resistant ovarian cancer.
Authors: Jian Chen, JianPing Zou, Haijuan Yu, Li Liu, Lele Zang, Yang Sun
Journal: Journal of Clinical Oncology (2024)

TPS5634 Background: Adebrelimab, a humanized anti-PD-L1 monoclonal antibody, selectively targets PD-L1 molecules to inhibit the PD-1/PD-L1 pathway, reversing tumor-induced immune tolerance and revitalizing the immune system's capacity to combat tumors. Fuzuloparib, a novel PARP inhibitor, impedes the activity of poly (ADP-ribose) polymerase, halting the DNA repair mechanism for single-stranded breaks, resulting in DNA damage accumulation and consequent cancer cell apoptosis. Emerging evidence strongly supports that PARP inhibitors significantly extend progression-free survival in homologous recombination-deficient (HRD)-positive ovarian cancer. The TOPACIO study demonstrated that the combination of niraparib and pembrolizumab for platinum-resistant ovarian cancer achieved an objective response rate (ORR) of 18%, with durable responses in patients. This underscores the potential of integrating PARP inhibitors with immune checkpoint inhibitors in clinical protocols. For platinum-resistant recurrent ovarian cancer, known for its challenging prognosis, we propose conducting exploratory clinical trials on the combination of adebrelimab and fuzuloparib, aiming to establish robust evidence for future clinical applications. Methods: This open-label, single-arm, Phase 2 study aims to evaluate the anti-tumor activity and safety of adebrelimab in combination with fuzuloparib in approximately 37 patients with HRD-positive, recurrent platinum-resistant epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer (hereinafter referred to as ovarian cancer). The primary endpoint is to determine the objective response rate of the combined treatment regimen, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints encompass disease control rate, progression-free survival overall survival, along with the assessment of safety and tolerability. Patients must be aged 18-70 years with an Eastern Cooperative Oncology Group performance status of 0–1 and have recurrent histologically confirmed ovarian cancer with HRD-positive tumor. Patients must have progressed within less than 6 months after the last treatment with platinum-containing chemotherapy. HRD status confirmed by testing BRCA gene, loss of heterozygosity, telomeric allelic imbalance and large-scale transition. Adebrelimab (20 mg/kg) is administered intravenously every 3 weeks and fuzuloparib (100mg) is administered orally twice daily as until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met. This clinical trial is in progress and 7 patients have been enrolled. Clinical trial information: NCT05753826 .