tbuckley/cabot-search huggingface dataset:
Real life data of KEYNOTE 522: The Cleveland Clinic experience.
Authors: Olga M. Lytvynova, Jenna Jwayyed, Hussein Awada, Tyler Birkholz, Asfand Yar Cheema, Kelly Fargo, Hamed Daw, Debra A Pratt, Baidehi Maiti
Journal: Journal of Clinical Oncology (2024)

e12612 Background: Triple-negative breast cancer (TNBC) constitutes approximately 15% of all breast cancers and predominantly affects younger women with a disproportionate impact on Black and Hispanic ethnicities. Historically, neoadjuvant therapy centered around chemotherapy alone. However, the KEYNOTE 522 trial has demonstrated improved outcomes with the incorporation of the PD-1 inhibitor Pembrolizumab alongside neoadjuvant chemotherapy. Methods: A retrospective cohort analysis of 106 patients treated with the KEYNOTE 522 regimen within Cleveland Clinic from January 2020 to July 2023. The objective is to evaluate the real-life experience, particularly concerning treatment tolerance and pathologic complete response rates (PCR). Results: Among the 106 female patients, 6.6% completed full neoadjuvant therapy without reporting adverse events (AE), achieving a 71.42% PCR rate. Complications were reported in various subgroups: 54.72% associated with paclitaxel and carboplatin, with discontinuation rates of 60.34%, reduction rates of 33.02%, and full continuation rates of 6.9%. The most prevalent AE included cytopenia (46.55%) and febrile neutropenia, along with other infections (27.59%). For patients discontinuing paclitaxel and carboplatin, the PCR was 68.57%, while with dose reductions, it was 68.75%. Complications related to doxorubicin and cyclophosphamide were reported in 16.04% of patients, with 47.06% either discontinuing or reducing dose, and 5.88% continuing full therapy. Febrile neutropenia, along with other infections (64.71%) and cytopenia (23.53%) were the prominent AE. The PCR for patients discontinuing or reduced doxorubicin and cyclophosphamide was 62.50%. Pembrolizumab-related complications were reported in 16.98% of patients, with a 50% discontinuation rate. The most common AE was dermatologic toxicities (27.78%). The PCR for patients discontinuing pembrolizumab was 83.33% versus 62.5% for those continuing full therapy. Conclusions: This retrospective analysis highlights infections and cytopenias as the primary adverse reactions. Notably, the dose reduction or discontinuation of agents did result in a deterioration of PCR rate compared to patients completing full therapy. Remarkably, PCR was improved for the pembrolizumab discontinuation group, perhaps suggesting a correlation between autoimmune toxicities and improved response. Additional prospective study with larger sample size is needed to understand whether all patients benefit from completing the Keynote 522 regimen. [Table: see text]
Feasibility of using simple diet self-assessment tool (SDSAT) to establish trajectory of dietary intake for patients undergoing chemotherapy.
Authors: Ming-Hua Cong
Journal: Journal of Clinical Oncology (2024)

e13805 Background: Chemotherapy is often accompanied by impaired dietary intake, which is associated with poor clinical outcomes without effective intervention. Predicting dietary changes during chemotherapy enables early nutritional support, but the dynamic pattern and interindividual variability in dietary intake during chemotherapy remain unclear. Our aim was thus to assess the feasibility of using the Simple Diet Self-Assessment Tool (SDSAT) to establish dietary intake trajectories in patients receiving chemotherapy. Methods: This study used data from an ongoing, prospective cohort study (Patient-Reported Outcome Management Including Surveillance and Intervention in Nutritional Group) of patients receiving chemotherapy in 2021 and 2022. Diet was assessed using the SDSAT once before the treatment and at least three times during one chemotherapy cycle. We applied a group-based trajectory model to identify trajectories of dietary intake. The 24-hour dietary recall (24HR) was used to verify the validity of energy and protein intake estimated by SDSAT; compliance with SDSAT was also assessed. Results: Five trajectory groups were identified for food intake based on 217 entries by 56 patients. The compliance rate accounted for 81.11% for ≥4 cumulative responses per cycle. The agreement between the SDSAT score and the dietary energy and protein intake estimated from 24HR was high (κ: 0.888–1.0, P&lt;0.001). Groups 1 and 2 had significantly lower dietary energy/protein intake than Groups 4 and 5 (P&lt;0.001) but with distinct dietary patterns. Group 4 was the most common dietary trajectory (35.10%). Furthermore, Groups 1, 2, and 3 had significantly weaker handgrip strength (OR: 1.12, 95% CI: 1.02–1.22, P=0.016) compared with Groups 4 and 5. Conclusions: SDSAT was feasible to establish dietary trajectories during one chemotherapy cycle. Longitudinal analysis highlights the interindividual differences in dietary intake patterns among patients receiving chemotherapy and may help to inform proactive and individually tailored nutritional interventions.
Serial testing to assess cognitive function in patients with cancer being treated with immunotherapy.
Authors: Shobha Shahani, Ali Ajrouch, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2024)

TPS1644 Background: The advent of immunotherapy (IT) has revolutionized lung cancer treatment, becoming a primary modality from Stages Ib to IV. While the short-term side effects of IT are well documented, its long-term impact on cognitive function are under explored. This is a crucial area of investigation given the significant impact of cognitive health on the quality of life in cancer survivors. Preclinical investigations suggest neurocognitive alterations in IT-treated patients, evidenced by increased microglial activation and cytokine release, contributing to observed cognitive deficits such as impaired cued fear memory and object recognition. This study leverages the Montreal Cognitive Assessment (MoCA) to investigate these potential cognitive changes in a clinical setting, aiming to provide crucial insights into the long-term effects of IT. Methods: This single-center, open-label pilot study enrolls patients with various cancer types and stages undergoing IT. Exclusion criteria include prior history of underlying cognitive dysfunction, dementia, depression or psychiatric illness, history of brain metastasis or radiation. The study compromises three cohorts: those receiving IT alone, those undergoing chemo-immunotherapy, and a control group with no active treatment (in remission with prior history of cancer and have received IT in the past). Each of the IT and chemo-immunotherapy groups will include 72 patients, while the control group will consist of 40 participants. Baseline cognitive function is assessed using the MoCA scale, with follow-up assessments at 3 and 6 months from baseline. Patient enrollment commenced in April 2022, with 4 patients enrolled in the IT group, 16 in the chemo-IT group, and 32 in the control group. The primary objective is to assess the Cognitive function change in each individual group of patients. The secondary objective is to assess change of MoCA scores after 3 months and 6 months in patients receiving immunotherapy alone in lung cancer patients. The changes in MoCA scores will be plotted and summarized with mean change, standard deviation of change and standard errors of mean change. MoCA scores at baseline and at 6 months will be compared using paired t-tests. The study will analyze the rate of change in MoCA scores over time, comparing outcomes across the treatment cohorts. Clinical trial information: NCT06160700 .
Prognostic factors of grade 4 IDH-mutant astrocytoma.
Authors: Muhammad Asad Maqbool, Robert B. Jenkins, Cristiane M. Ida, Terry C. Burns, Sani Haider Kizilbash
Journal: Journal of Clinical Oncology (2024)

e14019 Background: The data on the prognostic factors of grade 4 IDH-mutant astrocytoma remains limited since the 2021 update of the WHO classification of Central Nervous System tumors. This update recognizes the importance of molecular characteristics and confers a grade 4 diagnosis based on the presence of at least one of either necrosis, microvascular proliferation, or CDKN2A/B homozygous deletion. This study sought to determine the factors that impact prognosis of patients with grade 4 IDH-mutant astrocytoma. Methods: A retrospective review was performed on all patients diagnosed with grade 4 IDH-mutant astrocytoma on initial diagnosis (as defined by the 2021 WHO classification) across the three Mayo clinic campuses (Minnesota, Florida, Arizona) between 2002 and 2023. Datapoints collected included demographic, clinical, imaging, histological and molecular variables. Factors impacting survival outcomes (overall survival [OS] and progression free survival [PFS]) were evaluated using Cox regression models. Results: Sixty-two patients with grade 4 IDH-mutant astrocytoma were identified (43 based on histological criteria alone, 10 based on molecular criteria alone, and 9 based on both). The median age of the patients was 36 years, with 64.5% of the patients identified as male and 93.3% as white. 100% (n=58) of these patients received standard treatment after surgery (radiation/temozolomide). The median follow up was 3.3 years. The median PFS and OS were 3.2 and 6.9 years, respectively. The OS was impacted by an unfavorable tumor location (either tumor involving the midline or at least 3 brain lobes; 2.4 years vs. 12.8 years, HR 10.8 [95% CI 3.29-35.6], p&lt;0.001) and CDKN2A/B homozygous deletion (2.5 years vs. NR, HR=4.3 [95% CI 1.5-12.3], p=0.0065). The PFS was impacted by an unfavorable tumor location (1.4 years vs. 4.6 years, HR=5.3 [95% CI 2.21-12.7], p=0.002), CDKN2A/B homozygous deletion (1.4 years vs. 4.6 years, HR=6.2 [95% CI 2.71-14.2], p&lt;0.001) and MGMT promoter hypermethylation (4.6 years vs. 1.4 years, HR=0.369 [95% CI 0.154-0.883], p=0.025). Age, sex, tumor size and the use of tumor-treating fields did not significantly affect survival outcomes. Using multivariable analyses, PFS remained significantly impacted by CDKN2A/B homozygous deletion (HR=11.3 [95% CI 3.23-39.0], p=0.0001) and MGMT promoter hypermethylation (HR=0.243 [95% CI 0.082-0.717], p=0.0104), but not by an unfavorable tumor location (p=0.819). Conclusions: Both CDKN2A/B homozygous deletion and MGMT status may independently influence the progression-free survival of patients with grade 4 IDH-mutant astrocytoma.
A meta-analysis analyzing the efficacy of trastuzumab-deruxtecan (T-DXd) on central nervous system (CNS) disease in patients with metastatic breast cancer (mBC).
Authors: Prashanth Ashok Kumar, Michael Sandhu, Metlapalli Venkata Sravanthi, Devashish Desai, Vishnu Charan Suresh Kumar, Sam Benjamin
Journal: Journal of Clinical Oncology (2024)

e14012 Background: CNS metastasis from mBC portends a poor prognosis. We sought to analyze CNS activity of T-DXd through a meta-analysis. Methods: A systematic search with terms encompassing BC and T-DXd was conducted in PubMed, Embase, Scopus, and Cochrane on November 23 2023. There were no search restrictions. A total of 2318 records were identified, and duplicates were removed using Mendeley. 1189 records that remained were imported into Rayyan, and the titles were screened independently by 2 reviewers. 47/75 full texts were relevant, of which 12 [7 clinical trials and 5 retrospective study] were included for analysis. Only studies that provided stratified CNS response data for mBC were included. RevMan was used to analyze the Risk Ratio (RR) and Odds Ratio (OR) with 95% Confidence Interval (CI), derived from Random Effects (RE) model with Mantel-Haenszel (MH) method. Binary RE Pooled Proportions (PP) using DerSimonian-Laird method were determined using OpenMeta. Visual inspection of our funnel plots revealed no bias. Results: The T-DXd cohort had a total of 377 patients with a median age of 54.2 years (42.5-69). Control group (T-DM1-1, Chemotherapy-2 studies) had 86 patients with a median age of 54.5 years (54.2-54.7). All studies had previously treated patients and most of the patients received local therapy. PP with T-DXd for CNS Complete Response (CR) was 4.8% (2-7.6%). Partial Response (PR) was 50.1% (32.4-67.7%) and Stable Disease (SD) was 28.9 (20.5-37.3%). PP of Objective Response Rate (ORR) (CR+PR) was 60.9% (48.3-73.5%). Drug discontinuation rate was 18% (12.2-23.9%) and pneumonitis rate was 14.5% (9.4-19.6%). RR for Event/Progressive Disease (PD) comparing T-DXd and control group was not significant [0.96 (0.77,1.2) p=0.74, I²=0%], nor was OR for Disease Control Rate (DCR) (CR+PR+SD) [1.11 (0.63,1.96) p=0.64, I²=0%] (Table). The median Progression Free Survival (PFS) was 14.1 (8.5-18.1) months for the T-DXd and 4.3 (3-5.6) months for the control group. Conclusions: Although direct comparison between the pooled T-DXd and control group failed to reveal a difference, the pooled ORR from 10/12 studies was clinically significant at 60.9%. The median PFS for T-DXd was also longer. T-DXd could be a viable treatment option for pretreated HER2+ and low mBC with CNS metastasis. Limitation of our study is the heterogeneity between the studies, entailing the need for future clinical trials in this setting. [Table: see text]
Breaking barriers for cancer clinical trials: A multi-tiered interventional approach to boost racial and ethnic minority participation in early-phase studies.
Authors: Hadi Erfani, Jacob Stephen Thomas, Diana L. Hanna, Anastasia Martynova, Lydia D. Chow, Jorge J. Nieva, Stephanie Kim, Rebecca Umayam, Jessica Levano, Lourdes Baezconde-Garbanati, Jennifer Tsui, Chanita Hughes Halbert, Anthony B. El-Khoueiry
Journal: Journal of Clinical Oncology (2024)

TPS1639 Background: Racial and ethnic minority populations are underrepresented in cancer clinical trials. The USC Norris Comprehensive Cancer Center (USC NCCC) has multiple clinical trial recruitment sites, including the Los Angeles General Medical Center (LAG), the largest safety-net hospital in the western USA. LAG partners with USC to provide cancer care to the underserved minority population of LAC, including clinical trials. As a result, between 2015-2022 a total of 120 LAG patients were accrued to phase I clinical trials; enrolled subjects were 66% Hispanic, 21% Asian, 4% Black, and 9% other. An interventional study was designed to further enhance the referral and participation of racial and ethnic minority patients from other Los Angeles County (LAC) safety-net facilities. The study is funded by the Stand up to Cancer Diversity in Early Development Clinical Trials Research Grants Program. Methods: This interventional study has 3 specific aims. First, to identify barriers to referral for minority and underserved patients: Qualitative interviews will be conducted with key stakeholders in the LAC safety net system which will uncover barriers to referring minority and underserved patients. A screening tool developed by the NCI to characterize barriers will be used. Second, to implement a multi-component program to enhance the referral of patients to early-phase clinical trials. The intervention addresses system-level, provider-level, and patient-level factors to improve the process, with a demonstration site compared to a non-demonstration site. Key features include a streamlined referral process for healthcare professionals with a singular centrally operated email managed by a specialized facilitator, weekly meetings to assign trials to prospective patients, and facilitation of approval and scheduling for referrals. We will educate providers regarding trials and exchange feedback on the referral process. We will extend resources to patients to assist with financial and transportation limitations. We will compare change in referral and enrollment rates at baseline and after the intervention for both the demonstration site and non-demonstration site. Third, to explore the impact of remotely conducted clinical trials: A clinical trial (NCT05340309) administers study drug subcutaneously and uses telemedicine visits, wearable sensors, and a smartphone app for monitoring. This pilot trial will be analyzed to determine the model’s impact on barriers to enrollment. The above interventions may provide a model that can be adapted in other healthcare delivery settings to optimize referral and enrollment of racial and ethnic minorities.
Adoption of decentralized trial elements in cancer clinical trials supporting FDA approvals during COVID-19.
Authors: Timil Patel, Amy Corneli, Pamela Balcazar, Craig H. Lipset, Sarah Calvert, Sabrena Mervin-Blake, Vinit Nalawade, Paul Gustav Kluetz
Journal: Journal of Clinical Oncology (2024)

e13802 Background: The COVID-19 pandemic significantly disrupted the conduct of cancer clinical trials. Facilitated by emergency FDA guidance, many sponsors integrated decentralized clinical trial (DCT) elements to prioritize patient safety and maintain access. The FDA’s Oncology Center of Excellence, in collaboration with the Clinical Trials Transformation Initiative (CTTI), assessed the adoption of DCT elements in registrational cancer clinical trials conducted during the pandemic that resulted in an FDA approval. Methods: CTTI sent trial sponsors a recruitment email with a link to an online survey and the name of the trial that resulted in an FDA approval. Sponsors were asked to select the DCT elements used in that trial prior to and in response to the pandemic, challenges faced when implementing these approaches, and the likelihood of using the approaches in the future. Data were collected from December 6, 2022 to January 17, 2023. Descriptive statistics were used to summarize sponsor responses. Results: Out of 52 eligible studies, 19 surveys were completed from 13 unique sponsors (37%; 12 pharmaceutical companies and 1 chose not to disclose). Sixty-three percent of sponsors identified as a large pharmaceutical company with a market cap of over $10 billion. The majority of cancer clinical trials (89%) occurred both in the United States and abroad, with almost all sponsors (95%) incorporating at least one DCT element during the pandemic. The most widely adopted DCT elements were remote site monitoring (89%), telemedicine (68%), remote laboratory assessments (63%), remote distribution of investigational product (58%) and local imaging assessments (47%). The main challenges in implementing DCT elements included site institutional policies (83%), site challenges with technology adoption (61%) and site regulatory restraints (56%). Many sponsors intend to incorporate some degree of decentralization in future cancer clinical trials, with remote site monitoring (95%), remote collection of patient-reported outcomes (68%), telemedicine (68%), and electronic informed consent (58%) being deemed "highly likely" or "likely" for future adoption. Conclusions: The COVID-19 pandemic accelerated the use of DCT elements in cancer clinical trials. This study represents the first systematic evaluation of the use of DCT elements in cancer clinical trials intended for regulatory submission and provides proof of concept that cancer trials with DCT elements can generate data suitable for FDA review and marketing approval. The appropriate use of DCT elements holds promise to expand clinical trial access and reduce patient burden. Further characterization and mitigation of clinical site-level challenges is warranted to encourage continued adoption of DCT elements in cancer clinical trials.
Linking in with advice and supports for men impacted by metastatic cancer: The LIAM Mc trial (NCT05946993).
Authors: Jack Gleeson, Anita Cahill, Katie E Johnston, Stephanie Corkery, Katarina Medved, Anne Marie Cusack, Laia Aran Raigal, Josephine Hegarty, Roisin M. Connolly, Mohamad M. Saab, Richard Martin Bambury, Brendan Noonan
Journal: Journal of Clinical Oncology (2024)

TPS1646 Background: Multidisciplinary supportive care interventions are key to preventing and managing adverse effects of cancer and its treatment for patients, reducing symptom and psychological burdens and enhancing quality of life (QoL). However, the optimal composition of these interventions for men with genitourinary (GU) cancers is poorly understood. The LIAM Mc Trial is an enhanced supportive care programme, funded by the Irish Cancer Society and designed with the input of patient representatives who highlighted the unmet needs of cancer survivors. An important aspect of the trial is to demonstrate how to improve the survivorship supports and services for underserved communities of men who experience disparities in cancer incidence, prognosis, outcome and QoL, and have not traditionally been the focus of such initiatives. Methods: Using an embedded mixed-method process evaluation this prospective trial aims to assess the feasibility and impact of a holistic 12-week survivorship programme amongst men with advanced GU cancers at an Irish Cancer Centre. The programme involves twice-weekly sessions with input from a dedicated physiotherapist, dietitian, and nurse specialist, along with education sessions from medical social worker and psycho-oncology specialists, and programme oversight provided by medical oncologists. Outcomes are measured at three timepoints; pre-intervention, immediately post-intervention and at 6 months post intervention, and will include EORTC QoL; muscle strength; body composition through bioelectrical impedance analysis and ultrasound; diet quality; cancer related symptom control; cancer related fatigue scores; feasibility outcomes, qualitative interviews and a process evaluation. Any man with a locally advanced or metastatic GU cancer who has recently completed a course of treatment or is stable on active anti-cancer treatment is eligible for the programme. Over the two-year study period the sample size target is 72 participants. The primary endpoint of the study is to evaluate the feasibility of introducing an enhanced supportive care programme as part of routine management for male cancer patients with metastatic disease. Acceptability, satisfaction with the programme and QoL changes are key secondary endpoints. Barriers to participation are also a key outcome under investigation. The study was activated in May 2023 with the first participants enrolled in June 2023. To date 17 men have enrolled with accrual completion anticipated in June 2025. Clinical trial information: NCT05946993 .