tbuckley/cabot-search huggingface dataset:
Clinical trial diversity (CTD) scorecards.
Authors: Sara L. Horton, Stanley Lewis, Kay Olmstead, Elizabeth Fassberg, Chris Komelasky, Bill Fitzsimmons
Journal: Journal of Clinical Oncology (2024)

e23042 Background: To ensure safety and efficacy, oncology clinical trials must include adequate participation by age, gender, race, and ethnicity subgroups. In November 2020, the US FDA issued Guidance for Industry to increase clinical trial diversity in pivotal clinical trial programs. CARER Group developed the CTD Scorecard to evaluate demographic diversity in registration trial programs for new drugs. Methods: Based on publicly available data, CTD Scorecard assigns each drug a letter grade (A, B, C, D, F) for demographic subgroups-age, race and ethnicity, as well as an overall grade. Scoring includes percentage of subgroup enrolled relative to US population, number of subgroup receiving study drug, and prevalence of disease in each subgroup. Results: From January 2022 to December 2023, US FDA approved 26 new oncology drugs. In this period, 8 trial programs were rated Grade B, 18 received Grade C. Notably, elderly, and female participation was better represented with 23 (88%) and 19 (90%) with Grade A or B respectively. Two trial programs each received Grade C for these subgroups. Asian representation was high, with 54% of programs scoring Grades A or B. Only one drug received Grade D for this demographic and no programs received Graded F. In contrast, Black and Hispanic populations showed significant underrepresentation. Fourteen (54%) of trial programs for Black and thirteen (50%) for Hispanic populations received Grades D or F. Notably, 20 (77% ) of trial programs had ≤10 Black participants receive study drug, with 6 programs having no Black participants receive study drug. Similarly, 14 (54%) of trial programs included ≤ 10 Hispanic participants receiving study drug, and 3 (12%) programs with no Hispanics receiving study drug. During this time, FDA issued Post-Market Requirements or Commitments (PMR/PMC) for 9(35% ) of oncology drugs due to premarket trial diversity shortfalls. However, by CTDs, 20 (77%) of the 26 approved drugs lacked adequate representation, yet did not receive Post-Marketing Requirements or Commitments. Conclusions: Oncology drug safety and efficacy can vary by age, race, sex, and ethnicity, necessitating diverse demographic participation in clinical trials. Alongside US FDA industry guidance, entities like the National Academy of Sciences, Engineering and Medicine and the GAO Report emphasize the need for trial diversity, bolstered by Federal Clinical Diversity Provision H.R. 2617 enacted in 2022. CARER’s scoring system evaluates clinical diversity age, sex, race and ethnicity, based on FDA data since January 2022. Age ≥65, female gender, and Asian race subgroups were generally well represented in clinical trial programs. Black and Hispanic groups show the lowest representation. Consistent use of PMC and PMR to new drugs may improve demographic inclusivity in trials lacking initial diversity.
Real-world quality analysis of palliative care utilization in patients with brain metastases at three academic institutes.
Authors: Rohit Singh, Alissa A. Thomas, Emily Kopp, Ryan Amidon, Wendy Novicoff, Samantha R Schuetz, Joe A Bovi, Guneet Sarai, Ausia N Iqbal, Camilo E. Fadul
Journal: Journal of Clinical Oncology (2024)

12080 Background: Brain metastases (BMETs) are a devastating complication of cancer, occurring in up to 30-50% of patients with advanced solid tumors. Median survival after diagnosis of BMETs can be limited, with 3-6 months survival for patients with poorer performance status (Updated Recursive Partition analysis [U-RPA] classification class 2b and 3). Early integration of palliative care (PC) can improve a patient’s quality of life. Per guidelines, patients with advanced cancer should be referred to an interdisciplinary team, including PC, early in the disease. We aimed to assess the utilization and impact of PC in patients with BMETs at three academic centers. Methods: We obtained data from the electronic medical record (EMR) of all patients diagnosed with BMETS at the University of Virginia, the Medical College of Wisconsin, and the University of Vermont between 1 January 2017 and 31 December 2019. Inclusion criteria were age 18+ years, diagnosis of BMETs secondary to a solid tumor malignancy (excluding leptomeningeal metastases), and &gt;3 months of follow-up treatment. Patients were included if considered at high risk for mortality, which was defined as KPS &lt;70 (U-RPA Class 3) or KPS 70-80 and age &gt; 65 (U-RPA Class 2b). Chi-squared and Fisher’s exact tests compared survival, hospice referral, emergency visits, readmissions, and advance directives (AD) on the file between the PC and non-PC groups. Results: In total, of the 309 patients that were assessed, 220 patients were class 2b, and 89 were class 3 per U-RPA classification. The mean age was 66 in both groups, and 167 (54%) were seen by PC. The median survival for patients seen by PC was 7.8 months compared to 8.3 months (p 0.056). There was no statistically significant difference in survival between the two groups. 80% of patients in the group seen by PC enrolled with hospice care compared to 58% in the non-PC group (p 0.0002). 80% of patients had an AD on file in the group seen by PC compared to 56% in the non-PC group (p &lt;0.0001). In terms of ED visits or re-hospitalization, there was a trend for more ED visits/readmissions in the group seen by PC compared to the non-PC group (p 0.057). Conclusions: In this real-world quality analysis, we found that there is under-utilization of formal PC consultation in patients with BMETs. There was no difference in survival between groups, indicating PC is not synonymous with end-of-life or hospice care. PC was associated with more patients completing ADs and more patients using hospice. Health systems and policy initiatives promoting palliative care utilization earlier in the disease course may support patient values and preferences at the end of life. [Table: see text]
The role of next-generation sequencing in achieving diagnostic precision for dermatofibrosarcoma protuberans and its fibrosarcomatous variant.
Authors: Steven Christopher Smith, Kieran Sweeney, Mark Gordon Evans, Kartik Angara, Celia Reynolds, Gretchen Hubbard, Soo J. Park, Andrew Elliott, Matthew James Oberley, Gina Z. D'Amato, Sosipatros A. Boikos, Armita Bahrami
Journal: Journal of Clinical Oncology (2024)

e23531 Background: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive skin and subcutaneous fibroblastic neoplasm, characterized by COL1A1:: PDGFB fusions and, less frequently, PDGFD fusions. Approximately 10-15% of DFSP cases progress to distant metastases, yet the genetic mechanisms behind this transformation to fibrosarcomatous DFSP (FS-DFSP) or metastatic development remain unclear. Reports of DFSP in deeper tissues suggest a broader occurrence than previously recognized. We hypothesize that conventional histopathology may not adequately identify certain DFSP variants, especially those in deep tissues, potentially missing critical opportunities for targeted therapy with FDA-approved tyrosine kinase inhibitors. Methods: We searched Caris’s database to identify solid tumors with PDGFB or PDGFD fusions, markers of DFSP or FS-DFSP. We reviewed histologic features and clinical information, along with exome sequencing and copy number amplifications. Significance was tested using Mann Whitney U and Fisher’s exact tests as appropriate. Results: We identified 59 cases with PDGFB or PDGFD fusions: 55 COL1A1:: PDGFB, 3 EMILIN2:: PDGFD, and 1 COL1A2:: PDGFB cases. Of these, 51 were primary specimens and 8 metastatic. The patients included 31 males and 28 females, with a median age of 49 years (range: 14-93). Primary tumors occurred mainly in the skin/subcutis or deep soft tissues (35 trunk, 9 head and neck, 7 lower extremity, 2 upper extremity), but 6 were found in visceral organs (4 uterus, 1 cervix, 1 lung). Histologically, 20 cases were conventional DFSP and 32 were FS-DFSP. Notably, 21 tumors (36%) had been initially misclassified; most of which had metastatic presentation, unusual histology, or atypical location. Tumor sequencing revealed a higher incidence of genetic changes in addition to the PDGFB/ PDGFD fusions: concurrent mutations were detected in 66% of FS-DFSP cases versus 25% of DFSP cases (p = 0.009). Moreover, tumor mutational burden was significantly higher in FS-DFSP than DFSP (p = 0.006). The most prevalent mutations were in the TERT promoter and NF1, found exclusively in FS-DFSP cases. Conclusions: Conventional histology commonly fails to recognize FS-DFSP, leading to missed opportunities for targeted therapy. This highlights the essential role of next-generation sequencing in achieving greater diagnostic accuracy for DFSP and its fibrosarcomatous variant. While no single gene mutation consistently differentiates DFSP from FS-DFSP, the occurrence of additional genetic alterations is notably more common in FS-DFSP cases.
Physical activity and dexamethasone for cancer related fatigue: A preliminary placebo controlled randomized control trial.
Authors: Sriram Yennu, Vicente Valero, Brandon George Smaglo, Michael J. Overman, Arvind Dasari, Robert A. Wolff, Kanwal Pratap Singh Raghav, Carlos Hernando Barcenas, Naifa Lamki Busaidy, Bryan M. Fellman, Karen Basen-Engquist, Debashish Tripathy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2024)

12050 Background: Despite high frequency and significant impact on quality of life, there are limited treatment options available for cancer related fatigue (CRF) in patients with advanced cancer. The primary aim of the study was to determine the feasibility (adherence, safety, and satisfaction) of the combination therapy, physical activity (PA) plus Dexamethasone (Dex); and PA plus placebo (Pl) for CRF. The secondary aim was to explore the effects of PA+Dex, and PA+Pl on CRF as assessed by Functional Assessment of Cancer Illness Therapy–fatigue (FACIT-F). Methods: In this phase 2, randomized, double blind, placebo controlled trial, patients with advanced cancer with CRF ≥ 4/10 on Edmonton Symptom Assessment Scale were eligible. Patients were randomized to standardized PA for 4 weeks plus either 4mg of Dex (PA+Dex arm), or Pl (PA+PL arm) BID for the first 7 days. Changes in FACIT-F scores from baseline to Day 8, and Day 29 were assessed. Other outcomes included change in quality-of-life scores. Results: A total of64 (89%) patients were evaluable. The median (IQR) changes in FACIT-F scores at Day 8 and Day 29 from baseline were 9 (2,16), P&lt; 0.001; 5.75 (0,12.5), P=0.015 for PA+ Dex arm, and 3.5 (-2.13, 10), P=0.054; 6.50 (2.5, 15.5), P=0.006 for PA+ Pl arm respectively. Exploratory Linear Mixed Model (LMM) analysis showed significant treatment effect of PA +Dex, with treatment having improvement of 5.63 units for FACIT-F scores (95% Cl 1.74,9.52), P=0.005. Effect sizes for improvement of FACIT-F scores at Day 8 and Day 29 were -3.49, -2.43 in PA+Dex arm; and -1.93, -2.72 in PA+Pl arm, respectively. Effect sizes for change in fatigue related symptoms and quality of life scores as assessed by Patient-Reported Outcome Measurement Information System-Fatigue T-scores, Multidimensional Fatigue Symptom Inventory-Short Form total, and Functional Assessment of Cancer Therapy -General scores at Day 8, and Day 29 in PA+ Dex arm were 2.93 (P=0.005), 2.82 (P=0.005); 2.27 (P=0.023), 2.68 (P=0.007); -2.39 (P=0.017), -3.26 (P=0.001) respectively. Adherence to Dex and Pl were 91% and 92%, respectively, Satisfaction rates with PA+Dex and PA+Pl arms were 98% and 79%, respectively. There was no significant difference in grade ≥3 adverse events between the two arms (P = 0.36). Conclusions: Satisfaction, and tolerability to the combination therapy, and medication adherence was excellent.PA + Dex significantly improved CRF at day 8 and 29. The improvement was sustained 3 weeks after discontinuation of Dex. Further larger studies are justified. Clinical trial information: NCT03583255 .
Association of mutational status with metastatic pattern, race, ethnicity, and overall survival (OS) in leiomyosarcoma (LMS).
Authors: Hayes Pearce, Chang Yu-Cherng, Brandon Edward Rose, Emily E. Jonczak, Julie Grossman, Gina Z. D'Amato, Marilyn Huang, Jonathan C. Trent, Francesco Alessandrino
Journal: Journal of Clinical Oncology (2024)

e23553 Background: LMS, one of the most common soft tissue sarcomas, can arise from the uterus, retroperitoneum, vessels, or extremities. It is unclear if the metastatic pattern and potentially the mutational status differs among the different types of LMS. We investigated the association between sites of metastases, mutations, race, ethnicity, and OS in different LMS types. Methods: This single-center retrospective study evaluated patients with biopsy-proven LMS that underwent genomic testing between January 2009 and May 2023. Association between genomic profile, sites of metastases, types of LMS (extremity, retroperitoneal, uterine, vascular), self-reported race and ethnicity was performed using Fisher’s exact test. Survival curves for self-reported race and ethnicity, mutations, sites of metastases, and types of LMS were estimated using the Kaplan-Meier method and compared with a log-rank test. Cox proportional hazard regression models were used to examine the association between OS with types of LMS, self-reported race and ethnicity, mutational status, and sites of metastases. Results: The study included 110 subjects (F/M:81/29; median age 57 years, 99/110 with metastatic disease). 27/110 (25%) subjects self-reported as Hispanic, and 27/110 (25%) as Black. The most common type of LMS was uterine (50/110, 45%), followed by retroperitoneal (27/110, 25%), extremities (23/110, 21%) and vascular (10/110, 9%). The most common mutation was TP53 (74/110, 67%), followed by RB1 (24/110, 22%). ER/PR expression was present in 25/110 subjects (23%). The lungs were the most common site of metastasis (79/99, 80%), followed by the liver (37/99, 37%), and pelvis (29/99, 29%). Peritoneal and pelvic metastases were more common in uterine LMS (p = 0.0001 and 0.002, respectively). Liver metastases were more common in retroperitoneal LMS (p = 0.03). TP53 mutation was more common in vascular LMS (p = 0.03), whereas intermediate/high tumor burden was more common in LMS arising from the extremities (p = 0.004). BRCA1/2 mutations were more common in subjects with liver (p = 0.02) and intramuscular metastases (p = 0.04). Pleural metastases (11/99, 11%) were associated with lower OS (Risk Ratio: 2.7; 95% CI: 1.13, 6.32; p = 0.02). ATRX mutation (17/110, 15%) was more common in Hispanic subjects (p = 0.005), in which it was associated with lower OS (p = 0.0007). Conclusions: The mutational status and metastatic pattern of LMS varies based on the LMS types, and potentially provides prognostic data. In our sample, OS was reduced in Hispanic subjects with ATRX mutation, and the presence of pleural metastases was also independently associated with shorter OS.
Discrepancies in therapeutic indications for the same oncology drugs among FDA, EMA, and Brazilian agency.
Authors: Camila Marchi Blatt, Mario Henrique Furlanetto Miranda, Rafael Balsini Barreto, Bárbara Andressa Uliana, Denize Bodnar
Journal: Journal of Clinical Oncology (2024)

e23035 Background: Divergent marketing approvals for oncology drugs among prominent agencies can prompt questions, especially when they are grounded in the same evidence. The aim of this study was to evaluate and compare the assessment and approval processes for novel products and indications by the FDA, EMA, and the Brazilian Health Regulatory Agency (ANVISA). Methods: Therapeutic indications for FDA-approved anticancer drugs from January 2019 to December 2023 were identified. Data, including approval dates, details on authorization procedures and evidence presented, were extracted from the databases of the FDA, EMA, and ANVISA. Only approvals for non-hematologic solid tumors were considered. All data were publicly available, and ethical approval was not required. No patient involvement occurred in this study. Results: Between 2019 and 2023, the FDA granted approval for 154 therapeutic indications for marketing authorization, resulting from 148 pivotal trials. The predominant cancer types during this period were non-small cell lung cancer (31 approvals [20.1%]). Most trials were in phase III (66.8%) and randomized (68.1%). Additionally, 41 (26.6%) received accelerated approvals, with 6 subsequently obtaining regular approvals. Among the therapies, 66 trials (42.8%) involved active comparators, while 53 (34.4%) and 35 (22.7%) were single-arm and placebo-controlled trials, respectively. Approximately half (74 [48%]) of the therapies were approved for metastatic first-line treatment, 54 (35%) for second-line treatment, and the rest for neoadjuvant and/or adjuvant treatment. Regarding endpoint characteristics supporting approval, the most prevalent was a combination of objective response rate (ORR) + duration of response (DoR) (38 [24.6%]), followed by progression-free survival (PFS) + overall survival (OS) (31 [20.1%]). When comparing the 154 FDA-approved indications, 50 (32.4%) were not approved by EMA, and 60 (38.9%) were not approved by ANVISA. Furthermore, in 33 cases (21.4%), there were disparities in clinical indications between the FDA and EMA, primarily related to the target population specification, with 10 cases (6.4%) attributed to programmed death ligand-1 (PD-L1) expression. Notably, in these instances, the FDA approved the drug regardless of PD-L1 expression, while the EMA required a percentage of cells with PD-L1 expression. In all these cases, ANVISA aligned with the FDA's assessment. Conclusions: Significant clinical disparities were identified in the outcomes of the approval process for oncology products among the FDA, EMA, and ANVISA. Additional efforts are needed to standardize decision-making across regulatory systems.
The effectiveness of adjuvant therapy in adult patients with spindle cell/sclerosing rhabdomyosarcoma: A single-center retrospective study.
Authors: Zijing Liu, Jie Liu, Yaotiao Deng, Yu Jiang
Journal: Journal of Clinical Oncology (2024)

e23550 Background: In recent years, the WHO classification of soft tissue tumours has classified spindle cell/sclerosing rhabdomyosarcoma (RMS) as a novel subtype of RMS. However, the prognosis and standard treatment modalities for operable spindle cell/sclerosing RMS patients remain unclear. This study aims to investigate the effectiveness and influencing factors of postoperative adjuvant therapy in adult patients with spindle cell/sclerosing RMS. Materials and Methods: This single-center retrospective study enrolled adult patients with spindle cell/sclerosing RMS who underwent surgery and subsequent adjuvant therapy at West China Hospital, Sichuan University, from August 2014 to March 2023. The included patients initially underwent surgical excision, followed by one of the adjuvant treatments: radiotherapy, chemotherapy, or a combination of radiotherapy and chemotherapy. Disease-Free Survival (DFS) and Overall Survival (OS) were calculated for the included patients in this study. Univariate analysis and multivariate COX regression were conducted to determine prognostic factors. Results: This study included a total of 17 patients diagnosed with spindle cell/sclerosing RMS. Among them, 10 (58.8%) patients received postoperative adjuvant chemoradiotherapy, while 7 (41.2%) patients underwent postoperative chemotherapy alone. 12 (70.6%) patients received chemotherapy following the VAC regimen, and 5 (29.4%) patients received non-VAC chemotherapy. The prognosis analysis indicates that the median DFS was not reached, with a 1-year DFS rate of approximately 87.8% and a 2-year DFS rate of approximately 52.4%. The median OS was not reached, with a 1-year OS rate of 100% and a 2-year OS rate of approximately 92.9%. Univariate analysis shows that compared to undergoing non-R0 resection, undergoing R0 surgical resection significantly improves patient DFS (P = 0.02). Compared to no postoperative radiotherapy, receiving postoperative prophylactic radiotherapy significantly improved both DFS (P = 0.01) and OS (P = 0.02). In contrast, using VAC as adjuvant chemotherapy did not significantly increase DFS and OS compared to non-VAC regimens (P = 0.83 and 0.57, respectively). Multivariate Cox regression analysis demonstrated that the receipt of postoperative prophylactic radiotherapy independently predicted DFS (P = 0.03). Conclusions: In adult patients with spindle cell/sclerosing RMS, R0 resection, when compared with non-R0 resection, delays disease recurrence but does not enhance overall survival. Long-term outcomes may be improved in patients who receive postoperative adjuvant radiotherapy. However, choosing a VAC regimen as adjuvant chemotherapy may not contribute to an improved long-term prognosis when compared with a non-VAC regimen. Keywords: adjuvant therapy, spindle cell, sclerosing, rhabdomyosarcoma, effectiveness
Analyzing megestrol prescribing patterns in the Medicare cancer population in a community oncology network.
Authors: Gunjan Sharma, Erica Feinberg, Jody S. Garey, Puneeth Indurlal
Journal: Journal of Clinical Oncology (2024)

e23288 Background: Megestrol Acetate (Megestrol) used for appetite stimulation in cachexic cancer patients is listed as a potentially inappropriate medication to be avoided in patients 65 years and older per the American Geriatrics Society (AGS) Beers Criteria. It is also classified as a high-risk medication for elderly people by the Pharmacy Quality Alliance. However, due to the complexity of medication prescribing in geriatric cancer patients, some medications on the Beers Criteria may be used more often. We aim to review the use, and weight gain benefits of Megestrol in elderly patients with cancer. Methods: We obtained prescription data for Megestrol for episodes with patients 65 years and older for 15 practices in The US Oncology Network (The Network) participating in the Oncology Care Model (July 2016- June 2022). We evaluated the trends and patterns of Megestrol prescribing in The Network. We compared the documented weights before the initial prescription date (Pre-weight) within an episode to the weights immediately after a 12-week period (12-week weight) as documented in the Electronic Health Record (EHR) system. Results: Of 249,944 episodes, 4,957 (2%) episodes had Megestrol prescribed. Of the episodes with Megestrol, 3,464 (70%) had weight documented within the duration of a 6-month episode of care, with a mean weight of 67.3 kgs. The mean difference (0.8 kgs) between Pre-weights (mean = 67.6 kgs, std dev = 16.3 kgs, n = 2,112) and 12-week weights (mean = 66.8 kgs, std dev = 16.0 kgs, n = 2,112) was found to be significant (paired, one tail T-Test, p-value &lt; 0.0001, significance level = 0.01). Patients who received Megestrol showed weight loss instead of weight gain in the 12-week follow-up period. Summary statistics for the two cohorts are provided in Table 1. Table 1: Summary statistics for the two patient cohorts. Conclusions: Oncology providers generally follow Beer’s criteria with limiting Megestrol use in older age patients. Megestrol use did not appear to contribute to weight gain in older age cancer patients. We aim to look at Megestrol use and thromboembolic adverse events in cancer populations in future studies. CMMI Disclaimer: The statements contained in this document are solely those of the authors and do not necessarily reflect the views or policies of CMS. The authors assume responsibility for the accuracy and completeness of the information contained in this document.[Table: see text]