tbuckley/cabot-search huggingface dataset:
Detection and surveillance of circulating tumor cells in sarcoma for predicting therapy response and prognosis.
Authors: Qing Zhang, Zhe Wang, Yongkun Yang, Zhiping Deng, Feng Yu, Xia You, Peng He
Journal: Journal of Clinical Oncology (2024)

e23573 Background: Generally sarcomas are categorized as soft tissue and bone sarcomas and represent heterogenous group of malignancies with more than 70 distinct histologic subtypes. Due to their rarity and heterogeneity, sarcomas present particular challenges for accurate diagnosis, prognosis, and treatment. The presence and persistence of circulating tumor cells (CTCs) in the peripheral blood are believed to be associated with poor prognosis and distant metastases. A blood-based CTCs test is thus greatly needed for monitoring disease progression and predicting clinical outcomes. Methods: In this study, we developed a CTCs test for the detection and surveillance of sarcoma patients’ CTCs, and subsequently explored its clinical value. 123 patients with sarcomas were enrolled as the cohort for serial CTCs tests. Dynamic CTCs counting, in combination with therapy evaluation and post-treatment follow-up, was used to explore predicting pre- and post-chemotherapy evaluation and prognosis. Results: Quantification of CTCs demonstrated a significant increase in sarcoma patients compared to healthy individuals. Furthermore, patients in stage III-IV had a higher CTC count than those in stage I-II (p&lt;0.01), suggesting a correlation between CTCs and disease development. Remarkably, there was variation in the quantity of CTCs among different types of sarcomas. The highest number of CTCs was observed in undifferentiated small round cell sarcoma, followed by soft tissue tumor, while bone tumors had the lowest number. In addition, the number of CTCs in patients with positive PD-L1 expression was considerably greater than in those with negative expression (p&lt;0.01). The count of CTCs shown a substantial decrease following neoadjuvant chemotherapy treatment. There was a decline in the number of CTCs both before and after postoperative adjuvant chemotherapy treatment, however, there was no significant statistical discrepancy. The number of CTCs at the baseline was shown to be considerably larger in the group of patients with progressive disease or stable disease (PD+SD) compared to the group with partial response or complete response (PR+CR) (p&lt;0.05). This difference was particularly pronounced for interstitial-type CTCs (p&lt;0.01). Conclusions: The rate of presence of CTCs in the peripheral blood of sarcoma patients is high, and patients with an increased percentage of CTCs after treatment have a poor treatment effect. The dynamic monitoring of changes in CTCs counts after treatment has clinical significance for the timely detection of recurrence or metastasis. CTCs also showed a clinical value in prediction of therapy efficiency or prognosis, and may be clinically valuable for the whole course management of patients.
Systemic therapy in NF-1 associated malignant peripheral nerve sheath tumors (MPNST).
Authors: Pujita Munnangi, Bridgette L King, Y. Sabrina Chiang, Anthony Paul Conley, Dejka M. Araujo, J. Andrew Livingston, Joseph Aloysius Ludwig, Michael Nakazawa, Elise F Nassif Haddad, Vinod Ravi, Ravin Ratan, Maria Alejandra Zarzour, Shreyaskumar Patel, Keila E Torres, Neeta Somaiah
Journal: Journal of Clinical Oncology (2024)

11583 Background: MPNST are rare sarcomas that have a poor prognosis and are challenging to treat. Around 50% of MPNSTs are associated with NF1, 40% are sporadic, and 10% are radiation-associated. Doxorubicin (D) based chemotherapy (CT) regimens are commonly used in the front-line, and combinations have better response rates than single agents. Response to second-line regimens is not well documented. The objective of this study is to document efficacy of systemic regimens in MPNST as a benchmark for future novel therapeutics in this space. Methods: 72 patients (pts) with NF1-associated MPNSTs in an MD Anderson database were reviewed retrospectively from EMR. Variables collected included demographics, primary MPNST location, localized vs metastatic, and treatments received (+/- radiation, +/-surgery, +/- lines of CT). Responses (progressive disease (PD), stable disease (SD), partial response (PR)) as interpreted by treating physician and radiology reports and time on treatment for 1st and 2nd line chemotherapy regimens were assessed. Cox proportional-hazard regression was used to investigate associations of variables with overall survival (OS: from time of diagnosis to death or last follow-up). Results: Demographic and CT details are provided (Table). The median age at diagnosis was 34.5 yrs (range: 9-71). The most common MPNST location was the trunk (56.94%). D based regimens were the most frequent 1st-line CT (65.7%), and gemcitabine- docetaxel was the most frequent 2nd-line CT (33.3%). In pts with metastases, 74.4% got 1st line, 44.7% 2nd line, 25.5% 3rd line, and 12.7% got 4th line therapy. Median follow-up was 2.46 yrs (IQR 1.24-9.52). The median time on treatment for 1st and 2nd line CT was 110 (IQR 48-153) and 57 (IQR 41-133) days, respectively. In the multivariate COX model for the entire cohort, male sex (HR: 0.35, 95%CI: 0.18-0.68), lower extremity primary (HR: 0.09, 95%CI: 0.02-0.40), and absence of metastases at last follow up (HR: 0.05, 95%CI: 0.02-0.17) were associated with decreased risk of death. Additional analysis on efficacy and survival of the systemic therapy regimens will be presented at the meeting. Conclusions: In this study &lt; 50% pts with advanced NF1 related MPNST made it to 2nd line CT and outcomes were inferior to the predominantly D based 1st line regimens. This highlights an area of high unmet need. [Table: see text]
High-grade surface osteosarcoma: A National Cancer Database study of demographic characteristics.
Authors: Ahmed Dudic, Yanick Tade, Anton Sachs, Susan Rafie, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e23508 Background: High-grade surface osteosarcoma (HGSO) is an extremely rare malignant subtype of osteosarcoma. HGSO often affects long bones, particularly the femur, and is the rarest subtype of surface osteosarcomas. Though data is limited, current information suggests this cancer presents with a poor prognosis, generally affecting adults aged 20 to 40. Current treatment standards involve wide resection and chemotherapy. The National Cancer Database (NCDB) was examined to establish the demographic factors among HGSO patients and identify diagnostic and treatment trends. Methods: A retrospective cohort study from 2005-2020 was conducted using the NCDB. A total of 99 patients were found with a histologically confirmed diagnosis of high-grade surface osteosarcoma (ICD-9194-3). Factors such as gender, age, race, insurance status, rural/urban residence, treatments, mortality rates, and Charles/Deyo scores were analyzed using descriptive statistics, and trends in incidence were interpreted via regression analysis. Results: Yearly HGSO incidence rates increased from 2005 to 2020 (R2 = 0.19). The average age of diagnosis was 41 years (SD = 24.9, range = 10-90) with men diagnosed (54%) slightly more than women. The majority of patients were non-Hispanic white (73%), had private insurance (55%), and lived in a metropolitan area with over 250,000 in population (89%). The average patient was diagnosed at a hospital 40.4 miles away from their home (SD = 84.9, range 0.4-648.4 miles). Most patients (55%) were in stage II at diagnosis, and 86% of patients had a Charlson-Deyo comorbidity score of 0. The most common primary site of this malignancy was the long bones of the lower limb and associated joints (67%), while the upper extremities (8%) and pelvic bone (8%) served as less common primary sites. Surgery was the most common primary treatment (62%). Data from 69 patients revealed the 90-day mortality post-surgery was 3%. The mean survival rate was 70% at two years and 52% at five years. Conclusions: To the best of our knowledge, this study represents the first NCDB analysis of HGSO. Our analysis demonstrated that HGSO occurs most often, but not exclusively, within the lower extremity long bones, which may be an important diagnostic distinction. It was previously indicated that the average age at HGSO diagnosis is 20-40 years, but our analysis suggested it is closer to 40. Our analysis revealed a five-year survival rate of 52% which is worse than prior studies have indicated. Demographic data has revealed the majority of patients were non-Hispanic white, privately insured, and living within a metropolitan area. This trend may suggest access to healthcare resources is influencing this cancer’s diagnosis and treatment. Further research is warranted to explore whether the demographic patterns seen in HGSO are indicative of biological causes or socioeconomic factors that are significantly influencing diagnosis.
Update on GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab in previously treated sarcoma (NCT04535713).
Authors: Nadezhda Omelchenko, Sant P. Chawla, Anmol Dia Agarwal, Samantha Jeffrey, Luisa Sena Cota, Victoria Chua, Ania Moradkhani, Doris V. Quon, Steven Wong, Erlinda Maria Gordon
Journal: Journal of Clinical Oncology (2024)

e23569 Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. Hypothesis: The addition of nivolumab to this regimen will have synergistic effects and improve treatment outcomes. Objectives: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Methods: Inclusion criteria: Previously treated male and female subjects, &amp;gt; 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if the toxicity grade is &amp;lt;1. Results: Efficacy (n = 70). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 14 PR, 47 SD, 9 PD. ORR = 20%; DCR (CR+PR+SD) was 87%. Median PFS was 8.2 (95% CI: 5.85-10.55) months; 6- month PFS rate of 59%. Median OS was 17.6 (95% CI: 13.53-21.67) months, with 6-month OS of 84%. Safety (n = 75): Grade 3/4 TRAEs include thrombocytopenia (n = 26), white blood cell count decreased (n = 17), neutropenia (n = 16), fatigue (n = 15), anemia (n = 13), nausea (n = 9), anorexia (n = 5), diarrhea (n = 2), emesis (n = 1), febrile neutropenia (n = 1), sepsis (n = 1), rectal bleeding (n = 1), transaminitis (n = 1), dizziness (n = 1), shortness of breath (n = 1). There were no unexpected adverse events reported. Conclusions: Taken together, the data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713 .
Impact on biomarker documentation in community oncology by optimizing clinical decision support.
Authors: Daniel Rubin, Victoria Handy, Steven Gilmore, Aimee Ginsburg, Andrea Dickens, Josh Howell, Shannon Hough
Journal: Journal of Clinical Oncology (2024)

11182 Background: Timing of biomarker results is critical to informing the selection of appropriate precision medicine-based treatment options for patients. Prior studies have demonstrated that low rates of biomarker testing may be driven by poor documentation. Our clinical decision support (CDS) tool aims to provide community oncology clinicians with a clear picture of the ever-growing available treatments. Evaluation of CDS data revealed an excess of biomarker results documented as “unknown” thought to be related to results availability. Methods: During treatment selection in the CDS tool, providers answer various prompts related to the patient’s disease, staging, treatment intent, and biomarker results. Prompts are aligned with NCCN guidelines for the respective cancer type. Changes were implemented to ease providers’ documentation of biomarker results. For adjuvant (adjNSCLC) and metastatic NSCLC (mNSCLC), prompts were relocated to align with when biomarker results were likely to be available. For metastatic castrate resistant prostate cancer (mCRPC), some biomarkers are only needed after a patient has received prior docetaxel and hormone therapy, thus prompts were moved to that scenario. Re-prompting of biomarker status for subsequent therapy was also implemented if the initial response was “unknown.” We report changes in percentage of known biomarkers specifically in adjNSCLC, mNSCLC, and mCRPC. Descriptive statistics were used to describe the rates of known biomarkers, and a chi-square test was used to analyze differences from pre and post changes. Results: In this evaluation, 85,493 biomarkers were documented. In adjNSCLC and mNSCLC, biomarker prompt changes increased documentation of known biomarkers from 69% to 78% and 59% to 79% pre- to post-implementation. In adjNSCLC, ALK and PD-L1 recording increased by ≥10% (P&lt;0.00001). For mNSCLC, documentation increased for all known biomarkers (P&lt;0.00001), including ≥15% increases for 8 of 10 biomarkers. In mCRPC, known biomarker documentation improved from 34% pre-implementation to 61% post-implementation. BRCA1/2, MSI, MMR, TMB, and PSMA biomarker recording increased by ≥20% (P&lt;0.00001) after prompt changes. Selected biomarkers are shown in the table. Conclusions: Adjusting prompts in a CDS tool to align with the availability of biomarkers in clinical practice increased the documentation of known biomarker results for adjNSCLC, mNSCLC, and mCRPC. Based on these findings, similar changes are being implemented for other cancer types in the CDS tool. [Table: see text]
Delayed immune-related adverse events in patients with advanced melanoma treated with immune checkpoint inhibitors.
Authors: Arkhjamil Angeles, Eric Sonke, Thao Phuong Nguyen, Gaurav Bahl, Vincent Isaac Poon, Vanessa Bernstein, Alison Margaret Weppler, Kerry J. Savage
Journal: Journal of Clinical Oncology (2024)

12047 Background: Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of melanoma but can have serious or life-altering immune-related adverse events (irAEs). Most toxicities associated with ICIs occur within the first few months (mo) of treatment initiation, but delayed irAEs occurring 12 mo after ICI start are not well characterized. Further, clinical trials often have limited follow-up of AEs and thus, real world data is valuable. Methods: Patients (pts) ≥18 years with advanced melanoma who received ≥1 cycle of an ICI at BC Cancer from 2012-2019 with ≥12 mo of follow-up from time of ICI initiation were identified using the BC Cancer Registry and Pharmacy databases. Data on baseline clinicopathologic factors prior to the first cycle of ICI, and delayed irAE history and management were extracted. Delayed irAEs were graded using CTCAEv5. Results: In total, 530 pts treated with ≥1 cycle of an ICI were identified of which 309 pts had ≥12 mo of follow-up. Median follow-up for alive pts was 65.3 mo (13.0-143.5 mo). 96 (31%), 147 (48%), 19 (6%), and 47 (15%) pts received combination ICI (nivolumab/ipilimumab ± nivolumab maintenance), PD-1 inhibitor monotherapy (nivolumab or pembrolizumab), CTLA-4 inhibitor monotherapy (ipilimumab), and sequential CTLA-4 and PD-1 inhibitors, respectively. A total of 142 delayed irAEs were recorded in 94 (30%) pts. Median time to onset of delayed irAEs was 20.0 mo (12.2-80.6 mo). The most common delayed irAEs were dermatologic (27%), gastrointestinal (23%), and rheumatologic (20%). Most delayed irAEs were grade ≤2 (84%), but some were grade ≥3 (16%). Of individual delayed irAEs, 75 (51%) occurred on ICI treatment at time of onset, 39 (26%) after ≤3 mo of the last ICI cycle, and 34 (23%) after &gt;3 mo of the last ICI cycle. 79 (56%) and 20 (14%) delayed irAEs were treated with systemic steroids and immunomodulators, respectively. Further, 12 (8%) delayed irAEs led to hospitalization, and 64 (45%) required subspecialty consultation. Pts with a history of autoimmune disease were more likely to have a delayed irAE (p=0.02), as were pts who achieved a partial or complete response (p=0.02). There was a trend towards a greater frequency of delayed irAEs in pts treated with PD-1 (37%) compared with combination (28%), CTLA-4 (11%), or sequential CTLA-4 and PD-1 (28%) (p=0.068). Conclusions: Delayed irAEs occurred in almost a third of pts with advanced melanoma treated with ICIs and followed for at least 1 year. Extended follow-up to monitor for delayed irAEs should be considered as many events required immunosuppressive therapy and rarely, may be life threatening. [Table: see text]
Cross-sectional and longitudinal associations between PG-SGA criteria with survival of cancer patients.
Authors: Yu Min, Tingting Dai, Xuemei Li, Lei Cai, Jitao Zhou, Xingchen Peng
Journal: Journal of Clinical Oncology (2024)

e23277 Background: Malnutrition is prevalent in cancer patients and is associated with treatment efficacy and clinical outcomes. Whether the available malnutrition assessment tools contain optimal survival prediction value for cancer patients, especially from developing countries, remains unclear. Methods: In this retrospective cohort study, cancer patients were selected from our center between Nov 2019 and Sep 2023. According to the PG-SGA criteria, PG-SGA scores &lt; 4 referred to well-nourished, ≥ 4 PG-SGA scores &lt; 9 referred to malnutrition, and ≥ 9 referred to severe malnutrition. Kaplan-Meier (KM) curves were used to estimate the survival patterns of cancer patients with varied levels of PG-SGA scores. The Cox proportional hazard model was used to evaluate the association between baseline and longitudinal changes of PG-SGA scores with the all-cause mortality of cancer patients. Subgroup analysis with interaction tests was used to determine the high-risk subgroups. A series of sensitive analyses were performed to validate the findings we determined. Results: There were 1,415 cancer patients included in our study, with a mean age of 46 years old. The mean PG-SGA score was 2.42 in non-malnourished patients, 10.10 in malnourished patients, and 12.65 in severely malnourished patients, respectively. The KM curves showed that cancer patients with severe malnourished status (PG-SGA ≥9) presented the lowest short- and long-term survival probability, compared with the other two subgroups. A linear trend was observed between the PG-SGA scores and cancer mortality (p for overall test &lt; 0.001). The Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients [≥4 PG-SGA &lt; 9: hazard ratio (HR): 1.46, 95% confidence interval (CI): 1.09 – 1.96, p = 0.012; PG-SGA ≥9: HR = 1.78, 95%CI: 1.34 – 2.37, p &lt; 0.001]. Cancer patients with longitudinal increased PG-SGA scores ( &gt; 2 points) were observed to have a high risk for mortality (HR = 1.69, 95%CI: 1.04 – 2.74, p = 0.033). Compared with longitudinal changes in PG-SGA scores, the baseline PG-SGA scores showed significantly higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586, p &lt; 0.001). PG-SGA scores showed more pronounced predicting value among subgroups with features of younger age, normal and underweight body mass index, late cancer stage, without history of diabetes, smoking, radiotherapy, and immunotherapy. A series of sensitive analyses determined consistent correlations. . Conclusions: Our study validates the clinical value of baseline, as well as longitudinal changes of PG-SGA, scored status for predicting the survival of cancer patients. Our findings provide new insights into the identification and prevention strategies for malnourished conditions in cancer patients, resulting in improved cancer-related nursing in resource-limited regions.
Characterizing the transformation and diagnosis of atypical lipomatous tumors to dedifferentiated liposarcoma: Single-institutional outcomes.
Authors: Austin Yu, Lesly Honore, Anne Patricia Timmermann, Matthew Demetrious, Steven Gitelis, Ira Miller, Alan T. Blank
Journal: Journal of Clinical Oncology (2024)

e23560 Background: Atypical lipomatous tumor (ALT) is a locally aggressive, benign adipocytic tissue mass with risk of transformation into dedifferentiated liposarcoma (DDLS), a mixed-grade, non-lipogenic tumor with increased risk for metastasis and mortality. Studies have evaluated the dedifferentiation rate of DDLS but seldom report the methodology of obtaining their diagnosis, which is crucial due to their heterogeneous architecture and relatively low core needle biopsy (CNB) accuracy. We included a longitudinal cohort of ALT/DDLS patients characterizing how and when patients received their diagnoses. Methods: 168 patients diagnosed with ALT-only (n = 129), DDLS-only (n = 22), or both (n = 17) were included. Among DDLS patients, the presence of a prior ALT diagnosis along with time between their ALT and DDLS diagnosis was measured. Histology, location, results, and methods of each diagnosis were recorded including, CNB, surgical resection, or both. Disease-specific survival (DSS) and recurrence free-survival (RFS) were calculated with univariate/multivariate analysis for risk factors. Results: Among patients who received a diagnosis with CNB consistent with ALT, 7 were subsequently diagnosed with DDLS after surgical resection, representing 4.8% of ALT patients. Mean time between diagnoses was 2.3 months (STD 2.0). 5 (3.4%) patients were diagnosed with a DDLS recurrence after initial ALT diagnosis confirmed with CNB and surgical resection. Median time between diagnoses was 37.0 months (IQR 16.0, 63.0). 5 (3.4%) had tumors with a heterogeneous composition on initial surgical resection, described as an ALT with dedifferentiated components. 22 DDLS patients had no prior ALT diagnosis. 9 were diagnosed from both CNB and surgical resection, and 13 were diagnosed from surgical resection directly after clinical suspicion and imaging concerning for sarcoma. DSS in the DDLS was significantly lower than ALT-only DSS (p &lt; 0.0001). There was no significant difference in RFS. Conclusions: DDLS may arise after an extended period of time after ALT resection or simultaneously with an ALT diagnosis. Due to its varied diagnostic timeline and appearance, caution is advised when evaluating and treating ALT. [Table: see text]