bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trabectedin and radiotherapy in soft-tissue sarcoma (TRASTS) study: An international, prospective, phase II trial in localized myxoid liposarcoma—A collaborative Spanish (GEIS), Italian (ISG) and French (FSG) group study.
Authors: Gronchi Alessandro , Hindi Nadia , Blay Jean-Yves , Redondo Andres , Sanfilippo Roberta , Morosi Carlo , Cruz Jurado Josefina , Luna Fra Pablo , Martinez-Trufero Javier , Valverde Morales Claudia Maria , Romero Jesus , Peinado Javier , Sangalli Claudia , Sunyach Marie Pierre , Romagosa Cleofe , Ranchère-Vince Dominique , Gutierrez Antonio , De Tos Paolo , Martin Broto Javier 
Published: May 2020

11514 Background: Myxoid liposarcoma (ML) exhibits especial sensitivity to trabectedin (T). In prospective series, T showed responses in 44% of patients (pts) with ML. ML is also sensitive to radiation therapy (RT) and preclinical data suggested radiosensitizing properties of T. Preoperative short-course of T with concurrent low-dose RT was conducted in a multicenter, European, phase I/II trial. We present here the data from the phase II part in pts with centralized diagnosis of locally advanced, resectable ML. Methods: Pts received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8Gy/fraction). The phase I part of the study had the classic 3+3 design. Dose Levels for T were: -1 (1.1 mg/m2), 1 (1.3 mg/m2) and 2 (1.5 mg/m2) Results were already reported (EClincalMedicine 2019;9:35-43) and the dose selected for the phase 2 part was 1.5 mg/m2. RECIST responses were evaluated preoperatively at week 10. Surgical specimens were processed for histologic changes and residual tumor. Results: From July 2016 to September 2019, 47 pts (M/F 31/16) with median age 43y (18-77) and median tumor size 11 cm (3-25 cm), 20 low and 24 high grade (3 not available) were enrolled in the phase II part of the study. The major grade 3/4 toxicities were neutropenia (21.3%), ALT (14.9%), GGT (8.5%) and AST (8.5%) elevation. There were no deaths due to toxicity. 43/47 patients received the planned 3 pre-operative T cycles. All pts completed RT. 1 patient started RT before the first cycle of T and was excluded from the analysis. All pts were evaluable for response: 14 achieved PR (30%), 32 SD (70%). All pts underwent surgery (37 [86%] R0/ 5 [12%] R1/ 1 [2%] R2/ 3 not available). Median viable residual tumor was 10% (0-90) with 23/43 pts (53%) with ≤ 10% viable remaining tumor. Of them 6/43 (14%) had complete responses. At a median FU of 18 months (3-41) one pt developed local recurrence and 2 distant metastases. No deaths were observed. The corresponding 2-yr disease-free survival and overall survival were 97% (95% confidence interval 95-100) and 100%. Conclusions: T in combination with RT was feasible and well tolerated in the preoperative setting. The activity of the combination compares favorably with the administration of T/RT alone. This regimen could potentially become an alternative to anthracycline+ifosfamide concurrent to RT in high risk localized ML. Clinical trial information: NCT02275286 .
A phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (CKS).
Authors: Zer Alona , Icht Oded , Joseph Lilach , Avram Dana , Jacobi Oded , Fenig Eyal , Kurman Noga , Peretz Idit , Shamai Sivan , Merimsky Ofer , Ben-Ami Eitan , Shapira Roni , Schwarzbach Anna Ewa , Bernstine Hanna , Weitzen Rony , Vornicova Olga , Bar-Sela Gil , Stemmer Salomon M. , Lotem Michal 
Published: May 2020

11518 Background: CKS is a mesenchymal neoplasm associated with HHV8 infection. Though recombinant INFa is approved for treatment of AIDS-related KS, data is limited regarding the role of immune modulation in CKS therapy. Based on favorable responses in viral-induced cancers, we hypothesized that CTLA-4 and PD-1 blockade can induce tumor regression in CKS. We present pre-planned interim analysis of a phase II study of Nivo/Ipi in previously treated progressive CKS. Methods: CKS pts with progressive disease after > 1 line of systemic therapy and measurable disease received nivolumab 240mg d1,15,28 and ipilimumab 1mg/kg d1 q42 days until progression or toxicity. The primary endpoint was overall response rate (ORR) evaluated clinically, radiologically (RECIST) and metabolically (FDG-PET). Secondary endpoints include 6-months progression free survival rate (PFS) and safety. Exploratory endpoints included PD-L1/MMR by IHC, DNAseq (596 genes)/RNAseq (whole transcriptome) of tumor and matched blood specimens to explore CKS genomic traits and IO correlates: TMB and MSI status, MMR and PD-L1 protein expression, and immune gene transcript expression (PD-1, PD-L1, CTLA-4, and others) (Tempus Labs, Chicago, IL, USA). Results: Fifteen patients were enrolled and evaluable (Apr18-Jan20). Median age 72.5 (61-81), all male. At a median FU of 15.7 mo ORR as per RECIST was 66% (9 pts PR, 1 pt CR, 2 pts SD, 3 pts NE). Clinical ORR was 87% and metabolic ORR was 60%. Median PFS was not reached, 6mo PFS rate was 85% and 1y PFS rate was 75%. The safety profile was as expected with all pts experiencing G1 toxicity, 3 pts with G2 toxicity (1 hepatic, 2 asymptomatic lipase increase) and 2 pts with G3 toxicity (1 colitis, 1 asymptomatic lipase increase). One SAE was reported (TIA considered not related to therapy) and treatment was discontinued in 3 pts. Correlative results are available for 8 pts showing a trend for copy number loss in genes with tumor-suppressive activity (FOXA1, ELF3), no PDL1 expression, low TMB, microsatellite stability, but marked overexpression of CTLA-4, PD-1, PDL-1, CD40, OX40 and LAG3 RNA immune transcripts. Conclusions: The interim analysis of this prospective phase II study of nivolumab and low-dose ipilimumab demonstrates promising activity in progressive CKS, with 66% ORR and a 6mo PFS rate of 85%. Toxicity profile is as expected in this class of drugs. Correlative studies are preliminary, but warrant further investigation into genomic traits and immune gene expression profiles. Clinical trial information: NCT03219671. Clinical trial information: NCT03219671 .
A phase II study of anlotinib in treating patients with relapsed or metastatic primary malignant bone tumor.
Authors: Tang Lina , Niu Xiaohui , Wang Zhen , Cai Qiqing , Tu Chongqi , Fan Zhengfu , Yao Yang 
Published: May 2020

11525 Background: Primary malignant bone tumors are rare forms of cancer and include mainly bone sarcomas, which are categorized into 3 common types based on tissue origin: osteosarcoma, chondrosarcoma and Ewing sarcoma. A phase II trial was designed to explore the anlotinib activity in patients with relapsed or metastatic primary malignant bone tumor. Methods: Eligible pts were received 12mg of anlotinib once daily, 2 weeks on and 1 week off until progression or unacceptable toxicity. Key-eligibility criteria were aged 14-70 years, histologically confirmed diagnosis of osteosarcoma, chondrosarcoma, bone derived malignant fibrous histiocytoma, giant cell tumor, Ewing sarcoma and PNET, confirmed previous chemotherapy failure, ECOG 0-1(0-2 for amputation pts), required at least one measurable lesion. We observed PFS, OS, ORR, DCR and AE in this study. Results: From August 2018 to April 2019, 42 pts were included. Of 42 efficacy-evaluable pts, 25 were man, median age was 28 (14-68) years. There were 29 pts of osteosarcoma, 9 pts of chondrosarcoma, 3pts of Ewing sarcoma and 1 pt of bone derived malignant fibrous histiocytoma. The progression-free rate at 12 weeks (PFR12weeks), ORR and DCR were 71.3%, 9.52% and 78.57%. Median PFS was 5.26 months (95%CI = 3.48-8.44). Median OS was 11.40 months (95%CI = 10.09, [ ). Median PFS of osteosarcoma and chondrosarcoma was 4.83 months (95%CI = 3.48, 7.13 ) and 2.76 months (95%CI = 1.31, [ ) respectively. The most common Gr 3-5 anlotinib-related AEs were hypertension (19.05%), hypertriglyceridemia (9.52%), hand-foot syndrome (7.14%), and proteinuria (4.76%). Conclusions: The phase II study shows a promising activity of anlotinib in patients with relapsed or metastatic primary malignant bone tumor and an acceptable toxicity. Clinical trial information: NCT03527888 .
Maximum tumor dimension and tumor volume as prognostic factors in patients with newly diagnosed localized Ewing sarcoma (ES)- a report from the Children’s Oncology Group (COG).
Authors: Mascarenhas Leo , Buxton Allen , DuBois Steven G. , Wang Dian , Laack Nadia N. , Brown Kenneth L.B. , Pawel Bruce , Nadel Helen Ruth , Davis Justin , Hawkins Douglas S. , Grier Holcombe E. , Womer Richard B. , Stringham Del , Reed Damon R. , Janeway Katherine A. , Gorlick Richard Greg , Marina Neyssa , Bernstein Mark L. , Krailo Mark D. , Leavey Patrick ,   Bone Sarcoma Committee, Children's Oncology Group
Published: May 2020

11529 Background: Maximum tumor dimension > 8 cm. and large tumor volume have been reported to be adverse prognostic factors in patients with ES but have not been prospectively evaluated in the context of a phase 3 clinical trial with interval compressed chemotherapy. Methods: COG AEWS1031 (NCT01231906) was a randomized phase 3 clinical trial comparing interval compressed chemotherapy regimens in patients with newly diagnosed localized ES of bone and soft tissue. A correlative objective of AEWS1031 was to evaluate tumor size and volume as prognostic factors. Institution-reported dimensions of the primary tumor from baseline imaging were prospectively collected. For inclusion in this analysis, patients had to have at least 1 tumor dimension reported for tumor size analyses and dimensions in 3 axes for tumor volume analyses. Maximum dimension was dichotomized as less than vs. > / = 8cm. Tumor volume was dichotomized as less than vs. > / = 200 mL. Event-free (EFS) and overall survival (OS) from enrollment were calculated using Kaplan-Meier methods and compared between groups using a two-sided log-rank test. Hazard ratios (HR) and confidence intervals (CI) were calculated using the Cox model. Results: The 5-year EFS and OS of the 629 eligible patients was 78% (95% CI: 75-81%) and 87% (95% CI: 84-90%) respectively and there was no significant difference in both EFS and OS between the randomized interval compressed chemotherapy arms of AEWS1031. 590 of 629 (94%) patients were evaluable for maximum tumor dimension and 307 (52%) had tumors > / = 8 cm. Patients with tumors > / = 8 cm were at significantly increased risk for EFS events (p = 0.016) with estimated 5-year EFS of 73.7% (95% CI: 68.1 vs.78.4%) vs. 82.9% (95% CI 77.7-87.1%) for patients with tumors < 8 cm [HR: 1.53 (1.08-2.17)]. For tumor volume, 586 of 629 patients (93%) were evaluable and 180 (31%) had tumors > / = 200 mL. Patients with tumor volume > / = 200 mL were at significantly increased risk for EFS events (p = 0.003) with estimated 5-year EFS of 70% (95% CI: 62.3-76.4%) vs. 81.6% (95% CI: 77.2-85.2%) for patients with tumors < 200 mL [HR: 1.69 (1.2-2.39)]. Conclusions: Maximum tumor dimension and tumor volume as defined are both prognostic in patients with newly diagnosed localized ES treated with interval compressed chemotherapy. Clinical trial information: NCT01231906 .
Quality of life (QoL) and self-reported function with ripretinib in ≥4th-line therapy for patients with gastrointestinal stromal tumors (GIST): Analyses from INVICTUS.
Authors: Heinrich Michael C. , George Suzanne , Zalcberg John Raymond , Bauer Sebastian , Gelderblom Hans , Schoffski Patrick , Serrano Cesar , Jones Robin L. , Attia Steven , D'Amato Gina Z. , Chi Ping , Reichardt Peter , Becker Claus C. , Meade Julie Nicole , Ruiz-Soto Rodrigo , von Mehren Margaret , Blay Jean-Yves 
Published: May 2020

11535 Background: Ripretinib is a novel switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits KIT and PDGFRA kinase signaling through a dual mechanism of action. In INVICTUS (NCT03353753), a randomized, double-blind, placebo-controlled trial of ripretinib in ≥4th-line advanced GIST, ripretinib reduced the risk of disease progression or death by 85% vs placebo and had a favorable overall safety profile in patients previously treated with ≥3 prior TKIs. Methods: As part of the INVICTUS trial, patient reported outcome (PRO) measures were collected using EQ-5D-5L (EQ5D) and EORTC QLQ-C30 (C30). In prespecified and additional analyses, ANCOVA models were built to compare changes from baseline to cycle 2 day 1 (C2D1) for PRO measures within the ripretinib and placebo arms and determine the difference between treatment arms. PRO measures included the EQ5D visual analogue scale (VAS) and the C30 physical functioning (PF) and role functioning (RF) scales (all scores range from 0–100; higher scores are better). The C30 overall health and overall QoL questions were also assessed (scores range from 1–7; higher scores are better). Fixed effects included treatment arm, number of previous anticancer treatments (3 vs ≥4), and ECOG score at baseline (0 vs 1/2). Results: Overall, 129 patients were randomized and 128 received treatment (85 to ripretinib 150 mg QD; 43 to placebo). All PRO p-values are nominal, and no statistical significance is being claimed. VAS scores improved an average 3.7 points from baseline to C2D1 with ripretinib vs an average decline of 8.9 with placebo (P = 0.004; improvement or no change, 67% vs 41% of patients, respectively). Similarly, the average PF score improved 1.6 points with ripretinib and decreased 8.9 with placebo (P = 0.004; improvement or no change, 68% vs 44%). RF scores also improved an average of 3.5 points with ripretinib vs a decrease of 17.1 with placebo (P = 0.001; improvement or no change, 77% vs 50%). For the overall health and overall QoL questions, scores increased with ripretinib an average of 0.20 and 0.28, respectively, and decreased 0.78 and 0.76 with placebo (both P = 0.001; improvement or no change, 74% vs 47% and 79% vs 59%, respectively). Conclusions: Based on the 5 PRO measures assessed, when compared with placebo and best supportive care, ripretinib provided patient-benefit in advanced GIST with PRO measures of role and physical function, VAS, overall health, and overall QoL remaining stable. Clinical trial information: NCT03353753 .
A randomized trial of a palliative care intervention for patients on phase I studies.
Authors: Smith Thomas J. , Chung Vincent , Hughes Mark T. , Koczywas Marianna , Azad Nilofer Saba , Knight Louise , Cooper Rhonda , Ruel Nora , Ferrell Betty R. 
Published: May 2020

12001 Background: The purpose of this study was to test a Palliative Care Intervention for patients with solid tumors enrolled in phase I therapeutic trials. Methods: This randomized trial compared patients accrued to phase I Clinical Trials in groups of Usual Care compared to a Palliative Care Intervention (PCI) in two comprehensive cancer centers. The PCI included assessment of quality of life (QOL) and symptoms, an interdisciplinary meeting to discuss the care plan, including goals of care, and two nurse-delivered teaching sessions. Subjects (n=479) were followed for 24 weeks, with 12 weeks as the primary outcome point. Results: Outcomes revealed that relative to Usual Care, PCI subjects showed less Psychological Distress (1.9 in Intervention and 1.2 in Control pts, p=0.03) and a trend toward improved QOL (3.7 versus 1.6, p=0.07), with differences between sites. We observed high rates of symptom-management admissions (41.3%) and low rates of Advance Directive completion (39%), and use of supportive care services including hospice (30.7%, for only1.2 months duration), despite a median survival for all patients in both groups of 10.1 months from initiating a phase 1 study until death. Patient satisfaction with oncology care was already high at baseline, and we did not see clinically significant changes in those scores by week 12. Conclusions: Palliative care interventions can improve QOL outcomes and distress for patients participating in phase 1 trials. Greater integration of PC is needed to provide quality care to these patients and to support transitions from treatment to supportive care, especially at the end of life. Clinical trial information: NCT01828775 .
A geriatric assessment (GA) intervention to reduce treatment toxicity in older patients with advanced cancer: A University of Rochester Cancer Center NCI community oncology research program cluster randomized clinical trial (CRCT).
Authors: Mohile Supriya Gupta , Mohamed Mostafa Refaat , Culakova Eva , Xu Huiwen , Loh Kah Poh , Magnuson Allison , Flannery Marie Anne , Ramsdale Erika E. , Dunne Richard Francis , Gilmore Nikesha , Obrecht Spencer , Patil Amita , Plumb Sandy , Lowenstein Lisa M , Janelsins Michelle Christine , Mustian Karen Michelle , Hopkins Judith O. , Berenberg Jeffrey L. , Gaur Rakesh , Dale William 
Published: May 2020

12009 Background: GA evaluates aging-related domains (e.g., function) known to be associated with cancer treatment toxicity. In this CRCT, we evaluated if providing a GA summary with management recommendations to oncologists can reduce toxicity in older patients (pts) with advanced cancer receiving chemotherapy and/or other agents with a high reported prevalence of grade 3-5 toxicity. Methods: Pts aged > 70 with incurable solid tumors or lymphoma and > 1 impaired GA domain starting a new treatment regimen were enrolled. Community oncology practices were randomized to intervention (oncologists received GA summary/recommendations for impairments) or usual care (none given). The primary outcome was proportion of pts who experienced any grade 3-5 toxicity (CTCAE v.4) within 3 months. Practice staff prospectively captured toxicities; blinded oncology clinicians reviewed medical records to verify. Secondary outcomes included 6 month overall survival (OS) and treatment intensity (standard vs reduced). Outcomes were analyzed using generalized linear mixed/Cox models with Arm as a fixed effect, controlling for practice. Results: From 2013-19, 718 pts were enrolled from 41 practices. Age (mean 77 yrs), sex (43% women), number of impaired GA domains (median 4/8), and treatment type (chemotherapy 88%) were not different by Arm. More pts in intervention were Black (12% vs 3%, p<0.01), had GI cancer (38% vs 31%, p<0.01), and had prior chemotherapy (31% vs 23%, p=0.02). Pts in intervention experienced a lower proportion of grade 3-5 toxicity (175/349; 50%) than pts in usual care (262/369; 71%). The relative risk (RR: intervention vs usual care) of grade 3-5 toxicity was 0.74 (95% CI: 0.63-0.87; p=0.0002); the difference was mostly driven by non-heme toxicities (RR 0.73; 95% CI: 0.53-1.0, p<0.05). OS was not significantly different (71% vs 74%, p=0.3). More pts in intervention received reduced intensity treatment at cycle 1 (49% vs 35%, RR 0.81, p=0.01). Dose modifications due to toxicity were lower in intervention (42% vs 58%, p<0.0001), but results were not significant after controlling for practice (RR 0.85; 95% CI: 0.67-1.08, p=0.2). Conclusions: Providing GA information to oncologists reduces the proportion of older pts who experience grade 3-5 toxicity from high-risk palliative cancer treatment, without compromising OS. Reduced treatment intensity at cycle 1 may explain these results. Funding: R01CA177592, U01CA233167, UG1CA189961. Clinical trial information: NCT02054741 .
Impact of baseline symptom burden as assessed by patient-reported outcomes (PROs) on overall survival (OS) of patients with metastatic cancer.
Authors: Batra Atul , Cuthbert Colleen Ann , Harper Andrew , Yang Lin , Boyne Devon J. , Rigo Rodrigo , Cheung Winson Y. 
Published: May 2020

12020 Background: Patients with metastatic cancer experience variable symptom burden, but serial symptom assessments using PROs may be challenging to implement in routine clinical practices. We aimed to determine if a single measurement of symptom burden at the time of metastatic diagnosis is associated with survival. Methods: We examined prospectively collected baseline PROs of patients newly diagnosed with metastatic breast, lung, colorectal, or prostate cancer using the revised Edmonton Symptom Assessment System (ESASr) questionnaire from a large province (Alberta, Canada) between 2016 and 2019. The ESASr was categorized into physical (PH), psychosocial (PS), and total symptom (TS) domains whereby scores were classified as mild (0-3), moderate (4-6), or severe (7-10). Multivariable Cox proportional hazards models were constructed to evaluate the effect of baseline symptom scores on OS. Results: We identified 1,315 patients, of whom 57% were men and median age was 66 (IQR, 27-93) years. There were 180, 601, 240, and 294 patients with breast, lung, colorectal, and prostate cancer, respectively. Approximately one-quarter of all patients reported moderate to severe PH, PS, and TS scores, with lung cancer patients experiencing the highest symptom intensity across all domains ( P<0.0001). While age did not affect symptom scores, women were more likely to report severe PH, PS, and TS scores as compared to men ( P=0.02, 0.002, and 0.007, respectively). On multivariable Cox regression analysis, older age (HR 1.02, 95% CI, 1.02-1.03, P<0.0001) and female sex (HR 1.67, 95% CI, 1.39-1.99, P<0.0001) were predictive of worse OS as were severe baseline PH and TS scores (see Table) . However, baseline PS scores were not related to OS. Conclusions: A single assessment of baseline symptom burden using the ESASr in patients with metastatic cancer has significant prognostic value. This may represent a feasible first step toward routine collection of PROs in real-world settings where serial symptom measurements can be challenging to implement. [Table: see text]