bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic role of MRP1 in localized high-risk soft tissue sarcoma (STS): Translational research associated to randomized phase III trial (ISG-STS 1001).
Authors: Martin Broto Javier , Moura David Silva , Ramos Rafael , Braglia Luca , Collini Paola , Renne Salvatore L , Romagosa Cleofe , Coindre Jean Michel , Velasco Valerie , Merlo Domenico F , Palmerini Emanuela , Stacchiotti Silvia , Quagliuolo Vittorio , Lopez-Pousa Antonio , Grignani Giovanni , Blay Jean-Yves , Brunello Antonella , Picci Piero , Casali Paolo Giovanni , Gronchi Alessandro 
Published: May 2020

11543 Background: The ceiling-drug effect seen for most active drugs in STS could be related, partially, to multidrug resistance mechanisms (MDRM). We previously reported the independent prognostic role for RFS and OS of MRP1 in high-risk localized STS of limbs and trunk-wall treated with epirubicin and ifosfamide (Mol Cancer Ther.2014 13(1):249-59). A translational study was carried out within the randomized phase III trial of epirubicin plus ifosfamide vs histotype-tailored neoadjuvant chemotherapy (NCT01710176), to investigate MRP1 prognostic value using the trial population as validation set. Methods: Patients enrolled in the trial were invited to participate, through the informed consent, to this analysis. IHC used QCRL-1 (Santa Cruz biotechnology) MRP1 monoclonal antibody. TMAs were built on the highest-grade area of each tumor, being the procedure blinded for clinical data. MRP1 expression was grouped as low (≤ 25% positive cells) vs high ( > 25% positive cells) expression. For data analysis, patients were grouped as A) epirubicin plus ifosfamide control arm and B) histotype-tailored experimental arm. Drugs used in group B were: gemcitabine-docetaxel (UPS), gemcitabine-DTIC (LMS), trabectedin (High-grade (HG) myxoid LPS), ifosfamide-etoposide (MPNST) and high-dose ifosfamide (SS). Prognostic value of MRP1’s extension was analyzed using Cox’s proportional hazard regression. A p-value < 0.05 was considered statistically significant. Results: 175 patients were analyzed (median age 49; males 61%) with median follow-up of 4.66 y. Group A (n = 88) included HG-myxoid LPS (27%), SS (25%), UPS (24%), LMS (12%) MPNST (10%) and others (2%); group B (n = 87) included UPS (38%), SS (24%), HG-myxoid LPS (20%), LMS (10%) and MPNST (8%). MRP1 high extension was distributed as follows: 48% (A) and 57% (B). High MRP-1 expression showed significantly worse prognosis for disease-free survival (DFS) (HR 2.71 (1.31-5.62) p = 0.007) and a trend towards worse OS (HR = 2.75 (0.97-7.81) p = 0.058) in group A. No correlation was seen between MRP-1 expression and DFS (p = 0.384) or OS (p = 0.665), in group B. Conclusions: MRP1 overexpression was related to significant worse prognosis in 2 prospective randomized series of high-risk, localized, STS treated with neoadjuvant epirubicin and ifosfamide. These agents are both substrate of MRP1; this could add rationale for a possible predictive role, as MDRM, for the two most active drugs in STS. A trial combining epirubicin, ifosfamide and MRP1 inhibitor is currently under design.
SAR-096: A phase II trial of ribociclib in combination with everolimus in advanced dedifferentiated liposarcoma (DDL), and leiomyosarcoma (LMS).
Authors: Movva Sujana , von Mehren Margaret , Handorf Elizabeth A. , Morgan Jeffrey A. , Nathenson Michael , Thornton Katherine Anne , Tetzlaff Eric Daniel , Barker Emma , Thibodeau Linda , Harley Allisa Cherae , King April , Veggeberg Rosanna , Leshner Juliet A. , Rink Lori , George Suzanne 
Published: May 2020

11544 Background: Inhibition of CDK4 is being studied in a variety of sarcomas, especially dedifferentiated liposarcoma (DDL) where prolonged progression free survival has been noted. Exposure to CDK4 inhibitors in Rb+ leiomyosarcoma (LMS) cell lines leads to decreased cell proliferation, and increased senescence, and G0/G1-phase arrest. When combined, ribociclib a CDK4 inhibitor and everolimus, an mTOR inhibitor show synergistic growth inhibition in multiple tumor models. Methods: Patients (pts) were enrolled to one of two cohorts: DDL or Rb+ LMS. LMS pts were required to have 1 prior line of therapy; DDL pts required no prior therapy. There were no limits to prior therapies in either group. Progression on prior therapy and measurable disease by RECIST 1.1 was also required. Ribociclib was given at 300 mg daily for 21/28 days and everolimus was given continuously at 2.5 mg daily in 28 day cycles. The primary endpoint was progression free rate at 16 weeks. A Simon two-stage design was utilized and if at least 8 out of 24 pts were progression free at 16 weeks, the treatment was declared promising for the cohort. Here in we present data on the LMS cohort. Results: Twenty-four LMS pts, 83% (n = 20) female, 58% (n = 14) uterine primary were treated. Median prior lines of therapy was 3.5 (range 1-9). Of 22 pts with complete data, 6 (27.2%) met the primary endpoint of non-progression at 16 weeks. Median PFS was 19.6 weeks (range 2.8-84), with progression as best response occurring in 13 pts. There were no objective responses. Five pts who had progressive disease on multiple lines of therapy experienced prolonged progression free survival (23-84 weeks). Grade 3-4, toxicities included neutropenia (29%), thrombocytopenia (12.5%) and leucopenia (12.5%) being most common. Tissue samples pre and on therapy as well as blood were collected in 21 and 18 pts respectively to evaluate pharmacodynamic changes. Conclusions: Final data on the primary endpoint for the LMS cohort is pending; it is notable that several heavily pre-treated LMS pts experienced prolonged progression free survival for > 9 months. Updated results and biology correlatives will be presented. Clinical trial information: NCT03114527 .
A phase I trial of pomalidomide in combination with liposomal doxorubicin in patients with Kaposi sarcoma with or without other KSHV-associated diseases.
Authors: Ramaswami Ramya , Lurain Kathryn Anne , Widell Anaida , Goncalves Priscila Hermont , Ekwede Irene , Figg William Douglas , Peer Cody J. , Mangusan Ralph , George Jomy , Steinberg Seth M. , Khetani Vikram , Whitby Denise , Uldrick Thomas S. , Yarchoan Robert 
Published: May 2020

11552 Background: Kaposi sarcoma herpesvirus (KSHV, also known as human herpesvirus 8 [HHV-8]), is the causative agent of Kaposi sarcoma (KS), a multicentric angioproliferative tumor, a form of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). KS can be difficult to treat when it occurs with KSHV-MCD or KICS; resulting in high mortality rates. Liposomal doxorubicin (LD) is an FDA-approved treatment for KS. Pomalidomide, an oral immunomodulatory drug, is safe and has demonstrated activity in KS, but the activity of the combination (pomalidomide+LD) in KS alone or with KSHV-associated diseases is unknown. Methods: The primary objective was to evaluate safety and tolerability of pomalidomide+LD in two groups of patients with KS requiring systemic therapy: Group I (GI)- KS alone; Group II (GII)- KS with concurrent KSHV-MCD or KICS. Patients received LD at 20 mg/m2 intravenously on day 1 of a 28-day cycle combined with pomalidomide once daily on days 1 to 21 at escalating dose levels (DL) (I - 2mg, II - 3mg, or III- 4mg) in a 3+3 design until plateau of response or other pre-specified criteria. Patients received 81mg of aspirin daily as thromboprophylaxis. KS responses were evaluated using the modified AIDS Clinical Trial Group criteria. Results: Thirty-four cisgender men, all with T1-stage KS [21 patients (62%) in GI and 13 patients (38%) in GII] were treated; 32 (94%) were HIV-infected and 22 (65%) had prior chemotherapy for KS (15/21 GI and 7/13 GII). There were no dose-limiting toxicities (DLTs) at DLIII for GI, and additional patients were treated at DLIII. In GII, grade 3 rash and pharyngeal edema were DLTs observed at 3mg of pomalidomide. Overall a median of 6 cycles were administered; the most common grade 3/4 toxicity was neutropenia. Among evaluable patients receiving >2 cycles,17/21 patients in GI had a response (all partial) (81% [95% confidence interval (CI) 58-95%]) and 5/10 patients in GII had a response (4 partial and 1 complete) (50% [95% CI 19-81%]). Conclusions: Pomalidomide+LD was well-tolerated and active in heavily pretreated patients with KS alone. In patients with KS and other KSHV-associated diseases, activity was noted but less well-tolerated. Clinical trial information: NCT02659930 .
Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): Report of LMS cohort.
Authors: Nathenson Michael , Choy Edwin , Carr Neena D , Hibbard Hayley D , Mazzola Emanuele , Catalano Paul J. , Thornton Katherine Anne , Morgan Jeffrey A. , Cote Gregory Michael , Merriam Priscilla , Wagner Andrew J. , Demetri George D. , George Suzanne 
Published: May 2020

11559 Background: Responses to single agent PD-1/PD-L1 inhibitors in STS remain limited with occasional responses in undifferentiated pleomorphic sarcomas (UPS), liposarcomas (LPS), and other sarcomas, and rare responses in leiomyosarcoma (LMS). Since cytotoxics and/or targeted therapies such as CDK4/6 inhibitors may alter the tumor microenvironment (TME) and potentiate the effect of immunotherapy, combination approaches may be needed to potentiate STS immunotherapy. The mechanism by which eribulin controls LPS may involve TME modification, and therefore it is attractive to test in combination with pembrolizumab in STS subtypes. This report summarizes the results from the LMS cohort from this ongoing trial. Methods: Pts treated with at least one prior therapy received eribulin 1.4mg/m2 (day 1, 8) and pembrolizumab 200mg (day 1), every 21 days. Pts continued therapy until progressive disease, death, or unacceptable toxicity. Primary endpoint was progression-free survival (PFS) at 12 weeks, with 60% PFS at 12 weeks required to deem the combination promising. Tumor assessments (RECIST 1.1) were performed at screening and every 6 weeks thereafter. Secondary endpoints included overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Results: Nineteen pts with LMS were enrolled from May 2019 to Sept 2019. The median age was 62 (range 48-80). Eleven (58%) patients had uterine LMS. The median # of prior therapies was 4 (range 1-7). The median follow-up was 19.7 weeks. The PFS at 12 weeks was 42.1% (90% CI: 27.0%-65.5%), with median PFS of 11.1 weeks. Median OS was not reached during the follow-up period. There was 1 partial response, and 5 confirmed stable disease for ORR of 5.3% and CBR of 26.3%, after 12 weeks. The rate of grade 3 or higher toxicity was 68% overall, most commonly neutropenia, anemia, weight loss, diarrhea, elevations of lipase, and alkaline phosphatase. These side effects were reversible. The most common adverse events were fatigue, neutropenia, anorexia, AST increase, and nausea. Conclusions: Eribulin and pembrolizumab in LMS did not meet the predefined endpoint for efficacy. The LPS and “other STS subtype” cohorts of this trial are actively enrolling. Clinical trial information: NCT03899805 .
Cost-utility analysis of surveillance strategies for soft tissue sarcoma recurrence.
Authors: Chau Bonny , Zimmermann Marita , Wagner Michael , Cranmer Lee D. 
Published: May 2020

11565 Background: Soft tissue sarcomas (STS) are uncommon malignancies with significant biological and clinical variation. After primary curative therapy, patients enter a program of surveillance for recurrence with periodic chest x-rays (CXR) or computed tomography (CT). We compared costs and health outcomes of CXR and CT at a range of frequencies and durations of follow-up. Methods: We used a Markov model to simulate a cohort of 10,000 STS patients through their surveillance experience for lung metastasis after completion of definitive treatment for stage II or III primary disease. Health states in the model were no evidence of disease, recurrence, and death. We assessed the method of chest imaging, duration of follow-up, and interval (every 3 months or 6 months) of surveillance in the first 3 years. Cost effectiveness was assessed for each screening modality and screening frequency. Recurrence probabilities, utilities, treatment costs, and other parameters were from previously published data. Outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER). Results: The initial evaluation comparing screening every 3 months for 3 years, every 6 months for years 4 and 5, and annually from years 6 to 10 resulted in 632,264 QALYs and $1,038,351,481 costs for CT, compared to 631,834 QALYs and $746,019,937 for CXR, resulting in an ICER of $679,322/QALY. In comparing screening intervals, less frequent screening intervals of every 6 months compared to every 3 months for the first three years using CT resulted in an ICER of $690,527/QALY and for CXR, the ICER was $271,423/QALY. In comparing screening duration between 6 years and 10 years of follow-up, strategies with longer follow-up resulted in slightly higher QALYs in each of the comparison scenarios, at a much higher cost. Conclusions: In our evaluation, more frequent screening the first 3 years and longer duration of surveillance resulted in higher QALYs in both screening modalities. However, in the comparisons the ICERs exceed common willingness to pay thresholds of $150,000/QALY gained; CXR is the more cost-effective imaging modality. Limitation of this model includes the simplification of disease progression and heterogeneity in STS.
Multisite randomized trial of integrated palliative and oncology care for patients with acute myeloid leukemia (AML).
Authors: El-Jawahri Areej , LeBlanc Thomas William , Kavanaugh Alison , Webb Jason , Jackson Vicki A. , Campbell Toby Christopher , O'Connor Nina , Luger Selina M. , Gafford Ellin , Gustin Jillian , Bhatnagar Bhavana , Fathi Amir Tahmasb , Hobbs Gabriela , Foster Julia , Nicholson Showly , Davis Debra M. , Addis Hilena , Vaughn Dagny , Horick Nora K. , Temel Jennifer 
Published: May 2020

12000 Background: Patients with AML receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). We sought to examine the effect of integrated palliative and oncology care on QOL, mood, post-traumatic stress (PTSD) symptoms, and EOL outcomes in patients with AML. Methods: We conducted a multi-site randomized trial of integrated palliative and oncology care (n = 86) versus usual oncology care (n = 74) for patients with AML undergoing intensive chemotherapy. Patients assigned to the intervention were seen by palliative care clinicians at least twice per week during their hospitalization for induction chemotherapy and all subsequent hospitalizations. Patients completed the Functional Assessment of Cancer Therapy-Leukemia, the Hospital Anxiety and Depression Scale, and the PTSD Checklist to assess their QOL, mood, and PTSD symptoms at baseline, weeks 2, 4, 12, and 24. The primary endpoint was QOL at week-2. We used analysis of covariance and mixed linear effect models, controlling for baseline scores, to assess the effect of the intervention on patient-reported outcomes. Results: Between 1/2017 and 7/2019, we enrolled 160/235 (68.1%) of eligible patients. Compared to those receiving usual care, intervention patients reported better QOL (107.59 vs. 116.45, P = 0.039) and lower depression (7.20 vs. 5.68, P = 0.021), anxiety (5.94 vs. 4.53, P = 0.018), and PTSD symptoms (31.69 vs. 27.79, P = 0.009) at week 2. Intervention effects were sustained up to week 24 for QOL (B = 2.35, P = 0.048), depression (B = -0.42, P = 0.039), anxiety (B = -0.38, P = 0.042), and PTSD symptoms (B = -1.43, P = 0.002). Among deceased participants, those receiving the intervention were more likely to report discussing their EOL care preferences with their clinicians (75.0% vs. 40.0%, P = 0.009) and less likely to receive chemotherapy in the last 30 days of life (34.9% vs. 65.9%, P = 0.008). There was no difference in hospice utilization or hospitalization at the EOL. Conclusions: The integrated palliative and oncology care model for patients with AML receiving intensive chemotherapy led to substantial improvements in patients’ QOL, psychological distress, and EOL care. Thus, palliative care should be considered a new standard of care for patients with AML. Clinical trial information: NCT02975869 .
Effects of YOCAS yoga, cognitive behavioral therapy, and survivorship health education on insomnia: A URCC NCORP Research Base Phase III RCT in 740 cancer survivors.
Authors: Mustian Karen Michelle , Lin Po-Ju , Culakova Eva , Bautista Javier , Xu Huiwen , Mohile Supriya Gupta , Janelsins Michelle Christine , Peppone Luke Joseph , Kleckner Amber , Kleckner Ian , Loh Kah Poh , Dunne Richard Francis , Gilmore Nikesha , Conlin Alison Katherine , Gococo Kim Ong , Jaslowski Anthony John 
Published: May 2020

12005 Background: Insomnia, a prevalent and troublesome side effect experienced by cancer survivors, significantly impairs recovery and survival. We conducted a nationwide, multicenter, phase III, blinded, randomized controlled trial testing whether 1) yoga is superior to survivorship health education (SHE) and 2) yoga is non-inferior to cognitive behavioral therapy for insomnia (CBT-I) for treating insomnia in survivors. Methods: The trial was conducted via the University of Rochester Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base. Participants were cancer survivors between 2-60 months post adjuvant therapy, with insomnia, no metastatic disease, and no yoga participation during the previous 3 months. Survivors were randomized into 1) YOCAS yoga (2x/wk; 75 min/sess for 4 wks with pranayama, asana, and dhyana, N = 251), 2) CBT-I (1x/wk, 90 min/sess for 8 wks with sleep hygiene, stimulus control, sleep restriction, and cognitive therapy, N = 238), or 3) SHE (2x/wk; 75 min/sess for 4 wks with ASCO-recommended survivorship education, N = 251). Insomnia was assessed pre- and post-intervention via the Insomnia Severity Index. Results: 740 eligible cancer survivors were enrolled (93% female, mean age = 56 + 11, 75% breast cancer). ANCOVAs with baseline values as covariates revealed YOCAS is significantly better than SHE for treating insomnia at post-intervention (CS = change score; CS mean diff = -1.43, SE = 0.42, p < 0.01). Yoga participants demonstrated greater improvements in insomnia from pre- to post-intervention (CS = -3.61, SE = 0.30) compared to SHE participants (CS = -2.19, SE = 0.33, all p < 0.01). Intent-to-treat analyses of non-inferiority (non-inferiority margin set at 1.15 a priori) showed YOCAS is inferior to CBT-I (CS mean diff = 3.52, CI = 2.55 - 4.50, p < 0.01). However, analyses of non-inferiority using the optimal treatment effect in fully compliant survivors were inconclusive regarding whether YOCAS is non-inferior to CBT-I for treating insomnia (CS mean diff = 2.20, CI = 0.42 - 3.98, p = 0.09). Significantly more survivors withdrew from CBT-I and SHE due, in part, to disliking the interventions compared to YOCAS (30%, 25%, and 16%, respectively, p < 0.01). Conclusions: YOCAS yoga is better than SHE and results are inconclusive as to whether yoga is non-inferior to CBT-I for treating insomnia among survivors. Clinicians should consider prescribing YOCAS and CBT-I for survivors reporting insomnia. Funding: NCI UG1CA189961, R01CA181064, T32CA102618. Clinical trial information: NCT02613364 .
Results of crossover phase II component of randomized placebo-controlled trial evaluating oral THC/cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV).
Authors: Grimison Peter S. , Stockler Martin R. , Kirby Adrienne , Walsh Anna , Lintzeris Nicholas , Cheung Yvonne , Mersiades Antony , Tognela Annette , Haber Paul , Simes John , Morton Rachael L. , Olver Ian N. , McGregor Iain , Gedye Craig , Fox Peter , Briscoe Karen P. , Aghmesheh Morteza , Abdi Ehtesham A. , Clarke Stephen John , Della-Fiorentina Stephen 
Published: May 2020

12008 Background: The aim of this multi-centre, randomised, double-blinded, placebo-controlled, phase 2/3 trial is to determine efficacy of addition of oral cannabis in adults with any malignancy of any stage, experiencing CINV during moderate-highly emetogenic intravenous chemotherapy, despite guideline-consistent anti-emetic prophylaxis, requiring ≥ 2 chemotherapy cycles. Here we report the crossover phase 2 component results. Methods: Treatment consisted of 1 cycle of oral THC 2.5mg/CBD 2.5mg (TN-TC11M) capsules tds days -1 to 5 and 1 cycle matching placebo in a crossover design, then blinded patient preference for a 3rd cycle. Primary end-point is difference in proportion of patients with ‘complete response’ (no emesis & no use of rescue medications) during 0-120 hours from chemotherapy between cycles. 80 patients provides 80% power with 2p of 0.1 to detect a 20% difference. Results: 81 patients recruited (2016-9). 72 completing 2 cycles are included in efficacy analyses. 78 not withdrawing consent are included in safety analyses. Median age was 55 years (range 29-80), 78% were female, 42% report historic cannabis use, 55% were treated with curative intent. Most common regimens were AC (26%), FOLFOX (17%). All received steroids & 5-HT3 antagonist, 79% received NK-1 antagonist, 4% received olanzapine. Efficacy is shown in table. 83% preferred cannabis to placebo. Most common bothersome cannabinoid-related adverse events (cannabis, placebo) were sedation (19%,4%), dizziness (10%,1%), disorientation (3%,0%). No SAEs were attributed to THC/CBD. Conclusions: Addition of oral THC/CBD to standard anti-emetics was associated with less nausea & vomiting but additional side effects. Most preferred THC/CBD to placebo. Based on these positive results, the definitive parallel phase 3 trial component continues (additional n=170). Acknowledgements: Trial participants, investigators, research staff. Funding from NSW Government Dept of Health. Clinical trial information: ACTRN12616001036404 . [Table: see text]