bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune signature and molecular profiling of radiation-induced sarcoma (RIS).
Authors: Malone Eoghan Ruadh , Anderson Nathaniel , Lewin Jeremy Howard , O'Sullivan Brian , Dickson Brendan , Shlien Adam , Abdul Razak Albiruni Ryan 
Published: March 2020

11040 Background: RIS is a rare subset of soft tissue sarcoma (STS) with poor prognosis and limited treatment options. We hypothesize that subsets of STS that carry genomic complexity, such as RIS, will have a neoepitope and immune signature that predicts response to immunotherapy as these mutations act as strong antigenic targets for eliciting immune response. Methods: Cases of RIS were identified from an institutional database. Formalin fixed paraffin embedded (FFPE) samples were stained for PD-1, PD-L1, CD3, CD4, CD8. Immune scoring was performed. Tumor-infiltrating lymphocytes (TILs) were assessed using a 4-tiered scale: 0 (no lymphocytes); 1 (1-10/HPF); 2 (11-50/HPF), 3 (51-100/HPF); 4 ( > 100/HPF). TIL staining with PD-1 and PD-L1 was also scored whereby the overall percentage of positive cells on the entire slide was quantified. Tumor DNA was extracted from FFPE samples and underwent whole exome sequencing (WES). Results: FFPE samples from 20 cases of RIS were selected for analysis. PD-1 and PD-L1 expression (threshold set at ≥ 1% positive cells) was seen in 35% and 45% of the cases respectively. CD3+, CD4+, CD8+ T cell infiltration (threshold set ≥ 11 cells /HPF) was seen in 45%, 15% and 20% of cases respectively. 12 exomes of unpaired RIS samples were successfully sequenced. The most common histologies were angiosarcoma (n = 3), undifferentiated spindle cell sarcoma (n = 3), de-differentiated liposarcoma (n = 2) and radiation induced spindle cell sarcoma (n = 2). Provisional analysis did not reveal any pattern to the relative mutational burden between the RIS’s. There does however seem to be relatively higher rate of mutation than that seen in other cancer subtypes. Half the samples had at least one pathogenic or likely pathogenic variant. Different HRAS mutations were seen in two samples (sarcoma NOS and angiosarcoma) and FGFR4 mutation was present in two samples, both spindle cell sarcomas. Conclusions: To our knowledge this is the first study to investigate the immune profile in RIS. Up to 45% of these tumors were positive for PD1/PDL1 expression, as well as presence of tumour infiltrating lymphocytes. Results from WES demonstrate that RIS may benefit from immunotherapy due to a relatively higher mutational burden.
Improved local relapse-free and overall survival with secondary surgery after a first R1 or R2 resection in soft tissue sarcoma (STS) of the limbs or trunk wall: An analysis 10,931 patients (pts) in NETSARC.
Authors: Gouin Francois , Stoeckle Eberhard , Bonvalot Sylvie , Honoré Charles , Decanter Gauthier , Anract Philippe , Bompas Emmanuelle , Ferron Gwenael , Sirveaux Francois , Rochwerger Richard , Carrere Sebastien , DiMarco Antonio , Ropars Mikael , Le Nail Loic-Romée , Marco Oren , Guiramand Jerome , Italiano Antoine , Le Cesne Axel , Penel Nicolas , Blay Jean-Yves ,   French Sarcoma Group - Group Etude Tumeur Osseuses FSG-GETO
Published: March 2020

11056 Background: We previously reported that secondary resection (2Surg) improved local relapse free (LRFS) but not overall survival (OS) in a retrospective series of pts with localized STS after unplanned 1st excision. Here we investigated the impact of 2Surg specifically after a first R1 or R2 resection in the 10931 pts with STS of the limb or trunk wall included in the nationwide NETSARC database from 2010 to 2017. Methods: NETSARC (netsarc.org) is a network of 26 reference sarcoma centers with specialized multidisciplinary tumor boards (MDT), funded by the French NCI (INCa). Since 2010, presentation to an MDTB and second pathological review are mandatory for sarcoma pts. Statistics were performed with SPSS23.0. LRFS, metastasis-free survival (MFS), OS compared with the logrank test. Results: The series included 5598 (51.2%) males. Median age was 56.7. Tumor sites: 5295 (49.4%) lower limb, 3670 (33.6%) trunk wall. 1966 (18.0%) upper limb. As previously reported in the entire series, local RFS (LRFS) and RFS (p<0.001), but not OS, were superior for pts presented to a NETSARC MDT (NMDT), or operated in a NETSARC center (N=4417, 41%). LRFS & OS were best for pts presented to a NMDT AND operated in NETSARC centers; while the worst LRFS & OS were observed in pts presented in a NMDT but not operated there (p<0.001). Among the 2081 pts with a first R1 resection in whom 2Surg was documented, 1047 (50.3%) were reoperated. R1 reoperated pts had a superior LRFS, metastatic free survival (MFS) and OS (p<0.001). LRFS (p<0.001), MFS (p=0.05) and OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. There were 823 pts with a first surgery with R2 resection in whom 2Surg was documented: 619 (75.2%) were reoperated. R2 reoperated patients had a superior LRFS and OS (p=0.01). MFS was not different. LRFS (p<0.001) & OS (p<0.001) were superior after 2Surg only in pts operated 1st outside a Netsarc center. 2028 (%) pts had 2Surg. Pts for whom 2Surg was in a NetSARC center had a superior LRFS (p<0.001) and OS (p=0.01) when operated first outside a NETSARC center. Conclusions: In this nationwide series of limb or trunk wall STS, 2Surg after a R1 or R2 primary excision improves LRFS & OS when the pts were operated 1st outside a reference center. 2Surg in a NETSARC center was associated with a better LRFS and OS.
A phase I/II investigation of nivolumab and ABI-009 (nab-sirolimus) in advanced undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), chondrosarcoma (CS), osteosarcoma (OS), and Ewing sarcoma: Preliminary efficacy and safety results.
Authors: Gordon Erlinda Maria , Chua-Alcala Victoria S. , Kim Katherine , Baby Rekha , Angel Nicole , Quon Doris , Wong Steven , Chawla Sant P. 
Published: March 2020

11057 Background: Immune checkpoint inhibitors that promote sustained T cell activation may have synergistic activity with an mTOR inhibitor. This phase 1/2 study is aimed to investigate if ABI-009 a novel albumin-bound mTOR inhibitor is feasible and improve clinical outcomes in combination with nivolumab. Methods: Eligible patients with advanced UPS, LPS, CS, OS, or Ewing sarcoma are treated with the standard dose of nivolumab (240 mg given IV every 3 weeks, Day 1 of every 21-day Cycle). ABI-009 will be given IV on Days 8 and 15 of each cycle starting on Cycle 2 following the 2nd nivolumab dose. Phase 1 portion is a dose-finding study using the 3+3 design. The starting dose of ABI-009 is 56 mg/m2, and sequentially escalating doses are 75 and 100 mg/m2. The primary endpoint is to identify the maximum-tolerated dose (MTD) of ABI-009 + nivolumab, secondary endpoints include disease control rate, progression-free survival (PFS), and overall survival (OS). Exploratory endpoints include correlation of PFS and OS with PD-L1 and other biomarkers. The Phase 2 part of study will enroll 31 additional patients to further assess efficacy and safety at the MTD. Results: 9 patients were treated in Phase 1 (n = 3 each dose level); 5/9 patients had OS, 3/9 CS, and 1 had Ewing sarcoma. No dose-limiting toxicities (DLTs) were observed, the MTD was not reached, and 100 mg/m2 ABI-009 was designated as the recommended phase 2 dose. Safety analysis: At Dose 1: Grade 3 treatment-related adverse events (TRAEs) included hyper dyslipidemia (n = 1), and hyperglycemia (n = 1). At Dose 2: Grade 3 TRAEs included increased ALT (n = 1). At Dose 3: Grade 3 TRAEs included hypophosphatemia (n = 1). Seven of 9 patients have discontinued treatment: 5 patients due to PD, 2 with SD opted to stop treatment due to drug-related Grade 2 AEs (pruritus, acneiform rash, and 2 with SD are still on therapy at Dose 3. The median PFS at dose level 3 has not yet been reached. Conclusions: The MTD was not reached and Dose 3 (100 mg/m2) has been designated as the phase 2 dose of ABI- 009, combinable with nivolumab. Enrollment to phase 2 is ongoing. Clinical trial information: NCT03190174.
Activity of hormonal treatment in uterine smooth muscle tumors of uncertain malignant potential (STUMP): A mono-institutional referral center experience in advanced disease.
Authors: Sanfilippo Roberta , Sbaraglia Marta , Fumagalli Elena , Baldi Giacomo Giulio , Fucà Giovanni , Morosi Carlo , Barisella Marta , Dei Tos Angelo Paolo , Casali Paolo Giovanni 
Published: March 2020

11066 Background: STUMP ecompass a group of uterine mesenchymal neoplasms in which the clinical behavior cannot be predicted on morphological grounds. A malignant clinical evolution is seen in approximately 10-20% of cases. When STUMP relapse, the label of “low-grade leiomyosarcoma” is sometimes found to be appropriate, though current histopathological criteria for uterine leiomyosarcoma (so called “Stanford criteria”) would exclude even the existence of low-grade uterine smooth muscle neoplasms. As they express ER and PR, hormonal treatment with GnRH inhibitors or aromatase inhibitors (AIs) may represent a therapeutic option. Methods: From October 2015, we have been treating with hormonal therapy relapsing patients with an initial diagnosis of STUMP, whose pathological aspect on retrospect was consistent with a “low-grade uterine leiomyosarcoma”. We identified 8 patients. Pathological diagnosis was centrally reviewed by expert sarcoma pathologists. Results: Eight pts were treated: 7 in first line; 1 pt in 4th line, following failure of chemotherapy (gemcitabine and taxotere, adriamycin and dacarbazine, trabectedin). Two premenopauseal pts were treated with GnRH inhibitors, 2 with a combination of GnRh inhibitors and an aromatase inhibitor, 3 with aromatase inhibitors only and 1 with selective progesterone-receptor modulator. 7 patients are evaluable for response and all of them had a partial response as best response. Median progression-free survival was 31 months. Conclusions: In our series, all patients with a centrally reviewed diagnosis retrospectively consistent with a “low grade uterine leiomyosarcoma” responded to hormonal treatment. Therefore, these pts may make up a subgroup with therapeutic and prognostic relevance. “Stanford criteria” need to be re-assessed, in an effort to improve prognostic and therapeutic stratification of uterine smooth muscle neoplasms, possibly shrinking the scope of currently defined STUMP.
Osteonecrosis of the jaw in patients with cancer receiving zoledronic acid for bone metastases: SWOG S0702, NCT00874211.
Authors: Van Poznak Catherine H. , Unger Joseph M. , Darke Amy K. , Moinpour Carol , Bagramian Robert A. , Schubert Mark M. , Hansen Lisa Kathryn , Floyd Justin D. , Dakhil Shaker R. , Lew Danika L. , Wade James Lloyd , Fisch Michael Jordan , Henry Norah Lynn , Hershman Dawn L. , Gralow Julie 
Published: March 2020

11502 Background: Osteonecrosis of the jaw (ONJ) may occur in cancer patients (pts) with metastatic bone disease (MBD) treated with bone modifying agents. No large prospective studies have precisely determined the incidence of ONJ. A better understanding of the true incidence and predictors of ONJ is needed. Methods: SWOG S0702 was a prospective observational study that assessed the cumulative incidence (CI) of ONJ at 3 years in pts with MBD from any malignancy receiving zoledronic acid (Zol). Participants must have had either limited or no prior exposure to bone modifying agents and a clinical care plan that included use of Zol within 30 days of registration. Cancer treatments, bone modifying agents (including Zol), and dental care were administered as clinically indicated and were not directed by S0702. Baseline and every 6 m followup dental exams were recommended. Report forms (medical, dental and pt reported outcomes) were submitted every 6 m but if ONJ was diagnosed, follow up interval became every 3 m. Protocol defined ONJ required exposed bone in the maxillofacial region present 8 weeks or more in a pt who was receiving or had been exposed to a bisphosphonate, and had not had radiation therapy to the craniofacial region. Results: The study enrolled 3,491 evaluable pts (breast 1,120; myeloma 580; prostate 702, lung 666, other 423) between 2009-2013. About 2/3 of pts had a baseline dental exam. Overall, 87 pts had confirmed ONJ. The cumulative incidence of ONJ was 0.8% at year 1 (95% CI: 0.5%-1.1%), 2.0% at year 2 (95% CI: 1.5%-2.5%), and 2.8% at year 3 (95% CI: 2.3-3.5%). Rates of 3-year confirmed ONJ were highest in myeloma pts (4.3%; 95% CI, 2.8%-6.4%). Pts with planned Zol dosing intervals of every 3-4 weeks (n = 3,032, 87.2%) were much more likely to experience ONJ than pts with planned dosing intervals of 5 weeks or greater (n = 447, 12.8%; 3.2% vs 0.7%; HR = 4.80, 95% CI, 1.52-15.18, p = .008). Fewer total number of teeth, the presence of dentures and any oral surgery at baseline were all associated with a higher rate of ONJ. Conclusions: About 1 in 40 patients receiving Zol for MBD developed ONJ. S0702 provides information to guide stratification of risk for developing ONJ in pts with MBD receiving Zol. Cancer type, oral health and frequency of Zol dosing affect risk of ONJ. Clinical trial information: NCT00874211.
Olanzapine (OLN) versus aprepitant (APR) in patients receiving high-emetogenic chemotherapy: Final results of randomized phase II trial.
Authors: Rumyantsev Alexey , Glazkova Elena , Nasyrova Rukhshona , Ignatova Ekaterina , Chitia Lia , Popova Anna , Chekini Dzhennet , Kochetkova Yaroslava , Kit Sergei , Elsnukaeva Kheda , Menshikova Sophia , Sekhina Olga , Pokataev Ilya , Tyulyandina Alexandra , Stenina Marina , Frolova Mona A. , Bulanov Anatoly , Fedyanin Mikhail , Tryakin Alexey , Tjulandin Sergei 
Published: March 2020

11504 Background: Management of chemotherapy-induced nausea and vomiting (CINV) remains challenging. OLN might provide several benefits over APR which is current standard of care – particularly in terms of nausea control and cost effectiveness. However, sedation associated with recommended doses of olanzapine precludes its wide use in oncology practice. Methods: This was randomized phase II single center study aimed to compare OLN and APR in CINV prophylaxis. Key inclusion criteria were: chemo- and radio-therapy naïve patients, planned administration of high-emetogenic chemotherapy (cisplatin, carboplatin AUC≥4, doxorubicin etc). Patients were randomized 1:1 ratio in the following arms: olanzapine 5 QD day 0-4 or aprepitant 125 mg day 1, 80 mg day 2,3. All patients received ondansetron 16 mg day 1 and dexamethasone 8 mg day 1-3. Primary endpoint was complete nausea control (no nausea and no rescue medication) 0-120 hours after chemotherapy. Complete response (no emesis and no rescue medication) was a key secondary end point. Nausea was assessed using MASCC Antiemesis Tool. Sample size: 94 patients to increase nausea control rate from 40 to 70% (α = 0.05; β = 0.80; 10% of estimated data loss). Results: We included in the analysis 93 patients who could be evaluated. The groups were well balanced, median age was 49 years, vast majority of patients (95.6%) were females. The proportion of patients with complete nausea control in OLN and APR groups was 44.2% and 24.0% respectively (RR 2.5; 95% CI 1.04-6.08; p = 0.039). Complete response was achieved in 74.4% and 54.0% patients respectively (RR 2.48; 95% CI 1.026-5.99; p = 0.041). No differences in rates of undesired sedations were detected. Conclusions: Our data suggests superiority of OLN regimen in terms of nausea control. This regimen deserves further investigation. Clinical trial information: NCT03478605.
Safety of pregnancy following breast cancer (BC) in patients (pts) carrying a BRCA mutation (mBRCA): Results of an international cohort study.
Authors: Lambertini Matteo , Ameye Lieveke , Hamy Anne-Sophie , Zingarello Anna , Poorvu Philip Daniel , Carrasco Estela , Grinshpun Albert , Han Sileny , Rousset-Jablonski Christine , Ferrari Alberta , Paluch-Shimon Shani , Cortesi Laura , Senechal Claire , Miolo Gianmaria , Pogoda Katarzyna , Perez-Fidalgo Jose Alejandro , De Marchis Laura , Del Mastro Lucia , Peccatori Fedro , Azim Hatem A. 
Published: March 2020

11506 Background: Very limited data are available on the safety of pregnancy and reproductive outcomes in mBRCA pts with prior BC history. We report the results of the largest study to date addressing these questions. Methods: This international, multicenter, hospital-based, retrospective cohort study included consecutive pts with invasive early BC (stage I-III) diagnosed between Jan-2000 and Dec-2012 at the age of ≤40 years and carrying a deleterious germline mBRCA. Primary endpoints were pregnancy rate and disease-free survival (DFS); overall survival (OS) and pregnancy outcomes were secondary endpoints. To account for guarantee-time bias, we performed two survival analyses: 1) Case-control approach matching pregnant and non-pregnant (1:3) pts for classic prognostic factors (each non-pregnant control had a disease-free interval ≥ than the time elapsing between BC diagnosis and date of pregnancy of the matched pregnant case); 2) Extended Cox model with time-varying covariates including all pts. Results: 1,252 mBRCA BC pts (811 mBRCA1, 430 mBRCA2, 11 mBRCA1&2) were included from 30 centers worldwide, of whom 195 pts had a pregnancy (pregnancy rate = 16% [95% CI 14-18]) after a median 4.5 years (range 3.1-6.7 years) following BC diagnosis. Pregnant pts were younger and had more ER-negative tumors (all p < 0.01). 16 (8.2%) and 20 (10.3%) pts had an induced and spontaneous abortion, respectively. Among the 150 (76.9%) pts who conceived (n = 170 babies), pregnancy complications and congenital anomalies were described in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up was 8.3 years (range 8.1-8.7 years). In the case-control analysis, pregnant pts had better DFS (HR 0.71; 95% CI 0.51-0.99; p = 0.045), with no difference in OS (HR 0.86; 95% CI 0.44-1.67; p = 0.65). Subgroup analysis suggested that the superior outcome was restricted to mBRCA1 pregnant pts (p-interaction < 0.01). Similar results were obtained in the second supportive analysis. Conclusions: Pregnancy following BC is safe in mBRCA pts, particularly mBRCA1, with no detrimental impact on maternal prognosis or fetal outcomes . These findings are of paramount importance for fertility counseling in young mBRCA BC pts.
Cognitive rehabilitation program to improve cognition of cancer patients treated with chemotherapy: A randomized controlled multicenter trial.
Authors: Dos Santos Mélanie , Rigal Olivier , Léger Isabelle , Licaj Idlir , Dauchy Sarah , Levy Christelle , Noal Sabine , Segura Carine , Delcambre Corinne , Allouache Djelila , Parzy Aurélie , Lange Marie , Capel Aurélie , Grellard Jean-Michel , Clarisse Bénédicte , Lefel Johan , Joly Florence 
Published: March 2020

11521 Background: Cognitive impairment induced by cancer chemotherapy (CT) has been identified as an important side-effect with negative impact on quality of life (QoL) without specific treatment. We evaluated the impact of computer-assisted cognitive rehabilitation (CR) on cognitive complaint, objective cognitive dysfunction and QoL among cancer patients treated with CT. Methods: We included cancer patients with cognitive complaint occurring during CT or within 5 years of the end of CT. Patients were randomly assigned in a 1:1:1 ratio to face-to-face CR with a neuropsychologist (group A), home cognitive exercises (group B) or phone follow-up (group C) with 9 sessions over 3 months. Cognition was assessed by the Functional Assessment of Cancer Therapy Cognitive Function (FACT-Cog) completed by a neuropsychological battery of test and QoL assessment by the FACT-General (FACT-G). The primary endpoint was the proportion of patients with 7-point improvement in the perceived cognitive impairments (PCI) of the FACT-Cog between baseline (T0) and the end of the program (T3). Results: 167 patients were enrolled, median age was 50 years [43-59] and 96% were women with mainly breast cancer. Compliance rate with completion of all sessions was 76, 61 and 75% respectively. Proportion of patients with 7-point PCI improvement were 73, 55 and 56% without reaching the statistically significant difference between group A and B (p = 0.07) and group A and C (p = 0.08). The mean difference in PCI score were 17, 10 and 10 (p = 0.03). Patients with CR improved their working memory with significant difference between group A and C (1.4 versus 0.3, p < 0.001) but not between group A and B (1.4 versus 1.1, p = 0.43). There was a significant impact of CR on the FACT-Cog subscale score of QoL (p = 0.01) in favor of the group A, but not on the different dimensions of the FACT-G. Patients in group A presented improvement in depression compared to group B and C: -6.5 versus -1.7 and -2.3 (p = 0.03). Conclusions: CR with a neuropsychologist improves cognitive complaint. Cognitive stimulation showed improvements in working memory. CR was associated with better QoL linked to cognitive disorders and lower levels of depression. Clinical trial information: NCT01788618.
Prognostic understanding in hematologic malignancies: A multicenter longitudinal study.
Authors: Loh Kah Poh , LeBlanc Thomas William , Lee Stephanie , Back Anthony , Duberstein Paul , Mohile Supriya Gupta , Epstein Ronald M. , El-Jawahri Areej 
Published: March 2020

11524 Background: Accurate prognostic understanding facilitates the receipt of goal-concordant medical care. Few studies have evaluated prognostic understanding in patients with hematologic malignancies. In this secondary analysis of a multicenter, longitudinal study of patients with hematologic malignancies referred for a second opinion hematology subspecialty consultation, we assessed changes in prognostic understanding after consultation, and predictors of post-consultation patient-oncologist prognostic discordance. Methods: Patients were recruited from 4 academic centers. Before and 1-7 days after consultation, patients were asked about their perceived chance of cure (options < 10%, 10-19%, and up to 90-100% in 10% increments, and “do not wish to answer”). Oncologists were asked the same question after consultation. Discordance was defined as a difference in response by 2 levels in the patient-oncologist dyads. We used multivariate analysis to assess the demographic and clinical predictors of patient-oncologist discordance. Results: We included 216 patients (median age 55 years, range 22-79) and 46 oncologists (47, 30-70). Overall, ≥On multivariate analysis, discordance before consultation [Odds Ratio (OR) 6.05, 95% Confidence Interval (CI) 2.96-12.36) and < college education (vs. post-graduate education; OR 2.34, 95% CI 1.09-5.14) were associated with discordance after consultation. Other patient demographics, comorbidity, cancer type, psychological distress, social support, decision-making preference, and coping strategies were not associated with discordance. Conclusions: Patient-oncologist concordance in prognostic understanding improved after subspecialty consultation, but over half of patients’ views of their prognosis remained discordant with those of their oncologists. Interventions to improve patient-oncologist communication about prognosis are needed, especially in patients with lower education level.