bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase (Ph) 1b/2 evaluation of olaratumab in combination with gemcitabine and docetaxel in advanced soft tissue sarcoma (STS).
Authors: Attia Steven , Villalobos Victor Manuel , Hindi Nadia , Van Tine Brian Andrew , Wagner Andrew J. , Chmielowski Bartosz , Levy Donna Elise , Ceccarelli Matteo , Jones Robin Lewis , Dickson Mark Andrew 
Published: June 2021

11517 Background: Doxorubicin (doxo) remains standard first-line therapy for advanced STS. Doxo in combination with olaratumab (O) demonstrated superior clinical activity compared to doxo alone in a Ph 2 trial (NCT01185964), although this was not confirmed in the subsequent Ph 3 trial (NCT02451943). Gemcitabine (G) plus docetaxel (D) is a second line therapy for advanced STS. Here, we report a concurrent Ph 2 study that explored a second-line addition of O to G and D for advanced STS (ANNOUNCE 2 NCT02659020). Methods: Adult patients (pts) with unresectable locally advanced or metastatic STS, ≤ 2 prior lines of systemic therapy, and ECOG PS 0-1 were eligible. Pts were enrolled from 2 cohorts: O-naïve and O-pretreated. In both cohorts, pts were randomized 1:1 to either O, G plus D or placebo (PBO), G plus D. Pts received 21-day cycles of O (20 mg/ kg cycle 1 and 15 mg/kg other cycles, day (d) 1 and d8), G (900 mg/m2, d1 and d8) and D (75 mg/m2, d8). Pts continued treatment until progression, toxicity, or withdrawal. Randomization was stratified by histology (leiomyosarcoma [LMS] vs non-LMS), prior systemic therapy, ECOG PS, and prior pelvic radiation. The primary objective was overall survival (OS) in the O-naïve population using an alpha level of 0.20. Secondary endpoints included OS (O-pretreated) and other efficacy parameters, as well as safety and pharmacokinetics (PK). Results: 167 pts were enrolled in the O-naïve cohort and 89 pts in the O-pretreated cohort. Baseline patient characteristics were well balanced. OS for O-naïve pts was 16.8 vs 18.0 months (m) (hazard ratio [HR] = 0.95, 95% CI: 0.64-1.40; p = 0.78) for the investigational vs control arm, respectively. Other efficacy outcomes are presented in the table. Safety was manageable across treatment arms. PK parameter estimates for O were consistent with previous studies. Conclusions: There was no statistically significant difference in OS between the two arms in the O-naïve population. However, while not statistically significant, the combination of O, G and D demonstrated favorable OS in the O-pretreated cohort, and PFS and objective response rate (ORR) in both cohorts. For O-naïve pts, a clinically meaningful progression-free survival (PFS) improvement was observed. Further investigations in specific histological subtypes are ongoing. Clinical trial information: NCT02659020. [Table: see text]
ABCB1/P-glycoprotein (Pgp) expression as stratification factor for treatment of patients with non-metastaticextremity high-grade osteosarcoma: A merged analysis of an Italian (ISG) and a Spanish (GEIS) sarcoma groups' multicentric prospective trials.
Authors: Palmerini Emanuela , Marquez Catalina , Meazza Cristina , Tamburini Angela , Bisogno Gianni , Sirvent Francisco José Bautista , Ferraresi Virginia , Asaftei Sebastian Dorin , Milano Giuseppe Maria , Luksch Roberto , Canete Adela , Echebarria Aizpea , Quintero Víctor , Mata Cristina , Bertulli Rossella , Longhi Alessandra , Picci Piero , Fagioli Franca , Hindi Nadia , Ferrari Stefano 
Published: June 2021

11527 Background: Overexpression of ABCB1/P-glycoprotein (Pgp) predicts poor outcome in retrospective osteosarcoma series.Two prospective trials with Pgp expression and post-induction histologic response as stratification factors were activated in Italy (ISG/OS-2) and Spain (GEIS-33). Methods: Patients ≤ 40 years with extremity non-metastatic high-grade osteosarcoma were eligible. Analysisi of Pgp expression from diagnostic biopsy was centralized. Preoperatively, all patients received methotrexate, adriamycin, cisplatinum (MAP). Surgery was performed at week 8. All patients received a dose of adriamycin following surgery. In case of Pgp overexpression (Pgp+), mifamurtide (2 mg/m2 twice/week for 3 months then weekly for 6 months) was added after surgery, with 4 consecutive cycles of ifosfamide 3 gr/m2/day, day 1-5 (HDIFO) in case of poor histologic response (necrosis < 90%) to MAP. Patients without overexpression of Pgp (Pgp-) received MAP postoperatively, regardless the pathological response. From March 2013, an amendment increased high dose methotrexate cumulative dose from 60 g/m2 (5 cycles) to 120 mg/m2 (10 cycles). The post-amendment regimen was adopted in the observational prospective study by GEIS. Here we present the merged analysis of ISG/OS-2 patients treated post-amendment and GEIS-33. Results: From March 2013 to April 2018, 274 patients were included. Median age was 14 years (range 4-38), male/female: 163/111; 90 were Pgp-, 164 were Pgp+, 20 not evaluable. With a median follow-up of 48 months (1.3-78.5 months), the 3-year EFS and OS were 71.9% (95%CI 66-76.9) and 88% (95%CI: 83.2-91.5) respectively, with no inferior survival for Pgp positive patients and improved survival for good responders (Table). Conclusions: In this prospective uncontrolled study with a risk-adapted strategy for non-metastatic osteosarcoma, survival is superior to that of all ISG/GEIS previous series. The 3-year EFS of 71.9% compares favorably with other reports. Pgp+ patients performed well in this study, in which mifamurtide and HDIFO were added after a poor response to MAP. Clinical trial information: NCT01459484; NCT04383288. [Table: see text]
Accumulation of genome-wide somatic loss of heterozygosity (LOH) as a prominent feature of advanced malignant soft tissue tumors and association with the BRCAness status, suppression of immune responses, and lower survival rates.
Authors: Takahashi Katsuhito , Miyaji Yasutomo , Ohkuma Ryotaro , Higuchi Hajime , Komohara Yoshihiro , Aida Shinsuke , Yashima Jun , Yamamoto Hiromasa , Suzawa Ken , Takahashi Yuko , Toyooka Shinichi , Ashimine Hiroya , Oyama Yu , Narahara Hiroyuki , Yotsumoto Junko , Ishida Hiroo , Tsunoda Takuya , Sasaki Yasutsuna , Ono Yasuo , Teraoka Satoshi 
Published: June 2021

11533 Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Recent genomic analysis revealed widespread CNA and the cumulative burden of cancer-related pathogenic germline mutations/variants, their clinical and therapeutic significance were unknown. Methods: We recruited 155 patients with advanced malignant soft tissue tumors (135 female and 20 male, mean age 51 at analysis, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) with confirmed metastasis/recurrence and information on familial cancer burden. Whole exome sequencing was performed in both blood and tumor samples as described in 2018ASCO. The copy number of BRCA2 gene was determined by the MLPA method. Tumor immune microenvironment was assessed by immunohistochemistry. The MSI status was analysed by PCR. Results: We analyzed the LOH status in 595 COSMIC genes and found that genome-wide accumulation of somatic LOH of polygenic germline mutations/variants. Patients with more than 33% LOH genes (n=102) in the total of somatic and LOH mutations showed significantly lower OS rates compared with those (n=53) with less LOH genes (5-year survival rates; 49 vs 75%, p=0.010), which constitute 78% of LMS (n=78/100) and 26% of LPS (n=5/19). Total of 41 patients (26%, n=41/155) including 33 LMS (33%, n=33/100) showed LOH in the BRCA2 locus with hemizygous VUS. Those patients with BRCA2 LOH (n=41) showed significantly lower OS rates compared with those without BRCA2 LOH (n=114) (5-year survival rates; 43 vs. 64%, p=0.019). Neither TMB nor the MSI status was associated with LOH. In contrast, accumulation of somatic LOH (mean LOH values of 71.7 vs. 15.7%) was clearly and negatively associated with CD8+T-cell immune infiltrates (T-cells; 44±23 vs 555±180/mm2, n=7, p=0.016), CD20+B-cell accumulation in tertiary lymphoid structures (TLS) (TLS; 0.57±0.43 vs. 20.1±6.1/tumor, n=7, p=0.008) and low levels of neutrophil-to-lymphocyte ratio (NLR) (NLR; 3.63±0.45 vs. 1.71±0.17, n=7, p=0.002), hallmarks of the immunological response to tumors. Conclusions: This study suggests that in advanced malignant soft tissue tumors, accumulation of genome-wide LOH of germline mutations/variants is associated with the BRCAness status and suppression of the immune responses to tumors, and thus influences therapeutic response and survival of the patients.
Durvalumab and pazopanib in patients with advanced soft tissue sarcoma: A single-center, single-arm, phase 2 trial.
Authors: Kim Hyo Song , Cho Hee Jin , Yun Kum-Hee , Lee Young Han , Kim Sung Hyun , Baek Wooyeol , Jeon Min Kyung 
Published: June 2021

11551 Background: Based on the central role played by the vascular endothelial growth factor receptor (VEGFR) in immunosuppression, we assessed the activity and safety of VEGFR inhibitor pazopanib plus anti-PD-L1 blockade durvalumab in soft tissue sarcoma (STS). Methods: We did a single-arm, single-center, phase 2 study that enrolled patients with metastatic or locally advanced STS aged 19 years or older, ECOG PS 0-1, with at least one measurable lesion, and received at least one previous line of systemic therapy. Patient were given pazopanib 800 mg orally daily and durvalumab 1500 mg intravenously for 60 min every 3 weeks. The primary endpoint was investigator-assessed objective response. Results: Between September 2019 and October 2020, 47 participants were enrolled, of whom 46 (97.9%) were evaluable for the efficacy analyses. With a median follow up of 12.3 months, complete and partial response (PR) was achieved in 1 (2.2%) and 12 (26.1%) patients, resulting in 28.3 % of objective response rate. Median time to achieve PR was 1.4 months and median duration of response was 11.0 months. The most common treatment-related adverse events of any grade include fatigue (20 [42.6%]), anorexia (17 [36.2%]), diarrhea (17 [36.2%]), and AST elevation (16, [34.0%]). Thirty-one patients (67.3%) had progressive disease, and the median progression free survival was 8.6 months (95% CI 3.6-13.6). Conclusions: Durvalumab and pazopanib showed encouraging activity in patients with advanced STS. Molecular predictors with whole exome and RNA sequencing will be presented. Clinical trial information: NCT03798106.
Retrospective world-wide registry on the efficacy of immune checkpoint inhibitors in alveolar soft part sarcoma: Updated results from sixty patients.
Authors: Hindi Nadia , Rosenbaum Evan , Jonczak Emily , Hamacher Rainer , Rutkowski Piotr , Skryd Anthony , Connolly Elizabeth , Blay Jean-Yves , Gutierrez Antonio , Bogefors Carolina , Gelderblom Hans , Boye Kjetil , Henon Clemence , Martinez-Trufero Javier , Lopez-Martin Jose A. , Redondo Andrés , Valverde Claudia , Vincenzi Bruno , Tap William D. , Martin Broto Javier 
Published: June 2021

11564 Background: Alveolar soft-part sarcoma (ASPS) is a highly metastasizing ultra-rare sarcoma subtype, frequently affecting young adults. Conventional cytotoxic drugs are not effective in ASPS, but antiangiogenics demonstrated significant improvement in tumor burden reduction and PFS in the only ever conducted comparative trial. Immune check-point (PD-1/PD-L1) inhibitors (ICI) are emerging promising drugs in the therapy of ASPS, from small reported retrospective and prospective series. A world-wide registry has been set up with the aim of exploring the efficacy of ICI in ASPS. Methods: Data from adult patients (pts) diagnosed with ASPS and treated with PD- 1/PD-L1 inhibitors for advanced disease in expert sarcoma centers from Europe, Australia and US was retrospectively collected. IRB approval was obtained. Demographics, data related to treatments and outcome were considered. Radiologic assessment was based on RECIST 1.1. Progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. An updated analysis of this series is presented here. Results: Sixty ASPS pts (27 female/33 male) with a median age at diagnosis of 25y (range 3-61) were registered. Primary tumor arose in limbs in 47 pts (78%) and 41 pts (68%) were metastatic at diagnosis. 52/60 pts (87%) had received previous systemic therapy (including chemotherapy in 19 pts and antiangiogenics in 47pts), with a median of one previous line (0-6). All pts received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 31 pts (52%) and combination in 29 pts (48%) (23 with an antiangiogenic agent). 29/60 pts (48%) received ICI within a clinical trial. Among the 52 evaluable pts, there was 1 complete response (CR) and 20 partial responses (PR) (ORR 40.4%). After a median follow-up of 21 months -mos- (range 4-59), 37/60 pts have progressed to ICI, with a median PFS of 13.4 mos (95% CI 10.1-16.7). Eleven pts received a subsequent line of ICI with a median PFS of 26 mos (95%CI 0-57). 16 pts have died, being the median OS from ICI initiation 38 mos (95% CI 33-43). The 12-mos and 24-mos OS rates were 94% and 70% respectively. Conclusions: This registry constitutes the largest available series of ASPS treated with immune check-point inhibitors. Our results suggest that treatment with ICI provide long-lasting disease control and prolonged OS in pts with advanced ASPS, an ultra-rare entity with limited active therapeutic options. The results on subsequent ICI lines suggest a lack of cross-resistance among different ICI therapies.
Assessing the risk of severe post-treatment (tx) cancer-related fatigue (CRF) among breast cancer survivors (BCS) in the CANcer TOxicity (CANTO) cohort.
Authors: Di Meglio Antonio , Havas Julie , Martin Elise , Pistilli Barbara , Menvielle Gwenn , Dumas Agnes , Charles Cecile , Everhard Sibille , Martin Anne-Laure , Coutant Charles , Tarpin Carole , Vanlemmens Laurence , Levy Christelle , Rigal Olivier , Delaloge Suzette , Ganz Patricia A. , Partridge Ann H. , Andre Fabrice , Michiels Stefan , Luis Ines Maria Vaz Duarte 
Published: June 2021

12022 Background: CRF is among the most common and troublesome symptoms experienced by BCS. While preventing severe post-tx CRF is a major survivorship need, limited tools exist to predict this risk. We aimed to describe the long-term prevalence rates and to identify BCS that are more likely to develop severe CRF. Methods: CANTO is a multicenter, prospective clinical study of stage I-III BCS (NCT01993498). Longitudinal data were collected at diagnosis (dx), 0.5 (T1), 1 (T2) and 3 (T3) years post-tx. The primary outcome of interest was severe post-tx global CRF (score ≥ 40/100, EORTC QLQ-C30). Secondary outcomes were physical, emotional and cognitive dimensions of CRF (QLQ-FA12). Multivariable logistic regression models retained associations with severe CRF by bootstrapped Augmented Backwards Elimination, validated using 10-fold internal cross-validation and overoptimism-corrected AUC. Results: Among 6619 BCS, mean age at dx was 56.5 years (SD 11.5), mean BMI was 25.9 Kg/m2 (SD 5.4), 53.3% and 80.8% received chemotherapy (CT) and hormonotherapy (HT), respectively. Prevalence rates of severe global CRF were 25.0% (dx), 35.6% (T1), 34.0% (T2) and 31.6% (T3). Severe post-tx global CRF was consistently associated with higher BMI, worse insomnia and pain, and severe pre-tx CRF. Receipt of CT increased odds of severe CRF at T1, whereas associations of HT with CRF emerged at T2 and T3 (Table). The estimated risk of severe CRF at T3 was 14% for a BCS with BMI 23.0 Kg/m2 and no concomitant symptoms at dx, whereas it was 82% for a BCS with BMI 32.0 Kg/m2, severe insomnia, pain and pre-tx CRF, receiving HT. Anxiety and depression at dx were consistently retained in models of severe post-tx emotional and cognitive CRF (all p <.05). Conclusions: Over 1/3 BCS endured persistent, severe global CRF, particularly those that were medically more fragile and reported heavier pre-tx symptom burden. A transient impact of CT on CRF was evident on the short aftermath of tx, whereas exposure to HT seemed to affect CRF on the longer run. Consistent factors flag BCS whose risk of severe CRF is high and who should be upfront targeted and aggressively helped. Dimension-specific risk factors can guide prevention of distinct CRF symptoms. Clinical trial information: NCT01993498. [Table: see text]
Change in the comprehensive geriatric assessment scores at day 30 post-cancer treatment in geriatric oncology patients.
Authors: Tannous Toufic , Debs Dany , Ceyhan Erkan , Somasundar Ponnandai Sadasivan 
Published: June 2021

12048 Background: The comprehensive geriatric assessment (CGA) is a multidimensional tool for assessing the functional, cognitive, nutritional and frailty status of patients above 65 years of age with cancer. It includes several components: patient health questionnaire (PHQ-9), timed up and go (TUG), mini mental status exam (MMSE), mini nutritional assessment (MNA), Poly Pharmacy (PP), activities of daily living (ADL), instrumental activities of daily living (IADL) and comorbidities. Previous studies showed that some baseline CGA scores (pre-treatment) are predictors of mortality. However, to our knowledge, there has been no study evaluating the change of those scores in response to treatment at different time periods. We sought to evaluate the evolution of the CGA scores after 30 days post-treatment. Methods: We conducted a single institution, prospective cohort registry of patients with solid cancers aged 65 or older in Rhode Island from 2013-2018. All patients underwent a CGA before starting treatment (day 0) and post-treatment (day 30). Treatment included surgery, chemotherapy, radiation, or any combination. Baseline demographic characteristics as well as CGA components were abstracted. TUG, MMSE, PHQ-9, IADL, PP, BMI, MNA and ADL performed at day 0 and 30 were collected. The mean for each score was obtained at both days. Student T test was used to test for significance for nominal data and Chi square test for ordinal data. A P value of less than 0.05 was deemed statistically significant. Results: 283 patients were enrolled. The mean age was 76 (+-6.86) of which 54% were females. 92% of patients were white and 8% were black. Colorectal and lung cancer were among the most common. The mean Charleston comorbidity index was 12.3 (+-3.2). The mean BMI decreased from 26.92 (+-5.84) at day 0 to 26.1 (+-5.45) at day 30 (p < 0.01). The mean IADL decreased from 5.93 (+-2.03) to 5.2 (+-2.12) (p < 0.01). At day 0, one patient had impaired ADLs compared to 7 patients at day 30 (p = 0.03). PHQ-9, MMSE, MNA, TUG and PP scores did not significantly differ at day 30 post treatment (Table). Conclusions: The ADL, IADL and BMI scores showed a statistically significant change at Day 30, indicating deteriorating scores in those patients. Our study showed that ADL, IADL and BMI were the only variables that worsened at day 30 post-treatment compared to PHQ-9, MMSE, MNA, TUG and PP. This suggests that they may be used as early markers of clinical deterioration in geri-onc patients undergoing treatment. More studies are needed to assess their prognostic significance.[Table: see text]
Impact of using volumetric dosimetry to screen childhood cancer survivors for radiation-related late effects.
Authors: Cohen-Cutler Sally , Kaplan Cameron , Olch Arthur , Wong Kenneth , Malvar Jemily , Constine Louis S. , Freyer David R. 
Published: June 2021

12066 Background: Late effects screening guidelines for survivors of childhood cancer treated with radiation therapy currently use irradiated regions (IR) rather than volumetric dosimetry (VD), which more precisely identifies organs-at-risk (OAR). We recently showed that VD reduced mean number of recommended screening diagnostic imaging studies and procedures by 37.0% per patient (p<0.001).1 Here we have incorporated chemotherapy and refined volumetric dosimetry dose thresholds. Methods: This was a cross-sectional cohort study of patients (n=132) treated for cancer using computerized tomography-planned irradiation at Children’s Hospital Los Angeles from 2000-2016. For each patient, both VD and IR methods were used to determine radiation exposure to the cochlea, heart, lung, breast, and colon. Dose thresholds for VD were based on those supplied in the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines. Relevant chemotherapy exposures were recorded. Under each method, COG Long-Term Follow-Up Guidelines were applied to determine potential chemotherapy- and radiation-related late effects and their correlative screening practices (complete audiologic evaluation, pure tone audiometry, mammogram, breast MRI, echocardiogram, pulmonary functions test, and/or colonoscopy). Identified OAR were compared using Exact McNemar’s test. Total numbers of screening practices were computed using VD and IR and compared. Results: Median age at end of treatment was 10.6 years (range 1.4-20.4). The most frequent cancer type was brain tumor (45%), followed by bone and soft tissue tumor (39%) and leukemia/lymphoma (16%). Head/brain was the most commonly irradiated region (61%), followed by abdomen (22%). Anthracyclines were received by 25% of patients at < 250 mg/m2 and by 16% at ≥ 250 mg/m2. With use of VD, fewer patients were flagged for screening for each organ of interest: cochlea (-21.3%, p<0.001), heart (-22.5%, p<0.001), lung (-13.8%, p=0.219), breast (-25%, p=0.625), colon (-51.9%, p<0.001). Over the lifetime of this cohort, use of VD resulted in recommendations for 1,333 fewer pure tone audiometric tests (-21.5%), 9 fewer complete audiologic evaluations (-16.1%), 4 fewer pulmonary function tests (-13.8%), 112 fewer mammograms (-25.0%) and breast MRIs (-25.0%), 349 fewer echocardiograms (-16.1%), and 275 fewer colonoscopies (-51.9%). Conclusions: Use of VD rather than IR significantly reduces guideline-based screening for radiation-related late effects in long-term childhood cancer survivors. This work forms the basis for a comparative cost-effectiveness analysis of these two approaches. (1) Cohen-Cutler et al, Cancer Medicine, 2020.