bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational study associated to a phase II study evaluating the activity of pazopanib in patients (pts) with advanced/metastatic liposarcoma (LPS): A joint Spanish Sarcoma Group (GEIS) and German Interdisciplinary Sarcoma Group (GISG) study.
Authors: Valverde Morales Claudia Maria , Fernandez Serra Antonio , Ramírez-Calvo Marta , Lopez-Martin Jose A. , Romagosa Cleofe , Carrasco Juan Antonio , Bauer Sebastian , Martinez Trufero Javier , Jurado Josefina Cruz , Reichardt Peter , Serrano Cesar , Grünwald Viktor , Luna Fra Pablo , Persiva Oscar , Varona Diego , Morales-Barrera Rafael , Kasper Bernd , Martin Broto Javier , Ruiz-Sauri Amparo , Lopez-Guerrero Jose Antonio 
Published: March 2020

11067 Background: GEIS 30 was a phase II study showing moderate activity of pazopanib in well-differentiated/dedifferentiated LPS (cohort A:37 pts, Progression free Survival (PFS) at 12 weeks (w) 43.2%) and no activity in Myxoid/round cell LPS (cohort B: 15 pts, PFS at 12w 13.3%). The present study aims to identify tumor and plasma biomarkers that are differently expressed in long responders (LRs) PFS > 24 w. Methods: Serum samples and paraffin-blocks at diagnosis were collected for 28 pts in cohort A and 11 in B. A total of 13 pts were LRs. Serum samples were obtained at baseline, after 3 w of treatment and at progression. A panel of 15 cytokines and growth factors were evaluated using Luminex technology (Millipore). Paraffin-blocks were evaluated for microvessel density (MVD) by CD31 immunostaining and Image Pro-Plus 7.0 Image Analysis System (Media-Cybernetics). For RNA expression analysis, the Oncology Biomarker Panel with probes for 2559 transcripts was used (HTG Molecular Diagnostics). Results: Serum cytokines showed that expression of angiopoietin (AGO) and BMP9 decreases during treatment, whereas GCSF increases. In addition, AGO and BMP overexpression at baseline was associated with worse prognosis in arm A (p = 0.09) and B (p = 0.01) respectively. No differences between study arms and outcome were appreciated by MVD. Gene expression revealed differences in some immunomodulators: PDL-1 was correlated with serum cytokines VEGFD (p = 0.04) and LEPTIN (p = 0.02); and PD-1 with VEGFD (p = 0.04), LEPTIN (p = 0.02), VEGFA (p = 0.02) and ANGIO (p = 0.03). PD1, in addition,was overexpressed in LRs (p = 0.05). Interestingly, three groups were identified in cohort A according to gene expression: Cluster 1, characterized by short-responder patients with the shortest overall survival, whereas cluster 3 (40% LRs) and 2 (63.6% LRs) showed longer survival rates (14.3%, 45.5% and 30% respectively) (p = 0.001). Conclusions: Gene expression profiling unveils three WD/DD-LPS biotypes according to their response to pazopanib, which could be potentially used to select pts for treatment
Frequent mutations of genes predisposing to Rho GTPase signal activation and autophagy inhibition in metastatic soft tissue sarcoma unveiled by paired somatic and germline genomic analyses.
Authors: Takahashi Katsuhito , Motoki Ayako , Yashima Jun , Masaki Noriyuki , Sano Hiroko , Yamamoto Hiromasa , Sou Junichi , Takahashi Yuko , Toyooka Shinichi , Oyama Yu , Nomori Hiroaki , Narahara Hiroyuki , Yotsumoto Junko , Ono Yasuo , Tonsho Makoto , Teraoka Satoshi 
Published: March 2020

11071 Background: Soft tissue sarcoma (STS) is well-known rare cancer with few therapeutic options. Although recent genomic analyses of sarcoma revealed few somatic mutations, massive copy number variations (CNV) and chromoplexy which correlate with worse clinical outcomes, their molecular and genomic mechanisms remain to be understood. Methods: We recruited 116 patients (102 female and 14 male, mean age 50, 80 LMS, 14 LPS, 3 AS and others) and performed whole exome sequencing with the methods as reported in ASCO2018. In addition to somatic mutations, we evaluated germline and CNV contributions in tumor to find LOH mutations by Strelka and Virmid analysis softwares. Results: Of the total of 135-4717 (mean 1129) mutations in tumors, 3-111 (mean 32) mutations were found in 595 COSMIC genes including both somatic and LOH mutations. Less than 33% LOH in the total of somatic and LOH mutations significantly correlated with improved 5-year survival rate as compared with patients with more LOH (81% vs 52%, P=0.01). Among the 224 genes reported in somatic mutations of sarcoma, damaging mutations in ARHGAPs, Rho GTPase signal inactivating genes, were most frequently detected in 59% of total (n=116) and 63% of leiomyosarcoma (n=80) patients as in somatic and/or LOH mutations. Patients with ARHGAP mutations were significantly reduced 5-year survival rates as compared with patients without mutation (51% vs 76%, P=0.007). Among the 163 genes involved in autophagy, a key silencing process for active RhoGTPase, one or more damaging mutations as in somatic and/or LOH mutations were found in 87% in total and 96% in leimyosarcoma patients. Conclusions: Our results, for the first time, suggest an important role of mutations in genes involved in Rho GTPase and autophagy signaling, both well known regulator of chromosomal stability, invasion and metastasis of tumor cells, and thus implicate a potential therapeutic target in STS.
Retrospective analysis of adjuvant treatment for localized, operable uterine leiomyosarcoma.
Authors: Chantharasamee Jomjit , Wong Karlton , Potivongsajarn Pasathorn , Aqorbani Amir , Chmielowski Bartosz , Cohen Joshua Garrett , Nelson Scott D. , Moatamed Neda A. , Brackert Sandra , Kalbasi Anusha , Rao Jianyu , Singh Arun S. 
Published: March 2020

11072 Background: Surgery is the standard of care for uterine leiomyosarcoma, but recurrence rates are high and outcomes are poor. Standard adjuvant treatment of localized uterine leiomyosarcoma(uLMS) has not yet been established as clinical trials to address this question have been small or hindered by slow accrual. Methods: We reviewed the medical records of patients with uLMS who underwent upfront surgery between 2000-2018. We evaluated the clinical characteristics and adjuvant therapy on outcomes. Patient characteristics and treatment outcomes were described using descriptive statistics. Kaplan-Meier survival analysis was used for DFS. Cox proportional hazard regression was used to compare difference between groups. Results: 59 patients with a median age of 52 years were analyzed and the median time from surgery to adjuvant treatment was 47 days. 48/59 (81.4%) underwent TAH-BSO. 64.4% were FIGO stage I, 16.9% were stage II and 6.7% were stage III. The median tumor size was 11 cm (range: 3-21cm) and the median mitotic rate was 13 mitoses/ 10 high-power fields (HPF), (range: 1-63). 34/59 (57.6%) of patients received adjuvant chemotherapy +/- radiation therapy and 25 patients (42.3%) did not receive adjuvant treatment. With a median follow-up time of 42.8 months, 42 patients (71.2%) had disease relapse and 15 (35.7%) had pulmonary metastases. The median disease-free survival (mDFS) for all patients was 23.1 months. Any adjuvant treatment (chemotherapy or radiation) had a trend toward longer mDFS than no adjuvant treatment (36.6 vs 13.6 months, p = 0.14). Patients who had adjuvant chemotherapy had a non-significant longer mDFS compared to who did not receive any adjuvant treatment (33.8 vs 13.6 months, p = 0.18). Patients with stage I disease had trend towards higher mDFS in the chemotherapy group, it was not statistically significant (29.7 vs 16.6 months, p = 0.59). Multivariate analysis found that the independent prognostic factors for worse DFS included tumor size larger than 10 cm, and mitotic rate over 10/ 10HPF. More morcellated specimens were found in non-adjuvant treatment arm (36%) compare to 8% in adjuvant arm. In the non-treatment arm, 14 patients had recurrences within 6 months. Conclusions: In a retrospective uLMS population, the mDFS was 23.1 months. Tumor size > 10cm and mitotic rate > 10/10 HPF were independent prognostic factors for lower DFS. The non-treatment group had a significantly higher number of patient with morcellization and relapsed within 6 months, confounding analyses of the impact of adjuvant chemotherapy.
Efficacy and dosimetry prognostic factors of image guided 125I seed implantation for locally recurrent soft tissue sarcoma.
Authors: Jiang Weijuan , Jiang Ping , Qu Ang , Wang Junjie , Sun Haitao 
Published: March 2020

11073 Background: To observe the effect of ultrasound / CT guided radioactive 125I seed implantation in the treatment of recurrent soft tissue sarcoma and its relationship with physical dosimetry prognostic factors. Methods: The data of 37 patients with recurrent soft tissue sarcoma who received ultrasound/CT-guided 125I seed implantation from November 2005 to December 2015 were retrospectively analyzed. The local progression-free survival rate and overall survival rate were evaluated. The relationship of local progression-free survival rate and overall survival with physical dosimetric parameters was analyzed. Results: Thirty-seven patients, 20 males and 17 females, with a median age of 53 years (16-79 years), received a median radiation dose of 60 Gy (28 Gy-120 Gy). The median tumor volume was 46.8 cm3 (0.5-252.2 cm3), the median particle activity was 0.67 mCi (0.4-0.84 mCi), and the median implanted particle number was 60 (3-158). The median follow-up time was 20 months (range: 1~144 months). The median overall survival time was 20.0 months (95% CI 16.4-23.6 months). The overall survival rates of 1, 3 and 5 years were 62.2%, 34.3% and 27.7% respectively. The median local progression-free time was 63.0 months. The 1-year, 3-year and 5-year local progression-free survival rates were 68.9%, 55.0% and 47.1%, respectively. Correlation analysis showed that HI was positively correlated with total survival and local progression-free survival (P = 0.001). Multivariate analysis showed that HI ( > 0.25) was an independent prognostic factor for long overall survival (P = 0.048, HR 0.39), and D90 ( > 110 Gy) was an independent prognostic factor for long local progression-free survival (P = 0.024, HR 0.17). Conclusions: Ultrasound/CT guided 125I seed implantation is a safe and effective method for the treatment of recurrent soft tissue sarcoma with high local control rate. The HI and D90 of the postoperative plan maybe affect the therapeutic efficacy.
A randomized, double-blind, placebo-controlled phase III trial evaluating olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: J-FORCE Study.
Authors: Hashimoto Hironobu , Abe Masakazu , Nakao Masahiko , Mizutani Hideaki , Sakata Yasuhiko , Fujita Yukiyoshi , Nishimura Tomoyasu , Hirano Katsuya , Okada Hideaki , Inui Naoki , Sakata Yukio , Iihara Hirotoshi , Zenda Sadamoto , Uchitomi Yosuke , Yamaguchi Takuhiro , Hoshina Yukari , Yanai Takako , Iwasa Satoru , Yamamoto Noboru , Ohe Yuichiro 
Published: March 2020

11503 Background: Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC). Guidelines suggest that a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV in patients receiving cisplatin-based chemotherapy. Methods: Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the OLZ, with a one-sided alpha of 2.5% and a power of 80%. Results: A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the OLZ 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo ( p < 0.001). Other efficacy results are summarized in Table. The most common treatment-related adverse events was somnolence (43.1% for OLZ vs. 33.0% for placebo). Conclusions: OLZ 5 mg combined with APR, PALO and DEX can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN000024676. [Table: see text]
Randomized controlled trial (RCT) of a patient navigation (PN) intervention to increase early access to supportive care (SC) for patients with metastatic cancer in a resource-limited setting.
Authors: Soto Perez De Celis Enrique , Chavarri Guerra Yanin , Ramos-Lopez Wendy Alicia , Covarrubias-Gómez Alfredo , Navarro-Lara Africa , Quiroz Paulina , Sanchez Sofia , Alcocer Natasha , Alcalde Castro Mirza , Aguilar Velazco Jose Carlos , Bukowski Alexandra , Chavarri Maldonado Juan Alberto , Contreras-Garduño Sergio , Krush Lindsay , Inoyo Itoro E. , Medina-Campos Andrea , Moreno-García María Luisa , Pérez-Montessoro Viridiana , Goss Paul E. 
Published: March 2020

11505 Background: Early integration of SC to the treatment of advanced cancer can improve outcomes, but this may be challenging in developing countries due to a lack of resources and knowledge. In this RCT, we examined whether PN could improve early access to SC among Mexican patients with metastatic solid tumors as recommended by ASCO guidelines. Methods: Adult patients with newly-diagnosed metastatic cancer were randomly assigned to PN or standard oncologic care. At baseline, a navigator assessed the patients’ SC needs (depression, anxiety, fatigue, pain, caregiver burden) using validated questionnaires administered with an electronic tablet. For those in the PN arm, a personalized SC plan was created and implemented by a multidisciplinary team (palliative care, physical therapy, geriatrics, psychology, psychiatry). The primary outcome was access to SC, defined as receipt of SC interventions in the first 3 months (mo) after diagnosis. Secondary outcomes included advanced directive (AD) completion (for patients with expected survival ≤6 mo in accordance to Mexican law), changes in SC needs, and changes in quality of life (assessed using FACT-G). Results: 133 patients (median age 60, range 23-93; 52% male) were randomized (66 PN, 67 control). 61% of patients had gastrointestinal tumors. 94% of patients in the PN arm completed baseline assessments and received recommendations from the navigator. At 3 mo, 37 patients died or were lost to follow-up (16 PN, 21 control; p = 0.45), and 96 completed assessments. SC interventions were provided to 73% of patients in the PN arm and 24% of controls (p < 0.01). In the PN arm, 48% of 29 eligible patients completed AD, compared to 0% of eligible controls (p < 0.01). At 3 mo, patients in the PN arm were significantly less likely to report moderate/severe pain than controls (10 vs 33%, p = 0.006). There were no significant differences in other symptoms or in FACT-G scores (76 vs 76.3, p = 0.46) between PN and control arms at 3 mo. Conclusions: PN can lead to significant improvements in early access to SC, AD completion, and pain control among patients with metastatic cancer treated in a resource-limited setting. Clinical trial information: NCT03293849.
Predictive factors of grade 3-5 toxicity in older patients with cancer treated with chemotherapy: A prospective multicenter study.
Authors: Feliu Batlle Jaime , Basterretxea Laura , Torregrosa Maria Dolores , Llabres Elisenda , Losada Vila Beatriz , Jimenez-Munarriz Beatriz , Rebollo Maite Antonio , Custodio Ana B. , Girones Regina , Cruz Patricia , Sanchez Mar Munoz , Pinto Alvaro , Soler Gemma , Soria Comes Teresa , Telleria Hellis , Molina-Garrido MJ 
Published: March 2020

11509 Background: Older patients have increased risk of toxicity from chemotherapy. The purpose of this study was to analyse predictive factors for developing grade 3-5 toxicity in older patients treated with chemotherapy. Methods: This prospective multicenter study included 500 cancer patients ≥ 70 years between Feb 2014 and Jun 2018. A prechemotherapy assessment including sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status) was performed. Logistic regression was used to examine the association between these factors and the development of grade 3-5 toxicity. Results: Mean age of the patients was 77 years (70-92), ECOG PS 0/1/2: 25%/63%/12%. 223 (45%) had a primary dose reduction.167 (33%) patients developed grade 3-5 toxicity (28% grade 3, 5% grade 4, 1% grade 5). Univariate analysis found a higher risk of grade 3-5 toxicity in patients with creatinine clearance ≤ 60 mL/min, IADL ≤7, VES13 ≥ 6, and the administration of standard chemotherapy doses. In multivariable analysis, only the chemotherapy dose (odds ratio [OR] 1.179; 95% confidence interval [CI] 1.215–2.655) and creatinine clearance (odds ratio [OR] 0.989; 95% confidence interval [CI] 0.981–0.997) were independently associated with toxicity. Conclusions: Renal function and chemotherapy dose were significant predictors of grade 3-5 toxicity among older patients treated with chemotherapy.
Outcomes that matter to patients: The Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) study—Analysis of 471 patients.
Authors: Montroni Isacco , Ugolini Giampaolo , Spinelli Antonino , Ercolani Giorgio , Jacklitsh Michael T. , Rostoft Siri , Somasundar Ponnandai Sadasivan , Van Leeuwen Barbara , de Liguori Carino Nicola , Saur Nicole M. , Ferrari Giovanni , Ghignone Federico , Sermonesi Giacomo , Di Candido Francesca Rita , Foca Flavia , Zingaretti Chiara , Vertogen Bernadette , Audisio Riccardo ,   SIOG Surgical Task Force/ESSO GOSAFE Study Group
Published: March 2020

11511 Background: Older cancer patients value functional outcomes as much as survival but surgical studies lack functional recovery (FR) data. The international, multicenter GOSAFE study (ClinicalTrials.gov NCT03299270) aims to evaluate patients’ quality of life (QoL)and FR after cancer surgery and to assess predictors of FR. Methods: GOSAFE prospectively collects functional and clinical data before and after major elective cancer surgery on senior adults (≥70 years). Surgical outcomes are recorded (30 days, 90 days, and 180 dayspost-operatively) with QoL(EQ-5D-3L) and FR (Activities of Daily Living (ADL) + Timed Up and Go (TUG) + MiniCog), 28centers are prospectively enrolling patients; accrual ends February 2019. Results: 643 patients underwent major cancer surgery with curative(94%) or palliative (6%) intent (February 2017-September 2018). Median age was 78(range 70-94); 51.6% males, ASA III-IV 52%. Patients dependent (ADL < 5) were 8%. Frailty was detected by G8 > 14 in 32% and fTRST≥2 in 36% of patients. 639 (99%) lived at home, 32% lived alone, and 88% were able to go out. Major comorbidities (CCI > 6) were detected in 36% and 22% had cognitive impairment according to MiniCog (5% self-reported). 26% had > 3 kg weight loss, 30% were hospitalized in the last 90 days, 45% had ≥3 medications (6% none). For 471 patients, a 90-day comprehensive evaluation was available. Postoperative morbidity was 42% (30 day) and 63.3% (90 day), but Clavien-Dindo III-IV complications were only 11.2% and 17.6%. 90-day mortality was 7.4% (5% 30-day). QoL improved 90 days after surgery (mean EQ-5D index from 0.76 to 0.80). Patients with EQ-5D VAS score > 60 raised from 73.9% at baseline to 82.8% at 90 days. 29% had complete FR (ADL score > 4, MiniCog > 2, TUG < 20). Decreased functional capacity was seen in 23.4% of patients alive at 90-days. Conclusions: GOSAFE is the largest prospective study on older cancer patients undergoing major surgery. Interim analysis reports decreased functional capacity in a quarter of patients. The study will allow clinicians to associate clinical outcomes with individual factors of the preoperative assessment and create a user-friendly tool to predict outcomes that matter to patients.
A randomized controlled trial of a novel artificial intelligence-based smartphone application to optimize the management of cancer-related pain.
Authors: Kamdar Mihir , Centi Amanda Jayne , Agboola Stephen , Fischer Nils , Rinaldi Simone , Strand Jacob J. , Traeger Lara , Temel Jennifer S. , Greer Joseph , El-Jawahri Areej , Jackson Vicki , Kvedar Joseph , Jethwani Kamal 
Published: March 2020

11514 Background: Cancer pain is a significant problem that impairs patient quality of life and increases healthcare utilization. ePAL is a smartphone application that utilizes patient-reported outcomes (PROs) and artificial intelligence (AI) to optimize cancer pain management. This randomized controlled trial examined the impact of ePAL on cancer pain severity, attitudes toward cancer pain, and healthcare utilization. Methods: Patients with pain from metastatic solid tumors (n = 112) undergoing treatment in a palliative care clinic were randomized to either a control group (n = 56) that received usual care or an intervention group (n = 56) that received ePAL in addition to usual care for 8 weeks. Measures of pain severity (Brief Pain Inventory), attitudes towards cancer treatment (Barriers Questionnaire II) and anxiety (General Anxiety Disorder-7) were assessed. We used repeated measures mixed modeling to assess change in outcome measures over time. We also conducted a chart review to identify pain-related hospital admissions and emergency department (ED) visits and compared risk between study groups. Results: Pain severity (BPI) and negative attitudes toward cancer treatment (BQ-II) decreased significantly for those assigned to ePAL compared to controls (ß = -0.09, p = 0.034 and ß = -0.037, p = 0.042, respectively). Patients assigned to ePAL reported higher anxiety scores compared to controls (ß = 0.21, p = 0.015). Patients assigned to ePAL had significantly fewer pain-related hospital admissions (n = 4 vs. n = 20, per patient risk ratio 0.31, p = 0.018) and fewer pain-related admissions through the ED (n = 2 vs. n = 14, per patient risk ratio 0.18, p = 0.008) compared to control group. Conclusions: To our knowledge, this is the first mobile app to utilize patient reported outcomes and artificial intelligence to significantly decrease pain scores and pain-related hospitalizations in patients with cancer-related pain. Future directions include examining the efficacy of ePAL in settings with limited access to palliative care.