bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting survival in primary resected retroperitoneal soft tissue sarcoma: A specific nomogram built on three major sarcoma center data sets.
Authors: Gronchi Alessandro , Miceli Rosalba , Shurell Elizabeth , Eilber Frederick C. , Eilber Frederick R. , Anaya Daniel A. , Lev Dina , Colombo Chiara , Pollock Raphael E. 
Published: March 2020

10000 Background: To build a specific nomogram for predicting postoperative overall survival (OS) in primary retroperitoneal soft tissue sarcoma (RPS). A few single institutions attempts are already available, but due to the rarity of the disease they are based on limited number of cases with inherent limitations. In an attempt to improve the predictive capability of such a prognostic model we utilized series from 3 major sarcoma centers. Methods: We included patients with primary localized RPS resected with curative intent between 1999 and 2009 at 3 institutions (1 European and 2 North Americans). Univariable (Kaplan Meier plots) and multivariable (Cox model) analyses were carried out. Prognostic covariates were: Age (modeled as continuous covariate using 3 knot restricted cubic spline transformation); Tumor size (modeled as continuous covariate using 3 knot restricted cubic spline transformation); Grade (I,II,III); Histological subtype (Leiomyosarcoma, DD Liposarcoma, WD Liposarcoma, MPNST, Pleomorphic Sa, SFT, Other); Multifocality (no,yes); Quality of surgery (macroscopically complete, incomplete); radiation therapy (RT, done/not done). A backward selection procedure, based on the Akaike Information Criterion (AIC), was applied to select the Cox model covariates. The model discriminative ability was estimated by means of bootstrap-corrected Harrel C statistic. Results: 526 patients were identified. At a median follow-up of 45 months (interquartile range: 22‑72 months) 174 deaths were recorded. 5-yr and 7yr OS (95% confidence interval) were 56.4% (51.1,62.2%) and 50.1% (44.1,57.0%). The backward selection procedure by AIC criterion lead to exclude RT from the covariates set. All other covariates proved to be statistically significant in the final multivariable Cox model. The Bootstrap-corrected Harrell C statistic was 0.74. Of interest, size of the tumor and age of the patient had a bimodal contribution to the risk of death and the combination of histological subtype and grade proved significant. Conclusions: A new multi-institution RPS specific nomogram is now available for prognostication in the clinic and patient selection in clinical trials.
Growth modulation index and RECIST-based STBSG-EORTC criteria for the assessment of drug activity in advanced soft tissue sarcoma (ASTS) patients (pts).
Authors: Cousin Sophie , Blay Jean-Yves , Bertucci François , Isambert Nicolas , Italiano Antoine , Bompas Emmanuelle , Ray-Coquard Isabelle , Perrot Delphine , Bui Nguyen Binh , Chaix Marie , Chaigneau Loic , Corradini Nadege , Penel Nicolas 
Published: March 2020

10014 Background: Despite promising phase II trial results, most of new drugs failed to improve the overall survival (OS) in ASTS pts. The choice of the endpoint in early trials remains crucial. We have evaluated the Growth Modulation Index (GMI) as potential endpoint. The GMI is defined as the Time To Progression with the second (or n+1) line of chemotherapy (TTP2) divided by the TTP with the first (or n) line (TTP1). Methods: We have carried out a retrospective multicenter study in pts receiving second-line chemotherapy after failure/intolerance to doxorubicin-based regimens. Data collected included best response(s), TTP1 & TTP2 and OS. Treatments have been classified as "active" treatment according to the EORTC- STBSG criteria (3-month Progression-free rate >40% or 6-month PFR>14%: including trabectedin, ifosfamide, gemcitabine+docetaxel for all subtypes and weekly paclitaxel for angiosarcoma) versus non-active drugs. Comparisons used chi-2 tests and Log-rank tests. We performed a logistic regression analysis for identifying factors associated with longer GMI. Results: The study population consisted in 106 men and 121 women, the median age was 57 years. 110 pts (48.4%) have received "active drugs". The median TTP1, TTP2 and GMI were 197 days, 134 days and 0.75, respectively. The median OS was 446 days. 70 pts experienced GMI>1.33 (30.6%). There was a strong relation between best objective response and GMI (p<0.0001). The treatment with "active drug" was not associated with an improvement of the OS: 490 days 407 versus days (p=0.524). The median OS of pts with GMI<1, GMI=[1.00-1.33] and GMI>1.33 were 324, 302 and 710 days, respectively (p<0.0001). None of the following factors were associated with GMI>1.33 in logistic regression analysis: age, gender, histological subtypes, grade, metastasis locations, interval between diagnosis & metastasis, association with ifosfamide or dacarbazine in 1st-line regimen or treatment with "active drug" in second-line. Conclusions: GMI seems to be an interesting endpoint providing additional information compared to classical criteria. GMI>1.33 is associated with significant improvement of the OS.
Efficacy and safety of panobinostat (LBH-589), a histone-deacetylase inhibitor (HDACi), in patients (pts) with advanced, previously treated soft tissue sarcoma (STS) and sex cord tumors (SCT): A study from the French Sarcoma Group.
Authors: Cassier Philippe Alexandre , Lefranc Anne , Penel Nicolas , Chevreau Christine , Bui Nguyen Binh , Le Cesne Axel , Ray-Coquard Isabelle Laure , Chabaud Sylvie , Amela Eric , Berge Yann , Domont Julien , Italiano Antoine , Duffaud Florence , Cadore Anne Claire , Polivka Valentine , Blay Jean-Yves 
Published: March 2020

10027 Background: Treatment options are limited for pts with advanced pretreated STS. HDACi have shown activity in preclinical models of STS and SCT Methods: Pts with advanced pretreated STS and SCT were enrolled in this open label, single arm, multicenter phase II study. Panobinostat was given orally, 40 mg thrice per week. The primary end-point was 3-month progression-free rate according to RECIST 1.1 using central review. Fleming-A’Hern single-stage design for phase II trials was used, and assuming a type I error alpha of 5% with 90% power, 15/47 pts were needed to be progression free at 3 months to reject a rate of 20%. Results: Fifty three pts were enrolled between January 2010 and January 2011. Median age was 59 (range 21-79) years, and 22 (42%) pts were males, 13 had translocation-related sarcoma (TRS) and 4 had SCT. All but 5 pts had metastatic disease. The most common sites were the lung and the liver. All but one pt had documented disease progression prior to study entry. The median number of prior lines of therapy was 2 (range 1-7). Panobinostat dose was lowered to 20 mg thrice a week after 11 pts were enrolled based on the recommendation of an independent safety committee. Fifty-two pts were evaluable for toxicity (1 pt never received treatment), 48 pts (92%) reported at least one adverse event (AE) and 22 (42%) reported at least one treatment-related grade 3 or 4 AE. The most common grade 3/4 AEs were thrombocytopenia, fatigue and anemia. Fifty pts were evaluable for the primary end-point, of these, 12 pts (24%, 95%CI[13-38%]) were progression-free at 3 months, including 4/13 pts (31%, 95%CI[9-61%]) with TRS and 2/4 pts (50%, 95%CI[7-93%]) with SCT. No CR was seen, two patients (4%) with SCT had a PR and 19 pts (37%) had SD as their best response. Seven pts were progression-free at 6 months: 2 pts with SCT, 2 with TRS, 1 with liposarcoma, 1 with malignant solitary fibrous tumor and 1 with leiomyosarcoma. Conclusions: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited although some patients had prolonged SD. Activity in pts with SCT warrants further investigation.
Characteristics of sarcoma patients with long-term response to gemcitabine and paclitaxel.
Authors: Katz Daniela , Elyan Firas , Sonnenblick Amir , Merimsky Ofer , Ospovat Inna , Cohen Orit , Salmon Asher , Nechushtan Hovav , Edelmann David , Peretz Tamar , Peylan-Ramu Nili 
Published: March 2020

10034 Background: The combination of fixed-dose-rate gemcitabine and docetaxel has demonstrated efficacy in advanced uterine leiomyosarcoma and nonleiomyosarcoma sarcomas. We evaluated the tolerability and efficacy of modified taxol-gemcitabine (GemTax) protocol for patient with advanced sarcoma. The protocol was designed on a weekly basis to reduce toxicity. The purpose of this retrospective study was to evaluate the characteristics of long term-responders (≥12 treatments) to weekly GemTax, among pre-treated advanced high-grade sarcoma patients. Methods: From May 2004 to October 2011, 48 advanced sarcoma patients were treated with combination paclitaxel (60-90 mg/m2) and gemcitabine (600-900 mg/m2 over 100 min), on days 1,8 of every 3-week cycle or on days 1, 8 and 15 of every 4-week cycle at a wide-range treatment lines. Two patients are still on the protocol. Results: Fifteen patients (6 males and 9 females) completed 12 weekly treatments or more (mean 22.3 range 12-37) of which 4 completed >30 treatments. These include 5 leiomyosarcomas (one retroperitoneal), 2 uterine leiomyosarcomas, 3 MFH, 2 spindle sarcoma, 1 osteosarcoma, 1 adamantimoma and 1 pleomorphic rhabdomyosarcoma. GemTax was administered as 1st or 2nd line treatment in 2 and 8 patients, respectively, and as 3rd -6th line in 5. Of these patients, none achieved complete response (CR), 7/15 (47%) achieved a partial response (PR) and 8/15 (53%) had stable disease (SD). Median treatment duration was 10.3 months (range 4-22) Median progression-free survival was 28.85 months (range 5-84 months), and median overall survival was 51.2 months (range 16-95 months). A lower starting dose of paclitaxel (60-70 mg/m2) and gemcitabine (600-700 mg/m2) characterized the 4 patients with responses >30 cycles. Only five patients required dose reduction ranging between 10-40% due to grade 3 hematological toxicity. None of these patients, however, had febrile neutropenia, or bleeding events, and all non-hematologic toxicities including neurotoxicity were manageable. Conclusions: GemTax is a reasonable treatment option for patients with advanced pre-treated high-grade sarcomas. The regimen is well tolerated and dose adjustments do not seem to impact response.
Effect of metastasis surgery on overall survival in patients (pts) with advanced soft tissue sarcoma (ASTS): A subanalysis of the PALSAR trials.
Authors: Kotecki Nuria , Bui Nguyen Binh , Blay Jean-Yves , Mathoulin-Pelissier Simone , Chevreau Christine , Thariat Juliette , Cupissol Didier , Bay Jacques-Olivier , Coindre Jean-Michel , Lotz Jean-Pierre , Jimenez Marta , Brouste Veronique , Guillemet Cecile , Italiano Antoine , Penel Nicolas 
Published: March 2020

10035 Background: The role of surgery in pts with ASTS remains controversial. We have conducted an exploratory retrospective analysis of the role of metastasis surgery in ASTS pts receiving 1st-line chemotherapy (CT). Methods: The database includes all pts enrolled in PALSAR-1 and PALSAR-2 trials [Fayette 2009; Bui-Nguyen 2011], treated with dose-intensified MAID or high-dose CT with peripheral blood stem cells support as 1st-line treatment of ASTS. In our analysis, the primary endpoint is overall survival (OS). Log-ranks are used for univariate analysis and Cox model for multivariate analysis. Impact of treatments had been evaluated after adjustment to confounders (Cox Model). Confounders were defined as parameters with significantly different distribution in pts who underwent metastasis surgery and those who did not (p<0.05) and significantly associated with OS (p<0.05). Results: The database consists of 410 pts (160 in PALSAR-1 and 248 in PALSAR-2) with a median age of 43. Among them, 77 patients (18%) underwent metastasis surgery. At the end of the treatment, 61 pts experienced complete response (CR), 45 with CT alone and 16 with metastasis surgery and CT. The median follow-up was 29 months. The median OS was 35.7 months (29.9-41.5). The following parameters are associated with longer OS in univariate analysis: primary location (p=0.0001), performance status (p=0.010) and absence of liver metastasis (p=0.001). We identified 4 factors associated with metastasis surgery (n=76): limb/trunk primaries, young age, absence of liver metastasis and absence of progression of the target lesions after 4 cycles. The sole identified confounder was primary location. In multivariate analysis the 2 categories of patients experiencing significant longer OS are those with CR without surgery (HR=2.2, [1.7-5.8], p=0.0001) and those with CR following metastasis surgery (HR=3.8, [2.3-6.2], p=0.0001). Conclusions: Among the pts with ASTS receiving poly-CT as 1st-line treatment, the OS of pts experiencing CR with or without metastasis surgery appears similar. Metastatis surgery without CR does not offer significant OS advantage.
Palliative ambulatory 14-day infusional ifosfamide in the outpatient setting for treatment of advanced soft tissue sarcomas (STS): “Old wine in a new bottle.”
Authors: Alam Salma Moona , Benson Charlotte , Olmos David , Jones Robin Lewis , Mitchell Scott , Al-muderis Omar , Dunlop Alison , Propert-Lewis Cerys , Scurr Michelle R. , Judson Ian Robert 
Published: March 2020

10039 Background: Ifosfamide (IFO) has recognised activity in soft tissue sarcomas. There is evidence for improved cytotoxicity and tolerability utilising a prolonged 14 day infusional outpatient regimen compared with the standard 3-day regimen (Loeffler et al 1990). We undertook a retrospective review of all patients treated with this regimen from September 2008 - December 2011 to determine toxicity and treatment response. Methods: Pts. were identified from our database and demographics, histological subtype, toxicity and survival outcomes were collected. IFO was given via central venous access using 2 x 7 day pumps at 1g/m2/day with mesna for 14 days q 4 weekly. Oral sodium bicarbonate was used to maintain alkaline urine with oral mesna for haematuria, and thiamine for symptoms of encephalopathy as required. Results: 29 patients (pts), with advanced sarcoma, median age 56 years (27-76 yrs), 14F 15 M, median number of cycles = 1 ( 1-9). At baseline: PS 0=1, 1=24, 2=4. 18 pts had de-differentiated liposarcoma (D-LPS), 6 synovial sarcoma, 5 had other subtypes. 12 pts received only 1 cycle, with 5 stopping due to encephalopathy. Ten patients developed encephalopathy, 9 occurring in cycle 1, other toxicity was tolerable, with Gr 2-3 nausea (15 pts) and vomiting (9pts) and only 2 Gr 3 episodes of myelotoxicity for all cycles. 4 patients achieved PR, (2 with D-LPS and 2 with Synovial sarcoma) 11 pts. had SD. Median PFS was 19 months and OS was 12.5 months. 2 pts. with D-LPS had a sustained prolonged response of 15 and 16 months. Conclusions: Infusional IFO is generally well tolerated; however a significant incidence of neurotoxicity was seen. Pts. with D-LPS demonstrated best response to treatment, a sarcoma subtype that has previously failed to respond to systemic therapy. This regime warrants further investigation.
Clinical effectiveness of recombinant adenovirus human p53 gene combined with hyperthermia in treatment of advanced soft tissue sarcoma.
Authors: Xiao Shaowen , Zhang Shanwen 
Published: March 2020

10045 Background: Soft tissue sarcoma in advanced stage usually resist to both chemo- and radiotherapy. Several studies indicated that rAdp53 can reverse this resistance and enhance the effectiveness of radiotherapy, chemotherapy and hyperthermia. This study is to evaluate the efficacy and safety of recombinant adenovirus human p53 gene (rAdp53) combined with hyperthermia and radiation in treatment of advanced soft tissue sarcoma. Methods: From Nov. 2001 to July 2011, 30 patients with advanced soft sarcoma were enrolled in this study. All cases received hyperthermia treatment, once a week for total of 9 times, and intratumoral injection of rAdp53 at dose of 1x1012 virus particles (vp) for 8 times. Radiation were given 48 hours after the first rAdp53 injection at a dose of 2Gy/f, five fractions a week for a total dose 16~70Gy /8~35f/2~8w, at an average of 56.3±5.3 Gy. Patients were monitored for response and adverse events. Results: The median follow-up time was 96 months. Among these patients, one case (3.3%) achieved complete response (CR), 9 (30%) cases had a partial response (PR), and 18 (60.0%) cases had a stable disease (SD). The overall clinical effectiveness rate (CR+PR+SD > 6months) was 83.3.0% (25/30). One-year survival rate is 56.6% (17/30), 2-year survival rate is 23.3% (7/30), 3-year survival rate is 10.0% (3/30), and 5-year survival rate is 6.7% (2/30). Overall median survival time was 18.1 months and median TTP was 13 months. No significant adverse events were noted, except for transient fever associated with rAdp53 administration. Conclusions: rAdp53 combined with hyperthermia and radiation is effective and safe modalities in treatment of advanced soft tissue sarcoma.
Rechallenge with ifosfamide-containing regimen as salvage option for patients with metastatic soft tissue sarcomas progressing after multiple pretreatments.
Authors: Hoiczyk Mathias , Kuschel Petra , Grabellus Florian , Geffken Mareike , Ahrens Marit , Schuler Martin H. , Bauer Sebastian 
Published: March 2020

10046 Background: Ifosfamide (I) is commonly used in first or second-line treatment of locally advanced or metastatic soft tissue sarcomas (STS). The clinical efficacy of a rechallenge with ifosfamide (IR) or I-containing regimen (ICR) is unclear. We conducted a retrospective analysis of our institutional database (n=1354) of pts who received IR or ICR. Methods: 66 STS pts were identified, who had received more than one I-based regimen. Ifosfamide retreatment was given in neoadjuvant (n=26), adjuvant (n=18) or metastatic settings (n=22) and most patient were pretreated with doxorubicin (D; 94%). PFS was determined from first administration of IR until disease progression, OS from R until last follow-up or death. ORR (RECIST) was assessed to determine the clinical benefit rate (CBR) defined as CR, PR plus SD. Covariates were age, gender, histology, pretreatment, dose intensity, response and toxicity. Results: Median age at time of first I was 45y (range: 17-74, 44% f 56% m). Median time from diagnosis until first ICR treatment was 4mo. Median time from first I until IR, which was given as median 3rd-line treatment (2-9 lines), was 17 mo. Histologies were 12 leiomyo-, 11 lipo- 13 pleomorphic,14 synovial, 4 rhabdomyosarcomas and 12 other subtypes. Pts received a median of I 9.6 g/m²/cycle and a median of 4 cycles. I was given as monotherapy (38%) or in combination (D: 45%, other 17%). Overall median PFS was 5mo with PFS-rates of 63% at 12 and 25% at 24 wks. Median PFS was 6 mo for ICR and 2 mo for IR. The median OS was 36 mo from time of first diagnosis of metastases or locally advanced disease. ORR was 29% for I/D combination (CBR 70%) and 12 % for I monotherapy (CBR: 52%). 22 pts received a second IR with a median of 2 cycles (27% PR; CBR:77%; 69% combinations). Most common toxicities for IR/ICR were neutropenia (42%), encephalopathy (21%) and neutropenic fever (18%). Dose reductions were necessary in 18% of pts and treatment was stopped in 8% due to toxicity. No significant cardiotoxicity was observed. Conclusions: Patients with soft tissue sarcomas who had at least disease stabilization after initial ifosfamide-based therapy may derive substantial clinical benefit from a rechallenge.
Geriatric high-grade soft tissue sarcoma (G-HG STS): An analysis of 116 patients (pts) evaluating prognostic factors and clinical outcomes stratified by histology.
Authors: Quek Richard Hong Hui , Harunal Rashid Mohamad Farid Rin , Pan Summer , Tan Mann Hong , Foo Leon Siang Shen , Sittampalam Kesavan , Sairi Alisa , Adam Kiraely , Hanafi Widayana , Lim Soon Thye , Tay Kevin , Soh Lay-Tin , Chin Francis , Teo Melissa , Poon Donald 
Published: March 2020

10051 Background: STS in geriatric pts is not well studied. We evaluated prognostic factors and clinical outcomes in elderly pts with HG STS. Methods: Single centre retrospective study. G-HG STS pts defined as age > 65 yrs seen in our centre from 2002 - 2011 with complete medical records were identified. Charlson age-comorbidity score was assessed for each pt. Results: 116 pts from 4 most common HG STS histo-types representing 69% of pts in the geriatric STS cohort were analysed; leiomyosarcoma (LMS, 14%), non well-differentiated liposarcoma (nWD-LPS, 9%), angiosarcoma (AS, 30%), and undifferentiated pleomorphic sarcoma (UPS, 47%). Median age was 72 yrs, 81% presented with localised disease; of 78% of these localised pts who had curative surgery, 49% received adjuvant therapy, of whom 92% had radiotherapy (RT) only. AS arises more commonly from the head/neck region (p<0.001) and fewer receive curative surgery (p=0.006). In 43 pts who had metastases either at diagnosis or relapse, 33% received first-line palliative chemotherapy with a response rate of 27% in evaluable pts. At a median follow-up of 15.8 mths, overall survival (OS) for the entire cohort was 25.1 mths, 30.5 vs 3.9 mths in pts presenting with localised vs metastatic disease respectively (p<0.0001). In pts who had curative surgery for localised disease, overall relapse-free survival (RFS) was 17.7mths; 26.8 mths vs 16.0 mths vs 7.3 mths vs 12.5 mths in LMS, nWD-LPS, AS and UPS respectively. In univariate analysis, adjuvant RT, non-head/neck primary and sarcoma subtype were associated with improved RFS. In multivariate analysis, adjuvant RT (p<0.001), sarcoma subtypes AS (p=0.011) and UPS (0.012) vs LMS remained significant. In pts with metastatic HG STS either at diagnosis or relapse, overall median OS was 5.9 mths; 5.9 mths (LMS), 30.5 mths (nWD-LPS), 6.4 mths (AS) and 4.3 mths (UPS). In univariate analysis, presence of bone metastases was significantly associated with inferior OS (p=0.0029). Charlson score did not correlate with RFS or OS. Conclusions: Prognosis of G-HG STS appears poor particularly in AS and UPS. Adjuvant RT improves outcomes in this group of pts and should not be omitted based on age alone.