bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prognostic nomogram for prediction of recurrence following surgical resection of desmoid tumors.
Authors: Crago Aimee Marie , Denton Brian , Mezhir James J. , Hameed Meera , Gonen Mithat , Singer Samuel , Brennan Murray F. 
Published: March 2020

10015 Background: Desmoid tumors can respond to novel chemotherapeutics (e.g., sorafenib). We sought to construct a postoperative nomogram identifying desmoid patients who are at high-risk for local recurrence and potential candidates for systemic therapy. Methods: Desmoid patients undergoing resection from 1982-2011 were identified from a single-institution prospective database. Cox regression analysis was used to create a desmoid-specific recurrence nomogram integrating clinical risk factors. Results: Desmoids were treated surgically in 495 patients (median follow-up 60 months). Of 439 patients undergoing complete gross resection, 100 recurred (92 within 5 years of operation). Five-year recurrence-free survival (RFS) was 71%. Only 8 patients died of disease, all after R2 resection (6 with intraabdominal desmoids). Radiation was associated with worse RFS (p<0.001). Multivariate analysis suggested associations between recurrence and extremity location, young age, and large tumors, but not margin (Table). Abdominal wall tumors had the best outcome (5-year RFS 92% vs. 34% in patients <25y.o. with large, extremity tumors). Age, site and size were used to construct an internally-validated nomogram (concordance index 0.703). Integration of margin, gender, depth, and presentation status (primary vs. recurrent disease) did not improve concordance significantly (0.707). Conclusions: A postoperative nomogram including only size, site and age predicts local recurrence and aids in counseling patients. Systemic therapies may be tested in young patients with large, extremity desmoids, but surgery alone is curative for most abdominal wall lesions. [Table: see text]
Activity of sorafenib in radiation-associated breast angiosarcomas harboring MYC and FLT4 amplifications.
Authors: D'Angelo Sandra P. , Antonescu Cristina R. , Keohan Mary Louise , Carvajal Richard D. , Dickson Mark Andrew , Gounder Mrinal M. , Moraco Nicole H. , Singer Samuel , Schwartz Gary K. , Tap William D. 
Published: March 2020

10019 Background: Angiosarcomas (ASs) are rare, aggressive vascular malignancies of endothelial cell differentiation which arise de novo or secondary to radiation therapy (RAS.) A subset of patients(pts) with AS harbor mutations in KDR (VEGFR-2) or overexpression of MYC and/or FLT4(VEGFR-3). MYC & FLT4 gene amplifications occur almost exclusively in RAS. These alterations provide a rationale for investigating agents that target angiogenesis in RAS. In a phase II trial of sorafenib, AS pts had a partial response (PR) of 14%; targeting the appropriate pt population may be essential. We hypothesize that co-amplification of MYC & FLT4 may be predictive of response to sorafenib. Methods: Using our institutional sarcoma database & data query system, we identified AS patients treated with sorafenib at Memorial Sloan-Kettering Cancer Center between 1992-2011. Molecular analysis performed on available tissue. With IRB approval, clinical information was collected. Results: We identified 10 women with RAS that received sorafenib. Average age 68 (range 51-84.) 7 pts had distant metastatic disease. Median lines of systemic therapy prior to sorafenib: 2 (range 1-4.) Sorafenib was first line in 60% of pts, administered at 400mg daily and adjusted for toxicity. Best responses included: complete response (CR) 2/9(22%), PR 1/9(11%), stable disease (SD) 5/9(56%) range 5-23m, progressive disease 1/9(11%) for a clinical benefit rate of (CR+PR+SD) 89%. Responses were seen in patients with lung metastases (n=2) and locally advanced disease (n=1) and were durable for 17, 42 and 26 months. Median duration on therapy was 15 months (range 0-42 months.) 7 pts underwent molecular analysis: co-amplification of MYC & FLT4 3 pts (30%); MYC amplification 4 pts (40%); KDR mutation 0 patients. Of the 3 responders, MYC & FLT4 co-amplification were observed in 2 patients and not evaluated in one. Conclusions: Sorafenib is active against RAS of the breast. In this small series, complete and partial responses were seen in patients with co-amplification of MYC & FLT4. This observation requires further study. Performing molecular studies on all AS pts will help define the pathophysiology of this deadly disease to guide rationale clinical trials.
Phase II study of sorafenib mesylate (So) in patients (pts) with evolutive and advanced epithelioid hemangioendothelioma (EHE) or hemangiopericytoma/solitary fibrous tumor (SFT).
Authors: Chevreau Christine , Le Cesne Axel , Ray-Coquard Isabelle , Bui Nguyen Binh , Bompas Emmanuelle , Isambert Nicolas , Chaigneau Loic , Bay Jacques-Olivier , Collard Olivier , Cottura Ewa , Domont Julien , Blay Jean-Yves , Fournier Charles , Clisant Stephanie , Gauthier Eric , Penel Nicolas ,   French Sarcoma Group (GSF/GETO)
Published: March 2020

10020 Background: There is no standard of care for both rare sarcomas. Regarding, the important vascularization of EHE and SFT, we explored the activity/toxicity of So in pts with these sarcomas. Methods: We conducted a multicenter one-step phase II trial of So (800 mg/d). The primary endpoint was the 9-months progression-free rate (9-PFR). According to EORTC criteria, So is considered as promising drug if 6-PFR≥14%. All pts have had documented progressive disease at entry. Results: 20 pts (15 EHE & 5 SFT) were enrolled from June 2009 to February 2011 in the 8 participating institutions. 12 men and 8 women. Median age was 57. The most common primaries were superficial trunk (8 cases) and liver (4 cases). PS were 0 in 10 cases, 1 in 7 cases and 2 in 3 cases. 16 pts had metastasic disease , especially in lung (15), liver (6) and bone (4). Eight pts received prior chemotherapy (Doxorubicin : n= 8 cases and taxane : n =3). The median So treatment duration was 124 days. 9 pts experienced grade-3 toxicities; the most frequent grade-3 toxic events were hand foot syndrome (5 pts), myalgia (1), stomatitis (1), anorexia (1), diarrhea (1) and arterial hypertension (1).Because of this toxicity, treatment discontinuation was necessary in 6 cases and dose reduction was necessary in 5 pts. The 9-PFR was 6/18 (33.3% [11.5-55.1]). The 2, 4 and 6 PFR were 15/18 (83.3%), 8/18 (44.4%) and 7/18 (38.8) respectively We observed 2 partial responses lasting 2 and 9 months in 2 pts with EHE. Analysis of the predictive value of circulating pre-angiogenetic biomarkers is ongoing. Conclusions: According to the STBSG-EORTC criteria (3-PFR≥40% & 6-PFR≥14%), So is a promising drug for EHE and SFT pts. Further trials is needed, especially a discontinuation randomized trial.
Advanced chondrosarcomas: Role of chemotherapy and survival.
Authors: Bui Nguyen Binh , Cioffi Angela , Piperno-Neumann Sophie , Chaigneau Loic , Bertucci François , Penel Nicolas , Duffaud Florence , Le Cesne Axel , Italiano Antoine 
Published: March 2020

10023 Background: There are no data about the role of chemotherapy in patients with advanced chondrosarcomas. Methods: From 2000 to 2011, 98 patients with a confirmed diagnosis of advanced chondrosarcomas were referred to one of the 8 participating institutions, and their medical records reviewed. Results: Median age was 46 years (range 16-82). The most frequent histological subtype was conventional chondrosarcoma (n=60, 61%). 83 patients (85%) had metastatic disease ( lung n=71, bone n=23, liver n=6) and 15 patients (15%) had locoregional unresectable disease. 30 patients (31%) had ≥ 2 metastatic sites. 63 patients (64%) received 1st-line combination agent chemotherapy. 70 patients (71%) received a 1st-line anthracycline-containing regimen (doxorubicin + cisplatin +/- ifosfamide: n=30, doxorubicin or pegylated liposomal doxorubicin: n=18, doxorubicin + ifosfamide +/- dacarbazine: n=16, others= 6). RECIST objective response was observed in 14 patients (14%), all but two treated with anthracyclines. 30 patients (31%) had stable disease > 6 months. Median progression-free survival (PFS) and overall survival (OS) were 5.3 months (95% CI: 2.8-7.7) and 19 months (95% CI: 14-24) respectively. Performance status (PS) ≥ 2 was the sole factor significantly associated with OS. Conclusions: Chemotherapy is associated with a 6-month non-progression rate of about 45% in patients with advanced chondrosarcoma. Best supportive care should be considered in patients with poor PS. These data should be used as a reference for response and outcome in the assessment of investigational drugs in advanced chondrosarcoma.
Phase I study of doxorubicin (D) plus anti-insulin-like growth factor 1 receptor (IGF-1R) antibody cixutumumab (IMC-A12) in advanced soft tissue sarcoma (STS).
Authors: Chugh Rashmi , Griffith Kent A. , Brockstein Bruce , Undevia Samir D. , Stadler Walter Michael , Schuetze Scott ,   University of Chicago Phase II Consortium
Published: March 2020

10028 Background: IGF1R is overexpressed in many STS, but its exact role in the biology of the disease is unclear. Anti-IGF1R antibody cixutumumab (C) has shown acceptable toxicity in a single-agent phase 2 study of STS. Here we performed a dose escalation study of C with D in STS. Methods: Eligible pts had advanced STS, ECOG ≤2, age>16, ≤1 prior chemotherapy, fasting glucose<120 mg/dL and acceptable organ function. C was administered IV over 60 min on D1,8,15 at one of three dose levels and D as a 48 hr infusion on D1 of a 21-day cycle. After 6 cycles of combination rx, pts with SD or better continued on single agent C. The Time-to-Event Continual Reassessment Method (TITE-CRM) was used to estimate the probability of DLT at each dose level and to assign patients to the dose with the estimated probability of DLT closest to but not exceeding 30%. Results: 30 pts with STS were enrolled between 9/08-1/12. Median age was 64 (range 29-80); 17M/13 F, 7 pts received prior chemo. One pt withdrew prior to rx; 5 pts are on active rx. Reasons for discontinuation were: progression (18), toxicity (3), death (1), pt decision (2). DLTs observed were hyperglycemia and mucositis. Grade 3 decrease in cardiac left ventricular ejection fraction was observed in 2 pts at dose level 2 after 4 or more cycles. Common G1/2 nonhematologic AEs: nausea (73%), fatigue (68%), pain (59%), diarrhea (41%), constipation (36%), hyperglycemia (32%), mucositis (32%), nail changes (27%), weight loss (27%). Gr3/4 toxicities in >10%: hyperglycemia (18%), lymphopenia (18%), anemia (14%), neutropenia (14%), thrombocytopenia (14%). Median PFS was 5.3 months, 95% CI 2.7 -7.9 months. Four of 22 pts (18%) evaluable for response achieved a PR. Conclusions: C and D is tolerable and the recommended phase II dosing is dose level 3. The potential of cardiotoxicity should be monitored and assessed further in ongoing studies of this regimen. [Table: see text]
Neoadjuvant treatment of locally advanced GIST: Results of APOLLON, a prospective, open label phase II study in KIT- or PDGFRA-positive tumors.
Authors: Hohenberger Peter , Langer Claus , Wendtner Clemens Martin , Hohenberger Werner , Pustowka Annette , Wardelmann Eva , Andre Elisabeth , Licht Thomas 
Published: March 2020

10031 Background: Imatinib may significantly downstage the metastatic GIST. This prospective, phase II, open-label trial of neoadjuvant imatinib evaluated the overall tumor response and progression rate of disease in locally advanced, non-metastic patients. Methods: Inclusion criteria were: KIT (n=39) or PDFRA (n=6) positive GIST, proven by biopsy and IHC. Tumors had to be locally advanced, potentially resectable, M0. Patients received 400 mg of imatinib daily (KIT exon 9 mutations: twice daily) for 6 months, in the absence of disease progression or unacceptable toxicity. At two months 18F-FDG-PET examination was performed to assess response in paralle to CT imaging. Adjuvant treatment postoperatively was not part of the study protocol (CST1571-BDE43, NCT00112632). Median follow-up is 36 months in 39 patients. Results: From 7/2005 to 10/ 2009, 41 patients (16f, 25 m, mean age 54 yrs) were recruited to the trial with an average tumor size of 10.8 cm. One patient died from myocardial infarction 3 weeks after start of treatment, all other patients completed the protocol. In two patients dose reduction/interruption due to toxicity was required. 34/41 patients underwent resection of the tumor after a median of 200 d (range 57-394), while two patients had to be operated early due to disease progression. R0 resections were performed in 30/34 patients, two patients showed M1 disease at resection. Five patients showed developed progression postop., resulting in a PFS rate at 3 years of 85.2%. No patient has died so far from the disease. Conclusions: Neoadjuvant treatment with imatinib for six months is a safe treatment in patients with locally advanced disease. The extent of the operation can be significantly downsized after pretreatment. Despite the fact that no adjuvant treatment was foreseen, the progression-free rate at 3 years postoperatively is promising.
Phase I trial of panobinostat (P) and imatinib (IM) in patients with treatment-refractory gastrointestinal stromal tumors (GIST).
Authors: Bauer Sebastian , Hilger Ralf A. , Grabellus Florian , Nagarajah James , Hoiczyk Mathias , Reichardt Annette , Ahrens Marit , Pink Daniel , Mühlenberg Thomas , Scheulen Max E. , Schuler Martin H. , Reichardt Peter 
Published: March 2020

10032^ Background: Panobinostat (LBH589; P) is a pan-deacetylase-inhibitor that has preclinical activity in combination with IM in GIST models in vitro and in vivo. Aim of this study was to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of escalating doses of P in combination with IM in patients with GIST who have failed IM and sunitinib treatment. Methods: This was a two-center phase I study using a 3+3 design with a prespecified expansion of the MTD cohort. IM was administered at a dose of 400mg qd. Following a 7 day run-in phase, escalating doses of P were added. The starting dose for P was 20 mg given as a three-times-per-week (MWF schedule) oral dose for 3 out of 4 weeks. Doses were increased by 10 mg if no dose limiting toxicities emerged. Blood samples were drawn for PK and biomarker assessments of IM, its main metabolite N-desmethyl-IM, and P using a validated RP-HPLC method. Acetylation of histone A3 was evaluated in peripheral blood mononuclear cells (PBMNC) as pharmacodynamic marker for P activity. Metabolic response using PET (EORTC-PET study criteria) was assessed on day 7 of IM run-in and after 3 weeks of combined treatment with IM and P. Results: In total 12 extensively pretreated (median 5 pretreatments) pts (4 f, 8 m; median age 56 y, 34-75 y) received study treatment at 2 dose levels (DL). 2 dose-limiting toxicities (grade 4 thrombocytopenia) occurred at DL 2 (30 mg). Most common AEs were thrombocytopenia, anemia, fatigue, nausea, emesis, diarrhea, creatinine elevation, abdominal cramping, and weight loss. DL 1 (20mg) was declared MTD, and 5 additional pts were enrolled at DL1. Analysis of P and IM PK revealed mean peak concentration of 14.8 +/- 9.5 ng/ml for P (20 mg). IM plasma concentrations with 400 mg once-daily administration were 2.8 ± 1.1 μg/mL at peak and 1.2 ± 0.4 μg/mL at trough. Histone A3 acetylation was demonstrated in PBMNC from pts treated at DL 1. 11 pts were evaluable for PET response: 1 had mPR, 7 had mSD and 3 had mPD. Longest treatment duration was 17 weeks (median: 6wks). Conclusions: P in combination with IM is moderately tolerated. Evidence of target inhibition at the MTD was associated with limited clinical activity in heavily pretreated pts with GIST.
Analysis of a neoadjuvant regimen with a fixed dose of doxorubicin followed by a 10-day course of 27 Gy radiation in the treatment of soft tissue sarcoma (STS) of the extremity/trunk.
Authors: Mathews John , Maale Gerhard , Schwarz Donald E. , Strauss James Fredric , Feldman Mark , Posada Juan G. , Bhat Ashwini 
Published: March 2020

10037 Background: Local tumor control and preservation of limb function are major goals of treatment of STS. With current standard of combining limb-sparing surgery and 5-6 weeks of neoadjuvant or adjuvant 50-65 Gy radiation, reducing local recurrence has been a challenge with rates of 15-30%. Eilber et al. (Cancer Treatment Symposia 1985; 3:49-57) used a fixed daily dose of doxorubicin for three days with radiation of 35Gy. This yielded a 5% local recurrence, while wound complication rate was 35 %. We reduced the radiation dose to lower the wound complications rate. We report a cohort of patients treated in this manner at our institution. Methods: After a baseline echocardiogram, patients received a radiosensitizing dose of intravenous doxorubicin (30mg/day) for 3 consecutive days, then radiation with 2.7 Gy in 10 fractions, followed by limb sparing surgery. After IRB approval, we retrospectively analyzed records of 191 patients during the treatment period from 1991 to 2010. Data extracted included local tumor recurrences and wound complications defined as non-healed wound at 1 month, number of limb salvage surgeries and involvement of surgical margins. Results: Of the 191 patients, median age was 53 (range, 13-89). Stages at presentation included I, II, III and IV, with 2%, 33%, 61%, 4% respectively. The median follow up was 5 years. Of the 24 types of sarcomas treated, pleomorphic sarcoma was the most common at 21%. The local recurrence rate was 5% (95% CI, 2.7-8.6%) and local wound complications were 21% (95% CI, 15-28%). Most (172 or 90%) of patients were able to undergo limb salvage surgery while 19 (10%) required amputation. Of the 172 patients that had limb salvage, 97% (95% CI, 93-98%) had wide surgical margins, three had < 2 cm margins and two had involved margins. Conclusions: To our knowledge, this is the largest study showing that this short two week course of chemoradiation is effective in achieving high rate of local control, acceptable wound complication rate, wide surgical margins and limb salvage in the treatment of STS. Randomized trials are warranted to confirm results.
Early response to neoadjuvant chemotherapy (NAC) in combination with regional hyperthermia (RHT) to predict long-term survival for adult-type high-risk soft tissue sarcoma (HR-STS): Results of the EORTC-ESHO intergroup phase III study.
Authors: Issels Rolf D. , Kampmann Eric , Lindner Lars , Dieterle Nelli , Mansmann Ulrich Robert , Verweij Jaap , Kirchner Thomas , Wendtner Clemens Martin , Wessalowski Ruediger 
Published: March 2020

10054 Background: A randomized phase III completed trial showed that RHT added to NAC was beneficial in terms of local progression-free (LPFS), and disease-free (DFS) survival. Overall survival (OS) was improved in patients (pts) who completed the preoperative induction therapy with RHT (Lancet Oncol 2010). Here we analyzed both the radiographic (RR) and histopathologic (HR) response as early predictors for survival. Methods: 341 pts were randomized to receive 4 cycles of NAC + RHT (169 pts) or NAC alone (172 pts) as induction therapy. RR (CR/PR vs NC/PD) and HR (>75% vs <75% necrosis) were used to define responder vs non-responder. Predictive impact of response on LPFS, DFS, DDFS (distant disease-free survival) and OS was evaluated by intention-to-treat using Kaplan-Meier estimates and the log-rank test. Stratified (surgery before study entry yes/no; extremity vs non-extremity tumors) multivariate analyses were carried out by Cox regression. Results: Early response in pts with measurable disease was performed in 238 pts (103 pts not evaluable because of surgery before study entry). In the NAC+RHT group (114 pts) response rate was 49.1% (56 responders: RR: 18; HR: 22; RR + HR: 16) and substantially higher (p<0.001) compared to the NAC alone group (124 pts) which was 26,6% (33 responders: RR: 7; HR: 17; RR + HR: 9). In the NAC + RHT group, tumor response was associated with improved DFS (HR 0.58 CI 0.36-0.95; p=0.031) and OS (HR 0.50 CI 0.27-0.90; p=0.020) but not LPFS (HR 0.91 CI 0.49-1.71; p=0.78). For responders, OS median time was > 120 months vs 33 months for non-responders. For the entire NAC + RHT group (169 pts, including pts with surgery before study entry) response remained predictive for better OS (HR 0.54 CI 0.32-0.94; p=0.028) and was also associated with better DDFS (HR 0.47 CI 0.27-0.83; p=0.009). Conclusions: Adding RHT to NAC as induction therapy compared to NAC alone leads to significantly higher early response in almost half of the pts classified as responders which translates in better OS and prevention of distant metastases.
Targeting the androgen receptor (AR) in women with AR+ ER-/PR- metastatic breast cancer (MBC).
Authors: Gucalp Ayca , Tolaney Sara M. , Isakoff Steven J. , Ingle James N. , Liu Minetta C. , Carey Lisa A. , Blackwell Kimberly L. , Rugo Hope S. , Nabell Lisle , Forero-Torres Andres , Stearns Vered , Momen Lamia , Gonzalez Joseph , Giri Dilip D. , Patil Sujata , Feigin Kimberly , Hudis Clifford , Traina Tiffany A. ,   Translational Breast Cancer Research Consortium (TBCRC)
Published: March 2020

1006 Background: Patients (pts) with ER-/PR- MBC do not benefit from endocrine treatment (tx). Doane et al (Oncogene 2006;25:3994) described a subset of ER-/PR- BC with a gene expression profile similar to ER+ BC but characterized by AR expression and AR-dependent growth in vitro. Hence, we conducted a multicenter phase II trial (NCT00468715) of the AR antagonist, bicalutamide (B) for pts with AR+ ER-/PR- MBC. Methods: Pts with ER-/PR- (IHC <10%) MBC were consented to AR testing, confirmed centrally at MSKCC. If AR+ (DAKO IHC ≥10%), pts were eligible for tx if ECOG performance status (PS) <2 and normal organ function. No limit on prior tx except prior trastuzumab required if HER2+. Eligible AR+ pts who consented to tx received B 150mg orally daily in 28-day cycles (C). Toxicity assessed q4wks, response q12wks. Primary endpoint = clinical benefit rate (CBR): CR + PR + stable disease (ds) >6mo (SD). B would be considered worthy of further study if ≥4/28 pts have clinical benefit. Results: As of 12/21/11,436 pts consented for AR testing. 24 were ineligible, 12 await testing. 47/400 tested were AR+ (12%). 26 received tx with B (6 ineligible for tx, 15 are eligible for tx with B at progression (POD) if clinically appropriate and study slots remains). Two AR+ pts treated with B were ER+ and removed from study. Three have received tx <12wks. Treated pt characteristics (n=24): median(med)age 64 (41-83), PS 0 (0-1), HER2+ 1, visceral metastases 17. Prior chemotherapy: neo/adjuvant 16; med # regimens for MBC 1 (0-8). Med C# 3 (2-49+). Best response: (21 evaluable pts): CBR 19% (95% CI 5-42%), SD>6mo 4, CR/PR 0, SD<6mo 3, POD 14. Conclusions: ~12% of ER-/PR- MBC pts are AR+. For these pts, AR-inhibition with B is feasible, well tolerated, and has activity based on pre-specified criteria. This study has closed to accrual for AR testing as of 1/2012. These results of the primary endpoint are not expected to change by accrual of the 2 remaining pts. Supported by TBCRC/Breast Cancer Alliance/AstraZeneca. [Table: see text]