bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor immunotherapy targeting WT1 (Wilms’ tumor gene) peptide for bone and soft-tissue sarcomas: A preliminary report
Authors: Ueda T. , Kakunaga S. , Oka Y. , Oji Y. , Tsuboi A. , Hashimoto N. , Myoui A. , Aozasa K. , Sugiyama H. , Yoshikawa H. 
Published: March 2020

10042 Background: WT1 (Wilms’ tumor gene) is originally isolated as a tumor-suppressor gene in a subset of Wilms’ tumors, however, recent studies have indicated its oncogenic activity in various types of cancers, and demonstrated that WT1-specific cytotoxic T lymphocytes specifically kill WT1-expressing cancer cells, thus WT1 protein can be a molecular target for cancer immunotherapy as an attractive tumor rejection antigen. However, WT1 expression in human bone and soft-tissue sarcomas has been poorly understood. Methods: 1) The expression levels of WT1 gene were examined in 36 cases of various types of human bone and soft-tissue sarcomas using quantitative RT-PCR method. They included 12 MFH (11 soft-tissue, 1 bone), 9 osteosarcomas, 6 synovial sarcomas, 4 myxoid liposarcomas, 3 MPNST, one each case of angiosarcoma and clear cell sarcoma. 2) Then, we conducted a phase I/II clinical trial of tumor-specific immunotherapy targeting WT1 peptide for various kinds of cancers including 12 patients with locally advanced and/or metastatic sarcoma (bone 2, soft-tissue 10) which showed WT1 expression and HLA -A*2402. Patients were intracutaneously injected with 3.0mg of HLA- A*2402-restricted natural/or modified 9-mer WT1 peptide emulsified with Montanide ISA51 adjuvant weekly. After 12-times injection, clinical response was evaluated by RECIST. Results: 1) 28 (78%) out of 36 cases of various types of bone and soft-tissue sarcomas overexpressed the WT1 gene, and its expression at the protein level was confirmed by immunohistochemical analysis, suggesting a possibility of immunotherapy using WT1 peptide vaccine for sarcomas. 2) The clinical responses included 4 SD and 7 PD with a case of long-standing SD over 1.5 years. One patient discontinued treatment with patient's decision. There were no patients with objective response (PR/CR). Conclusion: The present preliminary study suggested that tumor immunotherapy using WT1 peptide vaccine can be a new treatment strategy for patients with bone and soft-tissue sarcomas. No significant financial relationships to disclose.
Efficacy and safety of adjuvant post-surgical therapy with imatinib in patients with high risk of relapsing GIST
Authors: Zhan W. H. ,   China Gastrointestinal Cooperative Group
Published: March 2020

10045 Background: GIST has a high recurrenc e rate and disease-related mortality even after completed resection of primary tumor. Imatinib(IM) has shown tremendous efficacy in treating patients with metastatic and unresectable GISTs. The primary objective of the study was to evaluate the efficacy and safety of adjuvant post-surgical therapy with IM in GIST patients who had high risk to relapse. Methods: This prospective, open-label, multi-center trial was conducted in 16 hospitals in China. Patient eligibility criteria included patients >18 years old, diagnosed with CD117+ GIST of either =5cm macroscopic tumor size or = 5/50 HPF in mitosis count pathologically. Patients were started on IM 400mg/d for at least 12 months within 4 weeks after completed resection. Primary endpoint was relapse or metastasis rates. Secondary endpoints were disease free survival (DFS), overall survival rate (OSR) and quality of life. From Aug 16 2004 to Sep 13 2005, 57 patients (34 men) enrolled in the trial and average age of patients was 50.6. The primary tumor location was stomach in 50.9%, small intestine in 38.6%. Tumors size was >5cm in 92.9% of patients, and 73.7% of patients had a mitosis count over 5/50 HPF. The majority of patients tested positive for CD34 (82.5%) and negative SMA, S-100 and Desmin results. Results: Of 57 patients, as of date of data cut-off (Dec 31, 2006) 51 patients were included in the ITT analysis and 43 patients (75.4%) finished at least 12 months of IM treatment, and Tumor relapses or metastasis were identified in 2 patients (3.92%) 350 and 680 days post-operation. No death was reported. Median DFS was 385 days. 57.89% of the safety population had adverse events. No serious adverse event reported. 50.88% of the safety population had adverse events related to the treatment of IM based on the determination of investigators. The score in quality of life showed no statistically significant difference between the baseline and the follow-up visits. Conclusions: IM is a promising adjuvant post-surgical therapy in patients with high risk of relapsing GIST. But the optimal doses and duration of adjuvant treatment are still unknown. On the basis of this study, a multi-institutional randomized controlled trial will be necessary. No significant financial relationships to disclose.
Verification of imatiNib cost-effectiveness in advanced gastrointestinal stromal tumor in British Columbia (VINCE)
Authors: Mabasa V. , Taylor S. C. , Chu C. C. , Moravan V. , Peacock S. , Knowling M. 
Published: March 2020

10049 Background: To evaluate the cost-effectiveness of imatinib in British Columbia Cancer Agency (BCCA) patients with advanced gastrointestinal stromal tumors (GIST) in terms of median overall survival (OS) and median progression-free survival (PFS). Results were also compared to imatinib literature reports. Methods: A pragmatic, retrospective medical record review identified BCCA patients with advanced GIST who received imatinib or historical treatment during successive, pre-specified time periods. Data was collected on survival, duration of therapy, progression free status, and cost of drug, labour and supplies. Primary outcome was the cost-effectiveness of imatinib based on median-OS (Kaplan Meier method). Secondary outcomes were cost-effectiveness based on median overall-PFS, cost of therapy per patient, 1-year OS, and 1-year PFS. This study was conducted from the perspective of the BCCA. Sensitivity analyses varying effectiveness over the 95% CI, cost over the range of treatment duration, discounting level at 0, 3 and 5%, and comparing effectiveness to literature controls were performed. Life expectancy (mean survival), was also calculated and used in the CE sensitivity analysis. Results: Forty-six and 47 patients in the imatinib and historical groups respectively were analyzed. Median-OS in the imatinib group was 66.7 months (95% CI 61.7, infinity) compared to 7.7 months (95% CI 6.0, 12.6) in the historical group. Median-PFS was 45.3 months (95% CI 24.4, infinity) and 5.6 months (95% CI 3.5, 8.5) respectively. The 1-year OS and 1-year PFS for the imatinib group was 95.4% (95% CI 82.9, 99.2) and 81.4% (95% CI 66.1, 91.1) compared to 32.6% (95% CI 20.0, 48.1) and 17.4% (95% CI 8.3 - 32.0) in the historical group. No difference was seen between the imatinib study results and literature reports. The annual incremental cost-effectiveness ratio was $15,882 per median life year gained and $23,603 per median year of PFS for imatinib. Conclusions: Imatinib for advanced GIST is a cost- effective treatment in BC. Results were robust across the range of sensitivity analyses performed. No significant financial relationships to disclose.
Evaluation of imatinib mesylate (IM) in patients with large volume gastrointestinal stromal tumors (GISTs)
Authors: Byrd D. M. , Demetri G. D. , Joensuu H. , von Mehren M. , Heinrich M. , Eisenberg B. , Fletcher J. , Corless C. , Fletcher C. , Heintz D. , Blanke C. D. 
Published: March 2020

10054 Background: GIST size is one of the most important prognostic markers for recurrence and poor survival. However, little information exists regarding the relationship between tumor volume and clinical outcome after treatment with IM. A phase II randomized clinical trial of two dose levels of IM (400 vs. 600 mg daily) in pts with incurable GIST was previously presented (Proc ASCO 2001; Combined GI Symp 2004 and 2007). With median follow-up of 64 months, we report additional analyses of the relationship between tumor volume and IM efficacy. Methods: Data on initial tumor bulk were prospectively collected, and 146 pts were separated into quartiles according to total tumor volume: < 39.1 cm2 (n=36), 39.1 = 102.16 cm2 (n=37), 102.16 = 262.6 cm2 (n=36), = 262.6 cm2 (n=37). Tumor bulk was correlated with standard efficacy outcomes. Results: The overall response rate (CR + PR) for all pts was 68.1% (95% CI 59.8% - 75.5%). Median time-to-progression (TTP) was 24 months, and overall survival (OS) was 57 months. The overall response rates for the four quartiles according to tumor burden (lowest to highest) were: 64%, 70%, 75%, and 65% respectively. Median TTP by quartile was: 57, 25, 18, and 17 months. Median OS for these same groups: not reached, 57, 47, and 35 months. The Kaplan-Meier estimates of patients alive at 64 months based on tumor bulk were 62%, 40%, 44%, and 31% respectively. Disease bulk was an independent prognostic factor for overall survival using a Cox regression model including sex, performance status, IM dose, gender, age, prior chemotherapy, and tumor volume, but not when baseline hemoglobin was included. Conclusions: Pts with bulky GISTs progress sooner and die more quickly than those with lesser tumor volumes, though other factors may contribute as well. Even pts with the bulkiest tumors frequently respond to treatment with IM, however. TTP for this population approaches 1.5 yrs, and median survival for these pts approximates 3 yrs. One-third of pts with extraordinarily bulky GISTs are long-term survivors. The potential relationship between baseline hemoglobin and tumor bulk requires further investigation. [Table: see text]
Phase III trial of ixabepilone plus capecitabine compared to capecitabine alone in patients with metastatic breast cancer (MBC) previously treated or resistant to an anthracycline and resistant to taxanes
Authors: Vahdat L. T. , Thomas E. , Li R. , Jassem J. , Gomez H. , Chung H. , Peck R. , Mukhopadhyay P. , Klimovsky J. , Roché H. 
Published: March 2020

1006 Background: Patients with MBC who have progressed after anthracyclines and taxanes have limited treatment options. Ixabepilone, a novel epothilone B analog, is active in resistant breast cancer. Methods: In this large multinational phase III trial, patients with MBC who were anthracycline pretreated and met predefined resistance criteria to taxanes were randomized to ixabepilone (40mg/m2 IV over 3h Q3w) + capecitabine (1,000mg/m2 PO BID Q14d) or capecitabine (1,250mg/m2 PO BID Q14d). The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), safety, and overall survival (available after 2007). Response and progression were assessed by an independent review committee (IRC) and the investigators (INV). Results: 752 patients were randomized. Median age was 53; 84% had visceral disease, 48% and 43% had 1 and =2 prior metastatic regimens. Median of 5 and 4 cycles of ixabepilone + capecitabine and capecitabine were administered. Ixabepilone + capecitabine was superior to capecitabine. Significant benefit was consistently maintained across predefined subgroups, including HER2-/ER- /PR- and HER2+. *Primary analysis of PFS; hazard ratio= 0.75. Grade (G) 3/4 adverse events included neuropathy (ixabepilone + capecitabine 23% vs capecitabine 0%), hand-foot syndrome (18% vs 17%), and fatigue (9% vs 3%). Neuropathy was cumulative and reversible (median time to resolution of G3/4 to baseline/G1 was 6 weeks). G3 and 4 neutropenia were reported in 32% and 36% vs 9% and 2%, respectively; febrile neutropenia was 5% with ixabepilone + capecitabine. Toxic death rate was 3% vs 1%. Patients with liver dysfunction were at greater risk. Conclusions: Ixabepilone + capecitabine has superior efficacy to capecitabine across endpoints and has a manageable safety profile in this heavily pretreated population. It offers a new potential option for patients with MBC. [Table: see text] No significant financial relationships to disclose.
Analysis of toxicity in a phase II study of sorafenib in soft tissue sarcoma (STS)
Authors: Keohan M. , D'Adamo D. , Qin L. , Saulle M. , Caltieri L. , Schuetze S. , Wright J. J. , Schwartz G. , Maki R. 
Published: March 2020

10061 Background: Sorafenib (BAY 43–9006) is an oral multi-targeted kinase inhibitor. Sorafenib causes dermatologic toxicity and hypertension, although the mechanisms are poorly understood. We observed significant toxicity requiring dose reductions in our phase II study of sorafenib in STS. Methods: 120 patients (40 M, 80 F; median age, 55 years) were treated between 10/05 and 12/06; accrual continues. All patients initially received sorafenib 400 mg BID. 118/120 registered patients were evaluable for toxicity. Clinical and laboratory variables were analyzed for association with dose reduction, using Kruskal-Wallis rank sum test for continuous variables and Fisher exact test for categorical variables. Variables significant at the p=0.05 level were further analyzed with a multivariate logistic regression model for their effects on dose reduction. Results: 53% of patients (63/118) required dose reductions, 53/63 for grade 2 or greater skin toxicity. Most common grade 3–4 drug-related toxicities included lymphopenia (14%), rash (12%), and hand-foot skin reaction (10%). Sex, height, weight, BSA and serum creatinine (Cr) were significantly associated with dose reduction by univariate analysis. Adjusting for sex and/or low serum Cr, BSA was not significantly associated with dose reduction. Sex and low serum Cr were borderline statistically significant predictors of dose reductions when both variables were included in a multivariate model. Only female sex remained a significant predictor when eliminating one outlier with BSA 2.83 (p=0.04). Conclusions: Female gender appears associated with skin toxicity, requiring dose reductions. Based on this multivariate analysis, a starting dose of 400 mg oral daily in women may limit side effects. Correlation with trough serum sorafenib levels is pending. This study is funded in part by NCI Grant P01-CA47179. No significant financial relationships to disclose.
Imatinib for the treatment of aggressive fibromatosis/desmoid tumors (AF/DT) failing local treatment: updated outcome and predictive factors for progression free survival. A FNCLCC French Sarcoma Group-GETO study
Authors: Fayette J. , Dufresne A. , Penel N. , Le Cesne A. , Bui Nguyen B. , Tubiana-Hulin M. , Guillemet C. , Chabaud S. , Jimenez M. , Blay J. Y. 
Published: March 2020

10062 Background: The optimal treatment of AF/DT failing local treatments is not defined. We report long term results and predictive factors for response to imatinib in AF/DT. Methods: Pts =18 years with advanced AF/DT from all sites in whom neither curative surgery nor radiotherapy (RT) was possible were eligible. Imatinib was given at the dose of 400mg/d (and increased to 800 mg/d if progression) during 1 year then stopped. Primary endpoint was the progression free at 3 months. A two stages Simon‘s optimal design was used with p0=10%, p1=30%, a=0.05 and 90% power (18 pts first stage, total of 35 evaluable pts). Predictive factors were investigated using tissue-microarrays (TMA) and KIT mutation analysis. Results: Between 09/2004 and 10/2005, 40 pts were included in 15 centers. Median age was 40 (range 20–72) with 30% males. Primary sites were extra abdominal, mesenteric, and abdominal wall in 69, 18, and 13% of pts respectively. 23% had received RT. Prior systemic treatments were: NSAID, hormonotherapy or chemotherapy (CT) in 33%, 45% and 20% of pts respectively. Median treatment duration of imatinib is 9 months (range 0.8–13.8). G4 and G3 toxicities were notified in 0 and 17 patients (42.5%) respectively: rash (4 pts), abdominal pain (3 pts), and vomiting (3 pts). 38 pts (95%) are evaluable at 3 months, with 1 (3%) CR, 3 (8%) RP, 31 (82%) SD and 3 (8%) PD. With a median follow-up of 13.8 months, 13 of the 40 pts had progressed. PFS at one year is 71% and 1 patient died (PD). 8 patients received an increased dose of imatinib upon progression under a 400mg/d dose: 3 reprogressed and 5 achieved tumor stabilization during 5+, 6+, 8+ months. PFS was correlated to weight or to previous CT, but not to gender, Gardner, age, PS, size, site. Using TMA, the expression of PDGFR β and a β catenin, E-cadherine, cyclinD1, M-CSFR, estrogen receptor β, ERK, phospho-Akt-Ser473, phospho-MEK1–2 were investigated. None of the CycD1+ tumors have progressed so far. 3 mutations of KIT exon 10 were detected in 10 patients tested. All achieved tumor control. Conclusions: Imatinib induces prolonged disease stabilization in the majority of evaluable patients with AF/DT. Prognostic factors were identified. [Table: see text]
A multivariate analysis of a series of 382 primary retroperitoneal sarcomas (RPS)
Authors: Rivoire M. , Bonvalot S. , Castaing M. , Stoeckle E. , Laplanche A. , Le Cesne A. ,   French Association of Surgery
Published: March 2020

10065 Background: A national retrospective study was conducted by the French Association of Surgery on primary RPS in order to define the best type of surgery and determine prognostic factors for abdominal recurrence and patient survival. There is still no consensus concerning the precise value of the extent of surgery and additional treatment modalities. Methods: Types of surgery were classified as: “systematic complete resection”, which is a systematic or partial resection of non-involved contiguous organs to achieve wide margins, “contiguously involved organ resection” and “simple complete resection”, a resection of the tumor with grossly negative margins. Survival was determined with the Kaplan-Meier method. Univariate and multivariate prognostic analyses were performed using logrank test and Cox model. Results: Data of 382 pts operated between 1985 and 2005 were retrospectively reviewed. Median age was 57 years (range 14–87). Median tumor size was 18 cm. Systematic complete resection, contiguously involved organ resection and simple complete resection were performed for 134 (35%), 153 (40%) and 87 (23%) pts, respectively. Eight pts (2%) had a biopsy without resection and 45 pts (12%) had macroscopic residual disease. Tumor was spilled during surgery for 76 pts (20%). Systematic complete resection and no spilling of the tumor were highly correlated with the number of pts operated by center (p-values <10-4). Histologic negative margins (136 pts, 36%) were highly correlated with systematic complete resection (p-value <10-4). Chemotherapy and radiotherapy were given to 135 (35%) and 122 pts (32%). Median survival was 6 years whereas median time to abdominal recurrence and metastasis were 4 and 15 years, respectively. On multivariate analysis, pre op biopsy, low grade, no spilling of the tumor, negative margins and number of pts operated by center were the significant factors predicting abdominal recurrence control whereas low grade, no spilling of the tumor and no macroscopic residual disease significantly predicted better overall survival. Conclusions: Tumor grade and quality of surgery were the two main prognostic factors for abdominal recurrence and overall survival. Surgical experience of these rare tumors and systematic complete resection decreased abdominal recurrence rate. No significant financial relationships to disclose.
The actin-bundling motility protein fascin and vascular endothelial growth factor (VEGF) are universally over-expressed in human angiosarcoma
Authors: Dim D. , Ravi V. , Tan J. , Hicks D. , Wong M. 
Published: March 2020

10068 Background: Angiosarcoma is a highly aggressive soft tissue malignancy with a dismal progression-free survival (PFS). Treatment options for disseminated disease are limited and present systemic therapies have not shown evidence of prolonging overall survival. In this regard, a greater understanding of the molecular and cellular basis of the tumor phenotype of this uncommon malignancy and how these features correlate to clinical behavior would be an important step towards identifying potential new molecular targets for therapy. Our previous work show that acquisition of the chemotherapy-resistant phenotype by angiosarcoma cells occurs concomitantly with a marked increase in cell motility and VEGF expression. Increased expression of the angiogenic factor VEGF and the motility protein fascin have been associated with more aggressive clinical course in a number of other tumor types and may play a direct role in the biologic behavior of these malignancies. Therefore, in the current study, we sought to characterize angiosarcoma by immunohistochemistry for the expression of VEGF and fascin, and compared the staining pattern to benign vascular tumors. Methods: 20 cases of angiosarcoma, and 5 cases of hemangioma were stained for tumor cell expression of VEGF and fascin using anti-VEGF polyclonal antibody (clone A-20, 1:50, Santa Cruz Biotechnology, Santa Cruz, CA) and antibody to fascin (clone 55K-2, 1:500, DakoCytomation, Carpinteria, CA). Results: Surprisingly, every case of angiosarcoma showed high expression for both VEGF and fascin with moderate to strong staining intensity in 75 to 100% of the tumor cells for each case. By comparison, both proteins were either absent or only weakly positive in hemangiomas. Conclusions: In the current study we found high levels of VEGF and fascin universally expressed in angiosarcomas, which was not the case for benign vascular tumors. These factors maybe part of the malignant phenotype for these tumors and contribute to an aggressive clinical course through enhanced cell motility and autocrine/paracrine signaling. Additional study will be needed to better define a role for these proteins in angiosarcoma and to determine if they might represent potential new molecular targets for therapy. No significant financial relationships to disclose.
Extra-abdominal fibromatosis: Can aggressive management be avoided in a subgroup of patients?
Authors: Bonvalot S. , Eldweny H. , Haddad V. , Missenard G. , Vanel D. , Terrier P. , Oberlin O. , Le Cesne A. , Le Péchoux C. 
Published: March 2020

10077 Background: The objective was to evaluate the impact of surgery as first-line treatment on event -free survival (EFS) of primary aggressive fibromatosis. Methods: Treatments were categorized into: surgery with or without radiotherapy and non surgical strategies with systemic treatment alone or wait and see policy. Event-free survival curves were estimated using the Kaplan-Meier method. Results: The sex ratio was 39 males/73 females. The median age at the time of the first diagnosis was 30 years. The median size of the primary was 60 mm. Eighty-nine patients (79.5%) had initial resection of their primary tumor followed by postoperative radiotherapy in 13 cases. Twenty-three patients (20.5%) did not undergo surgery but received systemic treatment or watch and wait policy. Median follow-up was 76 months. Three years EFS was 49%. In the univariate analysis, patients with microscopically complete surgery had a similar outcome to that of patients in the non-surgery group (65% vs 68% for 3-yr EFS respectively). Gender, age, tumor size, treatment period and strategy (surgery versus no surgery) were not statistically significant. Quality of resection according to margins and the tumor site were the only prognostic factors. There was a significant correlation between the tumor site and the quality of surgery (p= 0.0002). Tumor site was the only prognostic factor that remained in the multivariate analysis. Conclusions: Surgical removal as initial treatment was not found to influence the outcome. A subset of patients could be managed with a non aggressive policy. When surgery is finally necessary, it should be performed with the aim of achieving negative margins. Predictive biological factors influencing tumor evolution have to be defined No significant financial relationships to disclose.