bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective web-based collection of sarcoma cases diagnosed and treated in France: Experience of the NetSarc network of the French Sarcoma Tumor Boards.
Authors: Ducimetiere Francoise , Blay Jean-Yves , Le Cesne Axel , Bui Nguyen Binh , Penel Nicolas , Bompas Emmanuelle , Gouin Francois , Duffaud Florence , Coindre Jean-Michel , Rios Maria , Chevreau Christine , Kurtz Jean-Emmanuel , Isambert Nicolas , Anract Philippe , Piperno-Neumann Sophie , Bertucci François , Kerbrat Pierre , Guillemet Cecile , Lebbe Celeste , Ray-Coquard Isabelle ,   on behalf of the NetSarc Network
Published: March 2020

10056 Background: The management of sarcomas, as for all rare tumors, is hampered by the limited dissemination of medical knowledge. Management within a specialized multidisciplinary sarcoma tumor board (STB) improves compliance to clinical practice guidelines. Since 2010, a national network with a dedicated system for referral, gathering the 26 regional STBs, is supported by the French NCI. Its objectives are to monitor the management of sarcomas and give equal access to expertise and innovative treatments to all patients with sarcoma. We report here the first experience of a web-based data collection from these STBs. Methods: The expected incidence of sarcoma in France is 6.1/105/year, ie 4000 new cases per year. A website collecting all files discussed in the 26 STBs was generated from Jan 2010 ( www.netsarc.org ). The prospective collection of clinical data, STB decision and patient follow-up was implemented in the national database (40 items). Results: 7472 patients were accrued during 2 years, 6202 (83%) had sarcoma, 2860 (46%) were new cases, representing 36% of expected incident cases. The number of new cases discussed in STB increased between 2010 and 2011 (+38%). Patients were referred to the STB (2010-2011; % of cases) prior 1) to biopsy (9%-15%), 2) to first surgery (34%-39%), 3) to adjuvant treatment (35%-34%), after treatment (14%-8%) and at time of relapse (8%-4%). 15% had a metastases at initial diagnosis. The R0+R1 resection rates for primary surgery were 55% vs 42% within vs outside the STB centers of NetSarc. 8% of declared patients were proposed to inclusion into a clinical trial. Conclusions: This web-based tool enabled the description of the activity of the STB at the national level. Clinical practices improved between 2010 and 2011, but 64% of new cases of sarcoma were not discussed in the referent STB prior to surgery. The yearly follow-up of the database will help to monitor evolution of clinical practices.
Neoadjuvant chemoradiotherapy for patients with high-risk extremity and truncal sarcomas: A 10-year follow-up study.
Authors: Look Hong Nicole Jannelle , Hornicek Francis J , Harmon David C. , Choy Edwin , Chen Yen-Lin , Yoon Sam S. , Nielsen G. Petur , Szymonifka Jackie , Yeap Beow Yong , DeLaney Thomas F. , Mullen John Thomas 
Published: March 2020

10058 Background: Patients with high-risk extremity and truncal soft tissue sarcomas (STS) are at considerable risk for recurrence. A regimen of preoperative mesna, doxorubucin hydrochloride (Adriamycin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT), followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. The goal of this series is to study outcomes of our most recent cohort of patients treated on this regimen. Methods: We retrospectively reviewed records of 55 consecutive patients with STS of the extremity or superficial trunk who completed all phases of treatment at our institution from January 2000–July 2011. Clinicopathologic characteristics and patient outcomes were analyzed. Results: Fifty-five patients were analyzed and had a median age of 53 years (range 18-73). The median tumor size was 10.1cm (range 2.5-35.5 cm). Twenty-seven (49%) and 28 (51%) patients had grade 2 and 3 tumors, respectively. Margins were negative in 49 (89%) patients, and positive in 6 (11%) patients. At a median follow-up of 43 months, there were 7 (13%) locoregional, and 17 (31%) distant recurrences. The local and distant 5-year recurrence-free survival (RFS) rates were 92% and 64%, respectively. The 5-year overall (OS) and disease-specific survival rates were 86% and 89%, respectively. There were no treatment-related deaths or secondary myelodysplasias. There were no significant predictors of OS or RFS. Conclusions: Outcomes of a contemporary cohort of patients with extremity and truncal STS treated with an intense regimen of neoadjuvant chemoradiotherapy and surgery are consistent with previous reports from our institution and better than reports of chemotherapy alone. [Table: see text]
Effect of anti-β1 integrin antibody on lung seeding of osteosarcoma cells in live mice visualized by single-cell in vivo imaging.
Authors: Kimura Hiroaki , Tome Yasunori , Momiyama Masashi , Hayashi Katsuhiro , Bouvet Michael , Tsuchiya Hiroyuki , Hoffman Robert M. 
Published: March 2020

10072 Background: Integrins play a role in tumor growth and metastasis (Int. J. Cancer 129, 2905-2915, 2011). However, the effect of integrin inhibition has not been visualized on single cancer cells in vivo. In this study, we used a powerful subcellular in vivo imaging model to demonstrate how an anti-integrin antibody affects seeding and growth of osteosarcoma cells on the lung. Methods: The 143B human osteosarcoma cell line expressing red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nucleus was established. Using the double-labeled osteosarcoma cells, single cancer-cell seeding in the lung after i.v. injection of osteosarcoma cells was imaged in live mice. Results: The anti-b1 integrin monoclonal antibody, AIIB2, greatly inhibited the seeding of cancer cells on the lung while a control antibody had no effect. To image the efficacy of the anti-integrin antibody on spontaneous metastasis, mice with orthotopically-growing 143B-RFP cells in the tibia were also treated with AIIB2 or control anti-rat IgG1 antibody. After 3 weeks treatment, mice were sacrificed and primary tumors and lung metastases were evaluated with fluorescence imaging. AIIB2 significantly inhibited spontaneous lung metastasis but not primary tumor growth. In a separate experiment, the anti-β1 integrin antibody increased survival in the orthothopic osteosarcoma model. Conclusions: The efficacy of the anti-β1 integrin antibody against metastasis may be due to inhibition of lung seeding of the cancer cells. The increased survival of mice with orthotopically-growing 143B-RFP treated with AIIB2 may be due to inhibition of metastasis, which in turn may be inhibited by effect of the anti-β1 integrin on cancer-cell seeding in the lung.
Association of the genetic variants in the nucleotide excision repair genes XPA and XPC with cisplatin-induced hearing loss in patients with osteosarcoma.
Authors: Hagleitner Melanie M. , Coenen Marieke J.H. , Gelderblom Hans , Hoogerbrugge Peter , Guchelaar Henk-jan , Te Loo Dunja Maroeslea W.M. 
Published: March 2020

10077 Background: Cisplatin is a widely used and effective chemotherapeutic agent in the treatment of osteosarcoma. However, cisplatin-induced ototoxicity is a serious problem, affecting more than 60% of patients and compromising language and cognitive development. Unfortunately, individuals at risk to develop ototoxicity cannot be identified upfront. Genetic variants in genes involved in the metabolism of cisplatin may predispose to cisplatin-induced hearing loss and help to identify patients at risk. Methods: In a candidate gene pathway approach, we selected 224 SNPs in 30 candidate genes related to Platinum-DNA repair pathways and genotyped for a discovery group of 105 patients with osteosarcoma for these variants. Cisplatin-induced ototoxicity (n = 47), defined as the development of grade 2–4 hearing impairment using Common Terminology Criteria for Adverse Events (CTCAE version 3), showing a hearing loss of >25 dB at frequencies of 4–8 kHz, was associated with genetic variation. A replication study was performed in a independent cohort of 51 patients with osteosarcoma. Genotyping was performed using the Illumina GoldenGate assay. Association analysis and meta-analysis were performed using the whole genome association analysis toolset PLINK. Results: In the discovery cohort a total of 13 SNPs were significantly (p value < 0.05) associated with ototoxicity. Upon meta-analysis, addition of the replication set resulted in lower p-values for 2 SNPs. The two SNPs showing a strong association with hearing loss in patients with osteosarcoma were rs2805835 in the gene XPA (p-value 0.01, OR=2.7 (95%CI: 1.20-6.15) and rs2227999 in XPC (p-value 0.02; OR=3.2 (95% CI:1.19-8.80). Conclusions: The Nucleotide Excision Repair (NER) genes XPA and XPC form an important molecular mechanism by which cisplatin DNA adducts can be repaired and it has recently been shown that these genes have a high expression in the cochlea. Our data suggest that genetic variants in these genes, may contribute to cisplatin ototoxicity. This study should be viewed as the first step in the development of genetic markers to predict cisplatin-induced ototoxicity in individual patients.
Quantitative hormone receptors, triple-negative breast cancer (TNBC), and molecular subtypes: A collaborative effort of the BIG-NCI NABCG.
Authors: Cheang Maggie Chon U. , Martin Miguel , Nielsen Torsten O. , Prat Aleix , Rodriguez-Lescure Alvaro , Ruiz Amparo , Chia Stephen K. L. , Shepherd Lois E. , Voduc David , Bernard Philip Seth , Ellis Matthew James , Perou Charles M. , Di Leo Angelo , Carey Lisa A. ,   on behalf of Breast International Group-North American Breast Cancer Group
Published: March 2020

1008 Background: Most TNBC trials focusing on biology of the basal-like subtype (BLBC) allow borderline (1-10% staining) estrogen receptor (ER) and progesterone receptor (PgR) expression by immunohistochemistry (IHC); however the optimal ER and PgR cut points to enrich for non-luminal subtypes has not been studied. In this study,we compared quantitative ER/PgR status with gene expression-based intrinsic subtype in order to determine if borderline cases should be included in TNBC trials. Methods: ER, PgR, and HER2 status was determined by central review of tumors collected from three phase III randomized trials: GEICAM 9906 (n=820), NCIC CTG MA.5 (n=476) and MA.12 (n=398). PAM50 intrinsic subtyping (BLBC, HER2-enriched, Luminal A, Luminal B and Normal-like) was performed using the qRT-PCR-based assay. Quantitative ER/PgR expression by IHC and subtype was tested using ANOVA and Fisher’s exact test. Results: Of 1,694 tumors, 15% were BLBC, 21% HER2-Enriched, 33% Luminal A, 25% Luminal B and 4% Normal-like. BLBC subtypes were significantly associated with low expression of ER and PgR (median = 0.05%) compared to other subtypes (p < 0.001). The vast majority of BLBC (96%) did not express any ER or PgR protein by IHC. BLBC represented 73% of TNBC (borderline cases not included) and significantly more than the additional TNBC with borderline ER/PgR (p < 0.001). Within borderline ER/PgR and HER2-negative cases only, 17% were BLBC and 46% were luminal subtypes (Table). Conclusions: BLBC rarely express ER or PgR by IHC. The majority of borderline TNBC (1-10% ER/PgR) are not BLBC; half of them are categorized as luminal categories that may be endocrine sensitive. TNBC trials seeking to target BLBC tumor biology should use the ASCO/CAP guidelines of 0% as the cutoffs for ER and PgR negativity. [Table: see text]
Explored prognostic factors for survival in patients with advanced GIST treated with standard dose imatinib (IM): Results from the BFR14 phase III trial of the French Sarcoma Group.
Authors: Pérol David , Ray-Coquard Isabelle , Bui Nguyen Binh , Adenis Antoine , Rios Maria , Bertucci François , Duffaud Florence , Cupissol Didier , Chevreau Christine , Bompas Emmanuelle , Domont Julien , Chabaud Sylvie , Blay Jean-Yves , Le Cesne Axel 
Published: March 2020

10092 Background: Factors predicting progression free survival (PFS) and overall survival (OS) of patients (pts) with advanced GIST treated with 400 mg daily dose IM included in the BFR14 study with a median follow up of 54 months (CI95%:47-61) was investigated evaluating added prognostic factors. Methods: 434 pts were included in this prospective multicenter trial from June 2002 to July 2009. After 1, 3 and 5 yrs of IM 400mg/day, pts free from progression were randomly offered to continue or interrupt (I arm) IM. Prognostic factors for overall survival were investigated in the entire cohort (randomized and not randomized pts) included in the BFR14. Survival was defined from the date of inclusion to the date of death for OS or to the first occurrence of disease progression under imatinib or death for PFS. A multivariate cox model including statistical significant baseline characteristics tested in univariate were included in a backward procedure d to identify independent prognostic factors for PFS then OS. Results: As of January 2012, there were 285 progressions (65%) and 161 deaths (37%). The median PFS of the entire cohort was 29 months (CI95%: 24-33) and the 4 and 5-yrs PFS were 31% and 24% respectively. A low tumour volume at inclusion, PS (0), sex (female), CD34 positivity on tumor cells were the four independent prognostic factors of a higher PFS. The 5-yrs OS was 54% (CI95%: 48-60). A higher OS was independently predicted by gender (female), PS (0), platelets count (<400 giga/L) and CD34 expression on GIST cells. Median PFS and OS were slightly superior in this more recent series as compared to B2222 consistently with the improved outcome of patients with low tumor volume. Conclusions: OS and PFS are predicted by gender, PS and CD34 expression in this large series of pts treated with standard dose IM. The biological significance of CD34 expression on tumor cells has to be explored in GIST.
The role of surgical cytoreduction before imatinib therapy in patients with advanced GIST.
Authors: An Hojung , Ryu Min-Hee , Ryoo Baek-Yeol , Sohn Byeong Seok , Kim Ki-Hun , Oh Sung Tae , Yu Chang Sik , Yook Jeong Hwan , Kim Byung Sik , Kang Yoon-Koo 
Published: March 2020

10093 Background: Despite dramatic improvement of survival with introduction of imatinib mesylate, resistance to imatinib eventually develops in most of patients with advanced gastrointestinal stromal tumor (GIST). It is well known that baseline tumor size is an important factor related to imatinib resistance. We hypothesize that decreasing tumor size by surgery before starting imatinib may delay the emergence of resistance and improve prognosis in patients with advanced GIST. Methods: From 2001 to 2010, 102 patients with initially metastatic GIST and 147 patients with recurrent GIST were enrolled in this analysis. Patients with local relapse only were excluded because they were potentially curable by surgery alone. Patients were categorized into two groups according to the extent of cytoreduction; i.e., patients whose initial tumor bulk reduced >75% surgically before starting imatinib (group A) and the others (group B). Results: Among total 249 patients, 62 patients received initial surgery. 35 (14%) patients whose tumor bulk reduced > 75% were categorized into group A, and the remaining 214 (86%) were in group B. In group A, the median age was younger; more patients were initially metastatic; peritoneal metastases were more frequent; but liver metastases were less. The total tumor size was significantly reduced from median 122 mm before cytoreduction to 0 mm after on CT scans in group A. With a median follow-up of 42.7 months, progression-free survival (PFS) tended to be better in group A than in group B in univariate analysis (HR=0.60; 95% CI, 0.36-1.02; p=0.061), but PFS was not statistically different between the two groups in multivariate analysis (p=0.488). Meanwhile, absence of KIT exon 11 mutation (p=0.007), baseline total tumor size > 150mm (p=0.043), and granulocyte count > 5000/mm3 (p=0.009) remained independent poor prognostic factors. Conclusions: Despite marked decrease of total tumor size, the outcomes were not significantly improved in patients receiving initial cytoreduction more than 75% of baseline tumor bulk before starting imatinib. These results suggest that initial cytoreduction does not have beneficial role in advanced GIST, so imatinib should be still the first treatment of choice in this population.
Characteristics of gastrointestinal stromal tumor (GIST) patients receiving short-term versus long-term imatinib (IM) adjuvant therapy: A chart review analysis.
Authors: Guerin Annie , Conley Anthony Paul , Sasane Medha , Gauthier Genevieve , Schwiep Frances , Keir Christopher Hunt , Wu Eric Q. 
Published: March 2020

10094 Background: In clinical practice, significant variability is seen in duration of adjuvant IM use. The objective of this study is to compare characteristics of GIST pts receiving adjuvant IM for a short (6-12 months) vs extended period (≥24 months) to better understand factors that may influence treatment (trt) duration decisions. Methods: Physician prescribing patterns and clinical information on adult pts with primary resectable Kit positive GIST initiating IM ≤84 days post-surgery was collected from 248 U.S. oncologists using online data collection forms. In addition to physicians’ perception of short- vs long-term use, pts’ risk assessment, trt, demographics, and comorbidities were collected for 246 short-term and 395 long-term IM pts. Characteristics were compared using Wilcoxon and Chi-square tests. Results: While pts were similar in age [59.0 vs. 58.1, P =.23], ethnicity, and region of residence, the short-term group included fewer males (57.7% vs 69.6%, P <.01) and had a higher prevalence of cardiovascular (11.4% vs 5.8%, P = .01) and ischemic heart diseases (5.3% vs 1.5%, P<.01). Differences were also observed in indicators of pre-treatment risk profile (tumor size, location, and rupture during surgery, mitotic count, and Miettinen score) (Table). Findings were consistent with main reasons reported by physicians for prescribing adjuvant IM over longer duration; in addition to pt risk profile (76.6%), tolerability (70.6%), younger pts (59.7%), safety (39.1%), trt response (29.8%), and economic reasons (26.2%) were other reasons impacting trt decisions. Conclusions: Pt risk is an important factor in physicians’ decisions to prescribe adjuvant IM for extended duration. However, age, tolerability, and comorbidities, also play an important role. [Table: see text]
Effect of five years of imatinib on cure for patients with advanced GIST: Updated survival results from the prospective randomized phase III BFR14 trial.
Authors: Bertucci François , Ray-Coquard Isabelle Laure , Bui Nguyen Binh , Adenis Antoine , Rios Maria , Duffaud Florence , Cupissol Didier , Chevreau Christine , Bompas Emmanuelle , Domont Julien , Chabaud Sylvie , Pérol David , Blay Jean-Yves , Cesne Axel Le 
Published: March 2020

10095 Background: We previously demonstrated that interruption of imatinib (IM) after 1, 3, and 5 yrs in responding patients (pts) with advanced GIST is associated with rapid relapse but reintroduction of IM allowed tumor control in almost all pts. Here, we examined the outcome of patients randomized in the interruption arm (I arm), and notably the characteristics of those not yet progressing. Methods: This prospective multicenter BFR14 study was initiated in June 2002 and closed for inclusion in July 2009. Seventy-one non-progressing patients were randomized in the I arm after 1 (N=32), 3 (N=25) and 5 years (N=14) of IM 400 mg/day. IM (same dose) was reintroduced in case of progressive disease (PD). Results: The median follow-up (FU) from randomization was 74, 48 and 22 months for pts randomized at 1, 3 and 5 yrs of IM treatment respectively. Updated survival data (January 2012) are summarized in the table. Out of the 3 pts not progressing in the I arm at 1 yr, 1 pt had refused to stop IM and 1 pt had a localized GIST with small residual disease at inclusion. Out of the 3 pts not progressing in the I arm at 3 yrs, 1 pt had refused to stop IM and 2 pts were included after complete resection of both primary tumor and metastases with a small residual disease. The FU of pts randomized at 5 yrs was short but out of the 5 non progressive pts, 2 are considered in PD on functional imaging (January 2012), 2 had a locally advanced GIST subsequently operated during IM and before randomization, and 1 had no target lesion at inclusion (resection of synchronous metastases). Conclusions: All but one pts with residual masses under IM and randomized in the I arm have relapsed. Six out of 7 patients not yet progressing in the I arm had reached complete remission following surgery at inclusion or before randomization (initial resection/debulking of metastases). [Table: see text]
Genome-wide analysis and characterization of an online sarcoma cohort.
Authors: Barnholt Kimberly E , Do Chuong B , Kiefer Amy K , Nelson Marisa , Garber Judy Ellen , Robson Mark E. , Maki Robert G. , Demetri George D. , Wojcicki Anne 
Published: March 2020

10097 Background: Recruitment of an adequately sized cohort for genome-wide studies presents a serious challenge for rare diseases such as sarcoma. Traditional barriers to participation include proximity of clinical centers and motivation or ability to travel. 23andMe’s web-based platform provides increased accessibility to research participation, facilitating rapid recruitment of patients (pts) and enabling a large-scale genome-wide association study (GWAS) of sarcoma. Methods: Sarcoma pts were recruited through web and email campaigns, patient advocacy groups, physician offices, and events. Pts provide IRB-approved consent, complete surveys, and receive updates about research progress through an online account. In collaboration with an uncompensated panel of academic experts, an online survey was developed to collect patient-reported data on diagnosis, family history, symptoms and treatment. Results: This web-based approach has accrued the largest genotyped, recontactable sarcoma cohort to date. In 20 months, 772 sarcoma pts have enrolled, 683 have been genotyped and 611 have provided data online. The cohort is primarily of European ancestry (92%), disproportionately female (72%), with an average age of 51 (± 15 years). More than 88% of pts indicated a soft tissue sarcoma diagnosis, with leiomyosarcoma, liposarcoma and “malignant fibrous histiocytoma” being the most commonly reported subtypes. Over 36% of pts report undergoing active treatment of some type. Association scans were conducted across a set of 8,058,452 imputed SNPs, using 568 unrelated sarcoma cases of European ancestry and >70,000 unrelated population controls from the 23andMe database. Initial results have identified no significant genome-wide associations for general sarcoma risk, despite having >90% power to detect risk variants with >5% minor allele frequency and odds ratio >2.5, suggesting the absence of common variants with strong shared effects across sarcoma subtypes. Conclusions: This pilot study demonstrates feasibility of rapid recruitment and longitudinal engagement of pts through online technology. Such techniques may significantly accelerate, and in some cases fully enable, large-scale genomic studies of sarcoma and other rare diseases.