bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAPK7 gene: A target for multimodal therapies.
Authors: Tesser-Gamba Francine , Petrilli Antonio Sergio , Paniago Mario Del Giudice , Alves Maria Teresa Seixas , Garcia-Filho Reynaldo Jesus , Toledo Silvia R. C. 
Published: March 2020

10533 Background: Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. In a previous work we observed that the overexpression of MAPK7 gene was significantly associated to tumor progression, a poor response to treatment, and worse overall survival, suggesting that MAPK7 could play an important role in osteosarcoma tumorigenesis. This present study investigated if any genomic structural alteration could be related to MAPK7 overexpression in OS samples. Methods: The MAPK7 gene was fully sequenced in 33 OS samples (15 prechemotherapy,15 post-chemotherapy and 3 OS cell lines) using the 3500 Genetic Analyser (Applied Biosystem) and 15 custom primers pairs that amplified overlapping genomic fragments. Results: From the 30 patient samples analyzed, 16 could not be completely sequenced. Samples containing these deleted regions were significantly correlated to clinical and pathologic features of patients with OS. No deletions were observed in patients with the favorable outcome (non-metastatic at diagnosis, >90% degree of necrosis in the surgical specimen and with complete remission at end of treatment). There was no correlation found between deletions and overexpression in pre-chemotherapy, even in patients that after chemotherapy still overexpressed MAPK7. Conclusions: Progress related to improved survival of patients with OS is at a plateau, and the intensification of therapy or incorporation of new therapeutic agents has not been successful, especially in patients metastatic at diagnosis. To our knowledge, no molecular marker for OS that could be related to its development, evolution or progression has been described yet. Based on our findings, we observed that patients who have no genomic deletion of MAPK7 gene respond better to treatment and have a favorable outcome. Studies available to date suggest that a single targeted therapy may not provide clinically significant anti-tumor effects, therefore we believe that specific inhibitors of the MAPK/ERK pathway are emerging as a relevant addition to multimodal therapies.
Does a diagnosis of GIST predict a second primary cancer?
Authors: Smith Myles JF , Mahar Alyson L. , Law Calvin , Ko Yoo-Joung 
Published: March 2020

10537 Background: There have been reports of a high frequency of metachronous cancers in patients diagnosed with GIST. The purpose of this study was to identify and describe patients with GIST who develop second primary cancers, and to calculate standardized incidence ratios (SIRs) to quantify the risk of additional malignancy. Methods: This was a retrospective, population-based cohort study using SEER data. Individuals diagnosed with GIST from 2001-2009 were identified as having a malignant primary tumor in the digestive tract, and included the following sites: C15.0-C26.9; C48.0-48.8; C49.4-49.5; C80.9 and a recorded histology code of 8935 and 8936. This restricted timeframe was imposed to account for changes in the recording of GIST incidence. Individuals with a previous cancer diagnosis or diagnosed post mortem only were excluded. Multiple primary SIRs and 95% confidence intervals (CI) were calculated using SEER*Stat software (V.7.1.0) and compared to general population rates. The SIR was interpreted as an estimate of relative risk (RR). Comparison of characteristics between single and multiple cancer GIST patients was performed using chi-square tests, p-values of <0.05 were considered significant. Results: We identified n=1397 cases of GIST, of which 1291 analyzed. We observed a statistically significant increased incidence of second tumours in patients with a primary GIST (n=78, RR 1.36, 95% CI:1.1-1.7). Older age (p<0.001) and tumor grade (p=0.014) were associated with second primaries, with grade being the only significant variable remaining after logistic regression. In both sexes we observed a significantly increased incidence of kidney cancer (RR 4.3, 95% CI: 1.7-8.9). In females there was a 3 fold higher incidence of colon cancer (RR 2.96 95% CI: 1.2-6.1). Conclusions: Patients with a diagnosis of GIST have a higher incidence of second cancers when compared with standardized incidence in the general population. High grade GISTs were associated with an additional malignancy. Both sexes were observed to have increased incidence of kidney cancer, with females at an increased risk of developing colon cancer. As part of GIST surveillance, screening for colon cancer in females and kidney cancer in both sexes may be considered.
The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST.
Authors: Ryoo Baek-Yeol , Park Seong Joon , Ryu Min-Hee , Sohn Byeong Seok , Kim Hwa Jung , Kim Ki-Hun , Oh Sung Tae , Yu Chang Sik , Yook Jeong Hwan , Kim Byung Sik , Kang Yoon-Koo 
Published: March 2020

10550 Background: Several retrospective studies have suggested that surgical resection of residual lesions could be beneficial if resection was done after disease control (partial response or stable disease) with imatinib in patients with metastatic or recurrent GIST. However, the benefit of surgical resection has not been proven yet compared to imatinib alone. Therefore, we compared the outcomes of surgical resection of residual lesions after imatinib (SI group) with those of imatinib alone (IM group) in patients with metastatic or recurrent GIST controlled with imatinib treatment. Methods: A total of 134 patients with metastatic or recurrent GIST who showed at least 6 months of disease stabilization or response to imatinib were included in this retrospective analysis. Patients were categorized into SI (n=42) or IM (n=92) group. To reduce the selection bias, propensity scores and inverse-probability-weighting (IPTW) adjustment were used in the outcome analysis. Results: Patient and tumor characteristics were statistically similar between SI and IM groups, except median age (51 in SI, 58 in IM, p=0.002), and metastases to peritoneum (12 in SI, 56 in IM, p=0.001). The patients in SI group underwent surgery of residual disease after a median 19.1 months of imatinib treatment (range, 7.2-87.0). With a median follow-up of 58.9 months (range, 15.4-129.1), progression-free survival (PFS) and overall survival (OS) were significantly longer in SI group than in IM group (PFS, 87.7 vs 42.8 months, p=0,001; OS, not reached vs 88.8 months, p=0.001). Multivariate analysis revealed SI group as well as female sex, KIT exon 11 mutation, and low initial tumor burden were associated with longer PFS, and SI group and low initial tumor burden were associated with longer OS. Even after applying IPTW adjustment, SI group showed significantly better outcome in terms of PFS (hazard ratio [HR], 2.326; 95% CI, 1.034-5.236; p=0.0412) and OS (HR, 5.464; 95% CI, 1.460-20.408; p=0.0117). Conclusions: This study strongly suggests that surgical resection of the residual lesions after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST.
Sirolimus in advanced hemangioendothelioma.
Authors: Stacchiotti Silvia , Palassini Elena , Libertini Michela , Marrari Andrea , Bertulli Rossella , Morosi Carlo , Messina Antonella , Crippa Flavio , Dagrada Gianpaolo , Dei Tos Angelo Paolo , Gronchi Alessandro , Pilotti Silvana , Casali Paolo Giovanni 
Published: March 2020

10565 Background: Haemangioendothelioma (HE) is a very rare vascular tumor. The epithelioid variant is characterized by a specific t(1;3)(p36.3;q25) translocation, resulting in the WWTR1-CAMTA1 fusion product. We retrospectively reviewed patients with HE treated with sirolimus, an mTOR inhibitor, at our institution. Methods: We identified 12 patients (M/F: 4/8 – mean age: 46 years – epithelioid HE/ retiform HE: 10/2 – locally advanced/multifocal: 1/11 – pretreated: 6) with advanced HE who were treated with sirolimus, as a single agent, 5 mg/day, from 2005 on. They had evidence of progression in the 3 months before starting treatment. The daily dose of sirolimus was adjusted according to drug blood levels (range 10-20 ng/dl). Response was evaluated with CT/MRI/PET scans after 4-6 weeks of treatment, then every 3 months, by RECIST and Choi criteria. WWTR1 gene rearrangement was evaluated by FISH, and the histochemical expression of mTOR effectors, S6 and 4BP1, is ongoing. Results: 10 patients are evaluable for response (2 pts are too early). Sirolimus daily dose ranged from 3 to 6 mg/day. Best response by RECIST was PR = 1, SD = 6 (all >6 months, range 6-48+), PD = 3 cases. In 3 cases, a Choi response could be detected. PET response was observed in 6/6 evaluated case. Median PFS (range) was 24 (3-48) months. Two patients with evidence of tumor stabilization while under sirolimus stopped their treatment after 12 and 24 months of therapy, respectively, with evidence of interval progression in both. A new disease stabilization was obtained after restoring sirolimus. Conclusions: HE is known for its potentially long-lasting course, even in typical cases with multicentric/multifocal disease. Progressive HE may require a medical therapy, but is insensitive to cytotoxic chemotherapy, while mainly andecdotal responses were reported to interferon, bevacizumab and thalidomide. In this retrospective series, sirolimus resulted in a high proportion of mainly non-dimensional, possibly long-lasting, tumor responses.
Impact of adjuvant treatments on local and metastatic relapse of soft-tissue sarcoma patients in the setting of competing risks.
Authors: Italiano Antoine , Le Cesne Axel , Mendiboure Jean , Blay Jean-Yves , Piperno-Neumann Sophie , Chevreau Christine , Delcambre Corinne , Penel Nicolas , Terrier Philippe , Ranchere-Vince Dominique , Lae Marick , Le Guellec Sophie , Michels Jean-Jacques , Robin Yves Marie , Bonvalot Sylvie 
Published: March 2020

10575 Background: Competing risk is the risk of an event that interferes with the probability of experiencing the disease-specific outcome of interest. Indeed, the occurrence of a competing risk (for instance death by local relapse or another cause) may preclude the onset of the event of interest (for instance metastatic relapse) or at least modify its probability. Competing risk is ignored by Kaplan Meier method and standard Cox survival model. Methods: 3369 adult patients with localized STS were included prospectively in the French Sarcoma Group (GSF) database from January 1990 to December 2009. The outcomes of interest were the cumulative probabilities of local (LR) and of metastatic (MR) relapse with death as a competing event. Estimations and 95% confidence intervals (CIs) were computed with the cumulative incidence function. Results: Median follow-up was 4.5 years. 1-year and 5-year cumulative incidence of LR were 6.4% (95% CI 5.6-7.3) and 25.9% (95% CI 24.2-27.6), respectively. Age, histological subtype, anatomic site and grade were independently associated with the cumulative probability of LR. After adjustment to these prognostic factors, adjuvant radiotherapy was associated with a significant impact on LR (HR=0.5 95% CI 0.4; 0.6, p <0.001). The magnitude of this effect was similar whatever the grade or the anatomic site. Because of the competing effect of death, adjuvant chemotherapy had no significant impact on the cumulative probability of LR. 1-year and 5-year cumulative incidence of MR were 7.4% (95% CI 6.5-8.3) and 26.9% (95% CI 25.2-28.7), respectively. Tumor depth, histological subtype, tumor size and grade were independently associated with the cumulative incidence of MR. After adjustment to these prognostic factors, adjuvant chemotherapy was associated with a significant impact on MR (HR=0.5 95% CI 0.4-0.7, p < 0.001) in grade 3 but not in grade 2 patients (HR=1.3 95% CI 0.9-1.9, p= 0.1). Conclusions: Adjuvant radiotherapy was associated with improved LR outcome even in patients with high risk of competing death from metastatic disease or other causes. Adjuvant chemotherapy was associated with improved MR outcome in patients with grade 3 but not grade 2 disease.
Prognostic significance of radiologic and histologic response to neoadjuvant chemotherapy in localized synovial sarcoma.
Authors: Chakiba Camille , Terrier Philippe , Ranchere-Vince Dominique , Neuville Agnes , Aarab Terrisse Safae , Blay Jean-Yves , Perrin Christophe , Bompas Emmanuelle , Italiano Antoine 
Published: March 2020

10578 Background: The role of neoadjuvant and adjuvant chemotherapy in localized synovial sarcoma (SS) is still controversial. Histologic response to neoadjuvant chemotherapy is an independent prognostic variable in bone sarcomas. Data regarding the prognostic value of response to noeadjuvant chemotherapy in STS are limited. Methods: 68 patients with localized STS, treated with neoadjuvant anthracycline/ifosfamide-based chemotherapy and assessable for response to chemotherapy were included prospectively in the French Sarcoma Group (GSF) database from 1985 to 2011. All the cases were reviewed by the pathology subcommittee of the GSF. Radiological response to chemotherapy was assessed according to RECIST criteria. Good response was defined as partial response or stable disease according to RECIST and ≤10% recognizable tumor cells in the surgical specimen. Poor response was defined as stable or progressive disease according to RECIST and ≥ 50% recognizable tumors cells in the surgical specimen. All the other cases were defined as intermediate response. Results: Median age was 38 years. Median tumor size was 8 cm (range 2-20). 56% of tumors were located in the limbs and 52% were grade 3. Response to chemotherapy was considered as good in 9 cases (13%), intermediate in 20 cases (29.5%) and poor in 39 cases (57.5%). Median metastasis-free (MFS) and overall (OS) survivals were 45 (95% CI 11-79) and 84 months (95%CI 88-120), respectively. On univariate analysis, grade, tumor size and response to chemotherapy were significantly associated with metastasis-free survival (MFS). Radiological response according to RECIST has no prognostic value. On multivariate analysis, grade was the sole variable independently associated with MFS (HR=3.4, 95% CI 1.5-7.5, p=0.003). On univariate analysis, grade, and response to chemotherapy were significantly associated with overall survival (OS). On multivariate analysis, grade was the sole factor independently associated with OS (HR=2.5, 95% CI 1.2-5.7, p=0.03). Conclusions: Response to neoadjuvant chemotherapy may not have prognostic value in patients with SS. Grade represents the most significant predictive factor of outcome in this setting.
Poor prognostic features in angiosarcoma: A single institution retrospective study of 324 patients.
Authors: D'Angelo Sandra P. , Moraco Nicole H. , Qin Li-Xuan , Kuk Deborah , Carvajal Richard D. , Dickson Mark Andrew , Gounder Mrinal M. , Keohan Mary Louise , Antonescu Cristina R. , Singer Samuel , Schwartz Gary K. , Tap William D. 
Published: March 2020

10580 Background: Angiosarcoma (AS) is a rare, malignant endothelial cell tumor of vascular origin with a five year overall survival (OS) of approximately 35%. It is a heterogenous disease whose natural history is poorly defined. We sought to identify clinical and treatment outcomes to better define this disease. Methods: In a retrospective study using an institutional sarcoma database, we identified all patients(pts) with AS treated at Memorial Sloan-Kettering Cancer Center between 1992-2011 and collected their correlative clinical information.Kaplan-Meier method and Cox’s proportional-hazard models were used to determine OS and prognostic factors. Hazard ratios (HR) are listed with their 95%confidence intervals (CI). Results: We identified 324 pts, median age was 63 (range 15-94), 127(39%) were men. At presentation, 188 (58%), 19 (6%) and 117(36%) had localized disease (L), local recurrences (LR) or distant metastases (M), respectively. L sites included: RT breast 43 (23%,) head&neck 33 (18%,) scalp 30 (16%,) breast 26 (14%,) extremity 23 (12%,) abdomen/pelvis 14 (7%,) thorax 10 (5%) and trunk 9 (5%). The median OS is 3.3 years (2.44-4.33) for pts w L disease and 0.89 years (0.74-1.11) for pts with M disease. Among pts that presented with L disease, 29% had a LR and the median local relapse free survival (RFS) time was not reached (8.71-NA); 31% had distant recurrences with a median distant RFS of 12.8 yrs (4.13-NA.) Among L disease patients, older age (HR 1.04, 1.03-1.06, p <0.0001) and site were independent predictors of decreased OS. Visceral tumors arising in the abdominal/pelvis (AP) (HR 2.89, 1.27-6.61, p = 0.012) had worse OS compared to those arising the breast. Conclusions: AS remains an aggressive, heterogenous malignancy with poor OS and high rates of local and distant recurrences. Patients with M disease do poorly. Adverse prognostic factors include AP visceral tumors and older age. These factors could be helpful for stratification in future clinical trials. The identification of genomic differences is necessary to define therapeutic targets in AS.
Preoperative Tru-Cut biopsy (POB) for the diagnosis of retroperitoneal soft tissue sarcomas (RPS) and risk of local recurrence (LR) compared to primary surgery of the tumor.
Authors: Boccone Paola , D'Ambrosio Lorenzo , Galizia Danilo , Palesandro Erica , Aliberti Sandra , Manca Antonio , Bertotto Ilaria , Russo Filippo , Racca Manuela , Gatti Marco , Pignochino Ymera , Aglietta Massimo , Grignani Giovanni 
Published: March 2020

10583 Background: Regardless optimal surgery LR is still a major challenge in RPS affecting 60% of the patients (pts). To improve these results pre-operative radiotherapy +/- chemotherapy are under investigation. This strategy requires to perform a POB. The surgical removal of the whole needle track is mandatory for limb sarcomas, but it can hardly ever be achieved in RPS. We explored whether POB did increase the risk of LR in terms of tumor cell seeding (along the needle track) or in the tumor mass area. Methods: We scanned our prospectively (01/2000 to 12/2010) collected RPS database including 176 pts. Complete information (records, CT scans, biopsy-track, follow up data) were available and retrospectively examined in 100 pts. Pts were divided into: group A (POB), group B (direct surgery). The 7 year probability of disease free survival (DFS) was estimated for each pt (ASCO 2012 abs 10000). T student test and Fisher's exact test were used to compare the estimated DFS and the incidence of LR in the 2 groups, respectively. Kaplan-Meier method was used to estimate DFS and overall survival (OS). Results: In 51 male, 49 female, median age 58 years (22-81) RPS histotype distribution was: lipo 43, leio 28, pleomorphic 9 and other 20. RPS grades were: G1 29%, G2 32%, G3 39%. POB was performed in 25 pts (25%) without major complications. The baseline probability of 7 year DFS was 0.43 and 0.51 (p= .24) for group A and B, respectively. After a median follow up of 71 mos, LR was 8% and 23% (p> .05) for group A and B, respectively. No relapse along the needle track was detected. As expected, liposarcoma was associated with a higher rate of LR (Odds Ratio 5.6 CI 95% 2-13). Median DFS, local DFS and OS were 24, 88 and 71 months, respectively. Conclusions: With the limit of the retrospective nature of our data, we didn’t find any increased risk of LR for POB in RPS. Although surgery is still the standard therapy in RPS, knowledge of histotype and differential diagnosis might encourage to consider inclusion of pts into pre-operative clinical trials and to avoid surgery for other retroperitoneal tumors (e.g. lymphomas, germinal cell tumors, IgG4-related sclerosing disease).
The impact of patient-related factors on the occurrence of febrile neutropenia in breast cancer patients receiving (neo-)adjuvant chemotherapy with 5-fluorouracil, epirubicin, and cyclofosfamide (FEC) x6 or FEC x3 followed by docetaxel (D) x3.
Authors: Vulsteke Christof , Pfeil Alena , Brouwers Barbara , Schwenkglenks Matthias , Paridaens Robert , Pettengell Ruth , Dieudonné Anne-Sophie , Hatse Sigrid , Neven Patrick , Lambrechts Diether , Wildiers Hans 
Published: March 2020

1078 Background: Recently we described the impact of genetic variability on severe toxicity in breast cancer patients receiving (neo-) adjuvant FEC chemotherapy (Annals of Oncology 2013, In Press). We now further assessed the impact of a wide range of patient-related factors on FEC toxicity in routine clinical setting. Methods: Patients with early breast cancer receiving (neo-)adjuvant 6 cycles FEC or sequential 3 cycles of FEC and 3 cycles D were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint; CTC 3.0). Age at diagnosis, body mass index, body surface area, number of cycles received, germline genetic polymorphisms, and baseline biochemical variables (white blood cell count, absolute neutrophil count, platelets, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine) were available for most patients (missing data <10%). All patients had follow up for progression free survival (PFS) and overall survival (OS). Multivariate logistic regression analysis was performed including univariate associates of outcome with a p-value <0.25. Results: We identified 1,031 patients treated between 2000-2010 with 6x FEC (n=488) or 3x FEC followed by 3x D (n=543). 174 (16.9%) patients developed febrile neutropenia during FEC. After logistic regression analysis febrile neutropenia was found to be significantly associated with carriers of the rs45511401 variant T-allele in the MRP1 gene found in 12% of patients (p= 0.03, OR1.99, CI 1.07-3.71) and with increasing serum creatinine values (p=0.05 OR 4.58/CI 0.99-20.98); all other investigated patient-related parameters were not retained by the model. At a mean follow up of 5.2 years, the occurrence of febrile neutropenia was not correlated with PFS and OS. Conclusions: In this study, only the baseline level of serum creatinine and germline genetic polymorphisms in the MRP-1 gene were predictive for the occurrence of febrile neutropenia in patients receiving FEC chemotherapy. The occurrence of febrile neutropenia did not seem to impact on outcome.