bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation-associated versus sporadic osteosarcoma: A single-institution experience.
Authors: Siontis Brittany , Roberts Emily , Zhao Lili , McHugh Jonathan B. , Owen Dawn , Baker Laurence H. , Biermann J. Sybil , Schuetze Scott , Chugh Rashmi 
Published: September 2018

11018 Background: Osteosarcoma (osarc) can be a rare complication from radiation (rt) therapy. Radiation-associated osarc (RAO) is reported to have a worse prognosis than non rt-associated osarc with limited objective data comparing the two. We conducted a retrospective study comparing demographics, therapy and outcomes of sporadic osarc (SO) to RAO. This study was confined to adults. Methods: We identified patients (pts) > age 18 years (yr) with osarc treated at our institution between 1990 and 2016 using an institutional database. We categorized tumors as SO or RAO based on history of prior rt within field of osarc. We extracted data on demographics, treatment, and primary malignancy characteristics. Results: We identified 159 pts with osarc, 28 were RAO tumors. Results are in Table 1. Median follow-up was 2.8 yr (0.1-19.6 yr). For RAO, median time from rt to diagnosis was 11.5 yr (1.5-28 yr) with a median cumulative dose of 60 Gy (44-75.8 Gy). Median progression free survival (PFS) and overall survival (OS) were not significantly different in pts presenting with metastatic osarc; PFS 10.3 mo vs 4.8 mo (p=0.45) and OS 15.6 mo vs 6.1 mo (p=0.96) in SO vs RAO pts, respectively. For pts with localized osarc, median relapse-free survival (RFS) and OS were significantly different, not reached vs 12.2 mo (p<0.001) and not reached vs 27.6 mo (p=0.001) in SO vs RAO, respectively. Conclusions: In our series, there was a significant difference in age, size and location of RAO vs non rt-associated osarc. Overall, all osarc pts with metastatic disease at diagnosis fared poorly. Pts presenting with localized RAO had worse outcomes than patients with localized SO. This was not associated with a detectable difference in therapy rendered or treatment effect in resection specimens. [Table: see text]
Toxicity and efficacy of bolus (BOL) versus continuous intravenous (CIV) dosing of doxorubicin (DOX) in soft tissue sarcoma (STS): Post hoc analysis of a prospective randomized trial.
Authors: Cranmer Lee D. , Lu Yao , Ballman Karla V. , Loggers Elizabeth Trice , Pollack Seth 
Published: September 2018

11023 Background: DOX remains critical in STS treatment. Controversy exists regarding its optimal administration route (BOL vs CIV). BOL vs CIV could affect toxicity and/or efficacy. A randomized trial to assess this is unlikely. We conducted a post hoc analysis to explore differences in these routes of DOX administration. Methods: Data from a prospective randomized phase III study of doxorubicin with or without evofosfamide (TH-302) were used. At the discretion of treating physician, BOL or CIV DOX could be used. Grade 3-5 hematologic, non-hematologic and cardiac toxicities and treatment response were explored using multivariable logistic regression. OS and PFS were analyzed using Kaplan-Meier and Cox proportional hazards. Results: 640 subjects were enrolled (556 BOL, 84 CIV). Baseline differences in age, extent of disease and prior radiotherapy were controlled for in regression models. Hematologic toxicity was associated with age, performance status (PS) and cumulative (CUM) DOX dose. Non-hematologic toxicity was associated with age, PS, receipt of prior radiotherapy and CUM TH-302 dose. Cardiac toxicity was only associated with CUM DOX dose. Odds of response were strongly associated with CUM DOX dose (mg/m2, OR = 1.011, p < 0.0001), and, to a lesser extent, with CUM TH-302 dose (g/m2, OR = 1.081, p = 0.0008), STS subtype and prior radiotherapy. Comparing CIV to BOL DOX, neither OS (median 21.7m vs 18.3m, HR = 0.85, p = 0.29) nor PFS (median 6.1m vs. 6.1m, HR = 0.89, p = 0.43) was affected by manner of DOX administration (CIV vs BOL). Cox analyses indicated that factors reflecting tumoral biology and host status, rather than treatment received, were associated with OS (PS, histologic STS subtype, histologic grade, receipt of prior radiotherapy) and PFS (PS, treatment-related toxicity). Conclusions: Our analyses provide no evidence for superiority of either BOL or CIV administration of DOX as regards toxicity or efficacy in STS treatment. Thus, the logistically simpler BOL administration of DOX should be favored over CIV administration.
Neoadjuvant denosumab treatment of locally advanced giant cell tumor of bone (GCTB).
Authors: Rutkowski Piotr , Gaston Louie , Borkowska Aneta , Stacchiotti Silvia , Baldi Giacomo Giulio , Palmerini Emanuela , Casali Paolo Giovanni , Gronchi Alessandro , Parry Michael , Gelderblom Hans , Ferrari Stefano , Dijkstra P.D.Sander , Pienkowski Andrzej , Grimer Robert 
Published: September 2018

11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadjuvant Denosumab (Db) outside clinical trials in 6 European reference centers. Methods: From 138 pts (median age 30yrs) with histologically confirmed advanced GCTB treated with Db(2011-2016), we included into analysis 87pts who underwent surgery after preoperative Db. All 87 patients had locally advanced tumors with extensive soft tissue involvement(54) or penetration to joint, not amenable to limb-sparing surgery/primary curettage or with high risk of recurrence. In 39/42(93%) cases diagnosis was confirmed by H3F3Agene mutation. Median follow-up time -22 months. Results: Primary tumor was located in lower limb(54%; n = 47) -mostly in tibia(25%) and femur(23%), upper limb(33%; n = 29), and pelvis/axial skeleton/ribs(13%; n = 11). 68(78%) patients had primary tumors, 19(22%) recurrent tumors after surgery (+/-radiotherapy). Median Db duration was 7months (range 1.5-35months), 17pts received also Db postoperatively. 39(45%) had wide en-bloc resection -WE (+17 implantation of prosthesis), 48(55%) cases had intralesional curettage -C, no extremity amputation. Pts who underwent prosthetic replacement had longer median preoperative Db therapy as compared to pts without prosthesis. All pts demonstrated a response to Db Progression after surgical treatment was observed in 15 pts -13 of them after intralesional curettage (13/48, 27%); 9 patients underwent D re-challenge -all responded. Two-year progression-free survival (PFS; from Db start) rate was 80%, 91% in WE group vs 73% in C group (p = 0.04), one-year PFS (from operation date) rate was 84%: 92% in WE and 79% in C group(p = 0.01). Treatment was well tolerated with only 1 grade 3 toxicity. Conclusions: Our study confirms that Db is active in a neoadjuvant setting with excellent efficacy and short-term tolerability. It implies that neoadjuvant therapy with Db is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following Db raises questions about the optimal duration of preoperative treatment and if Db is indicated postoperatively.
Characterizing the end-of-life period in young patients with sarcomas.
Authors: Movva Sujana , von Mehren Margaret , Handorf Elizabeth , Tetzlaff Eric Daniel , Albanese Anjali , Murphy Kathleen , Chwistek Marcin 
Published: September 2018

11027 Background: There is a paucity of data surrounding the end-of life transition (EOLT) in young adult (YA) patients with sarcoma. Discussions surrounding prognosis, goals of care (GOC), hospice and death can be challenging in these patients as they may be at a particularly hopeful stage of their life. The purpose of this study is to better understand the EOLT in YA patients with sarcoma by determining the survival and number of lines of treatment at different periods in the disease course. In addition, the study aims to determine what impacts the decision to discontinue anti-cancer therapy. Methods: Fox Chase Cancer Center (FCCC) patients, 18-39 years old who died from sarcoma between January 2013 and December 2016 were included in this study. Patient demographics, tumor specific data, treatment and treatment decisions were collected from electronic medical records and retrospectively analyzed. Results: 38 FCCC patients who were diagnosed between the ages of 18-39 died between January 2013 and December 2016. Of these 21 patients were between the ages of 18-39 at the time of their death. Median age at death was 30 (range: 22-40). The most common histologies were Ewing Sarcoma, GIST (n = 3) and osteosarcoma, synovial sarcoma (n = 2). Median time from diagnosis of metastatic disease to death was 21.4 months. Median time from metastatic disease to discussion of GOC and hospice by any provider was 9.6 and 16.7 months respectively. The hospice discussion was held by the treating oncologist 87.5% (n = 16) of the time (outpatient 35.7% and inpatient 64.3%). 60% (n = 15) of patients/family selected hospice when it was originally presented to them (multi-organ failure, unarousable, paralysis). The hospice discussion was held at a median of 21 days prior to death and median time on hospice was 13 days (range: 1-63). Patients were treated a median of 54 days prior to their death (range: 6-1823). Median times on first, 2ndto last and last treatments were 273, 67 and 22.5 days respectively (P = 0.002). Conclusions: Focusing on this particular group of patients will generate benchmark data that can help counsel them about their specific expected survival and changes in clinical status as their disease progresses. We plan to compare this data with that of older patients.
Does MGMT (O6-methylguanine–DNA methyltransferase) have a role in metastatic Ewing sarcoma (ES) patients (pts) undergoing temozolomide (TMZ) and irinotecan (IRI)?
Authors: Palmerini Emanuela , Pasello Michela , Jones Robin Lewis , Manara Maria Cristina , Parra Alessandro , Picci Piero , Grignani Giovanni , Marchesi Emanuela , Cesari Marilena , Longhi Alessandra , Abate Massimo , Paioli Anna , D'Ambrosio Lorenzo , Fagioli Franca , Dorin Asaftei sebastian , Ferrari Stefano , Scotlandi Katia 
Published: September 2018

11030 Background: TMZ+IRI has significant activity in metastatic ES. Epigenetic silencing of the MGMT DNA gene by promoter methylation has been associated with response to TMZ in glioblastoma. Our aim was to assess if MGMT methylation 1) has a role in ES progression and 2) is predictive of response to TMZ. Methods: 1) In 10 ES cell lines presence of MGMT gene (Real-time PCR), methylation of its promoter (methylation-specific PCR) and protein expression (western blot) were assessed. MGMT protein (IHC) and methylation of its promoter was searched in 97 ES pts samples (74 localized; 23 metastatic). 2) In metastatic ES pts treated with TMZ+IRI, with pre-treatment FFPE tissue and measurable disease, the relation between RECIST response, PFS and MGMT expression (IHC) was assessed. Results: 1) The expression of MGMT gene and its protein was detected and concordant (p = 0.02) in all ES cell lines evaluated; methylation was a rare event. In ES tissue samples the methylation of the MGMT gene was found at a low intensity as compared with the unmethylated gene, but the protein expression was relatively low: 36% in localized, 65% in metastatic pts (p 0.03). 2) 24 pts (median age 19 years, range 3-50 years; F/M: 7/17) treated with TMZ + IRI from 2010 to 2015 were identified. Line of treatment: 8 patients were in 1st line; 16 ≥ 2nd line. Median n of cycles was 6 (range: 2-31). Pattern of metastases: 16 multiple sites, 4 lungs, 3 multiple sites + bone marrow, 1 bone. MGMT was positive in 63% of cases. ORR: 16.5% (1 CR , 3 PR); SD: 50% (13 pts); PD: 33.5% (7 pts). According to MGMT expression the ORR was 11% in negative and 20% in MGMT positive patients (p = 0.8). 6-mos PFS rate was 59% (38-80 %IC), no differece according to MGMT expression (pos 61% vs neg 56%, p 0.7). Conclusions: Whereas in cell lines the MGMT gene and its protein expression is a generalized event, in tissue samples MGMT protein is present in a minority of localized pts, and might be associate with tumor progression. Methylation of MGMT gene does not seem responsible for its regulation in ES, and post-transcriptional mechanisms are more likely to be involved. The presence of MGMT protein does not predict the response to TMZ + IRI in this small series.
Multicentric randomized phase II trial of gamma knife surgery (GKS) versus image-guided, intensity-modulated radiation therapy (IG-IMRT) in patients with sacrococcygeal chordoma.
Authors: Lu Shun , Lang Jin Yi , Wang Weidong , Feng Mei , Zou Bingwen , Peng Xinhao 
Published: September 2018

11033 Background: Chordoma is a rare slow-growing neoplasm arisen from cellular remnants of the notochord. About 30% occur in the sacrococcygeal region. Surgical resection is recommended treatment. Due to the high recurrence rate, adjuvant radiation therapy was suggested to receive as an effective method to improve local control rates. Methods: Thirty eight patients were pathologically diagnosed as non-metastatic sacrococcygeal chordoma from Aug. 2003 to May. 2015 were recruited retrospectively to analysis. All patients received surgical resection after diagnosed. Initial surgery included subtotal resection (24% of patients), and gross total resection (76% of patients). Among these patients, 25 patients treated with adjuvant IG-IMRT, while 13 patients treated GKS after surgical resection. The median follow-up was 40 months (range, 6–151 month) for all patients, The PTV of IG-IMRT group received total doses were 60 Gy (range, 56-74Gy), delivered with 2-2.2 Gy/fraction, while GKS group underwent a total of 6-8 sessions treatment. Results: For the IG-IMRT group and the GKS group, the 5-year overall survival and local control rates were 87.5% and 67.7%, respectively. And 5-year local control rates were 35% and 22.2%, respectively. In total, 18 patients progressed locally: 11 were in the IG-IMRT group and 7 in the GKS group. In comparison with GKS group, the IG-IMRT group has a better overall recurrence-free survival (p = 0.03), the significance remained after adjusted for surgery results, age and gender. Moreover, there is no significant difference of overall survival was found between these two groups. Conclusions: We report favorable local control and adverse event rates following IG-IMRT, and suggested IG-IMRT is the first choice of adjuvant radiation therapy for sacrococcygeal chordoma treatment.
Numerical, dimensional or mixed progression disease to imatinib as prognostic factor in patients with metastatic GIST.
Authors: Badalamenti Giuseppe , Incorvaia Lorena , Galvano Antonio , Assanto Giovanni Manfredi , Musso Emmanuela , De Luca Ida , Cesarin Alessandra , Ancona Chiara , Passiglia Francesco , Vincenzi Bruno , Grignani Giovanni , Pantaleo Maria A. , Gatto Lidia , Bartolotta Tommaso Vincenzo , Taibbi Adele , Russo Antonio 
Published: September 2018

11040 Background: The majority of GIST patients with advanced disease initially achieves disease control from imatinib treatment. Approximately 10% of patients progresses within 6 months of starting therapy (primary resistance) and also 50-60% of the responding patients develops progression disease within two years (secondary resistance). Progression disease (PD) can be numerical, dimensional or mixed. The known prognostic factors of risk stratification in local disease are tumor size, mitotic activity and anatomic site. In this retrospective analysis we explore several clinical factors affecting survival in metastatic setting. Methods: The population included in this large database of 128 patients with metastatic GIST was obtained examining data collected from four Oncologic Centres with expertise for the GIST management. The clinical factors analyzed were sex, tumor size, mitotic activity, anatomic site, KIT and PDGFRa mutational status, site of metastasis, FDG-PET status at progressing disease and pattern of tumor progression to I line imatinib 400, II line Imatinib 800 or Sunitinib, evaluated with CT scan or MRI: PD with dimensional growth (dimensional, dPD), with new lesions appearance (numerical, nPD) and with both numerical and dimensional growth (Mixed, mPD). Every factor has been correlated with Overall Survival (OS) measured in months. Survival analyses were performed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were executed to search for association with the outcome. Results: Univariate analysis showed significant value for primary tumor site (p < 0.0001), mitotic activity (p = 0.02), tumor size (p = 0.05) and PD pattern (p = 0.008): OS nPD group was 102.7 months, in dPD group 87 and in mPD group 70. The multivariate analysis confirm significant prognostic factors for OS tumor site (p = 0.0004) and PD pattern (p = 0.02). Conclusions: with the limitations of a retrospective analisys, this study shows for the first time the impact of pattern of progression on OS: patients with dPD have a worse prognosis than those with nPD or mPD, suggesting type of PD as an independent prognostic factor for OS in advanced GISTs.
Impact of pharmacogenomics on imatinib toxicity in gastrointestinal stromal tumors.
Authors: Zhuang Wei , Qiu Haibo , Wang Xueding , Xin Shuang , Huang Min , Zhou Zhiwei 
Published: September 2018

11043 Background: Imatinib-induced side effects are common, although most of these side effects are mild, some will be severe and lead to disruption of Imatinib treatment in gastrointestinal stromal tumor (GIST). It is necessary to explore a biological predictors to predict and optimal therapeutic strategy. But there were few studied conducted to explore the mechanisms of Imatinib-induced side effects. The present study comprehensively investigated the effects of genetic polymorphisms of cytokines involved in cell proliferation and metabolic enzymes and transporters involved in Imatinib metabolism on these side effects. Methods: A total of 154 GSIT patients treated with Imatinib were enrolled. 22 SNPs (single nucleotide polymorphisms) in KIT/ PDGFRA/ PDGFRB/ SHC1/ FLT1/ MAPK1/ EGFR/ CCL5/ CXCL14were detected using Agena Massarray matrix-assisted laser desorption / ionization-time of flight (MALDI-TOF) platform. Logistic regression analyses were performed to evaluate their effects on Imatinib-induced toxicities. This study was approved by the ethical committee of Sun Yat-Sen University Cancer Center. Results: Imatinibdose, FLT1 rs9951465, MAPK1 rs13515, PDGFRB rs55712339 and SHC1 rs3766920 were found to be correlated with the incidence of myelosuppression ( P= 0.027, 0.009, 0.002, 0.008, < 0.001, respectively), moreover, FLT1 rs9554314 was correlated with severe myelosuppression (Grade 0,1 vs. 2+, P= 0.009, OR (95%CI) = 3.042 (1.314-7,042)). Meanwhile, EGFR rs10228436 was found to be correlated with the incidence of skin rash ( P= 0.027), moreover, CCL5 rs4796120 and CXCL14 rs7716492 were correlated with severe skin rash (Grade 0,1 vs. 2+), with OR (95%CI) and p value were 8.542 (0.934-78.107), 13.504 (2.308-79.004) and 0.057, 0.020, respectively. Conclusions: This is the first comprehensive report on the biomarkers for Imatinib toxicities. These biomarkers might be able to distinguish patients with mild or more severe forms of Imatinib toxicities, thus enabling the optimization of Imatinib therapy and lead patients benefit from Imatinib treatment in a long-term.
Combined peripheral natural killer (NK) cell and circulating tumor cell (CTC) enumeration to enhance prognostic efficiency in patients (pts) with triple-negative breast cancer (TNBC).
Authors: Liu Xiao-ran , Shao Bin , Li Hui-ping , Yang Yan-lian , Rugo Hope S. , Kong Wei-yao , Song Guo-hong , Jiang Han-fang , Liang Xu , Yan Ying , Hu Zhi-yuan , Xu Guo-bing 
Published: September 2018

1105 Background: CTCs have emerged as an independent prognostic factor for metastatic breast cancer. However, the prognostic value of baseline CTCs regarding PFS in TNBC is still controversial, especially beyond first-line. We evaluated a novel combined NK cell/CTC detection system for enumeration to better understand the impact of cell count on prognosis in TNBC. Methods: 83 consecutive patients with metastatic TNBC were enrolled and received a new line of therapy (median=2, range: 1~5). Baseline circulating CTCs and NK cells were isolated and enumerated simultaneously prior to starting a new line of therapy using our previously published method targeting EpCAM (Bai et al. J Mater Chem B, 2014) and flow cytometry (antibodies against CD3-, CD45+, CD56+) respectively. The NK cell level was expressed as the proportion of total lymphocytes (%). Patients with normal to high NK cell proportion (≥ 9.15%) and > 2 CTC/2 ml were defined as NK resistant CTC, the rest were defined as non-NK resistant CTC. Results: 33 out of 83 TNBCs had first-line of therapy. Pts with ≤ 2 CTC/2 ml had a significantly longer median PFS than those with > 2 CTC/2 ml ( P = 0.028). The differences in median PFS were not significant ( P=0.110) for the entire group of pts with TNBC receiving different lines of therapy. Pts with non-NK resistant CTCs had a significantly longer median PFS than those with NK resistant CTCs ( P= 0.025), regardless of line of therapy. Conclusions: Including peripheral NK cell level into consideration can improve CTC prognostic efficiency in predicting PFS for TNBCs receiving different line of therapy. Further analysis of the unique biological features of NK-resistant CTCs and associated clinical consequence holds promise in guiding clinical practice. [Table: see text]
The incidence of other malignancies before and after sarcoma diagnosis: A population-based study.
Authors: Van Der Graaf Winette T.A. , Olga Husson , van Houdt Willem J. , Desar Ingrid M.E. , Ho Vincent K.Y. 
Published: September 2018

11076 Background: Sarcomas encompass a group of rare and heterogeneous mesenchymal malignancies with mostly unknown origin. Both exogenous risk factors, in particular radiotherapy, as well as genetic risk factors have been described. Second tumors next to sarcomas suggest associated risk factors. In the current study, we investigate the incidence of sarcomas and other malignancies by using population-based data from the Netherlands Cancer Registry. Methods: In 29,638 patients diagnosed with sarcoma between 1989 and 2015, with a median age of 59 years, we quantified the risk of other malignancies after sarcoma diagnosis using standardized incidence ratios (SIRs). In assessing associations with malignancies before sarcoma diagnosis, we focussed on previous radiotherapy. Skin carcinomas, with the exception of melanomas, were excluded. Results: In total, 3,381 (11.4%) sarcoma patients, median age 71years, had a previous malignancy (at a median age of 66 years). The most frequent sarcomas associated with prior tumors were angiosarcoma (34.5%) and gastrointestinal stromal tumours (20.6%). In the angiosarcoma group, 78.6% of patients had received prior radiotherapy for their previous tumors. Subsequent tumors (diagnosed in patients with median age of 69.5 years) after sarcoma diagnoses were detected in 2,523 patients with median age of 63 years (SIR 1.13; 95%CI: 1.09–1.18). Risks appear notably elevated for breast cancer (SIR 1.19; 95%CI: 1.06–1.34), lung cancer (SIR 1.15; 95%CI: 1.04–1.27), cancers of the urinary tract system (SIR 1.33; 95%CI: 1.14–1.53) and hematological cancers (SIR 1.31; 95%CI: 1.13–1.51). Median time until diagnosis of subsequent cancer was 52.7 months. Conclusions: Sarcoma patients have a markedly increased risk on another malignancy, either before or after the sarcoma diagnosis. Further research into genetic and exogenous risk factors may help to explain the associations.