bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD205, a target antigen for a novel ADC: Evaluation of antigen expression on TNBC, pancreatic adenocarcinoma and bladder urothelial carcinoma.
Authors: Massa Simona , Collini Paola , Spagnuolo Rosalin Dolores , Bertolotti Alessia , Garzone Giovanna , Pruneri Giancarlo , Carcangiu Maria Luisa , Kaplan Angelo , Rohlff Christian , Buontempo Serena , Matera Mariagiuseppa , Bussolo Vanessa , Merlino Giuseppe , Binaschi Monica , Rossi Cristina , Tonini Giulia , Fedi Valentina , Simonelli Cecilia , Capriati Angela , Pellacani Andrea Ugo 
Published: May 2019

e14726 Background: CD205 is a type I transmembrane surface protein belonging to the mannose receptor family with propensity for antigen uptake/internalization. CD205 is expressed in different cancer histotypes and seems to have a role in migration and invasion. For these features CD205 is an ideal candidate to be exploited as an ADC target. MEN1309/OBT076 (herein as MEN1309) is a humanized IgG1 antibody against CD205, conjugated through a cleavable linker to DM4. It has shown impressive anti-tumor activity when tested in high/low CD205 expressing xenografts for solid tumours and NHL. MEN1309 is under assessment in Phase I trials in EU (NCT03403725) and as OBT076 in USA. Methods: A retrospective evaluation of CD205 expression in 103 triple negative breast carcinomas (TNBC), 50 pancreatic adenocarcinomas (PAC) and 100 bladder urothelial carcinomas (UC) was performed at INT in Milan, Italy. Immunohistochemistry was performed on one FFPE representative sample per case, using a commercial anti-CD205 antibody. A semiquantitative score was applied to measure CD205 expression. Absence of staining tumor cells was scored as negative. Positivity was scored based on the percentages of neoplastic cells (NCs), with intensity of cytoplasmic staining ranging from 1 (weak) to 3 (strong). Membrane staining in NCs, immunoreactivity of the intratumoral/peritumoral inflammatory component and of normal tissue were scored as absent or present. Results: TNBC: 85% were positive, 70% in > 5% of NCs; 14% showed 2+/3+ staining intensity in > 50% of NCs. 57% of cases showed a membrane positivity. PAC: 100% were positive in > 5% of NCs; 50% showed 2+/3+ staining intensity in > 50% of NCs. 98% of cases showed a membrane positivity. UC: 67% were positive, 60% in > 5% of NCs; 10% showed 2+/3+ staining intensity in > 50% of NCs. 29% of cases showed a membrane positivity. Inflammatory component and normal tissue were positive in almost all cases. Conclusions: CD205 is heterogeneously expressed in the majority of TNBC and UC and in all PAC cases. The results of this study support the clinical investigation of MEN1309 in these tumor types.
IDH1 polymorphism G105G (rs11554137) as a prognostic factor in gliomas.
Authors: Franceschi Enrico , De Biase Dario , Tosoni Alicia , Paccapelo Alexandro , Acquaviva Giorgia , Pession Annalisa , Tallini Giovanni , Argento Chiara Maria , Bartolini Stefania , Brandes Alba Ariela 
Published: May 2019

e14734 Background: IDH mutational status is required for diagnosis according to the 2016 WHO criteria. The single nucleotide polymorphism (SNP) rs11554137 ( IDH1105GGT) at codon 105 of IDH1 has been reported in patients with several tumor types, including glioma. The aim of this study is to investigate the prognostic role of IDH1105GGT Methods: We analyzed our institutional data warehouse for consecutive patients (pts) with newly diagnosed, histologically proven grade II or Grade III gliomas. IDH sequencing was performed using the 454 GS-Junior next generation sequencer (NGS) (Roche Diagnostic, Mannheim, Germany). All analyses were performed on DNA from formalin fixed and paraffin embedded (FFPE) specimens. Results: The analysis included 77 pts with grade II (n = 51, 66.2%) or grade III glioma (n = 26, 33.8%). Median follow up of this study was 91 months. Patients received biopsy/partial resection/complete resection in 7.8%, 70.1% and 22.1%, respectively. Postsurgical RT and/or chemotherapy was delivered in 64.9% of pts. IDH mutations affecting codons 132 (for IDH1) and 172 (for IDH2) were found in 71 pts (92.2%). IDH1105GGTwas found in 11 pts (14.3%), mainly harboring also IDH mutations (81.8%), and was more frequent in grade 3 (30.8%) than in grade 2 gliomas (5.9%, P = 0.006). Pts harboring both IDH mutations and IDH1105GGTshowed a significantly longer progression-free survival compared with pts with IDH mutation alone (78.7 months vs 49.9 months, p = 0.041). Conclusions: IDH1105GGT represents a promising novel biomarker in IDH mutated grade 2 and 3 gliomas and warrants further investigations.
Receptor status conversion between primary and recurrent/metastatic breast cancer: A single institutional study.
Authors: Ramadas Poornima , Leibovitch Jennifer , Ramakrishna Karan , Krishnan Prathik , Wang Dongliang , Benjamin Sam 
Published: May 2019

e14735 Background: Hormone receptor and HER2 status have both predictive and prognostic implications in breast cancer (BC). Studies report differences of 3% to 54% for Estrogen receptor (ER), 5% to 78% for Progesterone receptor (PR), and 0% to 34% for HER2 between primary (P) and recurrent/metastatic breast cancer (RMBC). To evaluate this difference, we conducted an observational single institution study in adult patients (pts) ≥ 18 years with RMBC. Methods: After IRB approval, we conducted a retrospective chart review of pts diagnosed with RMBC between January 1st, 2010 and October 31st, 2018, with history of PBC. We recorded age at PBC diagnosis, stage, tumor type, receptor status, initial treatment, age at RMBC diagnosis, if biopsy performed, receptor status and survival. We studied the differences in ER, PR and HER2 receptors between P and RMBC. Descriptive statistics was used for analysis. Results: We found a total of 179 pts in the time interval. Median age was 54 ± 13.2 years at PBC diagnosis, 98.9% females, 1.1% males. 187 events were recorded. At PBC diagnosis, 27.4% had Stage I, 37.4% had Stage II and 31.8% had Stage III disease. Tumor type was ductal in 83.8% and lobular in 12.2%. 78.8% was ER+, 68.7% was PR+ and 14% was HER2+. 70.9% received chemotherapy, 12.8% received HER2 therapy and 67% received hormonal therapy. Age at RMBC was median of 61 ± 13.1 years. Biopsy was done in 93.3%. Time between PBC and RMBC ranged from 7 and 324 months. 31.3% had local recurrence and 68.7% had distant disease. In RMBC, 59.2% was ER+, 41.9% was PR + and 13.4% was HER2 +. 58.7% are alive and 38% deceased. With RMBC, 19.2% who were ER+ became ER-, 4.9% who were ER- became ER+, 37.5% who were PR+ became PR-, 8.6% who were PR- became PR+, 23.1% who were HER2+ became HER2-, 4.5% who were HER2 - became HER2+. In pts who became ER-/PR-, 88.5% received hormonal therapy and 61.5% received chemotherapy at the time of PBC. In pts who became HER2-, 83.3% received HER2 therapy at the time of PBC. Conclusions: In our study, we found a difference of 24.1% in ER, 46.1% in PR and 27.6% in HER2 between PBC and RMBC. It is recommended that patients with RMBC should have a biopsy to evaluate the receptor status as it would impact treatment and survival.
Analysis of lipid metabolism genes in advanced small cell lung cancer.
Authors: Merino Maria , Fernández Lara , Sereno Maria , Ramirez de Molina Ana , Moreno Juan , Colmenarejo Gonzalo , Gómez César , Lopez-Gomez Miriam , Falagan Sandra , Aguayo Cristina , Zambrana Francisco , Jimenez Gordo Ana Maria , Casado Enrique 
Published: May 2019

e14737 Background: Lung cancer is the leading cause of cancer death worldwide. Although most of the knowledge about metabolic dysregulation in cancer focuses on carbohydrates, the importance of alterations related to lipid metabolism is starting to be recognized. There is increasing data on lipid metabolism and non-small lung cancer, but much less is known about this in small cell lung cancer (SCLC). In order to improve our knowledge of these alterations we evaluated a genetic profile related to lipid metabolism and studied clinical outcomes. Methods: We performed a retrospective analysis of 22 genes related to lipid metabolism in 37 tumoral tissue samples of SCLC patients and evaluated clinical features and outcomes. Advanced SCLC patients enrolled from November 1, 2008 through December 31, 2015 were included in this analysis. Clinical data were collected from medical records at the time of enrollment. The study was approved by an Ethics Comittee and all patients signed an Informed Consent form. We used formalin-fixed, paraffin- embedded tumor tissue. Samples were deparaffinated and total RNA was extracted. A Taq-Man Low Density Array (Applied Biosystems) was specifically designed and gene-expression assays were performed in a HT-7900 Fast Real time PCR. RT-StatMiner software was used to detect and determine the quality control and differential expression analyses of data. Results: We included 37 patients, 73 % males and 27 % women, with a median age of 62. 29 patients (78%) had stage IV tumor and nearly all of them (92%) were treated with platinum- based chemotherapy. 11 % (4/37) received thoracic radiotherapy and 5% (2/37) received whole brain radiotherapy. 6 patients (16%) were on chronic treatment with metformin and 15 (40%) on statins. We performed a multivariable analysis and found that overexpression of two metabolic genes (a mitochondrial enzyme and a lipid metabolism regulator) led to longer overall survival. (HR 0.13 (0.04-0.42), p 0.0019, padjusted 0.04 and HR 0.11 (0.03-0.35) p 0.0006, padjusted 0.01, respectively). Conclusions: These genes contribute to normal functioning and regulation of lipid metabolism and could be considered as potential prognostic biomarkers. There is no previous evidence of association between levels of expression of these genes and overall survival in SCLC. Validation in a larger series of patients is ongoing.
Therapy alteration of solid tumors based on FoundationOne comprehensive genome profiling assay.
Authors: Karlin Kirill , Kahraman Abdullah , Curioni Fontecedro Alessandra , Moch Holger , Zoche Martin , Siebenhuener Alexander Rheinhard 
Published: May 2019

e14742 Background: Molecular profiling assays are becoming widely available and provide valuable information on tumor characteristics, which can identify targeted therapies or immunotherapies for cancer patients. However, the clinical utility of such tests remains unclear. Within our institution, we analyzed the clinical utility and subsequent treatment alterations of the FoundationOne Comprehensive Genome Profiling Test (FOne). Methods: We conducted a retrospective cohort review (2017 - 2018) of patients with solid tumors under standard diagnostic care who received FOne testing. We reviewed the therapies that were proposed by FOne and studied whether they led to a therapeutic alteration. Results: 71 patients were identified, of which the majority presented a progressive disease state (80%). Among the cancer types most frequently tested were adenocarcinoma of the colon (14%), prostate (8%), lung (4%), intrahepatic cholangiocarcinoma (8%) and breast invasive ductal carcinoma (4%). In 16 cases (22%), therapies suggested by FOne were approved in patient’s tumor type while in 30 cases (42%) therapies were approved in another tumor type. For an additional 13 cases (18%) only therapies tested in clinical trials were reported. 4 patients (6%) received a new therapy based on the FOne result: cancer of unknown primary (Everolimus due to a TSC1 mutation), cutaneous angiosarcoma (Pembrolizumab due to a high tumor mutational burden (TMB)), gastrointestinal neuroendocrine carcinoma (Ipilimumab and Nivolumab due to an intermediate TMB) and mucinous adenocarcinoma of the appendix (Talazoparib due to an ATM mutation). For 11 cases (15%), a new therapy option was identified by FOne, which due to the current treatment plan might be considered for later use. 3 cases (4%) were evaluated for potential clinical trial enrollment. Note that for an additional 6 patients (8%), the therapies proposed by FOne were already established on the basis of previous testing (e.g. smaller genomic panels, IHC, FISH). Conclusions: Overall, 18 (25%) patients received a new therapy option by FOne after standard of care diagnostics. Therapeutic alterations were observed particularly in patients with a rare or unknown tumor type.
p53 expression and clinical outcomes in untreated and treated breast cancer patients after long-term follow-up.
Authors: Yang Sherry X. , Huang Erich , Nguyen Dat 
Published: May 2019

e14745 Background: p53 alteration represents one of the hallmarks of malignant transformation. However, its role on treatment outcome remains controversial and is unknown in untreated patients in breast cancer. This study aims to evaluate p53 expression in association with clinical outcomes in untreated patients relative to those undergoing homogeneous therapy. Methods: p53 protein was examined by immunohistochemistry in 956 patients with stage I, II and III breast cancer. Overall survival (OS) and relapse-free survival (RFS) between p53-positive and -negative tumors in chemotherapy, radiation or endocrine therapy alone and no treatment groups were estimated by Kaplan-Meier method. OS and RFS were further assessed by multivariable Cox model that incorporates p53, age, tumor size and grade, estrogen receptor, and HER2 in specific treatment group(s). Results: p53 expression was detected in 22.7% of breast cancer. Median follow-up time was 115.5 months, with a range of 5 to 282 months. Expression of p53 was associated with younger age at diagnosis, higher tumor grade, ER/PR negativity, and HER2 positivity ( P< 0.001). Without any treatment including systemic and radiation therapy (n = 227), OS and RFS curves were overlapped from the beginning until the end of follow-up between p53-positive and -negative patients, respectively. In contrast, p53 was significantly associated with worse OS and RFS with univariate analysis and multivariate statistics of OS (HR 4.07, 95% CI 1.95-8.50; P< 0.001) and risk of relapse (HR 2.23, 95% CI 1.11-4.48; P= 0.025) by endocrine therapy alone (n = 130). Moreover, apparent trends for p53 toward unfavorable OS and RFS were observed in those undergoing homogeneous radiation therapy and chemotherapy, only within 150 months of follow-up. Conclusions: p53 is not associated with clinical outcomes in the absence of conventional therapy, and independently predicts worse survival and increased risk of recurrence after endocrine therapy.
Rectal cancer and pathologic complete response after preoperative chemoradiotherapy: Romanian single-center experience.
Authors: Bonci Eduard-Alexandru , Bobeş Valentin Ioan , Kirsch Timea , Ţîţu Ştefan , Adam Teodora-Irina , Vlad Ioan-Cătălin , Irimie Alexandru , Muntean Alina , Achimaş-Cadariu Patriciu 
Published: May 2019

e15002 Background: Current guidelines recommend neoadjuvant chemoradiation followed by total mesorectal excision for patients with locally advanced rectal cancer (LARC). After neoadjuvant chemoradiation, some of these patients achieve a pathologic complete response (pCR) of the primary tumor (ypT0) and seem to have improved oncologic outcomes. In the last years, a "wait-and-watch"/active surveillance or less radical surgery was proposed for these patients. The aim of this study was to analyze the overall survival (OS), disease-free survival (DFS), various clinicopathological factors and treatment factors in patients with LARC and ypT0 treated in our institution. Methods: Patients with LARC who received neoadjuvant chemoradiotherapy and achieved ypT0 on the surgical specimen were included in the present study. Clinical, pathological and surgical data from 51 patients was retrospectively collected between 1st of January 2012 and 31st of December 2017. Kaplan-Meier method and multivariate analysis were used to investigate the role of various clinicopathological factors and treatment characteristics in modulating the outcome for the patients included in the present study. Results: The study group included 18 females and 33 males having a mean age (+/- standard deviation) of 61 years (+/- 11,48) and 59 years (+/- 12,04), respectively. After a median follow-up of 19 months, OS was 88,24% and DFS was 98,03%. Classic open surgery was performed in all patients, low anterior resection and Miles resection was performed in 36 and 15 patients, respectively. Adjuvant chemotherapy was administered to 5 patients. Nodal status was ypT0N0 in 50 patients, ypT0N1 in one patient. Two of the recorded factors, stenosis and circumferential resection margin (CRM), appeared to play a significant role in modifying OS. Conclusions: Most of the patients with LARC treated with neoadjuvant chemoradiation and radical surgery seem to have a favorable long-term outcome but the stenosis and the involvement of CRM appears to predict the postoperative OS. Further studies are needed to determine the role of other factors in predicting OS and DFS in patients with LARC and ypT0.
Cost-effectiveness for metastatic colorectal cancer.
Authors: Yao Linli , Han Jiaqi , She Longjiang , Ding Dong , Liao Mengting , Hu Huabin , Zeng Shan , Shen Liangfang , Huang Jin 
Published: May 2019

e15003 Background: As standard third-line treatments for metastatic colorectal cancer, regorafenib and fruquintinib, compared with placebo, increase median overall survival by 2.5 months and 2.7 months, respectively. Given the incremental clinical benefit, we aim to estimate the cost effectiveness of regorafenib versus fruquintinib in the third-line treatment for patients with metastatic colorectal cancer from Chinese payer perspective. Methods: A mathematical Markov model was established to project the cost-effectiveness of regorafenib versus fruquintinib from the CONCUR and FRESCO clinical trials. Quality-adjusted-life-years (QALYs) were analyzed with extracted data from the trials. Willingness to pay (WTP) of $26508 was used. Drug costs were estimated from the perspectives of the health care system in the People’s Republic of China. One way sensitivity and scenario analyses were performed by varying potentially modifiable parameters of the model. Results: Fruquintinib, compared with regorafenib, provided an additional 0.028 QALYs (0.274 QALYs versus 0.246 QALYs) at less cost ($33536 versus $35607). Conclusions: Fruquintinib is more cost-effective than regorafenib as the third-line management for patients with metastatic colorectal cancer when WTP is $26508.
Cetuximab maintenance therapy in unresectable metastatic colorectal cancer patients with wild-type RAS and BRAF: A single-center retrospective study.
Authors: Jiang Tao , Lin Xiaoyan , Chen Hao , Zhen Jianwei , Du Bin , Liu Qing , Zhong Dongta , Yang Baoyu , Wang Xinli 
Published: May 2019

e15004 Background: Cetuximab plus FOLFIRI (leucovorin, fluorouracil and irinotecan) is preferred first line therapy for RAS and BRAF wild-type (RBWT) metastatic colorectal cancer (mCRC) patients. However, the side effects often require dose-reductions or discontinuation calling for maintenance strategies to reduce toxicity and preserve efficacy. Therefore, we evaluated efficacy and safety of cetuximab maintenance therapy after first-line treatment in unresectable mCRC patients with RBWT. Methods: This single center, retrospective study enrolled patients (aged 18-71 years) with untreated mCRC with RBWT, Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, with at least one measurable lesion according to response evaluation criteria in solid tumor (RECIST). All patients received first line cetuximab plus FOLFIRI every two weeks for 9-12 cycles, after which, patients with treatment response chose to either enter observation (stop treatment) or maintenance 1 (cetuximab plus irinotecan) group. After 6-12 cycles of maintenance 1, patients with treatment response entered maintenance 2 (cetuximab only). If patients progressed on maintenance 2, reintroduction of cetuximab plus FOLFIRI was suggested. Primary endpoint was failure-free survival (FFS); while secondary endpoints included disease control rate (DCR), objective remission rate (ORR) and progression free survival (PFS). Safety events were also evaluated. Results: Among 62 enrolled patients, 56 patients completed first-line treatment (DCR: 90.3%, ORR: 62.9%) and 30 patients entered maintenance 1 [median PFS1 (mPFS) =6.1 months, 95%CI: 6.0-6.2, DCR=60%, ORR=30%]. Of these, 18 entered maintenance 2 [mPFS2=6.6 months, 95%CI: 5.1-8.1, DCR=27.8%, ORR=5.6%]. The mFFS was significantly longer in maintenance 1 (12.8 months, 95%CI: 10.8-14.8) compared to observation group (3.0 months; hazard ratio [HR]: 0.21, 95%CI: 2.6-3.4, P<0.001). Overall mFFS was 19.0 (95%CI: 11.0-27.0) in maintenance and 9.5 months in observation group (HR: 0.195, 95%CI: 7.4-11.6; P<0.001). Rash acneiform, mucositis and asthenia were the common adverse events observed during maintenance treatment. Conclusions: Maintenance treatment with cetuximab after first line therapy significantly improved FFS, with acceptable safety profile in untreated mCRC RBWT patients.
Efficacy of quxie capsule in metastatic colorectal cancer: Update of a double-blind, randomized, placebo controlled trial.
Authors: Zhang Tong , He Wenting , Xu Yun , He Bin , Yang Yufei 
Published: May 2019

e15030 Background: To verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC). Methods: This is a update of a randomized, double-blind, placebo-controlled trial. Between April 2014 and July 2015, 121 patients were enrolled in the study. Sixty patients were eligible and randomized to the two groups at a 1:1 ratio. Treatment group received conventional therapy and Chinese herbal medicine combined with Quxie Capsule for 3 months. Control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). As of Dec 31st 2018, one patient in the control group was still alive, and all the other patients reached the main clinical endpoint. Median follow-up time was 19.4 months. Bo Ao Tong (Beijing) Medical Technology Co. Ltd. was responsible for the protocols of blind and block randomization. Results: The median OS were 23.9 months in the treatment group [95% confidence interval (CI) 15.9–28.5] vs. 14.3 months in the control group (95% CI 11.3–21.4) (Kaplan–Meier, Log-rank P=0.032), hazard ratio (95%CI)= 0.55 (0.31, 0.95), P=0.04. In the subgroups of left-sided colon, RAS wild type, non-targeted therapy, colon cancer and ≥second-line therapy, the median OS of the treatment group and the control group were respectively: 20.9 vs 12.2m, 17.4 vs 14.4m, 20.8 vs 12.0m, 25.1 vs 18.5m, 25.1 vs 12.0m ( P=0.037, 0.019, 0.022, 0.018, 0.007). There were no significant differences between the two groups in PFS. Conclusions: Quxie Capsule showed good efficacy, can reduce the risk of death and prolong the OS of patients with mCRC. Clinical trial information: ChiCTR-IOR-16009733.