bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors (PFs) of survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel (nab-P) plus gemcitabine (G) versus G alone in patients (pts) with metastatic pancreatic cancer (MPC).
Authors: Moore Malcolm J. , Von Hoff Daniel D. , Ervin Thomas J. , Arena Francis P. , Chiorean E. Gabriela , Infante Jeffrey R. , Hon Jeremy K. , Biakhov Mikhail Yu , Hingorani Sunil R. , Ganju Vinod , Weekes Colin D. , Scheithauer Werner , Ramanathan Ramesh K. , Tabernero Josep , Goldstein David , Wei Xinyu , Romano Alfredo 
Published: March 2020

4059^ Background: In MPACT, pts who received nab-P + G vs G had improved overall survival (OS; median 8.5 vs 6.7 mo; HR 0.72; p= 0.000015). Here we assessed potential PFs of OS. Methods: 861 pts with MPC were randomized 1:1, stratified by region, presence of liver metastases, and Karnofsky performance status (KPS), to nab-P + G or G. OS was described in subgroups. A step-wise multivariate analysis (with significance level for entry of 0.20 and for stay of 0.10) was performed to evaluate the treatment effect and identify possible predictors of OS. Results: Pts with poorer PFs had a shorter median OS, consistent with the literature, and OS consistently favored nab-P + G in pts with these PFs (Table). Region of Eastern Europe, age ≥ 65 years, poorer KPS, presence of liver metastases, and number of metastatic sites all predicted OS (increased risk of death). The treatment effect remained significant (HR 0.72; 95% CI, 0.605 - 0.849; p < 0.0001, Cox proportional hazards [CPH] model). In another multivariate analysis in which baseline CA19-9 was added to the final model described above, the treatment effect HR was 0.67 (95% CI, 0.573 - 0.794; p < 0.0001, CPH model). Baseline CA19-9, a predictor of OS by univariate analysis, was not predictive after correction for the above factors. Conclusions: In MPACT, the most important predictors of OS were KPS, age, presence of liver metastases, number of metastatic sites, and region. After correcting for these factors, assignment to nab-P + G was an independent significant predictor of improved survival. Clinical trial information: NCT00844649. [Table: see text]
Variable penetrance of CDH1 mutation diffuse gastric cancer: A genomic analysis.
Authors: Kelsen David Paul , Schrader Kasmintan A. , Khanin Raya , Tang Laura H. , Salo-Mullen Erin E. , Offit Kenneth , Joseph Vijai , Viale Agnes , Mirander Markenya , Coit Daniel G. , Strong Vivian E. , Janjigian Yelena Yuriy , Ilson David H. , Shah Manish A. 
Published: March 2020

4082 Background: CDH1 encodes E-cadherin; mutations (CDH1mut) increase the risk of diffuse gastric (DGC) and lobular breast cancers. Life-time risk of DGC is estimated at 80%. Current recommendations are prophylactic gastrectomy (PG) in CDH1mut carriers after age 20. Foci of DGC are found in some PG; others have none at PG, and some CDH1mut without PG never develop cancer. Identifying risk modifying alleles or other genomic events which increase the risk of DGC may improve understanding of DGC and may provide a biomarker for when to perform PG. Methods: For a Gastric Cancer Registry, we collected family pedigrees, germline DNA and FFPE tumor from CDH1mut DGC patients (pts) and their families. From 24 families, with 52 CDH1mut individuals, we identified 4 families in which a young CDH1mut pt developed advanced DGC while their CDH1mut parent and siblings had no clinical evidence of DGC. Several relatives had undergone PG with no DGC found. We hypothesize that there are risk modifying alleles and/or a “second hit” that causes variable penetrance and early onset of DGC in the young CDH1mut pts. Whole genome sequencing was performed on germ line DNA (Complete Genomics, Inc. Mountain View, CA); and whole exome sequencing on tumor specimens (MSKCC). Results: To date, 4 DGC pts and 8 relatives from 4 families have been studied. All 4 affected pts were women (ages 17, 25, 27, 42); their unaffected CDH1mut parents were 41, 51, 54, and 70 years old. The families are of Kenyan, Scandinavian, Italian, Eastern European, and Scottish origin. CDH1 mutations for the pts and their families were confirmed on WGS, and were as follows: 1451C>A(pro484his);c. 1792C>T (arg598ter);c. 1893dupA in exon 12;c. 1565+1G>A (IVS10+1G>A). Analysis of germline DNA for modifying alleles is being performed (Ingenuity Systems, Redwood, Ca.); whole exome sequencing of tumor to identify a possible "second hit" is underway. These data will be presented. Conclusions: Since at least some older pts with proven CDH-1mut do not develop DGC while their children do, CGH-1mut alone may not be sufficient to cause early onset DGC. We hope to identify the additional genomic events associated with early onset advanced DGC. Supported in part by grants from the Gerstner and DeGregorio Foundations.
Vascular endothelial growth factor expression in hepatitis C virus (HCV)-related advanced hepatocellular carcinoma (HCC) compared with hepatitis B virus (HBV)-related advanced HCC.
Authors: Shao Yu Yun , Hsieh Min-Shu , Huang Chung-Yi , Chang Yung-Ling , Hsu Chih-Hung , Cheng Ann-Lii 
Published: March 2020

4115 Background: HCC with different etiologic factors may result in activation of different signaling pathways. This study aimed to clarify if HBV-related HCC (HBV-HCC) and HCV-related HCC (HCV-HCC) may have difference in the expression of key molecules that are relevant to contemporary molecular targeted therapy. Methods: We enrolled patients diagnosed with advanced HCC from 2001 to 2011 who had tumor tissues obtained upon the diagnosis of advanced HCC at our center. Tumor slides were immunohistochemically stained for phosphorylated extracellular signal-regulated kinases (p-ERK), Raf kinase inhibitory protein (RKIP), and vascular endothelial growth factor (VEGF). The expressions of p-ERK and RKIP were evaluated according to percentages of positive-staining cells and graded as: 0: 0; 1+: 1-10%; 2+: 11-50%; 3+: > 50%. Grades 0 and 1 were considered negative, and grades 2 and 3 positive. VEGF staining was evaluated as strong or weak according to staining intensity. The staining results of VEGF were further recorded as H scores, defined as intensity (0, 1, 2, or 3) × percentages of positive staining. Results: In total, 131 patients were enrolled in this study; 94 (72%) patients had HBV-HCC, and 37 (28%) patients had HCV-HCC. HBV-HCC and HCV-HCC had similar expression of p-ERK (positive: 45% vs. 51%, p = 0.491) and RKIP (positive: 83% vs. 84%, p = 0.912). HCV-HCC was more likely to have strong VEGF staining than HBV-HCC (95% vs. 72%, p = 0.005) and higher H scores for VEGF staining (289.5 vs. 248.8, p< 0.001). In multivariate analysis adjusting for age, sex, macrovascular invasion, extrahepatic metastasis, and α-fetoprotein level, HCV-HCC remained an independent factor associated with strong VEGF staining. VEGF staining intensity was not associated with age, sex, macrovascular invasion, extrahepatic metastasis, and α-fetoprotein level. Conclusions: HCV-HCC has stronger VEGF expression than HBV-HCC. (This study was supported by the grant of NSC101-2314-B-002-141, 100CAP1020-2, and NTUH.101-N1965.)
A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: Final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study.
Authors: Yau Thomas Cheung , Cheung Foon Yiu , Lee Francis , Choo Su Pin , Wong Hilda , Toh Han Chong , Leung A. K. , Chan Pierre , Yau T. K. , Wong Joyce , Tang Y. F. , Lau Sze Man June , Cheung Tan To , Fan Sheung Tat , Poon Ronnie Tung Ping 
Published: March 2020

4117 Background: This is a single arm, multi-center, phase II study to assess the efficacy and tolerability of sorafenib, oxaliplatin and capecitabine combination for the treatment of advanced hepatocellular carcinoma (HCC) patients. Methods: Eligible patients received SECOX regime—sorafenib 400 mg bid (Day one-fourteen), oxaliplatin 85 mg/m2 (Day one) and capecitabine 1700 mg/m2(Day one-seven) every two weeks. Response assessment was based on RECIST 1.0 criteria. The primary endpoint was time-to-progression (TTP) and the secondary endpoints were tumor response rate (RR), progression-free survival (PFS), overall survival (OS) and tolerability. Results: A total of 51 patients were enrolled in the trial.The median age was 58 years (range, 28-81) and 84% of patients were chronic hepatitis B carriers. Ninety percent of recruited patients belonged to BCLC stage C disease and 41 (80%) patients had extra-hepatic metastasis. The best RR was 16% and they were all partial response. Another 62% of patients achieved stable disease for at least eight weeks. The median TTP was 5.29 months (95% CI 3.81-5.88 months), PFS 5.26 months (95% CI 3.75-5.88 months) and OS was 11.73 months (95% CI 8.87- 15.38 months). Diarrhea (75%), Hand-foot-skin reaction (73%) and transient liver function derangement were the most commonly encountered adverse events, with the majority of patients having grade one or two. No treatment-related death was reported. Conclusions: The SECOX regime indicates preliminary promising activity and safety in Asian population with advanced HCC. Our data support a randomized trial comparing SECOX versus sorafenib alone for treatment of advanced HCC. Clinical trial information: NCT00752063.
Impact of gender on survival of patients (pts) with hepatocellular carcinoma (HCC): A SEER analysis.
Authors: Yang Dongyun , Usher Josh , LoCoco Jordan , Pritesh Chaudhari , Lenz Heinz-Josef , El-Khoueiry Anthony B. 
Published: March 2020

4128 Background: The incidence of HCC is significantly higher in males (M) than females (F). Preclinical models suggest a role for estrogen in attenuating progression of HCC by various mechanisms such Il-6 suppression or estrogen receptor α-mediated inhibition of NF-κB activity. We investigated the impact of age and gender on survival in patients with HCC using the SEER data. Methods: We identified all patients diagnosed with HCC (ICD-O-3 Site code C22.0 and Histology Code 8170-8175) from 1988 to 2009 from the SEER registry. Pts with information on gender, age, ethnic background, and staging were included in the analysis. Exclusion criteria included fibrolamellar histology, diagnosis at autopsy or by death certificate, and absence of survival data. Hazard ratios (HR) for survival were derived using Cox regression model adjusted for race, year of diagnosis, marital status, treatment, birthplace, differentiation and tumor size. Results: A total of 38,250 pts were identified; 76% males; 50% White, 12% African American, 21% Asian, 16% Hispanic, and 1% Native American. 45% had liver limited disease (44%M, 50%F), 37% had macrovascular invasion (37%M, 35%F), 18% had metastatic disease (19%M, 15%F). Treatment information was available for pts diagnosed after 1998 (n=32,938): 11% received liver directed therapy, 11% had surgical resection, and 7% underwent liver transplantation. Median age at diagnosis was 61 years for M versus 68 years for F. HR for OS of F versus M was 0.83 (95%CI:0.78-0.89) for pts < 55 years old. In contrast, the OS HR of F versus M was 0.95 (95%CI:0.92-0.98) for pts ≥ 55 years old and 0.98 (95%CI: 0.94-1.01) for pts ≥ 65 years old. The F vs. M (<55 yrs old) HR for OS by stage of disease was: liver limited disease: HR 0.90, CI: 0.81-1.01; macrovascular invasion: HR 0.81, CI: 0.73-0.89; metastatic disease, HR 0.80, CI: 0.70-0.92. Conclusions: Females under the age of 55 appear to have superior survival compared to males with HCC based on a SEER data analysis. This finding is in line with preclinical reports of estrogen attenuation of HCC development and progression.
sVEGFR2 and circulating tumor cells to predict for the efficacy of pazopanib in neuroendocrine tumors (NETs): PAZONET subgroup analysis.
Authors: Grande Enrique , Casanovas Oriol , Earl Julie , Castellano Daniel E. , Garcia-Carbonero Rocio , Teule Alex , Duran Ignacio , Fuster Jose , Sevilla Isabel , Escudero Pilar , Sastre Javier , García-Donas Jesús , Ortega Luis , Diez Juan Jose , Soria Rivas Ainara , Capdevila Jaume 
Published: March 2020

4140 Background: The PAZONET trial (Grande et al, ESMO 2012) performed by the GETNE group analyzed the efficacy and safety of the use of pazopanib (800 mg/qd) in patients (pts) with progressive metastatic NETs that had been previously treated with other novel targeted agents. Here we report on the relationship between clinical outcome and circulating and tumor-related biomarkers. Methods: Kaplan-Meier analysis was used to correlate progression-free survival (PFS) with: blood circulating markers at baseline and after 12 weeks of treatment (VEGF-A and sVEGFR2 circulating plasma, Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC)), tumor functional status, Ki67, concomitant somatostatin analogues (SSA), chromogranin A (CgA) and primary tumor location. Results: 44 pts were enrolled, 42 were evaluable for response. sVEGFR2 decreased after 12 weeks of treatment (median decrease 20%, p<0.0001) and the duration of treatment with pazopanib was associated with a decrease in sVEGFR2 (p=0.0046). Pts with a decrease in sVEGFR2 of >20% and <=20% had a median progression-free survival (mPFS) of 12.6 and 9.1 months (mo) respectively (p=0.067). Pts with and without CTC at baseline had a mPFS of 5.8 and 9.1 mo respectively (p=0.12). VEGFA and CEC were not found to predict PFS. mPFS in the intention to treat population was 10.0 mo (95% CI 4.3-15.6). Significant differences in mPFS were found in concomitant SSA treatment (11.9 mo [10.6-13.2]) vs. pazopanib alone (4.8 mo [3.0-6.6]) (p=0.007); decrease of CgA (3.4 mo [0.0-6.8]) vs no decrease (11.2 mo [8.4-14.1]) (p=0.024) and pancreatic (12.8 mo [11.0-14.6]) vs gastrointestinal (10.0 mo [4.9-15.1]) vs other primary tumors (3.4 mo [0.0-7.0]). No differences in mPFS were seen in functioning (10.0 mo) and non-functioning tumors (9.3 mo) and Ki67 status (< 2% 10.0 mo, 3-10% 10.8 mo or >10% 4.1 mo). Conclusions: sVEGFR2 and baseline CTC are promising predictive biomarkers for pazopanib in NETs. The updated results confirm the efficacy of pazopanib as a sequencing treatment of pts with progressive NETs, particularly in those with pancreatic primary tumors. The combination of pazopanib and SSA seems to be synergistic. Clinical trial information: NCT01280201.
Survival and toxicity in patients with disseminated germ-cell cancer above 40 years of age.
Authors: Thomsen Frederik Birkebæk , Bandak Mikkel , Thomsen Maria Ferløv , Lauritsen Jakob , Christensen Ib Jarle , Gedske Daugaard Kirsten 
Published: March 2020

4532 Background: The aim was to analyze treatment related toxicity and survival in patients aged 40 years or above (40+) treated with standard chemotherapy for germ-cell cancer (GCC). Methods: The study population comprised 135 40+ patients with disseminated GCC treated between 1984 – 2011 with either 3 or 4 cycles bleomycin, etoposide and cisplatin (BEP). A control-group of 135 patients aged 18-35 years was randomly selected matched on year of BEP treatment. All patients were followed until death or October 1st2011. Cumulated doses of BEP as well as bone-marrow toxicity, renal- and lung functions were recorded before, during and after termination of treatment. The expected mortality was calculated by extracting survival data for each patient matched on the date and age at the time of diagnosis. The cause of death was categorized as GCC, other malignancy or other. Results: The cumulated doses of BEP were comparable between the two groups and, generally, BEP was equally well tolerated. 40+ patients had increased cancer specific mortality, HR = 4.8 (P = 0.005). Especially patients with disease progression after first line chemotherapy had increased mortality (P = 0.015). The year of treatment (P = 0.32), histology (P = 0.30), CCI (P = 0.99), tobacco use (P = 0.16), alcohol consumption (P = 0.21), prophylactic G-CSF (P = 0.61), reduced doses of bleomycin (P = 0.11) and decreased renal function (P = 0.18) were not significantly associated with GCC mortality. However, patients with impaired lung function (<80% of expected) prior to treatment had an increased risk of GCC mortality (FVC (P = 0.03), DLCO (P = 0.01) and FEV1(P = 0.05)). Moreover, the 5-year overall survival in the 40+ group was 82.5% compared to the expected 5-year survival of the background population of 96.2% (P <0.001) and the estimated 5-year survival of 97.0% in the control-group (P <0.001). Conclusions: Reduced treatment intensity, or treatment related toxicity could not explain the increased mortality in 40+ GCC patients compared to a younger control-group. The 40+ group has a significantly lower response rate to BEP and a significantly higher mortality in case of disease progression. The worse prognosis could be related to tumor biology or increased co-morbidity.
Efficacy and safety of enzalutamide (ENZA) monotherapy in hormone-naive prostate cancer (HNPC).
Authors: Smith Matthew Raymond , Borre Michael , Rathenborg Per , Werbrouck Patrick , Van Poppel Hendrik , Heidenreich Axel , Iversen Peter , Baskin-Bey Edwina , Perabo Frank , Phung De , Tombal Bertrand 
Published: March 2020

5001 Background: In locally-advanced prostate cancer, the antiandrogen bicalutamide (Bic) is used to maintain quality of life relative to castration therapy (LHRHa), but efficacy as a monotherapy is limited. ENZA is an oral androgen receptor (AR) inhibitor with higher AR–binding affinity vs Bic, and it prevents nuclear translocation, shows no DNA binding, and induces apoptosis. ENZA was approved in the US after prolonging overall survival in post-docetaxel metastatic castration resistant prostate cancer. This phase 2 study assessed ENZA monotherapy in patients (pts) with HNPC and noncastrate testosterone (T) ≥230 ng/dL. Methods: Pts with any stage HNPC (ECOG PS 0, life expectancy >1 y) requiring hormonal therapy received ENZA 160 mg/d for 25 wks. Primary endpoint was PSA response (≥80% decline at wk 25). Other endpoints were endocrine levels, pharmacokinetics, safety, and metabolic changes (body composition, bone biomarkers, lipids, and glycemic profiles). Results: 67 pts were enrolled. Median age was 73 y; 39% had metastases, 36% and 24% had prior prostatectomy and radiation, respectively. ENZA levels reached steady state after ~4 wks. Mean changes in metabolic outcomes at wk 25 included: –0.24% total body bone mineral density (BMD), –4.15% lean body mass, 6.85% fat body mass, 14.75% bone alkaline phosphatase, 4.55% total cholesterol, 6.48% triglycerides, –1.98% A1c, –0.10% fasting glucose, and 45.06% HOMA-IR. At wk 25, PSA response was 93% (62/67; 95% CI, 86%–99%); median PSA decrease was –99.6%. Mean T and estrogen increased 114% and 72%, respectively; other endocrine increases were observed, the highest was 185% for luteinizing hormone. Most common treatment-emergent AEs were grade 1 and included gynecomastia (36%), fatigue (34%), nipple pain (19%), and hot flush (18%). Five pts had serious AEs (none drug related). Conclusions: ENZA monotherapy achieved a high PSA response rate and marked PSA decline with efficacy similar to castration. In contrast to castration, BMD remained stable and metabolic variables (fat body mass, lipid and glycemic profiles) were not substantially impacted with ENZA monotherapy over the 6 month study period. Endocrine changes and AEs were consistent with potent AR inhibition. Clinical trial information: NCT01302041.
Follow-up results of NOAH, a randomized phase III trial evaluating neoadjuvant chemotherapy with trastuzumab (CT+H) followed by adjuvant H versus CT alone, in patients with HER2-positive locally advanced breast cancer.
Authors: Gianni Luca , Eiermann Wolfgang , Semiglazov Vladimir , Manikhas Alexey , Lluch Ana , Tjulandin Sergei , Zambetti Milvia , Vazquez Federico , Byakhov Mikhail J. , Lichinitser Mikhail , Climent Miguel Angel , Ciruelos Eva , Ojeda Belen , Mansutti Mauro , Bozhok Alla , Magazzu Domenico , Steinseifer Jutta , Valagussa Pinuccia , Baselga Jose 
Published: March 2020

503 Background: The monoclonal antibody trastuzumab (H) has been shown to improve event-free survival (EFS) and pathologic complete response (pCR) in patients with HER2-positive locally advanced or inflammatory breast cancer receiving neoadjuvant chemotherapy with or without one year of trastuzumab in the primary analysis of the NOAH study (Gianni L, Lancet 2010). Updated EFS and overall survival (OS) results are now presented. Methods: In this international, multicenter, open-label, randomized phase III trial patients with locally advanced or inflammatory breast cancer were randomized 1:1 to receive CT+H followed by adjuvant H versus CT alone. A parallel cohort of 99 comparable patients with HER2-negative disease was included and treated with the same chemotherapy regimen. The neoadjuvant chemotherapy regimen included doxorubicin, paclitaxel, cyclophosphamide, methotrexate and 5-fluorouracil. The primary objective was to compare EFS defined as time from randomization to disease recurrence or progression [local, regional, distant or contralateral] or death due to any cause). Results: After a median follow up of 5.4 years, the EFS benefit with trastuzumab was confirmed. Cardiac tolerability was good despite concurrent administration of trastuzumab with doxorubicin. Two patients (2%) developed reversible symptomatic congestive heart failure and are presently alive. Conclusions: Present analysis confirms the significant EFS benefit observed in the primary analysis of the NOAH study, and shows a strong trend towards improved OS with the addition of trastuzumab to chemotherapy. pCR rate may be considered as a possible primary endpoint and early indicator of benefit in future neoadjuvant studies of HER2-targeted agents. Clinical trial information: 86043495. [Table: see text]
Post-treatment alterations in 18F-dihydrotestosterone (FDHT) and FDG PET/CT in metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib.
Authors: Fox Josef J. , Haupt Eric C. , Humm John , Autio Karen A. , Rathkopf Dana E. , Vargas Hebert Alberto , Schöder Heiko , Hricak Hedvig , Larson Steven M. , Scher Howard I. , Morris Michael J. 
Published: March 2020

5073 Background: Cabo is a multitargeted kinase inhibitor that has demonstrated complete and partial responses in mCRPC as assessed byTc-99 MDP bone scintigraphy. FDG and FDHT PET/CT demonstrate glucose metabolism and androgen receptor binding, respectively. We are exploring these tracers as response biomarkers in mCRPC treated with cabo. Methods: Patients (pts) treated with cabo were scanned with FDHT and FDG PET at baseline and after 6, 12, and 24 weeks (wks) of treatment. 5 index lesions were selected at baseline for each PET modality. The hottest slices from each were averaged (SUVmaxavg) and measured on post-treatment scans. The concordance of the post-treatment alterations of the two tracers (rise vs. decline) was examined, as were PSA alterations. Results: All 16 pts had FDG avid and 15 had FDHT avid disease. Baseline median FDHTmaxavg was 10.84 (3.52 – 18.52) and FDGmaxavg was 6.26 (2.74 – 14.7). Post-treatment alterations are described (Table). Conclusions: Most pts with mCRPC demonstrate diminution of FDHT uptake after 6 and 12 wks of treatment with cabo. These declines are matched by FDG 50-60% of the time, and correlate with PSA declines even less frequently. The etiology of the extent and degree of FDHT declines, and lack of concordance with post-treatment PSA changes, warrant further investigation, and correlation with other imaging modalities and clinical outcomes. Clinical trial information: NCT00588185. [Table: see text]