bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of pegylated liposomial doxorubicin (PLD) and gemcitabine (G) in the treatment of hepatocellular carcinoma (HCC) not suitable for loco-regional therapy
Authors: Pastorelli D. , Cartei G. , Zustovich F. , Zovato S. , Artioli G. , Ceravolo R. , Nicoletto M. , Binato S. , Mattiazzi M. 
Published: March 2020

4585 Background: There is no gold standard pharmacological treatment for HCC not suitable for loco-regional therapy. Antracyclines have been often used for the chemotherapy of HCC with low efficacy and well known toxicity. Availability of new drugs and in particular of PLD could enhance the chance of treatment and contain side-effects. Gemcitabine is active against the most solid tumors. Patients and Methods: We enrolled 35 patients (PTS) with histological diagnosis of HCC not suitable for loco-regional treatment and adequate haematological function.; median age was 63.2 (range 44.0–77.4); male/female=29/6; PS=0 in 30 PTS, PS=1 in 4 PTS and PS=2 in 1 PT. Eighteen PTS had metastatic disease. Prior treatments were TACE in13 PTS, PEI in 9, surgery in 12, RFTA in 5 and chemotherapy in 3. Nineteen patients had Child-Pough A-B cirrhosis HBV-HCV related. PLD was administered at the dose of 30mg/m2 over a 60’ infusion every 28 days and G at the dose of 1,000mg/m2 over 30’ infusion days 1 and 8 every 28 days. Instrumental response evaluation was performed every 3 cycles and treatment was continued until disease progression or major toxicity evidence. Results: All PTS were valuable for toxicity: G1–2 toxicity was neutropenia in 5 PTS, thrombocytopenia in 7, mucositis in 3 and PPE in 3. G3–4 toxicity was neutropenia in 6 PTS and thrombocytopenia in 1. Thirty-four PTS were valuable for response with CR in 2, PR in 6, SD in 12 and PD in 14. Thirty-four PTS were valuable for TTP: median was 6.2+ months (range 1.9–31.7+). All PTS were valuable for OS: median was 8.8+ months (range 1.9–36.5+). Conclusions: The combination of PLD and G is safe and effective in treatment of HCC. No life-threatening toxicity was experienced and disease control rate was about 60%. No significant financial relationships to disclose.
Phase II study of gefitinib and docetaxel for patients (pts) with advanced pancreatic adenocarcinoma (APC) progressing after first-line therapy. Final results
Authors: Brell J. M. , Matin K. , Evans T. , Volkin R. L. , Keifer G. J. , Schlesselman J. J. , Dranko S. , Rath L. , Schmotzer A. , Ramanathan R. K. 
Published: March 2020

4586 Background: Gemcitabine is the standard-of-care for APC; the epidermal growth factor receptor (EGFR) inhibitor erlotinib is sometimes added to initial therapy. Pre-clinical data supports the addition of the EGFR inhibitor gefitinib to docetaxel, an agent with activity in APC. Because there is no standard treatment after gemcitabine failure, this combination was examined in a phase II study. Methods: Pts were required to have APC and have failed one prior treatment regimen; EGFR over-expression was not required. The initial docetaxel dose was 75 mg/m2 on day one every 21 days . Due to febrile neutropenia in 8 of 18 pts, the dose was reduced to 60 mg/m2. Gefitinib 250 mg/day orally was given continuously. Accrual of 41 pts was planned in a one-stage design to identify a targeted 50% improvement in median survival from 3.5 to 5.3 months (mo) by one-sided log-rank test (80% power, a = 0.05). Results: Forty five pts met eligibility and signed consent; 41 pts received treatment and were evaluable. Pt characteristics: 68% male, median age 63 yrs. (range 47 - 82). ECOG performance status (PS) 0 - 1 in all pts, except for 3 with PS of 2. Common treatment-related Grade 3 - 4 toxicities were: febrile neutropenia / infection in 11 pts (27%), with most events occurring at docetaxel dose of 75 mg/ m2 (8 of 18 pts); fatigue (7%), nausea (7%), diarrhea (5%) and vomiting (2%). Only 3 pts discontinued treatment due to toxicities and more than 2 cycles were administered to 40% of patients. The median survival was 4.7 mo (95% CI 2.9 - 5.7 mo). Time to progression was 1.8 months. There was one partial response (PR) and stable disease (SD) in 14 pts. Conclusion: The combination of gefitinib (250 mg/d) and docetaxel (60 mg/ m2) had evidence of some efficacy with one PR and SD in 14 pts. The median survival was 4.7 mo, somewhat lower than our intended target (5.3 mo). The tolerability and feasibility of second-line therapy for APC was demonstrated, and results of this study can be used as a benchmark to evaluate novel therapies in subsequent studies. (Supported by Astra Zeneca Pharmaceuticals) No significant financial relationships to disclose.
Smad4 is predictive for response in neoadjuvant treated esophageal squamous cell carcinoma
Authors: Brücher B. L. , Pühringer-Oppermann F. , Sarbia M. 
Published: March 2020

4591 Background: The evaluation of the prevalence of TGF-β1-pathway gene expressions (TGF-β1, Smad7 and Smad4) and its predictive value for histopathological response in patients with esophageal squamous cell carcinoma and neoadjuvant radiochemotherapy. Methods: RNA was prepared from pretherapeutic taken formalin-fixed and paraffin-embedded biopsies of 98 patients with histological proven locally advanced ESCC (cT3, cN0/+, cM0), who underwent preoperative combined simultaneous RTx/CTx with consecutive esophagectomy. All tumor biopsies underwent tumor-cell-microdissection, RNA-extraction and real-time TaqMan reverse transcriptase- polymerase chain reaction. RT-PCR-measurements were made by doublet measuring. Quantitative mRNA expression of TGFβ1 and its downstream effectors Smad4 and Smad7 was correlated with histopathological response by the percentage of residual tumor cells. Analysis was performed by dichotomized calculation and for determination of a cut-off by ROC-analysis. Results: Dichotomized analysis revealed the following median values: Smad4=0.098± 0.7 (CI: 0.024–0.396), Smad7=1.9250±1.7 (CI: 0.4–16.1) and TGFβ1=6.427±4.86 (CI: 0- 25.7). Cross-tabs-analysis for histopathological response disclosed the following correlations: TGFβ1 (p=0.671), Smad7 (p=0.672) and Smad4 (p=0.038). ROC-analysis revealed a Smad4-cut-off of 0.0635 by an area-under-curve of 6280 (p=0.038). Consecutive re-cross-tabs-analysis of histopathological response revealed a sensitivity of 80% (p=0.013). The pretherapeutic predictive value of Smad4 was 73%. Medians in survival was not reached during follow-up, whether TGFβ1 (p=0.519), Smad7 (p=0.5728) nor Smad4 (p=0.552). Histopathological responders showed a significant better survival compared to nonresponders (p<0.0001). Conclusions: High levels of Smad4 gene expression are significantly correlated with histopathological response. ROC-Analysis identified a cut-off of Smad4 with a sensitivity of 80% and a predictive value of 73%. No significant financial relationships to disclose.
Characteristics, treatment and outcome of patients with hepatocellular carcinoma (HCC) in the United States: An analysis of 328 patients from 1998–2005
Authors: Stadler Z. K. , Stuart K. E. 
Published: March 2020

4615 Background: International studies have described the clinical characteristics and outcomes of patients with HCC. However, patient demographics, tumor characteristics, extent of liver disease, risk factors, treatment and outcome are less well established in the United States (US) where HCC remains rare. Methods: We identified 328 patients presenting to Beth Israel Deaconess Medical Center with a new diagnosis of HCC from 1998–2005. Characteristics including risk factors, underlying liver disease, tumor morphology and treatment were entered into a retrospective database. Child-Pugh grade and Cancer of the Liver Italian Program (CLIP) score were determined. Survival analysis was performed and data compared to our previously published HCC cohort from 1985–1995. Results: Patient characteristics were: Median age: 62; Male: 81%; Alcohol use (EtOH): 44%; Hepatitis C (HCV): 38%; Hepatitis B (HBV): 21%; No Risk Factor: 15%. EtOH was more common in HCV (57%) than in HBV (18%) patients. Treatment modality was: liver transplantation (LT) 14.4%, surgical resection 7.8%, chemoembolization or radiofrequency ablation (CE/RFA) 36%, chemotherapy 22%, no treatment 16%. Median overall survival was 13.5 months. Significantly better median survival was associated with Child-Pugh grade A (20.3 mos.), uninodular tumor in <50% of liver (34.3 mos.), absence of portal vein thrombosis (19.2 mos.), CLIP score of 0 (42.5 mos.), background of HBV (32.9 mos.) and No EtOH (16.2 mos.). Treatment correlated with survival: LT, resection, or CE/RFA showed significantly better survival than chemotherapy or no treatment. In comparison to the 1985–95 cohort, median survival improved from 10 to 13.5 months. The 1998–05 cohort had more HBV/HCV (57% versus 20%), more favorable tumor characteristics, less severe liver disease, and more LT (14.4% versus 2.8%). Conclusions: In this single US institution, survival of HCC patients improved by 35% over two decades. Our results are consistent with nationwide trends of increased prevalence of viral infection, screening to find earlier disease, and more widespread use of aggressive treatments. Changing patterns of approaching the cirrhotic patient with HCC may be leading to slightly better results. No significant financial relationships to disclose.
Phase II study of gemcitabine, oxaliplatin in combination with bevacizumab (GEMOX-B) in patients with unresectable or metastatic biliary tract and gallbladder cancers
Authors: Clark J. W. , Meyerhardt J. A. , Sahani D. V. , Namasivayam S. , Abrams T. A. , Stuart K. , Bhargava P. , Blaszkowsky L. S. , Jain S. R. , Zhu A. X. 
Published: March 2020

4625 Background: Patients (Pts) with unresectable or metastatic biliary tract cancer (BTC) and gallbladder cancer (GBC) have a poor prognosis. Vascular endothelial growth factor (VEGF) expression has been detected in BTC and GBC. Increased angiogenesis has been correlated with advanced stage of disease and poor prognosis. Given reported activity of gemcitabine (GEM) and oxaliplatin (OX) in BTC/GBC and potential benefits of targeting the VEGF pathway with bevacizumab (B), we performed a study to examine the efficacy and tolerability of GEM, OX and B (GEMOX-B) in unresectable or metastatic BTC/GBC. Methods: Eligibility criteria included unresectable or metastatic measurable BTC/GBC, 0–1 prior chemotherapy regimens, performance status = 2, and adequate organ function. No clinically significant cardiovascular disease or history of active bleeding. Pts were treated with all 3 drugs intravenously on days 1 and 15 every 28 days (one cycle): B was given first at 10 mg/kg, followed by GEM at 1000 mg/m2 as dose rate infusion at 10 mg/m2/minute, and OX at 85 mg/m2. Whole body FDG-PET scan was obtained at baseline and after cycle 2. The primary endpoint of the study was progression-free survival (PFS). Results: 19 pts (10 BTC and 9 GBC) have been enrolled since May 17, 2006: median age = 69 (25–82), M/F = 13/6, ECOG 0/1/2 = 7/10/2. Treatment has been well tolerated with no grade 4–5 toxicities seen. Treatment related grade 3 toxicities included (number of pts): hypertension (2), neutropenia (1), transient SGPT elevation (1), proteinuria (1), neuropathy (1), and fatigue (1). Of 11 pts followed for at least 4 months, 3 had confirmed partial responses (PR), 5 had stable disease (SD) of at least 4 cycles, and 3 had progressive disease (PD) per RECIST criteria. Five pts had more than 50% decrease in CA19–9 levels. Of 16 PET studies analyzed, changes in SUV values from baseline to after 2 cycles of treatment were: 11 PRs, 4 SDs, 1 PD per EORTC criteria. Conclusions: GEMOX-B can be safely administered with tolerable safety profiles in patients with advanced BTC/GBC. Early evidence of antitumor activity was seen. A decreased SUV in FDG-PET following GEMOX-B treatment was observed in the majority of patients. No significant financial relationships to disclose.
Small cell carcinoma of the esophagus: Review of the Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: Ku G. Y. , Kelsen D. , Minsky B. , Rusch V. , Bains M. , Ilson D. H. 
Published: March 2020

4631 Background: Esophageal small cell carcinoma (ESC) is rare and accounts for <1% of all esophageal cancers. It is treated like pulmonary SC but the optimal approach of surgery, chemotherapy or radiotherapy is unknown. Prior series (Chest 107:179, Cancer 88:262) indicate a poor median overall survival (OS) of 7–12 months (mos), rare long-term (LT) survival and the need for surgery as part of curative therapy. Methods: We reviewed records of patients (pts) with ESC treated from 1980 to 2005. All pathology was reviewed at MSKCC. Results: 24 pts were identified, with records available for 21. 86% male, 14% female, median age 60, 67% smokers. 81% had pure SC histology, with 85% of tumors in the lower esophagus or gastroesophageal junction. 13/21 (62%) had limited disease (LD) by VALSG criteria. For extensive disease (ED), liver (63%) was most common metastatic site (mets). Treatment for LD was: chemotherapy (chemo) only (3 pts, 23%), surgery only (1 pt, 8%), surgery and adjuvant chemo (3 pts) and chemoradiation (CRT) without surgery (6 pts, 46%). The most common chemo given was cisplatin/carboplatin and etoposide (81%). Pts with ED received chemo alone. Overall median survival was 19.8 mos (range, 1.5 mos to 11.2+ years (yrs)); for LD Pts, 22.3 mos (range, 6 mos to 11.2+ yrs); for ED Pts, 10.9 mos (range, 1.5 mos to 2.2 yrs). At median follow-up of 32 mos, 5 pts are alive (4 without disease (NED) and 1 with disease); 2 pts are alive >5 yrs. 4 originally had LD and 3 of 4 received CRT only without surgery. None received whole brain radiation (WBXRT). 1 LD pt treated with surgery and adjuvant chemo recurred after 4 yrs, was salvaged with CRT and is NED 11.2 yrs after diagnosis. Of 18 pts with progression, 10 (56%) had new mets. Most common site was liver (4 pts) and only 1 pt had brain mets. Of 6 pts with LD who received CRT only, 3 recurred (1 local and 2 distant). Of 4 pts with LD who underwent surgery, all recurred (1 local, 3 distant). Conclusions: Pts with ESC with LD who received CRT without surgery can have LT survival. The role of surgery remains unclear. LT survival for 1 pt who underwent salvage CRT for recurrence after surgery argues for aggressive therapy for recurrence. Unlike pulmonary SC, brain mets are uncommon and WBXRT may not be needed for LT survival. No significant financial relationships to disclose.
A multi-center phase II study of S-1 plus paclitaxel as first-line therapy in patients with advanced or relapsed gastric cancer
Authors: Lee J. J. , Kim S. Y. , Chung H. C. , Lee K. H. , Song H. S. , Woo I. S. , Hong Y. S. , Kang W. K. , Choi J. H. , Choi I. S. 
Published: March 2020

4634 Background: S-1 is an oral prodrug of 5-fluorouracil (5-FU) including two modulators to enhance the antitumor effect and to decrease gastrointestinal toxicity. Paclitaxel has the synergistic antitumor effect with 5-FU. This study were planned to evaluate the efficacy and safety of S-1 and paclitaxel combination therapy in advanced gastric cancer. Methods: Eligible patients had untreated advanced or relapsed gastric cancer with measurable lesion(s), histologic proof, ECOG PS 0–2, adequate organ function, and signed informed consent. Treatment consisted of S-1 35mg/m2 p.o. b.i.d. on days 1–14 plus paclitaxel 70mg/m2 i.v. on days 1& 8 of a 21-day cycle. Measurable and/or unmeasurable lesion was assessed after every 2 courses with RECIST criteria. Results: A total of 56 patients (M/F=37/19) were enrolled. The median age was 59 years with advanced (n=43) and relapsed (n=13) gastric cancer. The common metastatic lesions were abdominal lymph nodes (71%), liver (39%), and peritoneum (21%). Out of 53 evaluable patients, there was 1 (2%) CR, 25 (47%) PRs, 21 (40%) SDs, and 6 (11%) PDs. Objective tumor response was 49%. Median duration of response was 5.4+months after the confirmation of response. Median follow-up was 9.6 month. Median PFS was 7.7 months and median survival was 14.6 months. Median number of cycle was 6 (range, 1–14). The relative dose intensity of S-1 and paclitaxel was 93%, both. The most common causes of delayed cycle and dose reduction were neutropenia and diarrhea, respectively. All 56 patients were assessed for safety. This treatment was well tolerated with grade 3/4 neutropenia in 14%/5%, grade 3 febrile neutropenia in 5%, grade 2/3 N/V in 21%/0%, anorexia in 18%/2%, diarrhea in 9%/4%, stomatitis in 7%/4%, and neuropathy 7%/0% of patients. Conclusions: S-1 and paclitaxel combination chemotherapy showed significant antitumor effect with manageable and tolerable toxicities in patients with advanced gastric cancer. (This study was partially supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (0412-CR01–0704–0001)) No significant financial relationships to disclose.
Different chromosomal alterations correlate with gene expression in African American (AA) versus Caucasian American (CA) prostate cancer (PC) patients
Authors: Jean-Gilles J. , Satagopan J. , Zhou Q. , Dash A. , Yu J. , Lee P. , Scher H. I. , Gerald W. , Osman I. 
Published: March 2020

5000 Background: We used a genome wide approach to identify chromosomal and gene expression alterations that might explain the aggressive clinical behavior of PC in AA compared with CA patients. Methods: We frequency matched 20 AA with 20 CA patients for potential confounding factors (PSA, age, Gleason grade, pathologic stage). We utilized array-CGH (Spectral Genomics), to identify noteworthy genomic regions with significantly different chromosomal alterations between the 2 groups. RNA samples were available for 19 AA and 14 CA patients. Gene expressions were examined using Affymetrix HG-U133 Plus 2.0 arrays. Correlations were examined between the noteworthy altered chromosomal regions and gene expression. Results: Regions of chromosomal gain or loss in each sample were determined using the circular binary segmentation approach coupled with an outlier detection method to identify singleton markers exhibiting alterations. We identified 28 chromosomal regions that were significantly different between the 2 cohorts (Fisher’s exact test). 11 regions (3q28- 29, 3q25–26, 4p12–14, 4p13, 9q21, 10q11, 11q14, 12p13, 14q12, 16p11, 20p11–20q11) were more commonly altered in AA patients compared to CA patients (P<0.005). The altered chromosomal regions were associated with corresponding gene expression changes. Gene ontology and pathway analyses showed a relatively short list of affected pathways: insulin, STAT, TGF-beta signalings, proteosome degradation, integrin- mediated cell adhesion, adipose and calcium metabolisms. Hierarchical clustering of the 33 patients (19 AA and 14 CA) based on the shortlist of gene expressions showed two clusters, one consisting of CA and the other with AA patients, with only 3 AA patients showing similar gene expression to CA group and vice versa. Conclusions: Data demonstrate the presence of biologic differences between the AA and CA cohort of patients studied and suggest that the disproportionately unfavorable outcome of PC in AA patients cannot solely be explained by advanced tumor at presentation. Validation in an independent larger sample size is a prerequisite before further conclusions can be made. No significant financial relationships to disclose.
A randomized, placebo-controlled trial of celecoxib in men prior to receiving prostatectomy for clinically localized adenocarcinoma of the prostate: Evaluation of drug-specific biomarker modulation
Authors: Carducci M. A. , Walczak J. R. , Heath E. , Nelson W. G. , DeMarzo A. M. , Zahurak M. , Dannenberg A. J. , Parnes H. , DeWeese T. L. , Partin A. W. 
Published: March 2020

5001 Background: Cyclooxygenase-2 (COX-2) has been postulated as a pharmacological target for preventing a variety of epithelial malignancies including prostate cancer (PCa). We conducted a randomized, double-blind study evaluating celecoxib (C) on biomarkers in normal and PCa tissue at prostatectomy (RRP). Methods: Patients with Gleason sum ≥ 7, pre-study PSA ≥ 15 ng/ml, clinical stage T2b, T2c, or any combination of PSA, Stage, or two or more cores positive for PCa received either C at 400 mg po bid or placebo for 4–6 wks pre-RRP. The primary endpoint was to compare and correlate tissue PG levels with histologic and secondary endpoints performed on prostate tissue and serum from the two comparable groups. Outcomes included PG levels, quantitative RT-PCR for mRNA levels of COX-1 and COX-2, oxidized DNA bases; measurement of apoptosis, proliferation, angiogenic-potential assays and histologic comparison of treated/untreated tissue specimens; PSA levels; and tissue levels of C. Estimates of change in endpoints required 30 patients per arm. Results: Seventy three subjects consented with 64 randomized and included in the intent to treat analysis; 2 had missing data for primary endpoints. Age, baseline PSA, race and Gleason score were comparable across treatment groups. The regimen was well tolerated with no serious adverse events. There was no treatment effect observed in the PG, COX mRNA levels or oxidized DNA base levels in the RRP specimens. Tumor tissue contained significantly less COX-2 mRNA levels than benign tissue (p=<0.0001). Of the markers of apoptosis and proliferation assessed, Ki-67 was higher in tumor samples, and p21 was less in C treated samples. Celecoxib was present in tumor tissue demonstrating that it reached the target, but there were no observed effects in the study endpoints. There was no toxicity greater grade 1 except hepatic toxicity in a placebo group subject. Conclusions: Our results show a lack of effect of C on PCa despite demonstrating that C was present in tissue samples. At this time, we cannot recommend further studies of C as a PCa preventative agent when dosed at 400 mg PO BID. The study was supported by a grant from the NCI, DCP (#NO1-CN-95000–46) and Pfizer, Inc. No significant financial relationships to disclose.