bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eligibility of patients with hepatocellular carcinoma for systemic treatment with sorafenib
Authors: Zimmermann L. C. , Schuette K. , Borschein J. , Csepregi A. , Malfertheiner P. 
Published: August 2020

e15673 Background: Sorafenib is the first systemic drug that effects prolonged overall survival in patients with advanced hepatocellular carcinoma (HCC) by almost three months with moderate toxicity. This study aims to evaluate how many patients diagnosed with HCC are candidates for systemic treatment and possibly benefit from it. Methods: All patients diagnosed with HCC in our hospital in between January 2006 and June 2008 were analysed regarding the presence and stage of liver cirrhosis, tumor stage and the treatment applied. Results: In a period of 30 months 182 patients were diagnosed with HCC (female n = 42, male n = 140, median age 66 (16–84)). 169 suffered from liver cirrhosis, 96 in Child A, 46 in Child B and 27 in Child C stage. 36 patients (19.8 %) were diagnosed with uninodular disease, in 17 patients (9.3%) 2 or 3 nodules were detected and 129 (70.9%) patients suffered from multinodular HCC. 79 patients received local ablative therapy or transarterial chemoembolisation, 15 underwent surgical resection, 29 patients were treated with best supportive care and 59 patients were candidates for systemic treatment. Out of these 25 either had no liver cirrhosis or were in stage Child A and 17 were in Child B stage and would therefore fit for therapy with sorafenib (23.1%). 17 pts with advanced disease and Child C cirrhosis did not fit for this treatment. Conclusions: Assuming that patients with advanced HCC and good or moderate liver function are candidates for systemic treatment with sorafenib every fifth patient is likely to benefit from the introduction of this treatment option. [Table: see text]
Adjuvant chemoradiotherapy with carboplatin and a fluoropyrimidine for resectable gastric and gastroesophageal junction cancer: A retrospective review of the Stanford experience
Authors: de Bruin M. A. , Kunz P. L. , Sharma V. B. , Norton J. A. , Bastidas J. , Chang D. T. , Koong A. C. , Koong A. C. , Balise R. R. , Ford J. M. , Fisher G. A. 
Published: August 2020

e15674 Background: The standard of care for the adjuvant treatment of resected gastric or gastroesophageal junction (GEJ) adenocarcinoma in the U.S. is post-operative 5FU and radiotherapy per the MacDonald regimen. At Stanford Cancer Center (SCC) we have adopted a modified regimen of chemoradiotherapy using carboplatin and a fluoropyrimidine. Methods: A retrospective review was performed of patients at SCC with T2-T4 or node positive gastric or GEJ cancer who underwent surgery with curative intent, and then received the following treatment. Carboplatin (AUC 6) was administered on days 1 and 22. Patients also received either 5FU at 200 mg/m2/day (via continuous infusion) plus leucovorin for six weeks, or capecitabine at 1,000 mg/po BID for 14 days, repeated every 21 days for 2 cycles. At week 8, infusional 5FU or capecitabine was combined with external beam radiotherapy to the gastric bed for five weeks (total 4,500 cGy). At week 14, patients repeated an additional 2 cycles of carboplatin and fluoropyrimidine as tolerated. Results: Forty-nine patients were identified. The majority (76%) were male. Median age at diagnosis was 57 years. Thirty-nine had gastric and 10 had GEJ cancers. With a mean follow up of 35 months, twenty-one patients (43%) have died; median disease free and overall survival have not been reached. Eighteen patients (37%) have recurred. The percentage of patients alive by stage was 100% (4/4) for stage IB, 62% (8/13) for stage 2, 53% (9/17) for stage IIIA, 33% (2/6) for stage IIIB and 22% (2/9) for stage IV. Grade 3 or 4 toxicities occurred in 27 patients (55%); most common were neutropenia (16), thrombocytopenia (11) and gastrointestinal toxicity in (8). Conclusions: Adjuvant chemoradiotherapy with carboplatin and a fluoropyrimidine after curative resection of gastric and GEJ cancer was well tolerated and yielded survival results similar to historical data. No significant financial relationships to disclose.
Predictive factors of outcome and clinical management of adjuvant S-1 chemotherapy for gastric cancer
Authors: Iwasa S. , Yamada Y. , Nakajima T. E. , Kato K. , Hamaguchi T. , Morita S. , Saka M. , Fukagawa T. , Katai H. , Shimada Y. 
Published: August 2020

e15676 Background: Adjuvant S-1 chemotherapy has become a standard treatment for stage II and III gastric cancer, following the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC). This study was designed to identify factors that can be used for predicting the outcome and clinical management of adjuvant S-1 chemotherapy in patients with stage II and III gastric cancer. Methods: We retrospectively examined 97 consecutive patients with stage II or III gastric cancer who received S-1 chemotherapy after gastrectomy to investigate factors associated with outcome and clinical management. S-1 (80 mg/m2/day) was orally administered twice daily for 28 consecutive days, followed by a 14-day rest period. As a rule, this protocol was continued for one year after gastrectomy. According to toxicity profiles, dose reduction or dose schedule modification was performed. Results: Patients consisted of 63 males and 34 females (median age, 59 years; range, 35–80 years), and those undergoing total gastrectomy/subtotal gastrectomy = 40/57. The median follow-up period after gastrectomy was 43.0 months (range, 5.3–73.4 months). As for adjuvant S-1 chemotherapy, dose reduction and dose schedule modification were conducted in 59% and 40% of the patients, respectively. Of the patients needing dose reduction, 79% underwent reduction within three months of treatment. The most common reason for dose reduction during the treatment period was anorexia (47%), followed by diarrhea (32%), leukopenia (24%) and rash (16%) with overlapping reasons. The duration period of the treatment was at least 3 months in 88%, at least 6 months in 82%, and scheduled 12 months in 73%. Twenty six patients discontinued treatment due to adverse event (20 patients), recurrent disease (2 patients) and other reasons (4 patients). The median duration until treatment discontinuation was 4.0 months. To date, 15 patients have recurrent disease. Significant predictive factors for recurrence were not statistically identified. Conclusions: Most patients (73%) could complete the scheduled treatment duration by dose reduction and dose schedule modification. No significant financial relationships to disclose.
Preoperative gemcitabine based chemoradiotherapy in locally advanced nonmetastatic pancreatic adenocarcinoma
Authors: Maximous D. , Abdel-Wanis M. E. , Aboziada M. A. , El-Sayed M. I. , Abd-Elsayed A. A. 
Published: August 2020

e15677 Background: Almost 30% of patients with pancreatic cancer present with locally advanced tumours in absence of distant metastasis. Because surgical resection is often contraindicated by vascular invasion, this disease has a dismal prognosis. The combination of gemcitabine with concurrent radiation therapy is a promising approach that is being investigated in patients’ unresectable pancreatic cancer. Aim of the work: The efficacy of preoperative gemcitabine based chemo-radiotherapy in increasing the resectability rate for patients locally advanced, non metastatic pancreatic cancer was assessed. Methods: 25 patients were treated by preoperative gemcitabine based chemo-radiotherapy. Approximately 6 weeks after completion of chemo radiation, evaluation was performed regarding tumour response and resectability. Pancreatico-duodenectomy was done for operable patients with surgical reconstruction. Results: Patients who achieved complete remission (CR) were 2 out of 25 patients while those achieved partial remission (PR) were 11 out of 25, 6 of them were considered operable. Thus Pancreatico- duodenectomy was done for 8 patients with surgical reconstruction. The postoperative 30 day mortality occurred only in one patient. The postoperative morbidity occurred in the form of minor biliary leakage occurred only in 1 patient & leakage from gastrointestinal anaestomosis in 1 patient. Out of 8 patients who underwent radical surgical resection, only one patient developed local recurrence and simultaneous liver metastasis during the follow up period. The median survival was 12 months. Conclusions: preoperative gemcitabine based chemoradiation might benefit patients with locally advanced non metastatic pancreatic cancer by increasing the resectability without significant acute toxicity. No significant financial relationships to disclose.
Comorbidity and survival of hepatocellular carcinoma patients at a VA medical canter
Authors: Zhong F. , Oliphant T. , Chang V. T. , Crump B. , Gonzalez M. L. , McPherson M. , Morales E. , Duque L. , Einhorn J. , Kasimis B. 
Published: August 2020

e15682 Background: To determine whether comorbidity indices predict survival in hepatocellular carcinoma (HCC) pts. Methods: In an IRB approved protocol, we reviewed the records of pts with tissue diagnosis of HCC seen at a VA Medical Center between 1/1/1999 to 12/31/2008. Comorbidity was assessed with four comorbidity indices, the Charlson Comorbidity Index (CMI), the Kaplan- Feinstein Index (KFI), the Cumulative Illness Rating Scale (CIRS), and VA Comorbidity Scale (VACS). Demographics, ECOG PS, stage, alpha-fetoprotein (AFP) at diagnosis, hepatitis B (HBV) and C (HCV) status, alcohol use, and iron overload were also reviewed. Cox survival regression analysis was performed. Results: There were 44 pts. All pts were men. The median (M) age at diagnosis was 60.5 years (range 35–86). The overall M survival was 230 days (4–2784). There were Stage I 12 (27%) pts, Stage II 7 (16%) pts, Stage III 14 (32%) pts, and Stage IV 11 (25%) pts. The M ECOG PS was 1.0 (0–4), stage 3 (1–4), CMI 5.75 (1–16), CIRS15 3.0 (1–5), CIRS16 6.0 (1–14), CIRS17 2.0 (0.83–5.0), CIRS18 0 (0–2), CIRS19 0 (0–1), KFI 3.0 (1–3), VACS 6.0 (2–9), and AFP 56.35 (1.1–379567). HBV was positive in 10 pts (23%), HCV 26 (59%) pts, alcohol use 37 (84%) pts, and iron overload 11 (25%) pts. In univariate survival analysis, stage (p<.038), ECOG PS (p<.001), AFP (p<.009), presence of iron overload (p<.006), and CMI (p<.019) were significant in predicting survival. However, age, HBV, HCV, alcohol use, CIRS15, CIRS16, CIRS17, CIRS18, KFI, and VACS were not significant for survival. In multivariate survival analyses that included stage and a comorbidity index, the CMI approaches significance (p<.077). Conclusions: In this sample, the CMI was a predictor for survival in pts with HCC. Further analysis in a larger sample is needed to provide a more definitive conclusion. This was supported by the New Jersey Commission for Cancer Research 09–1133-CCR-EO. No significant financial relationships to disclose.
Predicting renal functional outcomes after surgery for renal cortical tumors: A multifactorial retrospective analysis
Authors: Korets R. , Barlow L. , Laudano M. , Benson M. , McKiernan J. 
Published: August 2020

e16005 Background: Nephrectomy (Nx) is the standard of care for localized renal tumors. The risk of developing chronic renal insufficiency (CRI) increases after renal surgery. This study examines the functional outcomes for radical and partial Nx stratified by pre- and perioperative variables using estimated GFR. Methods: Using the Columbia Urologic Oncology Database, a retrospective analysis of patients treated with partial or radical Nx for renal cancer from 1988 to 2008 was conducted. Postoperative chronic renal function was measured using GFR as estimated by the MDRD study equation. Three primary outcomes were measured: 1) presence of new onset postoperative CRI (defined as GFR lower than 60 mL/min per 1.73 m2), 2) percent change in postoperative GFR from preoperative value, and 3) change in CRI stage postoperatively. Regression models were used to determine the effect of surgical procedure (radical vs partial Nx), approach, and multiple preoperative characteristics on functional outcomes. Results: 174 patients met the criteria for analysis after radical Nx and 102 after partial Nx for a total of 276 patients. 209 patients had preoperative GFR > 60, 67 had preoperative GFR < 60, and 6 had preoperative GFR < 30. After a minimum of 3 months postoperatively, 108/209 (52%) and 2/209 (1%) patients developed new-onset GFR <60 and <30, respectively. On multivariate analysis controlling for age, sex, race, diabetes and hypertension, preoperative CKD stage (p<0.001) and procedure (p<0.001) were both independent predictors of GFR progression to <60; similarly, preoperative CKD stage (p<0.001) and procedure (p<0.01) were independent predictors of percent change in postoperative GFR. Patient with worsened preoperative CRI stage were less likely to have further progression of CRI postoperatively (p<0.001) independent of the surgical procedure. Surgical approach was not an independent predictor of any renal functional outcomes measured. Conclusions: Patients undergoing renal surgery have a high rate of new-onset postoperative renal failure. After controlling for preoperative risk factors, patients undergoing radical Nx are at higher risk for decline in renal function. Surgical approach, however, was not a significant predictor for the development of CRI. No significant financial relationships to disclose.
Correlation of N-telopeptide of type I collagen (NTX) with survival and fractures in patients (pts) with bone metastases from renal cell carcinoma (RCC)
Authors: Brown J. E. , Lipton A. , Cook R. J. , Michaelson D. , Coleman R. E. , Saad F. 
Published: August 2020

e16016 Background: The osteolysis marker NTX has shown prognostic significance in pts with bone metastases from a broad range of solid tumors, but its potential in pts with RCC has not been investigated. Methods: This was an exploratory correlative analysis of NTX levels and outcomes in the RCC subset of pts treated with zoledronic acid (ZOL) in a 21-month phase III trial (Rosen et al. J Clin Oncol. 2002). In North American pts in this study, urinary NTX was measured approximately every 3 mo and was expressed per mmol creatinine (CR). Endpoints included overall survival (OS), disease progression in bone, and pathologic fractures. Relative risks and 95% confidence intervals for pts with elevated NTX (NTX ≥ 64 nmol/mmol CR) versus normal NTX (< 64 nmol/mmol CR) were calculated by Cox regression for baseline and most recent (≤ 6 mo prior) NTX assessments. Results: Among 55 ZOL-treated RCC pts, 29 had baseline NTX data (median = 60 nmol/mmol CR). Whereas baseline NTX levels showed trends for outcomes, recent NTX levels profoundly correlated with outcomes ( Table ). An elevated recent NTX measurement correlated with a > 13-fold increased risk of death and a > 11-fold increased risk of progression in bone. Correlations were also significant for first and all on-study fractures. Conclusions: In pts with RCC receiving ZOL, serial NTX assessments may provide important prognostic insight. Although based on a small sample size, correlations between recent NTX levels and outcomes in RCC pts are more profound than those previously reported in pts with other solid tumors (Brown et al. J Natl Cancer Inst. 2005). Elevated NTX could alert physicians to the need to more closely monitor bone lesions and intervene to prevent fractures in RCC pts. This may be especially important in the context of new systemic therapies that are improving the outlook in the advanced RCC setting. [Table: see text] [Table: see text]
Preclinical antitumor and antiangiogenic activity of a metronomic schedule of cisplatin against human transitional cell carcinoma (TCC)
Authors: Jian W. , Levitt J. M. , Lerner S. P. , Sonpavde G. 
Published: August 2020

e16018 Background: Conventional cisplatin every 3 weeks is frequently precluded in patients with TCC due to renal dysfunction. A metronomic schedule of other chemotherapeutic agents demonstrates anti-angiogenic and anti-tumor activity coupled with better tolerability. A rationale can be made to preclinically evaluate the activity of a metronomic (weekly or 3 days a week) schedule of cisplatin in a preclinical system of TCC. Methods: The activity of cisplatin was assessed in vitro against HUVECs (human umbilical vein endothelial cells). MTT, flow cytometry with Annexin-FITC and scratch assays were employed to assess proliferation, apoptosis and migration, respectively. The activity of cisplatin was evaluated in vivo in murine xenograft models of TCC. The subcutaneous xenografts included 5 × 106 RT4 or 5637 human TCC cells injected into 6- to 8-week-old female athymic BALB/c nu/nu mice. Cisplatin was administered 4 mg/kg IP (intraperitoneal) weekly for up to 6 weeks and compared with untreated mice. Then, 3 groups of tumor-bearing mice received either no therapy, cisplatin 6 mg/kg weekly or cisplatin 2 mg/kg for 3 days a week for up to 6 weeks. Tumor size is measured twice a week. Nephrotoxicity is assessed by serum creatinine and kidney histopathological examination. IHC (immunohistochemistry) of xenografts is performed to measure proliferation (ki-67), apoptosis (cleaved caspase-3) and angiogenesis (CD31). Results: Cisplatin demonstrated significant anti-proliferative, anti-migration and pro-apoptotic activity against HUVECs in vitro. Cisplatin 4 mg/kg weekly inhibited tumor growth, induced higher apoptosis and down-regulated angiogenesis and proliferation in vivo compared to controls. Results from the experiment comparing cisplatin 6 mg/kg weekly with 2 mg/kg 3 days a week (i.e. more metronomic, with potentially more anti-angiogenic and anti-tumor activity and less nephrotoxic) will be presented. Conclusions: A metronomic schedule of cisplatin inhibits tumor growth and demonstrates anti-angiogenic activity in a preclinical model of human TCC. The clinical evaluation of a metronomic schedule of cisplatin may be warranted. No significant financial relationships to disclose.
External validation of preoperative nomograms for predicting pathological stage of prostate cancer: Analysis of 716 Japanese cases
Authors: Kanao K. , Shinojima T. , Nakashima J. , Ohigashi T. , Kikuchi E. , Miyajima A. , Nakagawa K. , Oya M. 
Published: August 2020

e16078 Background: For the purpose of predicting pathological stage of prostate cancer, Partin et al have developed preoperative nomograms (Partin Tables). Partin tables were modified and updated twice to reflect a more contemporary condition of prostate cancer stage at diagnosis. Recently similar Tables using 1188 Japanese patients were also developed. Although the characteristics of prostate cancer are thought to vary between Asian and Western patients, there are few studies to validate the prognostic accuracy of Partin tables in Asian patients and there is no study to validate three Partin table simultaneously. In this study we evaluate the validity of thee Partin Tables and Japanese Tables for our 716 of Japanese cases. Methods: Seven hundred sixteen patients were analyzed retrospectively who underwent radical prostatectomy in our institute without neoadjvant endocrine therapy. In four Tables (Partin 97, 01, 07 and Japanese Tables) the patient's distributions were evaluated and the fitness for each models were also evaluated using AIC (Akaike's information criteria). The probabilities of organ confined disease for each case were calculated from four nomograms and external validation was performed using ROC analysis and calibration. Results: Preoperative clinical stage of our cases were 587 with T1c, 140 with T2a, 20 with T2b and 63 with T2c. PSA at diagnosis was 10.45±0.60 (mean±SE). AIC of each Tables was 975.0 in 97 Tables, 974.3 in 01 Tables, 975.4 in 07 Tables and 973.6 in Japanese Tables. The area under the ROC curve (AUC)of each Tables was 0.619 in 97 Tables, 0.623 in 01 Tables, 0.614 in 07 Tables and 0.614 in Japanese Tables. There were no difference of calibration plots in four Tables and in general actual probabilities of organ confined were lower than predicted probability. Conclusions: This study showed that four nomograms have no difference in discrimination and prediction ability to our cases, but when we use these nomograms it is necessary to estimate the probability to be low than predicted probability. No significant financial relationships to disclose.
Oral vinorelbine as a fixed-weekly schedule in taxanes-refractory advanced HRPC: A single institution experience
Authors: Rodriguez Garzotto A. , Sepulveda J. , Cortijo A. , Garcia L. , Garcia Rodriguez I. , Ciruelos E. , Rodriguez Antolin A. , Cortes-Funes H. , Castellano D. 
Published: August 2020

e16084 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC). Oral formulation of VRL represents a significant advance in the treatment of advanced cancer. The recommended doses are 60–80 mg/m2(d1–8 q3wks).We evaluated efficacy and toxicity of different VRL schedule administered as a fixed-weekly dose of 60 mg/m2. The purpose of this study was to evaluate the toxicity profile and efficacy of this schedule in terms of PSA response, objective response and clinical benefit (CB) response. Methods: Pts characteristics were: PS 0–2, adequate bone marrow, liver and renal functions. Oral VRL was adminestered at weekly dose of 60 mg/m2 until disease progression/intolerable toxicity. PSA response was defined as a >50% fall in PSA from baseline, confirmed by a second PSA value 4 or > weeks later. Pts with measurable soft tissue disease met traditional guidelines for tumour responses. Progression was defined by objective disease progression or PSA increase of >50% above nadir or >25% above baseline. Pts were monitored clinically and with serial PSA measurements every 1 week. Results: Thirty seven pts with progressive HR metastatic prostate cancer were evaluated. Mean (range) age was 67 years (50–88), median PSA level was 90 ng/ml (1- 4314), and median Gleason score was 7 (6–9). 23 (62%) pts had previous taxane chemotherapy and 14 pts (38%) were chemo-naive. Pts received a mean of 5.5 cycles (1cycle=3wks) (range:1–24). Median follow-up was 12 months. Thirty three of 37 Pts (97%) achieved a decline in serum PSA. CB response was achieved in 15 out of 37 pts(40%). The PSA response was observed in 13 pts (35%). Objective response was not observed and only 6 pts showed SD (16%). The relative dose-intensity was 94%. There were no reported grade 3–4 toxicities. Only 1 treatment discontinuation was observed (esopahgitis g2). Toxicities consisted primarily of g2 anemia (25%) and mild nausea (32%). Conclusions: Oral Vinorelbine administered as a fixed-weekly schedule of 60 mg/m2 is a safe regimen in pts with advanced HRPC. This regimen of oral vinorelbine is an effective and well-tolerated treatment in this setting, despite a major dose-intensity administered. Further studies will be evaluated in chemo-naive and/or elderly population. No significant financial relationships to disclose.