bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of S-1 in gemcitabine-refractory pancreatic cancer: A retrospective single-institution study
Authors: Nakai Y. , Isayama H. , Sasaki T. , Sasahira N. , Hirano K. , Tsujino T. , Tada M. , Kawabe T. , Omata M. 
Published: August 2020

e15648 Background: S-1 was reported to be active against gemcitabine (Gem)-refractory pancreatic cancer (PaC) in Japan and was introduced in February 2005 in our institution. The aim of this study was to elucidate the impact of S-1 on prognosis of patients with Gem- refractory PaC. Methods: A total of 108 patients (pts) with advanced PaC who were treated with Gem and had disease progression (PD) at the University of Tokyo Hospital were analyzed. The introduction rates of second-line chemotherapy and the causes of introduction failure were assessed. Prognostic factors for residual survival (RS) for Gem-refractory PaC were analyzed by the Cox proportional hazard model. Results: Of 108 pts with Gem-refractory PaC, 47 pts (PreS-1 Group) had PD before February 2005, the time of S-1 introduction in our institution, and 61 pts (PostS-1 Group) after February 2005. There were no differences in baseline characteristics at PD for Gem between PreS-1 and PostS-1 Groups, except for metastasis to peritoneum more prevalent in PreS-1 Group (44.7% in PreS-1 Group and 23.0% in PostS-1 Group, p=0.023). The introduction rate of second-line chemotherapy increased from 12.8% in PreS-1 Group to 45.9% in PostS-1 Group. Second-line chemotherapy was administered in 34 pts, 29 by S-1, 4 by 5-FU-based chemoradiation, and 1 by 5-FU. The causes of introduction failure of second line chemotherapy were poor PS in 64.9%, patients’ refusal in 16.2%, infection in 2.7%, adverse effects of Gem in 1.4% and jaundice in 1.4%. RR, PFS, and OS for second-line S-1 were 17.2%, 2.5 Mo, and 7.8 Mo, respectively. PFS for Gem was not prognostic of PFS for S-1 (2.5 Mo both in pts with PFS >6Mo and in pts with PFS <6Mo for Gem). RS after PD for Gem was prolonged from 3.1 Mo in PreS-1 Group to 6.5 Mo in PostS-1 Group (p<0.001). The Cox hazard model revealed PreS-1 Group (HR2.42, p=0.001) in addition to male gender (HR1.83, p=0.019), poor PS (HR3.52, p<0.001), liver metastasis (HR2.36, p=0.037), elevated LDH (per 100U/L increase) (HR 1.30, p=0.046), elevated CRP (HR 1.14, p=0.023) at PD for Gem as poor prognostic factors of RS for Gem-refractory PaC. Conclusions: Introduction of S-1 might lead to improvement of prognosis in patients with Gem-refractory PaC. No significant financial relationships to disclose.
Retrospective analysis of salvage percutaneous cryoablation of hepatocellular cancer (HCC) in liver
Authors: Daniels J. R. , Katz M. D. , Hart M. , Fong T. , Donovan J. A. , El-Khoueiry A. B. , Wallman M. A. 
Published: August 2020

e15649 Background: We report our initial experience with percutaneous cryoablation of HCC in liver. Prior published series are limited. Methods: We treated 30 lesions in 23 patients (pts): Child-Pugh class A, 13 pts; B, 8 pts.; C, 2 pts Candidate pts had residual disease after intra-arterial chemotherapy. Probe placement (2.4 mm, Endocare) occurred under general anesthesia with restricted tidal volume to facilitate computer tomographic (CT) localization. An average 2.7 probes (range 1- 5) achieved an estimated margin of 0.5 cm visualizing the ice ball after two 10 min freeze cycles. Median follow-up was 342 days (range 30–947) Results: Tumors ranged from 1.3 to 5.8 cm. Three pts died within 30 days: 2 following intra-peritoneal hemorrhage despite control of bleeding and 1 from ischemic liver injury following a TIPSS for hydrothorax in a pt with refractory ascites. Two additional pts had hemorrhage with recovery. Risk of bleeding was associated with ascites (P = 0.013). One pt had cutaneous needle tract tumor seeding caused by needle repositioning prior to freezing. Survivors remained clinically stable at the 2–3 month follow-up. At the 2 month evaluation 29 lesions had no residual enhancement by CT. One lesion required a second cryoablation procedure.There were no recurrences in any target lesion (30–947 days). Thirteen pts are alive without recurrence of whom 6 had liver transplant with no (4) or < 5% (2) residual disease. Three pts have had recurrence in non-target liver and have died. Multiple tumors at baseline predicts for hepatic recurrence. Two pts have died from complications of cirrhosis, and 2 are lost to follow-up. Conclusions: Percutaneous cryoablation effectively manages selected hepatic HCC tumors. Cirrhotic pts with ascites have significant risk for hemorrhage. We recommend peri-procedure paracentesis and an immediate post-procedure CT. [Table: see text]
Lapatinib and gemcitabine for metastatic pancreatic cancer: A phase II study
Authors: Safran H. , Miner T. , Bahary N. , Whiting S. , Lopez C. , Sun W. , Charpentier K. , Charpentier K. , Shipley J. , Anderson E. , McNulty B. 
Published: August 2020

e15653 Background: To determine the overall survival for patients with metastatic pancreatic cancer treated with lapatinib and gemcitabine. Methods: Patients with metastatic pancreatic cancer received lapatinib, 1,500 mg/day, and Gemcitabine, 1 gm/m2/week for 3 weeks followed by 1 week off, until disease progression. This multicenter phase II study was planned to enter 125 patients to evaluate if the treatment regimen could achieve a 1-year survival of 30% and a median survival of 7 months. An additional subset of 20 patients were to receive 2 months of single agent lapatinib followed by lapatinib and gemcitabine. Results: At a planned 6 month analysis, the Brown University Oncology Group Data Safety Monitoring Board terminated accrual after 29 patients due to futility analysis. The median survival was 4 months (95% CI, 2.0–5.5 months). The four patients who received single agent lapatinib all progressed at 1 month. Conclusions: Lapatinib is not effective in pancreatic cancer. Evaluation of HER2 inhibitors in pancreatic cancer is not warranted. [Table: see text]
TIP regimen in metastatic or recurrent esophageal cancer: An Indian experience
Authors: Batra U. , Doval D. C. , Talwar V. , Sharma J. B. , Sherali R. 
Published: August 2020

e15664 Background: Currently, there is no standard regimen for metastatic or recurrent upper or middle squamous cell esophageal cancer. Multiple agents including Taxanes, Ifosfamide have shown significant single agent efficacy in this subset of patients. We therefore undertook this study to test the first-line combination of TIP regimen (Paclitaxel, Ifosfamide and cisplatinum) in patients with metastatic carcinoma of the esophagus. Methods: This study evaluated the efficacy, tolerability and toxicity profile of the TIP regimen in patients with metastatic or recurrent carcinoma of the upper or middle squamous cell carcinoma of esophagus. Patients received Paclitaxel 135 mg/m2, Ifosfamide 1.3 gm/m2 day1–3, CDDP 75 mg/m2( split in day 1–2). Granulocyte Colony stimulating factors were not administered until the patient had prolonged Gr IV neutropenia or febrile neutropenia. Patients were evaluated after 3 cycles and at completion of treatment. Results: A total of 32 patients were treated with TIP regimen. 24 patients completed a median of 4 cycles of which 21 were evaluable for response assessment. 13 patients achieved a major response of which 5 patients had complete response. The median time to tumor progression was 7 months and the median survival was 13 months (range 2–36 months). The regimen was well tolerated with only 1 patient requiring dose reduction.Febrile Neutropenia occurred in 8 patients, all of whom recovered after treatment with antibiotics. There were no reported events of Gr IV peripheral neuropathy or mucositis. There were no treatment related deaths. In addition to the radiological responses, patients who responded had a significant better quality of life. Conclusions: The combination of Paclitaxel, Ifosfamide and Cisplatinum has significant activity in metastatic or recurrent esophageal cancer. This regimen is well tolerated with a high response rate. The ease of administration, cost effectiveness and suitable safety profile makes it an ideal first line regimen in metastatic esophageal cancer. No significant financial relationships to disclose.
Survival time and its prognostic factors in advanced unresected cholangiocarcinoma without chemoradiation
Authors: Park J. , Kim M. , Kim J. , Lee J. 
Published: August 2020

e15681 Background: To evaluate survival time and its prognostic factors contributing to survival of advanced unresected cholangiocarcinoma. Methods: We reviewed the experience of 330 patients with histologically proven unresected advanced intrahepatic and hilar cholangiocarcinoma and evaluated their survival time and significant prognostic factors. They did not receive any surgery, chemotherapy and radiotherapy and they underwent only palliative nonsurgical biliary drainage if it was needed to relieve biliary obstructive symptom. Results: Survival time of overall cholangiocarcinoma (median±SD) was 3.9±7.8 months; 3±5.3 months for intrahepatic cholangiocarcinoma, 5.9±10.1 months for hilar cholangiocarcinoma. By Kaplan-Meier survival analysis, intrahepatic cholangiocarcinoma patients survived significantly shorter than hilar cholangiocarcinoma patients. By multivariate analysis for intrahepatic cholangiocarcinoma, distant metastasis was independently associated with shorter survival time. Multivariate analysis for hilar cholangiocarcinoma showed initial CEA > 30 ng/dl were independent predictors of shorter survival. Conclusions: Patients with unresectable cholangiocarcinoma who do not undergo surgery, chemotherapy and/or radiotherapy have a dismal prognosis. We hope that the outcome of our study would help clinicians better predict the prognosis of cholangiocarcinoma patients not receiving such aggressive treatments. These data would be used as the comparable data for control groups of future studies to assess the outcome of newly designed or developed treatment method. No significant financial relationships to disclose.
Prospective cardiotoxicity screening during tyrosine kinase inhibitor therapy for renal cell carcinoma: An institutional experience
Authors: Witteles R. M. , Harshman L. C. , Telli M. , Srinivas S. 
Published: August 2020

e16003 Background: Tyrosine kinase inhibitors (TKI) can lead to cardiotoxicity either directly by causing left ventricular dysfunction, or indirectly by increasing blood pressure. In light of prior studies at our institution documenting a high rate of symptomatic heart failure in patients with renal cell carcinoma undergoing treatment with sunitinib, we instituted a prospective screening protocol to characterize the incidence and natural history of TKI-associated cardiotoxicity. Methods: From March-December 2008, patients receiving TKI therapy for renal cell carcinoma received cardiac biomarker screening (NT- BNP and Troponin I at baseline and after week 4 of each cycle) and transthoracic echocardiography (baseline, 1 month, 3 months, and every 3 months thereafter). If biomarkers were elevated or a decline in ejection fraction was observed, patients were referred for cardiology evaluation. Results: Twenty-six patients have been included since the protocol's initiation. No elevations in cardiac troponin I have been observed to date. Eight patients (31%) had elevations in NT-BNP (a sensitive marker for heart failure). The TKIs involved included sunitinib (5 patients), sorafenib (2 patients), and bevacizumab (1 patient). One patient who was treated with sunitinib had frank left ventricular systolic dysfunction. Seven of the eight patients with elevated NT-BNP values had baseline hypertension, and five patients had significant increases in blood pressure during TKI treatment. In all patients with follow-up biomarkers, NT-BNP levels fell after initiation of heart failure therapy. TKI treatment appeared to ‘unmask’ previously subclinical cardiac injury, including prior silent myocardial infarction (one patient), left ventricular hypertrophy (four patients), and valvular disease (three patients). Updated data from the ongoing screening protocol will be presented. Conclusions: The Stanford TKI screening protocol identified a high rate of subclinical cardiotoxicity and allowed for early initiation of heart failure therapy. Further studies are needed to determine if this approach can decrease cardiac morbidity and improve oncologic outcomes by preventing discontinuation or dose interruption of TKI therapy. [Table: see text]
Changes in circulating endothelial cells (CECs) during treatment with cisplatin-based chemotherapy for testicular cancer
Authors: Altena R. , De Haas E. C. , Tibbe A. G. , Smit A. J. , van Roon A. , Meijer C. , Boezen M. H. , van der Meer J. , Sleijfer D. T. , Gietema J. A. 
Published: August 2020

e16009 Background: Chemotherapy (CT)-induced endothelial damage is an important pathogenic factor for cardiovascular morbidity in testicular cancer (TC) patients (pts). Therefore, we studied early markers of endothelial damage as predictors of cancer treatment-related cardiovascular morbidity. Methods: We prospectively assessed markers of endothelial damage in TC pts treated at the University Medical Center Groningen, before, during, 4 weeks and one year after completion of standard CT (3 or 4 three weekly cycles with bleomycin, etoposide and cisplatin). The number of circulating endothelial cells (CECs), identified by CD146+, CD105+ and CD45− using the CellSearch system, and plasma levels of von Willebrand Factor (vWF) were measured. Results: 30 TC pts were included (median age 34 years, range 20–47). Before start of CT, CECs were not associated with disease stage or leukocyte count. The number of CECs progressively increased over the 9–12 week CT period [baseline: median (range) 25/mL (6–137); maximum number during CT: 134/mL (28–320; p<0.001); 4 weeks after completion of CT: 66/mL (18–316; p=0.005)]. One year post treatment, CECs were not different from baseline [N= 10; 13/mL (6–31; p=0.263)]. vWF levels also progressively increased during CT [baseline: median 105% (range 50–377); maximum level during CT: 289% (175–464; p<0.001); 4 weeks after completion of CT: vWF 124% (56–274; p=0.149)]. One year after CT, vWF levels were 115% (61–184; p=0.285). During CT, numbers of CECs and vWF levels correlated positively (r=0.283; p<0.001), whereas maximum CECs increase and maximum vWF increase were not associated (r=0.098; p=0.605). Two pts had a cerebral infarction during CT. In one pt, vWF increased before the event; in both pts CECs increased directly afterwards. Conclusions: During CT for disseminated TC, CECs and vWF progressively increased during consecutive cycles. CECs remained increased 4 wks after completion of CT, whereas vWF returned to baseline levels. The magnitude of changes was not equal in every pt. Therefore, both CECs and vWF might be early predictive markers for chemotherapy-induced cardiovascular toxicity, and may serve as intermediate endpoint in intervention studies. [Table: see text]
Expression and activation of ADAM15 in bladder cancer
Authors: Bucheit A. , Day K. , Day M. L. , Chadwick W. A. , Liebert M. , Hussain M. 
Published: August 2020

e16010 Background: ADAM15 is a member of the disintegrin family of metalloproteinases. These molecules function as membrane-bound proteases, and, when activated, cleave important membrane anchored growth factors such as heparin binding epidermal growth factor and cell adhesion molecules such as E-cadherin. This proteolysis may contribute to bladder cancer growth through release of growth factors and progression by altering cell adherence. We evaluated ADAM15 expression in bladder cancer cell lines and tissues. Methods: ADAM15 expression was assessed in human bladder cell lines, normal bladder and bladder cancer tissues. A datamining program (Oncomine) was used to evaluate previous array studies in bladder cancer. ADAM15 activation results in the release of a prodomain fragment. Expression and activation of ADAM15 in bladder cancer cell lines were monitored by enzyme-linked immunosorbent assay and western blotting using ADAM15 antibody (Millipore). Staining was performed on formalin-fixed, paraffin-embedded human tissues using ADAM15 antibody (Millipore) and the peroxidase- avidin-biotin complex (ABC) method. Results: Of 7 bladder cancer cell lines, 6 demonstrated expression of full length (100 kD) and “active” (90kD) ADAM15 molecules. Four of these cell lines showed release of the ADAM15 prodomain fragment, and 5 cell lines provided evidence for proteolytic activity, indicated by release of 80kD soluble E-cadherin molecule. Immunostaining of a bladder cancer tissue microarray revealed that normal urothelium expressed low levels of ADAM15, but focal overexpression of ADAM15 was observed in 17/29 bladder cancer specimens. Datamining of independent microarray analysis revealed that ADAM15 mRNA is upregulated in bladder cancer. Conclusions: ADAM15 is expressed in the majority of human bladder cancer specimens. Cell line studies indicate that ADAM15 can be activated, as indicated by release of the ADAM15 prodomain fragment. These results suggest that ADAM15 may be a therapeutic target to modulate bladder cancer growth and progression. Future studies will continue evaluation of the biology of ADAM15 in bladder cancer and evaluate if the soluble ADAM15 prodomain can be detected in plasma, serum or urine from patients with bladder cancer. No significant financial relationships to disclose.
Dose intensity of cisplatin and gemcitabine (CG) for muscle invasive urothelial bladder cancer (MIUBC) in the neoadjuvant versus adjuvant settings: The Fox Chase Cancer Center (FCCC) experience
Authors: Hoffman-Censits J. H. , Wong Y. , Li T. , Boorjian S. , Giri V. N. , Uzzo R. , Greenberg R. E. , Hudes G. , Chen D. Y. 
Published: August 2020

e16012 Background: Despite radical cystectomy (RC), subjects with MIUBC remain at risk of recurrence and optimal timing of chemotherapy remains unclear. Historically, we offered adjuvant (ADJ) CG to patients (pts) with T≥3 or node positive tumors. Since Dec 2005, neoadjuvant (NEO) CG treatment has been our preferred approach for pts with ≥T2 tumors. We compare our results with NEO and ADJ CG, including pathologic response after NEO CG. Methods: We reviewed records of patients who underwent RC for MIUBC and received at least 2 cycles of perioperative CG between Jan 2002 and Dec 2008at FCCC. We used Fisher's exact and Wilcoxon tests, as well as Generalized Estimating Equations (GEE), to compare baseline patient characteristics, dose intensity, completion, and complication rates in the ADJ and NEO groups. Results: Results of 22 ADJ and 17 NEO patients are shown below. Characteristics of age, gender, race, preop T stage and ECOG performance status (PS) ≤1 were similar. There was no significant difference in preoperative T stage between groups (p=0.2). The delivery of full doses (C 70mg/m2,G 1000 mg/m2) of GC were similar in the NEO vs the ADJ group. The delay between RC and chemotherapy may be shorter in the patients treated preoperatively, and trended toward significance (p=0.06). Reasons for dose modifications and delays are also shown in the Table . Of pts treated with NEO CG, 10/17 (55.7%) were ≤pT1 with 9 of those 10 pts also pN0 (52.9% of 17 pts) . 5/17 (29.4%) had positive lymph nodes at RC. Conclusions: CG for MIUBC is well tolerated in the NEO setting, with dose intensity comparable to that delivered adjuvantly. NEO pathologic downstaging with CG appears comparable to historical results with MVAC, and should be confirmed in larger, prospective studies. [Table: see text] No significant financial relationships to disclose.
Salvage chemotherapy with irinotecan and nedaplatin for cisplatin refractory germ cell tumors
Authors: Nakamura T. , Nonomura N. , Mikami K. , Shiraishi T. , Takaha N. , Okuyama A. , Miki T. 
Published: August 2020

e16022 Background: Only 20 - 30 % of patients with cisplatin (CDDP) refractory germ cell tumor (GCT) will remain continuously disease-free with salvage chemotherapy. The present study investigated the combination chemotherapy with irinotecan (Ir) and nedaplatin (CDGP), the second generation derivative of CDDP developed in Japan, as salvage chemotherapy for CDDP-refractory GCT. Methods: Between June 1998 and December 2007, 39 CDDP refractory GCT patients treated with irinotecan and CDGP (IrN therapy) were assessed retrospectively. IrN therapy consisted of Ir: 100–150 mg/m2 on day 1, 15 or 200–300 mg/m2 on day 2, CDGP: 100 mg/m2 on day 1 every four weeks with oral administration of Chinese-herb ‘Hange-shashinto’ and sodium bicarbonate for diarrhea. After tumor marker normalization, residual masses were resected and chemotherapy was continued in the case of without marker normalization. Results: The median age was 31 years old (range; 17–48). The median number of cycles of prior chemotherapy was 6 (range; 2–30). The median number of cycles of IrN therapy was 3 (range: 1–9). The response rate was 30.8% ( CR: 0%, PRm−: 15.4%, PRm+: 15.4% ) and the outcome was no evidence of disease (NED) 46.2%, alive with disease (AWD) 25.6% and dead 28.2%, respectively. Twenty-five patients with IrN therapy as 2nd (17 cases) and 3rd (8 cases) line salvage therapy showed that the response rate was 48% (CR: 0%, PRm−: 16.0%, PRm+: 16.0, NCm−: 16.0%) and the outcome was as follows; NED 64%, AWD 16% and dead 20%, respectively. On the other hand, 14 pts who had the treatment as fourth-line or more showed less response rate (PR: 28.5%) and worse outcome (NED 14.2%). Major adverse events more than grade 3 were neutropenia and thrombocytopenia. These adverse events were manageable. Grade 4 diarrhea which was major adverse event of CPT-11 was observed in only one case and there was no treatment related death. Conclusions: This study demonstrates that combination chemotherapy with CPT-11 and CDGP showed significant anticancer activity for patients with CDDP-refractory GCT without severe adverse events. These findings suggest that salvage IrN therapy may be one of the options as second- or third-line therapy. No significant financial relationships to disclose.