bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of paclitaxel and capecitabine (PX) combination as neoadjuvant chemotherapy for unresectable locally advanced gastric cancer.
Authors: Ko Yoon Ho , Hong Sook Hee , Roh Sang Young , Song Kyo Young , Jung Eun Sun , Jeon Hae Myung , Park Cho Hyun , Hong Young Seon 
Published: March 2020

e15164 Background: Unresectable locally advanced adenocarcinoma (AGC) of the stomach is associated with poor prognosis due to the lack of effective treatment. Neoadjuvant chemotherapy (NAC) has drawn more attention to the treatment of locally AGC in the current multidisciplinary treatment model. Paclitaxel and capecitabine (PX) has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established. This phase II study was performed to evaluate the efficacy and safety of neoadjuvant PX chemotherapy in patients with unresectable locally AGC. Methods: Patients with AGC, clinically unresectable because of local invasion and/ or conglomerated regional lymph nodes (station 7, 8, and 9) metastasis on based on laparoscopic staging, were enrolled. PX consisted of paclitaxel 175 mg/m2 i.v. on day 1, and capecitabine 835 mg/m2 twice daily p.o. on days 1–14 every 21 days. After three cycles of NAC, patients with clinically resectable AGC underwent surgical resection. Results: This trial was stopped for poor accrual after 18 patients were enrolled; 50% patients had tumors located in the proximal third of the stomach. Seventeen patients finished three cycles of chemotherapy. The overall response rate was 41.2% (7/17 cases), of which 71.4% (10/14 cases) metabolic response. Fourteen (77.8%) of the 18 patients enrolled underwent surgery, and 12 (85.7%) had an R0 resection. Pathological complete response was observed in one (7.1%) of patients. Toxicity was mild to moderate and there were no treatment-related deaths and no major surgical complications. With a median follow-up of 28.6 months (range 6.4-38.4 months), the 2-year survival rate for all patients was 71.1%. Subgroup analysis found R0 resection (35.7 months vs. 20.6 months, P= 0.005) and patients with pathologic N downstaging (P < 0.001) to have improved overall survival. Conclusions: Neoadjuvant chemotherapy with PX shows promising results in unresectable locally AGC patients without increased morbidity and mortality. Neoadjuvant PX may permit a larger chance of curative resection in unresectable locally AGC patients.
Frequency of BRCA1 5382insC mutations in Russian non-selected pancreatic cancer patients.
Authors: Kashintsev Alexey 
Published: March 2020

e15165 Background: Pancreatic cancer (PC) is known to be associated with BRCA2 mutations, while the role of BRCA1 in the increase of PC risk is less evident. BRCA1/2-driven tumors, including pancreatic cancer, are sensitive to platinating agents and PARP inhibitors. Epidemiology of BRCA1 mutations in Russia is characterized by a pronounced founder effect, with the allele BRCA1 5382insC being detected in 70-90% of all BRCA1 mutation carriers. Methods: 237 patients with consecutive patients with pancreatic cancer were by questionnaires, and 149 have provided their normal DNA to the study and underwent genotyping for BRCA 1 5382insC mutations. Results: Among all the patients in 105/237 (44.3%) patients reported first-degree relatives with various types of cancer, including 11/237 (4.6%) cases of pancreatic cancer. 2/149 genotyped patients carried BRCA1 5382insC allele. Both mutation carriers had first-degree family history of breast cancer. Conclusions: Given the simplicity of founder mutation detection, BRCA1 5382insC allele deserves to be tested in Slavic pancreatic cancer, especially in those reporting family history of BRCA1-associated tumors.
The impact of adjuvant delayed radiotheraphy (RT) on survival in patients with resected periampullary adenocarcinomas.
Authors: Yalcin Suayib , Kertmen Neyran , Yuce Deniz , Yildiz Ferah , Hamaloglu Erhan 
Published: March 2020

e15168 Background: Postoperative prognosis for ampullary carcinoma (AC) is superior to that of pancreatic cancer (PC), the former exhibiting higher complete surgical resection, lower recurrence and longer survival rates (1). Despite all the major recent advances in surgery, chemotherapy (CT) and RT, PC is still one of the most lethal malignancies, overall survival (OS) rates being as low as 5% at 5 years (2). This study was intended to evaluate survival in patients with resected periampullary cancer treated with adjuvant Gemcitabine (Gem) and cisplatin (Cis) with or without delayed RT (with Gem). Methods: This retrospective study involved 91 patients diagnosed and treated with periampullary cancer. Patients with adenocarcinoma of periampullary region with gross total tumor resection and lymph node dissection (R0 and R1 resections only) were included. Of 59 patients with PC, 38 received Gem and Cis for 3 cycles (3 months) before CRT. When delivered after Gem /RT, Gem and Cis were usually given for another 1-3 cycles. Twenty-seven patients received Gem and Cis alone over 6 cycles. Of 32 patients with non-pancreatic periampullary 23 received CT+CRT and 9 patients received CT alone. Results: Patients with non-pancreatic periampullary cancer had better OS (p:0.017) and disease free survival (DFS) ( p<0.001 ) compared to patients with PC. Median OS of patients with PC was 21 months. Both OS and DFS were superior in the RT arm compared to nonRT arm (p: 0.043 and p <0.001). In non-pancreatic periampullary cancer patients OS was 31 months in RT group and 51 months in non-RT group (p: 0.709). DFS was 29 months and 49.8 months respectively, p:0.504). Conclusions: The prognosis of PC was worse than non–pancreatic periampullary tumor. In PC adjuvant delayed RT improved patient outcome. Although OS and DFS were better in patients receiving CT alone, the difference was not statistically significant in non–pancreatic periampullary tumors.
S-1/docetaxel compared with the other standard S-1 based regimens as a first-line chemotherapy for patients with advanced gastric cancer.
Authors: Kusumoto Tetsuya , Ando Koji , Ida Satoshi , Kimura Yasue , Saeki Hiroshi , Oki Eiji , Morita Masaru , Maehara Yoshihiko 
Published: March 2020

e15173 Background: S-1 monotherapy or S-1/CDDP have remained important as a standard chemotherapy regimen for patients with advanced gastric cancer (AGC), based on the randomized phase III trials. Although S-1/docetaxel has been reported highly active and well tolerated for AGC by many researchers, it could not show the superiority compared with S-1 monotherapy in the recent international randomized trial. We have also demonstrated that it might be effective for patients with Stage III AGC in both preoperative and postoperative adjuvant setting. The aim of this study was to evaluate efficacy, toxicity and validity of S-1/docetaxel retrospectively, compared with the standard regimens. Methods: We conducted a retrospective review of the data of 89 patients with AGC who received chemotherapy who were given S-1-containing regimens as the first line chemotherapy; 15 patients treated with S-1 monotherapy, 21 with S-1/CDDP, and 53 with S-1/docetaxel. The objective response, adverse event (AE), progression-free survival (PFS), and overall survival (OS) were compared between the three groups. Results: The overall response rates (ORRs) were obtained 6.7%, 38.1% and 30.2% for S-1 monotherapy, S-1/CDDP, and S-1/docetaxel, respectively. The incidence of AEs was more frequent in S-1 based combined treatments than in the S-1 monotherapy, however there was no significant difference in the severe AEs between each group. Survival data showed that the PFSs were 121 days, 199 days and 178 days, respectively, and there was the significant difference between S-1 monotherapy and S-1/docetaxel (p<0.05). The overall survival showed that the MSTs were not significantly different. The conversion rate to the subsequent treatments following S-1 monotherapy was higher than the other treatments. Conclusions: S-1/docetaxel was active and well tolerated for the patients with ARGC as the first line. Although the Japanese guideline for treatment of gastric cancer recommends S-1 monotherapy or S-1/CDDP as the standard regimens, docetaxel could be applied for patients with AGC in case of CDDP-resistant or –naïve patients.
Feasibility and potential benefits of adjuvant chemotherapy with S-1 in patients with curative resected advanced biliary tract cancer: A multicenter trial.
Authors: Toyoki Yoshikazu , Ishido Keinosuke , Kudo Daisuke , Kimura Norihisa , Wakiya Taiichi , Umehara Yutaka , Tohyama Shigeru , Endoh Masaaki , Tateoka Hiroshi , Ohishi Susumu , Hakamada Kenichi 
Published: March 2020

e15179 Background: S-1 chemotherapy is reported to be effective for treating metastatic and unresectable biliary tract cancer (BTC). We assessed the safety and feasibility of adjuvant S-1 chemotherapy in patients with curative resected advanced BTC. Methods: Patients with pathological stage II, III, or IVa BTC (according to JSBS) who underwent radical resection received oral S-1 (80 mg/m2/day) for 2 consecutive weeks every 3 weeks (1 cycle). Patients were aged 20–80 years, had a performance status of <1, and provided informed consent. The treatment was repeated until 1 year after surgery. The primary endpoint was feasibility of the adjuvant chemotherapy with S-1. The secondary endpoints were safety, disease-free survival (DFS), and overall survival (OS). Results: We enrolled 40 patients, but 5 patients were excluded on the basis of eligibility criteria (4 patients) or no drug administration (1 patient). We analyzed data from 35 patients (29 men and 6 women with a median age of 68 years) between January 2009 and November 2011. The feasibilities of 6-month and 12-month administration of S-1 were 65.7% (95% confidence interval [CI]: 47.8–80.9%) and 45.7% (95% CI 28.8–63.4%), respectively. Grade 3 neutropenia and anemia were observed in 2.9% and 5.7% of cases, respectively. Grade 3 non-hematological toxicities included anorexia in 14.3%, fatigue in 8.6%, and nausea in 2.9% of cases. No grade 4 hematological or non-hematological toxicities were observed, and no treatment-related deaths occurred. The 1-year OS was 91.4% (95% CI: 76.6–97.2%), and the 1-year DFS was 68.6% (95% CI: 51.7–81.7%). Conclusions: Adjuvant chemotherapy with S-1 for curative resected advanced BTC patients was both safe and feasible. Although the follow-up period was insufficient to evaluate OS and DFS, adjuvant chemotherapy with S-1 is believed to have improved the prognosis.
Pain and other symptoms in patients with hepatocellular carcinoma (HCC): A qualitative analysis.
Authors: Butt Zeeshan , Mallick Rajiv , Mulcahy Mary Frances , Benson Al B. , Cella David , Kaiser Karen 
Published: March 2020

e15187 Background: HCC is the second leading cause of cancer related deaths worldwide and incidence is increasing. Most HCC patients are diagnosed late-stage and with pain. Understanding the nature of pain experienced by HCC patients is complicated by co-morbid (including other liver) diseases and treatment related pain. The purpose of this study was to identify pain symptoms that are important and relevant to HCC patients who have received systemic therapy. Methods: We conducted semi-structured thematic interviews with 10 HCC patients who were currently on or previously had received oral systemic therapy (e.g., sorafenib) and had not received local or loco-regional therapy (e.g., surgery, radiation or chemo-embolization) within 4 weeks of the interview. Interviews included open elicitation of key symptoms, side effects and concerns. Patients also completed selected pain items from the FACT-Hep; items had previously been validated for patients with hepatobiliary cancers. Results: Mean age was 58 years (range 33-77); 2 patients had co-morbid cirrhosis, 1 had co-morbid hepatitis, and 4 patients had cirrhosis and hepatitis. When asked to describe the symptoms, side-effects or other issues that most significantly impact their quality of life, patients most often mentioned fatigue (n=5), diarrhea (n=5), skin toxicities (n=5), and loss of appetite (n=4). Nine patients reported experiencing pain over their HCC treatment course. Abdomen (N=7) and lower back (N=3) were the most common sites of pain; 2 patients reported only experiencing temporary pain from prior chemoembolization. The other 7 patients experienced ongoing pain, partly attributed to systemic therapy, ascites, or metastases. Ongoing abdominal and back pain were frequently not attributed to a specific cause. All patients indicated that FACT-Hep items adequately assessed their pain. Conclusions: Although pain was not a major driver of quality of life and for a few HCC patients it was transient and treatment-related, the majority of patients experienced some persistent pain. Abdominal pain and back pain were the most common pain sites for HCC patients. These results support the relevance of pain symptoms that have been previously identified as important in HCC.
Clinical value of FDG PET/CT in predicting local failure in patients with esophageal cancer.
Authors: Fan Bingjie , Hu Man , Kong Li , Zhang Xiaoli , Fu Zheng , Yu Jinming 
Published: March 2020

e15197 Background: Local failure, including local residual tumor and local recurrence, is the most common failure patterns for patients with esophageal cancer (EC) treated with radiotherapy. The purpose of this study was to evaluate the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for predicting local failure in patients with EC. Methods: Twenty-two patients with biopsy-proven EC treated definitively with RT with or without chemotherapy were enrolled from June 2010 to August 2012. Dose of 60.4 - 70.2 Gy with 1.8 - 2.0Gy /fraction were delivered with three-dimensional conformal radiation therapy (CRT). All patients underwent FDG PET/CT scan prior to therapy. The patients were followed up every 3 months after treatment completion. Patients who developed local failure were confirmed with histological evidence or follow-up. Results: The follow up time was in the range of 5-30 months. Of 22 patients, 3 patients had local residual tumor, 2 patients experienced local recurrence. The mean SUVmax for patients with local failure was higher than that for patients without local failure (15.688±3.115 vs. 14.137± 4.397, p = 0.54). The local failure regions were mostly the regions with higher metabolic activity before radiotherapy. Conclusions: Patients with higher FDG-uptake may have higher risk to experienced local failure. The local failure regions were localized mostly in the higher FDG uptake regions of pre-therapeutically FGD PET/CT scans of the patients with EC.
Safety and activity of sunitinib in elderly patients (75 years or more) with metastatic renal cell carcinoma: Results of retrospective study in Paoli-Calmettes Cancer Institute in France.
Authors: Boulaamane Lamia , Rousseau Frederique , Cecile Maud , Braticevic Cecile , Dermeche Slimane , Walz Jochen , Salem Naji , Brunelle Serge , Thomassin Jeanne , Errihani Hassan , Gravis Gwenaelle ,   National Institute of Oncology
Published: March 2020

e15506 Background: Actual tolerability of cancer treatment is still poorly documented in elderly patients. Recently some retrospective reviews have been carried out to evaluate tolerability and efficacy of Sunitinib in elderly patients (> 65 years), with metastatic renal cell carcinoma (mRCC) enrolled in clinical trials. Yet data on routine clinical practice are still lacking. Methods: Between January 2009 and May 2012, 17 patients >= 75 years treated with Sunitinib for mRCC were reviewed, to assess toxicity, cause of treatment reduction or discontinuation. Correlation of toxicity with 7 domains comprehensive geriatric assessment (CGA), tumoral response and progression-free survival (PFS) were also analysed. Results: The median age was 79 years, and patients were followed-up until September 2012. The majority of patients were in the MSKCC favourable or intermediate-risk groups. Eleven patients have received Sunitinib in first line. The median dose received was 37.5mg. Grade II-III diarrhea was observed in 6 patients and grade I-II hand-foot syndrome in 9 patients. Treatment was stopped earlier (< 50 days) for 4 pts, due to severe toxicity: hospitalization in intensive care unit, oesophageal ulceration, asthenia and malnutrition. Temporary treatment discontinuation was observed for 3 pts. All patients underwent 7 domains CGA, and were classified according to Balducci scale. Correlation was not found between impairment at CGA with severe toxicity nor with response, but correlation was found between initial dose and treatment discontinuation. Sunitinib at level of 50 mg was associated with early and permanent treatment discontinuation, and initial dose reduction was associated with an acceptable safety profile and long time treatment duration. Response rate was 41.1% for partial response and 41.1% for stable disease. Median PFS was 23.3 months. Conclusions: This is the first retrospective study performed in elderly cancer patients aged over 75 years. There is no evident correlation between CGA impairment and toxicity profile of Sunitinib. Low starting and dose escalation in the absence of severe toxicity could be suggested.
Real-world treatment patterns in U.S. mRCC patients who fail two lines of targeted therapy.
Authors: Malangone Elisabetta , Gorritz Magdaliz , Stern Lee , Coombs John H. , Turnbull James D. , Liu Zhimei , Pal Sumanta Kumar 
Published: March 2020

e15511 Background: The treatment landscape for mRCC has undergone rapid growth in recent years with the approval of several targeted therapies (TTs). An analysis of real-world treatment patterns in patients who fail two lines of TT using the MarketScan database was recently presented (Pal S et al ASCO GU 2013 [Abstr 231]). The current study aimed to assess treatment patterns in mRCC patients who fail 2nd line TT using the PharMetrics database. Methods: Data were obtained from the PharMetrics database for patients with an RCC diagnosis and at least 3 lines of TT between January 1, 2004 and September 30, 2011. The PharMetrics database covers over 100 health plans across the U.S, and is plan-based, unlike MarketScan which is employer-based. Adult patients with at least 3 months of follow-up prior to initiation of 3rd line TT were included. Treatment patterns were examined for the final sample. Time to treatment discontinuation (TTD) was defined as the time from initiation of 1st line to end of 3rd line TT. Patients who did not switch to a 4th line TT were censored at end of 3rd line. Results: 377 mRCC patients initiated 3rd line therapy with sorafenib (So), sunitinib (Su), bevacizumab (Be), temsirolimus (Te), everolimus (Ev), or pazopanib (Pa). The sample was majority male (71%) with a mean age of 61 years (SD=10.5). The most common metastatic sites at any time were lung (76%) and bone (56%). The most common 1st line agent was Su (46%) and the most common 2nd line single agents were Te (26%) and Ev (17%). The most frequently used single agents in 3rd line were Te (23%), Be (17%) and Ev (15%). Third-line treatment choice differed by year; Te (49%) was most common in 2007 while Ev and Pa were most common between 2010 and 2011. The most common sequences were VEGF->mTOR->VEGF (41%), VEGF->VEGF->mTOR (22%), and VEGF->mTOR->mTOR (11%). The median TTD in months, adjusted for censoring were as follows (median (25th-75th percentile): VEGF->mTOR->VEGF: 36.9 (23.3-NA); VEGF->VEGF->mTOR: 27.7 (15.74-NA); VEGF->mTOR->mTOR: 29.9 (18.3-38.0). Conclusions: These results confirm those presented at ASCO GU. There is a growing number of TTs being prescribed in 3rd line mRCC patients. TTD results suggest an average treatment period of 32 months for the overall study sample.
Effect of sorafenib on cathepsin B-dependent BID-mediated apoptosis in cancer cells.
Authors: Santoni Giorgio , Amantini Consuelo , Santoni Matteo , Morelli Maria Beatrice , Farfariello Valerio , Nabissi Massimo , Liberati Sonia , Burattini Luciano , Bonfili Laura , Eleuteri Anna Maria , Mozzicafreddo Matteo , Berardi Rossana , Cascinu Stefano 
Published: March 2020

e15515 Background: Several tyrosine kinase inhibitors (TKIs), have been developed and approved for clinical use in multi-targeted cancer therapy. Among these, sorafenib is an orally available multikinase inhibitor approved for the treatment of the advanced renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Aim of our study was to evaluate the mechanisms responsible for the cytotoxic effects induced by in vitro use of µM doses of sorafenib in 5637 and J82 bladder cancer (BC) cell lines. Methods: The viability of BC cell lines were tested by MTT assay. Autophagy was evaluated by western blot analysis with the anti-LC3 and anti-p62 antibodies, acridine orange staining and cytofluorimetric analysis. Apoptosis, (ΔΨm) dissipation and ROS generation were determined by Annexin-V/PI, JC-1 and DCFDA staining, respectively and cytofluorimetric analysis. The cathepsin B activation was evaluated by western blot using an anti-cathepsin B antibody; the cathepsin B proteolytic activity was determined using the fluorogenic Z-Arg-Arg-AMC peptide and the fluorescence of the hydrolyzed 7-amino-4-methyl-coumarin was detected by a SpectraMax Gemini XPS microplate reader. Results: We found that sorafenib markedly reduced at µM dose the viability of BC cells. Treatment for 24h with 20µM of sorafenib, triggered “Incomplete autophagy”, that induced apoptosis of BC cells. Sorafenib by inducing an increased cathepsin B activity and pro-apoptotic protein BID activation, triggered a ROS-mediated-mitochondrial-dependent apoptosis of BC cells. Moreover, the increase of cathepsin B activity induced by sorafenib was inhibited by a specific tyrosine phosphatase inhibitor (e.g., orthovanadate) strongly suggesting for a contribute of tyrosine-phosphatases in sorafenib-induced apoptosis. Conclusions: Sorafenib by triggering incomplete autophagy, stimulates a cathepsin B-induced-BID-mediated-ROS- and mitochondrial-dependent apoptosis of BC cells, which is likely regulated by tyrosine-phosphatases.