bluuebunny/crossref_metadata_2025_split huggingface dataset:
Greater than 3-year follow-up of concomitant gemcitabine, capecitabine, and radiation therapy in locally advanced or incompletely resected pancreatic cancer.
Authors: Sherman William H. , Chu Kyung , Allendorf John , Chabot John A , Schrope Beth , Fine Robert 
Published: March 2020

e14708 Background: When either gemcitabine (G) or capecitabine (X) are combined with RT, the median survival is less than 12 months. Approximately 30% of patients progress during the 9 week period of treatment and re-assessment. The benefit of RT in the post-op setting has been questioned. Co-administration of G and X is synergistic against pancreatic cancer cells and both are radiation sensitizers. They were combined with RT. Methods: A retrospective analysis was done on 48 patients treated with GTX (G, docetaxel (T) and X) followed by radiation therapy with concomitant G and X. RT was delivered by conformal fields or IMRT in 180 cGy fractions to 5040 cGy. X, 1,000 mg/m2 was given days 1 to 10 and days 16 to 25 of RT and G, 750 mg/m2 over 90 minutes, was given on days 5, 10, 20 and 25 of RT. The end-points were toxicity and local disease control. Results: 14 patients with positive margin of resection were treated adjuvantly and 34 patients with arterial involvement were treated neo-adjuvantly. No patient developed evidence of metastasis within the 9 weeks after starting RT. There were no bowel perforations, pancreatitis or delayed strictures. The therapy was well tolerated. Grade 3/4 toxicities were: thrombocytopenia 29%, leucopenia 38%, anemia 43%, enteritis 10% and infection 8%. 2 patients had GI bleeding from telangectasias more than 6 months after completing RT. The group of 14 treated adjuvantly had survival of 100% at 1 year, 86% at 2 years. 7 (57%) are beyond 3 years and have not relapsed. 34 patients treated neo-adjuvantly had one year survival of 85%. Of the 34 patients, 16 (47%) are alive with a median survival of 24 months (95% CI 20.7, 31.7.) 22 had resections with a median OS of 25.7 M (range 8.8 to 74.8 M.) 13 have not relapsed (13.6 to 74.8 M.) On pathology, there were 3 CR’s (14%,) 6 (27%) with scattered microscopic disease and 13 (59%) with macroscopic residual disease. Conclusions: G and X can be combined safely with radiation therapy to achieve local control of pancreatic cancer. Our results suggest that the aforementioned therapy, when combined with surgery, increases the long-term disease-free survival over results reported in the literature.
Adjuvant chemoradiotherapy in patients (pts) with resectable gastric (GC) or gastroesophageal junction cancer (GEJC): A monoinstitutional experience.
Authors: Soini Barbara , Pani Giuseppe , Caffo Orazio , Frisinghelli Michela , Veccia Antonello , Brugnara Sonia , Caldara Alessia , DiPasquale MariaChiara , Ferro Antonella , Mussari Salvatore , Murgia Viviana , Russo Lucianna , Valduga Francesco , Tumulo Salvatore , Galligioni Enzo 
Published: March 2020

e14711 Background: Several studies have investigated the role of adjuvant chemotherapy ± radiotherapy showing conflicting results. In this retrospective study we report our monoinstitutional experience in pts with resectable GC or GEJC, treated with adjuvant chemoradiotherapy. Methods: Between January 2004 and August 2010 a consecutive series of 48 pts (34 male and 14 female) with a median age of 61 years (range 45-76) underwent a curative resection for GC or GEJC. All pts were treated with adjuvant chemoradiotherapy according to Mc Donald protocol (NEJM 2001;345:725-30). Thirty-three tumors (69%) were localized at the antrum or corpus level and 9 (19%) at the cardias. Thirty-one patients (64 %) had a T3-T4 tumor and 46 (95%) had nodal metastases.Treatment consisted of fluorouracil (5FU) 425 mg/m2 per day plus leucovorin (L) 20 mg/m2 per day, for 5 days, followed by radiotherapy 4500 cGy at 180 cGy per day, given 5 days per week for 5 weeks, with 5FU (400 mg/m2 per day) and L (20 mg/m2 per day) during the first four and the last three days of radiotherapy. One month after the completion of RT, two five-day cycles of 5FU (425 mg/m2 per day) plus L (20 mg/m2 per day) were given one month apart. Results: The treatment was completed in all but 4 pts: 2 pts stopped treatment due to chemotherapy side effects, 1 pt died due to intestinal perforation, and 1 pt declined radiotherapy. Major toxicities consisted of: grade 3/4 neutropenia in 6 pts (12%) and grade 3/4 gastrointestinal toxicity in 8 pts (16 %). At a median follow-up of 25.5 months (range 7 - 68), the median disease free-survival (DFS) was 41 months (2-y DFS 59%, 3-y DFS 53%) and the median overall survival (OS) was 57 months (2-y OS 77%, 3-y OS 68%). Conclusions: Concomitant chemo-radiotherapy appears in our experience a feasible adjuvant regimen in curatively resected node positive gastric cancer. Despite the short follow-up, local control and survival rates seem promising and comparable to those reported in the literature.
Neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy followed by surgery for esophageal/gastroesophageal junction adenocarcinoma: A single-institution experience.
Authors: Platz Timothy Alan , Nurkin Steven J. , Fong Mei Ka , Malhotra Usha , Yendamuri Saikrishna S. , Nava Hector R. , Warren Graham Walter , Salerno May Kilian 
Published: March 2020

e14712 Background: Esophageal and gastroesophageal junction (GEJ) adenocarcinoma is increasingly treated with trimodality therapy. We present our experience using carboplatin/paclitaxel and radiotherapy followed by surgery. Methods: Consecutive patients with distal esophageal/GEJ adenocarcinoma (≥T2 or N+) treated from July 2010 to October 2011 were identified. All patients received neoadjuvant carboplatin/paclitaxel with concurrent radiotherapy (CRT) to 50.4 Gy using an IMRT technique and then Ivor Lewis esophagogastrectomy. PET/CT was performed prior to and after CRT. Patient/treatment characteristics and tumor response were analyzed. Results: Over this timeframe,17 patients completed trimodality therapy using this regimen. All were male with a median age of 59 years (45-72). All tumors were grade 2-3 adenocarcinoma with mean tumor length of 4.4 cm (1-9). A median of 6 cycles (5-9) neoadjuvant carboplatin/paclitaxel were administered, 3 patients received additional adjuvant therapy. Average time from diagnosis to CRT completion was 78 days (44-141) and from CRT end to surgery was 62 days (35-92). Neoadjuvant CRT was well tolerated with mean weight loss of 3.5 kg. All pts had R0 resections. No anastomotic leaks or perioperative mortality occurred. Mean hospital stay was 13.6 days (8-28). Pathologic complete response (pCR) was seen in 41% of patients, microscopic residual disease (isolated tumor cells or <2mm) in 29%, and macroscopic residual disease remained in 29%. Mean SUV reduction was 41% (0-100). Of 12 patients with ≥35% SUV decrease, 50% had pCR and 25% had microscopic residual disease. Three patients had signet ring features; of these 2 had no SUV reduction and all had gross residual disease, including the only patient with pN disease. Conclusions: Trimodality therapyutilizing carboplatin/paclitaxel and CRT to 50.4 Gy IMRT followed by Ivor Lewis esophagogastrectomy was well tolerated and resulted in significant pathologic complete response or minimal residual disease. Further investigation of predictive factors for response is needed to best tailor therapy in the management of esophageal/GEJ adenocarcinoma.
Cumulative impact of algorithm-integrated multidisciplinary treatments for cholangiocarcinoma.
Authors: Hirschfeld Azriel , Bruckner Howard , Stega Jeanetta , Schwartz Myron E. 
Published: March 2020

e14732 Background: Pancreatic Ca (PC) treatments (rxs) are often applied to patients (pts) with cholangioC (CC). Analyses support parallel "testing" of neoadjuvant (NeoA) and adjuvant (A) rx for CC pts. The rxs below “doubled” phase II objective response (OR) and survival (OS) vs PC. Methods: With pre-registration and IRB consent over ten years: GFLIP>GFLIO >GFLIO docetaxel (D) -/+mitomycin -C (MM-C) (Bruckner ASCO 01, 05, 08, 11) were applied to pts with PC and CC; stage adjusted, “possible best" choices for PC rxs were applied as NeoA and A rxs for high risk CC pts. Risk was defined by: margin, +; size, large; location, surgical difficulty, central; LNs, involved (or suspect), number of sites (and distance); pathology, atypical, high virulence and relapse (second surgery). These are the worst half of resected pts. Pts with unresectable (U) and metastatic (IV) CC were eligible with or without prior failure of some of the rx drugs. Targeted rx (TT) was briefly added, bevacizumab (B) 5mg/kg or cetuximab (C), as needed, to convert stable disease (SD) to NeoA eligible OR. Gallbladder Ca (GBC) pts were also treated. The algorithm's goal was to both optimize surgery for tumor reduction to improve rx and to select “timely” drug partners to reduce tumor size and allow further surgery. Results: No fatal AEs; Of 16 high risk, Adjuvant, resected pts, at 18 mos, 14 are alive, 10/11at 2 yrs, 6/7 (86%) at 3 yrs, 1 lost contact CC U/ IV, N=28, 4 lost contact 16/19 (84%) alive at 18 mos; 12/16 alive at 2yrs; 8/12 alive at 3 yrs. This vs. 50% (18mo) MST (ASCO 11). Of 7 NeoA, 4/4 were alive at 3 yrs, 3 others alive < 3 yrs. (3 had best R with TT). *RR GFLIO ~ 60% add DMM-C ~ 60% € ~84% add TT ~20% €~ 87%. Conclusions: Rxs are safe, economical and well tolerated. € RR and OS adding (FI, D, D-MMC and selectively TT) are testworthy. Both 12 mos OS and NeoA/A are testworthy for GBC pts. B and C are individually active, safe and cost effective in brief NeoA usage applications. Low dose multi drug rxs are ideal safe platforms for TT. High serial € RR encourage 1° and 2° attempts at both debulking - strategic palliative and definitive surgery, ideally in trials to optimize (pt conditioning, eligibility) and compare NeoA vs A rxs.
The preclinical activity of lenalidomide in urothelial carcinoma (UC).
Authors: Levitt Jonathan M. , Chan Keith S. , Jian Weiguo , Lerner Seth P. , Sonpavde Guru 
Published: March 2020

e15002 Background: Lenalidomide is approved for multiple myeloma and deletion 5q myelodysplastic syndromes (MDS) and demonstrates immune modulation, anti-angiogenic activity and direct anti-tumor cytotoxicity. A rationale can be made to evaluate the preclinical activity of lenalidomide in urothelial carcinoma (UC) based on the importance of these pathways. Methods: The in vitro anti-tumor activity of lenalidomide was evaluated in 4 human (5637, TCC-SUP, RT4, RT112) and 1 murine (MB49) cell line. Anti-proliferative activity activity (MTT assay), apoptosis (Annexin-FITC immunohistochemistry [IHC], flow cytometry) and cell viability by colony forming assay were measured. In vivo examination of activity of daily oral lenalidomide 10 mg/kg orally once daily or placebo for 4 weeks is examined in a syngeneic immunocompetent mouse model employing MB49-Luc25 cells injected subcutaneously in C57BL/6 mice. Murine tumors will be studied for anti-tumor activity. Results: In vitro activity of lenalidomide was detected at low ~1 µM concentrations (attainable in human subjects) against a non-invasive human UC cell line (RT4). Long-term cultures of RT4 cells for 10 days with daily repletion of lenalidomide reduced cell viability and colony forming ability to 75.6% of controls. Induction of apoptosis in RT4 was demonstrated by Annexin-FITC IHC and flow cytometry compared to control (30.11 vs. 14.74%). Invasive human UC cells and murine MB49 cells did not demonstrate apoptosis with lenalidomide exposure in vitro. Futher, lenalidomide did not inhibit overall tumor growth in the syngeneic immunocompetent murine model; immune activity and stem cell directed activity will be presented. Conclusions: Lenalidomide demonstrated preclinical anti-tumor activity against non-invasive human UC cells. Given its favorable toxicity profile compared to cytotoxic chemotherapy, clinical evaluation in patients with non-muscle-invasive bladder cancer and recurrence after BCG therapy may be warranted.
Evaluation of ERCC1 and RRM1 as prognostic biomarkers in urothelial cancer (UC) treated with adjuvant platinum and gemcitabine chemotherapy.
Authors: Harshman Lauren Christine , Bepler Gerold , Quinn David I. , McKenney Jesse , Hawes Debra , Simon Noah , Srinivas Sandy , Dorff Tanya B. 
Published: March 2020

e15005 Background: Adjuvant (adj) treatment of UC generally entails platinum (plat)- and gemcitabine (gem)-based chemotherapy (chemo). Two candidate prognostic and predictive biomarkers are the excision repair cross-complementation group 1 gene (E1) and the regulatory subunit of ribonucleotide reductase (R1). Studies in advanced UC patients (pts) suggest that high E1 and R1 expression confers chemoresistance to cisplatin (cis) and gem respectively. We identified UC pts treated with adj chemo to assess for differences in time to recurrence (TTR) and overall survival (OS) based on tumoral E1/R1 expression and chemotherapy regimen. Methods: 184 pts, who received adj plat or gem for T2-4NxM0 UC from 1984-2009, were identified. Tissue microarrays were created from their primary bladder tumor and involved nodal tissue. E1 and R1 protein expression was assessed using AQUA (HistoRx). The median (med) values were established a priori as the cutoff for high and low expression. Medical records were retrospectively reviewed for pathology, treatment, and outcomes data. Results: 154 pts who had both clinical and gene expression data were eligible for analysis. Pts received cis (134), carboplatin (carbo, 20) and gem (62) based regimens. Med age was 65 yrs. The majority were male (79%) and had pT3 (48.7%) or nodal disease (53.2%). At med followup of 3.9 yrs, 53.4% have recurred. Med TTR and OS were 1.2 and 2.1 yrs. Primary tumor E1/R1 Spearman correlation was moderate at 0.49 but less between primary and nodal disease (E1 0.34, R1 0.23). Irrespective of chemo, E1 and R1 expression were not prognostic for TTR (E1 p=0.8, R1 p=0.3) or OS (E1 p=0.25, R1 p=0.83). Degree of E1 expression did not impact TTR or OS in plat-treated pts nor did R1 expression in gem-treated pts. Stage predicted increased TTR and OS (<0.00001). Cis-treated pts had significantly longer TTR (p=0.02) than carbo-treated pts. Conclusions: Tumoral E1 and R1 expression were not prognostic biomarkers for UC pts treated with adj plat and gem chemotherapy in our cohort. Our data was limited by missing tissue in 22% of planned pts. Reproducibility by a second laboratory and heterogeneity analysis between primary and nodal tissue will be presented.
The natural history, treatment pattern, and survival of the patients with micropapillary bladder.
Authors: Wang Jue 
Published: March 2020

e15015 Background: Micropapillary bladder carcinoma (MPBC) is a rare variant of urothelial carcinoma. The objective of this study was to examine the epidemiology, natural history, and prognostic factors of MPBC using population-based registry. Methods: The Surveillance, Epidemiology, and End Results (SEER) Program database was used to identify cases of MPBC by tumor site and histology codes. The clinical, demographic characteristics, treatment and survival of MPBC were examined. Results: A total of 98 cases of histology confirmed MPBC were identified between 2001 and 2007, this accounted for approximately 0.01% of all primary bladder tumors during the study period. Median age of the patients was 72 years (range 26-95). Of all the patients with MPBC, 56.1% had muscle invasive disease; 75.5% of patients had poorly or undifferentiated histology. A total of 30.6% of all patients (2.3% superficial disease; 52.7% of muscle-invasive MPBC) had radical or partial cystectomy. By logistic regression analysis, nonmuscle-invasive MPBC (OR 62.5, 95% CI 7.2-542.3) was associated with lower rate of utilization of cystectomy. The 1-, 3- and 5-year overall survival rate of MPBC were 84.5%, 57.3% and 42.3%. In multivariate analysis, tumor stage (HR 4.7, 95% CI 1.0-21.8) was found to be the only significant predictor for cancer-specific survival. Conclusions: The optimal therapy for MPBC remains undermined. Emphasis on early detection is needed to improve the outcome for patients with this malignancy.
Extensive lymph node dissection in the era of increasing perioperative chemotherapy for muscle-invasive urothelial carcinoma of the bladder.
Authors: Holder Dara Denise , Lin James , Whalen Micheal , McKiernan James M. , DeCastro Guarionex 
Published: March 2020

e15018 Background: The efficacy of perioperative chemotherapy (CHT) in the management of muscle invasive urothelial carcinoma of the bladder (UCB) has been attributed to its ability to eliminate occult disease, which when coupled with a cystectomy can reduce recurrence. The therapeutic role of lymphadenctomy (LND), with an appropriate template and nodal yield, during radical cystectomy (RC) is well established. To date, there have been no studies examining the integrative effect of an extended LND and the use of perioperative CHT for patients with muscle-invasive UCB. As such we examined the interaction between survival and extent of LND based on whether patients received perioperative CHT or RC only. Methods: Review of our urologic oncology database yielded 314 patients with cT2-4N0M0 UCB who underwent RC with and without perioperative CHT between 1990- 2011. Extended lymph node dissection was defined as the removal of ≥11 nodes. Clinical and pathological variables were analyzed using Cox Hazard and Kaplan Meier models. The primary endpoints examined were overall (OS) and disease-specific (DSS) survival. Results: Two hundred and four (65%) patients were identified who underwent RC only, while 110 (35%) patients received perioperative CHT and RC. There was no significant difference between the 2 groups in common demographic and pathologic variables. Fifty-one percent of patients who underwent CHT and RC and 42% who underwent a RC only had an extensive LND (p=0.16), with a mean nodal yield of 9. Extended LND was associated with a non-significant decreased risk of death in the RC-only group (HR=0.54, CI: 0.23-1.20, p=0.14), and a non-significant increase in patients who underwent perioperative CHT (HR=1.25, CI: 0.71-2.81, p=0.56). Kaplan Meier analysis showed an increase in the probability of DSS at 2 years in the RC-only group who underwent an extended LND vs. a standard LND (0.96 vs. 0.84, p= 0.12) while no such trend was observed in the perioperative CHT patients (0.75 vs. 0.75, p=0.35). Conclusions: Surgical management of occult micrometastatic disease through extended LND improves survival in patients undergoing RC only, but offers no additional benefit over perioperative CHT.
Addition of darbepoetin alfa to sequential high-dose VIP chemotherapy for patients with advanced metastatic germ cell cancer.
Authors: Hartmann Joerg Thomas , Metzner Bernd , Binder Claudia , Mergenthaler Hans-Guenther , Rick Oliver , Sayer Herbert G , Mayer Frank , Beyer Joerg , Lorch Anja , Berdel Wolfgang E. , Frickhofen Norbert , Bokemeyer Carsten , Schleicher Jan , Gauler Thomas C. ,   German Testicular Cancer Study Group (GTCSG)
Published: March 2020

e15026 Background: High-dose VIP chemotherapy plus ABSCT given as first line treatment might be a strategy in patient with advanced germ cell tumors (GCT) with poor prognosis. The objective of the trial was to investigate the addition of darbepoetin alfa to HD-VIP in order to reduce anemia/red blood cell (RBC) transfusions. Methods: This was a randomized, open-label multicenter phase 2 study conducted in 20 hospitals. Darbepoetin 2.25 mcg/kg weekly or 500 mcg Q3W s.c., started with high dose VIP (dose level 6) was applied in arm B (arm A: HD-VIP alone). The primary objective was freedom from blood transfusions (FFT). Secondary objectives included objective remission rate (ORR) after chemotherapy, 24 mos PFS and OS, median course of hemoglobin (Hb) levels during 3 HD-VIP cycles as well as drug safety. Results: Between 7/2003 and 11/2008 108 pts were allocated to the study, and 106 were included in the intention-to-treat (ITT) analysis. By March 2011 the median follow-up time after randomization was 20 mos. Localisation of primary was gonadal in 66%, retroperitoneal in 19% and mediastinal in 14%s. A favourable treatment outcome (CR/NED/PR m-) in conjunction with secondary surgery (n = 76 pts) was achieved in 58% of pts with no difference between arms A and B. Overall FFT occurred in 2 pts (4.2%) in arm A and 3 pts (5.6%) in arm B, and in 23%/15%/15% and 15%/17%/19% of pts during cycles 1-3, respectively. No differences in baseline Hb, severity of anemia, no of RBC transfusions and area under the curve of Hb levels during HD-VIP was observed. Pts assigned to darbepoetin had similar treatment toxicity compared to those assigned to HD-VIP alone. 24-mos OS in arm A was 86.3% compared to 67.8% (p=.064) in Arm B. 2-year RFS was 66.8% in arm A vs 55.5% in Arm B (p=0.45). Darbopoetin was generally well tolerated with 2 pts discontinuing treatment due to thrombosis. Since compliance to study protocol was generally poor (6 out of 55 pts never received study drug during HD-VIP) a per-protocol analysis is in preparation. Conclusions: Based on ITT analysis, the addition of darbepoetin alfa to the high dose regimen compared to HD-VIP alone does not appear to impact on FFT, ORR, and 2-year survival rate in poor prognosis GCT pts (NCT00204633).
Comparison of standard versus high dose of paclitaxel with ifosfamide and cisplatin (TIP) in salvage therapy of germ cell tumors (GCTs).
Authors: Mardiak Jozef , Mego Michal , Miskovska Viera , Sycova-Mila Zuzana , Obertova Jana , Palacka Patrik , Usakova Vanda , Rajec Jan , Liskova Stefania , Vertakova-Krakovska Bibiana , Chovanec Michal , Salek Tomas , Reckova Maria 
Published: March 2020

e15028 Background: Currently, TIP with higher dose of paclitaxel (250mg/m2) is considered standard salvage chemotherapy in GCTs with good prognostic features. However, until 2007, we utilized regimen with standard dose of paclitaxel (175mg/m2). The aim of this study was to compare the efficacy of TIP with the standard versus higher dose of paclitaxel as first salvage therapy for patients with relapsed GCTs. Methods: This retrospective study included 64 patients with relapsed GCTs treated with TIP as first salvage therapy between 1998 and 2010 in two major cancer centers in Slovakia. Forty five patients (70%) patients had favorable prognostic features for response (testis primary tumor site and prior complete response to induction chemotherapy regimen). Four cycles of standard dose (175mg/m2, 37 patients) or higher dose (250 mg/m2, 27 patients) of paclitaxel (day 1) with ifosfamide 1.2 g/m2 (day 1-5) and cisplatin 20 mg/m2 (day 1-5) were given 21 days apart with G-CSF support, followed by resection of resectable radiographic residua. Results: Nineteen of 37 (51%) patients treated with standard dose of paclitaxel achieved favourable response (complete remission or partial remission with negative serum tumor markers) compared to 20 of 27 (74%) patients treated with higher dose of paclitaxel (p = 0.07). In median follow-up of 23.9 months 37 patients (58%) experienced disease relapse and 33 (52%) patients died. Patients treated with higher dose of paclitaxel had better progression-free survival (median: not reached vs. 7 months, HR = 0.54, 0.28 - 1.04; p = 0.06) and overall survival (median: not reached vs. 33 months, HR = 0.69, 0.34-1.39; p = 0.31) compared to patients treated with standard dose of paclitaxel. Conclusions: Our data support the hypothesis that higher dose of paclitaxel with ifosfamide and cisplatin is associated with better outcome compared to standard dose of paclitaxel in patients with relapsed GCTs treated in first relapse.