bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I, dose-finding study of orally administered S-1 in combination with epirubicin and oxaliplatin (EOS) in patients (pts) with advanced or metastatic gastrointestinal cancer (AGIC) and chemonaïve advanced esophagogastric cancer (AEGC).
Authors: Moehler Markus Hermann , Heinemann Volker , Obermannova Radka , Kubala Eugen , Melichar Bohuslav , Mahlberg Rolf , Weinmann Arndt , Scigalla Paul , Tesarova Marietta , Janda Petr , Biville-Hedouin Fabienne , Mansoor Wasat 
Published: February 2017

140 Background: S-1 (Teysuno), an oral fluoropyrimidine registered in Europe since 2011, provides a good efficacy and safety profile for the treatment (trt) of AEGC in combination with cisplatin. (FLAGS Study; J.A. Ajani. EJC2013). Because triplets with platinum compounds and anthracyclines are commonly used in AEGC, a phase I evaluating S-1 with fixed doses of oxaliplatin (130 mg/m² D1) and epirubicin (50 mg/m² D1) q3w in AGIC pts [cohorts 1 (C1) and 2 (C2)] and in chemonaïve AEGC pts [cohort 3 (C3)] was performed. Methods: Pts >18 years, ECOG/PS 0/1 were enrolled. Standard dose-limiting toxicity (DLT) evaluation was used. The maximum tolerate dose (MTD) was defined as the highest dose level at which less than <2/6 of pts experienced a DLT during Cycle 1. Once MTD was established, the cohort was expanded up to 12 pts. C1 and C2: S-1 dose was defined in cohort of pts (3+3 design): C1 20mg/m² BID (40 mg/m²/day); C2 25 mg/m² BID (50 mg/m²/d). Escalation to dose level (DL) 2 occurred only after DL1 (20mg/m²/BID) was safe according to DLT criteria. In C3 pts received S-1 25mg/m² BID. Results: 23 pts were evaluated. C1 and C2 included AGIC pts at all lines of trt. As in C1: 3 pts had no DLT, dose was increased and 3 pts were included in C2: after 1 DLT (≥Gr3 non-hematological toxicity), 2 more pts were included in C2 with a second DLT (febrile neutropenia). These 2 DLTs occurred in heavily pre-treated pts (3rd line) and led to closing of C2 and 3 additional pts were enrolled in expanded C1. MTD of S-1 was established 20 mg/m² BID. No DLT reported for chemo-naïve pts treated. Since EOS is used to treat AEGC in first line, a new C3 cohort with chemo-naïve pts was opened to again determine MTD of S-1: 6 pts in C3 were included. Here no DLT occurred and additional 6 pts confirmed dose of 25 mg/m² as the MTD. Conclusions: Based on these results, the recommended doses of S-1 in EOS regimen are 20 mg/m²/BID in heavily pre-treated AGIC pts and 25 mg/m²/BID in chemo-naïve AEGC pts. The triplets EOS could represent a well-tolerated alternative first line trt for AEGC pts. Clinical trial information: 2011-003471-11.
Distribution of FDG-avid nodes in esophageal cancer: Implications for radiotherapy target delineation.
Authors: Garcia Brandon , Goodman Karyn A. , Cambridge Lajhem , Dunphy Mark , Wu Abraham Jing-Ching 
Published: February 2017

151 Background: Clinical target volumes (CTV) for radiation therapy (RT) in esophageal cancer (EC) are based on standard expansions of the primary tumor volume. Data is needed to better define the regions at highest risk for occult disease, based on histology and location of the primary tumor. We therefore reviewed PET scans in EC patients to characterize the frequency and location of FDG-avid lymph node metastases (LNM). Methods: We identified 474 EC patients with reviewable pre-treatment PET-CT scans who received RT. Tumors were classified by histology and location: upper esophageal (above carina, 15%), or lower/GE junction (85%). Locations of suspicious LNM were classified using standard radiographic nodal atlases, and distances from primary tumor to paraesophageal LNM were also measured. Results: FDG-avid LNM were identified and characterized in 204 patients. The most common LNM in upper EC were supraclavicular (1), retrotracheal (3P) and paratracheal (4). The most common LNM in lower EC were paraesophageal (8), and those in the gastrohepatic space (abdominal stations 1, 3 and 7). Overall, 55% of paraesophageal LNM were adjacent to the primary tumor. Of upper esophageal tumors with paraesophageal LNM, 87% were adjacent to the tumor and none were >6cm from tumor. However, 57% of lower esophageal tumors with paraesophageal LNM had non-adjacent paraesophageal nodes, half of which were >5cm from the tumor. Conclusions: A more data-driven and individualized approach to CTV delineation could improve the therapeutic ratio of RT in esophageal cancer. These results can guide CTV delineation by indicating the potential distribution of nodal involvement in esophageal cancer according to tumor location and histology. Because most paraesophageal LNM are adjacent to primary tumor, the necessity for uniformly large, longitudinal CTV expansions along the esophagus is unclear. [Table: see text]
Efficacy and safety of perioperative chemotherapy with 5FU-cisplatine-cetuximab in gastric and gastroesophageal junction adenocarcinomas (GGOJA): A single-arm multicenter phase II trial (FFCD 0901).
Authors: Mariette Christophe , Piessen Guillaume , Monterymard Carole , Pezet Denis , Ferru Aurelie , Baconnier Mathieu , Adhoute Xavier , Tavan David , Bouche Olivier 
Published: February 2017

154 Background: Whilst perioperative chemotherapy (CT) combined with radical surgery offers a survival benefit over surgery alone in GGOJA, 3-year survival still needs to be improved. The purpose of this phase II study was to evaluate the efficacy and safety of the perioperative use of cetuximab combined with 5-fluorouracil and cisplatin in operable GGOJA. Methods: Untreated operable patients with a WHO Performance Status (PS) ≤ 2 and age ≤ 75 years, with localised GGOJA received 6 cycles of intravenous Cetuximab (500mg/m²), Cisplatine (50mg/m²) and LV5FU2s (folinic acid 400mg/m², 5FU bolus 400mg/m², and continuous infusion of 5FU 2400mg/m²) every 2 weeks. Surgery was planned 3-4 weeks after the end of neaodjuvant CT and postoperative CT planned for 6-8 weeks after surgery. The primary objective was a combined evaluation of tumoral response, assessed by centrally reviewed computed tomography, and major toxicities leading to neoadjuvant CT being discontinued. Sample size (63 patients) was calculated using Bryant and Day design (α=5%, Power=80%), expecting a rate of objective response of 45% and a percentage of patients without major toxicities of 90%. Results: 65 patients were enrolled from 2011 to 2013 with a median age of 60.5 years. 83.1% were men, 98.5% had a WHO PS<2, 30.8% had a gastric and 69.2% a junctional tumour, 28.5% had a stage II and 71.4% of patients a stage III tumour. With regard to the primary endpoint, 64 patients were evaluated, 29.7% (n=19) had an objective morphological tumour response and 95.3% (n=61) did not stop treatment prematurely due to major toxicity. 58 patients (89.2%) completed neoadjuvant CT as planned. The median duration of CT was 2.3 months and grade 3-4-5 toxicities were observed in 61.5% of patients. 60 patients (92.3%) underwent surgical resection with 24 significant complications (41.7%) and 2 postoperative deaths (3.4%). On histological analysis, 40 patients (71.4%) were non responders. Conclusions: Adding cetuximab to the neoadjuvant chemotherapy regimen in operable GGOJA is safe but does not show enough efficacy in the present study to meet the primary endpoint. Clinical trial information: NCT01360086.
Surgical treatment in extremely aged patients with gastric cancer.
Authors: Sudo Masanori , Nashimoto Atsushi , Matsuki Atsushi , Yabusaki Hiroshi , Aizawa Masaki 
Published: February 2017

163 Background: Average life expectancy is increased to 82.6-year-old nowadays in Japan, and there is the increase of the number of elderly patients diagnosed with gastric cancer. Methods: From 1991 to 2011, 5330 operations have been performed for patients diagnosed with gastric cancer in our hospital, and 78 patients (1.5%) were over 85-year-old (elder group). To analyze the problems of surgical treatment for the extremely aged patients, the clinic-pathological findings were investigated retrospectively and compared with those in 4494 patients under 75 years old (control group). Results: Median age of elderly group was 86 (85-95) and control group was 63 (19-75). Preoperative morbidity was higher in the elderly group than in control group (73.1% vs 23.2%,p<0.001). The operative prosedures such as local/proximal/distal/total were 9/0/49/20 in elderly group and 216/172/2983/1123 in control group. The ratio of D2/D3 nodal dissection was lower in elderly group than in control group (30.8/0% vs 48.1/5.4%). Operation-time/blood-loss was less invasive in elderly group (135min/70ml vs 165min/100ml,p<0.001), but the postoperative morbidity rate was higher in elderly group (24.4% vs 15.3%,p=0.029). Although the frequency of postoperative complications was similar in surgical field, (14.1% vs 13.1%), other morbidity such as pneumonia, cerebral infarction and renal impairment were more common in elderly group. There was no difference in postoperative hospital stay in two groups (15 days). The ratio of postoperative adjuvant chemotherapy was lower in elderly group (Stage II/III; 10.0/13.3% vs 54.2/67.9%). The best supportive care is highly selected in elderly group in case of recurrence (66.7% vs 11.9%). The overall 5-year survival rate of Stage I/II/III/IV was 70.6/70.0/30.3/0% in elderly group and 92.0/80.0/60.5/13.3% in control group. The ratio of non-cancer death was higher in elderly group (41% vs 14%,p<0.001). Conclusions: The postoperative morbidity and non-cancer death is higher in elderly group. With the restriction for treatment failure, appropriate surgical procedures such as minimally invasive surgery and attentive care for the morbidity would need for the extremely aged patients for their better quality of life.
Actionable locoregional failures (LRFs) after therapy of localized esophageal carcinoma (LEC): Surveillance strategies and their benefits.
Authors: Elimova Elena , Wang Xuemei , Qiao Wei , Sudo Kazuki , Wadhwa Roopma , Shiozaki Hironori , Planjery Venkatram , Charalampakis Nikolaos , Skinner Heath Devin , Lee Jeffrey H. , Weston Brian , Bhutani Manoop S. , Komaki Ritsuko , Rice David C. , Swisher Stephen , Blum Mariela A. , Maru Dipen M. , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: February 2017

21 Background: The goal of surveillance after local therapy (trimodality or bimodality) is to salvage patients with actionable LRF, however, the benefits of current surveillance strategies are not well documented. We report on a large cohort of LEC patients with actionable LRF. Methods: Between 2000 and 2013, 127 patients with actionable LRF were assessed. Histologic/cytologic confirmation of LRF was the gold standard. All surveillance tools (imaging and endoscopy) were assessed. Results: The majority of the patients were men (89%), had adenocarcinoma (79%), had their LRF identified through surveillance (85%) and most had no new symptoms (72%). For the 41 LRFs after trimodality, the sensitivity of PET/CT alone was 93% but the specificity was 67%. In trimodality patients with a positive PET/CT for LRF, only 44% had LRF confirmed by endoscopy and 56% LRFs confirm by additional testing (e.g., FNA, etc). Alternatively, in bimodality patients, endoscopy confirmed LRF in 81% (n=85; 1 patient not evaluable). Trimodality patients were at higher risk of subsequent (e.g., distant) relapse after LRF was documented than were bimodality patients (p=0.03); 78% of the relapses were distant. In bimodality patients, 99% of relapses (LRF and/or distant) occurred within 36 months of therapy while in trimodality patients, 90% of relapses occurred within 36 months of surgery. Conclusions: Our data suggest that PET/CT is more likely to detect LRFs than endoscopy in trimodality patients. However, in bimodality patients, endoscopy is more valuable than PET/CT for documenting LRFs. At least 3 years of surveillance are needed for all LEC patients. However, even after the salvage, distant relapses are common. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI).
Multimodality therapy for locally advanced esophageal cancer.
Authors: Paryani Nitesh N. , Ko Stephen , Hobbs Corey James , Kowalchik Kristin , Johnson Elizabeth , Kim Siyong , Vallow Laura , Peterson Jennifer Layton , Tzou Katherine S. , Buskirk Steven J. 
Published: February 2017

211 Background: The current standard of care for locally advanced esophageal cancer includes chemoradiotherapy with or without surgery. Radiation is usually delivered via a 3D technique. IMRT has been utilized in the treatment of multiple tumors and demonstrated similar efficacy while offering the possibility of decreased toxicity. Methods: Thirty-six patients were treated with IMRT and chemotherapy. Twenty-one patients underwent surgical resection. Eleven underwent open surgery and the remainder underwent minimally invasive surgery. Chemotherapy consisted primarily of 5-FU with oxaliplatin or cisplatin. All but two patients received 50.4 Gy; one patient received 41.4 Gy without surgery and one patient discontinued treatment after 25.2 Gy. Eleven patients required a treatment break during radiotherapy. The median age was 69 (range 46-87). Approximately two-thirds of tumors were adenocarcinomas located in the lower thorax. Two thirds of patients were staged as T3 and had positive lymph nodes. The median tumor size was 5 cm (range 2-13). Results: With a median follow-up of 21.3 months (range 2.4-44.8) and 33.9 months for survivors (range 3.7-44.8), overall survival at 24 months was 55%. The 24 month overall survival was 75% vs 24% for surgical and non-surgical patients, respectively. Seven patients had a complete pathologic response. Twenty-four patients experienced grade 3 or higher acute toxicity and there was one grade 5 toxicity. Acute toxicity was similar between surgery and non-surgery patients. Fourteen patients experienced grade 3 or higher late toxicity; 9 surgery and 5 non-surgery patients. The most frequent late toxicity was grade 3 stricture (21%). On multivariate analysis, advanced age (RR [10 year increase] 2.01, p=0.032) and heart maximum dose >55 Gy (RR 3.73, p=0.011) were associated with decreased survival. Conclusions: Patients who undergo surgery after chemoradiotherapy demonstrate improved survival; however, this may be related to underlying comorbidities that preclude surgery. IMRT appears to be a reasonable treatment option that may reduce complications from radiotherapy. Careful attention should be given to heart dose during treatment planning.
Effects of lanreotide autogel/depot (LAN) in pancreatic neuroendocrine tumors (pNETs): A subgroup analysis from the CLARINET study.
Authors: Phan Alexandria T. , Caplin Martyn E. , Pavel Marianne E. , Cwikla Jaroslaw B , Raderer Markus , Sedláčková Eva , Cadiot Guillaume , Wolin Edward M. , Capdevila Jaume , Wall Lucy , Rindi Guido , Langley Alison , Gomez-Panzani Edda , Ruszniewski Philippe B. ,   on behalf of the CLARINET Study Group
Published: February 2017

233 Background: The prognosis for patients with metastatic pNETs is generally poor and current treatment options can be complicated by safety considerations. In CLARINET, progression-free survival (PFS) was significantly prolonged with the somatostatin analog LAN 120 mg vs. placebo (PBO) in patients with metastatic grade 1 or 2 (Ki-67 <10%) non-functioning enteropancreatic NETs (hazard ratio [HR] for progressive disease [PD]/death: 0.47 [95% CI: 0.30, 0.73]. Here, we more fully characterize treatment effects in the pNET subgroup. Methods: CLARINET was a 96-week randomized double-blind trial. Patients received LAN 120 mg or PBO every 4 weeks, administered by deep s.c. injection (NCT00353496). Subgroup analyses were undertaken to investigate only the consistency of treatment effects as the study was not otherwise designed or powered for such analyses. Results: 91 patients with pNETs received LAN (n=42) or PBO (n=49). At baseline, mean age was 64 years in both groups; overall, 37% had hepatic tumor loads >25%, 95% had stable disease, 77% had received no previous treatment, and 38% had had previous surgery on the tumor. Median PFS in the pNET subgroup was not reached at study end with LAN vs. 12.1 months [95% CI: 9.4, 18.3] with PBO (HR for PD/death: 0.58 [0.32, 1.04]). (Median PFS for LAN at first planned analysis in the open-label extension study was 29.7 months [12.0, 32.4].) The incidence of adverse events (AEs) in the core study was 88% with both LAN and PBO, and the most common AE was diarrhea (LAN, 43%; PBO, 37%). Treatment-related AEs occurred in 55% of the LAN group and 24% of the PBO group. Serious AEs (SAEs) occurred in 29% vs. 43%, respectively; only three of these patients had treatment-related SAEs (two with LAN, one with PBO). Two patients in each group had AEs leading to withdrawal. Conclusions: The evidence in the pNET subgroup suggesting antitumor effects with LAN together with the favorable long-term safety profile support a positive benefit:risk profile for LAN as a first-line treatment for pNETs. Clinical trial information: NCT00353496.
Racial/ethnic disparities in liver cancer-attributable hepatitis infections in the U.S. population.
Authors: Moore Kevin J. , Dunn Erin , Tannenbaum Stacey L. , Koru-Sengul Tulay 
Published: February 2017

259 Background: According to the American Cancer Association, hepatitisB and Cinfections may raise liver cancer risk. We identify population-specific cancer-attributable hepatitis prevalence to discern disparities across race/ethnicity for liver cancer risk. Methods: Data from 1999-2012 National Health and Nutrition Examination Survey (NHANES) were used to determine prevalence, unadjusted odds ratios (OR) with 95% confidence intervals (95%CI) for non-Hispanic-Whites (NHW), non-Hispanic-Blacks (NHB), Mexican-Americans, other Hispanics, and other race of hepatitis, taking complex sampling design into account. Results: Among those sampled, the overall highest prevalence of hepatitis infection was 66.4% in NHW for hepatitis-C and the lowest prevalence was 1.4% in Mexican-Americans for hepatitis-B surface-antigen. NHB were more likely than NHW to have hepatitis-B infections of surface-antibody (OR=1.9; 95%CI=1.8-2.0), core-antibody (3.3; 3.1-3.6), surface-antigen (5.3; 3.6-7.7), and hepatitis-C infections (1.7; 1.5-2.0). Compared to NHW, other Hispanics had a higher burden of hepatitis-B infection of surface-antibody (1.5; 1.4-1.7) and core-antibody (2.5; 2.1-2.8); other race had the same higher infection pattern as other Hispanics in surface-antibody (2.4; 2.2-2.6) and core-antibody (6.7; 6.0-7.5). Surface-antibody was more prevalent (1.5; 1.4-1.6) while core-antibody was less prevalent (0.9; 0.8-0.9) among Mexican-Americans compared with NHW. Conclusions: The prevalence of hepatitis B and C infections varies across different race/ethnicities with NHB having the greatest burden compared with NHW. Population-based databases should collect more information regarding infection burden in at-risk groups in order to understand more about these disparities. Appreciating such gaps across demographics could assist in future efforts to decrease the burden of hepatitis and to provide a base for targeted liver cancer prevention programs via screening, vaccination, health promotion, and literacy.
C-reactive protein on postoperative day 3 as a predictor of infectious complications following gastric cancer resection.
Authors: Fujitani Kazumasa , Shishido Yuji , Yamamoto Kazuyoshi , Hirao Motohiro , Tsujinaka Toshimasa , Sekimoto Mitsugu 
Published: February 2017

26 Background: Postoperative infectious complications (PICs) after gastric cancer resection remain a clinically relevant problem. Early detection of PICs, before critical illness develops, may be of considerable clinical benefit. The aims of this study were to investigate the predictive factors for PICs and to define the clinical parameters for their early detection in patients with gastric cancer resection. Methods: Clinical data of 417 consecutive patients undergoing elective gastrectomy for primary gastric cancer between 2009 and 2012 were retrospectively analyzed. Diagnostic accuracy was determined by the area under the receiver operating characteristic curve (AUC). Univariate and multivariate logistic regression analyses identified clinical factors predicting PICs of grade III or more according to the Clavien-Dindo classification. Results: Forty-four patients developed PICs of grade ≥ III (10.6%, 95% confidence interval [CI] 7.6–13.5%). As a systemic inflammatory marker, C-reactive protein (CRP) on postoperative day (POD) 3 had superior diagnostic accuracy for PICs (AUC 0.802, 95% CI 0.735–0.870) with a calculated cut-off value of 17.7 mg/dl, yielding a sensitivity of 0.66 (95% CI 0.524–0.774) and a specificity of 0.84 (95% CI 0.821–0.850). Multivariate analysis identified CRP on POD 3 of 17.7 mg/dl or greater (odds ratio [OR] 8.094, 95% CI 3.568–19.342) as well as clinical stage ≥ II (OR 4.445, 95% CI 1.478–15.881) and operation time ≥ 250 min (OR 3.638, 95% CI 1.449–10.137) as significant predictive factors for PICs after gastrectomy. Conclusions: Elevated CRP levels on POD 3 will help physicians predict postoperative course and facilitate decision-making regarding the prompt, comprehensive clinical search and therapeutic approach for PICs.
Tumor profiling of biliary tract carcinomas to reveal distinct molecular alterations and potential therapeutic targets.
Authors: Holcombe Randall F. , Xiu Joanne , Pishvaian Michael J. , Millis Sherri Z. , Gatalica Zoran , Reddy Sandeep K. , Sicklick Jason K. , Fanta Paul T. , Kesari Santosh , Morse Michael 
Published: February 2017

285 Background: Extrahepatic cholangiocarcinoma (EHCC), intrahepatic cholangiocarcinoma (IHCC), and gallbladder carcinoma (GBCA) are rare tumors with poor prognosis that tend to be chemo-resistant. The underlying molecular alterations and their correlation with altered responses to therapies are not well understood. We hypothesized that delineation of different molecular alterations in the cancer types might potentially yield different therapeutic options. Methods: 815 cases (126 EHCC, 434 IHCC, 244 GBCA, 11 NOS) were tested by a commercial multiplatform profiling service (Caris Life Sciences, Phoenix, AZ). Tests included sequencing (Sanger, NGS), gene amplification (CISH/FISH), and protein expression (IHC). Results: 24 of 47 genes tested had mutations, with the highest rates in TP53 (28%), KRAS (18%), IDH1 (9%), and SMAD4 (6%). BRCA1/2 mutations were seen in 3/41 (7.3%) and 5/40 (12.5%) cases. Overall,IHC showed high TOPO1, TOP2A, PD-1, SPARC and PD-L1 in 56%, 49%, 40%, 39% and 15% of cases and low RRM1, ERCC1 and TS in 82%, 72% and 79%, respectively, suggesting potential utility of chemotherapeutic and immunomodulatory agents targeting these alterations in selected cases. Mutually exclusive protein loss of chromatin modifiers BAP1 and PBRM1 were seen in 17% and 27%. ROS1 break-apart FISH showed negative results in 16 cases tested. Comparing the three carcinomas (EHCC, IHCC and GBCA, Table), EHCC had the highest KRAS mutation rate; IHCC had the highest IDH1 mutation; GBCA and EHCC had significantly higher TP53 mutation and HER2 amplification than IHCC.IDH1 and TP53 mutations were mutually exclusive, and IDH1-mutated IHCC had higher P-glycoprotein expression than TP53-mutated IHCC (82% vs. 37%). GBCA had high TOP2A by FISH and IHC, and a high loss of PBRM1(all p<0.05). Conclusions: Multiplatform cancer profiling reveals distinctbiomarker characteristics of biliary tract carcinomas, offering insights into disease biology and suggests potential sensitivity to novel and conventional therapies. Further analyses with clinical correlation are warranted. [Table: see text]