bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictors of survival after trimodality therapy for esophageal adenocarcinoma: Analysis from the National Cancer Database.
Authors: Eng Oliver , Nelson Rebecca A. , Chao Joseph , Erhunmwunsee Loretta , Raz Dan , Kim Jae Y. 
Published: March 2017

116 Background: Trimodality therapy with neoadjuvant chemoradiation followed by surgery has been shown to improve survival compared to surgery alone for the treatment of locally advanced esophageal cancer, but there is considerable variation in survival in this population. We sought to analyze factors associated with survival after trimodality therapy in esophageal adenocarcinoma. Methods: We identified 4,679 patients from the National Cancer Database (NCDB) who received chemotherapy and radiation prior to surgery for esophageal adenocarcinoma from 2006-2013. Patients with stage IV disease and unknown pathological nodal status were excluded. We performed a multivariate analysis using a Cox proportional hazards model to identify independent predictors of overall survival. Results: On multivariate analysis, pathologic characteristics associated with decreased overall survival included stage, lymphovascular invasion, and positive surgical margins. Insurance status, age, and comorbidity index were also associated with decreased survival. We found that patients treated at academic programs (HR 0.85, CI 0.78-0.92, p=0.0001) and those who received additional adjuvant chemotherapy had improved survival (HR 0.86, CI 0.75-1.00, p=0.0452), but the vast majority of patients receiving trimodality therapy (4,306; 92.0%) did not receive adjuvant chemotherapy. Patients who received adjuvant chemotherapy were more likely to have private insurance (69 vs. 53%, p<0.0001). Compared to private insurance, Medicaid (HR 1.43, CI 1.20-1.70, p<0.0001), Medicare (HR 1.21, CI 1.07-1.36, p=0.0026), or having no insurance (HR 1.49, CI 1.16-1.90, p=0.0015) were all negative predictors of overall survival. Conclusions: There is wide variation in survival following trimodality therapy for esophageal adenocarcinoma. Both tumor characteristics and patient characteristics play a role. Adjuvant chemotherapy appears to be associated with improved survival, but only a minority of patients receive adjuvant chemotherapy in this setting. Insurance status and treatment setting are independent predictors of overall survival after trimodality therapy and may indicate treatment disparities.
Serial monitoring of imatinib pharmacokinetics (PK) in perioperative imatinib treatment in patients (pts) with gastrointestinal stromal tumors (GISTs): Results from the multinational phase II trial.
Authors: Yoo Changhoon , Ryu Min-Hee , Kurokawa Yukinori , Yang Han-Kwang , Nishida Toshirou , Kong Seong-Ho , Tsujinaka Toshimasa , Lee Kyung Hee , Yabusaki Hiroshi , Song Hong-Suk , Akabane Hiromitsu , Im Seock-Ah , Tanabe Kazuaki , Kang Hye Jin , Nomura Takashi , Kang Byung Wook , Nakamura Tetsu , Okubo Masaaki , Taniguchi Hirokazu , Kang Yoon-Koo 
Published: March 2017

118 Background: Imatinib plasma levels may be affected by the duration of exposure to imatinib and resection of the stomach. Therefore, we performed PK study to monitor imatinib plasma levels serially in the multinational phase II trial of perioperative imatinib for pts with large ( ≥ 10 cm) gastric GISTs without distant metastasis. Methods: In this trial conducted in Japan and Korea, 53 pts received neoadjuvant imatinib 400 mg daily and 40 pts received adjuvant imatinib after surgery. Blood samples for imatinib trough levels (Cmin) were collected after 1, 3, 6 months of each neoadjuvant and adjuvant imatinib and measured by using liquid chromatography-tandem mass spectrometry. For the comparison of imatinib Cmin between different time points, values were dose-adjusted and log-transformed. Results: During the neoadjuvant treatment, imatinib Cmin (mean ± standard deviation) was 2253.0 ± 1148.0 ng/mL (n = 49), 1623.3 ± 832.4 ng/mL (n = 47), and 1852.0 ± 1572.4 ng/mL (n = 45) after 1, 3, and 6 months of imatinib, respectively. During the postoperative treatment, imatinib Cmin was 1436.1 ± 852.8 ng/mL (n = 31), 1357.8 ± 646.4 ng/mL (n = 33), and 1084.2 ± 360.8 ng/mL (n = 31) after 1, 3, and 6 months of imatinib, respectively. In the neoadjuvant setting, imatinib Cmin was significantly reduced after 3 months (p = 0.0001) and 6 months (p = 0.004) compared to the value at 1 month. In 36 patients that imatinib Cmin was measured at both preoperative and postoperative setting, imatinib Cmin was significantly reduced after surgery (1732.4 ± 997.9 ng/mL vs 1282.8 ± 557.3 ng/mL; p = 0.04). The magnitude of changes in imatinib Cmin after surgery was greatest in patients who underwent total gastrectomy (10.6%, n = 2) followed by proximal gastrectomy (8.4%, n = 3), and wedge resection (3.3%, n = 30). There were no significant relationships between imatinib Cmin and toxicity or objective response. Conclusions: Imatinib exposure was reduced until approximately 3 months after imatinib treatment. It was also significantly reduced after surgery and the magnitude of changes might be affected by the extent of surgical resection of stomach.
Postoperative mortality after esophageal and gastric cancer surgery: Does age still matter? Results from a nationwide study.
Authors: Mariette Christophe , Pasquer Arnaud , Renaud Florence , Hec Flora , Gandon Anne , Vanderbeken Marguerite , Degisors Sebastien , Caranhac Gilbert , Piessen Guillaume ,   FREGAT Working Group
Published: March 2017

122 Background: More than age, patient comorbidity is increasingly considered as the prominent predictor of postoperative mortality (POM) in esophageal and gastric cancer surgery, leading a growing number of elderly to be operated on. However, the respective impact of age and comorbidity on POM remains to be elucidated. The study objective was to investigate the impact of age on POM according to patient comorbidity. Methods: All consecutive patients who underwent esophageal or gastric cancer surgery between 2010 and 2012 in France were included (n = 11,196). The 30-day POM was compared by age groups (20-39, 40-59, 60-79, ≥ 80) and stratified according to the Charlson score (0, 1-2, ≥ 3). The consistency across esophageal (n = 3286) and gastric (n = 7910) subgroups and variations between 30-day and 90-day POM were analyzed. Results: Patients ≥ 60 years represented 73.8% of cases. A linear increase in 30-day and 90-day POM was observed with increasing age, with rates of 0.9% and 2.1%, 2.4% and 5.4%, 4.8% and 8.8%, and 9.3% and 15.9% in 20-39, 40-59, 60-79, ≥ 80 years age groups, respectively ( P< 0.001). Comparing 20-39 and ≥ 80 years age groups, 30-day POM was 1.0% vs. 7.0% for Charlson 0 ( P< 0.001), 3.1% vs. 11.1% for Charlson1-2 ( P< 0.001) and 0% vs. 19.5% for Charlson ≥ 3 ( P= 0.020) patients. A similar linear increase of POM by growing age groups was observed for 90-day POM and in esophagus and stomach subgroups. By multivariable analysis age groups (OR 1.03 95%CI 1.02-1.04, p < 0.001) and Charlson score (OR 1.56 95%CI 1.43-1.70, p < 0.001) were independent predictors of POM. Conclusions: Age and patient comorbidity have a similar and cumulative impact on POM after esophageal and gastric cancer surgery.
Retrospective review of subsequent treatments (tx) for esophagogastric adenocarcinomas (EGA) refractory to FOLFOX.
Authors: Kelly Ciara Marie , Janjigian Yelena Yuriy , Kelsen David Paul , Capanu Marinela , Chou Joanne F. , Ilson David H. , Ku Geoffrey Yuyat 
Published: March 2017

123 Background: FOLFOX is a preferred 1st-line tx for advanced EGA. We sought to characterize outcomes on subsequent tx and to see if MSK-IMPACT, a 410-gene next generation sequencing (NGS) platform, increases tx options. Methods: We retrospectively identified patients (pts) with advanced, Her2-negative EGA treated with 1st-line FOLFOX between Jan 2012 to Dec 2014. Clinicopathologic, tx and outcome data were analyzed. Overall survival (OS) was calculated from start of FOLFOX using Kaplan-Meier methods. Landmark analysis was used to compare OS and response status. Results: 185 pts were identified. The majority were Caucasian (82%), male (76%), ECOG PS 1 (67%), with poorly differentiated histology (72%) and de novo metastatic disease (84%). Median age was 64 years. The disease-control rate (DCR, partial response + stable disease) of FOLFOX was 80% [95%CI: 74%-85%]; 19% were FOLFOX primary refractory (FR). Median time-to-progression (TTP) on FOLFOX was 7 and 2 months (mo) for FOLFOX sensitive (FS) and FR pts, respectively. There was a higher proportion of females (26% vs. 14%, P = 0.18), gastric (43% vs. 23%, P = 0.051) and moderately differentiated tumors (26% vs. 12%, p = 0.113) in the FS vs. FR group. Six mo survival from the landmark time of 2 mo after initiation of FOLFOX was 83% [95%CI: 76%-89%], and 38% [95%CI: 20%-56%] for FS and FR pts, respectively (p < 0.01). A similar proportion of FS and FR pts received 2nd-line tx (65% vs. 69%). The DCR was similar in both groups (31% vs 29%). 2nd-line tx included: irinotecan- (51%) and taxane-based regimens (32%) or a clinical trial (CT) (13%). The median TTP on 2nd-line tx was similar in FS and FR groups (2.5 vs 2 mo). Ramucirumab was given in 14% of 2nd line regimens. 3rd-line chemo use was similar in both groups (37% vs 31%) but the DCR was lower in FR patients (18% vs. 9%). 51 pts had IMPACT; 1 pt (2%) enrolled onto a genotyped-matched CT. 14 pts received immunotherapy; 1 FS Pt has ongoing complete response 1+ year. Conclusions: Surprisingly, FS and FR pts derive similar, marginal benefit from 2nd-line tx, emphasizing the appropriateness of CT options in this setting. NGS rarely expanded tx options. Updated and in-depth NGS data will be presented.
Comparison of chemoradiotherapy (CRT) with carboplatin/paclitaxel (CP) versus cisplatin/5-FU (CF) for esophageal or junctional cancer: Experience from the Princess Margaret Cancer Centre.
Authors: Sim Hao-Wen , Chan Bryan , Natori Akina , Lim Charles Henry , Jiang Di Maria , Chen Eric Xueyu , Liu Geoffrey , Darling Gail Elizabeth , Swallow Carol Jane , Brar Savtaj Singh , Brierley James D. , Ringash Jolie , Wong Rebecca , Kim John , Rogalla Patrik , Hafezi-Bakhtiari Sara , Conner James , Knox Jennifer J. , Jang Raymond Woo-Jun , Elimova Elena 
Published: March 2017

126 Background: The optimal CRT regimen for neoadjuvant or definitive treatment of locoregional esophageal or gastroesophageal junctional (GEJ) cancer is uncertain. There has been no direct comparison between concurrent Cisplatin/5-FU (CF) as per the CALGB 9781 trial (50.4 Gy) or Carboplatin/Paclitaxel (CP) as per the CROSS trial (41.4 Gy). Methods: A retrospective analysis comparing CF and CP was performed in all patients (pts) with locoregional esophageal or GEJ cancer treated in 2012-2014. Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for age, performance status and Charlson comorbidity index. Pathological complete response (pCR) rates were compared using Fisher’s exact test. Results: 64/86 (74%) pts were male. Median age was 64 years (range: 34-84). Primary sites were esophageal (56%, with 60% squamous histology) and GEJ (44%, with 11% squamous). 22 pts received CRT in 2012 (100% CF), 33 pts in 2013 (58% CF, 42% CP) and 31 pts in 2014 (16% CF, 84% CP). Surgery was undertaken in 19 (41%) CF and 27 (68%) CP pts. Median follow-up was 38 months. We found no significant OS difference between CF and CP overall (HR 0.82, 95% CI: 0.43-1.56, p = 0.55) or in the subgroup having surgery (n = 46; HR 2.01, 95% CI: 0.62-6.55, p = 0.25). However, in the subgroup without surgery (n = 40), CF (n = 27) was superior to CP (n = 13)(HR 0.11, 95% CI: 0.03-0.38, p < 0.001). OS was similar by histology (adenocarcinoma/squamous) in all-comers (p = 0.96), and in CF (p = 0.66) and CP subgroups (p = 0.66). DFS results were similar to OS. There was a non-significant numerical difference in pCR rates between CF (31%) and CP (18%) (p = 0.45). Conclusions: Survival is similar for CF and CP CRT regimens in patients undergoing trimodality therapy. pCR rates were comparable but lower than previously reported. In contrast, in the absence of surgical resection, CP given for CRT results in significantly inferior outcomes. Clinicians may prefer CP for surgical candidates given its toxicity profile. However, when treating with definitive CRT, CF may be preferable to CP as a standard regimen.
Gastrectomy after chemotherapy: A new paradigm for the treatment of stage IV gastric cancer.
Authors: Seo Ho Seok , Park Cho Hyun , Song Kyo Young , Jung Yoon Ju 
Published: March 2017

127 Background: Although there are several traditional treatment modalities for stage IV gastric cancer including chemotherapy, radiation therapy, palliative surgery, or best supportive care, survival result is unsatisfactory. Recently, gastrectomy after chemotherapy which is called conversion surgery or adjuvant surgery was introduced. Methods: In total, 419 patients who were diagnosed stage IV gastric cancer from 2010 to 2015 in eight Catholic Medical Center affiliated hospitals were divided into four groups; 212 for chemotherapy only group (G1), 124 for chemotherapy after primary gastrectomy group (G2), 23 for gastrectomy after chemotherapy group (G3), and 60 for best supportive care group (G4). To compensate chemotherapy effects, cases of complete remission, partial response, and stable disease were selectively analyzed. To identify the factors that affected survival rate, the result of surgery and the intent of surgery of the G3 were analyzed. Results: Three-year survival rate of the G3 was significantly higher than that of the G1 (42.8% vs 12.0%, p = 0.001). In case of the patients with a response to chemotherapy, three-year survival rate showed similar result (G3 vs G1, 46.1% vs 18.4%, p = 0.011). In the G3, R0 resection and curative intent of resection showed better three-year survival rate (R0 vs R1 or R2, 61.1% vs 16.2%, p = 0.003, curative vs palliative, 62.3% vs 23.8%, p = 0.031). Conclusions: The present study showed that gastrectomy after chemotherapy might improve the survival rate for the patients with stage IV gastric cancer, especially who could undergo R0 resection.
Phase II study of S-1 plus docetaxel as first-line treatment for elderly patients with advanced gastric cancer (OGSG0902).
Authors: Matsuyama Jin , Imamura Hiroshi , Kawabata Ryohei , Kawase Tomono , Okada Kazuyuki , Nishikawa Kazuhiro , Kurokawa Yukinori , Fujitani Kazumasa , Shimokawa Toshio , Satoh Taroh 
Published: March 2017

129 Background: There is not enough evidence for the treatment of elderly patients with advanced gastric cancer. S-1 plus CDDP is one of the standard treatment for advanced gastric cancer in japan, but the efficacy remains insufficient due to the drug toxicity such as renal function disorders. The efficacy and safety of S-1 plus docetaxel as first-line treatment for elderly patients with unresectable advanced or recurrent gastric cancer were investigated. Methods: 75 years or older patients with unresectable advanced or recurrent gastric cancer were enrolled. Docetaxel was administered i.v. (40mg/m2) on day 1, while S-1 was administered orally (80mg/m2/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks. The primary endpoint was response rate (RR) of S-1 plus docetaxel; secondary endpoints were safety, progression free survival (PFS), time to treatment failure (TTF) and overall survival (OS). Sample size was set to be 30, which was determined to reject the response rate of 20% under the expectation of 40% with the power of 90% and two-sided alpha of 5%. Results: 31 patients were enrolled and assessable for efficacy. The response rate was 45.2% (95%CI 27.3-64.0, p = 0.001), and disease control rate was 77.4%. The median progression-free survival time was 5.8 months, the 1-year survival rate was 58.1%, and the median survival time was 16.1months. In 31 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (58%), febrile neutropenia (13%), anemia (10%), anorexia (10%), and fatigue (6%). Conclusions: These findings indicate that S-1 plus docetaxel as first-line treatment for elderly patients is feasible and shows promising efficacy against advanced gastric cancer. Clinical trial information: UMIN000002785.
Volumetric changes of the primary esophageal tumor during radiation therapy.
Authors: Laughlin Brady , Famoso Justin , Gloss John , Frankl Joseph , Elquza Emad , Howell Krisha 
Published: March 2017

134 Background: Management of esophageal cancer with radiotherapy requires weeks of daily treatments. The objective of this study is to identify edematous/obstructive changes in the esophageal tumor occurring during therapy and quantifying its change relative to the original tumor volume. Methods: A total of 66 patients were reviewed on a retrospective IRB-approved protocol between July 2012 – July 2016. The gross tumor volume (GTV) targeted with radiation (GTVsim) was constructed on a CT-simulation image. Cone beam CT images (CBCTs) were taken daily during treatment. GTVs (GTVCT#) were contoured on the CBCT on treatment days 1, 6, 11, 16, 21, and 25. Volumes for the GTVsim and each GTVCT# per patient were calculated. A conformality index (CI) was determined by visual confirmation of overlap and calculation of GTVCT#/GTVsim. The standard deviation (SD) was calculated. A theoretical max volume (GTVCTMAX) was determined per patient based on the upper range of 2SD from the average GTVCT# value. A theoretical PTV created from a 1cm (PTV1) and 0.5cm (PTV0.5) expansions were also calculated with associated CIs for PTVCTMAX/PTV1 and PTVCTMAX/PTV0.5. Results: Twenty-one patients had a total of 94 CBCT volumes. The median age was 67 years (53-83), sixteen patients were male, 5 female. T-stage was 1/2 in 5 patients and 3/4 in 15 patients. Chemotherapy was administered concurrently in 17 patients. Median duration of radiotherapy was 35 days (2-50). Results were analyzed by absolute volume comparison and CI calculations as noted in table 1.The median CI for PTVCTMAX/PTV1 was 0.40 (0.15-0.84) and PTVCTMAX/PTV0.5was 0.65 (0.34-0.89). Conclusions: Review of the weekly CBCTs demonstrated a larger tumor volume in the first day of therapy relative to the subsequent weeks, and even relative to the volume at the time of simulation. However, in projecting potential changes in maximum size of the individual tumors, 100% remained within standard PTV volumes constructed with a 1cm and 0.5cm expansions. [Table: see text]
The impact of proton beam therapy on blood cell count nadir during neoadjuvant chemoradiation therapy for esophageal cancer.
Authors: Shiraishi Yutaka , Xu Cai , Song Juhee , Komaki Ritsuko , Hobbs Brian P , Lin Steven H. 
Published: March 2017

137 Background: To analyze the blood cell count nadir, particularly grade 4 hematologic toxicities, in patients with esophageal cancer who were treated with neoadjuvant chemoradiation (nCRT) with either Proton Beam Therapy (PBT) or Intensity Modulated Radiation Therapy (IMRT) in a propensity-matched pair analysis. Methods: Esophageal cancer patients (n = 480) treated from 2005-2016 with nCRT with (n = 167) or without (n = 313) induction chemotherapy (ICT) were analyzed. White blood cell, neutrophil, lymphocyte and platelet counts nadir during ICT and CRT were obtained, and graded according to the CTCAE v.4.0. Univariate and multivariable logistic regression models to identify factors associated with increased risk of grade 4 lymphopenia were fitted. By propensity score matching, 136 PBT cases and 136 propensity score matched IMRT controls were selected for comparison. Results: In the entire study cohort during CRT (n = 480), 2 (0.4%), 1 (0.2%), 159 (33%), and 2 (0.4%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia, respectively. This is not seen in patients who received ICT (n = 167), as only 0 (0%), 2 (1.2%), 1 (0.6%) and 0 (0%) patients experienced grade 4 leukopenia, neutropenia, lymphopenia and thrombocytopenia during the ICT phase. Multivariable analyses identified older age (p = 0.0139), larger planning tumor volume (PTV) (p = 0.0213), distal vs upper/mid tumor location (borderline significance, p = 0.0779) and IMRT vs PBT (p < 0.0001) as factors associated with increased risk of grade 4 lymphopenia during CRT. Among the 272 propensity-matched patients treated with either PBT or IMRT, 24 (17.6 %) and 55 (40.4 %) patients experienced grade 4 lymphopenia, respectively (p < 0.001). Grade 4 lymphopenia correlates with poorer survival (p = 0.0587), lower progression free survival (p = 0.0384) and distant metastatic recurrence (p = 0.0185). Conclusions: The use of PBT may be an important modifying factor in altering the incidence of grade 4 lymphopenia during CRT in esophageal cancer. The dosimetric factors that can modulate this risk is a subject of continued investigation.
Underweight as a risk factor for esophageal squamous cellcarcinoma: A nationwide population-based study.
Authors: Choi Yoon Jin , Lee Dong Ho 
Published: March 2017

14 Background: Obesity is a well-known risk factor for the development of esophageal cancer (EC). However, the impact of underweight on esophageal squamous cell carcinoma (ESCC) has not been fully recognized to date. Therefore, we herein sought to determine the risk of EC in subjects with underweight. Methods: We analyzed the clinical data from a total of 264,084 individuals with the age of 40 years or older, who received healthcare checkups arranged by the national insurance program, between 2003 and 2008. Newly diagnosed EC was identified using the claims data during a median follow-up duration of 7.9 years. Results: The mean body mass index (BMI) of patients was 23.80 ± 3.05kg/m2, and 6,784 individuals (2.6%) were classified as being underweight (BMI < 18.5 kg/m2). During the study period, 278 individuals (0.1%) developed EC. It was determined that underweight and obesity—compared with normal weight—were significantly associated with 73% increased risk and 30% decreased risk of EC, respectively. Excess risk of EC in the underweight group was independent of age, gender, smoking, and alcohol consumption. Heavy alcohol use had a synergistically increasing effect for developing EC among those in the underweight group. Conclusions: The mean body mass index (BMI) of patients was 23.80 ± 3.05kg/m2, and 6,784 individuals (2.6%) were classified as being underweight (BMI < 18.5 kg/m2). During the study period, 278 individuals (0.1%) developed EC. It was determined that underweight and obesity—compared with normal weight—were significantly associated with 73% increased risk and 30% decreased risk of EC, respectively. Excess risk of EC in the underweight group was independent of age, gender, smoking, and alcohol consumption. Heavy alcohol use had a synergistically increasing effect for developing EC among those in the underweight group.