bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric adenocarcinoma prognosis in a multiracial population.
Authors: Acoba Jared David 
Published: January 2019

158 Background: Gastric adenocarcinoma is a major health issue, with a high prevalence among Asian and Pacific Islander populations. We analyzed a hospital tumor registry and demonstrated that in a multiracial population, patients who were uninsured and Filipinos with resectable disease had worse outcomes. To further investigate these findings, we performed a comprehensive analysis of the National Cancer Database. Methods: We analyzed data from 183,204 patients with gastric or gastroesophageal adenocarcinoma diagnosed between 2004 and 2015. Multivariable Cox proportional hazards regression models for survival were built adjusting for race, age at diagnosis, sex, insurance status, comorbidities, treatment facility type, histologic grade, stage, and treatment. Results: We included 86,663 patients in our analysis. Pacific Islanders presented at a younger age and higher stage. Asians had fewer comorbidities and were diagnosed at earlier stages. Older age (HR 1.97, 95% CI 1.92-2.03), lower income (HR 1.13, 1.11-1.16), more comorbidities (HR 1.59, 1.51-1.67), treatment at a community center (HR 1.22, 1.20-1.24), higher tumor grade (HR 2.00, 1.92-2.08), and advanced stage (HR 5.71, 5.57-5.85) were poor prognostic factors. Compared to whites, Asians had a more favorable prognosis (HR 0.74, 0.71-0.76). However, Filipino race was adversely associated with survival compared to other Asian races (HR 1.48, 1.29-1.69), even after adjusting for other prognostic factors. Conclusions: Asian race is an independent favorable prognostic factor. Among Asians, Filipinos did not fare as well even after adjusting for income, insurance status, comorbidities, stage and other prognostic factors. Further study in this area should be pursued. Given the differences in survival within the Asian race, studies exploring the relationship between race and cancer should consider analysis by subgroup.
Zolbetuximab combined with EOX as first-line therapy in advanced CLDN18.2+ gastric (G) and gastroesophageal junction (GEJ) adenocarcinoma: Updated results from the FAST trial.
Authors: Sahin Ugur , Tureci Özlem , Manikhas Georgy M. , Lordick Florian , Rusyn Andriy , Vynnychenko Ihor , Dudov Assen , Bazin Igor , Bondarenko Igor , Melichar Bohuslav , Dhaene Karl , Wiechen Kai , Maurus Daniel , Schuler Martin H. , Al-Batran Salah-Eddin 
Published: January 2019

16 Background: Physiologically, the tight junction protein CLDN18.2 is present only in the gastric mucosa. Upon malignant transformation, CLDN18.2 epitopes are exposed on the cell surface and accessible to targeted therapy. Zolbetuximab (formerly IMAB362) is a chimeric mAb that mediates specific killing of CLDN18.2+ cancer cells through immune effector mechanisms; single-agent activity has been reported in G/GEJ cancer. Methods: Patients (pts) with advanced HER2-negative (HER–) G/GEJ cancer with CLDN18.2 expression of ≥ 2+ staining intensity with the anti-CLDN18 43-14A mAb in ≥ 40% tumor cells were eligible (NCT01630083). Patients were randomized 1:1 to receive first-line EOX ± zolbetuximab (loading dose 800 mg/m2, then 600 mg/m2) Q3W. The study was extended with an exploratory arm of 1000 mg/m2 zolbetuximab + EOX Q3W (data not presented). Primary endpoint was PFS; secondary endpoints included OS, ORR, and safety/tolerability. Results: A total of 161 pts (G, n = 128; GEJ, n = 27; esophagus n = 6) were randomized to receive zolbetuximab (800/600 mg) + EOX (n = 77) or EOX alone (n = 84). In all, 45% of pts had diffuse type histology per Lauren’s classification. Median PFS was longer with zolbetuximab + EOX (7.5 mo) versus EOX alone (5.3 mo; P < 0.0005; HR 0.44; 95% CI 0.29, 0.67). Median OS (13 vs 8.4 mo; P = 0.0008; HR 0.56; 95% CI 0.40, 0.79) and ORR (39 vs 25%; P = 0.022) were also significantly higher with zolbetuximab + EOX versus EOX alone. Increased efficacy was more pronounced in pts with high CLDN18.2 expression (≥ 2+ staining intensity in ≥ 70% tumor cells). Zolbetuximab + EOX was generally well tolerated. Most AEs considered related to zolbetuximab and EOX (ie, nausea, vomiting, neutropenia, anemia) were of grade ≤ 2 severity; there was no significant increase in grade ≥ 3 events with the addition of zolbetuximab to EOX. Conclusions: Addition of zolbetuximab to first-line chemotherapy resulted in significantly longer PFS and OS and higher ORR with manageable toxicity. A phase III trial is evaluating the combination of zolbetuximab plus mFOLFOX6 as first-line treatment of CLDN18.2+/HER2-negative, advanced/metastatic G or GEJ adenocarcinoma (NCT03504397). Clinical trial information: NCT01630083.
Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection.
Authors: Shin Kabsoo , Kim In-Ho 
Published: January 2019

160 Background: The aim of this study is to compare capecitabine and oxaliplatin (XELOX) with S-1 based on disease-free survival, and to define the clinical impact of lymph node ratio to select a regimen. Methods: Patients who had curative resection and received either S-1 or XELOX as adjuvant chemotherapy for gastric cancer between Jan. 2011 and Dec. 2015, were analyzed using propensity score matching (PSM). Of the 412 patients enrolled, 301 received S-1 and 111 received XELOX and after PSM, the sample size of each group was 111 patients. And the groups were classified according to stage and lymph node ratio (0, > 0-0.1, > 0.1-025, > 0.25) and three-year disease-free survival (DFS) was evaluated. Results: In post-PSM analysis of all 222 patients, The three-year DFS rates in XELOX group was higher than in the S-1 group in all stage 3 (78% vs. 66.1%, p = 0.036), stage IIIC (64.1% vs. 42.0%, p = 0.038) and LNR > 0.25 (67.7.1% vs. 26.1%, p = 0.002). The hazard ratio of XELOX for recurrence compared with S-1 for stage IIIC and LNR > 0.25 was respectively 0.479 (95% CI 0.238~0.985, p = 0.046) and 0.351 (95% CI 0.162~0.758, p = 0.008). Conclusions: Adjuvant XELOX was more effective than S-1 for stage IIIC and LNR > 0.25 in gastric cancer after D2 dissection.
Surveillance and outcomes after curative resection for gastroesophageal adenocarcinoma (GEAC).
Authors: Jiang Di Maria , Suzuki Chihiro , Espin-Garcia Osvaldo , Pintilie Melania , Lim Charles Henry , Ma Lucy Xiaolu , Sun Peiran , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Chen Eric Xueyu , Liu Geoffrey , Swallow Carol Jane , Darling Gail Elizabeth , Wong Rebecca , Jang Raymond Woo-Jun , Elimova Elena 
Published: January 2019

162 Background: Although commonly performed, the benefit of routine surveillance testing (SvT) following curative resection of GEAC is undefined. We aimed to determine frequency of successful salvage therapy (SST) in patients (pts) with relapsed GEAC who were surveyed post curative therapy. Methods: Between 2011 and 2016, 210 consecutive pts with locally advanced GEAC underwent curative surgery and subsequent surveillance at Princess Margaret Cancer Center. SST was defined as any potentially curative therapy for recurrence which resulted in post-recurrence survival (PRS) two years without further relapse. Time-to-event outcomes were analyzed using Kaplan-Meier and Cox regression methods. Results: Median age was 64.1 years. Esophageal (14%), gastroesophageal junction (41%), and gastric adenocarcinomas (45%) were included. Pts received surgery alone (29%), surgery with perioperative chemotherapy (26%) or perioperative chemoradiation (45%) as primary curative therapy. At median follow-up of 33.6 months (m, range 6.0-122.4), 3- and 5-year overall survival (OS) rates were 68% (95% CI 61-75%) and 59% (95% CI 51-68%) respectively. SvT modalities included imaging (69%), endoscopy (19%), tumor markers (4%), and clinical visits only (9%). Recurrences occurred in 95 (45%) pts, 51% were surveillance-detected (SvDR), and 47% were non-SvDR. Types of recurrences included locoregional only (4%), distant (87%) or both (9%). Salvage therapy was attempted in 14 pts (7%) with SvDR and 1 with non-SvDR. In four pts with SvDR (1.9%) salvage therapy was successful with chemoradiation or surgery perioperative chemotherapy, six were unsuccessful, and 5 had immature follow-up. Compared with pts with non-SvDR, pts with SvDR had longer median OS (34.8 vs. 24.0m, p=0.03) and PRS (14.4 vs. 4.8m, p < 0.001), and similar time-to-relapse (15.6 vs. 12.0m, p = 0.67). Palliative chemotherapy was administered in 25 pts with SvDR and 18 pts with non-SvDR with similar median duration (3.5m vs. 3.3m, p=0.64). Conclusions: Following curative therapy, 96% of relapses were distant. SvT enabled SST in only 1.9% of pts, and did not extend duration of palliative chemotherapy. These data do not support the use of routine SvT in resected GEAC.
Survival benefit of gastric resection in the setting of metastatic gastric cancer.
Authors: Nguyen Trang , Vuong Brooke , Wang Mansen , Fischer Trevan D , Goldfarb Melanie , Bilchik Anton J. , Foshag Leland Jay 
Published: January 2019

166 Background: Prognosis remains poor for metastatic gastric cancer. Gastrectomy in the setting of stage IV disease is typically reserved for palliation of symptoms such as bleeding or obstruction. The potential survival benefit of resection on survival is controversial. The objective of this study is to determine using the National Cancer Database (NCDB) whether there was an increase in overall survival in patients diagnosed with metastatic cancer who underwent a gastrectomy in addition to chemotherapy. Methods: The NCDB was queried between 2004-2014 for patients with metastatic gastric cancer (adenocarcinoma, mucinous adenocarcinoma, or signet ring carcinoma) who received chemotherapy. Kaplan-Meier analysis and multivariate Cox proportional hazards regression analysis was done using SAS software. Results: A total of 20,599 patients met inclusion criteria. A minority of these patients (2,508; 12.2%) underwent gastric resection in addition to chemotherapy. The median overall survival for those who underwent gastrectomy was 14.1 months compared to 8.6 months for chemotherapy alone (p < 0.0001). Other factors influencing survival included age, race, Charlson-Deyo co-morbidity index, year of diagnosis, primary tumor site, grade, and metastasis to multiple organs. Following multivariate analysis, patients who underwent gastrectomy and chemotherapy had a 36% lower risk of death compared to patients that had received chemotherapy alone (HR 0.64, 95% CI 0.48–0.80, P < 0.0001). Conclusions: In this population analysis, the addition of gastrectomy to chemotherapy was associated with improved overall survival for patients with stage IV gastric cancer and should be considered for patients that are surgical candidates. Patients who underwent gastrectomy had a 36% decreased risk of death compared to those who had chemotherapy alone. However, only a small proportion of patients in the United States received multimodality treatment.
Prognostic significance of malnutrition in metastatic esophageal squamous cell carcinoma.
Authors: Taylor Kirsty , Espin-Garcia Osvaldo , Jiang Di Maria , Yokom Daniel , Ma Lucy Xiaolu , Lim Charles Henry , Chan Bryan Anthony , Sun Peiran , Sim Hao-Wen , Natori Akina , Liu Geoffrey , Darling Gail Elizabeth , Wong Rebecca , Chen Eric Xueyu , Jang Raymond Woo-Jun , Veit-Haibach Patrick , Rozenberg Dmitry , Elimova Elena 
Published: January 2019

171 Background: Disease related symptoms including anorexia, nausea and dysphagia lead patients with esophageal cancer to become malnourished. Malnourishment can result in systemic inflammation, reduced treatment tolerance, poorer quality of life and decreased overall survival. Currently weight loss is the main clinical measure of malnutrition, and thus we set out to evaluate the prognostic utility of alternative screening tools of malnutrition. Methods: Patients with metastatic esophageal squamous cell cancer (MESCC) attending the Princess Margaret Cancer Centre, between January 2011 and December 2016, were identified from the institutional gastroesophageal database. Nutritional Risk Score (NRS), Nutritional Risk Index (NRI) and Neutrophil Lymphocyte Ratio (NLR) were calculated and correlated with clinical-pathological variables and survival. Malnutrition was defined as NRS ≥ 3, NRI < 97.5 and NLR ≥ 3. Results: Of the 64 consecutive patients, 30 (47%) presented with de novo metastatic disease and 34 (53%) with recurrence. The median age was 62 years (range 40-85), 47 patients were ECOG PS ≤ 2 and 29 (45%) received systemic chemotherapy. 90% of patients experienced weight loss > 5% prior to diagnosis and median BMI was 20.1 (range 14.3-34.9). NRI identified 37 (58%) and NRS 45 (70%) patients as malnourished. Both were associated with poorer ECOG PS (p = 0.012 and p = 0.027 respectively). No difference was identified with sex, smoking status or albumin with univariate analysis. NRI did not associate significantly with age. Median overall survival was 5months; 8.1-9 months with normal nutrition and 2.8-3.2 months in malnourished patients. Kaplan Meier analysis revealed significant difference in overall survival (malnutrition vs. normal nutrition) using NRS (p = 0.029) and NRI (p = 0.001) but not weight (p = 0.509) or NLR (p = 0.69). Conclusions: Patients with MESCC identified as malnourished at the time of diagnosis have inferior survival outcomes. Malnutrition tools are superior to weight alone with respect to discriminating outcomes in this patient population. Further investigation is needed in larger patient cohorts; to identify those at risk, initiate early supportive interventions and improve patient outcomes.
Utility of radiation after neoadjuvant chemotherapy for surgically resectable esophageal cancer.
Authors: Macedo Francis Igor , Kelly Kristin , Yakoub Danny , Franceschi Dido , Livingstone Alan S , Merchant Nipun B. 
Published: January 2019

172 Background: Neoadjuvant chemotherapy (NAC) is the gold standard approach for locally advanced esophageal cancer (EC), however the addition of radiation remains largely controversial. We sought to investigate the role of neoadjuvant radiation in resectable EC by comparing outcomes of patients who underwent neoadjuvant chemotherapy with (NACR) or without radiation (NAC) using a large nationwide cohort. Methods: National Cancer Data Base (NCDB) was queried for patients with non-metastatic EC between 2010 and 2014. Kaplan-Meier, log-rank and Cox multivariable regression analysis were performed to calculate overall survival (OS). Logistic regression was used to identify factors associated with 90-day mortality and complete pathological response (pCR). Results: A total of 12,546 EC patients who underwent neoadjuvant therapy were included: the majority were males (84%), Caucasians (90.3%), and had adenocarcinoma (81.1%), cT3 (60.6%) and cN1 (49.1%). 11,269 (89.8%) patients had NACR, whereas 969 (7.7%), NAC alone. pCR rate was 14.1% (19.2%, NACR vs. 6.3%, NAC, p < 0.001). Neoadjuvant radiation was an independent predictor for improved pCR [HR 0.305, 95% CI 0.205-0.454, p < 0.001], however OS was similar in patients undergoing NAC with or without radiation (35.9 vs. 37.6 months, respectively, p = 0.393). This persisted regardless of tumor staging. There was a trend towards worse 90-day mortality after radiation (8.2%, NACR vs. 7.7%, NAC; HR 1.410, 95% CI 0.975-2.038, p = 0.068). In Cox regression, controlling for patient and disease-related factors, neoadjuvant radiation was an independent predictor of worse OS (HR 1.322, 965% CI 1.177-1.485, p < 0.001). Conclusions: This is the largest study comparing NACR versus NAC in resected EC. The addition of radiation to neoadjuvant chemotherapy is associated with improved pathological response rates, however it had deleterious effects in long-term and possibly, short-term survival. Our findings suggest that NAC without radiation may be the optimal neoadjuvant therapy in resectable EC, however further evidence with randomized clinical trials is warranted.
Incidence and prognosis of multiple organ involvement at gastric MALT lymphoma.
Authors: Kwon Tae Hun , Lee In Seok 
Published: January 2019

18 Background: MALT (mucosa-associated lymphoid tissue) lymphoma usually occurs in stomach but various MALT organs can be afflicted including salivary glands, ocular adnexa, lung, intestine and thyroid. In this study, we aimed to evaluate the prevalence and characteristics of gastric MALT lymphoma with multi-organ involvement. Methods: We retrospectively analyzed a total of 174 consecutive patients who had been diagnosed with gastric MALT lymphoma at Seoul St. Mary’s Hospital from January 2009 to May 2018. Clinical data were obtained from the medical records. At the time of diagnosis, neck, chest, abdominal CT, PET-CT and bone marrow biopsy were performed for the purpose of staging work-up. Organ involvement was identified by biopsy. Results: Nine out of 174 (5.2%) gastric MALT lymphoma patients were found to have multi-organ involvement. Three patients had biopsy proven lymphoma at lung, two patients had colon involvement, and two patients had ocular involvement. A patient with involvement at small bowel and duodenum were found, respectively. Seven patients were examined for Helicobacter infection. Two of them were positive for H. pylori infection and received eradication treatment. Except one patient treated with palliative care, eight patients underwent chemotherapy, in which two of them received additional radiation therapy and other two patients underwent bone marrow transplantation. Except one patient died of pneumonia during chemotherapy and one patient underwent palliative treatment, 7 patients had maintained complete remission. Conclusions: The overall prevalence of gastric MALT lymphoma with multi-organ involvement was 5.2%. The result suggests that the gastric MALT lymphoma patients require a careful investigation of other MALT organs. [Table: see text]
Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): A cohort of the ROAR basket trial.
Authors: Wainberg Zev A. , Lassen Ulrik Niels , Elez Elena , Italiano Antoine , Curigliano Giuseppe , De Braud Filippo G. , Prager Gerald , Greil Richard , Stein Alexander , Fasolo Angelica , Schellens Jan H. M. , Wen Patrick Y. , Boran Aislyn D. , Burgess Paul , Gasal Eduard , Ilankumaran Palanichamy , Subbiah Vivek 
Published: January 2019

187 Background: BTCs are rare, aggressive malignancies with poor prognoses. Treatment options and outcomes after first-line therapy are not well defined. Median progression-free survival (PFS) in second-line BTC is < 5 mo. Combined BRAF + MEK inhibition is efficacious in BRAF V600–mutated anaplastic thyroid cancer, melanoma, and lung cancer, but less so in BRAF V600E-mutated colorectal cancer. Activating BRAF V600E mutations have been reported in 0% to 20% of BTCs; thus, D (BRAF inhibitor) + T (MEK inhibitor) was evaluated as a treatment for pts with BRAF V600E–mutated BTC in the ROAR basket trial. Methods: In this phase II, open-label trial, pts with BRAF V600E mutations in 9 rare tumor types, including BTC, received D (150 mg BID) + T (2 mg QD) until unacceptable toxicity, disease progression, or death. Eligible pts had advanced or metastatic cancer and had been treated with ≥ 1 prior systemic therapy. The primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DOR), PFS, overall survival (OS), biomarker correlates, and safety. Results: Thirty-three pts with BTC had enrolled at data cutoff (January 3, 2018). BRAF V600E mutations were centrally confirmed in 30 of 33 pts with BTC (91%). Median age was 58 y, and 78% had received ≥ 2 prior lines of systemic therapy. 32 of 33 pts with BTC were evaluable. Investigator-assessed ORR was 41% (13/32; 95% CI, 24%-59%), with 6 of 13 responses ongoing at data cutoff, 7 of 13 pts (54%) had a DOR ≥ 6 mo. Median PFS was 7.2 mo (95% CI, 4.6-10.1 mo), and median OS was 11.3 mo (95% CI, 7.3-17.6 mo). Grade 3/4 adverse events in ≥ 3 pts were increased γ-glutamyltransferase (n = 3 [9%]) and decreased white blood cell count (n = 3 pts [9%]). Biomarker analyses demonstrate a heterogeneous genetic landscape, and suggest a higher baseline expression of MAPK pathway genes in the pts who did not respond to D + T. Conclusions: D + T demonstrated promising efficacy in pts with BTC, with a favorable safety profile. These pts should be considered for BRAF mutation analysis, and D + T should be considered for pts with BRAF V600E-mutated BTC. Clinical trial information: NCT02034110.
Impact of intramuscular fat accumulation on survival in stage II/III gastric cancer.
Authors: Waki Yuhei , Makuuchi Rie , Irino Tomoyuki , Kamiya Satoshi , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori 
Published: January 2019

19 Background: Intramuscular fat accumulation of skeletal muscle has been reported to be a prognostic factor in various cancers. To evaluate the intramuscular steatosis, intramuscular adipose tissue content (IMAC) measured by CT scan is thought to be an ideal method. However, this kind of study is very limited in curatively resected gastric cancer. So, this study was aimed to clarify the impact of IMAC on survival in stage II/III gastric cancer (GC). Methods: A total of 383 patients with pathological stage II/III GC after curative gastrectomy between January 2009 and December 2013 were included. IMAC was calculated by dividing the CT value of the multifidus muscles with that of the subcutaneous fat at the level of third lumbar vertebra. The IMAC cut-off values associated with cancer-specific survival (CSS) were separated by sex based on the maximum values of Youden index (sensitivity + specificity -1). Patients were classified into normal or high IMAC group according to this cut-off value. Clinicopathological factors and survival outcomes were compared between the two groups. Results: The median values of IMAC were -0.327 (IQR: -0.404- -0.250) in male and -0.239 (IQR: -0.335- -0.114) in female. The cut-off values of IMAC were -0.345 in male and -0.126 in female. Patients were classified into normal IMAC group (n = 204) and high IMAC group (n = 179). Patients in the high IMAC group were elderly, male, obese, having many comorbidities and with poor ECOG-PS compared to those in the normal IMAC group. Interestingly, despite the fact that no significant differences were observed in the pathological findings between the groups, the overall survival and CSS were significantly worse in the high IMAC group than in the normal IMAC group (p < 0.001 and p = 0.035). Moreover, the high IMAC was identified as an independent prognostic factor not only for overall survival but also for CSS (HR: 1.440, p = 0.021, HR: 1.646, p = 0.008, respectively). Conclusions: The high IMAC was significantly associated with worse survival, suggesting that IMAC represents certain oncological implications in patients with GC. Therefore, IMAC could be used as a new prognostic factor in curatively resected GC.