bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining cetuximab with FOLFOX regimen as the first-line therapy of KRAS wild-type advanced gastric cancer.
Authors: Yeh Yung-Sung 
Published: February 2017

157 Background: Gastric cancer is one of the most common cancers worldwide with a high incidence in Asian countries, including Taiwan. For patients with recurrent or non-resectable advanced gastric cancer (AGC), chemotherapy or the combination of target and chemotherapy was chosen for therapy in AGC patients. We prospectively analyzed the safety and efficacy of cetuximab combined with FOLFOX4 as the first-line setting in patients with AGC. Methods: From January 2010 to January 2013, a total of 20 patients with histologically confirmed unresectable advanced/recurrent gastric cancer were enrolled into this study. Direct sequencing of KRAS mutation status was performed before the treatment. All patients received cetuximab 500 mg/m2every 2 weeks, and chemotherapy was administered with FOLFOX regimen of oxaliplatin at 85 mg/m2 plus leucovorin 200 mg/m2 on the first day of treatment, followed by 5-fluorouracil (5-FU) via a 24-hour continuous infusion of 1000 mg/ m2 5-FU on days 1-2 biweekly. Therapy was continued until disease progression or intolerable adverse events or receiving surgical resection. Results: All tumor tissues of 20 AGC patients were KRAS wild-type. With the median therapy of 6 cycles (4-8 cycles), clinical efficacy, according to RECIST criteria, showed an overall response rate of 55% (11/20), and 20% (4/20) of patients exhibited stable disease as well as 25% (5/20) who had progressive disease. Radical resection could be obtained in 30% (3/10) of unresectable patients as the neoadjuvant therapy. The median time to progress (TTP) was 8.3 months and the median overall survival (OS) was 12.2 months. The grade III-IV adverse events was observed in 4 of 20 (20%) patients, including 15% of neutropenia (3/20), 5% of skin rash (1/20), 10% of nausea and vomiting (2/20) as well as 15% of asthenia (3/20). Conclusions: Cetuximab combined with FOLFOX as the first-line therapy for KRAS wild-type AGC patients appears to have favorable efficacy and safety, and the possibility of conversion to radical resection. Grade 3-4 adverse events were relatively uncommon. Despite this preliminary favorable outcome; however, a long-term result and large scale clinical trial is mandatory to verify it.
Prospective trial of proton reirradiation of locally recurrent esophageal cancer.
Authors: Berman Abigail T. , Fernandes Annemarie Therese , Both Stefan , Varillo Kristi , Ben-Josef Edgar , Metz James M. , Plastaras John Peter 
Published: February 2017

159 Background: Local recurrences of esophageal cancer occur in approximately 25% of patients and cause significant morbidity. Their treatment after esophagectomy and chemoradiation is particularly challenging. A second course of radiotherapy in a previously radiated field carries the risk of radiation-induced tissue injury. Proton therapy (PRT) may offer an advantage in the re-irradiation setting due to the lack of exit dose and potential sparing of normal tissues. Methods: Between 6/2011 and 8/2013, 10 adult patients (pts) with locally recurrent esophageal cancer, initially cT1b-T4N0-1, in or near prior treatment fields began reirradiation. Toxicity was graded according to the Common Toxicity Criteria version 4.0. Acute toxicity was defined as occurring within 90 days from start of PRT. Results: The median follow-up was 7.9 months (1-23) from the start of retreatment, and 15 months (2.4-27.8) from the development of local recurrence. Mean age was 70 (53-91). ECOG PS was 0 (n=4), 1 (4), 2 (2). Eight pts had intraluminal and two had paratracheal nodal recurrences. Eight of the pts had adenocarcinoma and two squamous cell carcinoma. Median CTV size was 138 cc (32-390). Seven received concurrent chemotherapy. The median total dose was 54.0 Gy (50.4-61.2); all pts were treated with PRT exclusively (9 double scatter and 1 uniform scanning), except for two pts who were treated with 15-30% IMRT. The median prior dose was 55.8 Gy (45-70). The median interval between radiation courses was 31.4 mos (12-105). Maximum acute toxicity was grade 2 (30%), 3 (30%), and 4 (40%). Of the grade 4 toxicities, one was an esophagopleural fistula and respiratory failure unlikely related to RT, and 3 were neutropenic toxicities possibly related to RT. Three pts developed metastatic disease at a median of 28 mos after starting RT. Three pts developed in-field locoregional recurrence at a median of 13 mos. Five pts died after a median of 13 mos. Conclusions: Preliminary results using PRT for reirradiation of esophageal cancers shows that local control can be achieved in a large proportion of pts with moderate but acceptable acute toxicity. Further follow-up on these pts is needed to assess the long-term utility of PRT reirradiation. Clinical trial information: NCT01126476.
Correlation of pretreatment nuclear GLI-1 labeling indices (LIs) with initial SUV (iSUV) in esophageal cancer (EC) patients undergoing trimodality therapy (TMT): A potential pathway to esophageal preservation.
Authors: Wadhwa Roopma , Wang Xuemei , Izzo Julie , Skinner Heath D. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Ross William A. , Hofstetter Wayne Lewis , Maru Dipen M. , Rice David C. , Sudo Kazuki , Shiozaki Hironori , Blum Mariela A. , Chen Qiongrong , Jin Jiankang , Song Shumei , Baladandayuthapani Veera , Ajani Jaffer A. 
Published: February 2017

18 Background: For the purpose of understanding clinical behavior of EC, imaging and biomarkers have not been correlated. We attempted to correlate iSUV with a variety of biomarkers (NF-kB, SHH, ALDH1, ABCB1, survivin, and BCRP) including pre-treatment nuclear Gli-1 LIs in patients with EC who had undergone TMT. Methods: 128 patients were analyzed. The iSUV and pre-treatment nuclear Gli-1 LIs were assessed among others. Post-treatment residual cancer status in the resected specimen was also correlated (P0=0% residual cells, P1=1-50% residual cells, and P2=>50% residual cells) with iSUV and nuclear Gli-1 LIs. The Kruskal-Wallis test was performed to find correlations between (1) iSUV and P status; and (2) between nuclear Gli-1 LIs and P status. Results: The Pearson’s correlation coefficient between iSUV and nuclear Gli-1 LIs was 0.21 (p = 0.02). Pre-treatment nuclear Gli-1 LIs were strongly associated with the P status (p<0.0001) but iSUV was not (as has been reported in the literature; PMID: 17532577, 23247658, and 23994746). iSUV, most likely, is not correlative with the P status because of its narrow range compared to that of nuclear Gli-1 LIs.Conclusions: Our data, for the first time, demonstrate that iSUV can be a surrogate for pre-treatment nuclear Gli-1 LIs in EC. This correlation can be exploited in the development of predictive strategies for esophageal preservation. Pre-treatment nuclear Gli-1 is a strong candidate for the biomarker-based predictive model(s). From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. Supported by UTMDACC Multidisciplinary Research Grants, CA138671, CA172741, and CA129926 From the NCI (JAA), and Generous Donors. [Table: see text]
Utility of PET/CT as initial staging work up for early pancreatic cancer.
Authors: Prithviraj Gopi Kesaria , Kothari Nishi , Yue Binglin , Kim Jongphil , Springett Gregory M. , Malafa Mokenge Peter , Hodul Pamela Joy , Kim Richard D. 
Published: February 2017

183 Background: In pancreatic cancer, early detection and complete surgical resection with negative margins offers the only cure for the disease. Work up to evaluate resectability includes triple phase helical scan CT of the pancreas and endoscopic ultrasound (EUS). A paucity of data exists in using PET/CT scan as staging work up in early resectable pancreatic cancer. The objective of our study was to determine if PET/CT prevents futile laparotomy by detecting occult metastatic disease in patients with resectable/borderline pancreatic cancer. Methods: We looked at our institutional PET/CT data base incorporating National Oncologic PET Registry (NOPR) with diagnosis of resectable or borderline pancreatic cancer from 2005-2012. Clinical, radiographic, and pathologic follow-up was evaluated, including age, gender, evidence of metastatic disease, and initial CA 19–9 levels. The impact of PET/CT on patient management was estimated by calculating the percentage of patients whose treatment plan was altered due to PET/CT. The confidence interval was computed using the exact binomial distribution. The effect on the change was evaluated by the multiple logistic regression model. The final model was selected using the backward elimination method. Results: 287 patients with early stage (resectable or borderline) pancreatic cancer who received PET/CT as part of initial staging workup were identified. Upon initial work up (CT + EUS), 62% of patients were considered resectable and 38% were borderline resectable. However, PET/CT findings changed the management in 11.9% (n=34) of patients (95% CI: 0.084 – 0.162). 33 patients were upstaged to stage IV and 1 patient was upstaged to stage III. Median time from CT to PET/CT was 5 days. Metastatic lesions were confirmed with biopsy in 21 patients. The proportion in the change in treatment plan is significantly higher in patients who were borderline resectable (p=0.005; OR=2.94; 95% CI: 1.38 – 6.26). In 204 patients who were taken to surgery, 17.7% (n=36) were found to have metastatic disease intraoperatively. Conclusions: PET/CT helped improve detection of occult metastases, ultimately sparing these patients a potentially unnecessary operation. The role of PET/CT scan should be validated in prospective study.
Association of adiponectin in patatin-like phospholipase domain-containing 3 (PNPLA3) associated hepatic steatosis.
Authors: Beg Muhammad Shaalan , Singal Amit G. , Ayers Colby , Saleem Sadia , Marrero Jorge A. , Yopp Adam C. , Scherer Philipp , Turer Aslan 
Published: February 2017

184 Background: The I148M polymorphism (rs738409) of the patatin-like phospholipase domain-containing 3 (PNPLA3) gene is strongly associated with hepatic triglyceride content (HTGC) and the development of nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH), which are themselves risk factors for hepatocellular cancer (HCC). Serum adiponectin affects insulin resistance and carcinogenesis and has also been associated with HTGC. Whether these risk factors are additive in predisposing to HTGC is unknown. We evaluated the impact of adiponectin and PNPLA3 genotypes on HTGC in a large community cohort. Methods: The Dallas Heart Study (DHS) is a multi-ethnic population based study of Dallas County residents. HTGC was quantified using H-MR spectroscopy. Univariate and multivariable logistic and linear regression models were generated to test the association between HTGC and log adiponectin stratified by PNPLA3 genotype (CC, CG and GG). Models were adjusted for age, gender, race, hypertension, diabetes, HOMA-IR and BMI. Results: There were 2,259 patients who had complete clinical, biochemical, imaging, and genotyping data and were included in this analysis. Median age was 44 and 47% were male. Race distribution was 48% Black, 32% White, and 18% Hispanic. The prevalences of PNPLA3 genotypes were 61% CC (wild type), 32% GC and 7% GG. The median concentration of adiponectin was 6.6 ug/ml. Adiponectin was an independent predictor HTCG across all genotypes after adjusting for covariates (CC b=-0.34, GC b=-0.42, GG b=-0.38, p<0.005 for each). HTGC decreased across gender and race-stratified quartiles of adiponectin for each PNPLA3 genotype, and the qualitative effect was greatest in the I148M homozygotes (table). Conclusions: Adiponectin is independently associated with hepatic steatosis across all three PNPLA3 genotypes. The combination of at-risk PNPLA3 genotypes and hypoadiponectemia is associated with a high risk of hepatic steatosis. Future studies will need to address downstream HCC risk and whether manipulation of adiponectin level may be of clinical benefit. [Table: see text]
Engraftment of resected pancreatic adenocarcinoma in SCID mice and patient survival following surgical resection: Roswell Park's experience.
Authors: Aranez Jose Luis , Jitawatanarat Potjana , Hylander Bonnie , Pitoniak Rose , Levea Charles , Repasky Elizabeth S , Ma Wen Wee 
Published: February 2017

185 Background: Preclinical models developed by implanting resected pancreatic cancer from human donors into immunocompromised (SCID) mice have been valuable in understanding the disease’s biology and developing therapies. The ability of resected tumors to engraft successfully has previously been reported to be a poor prognostic marker. This study was conducted to investigate the relationship between successful engraftment and clinical outcome by analyzing such a model developed at Roswell Park over the last decade. Methods: A retrospective review of 48 donor patients (27 males and 21 females) whose resected pancreatic adenocarcinoma was xenografted in SCID mice between 1999-2009 was conducted. The clinical outcome and baseline information were correlated with engraftment outcome. The expression of potential biomarkers correlating with engraftment was evaluated by performing immunohistochemistry on the initial donor surgical specimens. The expression was scored, assigned an average index value and categorized into groups (High vs Low expression) based on a median cutoff of values. Results: Resected tumors from 21 of the 48 donors successfully engrafted when implanted subcutaneously in SCID mice (44%). The baseline demographics and disease characteristics were balanced between engrafters versus non-engrafters. All of the engrafters and 26 (of 27) of non-engrafters received adjuvant treatment. The 2-year overall survival (OS) of patients whose tumors successfully engrafted was 17% compared to 39% in those whose tumors failed to engraft (P=0.09; hazard ratio 1.305 [95% CI 0.717-2.375]). Analysis to identify potential biological markers associated with engraftment success is underway. Conclusions: A review of the clinical outcome of patients whose tumors were procured and used for the patient-derived primary pancreatic cancer xenograft program at Roswell Park showed that successful engraftment in SCID mice is potentially a poor prognostic marker in patients with resectable pancreatic cancer. Our analysis did not reach statistical significance which is likely due to a smaller sample size but the potential link is consistent with that reported by others.
Prognostic value of metabolic tumor volume and total lesion glycolysis on preoperative 18F-FDG PET/CT in patients with pancreatic cancer.
Authors: Lee Jeong Won , Kang Chang Moo , Lee Sang Mi , Lee Jae-Hoon , Lee Jong Doo 
Published: February 2017

190 Background: In this study, we aimed to assess the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose (18F-FDG) PET/CT in pancreatic cancer patients who underwent resection with curative intent. Methods: Eighty-seven patients with pancreatic ductal adenocarcinoma who underwent 18F-FDG PET/CT and subsequent surgical resection with curative intent with (30 patients) or without (57 patients) neoadjuvant therapy were retrospectively enrolled in this study. The maximum standardized uptake value (SUVmax), MTV, and TLG were measured on 18F-FDG PET/CT in all patients. The prognostic significance of SUVmax, MTV, TLG, and tumor factors for predicting recurrence-free survival was evaluated by univariate and multivariate analyses. Results: Of the 87 patients enrolled, 57 (64%) experienced recurrence during the follow-up period, and the 1-year recurrence-free survival rate was 52%. Among the variables determined to be significant on univariate analysis including tumor size, pT stage, the presence of lymph node metastasis, SUVmax, MTV, and TLG, only tumor size, MTV, and TLG were significant prognostic factors on multivariate analysis (p < 0.05). Patients with low MTV (71%) or TLG (74%) had significantly higher 1-year recurrence-free survival rates than those with high MTV (42%) or TLG (38%; p < 0.05). In the 57 patients who did not undergo neoadjuvant treatment, MTV and TLG remained significant predictive factors for tumor recurrence, along with tumor size and SUVmax. Conclusions: MTV and TLG are independent prognostic factors for predicting recurrence in patients with pancreatic cancer. Thus, 18F-FDG PET/CT can provide useful prognostic information for patients undergoing resection of pancreatic cancer with curative intent irrespective of neoadjuvant treatment.
Upper gastrointestinal cancers: Are all carcinomas truly carcinomas?
Authors: Sagaert Xavier , Van Cutsem Eric , Tejpar Sabine , Prenen Hans , De Hertogh Gert , Nafteux Philippe , Haustermans Karin , Debiec-Rychter Maria 
Published: February 2017

20 Background: Poorly differentiated cancer of the upper GI tract is a challenging diagnosis for the pathologist, who will rely on a positive cytokeratin immunostaining to confirm the epithelial origin of the tumor. Being confronted with a highly unusual case (a poorly differentiated esophageal “carcinoma” with immunophenotypic and genetic sarcoma-like features, arising in the background of high grade Barrett dysplasia), we retrospectively investigated whether other cancer cases displayed the same unusual features. Methods: 34 poorly differentiated GI cancers were selected based on availability of FFPE. All cases were investigated by (1) immunohistochemistry for selected carcinoma and sarcoma markers (prekeratin, NCAM, vimentin, CD99) and by (2) FISH for presence/absence of abnormalities of 2 genes, SYT and EWS, that are frequently rearranged in synovial and Ewing’s sarcoma respectively. Results: 6/34 cases displayed an aberrant immunophenotype, with expression of NCAM, vimentin, and/or CD99. FISH revealed a substantial number (9/34) of SYT and EWS related anomalies: 1 EWS rearrangements, 1 SYT rearrangements, 1 SYT and 1 EWS focal amplification, and 4 aneuploidies. While EWS and SYT are (mostly) fused to ERG or SSX1/2 in Ewing’s and synovial sarcoma respectively, these genes were found to be intact in our EWS and SYT rearranged cases. Conclusions: Our data show that SYT & EWS abnormalities are recurrently occurring in poorly differentiated GI cancers that are (mis?)diagnosed as carcinomas. While EWS rearrangement has previously been described in cancer types other than Ewing’s sarcoma, SYT rearrangement was so far thought to be exclusive to the diagnosis of synovial sarcoma. In addition, EWS/SYT abnormalities in our series seemed to target cancers that are at risk of not responding well to the conventional chemoradiotherapy regimen. Of interest, the one “carcinoma” patient that started this study went into complete remission after being administered a sarcoma targeted therapy. We also infer from our results that good histologic assessment of GI cancers is essential for clinical trials aiming at targeted therapy, as not all carcinomas may present true carcinomas.
Long-term results of salvage endoscopic treatment for patients with local failure after chemoradiotherapy for esophageal squamous cell carcinoma.
Authors: Hatogai Ken , Yano Tomonori , Kojima Takashi , Onozawa Masakatsu , Doi Toshihiko , Kaneko Kazuhiro , Ohtsu Atsushi 
Published: February 2017

207 Background: Local failure is a major problem after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma (ESCC), and salvage surgery presents high morbidity and mortality rates. We have introduced photodynamic therapy (PDT) and endoscopic resection (ER) for local failures to develop a less invasive salvage treatment.The aim of this retrospective study was to clarify the long-term outcome of salvage endoscopic treatments (SET). Methods: Between 1998 and 2008, 716 patients with ESCC were treated with definitive CRT in our institution. There were 314 patients with incomplete response and 103 with local recurrence after achieving complete response (CR) once. The indication criteria of SET were as follows: 1) absence of lymph node and distant metastasis and 2) local failures limited within T2. ER was performed for local failures limited to T1b (SM1), and PDT was performed for lesions invading T1b (SM2) or T2, in patients who could not tolerate or who refused surgery. We assessed overall survival (OS), relapse-free survival (RFS), and also prognostic factors. This study was approved by an institutional review board. Results: A total of 164 patients with local failure underwent SET (ER: 58, PDT: 106). The characteristics before CRT were as follows: T1/2/3/4, 44/25/75/20; N0/1, 85/79; stage I/II/III/IV, 35/59/57/13; and those of before SET were as follows: T1/2, 126/38; residue/recurrence, 76/88. ER achieved curative resection in 51 (87.9%), and PDT achieved CR in 61 (57.5%) patients. With a median follow up period of 73 months, the OS and RFS rates at 5 years from SET were 38.6% (95% CI 31.0–46.2) and 28.1% (95% CI 21.0–35.2). Multivariate analysis revealed 2 preferable prognostic factors in common for OS and RFS, N0 before CRT (OS HR: 0.47 [95% CI 0.32–0.69], RFS HR: 0.61 [95%CI 0.43–0.87]) and a period from initiation of CRT to SET longer than 6 months (OS HR: 0.57 [95%CI 0.39–0.84], RFS HR: 0.67 [0.47–0.95]). After 5 years of follow up, 58 patients (35.4%) were alive without any metastasis under esophagus preservation. Conclusions: SET demonstrated a favorable outcome in an analysis of a large number of patients with local failure after definitive CRT for ESCC.
Prediction of nodal metastasis in clinical T1 gastric cancer.
Authors: Fujikawa Hirohito , Sakamaki Kentaro , Kawabe Taiichi , Hayashi Tsutomu , Aoyama Toru , Wakasugi Takehiro , Hasegawa Shinichi , Sato Tsutomu , Cho Haruhiko , Makuuchi Yousuke , Ogata Takashi , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Yoshikawa Takaki 
Published: February 2017

21 Background: Clinical T1 gastric cancer sometimes metastasizes to regional lymph nodes. Standard surgery is D2 gastrectomy for clinical T1N+ gastric cancer patients, however, clinical detection of nodal metastasis by Computed Tomography is unreliable, with only 4% sensitivity in our previous study. The present study aimed to predict pathological nodal metastases in clinical T1 gastric cancer. Methods: Patients were selected from the prospective database of Kanagawa Cancer Center between Oct 2000 and Oct 2007 based on the following criteria; (1) histologically proven adenocarcinoma of the stomach, (2) patients were diagnosed with clinical T1 by gastrointestinal endoscopy, (3) patients received radical surgery with D1 or more lymphadenectomy as a primary treatment. First, univariate logistic-regression model was used to select risk factors for prediction of pathological nodal metastasis by analyzing clinical factors of tumor location, clinical depth (cT1a or cT1b), macroscopic type, maximal tumor diameter, and pathological type. Then, the optimal cut-off value and predictive accuracy was determined by ROC curve using significant factors selected in logistic regression. Results: A total of 511 patients were entered into this study. Among these, pathological N+ was observed in 46 patients (9.0%). Clinical depth (p=0.002), tumor diameter (p<0.001) and pathological type (p=0.002) were significant risk factors for pathological nodal metastasis. Using these factors in multivariate logistic regression, the AUC was calculated to be 0.75. Cut-off value was different depending on the histology and clinical depth; 7.9 cm for differentiated type and 4.8 cm for undifferentiated type in cT1a and 4.3 cm for differentiated type and 1.1 cm for undifferentiated type in cT1b. Using these criteria, sensitivity and specificity for prediction of pathological nodal metastasis were 67.4% and 71.6%, respectively. Conclusions: Pathological nodal metastasis in clinical T1 gastric cancer was predictable by clinical depth, pathological type, and tumor size, however, specificity was not so high. D2 surgery is highly recommended for clinical T1 when the tumors satisfy these criteria.