bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using adjacent to tumor samples as normal controls in molecular investigations: Are we missing the earliest biomarkers?
Authors: Barra Williams Fernandes , Moreira Fabiano , Ribeiro-dos-Santos Arthur , Santos Sidney , Santos Andrea KCR , Demachki Samia , Assumpcao Monica B , Khayat Andre Salim , Assumpcao Carolina Barauna , Anaissi Ana Karyssa , Ishak Geraldo , Hage Pedro Antonio Mufarrej , Assumpção Paulo P 
Published: March 2017

80 Background: Recently, some papers aiming to warn the scientific community regarding possible misinterpretation due to using adjacent to tumor sample tissues as normal controls were published The main motivation for these alerts was the observation of important molecular alterations in tissues nearby a cancer, although been collected from non-tumor areas. Nevertheless the cancer field hypothesis has been recognized many years ago; this concept was not incorporated to current practice in molecular investigations. In this work we aim to investigate potential implications of using adjacent to tumor sample tissues as normal controls. Methods: Gastric Cancer (GC) and Adjacent Tissues (AT) paired fresh samples of 16 patients, and 16 samples from non-cancer patients (NC) were analyzed. miRNA sequencing was performed using Illumina Miseq platform. Statistical analysis was performed in R using DESeq2 tool to identify differential expressed miRNAs. Results: Comparing GC with NC tissue samples, we observed 21 miRNAs differentially expressed (p-value < 0.05 and |Log2(Fold-Change)| > 2), eight were down-regulated and 13 were up-regulated in GC. Comparing AT with NC tissue samples, 16 miRNAs were differentially expressed, two were down-regulated and 14 were up-regulated in AT. In both comparisons, GC and AT samples clustered together and clearly separated from NC samples. Comparing GC with AT samples, hsa-miR-196a-5p was significantly down-regulated in GC. Conclusions: AT tissues harbor molecular alterations distinguishing them from non-cancer patient’s samples. Combined analyses of the groups clearly demonstrated that AT resembles much more cancer profile than NC patient’s tissue prolife. Using AT samples as controls might impair the discovery of possible initial molecular events identifiable exclusively by using samples from non-cancer patients. The current strategy of molecular investigation must be revised.
Clinical trials versus clinical practice in colorectal cancer: Equivalent populations?
Authors: Magdaleno Cremades Alejandra , Ors Castaño María del Carmen , Ballester Espinosa María , Llopis Cuquerella Marta , Ramirez Belloch María del Rocío , Boix Aracil Vicente , Gómez González Lucía , Morales Giménez Roberto , Asensio Martinez Elena , Gallego Plazas Javier 
Published: March 2017

802 Background: Clinical trials are criticized due to inclusion of selected populations. The aim of this analysis is to compare populations included in clinical trials which justify treatment recommendations in stage III and IV colorectal cancer (CRC) to patient populations in our area. Methods: Data related to age, sex, primary tumor and stage of CRC patients consecutively diagnosed in Vega Baja Hospital and Elche University General Hospital were collected. Also data regarding the same variables were collected from the publications of clinical trials which justify adjuvant treatment in stage III colon cancer and combination treatment with chemotherapy and targeted therapies in stage IV CRC. Results: We analyzed 249 patients with stage III colon cancer and 237 patients with stage IV CRC from our area. In our experience, 56.6% of stage III colon cancer were males, and median age was 66.2 years (23 - 91), with 41.8% ≥ 70 years. In clinical trials supporting adjuvant treatment 54 - 56.1% of patients were males, and median age was 59 - 61 years (19-83), with 14 - 21.7% ≥ 70 years. In our experience 64.4% of stage IV CRC patients were males, and median age was 67.2 years (38-89), 76.4% primary tumor in colon. In clinical trials supporting combination treatment with chemotherapy and targeted therapies 60-67% of patients were males, and median age was 59.2 – 62 years, primary tumor in colon 57.9 – 81% (Table). Conclusions: Patient populations included in clinical trials which support standard treatment in CRC are younger to those in our area. This fact, added to the restrictions based on inclusion and exclusion criteria of clinical trials, justify the qualification of “selected” to these populations not being representative of our clinical practice. [Table: see text]
Genomic-directed therapy of gastrointestinal cancers by comprehensive genomic profile (CGP): Clinical and genomic characteristics at the John Theurer Cancer Center (JTCC).
Authors: Gonzalez Velez Miguel , Duma Narjust , Jaramillo Restrepo Valentina , Lopez-Zertuche Pablo , Parrondo Ricardo Daniel , Mariotti Veronica , Kothadia Sejal , Boseski Beth , Jennis Andrew , Gutierrez Martin 
Published: March 2017

803 Background: The routine use of comprehensive genomic profiling (CGP) has led to better genomic characterization, more personalized treatments and higher enrollment in clinical trials for many solid cancers. The aim of this study was to evaluate the clinical and genomic prolife of patients (pts) with gastrointestinal cancers (GIC) with the use of a CGP assay and their potential therapeutic benefit at a large comprehensive cancer center. Methods: We retrospectively analyzed 83 consecutive pts with GIC that had CGP at the JTCC between 01/2014-09/2016. Demographics, CGP results, and clinical characteristics were studied. Clinically relevant genomic alterations (CRGAs) were identified using the FoundationOne assay (Foundation Medicine, Cambridge, MA), and were defined as alterations linked to approved therapies and those under evaluation in genotype-driven clinical trials. Results: 83 pts with GIC were analyzed. 46.9% males and 53.0% females. The median age at diagnosis was 58.5 years. 73 (88%) patients were stage III/IV at diagnosis. Tumors consisted of colorectal (36%), gastric (24%), pancreatic (12%) and cholangiocarcinoma (6%). All the pts were found to have at least one genomic alteration (GA). CRGAs were identified in 63 (76%) of cases, with an average of 2 per pt. The most frequently identified GAs were TP53 43 (29.9%), APC 24 (16.7%), KRAS 31 (21.5%), ARID1A 12 (8.3%), PIK3CA 11 (7.6%), and SMAD4 11 (7.6%). Of the 63 pts with CRGAs, 23 (36%) received one of the therapies suggested by the NGS assay, and 9 (14%) were enrolled in a clinical trial. Conclusions: The use of CGP assay identified a high frequency of CRGAs in GIC pts. The assay provided information for genomic-directed therapy in 36% of the patients. The routine use of CGP in GIC may lead to pts receive more personalized treatments. The potential benefit of selected targeted therapies in individual cases suggests that larger studies of treatment guided by routine CGP in gastrointestinal malignancies are warranted.
Relations of changes in serum carcinoembryonic antigen (CEA) levels before and after chemoradiotherapy (CRT) and after surgery to histological response and outcomes in patients with locally advanced rectal cancer (LARC).
Authors: Saito Gota , Sadahiro Sotaro , Miyakita Hiroshi , Okada Kazutake , Tanaka Akira , Suzuki Toshiyuki 
Published: March 2017

804 Background: Multidisciplinary treatment had been a standard of care for locally advanced rectal cancer. Serum CEA had been reported as one of the predictive factors to CRT, however, serum CEA levels may change after CRT and surgery. We examined the relations of serum CEA before CRT, after CRT, and after surgery to histological response and outcomes. Methods: The subjects were 149 patients with cStage II or III adenocarcinoma of the rectum who underwent surgery after CRT from 2005 through 2013. A total dose of 40 to 45 Gy with concurrent oral UFT or S-1 was delivered. Surgery was performed 6 to 8 weeks after CRT. A serum CEA > 5 ng/mL was defined as positive. Patients with negative serum CEA before CRT were designated as group 1. Patients with positive serum CEA before CRT that became negative after CRT were designated as group 2. Patients with positive serum CEA after CRT that became negative after surgery were designated as group 3, and patients with positive serum CEA after CRT as well as after surgery were designated as group 4. The median follow-up period of the survivors was 60.4 months. Results: The numbers of patients in Groups 1, 2, 3, and 4 were 55 (37%), 41 (28%), 37 (25%), and 16 (11%), respectively. The incidences of pCR, T downstaging, and N downstaging did not differ significantly among the groups (p = 0.094, 0.060, and 0.346). Rates of marked regression (TRG Grade 1 or 2) were 55% in Group 1, 42% in Group 2, 16% in Group 3, 25% in group 4. The rates were significantly higher in groups 1 and 2 (p = 0.001).5y DFS was 76% in group 1, 75% in group 2, 77% in group 3, and 48% in group 4 and was significantly lower in group 4 (p = 0.024). 5y OS was 88% in group 1, 91% in group 2, 85% in group 3, and 68% in group 4 and was significantly lower in group 4 than that in groups 1 and 2 (p = 0.03, 0.019). Conclusions: In patients with rectal cancer who received CRT, changes in serum CEA levels before and after CRT and after surgery were intimately related to the histological response of the primary lesion. Patients who continued to have positive serum CEA levels after surgery had poor outcomes, strongly suggesting the presence of occult distant metastasis.
North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).
Authors: Shichinohe Toshiaki , Yuki Satoshi , Takahashi Norihiko , Nakatsumi Hiroshi , Kawamoto Yasuyuki , Kusumi Takaya , Ishiguro Atsushi , Sogabe Susumu , Iwanaga Ichiro , Hatanaka Kazuteru , Oomori Kazuyoshi , Nakamura Michio , Senmaru Naoto , Iwai Kazuhiro , Koike Masahiko , Sakamoto Naoya , Taketomi Akinobu , Hirano Satoshi , Ito Yoichi M , Komatsu Yoshito 
Published: March 2017

807 Background: FOLFOX and XELOX are standard adjuvant chemotherapy for resected stage III colon cancer. MOSAIC and XELOXA trials were performed outside of Japan, thus, we conducted a phase II study (NORTH/HGCSG1003) to assess the efficacy and safety of FOLFOX as adjuvant chemotherapy for Japanese patients(pts) with resected stage III colon cancer (UMIN ID: 000004590). Methods: This phase II study enrolled patients with resected stage III colon cancer. Patients received 12 cycles of FOLFOX4 or mFOLFOX6. Sample size was determined to be 243 pts. Primary endpoint was disease-free survival (DFS). We assumed an expected 3-year DFS rate of 81.2% in this study. Secondary endpoints included overall survival (OS) and safety. In this meeting, we present for the 3-year DFS rate. Results: From Sep 2010 to Mar 2013, 273 pts were enrolled at 28 institutions. Full analysis included 265 patients who received FOLFOX. Patients characteristics were as follows: median age ; 65(33-84), Male/female ; 131/134, PS 0/1 ; 258/7, stage IIIA/IIIB/IIIC ; 37/197/31, colon/rectosigmoid: 214/51. The most common grade 3-4 adverse events were neutrophil count decreased (48.1%), peripheral sensory neuropathy (6.4%), platelet count decreased (2.3%), and allergic reaction (1.5%). The median number of cycles of FOLFOX was 12, and the completion treatment rate was 80.4%. There was no treatment-related death. The 3-year DFS rate was 75.2 percent (95% confidence interval, 69.6 to 80.0). Conclusions: In Japanese patients with stage III colon cancer, FOLFOX is a well-tolerable regimen as adjuvant chemotherapy. In this trial, the 3-year DFS rate of primary endpoint was not meet the expectation (81.2%). However, the 3-year DFS rate in this trial was similar to several pivotal trials. We plan to do subset analysis. Clinical trial information: UMIN000004590.
Pathologic validation of ablation therapy for gastric epithelial neoplasia: comparison of argon plasma coagulations vs. coagulation forceps.
Authors: Kim Byung-Wook 
Published: March 2017

82 Background: Ablation therapy has been introduced as an alternative in the management of gastric epithelial neoplasia. However, most of previous studies were retrospective observational studies and has not been validated pathologically. The aim of this study was to validate the effect of ablation therapy for gastric epithelial neoplasia pathologically. Methods: After ablation therapy either by argon plasma coagulations (APC) or by coagulation forceps for gastric epithelial neoplasia, immediate endoscopic resection for the lesions was performed. Consequent histologic mappings for the lesions were followed for the residual tumors. Factors which can affect the residual tumors were analyzed. Results: Twenty nine patients among 33 patients who underwent APC (87.9%) and 21 patients among 26 patients who underwent coagulation forceps (80.8%) showed residual tumors. Factors such as type of coagulation therapy, size of the lesion, type of the lesion (elevated vs. flat) and coagulation time/cm2 of the lesion were not associated with complete removal of the lesions. Conclusions: Ablation therapy is inadequate for complete removal of gastric epithelial neoplasia and this therapy cannot replace endoscopic resection. Clinical trial information: KCT0001587.
Prognostic value of metastatic tumoral caveolin-1 expression in patients with resected gastric cancer.
Authors: Sun Der Sheng , Hong Soon Auck , Lee Han Hong , Won Hye Sung , Ko Yoon Ho 
Published: March 2017

83 Background: Caveolin-1 (Cav-1), as the main component of caveolae, has complex roles in tumourigenesis and clinical outcomes in a variety of human malignancies. We investigated Cav-1 in primary and metastatic tumor of gastric cancer (GC) and its association with clinical outcomes. Methods: All specimens evaluated were obtained from 145 patients with GC who had undergone curative gastrectomy. The primary outcomes measured were the expression levels of Cav-1 by immunohistochemistry and its association with clinicopathological parameters and patient survival. Results: Among the 145 patients, the frequency of high expression of stromal Cav-1 within primary tumor and tumoral Cav-1 protein in metastatic lymph node were 22.5% (18/145) and 16.6% (15/91). In the multivariate analysis tumoral Cav-1 protein in metastatic lymph node showed prognostic significance for relapse-free survival (RFS, HR, 3.934; 95% CI, 1.882–8.224; P < 0.001) and cancer-specific survival outcome (CSS, HR, 3.985; 95% CI, 1.620 – 8.623; P = 0.002). In addition, it remained as a strong indicator of poor prognosis for RFS (HR, 3.137; 95% CI, 1.445 – 6.810; P = 0.004) and CSS (HR, 2.509; 95% CI, 1.079 – 5.838; P = 0.033). Conclusions: High expression of tumoral Cav-1 protein in metastatic lymph node shows a strong negative association with the clinical outcomes in patients with curatively resected GC, suggesting that this protein have potential uses as novel prognostic markers.
Angiogenesis factors in esophageal tumors of various histogenesis.
Authors: Frantsiyants Elena Mikhaylovna , Kit Oleg Ivanovich , Kolesnikov Evgeniy N. , Cheryarina Natalia D. , Kozlova Larisa , Pogorelova Yulia A. 
Published: March 2017

87 Background: Study of biological nature of tumors can provide important information on the malignant process course and contribute to the drug therapy development. The purpose of the study was to analyze levels of some growth factors in tissues of malignant esophageal tumors of various histogenesis. Methods: Levels of VEGF-А and its receptor sVEGF-R1, VEGF-С and its receptor sVEGF-R2, EGF, IFR-1, IFR-2 and TGF-β1 were studied by the ELISA using standard test-systems in tissue samples obtained from 39 patients: 27 – esophageal squamous cell carcinoma (ESCC), 12 – esophageal adenocarcinoma (EA). All patients had stage II disease (G2, pTNM). Results: Development of the pathogenic vascularization mechanism in ESCC and EA tissues was found to have both similar and different characteristics associated with the expression of growth factors. Similarities included activation of VEGF-А, VEGF-С, VEGF-R1, VEGF-R3, TGF-β1 and EGF in tissues of malignant tumors despite their histogenesis, while differences involved IGF-I and IGF-II content. A strong positive correlation between levels of VEGF-А and IGF-1 (r = 76; p < 0.01), but not IGF-II, was registered in EA tissues only, while in ESCC we found the negative correlation between VEGF-А and IGF-1(r = - 81; p < 0.01) and VEGF-А and IGF-2 (r = -79; p < 0.01). The same was observed for VEGF-С: a strong positive correlation with IGF-1(r = 79; p < 0.01), but not with IGF-II in EA, and a strong negative correlation with IGF-1(r = - 83; p < 0.01) and IGF-2 (r = -87; p < 0.01) in ESCC. EGF appears to be the only VEGF-А and VEGF-С inductor in ESCC, as a strong correlation with it was noted: r = 75 (p < 0.01) and r = 77 (p < 0.01) respectively, while activators of angio- and lymphogenesis factors in EA were presented by IGF-1 and EGF (r = 76 at p < 0.01 and r = 79 at p < 0.01 with VEGF-А and VEGF-С, respectively). Conclusions: Apparently, the two histological types of esophageal cancer are two different diseases with their own pathogenesis, prognosis and therefore approach to the targeted therapy.
Effectiveness and limitations of staging laparoscopy for peritoneal metastases in advanced gastric cancer from the results of JCOG0501: A randomized trial of gastrectomy with or without neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer.
Authors: Hato Shinji , Iwasaki Yoshiaki , Mizusawa Junki , Terashima Masanori , Katai Hitoshi , Yoshikawa Takaki , Ito Seiji , Kaji Masahide , Fujita Junya , Hirao Motohiro , Yamada Makoto , Takagi Masakazu , Katayama Hiroshi , Nakamura Kenichi , Sano Takeshi , Sasako Mitsuru 
Published: March 2017

9 Background: In type 4 or large type 3 gastric cancer diagnosed as not having distant metastasis by imaging modalities, the incidence of peritoneal metastasis that was unexpectedly found during laparotomy was approximately 40%. Staging laparoscopy (SL) is a valuable method used for staging gastric cancer. This study aimed to clarify the effectiveness and limitations of SL for patients (pts) with type 4 or large type 3 gastric cancer. Methods: JCOG0501 is a randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for treating type 4 or large type 3 gastric cancer. Eligibility criteria included histologically proven gastric adenocarcinoma that was clinically type 4 or large type 3 gastric cancer and was diagnosed as R0/1-resectable using SL. Pts who underwent gastrectomy without neoadjuvant chemotherapy were included in this study. Results: In total, 316 pts (158 pts with and without neoadjuvant chemotherapy each) were enrolled between October 2005 and July 2013 from 44 institutions. Of the 158 pts without neoadjuvant therapy, 2 pts did not receive laparotomy. The remaining 156 pts were included in this analysis. Among them, except for 1 patient (P1), none were diagnosed with peritoneal metastases (P0) during SL. Among these 155 pts, 24 (15.5%) were diagnosed with peritoneal metastases at subsequent laparotomies (false-negative). Most of the overlooked peritoneal disseminated nodules were located in the intestinal mesentery (8 pts), transverse mesocolon (5 pts), or omental bursa (3 pts). The total number of peritoneal disseminated nodules at laparotomy was often ≤ 9 (1–3 nodules in 14 pts, 4–9 in 4 pts). Of the 156 included pts, 142 underwent R0/1-resection (91.0%) because some overlooked nodules were curatively resected. Conclusions: SL is a useful diagnostic tool to plan the management of type 4 and large type 3 gastric cancers, although the high false-negative rate cannot be ignored. In SL, detailed exploration of the mesentery, mesocolon, and omental bursa is recommended.
Phase II multi-institutional prospective trial of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer refractory to fluoropyrimidine with modified dose reduction criteria (CCOG1303).
Authors: Mochizuki Yoshinari , Kobayashi Daisuke , Kojima Hiroshi , Nakayama Hiroshi , Kawase Yoshihisa , Ishigure Kiyoshi , Shikano Toshio , Torii Koji , Kodera Yasuhiro 
Published: March 2017

91 Background: Nab-paclitaxel (nab-PTX) is a candidate as second-line chemotherapy for gastric cancer, with the response rate (RR) of 28% and overall survival (OS) of 9.2 months in that setting in Japan (J-0200). Adverse events (AE) of grade 3 or more were frequent and included neutropenia in 49%, leucopenia in 20% and peripheral nerve disorder (PND) in 24%. Modified dose reduction criteria to manipulate the doses earlier might be more practical, given the relative dose intensity (RDI) of paclitaxel (PTX) in the conventional weekly regimen. Phase II prospective trial was conducted to explore the efficacy and safety of nab-PTX with modified dose reduction criteria. Methods: Patients with histologically confirmed metastatic or recurrent gastric adenocarcinoma that progressed during the fluoropyrimidine-containing first-line chemotherapy were eligible. Patients pretreated with PTX were excluded. Nab-PTX (260 mg/m2) was administered triweekly. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia < 1000/mm3 and/or PND with grade 2 or more. Treatment was to be continued until PD, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression free survival (PFS). Secondary endpoints were OS, RR and toxicity. Results: A total of 50 patients were enrolled from 14 institutions, 47 of whom were eligible for efficacy analyses. The median number of treatment given was 4 cycles (range, 1-25). Of total administration throughout the trial of 280 cycles, dose reduction was needed in 52 cycles (22%). The RDI was 80%. The median PFS was 3.5 months (range, 0.4-20.2) that was equivalent to the expected value designed in the study. The median OS was 9.0 months (range, 1.4-22.1) and RR was 16% (95%CI 2-30). AE of grade 3 or more included neutropenia in 49%, leucopenia in 21% and PND in 11%. Febrile neutropenia occurred in 1 patient (2%). The median time to treatment failure was 3.5 months (range, 0.4-18.0). Conclusions: The modified dose reduction criteria for triweekly administration of nab-PTX resulted in decreased incidence of severe PND without fall in efficacy. Clinical trial information: UMIN000012247.