The Nationwide Cancer Genome Screening Project in Japan, SCRUM-Japan GI-screen: Efficient identification of cancer genome alterations in advanced esophageal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4062-4062
Author(s):  
Yuichiro Nakashima ◽  
Takashi Kojima ◽  
Hiroki Hara ◽  
Ken Kato ◽  
Takeshi Kajiwara ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Esophageal Cancer ◽  
Copy Number Variant ◽  
Cancer Genome ◽  
Loss Of Function ◽  
Advanced Esophageal Cancer ◽  
Surgical Specimen ◽  
Dna And Rna ◽  
Ffpe Tumor ◽  
Genome Screening

4062 Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. The objective is to evaluate the frequency of cancer genome alterations in aNon-CRC and to identify patients who are candidate for clinical trial for corresponding targeting agents. Methods: This study is ongoing with the participation of 20 major cancer centers. Patients with aNon-CRC, including advanced esophageal cancer (aEC), who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of aEC cohort. Results: As of October 31st in 2016, a total of 180 aEC samples were analyzed. The sequence with the OCP was successfully performed in 121 (67.2%). Out of 157 patients except for the 23 patients in which precise data is not collected, the proportion of sample and histology type is followed; surgical specimen 58.0%, squamous cell carcinoma 92.4%. The frequently detected mutations in 114 samples of which results were available were TP53 (77.2%), NFE2L2 (23.7%), CDKN2A (9.6%), PIK3CA (7.0%), RB1 (6.1%), and CNVs were CCND1 (37.7%), EGFR (7.9%), MYC (7.9%), SOX2 (6.1%), ATP11B (5.3%), NKX2-1 (5.3%). ERBB2 amplification was identified in 3 cases (2.6%) and FGFR3-TACC3fusion was identified in one case (0.9%). Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aEC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.

The Nationwide Cancer Genome Screening Project in Japan SCRUM-Japan, GI-screen: Efficient identification of cancer genome alterations in advanced gastric cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4041-4041
Author(s):  
Shigenori Kadowaki ◽  
Kohei Shitara ◽  
Satoshi Yuki ◽  
Shuichi Hironaka ◽  
Takeshi Kato ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Copy Number Variant ◽  
Cancer Genome ◽  
Loss Of Function ◽  
Dna And Rna ◽  
Ffpe Tumor ◽  
Genome Screening ◽  
Rare Gene ◽  
Accredited Laboratory

4041 Background: We have conducted the Nationwide Cancer Genome Screening Project in Japan since April 2015 using Next Generation Sequencing in advanced non-colorectal gastrointestinal (GI) cancer (aNon-CRC), called as the SCRUM-Japan GI-SCREEN. Methods: This study is ongoing with 20 major cancer centers. Patients with aNon-CRC, who plan to or receive chemotherapy were eligible. DNA and RNA were extracted from FFPE tumor samples and were analyzed by the Oncomine Cancer Research Panel (OCP) which allows to detect gene mutation, copy number variant (CNV) and fusions across 143 genes in a CLIA certified CAP accredited laboratory. The detected genomic variant data were classified according to whether genetic drivers of cancer including gain- and loss-of-function or single nucleotide variant based on the Oncomine Knowledgebase. In this presentation, we show the results of advanced gastric cancer (aGC) cohort. Results: As of October 31st in 2016, a total of 565 aGC samples were analyzed. The sequence with the OCP was successfully performed in 425 (75.2%). Out of 475 patients except for the 90 patients in which precise data is not collected, the proportion of histology type is followed; intestinal type 44.6%, diffuse type 54.5%, other 0.6%, unknown 0.2%. Out of 406 samples of which results were available, the frequently detected mutations were TP53 (47.8%), PIK3CA (8.6%), KRAS (5.4%), SMAD4 (4.9%), TET2 (4.4%), APC (3.9%), ERBB2 (3.7%) and CNVs were ERBB2 (10.8%), CCNE1 (9.4%), KRAS (3.7%), ZNF217 (3.2%), FGFR2 (2.7%), and MET (2.5%). FGFR3-TACC3 fusion, WIPF2- ERBB2 fusion and EGFR vIII were detected in 2, 1, and 2 cases, respectively. Conclusions: This nationwide screening system is efficient to detect rare gene alterations in aGC. This novel knowledge provides an intriguing background to investigate new target approaches and represents a progress toward more precision medicine. Clinical trial information: UMIN000016344.

Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

Esophagus ◽  
2012 ◽  
Vol 9 (2) ◽  
pp. 105-112
Author(s):  
Hajime Ishikawa ◽  
Motohiro Imano ◽  
Osamu Shiraishi ◽  
Atsushi Yasuda ◽  
Ying-Feng Peng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Esophageal Cancer ◽  
Phase I ◽  
Phase I Clinical Trial ◽  
Advanced Esophageal Cancer

scholarly journals Erratum to: Phase I clinical trial of vaccination with URLC10-derived peptide for patients with advanced esophageal cancer

Esophagus ◽  
2012 ◽  
Vol 9 (2) ◽  
pp. 113-113
Author(s):  
Hajime Ishikawa ◽  
Motohiro Imano ◽  
Osamu Shiraishi ◽  
Atsushi Yasuda ◽  
Ying-Feng Peng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Esophageal Cancer ◽  
Phase I ◽  
Phase I Clinical Trial ◽  
Advanced Esophageal Cancer

Helical tomotherapy for advanced esophageal cancer improves target conformity and homogeneity: A comparison with fixed-field intensity-modulated radiotherapy

2015 ◽  
Vol 11 (3) ◽  
pp. 3146-3155
Author(s):  
Luhua Wang
Keyword(s):  
Esophageal Cancer ◽  
Field Intensity ◽  
Helical Tomotherapy ◽  
Intensity Modulated Radiotherapy ◽  
Matched Pair ◽  
Conformity Index ◽  
Target Coverage ◽  
Advanced Esophageal Cancer ◽  
Fixed Field ◽  
Intensity Modulated

Purpose: To evaluate the usefulness of helical tomotherapy (HT) in the treatment of advanced esophageal cancer (EC) and compare target homogeneity, conformity and normal tissue doses between HT and fixed-field intensity-modulated radiotherapy (ff-IMRT).Methods: In all, 23 patients with cT3-4N0-1M0-1a thoracic EC (upper esophagus, 9 patients; middle esophagus, 6; distal esophagus, 6 and esophagogastric junction, 2) who were treated with ff-IMRT (60 Gy in 30 fractions) were re-planned for HT and ff-IMRT with the same clinical require­ments. Comparisons were performed using the Wilcoxon matched-pair signed-rank test.Results: Compared with ff-IMRT, HT significantly reduced the homogeneity index for thoracic, upper, middle and distal ECs by 38%, 31%, 36% and 33%, respectively (P < 0.05). The conformity index was increased by HT for thoracic, upper and middle ECs by 9%, 9% and 18%, respectively (P < 0.05). Target coverage was improved by 1% with HT (P < 0.05). The mean lung dose was significantly reduced by HT for thoracic and upper ECs (P < 0.05). The V20 (volume receiving at least 20 Gy) and higher dose volumes of the lungs were decreased by HT in all cases, but the differences were significant for thoracic, upper and distal ECs (P < 0.05), with reductions of 2.1%, 3.1% and 2.2%, respectively. HT resulted in a larger lung V5 for thoracic, upper, middle and distal ECs, with increases of 3.5%, 1.5%, 7.2% and 3.2%, respectively. Heart sparing was significantly better with HT than with ff-IMRT in terms of the V30 and V40 for thoracic, upper, middle and distal ECs (P < 0.05).Conclusions: Compared to ff-IMRT, HT provides superior target coverage, conformity and homogeneity, with reduced the volume of high doses to the lungs and heart for advanced EC. HT may be a treatment option for advanced EC, especially upper EC.

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