AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA
388
It is widely accepted that multiple genetic alterations are required for the development of gastrointestinal cancer. However, which and how many alterations are essential for carcinogenesis has not been fully clarified. To solve this problem, a comprehensive search was conducted of the Pub-Med Database for relevant reports pertaining comparative genomic hybridization (CGH) analyses, gene amplifications, homozygous deletion s, gene mutations, gene rearrangement, and aneuploidy in sporadic esophageal, gastric, colorectal, and pancreatic cancer. Individual data from CGH analyses, that included 418 esophageal cancers, 707 gastric cancers, 396 colorectal cancers, and 142 pancreatic cancers were converted into a matrix format, and frequencies of gains and losses at each chromosomal band were calculated. Frequencies of amplifications and homozygous deletions, and gene mutations were also calculated from several series of pooled analyses. The frequent genome alterations thus detected were (+, gain; -, loss): for esophageal cancer, +3q27 (43.8%), +8q24 (45.0%), +5p15 (34.2%), +20q13 (31.8%) -3p24 (30.6%), -18q22 (28.2%), -9p21 (27.0%), amplification at 11q13 (28.8%), mutation of TP53 (42%), mitochondrial DNA (23%), and CDKN2A (13.7%); for gastric cancer, +20q13 (38.9%), +8q23 (31.7%), -19p13 (20.9%), +17q21 (20.5%), mutation of TP53 (28%), mitochondrial DNA (25%); for colorectal cancer, +20q12-q13 (49.5%), -18q22 (48.2%), +13q21 (35.6%), +8q23 (30.8%), +7p15 (30.3%), -17p13 (29.8%), amplification at 20q13 (50.2), mutation of APC (56.6%), TP53 (37.3%), KRAS (34.5%), and mitochondrial DNA (32.0%); for pancreatic cancer, -18q22 (38.0%), -9p24 (32.4%), +8q24 (31.7%), -17p12 (30.3%), +20q13 (26.1%), +3q24 (21.8%), mutation of KRAS (59.5%), TP53 (40.3%), and CDKN2A (17.5%). The total values of frequencies of each genetic alteration that showed more than 10%, that represent the expected value of the occurrence, produced an estimate of the total number of genome alterations of 8.53 for esophageal, 4.12 for gastric, 7.31 for colorectal, and 5.57 for pancreatic cancer. Striking agreement with a previous estimation based on age-distribution of these cancers (Armitage and Doll, Br J Cancer 8: 1-12, 1954) suggested that genetic changes summarized here constitute a major factor in carcinogenesis and the importance of the development of molecular targeted therapy based on recurrent chromosomal gains and losses.
Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder that is usually diagnosed on the basis of high resolution computed tomography (HRCT) findings. It is unclear whether CPFE is an independent prognostic factor in patients with non-small-cell lung cancer (NSCLC). Therefore, we conducted a retrospective analysis to assess the impact of CPFE on the prognosis of patients with completely resected NSCLC. We retrospectively reviewed 365 patients diagnosed with NSCLC who underwent complete resection at the Tazuke Kofukai Medical Research Institute, Kitano Hospital between January 2007 and December 2012. Patients were classified into four groups according to chest HRCT findings: those with CPFE, those with fibrosis, those with emphysema or those with a normal lung except for the presence of a tumour. We evaluated disease-free survival (DFS) and overall survival (OS) using the two-tailed log-rank test and the Cox proportional hazards model. The two-tailed log-rank test demonstrated that the four groups had significantly different DFS and OS (P < 0.01). In the multivariate analysis, CPFE was found to be an independent prognostic factor for DFS and OS compared with a normal lung [hazard ratio (HR): 2.52; 95% confidence interval (CI): 1.24−5.13; P = 0.01 and HR: 4.53; 95% CI: 1.91−10.7; P < 0.01, respectively]. CPFE is a significant, unfavourable prognostic factor for NSCLC patients after curative resection.
Objectives The objective of this study was to compare the clinical outcomes between initially unresectable and recurrent advanced pancreatic cancer (APC) patients after palliative chemotherapy. Methods Data of a total of consecutive 269 patients with pathologically confirmed APC patients who received palliative chemotherapy between January 2006 and April 2012 were reviewed. Patients were classified into initially unresectable and recurrent group, and overall survival (OS) was compared between the 2 groups. Results The median OS was significantly longer in the recurrent group compared with the initially unresectable group (383 vs 308 days; hazard ratio [HR], 0.59; 95% confidence interval, 0.44–0.80; P < 0.01). After adjustment for distant metastasis, performance status, and levels of carbohydrate antigen 19-9, carcinoembryonic antigen, C-reactive protein, and lactate dehydrogenase, the status of recurrent or unresectable disease remained as an independent prognostic factor with a clinically relevant HR value (HR, 0.66; 95% confidence interval, 0.48–0.90; P = 0.01). In addition, the 2-year OS rate of the recurrent group was significantly higher than that of the unresectable group (24.2% vs 9.6%, P = 0.01). Conclusions Our results suggested that the status of recurrent or initially unresectable disease was an independent prognostic factor in APC patients receiving palliative chemotherapy.
