ABSTRACT
PURPOSE: To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT). METHODS AND MATERIALS: Genomic DNA of 159 patients with locally advanced rectal cancer treated with PCRT was genotyped for polymorphisms rs28362491 (NFKB1), rs1213266/rs5789 (PTGS1), rs5275 (PTGS2), and rs16944/rs1143627 (IL1B) using TaqMan single nucleotide polymorphism genotyping assays. The association between each genotype and pathologic response (poor response vs complete or partial response) was analyzed using logistic regression models. RESULTS: The NFKB1 DEL/DEL genotype was associated with pathologic response (odds ratio [OR], 6.39; 95% confidence interval [CI], 0.78-52.65; P=.03) after PCRT. No statistically significant associations between other polymorphisms and response to PCRT were observed. Patients with the NFKB1 DEL/DEL genotype showed a trend for longer disease-free survival (log-rank test, P=.096) and overall survival (P=.049), which was not significant in a multivariate analysis that included pathologic response. Analysis for 6 polymorphisms showed that patients carrying the haplotype rs28362491-DEL/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G (13.7% of cases) had a higher response rate to PCRT (OR, 8.86; 95% CI, 1.21-64.98; P=.034) than the reference group (rs28362491-INS/rs1143627-A/rs1213266-G/rs5789-C/rs5275-A/rs16944-G). Clinically significant (grade ≥2) acute organ toxicity was also more frequent in patients with that same haplotype (OR, 4.12; 95% CI, 1.11-15.36; P=.037). CONCLUSIONS: Our results suggest that genetic variation in NFKB-related inflammatory pathways might influence sensitivity to primary chemoradiation for rectal cancer. If confirmed, an inflammation-related radiogenetic profile might be used to select patients with rectal cancer for preoperative combined-modality treatment.
Subject(s)
Chemoradiotherapy/methods , NF-kappa B/genetics , Polymorphism, Genetic , Radiation Tolerance/genetics , Rectal Neoplasms/genetics , Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Capecitabine , Chemoradiotherapy/adverse effects , Cyclooxygenase 1/genetics , Cyclooxygenase 2/genetics , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Enteritis/genetics , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Inflammation/genetics , Inflammation/metabolism , Interleukin-1beta/genetics , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Proctitis/genetics , Pyridines/administration & dosage , Radiotherapy, Conformal/adverse effects , Radiotherapy, Conformal/methods , Rectal Neoplasms/pathology , Retrospective Studies , Young AdultABSTRACT
We present 39 patients with lip carcinoma treated with HDR, (needles) with 5-5.5 Gy per 8-10 fractions b.i.d. (total dose 40.5-45 Gy). Three-year cause-specific survival and local control are 91 and 88% (95% T1-2, 74% T4, p<0.05). Acute and chronic reactions are like LDR cases. We think that HDR results are equivalent to LDR.
