Small bowel adenocarcinoma: understaged and undertreated?

BACKGROUND: Primary small bowel adenocarcinoma (SBA) is a rare, chemoresistant tumor with an aggressive clinical nature. Surgery is the mainstay of therapy, but the extent of lymph node (LN) recovery necessary for optimal care of jejunoileal SBA is unknown. MATERIALS AND METHODS: The SEER database was queried to identify patients whose primary jejunoileal SBA was diagnosed between 1995 and 2005. Patients were grouped by AJCC stage and number of LNs recovered from the surgical specimen. RESULTS: Of 1444 patients with primary SBA, 93 (6.4%), 529 (36.6%), 356 (24.7%), and 466 (32.3%) were initially diagnosed with stage I, II, III, and IV disease, respectively. Five-year overall survival (OS) rate was 59.8%, 39.5%, 27.0%, and 3.2% for patients with stage I, II, III, and IV SBA, respectively. When ≥10 nodes were recovered, OS rate increased nonsignificantly in stage I (73.2% vs. 55.6%) and significantly in stage II (61.8% vs. 32.9%, P < .001) but was unchanged in stage III (27.4% vs. 27.3%, P = .13). Recovery of ≥10 nodes occurred in 26.9%, 23.6%, and 42.1% of patients with stage I, II, and III SBA, respectively. Multivariate analysis identified age, AJCC stage, site of primary tumor, recovery of ≥10 LNs, and number of positive nodes as significant for OS. CONCLUSIONS: We have found SBA staging is largely inadequate. Our results suggest recovery of ≥10 LNs ensures accurate staging. Improvement in stage II SBA OS after adequate LN may reflect a high degree of understaging in this dataset rather than a therapeutic effect of LAD.

Predictive utility of circulating methylated DNA in serum of melanoma patients receiving biochemotherapy.

PURPOSE: Currently, no validated blood-based assays accurately predict treatment response or outcome in melanoma patients. We hypothesized that methylation of tumor-related genes detected in serum DNA could predict disease outcome and therapeutic response in patients receiving concurrent biochemotherapy (BC) for metastatic melanoma. PATIENTS AND METHODS: American Joint Committee on Cancer stage IV melanoma patients (N = 50) had blood drawn before administration of BC. Patients (n = 47) were classified as BC responders or nonresponders. Responders (n = 23) demonstrated a complete or partial response following BC; nonresponders (n = 24) demonstrated progressive disease. Hypermethylation of Ras association domain family 1 (RASSF1A), retinoic acid receptor-beta2 (RAR-beta2), and O6-methylguanine DNA methyltransferase (MGMT) genes were assessed by methylation-specific polymerase chain reaction. RESULTS: Circulating methylated RASSF1A was significantly less frequent for responders (three of 23 patients; 13%) than nonresponders (10 of 24 patients; 42%; P = .028). Patients with RASSF1A, RAR-beta2, or at least one serum methylated gene had significantly worse overall survival than patients with no methylated genes (log-rank, P = .013, .021, and .01, respectively). Methylated RASSF1A was the only factor that significantly correlated with overall survival and BC response (risk ratio, 2.38; 95% CI, 1.16 to 4.86; P = .018; odds ratio = 0.21; 95% CI, 0.05 to 0.90; P = .036). CONCLUSION: Detection of circulating methylated DNA in serum can predict response to BC and disease outcome.