Prognostic Implications of Pathological Response to Neoadjuvant Chemoradiation in Pathologic Stage III Rectal Cancer.

OBJECTIVE: To evaluate the independent prognostic ability of the American Joint Committee on Cancer (AJCC) tumor regression scores within pathologic stage II and III rectal cancers. BACKGROUND: Response to neoadjuvant chemoradiation (nCRT) has been debated as a biologic surrogate for tumor biology and prognosis in rectal cancer. AJCC regression scores have been shown to correlate with prognosis. METHODS: Patient demographics, tumor characteristics, and AJCC scores (0 = complete response; 1 = isolated tumor cells remaining; 2 = residual cancer outgrown by fibrosis; 3 = extensive residual cancer) were assessed from 545 rectal cancer patients treated by nCRT followed by surgery at a single institution. Patients were classified as responders (score 0-2) or nonresponders (score 3). Survival analyses were performed using Cox proportional hazards models. RESULTS: Of 545 cases, 123 and 182 were pathologic stage II and III, respectively. Median follow-up was 4.9 years. AJCC regression scores were not independently prognostic within stage II cancers. However, AJCC scores were strongly associated with prognosis within stage III cancers (nonresponse 5-year overall survival [OS] 27% vs 67%, P < 0.001). Stage III responders (N = 139, 76.4%) had similar outcomes to stage II (5-year OS 67% vs 74%, P = 0.89). Conversely, stage III nonresponders (N = 43, 23.6%) approached stage IV outcomes (5-year OS 27% vs 18%, P = 0.09). On multivariable analysis, nonresponse (hazard ratio 3.2, 95% confidence interval 1.7-6.2), along with positive margin, abdominoperineal resection, and no adjuvant chemotherapy administration were independently associated with worse OS. CONCLUSIONS: AJCC response score after nCRT is a novel prognostic factor in pathologic stage III rectal cancer and may guide surveillance and adjuvant therapy decisions.

NPTX2 is associated with neoadjuvant therapy response in rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation (CRT) is recommended for locally advanced rectal cancer. Tumor response varies from pathologic complete response (pCR) to no tumor regression. The mechanisms behind CRT resistance remain undefined. In our previously generated complementary DNA microarrays of pretreatment biopsies from rectal cancer patients, neuronal pentraxin 2 (NPTX2) expression discriminated patients with pCR from those with residual tumor. As tumor response is prognostic for survival, we sought to evaluate the clinical relevance of NPTX2 in rectal cancer. MATERIALS AND METHODS: Real-time quantitative polymerase chain reaction was used to evaluate NPTX2 messenger RNA expression in individual rectal cancers before CRT. Tumors with NPTX2 expression <50% of normal rectum were defined as NPTX2-low and those with >50% were defined as NPTX2-high. NPTX2 levels were compared to response to therapy and oncologic outcomes using Mann-Whitney, Kruskal-Wallis, chi-square, and Mantel-Cox (log-rank) tests, as appropriate. RESULTS: Rectal cancers from 40 patients were included. The mean patient age was 56.8 years, and 30% were female. pCR was achieved in eight of 40 patients (20%). In these patients, messenger RNA NPTX2 levels were significantly decreased compared to those with residual cancer (fold change 30.4, P = 0.017). Patients with NPTX2-low tumors (n = 13) achieved improved response to treatment (P = 0.012 versus NPXT2-high tumors), with 38.5% and 46.1% of patients achieving complete or moderate response, respectively. Of patients with NPTX2-high tumors (n = 27), 11.1% and 18.5% achieved complete or moderate response, respectively. No recurrence or death was recorded in patients with NPTX2-low tumors, reflecting more favorable disease-free survival (P = 0.045). CONCLUSIONS: Decreased NPTX2 expression in rectal adenocarcinomas is associated with improved response to CRT and improved prognosis. Further studies to validate these results and elucidate the biological role of NPTX2 in rectal cancer are needed.

Venous thromboembolism in patients with head and neck cancer after surgery.

BACKGROUND: The purpose of this study was to report the incidence of venous thromboembolism (VTE) in patients with head and neck cancer after surgery. METHODS: This was a single-institution, retrospective cohort: 134 patients underwent resection and simultaneous microvascular reconstruction. The primary endpoint was identification of confirmed or suspicious VTE within 30 days of surgery. RESULTS: Two subjects (1.4%) with confirmed VTE (1 pulmonary embolism, 1 deep venous thrombosis) and 6 subjects (4.4%) with suspicious VTE (1 acute respiratory failure, 1 sudden cardiac arrest, and 4 cases of leg edema without imaging) were identified. The strongest predictors of possible VTE were prior VTE (p = .004; odds ratio [OR], 25.11; 95% confidence interval [CI], 1.13-556.40), red cell transfusion (p = .009; OR, 1.80; 95% CI, 1.16-2.80), high body mass index (p = .015, OR, 1.29, 95% CI, 1.05-1.58), and older age (p = .046; OR, 1.10; 95% CI, 1.00-1.19). CONCLUSION: The incidence of VTE in patients with head and neck cancer after resection and microvascular reconstruction ranged from 1.4% to 5.8%.