Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer.

OBJECTIVE: High rates of systemic failure in locally advanced rectal cancer call for a rational use of conventional therapies to foster tumor-defeating immunity. METHODS: We analyzed the high-mobility group box-1 (HMGB1) protein, a measure of immunogenic cell death (ICD), in plasma sampled from 50 patients at the time of diagnosis and following 4 weeks of induction chemotherapy and 5 weeks of sequential chemoradiotherapy, both neoadjuvant modalities containing oxaliplatin. The patients had the residual tumor resected and were followed for long-term outcome. RESULTS: Patients who met the main study end point-freedom from distant recurrence-showed a significant rise in HMGB1 during the induction chemotherapy and consolidation over the chemoradiotherapy. The higher the ICD increase, the lower was the metastatic failure risk (hazard ratio 0.26, 95% confidence interval 0.11-0.62, P = 0.002). However, patients who received the full-planned oxaliplatin dose of the chemoradiotherapy regimen had poorer metastasis-free survival (P = 0.020) than those who had the oxaliplatin dose reduced to avert breach of the radiation delivery, which is critical to maintain efficient tumor cell kill and in the present case, probably also protected the ongoing radiation-dependent ICD response from systemic oxaliplatin toxicity. CONCLUSION: The findings indicated that full-dose induction oxaliplatin followed by an adapted oxaliplatin dose that was compliant with full-intensity radiation caused induction and maintenance of ICD and as a result, durable disease-free outcome for a patient population prone to metastatic progression.

Disseminated central nervous system hemangioblastoma in a patient with no clinical or genetic evidence of von Hippel-Lindau disease-a case report and literature review.

BACKGROUND: Hemangioblastomas (HB) are benign tumors of the central nervous system (CNS) that can appear sporadic or as part of von Hippel-Lindau (VHL) disease. It is often curable with surgical resection, but upon relapse, the disease exhibits a treatment-refractory course. CASE REPORT: A patient treated for sporadic cerebellar HB relapsed 12 years post-surgery. She developed disseminated disease throughout the CNS, including leptomeningeal manifestations. Repeat surgery and craniospinal radiation therapy were unsuccessful. CONCLUSION: This case is in line with previous publications on disseminated non-VHL HB. Available treatment options are inefficient, emphasizing the need for improved understanding of HB biology to identify therapeutic targets.

Aspirin As Secondary Prevention in Patients With Colorectal Cancer: An Unselected Population-Based Study.

PURPOSE: Regular use of aspirin (acetylsalicylic acid) is associated with reduced incidence and mortality of colorectal cancer (CRC). However, aspirin as primary prevention is debated because of the risk of hemorrhagic adverse effects. Aspirin as secondary prevention may be more justified from a risk-benefit perspective. We have examined the association between aspirin use after the diagnosis of CRC with CRC-specific survival (CSS) and overall survival (OS). MATERIALS AND METHODS: An observational, population-based, retrospective cohort study was conducted by linking patients diagnosed with CRC from 2004 through 2011 (Cancer Registry of Norway) with data on their aspirin use (The Norwegian Prescription Database). These registries cover more than 99% of the Norwegian population and include all patients in an unselected and consecutive manner. Exposure to aspirin was defined as receipt of aspirin prescriptions for more than 6 months after the diagnosis of CRC. Multivariable Cox-proportional hazard analyses were used to model survival. The main outcome measures of the study were CSS and OS. RESULTS: A total of 23,162 patients diagnosed with CRC were included, 6,102 of whom were exposed to aspirin after the diagnosis of CRC (26.3%). The median follow-up time was 3.0 years. A total of 2,071 deaths (32.9%, all causes) occurred among aspirin-exposed patients, of which 1,158 (19.0%) were CRC specific. Among unexposed patients (n = 17,060), there were 7,218 deaths (42.3%), of which 5,375 (31.5%) were CRC specific. In multivariable analysis, aspirin exposure after the diagnosis of CRC was independently associated with improved CSS (hazard ratio [HR], 0.85; 95% CI, 0.79 to 0.92) and OS (HR, 0.95; 95% CI, 0.90 to 1.01). CONCLUSION: Aspirin use after the diagnosis of CRC is independently associated with improved CSS and OS.