Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review.

Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28  months (range, 6-90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3-4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study.

CTLA-4 blockade with monoclonal antibodies can lead to cancer regression in patients with metastatic melanoma (MM). CTLA-4 gene polymorphisms may influence the response to anti-CTLA-4 antibodies although few data are available regarding this issue. We analyzed six CTLA-4 single nucleotide polymorphisms (-1661A > G, -1577G > A, -658C > T, -319C > T, +49A > G, and CT60G > A) in 14 Italian MM patients and 45 healthy subjects. We found a significant association between the -1577G/A and CT60G/A genotypes and improved overall survival (Pc < 0.006, Bonferroni corrected), further confirmed by the diplotype analysis (-1577 & CT60 GG-AA diplotype, p < 0.001). A positive trend toward an association between these genotypes and response to therapy was also observed.