K. Underhill

Intensity-modulated radiotherapy for head-and-neck cancer in the community setting.

PURPOSE To review outcomes with intensity-modulated radiation therapy (IMRT) in the community setting for the treatment of nasopharyngeal and oropharyngeal cancer. METHODS AND MATERIALS Between April 2003 and April 2007, 69 patients with histologically confirmed cancer of the nasopharynx and oropharynx underwent IMRT in our practice. The primary sites included nasopharynx (11), base of tongue (18), and tonsil (40). The disease stage distribution was as follows: 2 Stage I, 11 Stage II, 16 Stage III, and 40 Stage IV. All were treated with a simultaneous integrated boost IMRT technique. The median prescribed doses were 70 Gy to the planning target volume, 59.4 Gy to the high-risk subclinical volume, and 54 Gy to the low-risk subclinical volume. Forty-five patients (65%) received concurrent chemotherapy. Toxicity was graded according to the Radiation Therapy Oncology Group toxicity criteria. Progression-free and overall survival rates were estimated with the Kaplan-Meier product-limit method. RESULTS Median duration of follow-up was 18 months. The estimated 2-year local control, regional control, distant control, and overall survival rates were 98%, 100%, 98%, and 90%, respectively. The most common acute toxicities were dermatitis (32 Grade 1, 32 Grade 2, 5 Grade 3), mucositis (8 Grade 1, 33 Grade 2, 28 Grade 3), and xerostomia (0 Grade 1, 29 Grade 2, 40 Grade 3). CONCLUSIONS Intensity-modulated radiotherapy in the community setting can be accomplished safely and effectively. Systematic internal review systems are recommended for quality control until sufficient experience develops.

The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.

Objective To explore the association of a functional germline variant in the 3′-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. Methods/Materials The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. Results The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant. Conclusions The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.