Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients.

BACKGROUND: Recent evidence suggests that ionizing radiation may be associated with unexpected side-effects in melanoma patients treated with concomitant BRAF inhibitors. A large multicenter analysis was carried out to generate reliable safety data and elucidate the mechanism. METHODS: A total of 161 melanoma patients from 11 European skin cancer centers were evaluated for acute and late toxicity, of whom 70 consecutive patients received 86 series of radiotherapy with concomitant BRAF inhibitor therapy. To further characterize and quantify a possible radiosensitization by BRAF inhibitors, blood samples of 35 melanoma patients were used for individual radiosensitivity testing by fluorescence in situ hybridization of chromosomal breaks after ex vivo irradiation. RESULTS: With radiotherapy and concomitant BRAF inhibitor therapy the rate of acute radiodermatitis ≥2° was 36% and follicular cystic proliferation was seen in 13% of all radiotherapies. Non-skin toxicities included hearing disorders (4%) and dysphagia (2%). Following whole-brain radiotherapy, rates of radiodermatitis ≥2° were 44% and 8% (P < 0.001) for patients with and without BRAF inhibitor therapy, respectively. Concomitant treatment with vemurafenib induced acute radiodermatitis ≥2° more frequently than treatment with dabrafenib (40% versus 26%, P = 0.07). In line with these findings, analysis of chromosomal breaks ex vivo indicated significantly increased radiosensitivity for patients under vemurafenib (P = 0.004) and for patients switched from vemurafenib to dabrafenib (P = 0.002), but not for patients on dabrafenib only. No toxicities were reported after stereotactic treatment. CONCLUSION: Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib.

Increasing the uptake of cervical smears: strategies implemented among general practitioners in Auckland.

AIM: To evaluate three strategies designed to increase the uptake of cervical smears among specified groups of women through a collaborative partnership between the Auckland Area Health Board and selected Auckland general practitioners. METHOD: Using action-based research general practitioners and practice nurses were engaged to initiate ways of inviting women in their practices to have cervical smears. Both formative and process evaluations were made. Concurrently, outcomes were measured in terms of call/recall systems, uptake rates and cost barriers. RESULTS: Where financial incentives were given to establish call/recall systems for older women, overall uptake rates increased by 21%, and by 154% for women over 45 years. Over one third of a targeted group of women aged between 60 and 70 years responded to an invitation to have a free smear. Of these 109 women, fourteen, with a median age of 67 years, had their first smear. Almost two thirds indicated that cost had never been a barrier. CONCLUSIONS: The determining factor for women having a cervical smear in all three strategies was a personal invitation from their general practitioner or practice nurse. Invitations were dependent upon having accurate call/recall systems. This evaluation of the collaborative process between Auckland Area Health Board and local general practitioners demonstrated how manager and provider partnerships can benefit the consumer.