The Family Lifestyles, Actions and Risk Education (FLARE) study: Protocol for a randomized controlled trial of a sun protection intervention for children of melanoma survivors.

BACKGROUND: Children of parents who had melanoma are more likely to develop skin cancer themselves owing to shared familial risks. The prevention of sunburns and promotion of sun-protective behaviors are essential to control cancer among these children. The Family Lifestyles, Actions and Risk Education (FLARE) intervention will be delivered as part of a randomized controlled trial to support parent-child collaboration to improve sun safety outcomes among children of melanoma survivors. METHODS: FLARE is a two-arm randomized controlled trial design that will recruit dyads comprised of a parent who is a melanoma survivor and their child (aged 8-17 years). Dyads will be randomized to receive FLARE or standard skin cancer prevention education, which both entail 3 telehealth sessions with an interventionist. FLARE is guided by Social-Cognitive and Protection Motivation theories to target child sun protection behaviors through parent and child perceived risk for melanoma, problem-solving skills, and development of a family skin protection action plan to promote positive modeling of sun protection behaviors. At multiple assessments through one-year post-baseline, parents and children complete surveys to assess frequency of reported child sunburns, child sun protection behaviors and melanin-induced surface skin color change, and potential mediators of intervention effects (e.g., parent-child modeling). CONCLUSION: The FLARE trial addresses the need for melanoma preventive interventions for children with familial risk for the disease. If efficacious, FLARE could help to mitigate familial risk for melanoma among these children by teaching practices which, if enacted, decrease sunburn occurrence and improve children's use of well-established sun protection strategies.

One-Decade-Spanning transgenerational effects of historic radiation dose in wild populations of bank voles exposed to radioactive contamination following the chernobyl nuclear disaster.

The concept of historic radiation doses associated with accidental radioactive releases and their role in leading to radiation-induced non-targeted effects on affected wild animals are currently being evaluated. Previous research studying Fukushima butterfly, Chernobyl bird and fruit fly populations shows that the effects are transgenerational, underlined by the principles of genomic instability, and varied from one species to another. To further expand on the responses of and their sensitivity in different taxonomically distinct groups, the present study sought to reconstruct historic radiation doses and delineate their effects on bank voles (Clethrionomys glareolus) found within a 400-km radius of the Chernobyl Nuclear Power Plant meltdown site. Historic dose reconstruction from the whole-body dose rates for the bank vole samples for their parental generation at the time of radioactive release was performed. Relationships between the historic doses and cytogenetic aberrations and embryonic lethality were examined via graphical presentations. Results suggest that genomic instability develops at the historic dose range of 20-51 mGy while a radioadaptive response develops at the historic dose range of 51-356 mGy. The Linear No-Threshold (LNT) relationship was absent at historic doses of lower than 356 mGy at all generations. However, LNT was apparent when the very high historic dose of 10.28 Gy in one sampling year was factored into the dose response curve for the bank vole generation 21-22. It is worth being reminded that natural mutation accumulation and other environmental stressors outside the realm of dose effects could contribute to the observed effects in a multiple-stressor environment. Nevertheless, the consistent development of genomic instability and radio-adaptive response across generations and sampling sites unearths the utmost fundamental radiobiological principle of transgenerational non-targeted effects. As a result, it calls for better attention and regulation from global governing bodies of environmental health protection.

Effects of historic radiation dose on the frequency of sex-linked recessive lethals in Drosophila populations following the Chernobyl nuclear accident.

Contrary to the effects of high doses of radiation, the effects of low doses of radiation are still being investigated. Low doses and their non-targeted effects in particular are of special interest for researchers. The accident that occurred at the Chernobyl Nuclear Power Plant (NPP) gives researchers the opportunity to view these effects outside of a laboratory environment. For this paper, the relationship between low historic radiation doses and the persistent genetic damage observed in populations of fruit flies (Drosophila melanogaster) around the Chernobyl NPP over 3 years will be investigated. Data from Zainullin et al. (1992) on the frequency of sex-linked recessive lethals (SLRLs) in D. melanogaster around the Chernobyl NPP. To calculate the absorbed historic external dose, a method based on the Gaussian plume model was used to find the external dose from both plume shine and ground shine. The dose attributed to the ground shine dose made a greater contribution to the overall absorbed external historic radiation dose than the plume shine dose. For earlier generations of Drosophila living in the radioactive contaminated sites, the SLRL frequencies appeared to correlate with the dose in a linear no-threshold relationship. The later descendent generations appeared to have developed a radio-adaptive-like response. This work contributes to the understanding of historic dose effects on wildlife health following the accidental release of high mount of radioactive materials into the environment.

Transgenerational effects of historic radiation dose in pale grass blue butterflies around Fukushima following the Fukushima Dai-ichi Nuclear Power Plant meltdown accident.

Low dose radiation effects have been investigated in Chernobyl for many years but there is uncertainty about initial doses received by many animal species. However, the Fukushima Dai-ichi Nuclear Power Plant accident opens an opportunity to study the effects of the initial low historic dose on directly exposed species and their progeny during a time where the contaminating radionuclides are decaying. In this paper, it is proposed that historic acute exposure and its resulting non-targeted effects (NTEs) may be partially involved in the high mortality/abnormality rates seen across generations of pale grass blue butterflies (Zizeeria maha) around Fukushima. Data from Hiyama et al. (2012) on the morphological abnormality frequencies in Z. maha collected around Fukushima and their progeny were used in this paper. Two dose reconstruction methods based on the Gaussian plume model were used to determine the external absorbed dose to the first exposed generation from both ground shine and plume shine. One method involved the use of the dose rate recorded at the time of collection and only took Cs-137 into account. The other involved using release rates and atmospheric conditions to determine the doses and considered Cs-137 and Cs-134. The reconstructed doses were plotted against the mortality rates and abnormality frequencies across generations. The mortality rates of the progeny from irradiated progenitors increased linearly with the increasing historic radiation doses reconstructed using both Cs-137 and Cs-134 sources. Additionally, a higher level of morphological abnormalities was observed in progeny than in the progenitors. The mean abnormality frequencies also increased throughout generations. As these results are a sign of NTEs being involved, it can be suggested that increasing mutation levels across generations may result, in part, from NTEs induced by the initial low dose received by the first exposed generation. However, continual accumulation of mutations over generations in their natural contaminated habitats remains a likely contributor into the observed outcome.

Long-term effects of ionizing radiation after the Chernobyl accident: Possible contribution of historic dose.

The impact of the Chernobyl NPP accident on the environment is documented to be greater than expected, with higher mutation rates than expected at the current, chronic low dose rate. In this paper we suggest that the historic acute exposure and resulting non-targeted effects (NTE) such as delayed mutations and genomic instability could account at least in part for currently measured mutation rates and provide an initial test of this concept. Data from Møller and Mousseau on the phenotypic mutation rates of Chernobyl birds 9-11 generations post the Chernobyl accident were used and the reconstructed dose response for mutations was compared with delayed reproductive death dose responses (as a measure of genomic instability) in cell cultures exposed to a similar range of doses. The dose to birds present during the Chernobyl NPP accident was reconstructed through the external pathway due to Cs-137 with an estimate of the uncertainty associated with such reconstruction. The percentage of Chernobyl birds several generations after the accident without mutations followed the general shape of the clonogenic survival percentage of the progeny of irradiated cells, and it plateaued at low doses. This is the expected result if NTE of radiation are involved. We suggest therefore, that NTE induced by the historic dose may play a role in generating mutations in progeny many generations following the initial disaster.

Brachytherapy dose-volume histogram commissioning with multiple planning systems.

The first quality assurance process for validating dose-volume histogram data involving brachytherapy procedures in radiation therapy is presented. The process is demonstrated using both low dose-rate and high dose-rate radionuclide sources. A rectangular cuboid was contoured in five commercially available brachytherapy treatment planning systems. A single radioactive source commissioned for QA testing was positioned coplanar and concentric with one end. Using the brachytherapy dosimetry formalism defined in the AAPM Task Group 43 report series, calculations were performed to estimate dose deposition in partial volumes of the cuboid structure. The point-source approximation was used for a 125I source and the line-source approximation was used for a 192Ir source in simulated permanent and temporary implants, respectively. Hand-calculated, dose-volume results were compared to TPS-generated, dose-volume histogram (DVH) data to ascertain acceptance. The average disagreement observed between hand calculations and the treatment planning system DVH was less than 1% for the five treatment planning systems and less than 5% for 1 cm ≤ r ≤ 5 cm. A reproducible method for verifying the accuracy of volumetric statistics from a radiation therapy TPS can be employed. The process satisfies QA requirements for TPS commissioning, upgrading, and annual testing. We suggest that investigations be performed if the DVH %Vol(TPS) "actual variance" calculations differ by more than 5% at any specific radial distance with respect to %Vol(TG-43), or if the "average variance" DVH %Vol(TPS) calculations differ by more than 2% over all radial distances with respect to %Vol(TG-43).

Treatment of base of tongue cancer with paclitaxel, ifosfamide, and cisplatinum induction chemotherapy followed by chemoradiotherapy.

OBJECTIVES/HYPOTHESIS: To assess the efficacy of paclitaxel, ifosfamide, and cisplatinum induction chemotherapy plus concurrent chemoradiation in the treatment of stage III and IV base of tongue cancer. STUDY DESIGN: Subgroup analysis of patients with base of tongue cancer enrolled in a single-institution prospective phase II trial, evaluating an organ-preservation approach in the treatment of locally advanced head and neck cancer. METHODS: Eighteen patients with tumors ranging from stage T2-T4, any N, or M0 were treated with a protocol of induction chemotherapy, with Taxol, ifosfamide, cisplatin every 21 days for up to three cycles. If the primary tumor exhibited a complete or partial response, patients were treated with radiation and weekly taxol and carboplatin for 7 weeks. Surgery was used for those with less than partial response or disease progression. Neck dissection was performed in cases with clinical or radiological evidence of persistent disease in the neck 6 to 8 weeks after completion of treatment. RESULTS: Sixteen patients were male and two were female; the average age was 55 years (range, 43-65). Fifteen patients had stage IV disease and three had stage III disease. Of the 18 patients initially enrolled, 17 patients had a complete response. All 17 patients had no evidence of loco-regional disease at a median follow-up of 29.6 months. Only 1 of them developed distant metastases 30 months after completion of treatment. Three patients required permanent percutaneous endoscopic gastrostomy tubes because of severe dysphagia associated with concurrent chemoradiation. CONCLUSIONS: The treatment regimen studied is remarkably effective in stage III and IV base of tongue cancer with 100% of patients completing the protocol alive to date. Although some patients required persistent percutaneous endoscopic gastrostomy use, no patient experienced significant enough toxicity during the protocol to delay or withdraw from treatment.