Reirradiation of head and neck cancer focusing on hypofractionated stereotactic body radiation therapy

Reirradiation is a feasible option for patients who do not otherwise have treatment options available. Depending on the location and extent of the tumor, reirradiation may be accomplished with external beam radiotherapy, brachytherapy, radiosurgery, or intensity modulated radiation therapy (IMRT). Although there has been limited experience with hypofractionated stereotactic radiotherapy (hSRT), it may have the potential for curative or palliative treatment due to its advanced precision technology, particularly for limited small lesion. On the other hand, severe late adverse reactions are anticipated with reirradiation than with initial radiation therapy. The risk of severe late complications has been reported to be 20- 40% and is related to prior radiotherapy dose, primary site, retreatment radiotherapy dose, treatment volume, and technique. Early researchers have observed lethal bleeding in such patients up to a rate of 14%. Recently, similar rate of 10-15% was observed for fatal bleeding with use of modern hSRT like in case of carotid blowout syndrome. To determine the feasibility and efficacy of reirradiation using modern technology, we reviewed the pertinent literature. The potentially lethal side effects should be kept in mind when reirradiation by hSRT is considered for treatment, and efforts should be made to minimize the risk in any future investigations

Prognostic value of gross tumor volume delineated by FDG-PET-CT based radiotherapy treatment planning in patients with locally advanced pancreatic cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>We aimed to assess whether gross tumor volume (GTV) determined by fusion of contrast-enhanced computerized tomography (CT) and 18F-fluoro-deoxy-D-glucose positron emission tomography-CT (FDG-PET-CT) based radiotherapy planning could predict outcomes, namely overall survival (OS), local-regional progression-free survival (LRPFS), and progression-free survival (PFS) in cases with locally advanced pancreas cancer (LAPC) treated with definitive concurrent chemoradiotherapy.</p> <p>Methods</p> <p>A total of 30 patients with histological proof of LAPC underwent 50.4 Gy (1.8 Gy/28 fractions) of radiotherapy concurrent with continuously infused 5-FU followed by 4 to 6 courses of maintenance gemcitabine. Target volume delineations were performed on FDG-PET-CT-based RTP. Patients were stratified into 2 groups: GTV lesser (GTV_L) versus greater (GTV_G) than cut off value determined by receiver operating characteristic (ROC) analysis, and compared in terms of OS, LRPFS and PFS.</p> <p>Results</p> <p>Median GTV delineated according to the FDG-PET-CT data was 100.0 cm³. Cut off GTV value determined from ROC curves was 91.1 cm³. At a median follow up of 11.2 months, median OS, LRPFS and PFS for the entire population were 10.3, 7.8 and 5.7 months, respectively. Median OS, LRPFS and PFS for GTV_Land GTV_Gcohorts were 16.3 vs. 9.5 (<it>p </it>= 0.005), 11.0 vs. 6.0 (<it>p </it>= 0.013), and 9.0 vs. 4.8 months (<it>p </it>= 0.008), respectively.</p> <p>Conclusions</p> <p>The superior OS, LRPFS and PFS observed in GTV_Lpatients over GTV_Gones suggests a potential for FDG-PET-CT-defined GTV size in predicting outcomes of LAPC patients treated with definitive C-CRT, which needs to be validated by further studies with larger cohorts.</p

A group-based HIV and sexually transmitted infections prevention intervention for lesbian, bisexual, queer and other women who have sex with women in Calgary and Toronto, Canada: study protocol for a non-randomised cohort pilot study

INTRODUCTION: The limited research that exists suggests that lesbian, bisexual queer (LBQ) and other women who have sex with women are at similar risk for sexually transmitted infections (STI) as heterosexual women. However, scant research has evaluated HIV and STI prevention strategies for LBQ women. The authors present the rationale and study protocol for developing and pilot testing a psychoeducational group-based HIV and STI prevention intervention with LBQ women in Calgary and Toronto, Canada. METHODS AND ANALYSIS: This is a multicentre non-randomised cohort pilot study. The target population is LBQ women in Calgary and Toronto, Canada. The authors aim to recruit 40 participants using purposive peer-driven recruitment methods. Participants will conduct a pretest followed by a 2-day group programme of six 2 h sessions addressing stigma, STI and HIV prevention, healthy relationships, safer sex self-efficacy, self-worth, social support and LBQ community engagement. Participants will conduct a post-test directly following the intervention and 6 weeks after the intervention. The primary outcome is safer sex practices; our prespecified index of clinically significant change is an effect size of 0.50. Secondary outcomes include: safer sex self-efficacy, STI testing frequency, STI knowledge, resilient coping, social support, sexual stigma, access to care, depression and self-esteem. We will conduct mixed-effects regression to calculate mean outcome pre–post test score change. ETHICS AND DISSEMINATION: Research ethics approval was attained from the Office of Research Ethics (REB: 29291), University of Toronto, Toronto, Ontario, Canada. Trial results will be published according to the Transparent Reporting of Evaluations with Non-randomised Designs (TREND) statement, regardless of the outcomes. TRIAL REGISTRATION NUMBER: This study is registered at http://clinicaltrials.gov, registration number NCT02067845

Small molecule GS-nitroxide ameliorates ionizing irradiation-induced delay in bone wound healing in a novel murine model

We studied radioprotection and mitigation by mitochondrial-targeted Tempol (GS-nitroxide, JP4-039), in a mouse injury/irradiation model of combined injury (fracture/irradiation). Right hind legs of control C57BL/6NHsd female mice, mice pretreated with MnSOD-PL, JP4-039, or with amifostine were irradiated with single and fractionated doses of 0 to 20 Gy. Twenty-four hours later, unicortical holes were drilled into the tibiae of both hind legs; at intervals, tibias were excised, radiographed, and processed for histology. Bone wounds irradiated to 20 or 30 Gy showed delayed healing at 21 to 28 days. Treatment with JP4-039 MnSOD-PL or amifostine, before or after single fraction 20 Gy or during fractionated irradiation followed by drilling accelerated wound healing at days 21 and 28. Orthotopic 3LL tumors were not protected by JP4-039 or amifostine. In nonirradiated mice, pretreatment with JP4-039 accelerated bone wound healing. This test system should be useful for the development of new small molecule radioprotectors

Intraesophageal administration of GS-nitroxide (JP4-039) protects against ionizing irradiation-induced esophagitis

Background/Aim: This study evaluated esophageal radioprotection by the Gramicidin S (GS) derived-nitroxide, JP4-039, a mitochondrial targeting peptide-isostere covalently-linked to 4-amino-Tempo, delivered in a novel swallowed oil-based (F15) formulation. Materials and Methods: C57BL/6HNsd female mice received intraesophageal F15 formulation containing JP4-039 (4 mg/ml in 100 μl volumes) 10 minutes before 28 or 29 Gy upper body irradiation compared to MnSOD-PL (100 μl containing 100 μg plasmid) 24 hours prior to irradiation. Subgroups received 1×107 C57BL/6HNsd, GFP + male bone marrow cells intravenously 5 days after irradiation. Results: JP4-039/F15 or MnSOD-PL increased survival compared to irradiated controls (p<0.0001 for either). Marrow injection further increased survival (p=0.0462 and 0.0351, respectively). Esophagi removed at 1, 3, 7, 14, 24, or 60 days showed bone marrow-derived cells in the esophagi. Conclusion: Intraesophageal GS-nitroxide radioprotection is mediated primarily through recovery of endogenous esophageal progenitor cells