Basis for the ICRP’s updated biokinetic model for systemic astatnie

The ICRP recently updated its biokinetic models for workers in a series of reports called the OIR (Occupational Intakes of Radionuclides) series. A new biokinetic model for astatine, the heaviest member of the halogen family, was adopted in OIR Part 5 (ICRP Publication 151, in press). This paper provides an overview of available biokinetic data for astatine; describes the basis for the ICRP’s updated model for astatine; and tabulates dose coefficients for intravenous injection of each of the two longest lived and most important astatine isotopes, 211At and 210At. Astatine-211 (T1/2 = 7.214 h) is a promising radionuclide for use in targeted α-particle therapy due to several favorable properties including its half-life and the absence of progeny that could deliver significant radiation doses outside the region of α-particle therapy. Astatine-210 (T1/2 = 8.1 h) is an impurity generated in the production of 211At in a cyclotron and represents a potential radiation hazard via its long-lived progeny 210Po (T1/2 = 138 d). Tissue dose coefficients for injected 210At and 211At based on the updated model are shown to differ considerably from values based on the ICRP’s previous model for astatine, particularly for the thyroid, stomach wall, salivary glands, lungs, spleen, and kidneys.

Influence of target dose heterogeneity on dose sparing of normal tissue in peripheral lung tumor stereotactic body radiation therapy

Objective To evaluate the influence of target dose heterogeneity on normal tissue dose sparing for peripheral lung tumor stereotactic body radiation therapy (SBRT). Methods Based on the volumetric-modulated arc therapy (VMAT) technique, three SBRT plans with homogeneous, moderate heterogeneous, and heterogeneous (HO, MHE, and HE) target doses were compared in 30 peripheral lung tumor patients. The prescription dose was 48 Gy in 4 fractions. Ten rings outside the PTV were created to limit normal tissue dosage and evaluate dose falloff. Results When MHE and HE plans were compared to HO plans, the conformity index of the PTV was increased by approximately 0.08. The median mean lung dose (MLD), V5, V10, V20 of whole lung, D2%, D1cc, D2cc of the rib, V30 of the rib, D2% and the maximum dose (Dmax) of the skin, and D2% and Dmax of most mediastinal organs at risk (OARs) and spinal cord were reduced by up to 4.51 Gy or 2.8%. Analogously, the median Dmax, D2% and mean dose of rings were reduced by 0.71 to 8.46 Gy; and the median R50% and D2cm were reduced by 2.1 to 2.3 and 7.4% to 8.0%, respectively. Between MHE and HE plans there was little to no difference in OARs dose and dose falloff beyond the target. Furthermore, the dose sparing of rib V30 and the mean dose of rings were negatively correlated with the rib and rings distance from tumor, respectively. Conclusions For peripheral lung tumor SBRT, target conformity, normal tissue dose, and dose falloff around the target could be improved by loosening or abandoning homogeneity. While there was negligible further dose benefit for the maximum target dose above 125% of the prescription, dose sparing of normal tissue derived from a heterogeneous target decreased as the distance from the tumor increased.

Hypofractionated Prostate Radiation Therapy: Adoption and Dosimetric Adherence Through Clinical Pathways in an Integrated Oncology Network

PURPOSE: Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. METHODS: Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. RESULTS: In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015-2017 to 85.6% in 2018 ( P < .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% ( P < .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P < .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P = 0.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P = .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. CONCLUSION: Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints.

Normal Tissue Dose Constraints for Multiple Lung Stereotactic Radiotherapy Treatments

Introduction: The role and use of stereotactic radiotherapy (SABR) is evolving rapidly. A key article by Hanna et al. (2017) provides an excellent overview of current evidence and suggestion of sensible dose constraints. Given the topical nature of this discussion we present a short retrospective analysis of treating multiple lung SABR patients at our centre. Method: We retrospectively analysed toxicity, both early (within 3 months of SABR) and late, and normal tissue dose constraints on all patients who had multiple lung lesions treated with SABR (using volumetric modulated arc therapy (VMAT) technique) at our tertiary centre over a 25-month period from April 2016 until May 2018. Results: We have treated 78 lung lesions in 37 patients with a combination of synchronous lung cancer primaries and lung metastases diagnoses. Median follow-up was 9 months. Almost all patients received treatment on the same day for multiple lesions. We report no grade 3 toxicities in any patient nor any unexpected side effects. 5 patients (14.7%) developed grade 2 pneumonitis. In all 5 patients, lung V12.5 was >20% (range 20.8-32.2%), yet only 1 patient exceeded acceptable lung V20 constraints. Regarding long-term toxicity, 66.6% of patients reported no treatment-related effects. Of 9 patients with long-term toxicity, 8 exceeded V12.5 constraint of <15%, indeed of these 5 were >20%. Lung V20 levels were acceptable for the majority of these. Local control of treated lesions at median follow-up in all comers was 86.2%. Discussion: Our findings show that multiple lung SABR is tolerable, safe with minimal long-term toxicity and acceptable early toxicity. Defining normal lung V12.5 of <15% (optimal) and <20% (acceptable) will significantly reduce the risk of pneumonitis and longer-term toxicity, proving itself more predictive than lung V20 levels for toxicity. Additionally, treating multiple lesions concurrently appears to bare no extra risk to patients.

Relationship Between the Dose Administered, Target Tissue Dose, and Toxicity Level After Acute Oral Exposure to Bifenthrin and Tefluthrin in Young Adult Rats

Most pyrethroid insecticides (PYRs) share a similar primary target site in mammals. However, the potency estimates of the lethal and sublethal effects of these compounds differ up to 103-fold. The aim of this study was to evaluate the relationship between the dose administered, the target tissue dose, and the effect of 2 highly toxic PYRs, tefluthrin (TEF; 0.1–9 mg/kg) and bifenthrin (BIF; 0.5–12 mg/kg), by using the oral route, a corn oil vehicle (1 ml/kg) and subcutaneous temperature (Tsc) monitoring assays in adult rats. The Tsc was determined at 30-min intervals for 5 h (TEF) or 4.5 h (BIF) after dosing. Rats were sacrificed at 6 h after dosing, and BIF and TEF concentrations were determined in blood (Bd), liver (Lv), and cerebellum (Cb) by using a GC-ECD system. The minimal effective dose of BIF (3 mg/kg) affecting Tsc was similar to that found in prior studies using other testing paradigms. Regarding TEF, a very steep relationship between the dose administered and toxicity was observed, with a near-threshold to low-effective range for Tsc at 0.1–6 mg/kg, and a near lethal syndrome at ≥ 7.5 mg/kg. At 6–7.5 mg/kg TEF, the Cb/Bd and Cb/Lv concentration ratios were both > 1. Conversely, for BIF, the Cb concentration was barely over the Bd concentration and the Cb/Lv concentration ratio remained < 1. Our results and previous findings call for more comprehensive consideration to establish the relevance of the distribution into target tissues and the tissue dosimetry for health risks through the exposure to PYRs in humans.