Dose prescription with spatial uncertainty for peripheral lung SBRT.

Current clinical practice is to prescribe to 95% of the planning target volume (PTV) in 4D stereotactic body radiotherapy (SBRT) for lung. Frequently the PTV margin has a very low physical density so that the internal target volume (ITV) receives an unnecessarily high dose. This study investigates the alternative of prescribing to the ITV while including the effects of positional uncertainties. Five patients were retrospectively studied with volumetric modulated arc therapy treatment plans. Five plans were produced for each patient: a static plan prescribed to PTV D95% , three probabilistic plans prescribed to ITV D95% and a static plan re-prescribed to ITV D95% after inverse planning. For the three probabilistic plans, the scatter kernel in the dose calculation was convolved with a spatial uncertainty distribution consisting of either a uniform distribution extending ±5 mm in the three orthogonal directions, a distribution consisting of delta functions at ±5 mm, or a Gaussian distribution with standard deviation 5 mm. Median ITV D50% is 23% higher than the prescribed dose for static planning and only 10% higher than the prescribed dose for prescription to the ITV. The choice of uncertainty distribution has less than 2% effect on the median ITV dose. Re-prescribing a static plan and evaluating with a probabilistic dose calculation results in a median ITV D95% which is 1.5% higher than when planning probabilistically. This study shows that a robust probabilistic approach to planning SBRT lung treatments results in the ITV receiving a dose closer to the intended prescription. The exact form of the uncertainty distribution is not found to be critical

Hierarchical Dobinski-type relations via substitution and the moment problem

We consider the transformation properties of integer sequences arising from the normal ordering of exponentiated boson ([a,a*]=1) monomials of the form exp(x (a*)^r a), r=1,2,..., under the composition of their exponential generating functions (egf). They turn out to be of Sheffer-type. We demonstrate that two key properties of these sequences remain preserved under substitutional composition: (a)the property of being the solution of the Stieltjes moment problem; and (b) the representation of these sequences through infinite series (Dobinski-type relations). We present a number of examples of such composition satisfying properties (a) and (b). We obtain new Dobinski-type formulas and solve the associated moment problem for several hierarchically defined combinatorial families of sequences.Comment: 14 pages, 31 reference

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: Efficacy and Toxicity in the DELINEATE Trial.

Purpose To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy.Methods and materials DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate- and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic resonance imaging. Fifty-five patients were treated in cohort A, and 158 patients were treated in cohort B; the first 50 sequentially treated patients in cohort B were included in this planned analysis. The primary endpoint was late Radiation Therapy Oncology Group rectal toxicity at 1 year. Secondary endpoints included acute and late toxicity measured with clinician- and patient-reported outcomes at other time points and biochemical relapse-free survival for cohort A. Median follow-up was 74.5 months for cohort A and 52.0 months for cohort B.Results In cohorts A and B, 27% and 40% of patients, respectively, were classified as having National Comprehensive Cancer Network high-risk disease. The cumulative 1-year incidence of Radiation Therapy Oncology Group grade 2 or worse rectal and urinary toxicity was 3.6% and 0% in cohort A and 8% and 10% in cohort B, respectively. There was no reported late grade 3 rectal toxicity in either cohort. Within cohort A, 4 of 55 (7%) patients had biochemical relapse.Conclusions Delivery of a simultaneous integrated boost to intraprostatic dominant nodules is feasible in prostate radiation therapy using standard and moderately hypofractionated regimens, with rectal and genitourinary toxicity comparable to contemporary series without an intraprostatic boost

Clinical Implementation of Robust Multi-isocentric Volumetric Modulated Arc Radiotherapy for Craniospinal Irradiation.

AIMS: To determine if multi-isocentric volumetric modulated arc radiotherapy for craniospinal irradiation (CSI-VMAT) can be implemented safely and accurately using robust optimisation in a commercially available treatment planning system. Our initial clinical experience is reported for the first 20 patients treated with the technique. MATERIALS AND METHODS: Patients received between 23.4 and 39.6 Gy (mode 23.4 Gy) in 13-22 fractions with CSI-VMAT. The heart mean dose was 4.2-10.3 Gy (median 5.3 Gy) for patients prescribed up to 24 Gy and 6.5-16.3 Gy (median 10.1 Gy) for patients receiving 35 Gy or more. The lung mean dose was 5.5-7.6 Gy (median 6.8 Gy) for patients prescribed up to 24 Gy and 6.9-11.1 Gy (median 10.0 Gy) for patients receiving 35 Gy or more. The robustness of the planning target volume D0.1cm3 and D99% to systematic errors in the isocentre superoinferior position of up to 5 mm was evaluated. These remained acceptable but were correlated to the length of the available beam overlap through the neck. RESULTS: As of January 2021, one patient was deceased after 508 days and one patient was lost to follow-up after completing treatment. The median follow-up was 399 days (range 175-756 days) and progression-free survival was 131 days (34-490 days). Acute toxicities at Common Terminology Criteria for Adverse Events v5.0 grade 3+ included lowered white blood cell count (16/20), decreased platelet count (8/20), nausea (5/20), vomiting (2/20), pharyngeal mucositis (1/20) and oral mucositis (1/20). Three patients developed grade 4 neutropenia or decreased white blood cell count. CONCLUSIONS: CSI-VMAT can be implemented safely and accurately using robust optimisation functions in a commercially available treatment planning system