Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase 1 Study of Stereotactic Ablative Radiation Therapy for Polymetastatic Disease.

Purpose: This phase 1 study aimed to assess the safety and feasibility of SABR therapy delivery to all sites of polymetastatic disease (>10 metastases).

Methods And Materials: A 3 + 3 study design was used with 5 dose levels from 6 Gy (6 Gy × 1) to 30 Gy (6 Gy weekly × 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity or more than 3 grade 3 toxicities within 6 weeks of treatment.

Planning for the Effect of the SC.24 Trial on Spine Stereotactic Body Radiation Therapy Utilization at a Tertiary Cancer Center.

Purpose: The goal of this study was to assess the potential real-world effect of the recently reported SC.24 trial on spine stereotactic body radiation therapy (SBRT) utilization. We estimated the proportion of patients treated with conventional radiation therapy (CRT) who would have been eligible for spine SBRT per trial inclusion criteria and analyzed the potential estimated increased costs to our institution.

Dosimetric Planning Comparison for Left-Sided Breast Cancer Radiotherapy: The Clinical Feasibility of Four-Dimensional-Computed Tomography-Based Treatment Planning Optimization.

Background: Adjuvant whole-breast radiotherapy (RT) is a significant part of the standard of care treatment after breast cancer (BC) conserving surgery. Modern techniques including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have constituted to better target coverage and critical organs sparing. However, BC survivors are at risk of developing radiation-induced cardiac toxicity.

Imaging Biomarkers in Prostate Stereotactic Body Radiotherapy: A Review and Clinical Trial Protocol.

Advances in imaging have changed prostate radiotherapy through improved biochemical control from focal boost and improved detection of recurrence. These advances are reviewed in the context of prostate stereotactic body radiation therapy (SBRT) and the ARGOS/CLIMBER trial protocol. ARGOS/CLIMBER will evaluate 1) the safety and feasibility of SBRT with focal boost guided by multiparametric MRI (mpMRI) and F-PSMA-1007 PET and 2) imaging and laboratory biomarkers for response to SBRT.

Defining radio-recurrent intra-prostatic target volumes using PSMA-targeted PET/CT and multi-parametric MRI.

Purpose: Our purpose was to evaluate intra-prostatic cancer volumes for salvage radiotherapy in men with recurrent prostate cancer confined to the prostate post-primary radiotherapy using mpMRI and 18F-DCFPyL PET/CT (PET).

Methods: Men with biochemical failure post-primary radiotherapy were enrolled in a multi-centre trial investigating mpMRI and PET. All men with isolated intra-prostatic recurrence are included in this secondary analysis.

Can Polymetastatic Disease Be ARRESTed Using SABR? A Dosimetric Feasibility Study to Inform Development of a Phase 1 Trial.

Purpose: Phase 2 randomized trials suggest that stereotactic ablative radiation therapy improves progression-free and overall survival in patients with oligometastatic cancer, with phase 3 trials currently testing stereotactic ablative radiation therapy in up to 10 metastases. Whether stereotactic radiation therapy could provide similar benefits in polymetastatic disease (>10 metastases) is unknown. We sought to evaluate the dosimetric feasibility of using stereotactic radiation therapy in polymetastatic disease in preparation for a phase 1 trial.

Improving geometric sparing and therapeutic effectiveness of lung SBRT for central and ultra-central tumors.

The use of stereotactic body radiotherapy (SBRT) for central- and ultra-central lung tumors is a major therapeutic challenge since there are trade-offs between delivering adequate dose to the tumor and minimizing toxicity to critical mediastinal organs. This work investigates improving the therapeutic effectiveness of such SBRT treatments by enhancing the geometric sparing of normal tissue and systematically applying a planning target volume (PTV) margin smaller than the conventional values. Using plans from 10 previously SBRT-treated patients, we retrospectively created highly conformal plans with a reduced PTV margin of 2 mm and compared them to the clinical plans with a standard 5 mm PTV margin.

Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy.

Background: Patients with polymetastatic cancer are most often treated with systemic therapy to improve overall survival and/or delay progression, with palliative radiotherapy reserved for sites of symptomatic disease. Stereotactic ablative radiotherapy (SABR) has shown promise in the treatment of oligometastatic disease, but the utility of SABR in treating all sites of polymetastatic disease has yet to be evaluated. This study aims to evaluate the maximally tolerated dose (MTD) of SABR in patients with polymetastatic disease.

Dosimetric Evaluation of PSMA PET-Delineated Dominant Intraprostatic Lesion Simultaneous Infield Boosts.

Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control.

Repopulation of interacting tumor cells during fractionated radiotherapy: stochastic modeling of the tumor control probability.

Purpose: Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the "five Rs" (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider "stem-like cancer cells" (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant.

The effect of non-targeted cellular mechanisms on lung cancer risk for chronic, low level radon exposures.

Purpose: The goal of the present study was to investigate the effect of non-targeted mechanisms on the shape of the lung cancer risk function at chronic, low level radon exposures relative to direct cellular radiation effects. This includes detrimental and protective bystander effects, radio-adaptive bystander response, genomic instability and induction of apoptosis by surrounding cells.

Methods: To quantify the dependence of these mechanisms on dose, analytical functions were derived from the experimental evidence presently available.

Modeling progression in radiation-induced lung adenocarcinomas.

Quantitative multistage carcinogenesis models are used in radiobiology to estimate cancer risks and latency periods (time from exposure to clinical cancer). Steps such as initiation, promotion and transformation have been modeled in detail. However, progression, a later step during which malignant cells can develop into clinical symptomatic cancer, has often been approximated simply as a fixed lag time.

Stochastic population dynamic effects for lung cancer progression.

The multistage paradigm is widely used in quantitative analyses of radiation-influenced carcinogenesis. Steps such as initiation, promotion and transformation have been investigated in detail. However, progression, a later step during which malignant cells produced in the earlier steps can develop into clinical cancer, has received less attention in computational radiobiology; it has often been approximated deterministically as a fixed, comparatively short, lag time.

Triggering-response model for radiation-induced bystander effects.

We propose a mechanistic model for radiation cell killing and carcinogenesis-related end points that combines direct and bystander responses. The model describes the bystander component as a sequence of two distinct processes: triggering of signal emission from irradiated cells and response of nonirradiated recipient cells; in principle it can incorporate microdosimetric information as well as the random aspects of signal triggering and recipient response. Late effects are modeled using a one-stage model based on the concepts of inactivation and initiation, which allows for the proliferation of normal and initiated cells; proliferation of initiated cells is analyzed using a stochastic, birth-death approach.

Radon progeny microdosimetry in human and rat bronchial airways: the effect of crossfire from the alveolar region.

The objectives of the present study were (1) to present a comprehensive analysis of the microdosimetric quantities in both human and rat bronchial airways and (2) to assess the contribution of the crossfire alpha particles emitted from the alveolar region to bronchial absorbed doses. Hit frequencies, absorbed doses and critical microdosimetric quantities were calculated for basal and secretory cell nuclei located at different depths in epithelial tissue for each bronchial airway generation for defined exposure conditions. Total absorbed doses and hit frequencies were slightly higher in rat airways than in corresponding human airways.

Second cancers after fractionated radiotherapy: stochastic population dynamics effects.

When ionizing radiation is used in cancer therapy it can induce second cancers in nearby organs. Mainly due to longer patient survival times, these second cancers have become of increasing concern. Estimating the risk of solid second cancers involves modeling: because of long latency times, available data is usually for older, obsolescent treatment regimens.

Internal microdosimetry of inhaled radon progeny in bronchial airways: advantages and limitations.

The objective of the present study was to identify advantages and limitations of the application of microdosimetric concepts for inhaled radon progeny activities in the lungs. The methods employed for this analysis were a recently developed Monte-Carlo microdosimetry code for the calculation of energy deposition in bronchial target cells and the Probability Per Unit Track Length (PPUTL) model, which relates these microdosimetric parameters to cellular radiation effects. The major advantages of internal microdosimetry of radon progeny in bronchial airways are: (i) quantitative characterisation of non-uniform dose distributions and identification of target sites with enhanced carcinogenic potential, (ii) quantification of low doses of alpha particles by the number of cells hit and the dose received by those cells, (iii) illustration of the random variations of cellular doses by specific energy distributions and (iv) establishment of a direct link to cellular radiobiological effects.

Clusters of DNA double-strand breaks induced by different doses of nitrogen ions for various LETs: experimental measurements and theoretical analyses.

The yields and clustering of DNA double-strand breaks (DSBs) were investigated in normal human skin fibroblasts exposed to gamma rays or to a wide range of doses of nitrogen ions with various linear energy transfers (LETs). Data obtained by pulsed-field gel electrophoresis on the dose and LET dependence of DNA fragmentation were analyzed with the randomly located clusters (RLC) formalism. The formalism considers stochastic clustering of DSBs along a chromosome due to chromatin structure, particle track structure, and multitrack action.

Alpha-hit, cellular dose, cell transformation and inactivation probability distributions of radon progenies in the bronchial epithelium.

A fluid dynamics based model has been used to determine the deposition patterns of inhaled radon daughters in a realistic approach of the bronchial airway geometry. The interaction of the emitted alpha particles with epithelial cells has been analyzed by applying a complex hit probability model (Bronchial Alpha Hit Model). The biological response of the hit cells has been calculated by the Probability-Per-Unit-Track-Length Model, which relates the probability of a specific biological effect to the track length of alpha particles as a function of the particles' LET.