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A critical aspect of highly potent regimens such as lung stereotactic body radiation therapy (SBRT) is to avoid collateral toxicity while achieving planning target volume (PTV) coverage. In this work, we describe four dimensional conformal radiotherapy (4D CRT) using a highly parallelizable swarm intelligence-based stochastic optimization technique. Conventional lung CRT-SBRT uses a 4DCT to create an internal target volume (ITV) and then, using forward-planning, generates a 3D conformal plan. In contrast, we investigate an inverse-planning strategy that uses 4DCT data to create a 4D conformal plan, which is optimized across the three spatial dimensions (3D) as well as time, as represented by the respiratory phase. The key idea is to use respiratory motion as an additional degree of freedom. We iteratively adjust fluence weights for all beam apertures across all respiratory phases considering OAR sparing, PTV coverage and delivery efficiency. To demonstrate proof-of-concept, five non-small-cell lung cancer SBRT patients were retrospectively studied. The 4D optimized plans achieved PTV coverage comparable to the corresponding clinically delivered plans while showing significantly superior OAR sparing ranging from 26% to 83% for Dmax heart, 10% to 41% for Dmax esophagus, 31% to 68% for Dmax spinal cord and 7% to 32% for V13 lung.

Survivors of childhood brain tumors may be at risk for early onset of metabolic syndrome, possibly secondary to surgery and/or radiation exposure. This study examines effects of radiation exposure to hypothalamus-pituitary-adrenal axis (HPA) on metabolic risk among survivors of childhood brain tumors. One hundred forty-two met inclusion criteria; 60 had tumor surgery plus radiation exposure (>1 Gray (Gy)) to HPA. The second subgroup of 82 subjects had surgery only and were not exposed to radiation. Both subgroups had survived for approximately 5 years at the time of study. All had clinical evaluation, vital signs, anthropometry, measurement of body composition by dual X-ray absorptiometry and fasting laboratory assays (metabolic panel, insulin, C-peptide, insulin-like growth factor-1, leptin and adiponectin). Body composition data for both subgroups was compared with the National Health and Nutrition Survey (NHANES) subgroup of similar age, gender and body mass index. Cranial surgery was associated with obesity of similar severity in both subgroups. However, survivors exposed to radiation to the HPA also had increased visceral fat mass and high prevalence of growth hormone deficiency and metabolic syndrome. Fat mass alone did not explain the prevalence of the metabolic syndrome in radiation exposure subgroup. Other factors such as growth hormone deficiency may have contributed to metabolic risk. We conclude that prevalence of metabolic syndrome among subjects exposed to hypothalamic radiation was higher than expected from hypothalamic obesity alone. Radiation exposure may exert untoward endocrinopathies due to HPA exposure that worsens metabolic risk. Early screening for metabolic syndrome in this population is indicated.

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To our knowledge, this is the first systematic investigation of functional avoidance in lung SAbR based on mapping and minimizing doses to individual bronchial segments. Our early results show that it is possible to substantially lower airway dosage. Such dosage reduction may potentially reduce the risk of radiation-induced airway injury, while satisfying clinically prescribed dosimetric objectives.