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Purpose: The safe clinical implementation of pencil beam scanning (PBS) proton therapy for lung tumors is complicated by the delivery uncertainties caused by breathing motion. The purpose of this feasibility study was to investigate whether a voluntary breath-hold technique could limit the delivery uncertainties resulting from interfractional motion., Methods and Materials: Data from 15 patients with peripheral lung tumors previously treated with stereotactic radiation therapy were included in this study. The patients had 1 computed tomographic (CT) scan in voluntary breath-hold acquired before treatment and 3 scans during the treatment course. PBS proton treatment plans with 2 fields (2F) and 3 fields (3F), respectively, were calculated based on the planning CT scan and subsequently recalculated on the 3 repeated CT scans. Recalculated plans were considered robust if the V95% (volume receiving ≥95% of the prescribed dose) of the gross target volume (GTV) was within 5% of what was expected from the planning CT data throughout the simulated treatment., Results: A total of 14/15 simulated treatments for both 2F and 3F met the robustness criteria. Reduced V95% was associated with baseline shifts (2F, P=.056; 3F, P=.008) and tumor size (2F, P=.025; 3F, P=.025). Smaller tumors with large baseline shifts were also at risk for reduced V95% (interaction term baseline/size: 2F, P=.005; 3F, P=.002)., Conclusions: The breath-hold approach is a realistic clinical option for treating lung tumors with PBS proton therapy. Potential risk factors for reduced V95% are small targets in combination with large baseline shifts. On the basis of these results, the baseline shift of the tumor should be monitored (eg, through image guided therapy), and appropriate measures should be taken accordingly. The intrafractional motion needs to be investigated to confirm that the breath-hold approach is robust., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To determine the potential association between genitourinary (GU) toxicity and planning dose-volume parameters for GU pelvic structures after high-dose intensity modulated radiation therapy in localized prostate cancer patients., Methods and Materials: A total of 268 patients who underwent intensity modulated radiation therapy to a prescribed dose of 86.4 Gy in 48 fractions during June 2004-December 2008 were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Dose-volume histograms of the whole bladder, bladder wall, urethra, and bladder trigone were analyzed. The primary endpoint for GU toxicity was an IPSS sum increase ≥10 points over baseline. Univariate and multivariate analyses were done by the Kaplan-Meier method and Cox proportional hazard models, respectively., Results: Median follow-up was 5 years (range, 3-7.7 years). Thirty-nine patients experienced an IPSS sum increase ≥10 during follow-up; 84% remained event free at 5 years. After univariate analysis, lower baseline IPSS sum (P=.006), the V90 of the trigone (P=.006), and the maximal dose to the trigone (P=.003) were significantly associated with an IPSS sum increase ≥10. After multivariate analysis, lower baseline IPSS sum (P=.009) and increased maximal dose to the trigone (P=.005) remained significantly associated. Seventy-two patients had both a lower baseline IPSS sum and a higher maximal dose to the trigone and were defined as high risk, and 68 patients had both a higher baseline IPSS sum and a lower maximal dose to the trigone and were defined as low risk for development of an IPSS sum increase ≥10. Twenty-one of 72 high-risk patients (29%) and 5 of 68 low-risk patients (7%) experienced an IPSS sum increase ≥10 (P=.001; odds ratio 5.19)., Conclusions: The application of hot spots to the bladder trigone was significantly associated with relevant changes in IPSS during follow-up. Reduction of radiation dose to the lower bladder and specifically the bladder trigone seems to be associated with a reduction in late GU toxicity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data., Methods and Materials: Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data., Results: The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range., Conclusions: Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Hodgkin lymphoma (HL) survivors are at an increased risk of stroke because of carotid artery irradiation. However, for early-stage HL involved node radiation therapy (INRT) reduces the volume of normal tissue exposed to high doses. Here, we evaluate 3-dimensional conformal radiation therapy (3D-CRT), volumetric-modulated arc therapy (VMAT), and proton therapy (PT) delivered as INRT along with the extensive mantle field (MF) by comparing doses to the carotid arteries and corresponding risk estimates., Methods and Materials: We included a cohort of 46 supradiaphragmatic stage I-II classical HL patients. All patients were initially treated with chemotherapy and INRT delivered as 3D-CRT (30 Gy). For each patient, we simulated MF (36 Gy) and INRT plans using VMAT and PT (30 Gy). Linear dose-response curves for the 20-, 25-, and 30-year risk of stroke were derived from published HL data. Risks of stroke with each technique were calculated for all patients. Statistical analyses were performed with repeated measures analysis of variance., Results: The mean doses to the right and left common carotid artery were significantly lower with modern treatment compared with MF, with substantial patient variability. The estimated excess risk of stroke after 20, 25, and 30 years was 0.6%, 0.86%, and 1.3% for 3D-CRT; 0.67%, 0.96%, and 1.47% for VMAT; 0.61%, 0.96%, and 1.33% for PT; and 1.3%, 1.72%, and 2.61% for MF., Conclusions: INRT reduces the dose delivered to the carotid arteries and corresponding estimated risk of stroke for HL survivors. Even for the subset of patients with lymphoma close to the carotid arteries, the estimated risk is low., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: Hodgkin lymphoma (HL) survivors are known to have increased cardiac mortality and morbidity. The risk of developing cardiovascular disease after involved node radiotherapy (INRT) is currently unresolved, inasmuch as present clinical data are derived from patients treated with the outdated mantle field (MF) technique., Methods and Materials: We included all adolescents and young adults with supradiaphragmatic, clinical Stage I-II HL treated at our institution from 2006 to 2010 (29 patients). All patients were treated with chemotherapy and INRT to 30 to 36 Gy. We then simulated a MF plan for each patient with a prescribed dose of 36 Gy. A logistic dose-response curve for the 25-year absolute excess risk of cardiovascular disease was derived and applied to each patient using the individual dose-volume histograms., Results: The mean doses to the heart, four heart valves, and coronary arteries were significantly lower for INRT than for MF treatment. However, the range in doses with INRT treatment was substantial, and for a subgroup of patients, with lymphoma below the fourth thoracic vertebrae, we estimated a 25-year absolute excess risk of any cardiac event of as much as 5.1%., Conclusions: Our study demonstrates a potential for individualizing treatment by selecting the patients for whom INRT provides sufficient cardiac protection for current technology; and a subgroup of patients, who still receive high cardiac doses, who would benefit from more advanced radiation technique., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Artifacts impacting the imaged tumor volume can be seen in conventional three-dimensional CT (3DCT) scans for planning of lung cancer radiotherapy but can be reduced with the use of respiration-correlated imaging, i.e., 4DCT or breathhold CT (BHCT) scans. The aim of this study was to compare delineated gross tumor volume (GTV) sizes in 3DCT, 4DCT, and BHCT scans of patients with lung tumors., Methods and Materials: A total of 36 patients with 46 tumors referred for stereotactic radiotherapy of lung tumors were included. All patients underwent positron emission tomography (PET)/CT, 4DCT, and BHCT scans. GTVs in all CT scans of individual patients were delineated during one session by a single physician to minimize systematic delineation uncertainty. The GTV size from the BHCT was considered the closest to true tumor volume and was chosen as the reference. The reference GTV size was compared to GTV sizes in 3DCT, at midventilation (MidV), at end-inspiration (Insp), and at end-expiration (Exp) bins from the 4DCT scan., Results: The median BHCT GTV size was 4.9 cm(3) (0.1-53.3 cm(3)). Median deviation between 3DCT and BHCT GTV size was 0.3 cm(3) (-3.3 to 30.0 cm(3)), between MidV and BHCT size was 0.2 cm(3) (-5.7 to 19.7 cm(3)), between Insp and BHCT size was 0.3 cm(3) (-4.7 to 24.8 cm(3)), and between Exp and BHCT size was 0.3 cm(3) (-4.8 to 25.5 cm(3)). The 3DCT, MidV, Insp, and Exp median GTV sizes were all significantly larger than the BHCT median GTV size., Conclusions: In the present study, the choice of CT method significantly influenced the delineated GTV size, on average, leading to an increase in GTV size compared to the reference BHCT. The uncertainty caused by artifacts is estimated to be in the same magnitude as delineation uncertainty and should be considered in the design of margins for radiotherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)