T. Zhuang

30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

PURPOSE To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. METHODS AND MATERIALS Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. RESULTS For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gy and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). CONCLUSIONS This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.

Dose calculation differences between Monte Carlo and pencil beam depend on the tumor locations and volumes for lung stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) has been increasingly used as an efficacious treatment modality for early‐stage non‐small cell lung cancer. The accuracy of dose calculations is compromised due to the presence of inhomogeneity. For the purpose of a consistent prescription, radiation doses were calculated without heterogeneity correction in several RTOG trials. For patients participating in these trials, recalculations of the planned doses with more accurate dose methods could provide better correlations between the treatment outcomes and the planned doses. Using a Monte Carlo (MC) dose calculation algorithm as a gold standard, we compared the recalculated doses with the MC algorithm to the original pencil beam (PB) calculations for our institutional clinical lung SBRT plans. The focus of this comparison is to investigate the volume and location dependence on the differences between the two dose calculations. Thirty‐one clinical plans that followed RTOG and other protocol guidelines were retrospectively investigated in this study. Dosimetric parameters, such as D1, D95, and D99 for the PTV and D1 for organs at risk, were compared between two calculations. Correlations of mean lung dose and V20 of lungs between two calculations were investigated. Significant dependence on tumor size and location was observed from the comparisons between the two dose calculation methods. When comparing the PB calculations without heterogeneity correction to the MC calculations with heterogeneity correction, we found that in terms of D95 of PTV: (1) the two calculations resulted in similar D95 for edge tumors with volumes greater than 25.1 cc; (2) an average overestimation of 5% in PB calculations for edge tumors with volumes less than 25.1 cc; and (3) an average overestimation of 9% or underestimation of 3% in PB calculations for island tumors with volumes smaller or greater than 22.6 cc, respectively. With heterogeneity correction, the PB calculations resulted in an average reduction of 23.8% and 15.3% in the D95 for the PTV for island and edge lesions, respectively, when compared to the MC calculations. For organs at risks, very small differences were found among all the comparisons. Excellent correlations for mean dose and V20 of lungs were observed between the two calculations. This study demonstrated that using a single scaling factor may be overly simplified when accounting for the effects of heterogeneity correction. Accurate dose calculations, such as the Monte Carlo algorithms, are highly recommended to understand dose responses in lung SBRT. PACS number: 87.53.Ly

A Histologic Basis for the Efficacy of SBRT to the lung

Purpose: Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early‐stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established. Methods: We analyzed 740 patients with early‐stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression. Results: Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3‐year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7–25.1), 8.7% (95% CI: 4.6–12.8), and 4.1% (95% CI: 0–9.6), respectively. Conclusion: Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.

Dose differences in intensity‐modulated radiotherapy plans calculated with pencil beam and Monte Carlo for lung SBRT

For patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy, early treatment plans were based on a simpler dose calculation algorithm, the pencil beam (PB) calculation. Because these patients had the longest treatment follow-up, identifying dose differences between the PB calculated dose and Monte Carlo calculated dose is clinically important for understanding of treatment outcomes. Previous studies found significant dose differences between the PB dose calculation and more accurate dose calculation algorithms, such as convolution-based or Monte Carlo (MC), mostly for three-dimensional conformal radiotherapy (3D CRT) plans. The aim of this study is to investigate whether these observed dose differences also exist for intensity-modulated radiotherapy (IMRT) plans for both centrally and peripherally located tumors. Seventy patients (35 central and 35 peripheral) were retrospectively selected for this study. The clinical IMRT plans that were initially calculated with the PB algorithm were recalculated with the MC algorithm. Among these paired plans, dosimetric parameters were compared for the targets and critical organs. When compared to MC calculation, PB calculation overestimated doses to the planning target volumes (PTVs) of central and peripheral tumors with different magnitudes. The doses to 95% of the central and peripheral PTVs were overestimated by 9.7%±5.6% and 12.0%±7.3%, respectively. This dose overestimation did not affect doses to the critical organs, such as the spinal cord and lung. In conclusion, for NSCLC treated with IMRT, dose differences between the PB and MC calculations were different from that of 3D CRT. No significant dose differences in critical organs were observed between the two calculations. PACS number: 87.53.Ly.For patients with medically inoperable early‐stage non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy, early treatment plans were based on a simpler dose calculation algorithm, the pencil beam (PB) calculation. Because these patients had the longest treatment follow‐up, identifying dose differences between the PB calculated dose and Monte Carlo calculated dose is clinically important for understanding of treatment outcomes. Previous studies found significant dose differences between the PB dose calculation and more accurate dose calculation algorithms, such as convolution‐based or Monte Carlo (MC), mostly for three‐dimensional conformal radiotherapy (3D CRT) plans. The aim of this study is to investigate whether these observed dose differences also exist for intensity‐modulated radiotherapy (IMRT) plans for both centrally and peripherally located tumors. Seventy patients (35 central and 35 peripheral) were retrospectively selected for this study. The clinical IMRT plans that were initially calculated with the PB algorithm were recalculated with the MC algorithm. Among these paired plans, dosimetric parameters were compared for the targets and critical organs. When compared to MC calculation, PB calculation overestimated doses to the planning target volumes (PTVs) of central and peripheral tumors with different magnitudes. The doses to 95% of the central and peripheral PTVs were overestimated by 9.7%±5.6% and 12.0%±7.3%, respectively. This dose overestimation did not affect doses to the critical organs, such as the spinal cord and lung. In conclusion, for NSCLC treated with IMRT, dose differences between the PB and MC calculations were different from that of 3D CRT. No significant dose differences in critical organs were observed between the two calculations. PACS number: 87.53.Ly

Stereotactic Radiosurgery for the Treatment of Primary and Metastatic Spinal Sarcomas

Purpose: Despite advancements in local and systemic therapy, metastasis remains common in the natural history of sarcomas. Unfortunately, such metastases are the most significant source of morbidity and mortality in this heterogeneous disease. As a classically radioresistant histology, stereotactic radiosurgery has emerged to control spinal sarcomas and provide palliation. However, there is a lack of data regarding pain relief and relapse following stereotactic radiosurgery. Methods: We queried a retrospective institutional database of patients who underwent spine stereotactic radiosurgery for primary and metastatic sarcomas. The primary outcome was pain relief following stereotactic radiosurgery. Secondary outcomes included progression of pain, radiographic failure, and development of toxicities following treatment. Results: Forty treatment sites were eligible for inclusion; the median prescription dose was 16 Gy in a single fraction. Median time to radiographic failure was 14 months. At 6 and 12 months, radiographic control was 63% and 51%, respectively. Among patients presenting with pain, median time to pain relief was 1 month. Actuarial pain relief at 6 months was 82%. Median time to pain progression was 10 months; at 12 months, actuarial pain progression was 51%. Following multivariate analysis, presence of neurologic deficit at consult (hazard ratio: 2.48, P < .01) and presence of extraspinal bone metastases (hazard ratio: 2.83, P < .01) were associated with pain relief. Greater pain at consult (hazard ratio: 1.92, P < .01), prior radiotherapy (hazard ratio: 4.65, P = .02), and greater number of irradiated vertebral levels were associated with pain progression. Conclusions: Local treatment of spinal sarcomas has remained a challenge for decades, with poor rates of local control and limited pain relief following conventional radiotherapy. In this series, pain relief was achieved in 82% of treatments at 6 months, with half of patients experiencing pain progression by 12 months. Given minimal toxicity and suboptimal pain control at 12 months, dose escalation beyond 16 Gy is warranted.

Impact of small MU/segment and dose rate on delivery accuracy of volumetric-modulated arc therapy (VMAT).

Volumetric‐modulated arc therapy (VMAT) plans may require more control points (or segments) than some of fixed‐beam IMRT plans that are created with a limited number of segments. Increasing number of control points in a VMAT plan for a given prescription dose could create a large portion of the total number of segments with small number monitor units (MUs) per segment. The purpose of this study is to investigate the impact of the small number MU/segment on the delivery accuracy of VMAT delivered with various dose rates. Ten patient datasets were planned for hippocampus sparing for whole brain irradiation. For each dataset, two VMAT plans were created with maximum dose rates of 600 MU/min (the maximum field size of 21×40 cm2) and 1000 MU/min (the maximum field size of 15×15 cm2) for a daily dose of 3 Gy. Without reoptimization, the daily dose of these plans was purposely reduced to 1.5 Gy and 1.0 Gy while keeping the same total dose. Using the two dose rates and three different daily doses, six VMAT plans for each dataset were delivered to a physical phantom to investigate how the changes of dose rate and daily doses impact on delivery accuracy. Using the gamma index, we directly compared the delivered planar dose profiles with the reduced daily doses (1.5 Gy and 1.0 Gy) to the delivered planar dose at 3 Gy daily dose, delivered at dose rate of 600 MU/min and 1000 MU/min, respectively. The average numbers of segments with MU/segment≤1 were 35±8, 87±6 for VMAT‐600 1.5 Gy, VMAT‐600 1 Gy plans, and 30±7 and 42±6 for VMAT‐1000 1.5 Gy and VMAT‐1000 1 Gy plans, respectively. When delivered at 600 MU/min dose rate, the average gamma index passing rates (1%/1 mm criteria) of comparing delivered 1.5 Gy VMAT planar dose profiles to 3.0 Gy VMAT delivered planar dose profiles was 98.28%±1.66%, and the average gamma index passing rate of comparing delivered 1.0 Gy VMAT planar dose to 3.0 Gy VMAT delivered planar dose was 83.75%±4.86%. If using 2%/2 mm and 3%/3 mm criteria, the gamma index passing rates were greater than 97% for both 1.5 Gy VMAT and 1.0 Gy VMAT delivered planar doses. At 1000 MU/min dose rate, the average gamma index passing rates were 96.59%±2.70% for 1.5 Gy VMAT planar dose profiles and 79.37%±9.96% for 1.0 Gy VMAT planar dose profiles when compared to the 3.0 Gy VMAT planar delivered dose profile. When using 2%/2 mm and 3%/3 mm criteria, the gamma index passing rates were greater than 93% for both 1.5 Gy VMAT and 1.0 Gy VMAT planar delivered dose. Under a stricter gamma index criterion (1%/1 mm), significant differences in delivered planar dose profiles at different daily doses were detected, indicating that the known communication delay between the MU console and MLC console may affect VMAT delivery accuracy. PACS number(s): 87.56.bd, 87.55.‐xVolumetric-modulated arc therapy (VMAT) plans may require more control points (or segments) than some of fixed-beam IMRT plans that are created with a limited number of segments. Increasing number of control points in a VMAT plan for a given prescription dose could create a large portion of the total number of segments with small number monitor units (MUs) per segment. The purpose of this study is to investigate the impact of the small number MU/segment on the delivery accuracy of VMAT delivered with various dose rates. Ten patient datasets were planned for hippocampus sparing for whole brain irradiation. For each dataset, two VMAT plans were created with maximum dose rates of 600 MU/min (the maximum field size of 21×40 cm2) and 1000 MU/min (the maximum field size of 15×15 cm2) for a daily dose of 3 Gy. Without reoptimization, the daily dose of these plans was purposely reduced to 1.5 Gy and 1.0 Gy while keeping the same total dose. Using the two dose rates and three different daily doses, six VMAT plans for each dataset were delivered to a physical phantom to investigate how the changes of dose rate and daily doses impact on delivery accuracy. Using the gamma index, we directly compared the delivered planar dose profiles with the reduced daily doses (1.5 Gy and 1.0 Gy) to the delivered planar dose at 3 Gy daily dose, delivered at dose rate of 600 MU/min and 1000 MU/min, respectively. The average numbers of segments with MU/segment≤1 were 35±8, 87±6 for VMAT-600 1.5 Gy, VMAT-600 1 Gy plans, and 30±7 and 42±6 for VMAT-1000 1.5 Gy and VMAT-1000 1 Gy plans, respectively. When delivered at 600 MU/min dose rate, the average gamma index passing rates (1%/1 mm criteria) of comparing delivered 1.5 Gy VMAT planar dose profiles to 3.0 Gy VMAT delivered planar dose profiles was 98.28%±1.66%, and the average gamma index passing rate of comparing delivered 1.0 Gy VMAT planar dose to 3.0 Gy VMAT delivered planar dose was 83.75%±4.86%. If using 2%/2 mm and 3%/3 mm criteria, the gamma index passing rates were greater than 97% for both 1.5 Gy VMAT and 1.0 Gy VMAT delivered planar doses. At 1000 MU/min dose rate, the average gamma index passing rates were 96.59%±2.70% for 1.5 Gy VMAT planar dose profiles and 79.37%±9.96% for 1.0 Gy VMAT planar dose profiles when compared to the 3.0 Gy VMAT planar delivered dose profile. When using 2%/2 mm and 3%/3 mm criteria, the gamma index passing rates were greater than 93% for both 1.5 Gy VMAT and 1.0 Gy VMAT planar delivered dose. Under a stricter gamma index criterion (1%/1 mm), significant differences in delivered planar dose profiles at different daily doses were detected, indicating that the known communication delay between the MU console and MLC console may affect VMAT delivery accuracy. PACS number(s): 87.56.bd, 87.55.-x.

Dosimetric effect of uncorrected rotations in lung SBRT with stereotactic imaging guidance

PURPOSE To evaluate the dosimetric impact of uncorrected rotations on the planning target volume (PTV) coverage for early stage non-small cell lung cancer patients treated with stereotactic body radiotherapy using Brainlab ExacTrac image guidance. METHODS Twenty-two patients were retrospectively selected. Two scenarios of uncorrected rotations were simulated with magnitude of 1°, 2°, 3° and 5°: (1) rotation around the treatment isocenter; and (2) roll and yaw rotations around a setup isocenter. The D95 of PTV from recalculated dose on the rotated CT was compared to that from the clinical plan. A logistic regression model was used to predict the probability of dose differences between recalculated and original plans that are less than 2% based on the rotation angle, PTV volume, and distance between the treatment and setup isocenter. RESULTS Logistic regression model showed the uncorrected isocentric rotations of up to 2.5° in all directions have negligible dosimetric impact. For non-isocentric rotations, a rotational error of 2° may cause significant under-dose of the PTV. Statistically significant (p<0.05) parameters in the logistic regression model were angle for isocentric rotations, angle and distance for non-isocentric roll rotations, and angle, distance and the PTV volume for non-isocentric yaw rotations. CONCLUSIONS The severity of the dose deviations due to uncorrected rotations depends on the type and magnitude of the rotation, the volume of the PTV, and the distance between the treatment and setup isocenter, which should be taken into consideration when making clinical judgment of whether the rotational error could be ignored.

Treatment plan quality and delivery accuracy assessments on 3 IMRT delivery methods of stereotactic body radiotherapy for spine tumors

Stereotactic body radiotherapy (SBRT) for spine tumors has demonstrated clinical effectiveness. The treatment planning and delivery techniques have evolved from dynamic conformal arc therapy, to fixed gantry angle intensity modulated radiotherapy (IMRT), and most recently to volumetric modulated arc therapy (VMAT). A hybrid-arc (HARC) planning and delivery method combining dynamic conformal arc therapy delivery with a number of equally spaced IMRT beams is proposed. In this study we investigated plan quality, delivery accuracy, and efficiency of 3 delivery techniques: IMRT, HARC, and VMAT. Patients who underwent spine SBRT treatments were randomly selected from an Institutional Review Board-approved registry. For each patient, the prescription dose was 14 to 16 Gy in a single fraction to cover >90% of the tumor (without planning margin) while constraining V10Gy ≤ 10% of the spinal cord and the maximum point dose (MPD) of the spinal cord ≤ 14 Gy. All cases were clinically treated with fixed gantry step-shoot IMRT plans and then re-planned with VMAT using Pinnacle 9.0 and with HARC using Brainlab iPlan 4.5. Student t-test was used to compare the dosimetric end points, including V16Gy to the planning target volume, homogeneity index, MPDPTV, the conformity index, V10Gy of the spinal cord, and MPDcord. To compare the accuracy of delivery, we delivered all plans on a phantom and conducted gamma index (GI) comparisons with 3 mm/3% and 2 mm/2% criteria. All plans met our clinical requirements. Among 3 techniques, there were no differences on dose coverage to the tumor volume, maximum dose to the spinal cord, and plan homogeneity index (p > 0.05). The average V10Gy of the spinal cord was 6.66 ± 0.03%, 5.49 ± 0.03%, and 4.76 ± 0.02% for IMRT, HARC, and VMAT plans, respectively. Accordingly, the conformity indices were 1.30 ± 0.11 and 1.29 ± 0.20, 1.53 ± 0.29, respectively. VMAT plans were significantly (p < 0.05) less conformal but significantly (p < 0.05) lower V10Gy of the spinal cord than those from HARC and IMRT plans. With delivery accuracy measured by GIs, the average GIs of 3%/3 mm were 92.6 ± 1.1%, 96.5 ± 2.7%, 99.0 ± 1.1% for IMRT, HARC, and VMAT plans, respectively. The differences were significant (p < 0.05). Accordingly, the average monitor units were 9238 ± 2242, 9853 ± 2548 and 5091 ± 910. The plan quality created from the 3 planning techniques can meet the clinical requirement. Adding arc beams in delivery such as in HARC and VMAT plans improves the delivery accuracy. VMAT is the most efficient delivery method.

Dosimetric differences between local failure and local controlled non-small cell lung cancer patients treated with stereotactic body radiotherapy: A matched-pair study

Concerns were raised about the accuracy of pencil beam (PB) calculation and potential underdosing of medically inoperable non‐small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). From our institutional series, we designed a matched‐pair study where each local failure and controlled patient was matched based upon several clinical factors, to investigate the dose difference between the matched‐pair.

Investigation of Brachial Plexus Dose that Exceeds RTOG Constraints in Apical Lung Tumors Treated by Five Fraction Stereotactic Body Radiation Therapy

Purpose/objectivess We sought to determine the rate of brachial plexopathy (BPX) in patients exceeding RTOG dose constraints for treatment of apical lung tumors. Materials/methods Patients with apical lung tumors treated with four- or five-fraction SBRT were identified from a prospective registry. Dosimetric data were obtained for ipsilateral subclavian vein (SCV) and anatomic BP (ABP) contours. Cumulative equivalent dose in 2 Gy equivalents (EQD2) was calculated for the SCV contour in patients with a history of prior ipsilateral RT. Five-fraction SBRT RTOG constraints of D0.03cc ≤32.0 Gy and D3cc ≤30.0 Gy were used. BPX was graded according to Common Terminology Criteria for Adverse Events 3.0. Results A total of 64 patients met inclusion criteria. Median follow-up was 21 months. Six patients (9.4%) had prior ipsilateral conventional fractionated RT with varying degrees of overlap with subsequent SBRT field. Eleven patients without prior ipsilateral RT exceeded D0.03cc ≤32.0 Gy to SCV (mean 43.8 Gy ± 5.8). No BPX was observed in these patients. Out of the six patients who had prior ipsilateral RT, three patients exceeded D0.03cc ≤32.0 Gy to SCV (44.2 Gy ± 11.3), with two of these patients developing Grade 2 BPX within one year of SBRT. The EQD2 cumulative maximum point dose to BP was 122.6 Gy and 184.7 Gy for the two patients who developed Grade 2 BPX. The D0.03cc was >10 Gy higher to the ABP contour than the SCV contour in 14 patients. Conclusion Without a history of prior ipsilateral RT, no BPX was observed at 21 month follow-up in 11 patients who exceeded the RTOG five-fraction BP constraint. This observation is hypothesis generating and more experience with longer follow-up is necessary to validate these findings. For tumors located in close proximity to apical structures, there was substantial variation in dose between the ABP and SCV contours.