Beyond conventional bounds: Surpassing system limits for stereotactic ablative (SAbR) lung radiotherapy using CBCT-based adaptive planning system.

PURPOSE: Online adaptive radiotherapy relies on a high degree of automation to enable rapid planning procedures. The Varian Ethos intelligent optimization engine (IOE) was originally designed for conventional treatments so it is crucial to provide clear guidance for lung SAbR plans. This study investigates using the Ethos IOE together with adaptive-specific optimization tuning structures we designed and templated within Ethos to mitigate inter-planner variability in meeting RTOG metrics for both online-adaptive and offline SAbR plans. METHODS: We developed a planning strategy to automate the generation of tuning structures and optimization. This was validated by retrospective analysis of 35 lung SAbR cases (total 105 fractions) treated on Ethos. The effectiveness of our planning strategy was evaluated by comparing plan quality with-and-without auto-generated tuning structures. Internal target volume (ITV) contour was compared between that drawn from CT simulation and from cone-beam CT (CBCT) at time of treatment to verify CBCT image quality and treatment effectiveness. Planning strategy robustness for lung SAbR was quantified by frequency of plans meeting reference plan RTOG constraints. RESULTS: Our planning strategy creates a gradient within the ITV with maximum dose in the core and improves intermediate dose conformality on average by 2%. ITV size showed no significant difference between those contoured from CT simulation and first fraction, and also trended towards decreasing over course of treatment. Compared to non-adaptive plans, adaptive plans better meet reference plan goals (37% vs. 100% PTV coverage compliance, for scheduled and adapted plans) while improving plan quality (improved GI (gradient index) by 3.8%, CI (conformity index) by 1.7%). CONCLUSION: We developed a robust and readily shareable planning strategy for the treatment of adaptive lung SAbR on the Ethos system. We validated that automatic online plan re-optimization along with the formulated adaptive tuning structures can ensure consistent plan quality. With the proposed planning strategy, highly ablative treatments are feasible on Ethos.

Adapt-On-Demand: A Novel Strategy for Personalized Adaptive Radiation Therapy for Locally Advanced Lung Cancer.

PURPOSE: Real-time adaptation of thoracic radiation plans is compelling because offline adaptive experiences show that tumor volumes and lung anatomy can change during therapy. We present and analyze a novel adaptive-on-demand (AOD) workflow combining online adaptive radiation therapy (o-ART) on the ETHOS system with image guided radiation therapy delivery on a Halcyon unit for conventional fractionated radiation therapy of locally advanced lung cancer (LALC). METHODS AND MATERIALS: We analyzed 26 patients with LALC treated with the AOD workflow, adapting weekly. We timed segments of the workflow to evaluate efficiency in a real-world clinic. Target coverage and organ at risk (OAR) doses were compared between adaptive plans (ADP) and nonadaptive scheduled plans (SCH). Planning robustness was evaluated by the frequency of preplanning goals achieved in ADP plans, stratified by tumor volume change. RESULTS: The AOD workflow was achievable within 30 minutes for most radiation fractions. Over the course of therapy, we observed an average 26.6% ± 23.3% reduction in internal target volume (ITV). Despite these changes, with o-ART, ITV and planning target volume (PTV) coverage (V100%) was 99.2% and 93.9% for all members of the cohort, respectively. This represented a 2.9% and 6.8% improvement over nonadaptive plans (P < .05), respectively. For tumors that grew >10%, V100% was 93.1% for o-ART and 76.4% for nonadaptive plans, representing a median 17.2% improvement in the PTV coverage (P < .05). In these plans, critical OAR constraints were met 94.1% of the time, whereas in nonadaptive plans, this figure was 81.9%. This represented reductions of 1.32 Gy, 1.34 Gy, or 1.75 Gy in the heart, esophagus, and lung, respectively. The effect was larger when tumors had shrunk more than 10%. Regardless of tumor volume alterations, the PTV/ITV coverage was achieved for all adaptive plans. Exceptional cases, where dose constraints were not met, were due to large initial tumor volumes or tumor growth. CONCLUSIONS: The AOD workflow is efficient and robust in responding to anatomic changes in LALC patients, providing dosimetric advantages over standard therapy. Weekly adaptation was adequate to keep pace with changes. This approach is a feasible alternative to conventional offline replanning workflows for managing anatomy changes in LALC radiation therapy.

In Silico Analysis of Adjuvant Head and Neck Online Adaptive Radiation Therapy.

Purpose: Recently developed online adaptive radiation therapy (OnART) systems enable frequent treatment plan adaptation, but data supporting a dosimetric benefit in postoperative head and neck radiation therapy (RT) are sparse. We performed an in silico dosimetric study to assess the potential benefits of a single versus weekly OnART in the treatment of patients with head and neck squamous cell carcinoma in the adjuvant setting. Methods and Materials: Twelve patients receiving conventionally fractionated RT over 6 weeks and 12 patients receiving hypofractionated RT over 3 weeks on a clinical trial were analyzed. The OnART emulator was used to virtually adapt either once midtreatment or weekly based on the patient's routinely performed cone beam computed tomography. The planning target volume (PTV) coverage, dose heterogeneity, and cumulative dose to the organs at risk for these 2 adaptive approaches were compared with the nonadapted plan. Results: In total, 13, 8, and 3 patients had oral cavity, oropharynx, and larynx primaries, respectively. In the conventionally fractionated RT cohort, weekly OnART led to a significant improvement in PTV V100% coverage (6.2%), hot spot (-1.2 Gy), and maximum cord dose (-3.1 Gy), whereas the mean ipsilateral parotid dose increased modestly (1.8 Gy) versus the nonadapted plan. When adapting once midtreatment, PTV coverage improved with a smaller magnitude (0.2%-2.5%), whereas dose increased to the ipsilateral parotid (1.0-1.1 Gy) and mandible (0.2-0.7 Gy). For the hypofractionated RT cohort, similar benefit was observed with weekly OnART, including significant improvement in PTV coverage, hot spot, and maximum cord dose, whereas no consistent dosimetric advantage was seen when adapting once midtreatment. Conclusions: For head and neck squamous cell carcinoma adjuvant RT, there was a limited benefit of single OnART, but weekly adaptations meaningfully improved the dosimetric criteria, predominantly PTV coverage and dose heterogeneity. A prospective study is ongoing to determine the clinical benefit of OnART in this setting.

Simulation and pre-planning omitted radiotherapy (SPORT): a feasibility study for prostate cancer.

This study explored the feasibility of on-couch intensity modulated radiotherapy (IMRT) planning for prostate cancer (PCa) on a cone-beam CT (CBCT)-based online adaptive RT platform without an individualized pre-treatment plan and contours. Ten patients with PCa previously treated with image-guided IMRT (60 Gy/20 fractions) were selected. In contrast to the routine online adaptive RT workflow, a novel approach was employed in which the same preplan that was optimized on one reference patient was adapted to generate individual on-couch/initial plans for the other nine test patients using Ethos emulator. Simulation CTs of the test patients were used as simulated online CBCT (sCBCT) for emulation. Quality assessments were conducted on synthetic CTs (sCT). Dosimetric comparisons were performed between on-couch plans, on-couch plans recomputed on the sCBCT and individually optimized plans for test patients. The median value of mean absolute difference between sCT and sCBCT was 74.7 HU (range 69.5-91.5 HU). The average CTV/PTV coverage by prescription dose was 100.0%/94.7%, and normal tissue constraints were met for the nine test patients in on-couch plans on sCT. Recalculating on-couch plans on the sCBCT showed about 0.7% reduction of PTV coverage and a 0.6% increasing of hotspot, and the dose difference of the OARs was negligible (<0.5 Gy). Hence, initial IMRT plans for new patients can be generated by adapting a reference patient's preplan with online contours, which had similar qualities to the conventional approach of individually optimized plan on the simulation CT. Further study is needed to identify selection criteria for patient anatomy most amenable to this workflow.

Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform.

Background and Purpose: A recently developed biology-guided radiotherapy platform, equipped with positron emission tomography (PET) and computed tomography (CT), provides both anatomical and functional image guidance for radiotherapy. This study aimed to characterize performance of the kilovoltage CT (kVCT) system on this platform using standard quality metrics measured on phantom and patient images, using CT simulator images as reference. Materials and Methods: Image quality metrics, including spatial resolution/modular transfer function (MTF), slice sensitivity profile (SSP), noise performance and image uniformity, contrast-noise ratio (CNR) and low-contrast resolution, geometric accuracy, and CT number (HU) accuracy, were evaluated on phantom images. Patient images were evaluated mainly qualitatively. Results: On phantom images the MTF10% is about 0.68 lp/mm for kVCT in PET/CT Linac. The SSP agreed with nominal slice thickness within 0.7 mm. The diameter of the smallest visible target (1% contrast) is about 5 mm using medium dose mode. The image uniformity is within 2.0 HU. The geometric accuracy tests passed within 0.5 mm. Relative to CT simulator images, the noise is generally higher and the CNR is lower in PET/CT Linac kVCT images. The CT number accuracy is comparable between the two systems with maximum deviation from the phantom manufacturer range within 25 HU. On patient images, higher spatial resolution and image noise are observed on PET/CT Linac kVCT images. Conclusions: Major image quality metrics of the PET/CT Linac kVCT were within vendor-recommended tolerances. Better spatial resolution but higher noise and better/comparable low contrast visibility were observed as compared to a CT simulator when images were acquired with clinical protocols.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Evaluation of Automated Treatment Planning and Organ Dose Prediction for Lung Stereotactic Body Radiotherapy.

PURPOSES: To evaluate whether the auto-planning (AP) module can achieve clinically acceptable treatment plans for lung stereotactic body radiotherapy (SBRT) and to evaluate the effectiveness of a dose prediction model. METHODS: Twenty lung SBRT cases planned manually with 50 Gy in five fractions were replanned using the Pinnacle (Philips Radiation Oncology Systems, Fitchburg, WI) AP module according to the dose constraint tables from the Radiation Therapy Oncology Group (RTOG) 0813 protocol. Doses to the organs at risk (OAR) were compared between the manual and AP plans. Using a dose prediction model from a commercial product, PlanIQ (Sun Nuclear Corporation, Melbourne, FL), we also compared OAR doses from AP plans with predicted doses. RESULTS: All manual and AP plans achieved clinically required dose coverage to the target volumes. The AP plans achieved equal or better OAR sparing when compared to the manual plans, most noticeable in the maximum doses of the spinal cord, ipsilateral brachial plexus, esophagus, and trachea. Predicted doses to the heart, esophagus, and trachea were highly correlated with the doses of these OARs from the AP plans with the highest correlation coefficient of 0.911, 0.823, and 0.803, respectively. CONCLUSION: Auto-planning for lung SBRT improved OAR sparing while keeping the same dose coverage to the tumor. The dose prediction model can provide useful planning dose guidance.

Validation of RTOG 0813 Proximal Bronchial Tree Constraints for Pulmonary Toxicity With Stereotactic Body Radiation Therapy for Central Non-small Cell Lung Cancer.

PURPOSE: Clinical validation of protocol-specified dosimetric constraints for the proximal bronchial tree (PBT) is limited for central non-small cell lung cancer treated with stereotactic body radiation therapy. We sought to validate Radiation Therapy Oncology Group (RTOG) PBT constraints with a large institutional data set. METHODS AND MATERIALS: Lesions ≤2 cm from the PBT treated with definitive stereotactic body radiation therapy from 2009 to 2016 were identified from a prospective registry of 1462 patients. Every PBT dose and volume combination, ranging from 0 cGy to 8000 cGy in increments of 10 cGy and volumes ranging from 0.03 cm3 to 50 cm3 in increments of 0.03 cm3, was analyzed. The sensitivity and specificity of these endpoints for identifying pulmonary toxicity were calculated. Pulmonary toxicity was classified as pneumonitis or nonpneumonitis toxicity (NPT) (fistula, stenosis, necrosis, hemoptysis, clinically significant pleural effusion). The optimal dosimetric predictor was chosen by calculation of F-score (highest sensitivity and specificity). RESULTS: The study included 132 patients, with 26.0-month median follow-up. Eight grade ≥2 NPT (2 grade 5) and 8 grade 2 pneumonitis toxicities were observed. The PBT dosimetric endpoint with the highest F-score for identification of grade 2 to 5 NPT was D0.03cc ≤5000 cGy and that for grade 3 to 5 NPT was D0.33cc ≤4710 cGy, with sensitivity and specificity of 87.5% and 76.6% and 100.0% and 85.7%, respectively. Applying the RTOG 0813 PBT constraints to our data set achieved a sensitivity and specificity of 33.3% and 92.1% for D4cc ≤1800 cGy and 37.5% and 92.7% for D0.03cc ≤5250 cGy for identification of grade 2 to 5 NPT. A PBT dosimetric correlation for pneumonitis toxicity could not be identified. CONCLUSIONS: This novel dosimetric analysis validates current RTOG constraints and emphasizes high-dose, small-volume constraints as better predictors for NPT. We demonstrated that a slightly lower maximum point dose PBT constraint may be optimal for identification of NPT. Validation of these findings in a larger cohort of patients with longer follow-up is necessary.

Spine radiosurgery in adolescents and young adults: early outcomes and toxicity in patients with metastatic Ewing sarcoma and osteosarcoma.

OBJECTIVE: There are limited data on spine stereotactic radiosurgery (SRS) in treating adolescent and young adult (AYA) patients. SRS has the advantages of highly conformal radiation dose delivery in the upfront and retreatment settings, means for dose intensification, and administration over a limited number of sessions leading to a decreased treatment burden. In this study, the authors report the oncological and toxicity outcomes for AYA patients with metastatic sarcoma treated with spine radiosurgery and provide clinicians a guide for considerations in dose, volume, and fractionation. METHODS: An institutional review board-approved database of patients treated with SRS in the period from October 2014 through December 2018 was queried. AYA patients, defined by ages 15-29 years, who had been treated with SRS for spine metastases from Ewing sarcoma or osteosarcoma were included in this analysis. Patients with follow-ups shorter than 6 months after SRS were excluded. Local control, overall survival, and toxicity were reported. RESULTS: Seven patients with a total of 11 treated lesions were included in this study. Median patient age was 20.3 years (range 15.1-26.1 years). Three patients had Ewing sarcoma (6 lesions) and 4 patients had osteosarcoma (5 lesions). The median dose delivered was 35 Gy in 5 fractions (range 16-40 Gy, 1-5 fractions). The median follow-up was 11.1 months (range 6.8-26.0 months). Three local failures were observed within the follow-up period. No acute grade 3 or greater toxicity was observed. One patient developed late grade 3 toxicity consisting of radiation enteritis. This patient had previously received radiation to an overlapping volume with conventional fractionation. SRS re-irradiation for this patient was also performed concurrently with chemotherapy administration. No late grade 4 or higher toxicities were observed. No pain flare or vertebral compression fracture was observed. Three patients died within the follow-up period. CONCLUSIONS: SRS for spine metastases from Ewing sarcoma and osteosarcoma can be considered as a treatment option in AYA patients and is associated with acceptable toxicity rates. Further studies must be conducted to determine long-term local control and toxicity for this treatment modality.

An image-based deep learning framework for individualizing radiotherapy dose.

Background: Radiotherapy continues to be delivered uniformly without consideration of individual tumor characteristics. To advance toward more precise treatments in radiotherapy, we queried the lung computed tomography (CT)-derived feature space to identify radiation sensitivity parameters that can predict treatment failure and hence guide the individualization of radiotherapy dose. Methods: We used a cohort-based registry of 849 patients with cancer in the lung treated with high dose radiotherapy using stereotactic body radiotherapy. We input pre-therapy lung CT images into a multi-task deep neural network, Deep Profiler, to generate an image fingerprint that primarily predicts time to event treatment outcomes and secondarily approximates classical radiomic features. We validated our findings in an independent study population (n = 95). Deep Profiler was combined with clinical variables to derive iGray, an individualized dose that estimates treatment failure probability to be <5%. Findings: Radiation treatments in patients with high Deep Profiler scores fail at a significantly higher rate than in those with low scores. The 3-year cumulative incidences of local failure were 20.3% (95% CI: 16.0-24.9) and 5.7% (95% CI: 3.5-8.8), respectively. Deep Profiler independently predicted local failure (hazard ratio 1.65, 95% 1.02-2.66, p = 0.04). Models that included Deep Profiler and clinical variables predicted treatment failures with a concordance index of 0.72 (95% CI: 0.67-0.77), a significant improvement compared to classical radiomics or clinical variables alone (p = <0.001 and <0.001, respectively). Deep Profiler performed well in an external study population (n = 95), accurately predicting treatment failures across diverse clinical settings and CT scanner types (concordance index = 0.77 [95% CI: 0.69-0.92]). iGray had a wide dose range (21.1-277 Gy, BED), suggested dose reductions in 23.3% of patients and can be safely delivered in the majority of cases. Interpretation: Our results indicate that there are image-distinct subpopulations that have differential sensitivity to radiotherapy. The image-based deep learning framework proposed herein is the first opportunity to use medical images to individualize radiotherapy dose.

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.

Investigation of brachial plexus dose that exceeds RTOG constraints for apical lung tumors treated with four- or 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.

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

INTRODUCTION: 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. METHODS: Eighteen pairs of NSCLC patients, treated with 50 Gy in five fractions, were selected. These patients were matched based on treatment intent, tumour size, histology and clinical follow-up. All PB calculated clinical plans were retrospectively recalculated with a MC algorithm. The D99 and DMean of the gross tumour volume (GTV) and D95 and DMean of the planning tumour volume (PTV) from PB and Monte Carlo (MC) calculation were compared between local failures and controls using the Mann-Whitney test. RESULTS: The mean PB calculated D95 of PTV was 50.4 Gy for both failures and controls (P = 0.85), indicating no planning differences between the groups. From MC calculations, the mean (±SD) of GTV D99 , GTV DMean , PTV D95 , PTV DMean were 47.6 ± 2.6/46.3 ± 2.4, 50.4 ± 2.1/49.8 ± 1.6, 44.4 ± 2.7/43.6 ± 3.1, 48.7 ± 2.4/48.2 ± 2.4 Gy for failure/controlled groups, respectively, and there was no significant difference between two groups (all P > 0.1). The dose differences between MC and PB calculations were in agreement with other literatures and there was no significant difference between two groups. CONCLUSIONS: While PB algorithms may overestimate tumour doses relative to MC algorithms, our matched-pair study did not find dose differences between local failure and local controlled cases.

Tumor Control and Toxicity for Common Stereotactic Body Radiation Therapy Dose-Fractionation Regimens in Stage I Non-Small Cell Lung Cancer.

PURPOSE: To examine the impact of stereotactic body radiation therapy (SBRT) dose on outcomes in early-stage non-small cell lung cancer in a large single-institution series. METHODS AND MATERIALS: We reviewed 600 patients treated from 2003 to 2012 for early-stage non-small cell lung cancer. The SBRT dose was at physician discretion on the basis of tumor size and location. Peripheral tumors were treated to 60 Gy in 3 fractions (homogeneous planning), 48-50 Gy in 4-5 fractions, or 30-34 Gy in 1 fraction. Central tumors were treated to 50 Gy in 5 fractions, 60 Gy in 8 fractions, or 50 Gy in 10 fractions. Patient, tumor, and treatment factors were assessed for their impact on patterns of failure, toxicity, and survival. RESULTS: An SBRT dose of 54-60 Gy in 3 fractions was associated with a statistically significant lower rate of local failure (LF) (4.3% at 2 years) compared with 30-34 Gy in 1 fraction (21%), 48-50 Gy in 4-5 fractions (15.5%), and 50-60 Gy in 8-10 fractions (13.3%). Lower pre-SBRT hemoglobin and higher positron emission tomography standardized uptake value were also associated with LF. Nodal failure, distant failure, and overall survival were similar between fractionation groups. Pulmonary toxicity (crude rate, any grade) was slightly higher for 3 fractions (5.0%) compared with 1 (3.2%) or 4-5 fractions (3.8%). Chest wall toxicity was also higher for 3 (23.7%) compared with 1 (8.6%) or 4-5 (7.7%) fraction regimens. CONCLUSIONS: Although higher biologically equivalent dose SBRT (150-180 Gy10) may be associated with slightly lower LF, it was also associated with mildly increased toxicity and no difference in other patterns of failure or overall survival.

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.

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.

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.

Stereotactic Body Radiotherapy for T3N0 Lung Cancer With Chest Wall Invasion.

INTRODUCTION: The role of stereotactic body radiotherapy (SBRT) for tumors involving the chest wall (CW) remains ill-defined. The Radiation Therapy Oncology Group 0236 trial allowed inclusion of T3N0 non-small-cell lung cancer (NSCLC) < 5 cm, although ultimately none were enrolled. No published data set investigating this population is available. MATERIALS AND METHODS: We queried an institutional review board-approved prospective SBRT registry to identify patients with tumors involving the CW, defined as radiographic evidence of frank soft tissue invasion or bony destruction. All patients underwent SBRT to a median dose of 50 Gy in 5 fractions and were followed up for tumor control, pain response, and toxicity. RESULTS: Of 820 NSCLC patients reviewed, 13 with CW involvement were identified. Of these 13 patients, 10 had primary T3N0 NSCLC and 3 had recurrent NSCLC. Their median age was 78 years, the Karnofsky performance status was 80, the Charlson score was 3, and the tumor diameter was 4.0 cm. The 1-year local, locoregional, and distant control rates were 89%, 62%, 80%, respectively. Of 9 patients with pretreatment tumor-related CW pain, 7 (78%) reported improvement after treatment. Regarding toxicity, 2 of 13 (15%) experienced new or worsening CW pain (both grade ≤ 2); 3 cases (23%) of grade 1-2 radiation pneumonitis developed. No patient exhibited late skin changes or fibrosis. CONCLUSION: SBRT for NSCLC involving the CW was well tolerated, with promising early rates of tumor control and no grade ≥ 3 toxicity. Tumor-related CW pain was relieved in most patients, and the treatment-related toxicity rates appeared acceptable. Further investigation in this subset of patients with NSCLC 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%/2mm 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 1000MU/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.

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.