Pulmonary Stereotactic Body Radiotherapy Research Articles

Improving interinstitutional and intertechnology consistency of pulmonary SBRT by dose prescription to the mean internal target volume dose

PurposeDose, fractionation, normalization and the dose profile inside the target volume vary substantially in pulmonary stereotactic body radiotherapy (SBRT) between different institutions and SBRT technologies. Published planning studies have shown large variations of the mean dose in planning target volume (PTV) and gross tumor volume (GTV) or internal target volume (ITV) when dose prescription is performed to the PTV covering isodose. This planning study investigated whether dose prescription to the mean dose of the ITV improves consistency in pulmonary SBRT dose distributions.Materials and methodsThis was a multi-institutional planning study by the German Society of Radiation Oncology (DEGRO) working group Radiosurgery and Stereotactic Radiotherapy. CT images and structures of ITV, PTV and all relevant organs at risk (OAR) for two patients with early stage non-small cell lung cancer (NSCLC) were distributed to all participating institutions. Each institute created a treatment plan with the technique commonly used in the institute for lung SBRT. The specified dose fractionation was 3 × 21.5 Gy normalized to the mean ITV dose. Additional dose objectives for target volumes and OAR were provided.ResultsIn all, 52 plans from 25 institutions were included in this analysis: 8 robotic radiosurgery (RRS), 34 intensity-modulated (MOD), and 10 3D-conformal (3D) radiation therapy plans. The distribution of the mean dose in the PTV did not differ significantly between the two patients (median 56.9 Gy vs 56.6 Gy). There was only a small difference between the techniques, with RRS having the lowest mean PTV dose with a median of 55.9 Gy followed by MOD plans with 56.7 Gy and 3D plans with 57.4 Gy having the highest. For the different organs at risk no significant difference between the techniques could be found.ConclusionsThis planning study pointed out that multiparameter dose prescription including normalization on the mean ITV dose in combination with detailed objectives for the PTV and ITV achieve consistent dose distributions for peripheral lung tumors in combination with an ITV concept between different delivery techniques and across institutions.

Treatment Outcomes after Pulmonary Stereotactic Body Radiotherapy for Oligometastatic or Oligorecurrent Lung Lesions

Abstract Objective Using ablative techniques like stereotactic body radiation therapy (SBRT) in patients with limited metastases may improve survival outcomes in select groups of patients. We review the outcomes of patients treated with oligometastatic/recurrent lung lesions in our centre and analyse variables that might have affected them. Methods A retrospective review of patients treated from Jan 2010 to Dec 2016 was conducted. The data was analysed using SPSS ver23. Results A total of 46 patients with 51 lung lesions were treated with SBRT. Majority of lesions were of lung and colorectal cancers. Histological confirmation was obtained in 50%. Median SBRT biological effective dose (BED) was 105.6Gy and median follow-up was 26.9 months. There were 12 (22.6%) local failures at last follow-up. Median progression free survival (PFS) was 13.7 months (95% CI: 3.9 -23.5 months). Median overall survival (OS) was 42.2 months (95% CI: 30.8 - 53.5 months). The 2 year PFS and OS was 32.6% and 81.9% respectively. There were 3 (6.5%) likely radiotherapy related grade 3-4 pulmonary toxicities. On univariate analysis, local control rates were better with a higher BED and in squamous cell histology. Progression free survival was better for patients with metachronous lesions, higher BED, controlled primary lesions and when treatment to all visible lesions was given. Only patients with solitary metastatic lesions had better OS (44.7 months) and PFS (21.9 months) on univariate analysis. Local failure and progression predicted for worst OS. Conclusion The patients in this study are heterogeneous. Survival outcomes were better in patients with solitary metastatic lesions. This may be due to selection of patients with indolent disease biology. Better PFS were seen with higher BED and when all visible lesions were ablated. Further studies are needed.

Long-term Follow-up and Patterns of Recurrence of Patients With Oligometastatic NSCLC Treated With Pulmonary SBRT

IntroductionThis multicenter study aims to analyze outcome as well as early versus late patterns of recurrence following pulmonary stereotactic body radiotherapy (SBRT) for patients with oligometastatic non–small-cell lung cancer (NSCLC). Materials and MethodsThis analysis included 301 patients with oligometastatic NSCLC treated with SBRT for 336 lung metastases. Although treatment of the primary tumor consisted of surgical resection, radiochemotherapy, and/or systemic therapy, pulmonary oligometastases were treated with SBRT. ResultsThe median follow-up time was 16.1 months, resulting in 2-year overall survival (OS), local control (LC), and distant control (DC) of 62.2%, 82.0%, and 45.2%, respectively. Multivariate analysis identified age (P = .019) and histologic subtype (P = .028), as well as number of metastatic organs (P < .001) as independent prognostic factors for OS. LC was superior for patients with favorable histologic subtype (P = .046) and SBRT with a higher biological effective dose at isocenter (P = .037), whereas DC was inferior for patients with metastases in multiple organs (P < .001) and female gender (P = .027). Early (within 24 months) local or distant progression was observed in 15.3% and 36.5% of the patients. After 24 months, the risk of late local failure was low, with 3- and 4-year local failure rates of only 4.0%, and 7.6%. In contrast, patients remained at a high risk of distant progression with 3- and 4-year failure rates of 13.3% and 24.1%, respectively, with no plateau observed. ConclusionSBRT for pulmonary oligometastatic NSCLC resulted in favorable LC and promising OS. The dominant failure pattern is distant with a continuously high risk of disease progression for many years.

Modeling radiation pneumonitis of pulmonary stereotactic body radiotherapy: The impact of a local dose–effect relationship for lung perfusion loss

PurposeTo investigate if a local dose–effect (LDE) relationship for perfusion loss improves the NTCP model fit for SBRT induced radiation pneumonitis (RP) compared to conventional LDEs. Methods and materialsMulti-institutional data of 1015 patients treated with SBRT were analyzed. Dose distributions were converted to NTD with α/β = 3 Gy. The Lyman–Kutcher–Burman NTCP model was fitted to the incidence grade ≥2 RP by maximum likelihood estimation with mean lung dose (MLD), equivalent uniform doses (EUD) using three LDE functions (power-law (EUDpower), logistic with 2 free parameters (EUDlog-free) and logistic with fixed parameters describing local perfusion loss (EUDPerfusion)) and volume above a threshold dose (Vx). Models were compared with the Akaike weights (Aw) derived from the Akaike information criteria (AIC). ResultsThe median time to grade ≥2 RP was 4.2 months and plateaued after 17 months at 5.4%. A strong dose–effect relationship for RP incidence was observed. The EUDPerfusion based NTCP model had the lowest AIC. The Aw were 0.53, 0.19, 0.11, 0.11, 0.05 for the EUDPerfusion, Vx, MLD, EUDlog-free and EUDpower LDEs respectively. ConclusionA LDE for perfusion loss provided modest improvement in NTCP model fit for SBRT induced radiation pneumonitis.

Early Impact of Pulmonary Fractionated Stereotactic Body Radiotherapy on Quality of Life:Benefit for Patients With Low Initial Scores (STRIPE Trial)

IntroductionQuality of life (QoL) of comorbid patients with pulmonary malignancies is a key issue in considering fractionated stereotactic body radiotherapy (SBRT) indication. This study investigates the early impact of SBRT on QoL. MethodsOne hundred patients with pulmonary lesions were treated with SBRT from February 2011 to December 2014 within the prospective, monocenter, phase II STRIPE trial. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core module (EORTC QLQ-C30) and the QLQ-LC13 lung cancer-specific questionnaire were used to evaluate QoL before, 2 and 7 weeks after SBRT, then every 3 months for 2 years. We report on the analysis of early changes from baseline to 7-week follow-up exam. Impact of patient- and treatment-related factors on the change in QoL was analyzed. ResultsQoL was assessed in 97 patients; compliance was 92% and 85% at baseline and 7 weeks after SBRT, respectively. No clinically relevant changes greater than or equal to 10 in the QoL/global health status (GHS), function scores and inquired symptoms were observed. Patients with baseline QoL below the median showed clinically relevant improvement in QoL/GHS (Δ16.7 ± 25.3, p = 0.003), emotional function (Δ14.4 ± 25.4, p = 0.013), and fatigue (Δ -10.1 ± 26.5, p = 0.089) in contrast to patients with high initial scores. No changes were observed in the dichotomized subgroups of initial Karnofsky index, Charlson Comorbidity Index, age, diagnosis, and tumor localization. ConclusionsIn short-term follow-up, QoL is well maintained after pulmonary SBRT. Especially patients with low initial QoL/GHS scores show benefit from SBRT with respect to QoL.

EP-2036: Dosimetric issues in pulmonary Stereotactic Body Radiotherapy (SBRT) treatments with Tomotherapy

EP-2036: Dosimetric issues in pulmonary Stereotactic Body Radiotherapy (SBRT) treatments with Tomotherapy

Safety and Efficacy of Stereotactic Body Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Routine Clinical Practice: A Patterns-of-Care and Outcome Analysis

To evaluate safety and efficacy of stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in a patterns-of-care and patterns-of-outcome analysis. The working group "Extracranial Stereotactic Radiotherapy" of the German Society for Radiation Oncology performed a retrospective multicenter analysis of practice and outcome after SBRT for stage I NSCLC. Sixteen German and Austrian centers with experience in pulmonary SBRT were asked to participate. Data of 582 patients treated at 13 institutions between 1998 and 2011 were collected; all institutions, except one, were academic hospitals. A time trend to more advanced radiotherapy technologies and escalated irradiation doses was observed, but patient characteristics (age, performance status, pulmonary function) remained stable over time. Interinstitutional variability was substantial in all treatment characteristics but not in patient characteristics. After an average follow-up of 21 months, 3-year freedom from local progression (FFLP) and overall survival (OS) were 79.6% and 47.1%, respectively. The biological effective dose was the most significant factor influencing FFLP and OS: after more than 106 Gy biological effective dose as planning target volume encompassing dose (N = 164), 3-year FFLP and OS were 92.5% and 62.2%, respectively. No evidence of a learning curve or improvement of results with larger SBRT experience and implementation of new radiotherapy technologies was observed. SBRT for stage I NSCLC was safe and effective in this multi-institutional, academic environment, despite considerable interinstitutional variability and time trends in SBRT practice. Radiotherapy dose was identified as a major treatment factor influencing local tumor control and OS.

Volume Modulated Arc Therapy (VMAT) for pulmonary Stereotactic Body Radiotherapy (SBRT) in patients with lesions in close approximation to the chest wall

Purpose: Chest wall pain and discomfort has been recognized as a significant late effect of radiation therapy in historical and modern treatment models. Stereotactic Body Radiotherapy (SBRT) is becoming an important treatment tool in oncology care for patients with intrathoracic lesions. For lesions in close approximation to the chest wall with motion management, SBRT techniques can deliver high dose to the chest wall. As an unintended target of consequence, there is possibility of imposing significant chest wall pain and discomfort as a late effect of therapy. The purpose of this paper is to evaluate the potential role of Volume Modulated Arc Therapy (VMAT) technologies in decreasing chest wall dose in SBRT treatment of pulmonary lesions in close approximation to the chest wall.Materials and Methods: Ten patients with pulmonary lesions of various sizes and tomography in close approximation to the chest wall were selected for retrospective review. All volumes including tumor target, chest wall, ribs, and lung were contoured with maximal intensity projection maps and four-dimensional computer tomography planning. Radiation therapy planning consisted of static techniques including Intensity Modulated Radiation Therapy compared to VMAT therapy to a dose of 60 Gy in 12 Gy fraction dose. Dose volume histogram to rib, chest wall, and lung were compared between plans with statistical analysis.Results: In all patients, dose and volume were improved to ribs and chest wall using VMAT technologies compared to static field techniques. On average, volume receiving 30 Gy to the chest wall was improved by 74%; the ribs by 60%. In only one patient did the VMAT treatment technique increase pulmonary volume receiving 20 Gy (V20).Conclusions: VMAT technology has potential of limiting radiation dose to sensitive chest wall regions in patients with lesions in close approximation to this structure. This would also have potential value to lesions treated with SBRT in other body regions where targets abut critical structures.

A novel respiratory motion compensation strategy combining gated beam delivery and mean target position concept – A compromise between small safety margins and long duty cycles

PurposeTo evaluate a novel respiratory motion compensation strategy combining gated beam delivery with the mean target position (MTP) concept for pulmonary stereotactic body radiotherapy (SBRT). Materials and methodsFour motion compensation strategies were compared for 10 targets with motion amplitudes between 6mm and 31mm: the internal target volume concept (planITV); the MTP concept where safety margins were adapted based on 4D dose accumulation (planMTP); gated beam delivery without margins for motion compensation (plangated); a novel approach combining gating and the MTP concept (plangated&MTP). ResultsFor 5/10 targets with an average motion amplitude of 9mm, the differences in the mean lung dose (MLD) between plangated and planMTP were <10%. For the other 5/10 targets with an average motion amplitude of 19mm, gating with duty cycles between 87.5% and 75% reduced the residual target motion to 12mm on average and 2mm safety margins were sufficient for dosimetric compensation of this residual motion in plangated&MTP. Despite significantly shorter duty cycles, plangated reduced the MLD by <10% compared to plangated&MTP. The MLD was increased by 18% in planMTP compared to that of plangated&MTP. ConclusionsFor pulmonary targets with motion amplitudes >10–15mm, the combination of gating and the MTP concept allowed small safety margins with simultaneous long duty cycles.

Dose–response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy

Purpose To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT). Materials and methods A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC ( n = 21) or pulmonary metastases ( n = 54). The majority of patients were treated with radiosurgery of 26 Gy to 80% ( n = 29) or three fractions of 12.5 Gy to 65% ( n = 40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/β ratio of 3 Gy for RP. Dose–volume parameters and incidences of RP ⩾ grade II SWOG were fitted using NTCP models. Results Eleven patients developed RP grade II. With an average MLD of 10.3 ± 5.6 Gy to the ipsilateral lung, a significant dose–response relationship was observed: the MLD was 12.5 ± 4.3 Gy and 9.9 ± 5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy ( V 2.5– V 50) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses. Conclusions The MLD and V 2.5– V 50 of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

Purpose To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT). Materials and methods Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference. Results Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4 mm and 6 mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio–caudal direction, respectively. Conclusion Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.

Four Dimensional Target Volume Generation in Pulmonary Stereotactic Body Radiotherapy

To evaluate the influence of breathing motion on four dimensional dose distributions in pulmonary stereotactic body radiotherapy (SBRT) and to calculate appropriate margins for compensation of breathing motion. For seven patients with eight pulmonary tumors a respiratory correlated 4D-CT study was acquired. Eight CT series equally distributed over the breathing cycle were reconstructed for each 4D-CT study (2 mm slice thickness). The GTV (macroscopic tumor including spiculae) was delineated in the CT pulmonary window in the CT series of end-exhalation and propagated into all other CT series using automatic image segmentation (Pinnacle treatment planning system v8.1s). No margin for generation of the CTV was applied. The CT series showing the lesion in the time-weighted mean tumor position was selected for treatment planning: a 3D-conformal treatment plan was generated with a dose prescription of 3 × 12.5 Gy to the CTV enclosing 80% isodose (plan-static). 4D dose distributions with consideration of tumor motion were calculated based on non-rigid model-based image registration (plan-4D). The treatment fields were increased symmetrically in steps of 4 mm (2 mm in each direction) to compensate for breathing motion. Predominant direction of tumor motion was superior-inferior (SI) in all lesions. Peak-to-peak tumor motion and SD of motion in SI-direction was 12.7 mm ± 4.8 mm and 5.0 mm ± 1.8 mm, respectively. The D95 to the CTV in plan-static was 38.1 Gy ± 2 Gy and the minimum dose (Dmin) 34 Gy ± 2.9 Gy. Consideration of tumor motion in plan-4D decreased the dose to the CTV to 30.2 Gy ± 2 Gy (D95) and to 25 Gy ± 1.3 Gy (Dmin), a reduction of 22% and 27% compared to plan-static. For complete compensation of 4D breathing motion of the D95 and the Dmin level, symmetrical margins of 3.7 mm ± 2.1 mm and 3.9 mm ± 2.4 mm around the CTV based on the mean tumor position were calculated, respectively. These margins are about 40% smaller than the margins used in the internal target volume concept (ITV; the hull of the CTVs in all phases of the breathing cycle). Margins of 2.5 mm ± 1.3 mm (D95) and 2.9 mm ± 1.7 mm (Dmin) were necessary if a 5% decrease of the dose to the CTV was accepted; the ITV concept resulted in margins more than twice as large. If the mean tumor position from a 4D-CT is selected for planning and if no margins are added to the CTV, breathing motion decreased the dose to the CTV by about 25%. Using 4D dose calculation the margins for compensation of breathing motion were significantly smaller compared to the ITV concept. Inter- and intra-fractional uncertainties are additional factors, which need to be considered in the process of target definition or addressed by image-guidance.