Quantification of the kV X-ray imaging dose during real-time tumor tracking and from three- and four-dimensional cone-beam computed tomography in lung cancer patients using a Monte Carlo simulation.

Knowledge of the imaging doses delivered to patients and accurate dosimetry of the radiation to organs from various imaging procedures is becoming increasingly important for clinicians. The purposes of this study were to calculate imaging doses delivered to the organs of lung cancer patients during real-time tumor tracking (RTTT) with three-dimensional (3D), and four-dimensional (4D) cone-beam computed tomography (CBCT), using Monte Carlo techniques to simulate kV X-ray dose distributions delivered using the Vero4DRT. Imaging doses from RTTT, 3D-CBCT and 4D-CBCT were calculated with the planning CT images for nine lung cancer patients who underwent stereotactic body radiotherapy (SBRT) with RTTT. With RTTT, imaging doses from correlation modeling and from monitoring of imaging during beam delivery were calculated. With CBCT, doses from 3D-CBCT and 4D-CBCT were also simulated. The doses covering 2-cc volumes (D2cc) in correlation modeling were up to 9.3 cGy for soft tissues and 48.4 cGy for bone. The values from correlation modeling and monitoring were up to 11.0 cGy for soft tissues and 59.8 cGy for bone. Imaging doses in correlation modeling were larger with RTTT. On a single 4D-CBCT, the skin and bone D2cc values were in the ranges of 7.4-10.5 cGy and 33.5-58.1 cGy, respectively. The D2cc from 4D-CBCT was approximately double that from 3D-CBCT. Clinicians should Figure that the imaging dose increases the cumulative doses to organs.

Pilot Study of the Safety and Efficacy of Dose Escalation in Stereotactic Body Radiotherapy for Peripheral Lung Tumors.

BACKGROUND: This pilot study aimed to evaluate the safety and efficacy of a dose escalation method for the treatment of peripheral lung tumors by administrating steep dose gradients in the target volumes via stereotactic body radiotherapy (SBRT). PATIENTS AND METHODS: Patients with peripheral lung tumors were enrolled onto this study and treated with SBRT using a total dose of 70 Gy in 4 fractions at target isocenter, covering the planning target volume surface with 70% of the isodose. The primary end point was the rate of grade 2 or higher radiation pneumonitis (RP) within 1 year. RESULTS: A total of 35 patients were enrolled onto this study between September 2014 and January 2016. Thirty-two patients with primary lung cancers and 3 patients with lung metastases were treated with SBRT. Grade 2 RP was observed in 4 patients within 1 year. No severe RP (grade 3 or higher) was observed within the follow-up period. The median follow-up period was 21.2 months (range, 4.2-31.7 months). Local recurrence was observed in a single patient with lung metastasis. No local recurrence was observed within the follow-up period in the 32 patients with primary lung cancer. The local control and overall survival rates at 2 years were 95.7% (95% confidence interval, 72.9-99.4) and 85.2% (95% confidence interval, 67.8-93.6), respectively. CONCLUSION: This dose escalation method with steep dose gradients using SBRT for peripheral lung tumors was safe in the subacute phases. These results also suggest that this method can obtain excellent local control rates.

Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). MATERIAL AND METHODS: Patients with MPM of clinical stage I-III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied. RESULTS: Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0-1 (18.2% vs. 60.0% at 3 years, p = .014). CONCLUSION: IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.

Dosimetric comparison of lung stereotactic body radiotherapy treatment plans using averaged computed tomography and end-exhalation computed tomography images: Evaluation of the effect of different dose-calculation algorithms and prescription methods.

The purpose of this article is to quantitatively evaluate differences in dose distributions calculated using various computed tomography (CT) datasets, dose-calculation algorithms, and prescription methods in stereotactic body radiotherapy (SBRT) for patients with early-stage lung cancer. Data on 29 patients with early-stage lung cancer treated with SBRT were retrospectively analyzed. Averaged CT (Ave-CT) and expiratory CT (Ex-CT) images were reconstructed for each patient using 4-dimensional CT data. Dose distributions were initially calculated using the Ave-CT images and recalculated (in the same monitor units [MUs]) by employing Ex-CT images with the same beam arrangements. The dose-volume parameters, including D95, D90, D50, and D2 of the planning target volume (PTV), were compared between the 2 image sets. To explore the influence of dose-calculation algorithms and prescription methods on the differences in dose distributions evident between Ave-CT and Ex-CT images, we calculated dose distributions using the following 3 different algorithms: x-ray Voxel Monte Carlo (XVMC), Acuros XB (AXB), and the anisotropic analytical algorithm (AAA). We also used 2 different dose-prescription methods; the isocenter prescription and the PTV periphery prescription methods. All differences in PTV dose-volume parameters calculated using Ave-CT and Ex-CT data were within 3 percentage points (%pts) employing the isocenter prescription method, and within 1.5%pts using the PTV periphery prescription method, irrespective of which of the 3 algorithms (XVMC, AXB, and AAA) was employed. The frequencies of dose-volume parameters differing by >1%pt when the XVMC and AXB were used were greater than those associated with the use of the AAA, regardless of the dose-prescription method employed. All differences in PTV dose-volume parameters calculated using Ave-CT and Ex-CT data on patients who underwent lung SBRT were within 3%pts, regardless of the dose-calculation algorithm or the dose-prescription method employed.

Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy.

PURPOSE: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). METHODS: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (Pt), and those markers with a 3D |TMDn| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (Pe) was calculated from a localization point consisting of one to three markers except Pt. Respiratory motion for Pt and Pe was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between Pt and Pe during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. RESULTS: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker's motion near the lung tumor. MRA showed that |aRM| in the left-right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left-right direction. The TLE calculated from the MRA ((MRA)TLE) increased as |TMD| and |aRM| increased and adversely decreased with each increment of n. The median 3D (MRA)TLE was 2.0 mm (range, 0.6-4.3 mm) for n = 1, 1.8 mm (range, 0.4-4.0 mm) for n = 2, and 1.6 mm (range, 0.3-3.7 mm) for n = 3. Although statistical significance between n = 1 and n = 3 was observed in all directions, the absolute average difference and the standard deviation of the (MRA)TLE between n = 1 and n = 3 were 0.5 and 0.2 mm, respectively. CONCLUSIONS: A large |TMD| and |aRM| increased the differences in TLE between each n; however, the difference in 3D (MRA)TLEs was, at most, 0.6 mm. Thus, the authors conclude that it is acceptable to continue fiducial marker-based radiotherapy as long as |TMD| is maintained at ≤58.7 mm for a 3D |aRM| ≥ 10 mm.

Dynamic tumor-tracking radiotherapy with real-time monitoring for liver tumors using a gimbal mounted linac.

PURPOSE: Dynamic tumor-tracking stereotactic body radiotherapy (DTT-SBRT) for liver tumors with real-time monitoring was carried out using a gimbal-mounted linear accelerator and the efficacy of the system was determined. In addition, four-dimensional (4D) dose distribution, tumor-tracking accuracy, and tumor-marker positional variations were evaluated. MATERIALS AND METHODS: A fiducial marker was implanted near the tumor prior to treatment planning. The prescription dose at the isocenter was 48-60 Gy, delivered in four or eight fractions. The 4D dose distributions were calculated with a Monte Carlo method and compared to the static SBRT plan. The intrafractional errors between the predicted target positions and the actual target positions were calculated. RESULTS: Eleven lesions from ten patients were treated successfully. DTT-SBRT allowed an average 16% reduction in the mean liver dose compared to static SBRT, without altering the target dose. The average 95th percentiles of the intrafractional prediction errors were 1.1, 2.3, and 1.7 mm in the left-right, cranio-caudal, and anterior-posterior directions, respectively. After a median follow-up of 11 months, the local control rate was 90%. CONCLUSIONS: Our early experience demonstrated the dose reductions in normal tissues and high accuracy in tumor tracking, with good local control using DTT-SBRT with real-time monitoring in the treatment of liver tumors.

Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer: Importance of Salvage Surgery.

INTRODUCTION: Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. METHODS: We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann-Whitney U test, χ2 test, or Fisher's exact test as appropriate. Survival outcomes were estimated with Kaplan-Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. RESULTS: Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. CONCLUSIONS: It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

Target localization errors from fiducial markers implanted around a lung tumor for dynamic tumor tracking.

PURPOSE: To assess target localization errors (TLEs) from implanted fiducial markers by three different centers of gravity (CG) and three different multiple regression analysis (MRA) approaches. METHODS: The three-dimensional (3D) positions of the markers were detected on the fluoroscopic images of 15 lung cancer patients, and the marker closest to the tumor was then assumed to be the target (Pt). The estimated target position (Pe) was calculated from three markers adjacent to the target (Pi, 1 ≤ i ≤ 3) using the equation Pe = aP1 + bP2 + cP3 + d. Pe was then calculated using three different CGs and three different MRAs. The TLE was calculated as the root-mean-square error of the difference between Pt and Pe calculated for each fraction. First, we compared the TLE of the first fraction to assess the intrafraction TLE of the six approaches tested. Second, interfraction TLEs were calculated to evaluate the robustness of the coefficients obtained in the first fraction. The interfraction TLE was defined as the difference between the TLE of a later and the first fraction. RESULTS: The mean plus two times the standard deviation of the intrafraction TLE was up to 4.3 mm in the CG approaches, while the MRA approaches provided TLEs within 1.5 mm. The mean plus two times the standard deviation of the interfraction TLE did not exceed 1.7 mm in any direction using either approach. CONCLUSIONS: The MRA approach was superior to the CG approach in terms of estimating the target position based on the implanted fiducial markers.

Baseline correction of a correlation model for improving the prediction accuracy of infrared marker-based dynamic tumor tracking.

We previously found that the baseline drift of external and internal respiratory motion reduced the prediction accuracy of infrared (IR) marker-based dynamic tumor tracking irradiation (IR Tracking) using the Vero4DRT system. Here, we proposed a baseline correction method, applied immediately before beam delivery, to improve the prediction accuracy of IR Tracking. To perform IR Tracking, a four-dimensional (4D) model was constructed at the beginning of treatment to correlate the internal and external respiratory signals, and the model was expressed using a quadratic function involving the IR marker position (x) and its velocity (v), namely function F(x,v). First, the first 4D model, F1st(x,v), was adjusted by the baseline drift of IR markers (BDIR) along the x-axis, as function F'(x,v). Next, BDdetect, that defined as the difference between the target positions indicated by the implanted fiducial markers (Pdetect) and the predicted target positions with F'(x,v) (Ppredict) was determined using orthogonal kV X-ray images at the peaks of the Pdetect of the end-inhale and end-exhale phases for 10 s just before irradiation. F'(x,v) was corrected with BDdetect to compensate for the residual error. The final corrected 4D model was expressed as Fcor(x,v) = F1st{(x-BDIR),v}-BDdetect. We retrospectively applied this function to 53 paired log files of the 4D model for 12 lung cancer patients who underwent IR Tracking. The 95th percentile of the absolute differences between Pdetect and Ppredict (|Ep|) was compared between F1st(x,v) and Fcor(x,v). The median 95th percentile of |Ep| (units: mm) was 1.0, 1.7, and 3.5 for F1st(x,v), and 0.6, 1.1, and 2.1 for Fcor(x,v) in the left-right, anterior-posterior, and superior-inferior directions, respectively. Over all treatment sessions, the 95th percentile of |Ep| peaked at 3.2 mm using Fcor(x,v) compared with 8.4 mm using F1st(x,v). Our proposed method improved the prediction accuracy of IR Tracking by correcting the baseline drift immediately before irradiation.

Pretreatment Modified Glasgow Prognostic Score Predicts Clinical Outcomes After Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: This study aimed to evaluate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) in patients with non-small cell lung cancer (NSCLC) who received stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: Data from 165 patients who underwent SBRT for stage I NSCLC with histologic confirmation from January 1999 to September 2010 were collected retrospectively. Factors, including age, performance status, histology, Charlson comorbidity index, mGPS, and recursive partitioning analysis (RPA) class based on sex and T stage, were evaluated with regard to overall survival (OS) using the Cox proportional hazards model. The impact of the mGPS on cause of death and failure patterns was also analyzed. RESULTS: The 3-year OS was 57.9%, with a median follow-up time of 3.5 years. A higher mGPS correlated significantly with poor OS (P<.001). The 3-year OS of lower mGPS patients was 66.4%, whereas that of higher mGPS patients was 44.5%. On multivariate analysis, mGPS and RPA class were significant factors for OS. A higher mGPS correlated significantly with lung cancer death (P=.019) and distant metastasis (P=.013). CONCLUSIONS: The mGPS was a significant predictor of clinical outcomes for SBRT in NSCLC patients.

A multi-centre analysis of treatment procedures and error components in dynamic tumour tracking radiotherapy.

PURPOSE: This study aimed to compare procedures for dynamic tumour tracking (DTT) using a gimbal-mounted linac between centres in Japan (KU-IBRI) and Belgium (UZB), to quantify tracking error (TE), and to estimate tumour-fiducial uncertainties and PTV margins. METHODS: Twenty-two patients were evaluated. TE was divided into components originating from the patient, fraction, segment, and residuals. RESULTS: KU-IBRI applied DTT to lung cancer, while UZB treated both the lung and liver. Patients from UZB were younger and had a higher body mass index. DTT procedures differed in the use of body fixation, correction for set-up error, type of fiducial markers, and goodness of fit of correlation model. TE was larger at UZB in the intra-fraction components, whereas the tumour-fiducial uncertainties were estimated to be larger at KU-IBRI. These results ultimately led to similar PTV margins at both centres (2.1, 4.2, and 2.6 mm for KU-IBRI; 2.4, 3.6, and 2.0 mm for UZB in LR, AP, and SI, respectively, for 99% coverage of patients). CONCLUSION: Several differences in procedures and patient characteristics were observed that affected TE and tumour-fiducial uncertainties. This analysis confirmed similar accuracy in DTT delivery and adequate PTV margins in the different centres based on their local specific workflows.

Influence of the correlation modeling period on the prediction accuracy of infrared marker-based dynamic tumor tracking using a gimbaled X-ray head.

PURPOSE: To assess the utility of 10 s and 20 s modeling periods, rather than the 40 s currently used, in the clinical construction of practical correlation models (CMs) in dynamic tumor tracking irradiation using the Vero4DRT. METHODS: The CMs with five independent parameters (CM parameters) were analyzed retrospectively for 10 consecutive lung cancer patients. CM remodeling was performed two or three times per treatment session. Three different CMs trained over modeling periods of 10, 20, and 40 s were built from a single, original CM log file. The predicted target positions were calculated from the CM parameters and the vertical displacement of infrared markers on the abdomen (PIR) during the modeling. We assessed how the CM parameters obtained over modeling periods of T s (T = 10, 20, and 40 s) were robust to changes in respiratory patterns after several minutes. The mimic-predicted target positions after several minutes were computed based on the previous CM parameters and PIR during the next modeling. The 95th percentiles of the differences between mimic-predicted and detected target positions over 40 s (E95robust,T: T = 10, 20, and 40 s) were then calculated. RESULTS: Strong correlations greater than 0.92 were observed between the E95robust,20 and E95robust,40 values. Meanwhile, irregular respiratory patterns with inconsistent amplitudes of motion created differences between the E95robust,10 and E95robust,40 values of ≥10 mm. CONCLUSIONS: The accuracies of CMs derived using 20 s were almost identical to those obtained over 40 s, and superior to those obtained over 10 s.

Stereotactic Body Radiotherapy for Synchronous Primary Lung Cancer: Clinical Outcome of 18 Cases.

BACKGROUND: Previous reports have shown that curative surgical approaches for synchronous primary lung cancer (SPLC) yielded excellent treatment outcomes. However, patients with SPLC are often unsuitable for such surgery as a result of poor general condition or other medical comorbidities. The effectiveness and feasibility of stereotactic body radiotherapy (SBRT) as a definitive treatment for SPLC are not well understood. PATIENTS AND METHODS: We retrospectively reviewed the records of the patients who received lung SBRT between July 2007 and December 2012 at our institution and identified patients with SPLC. The clinical outcome was analyzed for each patient. The first progression site was classified as local, regional, distant, or new primary lung cancer. RESULTS: A total of 18 patients were eligible. Fifteen patients received SBRT for both lesions, and 3 patients received surgery for one tumor and SBRT for the other. The median follow-up time was 34.3 months (range, 12.2-64.7 months). The median overall and progression-free survival was 45.6 months (95% confidence interval [CI] 21.0-60.6) and 25.3 months (95% CI, 13.1-50.6 months), respectively. The 3-year overall survival and progression-free survival rates were 69.1% (95% CI, 40.7-85.9) and 43.2% (95% CI, 20.2-64.4), respectively. Eleven patients (61%) experienced disease progression. The first progression site was local in 4 (22%), regional in 5 (28%), distant in 3 (17%), and new primary lung cancer in 2 patients (11%). Grade 3 radiation pneumonitis was observed in 2 patients (11%). CONCLUSION: SBRT for SPLC is a highly effective local treatment with limited toxicity, although the progression rate seems relatively high.

Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer.

BACKGROUND: Previous comparative reports of stereotactic body radiotherapy (SBRT) and surgery for non-small cell lung cancer (NSCLC) suffered from short follow-up, mixed extents of resection and inclusion of benign lesion. We aimed to make comparisons of long-term outcomes between a pure series of video-assisted thoracoscopic surgery (VATS) lobectomy and SBRT for biopsy-proven clinical stage I NSCLC. METHODS: We retrospectively compared overall survival (OS), cause-specific survival (CSS), recurrence-free survival (RFS), local control, regional lymph node (LN) control, and distant control between VATS lobectomy (n = 413) and SBRT (n = 104) for biopsy-proven clinical stage I NSCLC at our institution between 2003 and 2009. Propensity score matching was used to adjust the confounding effects in estimating treatment hazard ratios. Forty-one VATS lobectomy patients and 41 SBRT patients were matched blinded to outcome (1:1 ratio, caliper distance; 0.5). RESULTS: After propensity score matching, the follow-up period of the whole cohort ranged from 5 to 120 months with a median of 48. After propensity score matching there were significant differences in OS (p = 0.0016), CSS (p = 0.0015), RFS (p < 0.0001), local control (p = 0.0019), and distant control (p < 0.0001) and no significant difference in regional LN control (p = 0.11). The VATS lobectomy patients and SBRT patients had 68.5% and 37.3% of 5-year OS, 83.5% and 56.7% of 5-year CSS, and 60.4% and 19.5% of 5-year RFS, respectively. CONCLUSIONS: Our results suggest VATS lobectomy may offer significantly more favorable long-term outcomes than SBRT in potentially operable patients with biopsy-proven clinical stage I NSCLC.

Impact of pretreatment interstitial lung disease on radiation pneumonitis and survival after stereotactic body radiation therapy for lung cancer.

INTRODUCTION: To investigate the impact of pre-existing radiological interstitial lung disease (ILD) findings on the incidence of radiation pneumonitis (RP) and clinical outcomes after stereotactic body radiation therapy (SBRT) for stage I non-small-cell lung cancer. METHODS: We included 157 consecutive patients who underwent SBRT alone for stage I non-small-cell lung cancer and whose pretreatment lung computed tomography images were available for retrospective review. The pretreatment computed tomography images were evaluated retrospectively for the presence of ILD. The incidence of RP, overall survival (OS) rate, and the incidence of disease progression and local progression were evaluated between patients with ILD (ILD[+]) and without ILD (ILD[-]). RESULTS: Pre-existing ILD was identified in 20 patients. The median follow-up period was 39.5 months. The incidences of RP worse than grade 2 (≥ Gr2 RP) and worse than grade 3 (≥ Gr3 RP) were significantly higher in ILD(+) than ILD(-) (1 year ≥ Gr2 RP rate, 55.0% versus 13.3%; p < 0.001 and 1year ≥ Gr3 RP rate 10.0% versus 1.5%; p = 0.020). Multivariate analysis also indicated that ILD(+) was a risk factor for ≥ Gr2 and ≥ Gr3 RP, and the volume of the irradiated lung. The OS rate tended to be worse in ILD(+) than ILD(-) (3-year OS, 53.8% versus 70.8%; p = 0.28). No difference was observed in the disease progression or local progression rates. CONCLUSIONS: Pre-existing ILD was a significant risk factor for symptomatic and severe RP. Prescreening for ILD findings is important for determining the radiation pneumonitis risk when planning SBRT.

Comparison of long-term survival outcomes between stereotactic body radiotherapy and sublobar resection for stage I non-small-cell lung cancer in patients at high risk for lobectomy: A propensity score matching analysis.

BACKGROUND: The aim of this study was to perform a survival comparison between stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small-cell lung cancer (NSCLC) at high risk for lobectomy. METHODS: All patients who underwent SBRT or SLR because of medical comorbidities for clinical stage I NSCLC were reviewed retrospectively. Propensity score matching (PSM) was performed to reduce selection bias between SLR and SBRT patients based on age, gender, performance status, tumour diameter, forced expiratory volume in 1 second (FEV1) and Charlson comorbidity index (CCI). RESULTS: One hundred and fifteen patients who underwent SBRT and 65 SLR were enrolled. The median potential follow-up periods for SBRT and SLR were 6.7 and 5.3 years, respectively. No treatment-related deaths were observed. Before PSM, the 5-year overall survival (OS) was 40.3% and 60.5% for SBRT and SLR, respectively (P=0.008). PSM identified 53 patients from each treatment group with similar characteristics: a median age of 76 years, a performance status of 0-1, a median tumour diameter of ∼20 mm, a median FEV1 of ∼1.8L and a median CCI of 1. The difference in OS became insignificant between the matched pairs (40.4% and 55.6% at 5 years with SBRT and SLR; P=0.124). The cumulative incidence of cause-specific death was comparable between groups (35.3% and 30.3% at 5 years, P=0.427). CONCLUSION: SBRT can be an alternative treatment option to SLR for patients who cannot tolerate lobectomy because of medical comorbidities.

Prediction of clinical outcome after stereotactic body radiotherapy for non-small cell lung cancer using diffusion-weighted MRI and (18)F-FDG PET.

PURPOSE/OBJECTIVES: To evaluate the use of diffusion-weighted magnetic resonance imaging (DW-MRI) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for predicting disease progression (DP) among patients with non-small cell lung carcinoma (NSCLC) treated with stereotactic body radiotherapy (SBRT). MATERIALS/METHODS: Fifteen patients with histologically confirmed stage I NSCLC who underwent pre-treatment DW-MRI and PET and were treated with SBRT were enrolled. The mean apparent diffusion coefficient (ADC) value and maximum standardised uptake value (SUVmax) were measured at the target lesion and evaluated for correlations with DP. RESULTS: The median pre-treatment ADC value was 1.04×10(-3) (range 0.83-1.29×10(-3))mm(2)/s, and the median pre-treatment SUVmax was 9.9 (range 1.6-30). There was no correlation between the ADC value and SUVmax. The group with the lower ADC value (≤1.05×10(-3)mm(2)/s) and that with a higher SUVmax (≥7.9) tended to have poor DP, but neither trend was statistically significant (p=0.09 and 0.32, respectively). The combination of the ADC value and SUVmax was a statistically significant predictor of DP (p=0.036). CONCLUSION: A low ADC value on pre-treatment DW-MRI and a high SUVmax may be associated with poor DP in NSCLC patients treated with SBRT. Using both values in combination was a better predictor.

Evaluation of dynamic tumour tracking radiotherapy with real-time monitoring for lung tumours using a gimbal mounted linac.

PURPOSE: To evaluate feasibility and acute toxicities after dynamic tumour tracking (DTT) irradiation with real-time monitoring for lung tumours using a gimbal mounted linac. MATERIALS AND METHODS: Spherical gold markers were placed around the tumour using a bronchoscope prior to treatment planning. Prescription dose at the isocentre was 56 Gy in 4 fractions for T2a lung cancer and metastatic tumour, and 48 Gy in 4 fractions for the others. Dose-volume metrics were compared between DTT and conventional static irradiation using in-house developed software. RESULTS: Of twenty-two patients enrolled, DTT radiotherapy was successfully performed for 16 patients, except 4 patients who coughed out the gold markers, one who showed spontaneous tumour regression, and one where the abdominal wall motion did not correlate with the tumour motion. Dose covering 95% volume of GTV was not different between the two techniques, while normal lung volume receiving 20 Gy or more was reduced by 20%. A mean treatment time per fraction was 36 min using DTT. With a median follow-up period of 13.2 months, no severe toxicity grade 3 or worse was observed. CONCLUSIONS: DTT radiotherapy using a gimbal mounted linac was clinically feasible for lung treatment without any severe acute toxicity.

The impact of abdominal compression on outcome in patients treated with stereotactic body radiotherapy for primary lung cancer.

The aim of this study was to evaluate the impact of abdominal compression (AC) on outcome in patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer. We retrospectively reviewed data for 47 patients with histologically proven non-small cell lung cancer and lung tumour motion ≥ 8 mm treated with SBRT. Setup error was corrected based on bony structure. The differences in overall survival (OS), local control (LC) and disease-free survival (DFS) were evaluated to compare patients treated with AC (n = 22) and without AC (n = 25). The median follow-up was 42.6 months (range, 1.4-94.6 months). The differences in the 3-year OS, LC and DFS rate between the two groups were not statistically significant (P = 0.909, 0.209 and 0.639, respectively). However, the largest difference was observed in the LC rate, which was 82.5% (95% CI, 54.9-94.0%) for patients treated without AC and 65.4% (95% CI, 40.2-82.0%) for those treated with AC. After stratifying the patients into prognostic groups based on sex and T-stage, the LC difference increased in the group with an unfavourable prognosis. The present study suggests that AC might be associated with a worse LC rate after SBRT using a bony-structure-based set-up.

Intrafractional tracking accuracy in infrared marker-based hybrid dynamic tumour-tracking irradiation with a gimballed linac.

PURPOSE: To verify the intrafractional tracking accuracy in infrared (IR) marker-based hybrid dynamic tumour tracking irradiation ("IR Tracking") with the Vero4DRT. MATERIALS AND METHODS: The gimballed X-ray head tracks a moving target by predicting its future position from displacements of IR markers in real-time. Ten lung cancer patients who underwent IR Tracking were enrolled. The 95th percentiles of intrafractional mechanical (iEM(95)), prediction (iEP(95)), and overall targeting errors (iET(95)) were calculated from orthogonal fluoroscopy images acquired during tracking irradiation and from the synchronously acquired log files. RESULTS: Averaged intrafractional errors were (left-right, cranio-caudal [CC], anterior-posterior [AP])=(0.1mm, 0.4mm, 0.1mm) for iEM(95), (1.2mm, 2.7mm, 2.1mm) for iEP(95), and (1.3mm, 2.4mm, 1.4mm) for iET(95). By correcting systematic prediction errors in the previous field, the iEP(95) was reduced significantly, by an average of 0.4mm in the CC (p<0.05) and by 0.3mm in the AP (p<0.01) directions. CONCLUSIONS: Prediction errors were the primary cause of overall targeting errors, whereas mechanical errors were negligible. Furthermore, improvement of the prediction accuracy could be achieved by correcting systematic prediction errors in the previous field.