Yukinori Matsuo

Survey of Stereotactic Body Radiation Therapy in Japan by the Japan 3-D Conformal External Beam Radiotherapy Group

PURPOSE To recognize the current status of stereotactic body radiotherapy (SBRT) in Japan, using a nationwide survey conducted by the Japan 3-D Conformal External Beam Radiotherapy Group. METHODS AND MATERIALS The questionnaire was sent by mail to 117 institutions. Ninety-four institutions (80%) responded by the end of November 2005. Fifty-three institutions indicated that they have already started SBRT, and 38 institutions had been reimbursed by insurance. RESULTS A total of 1111 patients with histologically confirmed lung cancer were treated. Among these patients, 637 had T1N0M0 and 272 had T2N0M0 lung cancer. Metastatic lung cancer was found in 702 and histologically unconfirmed lung tumor in 291 patients. Primary liver cancer was found in 207 and metastatic liver cancer in 76 patients. The most frequent schedule used for primary lung cancer was 48 Gy in 4 fractions at 22 institutions (52%), followed by 50 Gy in 5 fractions at 11 institutions (26%) and 60 Gy in 8 fractions at 4 institutions (10%). The tendency was the same for metastatic lung cancer. The average number of personnel involved in SBRT was 1.8 radiation oncologists, including 1.1 certified radiation oncologists, 2.8 technologists, 0.7 nurses, and 0.6 certified quality assurance personnel and 0.3 physicists. The most frequent amount of time for treatment planning was 61-120 min, for quality assurance was 50-60 min, and for treatment was 30 min. There were 14 (0.6% of all cases) reported Grade 5 complications: 11 cases of radiation pneumonitis, 2 cases of hemoptysis, and 1 case of radiation esophagitis. CONCLUSION The current status of SBRT in Japan was surveyed.

Dose--volume metrics associated with radiation pneumonitis after stereotactic body radiation therapy for lung cancer.

PURPOSE To identify dose-volume factors associated with radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for lung cancer. METHODS AND MATERIALS This study analyzed 74 patients who underwent SBRT for primary lung cancer. The prescribed dose for SBRT was uniformly 48 Gy in four fractions at the isocenter. RP was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v.3. Symptomatic RP was defined as grade 2 or worse. Optimal cut-offs dividing the patient population into two subgroups based on the incidence of symptomatic RP were sought using the following dose-volume metrics: PTV volume (ml), mean lung dose (Gy), and V5, V10, V15, V20, V25, V30, V35, and V40 (%) of both lungs excluding the PTV. RESULTS With a median follow-up duration of 31.4 months, symptomatic RP was observed in 15 patients (20.3%), including 1 patient with grade 3. Optimal cut-offs for pulmonary dose-volume metrics were V25 and V20. These two factors were highly correlated with each other, and V25 was more significant. Symptomatic RP was observed in 14.8% of the patients with V25 <4.2%, and the rate was 46.2% in the remainder (p = 0.019). PTV volume was another significant factor. The symptomatic RP rate was significantly lower in the group with PTV <37.7 ml compared with the larger PTV group (11.1% vs. 34.5%, p = 0.020). The patients were divided into three subgroups (patients with PTV <37.7 ml; patients with, PTV ≥37.7 ml and V25 <4.2%; and patients with PTV ≥37.7 ml and V25 ≥4.2%); the incidence of RP grade 2 or worse was 11.1%, 23.5%, and 50.0%, respectively (p = 0.013). CONCLUSIONS Lung V25 and PTV volume were significant factors associated with RP after SBRT.

Prognostic Factors in Stereotactic Body Radiotherapy for Non–Small-Cell Lung Cancer

PURPOSE To investigate the factors that influence clinical outcomes after stereotactic body radiotherapy (SBRT) for non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS A total of 101 consecutive patients who underwent SBRT with 48 Gy in 4 fractions for histologically confirmed Stage I NSCLC were enrolled in this study. Factors including age, maximal tumor diameter, sex, performance status, operability, histology, and overall treatment time were evaluated with regard to local progression (LP), disease progression (DP), and overall survival (OS) using the Cox proportional hazards model. Prognostic models were built with recursive partitioning analysis. RESULTS Three-year OS was 58.6% with a median follow-up of 31.4 months. Cumulative incidence rates of LP and DP were 13.2% and 40.8% at 3 years, respectively. Multivariate analysis demonstrated that tumor diameter was a significant factor in all endpoints of LP, DP, and OS. Other significant factors were age in DP and sex in OS. Recursive partitioning analysis indicated a condition for good prognosis (Class I) as follows: female or T1a (tumor diameter ≤20 mm). When the remaining male patients with T1b-2a (>20 mm) were defined as Class II, 3-year LP, DP, and OS were 6.8%, 23.6%, and 69.9% in recursive partitioning analysis Class I, respectively, whereas these values were 19.9%, 58.3%, and 47.1% in Class II. The differences between the classes were statistically significant. CONCLUSIONS Tumor diameter and sex were the most significant factors in SBRT for NSCLC. T1a or female patients had good prognosis.

Salvage Lung Resection for Non-small Cell Lung Cancer After Stereotactic Body Radiotherapy in Initially Operable Patients

Background: Stereotactic body radiotherapy (SBRT) has emerged as a curative treatment for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). Since NSCLC recurs locally in 10% of the patients treated with SBRT, salvage lung resection after SBRT may be considered in these cases. To further understand the indications for salvage surgery and the pathogenesis of tumor recurrence in these patients, we retrospectively reviewed cases treated at our institution. Methods: SBRT has been performed in patients with early-stage NSCLC at Kyoto University Hospital. We encountered 5 patients who underwent salvage lung resection for NSCLC after SBRT. Results: All the patients were initially operable, but they chose SBRT. After SBRT, the tumors shrank initially in all patients, but increased in size within 18 months of SBRT in the case of 4 patients. During surgical extirpation, we did not find any significant SBRT-related adhesions in any of the patients. Conclusions: We have successfully treated 5 patients who underwent salvage lung resection for early-stage NSCLC after SBRT. We found that surgical resection was feasible after SBRT.

Evaluation of mass-like consolidation after stereotactic body radiation therapy for lung tumors

BackgroundThe purpose of this study was to evaluate the characteristics of mass-like consolidation of the lung on computed tomography (CT) after stereotactic body radiation therapy (SBRT) retrospectively.MethodsForty lung tumors in 37 patients who underwent SBRT were evaluated. Mass-like consolidation was defined as a dense consolidation that newly appeared over or around the original tumor, which included radiation-induced lung injury (RILI) and local recurrence. Time of appearance, initial CT findings (ectatic bronchi and conformity to dose distribution) and serial changes in the size of the mass-like consolidation were evaluated.ResultsMass-like consolidation appeared in 27 (68%) of 40 tumors at a median of 5 months after SBRT. Follow-up examination revealed that 24 (89%) of the 27 mass-like consolidations were RILI and 3 (11%) were local recurrence. There were no significant differences in the initial CT findings between RILI and local recurrence. The size of the mass-like consolidation varied in the 12 months after SBRT. After 12 months or more, however, the size did not increase in any of the RILI cases, but it did increase in all recurrence cases.ConclusionMass-like consolidations were observed in 68% of cases at a median of 5 months after SBRT. Although most of the mass-like consolidations were RILI, local recurrence was observed in a few cases. Early detection of local recurrence after SBRT was difficult.

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.

Characterization of FDG-PET images after stereotactic body radiation therapy for lung cancer.

BACKGROUND AND PURPOSE The purpose was to characterize (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) findings after stereotactic body radiation therapy (SBRT) for lung cancer. MATERIALS AND METHODS This was a retrospective review of 32 FDG-PET scans from 23 patients who underwent SBRT for lung cancer and who showed no evidence of local recurrence. The FDG uptake by lesions was assessed visually using a 3-point scale (0, none or faint; 1, mild; or 2, moderate to intense), and the demarcation (ill- or well-defined) was evaluated. For semi-quantitative analysis, the maximum standardized uptake value (SUVmax) was calculated. RESULTS Grade 2 intensity was observed in 70%, 33%, 30%, and 0% of PET scans performed <6, 6-12, 12-24, and >24 months, respectively, after SBRT; well-defined demarcation was observed in 80%, 33%, 40%, and 17%, respectively, and the respective means of the SUVmax were 4.9, 2.6, 3.0, and 2.3. The SUVmax was significantly higher for scans performed at <6 months than at 6-12 or >24 months. CONCLUSIONS FDG uptake tended to be intense and well-defined at early times after SBRT, especially within 6 months, and was faint and ill-defined at later periods. Moderate to intense FDG uptake observed soon after SBRT does not always indicate a residual tumour.

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.

Geometrical differences in target volumes between slow CT and 4D CT imaging in stereotactic body radiotherapy for lung tumors in the upper and middle lobe

Since stereotactic body radiotherapy (SBRT) was started for patients with lung tumor in 1998 in our institution, x-ray fluoroscopic examination and slow computed tomography (CT) scan with a rotation time of 4 s have been routinely applied to determine target volumes. When lung tumor motion observed with x-ray fluoroscopy is larger than 8 mm, diaphragm control (DC) is used to reduce tumor motion during respiration. After the installation of a four-dimensional (4D) CT scanner in 2006, 4D CT images have been supplementarily acquired to determine target volumes. It was found that target volumes based on slow CT images were substantially different from those on 4D CT images, even for patients with lung tumor motion no larger than 8 mm. Although slow CT scan might be expected to fare well for lung tumors with motion range of 8 mm or less, the potential limitations of slow CT scan are unknown. The purpose of this study was to evaluate the geometrical differences in target volumes between slow CT and 4D CT imaging for lung tumors with motion range no larger than 8 mm in the upper and middle lobe. Of the patients who underwent SBR between October 2006 and April 2008, 32 patients who had lung tumor with motion range no larger than 8 mm and did not need to use DC were enrolled in this study. Slow CT and 4D CT images were acquired under free breathing for each patient. Target volumes were manually delineated on slow CT images (TV(slow CT)). Gross tumor volumes were also delineated on each of the 4D CT volumes and their union (TV(4D CT)) was constructed. Volumetric and statistical analyses were performed for each patient. The mean +/- standard deviation (S.D.) of TV(slow CT)/TV(4D CT) was 0.75 +/- 0.17 (range, 0.38-1.10). The difference between sizes of TV(slow CT) and TV(4D CT) was not statistically significant (P = 0.096). A mean of 8% volume of TV(slow CT) was not encompassed in TV(4D CT) (mean +/- S.D. = 0.92 +/- 0.07). The patients were separated into two groups to test whether the quality of target delineation on slow CT scans depends on respiratory periods below or above the CT rotation time of 4 s. No significant difference was observed between these groups (P = 0.229). Even lung tumors with motion range no larger than 8 mm might not be accurately depicted on slow CT images. When only a single slow CT scan was used for lung tumors with motion range of 8 mm or less, 95% confidence values for additional margins for TV(slow CT) to encompass TV(4D CT) were 4.0, 5.4, 4.9, 5.1, 1.8, and 1.7 mm for lateral, medial, ventral, dorsal, cranial, and caudal directions, respectively.

Impact of motion velocity on four-dimensional target volumes: a phantom study.

This study aims to assess the impact of motion velocity that may cause motion artifacts on target volumes (TVs) using a one-dimensional moving phantom. A 20 mm diameter spherical object embedded in a QUASAR phantom sinusoidally moved with approximately 5.0 or 10.0 mm amplitude (A) along the longitudinal axis of the computed tomography (CT) couch. The motion period was manually set in the range of 2.0-10.0 s at approximately 2.0 s interval. Four-dimensional (4D) CT images were acquired by a four-slice CT scanner (LightSpeed RT; General Electric Medical Systems, Waukesha, WI) with a slice thickness of 1.25 mm in axial cine mode. The minimum gantry rotation of 1.0 s was employed to achieve the maximum in-slice temporal resolution. Projection data over a full gantry rotation (1.0 s) were used for image reconstruction. Reflective marker position was recorded by the real-time positioning management system (Varian Medical Systems, Palo Alto, CA). ADVANTAGE 4D software exported ten respiratory phase volumes and the maximum intensity volume generated from all reconstructed data (MIV). The threshold to obtain static object volume (V0, 4.19 ml) was used to automatically segment TVs on CT images, and then the union of TVs on 4D CT images (TV(4D)) was constructed. TVs on MIV (TV(MIV)) were also segmented by the threshold that can determine the area occupied within the central slice of TV(MIV). The maximum motion velocity for each phase bin was calculated using the actual averaged motion period displayed on ADVANTAGE 4D software (T), the range of phases used to construct the target phase bin (phase range), and a mathematical model of sinusoidal function. Each volume size and the motion range of TV in the cranial-caudal (CC) direction were measured. Subsequently, cross-correlation coefficients between TV size and motion velocity as well as phase range were calculated. Both misalignment and motion-blurring artifacts were caused by high motion velocity, Less than 6% phase range was needed to construct the 4D CT data set, except for T of 2.0 s. While the positional differences between the TV and ideal centroid in the CC direction were within the voxel size for T > or = 6.0 s, the differences were up to 2.43 and 4.15 mm for (A,T) = (5.0 mm, 2.0 s) and (10.0 mm, 2.0 s), respectively. The maximum volumetric deviations between TV sizes and V0 were 43.68% and 91.41% for A of 5.0 and 10.0 mm, respectively. TV(MIV) sizes were slightly larger than TV(4D) sizes. Volumetric deviation between TV size and V0 had a stronger correlation with motion velocity rather than phase range. This phantom study demonstrated that motion artifacts were substantially reduced when the phantom moved longitudinally at low motion velocity during 4D CT image acquisition; therefore, geometrical uncertainties due to motion artifacts should be recognized when determining TVs, especially with a fast period.