Yoshiki Norihisa

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.

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.

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.

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.

Current status of stereotactic body radiotherapy for lung cancer

Stereotactic radiotherapy (SRT) for extracranial tumors has been recently performed to treat lung and liver cancers, and has subsequently been named stereotactic body radiotherapy (SBRT). The advantages of hypofractionated radiotherapy for treating lung tumors are a shortened treatment course that requires fewer trips to the clinic than a conventional program, and the adoption of a smaller irradiated volume allowed by greater setup precision. This treatment is possible because the lung and liver are considered parallel organs at risk. The preliminary clinical results, mostly reported on lung cancer, have been very promising, including a local control rate of more than 90%, and a relatively low complication rate. The final results of a few clinical trials are awaited. SBRT may be useful for the treatment of stage I lung tumors.

Preliminary Report of Late Recurrences, at 5 Years or More, after Stereotactic Body Radiation Therapy for Non-small Cell Lung Cancer

Introduction: Long-term outcomes remain unknown after stereotactic body radiation therapy (SBRT). We observed a few patients who developed disease progression late, at 5 years or more, after SBRT. In this report, we describe the characteristics of those patients with late recurrence after SBRT. Methods: We retrospectively reviewed patients who underwent SBRT for non-small cell lung cancer with histological confirmation between January 1999 and December 2005 at our institution. During this period, 48 Gy of SBRT in four fractions at the isocenter was prescribed for all patients. Results: In total, 66 patients were eligible. With a median follow-up period of 35.9 months, the 5-year overall survival and disease-free survival rates were 44.6% (95% confidence interval, 33.5–59.5%) and 33.8% (95% confidence interval, 23.6–48.4%), respectively. Of the patients, 16 survived without disease progression for 5 years or more after SBRT. Of these, four patients developed late recurrence at 76, 101, 108, and 109 months after SBRT. Three of the patients were females with adenocarcinomas; the other was a male with squamous cell carcinoma. The initial sites of recurrence were local in two patients, distant in one, and simultaneously local and distant in one. A total of two patients with local recurrence alone were still alive at 138 months after SBRT. Conclusions: The rate of late recurrence was not negligible in long-term survivors after SBRT. Our experiences indicate that long-term follow-up is needed after SBRT for non-small cell lung cancer.

Measurement of Interfraction Variations in Position and Size of Target Volumes in Stereotactic Body Radiotherapy for Lung Cancer

PURPOSE To investigate the interfraction variations in volume, motion range, and position of the gross tumor volume (GTV) in hypofractionated stereotactic body radiotherapy (SBRT) for lung cancer using four-dimensional computed tomography. METHODS AND MATERIALS Four-dimensional computed tomography scans were acquired for 8 patients once at treatment planning and twice during the SBRT period using a stereotactic body frame. The image registration was performed to correct setup errors for clinical four-dimensional computed tomography. The interfraction variations in volume, motion range, and position of GTV were computed at end-inhalation (EI) and end-exhalation (EE). RESULTS The random variations in the GTV were 0.59 cm(3) at EI and 0.53 cm(3) at EE, and the systematic variations were 3.04 cm(3) at EI and 3.21 cm(3) at EE. No significant variations in GTV were found during the SBRT sessions (p = .301 at EI and p = .081 at EE). The random variations in GTV motion range for the upper lobe in the craniocaudal direction were within 1.0 mm and for the lower lobe was 3.4 mm. The interfraction variations in the GTV centroid position in the anteroposterior and craniocaudal directions were mostly larger than in the right-left direction; however, no significant displacement was observed among the sessions in any direction. CONCLUSION For patients undergoing hypofractionated SBRT, interfraction variations in GTV, motion range, and position mainly remained small. An additional approach is needed to assess the margin size.

Comparison of three radiotherapy treatment planning protocols of definitive external-beam radiation for localized prostate cancer

BackgroundThree radiotherapy treatment planning (RTTP) protocols for definitive external-beam radiation for localized prostate cancer, designed and clinically applied at Kyoto University, were compared.MethodsTreatment plans were created according to three different RTTP protocols (old three-dimensional conformal radiotherapy [3D-CRT], new 3D-CRT, and intensity-modulated radiotherapy [IMRT]) on computed tomography (CT) data sets of five patients with localized prostate cancer. The dynamic-arc conformal technique was used in the 3D-CRT protocols. Differences in dose distribution were evaluated and compared based on dose-volume histogram (DVH) analyses.ResultsThe coverage of the clinical target volume (= prostate alone) was comparable among the three RTTP protocols. However, the average values for the percent volume that received at least 95% of the prescription dose (V95), the percent of the prescription dose covering 95% of the volume (D95), and the conformity index of the planning target volume (PTV) were 99%, 97%, and 0.88 for the IMRT; 93.9%, 94.5%, and 0.76 for the new 3D-CRT; and 59.6%, 82.9%, and 0.6 for the old 3D-CRT protocol, respectively. Inhomogeneity of doses to the PTV was larger with the IMRT protocol than with the new 3D-CRT protocol. Doses to both the rectal wall and bladder wall were almost comparable with the new 3D-CRT and IMRT protocols, but were lower with the old 3D-CRT protocol, due to the lowest prescription dose and incomplete dose coverage of the PTV.ConclusionThe old 3D-CRT protocol could not achieve the goals for the PTV set in the IMRT protocol. The new 3D-CRT and IMRT protocols were generally comparable in terms of both the PTV coverage and normal tissue-sparing, although the IMRT protocol achieved the most conformal dose distribution to the PTV, in return for a larger, but acceptable, dose inhomogeneity.