Katsuyuki Sakanaka

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.

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.

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.

Dosimetric evaluation of the impacts of different heterogeneity correction algorithms on target doses in stereotactic body radiation therapy for lung tumors

Heterogeneity correction algorithms can have a large impact on the dose distributions of stereotactic body radiation therapy (SBRT) for lung tumors. Treatment plans of 20 patients who underwent SBRT for lung tumors with the prescribed dose of 48 Gy in four fractions at the isocenter were reviewed retrospectively and recalculated with different heterogeneity correction algorithms: the pencil beam convolution algorithm with a Batho power-law correction (BPL) in Eclipse, the radiological path length algorithm (RPL), and the X-ray Voxel Monte Carlo algorithm (XVMC) in iPlan. The doses at the periphery (minimum dose and D95) of the planning target volume (PTV) were compared using the same monitor units among the three heterogeneity correction algorithms, and the monitor units were compared between two methods of dose prescription, that is, an isocenter dose prescription (IC prescription) and dose–volume based prescription (D95 prescription). Mean values of the dose at the periphery of the PTV were significantly lower with XVMC than with BPL using the same monitor units (P < 0.001). In addition, under IC prescription using BPL, RPL and XVMC, the ratios of mean values of monitor units were 1, 0.959 and 0.986, respectively. Under D95 prescription, they were 1, 0.937 and 1.088, respectively. These observations indicated that the application of XVMC under D95 prescription results in an increase in the actually delivered dose by 8.8% on average compared with the application of BPL. The appropriateness of switching heterogeneity correction algorithms and dose prescription methods should be carefully validated from a clinical viewpoint.

Differences in dose-volumetric data between the analytical anisotropic algorithm and the x-ray voxel Monte Carlo algorithm in stereotactic body radiation therapy for lung cancer

The objective of this study was to evaluate the differences in dose-volumetric data obtained using the analytical anisotropic algorithm (AAA) vs the x-ray voxel Monte Carlo (XVMC) algorithm for stereotactic body radiation therapy (SBRT) for lung cancer. Dose-volumetric data from 20 patients treated with SBRT for solitary lung cancer generated using the iPlan XVMC for the Novalis system consisting of a 6-MV linear accelerator and micro-multileaf collimators were recalculated with the AAA in Eclipse using the same monitor units and identical beam setup. The mean isocenter dose was 100.2% and 98.7% of the prescribed dose according to XVMC and AAA, respectively. Mean values of the maximal dose (D(max)), the minimal dose (D(min)), and dose received by 95% volume (D₉₅) for the planning target volume (PTV) with XVMC were 104.3%, 75.1%, and 86.2%, respectively. When recalculated with the AAA, those values were 100.8%, 77.1%, and 85.4%, respectively. Mean dose parameter values considered for the normal lung, namely the mean lung dose, V₅, and V₂₀, were 3.7Gy, 19.4%, and 5.0% for XVMC and 3.6Gy, 18.3%, and 4.7% for the AAA, respectively. All of these dose-volumetric differences between the 2 algorithms were within 5% of the prescribed dose. The effect of PTV size and tumor location, respectively, on the differences in dose parameters for the PTV between the AAA and XVMC was evaluated. A significant effect of the PTV on the difference in D₉₅ between the AAA and XVMC was observed (p = 0.03). Differences in the marginal doses, namely D(min) and D₉₅, were statistically significant between peripherally and centrally located tumors (p = 0.04 and p = 0.02, respectively). Tumor location and volume might have an effect on the differences in dose-volumetric parameters. The differences between AAA and XVMC were considered to be within an acceptable range (<5 percentage points).

Efficacy of salvage stereotactic radiotherapy for recurrent glioma: impact of tumor morphology and method of target delineation on local control

In this study, we assessed the efficacy of salvage stereotactic radiotherapy (SRT) for recurrent glioma. From August 2008 to December 2012, 30 patients with recurrent glioma underwent salvage SRT. The initial histological diagnoses were World Health Organization (WHO) grades II, III, and IV in 6, 9, and 15 patients, respectively. Morphologically, the type of recurrence was classified as diffuse or other. Two methods of clinical target delineation were used: A, a contrast‐enhancing tumor; or B, a contrast‐enhancing tumor with a 3–10‐mm margin and/or surrounding fluid attenuation inversion recovery (FLAIR) high‐intensity areas. The prescribed dose was 22.5–35 Gy delivered in five fractions at an isocenter using a dynamic conformal arc technique. The overall survival (OS) and local control probability (LCP) after SRT were calculated using the Kaplan–Meier method. A univariate analysis was used to test the effect of clinical variables on OS/LCP. The median follow‐up period was 272 days after SRT. The OS and LCP were 83% and 56% at 6 months after SRT, respectively. Morphologically, the tumor type correlated significantly with both OS and LCP (P = 0.006 and <0.001, respectively). The method of target delineation also had a significant influence on LCP (P = 0.016). Grade 3 radiation necrosis was observed in two patients according to Common Terminology Criteria for Adverse Events, version 3. Salvage SRT was safe and effective for recurrent glioma, especially non‐diffuse recurrences. Improved local control might be obtained by adding a margin to contrast‐enhancing tumors or including increased FLAIR high‐intensity areas.

Long-term complications of definitive chemoradiotherapy for esophageal cancer using the classical method

Chemoradiation therapy is widely used to treat both inoperable and operable patients, and is less invasive than surgery. Although the number of long-term survivors who have received chemoradiation therapy is increasing, the long-term toxicity pattern and cumulative incidence of toxicity regarding this modality are poorly understood. Classically, chemoradiation therapy for esophageal cancer consists of an anterior–posterior field and a subsequent oblique boost field. We retrospectively analyzed patients who were treated with definitive chemoradiation therapy for esophageal cancer using this classical method from 1999 to 2008. For the assessment of toxicity, the National Cancer Institute Common Toxicity Criteria Version 3.0 was adopted. A total of 101 patients were analyzed. The median follow-up time was 16 months for all patients and 62 months for the surviving patients. Eleven patients experienced late toxicities of ≥Grade 3. Two patients died of late toxicities. The 3- and 5-year cumulative incidences for the first late cardiopulmonary toxicities of ≥Grade 3 were 17.4% and 20.8%, respectively. Cardiopulmonary effusions were observed within the first 3 years of completion of the initial treatment in seven out of eight patients. Sudden death and cardiac ischemia were observed over a 10-year period. Older age was found to be a risk factor for late toxicity after definitive chemoradiation therapy for esophageal cancer. Substantial toxicities were observed in patients who had received chemoradiation therapy for esophageal cancer using the classical method. To minimize the incidence of late toxicity, more sophisticated radiation techniques may be useful.

Differences in the dose–volume metrics with heterogeneity correction status and its influence on local control in stereotactic body radiation therapy for lung cancer

The purpose of this study is to evaluate the dose–volume metrics under different heterogeneity corrections and the factors associated with local recurrence (LR) after stereotactic body radiation therapy (SBRT) for non-small-cell lung cancer (NSCLC). Eighty-three patients who underwent SBRT for pathologically proven stage I NSCLC were reviewed retrospectively. The prescribed dose was 48 Gy in four fractions at the isocenter (IC) under heterogeneity correction with the Batho power law (BPL). The clinical plans were recalculated with Eclipse (Varian) for the same monitor units under the BPL and anisotropic analytical algorithm (AAA) and with no heterogeneity correction (NC). The dose at the IC, dose that covers 95% of the volume (D95), minimum dose (Min), and mean dose (Mean) of the planning target volume (PTV) were compared under each algorithm and between patients with local lesion control (LC) and LR. The IC doses under NC were significantly lower than those under the BPL and AAA. Under the BPL, the mean PTV D95, Min and Mean were 8.0, 9.4 and 7.4% higher than those under the AAA, and 9.6, 9.2 and 4.6% higher than those under NC, respectively. Under the AAA, all dose–volumetric parameters were significantly lower in T1a patients than in those with T1b and T2a. With a median follow-up of 35.9 months, LR occurred in 18 patients. Between the LC and LR groups, no significant differences were observed for any of the metrics. Even after stratification according to T-stage, no significant difference was observed between LC and LR.

Dosimetric Advantage of Intensity-Modulated Radiotherapy for Whole Ventricles in the Treatment of Localized Intracranial Germinoma

PURPOSE To investigate the dosimetric advantage of intensity-modulated radiotherapy (IMRT) for whole ventricles (WV) in patients with a localized intracranial germinoma receiving induction chemotherapy. METHODS AND MATERIALS Data from 12 consecutive patients with localized intracranial germinomas who received induction chemotherapy and radiotherapy were used. Four-field coplanar three-dimensional conformal radiotherapy (3D-CRT) and seven-field coplanar IMRT plans were created. In both plans, 24 Gy was prescribed in 12 fractions for the planning target volume (PTV) involving WV and tumor bed. In IMRT planning, optimization was conducted to reduce the doses to the organs at risk (OARs) as much as possible, keeping the minimum dose equivalent to that of 3D-CRT. The 3D-CRT and IMRT plans were compared in terms of the dose-volume statistics for target coverage and the OARs. RESULTS IMRT significantly increased the percentage volume of the PTV receiving 24 Gy compared with 3D-CRT (93.5% vs. 84.8%; p = 0.007), while keeping target homogeneity equivalent to 3D-CRT (p = 0.869). The absolute percentage reduction in the irradiated volume of the normal brain receiving 100%, 75%, 50%, and 25% of 24 Gy ranged from 0.7% to 16.0% in IMRT compared with 3D-CRT (p < 0.001). No significant difference was observed in the volume of the normal brain receiving 10% and 5% of 24 Gy between IMRT and 3D-CRT. Conformation number was significantly improved in IMRT (p < 0.001). For other OARs, the mean dose to the cochlea was reduced significantly in IMRT by 22.3% of 24 Gy compared with 3D-CRT (p < 0.001). CONCLUSIONS Compared with 3D-CRT, IMRT for WV improved the target coverage and reduced the irradiated volume of the normal brain in patients with intracranial germinomas receiving induction chemotherapy. IMRT for WV with induction chemotherapy could reduce the late side effects from cranial irradiation without compromising control of the tumor.