N. Ueki

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.

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.

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.

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.

Intra- and interfractional variations in geometric arrangement between lung tumours and implanted markers

PURPOSE To quantify the intra- and interfractional variations between lung tumours and implanted markers. MATERIALS AND METHODS Gold markers were implanted transbronchially around a lung tumour in fifteen patients. They underwent four-dimensional computed tomography scans twice, and the centroids of the tumour and markers were determined. Intrafractional variations were defined as the residual tumour motions relative to the markers due to respiration from the end-exhale phase. Interfractional variations were defined as the residual setup errors after correction for the position of the implanted markers in end-exhale phase images. RESULTS The intrafractional variations differed between patients. The root mean squares of standard deviations for each phase were 0.6, 0.9, and 1.5mm in the right-left, anterior-posterior, and superior-inferior directions, respectively. The maximum difference in intrafractional variation among 10 phases was correlated with the amplitude of tumour motion in all directions and the tumour-marker distance in the anterior-posterior and superior-inferior directions. The interfractional variations were within 2.5mm. CONCLUSIONS The intrafractional variations differed according to the amount of tumour motion and the tumour-marker distance. Additionally, interfractional variations of up to 2.5mm were observed. Thus, a corresponding margin should be considered during implanted marker-based beam delivery to account for these variations.

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

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, &khgr;2 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.

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.

Osteoradionecrosis of the cervical vertebrae in patients irradiated for head and neck cancers

Osteoradionecrosis (ORN) is one of the common late adverse effects that follow radiation therapy for head and neck cancers. ORN usually develops on the mandible and less frequently on the maxilla. We present three cases of ORN of the cervical vertebrae, which is rarely reported. Two patients suffered from secondary osteomyelitis after neoadjuvant chemotherapy followed by definitive concurrent chemoradiation therapy with a hyperfractionated and an accelerated hyperfractionated regimen, respectively. For these patients, the high intensity of treatment was considered the cause of ORN. The third patient underwent concurrent chemoradiation therapy for upper thoracic esophageal cancer and subsequently underwent endoscopic laser resection and radiation therapy for hypopharyngeal cancer. ORN developed in the area of reirradiation. In this case, an excessive radiation dose was considered the cause. ORN of cervical vertebrae, different from that of the mandible and maxilla, has a risk of radiculopathy and myelopathy. In the future, ORN of cervical vertebrae will increase because metachronous double cancers will increase and opportunities for reirradiation, in turn, will increase. To prevent this, it is necessary to optimize the treatment schedule for radiation therapy, including the total dose, fractionation, and concurrent chemotherapy, and to decrease the volume of cervical vertebrae within the irradiation field.