Bronchial Stenosis in Central Pulmonary Tumors Treated With Stereotactic Body Radiation Therapy.

PURPOSE: Stereotactic body radiation therapy (SBRT) in lung tumors has an excellent local control due to the high delivered dose. Proximity of the proximal bronchial tree (PBT) to the high dose area may result in pulmonary toxicity. Bronchial stenosis is an adverse event that can occur after high dose to the PBT. Literature on the risk of developing bronchial stenosis is limited. We therefore evaluated the risk of bronchial stenosis for tumors central to the PBT and correlated the dose to the bronchi. METHODS AND MATERIALS: Patients with a planning tumor volume (PTV) ≤2 cm from PBT receiving SBRT (8 × 7.5 Gy) between 2015 to 2019 were retrospectively reviewed. Main bronchi and lobar bronchi were manually delineated. Follow-up computed tomography scans were analyzed for bronchial stenosis and atelectasis. Bronchial stenosis was assessed using Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4). Patient, tumor, dosimetric factors and survival were evaluated between patients with and without stenosis using uni- and multivariate and Kaplan-Meier analysis. RESULTS: Fifty-one patients were analyzed with a median age of 70 years and World Health Organization (WHO) performance status ≤1 in 92.2%. Median follow-up was 36 months (interquartile range [IQR], 19.6-45.4) and median overall survival 48 months (IQR 21.5-59.3). In 15 patients (29.4%) bronchial stenosis was observed on follow-up computed tomography scan. Grade 1 stenosis was seen in 21.6% (n = 11), grade 2 in 7.8% (n = 4). No grade ≥3 stenosis was observed. Median time to stenosis was 9.6 months (IQR 4.4-19.2). Patients who developed stenosis had significantly larger gross tumor volume with a median of 19 cm3(IQR 7.7-63.2) versus 5.2 cm3 (IQR 1.7-11.3, P <.01). Prognostic factors in multivariate analysis for stenosis were age (P = .03; odds ratio [OR] 1.1), baseline dyspnea (P = .02 OR 7.7), and the mean lobar bronchus dose (P = .01; OR 1.1). CONCLUSIONS: Low-grade (≤2) lobar bronchial stenosis is a complication in approximately one-third of patients after SBRT for lung tumors with a PTV ≤2 cm from PBT. Prognostic risk factors were age, baseline dyspnea and mean dose on a lobar bronchus.

The dynamics and prognostic value of FDG PET-metrics in weekly monitoring of (chemo)radiotherapy for NSCLC.

PURPOSE: To test if the relative change in FDG-PET SUVmax over the course of treatment was associated with disease progression and overall survival. Additionally, the prognostic values of other first-order PET-metric changes were investigated. METHODS: The study included 38 patients with stage II-III NSCLC, who underwent concurrent chemoradiotherapy. Patients received two pre-treatment FDG-PET scans and four during-treatment scans at weekly intervals. SUVmax was normalized to the start of treatment and analyzed using linear regression. Linear regression coefficients of other first order PET-metrics were grouped according to dissimilarity. Associations to patient outcome were analyzed using Cox hazard ratio. RESULTS: Twenty-eight patients satisfied the criteria for analysis. All PET-metrics demonstrated a strong linear correlation with time during treatment [median R-range: -0.87: -0.97]. No strong associations (p > 0.10) were found for the relative slope of SUVmax to patient outcomes. Other first-order metrics did correlate with outcome but the single imaging time-point maximizing the association of PET response with outcome varied per PET metric and outcome parameter. CONCLUSION: All investigated FDG PET metrics linearly decreased during treatment. Relative change in SUVmax was not associated to patient outcome while several other first order PET-metrics were related to patient outcome. A single optimal imaging time-point could not be identified.

Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial.

BACKGROUND: Most patients with extensive stage small-cell lung cancer (ES-SCLC) who undergo chemotherapy, and prophylactic cranial irradiation, have persistent intrathoracic disease. We assessed thoracic radiotherapy for treatment of this patient group. METHODS: We did this phase 3 randomised controlled trial at 42 hospitals: 16 in Netherlands, 22 in the UK, three in Norway, and one in Belgium. We enrolled patients with WHO performance score 0-2 and confirmed ES-SCLC who responded to chemotherapy. They were randomly assigned (1:1) to receive either thoracic radiotherapy (30 Gy in ten fractions) or no thoracic radiotherapy. All underwent prophylactic cranial irradiation. The primary endpoint was overall survival at 1 year in the intention-to-treat population. Secondary endpoints included progression-free survival. This study is registered with the Nederlands Trial Register, number NTR1527. FINDINGS: We randomly assigned 498 patients between Feb 18, 2009, and Dec 21, 2012. Three withdrew informed consent, leaving 247 patients in the thoracic radiotherapy group and 248 in the control group. Mean interval between diagnosis and randomisation was 17 weeks. Median follow-up was 24 months. Overall survival at 1 year was not significantly different between groups: 33% (95% CI 27-39) for the thoracic radiotherapy group versus 28% (95% CI 22-34) for the control group (hazard ratio [HR] 0.84, 95% CI 0.69-1.01; p=0.066). However, in a secondary analysis, 2-year overall survival was 13% (95% CI 9-19) versus 3% (95% CI 2-8; p=0.004). Progression was less likely in the thoracic radiotherapy group than in the control group (HR 0.73, 95% CI 0.61-0.87; p=0.001). At 6 months, progression-free survival was 24% (95% CI 19-30) versus 7% (95% CI 4-11; p=0.001). We recorded no severe toxic effects. The most common grade 3 or higher toxic effects were fatigue (11 vs 9) and dyspnoea (three vs four). INTERPRETATION: Thoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with ES-SCLC who respond to chemotherapy. FUNDING: Dutch Cancer Society (CKTO), Dutch Lung Cancer Research Group, Cancer Research UK, Manchester Academic Health Science Centre Trials Coordination Unit, and the UK National Cancer Research Network.

Management of radiation oncology patients with a pacemaker or ICD: a new comprehensive practical guideline in The Netherlands. Dutch Society of Radiotherapy and Oncology (NVRO).

Current clinical guidelines for the management of radiotherapy patients having either a pacemaker or implantable cardioverter defibrillator (both CIEDs: Cardiac Implantable Electronic Devices) do not cover modern radiotherapy techniques and do not take the patient's perspective into account. Available data on the frequency and cause of CIED failure during radiation therapy are limited and do not converge. The Dutch Society of Radiotherapy and Oncology (NVRO) initiated a multidisciplinary task group consisting of clinical physicists, cardiologists, radiation oncologists, pacemaker and ICD technologists to develop evidence based consensus guidelines for the management of CIED patients. CIED patients receiving radiotherapy should be categorised based on the chance of device failure and the clinical consequences in case of failure. Although there is no clear cut-off point nor a clear linear relationship, in general, chances of device failure increase with increasing doses. Clinical consequences of device failures like loss of pacing, carry the most risks in pacing dependent patients. Cumulative dose and pacing dependency have been combined to categorise patients into low, medium and high risk groups. Patients receiving a dose of less than 2 Gy to their CIED are categorised as low risk, unless pacing dependent since then they are medium risk. Between 2 and 10 Gy, all patients are categorised as medium risk, while above 10 Gy every patient is categorised as high risk. Measures to secure patient safety are described for each category. This guideline for the management of CIED patients receiving radiotherapy takes into account modern radiotherapy techniques, CIED technology, the patients' perspective and the practical aspects necessary for the safe management of these patients. The guideline is implemented in The Netherlands in 2012 and is expected to find clinical acceptance outside The Netherlands as well.

Tumor volume as prognostic factor in chemoradiation for advanced head and neck cancer.

BACKGROUND: Tumor volume is an important predictor of outcome in radiotherapy alone. Its significance in concomitant chemoradiation (CCRT) is much less clear. We analyzed the prognostic value of primary tumor volume for advanced head and neck squamous cell carcinoma (HNSCC) treated with CCRT. METHODS: Three hundred sixty patients treated with definitive CCRT for advanced HNSCC were selected. The pretreatment MRI or CT scan was used to calculate the primary tumor volume. Median follow-up was 19.8 months. RESULTS: The average primary tumor volume was 37.0 cm³ (range, 2.1-182.7 cm³; median, 28.7 cm³). Multivariate analysis showed a significant effect of tumor volume on local control. The hazard ratio for a local recurrence increased by 14% per 10 cm³ volume increase (95% CI, 8% to 21%). There was no significant independent effect of T and N status on local control. CONCLUSION: For advanced HNSCC, tumor volume is more powerful for predicting outcome after CCRT than TNM status.

HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors.

PURPOSE: The purpose of this study was to combine gene expression profiles and clinical factors to provide a better prediction model of local control after chemoradiotherapy for advanced head and neck cancer. MATERIAL AND METHODS: Gene expression data were available for a series of 92 advanced stage head and neck cancer patients treated with primary chemoradiotherapy. The effect of the Chung high-risk and Slebos HPV expression profiles on local control was analyzed in a model with age at diagnosis, gender, tumor site, tumor volume, T-stage and N-stage and HPV profile status. RESULTS: Among 75 patients included in the study, the only factors significantly predicting local control were tumor site (oral cavity vs. Pharynx, hazard ratio 4.2 [95% CI 1.4-12.5]), Chung gene expression status (high vs. Low risk profile, hazard ratio 4.4 [95% CI 1.5-13.3]) and HPV profile (negative vs. Positive profile, hazard ratio 6.2 [95% CI 1.7-22.5]). CONCLUSIONS: Chung high-risk expression profile and a negative HPV expression profile were significantly associated with increased risk of local recurrence after chemoradiotherapy in advanced pharynx and oral cavity tumors, independent of clinical factors.