Fatal bilateral pneumonitis after locoregional thoracic chemoradiation in a transplanted patient under immunosuppressive therapy

Background: After thoracic radiotherapy a pneumonitis may occur, mostly confined to the irradiated volume of the lung. In general, it resolves spontaneously without long-term effects. Case Report: A 68-year-old man was diagnosed with a stage IIIA adenocarcinoma of the lung and was treated with sequential chemoradiation. He had a heart and kidney transplant for which an immunosuppressant was taken. During the fourth week of radiotherapy, he developed a bilateral interstitial pneumonia. Despite antibiotics and steroids, the patient died twelve days after the onset of complaints due to respiratory failure. Autopsy showed in all pulmonary lobes extensive diffuse alveolar damage, probably leading to respiratory insufficiency and death. Literature and Conclusion: Bilateral pneumonitis after radiotherapy is thought to be an immunologically-mediated response, which usually resolves without long-term effects. Since in radiation pneumonitis an increase in T-cells is described, the suppression of these cells by an immunosuppressant might have exaggerated the pulmonary toxicity

Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study

Objectives: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. Materials and methods: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. Results: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. Conclusion: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations

Differences in Longitudinal Health Utility between Stereotactic Body Radiation Therapy and Surgery in Stage I Non-Small Cell Lung Cancer

INTRODUCTION: There is an ongoing debate on the optimal treatment for stage I NSCLC, with increasing evidence for comparable health outcomes after surgery and stereotactic body radiation therapy (SBRT). For clinical decision making, the experienced quality of life, summarized as health utility, is of importance to choosing between treatments. In this study, we evaluated differences in longitudinal health utility in stage I NSCLC in the first year after surgical resection versus after SBRT before any recurrence of disease. We also assessed the impact of potential prognostic variables on health utility. METHODS: Prospectively collected databases containing data on patients with stage I NSCLC treated with either SBRT or surgery were pooled from two large hospitals in the Netherlands. Quality of life data were measured by the Quality of Life Questionnaire-Core 30 questionnaire at baseline and 3, 6, and 12 months after treatment. Health utility (measured using the European Quality of Life Five-Dimension questionnaire) was calculated from the Quality of Life Questionnaire-Core 30 questionnaire by using a mapping algorithm. Propensity score matching was used to adjust for selection bias. Treatment effects were estimated for the matched patients by using a longitudinal mixed model approach. RESULTS: After correction for Eastern Cooperative Oncology Group score, sex, and age, the difference in 1-year averaged health utility between the SBRT and surgery groups was 0.026 (95% confidence interval: 0.028-0.080). Differences in health utility decreased over time. CONCLUSIONS: A small but not statistically significant difference in health utility was found between patients with stage I NSCLC treated with surgery and those treated with SBRT. Current analysis strengthens existing evidence that SBRT is an equivalent treatment option for early-stage NSCLC. Comparative cost-effectiveness remains to be determined

Improving survival prediction of oesophageal cancer patients treated with external beam radiotherapy for dysphagia

Introduction: The recent POLDER trial investigated the effects of external beam radiotherapy (EBRT) on dysphagia caused by incurable oesophageal cancer. An estimated life expectancy of minimally three months was required for inclusion. However, nearly one-third of the included patients died within three months. The aim of this study was to investigate if the use of prediction models could have improved the physician’s estimation of the patient’s survival. Methods: Data from the POLDER trial (N = 110) were linked to the Netherlands Cancer Registry to retrieve patient, tumour, and treatment characteristics. Two published prediction models (the SOURCE model and Steyerberg model) were used to predict three-month survival for all patients included in the POLDER trial. Predicted survival probabilities were dichotomised and the accuracy, sensitivity, specificity, and the area under the curve (AUC) were used to evaluate the predictive performance. Results: The SOURCE and Steyerberg model had an accuracy of 79% and 64%, and an AUC of 0.76 and 0.60 (p =.017), respectively. The SOURCE model had higher specificity across survival cut-off probabilities, the Steyerberg model had a higher sensitivity beyond the survival probability cut-off of 0.7. Using optimal cut-off probabilities, SOURCE would have wrongfully included 16/110 patients into the POLDER and Steyerberg 34/110. Conclusion: The SOURCE model was found to be a more useful decision aid than the Steyerberg model. Results showed that the SOURCE model could be used for three-month survival predictions for patients that are considered for palliative treatment of dysphagia caused by oesophageal cancer in addition to clinicians’ judgement

Prophylactic cranial irradiation versus observation in radically treated stage III non–small-cell lung cancer : A randomized phase III NVALT-11/DLCRG-02 study

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non–small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC—staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging—were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point—development of symptomatic brain metastases at 24 months—was defined as one or a combination of key symptoms that suggest brain metastases—signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms—and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases (P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity

Weekly Chemoradiation (Docetaxel/Cisplatin) Followed by Surgery in Stage III NSCLC; a Multicentre Phase II Study

Background: This prospective study analyzed the feasibility and efficacy of weekly concurrent chemoradiation (docetaxel/cisplatin) followed by surgery. The primary endpoint was radiological response. Patients and Methods: Six chemotherapy (docetaxel/cisplatin) cycles were administered on days 1, 8, 15, 22, 29 and 36 with concurrent thoracic radiotherapy in fractions of 1.8 Gy, to a total dose of 45 Gy. Patients underwent surgery depending on results of invasive mediastinal re-staging. Results: Forty-two out of 45 NSCLC stage III patients were evaluable. Nineteen patients showed partial/complete response (46%), 14 stable disease (34%) and eight (20%) progressive disease. Toxicity was mild. The 30-day postoperative mortality was 4.2%. Twenty-four patients (59%) proceeded to surgery and 20 (49%) underwent a complete resection (R0). Conclusion: Weekly concurrent chemoradiation (docetaxel/cisplatin) in stage III NSCLC results in a radiological response rate of 46% and mediastinal downstaging in 56%. Complete resection in downstaged patients was achieved in 49% of all patients

Prophylactic cranial irradiation versus observation in radically treated stage III non–small-cell lung cancer: A randomized phase III NVALT-11/DLCRG-02 study

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non–small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC—staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging—were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point—development of symptomatic brain metastases at 24 months—was defined as one or a combination of key symptoms that suggest brain metastases—signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms—and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases (P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity

Cost-effectiveness of stereotactic body radiation therapy versus video assisted thoracic surgery in medically operable stage I non-small cell lung cancer: A modeling study

OBJECTIVES: Stage I non-small cell lung cancer (NSCLC) can be treated with either Stereotactic Body Radiotherapy (SBRT) or Video Assisted Thoracic Surgery (VATS) resection. To support decision making, not only the impact on survival needs to be taken into account, but also on quality of life, costs and cost-effectiveness. Therefore, we performed a cost-effectiveness analysis comparing SBRT to VATS resection with respect to quality adjusted life years (QALY) lived and costs in operable stage I NSCLC. MATERIALS AND METHODS: Patient level and aggregate data from eight Dutch databases were used to estimate costs, health utilities, recurrence free and overall survival. Propensity score matching was used to minimize selection bias in these studies. A microsimulation model predicting lifetime outcomes after treatment in stage I NSCLC patients was used for the cost-effectiveness analysis. Model outcomes for the two treatments were overall survival, QALYs, and total costs. We used a Dutch health care perspective with 1.5 % discounting for health effects, and 4 % discounting for costs, using 2018 cost data. The impact of model parameter uncertainty was assessed with deterministic and probabilistic sensitivity analyses. RESULTS: Patients receiving either VATS resection or SBRT were estimated to live 5.81 and 5.86 discounted QALYs, respectively. Average discounted lifetime costs in the VATS group were €29,269 versus €21,175 for SBRT. Difference in 90-day excess mortality between SBRT and VATS resection was the main driver for the difference in QALYs. SBRT was dominant in at least 74 % of the probabilistic simulations. CONCLUSION: Using a microsimulation model to combine available evidence on survival, costs, and health utilities in a cost-effectiveness analysis for stage I NSCLC led to the conclusion that SBRT dominates VATS resection in the majority of simulations