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

Treatment of stage III non-small cell lung cancer and limited-disease small-cell lung cancer

This thesis concerns the treatment of stage III non-small cell lung cancer (NSCLC) and limited disease small-cell lung cancer (SCLC). We described a systematic review on the clinical results of radiotherapy, combined or not with chemotherapy, for inoperable NSCLC stage III with the aim to define the best sequence of radiotherapy and chemotherapy. We concluded that concurrent chemoradiotherapy demonstrated increased efficacy over sequential chemo-radiotherapy and should be the treatment of choice. The 5-year survival has increased from about 7% for radiotherapy alone to 10% for sequential and to about 15% for concurrent chemoradiotherapy. However, the concurrent chemo-radiotherapy schedules were associated with higher toxicity as compared to sequential therapy with the same drug doses. We investigated the influence of the waiting time for radiotherapy, i.e. the interval between end of induction chemotherapy and start radiotherapy, on the rate of tumour growth for patients with NSCLC stage III. We demonstrated that in the waiting time rapid tumour progression occurs as result of accelerated tumour cell proliferation. The mean waiting time was 80.3 days; in this period the median tumour volume increased with a factor of about 6. As a consequence, the gain obtained with induction chemotherapy with regards to volume reduction was lost in the waiting time for radiotherapy. Stage III NSCLC is correlated with tumour volumes in excess of 100 cm3. The tumour control probability analysis revealed that for tumours of that size local cure is almost impossible with the doses usually applied in radiotherapy. Due to the accelerated cell proliferation observed, we recommend that radiotherapy should start as soon as possible, preferably within two to three weeks after the last chemotherapy cycle. We investigated whether gemcitabine (dFdC) may cause radiosensitization. The radiosensitizing effect of dFdC might be less in normal healthy tissue and more restricted to undifferentiated tumour cells, making it a tumour-selective radiosensitizer. We tested whether dFdC acted as radiosensitizer in undifferentiated and well-differentiated rat tumours and on rat foot skin. We used undifferentiated L44 lung tumours in BN rats and MLL prostate tumours in Copenhagen rats, and well-differentiated L42 lung tumours in WAG/Rij rats. Radiosensitization was observed in the undifferentiated tumours but not in the well-differentiated tumour or the skin. Our data support further trials to evaluate the usefulness of dFdC as radiosensitizer in undifferentiated tumours. We described the results of a phase II national multicentre study with weekly docetaxel/cisplatin and concurrent thoracic radiotherapy followed, whenever possible, by surgery in patients with stage III non-small cell lung cancer. The 3-years overall survival was 38% and this is an encouraging result. We analysed the treatment results of our patients’ population with limited-disease small-cell lung cancer. They were treated with chemotherapy only and chemotherapy combined with radiotherapy. The treatment schemes with curative intention were sequential and concurrent chemoradiotherapy, both combined with prophylactic cranial irradiation. Our results indicate that the concurrently applied chemoradiotherapy resulted in longer median survival time and higher overall survival than sequential chemoradiotherapy, chemotherapy with palliative radiotherapy or chemotherapy only

Fatal Bilateral Pneumonitis After Locoregional Thoracic Chemoradiation in a Transplanted Patient Under Immunosuppressive Therapy

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Patient-reported outcomes after external beam radiotherapy versus brachytherapy for palliation of dysphagia in esophageal cancer: A matched comparison of two prospective trials

Contains fulltext : 229287.pdf (Publisher’s version ) (Open Access)BACKGROUND AND PURPOSE: A matched comparison of external beam radiotherapy (EBRT) versus brachytherapy recently demonstrated that EBRT appears at least as effective for palliating dysphagia in patients with incurable esophageal cancer. The aim of this analysis was to compare patient-reported outcomes (PROs) after EBRT versus brachytherapy. MATERIALS AND METHODS: In a multicenter prospective cohort study, patients with incurable esophageal cancer requiring palliation of dysphagia were included to undergo EBRT (20 Gy in 5 fractions). This EBRT cohort was compared to the single-dose 12 Gy brachytherapy cohort of the previously reported SIREC-trial. Propensity score matching was applied to adjust for baseline imbalances. The primary endpoint of dysphagia improvement was reported previously. PROs were secondary outcomes and assessed at baseline and 3 months after treatment using EORTC QLQ-C30 and QLQ-OES18 questionnaires. RESULTS: A total of 115 enrolled EBRT patients and 93 brachytherapy patients were eligible. After matching, 69 well-balanced pairs remained. At follow-up, significant deteriorations in functioning (i.e. physical, role, social), pain, appetite loss, and trouble with taste were observed after brachytherapy. In the EBRT group, such deterioration was observed only for role functioning, while significant improvements in trouble with eating and pain were found. Between-group comparison showed mostly comparable PRO changes, but significantly favored EBRT with regard to nausea, vomiting, pain, and appetite loss. CONCLUSION: Short course EBRT results in similar or better PROs at 3 months after treatment compared to single-dose brachytherapy for the palliation of malignant dysphagia. These findings further support its use and inclusion in clinical practice guidelines