Assessment of radiation pneumonitis and predictive factors in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

PURPOSE: Radiation pneumonitis (RP) is a dose-limiting toxicity associated with increased mortality for patients with non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). This study aims to assess the incidence of symptomatic RP (grade 2-5), rate of recovery and associated predictive factors. MATERIAL AND METHODS: We performed a retrospective population-based study including 602 patients with NSCLC who were treated with CRT between 2002 and 2016. RP and rate of recovery were analysed using Common Terminology Criteria for Adverse Events version 4.0. Stepwise logistic regression was performed to analyse potential predictive factors for the two endpoints RP grade ≥ 2 and RP grade ≥ 3. RESULTS: A total of 136 (23%) patients developed symptomatic RP and 37 (6%) developed RP grade ≥ 3. A total of 67 (71%) recovered, whereas the remaining 27 (29%), with the major proportion of patients belonging to the RP grade ≥ 3 group, suffered from prevailing sequelae. On multivariable analysis, the selected model for predicting RP grade ≥ 2 included the factors V20, smoking status, average fractions per week and chemotherapy agent. V20 and age were selected factors for RP grade ≥ 3. INTERPRETATION: The results suggest that regardless of all proposed factors predictive for RP, the most important influenceable significant factor still is dose to the lung. The main aim should be to avoid RP grade ≥ 3, where a substantial proportion of patients suffer from prevailing sequalae. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased. e factor still is dose to the lung. Consequently, the technical improvement and precision of radiotherapy delivery should continue to focus on lung sparing techniques also in the ongoing immunotherapy-containing schedules where the risk of pneumonitis may be increased.

Impact of delineation errors on the estimated organ at risk dose and of dose errors on the normal tissue complication probability model.

BACKGROUND: Normal tissue complication probability (NTCP) models are often based on doses retrieved from delineated volumes. For retrospective dose-response studies focusing on organs that have not been delineated historically, automatic segmentation might be considered. However, automatic segmentation risks generating considerable delineation errors and knowledge regarding how these errors impact the estimated organ dose is important. Furthermore, organ-at-risk (OAR) dose uncertainties cannot be eliminated and might affect the resulting NTCP model. Therefore, it is also of interest to study how OAR dose errors impact the NTCP modeling results. PURPOSE: To investigate how random delineation errors of the proximal bronchial tree, heart, and esophagus impact the estimated OAR dose, and to investigate how random errors in the doses used for dose-response modeling affect the estimated NTCPs. METHODS: We investigated the impact of random delineation errors on the estimated OAR dose using the treatment plans of 39 patients treated with conventionally fractionated radiation therapy of non-small-cell lung cancer. Study-specific reference structures were defined by manually contouring the proximal bronchial tree, heart and esophagus. For each patient and organ, 120 reshaped structures were created by introducing random shifts and margins to the entire reference structure. The mean and near-maximum dose to the reference and reshaped structures were compared. In a separate investigation, the impact of random dose errors on the NTCP model was studied performing dose-response modeling with study sets containing treatment outcomes and OAR doses with and without introduced errors. Universal patient populations with defined population risks, dose-response relationships and distributions of OAR doses were used as ground truth. From such a universal population, we randomly sampled data sets consisting of OAR dose and treatment outcome into reference populations. Study sets of different sizes were created by repeatedly introducing errors to the OAR doses of each reference population. The NTCP models generated with dose errors were compared to the reference NTCP model of the corresponding reference population. RESULTS: A total of 14 040 reshaped structures with random delineation errors were created. The delineation errors resulted in systematic mean dose errors of less than 1% of the prescribed dose (PD). Mean dose differences above 15% of PD and near-maximum doses differences above 25% of PD were observed for 211 and 457 reshaped structures, respectively. Introducing random errors to OAR doses used for dose-response modeling resulted in systematic underestimations of the median NTCP. For all investigated scenarios, the median differences in NTCP were within 0.1 percentage points (p.p.) when comparing different study sizes. CONCLUSIONS: Introducing random delineation errors to the proximal bronchial tree, heart and esophagus resulted in mean dose and near-maximum dose differences above 15% and 25% of PD, respectively. We did not observe an association between the dose level and the magnitude of the dose errors. For the scenarios investigated in this study, introducing random errors to OAR doses used for dose-response modeling resulted in systematic underestimations of the median NTCP for reference risks higher than the universal population risk. The median NTCP underestimation was similar for different study sizes, all within 0.1 p.p.