AIMS:In patients with locally advanced non-small cell lung cancer (LA-NSCLC), curative-intent radiotherapy (RT) or chemoradiotherapy (CRT) is associated with considerable toxicity, and approximately half of the patients die within two years. A better understanding of early mortality is needed to improve patient selection and guide supportive interventions. In this population-based, nationwide cohort study, we investigated the incidence, temporal distribution, and risk factors of early mortality. MATERIALS AND METHODS:Patients with stage II-III NSCLC treated with curative-intent RT/CRT in Denmark from 2010-2017 were included. Patients treated with preoperative or postoperative RT/CRT or stereotactic body radiation therapy were excluded. Early mortality was defined as all-cause death within 180 days from RT/CRT initiation. Multiple logistic regression was used to assess the impact of clinical and demographic variables. RESULTS:We included 1742 patients. The early mortality rate was 10%. The temporal distribution of deaths was uniform across the first year following RT/CRT, indicating the absence of a high-risk period. In multivariable analysis, increasing age and performance status, male sex, and unspecified histology (NSCLC not otherwise specified) were associated with an increased risk. By contrast, the Charlson Comorbidity Index (CCI), TNM stage, and treatment period did not significantly alter the risk of early mortality. Overall survival rates improved throughout the inclusion period but early mortality rates did not. CONCLUSION:No high-risk period for early mortality could be identified. Early mortality was not associated with CCI and other tools should be explored to quantify comorbidity for risk stratification in this setting.

Purpose/Objective(s) Image biomarkers on planning PET/CT-scans are potential prognostic tools in patient-specific predisposition to first site of failure in the treatment of locally advanced NSCLC-patients (LA-NSCLC) with curative intended chemo-/radiotherapy (cCRT). Materials/Methods Patients treated with cCRT for LA-NSCLC at a single institution from 2012-2018 were retrospectively included (N=197). Planning PET/CT scans were analyzed (commercially available software) with respect to selected image biomarkers (volume and sphericity of GTV-T on CT and SUVpeak and percentage of GTV-T volume with PET-signal above 50% of SUVpeak on PET). Clinical baseline characteristics (gender, stage, histology, performance status (PS)) were collected. Progression was scored as either loco-regional (LR), distant metastasis (M), simultaneous loco-regional and distant (LR+M) or death with no evidence of disease (DNED). Data were analyzed with a Fine and Gray competing risk analysis and variables included are shown in table 1. For each failure mode, subdistributed hazard ratios (sHR) with 95%-confidence intervals are reported. Results Median follow-up-time was 24 months. Significant predictors of LR failure were histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC), sHR=2.05 [1.02-4.13], p=0.045) and SUVpeak (sHR=1.079 pr. SUV-increase [1.01-1.16], p=0.03). Histology remained a significant predictor for M failure (sHR=0.195 [0.07-0.52], p<0.01). No significant predictive parameters for LR+M-failure or DNED were found. Comparing cumulative incidences between the four groups (divided by histology and SUVpeak above/below median) using Fine-Gray test showed significant differences between the four groups in terms of LR-failure (P<0.01), M-failure (p<0.01) and LR+M-failure (p<0.01). LR-failures 2 years after treatment were similar for SCC regardless of SUVpeak (37% vs. 32%). Meanwhile, AC with SUVpeak above median had a significantly higher risk of LR-failure after 2 years than AC with SUVpeak below median (27% vs. 8%). M-failure after 2-years varied with histology but not with SUVpeak (AC: 35% vs. 28%, SCC: 9% vs. 5%). Conclusion In a competing risk analysis of 197 LA-NSCLC patients treated with cCRT, histology and SUVpeak prior to cCRT were identified as significant predictors of LR-failure. Patients with AC displayed a lower risk of LR-failure if SUVpeak was below median, which separated this group from the remaining patients. In general, AC were significantly more prone to M-failure than SCC.

Purpose/Objective(s) In patients with refractory ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) showed promising results for otherwise untreatable patients. The STOPSTORM.eu project coordinates European efforts to validate STAR. The primary goal of this critical structures benchmark study was to harmonize contouring of organs at risk (OARs) for STAR within the STOPSTORM.eu consortium. The results enable to refine protocols and guidelines to ensure treatment harmonization. Materials/Methods Three STAR cases were selected for this benchmark study and sent to all radiation oncology centers within the consortium. Every case had a contrast-enhanced cardiac CT which was already deformed to the primary planning-CT to contour the OARs in detail. Every center was asked to contour 31 OARs according to literature-based guidelines. The resulting structure sets were qualitatively evaluated in an oncology imaging informatics system (technology company). For all structures and specific subset of structures the Dice coefficient (DICE) was calculated in a treatment planning system for all possible combinations of two centers. Results Twenty centers participated in the critical structure contouring benchmark. Contouring of the structures was performed with high accuracy according to the provided guidelines. The contours of common OARs, such as the heart, stomach, esophagus, bronchus, aorta and spinal canal in had a high conformity (median DICE resp. 0.92, 0.78, 0.71, 0.57, 0.87 and 0.71). In the substructures of the heart (chambers, valves, arteries, and nodes), deviations in the contours occurred more frequently. While the cardiac chambers had a high conformity value (median DICE of 0.84), the valves, arteries and nodes had lower values (median DICE of resp. 0.16, 0.31 and 0.26). However, these structures do not yet have a consensus for treatment planning purposes and late toxicity but need to be contoured correctly for future analysis within the STOPSTORM.eu project. Conclusion This large and unique STOPSTORM.eu multi-center critical structures benchmark study showed a high accuracy regarding standard critical structures. For cardiac substructures some deviations occurred resulting in the development of new definitions for contouring these structures within the consortium. In addition, a close collaboration between radiation oncologist and cardiac electrophysiologist is warranted to reach optimal and effective STAR treatment.

Purpose or ObjectiveThe RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response.Selumetinib (AZD6244/ ARRY-142886) an inhibitor of MEK, has been shown to enhance the effect of radiotherapy (RT) in preclinical studies. Material and MethodsThis single-arm, single-centre, open-label phase I trial, recruited patients with stage III non-small cell lung cancer (NSCLC) unsuitable for concurrent chemoradiotherapy or stage IV with dominant thoracic symptoms.Enrolment to the dose-finding stage used a Fibonacci 3+3 design (maximum number=18) followed by recruitment of an expanded cohort (n=15).Oral selumetinib was administered at a starting dose of 50mg twice daily commencing 7 days before RT, then in combination with thoracic radiotherapy (TRT) for 6-6.5 weeks (60-66Gy in 30-33 fractions).The primary objective was to determine the recommended Phase 2 dose. ResultsFrom 06/10-02/15, 21 patients were enrolled.Median age 63 years (range 50-73).M:F ratio 12(57%):9(43%).ECOG PS 0:1, 7(33%):14(67%).Stage III 16(76%):IV 5(24%).Mean GTV 64cm3 (range 0.8-223.73).In the dose-finding stage, 2 out of a total of 6 patients experienced dose-limiting toxicities (DLT) but only one DLT (G3 diarrhoea) was treatment-related.Despite meeting the pre-defined criteria for escalation, the trial management group elected to treat the expanded cohort (n=15) at the starting dose.All 21 received induction chemotherapy and completed TRT as planned.Compliance to selumetinib was >80%.The most common adverse events are listed in table 1.There were 2 survivors (24 & 26 months) at analysis.The 1-year survival was 38%, stage III 44% vs stage IV 20%, 2-year survival was 24%, stage III 31% vs stage IV 0%.The main cause of disease progression was distant metastases in 10/21 (48%).

Purpose or Objective: MLC and couch tracking are promising techniques for intrafractional tumor motion management. However, both techniques have their limitations that result in residual dosimetric errors: MLC tracking perpendicular to the MLC leaves is limited by the finite MLC leaf width, while couch tracking has slower dynamics than the MLC and might be uncomfortable for the patient. Here, we suggest a range of potential hybrid MLC-couch tracking strategies and test the performance of each strategy with extensive tracking simulations.

Purpose or Objective: MLC and couch tracking are promising techniques for intrafractional tumor motion management. However, both techniques have their limitations that result in residual dosimetric errors: MLC tracking perpendicular to the MLC leaves is limited by the finite MLC leaf width, while couch tracking has slower dynamics than the MLC and might be uncomfortable for the patient. Here, we suggest a range of potential hybrid MLC-couch tracking strategies and test the performance of each strategy with extensive tracking simulations.

_____________________________________________________________________________________________________VMAT treatments, and it is based on correlation functions between EPID signals and doses in patient.The software is easy to implement for Varian, Elekta and Siemens linacs, and it is connected with the Record and Verify system of the Center, supplying the results in a few seconds.The method supplies two tests (i) the ratio R=(Diso/Diso,TPS) between the reconstructed and computed isocentre dose, with pass criteria of ±5% and (ii) a 2D γ-analysis between EPID images with the following pass criteria: the percentage of the points Pγ<1 should be higher than 90% for 3DCRT and 95% for IMRT and VMAT; the γ-mean should be less than 0.5 and 0.3 for 3DCRT and IMRT-VMAT respectively. Results:The percentage of the off-tolerance tests ranged between 10% and 17%, depending on the type of treatment checked.The causes of dosimetric discrepancies, in order of frequency were: setu-up variations, attenuators left in the field, morphological changes, TPS implementation and linac output factor.All the causes of the off-tolerance tests were justified and, once removed, the mean R values of all patients were within 5% and the γ-analysis indexes satisfied the specific pass criteria.The discrepancies due to patient morphological changes triggered new TC or CBCT scans to verify the need of an adaptive plane.Some of these cases have been discussed by radiotherapists and physicists. Conclusion:The multicenter result proved: (i) the great utility to obtain IVD tests in quasi real time, (ii) the positive role of the physicists during the dose-delivery step, (iii) SOFTDISO allows to understand the causes of dose discrepancies triggering adequate QC, and once the causes of errors were removed all the pass criteria were respected (iv) the role of IVD to intercept patient morphological changes to examine for eventual adaptive radiotherapy strategy.

3rd ESTRO Forum 2015 did not contribute significantly and was thus not incorporated.Model 2 incorporated the number of ``High Risk nodal stations``(0, 1-2 or ≥3), gender and cT4.Model 3 comprised esophageal Dmean and Dmax, gender and total GTV.Model 1 had an AUC of 0.62, which decreased to 0.58 after correction for overfitting.Model 2 yielded an AUC of 0.73 (corrected for overfitting: AUC=0.70) and model 3 had an AUC of 0.69 (corrected for overfitting: 0.67).In a secondary analysis, the number of nodal stations close to the esophagus correlated with esophageal Dmean and Dmax: 0.53 (p<0.001) and 0.40 (p<0.001),respectively.Conclusions: In SCLC patients referred for treatment with accelerated concurrent chemo-irradiation, a predictive model for esophagitis grade ≥3 using only clinical variables (gender, number of nodal stations close to the esophagus and cT4-stage) performs at least as well as a model incorporating planning parameters.This allows clinicians to directly identify high-risk patients.External validation is ongoing.