Abstract Book

ESTRO 37

S389

Material and Methods This study included 217 stage I non-small cell lung cancer patients across 2 institutions whom received SBRT (either 3D-CRT or VMAT). The most common fractionation scheme given was 60 Gy in 3 fractions. The endpoints considered were distant metastasis (DM), loco-regional control (LRC) and radiation pneumonitis (RP) (grade 3+ based on Common Terminology Criteria for Adverse Events (CTCAE) v4.0). The dose (converted to EQD2) in a proximal region directly outside of the PTV was computed. An analysis of dosimetric factors that included the mean dose in regions of variable thickness around the PTV (from 0 to 100 mm) was performed. For each of these factors, area under the curve (AUC) and odds ratios with respect to the outcome parameters: DM, LRC and RP were estimated. Confidence intervals were calculated and a two-tailed p -test was performed for all computed odds ratios. Kaplan-Meier analysis was performed along with an examination of the mean dose fall-off extending outwards from the PTV compared between patients of differing outcomes. A multivariate logistic regression analysis of possible confounding factors including tumor location, tumor size, cancer type, homogeneity index and fractionation scheme was performed. Results Thirty-seven (17%) patients developed DM after a median follow-up of 24 months. A comparison of the mean dose fall-off between the patients who developed DM and those who did not, demonstrated that the mean dose outside the PTV, delivered to a region of thickness 30 mm had an AUC of 0.82 and an odds ratio with respect to DM of 0.09 (95% CI: 0.03,0.24); p < 0.0001. Two years after treatment completion, the rate of DM in patients where the mean dose delivered to this region was higher than 20.8 Gy 2 was only 5% compared to nearly 60% in those who received a dose lower than 20.8 Gy 2 . The KM curve representing the separation between patients who received more than the threshold dose (blue) and those who received less (red) is shown below (hazard ratio of 24.17 (95% CI: 10.74-54.36); p <0.0001). No correlations were found between any of the factors and either LRC or RP. Similarly, no confounding factors were found.

We report on the results from second interim analysis on toxicity from the Danish NARLAL2 trial (Novel Approach on Radiotherapy for LA-NSCLC). Material and Methods NARLAL2 is a multi-centre, randomized phase III trial testing an isotoxic FDG-PET driven, inhomogeneous dose escalation in 33 fractions (F) against standard homogenous RT 66 Gy in 33 F (NCT02354274). There is an extended QA-program along with this protocol including procedure before recruitment, during, and after treatment. This includes workshops, on-site visit, dose plan uploading to dose-planning bank, daily imaging, adaptive strategy etc (Moeller el al, Radiother Oncol. 2017 Aug;124(2):311-317 ). In order to avoid excess toxicity with this dose escalation we planned interim analysis to evaluate acute and semi acute toxicity when the first 20, 40, and 60 patients (pts) enrolled in the dose escalated arm had three months follow-up. Observation of ≥10% acute radiation related non-hematologic toxicity of grade ≥4 in the escalated arm was regarded unacceptable, and the study would be stopped for further assessment. Using the method of O´Brien-Flemming, the stopping rules are activated if 7 of first 20 pts in the dose-escalated arm experienced toxicity as described. Likewise, 9 of the first 40 pts etc. Late toxicity would be evaluated after a minimum of 12 months potential follow-up after end of RT, but up to 5% grade ≥4 is considered acceptable. Enrolment for this trial started on 2015 with planned 330 pts. Results Four centres are currently enrolling pts and another 4 centres are to start. A number of 101 pts have been randomized Oct 2017, with 53 pts treated in the escalated arm. At the first interim analysis on acute/ semi acute toxicity, 2 pts experienced grade ≥4 (haemoptysis and infection), but neither of these were related to the RT. At the second interim analysis, one further patient experienced grade ≥4 (vena cava superior syndrome), which might be related to the RT. The point for the first interim analysis on late toxicity has not yet been reached. Conclusion PET-FDG driven inhomogeneous dose escalation in LA- NSCLC pts seems safe according to acute-semi acute toxicity in this isotoxic setting evaluated in 2 interim analyses for acute/semi-acute toxicicty. PO-0755 Can dose proximal to the PTV influence the risk of distant metastases in SBRT lung cancer patients? A. Diamant 1 , A. Chatterjee 1 , I. El Naqa 2 , H. Bahig 3 , E. Filion 3 , C. Robinson 4 , S. Faria 5 , H. Al-Halabi 5 , K. Adil 5 , J. Seuntjens 1 1 McGill University, Medical Physics Unit, Montréal, Canada 2 Michigan University, Department of Radiation Oncology, Ann Arbor, USA 3 Centre Hospitalier de Université de Montréal, Department of Radiation Oncology, Montréal, Canada 4 University of Washington in St. Louis, Department of Radiation Oncology, St. Louis, USA 5 McGill University Health Centre, Department of Radiation Oncology, Montréal, Canada Purpose or Objective In an era where little is known about the “abscopal” (out of the field) effects of lung SBRT, this study assessed possible effects of the dose to the region directly outside of the PTV. We looked for correlations between the dose to this region and the risk of cancer recurrence after SBRT in patients with primary stage I non-small cell lung cancer.

Conclusion The results of our study suggest that the dose received by the “abscopal” region proximal to the PTV has a significant impact on the risk of distant metastases. This risk may be attributed to inadequate dose coverage due to the omission of a CTV resulting in microscopic disease extensions not receiving a tumoricidal dose. Should these results be further verified, caution should be taken, particularly when a treatment plan results in a steep dose gradient extending outwards from the PTV.