ESTRO 36 Abstract Book

S67 ESTRO 36 _______________________________________________________________________________________________

Results Almost 50% of the patients had tumour motion amplitudes of less than 5mm. For these patients, the simulated dose degradation per fraction was much smaller than for patients with larger motion amplitudes, with 2% versus 12 % average absolute reduction of the V95 (p<0.01), and an average increase in absolute V107 of 2% vs 9% (p<0,01). In no patient case studied was the minimum dose in the target degraded to below 80% of the prescribed dose, and rarely increased above 120%. Simulating a 33-fraction treatment, the mean reduction of the V95 was below 1% for patients with motion amplitudes below 5mm, while for patients with larger motion, V95 was degraded on average by 4% with worst case scenarios of 4% versus 19% (p<0.01), cf. Fig. 1. V107 had an average increase of about 0% and 1% (n.s.), with worst case values of 5% and 15%. The additional analysis of one patient case with a repeated CT revealed a large increase of tumour motion by about 5mm during treatment, resulting in a large dose degradation and partial miss of the target (V95<70%), cf. Fig. 2.

of fractionated treatment. Furthermore, the tumour motion needs to be assessed during treatment for all patients to quickly react to possible changes in motion which might require a treatment adaptation.

Proffered Papers: Lung

OC-0139 Induction of pulmonary hypertension may explain early mortality after thoracic radiotherapy P. Van Luijk 1 , T.M. Gorter 2 , T.P. Willems 3 , R.P. Coppes 1 , J. Widder 1 , J.A. Langendijk 1 1 University Medical Center Groningen, Department of Radiation Oncology, Groningen, The Netherlands 2 University Medical Center Groningen, Department of Cardiology, Groningen, The Netherlands 3 University Medical Center Groningen, Department of Radiology, Groningen, The Netherlands Purpose or Objective Studies of primary or postoperative radiotherapy for thoracic tumours, such as for lung and oesophageal cancer) suggest increased early post-treatment mortality with escalated dose (e.g. RTOG0617, INT0123). This increase in mortality is largely unexplained and is not due to currently-recognized cardiac and pulmonary toxicities. We have previously shown in rats that thoracic irradiation can also lead to pulmonary hypertension (PH) secondary to endothelial cell loss and pulmonary vascular remodelling (1). PH is a progressive and lethal disease that might explain the early mortality after thoracic radiotherapy. However, since detection of PH requires specialized diagnostics, PH has not been assessed in RT patients so far. Therefore, the main objective of this first- in-human translational study was to test the hypothesis that thoracic radiotherapy can induce PH. Material and Methods Patients with locally advanced NSCLC undergoing standard concurrent chemoradiotherapy (60 Gy in 5 weeks) were included in this prospective cohort study (clinicaltrials.gov; NCT02377934). Since PH typically decreases pulmonary arterial blood flow (PAF) and acceleration time (PAcT), these were measured using cardiac MRI before and at 6 and 12 weeks after radiotherapy. To establish treatment dependence, changes in PAF and PAcT were tested for correlation with mean dose to the lungs. Results PAF was reduced by 0.5-0.6 l/min in individual (left/right) lungs receiving >15 Gy. The reduction in PAF was significantly correlated with mean radiation dose to that lung (p=0.04 and p<0.01 at 6 and 12 weeks after radiotherapy, respectively). In addition, in patients receiving >15 Gy mean dose to their total lung volume, PAcT was decreased by 30-40 ms, and this reduction in PAcT again was correlated with dose (p=0.03 and p=0.07 at 6 weeks and 12 weeks after radiotherapy respectively). Both hemodynamic changes are strong indicators for PH. Therefore, these results indicate that PH occurs in patients treated with thoracic radiotherapy. Conclusion In line with our preclinical data we found that thoracic radiotherapy may induce pulmonary hypertension, which might in turn explain observed early mortality in patients treated with thoracic radiotherapy. Additional investigations are needed to characterise the incidence and clinical impact of radiotherapy-induced PH and to develop prevention and treatment strategies to ameliorate its consequences in terms of quality of life and survival of these patients.

Conclusion Motion amplitude is an indicator of dose degradation caused by the interplay effect. Fractionation reduces the dose degradation to such an amount that rescanning might be unnecessary for patients with a small tumour motion less than 5mm. Patients with larger tumour motion should not be treated without any kind of motion mitigation technique (e.g. rescanning , gating or breath hold) to prevent tumour underdosage persisting through to the end