B. Stam

Dose to heart substructures is associated with non-cancer death after SBRT in stage I–II NSCLC patients

BACKGROUND AND PURPOSE To investigate potential associations between dose to heart (sub)structures and non-cancer death, in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT). METHODS 803 patients with early stage NSCLC received SBRT with predominant schedules of 3×18Gy (59%) or 4×12Gy (19%). All patients were registered to an average anatomy, their planned dose deformed accordingly, and dosimetric parameters for heart substructures were obtained. Multivariate Cox regression and a sensitivity analysis were used to identify doses to heart substructures or heart region with a significant association with non-cancer death respectively. RESULTS Median follow-up was 34.8months. Two year Kaplan-Meier overall survival rate was 67%. Of the deceased patients, 26.8% died of cancer. Multivariate analysis showed that the maximum dose on the left atrium (median 6.5Gy EQD2, range=0.009-197, HR=1.005, p-value=0.035), and the dose to 90% of the superior vena cava (median 0.59Gy EQD2, range=0.003-70, HR=1.025, p-value=0.008) were significantly associated with non-cancer death. Sensitivity analysis identified the upper region of the heart (atria+vessels) to be significantly associated with non-cancer death. CONCLUSIONS Doses to mainly the upper region of the heart were significantly associated with non-cancer death. Consequently, dose sparing in particular of the upper region of the heart could potentially improve outcome, and should be further studied.

Dose–effect analysis of radiation induced rib fractures after thoracic SBRT

BACKGROUND AND PURPOSE To determine a dose-effect relation for radiation induced rib fractures after stereotactic body radiation therapy (SBRT) in early stage non-small cell lung cancer (NSCLC). Automatic rib delineation has enabled the analysis of a large patient group. MATERIAL AND METHODS Four-hundred and sixty-six patients with stage I/II NSCLC received SBRT with a median of 54Gy in 3 fractions. The optimal EQD2-corrected dose parameter to predict (a)symptomatic fractures was found using Cox regression. Three normal tissue complication probability (NTCP) models based on this optimal parameter were constructed: (1) at a median follow up (FU) of 26months, (2) for all data, with time to toxicity taken into account and (3) at a FU of 26months, excluding low dose ribs. RESULTS The median time to fracture was 22 (range 5-51) months. Maximum rib dose best predicted fractures. The TD50 (dose with 50% complication) of the second NTCP model was 375Gy. The TD50 was significantly higher for the other models indicating an under-estimation of the dose effect at the median follow-up time and/or when excluding low dose ribs. CONCLUSIONS The risk of symptomatic rib fractures after SBRT was significantly correlated to dose, and was <5% at 26months when Dmax<225Gy.

Heart dose associated with overall survival in locally advanced NSCLC patients treated with hypofractionated chemoradiotherapy

Association of heart dose and overall survival was investigated in a cohort including 469 locally-advanced NSCLC patients receiving daily low-dose hypofractionated chemo-radiotherapy. Significant associations were found over a range of dose parameters. Multivariate analysis showed significant associations of heart_V2Gy:HR=1.007%-1 (95% CI:1.002-1.013; p=0.006), age:HR=1.026year-1 (1.011-1.042; p=0.001) and GTV volume:HR=1.001cc-1 (1.000-1.002; p=0.006) with overall survival.

Validation of automatic segmentation of ribs for NTCP modeling.

BACKGROUND AND PURPOSE Determination of a dose-effect relation for rib fractures in a large patient group has been limited by the time consuming manual delineation of ribs. Automatic segmentation could facilitate such an analysis. We determine the accuracy of automatic rib segmentation in the context of normal tissue complication probability modeling (NTCP). MATERIALS AND METHODS Forty-one patients with stage I/II non-small cell lung cancer treated with SBRT to 54 Gy in 3 fractions were selected. Using the 4DCT derived mid-ventilation planning CT, all ribs were manually contoured and automatically segmented. Accuracy of segmentation was assessed using volumetric, shape and dosimetric measures. Manual and automatic dosimetric parameters Dx and EUD were tested for equivalence using the Two One-Sided T-test (TOST), and assessed for agreement using Bland-Altman analysis. NTCP models based on manual and automatic segmentation were compared. RESULTS Automatic segmentation was comparable with the manual delineation in radial direction, but larger near the costal cartilage and vertebrae. Manual and automatic Dx and EUD were significantly equivalent. The Bland-Altman analysis showed good agreement. The two NTCP models were very similar. CONCLUSIONS Automatic rib segmentation was significantly equivalent to manual delineation and can be used for NTCP modeling in a large patient group.

OC-0399: Dose to heart substructures is associated with non-cancer death after SBRT in stage I NSCLC patients

Material and Methods: From 2006-2013 801 patients with early stage NSCLC were treated with CBCT guided SBRT (median 54 Gy in 3 fractions) in 5 institutes for whom treatment plans were available. 565 patients were analyzed after exclusion of synchronous or metachronous tumors (n=80), follow-up<1y (n=63), or death from cancer (93).An average anatomy was constructed based on 109 patients of the 5 institutes using deformable image registration. Subsequently, all patients were registered to this average anatomy and the corresponding dose distribution was deformed accordingly [1]. The heart and substructures right atrium, left atrium, right ventricle, left ventricle, superior vena cava, descending aorta and left pulmonary artery were contoured on the average anatomy. For each (sub)structure dosimetric parameters DV (V: 0 cc-max), VD (D: 0 Gy-max), EUDn (n: 0.1-10) were obtained.Associations of these dosimetric parameters with death were evaluated using univariate Cox regression. Per (sub)structure the parameter with the lowest Akaike information criterion was selected and used in subsequent analyses. Correlations between all (sub)structures were assessed prior to inclusion in a multivariate Cox regression. Finally, the (sub)structure(s) that remained significant in the first multivariate analysis were included in a second multivariate analysis, also including; performance status, age, gender, biological dose, distance to bronchus, comorbidity index, lung-function, tumor diameter, T-stage, institute and pack years smoking.

99PD: Modelling of pulmonary function test changes after stereotactic body radiotherapy for stage I NSCLC

J. Roesch1, B. Stam2, J. Belderbos2, H. Peulen2, M. Flentje3, M. Giuliani4, A. Hope4, M. Werner-Wasik5, Y. Hong6, I. Grills6. 1 Department of Radiation-Oncology, Universitätsspital Zürich, Zurich, Switzerland , 2 Radiotherapy, The Netherlands Cancer Institute, Amsterdam, Netherlands, 3 Department of Radiation Oncology, University Hospital Wuerzburg, Würzburg, Germany, 4 Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 5 Department of Radiation Oncology, Thomas Jefferson Univ Hospital, Philadelphia, PA, USA, 6 Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA