Session Item

Radiation therapy (RT) of thoracic cancers may cause acute severe radiation dermatitis (RD) with a profound impact on the quality of a patient''s life.  In general, modern RT techniques have achieved a reduction in RD incidence. However, the risk of a potential increase of skin toxicity has long been considered a peculiar drawback of proton therapy.  Aim of this study was to develop normal tissue complication probability (NTCP) models for severe RD in thoracic cancer patients treated with Intensity-Modulated RT (IMRT) or Passive Scattering Proton Therapy (PSPT).

We analyzed 166 Non-Small-Cell Lung Cancer (NSCLC) patients prospectively treated at a single institution with IMRT (103 patients) or PSPT (63 patients). All patients were treated to a prescribed dose of 60 to 74 Gy in conventional daily fractionation with concurrent chemotherapy. Median patient age was 66 years (range: 33–85 years). RD was scored according to CTCAE v3 scoring system. For each patient, the epidermis structure (skin) was automatically defined by an in house developed segmentation algorithm. The absolute dose-surface histogram (DSH) of the skin were extracted and normalized using the Body Surface Area (BSA) index as scaling factor. Patient and treatment-related characteristics were analyzed. Two different NTCP approaches were adopted: the pure dosimetric Lyman-Kutcher-Burman (LKB) model recast for DSH and the multivariable (MV) logistic model allowing for the inclusion of non-dosimetric predictors. Models were internally validated by Leave-One-Out (LOO) method. Model performances were evaluated by the area under the receiver operator characteristic curve (ROC-AUC) and the calibration plot parameters.

By the end of RT, 118 of 166 (71%) patients developed acute RD of any degree. Fifteen of 166 (9%) patients developed severe dermatitis (grade 3) at a median time of 41 days (range: 28-51). RT technique did not impact RD incidence. Total gross tumor volume (GTV) size was the only non dosimetric variable significantly correlated with severe RD (p=0.027). MV modelling for severe RD resulted in a single variable model including S_20Gy, the relative skin surface receiving more than 20 Gy (OR= 31.4, 95%CI 7.5-131.7). The cut off for S_20Gy was 1,1% of the BSA. LKB model parameters were TD50 = 9.5 Gy [5.9-18.4], m= 0.24 [0.17-0.35], n=0.62 [0.36-0.92]

Both NTCP models showed comparable good discrimination (LOO ROC-AUC = 0.8 (95%CI 0.6-0.9) and calibration at cross validation (Figure).

Despite skin toxicity has long been considered a potential limiting factor in the clinical use of PSPT, no significant differences in RD incidence was found between RT modalities. Once externally validated, the availability of NTCP models for robust prediction of severe RD may advance treatment planning optimization. In addition, severe acute skin reactions may be prodromal of consequential skin late effects. Prediction and, possibly, prevention of these acute reactions may also avoid late effects.