NTCP Models for Severe Radiation Induced Dermatitis After IMRT or Proton Therapy for Thoracic Cancer Patients

Abstract

Radiation therapy (RT) of thoracic cancers may cause severe radiation dermatitis (RD), which impacts on the quality of a patient's life. Aim of this study was to analyze the incidence of acute RD and 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. 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. The Lyman-Kutcher-Burman (LKB) NTCP model recast for DSH and the multivariable logistic model were adopted. Models were internally validated by Leave-One-Out method. Model performance was evaluated by the area under the receiver operator characteristic curve, and calibration plot parameters. Fifteen of 166 (9%) patients developed severe dermatitis (grade 3). 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). Multivariable logistic modeling resulted in a single variable model including S 20Gy , the relative skin surface receiving more than 20 Gy (OR = 31.4). The cut off for S 20Gy was 1.1% of the BSA. LKB model parameters were TD 50 = 9.5 Gy, m = 0.24, n = 0.62. Both NTCP models showed comparably high prediction and calibration performances. 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 prediction of severe RD may advance treatment planning optimization.

Radiation Pneumonitis in Thoracic Cancer Patients: Multi-Center Voxel-Based Analysis

“…A group of patients was treated for Hodgkin lymphoma (HL) at the University “Federico II” of Napoli (Comitato Etico per le Attività Biomediche, IRB 222-10) with 3D conformal RT (3D-CRT) [ 15 , 16 ]. A second group was treated for locally advanced non-small cell lung cancer (NSCLC) at the University of Texas MD Anderson Cancer Center of Houston (IRB 2008-0133) with image-guided intensity-modulated RT (IMRT), and a third one with passive-scattering proton therapy (PSPT) [ 17 , 18 ]. Lastly, a group of patients was treated for NSCLC at the Memorial Sloan Kettering Cancer Center of New York (IRB #16-142) with stereotactic body RT (SBRT) [ 19 ].…”

“…More details on the protocols and treatment characteristics for each cohort are published elsewhere [ 3 , 13 , 18 , 19 ].…”

A Review of the Robust Optimization Process and Advances with Monte Carlo in the Proton Therapy Management of Head and Neck Tumors

“…However, more and more evidence suggests that variable RBE calculation should be performed for patients undergoing proton therapy. Some higher-than-expected toxic effects such as brain necrosis [ 34 , 35 ] and skin toxicities [ 36 ] are possibly related to higher-than-expected RBE doses in some anatomic regions. Figure 6 displays dose distributions with constant RBE of 1.1 and variable RBE model in the right brachial plexus region in a patient who developed arm injury after proton treatment in our center.…”

Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence

“…Finally, an NTCP model has been developed by Palma et al [33] for severe radiation dermatitis based on IMRT and IMPT on NSCLC cohort. Cutaneous toxicity has not been evaluated specifically for HL proton therapy, but Fellin et al [34] found that breast proton therapy could increase skin morbidity compared with IMRT if the skin were not considered as an OAR.…”