Lung Cancer

PD 16 - Lung 4 - Poster Discussion

1137 - Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Lung Cancer Patients Treated With Proton Beam Therapy

Wednesday, October 24
11:12 AM - 11:18 AM
Location: Room 217 C/D

Updating Photon-Based Normal Tissue Complication Probability Models for Pneumonitis in Lung Cancer Patients Treated With Proton Beam Therapy
V. Jain1, A. van der Schaaf2, M. Frick1, A. Doucette3, C. B. Simone II4, C. Chinniah1, A. Nieznik2, R. Wijsman2, J. A. Langendijk2, and A. T. Berman3; 1Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 2University of Groningen, University Medical Center Groningen, Department of Radiation Oncology, Groningen, Netherlands, 3University of Pennsylvania, Department of Radiation Oncology, Philadelphia, PA, 4Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD

Purpose/Objective(s): Proton beam therapy (PBT) may reduce the risk of radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (LA-NSCLC). However, no validated models currently exist. Our goal was to externally validate and recalibrate photon-based normal tissue complication probability (NTCP) models for RP in a cohort with LA-NSCLC treated with contemporary doses of chemoradiation (CRT) using PBT. We evaluated the performance of the QUANTEC pneumonitis (QP) model, QUANTEC model adjusted for clinical risk factors (AQP), as well as the newer NQP model (ESTRO 2017, which has a steeper slope and includes current smoking) for predicting RP from PBT.

Materials/Methods: The external validation cohort consisted of 110 consecutive patients with LA-NSCLC treated with CRT using PBT. Patient, tumor, dosimetric, and other treatment characteristics were collected. RP was retrospectively scored at 3 and 6 months post treatment using CTCAE v4.0. Model performance was tested for goodness of fit (log-likelihood), discrimination (area under the curve, AUC), and calibration (Hosmer-Lemeshow test, HL-test). A closed testing procedure was performed to test the need for model updating, either by recalibration-in-the-large (re-estimation of model intercept), recalibration (re-estimation of intercept and slope) or model revision (re-estimation of all coefficients).

Results: There were 23 events (21%) of Grade 2 or higher RP. On univariable analysis, mean lung dose (p<0.001), V5 (p=0.002), V20 (p= 0.002), V40 (p<0.001) and total lung volume (p=0.02, protective factor) were found to be significantly associated with RP. The closed testing procedure indicated adjustment of the intercept only for all three models.
Intercept Adjustment Calibration Slope (not adjusted) Log-Likelihood AUC HL-test (p-value)
QP 0.48 1.97 -51.8 0.72 0.002
AQP 0.63 0.90 -53.1 0.69 0.36
NQP -1.18 0.90 -49.0 0.74 0.20
The overall best performance was found for the NQP model with adjusted intercept. Recalibration of the slope or refitting the entire model did not significantly improve the model. Model-extension by adding other predictors like total lung volume, V5, V20 and V40, which were found to be significant on univariate analysis, also did not significantly improve the model.

Conclusion: The similarity between dose response relationship for PBT and photons for normal tissue complications has been an assumption until now; however, the widely-used QP and AQP models did not fit PBT data well for our cohort. We demonstrate that the recently presented NQP NTCP model that was developed for photons can also be valid for PBT with minor modifications. The negative intercept adjustment needed for protons is intriguing and indicates that the complication rate for protons was lower than expected by the model. This model, if further validated, can provide the critical need to predict RP using PBT and facilitate model-based treatment modality selection.

Author Disclosure: V. Jain: None. A. van der Schaaf: None. M. Frick: None. A. Doucette: Employee; Children's Hospital of Philadelphia. C.B. Simone: Employee; Nemours/Alfred I. duPont Hospital for Children. Chair, Executive Council; Chair, Lung Committee; Proton Collaborative Group (PCG). Editor-in-Chief; Annals of Palliative Medicine. Chair, Lung Resource Panel; American Society for Radiation Oncology. C. Chinniah: None. A. Nieznik: None. R. Wijsman: Employee; Rinjstate Hospital. J.A. Langendijk: Research Grant; Philips. Research Agreement; Philips.

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