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W. Van Elmpt
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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-021 - Lung Damage Quantification on CT Scans Strengthens Radiation-Induced Lung Toxicity Prediction Models (ID 2932)
09:30 - 09:30 | Author(s): W. Van Elmpt
- Abstract
Background:
Predictive models for radiation-induced lung toxicity have shown a lack of validation and low values of area under the curve (AUC) below 0.7, for various reasons. Radiation-induced lung tissue damage scored as density changes on CT scans proved to be a less multifactorial endpoint compared to dyspnea. Its continuous variation in the patient population is an indication that it could be an expression of patient-specific radiosensitivity variation. This study explores the advantage of incorporating patient-specific lung damage measures in the classical predictive models based on mean lung dose (MLD).
Methods:
61 stage I-IV lung cancer patients treated with chemoradiotherapy were retrieved from two hospitals. Prescribed dose was 66 Gy in fractions of 2 Gy (concurrent) or 2.75 Gy (sequential). Baseline and follow-up dyspnea scores were retrospectively assessed according to CTCAE 4.0. Image analysis of the radiation-induced lung damage was performed by comparison of the baseline planning CT~0~ and the non-rigidly registered follow-up CT~fup~. The median Hounsfield Unit increase (∆HU=HU~fup~-HU~0~) was calculated per dose bin of 5 Gy. The local dose-∆HU response curve was described using a sigmoidal model. This resulted in a sigmoidal parameter D~50~ (corresponding to 50% of the saturation level of ∆HU) for each patient, as an expression of the patient-specific lung tissue radiosensitivity. Logistic models predicting dyspnea increase with respect to the baseline score were then built using MLD and D~50~ as covariates. The likelihood-ratio identified significant differences between nested models.
Results:
Dyspnea score increase by 2 grades was observed in 9 patients (14,8%), while an increase by 1 grade was observed in 29 patients (47.5%). The average timepoint of CT~fup~ was 2.3 months after end of radiotherapy. For 51 patients the sigmoidal dose-∆HU fits were acceptable (sum of squared residuals below 10 HU per datapoint on average). 10 of these patients did not show any dose response in the analysed dose range. The 41 reacting patients showed large variation in D~50 ~(median: 34.8 Gy, range: 12.1 Gy-70.0 Gy) and were further analysed. Predictive models based on MLD alone had AUCs of 0.71 and 0.65 for dyspnea increase by 1 and 2 grades respectively. Incorporating the CT damage measure D~50~ as second covariate resulted in models with 0.73 and 0.83 respectively. The advantage of incorporating D~50~ was significant in the second fit (p=0.05).
Conclusion:
A significant improvement of predictive models for radiation-induced lung toxicity was achieved using patient-specific lung damage measured on CT scans. An early detection of the patient-specific D~50~ through dedicated per-treatment imaging optimized for the detection of lung tissue changes is crucial for the clinical implementation of the model. Future work analysing more CT features could also improve the model.
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P3.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 208)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.01-044 - FDG-PET/CT Based Response Prediction of Stage IV NSCLC Treated with Paclitaxel-Carboplatin-Bevacizumab with or without Nitroglycerin (ID 1229)
09:30 - 09:30 | Author(s): W. Van Elmpt
- Abstract
Background:
A prospective study in stage IV non-small cell lung cancer (NSCLC) patients was performed to assess the predictive value of early response of the primary tumor evaluated by [18F]FDG-PET/CT to bevacizumab containing combination therapy with or without nitroglycerin (NTG) patches as first line treatment. NTG is a vasodilator which is hypothesized to increase tumor blood flow thereby decrease hypoxia, and 1) leading to a decrease in [18F]FDG uptake, and 2) facilitating early response assessment using [18F]FDG to predict treatment outcome.
Methods:
In total, 223 patients were randomized between carboplatin-paclitaxel-bevacizumab (PCB) with or without NTG (day -2 to +3; NVALT12 trial, NCT01171170). 78 patients were available for image analysis having undergone an [18F]FDG-PET/CT scan prior to the first cycle of chemotherapy and a second (optional) [18F]FDG-PET/CT scan at day 1-2 after start of the second cycle. The primary gross tumor volume (GTV) was delineated on both PET/CT scans. On the [18F]FDG-PET scan, the maximum standardized uptake value (SUV), mean SUV, peak SUV and total lesion glycolysis (TLG defined as SUVmean*CTvolume) were calculated and correlated with progression-free survival (PFS) and overall survival (OS). Early response assessment was quantified using relative changes in [18F]FDG-PET uptake parameters of the GTV expressed as delta. The median of the parameter of interest was used as cut-off value for both study arms for analysis using cox regression. Furthermore response was assessed according to PERCIST and RECIST.
Results:Hazard ratio os SUV parameters > versus < the median for PFS and OS
1) On average no decrease in [18F]FDG-PET uptake was observed for the experimental NTG group. However, patients in the experimental group showed a significantly larger variation in most SUV parameters of the second PET/CT scan compared to control group without NTG. 2) In table 1 the hazard ratios are shown for the relative delta SUVmax, SUVmean, SUVpeak and TLG for both study arms. In the experimental group, patients with a small delta TLG (<64%) had a shorter PFS than patients with a larger change in TLG (HR:1.064; 95% CI 1.002-1.131; p=0.043). Response assessed by PERCIST and RECIST did not predict for a longer PFS or OS.SUV parameter median PFS OS HR (p-value) 95% CI HR (p-value) 95% CI Delta PCB+NTG (%) SUVmax 40.4 1.026 (0.408) 0.966-1.090 1.006 (0.844) 0.945-1.071 SUVmean 39.9 1.048 (0.127) 0.987-1.113 1.034 (0.279) 0.973-1.099 SUVpeak 42.3 1.035 (0.258) 0.975-1.100 1.016 (0.615) 0.955-1.082 TLG 64.5 1.064 (0.043) 1.002-1.131 1.039 (0.221) 0.977-1.106 Delta PCB (%) SUVmax 53.2 1.027 (0.454) 0.957-1.103 1.009 (0.810) 0.939-1.084 SUVmean 51.6 1.027 (0.465) 0.957-1.102 1.011 (0.766) 0.941-1.086 SUVpeak 53.9 1.040 (0.281) 0.969-1.116 1.018 (0.623) 0.947-1.094 TLG 75.9 0.994 (0.873) 0.927-1.066 0.998 (0.951) 0.928-1.072
Conclusion:
Adding NTG did not result in a decrease in [18F]FDG-PET uptake compared to patients without NTG although NTG increased variability of the measured SUV parameters. Patients in the experimental NTG arm without an early response on [18F]FDG-PET/CT imaging had a worse PFS than patients with a response. For the group without NTG no difference was observed. Also, RECIST and PERCIST were not predictive.
