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P. Lambin
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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): P. Lambin
- 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.
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-086 - REQUITE: Validating Predictive Models and Biomarkers of RT Toxicity to Reduce Side Effects and Improve QOL (ID 2864)
09:30 - 09:30 | Author(s): P. Lambin
- Abstract
Background:
Recently the first replicated genetic associations for radiotherapy-induced adverse reactions were reported. These should improve the power of toxicity prediction models, opening the way to an optimised radiotherapy delivery and interventions to alleviate the side effects. The European Union funded REQUITE consortium aims to validate known predictors of adverse reactions and to develop statistical models resulting in clinically useful models. The focus of the project is on breast, prostate and lung cancer. As the barrier to clinical impact is the lack of validated statistical models incorporating genetic predictors, and the barrier to validation is the lack of standardised data collection, the main objectives of the REQUITE project are the following: Perform a multi-centre cohort study collecting blood samples, epidemiology and treatment data, longitudinal side effect and quality of life (QOL) data (before and after treatment: years 1 and 2 for breast and prostate cancer; with additional 3 and 6 month timepoints for lung cancer). Produce a centralized database and biobank of DNA for 5300 patients. Validate published biomarkers of radiosensitivity. Validate clinical predictors of radiotherapy toxicity in breast, prostate and lung cancer and incorporate biomarker data. Design interventional trials to reduce long-term side effects. Provide a resource for dissemination and exploitation to the radiotherapy community.
Methods:
The central activity of the project is a multi-centre, observational study organized through WP2. Enrolment will proceed for two years in nine centres (eight in Europe and one in the United States), with another two years of follow-up. The primary endpoints are change in breast appearance at two years (breast), rectal bleeding at two years (prostate) and pneumonitis at 6 months (lung). An integrated study database is designed. Blood samples are collected before radiotherapy. Tracking, biobanking and DNA extraction is handled in WP3. Validation of biomarkers (genetic markers and apoptosis assays) as predictive factors is carried out in WP4. Some clinical factors have suggested predictive value for radiotherapy side effects, but there is no consensus. In WP5 these will be validated in existing cohorts. Finally, in WP6, predictive models will be used to design clinical interventional trials and produce protocols that seek to lower radiotherapy side effects, in those individuals at high risk of developing them, without affecting tumour control. Patient advocates will play an essential role in this effort.
Results:
Standardised data collection forms were generated. Questionnaires for collecting patient reported toxicity according to Common Toxicity Criteria for Adverse Events were developed in different languages. These forms and questionnaires are available at http://www.requite.eu/. A centralised database for electronic data capture and storage was developed. Ethical approval for the observational study was obtained in all centres. More than 1300 patients were enrolled in the REQUITE study to this date.
Conclusion:
Centralised collection of standardised data and biobanking is practical for lung cancer patients undergoing radiotherapy in routine clinical practice in a multi-centre, multi-national setting.
