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OA05 - Treatment Advances in SCLC (ID 373)
- Event: WCLC 2016
- Type: Oral Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:A. Ardizzoni, J. Pujol
- Coordinates: 12/05/2016, 14:20 - 15:50, Strauss 2
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OA05.07 - Prognostic Value of Circulating Tumour Cells in Limited-Disease Small Cell Lung Cancer Patients Treated on the CONVERT Trial (ID 5431)
15:25 - 15:35 | Author(s): C. Dive
- Abstract
- Presentation
Background:
Circulating tumour cells (CTCs) are prevalent in patients with small cell lung cancer (SCLC) (Hou et al. JCO 2012) but their clinical utility is not known for patients with limited disease (LD) who receive concurrent chemoradiation. Here we report on a patient subgroup who underwent CTC analysis and treatment on the Concurrent ONce-daily (OD) VErsus Twice-daily (BD) RadioTherapy (CONVERT) trial (Faivre-Finn Proc. ASCO 2016) that demonstrated a non-significant difference in the primary endpoint of two-year survival for the OD (51%) and BD (56%) arms.
Methods:
Blood samples (7.5mls) were collected at baseline, prior to any treatment from patients who were enrolled to the CONVERT trial at The Christie Hospital site, Manchester, UK. CTCs were enumerated prospectively using the Cellsearch platform. Patients were randomised 1:1 to receive 45Gy in 30 twice-daily fractions over 3 weeks (Arm 1) or 66Gy in 33 once-daily fractions over 6.5 weeks (Arm 2) starting on day 22 of cycle 1 chemotherapy (4 to 6 cycles of Cisplatin 25mg/m2 days 1-3 or 75mg/m2 day 1 with Etoposide 100mg/m2 days 1-3), followed by prophylactic cranial irradiation if indicated. Radiotherapy planning was with a 3D conformal technique or intensity modulated radiotherapy. Staging by Positron Emission Tomography (PET) was permitted. Standard statistical methods were used to examine associations between CTC number (CTC#), clinical factors and outcomes.
Results:
Of 547 patients randomised between April 2008 and November 2013, 79 patients (41 in Arm1 and 38 in Arm 2) underwent CTC enumeration (CTC subgroup). The clinical demographics and median overall survival (OS) of the CTC subgroup did not differ significantly from the overall study population. The median number (range) of CTCs per 7.5mls blood for all 79 patients was 1 (0-3750) and for arm 1 and arm 2 patients respectively, 12 (0-164) and 158 (0-3750) (p=0.495). There was a trend for association of CTC# with higher TNM stage. CTC# was significant for survival in univariate and multivariate analysis. The median (95% CI) OS for ≥15 CTCs (n=18) was 6.01 (4.2-11.5) months compared to 30.77 (19.7-39.3) months for < 15 CTCs (n=61), p <0.001. The positive predictive value of CTC# ≥15 for survival ≤ 2 years is 100%, and ≤ 1 year is 72%. CTC# also predicted for worse outcome in patients who had undergone PET staging.
Conclusion:
CTC# is highly prognostic for poor survival in patients with LD-SCLC, treated with concurrent chemoradiotherapy, and could aid treatment decision making for this disease.
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P2.05 - Poster Session with Presenters Present (ID 463)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiotherapy
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.05-058 - Blood Biomarkers of Inflammation, Tumour Burden and Proliferation Predict Radiotherapy Response and Toxicity in Lung Cancer (ID 5587)
14:30 - 14:30 | Author(s): C. Dive
- Abstract
Background:
There is an unmet need to develop non-invasive biomarkers that can be used to tailor radiotherapy and select patients for future mechanism-based therapy-radiotherapy combination trials. The aim of this study is to assess blood biomarkers of radiotherapy response and toxicity in patients with lung cancer.
Methods:
This is a prospective exploratory study conducted at the Christie NHS Foundation Trust (Manchester, UK). Blood samples were collected prior, during and post-radiotherapy and at the time of relapse. A panel of 26 biomarkers were evaluated; M30 and M65 (apoptosis/ cell death), CA-IX and Osteopontin (hypoxia), Ang-1, Ang-2, FGFb, IL-8, PDGFb, PIGF, Tie-2, VEGFA, VEGFC, VEGFR-1 and VEGFR-2 (angiogenesis), E-selectin, IL-1b, IL-6, IL-10, IL-12 and TNFα (inflammation), CYFRA 21-1, EGF, KGF and VCAM-1 (tumour burden, proliferation and invasion) and HGF (multiple processes). Clinical, demographic and treatment data as well as routine haematology and biochemistry test results were collected. Blood sampling and analysis were performed in a good clinical practice-compliant laboratory. Univariate analysis was performed on patients with small-cell and non-small cell lung cancer (NSCLC) while multivariate analysis focused on patients with NSCLC. All statistical analyses were performed in R v3.1.1.
Results:
Between March 2010 and February 2012, blood samples form 78 patients were analysed. Forty eight (61.5%) were treated with sequential chemo-radiotherapy, 61 (78.2%) harboured NSCLC while 66 (84.6%) had stage III disease. TNFα, IL-1b, KGF and IL-12 accounted for the bulk of the variability between patients at baseline. Of these, high TNFα (hazard ratio (HR); 2.27, 95% confidence interval (CI); 1.22-4.23, log-rank p=0.008) and IL-1b (HR; 4.02, 95% CI; 2.04-7.93, log-rank p<0.001) were the strongest covariates of survival. Of routinely-collected laboratory tests, neutrophil count was a significant covariate of survival (HR; 1.07, 95% CI; 1.02-1.11, log-rank p=0.017). A multivariate survival predication model for NSCLC was created by combining baseline IL-1b and neutrophil count. The addition of early-treatment (week 3) CYFRA 21-1 to this model modestly improved the survival prediction concordance probability (0.75; p=0.029 to 0.78; p=0.004). Chemotherapy was strongly correlated with acute oesophagitis (p<0.001) while KGF was weekly correlated (p=0.019). The addition of KGF did not improve a multivariate toxicity prediction model based on chemotherapy. None of the tested variables correlated with acute pneumonitis.
Conclusion:
Blood biomarkers of inflammation and proliferation and early-treatment tumour burden could provide additional information about radiotherapy response and toxicity in patients with lung cancer. Following independent validation, the proposed biomarkers could be integrated within future mechanism-based therapy-radiotherapy combination trials.
