The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

Abstract

Abstract. The prognostic quality of increased osteopontin (OPN) plasma levels has been demonstrated for the chemotherapy and surgery of lung cancer. There is also evidence in the literature that tumor volume impacts prognosis in definitive radiotherapy (RT) of (lung) cancer. We previously demonstrated that elevated plasma levels of OPN before, and increasing OPN plasma levels after RT significantly correlate with survival and outcome after curative-intent RT of non-small-cell lung cancer (NSCLC). Tumor volume was also associated with prognosis. The present prospective clinical study investigated the prognostic interrelation of OPN plasma levels and tumor volume and their changes in the radical RT of NSCLC. We evaluated a subset of patients (n=27) with inoperable, non-metastasized NSCLC of the previously published patient collective. Patients were treated with radical radiochemotherapy (2 Gy ad 66 Gy). OPN plasma concentrations were determined by ELISA before (t0), at the end (t1), and 4 weeks after RT (t2). GTV was delineated PET-and CT-correlated before RT (GTV1) and after 40 Gy (GTV2). The course of OPN during and after RT and the change of GTV during RT was monitored over time and correlated with prognosis. Median GTV2 after 40 Gy (63 ml) was significantly lower than pre-RT GTV1 (90 ml, P<0.0001). Median OPN before (t0), at the end of (t1) and four weeks after RT (t2) was 846, 777 and 624 ng/ml and not significantly different. GTV significantly declined by 39 ml during RT (P<0.0001) and OPN non-significantly decreased by 56 ng/ml during (t0 to t1) and by 54 ng/ml after RT (t1 to t2). No correlations were determined between absolute OPN and GTV values or their relative changes during RT. In univariate analysis, only GTV2 significantly predicted overall survival (OS, P=0.03). In multivariate analysis, both OPN t1 (P<0.001) and GTV2 (P= 0.001) remained significant predictors of OS. Relative OPN plasma level changes after (t1 to t2) and GTV changes during RT (GTV 1 to GTV 2) significantly predicted OS (P=0.02). The combination of absolute GTV values before RT (GTV1) and GTV changes during RT (GTV1 to 2) were significantly associated with OS in both uni-and multivariate analysis (P=0.03). The combination of absolute OPN plasma levels and their changes with GTV and its changes did not reach statistical significance. The lack of a significant correlation between OPN and GTV together with the finding that OPN and GTV remained independent predictors of survival outcome but were not associated with OS in combination supports the hypothesis that tumor volume (GTV) and OPN plasma levels (both their changes and absolute values) are not interrelated in terms of prognosis but do possess each parameter separately, a prognostic quality in the radical RT of NSCLC which justifies further prospective studies to validate these results.

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer—results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group

“…In the literature, the prediction of outcome based on GTV changes during RT remains inconclusive [4]. While some studies [15,18,19] reported a tumor volume reduction or the reduction ratio to be associated with improved OS or PFS after RT, others (Van Elmpt et al) could not confirm these results. There are also conflicting results indicating an inferior OS in patients with a higher tumor volume reduction during RT [20].…”

“…Thus, re-evaluation of GTV during RT was predominantly carried out between 40 and 50 Gy in order to adapt the treatment plan for tumor volume changes. Clinical evidence also suggests significant tumor volume changes after 30–50 Gy [ 17 , 18 ]. While no significant effect of relative GTV changes during RT on OS was found in our dataset, absolute GTV detected during RT between 40 and 50 Gy in our study significantly impacted OS in both the crude and the adjusted model.…”

Hypoxia in Lung Cancer Management: A Translational Approach

“…They all correlated with clinical parameters associated with OS and a combined consideration of expression for those three markers was independently associated with poor outcome. Validation was then obtained in larger NSCLC cohorts, especially focused on OPN plasma levels [ 142 , 143 , 179 ]. HIF-1α serum levels in 80 patients harbouring NSCLC and undergoing chemoradiotherapy in a curative intent were assessed [ 137 ]: soluble HIF-1α levels were decreased during and after treatment compared to the initial point, suggesting serum HIF-1α concentrations as a potential marker to monitor tumour response during chemoradiation.…”

Evaluation of kininogen 1, osteopontin and α‑1‑antitrypsin in plasma, bronchoalveolar lavage fluid and urine for lung squamous cell carcinoma diagnosis

“…High OPN levels in plasma were associated with higher levels of hypoxia in tumors and a higher risk of recurrence in patients with early stage NSCLC (33). In individuals with advanced lung cancer, higher circulating OPN levels were associated with a poorer prognosis and worse therapeutic responses (34)(35)(36). Prior to this study, BALF and urine OPN levels had not been assessed.…”