Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy.

IF 3.3 2区医学 Q2 ONCOLOGY Radiation Oncology Pub Date : 2024-11-07 DOI:10.1186/s13014-024-02546-y

Fiorella Di Pastena, Gregory Pond, Evangelia E Tsakiridis, Andre Gouveia, Elham Ahmadi, Olga-Demetra Biziotis, Amr Ali, Anand Swaminath, Gordon Okawara, Peter M Ellis, Bassam Abdulkarim, Naseer Ahmed, Andrew Robinson, Wilson Roa, Mario Valdes, Peter Kavsak, Marcin Wierzbicki, James Wright, Gregory Steinberg, Theodoros Tsakiridis

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Abstract

Introduction: Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated in OCOG-ALMERA (NCT02115464), a phase II randomized clinical trial, that investigated metformin in combination with standard of care concurrent chemoradiotherapy (cCRT). OCOG-ALMERA was not able to demonstrate benefit in the metformin arm. Therefore, biomarker studies are needed to better define stratification parameters for future trials.

Methods: Patients were randomized to treatment with platinum-based chemotherapy and concurrent chest radiotherapy (60-66 Gy), with or without metformin (2000 mg/d). The trial collected tumor volume parameters, survival outcomes, and patient blood plasma at baseline, during (weeks 1 and 6) and 6 months after cCRT. Plasma GDF15 levels were assayed with the ELISA method. Statistical analyses explored associations between GDF15, survival outcomes, and radiotherapy tumor volumes.

Results: Baseline plasma levels of GDF15 were elevated in study patients, they increased during cCRT (p < 0.001), and the addition of metformin was associated with a further increase (week 6, p = 0.033). Baseline GDF15 levels correlated with the radiotherapy gross target volume (GTV, p < 0.01), while week 1 of radiotherapy levels correlated with radiotherapy planned target volume (PTV, p < 0.006). In multivariate analysis, baseline plasma GDF15 was prognostic for poor relapse-free (RFS) and overall survival (OS) (p = 0.005 and p = 0.002, respectively).

Conclusions: GDF15 is a plasma marker that responds to the treatment of unresected LA-NSCLC with cCRT and metformin. GDF15 levels correspond with tumor volume and increased GDF15 levels predict for poor RFS and OS. These results require validation in larger clinical trial datasets.

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生长分化因子15（GDF15）可预测化放疗治疗的未切除局部晚期非小细胞肺癌患者的无复发和总生存期。

简介生长分化因子15（GDF15）是TGFβ家族的一种细胞因子。在此，我们分析了参加OCOG-ALMERA（NCT02115464）II期随机临床试验的局部晚期非小细胞肺癌（LA-NSCLC）患者体内的GDF15水平。OCOG-ALMERA 未能证明二甲双胍治疗组的获益。因此，需要进行生物标志物研究，以便为未来的试验更好地确定分层参数：患者随机接受铂类化疗和同期胸部放疗（60-66 Gy），同时服用或不服用二甲双胍（2000 mg/d）。试验收集了肿瘤体积参数、生存结果以及患者在基线、cCRT期间（第1周和第6周）和6个月后的血浆。血浆中的GDF15水平采用ELISA方法进行检测。统计分析探讨了GDF15、生存结果和放疗肿瘤体积之间的关联：结果：研究患者的血浆 GDF15 水平基线升高，且在 cCRT 期间升高（p 结论：GDF15 是一种血浆蛋白，与放疗相关：GDF15是一种血浆标志物，它对使用cCRT和二甲双胍治疗未切除的LA-NSCLC有反应。GDF15水平与肿瘤体积相对应，GDF15水平升高预示着RFS和OS较差。这些结果需要在更大的临床试验数据集中进行验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Radiation Oncology ONCOLOGY-RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

CiteScore

6.50

自引率

2.80%

发文量

181

审稿时长

3-6 weeks

期刊介绍： Radiation Oncology encompasses all aspects of research that impacts on the treatment of cancer using radiation. It publishes findings in molecular and cellular radiation biology, radiation physics, radiation technology, and clinical oncology.