Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy
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 investigat...
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BMC
2024-11-01
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| Series: | Radiation Oncology |
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| Online Access: | https://doi.org/10.1186/s13014-024-02546-y |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fiorella Di Pastena |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8cdf62e782fd48eb9e23a13a2e40ddfb |
| institution | Kabale University |
| issn | 1748-717X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj-art-8cdf62e782fd48eb9e23a13a2e40ddfb2024-11-10T12:36:06ZengBMCRadiation Oncology1748-717X2024-11-011911910.1186/s13014-024-02546-yGrowth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapyFiorella Di Pastena0Gregory Pond1Evangelia E. Tsakiridis2Andre Gouveia3Elham Ahmadi4Olga-Demetra Biziotis5Amr Ali6Anand Swaminath7Gordon Okawara8Peter M. Ellis9Bassam Abdulkarim10Naseer Ahmed11Andrew Robinson12Wilson Roa13Mario Valdes14Peter Kavsak15Marcin Wierzbicki16James Wright17Gregory Steinberg18Theodoros Tsakiridis19Centre for Metabolism, Obesity and Diabetes Research, McMaster UniversityDepartment of Oncology, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityDepartment of Oncology, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityDepartment of Oncology, McMaster UniversityDepartment of Oncology, McMaster UniversityDepartment of Oncology, McMaster UniversityDepartment of Oncology, McGill UniversityCancer Care ManitobaQueen’s UniversityCross Cancer InstituteGrand River Cancer CenterDepartment of Pathology and Molecular Medicine, McMaster UniversityRadiation Physics Program, Juravinski Cancer CentreDepartment of Oncology, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityCentre for Metabolism, Obesity and Diabetes Research, McMaster UniversityAbstract 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.https://doi.org/10.1186/s13014-024-02546-yLung cancer biomarkerGDF15Concurrent chemoradiotherapyMetformin |
| spellingShingle | 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 Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy Radiation Oncology Lung cancer biomarker GDF15 Concurrent chemoradiotherapy Metformin |
| title | Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy |
| title_full | Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy |
| title_fullStr | Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy |
| title_full_unstemmed | Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy |
| title_short | Growth differentiation factor 15 (GDF15) predicts relapse free and overall survival in unresected locally advanced non-small cell lung cancer treated with chemoradiotherapy |
| title_sort | growth differentiation factor 15 gdf15 predicts relapse free and overall survival in unresected locally advanced non small cell lung cancer treated with chemoradiotherapy |
| topic | Lung cancer biomarker GDF15 Concurrent chemoradiotherapy Metformin |
| url | https://doi.org/10.1186/s13014-024-02546-y |
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