Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617
<b>Background</b>: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). <b>Methods</b>: This is a secondary stu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/24/6193 |
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| author | Jian-Yue Jin Chen Hu Ying Xiao Hong Zhang Rebecca Paulus Susannah G. Ellsworth Steven E. Schild Jeffrey A. Bogart Michael Chris Dobelbower Vivek S. Kavadi Samir Narayan Puneeth Iyengar Cliff Robinson Joel S. Greenberger Christopher Koprowski Mitchell Machtay Walter Curran Hak Choy Jeffrey D. Bradley Feng-Ming (Spring) Kong |
| author_facet | Jian-Yue Jin Chen Hu Ying Xiao Hong Zhang Rebecca Paulus Susannah G. Ellsworth Steven E. Schild Jeffrey A. Bogart Michael Chris Dobelbower Vivek S. Kavadi Samir Narayan Puneeth Iyengar Cliff Robinson Joel S. Greenberger Christopher Koprowski Mitchell Machtay Walter Curran Hak Choy Jeffrey D. Bradley Feng-Ming (Spring) Kong |
| author_sort | Jian-Yue Jin |
| collection | DOAJ |
| description | <b>Background</b>: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). <b>Methods</b>: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. <b>Results</b>: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, <i>p</i> = 0.005) and LPFS (HR = 1.09, <i>p</i> = 0.02) but PFS (HR = 1.05, <i>p</i> = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. <b>Conclusions</b>: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan. |
| first_indexed | 2024-03-10T04:31:52Z |
| format | Article |
| id | doaj.art-7e048ba4dad24946ad8bd4f31afdd48f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T04:31:52Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7e048ba4dad24946ad8bd4f31afdd48f2023-11-23T04:05:03ZengMDPI AGCancers2072-66942021-12-011324619310.3390/cancers13246193Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617Jian-Yue Jin0Chen Hu1Ying Xiao2Hong Zhang3Rebecca Paulus4Susannah G. Ellsworth5Steven E. Schild6Jeffrey A. Bogart7Michael Chris Dobelbower8Vivek S. Kavadi9Samir Narayan10Puneeth Iyengar11Cliff Robinson12Joel S. Greenberger13Christopher Koprowski14Mitchell Machtay15Walter Curran16Hak Choy17Jeffrey D. Bradley18Feng-Ming (Spring) Kong19Department of Radiation Oncology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USANRG Oncology Statistics and Data Management Center, Philadelphia, PA 19103, USAAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19103, USADepartment of Radiation Oncology, School of Medicine, University of Maryland, Maryland, MD 20742, USANRG Oncology Statistics and Data Management Center, Philadelphia, PA 19103, USADepartment of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 16251, USADepartment of Radiation Oncology, Mayo Clinic Hospital, Phoenix, AZ 85054, USADepartment of Radiation Oncology, State University of New York Upstate Medical University, Syracuse, NY 13210, USADepartment of Radiation Oncology, University of Alabama at Birmingham Cancer Center, Birmingham, AL 35233, USAUSON-Texas Oncology-Sugar Land, Sugar Land, TX 77479, USAMichigan Cancer Research Consortium CCOP, Ann Arbor, MI 48106, USADepartment of Radiation Oncology, University of Texas Southwestern Medical School, Dallas, TX 75235, USADepartment of Radiation Oncology, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 16251, USAChristiana Care Health Services, Inc. CCOP, Newark, DE 19718, USADepartment of Radiation Oncology, Penn State University Cancer Institute, Hershey, PA 17033, USADepartment of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USADepartment of Radiation Oncology, University of Texas Southwestern Medical School, Dallas, TX 75235, USADepartment of Radiation Oncology, Washington University in St. Louis, St. Louis, MO 63108, USADepartment of Clinical Oncology, Hong Kong University Shenzhen Hospital, Shenzhen 518009, China<b>Background</b>: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). <b>Methods</b>: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. <b>Results</b>: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, <i>p</i> = 0.005) and LPFS (HR = 1.09, <i>p</i> = 0.02) but PFS (HR = 1.05, <i>p</i> = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. <b>Conclusions</b>: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.https://www.mdpi.com/2072-6694/13/24/6193non-small-cell lung cancerradiotherapysurvivalradiation-induced immune toxicity |
| spellingShingle | Jian-Yue Jin Chen Hu Ying Xiao Hong Zhang Rebecca Paulus Susannah G. Ellsworth Steven E. Schild Jeffrey A. Bogart Michael Chris Dobelbower Vivek S. Kavadi Samir Narayan Puneeth Iyengar Cliff Robinson Joel S. Greenberger Christopher Koprowski Mitchell Machtay Walter Curran Hak Choy Jeffrey D. Bradley Feng-Ming (Spring) Kong Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 Cancers non-small-cell lung cancer radiotherapy survival radiation-induced immune toxicity |
| title | Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 |
| title_full | Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 |
| title_fullStr | Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 |
| title_full_unstemmed | Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 |
| title_short | Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617 |
| title_sort | higher radiation dose to the immune cells correlates with worse tumor control and overall survival in patients with stage iii nsclc a secondary analysis of rtog0617 |
| topic | non-small-cell lung cancer radiotherapy survival radiation-induced immune toxicity |
| url | https://www.mdpi.com/2072-6694/13/24/6193 |
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