Hannah Sophie Penzl , David Alexander Ziegler , Markus Anton Schirmer , Jona Bensberg , Sonia Ziegler , Benedikt Kieslich , Carla Marie Zwerenz , Andrea Hille , Leif Hendrik Dröge , Martin Leu , Manuel Guhlich , Lisa von Diest , Laura Anna Fischer , Mahalia Zoe Anczykowski , Tobias Overbeck , Alexander von Hammerstein-Equord , Friederike Braulke , Stefan Rieken , Rami El Shafie
{"title":"辐射剂量对免疫细胞(EDIC)对小细胞肺癌(SCLC)肿瘤预后的影响","authors":"Hannah Sophie Penzl , David Alexander Ziegler , Markus Anton Schirmer , Jona Bensberg , Sonia Ziegler , Benedikt Kieslich , Carla Marie Zwerenz , Andrea Hille , Leif Hendrik Dröge , Martin Leu , Manuel Guhlich , Lisa von Diest , Laura Anna Fischer , Mahalia Zoe Anczykowski , Tobias Overbeck , Alexander von Hammerstein-Equord , Friederike Braulke , Stefan Rieken , Rami El Shafie","doi":"10.1016/j.radonc.2025.111122","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy (RT) is an essential part of small-cell lung cancer (SCLC) treatment. It can however deplete circulating lymphocytes, impairing systemic immune surveillance and potentially reducing the efficacy of immune checkpoint inhibitors (ICIs). The Effective Dose to Immune Cells (EDIC) quantifies RT-induced immune suppression and has been linked to survival in non-small cell lung cancer (NSCLC), but its prognostic significance in SCLC remains unclear.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analyzed 220 patients with SCLC who received thoracic RT at a German tertiary cancer center between 2006 and 2020. EDIC was calculated from treatment plans using the model developed by Jin et al., which approximates the dose to circulating immune cells based on the dose to circulating blood. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LPFS). Multivariable Cox regression identified independent prognostic factors.</div></div><div><h3>Results</h3><div>The median OS was 17.7 months (Q1–Q3: 11.6–38.8, 95 % CI: 16.0–19.3). In LD-SCLC, higher EDIC (> 4.9 Gy) was independently associated with shorter OS (HR 1.62, p = 0.011), PFS (HR 1.57, p = 0.037), and DMFS (HR 1.72, p = 0.017), but not LPFS (p = 0.308). In contrast, EDIC showed no prognostic impact in ED-SCLC. Other independent prognostic factors in LD-SCLC included prophylactic cranial irradiation (HR 0.43, p < 0.001) and bi-daily fractionation (HR 0.41, p = 0.002).</div></div><div><h3>Conclusion</h3><div>Higher EDIC is an independent negative prognostic factor in LD-SCLC, correlating with shorter OS, PFS, and DMFS, but had no prognostic relevance in ED-SCLC in this analysis. As immunotherapy becomes part of LD-SCLC treatment, immune-preserving RT strategies should be developed to optimize patient outcomes.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"212 ","pages":"Article 111122"},"PeriodicalIF":5.3000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of radiation dose on immune cells (EDIC) on oncologic outcome in small cell lung cancer (SCLC)\",\"authors\":\"Hannah Sophie Penzl , David Alexander Ziegler , Markus Anton Schirmer , Jona Bensberg , Sonia Ziegler , Benedikt Kieslich , Carla Marie Zwerenz , Andrea Hille , Leif Hendrik Dröge , Martin Leu , Manuel Guhlich , Lisa von Diest , Laura Anna Fischer , Mahalia Zoe Anczykowski , Tobias Overbeck , Alexander von Hammerstein-Equord , Friederike Braulke , Stefan Rieken , Rami El Shafie\",\"doi\":\"10.1016/j.radonc.2025.111122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Radiotherapy (RT) is an essential part of small-cell lung cancer (SCLC) treatment. It can however deplete circulating lymphocytes, impairing systemic immune surveillance and potentially reducing the efficacy of immune checkpoint inhibitors (ICIs). The Effective Dose to Immune Cells (EDIC) quantifies RT-induced immune suppression and has been linked to survival in non-small cell lung cancer (NSCLC), but its prognostic significance in SCLC remains unclear.</div></div><div><h3>Materials and methods</h3><div>We retrospectively analyzed 220 patients with SCLC who received thoracic RT at a German tertiary cancer center between 2006 and 2020. EDIC was calculated from treatment plans using the model developed by Jin et al., which approximates the dose to circulating immune cells based on the dose to circulating blood. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LPFS). Multivariable Cox regression identified independent prognostic factors.</div></div><div><h3>Results</h3><div>The median OS was 17.7 months (Q1–Q3: 11.6–38.8, 95 % CI: 16.0–19.3). In LD-SCLC, higher EDIC (> 4.9 Gy) was independently associated with shorter OS (HR 1.62, p = 0.011), PFS (HR 1.57, p = 0.037), and DMFS (HR 1.72, p = 0.017), but not LPFS (p = 0.308). In contrast, EDIC showed no prognostic impact in ED-SCLC. Other independent prognostic factors in LD-SCLC included prophylactic cranial irradiation (HR 0.43, p < 0.001) and bi-daily fractionation (HR 0.41, p = 0.002).</div></div><div><h3>Conclusion</h3><div>Higher EDIC is an independent negative prognostic factor in LD-SCLC, correlating with shorter OS, PFS, and DMFS, but had no prognostic relevance in ED-SCLC in this analysis. As immunotherapy becomes part of LD-SCLC treatment, immune-preserving RT strategies should be developed to optimize patient outcomes.</div></div>\",\"PeriodicalId\":21041,\"journal\":{\"name\":\"Radiotherapy and Oncology\",\"volume\":\"212 \",\"pages\":\"Article 111122\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Radiotherapy and Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0167814025046262\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Radiotherapy and Oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0167814025046262","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:放射治疗(RT)是小细胞肺癌(SCLC)治疗的重要组成部分。然而,它可以消耗循环淋巴细胞,损害全身免疫监视,并可能降低免疫检查点抑制剂(ICIs)的功效。免疫细胞有效剂量(EDIC)量化了rt诱导的免疫抑制,并与非小细胞肺癌(NSCLC)的生存有关,但其在SCLC中的预后意义尚不清楚。材料和方法:我们回顾性分析了2006年至2020年间在德国三级癌症中心接受胸部放疗的220例SCLC患者。使用Jin等人开发的模型从治疗方案中计算出EDIC,该模型根据循环血液剂量近似于循环免疫细胞的剂量。主要终点是总生存期(OS),次要终点是无进展生存期(PFS)、远端无转移生存期(DMFS)和局部无进展生存期(LPFS)。多变量Cox回归确定了独立的预后因素。结果:中位OS为17.7 个月(Q1-Q3: 11.6-38.8, 95% % CI: 16.0-19.3)。LD-SCLC,高EDIC(> 4.9 Gy)是独立与短OS (HR 1.62, p = 0.011),PFS (HR 1.57, p = 0.037),和时间(HR 1.72, p = 0.017),但不是lpf (p = 0.308)。相比之下,EDIC对ED-SCLC的预后没有影响。结论:较高的EDIC是LD-SCLC的独立负面预后因素,与较短的OS、PFS和DMFS相关,但在本分析中与ED-SCLC的预后无相关性。随着免疫治疗成为LD-SCLC治疗的一部分,应该开发免疫保留RT策略来优化患者的预后。
Impact of radiation dose on immune cells (EDIC) on oncologic outcome in small cell lung cancer (SCLC)
Background
Radiotherapy (RT) is an essential part of small-cell lung cancer (SCLC) treatment. It can however deplete circulating lymphocytes, impairing systemic immune surveillance and potentially reducing the efficacy of immune checkpoint inhibitors (ICIs). The Effective Dose to Immune Cells (EDIC) quantifies RT-induced immune suppression and has been linked to survival in non-small cell lung cancer (NSCLC), but its prognostic significance in SCLC remains unclear.
Materials and methods
We retrospectively analyzed 220 patients with SCLC who received thoracic RT at a German tertiary cancer center between 2006 and 2020. EDIC was calculated from treatment plans using the model developed by Jin et al., which approximates the dose to circulating immune cells based on the dose to circulating blood. The primary endpoint was overall survival (OS), secondary endpoints were progression-free survival (PFS), distant metastasis-free survival (DMFS), and local progression-free survival (LPFS). Multivariable Cox regression identified independent prognostic factors.
Results
The median OS was 17.7 months (Q1–Q3: 11.6–38.8, 95 % CI: 16.0–19.3). In LD-SCLC, higher EDIC (> 4.9 Gy) was independently associated with shorter OS (HR 1.62, p = 0.011), PFS (HR 1.57, p = 0.037), and DMFS (HR 1.72, p = 0.017), but not LPFS (p = 0.308). In contrast, EDIC showed no prognostic impact in ED-SCLC. Other independent prognostic factors in LD-SCLC included prophylactic cranial irradiation (HR 0.43, p < 0.001) and bi-daily fractionation (HR 0.41, p = 0.002).
Conclusion
Higher EDIC is an independent negative prognostic factor in LD-SCLC, correlating with shorter OS, PFS, and DMFS, but had no prognostic relevance in ED-SCLC in this analysis. As immunotherapy becomes part of LD-SCLC treatment, immune-preserving RT strategies should be developed to optimize patient outcomes.
期刊介绍:
Radiotherapy and Oncology publishes papers describing original research as well as review articles. It covers areas of interest relating to radiation oncology. This includes: clinical radiotherapy, combined modality treatment, translational studies, epidemiological outcomes, imaging, dosimetry, and radiation therapy planning, experimental work in radiobiology, chemobiology, hyperthermia and tumour biology, as well as data science in radiation oncology and physics aspects relevant to oncology.Papers on more general aspects of interest to the radiation oncologist including chemotherapy, surgery and immunology are also published.