Radiotherapy-related lymphopenia affects overall survival in patients with lung cancer

Published on Apr 1, 2019in Journal of Thoracic Oncology13.357
· DOI :10.1016/J.JTHO.2020.06.008
A. Abravan3
Estimated H-index: 3
(University of Manchester),
Corinne Faivre-Finn50
Estimated H-index: 50
(University of Manchester)
+ 2 AuthorsMarcel van Herk75
Estimated H-index: 75
(University of Manchester)
Abstract Introduction Lymphopenia following radiotherapy has an adverse effect on patient’s outcome. However, the relationship between radiotherapy dose delivery and lymphopenia is not fully understood. This work is utilizing image-based data mining to identify anatomical regions where the received dose is correlated with severe lymphopenia. Methods 901 lung cancer patients were analyzed. A Cox model was used to assess prognostic factors of overall survival (OS). Two matched groups were defined-patients with and without lymphopenia≥G3-based on tumor volume, baseline lymphocytes, and delivered dose. Then, data mining was used to identify regions where dose correlates significantly with lymphopenia≥G3. For this, dose matrices were aligned using registration of the computed tomography (CT) images to one reference patient. Mean dose distributions were obtained for the two groups and organs of significance were detected. Dosimetric parameters from the identified organs that had the highest correlation with lymphocytes at nadir were selected. Multivariable analysis was conducted for lymphopenia≥G3 on the full lung cohort and the model was tested on 305 esophageal cancer patients. Results Adjusted Cox regression showed that lymphopenia≥G3 was an independent factor of OS. The anatomical regions identified were heart, lung, and thoracic vertebrae. Dosimetric parameters for lymphopenia included vertebrae V20, mean lung dose and, mean heart dose which was further validated in the esophageal cancer cohort. Conclusions We have shown severe lymphopenia during radiotherapy is a significant poor prognostic factor for OS in lung cancer patients and could be mitigated by minimizing vertebrae V20, mean lung and heart dose to limit irradiation of stem cells and blood pool.
📖 Papers frequently viewed together
1 Citations
55 Citations
4 Citations
#1Azadeh Abravan (University of Oslo)H-Index: 3
#2Hanne Astrid Eide (Oslo University Hospital)H-Index: 4
Last. Eirik Malinen (University of Oslo)H-Index: 22
view all 4 authors...
Abstract Background Lymphopenia during radiotherapy (RT) may have an adverse effect on treatment outcome. Still, the relationship between RT dose and lymphopenia is not completely understood. The aim of this study was to investigate associations between lymphopenia and RT parameters in patients with advanced lung cancer. Moreover, potential prognostic blood biomarkers have been studied. Material and Methods Sixty-two advanced stage non-small cell lung cancer patients were retrospectively analyze...
4 CitationsSource
#1J.Y. Jin (Case Western Reserve University)H-Index: 4
#2Todd R. Mereniuk (IU: Indiana University)H-Index: 5
Last. Susannah G. Ellsworth (IU: Indiana University)H-Index: 13
view all 7 authors...
Abstract Introduction Associations between radiation-induced lymphopenia (RIL) and survival have been extensively reported. However, the immune system is not considered as an organ-at-risk (OAR) in radiotherapy. This study aimed to develop the framework of an immune OAR model that may be utilized to predict and minimize RIL. Methods A dynamic model was first developed for lymphocyte trafficking among 5 compartments of the immune system. Radiation dose to the circulating lymphocytes in each compa...
9 CitationsSource
#1Peter S.N. van Rossum (UU: Utrecht University)H-Index: 5
#2Wei Deng (University of Texas MD Anderson Cancer Center)H-Index: 4
Last. Steven H. Lin (University of Texas MD Anderson Cancer Center)H-Index: 42
view all 11 authors...
Abstract Introduction In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia. Methods and Materials A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patie...
18 CitationsSource
#1Colton J. Ladbury (University of Colorado Denver)H-Index: 1
#2Chad G. Rusthoven (University of Colorado Denver)H-Index: 25
Last. Sameer K. Nath (University of Colorado Denver)H-Index: 21
view all 5 authors...
Purpose The significance of radiation dose to the host immune system during the treatment of stage III non-small cell lung cancer (NSCLC) is unknown, but higher doses were associated with worse tumor control and overall survival (OS) in a secondary analysis of RTOG 0617. In this study, we sought to assess the impact of the estimated dose of radiation to immune cells (EDRIC) on cancer-specific outcomes in an independent cohort of patients treated at our institution. Methods and Materials We retro...
49 CitationsSource
#1Eun Hye Lee (Yonsei University)H-Index: 8
#2Eun Young Kim (Yonsei University)H-Index: 23
Last. Moo Suk Park (Yonsei University)H-Index: 31
view all 13 authors...
Solid malignancies are associated with the development of Pneumocystis jirovecii pneumonia (PJP). This study aimed to evaluate the risk factors for PJP among patients with lung cancer. This retrospective case-control study compared patients who had lung cancer with PJP (n = 112) or without PJP (n = 336) matched according to age, sex, histopathology, and stage. PJP definition was based on (i) positive PCR or direct immunofluorescence results for pneumocystis, (ii) clinical symptoms and radiologic...
11 CitationsSource
#1Luke R.G. Pike (Brigham and Women's Hospital)H-Index: 13
#2Andrew Bang (Brigham and Women's Hospital)H-Index: 8
Last. Jonathan D. Schoenfeld (Brigham and Women's Hospital)H-Index: 26
view all 14 authors...
Purpose Therapeutic radiation has conflicting immune effects: radiation therapy (RT)-induced immunogenic cell death can contribute to immune response, but lymphocytes are also sensitive to RT. It is unknown whether palliative RT leads to lymphopenia in patients treated with immune checkpoint inhibitors (ICIs) and whether this affects outcomes. As such, we sought to assess the impact of palliative RT on circulating lymphocyte count and neutrophil-to-lymphocyte ratio in patients being treated with...
61 CitationsSource
#1Marie Warny (UCPH: University of Copenhagen)H-Index: 4
#2Jens Helby (Copenhagen University Hospital)H-Index: 5
Last. Stig E. Bojesen (UCPH: University of Copenhagen)H-Index: 85
view all 5 authors...
Background Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population. Methods and findings Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with ava...
61 CitationsSource
#1Scott J. Antonia (Katholieke Universiteit Leuven)H-Index: 80
#2A. VillegasH-Index: 9
Last. Mustafa OzgurogluH-Index: 31
view all 33 authors...
Abstract Background An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non–small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. Methods We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of ...
1,119 CitationsSource
#1Jonathan McAleese (Belfast City Hospital)H-Index: 10
#2L. Mooney (Belfast City Hospital)H-Index: 1
Last. Gerard G Hanna (Belfast City Hospital)H-Index: 17
view all 6 authors...
3 CitationsSource
#1J. Contreras (WashU: Washington University in St. Louis)H-Index: 7
#2Alexander J. Lin (WashU: Washington University in St. Louis)H-Index: 14
Last. Clifford G. Robinson (WashU: Washington University in St. Louis)H-Index: 30
view all 10 authors...
Abstract Purpose Studies have associated increased radiation therapy (RT) heart dose with cardiac toxicity. Others have correlated RT-related immunosuppression with worsened survival. Given the large vascular volumes irradiated during locally advanced non-small cell lung cancer (LA-NSCLC) treatment, we hypothesized an association between increased heart dose and immunosuppression. Methods We identified 400 LA-NSCLC patients treated with definitive RT ± chemotherapy between 2001 and 2016. Absolut...
41 CitationsSource
Cited By23
#1Xin Zhao (Hebei Medical University)H-Index: 1
#2Yan Zhang (Hebei Medical University)
Last. Yaguang HanH-Index: 1
view all 4 authors...
Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had long...
#1Arezoo Modiri (UMB: University of Maryland, Baltimore)H-Index: 8
#2Ivan R. Vogelius (UCPH: University of Copenhagen)H-Index: 29
Last. Lena Specht (UCPH: University of Copenhagen)H-Index: 70
view all 6 authors...
At its core, radiation therapy (RT) requires balancing therapeutic effects against risk of adverse events in cancer survivors. The radiation oncologist weighs numerous disease and patient-level factors when considering the expected risk-benefit ratio of combined treatment modalities. As part of this, RT plan optimization software is used to find a clinically acceptable RT plan delivering a prescribed dose to the target volume while respecting pre-defined radiation dose-volume constraints for sel...
#1Xin Zhang (Chongqing University)
#2D. Yang (Chongqing University)H-Index: 4
Last. Wei Zhou (Chongqing University)
view all 10 authors...
Purpose We sought to compare the symptomatic radiation pneumonitis (RP) in lung cancer patients treated with helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT), and examine the predictive value of circulating lymphocyte subsets affecting the occurrence of RP. Patients and Methods Circulating lymphocyte subsets, clinical characteristics, dosimetric parameters and pulmonary function were collected from 130 lung cancer patients treated with HT (n = 53) or IMRT (n = 77) from 201...
#1Casey W. Williamson (UCSD: University of California, San Diego)H-Index: 8
#2Igor SirákH-Index: 13
Last. Michael T. McHale (UCSD: University of California, San Diego)H-Index: 21
view all 19 authors...
Abstract null null Purpose null To test effects of positron emission tomography (PET)–based bone marrow–sparing (BMS) image-guided intensity modulated radiation therapy (IG-IMRT) on efficacy and toxicity for patients with locoregionally advanced cervical cancer. null null null Methods and Materials null In an international phase II/III trial, patients with stage IB-IVA cervical carcinoma were treated with either PET-based BMS-IG-IMRT (PET-BMS-IMRT group) or standard image-guided IMRT (IMRT group...
#1Qian Zhao (Peking Union Medical College)
#2Butuo Li (Peking Union Medical College)H-Index: 1
Last. Linlin Wang (Peking Union Medical College)H-Index: 6
view all 7 authors...
BACKGROUND Many tools have been developed to predict the efficacy of immunotherapy, such as lung immune prognostic index (LIPI), EPSILoN [Eastern Cooperative Oncology Group performance status (ECOG PS), smoking, liver metastases, lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR)], and modified lung immune predictive index (mLIPI) scores. The aim of this study was to determine the ability of three predictive scores to predict the outcomes in Chinese advanced non-small cell lung ca...
#1A Punjabi (University of Manchester)
#3A. Cheng (University of Manchester)
Last. Matthew Evison (University of Manchester)H-Index: 13
view all 24 authors...
AIMS The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. MATERIALS AND METHODS A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 201...
Purpose null Emerging evidence suggests a detrimental prognostic association between radiation-induced lymphopenia (RIL) and pathologic response, progression-free survival, and overall survival (OS) in patients who undergo radiation therapy for cancer. The aim of this study was to systematically review and meta-analyze the prognostic impact of RIL on OS in patients with solid tumors. null null null Methods and Materials null PubMed/MEDLINE and Embase were systematically searched. The analysis in...
#1Giuseppe Palma (National Research Council)H-Index: 14
#2Serena MontiH-Index: 14
Last. Laura CellaH-Index: 25
view all 7 authors...
This study investigates the dose–response patterns associated with radiation pneumonitis (RP) in patients treated for thoracic malignancies with different radiation modalities. To this end, voxel-based analysis (VBA) empowered by a novel strategy for the characterization of spatial properties of dose maps was applied. Data from 382 lung cancer and mediastinal lymphoma patients from three institutions treated with different radiation therapy (RT) techniques were analyzed. Each planning CT and bio...
2 CitationsSource
#1Jonathan McAleese (Belfast City Hospital)H-Index: 10
#2L. Mooney (Belfast City Hospital)H-Index: 1
Last. Gerard Walls ('QUB': Queen's University Belfast)H-Index: 7
view all 3 authors...
Abstract null null Aims null Lung cancer is the leading cause of cancer death. Radiotherapy given in the curative setting is associated with a 3% risk of death from Pneumocystis jirovecii pneumonia (PJP). Prolonged courses of high-dose steroids also increase the risk of PJP. International guidelines recommend the use of chemoprophylaxis with trimethoprim-sulfamethoxazole for patients at high risk. We assessed the effect of an intervention designed to reduce the impact of PJP. null null null Mate...
#1Abraham George Smith (UCPH: University of Copenhagen)H-Index: 3
#2Jens PetersenH-Index: 15
Last. Ivan R. VogeliusH-Index: 29
view all 8 authors...
Organ-at-risk contouring is still a bottleneck in radiotherapy, with many deep learning methods falling short of promised results when evaluated on clinical data. We investigate the accuracy and time-savings resulting from the use of an interactive-machine-learning method for an organ-at-risk contouring task. We compare the method to the Eclipse contouring software and find strong agreement with manual delineations, with a dice score of 0.95. The annotations created using corrective-annotation a...