Pretreatment Immune Parameters Predict for Overall Survival and Toxicity in Early-Stage Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Shaverdian, Narek; Veruttipong, Darlene; Wang, Jason; Schaue, Dörthe; Kupelian, Patrick A.; Lee, Percy

doi:10.1016/j.cllc.2015.07.007

Cited by 61 publications

(62 citation statements)

References 31 publications

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“…Elevated proportions of Treg cells indicated rapid tumor progression after radiotherapy, which may because of the suppressor function of Treg cells and their resistance to radiation [22, 23]. In addition to lymphocyte subsets, we also observed that lymphocyte counts and NLR were correlated with survival without relapse, which were consistent with published studies [24, 25]. The predictive value of NLR, platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) were previously investigated in various kinds of cancer [24, 26–28].…”

Section: Discussionsupporting

confidence: 90%

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Liu

Meng

et al. 2017

Oncotarget

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BackgroundStudies increasingly focus on the impact of radiotherapy on immunity; however, the role of peripheral cellular immunity prior to radiotherapy in cancer patients remains largely unknown. In this study, we investigated the predictive roles of lymphocyte subsets on tumor progression in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy, and their expression in NSCLC patients at first relapse.MethodsWe enrolled 70 NSCLC patients and 14 age- and sex-matched healthy donors and tested the lymphocyte subsets in their peripheral blood by flow cytometry. Among them, 40 newly diagnosed patients received radiotherapy and were enrolled to investigate the predictive value of lymphocyte subsets on tumor progression after radiotherapy by uni- and multivariate analyses; 30 patients at first relapse were included to evaluate the differences of lymphocyte subsets between them and first diagnosed patients and healthy volunteers.ResultsIncreased proportions of regulatory T cells, CD8+ T cells, and CD8+CD28- T cells and decreased CD4+ T cells and CD4/CD8 ratios were observed in NSCLC patients at first relapse compared to newly diagnosed patients. In the 40 first diagnosed patients undergoing radiotherapy, uni- and multivariate analyses showed that increased level of regulatory T cells correlated with poor progression-free survival (hazard ratio = 2.55 and 3.76, P = 0.022 and 0.010, respectively).ConclusionsPeripheral regulatory T cells were increased and independently predict tumor progression in NSCLC patients undergoing radiotherapy, suggesting the promising combination of radiotherapy and immunotherapy.

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Section: Discussionsupporting

confidence: 90%

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Liu

Meng

et al. 2017

Oncotarget

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“…An elevated pretreatment PLR has been shown to predict poor outcome in the setting of SRS for early-stage NSCLC. Furthermore, hypoalbuminemia has been validated to serve as a marker for systemic inflammation (11), and is found to predict disease recurrence after complete resection of early-stage NSCLC (9,10). Therefore, although novel in the setting of brain SRS, our finding that markers of systemic inflammation prior to SRS predict poor outcome is supported by these previous data in different treatment settings.…”

Section: Discussionsupporting

confidence: 74%

“…Pre-treatment markers of systemic inflammation, including an elevated platelet-to-lymphocyte ratio (PLR), elevated neutrophil count, low lymphocyte count and low serum albumin concentration, have been found to predict responses to anti-neoplastic therapies and disease outcomes across multiple different malignancies (5)(6)(7)(8)(9)(10)(11). However, these markers and the role the systemic immune system plays in treatment outcomes in the setting of SRS for brain metastases have yet to be fully evaluated.…”

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confidence: 99%

Pro-inflammatory State Portends Poor Outcomes with Stereotactic Radiosurgery for Brain Metastases

Shaverdian

Wang

Levin-Epstein

et al. 2016

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LC, poor initial MR, poor OS and poor intracranial control (p=0.01, p=0.01, p=0.02 and p=0.03, respectively). A lower percentage of lymphocytes predicted for poor LC and poor MR (p=0.01 and p=0.02), and an elevated PLR predicted for poor OS and poor LC (p=0.05 and p=0.04). Additionally, a lower pretreatment albumin concentration predicted for poor LC and OS (p=0.01 and p=0.03) . Conclusion: Pretreatment systemic inflammation is associated with poor outcomes post-SRS.Metastatic brain tumors are the most common intracranial neoplasms, with an incidence that continues to rise as a result of advances in neuroimaging and more effective systemic therapies. Population-based studies suggest that up to 45% of all patients with cancer develop brain metastases and that the majority of brain metastases originate from lung cancer, breast cancer and melanoma (1). The standard-of-care for brain metastases continues to evolve given innovations in radiation technology, surgical techniques and systemic therapies. However, among patients not requiring surgical resection, stereotactic radiosurgery (SRS) represents an effective and favored treatment modality with high rates of local control (2-4).Pre-treatment markers of systemic inflammation, including an elevated platelet-to-lymphocyte ratio (PLR), elevated neutrophil count, low lymphocyte count and low serum albumin concentration, have been found to predict responses to anti-neoplastic therapies and disease outcomes across multiple different malignancies (5-11). However, these markers and the role the systemic immune system plays in treatment outcomes in the setting of SRS for brain metastases have yet to be fully evaluated. There is a growing use of immunotherapy among patients with advanced cancer, and recent studies are suggesting improvements in outcomes with the combination of SRS and immunotherapy with checkpoint inhibition for treatment of brain metastases (12). Therefore, further exploring the role the systemic immune system plays in brain radiosurgery outcomes is now essential.Although the blood-brain barrier selectively isolates the central nervous system, circulating systemic immune cells are capable of migrating from the cerebral vessels into the brain parenchyma in response to various stimuli (13). Additionally, multiple studies have established that there is substantial cross-talk between systemic immune responses and inflammatory cells in the brain (14,15). Interestingly, pathological studies on brain metastases post-SRS have identified an inflammatory cellular response to be characteristic, suggesting an interaction between the immune system and SRS outcomes (16). We therefore sought to further evaluate the relationship between outcomes brain SRS and immune responses. We determined if pretreatment immune parameters associated with systemic inflammation would predict the initial response to SRS seen on the first post-treatment magnetic resonance imaging (MRI), and for local control, distant intracranial control and overall survival in the setting of SRS for b...

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“…Numerous other studies have investigated the optimal NLR in a variety of malignancies [10–12, 14, 15]. The dichotomous cut point used for NLR to best predict OS has ranged from 2.18 to 7.5.…”

Section: Discussionmentioning

confidence: 99%

“…As such, multiple investigators have shown that elevated neutrophil-to-lymphocyte ratio (NLR) is associated with worse outcomes in multiple malignancies [10–12]. While the blood brain barrier can limit intracranial penetration of non-lipidophilic molecules, recent evidence suggests inflammatory cells are able to cross into the brain [13].…”

Section: Introductionmentioning

confidence: 99%

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

et al. 2018

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Introduction Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocytepredominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain métastasés (BM). Methods BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. Results 188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR >6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. >6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR >6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03–2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30–2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes. Conclusion Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

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Pretreatment Immune Parameters Predict for Overall Survival and Toxicity in Early-Stage Non–Small-Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Cited by 61 publications

References 31 publications

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Predictive value of peripheral regulatory T cells in non-small cell lung cancer patients undergoing radiotherapy

Pro-inflammatory State Portends Poor Outcomes with Stereotactic Radiosurgery for Brain Metastases

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

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