Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

Huang, Jiayi; DeWees, T.A.; Badiyan, Shahed N.; Speirs, Christina K.; Mullen, D.; Fergus, S.; Tran, David; Linette, G P; Campian, Jian; Chicoine, Michael R.; Kim, Albert H.; Dunn, Gavin P.; Simpson, Joseph R.; Robinson, Clifford G.

doi:10.1016/j.ijrobp.2015.04.005

Cited by 84 publications

(76 citation statements)

References 29 publications

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“…The lower level of baseline TLC in patients who received short course of RT may be a poor prognostic characteristic which might contribute to the shorter survival in these patients. This was another unexpected finding, as a previous report from Huang et al demonstrated that higher brain volume receiving 25 Gy was one of the predictors of acute severe lymphopenia [19]. Another group showed the percentage of circulating lymphocyte damaged was proportionally related to the fractions of RT treatment [18].…”

Section: Discussionmentioning

confidence: 86%

“…Receiving 60 Gy in 30 fractions exposes nearly all circulating cells to potentially lymphotoxic doses of RT [18]. Most recently, a study of 183 patients with high grade gliomas evaluated for predictors of lymphopenia, and found that higher brain volume receiving 25 Gy was one of the predictors of severe lymphopenia [19]. Together this evidence suggests that RT might play a major role in TRL.…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, in our study of elderly patients with a median age of 71 years, only 57 % patients had a normal baseline TLC. This is likely due to advanced age, relative poor KPS (90 vs. 70), and nutrition status compared to younger patients [11, 19, 22, 23]. Second, both univariate and multivariate analyses suggested that patients receiving >45 Gy of RT were associated with longer OS than those receiving ≤45 Gy of RT.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, a study of 183 patients with glioblastoma (GBM) evaluated for predictors of lymphopenia, and found that older age, female sex, lower baseline TLC, and higher brain volume receiving 25 Gy were predictors of severe lymphopenia. In this study, 29 % of patients developed severe TRL with TLC less than 500 cell/mm 3 [19]. …”

Section: Introductionmentioning

confidence: 99%

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Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

et al. 2016

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Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers. This retrospective study is designed to evaluate whether elderly GBM patients (age ≥65) develop similar TRL after RT/TMZ and whether such TRL is associated with decreased survival. Serial total lymphocyte counts (TLC) were retrospectively reviewed in patients (age ≥65) with newly diagnosed GBM undergoing RT/ TMZ and associated with treatment outcomes. Seventy-two patients were eligible: median KPS 70, median age 71 years (range 65–86) with 56 % of patients >70 years, 53 % female, 31 % received RT ≤45 Gy. Baseline median TLC was 1100 cells/mm3 which fell by 41 % to 650 cells/ mm3 2 months after initiating RT/TMZ (p < 0.0001). Patients with TLC <500 cells/mm3 at 2 months had a shorter survival than those with higher TLCs with a median overall survival of 4.6 versus 11.6 months, respectively. Multivariate analysis revealed a significant association between TRL and survival (HR 2.76, 95 % CI 1.30–5.86, p = 0.008). Treatment-related lymphopenia is frequent, severe, and an independent predictor for survival in elderly patients with GBM. These findings add to the body of evidence that immunosuppression induced by chemoradiation is associated with inferior clinical outcomes. Prospective studies are needed to confirm these findings suggesting that immune preservation is important in this cancer.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

et al. 2016

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“…19,20 Although studies to evaluate the effect of irradiation on lymphocytes showed that radiation-related lymphopenia was associated with organ-specific (lung 14 and brain 21 ) dose-volume parameters, dosimetric predictors applicable at various treatment sites remained to be identified.…”

Section: Introductionmentioning

confidence: 99%

Dosimetric predictors of treatment-related lymphopenia induced by palliative radiotherapy: predictive ability of dose-volume parameters based on body surface contour

Saitô

Toya

Matsuyama

et al. 2016

Radiology and Oncology

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BackgroundRadiation-related lymphopenia has been associated with poor patient outcome. Our aim was to identify predictors of lymphopenia after palliative radiotherapy, with a focus on dose-volume parameters.Patients and methodsTo retrospectively assess patients with various cancers who had undergone palliative radiotherapy, we delineated three organs at risk: the volume enclosed by the body surface contour (body A), the volume left after excluding air, pleural effusion, ascites, bile, urine, and intestinal content (body B), and the volume of the bone marrow (BM). We then noted the absolute volume of the three organs at risk that had received 5-30 Gy, and assessed the predictive value for post-treatment lymphopenia of grade 3 or higher (LP3+).ResultsOf 54 patients, 23 (43%) developed LP3+. Univariate logistic regression analysis showed that body A V5, body A V10, body B V5, body B V10, the number of fractions, and splenic irradiation were significant predictors of LP3+ (p < 0.05). By multivariate analysis, body A V5, body A V10, body B V5, body B V10, and the number of fractions retained significance (p < 0.05). BM dose-volume parameters did not predict lymphopenia.ConclusionsHigher body A and body B dose-volume parameters and a larger number of fractions may be predictors of severe lymphopenia after palliative radiotherapy.

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Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio With Poor Clinical Outcomes in Patients With Human Papillomavirus–Negative Oropharyngeal Cancers

Lin

Gang²,

Rao

et al. 2019

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE Better biomarkers are needed for human papillomavirus (HPV)-negative oropharyngeal cancer (OPC) to identify patients at risk of recurrence. Lymphopenia and an elevated ratio of neutrophils to lymphocytes (NLR) have been associated with poor disease outcomes in a number of solid tumors. OBJECTIVE To test the hypothesis that postradiotherapy lymphopenia and elevated NLR are associated with poor clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS This single-institution retrospective analysis included patients with HPV-negative OPC treated from January 1, 1997, through January 4, 2017. Median follow-up was 37 months (range, 2-197 months). A total of 108 patients with HPV-negative OPC and at least 1 complete blood cell count 2 to 12 months after the start of radiotherapy were included. Data were analyzed from August 26 to September 7, 2017. INTERVENTIONS Surgery followed by radiotherapy vs definitive radiotherapy, with or without chemotherapy. MAIN OUTCOMES AND MEASURES Absolute lymphocyte (ALC) and absolute neutrophil (ANC) counts were tested as variables affecting locoregional control, recurrence-free survival, and overall survival. RESULTS Of a total of 108 patients included in the analysis (87.0% male; mean age, 56 years [range, 35-84 years]), 57 received surgery followed by postoperative radiotherapy and 51 received definitive radiotherapy. During treatment, 67 of 79 patients (84.8%) had grades 3 to 4 lymphopenia and 17 of 79 (21.5%) had grade 4 lymphopenia. The ANC recovered by 6 months after radiotherapy, but ALC remained depressed to 1 year after radiotherapy. Posttreatment lymphopenia and elevated NLR were associated with worse recurrence-free and overall survival. The estimated 3-year LRC in patients with and without grades 3 to 4 lymphopenia at 3 months after radiotherapy start was 73% vs 82% (hazard ratio [HR], 0.58; 95% CI, 0.19-1.8); estimated 3-year recurrence-free survival, 36% vs 63% (HR, 0.45; 95% CI, 0.23-0.87); and estimated 3-year overall survival, 34% vs 64% (HR, 0.45; 95% CI, 0.23-0.88). In multivariable analysis, an association with worse overall survival was found for definitive radiotherapy (HR, 3.3; 95% CI, 1.6-7.1) and grades 3 to 4 lymphopenia (HR, 2.6; 95% CI, 1.3-5.5) at 3 months after radiotherapy. CONCLUSIONS AND RELEVANCE Lymphopenia and NLR as early as 3 months after treatment start may serve as biomarkers of clinical outcomes in patients with HPV-negative OPC. These patients may benefit from adjuvant treatment intensification or closer surveillance.

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Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma

Cited by 84 publications

References 29 publications

Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma

Dosimetric predictors of treatment-related lymphopenia induced by palliative radiotherapy: predictive ability of dose-volume parameters based on body surface contour

Association of Posttreatment Lymphopenia and Elevated Neutrophil-to-Lymphocyte Ratio With Poor Clinical Outcomes in Patients With Human Papillomavirus–Negative Oropharyngeal Cancers

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