Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma

Rudra, Soumon; Hui, Caressa; Rao, Yuan James; Samson, Pamela; Lin, Alexander; Chang, Xiao; Tsien, Christina; Fergus, S.; Mullen, D.; Yang, Deshan; Thotala, Dinesh; Hallahan, Dennis E.; Campian, Jian; Huang, Jiayi

doi:10.1016/j.ijrobp.2018.01.069

Cited by 71 publications

(69 citation statements)

References 26 publications

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“…Further proof of the effects of field size on lymphopenia risk was provided by a study of 210 patients with glioblastoma who were treated with conventional (T1 + T2 magnetic resonance imaging abnormalities + 1.5-2.5 cm margin) versus limited-margin fields (T1 abnormality + 1.8-2 cm margin). 4 Limited-margin radiation was associated with a significant reduction in the planning target volume (PTV) size as well as the brain V25 and, importantly, with a significantly higher median postradiation ALC (1100 vs 900 cells/μL in limited- vs conventional-margin group). In addition, patients treated with limited-margin RT had a lower absolute risk of grade ≥3 radiation-induced lymphopenia (16% vs 34%), although this difference was not statistically significant.…”

Section: Summary Of Contemporary Data: Field Size and Fractionation Ementioning

confidence: 99%

“…Multiple recent studies have identified radiation-induced lymphopenia (RIL) as a negative prognostic factor in several treatment-refractory solid tumors, including high-grade glioma, 4 , 5 , 6 , 7 head and neck cancer, 8 non-small 9 , 10 and small cell lung cancer, 11 esophageal cancer, 12 resected 13 and unresectable 14 pancreatic cancer, and cervical cancer. 15 As summarized in Table 1 , the risk and severity of RIL appears to be independent of steroid use or concurrent chemotherapy, because this toxicity occurs in 40% to 70% of patients treated with fractionated RT, regardless whether corticosteroid drugs or lymphotoxic chemotherapy agents are administered concurrently with RT.…”

Section: Introductionmentioning

confidence: 99%

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Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors

Ellsworth

2018

Advances in Radiation Oncology

127

109

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PurposeRadiation-induced lymphopenia (RIL) is the result of direct toxicity to circulating lymphocytes as they traverse the irradiated field, occurs in 40% to 70% of patients who undergo conventional external beam radiation therapy, and is associated with worse outcomes in multiple solid tumors. As immunotherapy strategies evolve, a better understanding of radiation's effects on the immune system is needed in order to develop rational methods of combining RT with immunotherapy.Methods and materialsThis paper is a review of the available literature on the clinical significance and dosimetric predictors of radiation-induced toxicity to the immune system.ResultsAn association between severe RIL and inferior survival has been described in multiple solid tumors, including glioma, lung cancer, and pancreatic cancer. RIL risk is correlated with field size, dose per fraction, and fraction number. SBRT and proton therapy techniques are associated with lower RIL risk.ConclusionsThe immune system should be considered an organ at risk during RT, and absolute lymphocyte count is an important biomarker of RT-induced immunotoxicity. Radiation dose and technique affect the risk and severity of RIL. Further research is needed to accurately characterize RT-induced immunotoxicity and develop strategies to prevent or mitigate this clinically significant side effect.

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Section: Summary Of Contemporary Data: Field Size and Fractionation Ementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors

Ellsworth

2018

Advances in Radiation Oncology

127

109

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“…Three or four weeks after completion of CCRT, two additional cycles of consolidation chemotherapy (docetaxel 75mg/m 2 on day 1 and cisplatin 25mg/m 2 on days 1-3) were performed at 3-or 4-weeks intervals. (b) Patients were administered oral S-1 (70 mg/m 2 , twice per day) alone on days 1-14 and days [29][30][31][32][33][34][35][36][37][38][39][40][41][42].…”

Section: Treatments and Assessmentsmentioning

confidence: 99%

Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy

Zhou

Zhu

et al. 2019

The Oncologist

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Background Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). Materials and Methods A total of 286 patients with stage II–IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count <1,000 cells per mm3 at diagnosis, and treatment‐related lymphopenia was defined as total lymphocyte count <200 cells per mm3 with 6 weeks after starting CCRT. Univariate and multivariate logistic regression methods were used to analyze factors associated treatment‐related lymphopenia and treatment response. Results Lymphopenia was observed in 44 patients (15.4%) at initial diagnosis. Pretreatment lymphopenia was significantly associated with greater tumor length, worse T status, body mass index ≤18.5 kg/m2, and weight loss ≥3 kg in the previous 3 months. Six weeks after starting CCRT, 89 patients (31%) developed treatment‐related lymphopenia. Tumor progression and cancer‐related death were more frequently observed in treatment‐related lymphopenia group than those without (76.4% vs. 52.8% and 58.4% vs. 39.6%). A complete response (CR) was achieved in 62 patients (21.7%). In multivariate analysis, treatment‐related lymphopenia was significantly associated with lack of clinical CR, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment‐related lymphopenia. Conclusion Treatment‐related lymphopenia during CCRT is an independent predictor for poor treatment response in ESCC. Implications for Practice A total of 286 patients with locally advanced esophageal squamous cell carcinoma were treated with concurrent chemoradiotherapy (CCRT), and treatment‐related lymphopenia occurred in 31% of patients within 6 weeks from the start of CCRT. Treatment‐related lymphopenia was significantly associated with lack of treatment response, and older age, lower tumor location, greater tumor length, and larger planning target volume were independent predictors of treatment‐related lymphopenia. Lymphocyte count is an inexpensive biomarker that may be easily used by clinicians to identify patients who are most likely to benefit from CCRT.

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“…One other publication also correlated baseline lymphopenia with RRL 14 ; however, other publications have not found baseline lymphopenia to be predictive for OS, including the recent meta-analysis by Grossman et al. 12 , 20 Further investigation into this subject may be helpful.…”

Section: Discussionmentioning

confidence: 99%

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Schad

Dutta

Muller

et al. 2019

Advances in Radiation Oncology

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Purpose Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL). Methods and materials The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes. Results Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/μL) versus 26.3% of non-PNI patients ( P < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL ( P < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61; P < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11; P = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6; P = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses. Conclusions The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.

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Effect of Radiation Treatment Volume Reduction on Lymphopenia in Patients Receiving Chemoradiotherapy for Glioblastoma

Abstract: Limited-field RT is associated with less lymphopenia after RT plus temozolomide and does not adversely affect PFS or OS. Brain V25 Gy is confirmed as an important dosimetric predictor for ASL.

Cited by 71 publications

References 26 publications

Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors

Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors

Lymphopenia in Esophageal Squamous Cell Carcinoma: Relationship to Malnutrition, Various Disease Parameters, and Response to Concurrent Chemoradiotherapy

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

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