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

Saitô, Tetsuo; Toya, Ryo; Matsuyama, Tomohiko; Semba, Akiko; Oya, Natsuo

doi:10.1515/raon-2016-0050

Cited by 19 publications

(15 citation statements)

References 28 publications

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“…The mechanism of RIL is not completely understood, although circulating lymphocytes in peripheral vessels are directly killed as they pass through radiation treatment fields (28). Because larger radiation fields and longer TBT expose circulating lymphocytes to more radiation, the reduction in TLC should be proportional to the target volume and TBT (14,16,29), a supposition supported by our results. Irradiation of bone marrow or lymphatic tissue may also cause direct destruction of lymphocytes.…”

Section: Discussionsupporting

confidence: 79%

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Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Zhao

Chen

et al. 2020

Front. Oncol.

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Background: To investigate the role of stereotactic body RT (SBRT) in decreased total peripheral lymphocyte count (TLC) in patients with early-stage lung cancer and to explore possible risk factors for RT-induced lymphopenia. Materials and Methods:We analyzed the TLCs and lymphocyte subsets of 76 patients in our prospective clinical database who received SBRT for early-stage lung cancer treatment. Relationships between clinical factors or dosimetric parameters and TLC were evaluated using Spearman's correlation analysis and Chi-square tests for continuous and categorical variables, respectively. Multivariate linear regression analysis was used to control for confounding factors. Kaplan-Meier analysis with a log-rank test and a multivariate Cox regression model were used for survival analysis.Results: Most patients (64/76, 84.2%) experienced decreased absolute lymphocyte counts following SBRT, as well as shifts in lymphocyte subset distributions. Spearman's correlation coefficients between post-SBRT TLC and the percentage of the lung and heart receiving 5 to 50 Gy (in 5 Gy increments) shown that most lung DVH parameters [V(10)-V(50)] were significantly negatively correlated with post-SBRT TLC, while only heart V(5), V(20), V(25), V(30), and V(45) were significant. Univariate analyses revealed that a lower Pre-SBRT TLC level, higher mean lung dose, longer treatment duration, and longer TBT were significantly associated with a lower Post-SBRT TLC level (all P < 0.05).Stepwise multivariate linear regression, which incorporated all of the significantly clinical variables and SBRT-related parameters in univariate analysis, revealed that lower pre -SBRT TLC (P < 0.001), higher heart V5 (P = 0.002), and longer total beam-on time (TBT) (P = 0.001) were the independent risk factors for decrease in post-SBRT TLC. Patients with lower post-SBRT TLC and longer TBT exhibited significantly inferior progression-free survival (PFS) (P < 0.001 and P = 0.013) and overall survival (P = 0.006 and P = 0.043).Conclusions: G2 and more severe lymphopenia after SBRT might be an independent prognostic factor for poorer outcome in early-stage lung cancer. Lowering heart V5 and TBT when designing SBRT plans may spare circulating lymphocytes and have the potential to further improve survival outcomes.

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Section: Discussionsupporting

confidence: 79%

“…The degree of RIL depends on the RT total dose, target volume, and number of fractions given (13)(14)(15)(16), although many prior studies of RIL have focused on conventional fractionated radiotherapy (CFRT) (5). Anti-tumor immunity alterations caused by stereotactic body radiation therapy (SBRT) and CFRT differ distinctly (17,18).…”

Section: Introductionmentioning

confidence: 99%

Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Zhao

Chen

et al. 2020

Front. Oncol.

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“…Because of this consideration, a possibility exists that the observed HR of 3.42 underrepresents the full effect of PNI on RRL incidence. The observed correlation between PNI and RRL comports with the results of several other papers that showed that increased treatment volumes were associated with higher rates of RRL 11 , 13 , 14 , 15 , 17 , 18 (though there is no uniform agreement on this subject 16 ), and these results merit further investigation for PNI in prostate cancer.…”

Section: Discussionsupporting

confidence: 86%

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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“…Yuan et al and Saito et al have found in a breast and a palliative cohort, respectively, that LP was correlated with the number of fractions, independent of overall dose. 52,53 Secondly, irradiating larger Gross Tumour Volumes in NSCLC patients has been associated with lower lymphocyte count but not with lower total leukocyte, neutrophil, or monocyte counts during RT. 24 Thirdly, if lymphopoietic sites or organs containing large blood volumes are within the planning target volume, it will contribute to (longer duration of) LP.…”

Section: Factors That Influences Lpmentioning

confidence: 99%

Lymphocyte-Sparing Radiotherapy: The Rationale for Protecting Lymphocyte-rich Organs When Combining Radiotherapy With Immunotherapy

Lambin

Lieverse

Eckert

et al. 2020

Seminars in Radiation Oncology

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

Cited by 19 publications

References 28 publications

Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Prognosis and Risk Factors of Radiation-Induced Lymphopenia in Early-Stage Lung Cancer Treated With Stereotactic Body Radiation Therapy

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Lymphocyte-Sparing Radiotherapy: The Rationale for Protecting Lymphocyte-rich Organs When Combining Radiotherapy With Immunotherapy

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