The effects of local irradiation on circulating lymphocytes in dogs receiving fractionated radiotherapy

Kent, Michael S.; Emami, Shaheen; Rebhun, Robert B.; Théon, Alain P; Hansen, Katherine; Sparger, Ellen E.

doi:10.1111/vco.12531

Cited by 6 publications

(6 citation statements)

References 28 publications

(39 reference statements)

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“…We showed significant differences in absolute lymphocyte count and neutrophillymphocyte ratio within 90 days of treatment with worsened lymphopenia grade in 66.7% of these patients. This is consistent with the literature (45,79). Unfortunately, the sample size of available patients was too small for further analysis of the effect of post-SBRT lymphopenia on survival outcome and what demographic or tumor factors may influence these changes.…”

Section: Discussionsupporting

confidence: 89%

“…Adoptive cellular therapy using activated canine natural killer cells has been investigated in an osteosarcoma model (42), while modulation of the canine tumor microenvironment through radiation and immunotherapy has been investigated using indoleamine deoxygenase inhibition (43) as well as nanotechnology-based immune adjuvants (44). Additionally, dogs receiving fractionated radiotherapy developed significant and sustained lymphopenia after treatment (45), which has been similarly shown in human radiation therapy to effect clinical outcomes in oropharyngeal tumors (46). Moving forward, investigations into the combined use of SBRT with immunotherapy in canine cancer patients may serve as a translational model due to the similar immunomodulatory effects as human cancers (47).…”

Section: Introductionmentioning

confidence: 99%

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Response of Canine Soft Tissue Sarcoma to Stereotactic Body Radiotherapy

et al. 2021

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Canine soft tissue sarcoma (STS) has served as a preclinical model for radiation, hyperthermia, experimental therapeutics, and tumor microenvironmental research for decades. Stereotactic body radiotherapy (SBRT) demonstrates promising results for the control of various tumors in human and veterinary medicine; however, there is limited clinical data for the management of STS with SBRT. In this retrospective study, we aimed to define overall efficacy and toxicity of SBRT for the treatment of macroscopic canine STS to establish this preclinical model for comparative oncology research. Fifty-two canine patients met inclusion criteria. Total radiation dose prescribed ranged from 20–50 Gy delivered in 1–5 fractions. Median progression-free survival time (PFST) was 173 days and overall survival time (OST) 228 days. Best overall response was evaluable in 46 patients, with 30.4% responding to treatment (complete response n = 3; partial response n = 11). For responders, OST significantly increased to 475 days vs. 201 days (P = 0.009). Prognostic factors identified by multivariable Cox regressions included size of tumor and metastasis at presentation. Dogs were 3× more likely to progress (P = 0.009) or 3.5× more likely to experience death (P = 0.003) at all times of follow up if they presented with metastatic disease. Similarly, every 100-cc increase in tumor volume resulted in a 5% increase in the risk of progression (P = 0.002) and death (P = 0.001) at all times of follow up. Overall, 30.8% of patients developed acute toxicities, 7.7% grade 3; 28.8% of patients developed late toxicities, 11.5% grade 3. Increased dose administered to the skin significantly affected toxicity development. SBRT serves as a viable treatment option to provide local tumor control for canine macroscopic STS, particularly those with early-stage disease and smaller tumors. The results of this study will help to define patient inclusion criteria and to set dose limits for preclinical canine STS trials involving SBRT.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Response of Canine Soft Tissue Sarcoma to Stereotactic Body Radiotherapy

et al. 2021

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“…Because of the targeted nature of IM/IGRT, it was expected that concurrent use of chemoradiation for CGUC would be well tolerated. However, given that dogs undergoing definitive intent RT are known to experience clinically relevant decreases in total white blood cell count, it is not surprising that severe cytopenias might result from the combination of relatively high dose RT with cytotoxic chemotherapy 20,21 . Indeed, in our study, 56% of dogs that received concurrent MTX and RT developed hematopoietic adverse events, and 64% were classified as grade 3 or 4 complications.…”

Section: Discussionmentioning

confidence: 65%

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti‐inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study

Clerc-Renaud

Gieger

LaRue

et al. 2021

Veterinary Internal Medicne

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Background Locoregional tumor control and prolonged survival for dogs with genitourinary carcinoma (CGUC) reportedly are achievable using treatment with radiotherapy (RT) with or without adjunctive chemotherapy and nonsteroidal anti‐inflammatory drugs (NSAIDs). Objectives To characterize event‐free and overall survival after treatment of CGUC using NSAIDs, mitoxantrone (MTX), and a standardized RT protocol (57 Gy in 20 fractions). Animals Fifty‐one client‐owned dogs treated between 2008 and 2017. Methods Dogs were retrospectively categorized into treatment groups: (a) first‐line concurrent chemoradiotherapy (≥1 dose of MTX started within 1 month of RT); (b) first‐line chemotherapy (MTX administered for >1 month before RT without tumor progression); (c) RT as a salvage procedure (MTX, surgery or both with subsequent locoregional tumor progression before RT). Treatment‐induced toxicoses, event‐free survival (EFS), and overall survival times (OSTs) were recorded. The influence of demographics, staging, and treatment‐related factors on survival was assessed using Cox proportional hazards modeling. Results Median EFS and OST for all dogs were 260 and 510 days with no significant differences among groups 1 (n = 39), 2 (n = 4), and 3 (n = 8). Both EFS and OST were shorter in dogs with moderate to severe clinical signs ( P < .001 and P < .001, respectively); OST was shorter in dogs with prostatic involvement ( P = .02). Permanent urinary incontinence developed in 16 dogs (31%) at a median of 70 days postirradiation; other toxicoses were mild and self‐limiting. Conclusions and Clinical Importance Mild clinical signs and lack of prostate involvement were associated with favorable prognosis for survival. Client education regarding the risk of urinary incontinence is warranted.

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“…[ 18 ] RT caused significant lymphopenia compared with baseline. [ 19 ] Lymphopenia may be associated with poor outcomes in cancer patients treated with RT. [ 20 ] A study showed that pretreatment lymphopenia is an independent prognostic factor for patients with EC.…”

Section: Discussionmentioning

confidence: 99%

Impact of radiotherapy on circulating lymphocyte subsets in patients with esophageal cancer

Song

Tian

et al. 2020

Medicine

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Radiotherapy (RT) can affect the immune function of patients with cancer. The purpose of this study was to investigate the effect of RT on lymphocyte and its subsets in patients with esophageal cancer (EC). All patients received RT with a mean dose of 5369 cGy (gray). Blood parameters were measured in 31 patients on 3 occasions (before, at the end of radiotherapy, and at 3 months follow-up). The whole blood count and lymphocyte subsets were measured and correlated with short time efficiency and radiation dose parameters. White blood count (WBC) and lymphocyte count (ALC) were greatly decreased at the end of radiotherapy, and the percentages of CD3+, CD3+CD8+ T cells were significantly increased, on the other hand, a decrease in the CD4/CD8 ratio was observed. The percentages of CD3-CD16/56+NK cells and CD19+ B cell were decreased at the end of RT compared with prior RT. The percentages of CD3+ T cells before RT and the WBC and ALC count after RT can be used as prognostic indicators for survival. The PTV dose can cause significant changes in lymphocytes count after RT. CD3+T cells after RT were significantly correlated with mean heart dose and heart V50. Our study identified that RT causes changes in lymphocyte subsets, and these changes may indicate differences in immune function between individuals. Radiotherapy plan should be designed to minimize normal tissue dose to reduce the impact on WBC and lymphocytes.

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The effects of local irradiation on circulating lymphocytes in dogs receiving fractionated radiotherapy

Cited by 6 publications

References 28 publications

Response of Canine Soft Tissue Sarcoma to Stereotactic Body Radiotherapy

Response of Canine Soft Tissue Sarcoma to Stereotactic Body Radiotherapy

Treatment of genitourinary carcinoma in dogs using nonsteroidal anti‐inflammatory drugs, mitoxantrone, and radiation therapy: A retrospective study

Impact of radiotherapy on circulating lymphocyte subsets in patients with esophageal cancer

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