Effects of combined sunitinib and extracranial stereotactic radiotherapy on bone marrow hematopoiesis

Abstract

Abstract. There is considerable interest in deploying stereotactic body radiotherapy in combination with immune therapy for patients with extracranial oligometastases. In addition to angiogenesis inhibition, sunitinib appears to mediate antitumor immunity through effects on circulating monocytic cells. The current study investigated the effects of combined sunitinib and stereotactic radiotherapy on hematopoiesis. As part of a phase I/II clinical trial utilizing concurrent sunitinib (25-50 mg on days 1-28) and image-guided radiation therapy (40-50 Gy in 10 fractions starting on days 8-19) for patients with metastatic cancer, the complete blood count, platelet count and automatic differential were performed pretreatment and on days 8 and 19. On average, sunitinib monotherapy for 7 days resulted in a 33% decrease in monocytes and an 18% decrease in neutrophils (P<0.01 for all). Compared to sunitinib alone, combined sunitinib and radiation resulted in a further decrease in neutrophils, lymphocytes and platelets (P<0.05). Following sunitinib and radiation treatment, a greater than average decrease in monocytes (≥200/µl) was associated with a significant increase in progression-free and overall survival times. This exploratory study provides further evidence that monocytes represent a potential biomarker in patients with solid tumors treated with sunitinib.

Prognostic role of baseline neutrophil‑to‑lymphocyte ratio in metastatic solid tumors

“…Although neutrophils and lymphocytes are non-specific parameters that are affected by concurrent infection, inflammation, corticosteroids, chemotherapy and radiation therapy, baseline NLR is a promising, readily available and cost-effective biomarker that adds prognostic value to known clinical and laboratory prognostic factors (3,8,18). In the present study, patients with an NLR >4 with metastatic disease that were referred to radiation oncology had a median survival of 4.1 months.…”

“…The prognostic role of baseline NLR has been demonstrated in 100 studies for several types of solid tumors (3). To date, limited data has been provided for NLR in patients treated with radiation, particularly in those with metastatic solid tumors (8,9). Previous studies have demonstrated that patients with metastatic disease treated with radiation tend to have a baseline NLR of 4-5 (8,9).…”

“…To date, limited data has been provided for NLR in patients treated with radiation, particularly in those with metastatic solid tumors (8,9). Previous studies have demonstrated that patients with metastatic disease treated with radiation tend to have a baseline NLR of 4-5 (8,9). By contrast, the baseline NLR for the general population is 1.65-2.15 (10,11).…”

Radiotherapy and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitors in Renal Cancer

“…Thirty-three percent of patients experienced toxicity of grade 3 or higher, and 2 fatal hemorrhages were recorded. Surprisingly, compared to sunitinib alone, the sunitinib-RT combination resulted in further reduction in hemo poiesis [19]. …”

Dendritic Cell-Based Immunotherapy in Advanced Sarcoma and Neuroblastoma Pediatric Patients: Anti-cancer Treatment Preceding Monocyte Harvest Impairs the Immunostimulatory and Antigen-Presenting Behavior of DCs and Manufacturing Process Outcome

“…Regorafenib hematological toxicity has been explained by the TK inhibition of FMS like tyrosine kinase 3 (FLT-3) and stem cell factor (c-KIT ligand), which represent hematopoietic growth receptors (15, 16). Reduction in the circulating monocyte count after sunitinib has been shown (17). Monocytes are also highly sensitive to the methylating agent temozolomide (TMZ) (18, 19).…”