Myeloid-Derived Cells in Tumors: Effects of Radiation

The discrepancy between the in vitro and in vivo response to radiation is readily explained by the fact that tumors do not exist independently of the host organism; cancer cells grow in the context of a complex microenvironment composed of stromal cells, vasculature, and elements of the immune system. As the antitumor effect of radiotherapy depends in part on the immune system, and myeloid-derived cells in the tumor microenvironment modulate the immune response to tumors, it follows that understanding the effect of radiation on myeloid cells in the tumor is likely to be essential for comprehending the antitumor effects of radiotherapy. In this review, we describe the phenotype and function of these myeloid-derived cells, and stress the complexity of studying this important cell compartment owing to its intrinsic plasticity. With regard to the response to radiation of myeloid cells in the tumor, evidence has emerged demonstrating that it is both model and dose dependent. Deciphering the effects of myeloid-derived cells in tumors, particularly in irradiated tumors, is key for attempting to pharmacologically modulate their actions in the clinic as part of cancer therapy

Resection Followed by Involved-Field Fractionated Radiotherapy in the Management of Single Brain Metastasis

Introduction: We expanded upon our previous experience using involved-field fractionated radiotherapy (IFRT) as an alternative to whole brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) for patients with surgically resected brain metastases.Material and Methods: All patients with single brain metastases who underwent surgical resection followed by IFRT at our institution from 2006-2013 were evaluated. Local recurrence-free survival, distant failure-free survival and overall survival were determined. Analyses were performed associating clinical variables with local recurrence and distant failure. Salvage approaches and toxicity of treatment for each patient were also assessed.Results: Median follow-up was 19.1 months. Fifty-six patients were treated with a median dose of 40.05 Gy/15 fractions with IFRT to the resection cavity. Local recurrence-free survival was 91.4%, distant failure-free survival was 68.4%, and overall survival was 77.7% at 12 months. No variables were associated with increased local recurrence, however melanoma histopathology and infratentorial location were associated with distant failure on multivariate analysis. Local recurrences were salvaged in 5/8 patients, and distant failures were salvaged in 24/29 patients. Two patients developed radionecrosis.Conclusions: Adjuvant IFRT is feasible and safe for well-selected patients with surgically resected single brain metastases. Acceptable rates of local control and salvage of distal intracranial recurrences continue to be achieved with continued follow-up

Body weights [g (mean ± SEM)] of proton irradiated and control rats.

A. The overall effect on body weights by exposure group, averaged across sex and week. B. Body weights of females by weeks. C. Body weights of males by weeks. While there was an exposure × sex interaction, both females and males dosed with 8 Gy were lighter than controls. See text for a summary of the exposure × age interaction. ***p < 0.001 compared with controls. N = 14-19/sex/exposure at each week. Due to scheduling errors some of the body weights were missed on some weeks.</p

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The Cincinnati water maze latency [s (mean ± SEM)] and number of errors (mean ± SEM) of proton irradiated and control rats.

A. The overall effect on latency where irradiated groups took longer to locate the platform compared with controls. B. The learning curves for latency. There was an interaction of exposure x day that is described in the results. Differences between the controls and irradiated groups began after day 5 and from day 10 to 18 all groups except the 5-FLASH group took longer to locate the platform. C. The overall effect on errors where irradiated groups had more errors to locate the platform. D. The learning curves for errors. Similar to latency there was an exposure x day interaction that is described in the results. N = 19/sex/exposure except control male and 5-FLASH male = 18. *p < 0.05, **p < 0.01, and ***p < 0.001 compared with controls.</p