RESUMO
Purpose: Various radiation therapy (RT) dose/fractionation schedules are acceptable for palliation in multiple myeloma. Nine years of single-institution RT experience were reviewed to determine the influence of dose/fractionation and other factors pertinent to individualizing therapy. Methods and Materials: In total, 152 items were identified from Current Procedural Terminology codes for multiple myeloma treatment from 2012 through June 30, 2021. After exclusions, 205 sites of radiation in 94 patients were reviewed. Data were captured from treatment planning and clinical records. To statistically assess the association between biological effective dose (BED10) and variables of interest, BED was first dichotomized to <24 Gy versus ≥24 Gy. Multivariate analysis used SAS software and a generalized estimating equation approach to account for multiple observations per patient. Results: Fractions of 1.8 to 8 Gy were used in 1 to 25 fractions. Most patients had no significant toxicity. Grade 1 toxicity was more likely with greater BED radiation courses, as expected (20% vs 12% for BED <24 Gy). Pain relief was complete or very good for most sites, with <3% reporting no pain relief. Eleven sites in 9 patients required retreatment. All retreatment sites had palliation that was lasting, with a median of 22 months to last follow-up or death after repeat course (range, 0.5-106 months). There was a trend for better pain control and less risk of fracture retreatment with BED ≥24 Gy. Conclusions: Most patients had good palliation without toxicity. BED ≥24 Gy caused 8% greater risk of grade 1 toxicity and trended toward better pain control plus reduced risk of fracture retreatment.
RESUMO
BACKGROUND: Mutations affecting cilia proteins have an established role in renal cyst formation. In mice, the rate of cystogenesis is influenced by the age at which cilia dysfunction occurs and whether the kidney has been injured. Disruption of cilia function before postnatal day 12-14 results in rapid cyst formation; however, cyst formation is slower when cilia dysfunction is induced after postnatal day 14. Rapid cyst formation can also be induced in conditional adult cilia mutant mice by introducing renal injury. Previous studies indicate that macrophages are involved in cyst formation, however the specific role and type of macrophages responsible has not been clarified. METHODS: We analyzed resident macrophage number and subtypes during postnatal renal maturation and after renal injury in control and conditional Ift88 cilia mutant mice. We also used a pharmacological inhibitor of resident macrophage proliferation and accumulation to determine the importance of these cells during rapid cyst formation. RESULTS: Our data show that renal resident macrophages undergo a phenotypic switch from R2b (CD11clo) to R2a (CD11chi) during postnatal renal maturation. The timing of this switch correlates with the period in which cyst formation transitions from rapid to slow following induction of cilia dysfunction. Renal injury induces the reaccumulation of juvenile-like R2b resident macrophages in cilia mutant mice and restores rapid cystogenesis. Loss of primary cilia in injured conditional Ift88 mice results in enhanced epithelial production of membrane-bound CSF1, a cytokine that promotes resident macrophage proliferation. Inhibiting CSF1/CSF1-receptor signaling with a CSF1R kinase inhibitor reduces resident macrophage proliferation, R2b resident macrophage accumulation, and renal cyst formation in two mouse models of cystic disease. CONCLUSIONS: These data uncover an important pathogenic role for resident macrophages during rapid cyst progression.