Effect of Bisphosphonates on Skeletal Related Events in Long Bone Metastases of Renal Cell Carcinoma: A Systematic Review.

Bone metastases (BMs) in patients with renal cell carcinoma (RCC) are lytic lesions which are prone to skeletal related events (SREs) such as (pending) pathological fractures or bone pain requiring radiotherapy or surgery. The aim of this review is to assess whether the use of bisphosphonates in patients with RCC and BMs in the long bones results in reduced SRE rate. A systematic review of literature was conducted, using PubMed, Embase, Medline, Web of Science, Cochrane, and Google Scholar (date 1971 till June 2021). All clinical studies on bisphosphonates in patients with RCC and BMs in long bones were retrieved. Primary outcome measure was SRE rate of BMs in long bones. Secondary outcome was fracture rate of BMs in long bones. Fourteen relevant articles were selected. Bisphosphonates reduced the mean skeletal morbidity rate by 0.4-0.95 SREs/year and had a pooled SRE rate of 38.3% (95% confidence interval [CI] 28.4%-49.3%). When bisphosphonates were added to radiotherapy the pooled SRE rate was 18.4% (95% CI, 10.5%-30.3%). In addition, pooled effect sizes showed a significant SRE risk reduction (RR 0.45, 95% CI, 0.24-0.85) in the bisphosphonates combined with radiotherapy group. There was limited reported data on rate of pathological fractures. In general, bisphosphonates reduce the SRE rate in RCC patients with BMs. The level of evidence for the effect of bisphosphonates on the rate of pathological fractures in patients with long BMs of RCC is low.

Anti-GD2 Based Immunotherapy Prevents Late Events in High-Risk Neuroblastoma Patients over 18 Months at Diagnosis.

BACKGROUND: Anti-GD2 based immunotherapy has improved overall (OS) and event free survival (EFS) for high-risk neuroblastoma (HR-NBL) patients. Here, we evaluate the long-term efficacy of anti-GD2 immunotherapy in combination with isotretinoin, GM-CSF, and IL-2. METHODS: Dutch HR-NBL patients treated with immunotherapy according to the COG-ANBL0032 protocol (n = 47) were included and compared to historical controls (n = 37) treated with single-agent isotretinoin maintenance therapy. Survival time was calculated from start of the maintenance therapy. RESULTS: The study and control group were similar concerning baseline characteristics. In the complete cohort, 5 year OS was 64 ± 7% and 49 ± 8% for the immunotherapy group and the control group, respectively (p = 0.16). Five year EFS was 57 ± 7% and 41 ± 8%, respectively (p = 0.16). In the subgroup of patients ≥ 18 months, 5-yr OS was 63 ± 8% and 39 ± 9, respectively (p = 0.04) and EFS 54 ± 8% and 29 ± 8%, respectively (p = 0.05). Landmark analysis for EFS with landmark point at 6 months after start of maintenance suggests a larger effect on the prevention of late than early events. CONCLUSIONS: This study is the first to confirm the results of the COG-ANBL0032 study in a cohort treated with a different induction regimen. Anti-GD2 immunotherapy prevents late events, most significantly in patients older than 18 months of age at diagnosis.