Low bone mineral density is associated with hypogonadism and cranial irradiation in male childhood cancer survivors

Summary: We investigated if bone mineral density was related to testosterone deficiency and/or previous cancer treatment in men who were childhood cancer survivors. Men with untreated testosterone deficiency or previous treatment with cranial irradiation were at increased risk of impaired bone health. Prevention of osteoporosis should be considered in their follow-up. Introduction: Childhood cancer survivors (CCS) are at increased risk of hypogonadism. Reduced bone mineral density (BMD) has been reported in CCS but it is unclear whether this is due to hypogonadism or a direct effect of cancer therapy. This study investigated BMD in CCS, and association with hypogonadism, previous treatment and cancer type. Methods: Investigation of 125 CCS (median age 33.7 at inclusion; 9.6 at diagnosis) and 125 age-matched population controls. Serum testosterone and luteinizing hormone were assayed and BMD at total hip and lumbar spine L1–L4 measured. The mean difference in BMD (g/cm2; 95% CI) between CCS and controls was analysed. Odds ratios (OR; 95% CI) for low BMD were also calculated. Results: Overall, BMD in the CCS cohort did not significantly differ from controls. However, compared with eugonadal CCS, the CCS with untreated hypogonadism had lower BMD at the hip (mean difference − 0.139 (− 0.210; − 0.067); p < 0.001) and spine (− 0.102 (− 0.174; − 0.030); p = 0.006). They also had a higher risk of low hip BMD (OR 4.1 (1.3; 14); p = 0.018). CCS treated with cranial irradiation also had lower BMD (hip − 0.076 (− 0.133; − 0.019); p = 0.009; spine − 0.071 (− 0.124; − 0.018); p = 0.009) compared with controls. The latter associations remained statistically significant after adjustment for hypogonadism. Conclusions: CCS with hypogonadism or previously treated with cranial irradiation are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow-up of these men

Risk of low bone mineral density in testicular germ cell cancer survivors : Association with hypogonadism and treatment modality

The cure rate of testicular cancer exceeds 95%, but testicular cancer survivors (TCS) are at increased risk of hypogonadism (HG). It has been suggested that TCS have reduced bone mineral density (BMD), but it is unclear whether this is related to HG or a direct effect of cancer therapy. The aim of this study was to evaluate whether TCS have decreased BMD, and if BMD is related to HG and/or the cancer treatment given. We investigated 91 TCS (mean age at diagnosis: 31 years; mean 9.3 years follow-up) and equal number of age matched controls (mean age at inclusion 40.3 years and 41.2 years, respectively). Total testosterone and LH were measured. BMD was determined using dual-energy X-ray absorptiometry (DXA). Low BMD (LBD) was defined as Z-score <-1. Compared to eugonadal TCS, both TCS with untreated HG (mean difference: -0.063 g/cm2; 95% CI: -0.122; -0.004 p = 0.037) and TCS receiving androgen replacement (mean difference -0.085 g/cm2; 95% CI: -0.168; -0.003; p = 0.043) presented with statistically significantly 6-8% lower hip BMD. At the spine, L1-L4, an 8% difference reached the level of statistical significance only for those with untreated HG (mean difference: -0.097 g/cm2; 95% CI: -0.179; -0.014; p = 0.022). TCS with untreated HG had significantly increased OR for spine L1-L4 LBD (OR = 4.1; 95% CI: 1.3; 13; p = 0.020). The associations between the treatment given and BMD were statistically non-significant, both with and without adjustment for HG. In conclusion, TCS with HG are at increased risk of impaired bone health. Prevention of osteoporosis should be considered as an important part in future follow up of these men

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry

BACKGROUNDConventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS.MATERIALS AND METHODSData from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome.RESULTSSeventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively.CONCLUSIONSThis registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options