Time to resolution of iodine-123 metaiodobenzylguanidine (123 I-MIBG) avidity and local control outcomes for high-risk neuroblastoma following radiation therapy.
Journal of medical imaging and radiation oncology
INTRODUCTION: 123 I-MIBG scan is used in neuroblastoma (NB) to monitor treatment response. Time to resolution of 123 I-MIBG avidity after radiation therapy (RT) is unknown. We sought to determine time to resolution of 123 I-MIBG avidity after RT and local failure (LF) rate.METHODS: We performed a retrospective review of children with high-risk NB who underwent 123 I-MIBG scans pre- and post-RT from 2003 to 2019. Time from RT to resolution of 123 I-MIBG activity was analysed. LF and cumulative incidence of local progression (CILP) after RT stratified by site, presence of residual disease and use of boost RT were determined.RESULTS: Forty-two patients with median age 3.9years (1.9-4.7years) were included, with median follow-up time 3.9years (1.4-6.9). Eighty-six lesions were treated with RT to median dose of 21.6Gy. Eighteen of 86 lesions were evaluable for time to resolution of MIBG avidity after RT, with median resolution time of 78days (36-208). No LF occurred among 26 patients who received RT to primary sites after GTR, versus 4/12 (25%) patients treated with residual primary disease. 2-year CILP was 19% (12% primary disease 25% metastatic disease (P=0.18)). 2-year CILP for non-residual primary, residual primary, non-residual metastatic and residual metastatic lesions was 0%, 42%, 11% and 30% respectively (P=0.01) and for boosted and non-boosted residual lesions was 29% and 35% (P=0.44).CONCLUSION: Median time to MIBG resolution after RT was 78days. Primary lesions without residual disease had excellent local control. LF rate was higher after RT for residual disease, with no benefit for boost RT.
View details for DOI 10.1111/1754-9485.13487
View details for PubMedID 36300562
Do Steroids Matter? A Retrospective Review of Premedication for Taxane Chemotherapy and Hypersensitivity Reactions.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE: Despite the widespread use of the taxanes paclitaxel and docetaxel for a variety of cancers and their well-known association with hypersensitivity reactions (HSRs), there is still significant variation in the prescribing practices of steroids for premedication. Premedication almost always includes dexamethasone, which can be associated with multiple adverse effects if taken for extended periods of time. This study reviews the pattern of steroid premedication in patients who received paclitaxel or docetaxel at Stanford Cancer Institute between January 2010 and June 2020.METHODS: We used an electronic query of the electronic medical record followed up with a manual review of patient charts to ask whether we could find a correlation between steroid premedication dosing and the incidence or severity of HSRs with the first taxane dose. Variables considered included steroid dose and route, dose and type of taxane, clinical cancer group, sex, and race.RESULTS: Five thousand two hundred seventeen patients were identified as having received paclitaxel or docetaxel, and 3,181 met criteria for our analysis. There were 264 (8.3%) HSRs. In adjusted multivariate analysis, we found no correlation of HSR rate or severity among any of the variables evaluated except gynecology oncology clinic patients, who had an increased risk (hazard ratio [HR] 1.34) of HSRs overall and high-grade HSRs (HR 2.34), and female patients, who had a higher rate of HSRs overall (HR 1.26), but not high-grade HSRs.CONCLUSION: Neither dexamethasone dose nor route correlated with subsequent HSRs. Given the potential for adverse events from repeated high-dose steroids, our findings suggest that routine use of lower doses, such as a single 10 mg dose of dexamethasone, as premedication for taxanes to prevent HSRs is preferable to the current prescribing guidelines.
View details for DOI 10.1200/JCO.21.01200
View details for PubMedID 34357780
Aged hematopoietic stem cells are refractory to bloodborne systemic rejuvenation interventions
JOURNAL OF EXPERIMENTAL MEDICINE
2021; 218 (7)
While young blood can restore many aged tissues, its effects on the aged blood system itself and old hematopoietic stem cells (HSCs) have not been determined. Here, we used transplantation, parabiosis, plasma transfer, exercise, calorie restriction, and aging mutant mice to understand the effects of age-regulated systemic factors on HSCs and their bone marrow (BM) niche. We found that neither exposure to young blood, nor long-term residence in young niches after parabiont separation, nor direct heterochronic transplantation had any observable rejuvenating effects on old HSCs. Likewise, exercise and calorie restriction did not improve old HSC function, nor old BM niches. Conversely, young HSCs were not affected by systemic pro-aging conditions, and HSC function was not impacted by mutations influencing organismal aging in established long-lived or progeroid genetic models. Therefore, the blood system that carries factors with either rejuvenating or pro-aging properties for many other tissues is itself refractory to those factors.
View details for DOI 10.1084/jem.20210223
View details for Web of Science ID 000663429700003
View details for PubMedID 34032859
View details for PubMedCentralID PMC8155813
Autophagy maintains the metabolism and function of young and old stem cells
2017; 543 (7644): 205-+
With age, haematopoietic stem cells lose their ability to regenerate the blood system, and promote disease development. Autophagy is associated with health and longevity, and is critical for protecting haematopoietic stem cells from metabolic stress. Here we show that loss of autophagy in haematopoietic stem cells causes accumulation of mitochondria and an activated metabolic state, which drives accelerated myeloid differentiation mainly through epigenetic deregulations, and impairs haematopoietic stem-cell self-renewal activity and regenerative potential. Strikingly, most haematopoietic stem cells in aged mice share these altered metabolic and functional features. However, approximately one-third of aged haematopoietic stem cells exhibit high autophagy levels and maintain a low metabolic state with robust long-term regeneration potential similar to healthy young haematopoietic stem cells. Our results demonstrate that autophagy actively suppresses haematopoietic stem-cell metabolism by clearing active, healthy mitochondria to maintain quiescence and stemness, and becomes increasingly necessary with age to preserve the regenerative capacity of old haematopoietic stem cells.
View details for DOI 10.1038/nature21388
View details for Web of Science ID 000395688700031
View details for PubMedID 28241143
View details for PubMedCentralID PMC5344718