Late toxicity within a Phase III clinical trial of IG-IMRT in cervix cancer (PARCER): Reanalysis with time weighted adverse event reporting (MOSES).

BACKGROUND AND PURPOSE: This post-hoc analysis was performed to report the impact of Image guided intensity modulated radiotherapy (IG-IMRT) and three-dimensional conformal radiotherapy (3D-CRT) across organ system and grades of toxicity within PARCER trial (NCT01279135). Primary endpoint of PARCER focused on grade ≥ 2 late gastrointestinal (GI) toxicity using Common Terminology Criteria for Adverse Events (CTCAE). We now analyze all adverse events using CTCAE and time and severity weighted toxicity reporting method (MOSES). MATERIALS AND METHODS: MOSES was calculated separately for GI, genitourinary (GU)/GI, and any late toxicities (GI, GU, lymphedema, fatigue, vaginal stenosis, fibrosis and constitutional symptoms) by imputing proportionate time weightage to CTCAE. Cumulative MOSES (C-MOSES) for multiple system and multiorgan toxicity was determined. Difference in arms was analyzed as time-to-event and intention-to-treat analysis using CTCAE grade ≥ 1 and C-MOSES ≥ 0.70. RESULTS: We observed no difference in the 3-year cumulative incidence of CTCAE grade ≥ 1 GI, GI or GU, or any late toxicity between treatment arms. However, while using C-MOSES, HR of 0.59 (95% CI 0.38-0.92, p = 0.017), 0.68 (95% CI: 0.44-1.05, p = 0.08) and 0.72 (95% CI: 0.52-0.99, p = 0.04) was observed for GI, GI or GU, or any late toxicity within IG-IMRT respectively. CONCLUSION: This demonstrates superior discrimination of intervention effects using MOSES which demonstrates superiority of IG-IMRT.

WORLDWIDE CASE FATALITY RATIO OF COVID-19 OVER TIME

BackgroundThe case fatality ratio (CFR) of coronavirus disease 2019 (COVID-19) has been reported to be variable among different countries and regions but few analyses have tracked this ratio worldwide over time. MethodsThe primary objective was to assess the time-course evolution of CFR of COVID-19 in all countries with available data and secondary objective was to evaluate associations between country-wise CFR and country-level health, human development, demographic and economic parameters. Day-wise data of COVID-19 cases and deaths for each country was extracted from a public repository and countries with at least 1000 cases on cutoff date were clustered by unsupervised k-means on the basis of deaths per 100000 population (DP100K). Day-wise CFR (cumulative deaths divided by cumulative cases, multiplied by 100) for each country and cluster (country group) was plotted as time-series and country-level parameters were tested for association with CFR using weighted multiple linear regression. ResultsOn September 24, 2020 there were 32140504 cumulative COVID-19 cases and 981792 deaths reported from 184 countries for a worldwide CFR of 3.06 % (95%CI 3.05 -3.07). Unsupervised k-means clustering in 157 countries with at least 1000 reported cases resulted in Clusters (country groups) A, B, C, D and E with centroid DP100K and CFR of 0.100 and 2.51 (95% CI 2.42-2.61), 0.503 and 2.28 (95% CI 2.23-2.33), 1.816 and 1.73 (95% CI 1.71-1.75), 7.395 and 1.76 (95% CI 1.75-1.76), and 36.303 and 3.82 (95% CI 3.82-3.83), respectively. In a log-log analysis DP100K and CFR were significantly positively correlated (R=0.3570, p<0.001) with each other. All country groups and majority of included countries showed a pattern of gradually increasing CFR from the beginning of pandemic, followed by a plateau and then a steady decline in CFR. Among 10 country-level parameters, GDP per capita ({beta}=-0.483, p=0.000), hospital beds per population ({beta}=-0.372, p<0.001), mortality from air pollution ({beta}=-0.487, p=0.003) and population density ({beta}=-0.570, p< 0.000) were significantly negatively associated while maternal mortality ratio ({beta}=0.431, p=0.000) and age ({beta}=0.635, p<0.000) were positively associated with CFR. ConclusionsThe CFR of COVID-19 has gradually increased over time in majority of countries at various stages of the pandemic, followed by a plateau and a steady decline. Population level COVID-19 mortality burden and CFR are significantly positively associated with each other.

Is long term storage of cryopreserved stem cells for hematopoietic stem cell transplantation a worthwhile exercise in developing countries?

BACKGROUND: Stem cell units (SCUs) that are cryopreserved prior to both autologous and allogeneic hematopoietic stem cell transplants (for donor lymphocyte infusion) remain unused or partially used several times, and become an increased burden to blood banks/SCU repositories. Because of the scarcity of data regarding the duration for which the storage is useful, there is no general consensus regarding disposal of SCUs. METHODS: We conducted a retrospective audit of SCU utilization in 435 patients who planned to undergo either autologous stem cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to January 2015. RESULTS: Our cohort consisted of 1,728 SCUs stored for conducting auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs) after allo-SCT. Stem cells were not infused in 12.5% of patients who had planned to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized, with a second auto-SCT being performed only in 4 patients. Ninety-four percent of SCUs intended for carrying out DLIs remained unused, with only minimal usage observed one year after undergoing allo-SCT. CONCLUSION: The duration of storage of unused SCUs needs to be debated upon, so that a consensus can be reached regarding the ethical disposal of SCU.