Abstract Background: SCT is a standard therapeutic approach for patients with MM and has contributed to improved outcomes. While SCT utilization in MM has increased for all racial-ethnic subgroups over time, population-based studies have repeatedly shown that racial minorities are less likely to receive it. We explored factors that determine SCT utilization among patients within a given race to understand intra-racial disparities and how to address them in order to maximize the use of this imperative treatment among eligible patients. Methods: The 2016 National Cancer Database (NCDB) for MM with patients diagnosed between 2004-2013 was studied. Cases without information on the selected patient or facility characteristics evaluated in this analysis, including SCT use, race, median income, insurance status or facility type of initial MM diagnosis and/or treatment were excluded. The association between utilization of SCT as part of initial therapy of MM and socio-demographic factors was studied stratifying patients into mutually exclusive racial-ethnic subgroups non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA) and others using multivariate GEE logistic regression analysis (clustered on facility ID). Interactions between race and patient/facility characteristics and SCT utilization were tested using similar methods but including all races. Results: Of the 123480 unique MM patients in NCDB diagnosed between 2004-2013, 111799 met the inclusion criteria. Of these, 15021 patients (13.4%) received SCT as part of initial MM therapy. Of those who received SCT, 77.5% were NHW (14.4% of all NHW), 15.1% NHB (10.3% of all NHB), 5.2% Hispanics (13.2% of all Hispanics), 2% NHA (15.5% of all NHA) and <1% others. There was no difference by gender but significantly reduced odds of receiving SCT were noted for every 10-year increase in age at diagnosis for all racial subgroups. NHA were the only subgroup not to have a significant year-wise increase over time in odds of receiving SCT between 2004-2013. A significant increase in SCT utilization was seen with increasing median income (quartiles; 2008-2012 data), for NHW and Hispanics but not for NHB and NHA, while increased education (% population with high-school degree; 2008-2012 data) was associated with a significant increase in SCT use for NHW and NHB, but not among Hispanics or NHA. An increase in great circle distance (GCD) from the treating facility as well as a lower Charlson-Deyo comorbidity index (CCI) was associated with significantly increased odds of receiving SCT for all racial groups. Insurancepayer status significantly affected odds of receiving SCT among all races with those having private insurance to be most likely to receive SCT among NHW, NHB and Hispanics while those with "other government" insurance payer type being most likely among NHA. Among treating facility characteristics, patients of all races were more likely to receive SCT if treated at an academic/researchfacility (including NCI-designated centers) or centers with highest quartile of patientvolume seen. For analysis by geographicalregion, NHW and NHA had the highest odds of receiving SCT in mountain region but there was no impact of geography on SCT for NHB or Hispanics. Odds ratio (OR) of receiving SCT as part of initial MM therapy by socio-demographic and facility characteristics for patients of individual racial subgroups are shown in Table 1. A significant interaction between odds of receiving SCT and various racial subgroups was noted for patient age at diagnosis (p<.001, decreased odds among NHW and NHA), GCD from treating facility (p=0.013, increased odds among NHB and NHA), CCI (p=0.043, decreased odds among NHA) and treatment facility volumes (p=0.046, increased odds among NHA and Hispanics). Conclusions: In the largest analysis exploring socio-demographic factors affecting SCT utilization in MM we note a significant disparity within races for who gets SCT as a part of initial MM management and who does not. While some of these factors are non-modifiable, others including access to healthcare, income, insurance and literacy levels, proximity to treatment center, treating facility type as well as volumes are modifiable and appear to be barriers to SCT among in some races, while not in others. These must be addressed to minimize disparities within racial subgroups, especially the minorities and realize maximal benefit of SCT for MM. Disclosures Ailawadhi: Novartis: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Sher: LAM Therapeutics, Inc: Research Funding.
Bedside Clinicians’ Perceptions on the Contributing Role of Diagnostic Errors in Acutely Ill Patient Presentation: A Survey of Academic and Community Practice
Objectives This study aimed to explore clinicians’ perceptions of the occurrence of and factors associated with diagnostic errors in patients evaluated during a rapid response team (RRT) activation or unplanned admission to the intensive care unit (ICU). Methods A multicenter prospective survey study was conducted among multiprofessional clinicians involved in the care of patients with RRT activations and/or unplanned ICU admissions (UIAs) at 2 academic hospitals and 1 community-based hospital between April 2019 and March 2020. A study investigator screened eligible patients every day. Within 24 hours of the event, a research coordinator administered the survey to clinicians, who were asked the following: whether diagnostic errors contributed to the reason for RRT/UIA, whether any new diagnosis was made after RRT/UIA, if there were any failures to communicate the diagnosis, and if involvement of specialists earlier would have benefited that patient. Patient clinical data were extracted from the electronic health record. Results A total of 1815 patients experienced RRT activations, and 1024 patients experienced UIA. Clinicians reported that 18.2% (95/522) of patients experienced diagnostic errors, 8.0% (42/522) experienced a failure of communication, and 16.7% (87/522) may have benefitted from earlier involvement of specialists. Compared with academic settings, clinicians in the community hospital were less likely to report diagnostic errors (7.0% versus 22.8%, P = 0.002). Conclusions Clinicians report a high rate of diagnostic errors in patients they evaluate during RRT or UIAs.
Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force
Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.
Comparison of the investigational device exemption and post‐approval trials of the Melody transcatheter pulmonary valve
AbstractObjectiveWe compared 5‐year outcomes of transcatheter pulmonary valve (TPV) replacement with the Melody TPV in the post‐approval study (PAS) and the investigational device exemption (IDE) trial.BackgroundAs a condition of approval of the Melody TPV after the IDE trial, the Food and Drug Administration required that a PAS be conducted to evaluate outcomes of TPV replacement in a “real‐world” environment. The 5‐year outcomes of the PAS have not been published, and the IDE and PAS trials have not been compared.MethodsThe cohorts comprised all patients catheterized and implanted at 5 IDE sites and 10 PAS sites. Differences in trial protocols were detailed. Time‐related outcomes and valve‐related adverse events were compared between the two trials with Kaplan–Meier curves and log‐rank testing.Results167 patients (median age, 19 years) were catheterized and 150 underwent TPV replacement in the IDE trial; 121 were catheterized (median age, 17 years) and 100 implanted in the PAS. Freedom from hemodynamic dysfunction (p = .61) or any reintervention (p = .74) over time did not differ between trials. Freedom from stent fracture (p = .003) and transcatheter reintervention (p = .010) were longer in PAS, whereas freedom from explant (p = .020) and TPV endocarditis (p = .007) were shorter. Clinically important adverse events (AEs) were reported in 14% of PAS and 7.2% of IDE patients (p = .056); the incidence of any particular event was low in both.ConclusionsHemodynamic and time‐related outcomes in the PAS and IDE trials were generally similar, confirming the effectiveness of the Melody TPV with real‐world providers. There were few significant complications and limited power to identify important differences in AEs. The lack of major differences in outcomes between the two studies questions the usefulness of mandated costly post‐approval studies as part of the regulatory process for Class III medical devices.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
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Background: Mucinous pancreatic cysts are well reported to transform into pancreatic adenocarcinoma, whereas nonmucinous cysts are mostly benign with low risk for malignant transformation. Nonsurgical methods of differentiating mucinous and nonmucinous pancreatic cysts are challenging and entail a multi investigational approach. Low intracystic glucose levels have been evaluated in multiple studies for its accuracy in differentiating mucinous from nonmucinous cysts of the pancreas. Methods: Multiple databases were searched and studies that reported on the utility of intracystic glucose levels in diagnosing mucinous pancreatic cysts were analyzed. Meta-analysis was conducted using the random-effects model, heterogeneity was assessed by I 2%, and pooled diagnostic test accuracy values were calculated. Results: Seven studies were included in the analysis from an initial total of 375 citations. The pooled sensitivity of low glucose in differentiating mucinous pancreatic cyst was 90.5% [95% confidence interval (CI): 88.1-92.5; I 2=0%] and the pooled specificity was 88% (95% CI: 80.8-92.7; I 2=79%). The sensitivity at a glucose cut-off of 50 was 90.1% (95% CI: 87.2-92.5; I 2=0%) and the specificity was 85.3% (95% CI: 76.8-91.1; I 2=76%). The sensitivity of glucose levels in pancreatic cyst fluid taken by endoscopic ultrasound guided fine-needle aspiration was 90.8% (95% CI: 87.9-93.1; I 2=0%) and the specificity was 90.5% (95% CI: 81.7-95.3; I 2=83%). The sensitivity of point-of-care glucometers was 89.5% (95% CI: 87.9-93.1; I 2=0%) and specificity was 83.9% (95% CI: 68.5-92.6; I 2=43%). Conclusions: Low glucose level at a cut-off of 50 mg/dL on fluid samples collected by endoscopic ultrasound guided fine-needle aspiration and analyzed by point-of-care glucometer achieves excellent diagnostic accuracy in differentiating mucinous pancreatic cysts.
Photodynamic Therapy (PDT), Radiofrequency Ablation (RFA) With Biliary Stents in Palliative Treatment of Unresectable Extrahepatic Cholangiocarcinoma
Background and Aim: Extrahepatic unresectable cholangiocarcinoma carries a dismal prognosis. In addition to biliary drainage by stent placement; photodynamic therapy (PDT) and radiofrequency ablation (RFA) have been tried to prolong survival. In this meta-analysis, we appraise the current known data on the use of PDT, RFA in the palliative treatment of extrahepatic unresectable cholangiocarcinoma. Methods: We searched multiple databases from inception through July 2020 to identify studies that reported on PDT and RFA. Pooled rates of survival, stent patency, 30-, 90-day mortality, and adverse events were calculated. Study heterogeneity was assessed using I 2% and 95% prediction interval. Results: A total of 55 studies (2146 patients) were included. A total of 1149 patients underwent treatment with PDT (33 studies), 545 with RFA (22 studies), and 452 patients with stent-only strategy. The pooled survival rate with PDT, RFA, and stent-only groups was 11.9 [95% confidence interval (CI): 10.7-13.1] months, 8.1 (95% CI: 6.4-9.9) months, and 6.7 (95% CI: 4.9-8.4) months, respectively. The pooled time of stent patency with PDT, RFA, and stent-only groups was 6.1 (95% CI: 4.2-8) months, 5.5 (95% CI: 4.2-6.7) months, and 4.7 (95% CI: 2.6-6.7) months, respectively. The pooled rate of 30-day mortality with PDT was 3.3% (95% CI: 1.6%-6.7%), with RFA was 7% (95% CI: 4.1%-11.7%) and with stent-only was 4.9% (95% CI: 1.7%-13.1%). The pooled rate of 90-day mortality with PDT was 10.4% (95% CI: 5.4%-19.2%) and with RFA was 16.3% (95% CI: 8.7%-28.6%). Conclusion: PDT seemed to demonstrate better overall survival and 30-day mortality rates than RFA and/or stent-only palliation.
Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma
Abstract Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.
Awareness of myeloma care and the global impact of treatment: An international internet-based prospective study
Objective Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. Methods We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. Results The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). Conclusions We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction