How Many Cancer Clinical Trials Can a Clinical Research Coordinator Manage? The Clinical Research Coordinator Workload Assessment Tool.

PURPOSE: Cancer clinical trials (CTs) are now more complex than ever before and require dedicated personnel (clinical research coordinators [CRCs]) to perform regulatory and administrative activities and protocol- and patient-related procedures. We developed a simple tool to measure the workload (WL) of CRCs involved in cancer research and to estimate personnel requirements within a Clinical Trial Center. METHODS: A literature review and 2-month period in which CRCs recorded their activities in a diary provided valuable information that led to the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Workload Assessment Tool (IWAT) being divided into three sections: Protocol, On-Treatment Patients, and Follow-Up Patients. Twelve full-time senior CRCs from three sites of the Network measured their monthly WL for 30 months to evaluate IWAT reproducibility and accuracy. RESULTS: The IWAT proved to be a user-friendly tool (3-6 minutes required for each CT), with high reproducibility (interobserver reproducibility ranged from 82% to 100% for each IWAT item). In December 2017, the Network had 185 ongoing CTs, with a median of 2.5 active centers for each CT. On the basis of 448 total IWAT measures by CRCs, the majority of trials were academic (57%) or dealt with advanced disease (77%). The median IWAT WL score for each study was 20.98 ± 22.90 (range, 2-188) and 475 ± 229 (range, 150 [junior staff] - 930 [extreme heavy WL]) for each CRC. On the basis of our experience, a monthly WL score of 500-600 was considered an appropriate value for a full-time CRC. CONCLUSION: The IWAT could prove useful in evaluating CT complexity, estimating appropriate CRC WLs, and defining personnel requirements. Independent validation by other CRCs working in different organizational contexts and in different countries is needed.

Metastatic neuroendocrine neoplasia treatments in patients over 70 years of age.

The incidence of neuroendocrine neoplasia (NEN) is higher in individuals ≥70 years of age (elderly) who are underrepresented in clinical trials because of comorbidities and low performance status. We retrospectively analyzed the outcome of elderly patients with metastatic NEN (mNEN). Comorbidities were summarized by Charlson Comorbidity Index (CCI), Kaplan-Meier method was applied to estimate overall survival (OS) and Cox's proportional hazard model was used to assess the impact of known prognostic factors. We retrieved data on 145 mNEN patients aged ≥70 years seen at our center from June 2007 to March 2016. Fifty-six (38.6%) were aged ≥75 years. ECOG PS was 0 in 45.7% of cases and CCI was 0 in 41.0% and 1 in 37.4%. A total of 75.4% of patients had grade (G)1/G2 NEN and 24.6%, G3. Octreoscan/Gallium PET/CT and FDG-PET/CT were positive in 94.2% and 70.3% of cases, respectively. Median follow-up was 72.3 (53.2-85.1) months. Seventy-nine patients received first-line somatostatin analogs (SSA), 23 peptide receptor radionuclide therapy (PRRT) and 36 chemotherapy (CHT). Seven did not undergo first-line therapy and 102 received more than one line. Median overall survival (mOS) was 5.1 years (95% CI: 3.4-6.6). No differences in mOS were seen according to CCI. First-line PRRT patients had a mOS of 6.5 years (95% CI: 3.3-not reached (NR)), SSA 5.7 years (95% CI: 4.2-7) and CHT 5.9 years (95% CI: 0.4-NR). mOS in CHT-treated G3 patients was 1.5 years (1.0-2.5). ECOG PS and FDG PET/CT were identified as independent prognostic factors. Results suggest that the above treatments positively impacted OS in elderly mNEN patients, including those aged ≥75 years.

Post-marketing surveillance of CustomBone Service implanted in children under 7 years old.

BACKGROUND: The CustomBone Service is a bioceramic implant suitable for cranial repair in both adults and children, although there are no clinical data about its use in children under 7 years of age. This surveillance study investigates the outcome in this age group. METHOD: Twenty-eight children under 7 years old (range, 2.5-6 years) received CustomBone Service from July 2006 to May 2013 in 16 international hospitals. Data of 23 children (12 males and 11 females), harboring 24 prosthesis, were available with a minimum follow-up of 1 year. FINDINGS: Sites of the cranial defect were frontal or parietal (20.8 % each), parieto-temporal (16.7 %), fronto-parietal or occipital (12.5 % each), fronto-parieto-temporal or fronto-temporal (8.3 % each). Initial diseases were trauma (54.2 %), malformation (37.5 %), or tumor of the bone/skin (8.3 %). Rupture of the implant occurred in a single case during the implant (1/26 surgeries, 3.8 %) and the cranial repair was achieved by means of the back-up prosthesis. Five adverse events were registered during the follow-up period consisting of three cases of fracture and two of exposure/infection of the prosthesis. All cases required the removal of the device (20.8 %). CONCLUSIONS: The failure rate of CustomBone Service under 7 years of age was higher than reported in adults and children over 7 years old (20.8 vs. 3.8 %), However, CustomBone Service may be considered a valid option under 7 years old since other materials are burdened by more significant rates of complications in the long-term period. Due to specific properties of this material, indication to CustomBone Service in toddlers should be carefully evaluated by the surgeon on a case-by-case basis.

HIV-1 Tat protein concomitantly down-regulates apical caspase-10 and up-regulates c-FLIP in lymphoid T cells: a potential molecular mechanism to escape TRAIL cytotoxicity.

In this study, we showed the existence of a positive correlation between the amount of human immunodeficiency virus-type 1 (HIV-1) RNA in HIV-1 seropositive subjects and the plasma levels of TRAIL. Since it has been previously demonstrated that HIV-1 Tat protein up-regulates the expression of TRAIL in monocytic cells whereas tat-expressing lymphoid cells are more resistant to TRAIL cytotoxicity, we next investigated the effect of Tat on the expression/activity of both apical caspase-8 and -10, which play a key role in mediating the initial phases of apoptosis by TRAIL, and c-FLIP. Jurkat lymphoblastoid human T cell lines stably transfected with a plasmid expressing wild-type (HIV-1) tat gene showed normal levels of caspase-8 but significantly decreased levels of caspase-10 at both mRNA and protein levels with respect to Jurkat transfected with the control plasmid or with a mutated (cys22) non-functional tat cDNA. A significant decrease of caspase-10 expression/activity was also observed in transient transfection experiments with plasmid carrying tat cDNA. Moreover, c-FLIP(L) and c-FLIP(S) isoforms were up-regulated in tat-expressing cells at both mRNA and protein level in comparison with control cells. Taken together, these results provide a molecular basis to explain the resistance of tat-expressing Jurkat cells to apoptosis induced by TRAIL and, possibly, to other death-inducing ligands.