Application of the research electronic data capture (REDCap) system in a low- and middle income country- experiences, lessons, and challenges.

The challenges of reliably collecting, storing, organizing, and analyzing research data are critical in low- and middle-income countries (LMICs), particularly in Sub-Saharan Africa where several healthcare and biomedical research organizations have limited data infrastructure. The Research Electronic Data Capture (REDCap) System has been widely used by many institutions and hospitals in the USA for data collection, entry, and management and could help solve this problem. This study reports on the experiences, challenges, and lessons learned from establishing and applying REDCap for a large US-Nigeria research partnership that includes two sites in Nigeria, (the College of Medicine of the University of Lagos (CMUL) and Jos University Teaching Hospital (JUTH)) and Northwestern University (NU) in Chicago, Illinois in the United States. The largest challenges to this implementation were significant technical obstacles: the lack of REDCap-trained personnel, transient electrical power supply, and slow/intermittent internet connectivity. However, asynchronous communication and on-site hands-on collaboration between the Nigerian sites and NU led to the successful installation and configuration of REDCap to meet the needs of the Nigerian sites. An example of one lesson learned is the use of Virtual Private Network (VPN) as a solution to poor internet connectivity at one of the sites, and its adoption is underway at the other. Virtual Private Servers (VPS) or shared online hosting were also evaluated and offer alternative solutions. Installing and using REDCap in LMIC institutions for research data management is feasible; however, planning for trained personnel and addressing electrical and internet infrastructural requirements are essential to optimize its use. Building this fundamental research capacity within LMICs across Africa could substantially enhance the potential for more cross-institutional and cross-country collaboration in future research endeavors.

Radiation and hormonal therapy for primary treatment of stage I endometrial cancer and long-term survival.

OBJECTIVES: Estimate the association between non-surgical management (NSM) (e.g. hormonal or radiation therapy) and overall survival among women with stage I endometrioid endometrial cancer (EEC) and identify patient and facility characteristics associated with receipt of NSM. METHODS: Women >45 years of age with clinical stage I EEC were identified in the National Cancer Database from 2004 to 2016. Women treated with NSM were compared with women treated initially with hysterectomy. Patient and facility characteristics associated with NSM were evaluated using logistic regression models. Association with overall survival was examined using log-rank tests, Kaplan-Meier curves, and Cox proportional hazards regression models with and without propensity score matching (PSM). RESULTS: A total of 112,469 women underwent treatment for stage I EEC between 2004 and 2016. 2776 (3%) received NSM, of whom 1987 (71%) received radiation therapy, 688 (25%) received hormonal therapy, and 101 (4%) received both. Older age, black race, higher Charlson-Deyo scores, Medicaid insurance, and low annual facility hysterectomy volume were associated with receiving NSM. The 5-year survival rate was 40% (95%CI: 37%-42%) for women with NSM compared to 89% (95%CI: 88%-89%) for hysterectomy. Women treated with NSM died at a faster rate than those who underwent primary hysterectomy (HR 7.6, 95%CI: 7.2-8.0; p < 0.001). This statistically significant difference in survival persisted in adjusted Cox proportional hazards models and after PSM. CONCLUSIONS: Women treated with NSM had a significantly higher risk of death compared to those undergoing hysterectomy for stage I EEC. Caution should be used when selecting patients for NSM given its worse outcomes.

Response-adapted volume de-escalation (RAVD) in locally advanced head and neck cancer.

BACKGROUND: Efforts to reduce the late toxicity associated with chemoradiation (CRT) for locally advanced head and neck squamous cell cancer (LA-HNSCC) have focused on radiotherapy (RT) dose de-escalation. In this phase I/II protocol investigating the addition of everolimus to induction chemotherapy (IC), we incorporated a novel response-adapted volume de-escalation (RAVD) approach using IC response to guide the extent of RT volume reduction. PATIENTS AND METHODS: Patients with measurable LA-HNSCC received two cycles of IC (cisplatin, paclitaxel, cetuximab ± everolimus). Patients with ≥50% reduction in the sum of tumor diameters [good response (GR)] received TFHX (paclitaxel, fluorouracil, hydroxyurea, and 1.5 Gy twice daily RT every other week) to a dose of 75 Gy with the single planning target volume (PTV1) encompassing exclusively gross disease. Patients with <50% response [non-response (NR)] were treated with TFHX encompassing PTV1 and the next nodal station at risk (PTV2) to a dose of 45 Gy followed by a sequential boost to PTV1 to a dose of 75 Gy. RESULTS: Ninety-four patients were enrolled. Randomization to everolimus was discontinued on interim analysis after 50 patients due to futility. IC response was evaluable in 89 patients. Thirty-seven patients (41.6%) had GR and 52 (58.4%) had NR. There was a trend for improved progression-free (P = 0.086) but not overall survival (P = 0.94) for GR versus NR. The 2-year PFS and OS were 86.0% and 83.5% for GR and 68.7% and 85.4% for NR, respectively. NR were significantly more likely to undergo G-tube placement during treatment (50.0% GR versus 73.5% NR, P = 0.040) and be G-tube dependent at 6-month follow-up (5.7% GR versus 32.6% NR, P = 0.005). CONCLUSIONS: The addition of everolimus to IC was not beneficial. The elimination of elective nodal coverage in patients with GR to IC did not appear to compromise outcomes and resulted in significantly decreased late toxicity. Further investigation of RAVD is warranted. CLINICALTRIALSGOV: NCT01133678.

Oral cavity tumors in younger patients show a poor prognosis and do not contain viral RNA.

BACKGROUND: Oral cavity and in particular oral tongue cancers occur with a rising incidence in younger patients often lacking the typical risk factors of tobacco use, alcohol use, and human papilloma virus (HPV) infection. Their prognosis when treated with chemoradiation has not been well studied and responsible risk factors remain elusive. A viral etiology (other than HPV) has been hypothesized. METHODS: First we analyzed outcomes from 748 head and neck cancer patients with locoregionally advanced stage tumors treated with curative-intent chemoradiation by anatomic site. Second, we analyzed seven oral tongue (OT) tumors from young, non-smokers/non-drinkers for the presence of viral mRNA using short-read massively-parallel sequencing (RNA-Seq) in combination with a newly-developed digital subtraction method followed by viral screening and discovery algorithms. For positive controls we used an HPV16-positive HNC cell line, a cervical cancer, and an EBV-LMP2A transgene lymphoma. RESULTS: Younger patients with oral cavity tumors had worse outcomes compared to non-oral cavity patients. Surprisingly none of the seven oral tongue cancers showed significant presence of viral transcripts. In positive controls the expected viral material was identified. CONCLUSION: Oral cavity tumors in younger patients have a poor prognosis and do not appear to be caused by a transcriptionally active oncovirus.

Cause-specific mortality following radical prostatectomy.

BACKGROUND: To evaluate cause-specific mortality following radical prostatectomy (RP) in a population cohort of US men adjusting for competing risks. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to identify 120,392 men undergoing RP for clinically localized prostate cancer between 1988 and 2003. Cause-specific mortality data were extracted through 2006 and cumulative incidence was estimated using a competing risks approach. RESULTS: The stage distribution of the cancers was 32% local, 28% regional, 40% unknown, and 80% of tumors Gleason ≤ 7. Median follow-up was 7 years. The 15-year prostate cancer-specific mortality was 5.3% and the non-prostate cancer mortality was 30.6%. Stage, grade and race had minimal impact on non-prostate cancer mortality. At 15 years following surgery, mortality due to cardiovascular diseases was 11%, other cancers 9.1%, and other causes 10.5%. Among men ≥ 65 years, 15-year cancer-specific mortality was 6% and non-prostate cancer mortality was 40.8%. CONCLUSIONS: Following RP, death from cardiovascular diseases, other cancers, and other causes is far more common than death from prostate cancer. In men diagnosed with prostate cancer, significant efforts should be made to prevent, diagnose, and treat these diseases.

Phase II trial of pemetrexed-based induction chemotherapy followed by concomitant chemoradiotherapy in previously irradiated patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Concurrent chemoreirradiation therapy (CRRT) offers a therapeutic option for patients with locoregionally recurrent squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that response to induction chemotherapy (IC) would improve outcome and predict increased survival. PATIENTS AND METHODS: Subjects with recurrent SCCHN not amenable to standard therapy were eligible. IC consisted of two 28-day cycles of gemcitabine and pemetrexed on days 1 and 14, followed by surgical resection, if appropriate, and/or CRRT consisting of carboplatin, pemetrexed, and single daily fractionated radiotherapy. RESULTS: Thirty-five subjects were enrolled, 31 were assessable for response, with 11 responders [response rate = 35%; 95% confidence interval (CI) 19.2-54.6]. Among 24 subjects who started CRRT, 11 were assessable for radiographic response, 4 complete response, 2 partial response, and 5 progressive disease. Median progression-free survival and overall survival (OS) were 5.5 months (95% CI 3.6-8.3) and 9.5 months (95% CI 7.2-15.4), respectively. One-year OS was 43% (95% CI 26% to 58%). Subjects who responded to IC had improved survival (P = 0.02). Toxic effects included mucositis, dermatitis, neutropenia, infection, hemorrhage, dehydration, and pain. CONCLUSIONS: The combination of pemetrexed plus gemcitabine was active and well tolerated in recurrent SCCHN. Response to IC may help stratify prognosis and offer an objective and dynamic metric in recurrent SCCHN patients being considered for CRRT.

Topoisomerase IIalpha in Wilms' tumour: gene alterations and immunoexpression.

BACKGROUND: Topoisomerase IIalpha (topoIIalpha) is an essential enzyme gene in regulating DNA structure and cell proliferation and is encoded by the TOP2A. Using cDNA microarray analysis, TOP2A has been reported to be one of the top genes overexpressed in Wilms' tumour. AIM: To evaluate the role of TopoIIalpha in Wilms' tumorigenesis and its prognostic value. METHODS: TOP2A gene copy numbers were determined using the fluorescence in situ hybridisation technique, and protein expression levels of TopoIIalpha by immunostaining in 39 samples of primary and 18 samples of metastatic Wilms' tumour. RESULTS: TOP2A gene amplification was detected only in anaplastic Wilms' tumours, and none of the Wilms' tumours showed deletion of the TOP2A gene. TopoIIalpha protein overexpression was detected in 97% of Wilms' tumours, and correlated strongly with proliferation, as measured by Ki-67 (r = 0.85). The high TopoIIalpha expression was associated with the presence of vascular invasion, prominent apoptosis, metastases and adverse clinical outcomes (p<0.05). CONCLUSIONS: Our findings suggest that TopoIIalpha overexpression in Wilms' tumours is caused by a change at the transcription level, except for anaplastic Wilms' tumours, in which gene amplification was present. High levels of TopoIIalpha protein are correlated with tumour aggressiveness. The assessment of TopoIIalpha expression in Wilms' tumour may have prognostic value.