ResearchPad - original-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Results of the ADHERE upper airway stimulation registry and predictors of therapy efficacy]]> https://www.researchpad.co/article/elastic_article_7106 The ADHERE Registry is a multicenter prospective observational study following outcomes of upper airway stimulation (UAS) therapy in patients who have failed continuous positive airway pressure therapy for obstructive sleep apnea (OSA). The aim of this registry and purpose of this article were to examine the outcomes of patients receiving UAS for treatment of OSA.Study DesignCohort Study.MethodsDemographic and sleep study data collection occurred at baseline, implantation visit, post‐titration (6 months), and final visit (12 months). Patient and physician reported outcomes were also collected. Post hoc univariate and multivariate analysis was used to identify predictors of therapy response, defined as ≥50% decrease in Apnea‐Hypopnea Index (AHI) and AHI ≤20 at the 12‐month visit.ResultsThe registry has enrolled 1,017 patients from October 2016 through February 2019. Thus far, 640 patients have completed their 6‐month follow‐up and 382 have completed the 12‐month follow‐up. After 12 months, median AHI was reduced from 32.8 (interquartile range [IQR], 23.6–45.0) to 9.5 (IQR, 4.0–18.5); mean, 35.8 ± 15.4 to 14.2 ± 15.0, P < .0001. Epworth Sleepiness Scale was similarly improved from 11.0 (IQR, 7–16) to 7.0 (IQR, 4–11); mean, 11.4 ± 5.6 to 7.2 ± 4.8, P < .0001. Therapy usage was 5.6 ± 2.1 hours per night after 12 months. In a multivariate model, only female sex and lower baseline body mass index remained as significant predictors of therapy response.ConclusionsAcross a multi‐institutional study, UAS therapy continues to show significant improvement in subjective and objective OSA outcomes. This analysis shows that the therapy effect is durable and adherence is high.Level of Evidence2 Laryngoscope, 130:1333–1338, 2020 ]]> <![CDATA[Twelve‐month outcomes of a bioabsorbable implant for in‐office treatment of dynamic nasal valve collapse]]> https://www.researchpad.co/article/elastic_article_7093 To examine 12‐month outcomes for in‐office treatment of dynamic nasal valve collapse (NVC) with a bioabsorbable implant.Study DesignProspective, multicenter, nonrandomized study.MethodsOne hundred sixty‐six patients with severe‐to‐extreme class of Nasal Obstruction Symptom Evaluation (NOSE) scores were enrolled at 16 U.S. clinics (November 2016–July 2017). Patients were treated with a bioabsorbable implant (Latera, Spirox Inc., Redwood City, CA) to support the lateral wall, with or without concurrent inferior turbinate reduction (ITR), in an office setting. NOSE scores and Visual Analog Scale (VAS) were measured at baseline and 1, 3, 6, and 12 months postoperatively. The Lateral Wall Insufficiency (LWI) score was determined by independent physicians observing the lateral wall motion video.ResultsOne hundred five patients were treated with implant alone, whereas 61 had implant + ITR. Thirty‐one patients reported 41 adverse events, all of which resolved with no clinical sequelae. Patients showed significant reduction in NOSE scores throughout 12 months postoperatively (77.4 ± 13.4 baseline vs. 36.2 ± 22.7 at 1 month postoperatively, 33.0 ± 23.4 at 3 months, 32.1 ± 24.6 at 6 months, and 30.3 ± 24.3 at 12 months; P < 0.001). They also showed significant reduction in VAS scores postoperatively (69.7 ± 18.1 baseline vs. 31.3 ± 27.1 at 12 months postoperatively, P < 0.001). These results were similar in patients treated with implant alone and those treated with the implant + ITR. Consistent with patient‐reported outcomes, postoperative LWI scores were demonstrably lower (1.42 ± 0.09 and 0.93 ± 0.08 pre‐ and postoperatively, P < 0.001).ConclusionIn‐office treatment of dynamic NVC with a bioabsorbable implant improves clinical evidence of LWI at 6 months and improves nasal obstructive symptoms in a majority of patients up to 12 months.Level of Evidence2b Laryngoscope, 130:1132–1137, 2020 ]]> <![CDATA[Descriptive analysis of postmarket surveillance data for hip implants]]> https://www.researchpad.co/article/elastic_article_6824 Recent safety issues involving medical devices have highlighted the need for better postmarket surveillance (PMS) evaluation. This article aims to describe and to assess the quality of the PMS data for a medical device and, finally, to provide recommendations to improve the data gathering process.MethodsA descriptive analysis of medical device reports (MDRs) on the use of MRA, a specific type of hip implant replacement submitted to the Food and Drug Administration Manufacturer and User Facility Device Experience database from 1 January 2008 to 31 December 2017. The number of reports was described as the number of MDRs per unique MDR number and stratified by different variables. The quality was assessed by the level of completeness of the collected PMS data.ResultsThe total number of reports related to MRA was 2377, and the number of MDRs per year ranged between 84 in 2009 and 452 in 2017. Most of the reports were reported by manufacturer Depuy Johnson & Johnson and were reported by a physician. In 44.9% of the reports, the device problem was reported as “Unknown.” When the device problem was known, in the majority of cases, it was related to an implant fracture. The quality of the collected data was assessed as low due to missing information.ConclusionThe underlying data should meet high quality standards to generate more evidence and to ensure a timely signal generation. This case study shows that the completeness and quality of the MDRs can be improved. The authors propose the development of tools to ensure a more dynamic complaint data collection to contribute to this enhancement. ]]> <![CDATA[OncoMX: A Knowledgebase for Exploring Cancer Biomarkers in the Context of Related Cancer and Healthy Data]]> https://www.researchpad.co/article/N462bd4a0-032c-4efa-9990-c71ccbd2af6a

PURPOSE

The purpose of OncoMX1 knowledgebase development was to integrate cancer biomarker and relevant data types into a meta-portal, enabling the research of cancer biomarkers side by side with other pertinent multidimensional data types.

METHODS

Cancer mutation, cancer differential expression, cancer expression specificity, healthy gene expression from human and mouse, literature mining for cancer mutation and cancer expression, and biomarker data were integrated, unified by relevant biomedical ontologies, and subjected to rule-based automated quality control before ingestion into the database.

RESULTS

OncoMX provides integrated data encompassing more than 1,000 unique biomarker entries (939 from the Early Detection Research Network [EDRN] and 96 from the US Food and Drug Administration) mapped to 20,576 genes that have either mutation or differential expression in cancer. Sentences reporting mutation or differential expression in cancer were extracted from more than 40,000 publications, and healthy gene expression data with samples mapped to organs are available for both human genes and their mouse orthologs.

CONCLUSION

OncoMX has prioritized user feedback as a means of guiding development priorities. By mapping to and integrating data from several cancer genomics resources, it is hoped that OncoMX will foster a dynamic engagement between bioinformaticians and cancer biomarker researchers. This engagement should culminate in a community resource that substantially improves the ability and efficiency of exploring cancer biomarker data and related multidimensional data.

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<![CDATA[Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer]]> https://www.researchpad.co/article/N1d48f137-3423-4c06-b1a1-53b1b4a43b5b

PURPOSE

To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer.

MATERIALS AND METHODS

Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons.

RESULTS

Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2.

CONCLUSION

A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.

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<![CDATA[Cascading After Peridiagnostic Cancer Genetic Testing: An Alternative to Population-Based Screening]]> https://www.researchpad.co/article/N409e256e-242f-4fa9-8731-8aff6a79763c

PURPOSE

Despite advances in DNA sequencing technology and expanded medical guidelines, the vast majority of individuals carrying pathogenic variants of common cancer susceptibility genes have yet to be identified. An alternative to population-wide genetic screening of healthy individuals would exploit the trend for genetic testing at the time of cancer diagnosis to guide therapy and prevention, combined with augmented familial diffusion or “cascade” of genomic risk information.

METHODS

Using a multiple linear regression model, we derived the time interval to detect an estimated 3.9 million individuals in the United States with a pathogenic variant in 1 of 18 cancer susceptibility genes. We analyzed the impact of the proportion of incident patients sequenced, varying observed frequencies of pathogenic germline variants in patients with cancer, differential rates of diffusion of genetic information in families, and family size.

RESULTS

The time to detect inherited cancer predisposing variants in the population is affected by the extent of cascade to first-, second-, and third-degree relatives (FDR, SDR, TDR, respectively), family size, prevalence of mutations in patients with cancer, and the proportion of patients with cancer sequenced. In a representative scenario, assuming a 7% prevalence of pathogenic variants across cancer types, an average family size of 3 per generation, and 15% of incident patients with cancer in the United States undergoing germline testing, the time to detect all 3.9 million individuals with pathogenic variants in 18 cancer susceptibility genes would be 46.2, 22.3, 13.6, and 9.9 years if 10%, 25%, 50%, and 70%, respectively, of all FDR, SDR, and TDR were tested for familial mutations.

CONCLUSION

Peridiagnostic and cascade cancer genetic testing offers an alternative strategy to achieve population-wide identification of cancer susceptibility mutations.

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<![CDATA[Outcome of Oncology Patients Infected With Coronavirus]]> https://www.researchpad.co/article/N7fa60333-eefe-4912-90e0-d2da2afef24f

PURPOSE

This study investigated the features of oncology patients with confirmed Middle East respiratory syndrome (MERS) at the Ministry of National Guard Health Affairs-Riyadh during the outbreak of June 2015 to determine the clinical course and outcome of affected patients.

METHODS

The patients’ demographic information, cancer history, treatment pattern, information about MERS-coronavirus (CoV) infection, history of travel, clinical symptoms, test results, and outcome were collected and analyzed as part of a quality improvement project to improve the care and safety of our patients. Only patients with confirmed infection were included.

RESULTS

A total of 19 patients were identified, with a median age of 66 years (range, 16-88 years), and 12 patients (63%) were males. The most common underlying disease was hematologic malignancies (47.4%), followed by colorectal cancer (21%) and lung cancer (15.8%). Hypertension and diabetes mellitus were the most common comorbidities (57.9% and 52.6%, respectively). Infection was diagnosed by nasopharyngeal swab in all patients. All patients contracted the infection during their hospitalization for other reasons. Sixteen patients (80%) were admitted to the intensive care unit; 13 patients (81%) had acute respiratory distress syndrome, 11 were intubated (68.75%), 9 had acute renal injury (56.25%), and 3 required dialysis (18.75%). Only 3 patients (15.8%) with early-stage cancers survived. Patients with hematologic malignancies and advanced solid tumors had a 100% case fatality rate. The majority of the causes of death were due to multi-organ failure and septic shock.

CONCLUSION

MERS-CoV infection resulted in a high case fatality rate in patients with malignancy. Therefore, it is critical to implement effective primary preventive measures to avoid exposure of patients with cancer to the virus.

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<![CDATA[Feasibility of Brigade-Style, Multiphasic Cancer Screening in Rural Honduras]]> https://www.researchpad.co/article/Na68de7f5-83f7-482a-8505-ad82158b3d2b

PURPOSE

To evaluate the feasibility of brigade-style, multiphasic cancer screening in Honduras, exploring data from 3 screening events that each tested for multiple cancers on single occasions.

METHODS

This series of 3 studies each used a single-arm, post-test–only design to explore the feasibility of implementing multiphasic, community-based cancer screening at the same rural location in 2013, 2016, and 2017. The 2013 event for women screened for 2 cancers (breast and cervix), and the 2016 event for women screened for 3 cancers (breast, cervix, and thyroid). The 2017 event for men screened for 5 cancers (skin, prostate, colorectal, oropharynx, and testes).

RESULTS

Totals of 473 and 401 women participated in the 2013 and 2016 events, respectively, and 301 men participated in the 2017 event. Staffing for each event varied from 33 to 44 people and relied primarily on in-country medical students and local community members. High rates (mean, 88%) of compliance with referral for follow-up testing at clinics and primary care facilities were observed after the screening events.

CONCLUSION

The multiphasic, community-based approach proved feasible for both women and men and resulted in high rates of compliance with follow-up testing. This approach appears highly replicable: it was conducted multiple times across the years with different screening targets, which could be further scaled elsewhere using the same technique.

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<![CDATA[MLCD: A Unified Software Package for Cancer Diagnosis]]> https://www.researchpad.co/article/N848b0810-ca6e-4a57-b2d2-f63dea367409

PURPOSE

Machine Learning Package for Cancer Diagnosis (MLCD) is the result of a National Institutes of Health/National Cancer Institute (NIH/NCI)-sponsored project for developing a unified software package from state-of-the-art breast cancer biopsy diagnosis and machine learning algorithms that can improve the quality of both clinical practice and ongoing research.

METHODS

Whole-slide images of 240 well-characterized breast biopsy cases, initially assembled under R01 CA140560, were used for developing the algorithms and training the machine learning models. This software package is based on the methodology developed and published under our recent NIH/NCI-sponsored research grant (R01 CA172343) for finding regions of interest (ROIs) in whole-slide breast biopsy images, for segmenting ROIs into histopathologic tissue types and for using this segmentation in classifiers that can suggest final diagnoses.

RESULT

The package provides an ROI detector for whole-slide images and modules for semantic segmentation into tissue classes and diagnostic classification into 4 classes (benign, atypia, ductal carcinoma in situ, invasive cancer) of the ROIs. It is available through the GitHub repository under the Massachusetts Institute of Technology license and will later be distributed with the Pathology Image Informatics Platform system. A Web page provides instructions for use.

CONCLUSION

Our tools have the potential to provide help to other cancer researchers and, ultimately, to practicing physicians and will motivate future research in this field. This article describes the methodology behind the software development and gives sample outputs to guide those interested in using this package.

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<![CDATA[Treatment Patterns for Chronic Comorbid Conditions in Patients With Cancer Using a Large-Scale Observational Data Network]]> https://www.researchpad.co/article/N5332c77b-5909-40dd-9767-9b1f84211c93

PURPOSE

Patients with cancer are predisposed to developing chronic, comorbid conditions that affect prognosis, quality of life, and mortality. While treatment guidelines and care variations for these comorbidities have been described for the general noncancer population, less is known about real-world treatment patterns in patients with cancer. We sought to characterize the prevalence and distribution of initial treatment patterns across a large-scale data network for depression, hypertension, and type II diabetes mellitus (T2DM) among patients with cancer.

METHODS

We used the Observational Health Data Sciences and Informatics network, an international collaborative implementing the Observational Medical Outcomes Partnership Common Data Model to standardize more than 2 billion patient records. For this study, we used 8 databases across 3 countries—the United States, France, and Germany—with 295,529,655 patient records. We identified patients with cancer using SNOMED (Systematized Nomenclature of Medicine) codes validated via manual review. We then characterized the treatment patterns of these patients initiating treatment of depression, hypertension, or T2DM with persistent treatment and at least 365 days of observation.

RESULTS

Across databases, wide variations exist in treatment patterns for depression (n = 1,145,510), hypertension (n = 3,178,944), and T2DM (n = 886,766). When limited to 6-node (6-drug) sequences, we identified 61,052 unique sequences for depression, 346,067 sequences for hypertension, and 40,629 sequences for T2DM. These variations persisted across sites, databases, countries, and conditions, with the exception of metformin (73.8%) being the most common initial T2DM treatment. The most common initial medications were sertraline (17.5%) and escitalopram (17.5%) for depression and hydrochlorothiazide (20.5%) and lisinopril (19.6%) for hypertension.

CONCLUSION

We identified wide variations in the treatment of common comorbidities in patients with cancer, similar to the general population, and demonstrate the feasibility of conducting research on patients with cancer across a large-scale observational data network using a common data model.

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<![CDATA[Colorectal Cancer in Northern Tanzania: Increasing Trends and Late Presentation Present Major Challenges]]> https://www.researchpad.co/article/N2a187834-e987-4f3e-9744-0acc01077ce3

PURPOSE

A trend of increasing incidence of colorectal cancer (CRC) has been observed in northern Tanzania. Studies have shown a six-fold increase in CRC in the past decade, with 90% of patients presenting in late stages, with resultant high morbidity and mortality rates. In this study, we aimed to document the burden of CRC in the northern zone of Tanzania from 1998 to 2018, focusing on patient presentation, clinical features, and treatment at a tertiary hospital.

METHODS

Pathological and clinical records for all patients from 1998 to 2018 were identified and reviewed. Records of patients whose CRC was diagnosed histologically were retrospectively reviewed.

RESULTS

Approximately 313 CRC cases were documented. The majority age group (29.1%) was between 50 and 64 years (mean [standard deviation], 54.28 [16.75] years). However, together, the age groups of patients younger than 50 years was 41.5% (n = 130). Of 174 patients with complete records, most (29.3%) were between 35 and 49 years of age. The median age was 52 (interquartile range, 40-67) years. Men accounted for 62.1% of patients and were mostly from the Kilimanjaro region. More than half (54.7%) presented > 3 months after symptom debut; 62.6% first sought care at lower-level health facilities. Most (64.9%) presented as emergencies, necessitating colostomy for fecal diversion as the initial surgical procedure in 60.3% of patients. Colonoscopy was performed for 38.6% of the study participants. Most tumors (72.7%) originated from the sigmoid and rectum. Adenocarcinoma was the most prevalent histologic type.

CONCLUSION

High proportions of young individuals with CRC pose great concern and a need for further appraisal. Furthermore, late emergency presentation and low colonoscopy rates highlights underlying system challenges and need for education campaigns.

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<![CDATA[Cancer Imaging Phenomics via CaPTk: Multi-Institutional Prediction of Progression-Free Survival and Pattern of Recurrence in Glioblastoma]]> https://www.researchpad.co/article/N4aa69618-fc33-4b62-bf4f-a48f14d8d52f

PURPOSE

To construct a multi-institutional radiomic model that supports upfront prediction of progression-free survival (PFS) and recurrence pattern (RP) in patients diagnosed with glioblastoma multiforme (GBM) at the time of initial diagnosis.

PATIENTS AND METHODS

We retrospectively identified data for patients with newly diagnosed GBM from two institutions (institution 1, n = 65; institution 2, n = 15) who underwent gross total resection followed by standard adjuvant chemoradiation therapy, with pathologically confirmed recurrence, sufficient follow-up magnetic resonance imaging (MRI) scans to reliably determine PFS, and available presurgical multiparametric MRI (MP-MRI). The advanced software suite Cancer Imaging Phenomics Toolkit (CaPTk) was leveraged to analyze standard clinical brain MP-MRI scans. A rich set of imaging features was extracted from the MP-MRI scans acquired before the initial resection and was integrated into two distinct imaging signatures for predicting mean shorter or longer PFS and near or distant RP. The predictive signatures for PFS and RP were evaluated on the basis of different classification schemes: single-institutional analysis, multi-institutional analysis with random partitioning of the data into discovery and replication cohorts, and multi-institutional assessment with data from institution 1 as the discovery cohort and data from institution 2 as the replication cohort.

RESULTS

These predictors achieved cross-validated classification performance (ie, area under the receiver operating characteristic curve) of 0.88 (single-institution analysis) and 0.82 to 0.83 (multi-institution analysis) for prediction of PFS and 0.88 (single-institution analysis) and 0.56 to 0.71 (multi-institution analysis) for prediction of RP.

CONCLUSION

Imaging signatures of presurgical MP-MRI scans reveal relatively high predictability of time and location of GBM recurrence, subject to the patients receiving standard first-line chemoradiation therapy. Through its graphical user interface, CaPTk offers easy accessibility to advanced computational algorithms for deriving imaging signatures predictive of clinical outcome and could similarly be used for a variety of radiomic and radiogenomic analyses.

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<![CDATA[Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma]]> https://www.researchpad.co/article/N4da8bc91-afa6-457f-ae03-6948dae5b797

PURPOSE

The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies.

METHODS

This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point.

RESULTS

After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%).

CONCLUSION

Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

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<![CDATA[Young Women With Breast Cancer in Mexico: Results of the Pilot Phase of the Joven & Fuerte Prospective Cohort]]> https://www.researchpad.co/article/N78f19ec6-edde-4f4e-8e12-2c2e842ae043

PURPOSE

The pilot-phase report of the Joven & Fuerte prospective cohort broadly characterizes and assesses the needs of Mexican young women with breast cancer (YWBC).

PATIENTS AND METHODS

Women age ≤ 40 years with nonmetastatic primary breast cancer were consecutively accrued from 2 hospitals. Data were collected at the first/baseline oncology visit and 2 years later using a sociodemographic survey, European Organisation for Research and Treatment of Cancer Quality-of-Life (QOL) Questionnaire Core 30 (QLQ-C30) and Breast Cancer–Specific QOL Questionnaire (QLQ-BR23), Hospital Anxiety and Depression Scale (HADS), Female Sexual Functioning Index (FSFI), Sexual Satisfaction Inventory, and patients’ medical records. Pearson χ2 and 2-sided t tests were used for statistical analysis. An unadjusted P value < .05 was considered significant.

RESULTS

Ninety patients were included, all with government health care coverage. Most had low monthly household incomes (98%) and at least a high school education (59%). There was a considerable prevalence of unpartnered patients (36%) and unmet parity (25%). Patients’ most common initial symptom was a palpable mass (84%), and they were most frequently diagnosed with stage III disease (48%), with 51% having had a physician visit ≤ 3 months since detection but 39% receiving diagnosis > 12 months later. At baseline, 66% of patients were overweight/obese, and this proportion had significantly increased by 2 years (P < .001). Compared with baseline, global QLQ-C30 had improved significantly by 2 years (P = .004), as had HADS-Anxiety (P < .001). However, both at baseline and at 2 years, nearly half of patients exhibited FSFI sexual dysfunction.

CONCLUSION

These preliminary findings demonstrate that YWBC in Mexico have particular sociodemographic and clinicopathologic characteristics, reinforcing the necessity to further describe and explore the needs of these young patients, because they may better represent the understudied and economically vulnerable population of YWBC in limited-resource settings.

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<![CDATA[Substandard Cisplatin Found While Screening the Quality of Anticancer Drugs From Addis Ababa, Ethiopia]]> https://www.researchpad.co/article/Nd0f2fafb-6b8c-4407-a233-ed20f4158945

PURPOSE

A postmarket evaluation of chemotherapy dosage forms in Ethiopia was conducted to test the accuracy of the chemoPAD, a paper analytical device for drug quality screening.

MATERIALS AND METHODS

In September of 2018 in Addis Ababa, Ethiopia, 41 anticancer drug dosage forms (representing 4 active ingredients, 5 brands, and 7 lot numbers) were collected and were rapidly screened for quality using a chemotherapy paper analytical device (chemoPAD). Confirmatory analysis via high performance liquid chromatography was conducted.

RESULTS

The chemoPAD showed that the correct active pharmaceutical ingredient was present in doxorubicin, methotrexate, and oxaliplatin injectable dosage forms. However, 11 of 20 cisplatin samples failed the screening test. Confirmatory assay by high-performance liquid chromatography showed that all 20 cisplatin samples—comprising three lot numbers of a product stated to be Cisteen—were substandard, containing on average 54% ± 6% of the stated cisplatin content. Inductively coupled plasma optical emission spectroscopy analysis of five representative samples found 57% to 71% of the platinum that should have been present. The sensitivity of the chemoPAD for detection of falsified products could not be measured (as none were present in these samples), but the selectivity was 100% (no false positives). The sensitivity for detection of substandard products was 55%, and the selectivity was 100% (no false positives).

CONCLUSION

Although instrumental analysis by pharmacopeia methods must remain the gold standard for assessing overall drug quality, these methods are time consuming and patients could be exposed to a bad-quality drug while clinical workers wait for testing to be performed. The chemoPAD technology could allow clinicians to check at the point of use for serious problems in the quality of chemotherapy drugs on a weekly or monthly schedule.

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<![CDATA[Pazopanib and Oral Cyclophosphamide in Women With Platinum-Resistant or -Refractory Epithelial Ovarian Cancer]]> https://www.researchpad.co/article/Nca057d5e-8b8b-47bb-b9db-a64f5615e96e

PURPOSE

Women with recurrent, multiply-treated epithelial ovarian cancer (EOC) have unfavorable prognosis with limited treatment options after failure of platinum-based regimens. We report here a retrospective analysis of women with recurrent, platinum-resistant EOC treated with an oral regimen of pazopanib and cyclophosphamide.

PATIENTS AND METHODS

Women with recurrent platinum-resistant or -refractory EOC were treated with pazopanib (600 mg orally daily in 2 divided doses, 400 and 200 mg) and cyclophosphamide (50 mg orally daily for 21 days every 28 days) until disease progression or unacceptable toxicity.

RESULTS

Twenty patients (17 with platinum-resistant and 3 with platinum-refractory disease) were treated between April 2014 and April 2018. Patients had a median age of 52 years (range, 40-60 years) and median of 4 previous lines of chemotherapy (range, 2-8 previous lines), including 3 patients with progressive disease on bevacizumab. Patients received a median of 6 cycles (range, 2-48 cycles) of pazopanib and cyclophosphamide, with best responses of partial response in 9 patients (45%, including 1 of 3 patients treated previously with bevacizumab), stable disease in 6 patients (30%), and disease progression in 5 patients (25%). The median progression-free survival time was 5.5 months, and median overall survival was 9.5 months. Common adverse events (grade 3 or 4) were fatigue (25%), diarrhea (15%), hand-foot syndrome (10%), mucositis (10%), transaminitis (5%), and hypertension (5%). Dose reduction as a result of toxicity was required in 14 patients (70%), and no patient stopped treatment as a result of toxicity.

CONCLUSION

Pazopanib plus oral cyclophosphamide is a well-tolerated regimen with clinically relevant benefit in patients with platinum-resistant or -refractory EOC.

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<![CDATA[Fecal Immunochemical Test as a Screening Method for Colorectal Cancer in University College Hospital Ibadan, Nigeria]]> https://www.researchpad.co/article/N75634436-3830-4fe5-8413-77a4f8e3df12

PURPOSE

Colorectal cancer (CRC) is a disease of public health importance because of the increasing incidence of the disease and presentation in advanced stage of the disease in Western Africa. CRC is amenable to screening because of the long course of premalignant lesions before final development of the disease. Despite this, the practice of CRC screening is inadequate at the sites in this study. The fecal immunochemical test (FIT) is one of the recommended noninvasive methods for CRC screening. It has a sensitivity of 96%, specificity of 90%, and an overall accuracy of 95%. We aimed to determine the practicability of FIT for CRC screening in patients aged 40 to 75 years who attended primary care clinics in the University College Hospital, Ibadan, Nigeria.

PATIENTS AND METHODS

A total of 422 patients selected by systematic random sampling were recruited and offered free FIT screening. Participants with a positive finding had additional GI examination, including a digital rectal examination, proctoscopy, and colonoscopy, if no lesion was biopsied during proctoscopy.

RESULTS

The mean (± standard deviation) age of the respondents was 62 ± 9.61 years. The prevalence of a positive FIT in the study was 10.1%. The FIT was not completed by 3.8% of patients, and the rate of completion of additional evaluation after a positive FIT reduced as the investigations became invasive, with 36.8% and 71.1% noncompletion rates for proctoscopy and colonoscopy, respectively.

CONCLUSION

A FIT-based screening for age and risk-appropriate patients is practical in this environment, where the capacity and acceptability of colonoscopy are limited.

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<![CDATA[Predictors of Survival After Head and Neck Squamous Cell Carcinoma in South America: The InterCHANGE Study]]> https://www.researchpad.co/article/Nf30422d4-0a39-4767-a46a-8f61c991b7c3

PURPOSE

Head and neck squamous cell carcinoma (HNSCC) incidence is high in South America, where recent data on survival are sparse. We investigated the main predictors of HNSCC survival in Brazil, Argentina, Uruguay, and Colombia.

METHODS

Sociodemographic and lifestyle information was obtained from standardized interviews, and clinicopathologic data were extracted from medical records and pathologic reports. The Kaplan-Meier method and Cox regression were used for statistical analyses.

RESULTS

Of 1,463 patients, 378 had a larynx cancer (LC), 78 hypopharynx cancer (HC), 599 oral cavity cancer (OC), and 408 oropharynx cancer (OPC). Most patients (55.5%) were diagnosed with stage IV disease, ranging from 47.6% for LC to 70.8% for OPC. Three-year survival rates were 56.0% for LC, 54.7% for OC, 48.0% for OPC, and 37.8% for HC. In multivariable models, patients with stage IV disease had approximately 7.6 (LC/HC), 11.7 (OC), and 3.5 (OPC) times higher mortality than patients with stage I disease. Current and former drinkers with LC or HC had approximately 2 times higher mortality than never-drinkers. In addition, older age at diagnosis was independently associated with worse survival for all sites. In a subset analysis of 198 patients with OPC with available human papillomavirus (HPV) type 16 data, those with HPV-unrelated OPC had a significantly worse 3-year survival compared with those with HPV-related OPC (44.6% v 75.6%, respectively), corresponding to a 3.4 times higher mortality.

CONCLUSION

Late stage at diagnosis was the strongest predictor of lower HNSCC survival. Early cancer detection and reduction of harmful alcohol use are fundamental to decrease the high burden of HNSCC in South America.

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<![CDATA[SlicerDMRI: Diffusion MRI and Tractography Research Software for Brain Cancer Surgery Planning and Visualization]]> https://www.researchpad.co/article/N5117ff89-1cc2-489b-9f6c-323db140a822

PURPOSE

We present SlicerDMRI, an open-source software suite that enables research using diffusion magnetic resonance imaging (dMRI), the only modality that can map the white matter connections of the living human brain. SlicerDMRI enables analysis and visualization of dMRI data and is aimed at the needs of clinical research users. SlicerDMRI is built upon and deeply integrated with 3D Slicer, a National Institutes of Health–supported open-source platform for medical image informatics, image processing, and three-dimensional visualization. Integration with 3D Slicer provides many features of interest to cancer researchers, such as real-time integration with neuronavigation equipment, intraoperative imaging modalities, and multimodal data fusion. One key application of SlicerDMRI is in neurosurgery research, where brain mapping using dMRI can provide patient-specific maps of critical brain connections as well as insight into the tissue microstructure that surrounds brain tumors.

PATIENTS AND METHODS

In this article, we focus on a demonstration of SlicerDMRI as an informatics tool to enable end-to-end dMRI analyses in two retrospective imaging data sets from patients with high-grade glioma. Analyses demonstrated here include conventional diffusion tensor analysis, advanced multifiber tractography, automated identification of critical fiber tracts, and integration of multimodal imagery with dMRI.

RESULTS

We illustrate the ability of SlicerDMRI to perform both conventional and advanced dMRI analyses as well as to enable multimodal image analysis and visualization. We provide an overview of the clinical rationale for each analysis along with pointers to the SlicerDMRI tools used in each.

CONCLUSION

SlicerDMRI provides open-source and clinician-accessible research software tools for dMRI analysis. SlicerDMRI is available for easy automated installation through the 3D Slicer Extension Manager.

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<![CDATA[CIViCpy: A Python Software Development and Analysis Toolkit for the CIViC Knowledgebase]]> https://www.researchpad.co/article/N2b318ddc-a380-44cd-9624-77c382823503

PURPOSE

Precision oncology depends on the matching of tumor variants to relevant knowledge describing the clinical significance of those variants. We recently developed the Clinical Interpretations for Variants in Cancer (CIViC; civicdb.org) crowd-sourced, expert-moderated, and open-access knowledgebase. CIViC provides a structured framework for evaluating genomic variants of various types (eg, fusions, single-nucleotide variants) for their therapeutic, prognostic, predisposing, diagnostic, or functional utility. CIViC has a documented application programming interface for accessing CIViC records: assertions, evidence, variants, and genes. Third-party tools that analyze or access the contents of this knowledgebase programmatically must leverage this application programming interface, often reimplementing redundant functionality in the pursuit of common analysis tasks that are beyond the scope of the CIViC Web application.

METHODS

To address this limitation, we developed CIViCpy (civicpy.org), a software development kit for extracting and analyzing the contents of the CIViC knowledgebase. CIViCpy enables users to query CIViC content as dynamic objects in Python. We assess the viability of CIViCpy as a tool for advancing individualized patient care by using it to systematically match CIViC evidence to observed variants in patient cancer samples.

RESULTS

We used CIViCpy to evaluate variants from 59,437 sequenced tumors of the American Association for Cancer Research Project GENIE data set. We demonstrate that CIViCpy enables annotation of > 1,200 variants per second, resulting in precise variant matches to CIViC level A (professional guideline) or B (clinical trial) evidence for 38.6% of tumors.

CONCLUSION

The clinical interpretation of genomic variants in cancers requires high-throughput tools for interoperability and analysis of variant interpretation knowledge. These needs are met by CIViCpy, a software development kit for downstream applications and rapid analysis. CIViCpy is fully documented, open-source, and available free online.

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