Biomarker Inference and the Timing of Next-Generation Sequencing in a Multi-Institutional, Cross-Cancer Clinicogenomic Data Set.

PURPOSE: Observational clinicogenomic data sets, consisting of tumor next-generation sequencing (NGS) data linked to clinical records, are commonly used for cancer research. However, in real-world practice, oncologists frequently request NGS in search of treatment options for progressive cancer. The extent and impact of this dynamic on analysis of clinicogenomic research data are not well understood. METHODS: We analyzed clinicogenomic data for patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancers in the American Association for Cancer Research Biopharmaceutical Consortium cohort. Associations between baseline and time-varying clinical characteristics and time from diagnosis to NGS were measured. To explore the impact of informative cohort entry on biomarker inference, statistical interactions between selected biomarkers and time to NGS with respect to overall survival were calculated. RESULTS: Among 7,182 patients, time from diagnosis to NGS varied significantly by clinical factors, including cancer type, calendar year of sequencing, institution, and age and stage at diagnosis. NGS rates also varied significantly by dynamic clinical status variables; in an adjusted model, compared with patients with stable disease at any given time after diagnosis, patients with progressive disease by imaging or oncologist assessment had higher NGS rates (hazard ratio for NGS, 1.61 [95% CI, 1.45 to 1.78] and 2.32 [95% CI, 2.01 to 2.67], respectively). Statistical interactions between selected biomarkers and time to NGS with respect to survival, potentially indicating biased biomarker inference results, were explored. CONCLUSION: To evaluate the appropriateness of a data set for a particular research question, it is crucial to measure associations between dynamic cancer status and the timing of NGS, as well as to evaluate interactions involving biomarkers of interest and NGS timing with respect to survival outcomes.

Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.

Smartphone-Enhanced Training, QA, Monitoring, and Evaluation of a Platform for Secondary Prevention of Cervical Cancer: Opportunities and Challenges to Implementation in Tanzania.

PURPOSE: Until human papillomavirus (HPV)-based cervical screening is more affordable and widely available, visual inspection with acetic acid (VIA) is recommended by the WHO for screening in lower-resource settings. Visual inspection will still be required to assess the cervix for women whose screening is positive for high-risk HPV. However, the quality of VIA can vary widely, and it is difficult to maintain a well-trained cadre of providers. We developed a smartphone-enhanced VIA platform (SEVIA) for real-time secure sharing of cervical images for remote supportive supervision, data monitoring, and evaluation. METHODS: We assessed programmatic outcomes so that findings could be translated into routine care in the Tanzania National Cervical Cancer Prevention Program. We compared VIA positivity rates (for HIV-positive and HIV-negative women) before and after implementation. We collected demographic, diagnostic, treatment, and loss-to-follow-up data. RESULTS: From July 2016 to June 2017, 10,545 women were screened using SEVIA at 24 health facilities across 5 regions of Tanzania. In the first 6 months of implementation, screening quality increased significantly from the baseline rate in the prior year, with a well-trained cadre of more than 50 health providers who "graduated" from the supportive-supervision training model. However, losses to follow-up for women referred for further evaluation or to a higher level of care were considerable. CONCLUSION: The SEVIA platform is a feasible, quality improvement, mobile health intervention that can be integrated into a national cervical screening program. Our model demonstrates potential for scalability. As HPV screening becomes more affordable, the platform can be used for visual assessment of the cervix to determine amenability for same-day ablative therapy and/or as a secondary triage step, if needed.

Community health workers and early detection of breast cancer in low-income and middle-income countries: a systematic scoping review of the literature.

BACKGROUND: Breast cancer is the leading cause of female mortality in low-income and middle-income countries (LMICs). Early detection of breast cancer, either through screening or early diagnosis initiatives, led by community health workers (CHWs) has been proposed as a potential way to address the unjustly high mortality rates. We therefore document: (1) where and how CHWs are currently deployed in this role; (2) how CHWs are trained, including the content, duration and outcomes of training; and (3) the evidence on costs associated with deploying CHWs in breast cancer early detection. METHODS: We conducted a systematic scoping review and searched eight major databases, as well as the grey literature. We included original studies focusing on the role of CHWs to assist in breast cancer early detection in a country defined as a LMIC according to the World Bank. FINDINGS: 16 eligible studies were identified. Several roles were identified for CHWs including awareness raising and community education (n=13); history taking (n=7); performing clinical breast examination (n=9); making onward referrals (n=7); and assisting in patient navigation and follow-up (n=4). Details surrounding training programmes were poorly reported and no studies provided a formal cost analysis. CONCLUSIONS: Despite the relative paucity of studies addressing the role of CHWs in breast cancer early detection, as well as the heterogeneity of existing studies, evidence suggests that CHWs can play a number of important roles in breast cancer early detection initiatives in LMICs. However, if they are to realise their full potential, they must be appropriately supported within the wider health system.