Outcome prediction of head and neck squamous cell carcinoma by MRI radiomic signatures.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) shows a remarkable heterogeneity between tumors, which may be captured by a variety of quantitative features extracted from diagnostic images, termed radiomics. The aim of this study was to develop and validate MRI-based radiomic prognostic models in oral and oropharyngeal cancer. MATERIALS AND METHODS: Native T1-weighted images of four independent, retrospective (2005-2013), patient cohorts (n = 102, n = 76, n = 89, and n = 56) were used to delineate primary tumors, and to extract 545 quantitative features from. Subsequently, redundancy filtering and factor analysis were performed to handle collinearity in the data. Next, radiomic prognostic models were trained and validated to predict overall survival (OS) and relapse-free survival (RFS). Radiomic features were compared to and combined with prognostic models based on standard clinical parameters. Performance was assessed by integrated area under the curve (iAUC). RESULTS: In oral cancer, the radiomic model showed an iAUC of 0.69 (OS) and 0.70 (RFS) in the validation cohort, whereas the iAUC in the oropharyngeal cancer validation cohort was 0.71 (OS) and 0.74 (RFS). By integration of radiomic and clinical variables, the most accurate models were defined (iAUC oral cavity, 0.72 (OS) and 0.74 (RFS); iAUC oropharynx, 0.81 (OS) and 0.78 (RFS)), and these combined models outperformed prognostic models based on standard clinical variables only (p < 0.001). CONCLUSIONS: MRI radiomics is feasible in HNSCC despite the known variability in MRI vendors and acquisition protocols, and radiomic features added information to prognostic models based on clinical parameters. KEY POINTS: • MRI radiomics can predict overall survival and relapse-free survival in oral and HPV-negative oropharyngeal cancer. • MRI radiomics provides additional prognostic information to known clinical variables, with the best performance of the combined models. • Variation in MRI vendors and acquisition protocols did not influence performance of radiomic prognostic models.

Improved high-dimensional prediction with Random Forests by the use of co-data.

BACKGROUND: Prediction in high dimensional settings is difficult due to the large number of variables relative to the sample size. We demonstrate how auxiliary 'co-data' can be used to improve the performance of a Random Forest in such a setting. RESULTS: Co-data are incorporated in the Random Forest by replacing the uniform sampling probabilities that are used to draw candidate variables by co-data moderated sampling probabilities. Co-data here are defined as any type information that is available on the variables of the primary data, but does not use its response labels. These moderated sampling probabilities are, inspired by empirical Bayes, learned from the data at hand. We demonstrate the co-data moderated Random Forest (CoRF) with two examples. In the first example we aim to predict the presence of a lymph node metastasis with gene expression data. We demonstrate how a set of external p-values, a gene signature, and the correlation between gene expression and DNA copy number can improve the predictive performance. In the second example we demonstrate how the prediction of cervical (pre-)cancer with methylation data can be improved by including the location of the probe relative to the known CpG islands, the number of CpG sites targeted by a probe, and a set of p-values from a related study. CONCLUSION: The proposed method is able to utilize auxiliary co-data to improve the performance of a Random Forest.

The FA/BRCA Pathway Identified as the Major Predictor of Cisplatin Response in Head and Neck Cancer by Functional Genomics.

Patients with advanced stage head and neck squamous cell carcinoma (HNSCC) are often treated with cisplatin-containing chemoradiation protocols. Although cisplatin is an effective radiation sensitizer, it causes severe toxicity and not all patients benefit from the combination treatment. HNSCCs expectedly not responding to cisplatin may better be treated with surgery and postoperative radiation or cetuximab and radiation, but biomarkers to personalize chemoradiotherapy are not available. We performed an unbiased genome-wide functional genetic screen in vitro to identify genes that influence the response to cisplatin in HNSCC cells. By siRNA-mediated knockdown, we identified the Fanconi anemia/BRCA pathway as the predominant pathway for cisplatin response in HNSCC cells. We also identified the involvement of the SHFM1 gene in the process of DNA cross-link repair. Furthermore, expression profiles based on these genes predict the prognosis of radiation- and chemoradiation-treated head and neck cancer patients. This genome-wide functional analysis designated the genes that are important in the response of HNSCC to cisplatin and may guide further biomarker validation. Cisplatin imaging as well as biomarkers that indicate the activity of the Fanconi anemia/BRCA pathway in the tumors are the prime candidates. Mol Cancer Ther; 16(3); 540-50. ©2016 AACR.

Estimation of the serial interval of pertussis in Dutch households.

Increasing incidence has led to the re-appearance of pertussis as a public health problem in developed countries. Pertussis infection is usually mild in vaccinated children and adults, but it can be fatal in infants who are too young for effective vaccination (≤3 months). Tailoring of control strategies to prevent infection of the infant hinges on the availability of estimates of key epidemiological quantities. Here we estimate the serial interval of pertussis, i.e., the time between symptoms onset in a case and its infector, using data from a household-based study carried out in the Netherlands in 2007-2009. We use statistical methodology to tie infected persons to probable infector persons, and obtain statistically supported stratifications of the data by person-type (infant, mother, father, sibling). The analyses show that the mean serial interval is 20 days (95% CI: 16-23 days) when the mother is the infector of the infant, and 28 days (95% CI: 23-33 days) when the infector is the father or a sibling. These time frames offer opportunities for early mitigation of the consequences of infection of an infant once a case has been detected in a household. If preventive measures such as social distancing or antimicrobial treatment are taken promptly they could decrease the probability of infection of the infant.

Effectiveness of personal protective equipment and oseltamivir prophylaxis during avian influenza A (H7N7) epidemic, the Netherlands, 2003.

We analyzed the effectiveness of personal protective equipment and oseltamivir use during the 2003 avian influenza A (H7N7) epidemic in the Netherlands by linking databases containing information about farm visits, human infections, and use of oseltamivir and personal protective equipment. Using a stringent case definition, based on self-reported conjunctivitis combined with a positive hemagglutination-inhibition assay, we found that prophylactic treatment with oseltamivir significantly reduced the risk for infection per farm visit from 0.145 (95% confidence interval [CI] 0.078-0.233) to 0.031 (95% CI 0.008-0.073). The protective effect was ≈79% (95% CI 40%-97%). These results are comparable with the reported effect of prophylactic treatment with oseltamivir on human seasonal influenza. No significant protective effect was found for use of respirators or safety glasses, possibly because of limitations of the data.