Otorhinolaryngological Toxicities of New Drugs in Oncology

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s12325-017-0512-0"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

Reasons for screen failures in matched cases.

<p>Reasons for screen failures in matched cases.</p

Types of phase 1 clinical trials in which cases and controls were included.

<p>Types of phase 1 clinical trials in which cases and controls were included.</p

Patient characteristics at the time of signing the informed consent form (inclusion).

<p>Patient characteristics at the time of signing the informed consent form (inclusion).</p

DNA concentrations (ng/mL) classified by tumor types.

<p>Box and whisker plots showing 25^th, 50^th and 75^th percentiles, upper and lower adjacent values (whiskers) and Tukey outliers (•). P value is for a two-sided unpaired t-test on log10 DNA concentrations using Welch's correction for unequal variances.</p

Characteristics of healthy volunteers (n = 20).

<p>Characteristics of healthy volunteers (n = 20).</p

Univariate and multivariate analysis.

<p>Univariate and multivariate analysis.</p

cpDNA concentrations for mutational detection by Sequenom OncoCarta panel (v1.0).

<p><b>2A:</b> Nonparametric ROC analyses were used to assess the limit of the Sequenom platform to detect OncoCarta panel mutations in cpDNA. Each dot on the graph corresponds to the sensitivity and specificity at one of the observed concentrations. Mutations were considered ‘available for detection’ if they were detected in the patient's FFPE tissue. Mutations were detected in FFPE samples from 37 patients. The concentration of cpDNA with the optimal ability to detect a mutation is 29.95 ng/ml (Likelihood ratio = 7.3043). The AUC calculated is 0.8075 (95% CI 0.6552–0.9598). Patients whose FFPE was unavailable or tested negative for mutations were excluded from the analysis. The specificity reference lines for quartiles of DNA concentrations are indicated in red dashed lines. <b>2B:</b> Graph showing the types of mutations and cpDNA concentrations at which they were detected in different tumors. Mutations were detected in six oncogenes. Symbols represent different tumor types.</p

Patient characteristics (n = 104).^*

*<p>One patient was subsequently found to be ineligible for this study as he had not exhausted all lines of available antitumor treatments.</p>**<p>Includes non-small cell lung cancer (NSCLC), mesothelioma, sarcoma, glioblastoma, adenocarcinoma of unknown primary (ACUP), cholangiocarcinoma, and cervical, endometrial, duodenal, esophageal, pancreatic and renal cancers.</p>***<p>cpDNA was collected from 101 (97%) patients; it was not possible to draw blood from 1 patient for technical reasons and blood was not collected from 2 patients due to logistical errors.</p

Relationship between cpDNA concentration and survival.

<p>(<b>3A</b>) Kaplan-Meier graph showing survival curves by cpDNA concentration in 101 patients with advanced solid tumors. Patients in the unfavorable category had concentrations greater than a healthy volunteer cohort maximum of 13.3 ng/ml (logrank p = 0.0383). (<b>3B</b>) Survivor function estimated from univariate Cox regression showing predicted survival curves for a range of cpDNA concentrations. A hazard ratio of 2.4 (p = 0.002) is depicted between adjacent curves.</p