Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma

Background: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. Methods: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. Results: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). Conclusions: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma

Serum selenium levels and the risk of progression of laryngeal cancer.

Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival has not been evaluated.We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry.The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94).This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis

Correction: Serum selenium levels and the risk of progression of laryngeal cancer.

[This corrects the article DOI: 10.1371/journal.pone.0184873.]

Five-year overall survival among laryngeal patients by serum selenium levels.

<p>Five-year overall survival among laryngeal patients by serum selenium levels.</p

Characteristics of the study population (n = 296).

<p>Characteristics of the study population (n = 296).</p

Age- and sex-adjusted hazard ratios and 95% confidence intervals for low (quartile 1) versus high (quartile 4) serum selenium levels on survival from laryngeal cancer.

<p>Age- and sex-adjusted hazard ratios and 95% confidence intervals for low (quartile 1) versus high (quartile 4) serum selenium levels on survival from laryngeal cancer.</p

Hazard ratios and 95% confidence intervals for various factors on survival from laryngeal cancer.

<p>Hazard ratios and 95% confidence intervals for various factors on survival from laryngeal cancer.</p