The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC).
Background
Reports of head and neck ultrasound examinations are frequently written by hand as free texts. Naturally, quality and structure of free text reports is variable, depending on the examiner’s individual level of experience. Aim of the present study was to compare the quality of free text reports (FTR) and structured reports (SR) of head and neck ultrasound examinations.
Methods
Both standard FTRs and SRs of head and neck ultrasound examinations of 43 patients were acquired by nine independent examiners with comparable levels of experience. A template for structured reporting of head and neck ultrasound examinations was created using a web-based approach. FTRs and SRs were evaluated with regard to overall quality, completeness, required time to completion, and readability by four independent raters with different specializations (Paired Wilcoxon test, 95% CI) and inter-rater reliability was assessed (Fleiss’ kappa). A questionnaire was used to compare FTRs vs. SRs with respect to user satisfaction (Mann-Whitney U test, 95% CI).
Results
By comparison, completeness scores of SRs were significantly higher than FTRs’ completeness scores (94.4% vs. 45.6%,
p
< 0.001), and pathologies were described in more detail (91.1% vs. 54.5%,
p
< 0.001). Readability was significantly higher in all SRs when compared to FTRs (100% vs. 47.1%,
p
< 0.001). The mean time to complete a report, however, was significantly higher in SRs (176.5 vs. 107.3 s,
p
< 0.001). SRs achieved significantly higher user satisfaction ratings (VAS 8.87 vs. 1.41,
p
< 0.001) and a very high inter-rater reliability (Fleiss’ kappa 0.92).
Conclusions
As compared to FTRs, SRs of head and neck ultrasound examinations are more comprehensive and easier to understand. On the balance, the additional time needed for completing a SR is negligible. Also, SRs yield high inter-rater reliability and may be used for high-quality scientific data analyses.
Purpose
Obstructive sleep apnea (OSA) is associated with severe daytime sleepiness and reduced quality of life. These symptoms are also present in patients with squamous cell carcinoma of the head and neck (SCCHN) before, during and after treatment, so that comorbidity cannot be excluded. The aim was to evaluate the prevalence of OSA and its impact on the quality of life in patients with oropharyngeal, hypopharyngeal and lateral tongue SCCHN in a prospective study.
Methods
We performed cardiorespiratory home sleep apnea testing and recorded sleep-related patient-reported outcomes in 33 patients with confirmed oropharyngeal, hypopharyngeal and lateral tongue SCCHN. We correlated the sleep-related variables to oncologic variables and endpoints.
Results
Five female and 28 male patients with SCCHN (aged 46–77 years) were recruited. Thirty patients (90%) had OSA as defined by an Apnea/Hypopnea Index (AHI) > 5 /h before treatment. Evaluation after treatment, which was possible in 17 patients, showed OSA in 16 patients (94%). Radiologic primary tumor size showed significant positive correlation with AHI and apnea-index. Tumor recurrence and tumor-related mortality showed significant positive association with AHI. PSQI of these patients showed at least a moderate sleep disturbance. EORTC QLQ c30 questionnaire showed reduced values for all tested qualities, in particular for fatigue, insomnia, pain and financial distress.
Conclusion
Obstructive sleep apnea is a significant comorbidity in patients with SCCHN. Pre-interventional AHI may be correlated with the oncologic outcome. Further research is needed to further describe the course of OSA and its treatment before, during and after therapy.
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