Associations between testosterone and patient reported sexual outcomes among male and female head and neck cancer patients before and six months after treatment: A pilot study.

OBJECTIVES: To investigate associations between testosterone and patient reported sexual problems and need for sexual care in head and neck cancer patients at time of diagnosis and 6 months after treatment. PATIENTS AND METHODS: Data and samples were used of 40 patients (20 men, 20 women) before and 6 months after treatment. Outcome measures were total testosterone level (TT) and free testosterone index (FTI), testosterone insufficiency (TI), the EORTC QLQ-HN35 Sexuality subscale, the subscales of the International Index of Erectile Function (IIEF), Female Sexual Function Index (FSFI), and the Sexuality subscale of the Short-Form Supportive Care Needs Survey (SCNS-SF34). RESULTS: In men, higher FTI before treatment was significantly associated with better IIEF Orgasm (p = 0.020) and at 6 months follow-up with IIEF Desire (p = 0.019). Before treatment, insufficient testosterone was present in 5 males (25%) and in 3 at follow-up (15%) (2 patients who had TI before treatment plus one). In women, higher TT at follow-up was significantly associated with better EORTC Sexuality (p = 0.031) and FSFI Satisfaction (p = 0.020); FTI at follow-up was associated with FSFI Satisfaction (p = 0.012). Before treatment, TI was present in 2 women (10%) and in 3 (15%) at follow-up (the same 2 patients plus one). CONCLUSION: This pilot study showed that testosterone seems to be associated with patient reported sexual outcomes among male and female head and neck cancer patients. It is estimated that 10-25% of HNC patients may have testosterone insufficiency before treatment and/or at 6 months after treatment.

The important role of cisplatin in the treatment of HPV-positive oropharyngeal cancer assessed by real-world data analysis.

OBJECTIVES: The prognostic advantage of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) resulted in the initiation of treatment de-intensification studies. Two randomized controlled trials (RCTs) reported inferior survival of HPV-positive OPSCC treated with radiotherapy plus cetuximab compared to standard of care radiotherapy plus cisplatin. In this study we investigated whether the important role of cisplatin in the treatment of HPV-positive OPSCCs would also emerge from causal inference analyses of real-world data. MATERIAL AND METHODS: A retrospective cohort of 263 advanced-stage OPSCC-patients from 5 European clinics was studied, treated with radiotherapy (RT) alone or cisplatin-based chemoradiotherapy (CRT) based on standard clinical indications. Causal inference was applied to adjust for treatment assignment, thereby simulating a randomized setting. Average treatment effect of concurrent cisplatin on overall survival (OS) probability was estimated using Bayesian Additive Regression Trees (BART) and Bayesian logistic regression. RESULTS: Significantly better survival probabilities were found for HPV-positive OPSCC treated with CRT compared to RT alone (3-year OS probability 0.961 versus 0.798, p = 0.008). CONCLUSION: This study using causal inference of retrospective patient data confirms the important role of cisplatin in the treatment of HPV-positive OPSCC. Causal inference analyses of real-world data complements the evidence from the published RCTs.

Comparison of different guidelines for oral cancer.

BACKGROUND: Guidelines should provide accessible and reliable information for decision-making. Also, they should be translatable to multiple settings, allowing their use in diverse situations. METHODS: We searched in GOOGLE, PUBMED, SCIELO, and SCOPUS for guidelines on oral squamous cell carcinoma. They were evaluated using the AGREE II protocol. RESULTS: We identified 16 guidelines that fulfilled inclusion criteria. The mean score and range for each AGREE II domain were: "scope and purpose" 74.1% (6-100.0%); "stakeholder" 78.6% (0-100.0%); "rigor of development" 71.4% (0-100.0%); "clarity of presentation" 71.4% (6-100.0%); "applicability" 50.0% (0-85.7%); "editorial independence" 57.1% (14.3-85.7%) and "overall assessment" 57.1% (14.3-100.0%). CONCLUSION: Guidelines for oral cancer present variable quality. Among those available, only four surpassed the 70% AGREE II score threshold.

Characterization of a head and neck cancer-derived cell line panel confirms the distinct TP53-proficient copy number-silent subclass.

INTRODUCTION: Head and neck squamous cell carcinomas (HNSCC) arise in the mucosal lining of the upper aerodigestive tract. Risk factors are exogenous carcinogen exposure, human papillomavirus (HPV) infection, and genetic predisposition such as Fanconi anemia (FA). Clinically, tumors are stratified based on stage, site and HPV-status. The majority of HPV-positive and -negative HNSCC is characterized by frequent copy number (CN) changes and an abrogated p53-pathway. A third genetically-defined HPV-negative subclass of HNSCC is emerging: tumors that lack gross chromosomal changes (CN-silent), are mostly TP53-proficient, and have a relatively favorable prognosis. METHODS: A representative panel of HPV-positive, HPV-negative and FA-HNSCC-derived cell lines was genetically characterized. RESULTS: Despite apparent differences in etiology, FA-HNSCC cell lines show comparable genetic alterations as sporadic non-FA-HNSCC-derived cell lines. Furthermore, we identified a near diploid CN-silent HPV-negative HNSCC line: VU-SCC-040. Molecular characterization uncovers the absence of TP53 mutations, a functional p53-pathway and a CASP8 mutation. TP53 gene knockout using CRISPR-Cas9 resulted in resistance to MDM2 inhibition. Whereas p53-status is often proposed as a predictive biomarker for treatment response, TP53-knockout did not change sensitivity to cisplatin, Chk1 and Wee1 inhibition. Additionally, 84 CN-silent tumors were identified in the HNSCC PanCancer cohort and shown to be enriched for female gender, HRAS and CASP8 mutations. CONCLUSION: FA-derived HNSCC cell lines share comparable CN-profiles and mutation patterns as sporadic HPV-negative HNSCC. In contrast, a subclass of CN-silent, HPV-negative and TP53 wild-type HNSCC separates from the majority of HNSCC tumors. We show that VU-SCC-040 is a HNSCC cell model representative of this subclass.

Surgical quality assurance in head and neck cancer trials: an EORTC Head and Neck Cancer Group position paper based on the EORTC 1420 'Best of' and 24954 'larynx preservation' study.

Quality improvement of care for patients with head and neck cancer remains a constant objective for the multidisciplinary team of physicians managing these patients. The purpose of quality assurance (QA) for head and neck surgical oncology and surgical trials however differs. While QA for the general head and neck patient aims to improve global outcome through structural changes of health-care systems, QA for surgical trials pursues the goal to help providing meaningful results from a clinical trial through the definition of structure, process and outcome measures within the trial. Establishing a QA program for surgical trials is challenging largely due to the variation in the execution of surgical techniques. Within this article, we describe the surgical QA program, which was developed for the phase III European Organisation for Research and Treatment of Cancer (EORTC) 1420 study, a trial assessing swallowing function after transoral surgery compared with radiation therapy. We propose based on our experience to further develop surgical QA for surgical clinical trials by introducing two separate components, one adaptable and one non-adaptable. The adaptable is tailored to the scientific question and specific procedure; the non-adaptable consists of minimal structural requirements of the clinical unit to participate in surgical trials at EORTC as well as guidelines and incentives for protocol adherence based on our experience in EORTC 24954. Finally, we strongly believe that surgical QA designed for clinical trials may serve as a basis for the development of QA surgical guidelines in clinical practice.

Tumors of the parapharyngeal space: the VU University Medical Center experience over a 20-year period.

BACKGROUND: Tumors of the parapharyngeal space (PPS) are rare, accounting for 0.5-1.5% of all head and neck tumors. The anatomy of the PPS is responsible for a wide variety of tumors arising from the PPS. This series of 99 PPS tumors provides an overview of the clinical course and management of PPS tumors. MATERIALS AND METHODS: This retrospective study included clinical data from patients treated for PPS tumors from 1991 to 2012 (warranting at least a 4-year follow-up) at the VU University Medical Center, Amsterdam, The Netherlands. RESULTS: Fifty percent were salivary gland tumors, 41% were neurogenic and 9% had a different origin. 18.2% of the PPS tumors were malignant. The most reported symptom at presentation was swelling of the neck and throat. In 14%, the PPS tumor was an accidental finding following imaging for other diagnostic reasons. Cytology showed an accuracy rate of 73.1% (19/26). The positive predictive value of a malignant cytology result was 86% (95% CI 42.1-99.6%). Surgery was performed in 55 patients (56%). The most frequently performed approach (56%) was the cervical-transparotid approach, followed by the cervical (25%), transmandibular (16%) and transoral (2%) approach. Nine patients died of the disease, of which seven patients had a malignant salivary gland tumor, one patient had a pleomorphic adenoma at first diagnosis which degenerated into carcinoma ex pleomorphic adenoma and one patient died of metastatic renal cell carcinoma. CONCLUSION: This large single-centre report on PPS tumors shows that careful diagnostic work up and proper surgical planning are important in this specific and rare group of head and neck tumors. Surgery was the main treatment (56%) for parapharyngeal tumors. Management of parapharyngeal neurogenic neoplasms generally consists of active surveillance due to peri-operative risk for permanent cranial nerve damage. The histopathological diagnoses were consistent with previous reports.

The adverse impact of surveillance intervals on the sensitivity of FDG-PET/CT for the detection of distant metastases in head and neck cancer patients.

The presence of distant metastases at initial evaluation influences treatment selection, since no effective systemic treatment for disseminated head and neck squamous cell carcinoma (HNSCC) is currently available. The reported sensitivity for the detection of distant metastases by contrast-enhanced (ce)CT and FDG-PET(/CT) differs substantially between studies. We hypothesized that these sensitivity values are highly dependent on the reference standard use, e.g., follow-up term. Therefore, we analyze our results of FDG-PET/CT (including chest ceCT) with long-term follow-up and compare these findings with data from the literature, with particular interest in the different reference standards. Forty-six HNSCC patients with high-risk factors underwent pretreatment screening for distant metastases by FDG-PET/CT (including chest ceCT). In 16 (35%) patients, distant metastases were detected during screening (6 patients) or during a mean follow-up of 39.4 months after screening (10 patients). The sensitivity and negative predictive value were 83.3 and 97.2% when 6 months, 60.0 and 89.9% when 12 months, and 37.5 and 72.2% when 30 months follow-up were used as reference standard, respectively. This is comparable with reported studies with similar reference standards. This critical appraisal on the reference standards used in our and reported studies shows room for improvement for the detection of distant metastases to refrain more patients from unnecessary extensive locoregional treatment for occult metastatic HNSCC.

Risk Groups for Survival in HPV-Positive and HPV-Negative OPSCC.

Over the last three decades, it has become clear that infection with high-risk human papillomavirus (HPV) is etiologically linked to the development of head and neck squamous cell carcinomas, particularly those carcinomas that arise in the oropharyngeal region.

Oral cancer trends in a single head-and-neck cancer center in the Netherlands; decline in T-stage at the time of admission

Objectives: In this study we evaluated the possible epidemiologic changes of oral cancer patients in the Netherlandsbetween the years 1980-1984 and 2000-2004. We specifically studied the differences in male-female ratio,age, TNM-stage, site distribution, and alcohol and tobacco use. Materials and Methods: Patients from the VU UniversityMedical Center with an oral squamous cell carcinoma of the oral cavity registered in 1980-1984 (n=200),group 1, were compared to patients registered in 2000-2004 (n=184), group 2. Trends in prevalence, site distribution,TNM-stage, alcohol and tobacco use, age and gender were studied. Results: The male-female ratio has decreased from 1.8 to 1.2. There were no differences in age between the two groups of patients. The site distributionwas similar in both groups. The most commonly involved sites were the tongue and the floor of mouth. In group2 more patients were diagnosed with a T1 tumour. There were no differences in tobacco use between the two differentgroups. There were much more light drinkers (0-2 drinks per day) in group 2 than in group 1, whereas therewere more heavy drinkers (>4 per day) in group 1 than in group 2 (p<0.001). This was observed in both male and female patients. Conclusion: In our study there were no significant differences between the patients registered inthe years 1980-1984 and 2000-2004 regarding the mean age of the patients, site distribution and smoking habits.The male-female ratio has decreased. In the recent group more patients were staged T1N0 and there was a strong decrease of the patients who were heavy drinkers (AU)