Trends in treatment, incidence and survival of hypopharynx cancer: a 20-year population-based study in the Netherlands.

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1-T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991-2000 to 34% in 2001-2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (± adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 disease.

Predictive factors for pharyngocutaneous fistulization after total laryngectomy.

OBJECTIVES: Postoperative complications, especially pharyngocutaneous fistulization (PCF), are more frequent after total laryngectomy (TL) performed for salvage after (chemo)radiotherapy than after primary TL. The aim of this study was to identify the incidence of PCF, predictive factors for PCF, and the relationship of PCF to survival. METHODS: We performed a retrospective chart review of 217 consecutive patients treated with TL between 2000 and 2010. Univariate and multivariable analysis with logistic regression was used to identify factors associated with PCF. We used a Kaplan-Meier survival analysis. RESULTS: The overall incidence of PCF was 26.3% (57 of 217 cases). The incidence of PCF after primary TL was 17.1% (12 of 70), that after salvage TL was 25.5% (25 of 98), that after TLE for a second primary was 37.5% (9 of 24), and that after TL for a dysfunctional larynx was 44.0% (11 of 25). The predictive factors for PCF were hypopharynx cancer (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.74 to 7.71; P = .001), an albumin level of less than 40 g/L (OR, 2.20; 95% CI, 1.12 to 4.33; P = .022), previous chemoradiotherapy (OR, 3.38; 95% CI, 1.34 to 8.52; P = .010), more-extended pharyngeal resection (P = .001), and pharynx reconstruction (P = .002). The median duration of survival was 30 months (95% CI, 17.5 to 42.5); the 2-year overall survival rate was 54%. The median duration of survival of patients with PCF was 23 months (95% CI, 9.4 to 36.6), and that of those without PCF was 31 months (95% CI, 15.0 to 47.0; P = .421). The 2-year overall survival rate was 48% in patients with PCF and 57% in those without PCF (P = .290). CONCLUSIONS: Incidence of PCF after TL is significantly higher in patients with hypopharynx cancer, previous chemoradiotherapy, a low albumin level, more-extended pharyngeal resection, or pharynx reconstruction. The occurrence of PCF does not influence the rate of survival.

Optimizing Survival Predictions of Hypopharynx Cancer: Development of a Clinical Prediction Model.

OBJECTIVES: To develop and validate a clinical prediction model (CPM) for survival in hypopharynx cancer, thereby aiming to improve individualized estimations of survival. METHODS: Retrospective cohort study of hypopharynx cancer patients. We randomly split the cohort into a derivation and validation dataset. The model was fitted on the derivation dataset and validated on the validation dataset. We used a Cox's proportional hazard model and least absolute shrinkage and selection operator (LASSO) selection. Performance (discrimination and calibration) of the CPM was tested. RESULTS: The final model consisted of gender, subsite, TNM classification, Adult Comorbidity Evaluation-27 score (ACE27), body mass index (BMI), hemoglobin, albumin, and leukocyte count. Of these, TNM classification, ACE27, BMI, hemoglobin, and albumin had independent significant associations with survival. The C Statistic was 0.62 after validation. The model could significantly identify clinical risk groups. CONCLUSIONS: ACE27, BMI, hemoglobin, and albumin are independent predictors of overall survival. The identification of high-risk patients can be used in the counseling process and tailoring of treatment strategy or follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:2166-2172, 2020.

18F-NaF PET/CT imaging of bone formation induced by bioactive glass S53P4 after mastoid obliteration.

PURPOSE: Bioactive glass has been successfully used for surgical treatment of chronic infections in bone and bone cavities. Besides infection control, new bone formation is induced by the bioactive glass which is considered to have osteoconductive properties. Evaluation of postsurgical changes after bone graft surgery is generally performed with conventional radiographs or CT/MR imaging, but 18F-NaF PET/CT might be more suitable since it has a high and rapid bone uptake, accompanied by a fast blood clearance leading to a high bone to background ratio. CASE: Obliteration with S53P4 bioactive glass of the mastoid and middle ear was performed in a patient suffering from chronic otitis media. Control of the chronic otitis media was achieved, and follow-up imaging after 3 years with 18F-NaF PET/CT showed increased uptake in the obliterated cavity indicating new bone formation. CONCLUSION: 18F-NaF PET/CT is able to detect new bone formation after obliteration of the mastoid with S53P4 bioactive glass.

Postlaryngectomy prosthetic voice rehabilitation outcomes in a consecutive cohort of 232 patients over a 13-year period.

BACKGROUND: With the increasing necessity for total laryngectomy (TL) after prior (chemo)radiotherapy, prosthetic vocal rehabilitation outcomes might have changed. METHODS: Retrospective cohort study including all patients laryngectomized between 2000 and 2012 with a voice prosthesis (VP) in the Netherlands Cancer Institute. RESULTS: Median device lifetimes of the standard Provox2 and Vega VPs are 63 and 66 days, respectively, and for the problem-solving ActiValve Light and Strong VPs 143 and 186 days, respectively. In multivariable analysis, salvage TL and TL for a dysfunctional larynx (compared to primary TL) were associated with a shorter device lifetime. Almost half of the patients (48%) experienced tracheoesophageal puncture tract-related problems, and this concerned 12% of all VP replacements. CONCLUSIONS: Compared to historical cohorts, device lifetimes of regular Provox2 and Vega voice prostheses have decreased. Complications are not occurring more frequently but affect more patients. Nevertheless, the clinical reliability and validity of prosthetic voice rehabilitation is still sound.

Development and external validation of a risk-prediction model to predict 5-year overall survival in advanced larynx cancer.

OBJECTIVES/HYPOTHESIS: TNM-classification inadequately estimates patient-specific overall survival (OS). We aimed to improve this by developing a risk-prediction model for patients with advanced larynx cancer. STUDY DESIGN: Cohort study. METHODS: We developed a risk prediction model to estimate the 5-year OS rate based on a cohort of 3,442 patients with T3T4N0N+M0 larynx cancer. The model was internally validated using bootstrapping samples and externally validated on patient data from five external centers (n = 770). The main outcome was performance of the model as tested by discrimination, calibration, and the ability to distinguish risk groups based on tertiles from the derivation dataset. The model performance was compared to a model based on T and N classification only. RESULTS: We included age, gender, T and N classification, and subsite as prognostic variables in the standard model. After external validation, the standard model had a significantly better fit than a model based on T and N classification alone (C statistic, 0.59 vs. 0.55, P < .001). The model was able to distinguish well among three risk groups based on tertiles of the risk score. Adding treatment modality to the model did not decrease the predictive power. As a post hoc analysis, we tested the added value of comorbidity as scored by American Society of Anesthesiologists score in a subsample, which increased the C statistic to 0.68. CONCLUSIONS: A risk prediction model for patients with advanced larynx cancer, consisting of readily available clinical variables, gives more accurate estimations of the estimated 5-year survival rate when compared to a model based on T and N classification alone. LEVEL OF EVIDENCE: 2c. Laryngoscope, 128:1140-1145, 2018.

Tumor volume as a prognostic factor for local control and overall survival in advanced larynx cancer.

OBJECTIVES/HYPOTHESIS: Tumor volume has been postulated to be an important prognostic factor for oncological outcome after radiotherapy or chemoradiotherapy. This postulate was retrospectively investigated in a consecutively treated cohort of T3-T4 larynx cancer patients. STUDY DESIGN: Retrospective cohort study. METHODS: For 166 patients with T3-T4 larynx cancer (1999-2008), pretreatment computed tomography and magnetic resonance imaging scans were available for tumor volume delineation. Patients were treated with radiotherapy, chemoradiotherapy, or total laryngectomy with postoperative radiotherapy. Both a dedicated head and neck radiologist and the first author determined all tumor volumes. Statistical analysis was by Kaplan-Meier plots and Cox proportional hazard models. RESULTS: Patients with T3 larynx cancer had significantly smaller tumor volumes than patients with T4 larynx cancer (median = 8.1 cm(3) and 15.8 cm(3), respectively; P < .0001). In the group treated with total laryngectomy and postoperative radiotherapy, no association was found between tumor volume and local or locoregional control or overall survival. In the group treated with radiotherapy, a nonsignificant trend was observed between local control and tumor volume. In the chemoradiotherapy group, however, a significant impact of tumor volume was found on local control (hazard ratio = 1.07; 95% confidence interval = 1.01-1.13; P = .028). CONCLUSIONS: Tumor volume was not significantly associated with local control, locoregional control, or overall survival in the surgically treated group. In the group treated with radiotherapy, there was no statistically significant association, but a trend was observed between local control and tumor volume. Only in patients treated with concurrent chemoradiotherapy was a significant impact of tumor volume on local control found. LEVEL OF EVIDENCE: 4.

Trends in treatment and survival for advanced laryngeal cancer: A 20-year population-based study in The Netherlands.

BACKGROUND: The purpose of this study was to determine time trends for primary treatment modalities in advanced laryngeal cancer, overall survival (OS), and laryngectomy-free interval (LFI) over the last 2 decades in The Netherlands. METHODS: We conducted an analysis of T3 to T4 laryngeal cancer data from 2 combined national (population-based and pathology-based) cancer registries. RESULTS: A total of 2072 T3 cases (14.7%) and 1722 T4 cases (12.2%) were identified. Total laryngectomy as primary treatment modality decreased, whereas radiotherapy (RT) increased. For T3 disease, 5-year OS after primary total laryngectomy (+/- adjuvant RT), RT, and chemoradiotherapy (CRT) was 49%, 47%, and 45%, respectively. For T4 disease, this was 48%, 34%, and 42% (overall p < .0001), respectively. Five-year LFI for T3 disease was 81% (RT) and 77% (CRT), and for T4 disease it was 81% and 87%, respectively. CONCLUSION: From 1991 to 2010 total laryngectomy as primary treatment modality for advanced laryngeal cancer decreased and RT increased. T3 disease showed similar survival rates for all primary treatment modalities. For T4 disease, total laryngectomy (+ adjuvant RT) showed the best survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1247-E1255, 2016.

Biofilm formation on the Provox ActiValve: Composition and ingrowth analyzed by Illumina paired-end RNA sequencing, fluorescence in situ hybridization, and confocal laser scanning microscopy.

BACKGROUND: The most frequent cause of voice prosthesis failure is microbial biofilm formation on the silicone valve, leading to destruction of the material and transprosthetic leakage. The Provox ActiValve valve is made of fluoroplastic, which should be insusceptible to destruction. The purpose of this study was to determine if fluoroplastic is insusceptible to destruction by Candida species. METHODS: Thirty-three dysfunctional Provox ActiValves (collected 2011-2013). Biofilm analysis was performed with Illumina paired-end sequencing (IPES), assessment of biofilm-material interaction with fluorescence in situ hybridization (FISH), and confocal laser scanning microscopy (CLSM). RESULTS: IPES (n = 10) showed that Candida albicans and Candida tropicalis are dominant populations on fluoroplastic and silicone. Microbial diversity is significantly lower on fluoroplastic. Lactobacillus gasseri is the prevalent bacterial strain on most voice prostheses. FISH and CLSM (n = 23): in none of the cases was ingrowth of Candida species present in the fluoroplastic. CONCLUSION: Fluoroplastic material of Provox ActiValve seems insusceptible to destruction by Candida species, which could help improve durability of voice prostheses. © 2015 Wiley Periodicals, Inc. Head Neck 38: E432-E440, 2016.

T3-T4 laryngeal cancer in The Netherlands Cancer Institute; 10-year results of the consistent application of an organ-preserving/-sacrificing protocol.

BACKGROUND: Both organ-preserving concurrent (chemo)radiotherapy ((C)RT) and organ-sacrificing surgery (total laryngectomy) are used for treatment of advanced laryngeal cancer. The purpose of this study was to present the assessment of our treatment protocol for T3 (C)RT and T4 disease (total laryngectomy + postoperative RT). METHODS: We conducted a retrospective cohort study in 182 consecutive patients (1999-2008). The primary outcome was overall survival (OS) in relation to stage and treatment. RESULTS: One hundred two patients received RT (82.4% T3), 20 patients CRT (60.0% T3), and 60 patients total laryngectomy + RT (91.7% T4). Five-year OS: T3 52%, T4 48%, for RT 50%, for CRT 43%, and for total laryngectomy + RT 52%. Five-year laryngectomy-free interval was 72% after RT, and 83% after CRT. CONCLUSION: There were no differences in survival according to T classification or treatment modality. Because the majority of T3 laryngeal cancers were treated with (C)RT and the majority of T4 with total laryngectomy + RT, this gives food for thought on whether the present protocol for T3 laryngeal cancer is optimal.

Total laryngectomy for a dysfunctional larynx after (chemo)radiotherapy.

OBJECTIVE: To evaluate the functional outcomes after total laryngectomy (TLE) for a dysfunctional larynx in patients with head and neck cancer that is in complete remission after (chemo)radiotherapy. DESIGN: Retrospective cohort study. SETTING: Tertiary comprehensive cancer center. PATIENTS: The study included 25 patients from a cohort of 217 consecutive patients with TLE who were treated between January 2000 and July 2010. The inclusion criteria for this subgroup analysis were complete remission and functional problems for which TLE was considered to be the only resolution. Quality of life assessment was carried out using the European Organization for Research and Treatment of Cancer Quality of Life C30 and Head and Neck Module 35 questionnaires and an additional study-specific questionnaire covering functional aspects, such as swallowing and dyspnea, in more detail. INTERVENTION: Total laryngectomy. MAIN OUTCOME MEASURES: Morbidity, mortality, and functional outcomes. RESULTS The indication for TLE was chronic aspiration with or without recurrent pneumonia (n = 15 [60%]), debilitating dyspnea (n = 8 [32%]), and persistent profuse hemorrhage (radiation ulcer) (n = 2 [8%]). After TLE, 14 of the 25 patients (56%) had 20 major postoperative complications, including 11 pharyngocutaneous fistulas, requiring additional treatment. Tube feeding and recurrent pneumonia incidence had decreased from 80% and 28% to 29% and 0%, respectively, 2 years after surgery. Prosthetic voice rehabilitation was possible in 19 patients (76%). Two years after surgery, 10 of 14 patients (71%) still reported TLE-related pulmonary problems despite the consistent use of a heat and moisture exchanger. The 5-year overall survival rate was 35%. CONCLUSIONS: Total laryngectomy for a dysfunctional larynx tends to have a high complication rate. However, in this study, the initial functional problems (aspiration, recurrent pneumonia, and dyspnea) did not recur. Tube feeding was significantly reduced, and the quality of life of the surviving patients appeared to be reasonable.

Effectiveness of highly purified human menopausal gonadotropin in intra-uterine insemination.

OBJECTIVE: In assisted reproductive techniques it is important to find a balance between high pregnancy and acceptable multiple pregnancy rates. In IVF treatment, stimulation with highly purified human menopausal gonadotropin (hMG) results in comparable or even higher pregnancy rates at lower oocyte yields compared to recombinant FSH. Since highly purified hMG contains LH activity, a number of the advantages of highly purified hMG may be attributed to this LH activity. In IUI treatment the effectiveness of highly purified hMG has been barely investigated. The aim of this study was to examine the effectiveness of highly purified hMG in IUI patients treated with a mild stimulation protocol. STUDY DESIGN: In this retrospective study 378 patients were included, receiving 1400 IUI cycles between January 2006 and December 2007. Patients were first treated with three subsequent natural cycles without controlled ovarian hyperstimulation, followed by three subsequent cycles stimulated with highly purified hMG. Primary outcomes were ongoing pregnancy rate and multifollicular growth. Secondary outcomes were multiple pregnancy and miscarriage rates. Primary and secondary outcomes were expressed in percentages with associated 95% confidence intervals (95%CI). Differences in the outcomes between natural and stimulated cycles were calculated using χ(2) tests. Statistical differences were determined at P < 0.05. RESULTS: Ongoing pregnancy rates increased from 6% (95%CI 4.7-7.7) per natural cycle to 7.4% (95%CI 5.2-10.3) per highly purified hMG stimulated cycle (p = 0.34). The highest ongoing pregnancy rate was observed in the fifth treatment cycle (10.8% (95%CI 6.6-17)), which is significantly higher than the ongoing pregnancy rate in the unstimulated group (p = 0.03). In the highly purified hMG group three (9.7% (95%CI 3.3-24.9)) of the ongoing pregnancies were twin pregnancies, in the unstimulated group there was one (1.7% (95%CI 0.3-9.0)) twin pregnancy (p = 0.08). CONCLUSION: Our results indicate that mild stimulation with highly purified hMG in IUI treatment results in an acceptable balance between ongoing and multiple pregnancy rates. Future prospective trials should compare mild stimulation protocols to protocols directly starting with controlled ovarian hyperstimulation. Furthermore, these trials should compare other types and dosages of gonadotropins.