Physicians' clinical prediction of survival in head and neck cancer patients in the palliative phase.

BACKGROUND: The prognosis of patients with incurable head and neck cancer (HNC) is a relevant topic. The mean survival of these patients is 5 months but may vary from weeks to more than 3 years. Discussing the prognosis early in the disease trajectory enables patients to make well-considered end-of-life choices, and contributes to a better quality of life and death. However, physicians often are reluctant to discuss prognosis, partly because of the concern to be inaccurate. This study investigated the accuracy of physicians' clinical prediction of survival of palliative HNC patients. METHODS: This study was part of a prospective cohort study in a tertiary cancer center. Patients with incurable HNC diagnosed between 2008 and 2011 (n = 191), and their treating physician were included. Analyses were conducted between July 2018 and February 2019. Patients' survival was clinically predicted by their physician ≤3 weeks after disclosure of the palliative diagnosis. The clinical prediction of survival in weeks (CPS) was based on physicians' clinical assessment of the patient during the outpatient visits. More than 25% difference between the actual survival (AS) and the CPS was regarded as a prediction error. In addition, when the difference between the AS and CPS was 2 weeks or less, this was always considered as correct. RESULTS: In 59% (n = 112) of cases survival was overestimated. These patients lived shorter than predicted by their physician (median AS 6 weeks, median CPS 20 weeks). In 18% (n = 35) of the cases survival was correctly predicted. The remaining 23% was underestimated (median AS 35 weeks, median CPS 20 weeks). Besides the differences in AS and CPS, no other significant differences were found between the three groups. There was worse accuracy when predicting survival closer to death: out of the 66 patients who survived 6 weeks or shorter, survival was correctly predicted in only eight (12%). CONCLUSION: Physicians tend to overestimate the survival of palliative HNC patients. This optimism can result in suboptimal use of palliative and end-of-life care. The future development of a prognostic model that provides more accurate estimates, could help physicians with personalized prognostic counseling.

Elective neck treatment during salvage (pharyngo) laryngectomy.

PURPOSE: This study aimed at determining the importance of an elective neck dissection (END) in case of a cN0 laryngeal or hypopharyngeal carcinoma after (chemo) radiation. METHODS: Retrospective review was made of patients treated in a single tertiary center between 2002 and 2014. Influence of an END in case of a cN0 salvage laryngectomy on complications, recurrence-free survival and disease-specific survival was assessed. INCLUSION CRITERIA: squamous cell carcinoma and cN0 neck. EXCLUSION CRITERIA: second primary tumor in the head and neck, a total laryngectomy because of a dysfunctional larynx, or a previously performed neck dissection. RESULTS: Of the 86 included patients, 27 (31%) underwent an END, of which 1 had occult metastasis (4%). Of the remaining 59 patients (69%) without an END, 3 developed a regional recurrence (5%). The overall survival was significantly higher for patients who had an END (p = 0.037). The incidence of complications was not significantly different between the two groups. CONCLUSIONS: In light of the limited complications of an END and the poor prognosis of regional recurrence after previous (chemo)radiotherapy and a (pharyngo)laryngectomy, we advise consideration of an END at the time of a salvage laryngectomy.

Contributing Determinants to Hearing Loss in Elderly Men and Women: Results from the Population-Based Rotterdam Study.

To contribute to a better understanding of the etiology in age-related hearing loss, we carried out a cross-sectional study of 3,315 participants (aged 52-99 years) in the Rotterdam Study, to analyze both low- and high-frequency hearing loss in men and women. Hearing thresholds with pure-tone audiometry were obtained, and other detailed information on a large number of possible determinants was collected. Hearing loss was associated with age, education, systolic blood pressure, diabetes mellitus, body mass index, smoking and alcohol consumption (inverse correlation). Remarkably, different associations were found for low- and high-frequency loss, as well as between men and women, suggesting that different mechanisms are involved in the etiology of age-related hearing loss.

Noncompliance to guidelines in head and neck cancer treatment; associated factors for both patient and physician.

BACKGROUND: Decisions on head and neck squamous cell carcinoma (HNSCC) treatment are widely recognized as being difficult, due to high morbidity, often involving vital functions. Some patients may therefore decline standard, curative treatment. In addition doctors may propose alternative, nonstandard treatments. Little attention is devoted, both in literature and in daily practice, to understanding why and when HNSCC patients or their physicians decline standard, curative treatment modalities. Our objective is to determine factors associated with noncompliance in head and neck cancer treatment for both patients and physicians and to assess the influence of patient compliance on prognosis. METHODS: We did a retrospective study based on the medical records of 829 patients with primary HNSCC, who were eligible for curative treatment and referred to our hospital between 2010 and 2012. We analyzed treatment choice and reasons for nonstandard treatment decisions, survival, age, gender, social network, tumor site, cTNM classification, and comorbidity (ACE27). Multivariate analysis using logistic regression methods was performed to determine predictive factors associated with non-standard treatment following physician or patient decision. To gain insight in survival of the different groups of patients, we applied a Cox regression analysis. After checking the proportional hazards assumption for each variable, we adjusted the survival analysis for gender, age, tumor site, tumor stage, comorbidity and a history of having a prior tumor. RESULTS: 17 % of all patients with a primary HNSCC did not receive standard curative treatment, either due to nonstandard treatment advice (10 %) or due to the patient choosing an alternative (7 %). A further 3 % of all patients refused any type of therapy, even though they were considered eligible for curative treatment. Elderliness, single marital status, female gender, high tumor stage and severe comorbidity are predictive factors. Patients declining standard treatment have a lower overall 3-year survival (34 % vs. 70 %). CONCLUSIONS: Predictive factors for nonstandard treatment decisions in head and neck cancer treatment differed between the treating physician and the patient. Patients who received nonstandard treatment had a lower overall 3-year survival. These findings should be taken into account when counselling patients in whom nonstandard treatment is considered.

The Potential of MET Immunoreactivity for Prediction of Lymph Node Metastasis in Early Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: MET positivity is independently associated with survival in oral squamous cell carcinoma (OSCC). Since MET is a known orchestrator of invasive tumor growth, we investigated its association with LNM in early oral tongue squamous cell carcinoma (OTSCC). As it is recommended by the NCCN to use tumor depth of invasion (DOI) in making decisions on elective neck dissection (END), the results obtained for MET positivity were aligned with those for DOI > 4 mm. The cutoff value used in our institution. METHODS: Tumor samples from patients who underwent primary tumor resection and neck dissection between 1995 and 2013, were collected from the archives of the Leiden and Erasmus University Medical Center. Immunohistochemistry with D1C2 was performed to identify MET negative (< 10% uniform positivity) and MET positive (≥ 10% uniform positivity) cancers. ROC curve analysis and the Chi-squared test were used to investigate the association of MET positivity with LNM (pN+ and occult). Binary logistic regression was used to investigate the association of MET positivity with LNM. RESULTS: Forty-five (44.1%) of the 102 cancers were MET positive. Ninety were cN0 of which 20 were pN+ (occult metastasis). The remaining 12 cancers were cN+, of which 10 were proven pN+ and 2 were pN0. MET positivity was associated with LNM with a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 82.5% for pN+. For the occult group, the PPV was 36.8% and the NPV was 88.5%. Regression analysis showed that MET positivity is associated with pN+ and occult LNM (p-value < 0.05). CONCLUSION: MET positivity is significantly associated with LNM in early OTSCC, outperforming DOI. The added value of MET positivity could be in the preoperative setting when END is being considered during the initial surgery. For cases with DOI ≤ 4 mm, MET positivity could aid in the clinical decision whether regular follow-up, watchful waiting, or END is more appropriate. Realizing that these preliminary results need to be independently validated in a larger patient cohort, we believe that MET positivity could be of added value in the decision making on END in early OTSCC.

Phonological development in very-low-birthweight children: an exploratory study.

AIM: Very-low-birthweight (VLBW; birthweight<1500 g and/or gestational age <32 wks) children are at risk for speech problems. However, there are few studies on speech development in VLBW children at an early age. The aim of this study was to investigate phonological development in 2-year-old VLBW children. METHOD: Twenty VLBW children without major neurosensory impairment (7 males, 13 females; mean birthweight 971 g, SD 315; mean gestational age 28 wks, SD 1.81) and 20 term children (7 males, 13 females; mean birthweight 3503 g, SD 416; mean gestational age 40 wks, SD 1.26) were compared on measures of phonological development derived from 20-minute spontaneous speech samples of standardized mother-child play interaction as well as on standardized tests of cognitive and psychomotor development, language, and behaviour. RESULTS: VLBW children had significantly fewer acquired consonants (median 9, p=0.02) and a significantly lower phonological mean length of utterance (pMLU; median 4.1, p<0.01) than term children (median acquired consonants 10, median pMLU 5.0). INTERPRETATION: This study provides evidence for poor phonological development in even healthy VLBW children, compared with term-matched children, independent of their cognitive, psychomotor, and language development, and their behavioural functioning.

A novel immunohistochemical scoring system reveals associations of C-terminal MET, ectodomain shedding, and loss of E-cadherin with poor prognosis in oral squamous cell carcinoma.

Using tissue microarrays, it was shown that membranous C-terminal MET immunoreactivity and ectodomain (ECD) shedding are associated with poor prognosis in oral cancer. Seen the potential diagnostic value, extrapolation of these results to whole-tissue sections was investigated. Because MET orchestrates epithelial-to-mesenchymal transition (EMT), the results were benchmarked to loss of E-cadherin, a readout for EMT known to be associated with poor prognosis. C-terminal MET, N-terminal MET, and E-cadherin immunoreactivities were examined on formalin-fixed paraffin-embedded parallel sections of 203 oral cancers using antibody clones D1C2, A2H2-3, and NCH-38. Interantibody and intra-antibody relations were examined using a novel scoring system, nonparametric distribution, and median tests. Survival analyses were used to examine the prognostic value of the observed immunoreactivities. Assessment of the three clones revealed MET protein status (no, decoy, transmembranous C-terminal positive), ECD shedding, and EMT. For C-terminal MET-positive cancers, D1C2 immunoreactivity is independently associated with poor overall survival (hazard ratio [HR] = 2.40; 95% confidence interval [CI] = 1.25 to 4.61; and P = 0.008) and disease-free survival (HR = 1.83; 95% CI = 1.07-3.14; P = 0.027). For both survival measures, this is also the case for ECD shedding (43.4%, with HR = 2.30; 95% CI = 1.38 to 3.83; and P = 0.001 versus HR = 1.87; 95% CI = 1.19-2.92; P = 0.006) and loss of E-cadherin (55.3%, with HR = 2.21; 95% CI = 1.30 to 3.77; and P = 0.004 versus HR = 1.90; 95% CI = 1.20-3.01; P = 0.007). The developed scoring system accounts for MET protein status, ECD shedding, and EMT and is prognostically informative. These findings may contribute to development of companion diagnostics for MET-based targeted therapy.

The impact of ambient NO on online measurements of exhaled and nasal NO: the PIAMA study.

The guidelines of the American Thoracic Society (ATS) and the European Respiratory Society (ERS) for standardized measurements of exhaled nitric oxide (NO) state that for online measurements the inhaled air should be free of NO. As it is not always possible to create an NO-free environment, inhalation through an NO-scrubber is used. To describe the relationship between ambient NO and measurements of fractional exhaled NO (FENO) and nasal NO (nNO) investigated according to the ATS-ERS guidelines in a large population of children. The present work makes use of data collected during the 8-yr follow-up of the Dutch PIAMA birth cohort study. FENO and nNO were measured in three hospitals in a total of 1005 children with a NIOX chemiluminescence analyser. In two hospitals, almost half of the measured ambient NO levels exceeded 5 p.p.b. Maximum levels were >100 p.p.b. in all hospitals. Despite its large variation, ambient NO did not have an effect on FENO, but it did have a significant impact on nNO in two of the three centres. The currently recommended technique including inhalation through an NO scrubber effectively deals with variable levels of ambient NO on FENO. In contrast, ambient NO has an effect on measurements of nNO.

The influence of parental educational level on the development of atopic sensitization, wheezing and eczema during the first year of life.

Several studies have investigated the association between socioeconomic status and the occurrence of allergies. Nevertheless, the results remain contradictory. The aim of this study was to evaluate the associations between parental education and the occurrence of atopic sensitization, recurrent wheezing and eczema during the first year of life, differentiating between atopic and non-atopic disorders based on specific serum IgE. We conducted an aetiological study in 690 children, based on a prospective birth cohort project in which environmental and health information was gathered using questionnaires. At the age of 1 yr a blood sample was taken for quantification of specific IgE. Adjusted odds ratios and 95% confidence intervals were computed as measures of association between the outcomes and parental education. Parental educational level was positively associated with the occurrence of atopic sensitization (OR: 2.1; 95% CI: 1.0-4.4) and eczema (OR: 1.9; 95% CI: 1.1-3.4), but negatively with the occurrence of recurrent wheezing (OR: 0.4; 95% CI: 0.2-0.8) in the first year of life. Atopic recurrent wheezing was positively associated with the education of the parents, whereas non-atopic recurrent wheezing was negatively associated. When maternal and paternal education were considered separately, only maternal education had a significant influence. Our results suggest that aspects associated with a high maternal educational level may play an important role in the development of atopic disorders.

Survival of patients with head and neck cancer with metachronous multiple primary tumors is surprisingly favorable.

BACKGROUND: The objectives of this study are to determine the incidence and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) with multiple primary tumors (MPT) in the HN-region, lung, or esophagus. METHODS: Patient and tumor specific data of 1372 patients with HNSCC were collected from both the national cancer registry and patient records to ensure high-quality double-checked data. RESULTS: The total incidence of MPTs in the HN-region, lung, and esophagus in patients with HNSCC was 11% (149/1372). Patients with lung MPTs and esophageal MPTs had a significant worse 5-year survival than patients with HN-MPTs (29%, 14%, and 67%, respectively, P < 0.001). The 5-year survival rate for synchronous HN MPTs was only 25%, whereas it was surprisingly high for patients with metachronous HN MPT (85%, P < 0.001). CONCLUSIONS: One of 10 patients with HNSCC develop MPTs in the HN-region, lung, or esophagus. The 5-year survival of patients with metachronous HN MPTs was surprisingly favorable.

A visual analog scale can assess the effect of surgical treatment in children with chronic otitis media with effusion.

BACKGROUND: The OM-6 survey is a validated and multinationally accepted instrument to measure the treatment effect of otitis media in children. Routine use of the OM-6 in a busy general practice is not always possible and can lead to incomplete returned surveys. A simplified method is favoured when the aim is a continuous process of complete treatment-outcome-data collection. This study tests if a VAS can quantify how much a child suffers from chronic otitis media and how much this changes due to surgical treatment. The change in overall OM-6 scores due to surgical treatment, functions as the gold reference standard. Furthermore, this study tests if the VAS is faster to use than the OM-6 and if it leads to an improvement in complete data collection. METHODS: Prospective cohort follow-up study of 175 consecutive children with chronic otitis media in a paediatric otolaryngology practice in a metropolitan area. Data collected included patient's age, gender, clinical presentation, type of surgical procedure performed, overall OM-6 score and VAS score (at initial presentation and at follow-up), time needed to complete an OM-6 survey and VAS separately and number of incorrect OM-6 surveys and VAS questions returned. RESULTS: The VAS scores and overall OM-6 scores show a good, positive correlation at baseline (Spearman's rho=0.71). This correlation improves at follow-up, one and 6 months after intervention (rho=0.73 and rho=0.80, respectively). The change in VAS scores and overall OM-6 scores, interpreted as change due to surgical intervention, show a good positive correlation at follow-up (rho=0.70 and rho=0.77, respectively). The VAS is almost three times faster than the OM-6 (28s versus 81s). More than 13% of OM-6 surveys were returned incomplete. All VAS questions were returned correct. CONCLUSIONS: The VAS can be used as a simplified method for routine surgical treatment effect analysis in children with chronic otitis media.

The relationship between perceptual evaluation and objective multiparametric evaluation of dysphonia severity.

SUMMARY: The purpose of this study was to investigate the usefulness of the Dysphonia Severity Index (DSI) as an objective multiparametric measurement in assessing dysphonia. The DSI was compared with the score on Grade of the GRBAS scale. Investigated was also whether the DSI is related to severity of dysphonia, which was represented by different diagnosis groups. Furthermore, it was investigated whether the DSI can differentiate between a group of patients and a control group. A total of 294 patients with different voice pathologies were included. A control group consisted of 118 volunteers without any voice complaints. The voices of all participants were perceptually evaluated on Grade, and the DSI was measured. The groups of patients with voice complaints have a lower DSI and higher scores on Grade than the control group. The DSI was significantly lower when the score on Grade was higher. The DSI discriminates between patients with nonorganic voice disorders, vocal fold mass lesions, and vocal fold paresis/paralysis. To determine whether the DSI discriminates between patients and controls, the sensitivity and specificity for different DSI cutoff points were calculated. With a DSI cutoff of 3.0, maximum sensitivity (0.72) and specificity (0.75) were found. We conclude that the DSI is a useful instrument to objectively measure the severity of dysphonia.

The interobserver and test-retest variability of the dysphonia severity index.

OBJECTIVE: The purpose of this study was to investigate the interobserver variability and the test-retest variability of the Dysphonia Severity Index (DSI), a multiparametric instrument to assess voice quality. METHODS: The DSI was measured in 30 nonsmoking volunteers without voice complaints or voice disorders by two speech pathologists. The subjects were measured on 3 different days, with an interval of 1 week. RESULTS: The difference in DSI between two observers (interobserver difference) was not significant. The intraclass correlation coefficient for the DSI was 0.79. The standard deviation of the difference between two duplicate measurements by different observers was 1.27. CONCLUSION: Differences in measurements between different observers were not significant. The intraclass correlation coefficient of the DSI was 0.79, which is to be considered good. Differences in DSI within one patient need to be larger than 2.49 to be significant.

The Erasmus atelectasis classification: proposal of a new classification for atelectasis of the middle ear in children.

OBJECTIVES: Atelectasis presents a challenging, often progressive, problem in children. Because of the lack of a clinically practical classification, we introduce a new classification, which in our opinion is more useful in the pediatric age group. This alternative classification enables a more clinically relevant correlation between stage of disease and clinical sequelae and technical difficulty at surgery. STUDY DESIGN: Observational study of patients seen and operated at the Sophia Children's Hospital in Rotterdam, The Netherlands between 1989 and 2005. METHODS: Based on clinical appearance, each ear was placed into one of the five groups of the proposed classification and into one of the four stages of Sadé's classification. Preoperative air and bone conduction thresholds and air-bone gaps (ABG) were calculated using the four-tone pure-tone (500, 1,000, 2,000, and 4,000 Hz) averages for bone and air conduction. RESULTS: : Of the 248 ears in the study group, 72 were in stage I, with an ABG of 18.2 +/- 12.3 dB. Twenty-two were in stage II, with an ABG of 12.9 +/- 9.5 dB. In stage III, there were 32 ears, with an ABG of 11.6 +/- 10.0 dB. Thirty-one ears were in stage IV, with an ABG of 16.1 +/- 11.5 dB. Eighty-five ears were in stage V, with an ABG of 26.1 +/- 13.3 dB. When grouped according to Sadé's classification, 92 ears could not be classified. CONCLUSIONS: We found the currently proposed classification more useful in that it follows the natural progression of the disease and is more practical in determining operative procedures at each stage.

Prevalence of age-related hearing loss, including sex differences, in older adults in a large cohort study.

OBJECTIVES/HYPOTHESIS: To obtain actual status of age-related hearing loss in a general unscreened population of older Dutch adults and to investigate whether the prevalence or degree has changed over time. STUDY DESIGN: To investigate the prevalence and degree of hearing loss, we conducted a large prospective cohort study of older adults between February 2011 and July 2015. METHODS: Pure-tone air- and bone-conduction thresholds were measured for 4,743 participants. Results were compared to previous cohort studies. RESULTS: As expected, hearing loss increased with age. We found a correlation of R2 = 0.317 for men and R2 = 0.354 for women (right ears). A prevalence of hearing loss greater than 35 dB hearing level the average of 0.5/1/2/4 kHz in the better ear, was found in 33% of the male and almost 29% of the female participants aged 65 years and older. Compared with previous studies, men had less hearing loss at the frequencies of 2 kHz and above. Hearing thresholds in women were significantly higher at 4 and 8 kHz. The difference in hearing loss between men and women is significantly less than in earlier studies. CONCLUSIONS: Our study confirms that hearing loss is highly prevalent in the general unscreened population of older adults. However, the difference in hearing between sexes was considerably less than previously reported. This is probably due to changing lifestyle and environmental circumstances, LEVEL OF EVIDENCE: 2b Laryngoscope, 127:725-730, 2017.

Hearing Loss Progresses Faster in Patients With Growing Intracanalicular Vestibular Schwannomas.

OBJECTIVE: To determine whether certain patient and tumor characteristics influence the progression of hearing loss in vestibular schwannoma (VS) patients. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center, Erasmus Medical Centre in Rotterdam, The Netherlands. PATIENTS: One hundred fifty-five patients referred from 2000 through 2010 with intracanalicular, small or medium sized, unilateral VS, managed without active treatment. INTERVENTION: Wait and scan protocol with sequential magnetic resonance imaging and audiometry. MAIN OUTCOME MEASURES: Hearing loss as pure-tone average (PTA) in dB and progression of hearing loss expressed as the annual change in PTA or annual hearing decreasing rate (AHDR) in dB/yr. RESULTS: At presentation the mean hearing loss was 47 dB and the mean asymmetry between the tumor ear and the contralateral ear was 28 dB. The mean AHDR in wait and scan patients was 3.5 dB/yr (sd 4.6). Tumor growth was associated with the AHDR in patients with intracanalicular tumors. In patients with tumors extending into the cerebellopontine angle, we found a negative association between the AHDR and the PTA of the contralateral side. The explained variance, however, was low. No association was found between the AHDR and patient age, PTA in the tumor ear, tumor size, speech discrimination score at diagnosis or hypo-intensity of the cochlear fluids on magnetic resonance imaging. CONCLUSION: There is no association between hearing deterioration and clinical characteristics in our 155 VS patients. Hearing loss is associated with tumor growth in intracanalicular tumors only.

Surgery for recurrent laryngeal carcinoma after radiotherapy: partial laryngectomy or total laryngectomy for a better quality of life?

OBJECTIVE: To investigate the quality of life after partial laryngectomy versus total laryngectomy for recurrent laryngeal carcinomas after radiotherapy. STUDY DESIGN AND SETTING: A retrospective study performed at least one year after treatment. This study was performed in a university hospital. RESULTS: Twenty-three patients (N = 12 partial laryngectomy, N = 11 total laryngectomy) with recurrent laryngeal cancer after radiotherapy were included in the study. Three different questionnaires, 1) EORTC Quality of Life Questionnaire (QLQ)-C30 Dutch version 3.0, 2) EORTC-H & N 35, and 3) the Voice Handicap Index, were sent to all patients. The only major difference in quality of life of patients after partial laryngectomy versus total laryngectomy was found to be smell and taste related. No other differences were found. CONCLUSION: We did not find much difference in quality of life after treatment with a partial laryngectomy or a total laryngectomy in patients with recurrent laryngeal cancer after radiotherapy.

Prognosis: a variable parameter: dynamic prognostic modeling in head and neck squamous cell carcinoma.

BACKGROUND: In general, the estimated prognosis of patients with cancer is based on patient characteristics known at the time of diagnosis and presented as if a lifetime verdict. However, the prognosis of patients with cancer who survive the first critical years changes, along with the prognosis for those with local or regional recurrences or distant metastases. METHODS: This study concerns 2927 patients with a primary head and neck squamous cell carcinoma (HNSCC). We developed prognostic models after initial treatment and at different time points during follow-up. RESULTS: The developed models show the effects of survival time, recurrences, and distant metastasis during follow-up. The C-statistics ranged from 0.76 to 0.69. CONCLUSION: Prognosis is dynamic: the passage of time and the occurrence of life events change the predicted probabilities of survival. The models enhance our insight in the effect of recurrences and metastasis during follow-up and could be used for better patient counseling.