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Background and Purpose: The purpose of this large multicentre prospective cohort study was to identify which dose volume histogram parameters and pre-treatment factors are most important to predict physician-rated and patient-rated radiation-induced swallowing dysfunction (RISD) in order to develop predictive models for RISD after curative (chemo) radiotherapy ((CH) RT)., Material and Methods: The study population consisted of 354 consecutive head and neck cancer patients treated with (CH) RT. The primary endpoint was grade 2 or more swallowing dysfunction according to the RTOG/EORTC late radiation morbidity scoring criteria at 6 months after (CH) RT. The secondary endpoints were patient-rated swallowing complaints as assessed with the EORTC QLQ-H&N35 questionnaire. To select the most predictive variables a multivariate logistic regression analysis with bootstrapping was used., Results: At 6 months after (CH) RT the bootstrapping procedure revealed that a model based on the mean dose to the superior pharyngeal constrictor muscle (PCM) and mean dose to the supraglottic larynx was most predictive. For the secondary endpoints different predictive models were found: for problems with swallowing liquids the most predictive factors were the mean dose to the supraglottic larynx and radiation technique (3D-CRT versus IMRT). For problems with swallowing soft food the mean dose to the middle PCM, age (18-65 versus >65 years), tumour site (naso/oropharynx versus other sites) and radiation technique (3D-CRT versus IMRT) were the most predictive factors. For problems with swallowing solid food the most predictive factors were the mean dose to the superior PCM, the mean dose to the supraglottic larynx and age (18-65 versus >65 years). And for choking when swallowing the V60 of the oesophageal inlet muscle and the mean dose to the supraglottic larynx were the most predictive factors., Conclusions: Physician-rated and patient-rated RISD in head and neck cancer patients treated with (CH) RT cannot be predicted with univariate relationships between the dose distribution in a single organ at risk and an endpoint. Separate predictive models are needed for different endpoints and factors other than dose volume histogram parameters are important as well., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

A survey to evaluate the management of thyroid function testing was performed in the major institutions treating head and neck cancer in The Netherlands. In July 2006, a questionnaire considering laboratory tests, selection of patients, scheme and treatment of hypothyroidism was sent to physicians who treat head and neck cancer patients in 19 hospitals in the Netherlands including all eight head and neck centers of the Dutch Head and Neck Oncology Cooperative Group (Nederlandse Werkgroep Hoofd-Halstumoren; NWHHT). Thirty-two of thirty-nine (84%) questionnaires were returned. Twenty-four (75%) physicians tested only when symptoms were mentioned, 42% tested all patients treated with different treatment modalities (radiotherapy, chemotherapy or surgery). Most physicians screened annually (32%) or every 6 months (24%) on hypothyroidism. All physicians screened for TSH, 18 physicians (69%) tested free T4 as well. Fifty-eight percent of physicians referred their patients to another department for supplementation therapy when thyroid function is tested abnormal. Twenty physicians (65%) would appreciate guidelines on screening although 75% are aware of the guidelines of the Dutch Head and Neck Oncology Cooperative Group. There is a need for more clear and detailed guidelines in which recommendations on patients' selection, intervals and laboratory measurements of screening for hypothyroidism and its treatment are provided.

Background and Purpose: To investigate the association between radiation technique with patient-rated moderate and severe xerostomia and sticky saliva., Materials and Methods: One hundred and fifty patients treated with bilateral or unilateral irradiation for head and neck cancer were included. The salivary glands and the oral cavity were delineated on plannings-CT scans. Xerostomia and sticky saliva were assessed using the EORTC QLQ-H&N35 questionnaire at baseline and 6 and 12 months., Results: At 6 months a significant association between radiation technique and the mean parotid dose (MD(parb)) and xerostomia was observed (Odds ratio (OR)-technique: 2.55; p=0.04 and OR-MD(parb): 1.04; p=0.009). Considering the individual salivary glands, only the mean dose in the contralateral parotid gland (MD(parcl)) is associated with xerostomia (OR: 1.04; p<0.0001). Moreover, the threshold dose for a 50% probability (P50) on xerostomia increased from 21 Gy with bilateral to 44 Gy for unilateral irradiation., Conclusions: Both technique and MD(parb) influence the risk of xerostomia in irradiated patients. Of all individual salivary glands, only MD(parcl) is of utmost importance for xerostomia. The shift in the P50 observed for xerostomia suggests that sparing of the contralateral parotid gland is compensated by hyperfunction of the contralateral parotid gland.

Simple Summary: Many head and neck cancer patients report sexual problems. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. This effect seems to differ between men and women. Men reported change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction, while women reported change in desire, arousal, and orgasm. These findings are helpful to improve information on sexuality and sexual care in head and neck cancer patients. The aim of this study was to investigate changes in sexuality and sexual dysfunction in head and neck cancer (HNC) patients in the first two years after treatment, in relation to the type of treatment. Data were used of 588 HNC patients participating in the prospective NETherlands Quality of life and Biomedical Cohort Study (NET-QUBIC) from diagnosis to 3, 6, 12 and 24 months after treatment. Primary outcome measures were the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI). The total scores of the IIEF and FSFI were dichotomized into sexual (dys)function. In men, type of treatment was significantly associated with change in erectile function, orgasm, satisfaction with intercourse, and overall satisfaction. In women, type of treatment was significantly associated with change in desire, arousal, and orgasm. There were significant differences between treatment groups in change in dysfunctional sexuality. A deterioration in sexuality and sexual dysfunction from baseline to 3 months after treatment was observed especially in patients treated with chemoradiation. Changes in sexuality and sexual dysfunction in HNC patients were related to treatment, with an acute negative effect of chemoradiation. This effect on the various domains of sexuality seems to differ between men and women. [ABSTRACT FROM AUTHOR]

Objective: Head and neck cancer care is highly complex, and multidisciplinary team meetings (MDTs) are vital for improved outcomes. In the Netherlands, head and neck cancer care is practiced in eight high-volume head and neck oncologic centers (HNOC) and six affiliated hospitals preferred partner (PP) centers. Patients treated in the PP are presented and discussed in the HNOC. To evaluate the importance of these mandatory and decisive steps in decision making, we have assessed the changes in treatment. Materials and methods: Retrospective evaluation of head and neck cancer patients referred between January 2011 and October 2018 for a MDT evaluation to the HNOC was conducted. The differences in MDT recommendation were classified with regards to major and minor changes. Results: Management recommendation(MR) changed after 113 of 515 MDT discussions within the PP (487 patients; 22%), of which 86 cases (16%) were major changes. In 67 cases (59.3%), escalation of management was recommended, while in 43 cases (38.1%) de-escalation was recommended. Conclusion: There was a high rate of change of MRs, when comparing the PP recommendations with the HNOC recommendations. Since patient and tumor characteristics seem unable to predict these changes, we recommend all patients be seen for a clinical presentation, revision of diagnostics, and MDT discussion in a high volume HNOC. [ABSTRACT FROM AUTHOR]

Dysphagia represents one of the most serious adverse events after curative-intent treatments with a tremendous impact on quality of life in patients with head and neck cancers. Novel surgical and radiation therapy techniques have been developed to better preserve swallowing function, while not negatively influencing local control and/or overall survival. This review focuses on the current literature of swallowing outcomes after curative treatment strategies. Available results from recent studies relevant to this topic are presented, demonstrating the potential role of new treatment modalities for early- and intermediate-stage oropharyngeal cancers. Based on this, we present the rationale and design of the currently active EORTC 1420 "Best of" trial, and highlight the potential of this study to help prioritizing either surgery- or radiation-based treatment modalities for the treatment of oropharyngeal cancer in the future. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to evaluate active surveillance strategy in the clinically negative neck in maxillary squamous cell carcinoma (SCC). Methods One hundred fourteen consecutive patients diagnosed with oral maxillary SCC were analyzed retrospectively from 3 centers in The Netherlands. Analysis parameters included regional disease-free survival of N0 patients stratified for T classification, elective radiotherapy (RT) of the neck; and overall survival of the whole cohort, stratified by N classification; salvage neck surgery rates. Results Within the N0 cohort, 26.0% of the patients developed neck metastasis in the follow-up visits. Regional recurrence was not related to T classification or postoperative RT of the neck. Regional and locoregional recurrence were associated with diminished overall survival ( p < .05). Regional metastasis was operable in 22 of 26 cases (85%). Only 1 patient presented with inoperable neck metastasis without local recurrence. Conclusion Watchful waiting was feasible in this cohort. If meticulous follow-up is not available, elective neck dissection is recommended. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1794-1798, 2016 [ABSTRACT FROM AUTHOR]

Summary: Background and aims: We performed a systematic review to examine the effect of nutritional interventions on nutritional status, quality of life (QoL) and mortality in patients with head and neck squamous cell cancer (HNSCC) receiving radiotherapy or chemoradiotherapy. Methods: We searched Pubmed, EMBASE, CENTRAL and Cinahl from inception through January 3rd, 2012 to identify randomized controlled trials (RCTs) from a broad range of nutritional interventions in patients with HNSCC during (chemo)radiotherapy. Two reviewers independently assessed study eligibility and risk of bias, and extracted data. Results: Of 1141 titles identified, 12 study reports were finally included, describing 10 different studies with 11 interventions. Four out of 10 studies examined the effects of individualized dietary counseling, and showed significant benefits on nutritional status and QOL compared to no counseling or general nutritional advice by a nurse (p < 0.05). Three studies on oral nutritional supplements (ONS) were inconsistent about the effect on nutritional status compared with no supplementation. One study showed that nasogastric tube feeding had beneficial effects on nutritional status compared to ONS, but not in all patient groups (p < 0.04). One study showed benefits of percutaneous endoscopic gastronomy (PEG) feeding on nutritional status shortly after RT compared with nasogastric feeding (p = 0.001). Two studies showed that prophylactic PEG feeding was not superior over tube feeding if required. Conclusions: This review shows beneficial effects of individualized dietary counseling on nutritional status and QoL, compared to no counseling or standard nutritional advice. Effects of ONS and tube feeding were inconsistent. [Copyright &y& Elsevier]

Summary: Background & aims: Weight loss is a frequently observed problem in patients with head and neck cancer (HNC) during radiotherapy. It is still to be assessed whether hypermetabolism is contributing to this problem. The aim of this study was to investigate hypermetabolism before radiotherapy, and changes in resting energy expenditure (REE) in HNC patients during radiotherapy. Methods: REE was measured by indirect calorimetry in 71 patients with HNC before radiotherapy, after 3 and 6 weeks of radiotherapy, and 3 months after radiotherapy. The association between REE and tumour stage, CRP, and prior tumour surgery was analyzed by linear regression analyses. Forty healthy control subjects were one-to-one matched to 40 patients by gender, age and fat free mass (FFM) index to compare REE. Results: Before radiotherapy, REE was not significantly different between patients and controls, neither in absolute values (1568 ± 247 vs. 1619 ± 244 kcal/d; p = 0.29), nor after weight-adjustment (22.1 ± 3.5 vs. 21.5 ± 3.3 kcal/kg, p = 0.42) or FFM-adjustment (31.5 ± 4.9 vs. 30.7 ± 4.5 kcal/kg, p = 0.38). REE was independent of tumour stage, CRP, and prior tumour surgery. REE (kcal/d) decreased during radiotherapy and thereafter by 9% from pre-radiotherapy (p < 0.01). Weight and FFM also decreased significantly over time (p < 0.001). REE adjusted for FFM decreased in the first 3 weeks of radiotherapy with 4% (B = −1.39 kcal/kg FFM, p < 0.01), increased at the end of radiotherapy and decreased again 3 months after radiotherapy (B = −1.31 kcal/kg FFM, p = 0.04). Conclusions: Head and neck cancer patients had normal REE before radiotherapy. During radiotherapy, REE decreased continuously with ongoing weight loss. However, weight loss is not the only explaining factor, since REE expressed per kg FFM showed a much more divergent course which is currently unexplained. [Copyright &y& Elsevier]

The article presents a study which compares the molecular profiles of primary and recurring head and neck squamous cell carcinoma (HNSCC). It states that pre-radiotherapy (RT) lesions among 85 consecutive patients treated with primary RT were determined through TP53 gene status and instability at 10 microsatellite markers. It reveals that 50% of the HNSCC patients showed both TP53 mutation and microsatellite instability (MSI) status concordance before and after irradiation biopsies.

The aim of this study was to estimate the cost-effectiveness of 18FDG-PET in the selection for direct laryngoscopy in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy. The direct medical costs of 30 patients with suspicion of a recurrence were calculated from the first visit where suspicion was raised until one year after. A conventional strategy, in which all these patients underwent direct laryngoscopy, was compared to an 18FDG-PET strategy in which only patients with a positive or equivocal 18FDG-PET underwent direct laryngoscopy. A sensitivity analysis was performed to examine the influence of the type of camera and ‘setting’. The mean costs of an 18FDG-PET strategy were €399 less than a direct laryngoscopy strategy. The type of camera and setting had no influence. In patients with suspicion for recurrent laryngeal carcinoma after radiotherapy, 18FDG-PET seems to be effective and less costly in selecting patients for direct laryngoscopy. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to evaluate the effectiveness and safety of our careful observational strategy and neck dissections and the accuracy of ultrasound-guided fine-needle aspiration cytology, and to determine the prognostic factors for outcome and regional control after primary chemoradiation. Diagnostic evaluation of the regional status after concurrent chemoradiation for advanced head and neck cancer remains difficult, and the indications for a salvage neck dissection and its extent are not clearly defined. Methods In a series of 540 patients, there was suspicion of regional residual or recurrent disease after chemoradiation in 61 patients who underwent 68 salvage neck dissections and 68 patients who were considered unresectable. For the patients with salvage neck dissection, the accuracy of ultrasound-guided fine-needle aspiration cytology was determined. Disease control in the neck, disease-specific and overall survival, and parameters that may have prognostic value for the outcome were evaluated. Results Neck dissection specimens contained viable tumor in 26 (43%) patients. Of these, 13 had selective neck dissections and 13 modified radical neck dissections. Ultrasound-guided fine-needle aspiration cytology had a sensitivity of 80% and specificity of 42%. Nine patients developed a regional recurrence after salvage neck dissection (5 located in contralateral neck). Five-year regional control and overall survival rates were 79% and 36%, respectively. Significant prognostic factors for overall survival were surgical margins and “residual versus recurrent disease” in multivariate analysis. Conclusion Considering the good regional control rate and the high rate of unnecessary neck dissections with a theoretical planned neck dissection strategy, we conclude that a careful observational strategy is worthwhile and safe. For the evaluation of radiation treatment response, ultrasound-guided fine-needle aspiration cytology has a low specificity. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [ABSTRACT FROM AUTHOR]

Background. Treatment of head and neck mucosal melanoma remains a challenge. Surgery has traditionally been the main therapeutic approach. The role of postoperative radiotherapy has never been clearly established. Methods. The experience with a group of 42 patients (16 males, 26 females) with a primary head and neck mucosal melanoma is reported. Results. Eleven of 19 patients (57.9%) receiving surgery alone developed a regional lymphatic metastasis. For patients receiving postoperative radiotherapy (19 patients), regional metastatic spread occurred in 4 patients (21%). Percentages of local failure were 57.9% (11/19) and 26.3% (5/19) for patients treated with surgery alone and for those treated with surgery and radiotherapy, respectively. Distant metastases occurred in 10 of 19 patients (52.6%) receiving surgery alone and in 9 of 19 patients (47.3%) receiving both therapies. Conclusions. The present evaluation confirms a poor prognosis for patients with head and neck mucosal melanoma, independent of the treatment modality. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

Background Diagnosing recurrent laryngeal tumor after radiotherapy is challenging. The most reliable method is direct laryngoscopy under general anesthesia. However, many futile laryngoscopies are performed in disease-free patients. Imaging tests selecting patients for this invasive procedure would be useful. The aim of this systematic review was summarizing the available evidence and determining the diagnostic accuracy of CT, MRI, thallium-201 (201Tl) scintigraphy, and F-18-fluorodeoxyglucose positron emission tomography (18FDG-PET). Methods A systematic review was performed according to the guidelines of the Cochrane Collaboration. Two reviewers scored the articles according to A-, B-, and C-items. Statistical meta-analysis was performed producing summary pooled estimates of sensitivity and specificity. Results There were 8 eligible studies on 18FDG-PET. The validity of the 18FDG-PET studies was reasonable; the pooled estimates (95% CI) for sensitivity and specificity were 89% and 74%. Conclusion The diagnostic accuracy of 18FDG-PET is promising and warrants a randomized trial comparing a strategy based on conventional diagnostic work-up to one based on 18FDG-PET. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to analyze swallowing outcome in advanced oral/oropharyngeal cancer patients treated with microvascular reconstructive surgery and adjuvant radiotherapy. Methods. Eighty patients were included. Patient, tumor, and treatment factors were assessed. Postoperative videofluoroscopic swallowing studies (VFSS) and scintigraphy tests were performed at 6 (n = 54 vs 44) and 12 (n = 32 vs 37) months. Swallowing parameters such as the oropharyngeal swallow efficiency and the Penetration/Aspiration Scale were analyzed. Results. Impaired swallowing status was found at 6 months, which remained stationary at 12 months. Comorbid condition, larger tumors (T3-T4 vs T2), and resections of the base of tongue and soft palate combined (vs defects of other dynamic structures) were associated with most profound swallowing problems (p < .05). Conclusions. Swallowing difficulties are relatively frequent and can to a large extent be predicted. With the knowledge of this study, better counseling and vigilance as to swallowing difficulties may be possible. © 2007 Wiley Periodicals, Inc. Head Neck 2007 [ABSTRACT FROM AUTHOR]

Background. The clinical results of radiotherapy and endoscopic cordectomy for T1a glottic carcinoma are reported to be similar, but costs of both treatments may differ. Therefore, we retrospectively evaluated the costs, voice quality, quality of life, and clinical results of both treatments. Methods. Costs and effects from the first visit up to 2 years of follow-up were calculated, based on chart data of 35 and 54 patients who were treated with curative intent for T1a glottic carcinoma from 1995 to 1999 with radiotherapy and endoscopic cordectomy, respectively. Voice quality and quality of life were evaluated by means of patient questionnaires. Results. Total costs (in Euros) of radiotherapy and CO2-laser cordectomy were €8322 and €4434, respectively, including the costs of treating possible recurrences. The effects of both treatments were equal, including voice quality and quality of life. Conclusions. We conclude that endoscopic cordectomy is an efficient alternative for radiotherapy for these patients. © 2006 Wiley Periodicals, Inc. Head Neck, 2007 [ABSTRACT FROM AUTHOR]

Background. The purpose of this retrospective study was to determine the long-term effects of radiotherapy on hearing function in patients who underwent parotidectomy and postoperative radiotherapy for unilateral tumors of the parotid gland. Methods. An extensive set of tests was used to measure hearing loss. The mean dose on middle ear, cochlea, and Eustachian tube was estimated with a CT-planning system. Results. A hearing loss of ≥ 15 dB in 3 frequencies was found in 32% of the 52 patients included in the study. Patients with an asymmetrical hearing loss received a higher mean dose on the hearing structures (p < .002). The threshold dose for clinically relevant hearing loss was found at 50 Gy on the cochlea and Eustachian tube. Conclusions. Radiation-induced hearing loss is a common complication. A mean dose of > 50 Gy on the cochlea should be avoided. © 2006 Wiley Periodicals, Inc. Head Neck, 2006 [ABSTRACT FROM AUTHOR]

Background and Purpose: In head and neck squamous cell carcinoma (HNSCC) (chemo)radiotherapy is increasingly used to preserve organ functionality. The purpose of this study was to identify predictive pretreatment DWI- and 18F-FDG-PET/CT-parameters for treatment failure (TF), locoregional recurrence (LR) and death in HNSCC patients treated by (chemo)radiotherapy.Materials and Methods: We retrospectively included 134 histologically proven HNSCC patients treated with (chemo)radiotherapy between 2012-2017. In 58 patients pre-treatment DWI and 18F-FDG-PET/CT were performed, in 31 patients DWI only and in 45 patients 18F-FDG-PET/CT only. Primary tumor (PT) and largest lymph node (LN) metastasis were quantitatively assessed for TF, LR and death. Multivariate analysis was performed for 18F-FDG-PET/CT and DWI separately and thereafter combined. In patients with both imaging modalities, positive and negative predictive value in TF and differences in LR and death, were assessed.Results: Mean follow-up was 25.6 months (interquartile-range; 14.0-37.1 months). Predictors of treatment failure, corrected for TNM-stage and HPV-status, were SUVmax-PT, ADCmax-PT, total lesion glycolysis (TLG-LN), ADCp20-LN (P = 0.049, P = 0.024, P = 0.031, P = 0.047, respectively). TLG-PT was predictive for LR (P = 0.003). Metabolic active tumor volume (MATV-PT) (P = 0.003), ADCGTV-PT (P < 0.001), ADCSD (P = 0.048) were significant predictors for death. In patients with both imaging modalities SUVmax-PT remained predictive for treatment failure (P = 0.049), TLG-LN for LR (P = 0.003) and ADCGTV-PT for death (P < 0.001). Higher predictive value for treatment failure was found for the combination of SUVmax-PT and ADCmax-PT, compared to either one separately.Conclusion: Both DWI- and 18F-FDG-PET/CT-parameters appear to have predictive value for treatment failure, locoregional recurrence and death. Combining SUVmax-PT and ADCmax-PT resulted in better prediction of treatment failure compared to single parameter assessment. [ABSTRACT FROM AUTHOR]

This systematic review gives an extensive overview of the current state of functional imaging during (chemo)radiotherapy to predict locoregional control (LRC) and overall survival (OS) for head and neck squamous cell carcinoma. MEDLINE and EMBASE were searched for literature until April 2018 assessing the predictive performance of functional imaging (computed tomography perfusion (CTp), MRI and positron-emission tomography (PET)) within 4 weeks after (chemo)radiotherapy initiation. Fifty-two studies (CTp: n = 4, MRI: n = 19, PET: n = 26, MRI/PET: n = 3) were included involving 1623 patients. Prognostic information was extracted according the PRISMA protocol. Pooled estimation and subgroup analyses were performed for comparable parameters and outcome. However, the heterogeneity of included studies limited the possibility for comparison. Early tumoral changes from (chemo)radiotherapy can be captured by functional MRI and 18F-FDG-PET and could allow for personalized treatment adaptation. Lesions showed potentially prognostic intratreatment changes in perfusion, diffusion and metabolic activity. Intratreatment ADCmean increase (decrease of diffusion restriction) and low SUVmax (persistent low or decrease of 18F-FDG uptake) were most predictive of LRC. Intratreatment persistent high or increase of perfusion on CT/MRI (i.e. blood flow, volume, permeability) also predicted LRC. Low SUVmax and total lesion glycolysis (TLG) predicted favorable OS. The optimal timing to perform functional imaging to predict LRC or OS was 2-3 weeks after treatment initiation. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study is to evaluate the efficacy of 18 F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. Patients and methods 150 patients suspected of recurrent T2–4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to 18 F-FDG-PET only followed by direct laryngoscopy if PET was assessed ‘positive’ or ‘equivocal’ (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. Results Intention-to-treat analyses were performed on all randomized patients (CWU: n = 74, PWU: n = 76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60–81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19–40) ( p < 0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p = 0·17, and 29%, 7%, respectively, p = 0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference ( p = 0.32) in disease specific survival between both groups was found. Conclusion In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To evaluate the course of health-related quality of life (HRQOL) from diagnosis to 2years follow-up in patients with head and neck cancer (HNSCC) treated with chemoradiation (CRT). Materials and methods: 164 patients completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires 1week before and 6weeks and 6, 12, 18, and 24months after CRT. Patients were compared to a reference group. A linear mixed-model analysis was used to assess changes in HRQOL over time, and whether this was associated with age, gender, comorbidity, and tumor sublocation. Results: Significant differences for the majority of HRQOL scales were observed between patient and reference group at baseline, and follow-up. The course of HRQOL was different for survivors compared to non-survivors. In survivors, improvement over time was observed (in global quality of life, physical, role, and social function, fatigue, pain, swallowing, speech, social eating, and social contacts), while in non-survivors the pattern over time was either no changes in HRQOL or a deterioration (in physical function, social eating and contacts). In both survivors and non-survivors, emotional functioning improved after treatment, but deteriorated in the longer term. Patients with comorbidity reported worse physical function, and patients with oral/oropharyngeal cancer (compared to hypopharyngeal/laryngeal cancer) reported more oral pain and sexual problems, but fewer speech problems. Conclusions: The course of HRQOL of HNSCC patients during the first 2years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite. [Copyright &y& Elsevier]

Summary: Objectives: The incidences of hypo(para)thyroidism were assessed prospectively in 137 consecutive patients with laryngeal (84.7%) or hypopharyngeal (15.3%) carcinoma who were treated with surgery and/or radiotherapy between 2004 and 2006. Material and methods: Laboratory studies were performed in patients before primary or salvage treatment of a laryngeal or hypopharyngeal carcinoma and were repeated 6, 12, 18 and 24months after treatment. All patients were evaluated for the development of hypo(para)thyroidism, and the presence of autoantibodies. The association of hypothyroidism was analyzed against several patient parameters including tumor and treatment characteristics. Results: The incidence of hypothyroidism following treatment of laryngeal and hypopharyngeal carcinoma was 47.4%: 27.7% subclinical hypothyroidism and 19.7% clinical hypothyroidism. The median time to develop hypothyroidism was 10months. The incidence of hypoparathyroidism was 7.3%. Univariate analysis showed that patients with laryngectomy, hemithyroidectomy, neck dissection, paratracheal lymph node dissection and radiotherapy had a higher risk of developing hypothyroidism. Multivariate analysis showed laryngectomy, hemithyroidectomy, neck dissection and age to be predictive factors for the development of hypothyroidism. The combination of surgery and radiotherapy increased this risk. Hemithyroidectomy was the most important risk factor. Conclusion: The incidence rate of hypothyroidism after treatment for laryngeal or hypopharyngeal cancer in this largest prospective study is high (47.4%), especially after combination treatment. Based on the intervals between treatment and the development of hypothyroidism, thyroid testing before treatment, every 3months during the first year, every 6months the second year and annually thereafter is recommended as screening procedure. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). Methods and materials: The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. Results: The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. Conclusions: Dose distributions in the minor salivary glands in patients receiving 3D-CRT have limited significance with regard to patient-rated symptoms related to salivary dysfunction. Besides the parotid and submandibular glands, only the sublingual glands were significantly associated with sticky saliva. In addition, reliable risk estimation also requires information from other factors such as age and baseline subjective scores. When these selected factors are included in predictive models, instead of only dose volume histogram parameters, model performance can be improved significantly. [Copyright &y& Elsevier]

Abstract: Background and purpose: Although patients with early stage (T1/T2) laryngeal cancer (LC) are thought to have a low incidence of malnutrition, severe weight loss is observed in a subgroup of these patients during radiotherapy (RT). The objective of this study was to evaluate weight loss and nutrition-related symptoms in patients with T1/T2 LC during RT and to select predictive factors for early identification of malnourished patients. Methods: Of all patients with T1/T2 LC, who received primary RT between 1999 and 2007, the following characteristics were recorded: sex, age, TNM classification, tumour location, radiation schedule, performance status, quality of life, weight loss, and nutrition-related symptoms. The association between baseline characteristics and malnutrition (>5% weight loss during RT) was investigated by Cox regression analysis. Results: The study population consisted of 238 patients. During RT, 44% of patients developed malnutrition. Tumour location, TNM classification, RT on the neck nodes, RT dose, nausea/vomiting, pain, swallowing, senses problems, trouble with social eating, dry mouth and the use of painkillers were all significantly associated with malnutrition. In the multivariate analysis, RTs on both the neck nodes (HR 4.16, 95% CI 2.62–6.60) and dry mouth (HR 1.72, 95% CI 1.14–2.60) remained predictive. Nevertheless, RT on the neck nodes alone resulted in the best predictive model for malnutrition scores. Conclusions: Patients with early stage laryngeal cancer are at risk of malnutrition during radiotherapy. Radiotherapy on the neck nodes is the best predictor of malnutrition during radiotherapy. Therefore, we suggest to offer nutritional counselling to all the patients who receive nodal irradiation. [ABSTRACT FROM AUTHOR]

Summary: Radiation may cause radiation-induced cancers after a long latency period. In a group of 111 patients surgically treated for hypopharyngeal carcinoma, patients previously treated with radiotherapy for tuberculosis in the neck were compared to patients without previous radiotherapy. Seven patients (7.4%) underwent radiotherapy (median age 15years) and developed a hypopharyngeal carcinoma (median age 70years, median latency period 54.4year). Considering this long latency period and the localisation in the previous radiation field these tumours can be classified as potentially radiation-induced carcinomas. Patients with potentially radiation-induced carcinomas were significantly older when the hypopharyngeal carcinoma was diagnosed (p =0.048), were more frequently females (p =0.05) and had a worse 5-year regional control rate (p =0.048). When radiotherapy is considered in young patients the risk of induction of tumours has to be kept in mind. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: Timely detection of recurrent laryngeal tumor after radiation is an important predictive factor for curation as well as preservation of laryngeal function. Direct laryngoscopy under general anesthesia with taking of biopsies is the standard diagnostic procedure to detect recurrence when suspicion is raised. This, however, is an invasive and potentially damaging technique. Hence, a non-invasive diagnostic procedure, such as 18FDG-PET to stratify patients for direct laryngoscopy could be useful. 18FDG-PET is interpreted visually so that observer variation may affect clinical practice. In the present study, we therefore investigated this aspect of reproducibility. Patients and methods: Thirty consecutive patients suspected of recurrent laryngeal carcinoma after radiotherapy underwent 18FDG-PET and direct laryngoscopy under general anesthesia with taking of biopsies. 18FDG-PET scans were reported by nine nuclear medicine physicians and residents, using a three-point scaling system. The reference was the absence or appearance of a local recurrence in the 12 months following 18FDG-PET. Results: Eight patients had biopsy proven recurrent laryngeal carcinoma. Sensitivity of 18FDG-PET was 88% (95% CI 53–98%) and specificity was 82% (95% CI 62–93%). The observers had a moderate to reasonable agreement (weighted kappa 0.45 (95% CI 0.20–0.69)) vs. the clinical gold standard and interobserver kappa was 0.54 (95% CI 0.40–0.69). Conclusion: 18FDG-PET seems to be a promising technique to detect recurrent laryngeal carcinoma after radiotherapy, and selecting patients for direct laryngoscopy. This will avoid futile invasive procedures. Interobserver agreement and variability is reasonable using this technique, but training is necessary. Studies comparing different strategies to select patients for direct laryngoscopy in case of suspected recurrence are warranted. [Copyright &y& Elsevier]

Abstract: The RELAPS study (REcurrent LAryngeal carcinoma PET Study) was designed to determine whether FDG–PET is of value in the selection of patients for direct laryngoscopy under general anesthesia in patients with suspicion of recurrent laryngeal carcinoma after radiotherapy. In a randomized controlled clinical trial the current diagnostic practice, i.e. all patients undergo direct laryngoscopy, will be compared to a strategy in which FDG–PET selects the patients for laryngoscopy. All eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group NWHHT will participate in this multicenter trial. The study population consists of patients with clinical suspicion of recurrent T2–T4 laryngeal carcinoma after radiotherapy (without obvious signs of tumor) in whom a direct laryngoscopy under general anesthesia with taking of biopsies is indicated by the local physician. The primary efficacy endpoint is the difference in the number of futile indications for direct laryngoscopy between the conventional diagnostic arm and the FDG–PET based diagnostic arm. An indication for laryngoscopy is classified as futile if this laryngoscopy was negative and no recurrence was diagnosed within 6 months follow-up (gold standard). The FDG–PET based strategy may increase the risk of missing recurrent tumor compared to current practice. Safety endpoints include survival and morbidity due to laryngoscopy with taking of biopsies. Survival rates of both groups will have to be collected outside the time frame of the funded trial. Resectability of recurrent tumor and tumor negative surgical margins after total laryngectomy will be used as proxy endpoints. The trial will also compare quality of life and direct medical costs between both arms. [Copyright &y& Elsevier]

Purpose: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. Methods and Materials: A total of 288 patients with Stage I–IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. Results: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001). A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18–65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. Conclusions: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade ≥2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia. [Copyright &y& Elsevier]

Purpose: The aim of this study was to investigate the prognostic significance of epidermal growth factor (EGFr) expression in oral cavity squamous cell carcinoma (OCSCC) treated with curative surgery and postoperative radiotherapy. Methods and Materials: This retrospective study included 165 OCSCC patients. The expression of EGFr was assessed on paraffin-embedded tissue of the primary tumor by immunohistochemistry using a monoclonal antibody directed against EGFr. Intensity of the EGFr expression was scored by two authors blinded for the clinical outcome. Results: In the univariate analysis, locoregional control at 3 years (LRC) in the EGFr-negative cases was 69% compared with 77% in the EGFr-positive cases (p = 0.22). In the multivariate analysis for local control, a significant interaction was found between EGFr and overall treatment time of radiation (OTT). After stratification for EGFr expression, the OTT was of no importance in the EGFr-negative cases, whereas a significant difference in LRC was found in the EGFr-positive cases, in which the LRC after 3 years was 69% and 94% in case of an OTT of 0–42 days and >42 days, respectively (p = 0.009; hazard ratio = 3.42; 95% confidence interval, 1.28–8.96). No significant association was found between EGFr expression and overall survival. Conclusions: In the present study, no association was found between EGFr expression and outcome regarding locoregional control and overall survival. However, the results of the present study suggest that patients with squamous cell carcinoma of the oral cavity with high EGFr expression benefit more from a reduction of the overall treatment time of postoperative radiation than those with low EGFr expression. [Copyright &y& Elsevier]

Summary: For patients with squamous cell carcinoma of the upper aerodigestive tract, appropriate management of the regional lymph nodes is an important and often controversial issue that has significant influence on survival. Over the years radical treatment either by surgery or radiotherapy contributed to improvement in prognosis. Recently, a more conservative approach has achieved a similar level of cancer control with less morbidity. This review considers the issues of selection of patients for treatment of the neck, choice of modality and extent of therapy, treatment of the contralateral neck, management of recurrence and influence of the site and status of the primary lesion. [Copyright &y& Elsevier]

Summary: The objective of this study was to investigate the prognostic significance of the hemoglobin (Hb) levels at different timepoints in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Included were 111 patients. The hemoglobin levels were assessed before surgery (PreS-Hb), between surgery and radiotherapy (HbAAC), before postoperative radiotherapy (PreRT-Hb) and at the end of radiotherapy (EndRT-Hb). HbAAC takes into account the duration of anemia during the interval between surgery and radiotherapy. Higher HbAAC corresponds with lower Hb levels. Five year locoregional control (LRC) among patients with HbAAC⩾median was 72% and significantly worse as compared to the 88% in case of HbAAC < median (p =0.0097). Multivariate analysis for LRC showed that the HbAAC was a prognostic factor. Overall survival (OS) after 3 years was 77% in case of HbAAC < median and 34% in case of HbAAC⩾median (p <0.0002). Multivariate analysis for OS showed that the PreS-Hb and HbAAC were prognostic factors. Hb level between surgery and radiotherapy is an important prognostic factor for both LRC and OS among patients with SCCHN treated with surgery and postoperative radiotherapy. [Copyright &y& Elsevier]