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Copyright of Tijdschrift voor Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To identify associations between frailty and non-response to follow-up questionnaires, in a longitudinal head and neck cancer (HNC) study with patient-reported outcome measures (PROMs). Materials and methods: Patients referred with HNC were included in OncoLifeS, a prospective data-biobank, underwent Geriatric Assessment (GA) and frailty screening ahead of treatment, and were followed up at 3, 6, 12 and 24 months after treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Head and Neck 35. Statistical analysis for factors associated with non-response was done using Generalized Linear Mixed Models. Results: 289 patients were eligible for analysis. Mean age was 68.4 years and 68.5% were male. Restrictions in Activities of Daily Living [OR 4.46 (2.04–9.78)] and Instrumental Activities of Daily Living [OR 4.33 (2.27–8.24)], impaired mobility on Timed Up and Go test [OR 3.95 (1.85–8.45)], cognitive decline [OR 4.85 (2.28–10.35)] and assisted living (OR 5.54 (2.63–11.67)] were significantly associated with non-response. Frailty screening, with Geriatric 8 and Groningen Frailty Indicator, was also associated with non-response [OR, respectively, 2.64 (1.51–4.59) and 2.52 (1.44–4.44)]. All findings remained significant when adjusted for other factors that were significantly associated with non-response, such as higher age, longer study duration and subsequent death. Conclusion: Frail HNC patients respond significantly worse to follow-up PROMs. The drop-out and underrepresentation of frail patients in studies may lead to attrition bias, and as a result underestimating the effect sizes of associations. This is of importance when handling and interpreting such data. [ABSTRACT FROM AUTHOR]

Purpose: To identify trends in incidence and survival of NPC, subdivided by EBV status and histopathological subtype, over a 30-year period in the Netherlands. Methods: Anonymized data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Databank (PALGA) for the period 1989–2018 were linked to identify and classify NPC cases. Results: Incidence of NPC remained stable, with an annual percentage change (APC) of − 0.2. (95% CI − 0.9; 0.5). EBV testing became routine only in the last decade, the incidence of EBV-positive tumors remained stable over this period (APC 1.2, 95% CI − 1.3; 3.8). An increase in EBV-negative tumors (APC: 7.1, 95% CI 2.5; 11.9) and a decrease in untested tumors were found (APC: − 10.7, 95% CI − 15.7; − 5.7). The incidence of non-keratinizing, differentiated tumors increased (APC: 3.8, (95% CI 2.2; 5.5) while the incidence of other histological subtypes remained stable. Overall survival was better in patients diagnosed after 1998 (hazard ratio 0.8, 95% CI 0.6; 0.9). EBV status, histology, stage, and age were independently associated with relative excess risk of dying, but period of diagnosis was not. Conclusion: Testing for EBV increased over time, and a stable incidence of EBV-positive NPC over the last 10 years. The rising incidence of non-keratinizing, differentiated NPC mirrors data from the US and suggests a shift in non-endemic regions. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors. Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment. Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months. Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment. [ABSTRACT FROM AUTHOR]

Purpose: Treatment decision-making in advanced-stage laryngeal squamous cell carcinoma (LSCC) is difficult due to the high recurrence rates and the desire to preserve laryngeal functions. New predictive markers for radiosensitivity are needed to facilitate treatment choices. In early stage glottic LSCC treated with primary radiotherapy, expression of hypoxia (HIF-1α and CA-IX) and proliferation (Ki-67) tumour markers showed prognostic value for local control. The objective of this study is to examine the prognostic value of tumour markers for hypoxia and proliferation on locoregional recurrent disease and disease-specific mortality in a well-defined cohort of patients with locally advanced LSCC treated with primary, curatively intended radiotherapy. Methods: In pre-treatment biopsy tissues from a homogeneous cohort of 61 patients with advanced stage (T3–T4, M0) LSCC primarily treated with radiotherapy, expression of HIF-1α, CA-IX and Ki-67 was evaluated with immunohistochemistry. Demographic data (age and sex) and clinical data (T- and N-status) were retrospectively collected from the medical records. Cox regression analysis was performed to assess the relation between marker expression, demographic and clinical data, and locoregional recurrence and disease-specific mortality. Results: Patients with high expression of HIF-1α developed significantly more often a locoregional recurrence (39%) compared to patients with a low expression (21%) (p = 0.002). The expression of CA-IX and Ki-67 showed no association with locoregional recurrent disease. HIF-1α, CA-IX and Ki-67 were not significantly related to disease-specific mortality. Clinical N-status was an independent predictor of recurrent disease (p < 0.001) and disease-specific mortality (p = 0.003). Age, sex and T-status were not related to locoregional recurrent disease or disease-specific mortality. Conclusion: HIF-1α overexpression and the presence of regional lymph node metastases at diagnosis were independent predictors of locoregional recurrent disease after primary treatment with curatively intended radiotherapy in patients with locally advanced LSCC. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck cancer (HNC) and its treatment often negatively impact swallowing function. The aim was to investigate the course of patient-reported swallowing problems from diagnosis to 3, 6, 12, and 24 months after treatment, in relation to demographic, clinical, and lifestyle factors. Methods: Data were used of the Netherlands Quality of Life and Biomedical Cohort Study in head and neck cancer research (NET-QUBIC). The primary outcome measures were the subscales of the Swallowing Quality of Life Questionnaire (SWAL-QOL). Linear mixed-effects models (LMM) were conducted to investigate changes over time and associations with patient, clinical, and lifestyle parameters as assessed at baseline. Results: Data were available of 603 patients. There was a significant change over time on all subscales. Before treatment, 53% of patients reported swallowing problems. This number increased to 70% at M3 and decreased to 59% at M6, 50% at M12, and 48% at M24. Swallowing problems (i.e., longer eating duration) were more pronounced in the case of female, current smoking, weight loss prior to treatment, and stage III or IV tumor, and were more prevalent at 3 to 6 months after treatment. Especially patients with an oropharynx and oral cavity tumor, and patients receiving (C)RT following surgery or CRT only showed a longer eating duration after treatment, which did not return to baseline levels. Conclusion: Half of the patients with HNC report swallowing problems before treatment. Eating duration was associated with sex, smoking, weight loss, tumor site and stage, and treatment modality, and was more pronounced 3 to 6 months after treatment. [ABSTRACT FROM AUTHOR]

Purpose: A two-stage genome-wide association study was carried out in head and neck cancer (HNC) patients aiming to identify genetic variants associated with either specific radiotherapy-induced (RT) toxicity endpoints or a general proneness to develop toxicity after RT.Materials and Methods: The analysis included 1780 HNC patients treated with primary RT for laryngeal or oro/hypopharyngeal cancers. In a non-hypothesis-driven explorative discovery study, associations were tested in 1183 patients treated within The Danish Head and Neck Cancer Group. Significant associations were later tested in an independent Dutch cohort of 597 HNC patients and if replicated, summary data obtained from discovery and replication studies were meta-analysed. Further validation of significantly replicated findings was pursued in an Asian cohort of 235 HNC patients with nasopharynx as the primary tumour site.Results: We found and replicated a significant association between a locus on chromosome 5 and mucositis with a pooled OR for rs1131769*C in meta-analysis = 1.95 (95% CI 1.48-2.41; ppooled = 4.34 × 10-16).Conclusion: This first exploratory GWAS in European cohorts of HNC patients identified and replicated a risk locus for mucositis. A larger Meta-GWAS to identify further risk variants for RT-induced toxicity in HNC patients is warranted. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancer (HNC) patients often suffer from distress attributed to their cancer diagnosis which may disturb their sleep. However, there is lack of research about poor sleep quality among newly diagnosed HNC patients. Therefore, our aim was to investigate the prevalence and the associated factors of poor sleep quality among HNC patients before starting treatment.Materials and Methods: A cross-sectional study was conducted using the baseline data from NET-QUBIC study, an ongoing multi-center cohort of HNC patients in the Netherlands. Poor sleep quality was defined as a Pittsburgh Sleep Quality Index (PSQI) total score of > 5. Risk factors examined were sociodemographic factors (age, sex, education level, living situation), clinical characteristics (HNC subsite, tumor stage, comorbidity, performance status), lifestyle factors, coping styles, and HNC symptoms.Results: Among 560 HNC patients, 246 (44%) had poor sleep quality before start of treatment. Several factors were found to be significantly associated with poor sleep: younger age (odds ratio [OR] for each additional year 0.98, 95% CI 0.96-1.00), being female (OR 2.6, 95% CI 1.7-4.1), higher passive coping style (OR 1.18, 95% CI 1.09-1.28), more oral pain (OR 1.10, 95% CI 1.01-1.19), and less sexual interest and enjoyment (OR 1.13, 95% CI 1.06-1.20).Conclusion: Poor sleep quality is highly prevalent among HNC patients before start of treatment. Early evaluation and tailored intervention to improve sleep quality are necessary to prepare these patients for HNC treatment and its consequences. [ABSTRACT FROM AUTHOR]

Introduction: As a result of the increased use of radiotherapy (RT) and improved long-term overall survival of patients with cancers of the head and neck (HN), the frequency of radiation-induced sarcomas of the head and neck (RISHN) may be increasing. The main objective of this systematic review was to determine the existing evidence on the frequency, treatment, and outcome of RISHN.Methods: Using PRISMA guidelines we conducted a systematic review of the literature published from 2000 to 2020.Results: Our review includes data of 560 patients from 64 articles. The total frequency of RISHNs among the reviewed series was 0.15%. The most frequent location of the primary tumor treated by RT was the nasopharynx. The mean RT dose used was 62 Gy, mean latency interval between irradiation and occurrence of RISHN was 11.1 years, and the most common RISHN location was the sinonasal region. Osteosarcoma was the principal histology, followed by fibrosarcoma. Surgery was the most frequently applied treatment modality. Of all patients with RISHN, 40.7% died of this disease after a mean interval of 13.9 months.Conclusions: Notwithstanding the increased use of RT, the number of reported RISHNs has not increased substantially during the past two decades. Surgery with wide margins forms the best therapeutic option for these cases, but the outcome remains poor. [ABSTRACT FROM AUTHOR]

Purpose: Radiotherapy is a frequently applied treatment modality for brain tumors. Concomitant irradiation of normal brain tissue can induce various physiological responses. The aim of this study was to investigate whether acute and early-delayed effects of brain irradiation on glial activation and brain metabolism can be detected with positron emission tomography (PET) and whether these effects are correlated with behavioral changes. Procedures: Rats underwent 0-, 10-, or 25-Gy whole-brain irradiation. At 3 and 31 days post irradiation, 1-(2-chlorophenyl)-N-[11C]methyl-(1-methylpropyl)-3-isoquinoline carboxamide ([11C]PK11195) and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET scans were acquired to detect changes in glial activation (neuroinflammation) and glucose metabolism, respectively. The open-field test (OFT) was performed on days 6 and 27 to assess behavioral changes. Results: Twenty-five-gray-irradiated rats showed higher [11C]PK11195 uptake in most brain regions than controls on day 3 (striatum, hypothalamus, accumbens, septum p < 0.05), although some brain regions had lower uptake (cerebellum, parietal association/retrosplenial visual cortex, frontal association/motor cortex, somatosensory cortex, p < 0.05). On day 31, several brain regions in 25-Gy-irradiated rats still showed significantly higher [11C]PK11195 uptake than controls and 10-Gy-irradiated group (p < 0.05). Within-group analysis showed that [11C]PK11195 uptake in individual brain regions of 25-Gy treated rats remained stable or slightly increased between days 3 and 31. In contrast, a significant reduction (p < 0.05) in tracer uptake between days 3 and 31 was found in all brain areas of controls and 10-Gy-irradiated animals. Moreover, 10-Gy treatment led to a significantly higher [18F]FDG uptake on day 3 (p < 0.05). [18F]FDG uptake decreased between days 3 and 31 in all groups; no significant differences between groups were observed anymore on day 31, except for increased uptake in the hypothalamus in the 10-Gy group. The OFT did not show any significant differences between groups. Conclusions: Non-invasive PET imaging indicated that brain irradiation induces neuroinflammation and a metabolic flare, without causing acute or early-delayed behavioral changes. [ABSTRACT FROM AUTHOR]

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A correction to the article "The course of swallowing problems in the first 2 years after diagnosis of head and neck cancer" is presented which appeared in the previous issue of the periodical.

Purpose: To review the current aspects of knowledge related to the risk of cerebrovascular events in patients receiving head and neck radiotherapy.Methods: A literature search was performed in PubMed. Papers meeting selection criteria were reviewed.Results: We provide an update on the problem by identifying key studies that have contributed to our current understanding of the epidemiology, radiologic features, pathogenesis, and treatment of the disease. The incidence of carotid artery stenosis ranged from 18 to 38% in patients who underwent radiotherapy for head and neck cancer versus from 0 to 9.2% among the nonirradiated patients. Neck irradiation increases the intima-media thickness of the carotid artery wall. These changes are the earliest visible alteration in the carotid wall and are also detected with color Doppler ultrasonography. Endovascular treatment with a carotid angioplasty and stenting is the first-line treatment for most symptomatic patients.Conclusions: Radiation-induced atherosclerosis is a different and accelerated form of atherosclerosis, which implies a more aggressive disease with a different biologic behavior. The disease is characterized by a high rate of carotid artery stenosis compared to those observed in nonirradiated control group patients. To prevent the risk of stroke, surveillance and imaging with ultrasonography should enable detection of severe stenosis. Endovascular treatment with a carotid angioplasty and stenting has been proposed as an attractive and minimally invasive alternative for some radiation-induced stenoses. [ABSTRACT FROM AUTHOR]

Purpose: S-[11C]-methyl-L-cysteine ([11C]MCYS) has been claimed to offer higher tumor selectivity than L-[methyl- 11C]methionine ([11C]MET). We examined this claim in animal models.Procedures: Rats with implanted untreated (n = 10) or irradiated (n = 7, 1 × 25 Gy, on day 8) orthotopic gliomas were scanned after 6, 9, and 12 days, using positron emission tomography. Rats with striatal injections of saline (n = 9) or bacterial lipopolysaccharide (n = 9) were scanned after 3 days.Results: Uptake of the two tracers in untreated gliomas was similar. [11C]MCYS was not accumulated in salivary glands, nasal epithelium, and healing wounds, in contrast to [11C]MET, but showed 40 % higher accumulation in the healthy brain. Both tracers showed a reduced tumor uptake 4 days after irradiation and minor accumulation in inflamed striatum. [11C]MCYS indicated higher lesion volumes than [11C]MET (untreated tumor + 47 %; irradiated tumor up to + 500 %; LPS-inflamed striatum + 240 %).Conclusions: [11C]MCYS was less accumulated in some non-tumor tissues than [11C]MET, but showed lower tumor-to-brain contrast. [ABSTRACT FROM AUTHOR]

Purpose: Intensity-modulated radiation therapy (IMRT) has changed radiation treatment of head and neck cancer (HNC). However, it is still unclear if and how IMRT changes oral morbidity outcomes. In this prospective study, we assessed the outcome of reducing post-IMRT sequelae by means of pre-radiation dental screening and eliminating oral foci.Methods: All consecutive dentate patients > 18 years, diagnosed with primary oral or oropharyngeal carcinoma, referred for pre-treatment dental screening between May 2011 and May 2013, were included and followed for 2 years. Patients were treated with IMRT or IMRT with chemotherapy (CHIMRT). Dental screening data, demographic data, and data on oral sequelae during follow-up were recorded. Diagnosed oral foci were treated before start of the radiation therapy.Results: Oral foci were found in 44/56 (79%) patients, consisting predominantly of periodontal breakdown. Bone healing problems after radiotherapy occurred more often in patients with periodontal pockets ≥ 6 mm at baseline (19 vs. 4% in patients with pockets < 6 mm). Osteoradionecrosis developed in 4/56 patients (7%) during follow-up. In line with this observation, multiple logistic regression analysis showed that the periodontal inflamed surface area, which is higher in patients with more severe periodontal disease, predicted that a patient has a higher risk on developing osteoradionecrosis or bone healing problems (p = 0.028).Conclusions: Patients with severe periodontal disease before IMRT/CHIMRT are more prone to develop bone healing problems post-radiotherapy. [ABSTRACT FROM AUTHOR]

The background and purpose of this paper is to investigate adherence, exercise performance levels and associated factors in head and neck cancer (HNC) patients participating in a guided home-based prophylactic exercise program during and after treatment [swallowing sparing intensity modulated radiation therapy (SW-IMRT)]. Fifty patients were included in the study. Adherence was defined as the percentage of patients who kept up exercising; exercise performance level was categorized as low: ≤1, moderate: 1-2, and high: ≥2 time(s) per day, on average. Associations between 6- and 12-week exercise performance levels and age, gender, tumour site and stage, treatment, intervention format (online or booklet), number of coaching sessions, and baseline HNC symptoms (EORTC-QLQ-H&N35) were investigated. Adherence rate at 6 weeks was 70% and decreased to 38% at 12 weeks. In addition, exercise performance levels decreased over time (during 6 weeks: 34% moderate and 26% high; during 12 weeks: 28% moderate and 18% high). The addition of chemotherapy to SW-IMRT [(C)SW-IMRT] significantly deteriorated exercise performance level. Adherence to a guided home-based prophylactic exercise program was high during (C)SW-IMRT, but dropped afterwards. Exercise performance level was negatively affected by chemotherapy in combination with SW-IMRT. [ABSTRACT FROM AUTHOR]

Introduction: Fibroblast growth factor receptor family member proteins (FGFR1-4) have been identified as promising novel therapeutic targets and prognostic markers in a wide spectrum of solid tumors. The present study investigates the expression and prognostic value of four FGFR family member proteins in a large multicenter oral cavity squamous cell carcinoma (OCSCC) and oropharyngeal squamous cell carcinoma (OPSCC) cohort. Methods: Protein expression of FGFR1-4 was determined by immunohistochemistry on tissue microarrays containing 951 formalin-fixed paraffin embedded OCSCC and OPSCC tissues from the University Medical Center Utrecht and University Medical Center Groningen. Protein expression was correlated to overall survival using Cox regression models, and bootstrapping was performed as internal validation. Results: FGFR proteins were highly expressed in 39-64 % of OCSCC and 63-79 % of OPSCC. Seventy-three percent (299/412) of OCSCC and 85 % (305/357) of OPSCC highly co-expressed two or more FGFR family member proteins. FGFR1 protein was more frequently highly expressed in human papillomavirus (HPV)-negative OPSCC than HPV-positive OPSCC (82 vs. 65 %; p = 0.008). Furthermore, protein expression of FGFR family members was not related to overall survival in OCSCC or OPSCC ( p > 0.05). Conclusion: FGFR family members are frequently highly expressed in OCSCC and OPSCC. These FGFR family member proteins are therefore potential targets for novel therapies that are urgently required to improve survival of OCSCC and OPSCC patients. [ABSTRACT FROM AUTHOR]

The objective of this study is to assess swallowing and speech outcome after chemoradiation therapy for head and neck cancer, based on the patient-reported outcome measures Swallowing Quality of Life Questionnaire (SWAL-QOL) and Speech Handicap Index (SHI), both provided with cut-off scores. This is a cross-sectional study. Department of Otolaryngology/Head and Neck Surgery of a University Medical Center. Sixty patients, 6 months to 5 years after chemoradiation for head and neck squamous cell carcinoma. Swallowing Quality of Life Questionnaire (SWAL-QOL) and SHI, both validated in Dutch and provided with cut-off scores. Associations were tested between the outcome measures and independent variables (age, gender, tumor stage and site, and radiotherapy technique, time since treatment, comorbidity and food intake). Fifty-two patients returned the SWAL-QOL and 47 the SHI (response rate 87 and 78 %, respectively). Swallowing and speech problems were present in 79 and 55 %, respectively. Normal food intake was noticed in 45, 35 % had a soft diet and 20 % tube feeding. Patients with soft diet and tube feeding reported more swallowing problems compared to patients with normal oral intake. Tumor subsite was significantly associated with swallowing outcome (less problems in larynx/hypopharynx compared to oral/oropharynx). Radiation technique was significantly associated with psychosocial speech problems (less problems in patients treated with IMRT). Swallowing and (to a lesser extent) speech problems in daily life are frequently present after chemoradiation therapy for head and neck cancer. Future prospective studies will give more insight into the course of speech and swallowing problems after chemoradiation and into efficacy of new radiation techniques and swallowing and speech rehabilitation programs. [ABSTRACT FROM AUTHOR]

Purpose In left-sided breast cancer radiotherapy, tangential intensity modulated radiotherapy combined with breath-hold enables a dose reduction to the heart and left anterior descending (LAD) coronary artery. Aim of this study was to investigate the added value of intensity modulated proton therapy (IMPT) with regard to decreasing the radiation dose to these structures. Methods In this comparative planning study, four treatment plans were generated in 20 patients: an IMPT plan and a tangential IMRT plan, both with breath-hold and free-breathing. At least 97 % of the target volume had to be covered by at least 95 % of the prescribed dose in all cases. Specifically with respect to the heart, the LAD, and the target volumes, we analyzed the maximum doses, the mean doses, and the volumes receiving 5-30 Gy. Results As compared to IMRT, IMPT resulted in significant dose reductions to the heart and LAD-region even without breath-hold. In the majority of the IMPT cases, a reduction to almost zero to the heart and LAD-region was obtained. IMPT treatment plans yielded the lowest dose to the lungs. Conclusions With IMPT the dose to the heart and LAD-region could be significantly decreased compared to tangential IMRT with breath-hold. The clinical relevance should be assessed individually based on the baseline risk of cardiac complications in combination with the dose to organs at risk. However, as IMPT for breast cancer is currently not widely available, IMPT should be reserved for patients remaining at high risk for major coronary events. [ABSTRACT FROM AUTHOR]

The definitive universally accepted treatment for carotid body tumors (CBT) is surgery. The impact of surgery on cranial nerves and the carotid artery has often been underestimated. Alternatively, a few CBTs have been followed without treatment or irradiation. The goal of this study is to summarize the existing evidence concerning the efficacy and safety of surgery and external beam radiotherapy (EBRT) for CBT. Relevant articles were identified using strict criteria for systematic searches. Sixty-seven articles met the criteria which included 2,175 surgically treated patients. On the other hand, 17 articles including 127 patients treated with EBRT were found. Long-term control of the disease was obtained in 93.8 % of patients who received surgical treatment and in 94.5 % of the radiotherapy group. Surgery resulted in 483 (483/2,175 = 22.2 %) new cranial nerve permanent deficits, whereas in the EBRT group, no new deficits were recorded ( p = 0.004). The common/internal carotid artery was resected in 271 (12.5 %) patients because of injury or tumor encasement, with immediate reconstruction in 212 (9.7 %) patients. Three percent (60) of patients developed a permanent stroke and 1.3 % (26) died due to postoperative complications. The major complications rates and the mortality after completion of the treatment also were significantly higher in surgical series compared to EBRT series. This systematic analysis highlights evidence that EBRT offers a similar chance of tumor control with lower risk of morbidity as compared to surgery in patients with CBT. This questions the traditional notion that surgery should be the mainstay of treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate associations between voice quality and swallowing function in patients treated for oral or oropharyngeal cancer. Methods: Recordings of speech and videofluoroscopy of 51 patients after treatment for oral or oropharyngeal cancer were analysed. Acoustic voice parameters (fundamental frequency (F0), perturbation (jitter %, shimmer %), harmonics-to-noise ratio (HNR), and intensity (extracted from the vowels /a/, /i/, and /u/)) were compared to swallowing function parameters as assessed via videofluoroscopy (oral, oropharyngeal, and total transit time; estimated percent of oral, oropharyngeal, and total residue; oropharyngeal swallowing efficiency (OPSE), and the penetration/aspiration (PA-) scale). Results: Stepwise multivariate regression analyses revealed that jitter, shimmer, and HNR were not associated with swallowing function. Higher voice intensity in all three vowels /a/, /i/, and /u/ was significantly associated with a higher score on the PA-scale (more penetration and aspiration). Higher voice intensity and F0 were significantly associated with lower OPSE. Conclusion: Higher voice intensity was significantly associated with higher amount of penetration/aspiration, and higher voice intensity and fundamental frequency were significantly associated with swallowing inefficiency. Possible explanations may be found in overcompensation by increased laryngeal muscular strength resulting in increased intensity and pitch during phonation. However, the physiology of associated voice and swallowing function is yet unclear, and more research is recommended. [ABSTRACT FROM AUTHOR]

Post-therapy follow-up for patients with head and neck cancer other than upper aerodigestive tract squamous cell carcinoma should meet several objectives: to detect both local, regional or distant recurrences, to evaluate acute and long-term treatment-related side effects, to guide the rehabilitation process, and to provide psychosocial support when needed. To our knowledge, there are no published reports in the literature dedicated to the follow-up of patients with these tumours. A comprehensive literature search for post-treatment follow-up strategies spanning from 1980 to 2012 was performed on several databases. This review focuses on malignant salivary gland tumors, soft tissue sarcomas, cutaneous squamous cell carcinomas, and sinonasal adenocarcinomas. Given the varying biological behavior and treatment-related factors and based on the literature, different recommendations are made on the follow-up of patients with the above-mentioned tumors. [ABSTRACT FROM AUTHOR]

Background: Definitive (chemo)radiotherapy is employed in esophageal cancer patients as an alternative for patients considered medically unfit for surgery or having unresectable tumors. We evaluated a population-based cohort to improve the selection for intensified nonsurgical strategies and to identify prognostic factors. Methods: Patients who had squamous cell carcinoma (SCC) or adenocarcinoma (AC) were treated in four referral centers in the north-east Netherlands with definitive chemoradiotherapy (dCRT) or radiotherapy (dRT) between 1996 and 2008. Results: Of the 287 included patients, 110 were treated with dCRT and 177 with dRT. Median overall survival (OS) was 11 months (95 % confidence interval: 10-12 months), with OS of 22 and 8 % and disease-free survival (DFS) of 16 and 5 % at 2 and 5 years, respectively. DFS at 2 and 5 years was 24 and 9 % for SCC versus 10 and 2 % for AC patients ( P = 0.006). OS after 2 and 5 years was 29 and 14 % for SCC patients versus 17 and 3 % for AC patients ( P = 0.044). On multivariate Cox regression, SCC was an independent prognostic factor for DFS [ P = 0.020, hazard ratio (HR) = 0.71] and OS ( P = 0.047, HR = 0.76). On matched cohort analysis, DFS was higher in the dCRT group compared with dRT patients ( P = 0.016). The locoregional failure rate was lower in the dCRT group and in SCC patients ( P = 0.001 and 0.046). Conclusions: Long-term results and the local control rate in SCC patients were better after definitive (chemo)radiotherapy compared with in AC patients. SCC was an independent prognostic factor for survival. Definitive chemoradiotherapy leads to improved local control rate and DFS. [ABSTRACT FROM AUTHOR]

The management of head and neck squamous cell carcinomas does not end with the completion of ablative therapy. The oncologic objectives of post-treatment follow-up are to detect recurrences and second primary tumors; beyond that, follow-up should evaluate acute and chronic treatment-related side effects, guide the rehabilitation process, alleviate functional loss, manage pain, restore nutritional status and assess psychosocial factors. In this structured review, we address the questions of timing and the tools required to achieve a complete and coherent routine surveillance. Several guidelines and consensus statements recommend clinical examination as the cornerstone of follow-up which should be performed for at least 5 years, although there are no data in favor of any one particular follow-up program, and only low-level evidence suggests an improvement in oncologic outcomes by close follow-up. Baseline imaging (computed tomography and magnetic resonance imaging) should be obtained within 2-6 months after definitive therapy if used for treatment response evaluation. Metabolic response, if indicated, should be assessed preferably after 3 months in patients who undergo curative-intent therapy with (chemo)-radiotherapy. Chest computed tomography is more sensitive than plain radiography, if used in follow-up, but the benefit and cost-effectiveness of routine chest computed tomography has not been demonstrated. There are no current data supporting modifications specific to the surveillance plan of patients with human papillomavirus-associated disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate computerized monitoring of speech and swallowing outcomes and its impact on quality of life (QoL) and emotional well-being in head and neck cancer patients in an outpatient clinic. Methods: Sixty-seven patients, treated by single or multimodality treatment, completed the EORTC QLQ-C30 and QLQ-H&N35 questionnaires and the Hospital Anxiety and Depression Scale in an outpatient clinic, using a touch screen computer system (OncoQuest), at baseline (at time of diagnosis) and first follow-up (1 month after end of treatment). Results: Tumor sites included oral cavity ( n = 12), oropharynx ( n = 18), hypopharynx ( n = 8), and larynx ( n = 29). Tumor stage included carcinoma in situ ( n = 3), stage I ( n = 21), stage II ( n = 7), stage III ( n = 15), and IV ( n = 21). No speech or swallowing problems at baseline or follow-up were noted in 23 % (speech) and 41 % (swallowing) of patients. Twenty-one percent (speech) and 19 % (swallowing) had problems at baseline and returned to normal scores at follow-up, while 16 % (speech) and 19 % (swallowing) had normal scores at baseline and developed problems at follow-up. Forty percent (speech) and 21 % (swallowing) had persistent problems from baseline to follow-up. At baseline, speech problems were significantly related to tumor site and emotional distress. At baseline and follow-up, swallowing problems were significantly related to QoL and emotional distress. At follow-up, speech problems were significantly related to QoL, emotional distress, and swallowing problems. Conclusions: Monitoring speech and swallowing problems through OncoQuest in an outpatient clinic is feasible. Many patients report speech and swallowing problems, negatively affecting their QoL and emotional well-being. [ABSTRACT FROM AUTHOR]

In this prospective cohort study, we assessed voice outcome in patients before and up to 2 years after treatment for early glottic cancer either by radiotherapy or by laser surgery; 106 male patients, treated for T1aN0M0 glottic cancer either by endoscopic laser surgery ( n = 67) or by radiotherapy ( n = 39), participated in the study. Patients' voices were recorded and analysed pre-treatment and 3, 6, 12 and 24 months post-treatment at their routine visit at the outpatient clinic. Average fundamental frequency (F0), percent jitter, percent shimmer and normalized noise energy (NNE) were determined. After 2 years, local control rate was 95% in the radiotherapy group and 97% in the laser surgery group. Larynx preservation rate was 95% after radiotherapy and 100% after laser surgery. Voice outcome recovers more quickly in patients treated with laser surgery in comparison to radiotherapy: 3 months after laser surgery there is no longer a difference with regard to normal voices except for the fundamental frequency, which remains higher pitched, even in the longer term. For patients treated with radiotherapy it takes longer for jitter, shimmer and NNE to become normal, where jitter remains significantly different from normal voices even after 2 years. According to these results, we believe that laser surgery is the first treatment of choice in the treatment of selected cases of T1a glottic carcinomas with good functional and oncological results. [ABSTRACT FROM AUTHOR]

Purpose: F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus can be used to predict treatment outcome is undetermined. Methods: Ten medically inoperable patients with FDG PET-positive lung tumours were included. SBRT consisted of three fractions of 20 Gy delivered at the 80% isodose at days 1, 6 and 11. FDG PET was performed before, on day 6 immediately prior to administration of the second fraction of SBRT and 12 weeks after completion of SBRT. Tumour metabolism was assessed semi-quantitatively using the maximum standardized uptake value (SUV) and SUV. Results: After the first fraction, median SUV increased from 6.7 to 8.1 ( p = 0.07) and median SUV increased from 5.7 to 7.1 ( p = 0.05). At 12 weeks, both median SUV and median SUV decreased by 63% to 3.1 ( p = 0.008) and to 2.5 ( p = 0.008), respectively. Conclusion: SUV increased during treatment, possibly due to radiation-induced inflammation. Therefore, it is unlikely that F-FDG PET during SBRT will predict treatment success. [ABSTRACT FROM AUTHOR]

Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1-T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation. [ABSTRACT FROM AUTHOR]

The purpose was to determine if pre-radiotherapy (RT) and/or post-radiotherapy magnetic resonance (MR) imaging can predict response in patients with laryngeal carcinoma treated with RT. Pre- and post-RT MR examinations of 80 patients were retrospectively reviewed and associated with regard to local control. Pre-RT MR imaging parameters such as tumor involvement of specific laryngeal anatomic subsites including laryngeal cartilages and post-RT changes, i.e., complete resolution of the tumor or focal mass/asymmetric obliteration of laryngeal tissue and signal pattern on T2-weighted images, were evaluated. Local control was defined as absence of a recurrence at the primary site for 2 years. Local control rates based on pretreatment MR findings were 73% for low pre-RT risk-profile and 29% for high pre-RT risk-profile patients (p=0.0001). Based on posttreatment MR findings, local control rates were 100% score 1, 64% score 2, and 4% score 3 (p<0.0001). Using post-RT T2-weighted images, significant association was found between differences in signal pattern and local control: 77% hypointense, 54% isointense and 15% hyperintense lesions (p<0.001). Differences between means of delay of post-MRI examination were significantly associated with regard to local control (p=0.003); recurrent tumors followed 5 months after RT were more easily detectable on MRI than recurrent tumors within 4 months after RT. Sensitivity, specificity, accuracy, negative and positive predictive values of post-RT score 3 were 96%, 76%, 83%, 98% and 66%. Pre- and post-RT MRI evaluation of the larynx can identify patients at high risk for developing local failure. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma may involve the anterior commissure (AC) area of the laryngeal glottis, and can be grouped morphologically into four groups; (1) tumor confined to the AC, (2) tumor involving one cord and the AC, (3) tumor involving the AC and a portion of both vocal cords, and (4) tumor involving a greater part of one cord and crossing over to involve a variable length of the other cord. Some of these patients when evaluated by imaging, either CT and/or MRI, may demonstrate thyroid cartilage erosion or involvement, thereby upstaging a T1a, T1b into a T3 or a T4 glottic cancer. The majority of patients treated by radiotherapy have only been staged clinically, and hence a failure or recurrence rate of 15%. In patients treated surgically by endoscopic or external surgery, the local recurrence rates are similar at 15%. Therefore, future reporting of patients treated with AC involvement should be staged radiologically, to include CT or MRI, and documentation of the treatment results be reported in subgroups, according to whether there is no cartilage involvement, inner-table cartilage erosion, or through-and-through cartilage invasion. Should endoscopic cordectomy be used, then the type of surgery performed should be based on the classification as suggested by the European Laryngological Society. The use of the above recommendations would allow for more meaningful results to be reported and for cause specific analysis of failure of treatment techniques applied. [ABSTRACT FROM AUTHOR]

Persistence or recurrent cancer in the anterior commissure (AC) after primary radiotherapy may remain localized to its pretreatment anatomical site. If so, endoscopic CO2 laser excision, in experienced hands, may achieve complete tumor excision and result in cure for many patients. Occasionally, second and third recurrences may be similarly salvaged by further endoscopic surgery. The use of the vertical hemilaryngectomy is an alternative treatment for similar localized lesions, with a higher first time surgical tumor eradication rate, but with a more protracted hospitalization and a less satisfactory voice and swallowing outcome. In both types of such surgical salvage, CT scanning must demonstrate no evidence of cartilage invasion or destruction. When there is evidence of minimal thyroid cartilage invasion, then the supracricoid partial laryngectomy is an alternative conservation option, and is likely to result in a cure, with the retention of a voicing larynx without a stoma. When the tumor has increased in size from the original pretreatment dimension and/or site, then imaging must be used to identify possible cartilage invasion, in which case the likelihood of tumor eradication by endoscopic or external vertical partial laryngectomy is highly unlikely. The indications for the routine use of total laryngectomy for the treatment of recurrent or persistent cancer involving the AC must be reviewed; there is current evidence that cure can be achieved by a less radical procedure. However, total laryngectomy may remain the only treatment option for advanced or aggressive first time recurrence, or in patients who develop subsequent recurrence following previous less aggressive surgery (endoscopic or external). [ABSTRACT FROM AUTHOR]

We evaluated whether the implementation of a nationwide clinical practice guideline for diagnosis, treatment and follow-up of laryngeal carcinomas led to changes in hospital costs, balanced against clinical changes observed following the guideline’s implementation. Charts of 822 patients with larynx carcinoma (459 treated before the introduction of the guideline and 363 thereafter) in five hospitals were retrospectively investigated. In all phases, no differences in total hospital costs were observed after the guideline’s implementation. Total mean costs were € 3,207 (95%CI 3,091–3,395) for diagnosis, € 3,169 (2,153–4,182), € 5,026 (3,996–6,057), € 6,458 (5,579–7,337), € 8,037 (7,469–8,606), € 12,765 (10,763–14,769), € 19,227 (16,848–21,605) for treatment of dysplasia, carcinoma in situ, T1, T2, T3 and T4 carcinoma, respectively, and € 1,856 (1,491–2,220) for 1 year disease-free follow-up. In an earlier study, we observed several positive changes after the guideline’s implementation. Balanced against the equal costs before and after the guideline’s implementation, we conclude that the efficiency of the care process improved. [ABSTRACT FROM AUTHOR]

Detecting recurrent laryngeal carcinoma after radiotherapy for a primary tumour can be difficult. Early detection however, is an important prognostic factor. Although a biopsy should be performed in case of clinical suspicion, repeated negative biopsies do not exclude the presence of viable tumour. The trauma caused by biopsies in irradiated tissue may initiate infection, further oedema and failure to heal. We investigated these problems and evaluated the current care and its usefulness. A survey of the current practice concerning diagnostic procedures for detecting recurrent laryngeal carcinoma after radiotherapy in the major institutions treating head and neck cancer in The Netherlands was performed by means of a questionnaire. Furthermore, we performed a comprehensive analysis of the extent and yield of diagnostic work-up in a cohort of patients clinically suspected of a recurrence, who had undergone direct laryngoscopy between 1986 and 1998 in our institution, with a follow-up of at least 6 months. In case of suspected recurrence, 94% of the departments use direct laryngoscopy under general anaesthesia with the taking of biopsies as a diagnostic technique. Imaging does not play an important role. In our department 207 laryngoscopies were evaluated in 131 patients. In 70 patients the first laryngoscopy was negative. Of these initial negative laryngoscopies, 22 (31%) turned out to be false negative within 6 months. Thirty-seven patients remained disease free. They underwent 65 unnecessary laryngoscopies to come to this conclusion. In the decision to perform direct laryngoscopy, the conventional work up leaves room for improvement. Too many unnecessary laryngoscopies are performed. New imaging techniques such as FDG-PET or new applications of CT or MRI may improve the yield of direct laryngoscopy. [ABSTRACT FROM AUTHOR]

Idiopathic midline destructive disease is a rare disease, characterized by a progressive ulceration and destruction of midline facial structures. We report a case with localization on the palate for which she received radiotherapy. Later she developed a second localization on the posterior pharyngeal wall for which she was re-irradiated, without severe sequels. Twice a complete regression was observed. [ABSTRACT FROM AUTHOR]

The response of the major salivary glands, the parotid glands, to radiation dose is patient-specific. This study was designed to investigate whether parotid gland changes seen in weekly CT during treatment, quantified by delta-radiomics features (Δfeatures), could improve the prediction of moderate-to-severe xerostomia at 12 months after radiotherapy (Xer12m). Parotid gland Δfeatures were extracted from in total 68 planning and 340 weekly CTs, representing geometric, intensity and texture characteristics. Bootstrapped forward variable selection was performed to identify the best predictors of Xer12m. The predictive contribution of the resulting Δfeatures to a pre-treatment reference model, based on contralateral parotid gland mean dose and baseline xerostomia scores (Xerbaseline) only, was evaluated. Xer12m was reported by 26 (38%) of the 68 patients included. The most predictive Δfeature was the contralateral parotid gland surface change, which was significantly associated with Xer12m for all weeks (p < 0.04), but performed best for week 3 (ΔPG-surfacew3; p < 0.001). Moreover, ∆PG-surfacew3 showed a significant predictive contribution in addition to the pre-treatment reference model (likelihood-ratio test; p = 0.003), resulting in a significantly better model performance (AUCtrain = 0.92; AUCtest = 0.93) compared to that of the pre-treatment model (AUCtrain = 0.82; AUCtest = 0.82). These results suggest that mid-treatment parotid gland changes substantially improve the prediction of late radiation-induced xerostomia. [ABSTRACT FROM AUTHOR]