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Background: Organoids are in vitro three-dimensional structures that can be grown from patient tissue. Head and neck cancer (HNC) is a collective term used for multiple tumor types including squamous cell carcinomas and salivary gland adenocarcinomas., Methods: Organoids were established from HNC patient tumor tissue and characterized using immunohistochemistry and DNA sequencing. Organoids were exposed to chemo- and radiotherapy and a panel of targeted agents. Organoid response was correlated with patient clinical response. CRISPR-Cas9-based gene editing of organoids was applied for biomarker validation., Findings: A HNC biobank consisting of 110 models, including 65 tumor models, was generated. Organoids retained DNA alterations found in HNC. Comparison of organoid and patient response to radiotherapy (primary [n = 6] and adjuvant [n = 15]) indicated potential for guiding treatment options in the adjuvant setting. In organoids, the radio-sensitizing potential of cisplatin and carboplatin could be validated. However, cetuximab conveyed radioprotection in most models. HNC-targeted treatments were tested on 31 models, indicating possible novel treatment options with the potential for treatment stratification in the future. Activating PIK3CA mutations did not predict alpelisib response in organoids. Protein arginine methyltransferase 5 (PRMT5) inhibitors were identified as a potential treatment option for cyclin-dependent kinase inhibitor 2A (CDKN2A) null HNC., Conclusions: Organoids hold potential as a diagnostic tool in personalized medicine for HNC. In vitro organoid response to radiotherapy (RT) showed a trend that mimics clinical response, indicating the predictive potential of patient-derived organoids. Moreover, organoids could be used for biomarker discovery and validation., Funding: This work was funded by Oncode PoC 2018-P0003., Competing Interests: Declaration of interests H.C.’s full disclosure is given at https://www.uu.nl/staff/JCClevers/. H.C. is inventor of several patents related to organoid technology, is a co-founder of Xilis, Inc., and is currently an employee of Roche, Basel. E.D. is inventor on a patent related to head and neck organoid technology. R.M. is currently an employee of Roche Products, Welwyn. S.M.W. holds unrestricted research grants from Bayer, Pfizer, Roche, MSD, Amgen, and AstraZeneca, all paid to the UMCG., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Recurrences remain an important problem in laryngeal squamous cell carcinoma. Little has been described about histological characteristics of the primary laryngeal tumor that may be associated with recurrences. Identifying risk factors for recurrences might help in adapting treatment or follow-up. Using real-life population-based data, we aimed to identify histological features of the primary tumor associated with recurrences and overall survival., Material and Methods: Demographic, clinical and treatment information on all first primary invasive laryngeal tumors diagnosed in 2010-2014 (N = 3705) were extracted from the population-based nationwide Netherlands cancer registry (NCR) and linked to PALGA, the nationwide Dutch pathology registry, to obtain data on histological factors and recurrences. For a random 1502 patients histological information i.e., keratinization, perineural invasion (PNI+), vascular invasion (VI+), growth pattern, degree of differentiation, extracapsular spread (ECS+), cartilage- and bone invasion and extralaryngeal extension, was manually extracted from narrative pathology reports and analyzed for locoregional recurrence and overall survival using cox regression analysis., Results: In total, 299 patients developed a locoregional recurrence and 555 patients died. Keratinization (HR = 0.96 (95%CI: 0.68-1.34) p = 0.79), two or three adverse characteristics (PNI+, VI+, non-cohesive growth) (HR = 1.38 (95% CI: 0.63-3.01) p = 0.42), and ECS+ (HR = 1.38 (95% CI: 0.48-4.02) p = 0.55) were not associated to recurrence. For death, also no significant association was found., Conclusion: In this population-based real-life dataset on laryngeal carcinoma in the Netherlands, histological factors were not associated with locoregional recurrences or overall survival, but future studies should investigate the role of these features in treatment decisions., (© 2022. The Author(s).)

Background: In definitive radiation therapy for head and neck cancer, clinically uninvolved cervical lymph nodes are irradiated with a so-called 'elective dose' in order to achieve control of clinically occult metastases. As a consequence of high-resolution diagnostic imaging, occult tumor volume has significantly decreased in the last decades. Since the elective dose is dependent on occult tumor volume, the currently used elective dose may be higher than necessary. Because bilateral irradiation of the neck contributes to dysphagia, xerostomia and hypothyroidism in a dose dependent way, dose de-escalation to these regions can open a window of opportunity to reduce toxicity and improve quality of life after treatment., Methods: UPGRADE-RT is a multicenter, phase III, single-blinded, randomized controlled trial. Patients to be treated with definitive radiation therapy for a newly diagnosed stage T 2-4  N 0-2  M 0 squamous cell carcinoma of the oropharynx, hypopharynx or larynx are eligible. Exclusion criteria are recurrent disease, oncologic surgery to the head and neck area, concomitant chemotherapy or epidermal growth factor receptor inhibitors. In total, 300 patients will be randomized in a 2:1 ratio to a treatment arm with or without de-escalation of the elective radiation dose and introduction of an intermediate dose-level for selected lymph nodes. Radiation therapy planning FDG-PET/CT-scans will be acquired to guide risk assessment of borderline-sized cervical nodes that can be treated with the intermediate dose level. Treatment will be given with intensity-modulated radiation therapy or volumetric arc therapy with simultaneous-integrated boost using an accelerated fractionation schedule, 33 fractions in 5 weeks. The primary endpoint is 'normalcy of diet' at 1 year after treatment (toxicity). The secondary endpoint is the actuarial rate of recurrence in electively irradiated lymph nodes at 2 years after treatment (safety)., Discussion: The objective of the UPGRADE-RT trial is to investigate whether de-escalation of elective radiation dose and the introduction of an intermediate dose-level for borderline sized lymph nodes in the treatment of head and neck cancer will result in less radiation sequelae and improved quality of life after treatment without compromising the recurrence rate in the electively treated neck., Trial Registration: ClinicalTrials.gov Identifier: NCT02442375 .

Background: Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC) have a better survival than with HPV-negative oropharyngeal SCC. An (18) F-fluorodeoxyglucose positron emission tomography-CT ((18) F-FDG-PET-CT) may also provide prognostic information. We evaluated glycolytic characteristics in HPV-negative and HPV-positive oropharyngeal SCC., Methods: Forty-four patients underwent pretreatment (18) F-FDG-PET-CT. Standardized uptake values (SUVs) and metabolic active tumor volumes (MATVs) were determined for primary tumors. HPV status was determined with p16 immunostaining, followed by high-risk HPV DNA detection on the positive cases., Results: Twenty-seven patients were HPV-positive (61.4%). Median MATV was 2.8 mL (range = 1.6-5.1 mL) for HPV-positive and 6.0 mL (range = 4.4-18.7 mL) for HPV-negative tumors (p < .001). SUV values are volume dependent (partial volume effect), therefore, MATV was included as covariate in multivariate analysis. In this multivariate analysis, the maximum SUV in HPV-positive tumors was 3.9 units lower than in HPV-negative tumors (p = .01)., Conclusion: The (18) F-FDG-PET-CT parameters are lower in HPV-positive than in HPV-negative patients. Low pretreatment SUV values in HPV-positive oropharyngeal SCC may be at least partly explained by HPV-induced tumor changes., (© 2015 Wiley Periodicals, Inc.)

Background: The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma., Methods: Labeling index of Ki-67 (Li Ki-67) in immunohistochemically stained biopsies and the colocalization with carbonic anhydrase IX (CAIX) were related to tumor control and patient survival., Results: On average, node-positive patients had a higher Li Ki-67 (median 14% vs 8%; p < .01). In patients with a high Li Ki-67, the 5-year regional control and metastases-free survival were 79% versus 96% (p < .01) and 71% versus 88% (p = .05) for accelerated radiotherapy and ARCON, respectively. The 5-year local control and disease-specific survival were not significantly different. Patients with low Ki-67 expression had an excellent outcome with accelerated radiotherapy alone., Conclusion: Patients with laryngeal carcinomas with high proliferative activity are at increased risk of regional and distant metastases formation. This risk can be reduced by treatment with ARCON., (© 2014 Wiley Periodicals, Inc.)

Objectives: To assess disease-free survival (DFS) in head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy ([C]RT)., Methods: Pretreatment MR-images of 78 patients were retrospectively studied. Apparent diffusion coefficients (ADC) were calculated with two sets of two b-values: 0-750s/mm(2) (ADC750) and 0-1000s/mm(2) (ADC1000). One observer assessed tumor volume on T1-WI. Two independent observers assessed ADC-values of primary tumor and largest lymph node in two sessions (i.e. without and with including CE-T1WI in image analysis). Interobserver and intersession agreement were assessed with intraclass correlation coefficients (ICC) separately for ADC750 and ADC1000. Lesion volumes and ADC-values were related to DFS using Cox regression analysis., Results: Median follow-up was 18 months. Interobserver ICC was better without than with CE-T1WI (primary tumor: 0.92 and 0.75-0.83, respectively; lymph node: 0.81-0.83 and 0.61-0.64, respectively). Intersession ICC ranged from 0.84 to 0.89. With CE-T1WI, mean ADC-values of primary tumor and lymph node were higher at both b-values than without CE-T1WI (P<0.001). Tumor volume (sensitivity: 73%; specificity: 57%) and lymph node ADC1000 (sensitivity: 71-79%; specificity: 77-79%) were independent significant predictors of DFS without and with including CE-T1WI (P<0.05)., Conclusions: Pretreatment primary tumor volume and lymph node ADC1000 were significant independent predictors of DFS in HNSCC treated with (C)RT. DFS could be predicted from ADC-values acquired without and with including CE-T1WI in image analysis. The inclusion of CE-T1WI did not result in significant improvements in the predictive value of DWI. DWI without including CE-T1WI was highly reproducible., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background and Purpose: To evaluate the course of health-related quality of life (HRQOL) from diagnosis to 2 years 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 1 week before and 6 weeks and 6, 12, 18, and 24 months 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 2 years after CRT is different for survivors compared to non-survivors and is associated with comorbidity and tumor subsite., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Accelerated radiotherapy (AR) improves the poor prognosis associated with epidermal growth factor receptor (EGFR) overexpression frequently seen in head and neck carcinomas. Combining AR with carbogen and nicotinamide (ARCON) counteracts enhanced tumour cell proliferation- and hypoxia-related radioresistance. The purpose of this study was to investigate if EGFR expression levels are associated with response to ARCON in patients with carcinoma of the larynx. Patients (N=272) with advanced stage larynx carcinoma were randomised between AR alone and ARCON. Paraffin-embedded biopsies from these patients were processed for immunohistochemical staining of EGFR. EGFR fraction was quantitated by automated image analysis and related to clinical outcome. A large variation was observed in EGFR fraction between tumours with expression levels ranging from 0 to 0.93 (median fraction 0.4). No difference in 5-year locoregional control was found between low and high EGFR expressing tumours in the AR arm (69% versus 75%), which is in line with the established effect of AR in EGFR overexpressing tumours. There was, however, a significant association in the ARCON arm: patients with low EGFR levels had a better 5-year locoregional control (88% versus 72% p=0.02) and disease-specific survival (92% versus 77% p=0.01). ARCON improved locoregional control relative to AR only in patients with low EGFR expression (hazard ratio (HR) 0.34 p=0.009). In conclusion, only in tumours with a low EGFR fraction, adding hypoxia modification to AR has an additive beneficial effect on outcome. EGFR expression is a predictive biomarker for the selection of patients that will or will not respond to ARCON., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To report the results from a randomized trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen inhalation and nicotinamide (ARCON) in laryngeal cancer., Patients and Methods: Patients with cT2-4 squamous cell laryngeal cancer were randomly assigned to AR (68 Gy within 36 to 38 days) or ARCON. To limit the risk of laryngeal necrosis, ARCON patients received 64 Gy on the laryngeal cartilage. The primary end point was local control. Secondary end points were regional control, larynx preservation, toxicity, disease-free survival, and overall survival. In a translational side study, the hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies., Results: From April 2001 to February 2008, 345 patients were accrued. After a median follow-up of 44 months, local tumor control rate at 5 years was 78% for AR versus 79% for ARCON (P = .80), with larynx preservation rates of 84% and 87%, respectively (P = .48). The 5-year regional control was significantly better with ARCON (93%) compared with AR (86%, P = .04). The improvement in regional control was specifically observed in patients with hypoxic tumors and not in patients with well-oxygenated tumors (100% v 55%, respectively; P = .01). AR and ARCON produced equal levels of toxicity., Conclusion: Despite lack of benefit in local tumor control for advanced laryngeal cancers, a significant gain in regional control rate, with equal levels of toxicity, was observed in favor of ARCON. The poor regional control of patients with hypoxic tumors is specifically countered by ARCON treatment.

Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer., Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported., Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moist desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients., Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: The purpose was to evaluate the contralateral nodal control (CLNC) in postoperative patients with oral and oropharyngeal cancer treated with ipsilateral irradiation of the neck and primary site. Late radiation-induced morbidity was also evaluated., Methods and Materials: The study included 123 patients with well-lateralized squamous cell carcinomas treated with surgery and unilateral postoperative irradiation. Most patients had tumors of the gingiva (41%) or buccal mucosa (21%). The majority of patients underwent surgery of the ipsilateral neck (n = 102 [83%]). The N classification was N0 in 73 cases (59%), N1 or N2a in 23 (19%), and N2b in 27 cases (22%)., Results: Contralateral metastases developed in 7 patients (6%). The 5-year actuarial CLNC was 92%. The number of lymph node metastases was the only significant prognostic factor with regard to CLNC. The 5-year CLNC was 99% in N0 cases, 88% in N1 or N2a cases, and 73% in N2b cases (p = 0.008). Borderline significance (p = 0.06) was found for extranodal spread. Successful salvage could be performed in 71% of patients with contralateral metastases. The prevalence of Grade 2 or higher xerostomia was 2.6% at 5 years., Conclusions: Selected patients with oral or oropharyngeal carcinoma treated with primary surgery and postoperative ipsilateral radiotherapy have a very high CLNC with a high probability of successful salvage in case of contralateral metastases. However, bilateral irradiation should be applied in case of multiple lymph node metastases in the ipsilateral neck, particularly in the presence of extranodal spread. The incidence of radiation-induced morbidity is considerably lower as observed after bilateral irradiation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to compare intensity-modulated radiation therapy (IMRT) and three-dimensional conventional radiotherapy (3D-CRT) with regard to patient-rated xerostomia, Radiation Therapy Oncology Group (RTOG) acute and late xerostomia and health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma (HNSCC)., Methods and Materials: Included were 241 patients with HNSCC treated with bilateral irradiation +/- chemotherapy. Since 2000, all patients treated with HNSCC were included in a program, which prospectively assessed acute and late morbidity according to the RTOG and HRQoL on a routine basis at regular intervals. Before October 2004, all patients were treated with 3D-CRT (N = 150). After clinical implementation in October 2004, 91 patients received IMRT. In this study, the differences regarding RTOG toxicity, xerostomia, and other items of HRQoL were analyzed., Results: The use of IMRT resulted in a significant reduction of the mean dose of the parotid glands (27 Gy vs. 43 Gy (p < 0.001). During radiation, Grade 2 RTOG xerostomia was significantly less with IMRT than with 3D-CRT. At 6 months, the prevalence of patient-rated moderate to severe xerostomia and Grade 2 or higher RTOG xerostomia was significantly lower after IMRT versus 3D-CRT. Treatment with IMRT also had a positive effect on several general and head and neck cancer-specific HRQoL dimensions., Conclusions: IMRT results in a significant reduction of patient- and observer-rated xerostomia, as well as other head and neck symptoms, compared with standard 3D-CRT. These differences translate into a significant improvement of the more general dimensions of HRQoL.

Introduction: Recently, we found that swallowing dysfunction after curative (chemo) radiation (CH) RT has a strong negative impact on health-related quality of life (HRQoL), even more than xerostomia. The purpose of this study was to design a predictive model for swallowing dysfunction after curative radiotherapy or chemoradiation., Materials and Methods: A prospective study was performed including 529 patients with head and neck squamous cell carcinoma (HNSCC) treated with curative (CH) RT. In all patients, acute and late radiation-induced morbidity (RTOG Acute and Late Morbidity Scoring System) was scored prospectively. To design the model univariate and multivariate logistic regression analyses were carried out with grade 2 or higher RTOG swallowing dysfunction at 6 months as the primary (SWALL(6months)) endpoint. The model was validated by comparing the predicted and observed complication rates and by testing if the model also predicted acute dysphagia and late dysphagia at later time points (12, 18 and 24 months)., Results: After univariate and multivariate logistic regression analyses, the following factors turned out to be independent prognostic factors for SWALL(6months): T3-T4, bilateral neck irradiation, weight loss prior to radiation, oropharyngeal and nasopharyngeal tumours, accelerated radiotherapy and concomitant chemoradiation. By summation of the regression coefficients derived from the multivariate model, the Total Dysphagia Risk Score (TDRS) could be calculated. In the logistic regression model, the TDRS was significantly associated with SWALL(6months) ((p<0.001). Subsequently, we defined three risk groups based on the TDRS. The rate of SWALL(6months) was 5%, 24% and 46% in case of low-, intermediate- and high-risk patients, respectively. These observed percentages were within the 95% confidence intervals of the predicted values. The TDRS risk group classification was also significantly associated with acute dysphagia (P<0.001 at all time points) and with late swallowing dysfunction at 12, 18 and 24 months (p<0.001 at all time points)., Conclusion: The TDRS is a simple and validated measure to predict swallowing dysfunction after curative (CH) RT for HNC. This classification system enables identification of patients who may benefit from strategies aiming at prevention of swallowing dysfunction after curative (CH) RT such as preventive swallowing exercises during treatment and/or emerging IMRT techniques aiming at sparing anatomical structures that are involved in swallowing.

Purpose: To investigate the impact of treatment-related toxicity on health-related quality of life (HRQoL) among patients with head and neck squamous cell carcinoma treated with radiotherapy either alone or in combination with chemotherapy or surgery., Patients and Methods: The study sample was composed of 425 disease-free patients. Toxicity was scored according to the European Organisation for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) late radiation-induced morbidity scoring system. HRQoL was assessed using the EORTC Quality of Life Questionnaire C30. These assessments took place at 6, 12, 18, and 24 months after completion of radiotherapy. The analysis was performed using a multivariate analysis of variance., Results: Of the six RTOG scales investigated, two significantly affected self-reported HRQoL, salivary gland (RTOG(xerostomia)) and esophagus/pharynx (RTOG(swallowing)). Although RTOG(xerostomia) was reported most frequently, HRQoL was most affected by RTOG(swallowing), particularly in the first 18 months after completion of radiotherapy., Conclusion: Late radiation-induced toxicity, particularly RTOG(swallowing) and RTOG(xerostomia), has a significant impact on the more general dimensions of HRQoL. These findings suggest that the development of new radiation-induced delivery techniques should not only focus on reduction of the dose to the salivary glands, but also on anatomic structures that are involved in swallowing.

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.

Background and Purpose: In the present study, prognostic values of several CT-based pre-treatment nodal and treatment-related characteristics were evaluated among patients with squamous cell head and neck cancer treated with non-surgical modalities., Patients and Methods: Included were 79 patients with 210 pathological nodes, who underwent primary irradiation or chemoradiation. Several nodal characteristics were assessed on the planning CT scan. In addition, the 3D-dose distribution in the nodes was calculated by the planning system to allow for evaluation of underdosage in the pathological nodes and to correlate these results with control in the neck. Analysis was done on patient level (regional control) and node level (nodal control)., Results: For regional control, total nodal volume and the use of chemotherapy in addition to radiation were significant prognostic factors. For nodal control, also the presence of central necrosis and radiological extranodal spread were of importance. In case of radiotherapy alone, a minimal dose <95% of the prescribed dose was associated with worse control. In case of combined modality treatment, the minimal radiation dose was of less importance., Conclusions: Nodal volume and chemotherapy are the most important prognostic factors to control pathological nodes in the neck. Radiological central necrosis and extranodal growth, nodal volume and chemotherapy were significant prognostic factors for nodal control. Additionally, it appears that regional control in patients treated with primary radiation alone or with chemoradiation in case of a total nodal volume of more than 3.0 cm(3) results in an unacceptable high risk on regional recurrence.

Background and Purpose: In this prospective study, the effect of a second course of primary radiotherapy on locoregional control, survival and toxicity was investigated, in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma (HNSCC) in a previously irradiated area., Patients and Methods: A total of 34 patients with second primary (n=26) or locoregional recurrent (n=8) tumours were treated with a second course of high dose radiotherapy. Patients were selected for re-irradiation in case of inoperable and/or unresectable tumours. In most cases, the target volume for re-irradiation was confined to the gross tumour volume (GTV). No elective radiotherapy was applied in the former high-dose area. A total dose of 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation. The median follow-up period was 32 months., Results: The locoregional control rate after 2 years was 27%. The 3-year overall survival was 22%. The most frequently reported acute side-effect was acute mucositis resulting in swallowing complaints. Pharyngeal and oesophageal late morbidity was also the most important late side-effect. In general, acute and late radiation-induced morbidity remained within acceptable limits., Conclusions: In conclusion, primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity. To improve outcome in terms locoregional control and survival, future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy.

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 > or = 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 > or = 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.

Background and Purpose: To investigate the association between the mean salivary gland and oral cavity dose, with patient-rated moderate and severe xerostomia and sticky saliva., Patients and Methods: One hundred and fifty-seven patients treated with bilateral irradiation for head and neck cancer were included. The parotid and submandibular glands and the oral cavity were delineated on plannings-CT scans. At baseline and 6 and 12 months self-reported xerostomia and sticky saliva were assessed using the EORTC QLQ-H&N35 questionnaire., Results: At 6 months a significant association between the mean parotid (MD(par)) and mean submandibular dose (MD(subm)) and xerostomia was observed (OR - MD(par): 1.17; P=0.002 and OR - MD(subm): 1.08; P = 0.02). Between MD(par) and MD(subm), a significant interaction term was present. No significant association was found with the oral cavity dose. Xerostomia was reversible depending on MD(par) and MD(subm). Considering Sticky saliva, a significant association was found at 6 and 12 months with MD(subm) (OR: 1.03; P < 0.001). The P50 for sticky saliva increased with elapsing time., Conclusions: Both MD(par) and MD(subm) influence the risk of xerostomia in irradiated patients at 6 months. This probability as a function of the mean parotid dose significantly depended on the mean dose in the submandibular glands. Sticky saliva mainly depends on MD(subm).

Purpose: To evaluate the results of primary radiotherapy (RT) for squamous cell carcinoma of the nasal vestibule., Methods and Materials: A total of 56 patients with Stage T1 and T2 tumors (Wang classification) were treated with external beam RT (EBRT) with or without a boost using endocavitary brachytherapy. Of these, 32 were treated with EBRT and an additional boost with intermediate-dose-rate brachytherapy, 15 with EBRT and a boost with high-dose-rate brachytherapy, and 9 with EBRT alone., Results: The local control rate at 2 years was 80%. Most cases could be successfully salvaged with surgery, resulting in an ultimate local control rate of 95%. No statistically significant differences were noted among the different treatment approaches. Of the 56 patients, 12% developed lymph node metastases., Conclusion: Primary RT is an adequate treatment for Stage T1 and T2 squamous cell carcinoma of the nasal vestibule with excellent cosmetic results. The radiation technique used depends on the primary tumor extension and the experience of the treating radiation oncologist. In the case of N0 disease, elective treatment of the regional lymph nodes is not recommended.