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Purpose: Little is known about whether baseline health-related quality of life (HRQoL) scores also could predict occurrence radiotherapy-related toxicities, which we aim to assess in this study., Methods: This study analyzed data from 200 patients enrolled in randomized study investigating the utility of HRQoL. HRQOL was assessed at baseline and during follow up using QLQ-C30 questionnaire and major toxicity was considered as adverse event ≥ 3 according to NCI-CTCAE classification. Cox regressions adjusting for clinical and sociodemographic data were used to assess prognostic significance of HRQOL scores., Results: In multivariable analyses adjusted on clinical and sociodemographic data, every 10-point improvement in physical (HR = 0.74), role (HR = 0.87) and social (HR = 0.88) functioning was associated with 24%, 13% and 12% lower hazard of occurrence of major toxicity respectively while every 10 point-increase in dyspnea (HR = and loss appetite was associated with 15% and 16% increased hazard of major toxicity., Conclusion: Certain baseline HRQoL scores were found to be significantly associated with the occurrence of major toxicity., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To evaluate the educational impact on radiation oncology residents in training when introducing an automatic segmentation software in head and neck cancer patients regarding organs at risk (OARs) and prophylactic cervical lymph node level (LNL) volumes. Two cases treated by exclusive intensity-modulated radiotherapy were delineated by an expert radiation oncologist and were considered as reference. Then, these cases were delineated by residents divided into two groups: group 1 (control group), experienced residents delineating manually, group 2 (experimental group), young residents on their first rotation trained with automatic delineation, delineating manually first (M -) and then after using the automatic system (M +). The delineation accuracy was assessed using the Overlap Volume (OV). Regarding the OARs, mean OV was 0.62 (SD = 0.05) for group 1, 0.56 (SD = 0.04) for group 2 M - , and 0.61 (SD = 0.03) for group 2 M + . Mean OV was higher in group 1 compared to group 2 M - (p = 0.01). There was no OV difference between group 1 and group 2 M + (p = 0.67). Mean OV was higher in the group 2 M + compared to group 2 M - (p < 0.003). Regarding LNL, mean OV was 0.53 (SD = 0.06) in group 1, 0.54 (SD = 0.03) in group 2 M - , and 0.58 (SD = 0.04) in group 2 M + . Mean OV was higher in group 2 M + for 11 of the 12 analysed structures compared to group 2 M - (p = 0.016). Prior use of the automatic delineation software reduced the average contouring time per case by 34 to 40%. Prior use of atlas-based automatic segmentation reduces the delineation duration, and provides reliable OARs and LNL delineations., (© 2022. The Author(s) under exclusive licence to American Association for Cancer Education.)

Objectives: Head & Neck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in Head & Neck paragangliomas., Methods: This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed., Results: Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity., Conclusion: IMRT seems an ideal treatment, whether exclusive or post-operative for Head & Neck paragangliomas., Level of Evidence: 3 Laryngoscope, 133:607-614, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Background and Purpose: Major differences exist among proton therapy (PT) centres regarding PT delivery in adult cancer patient. To obtain insight into current practice in Europe, we performed a survey among European PT centres., Materials and Methods: We designed electronic questionnaires for eight tumour sites, focusing on four main topics: 1) indications and patient selection methods; 2) reimbursement; 3) on-going or planned studies, 4) annual number of patients treated with PT., Results: Of 22 centres, 19 (86%) responded. In total, 4233 adult patients are currently treated across Europe annually, of which 46% consists of patients with central nervous system tumours (CNS), 15% head and neck cancer (HNC), 15% prostate, 9% breast, 5% lung, 5% gastrointestinal, 4% lymphoma, 0.3% gynaecological cancers. CNS are treated in all participating centres (n = 19) using PT, HNC in 16 centres, lymphoma in 10 centres, gastrointestinal in 10 centres, breast in 7 centres, prostate in 6 centres, lung in 6 centres, and gynaecological cancers in 3 centres. Reimbursement is provided by national health care systems for the majority of commonly treated tumour sites. Approximately 74% of centres enrol patients for prospective data registration programs. Phase II-III trials are less frequent, due to reimbursement and funding problems. Reasons for not treating certain tumour types with PT are lack of evidence (30%), reimbursement issues (29%) and/or technical limitations (20%)., Conclusion: Across European PT centres, CNS tumours and HNC are the most frequently treated tumour types. Most centres use indication protocols. Lack of evidence for PT and reimbursement issues are the most reported reasons for not treating specific tumour types with PT., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Head and neck reconstructive surgery using a flap is increasingly common. Best practices and outcomes for postoperative radiotherapy (poRT) with flaps have not been specified. We aimed to provide consensus recommendations to assist clinical decision-making highlighting areas of uncertainty in the presence of flaps., Material and Methods: Radiation, medical, and surgical oncologists were assembled from GORTEC and internationally with the Head and Neck Cancer International Group (HNCIG). The consensus-building approach covered 59 topics across four domains: (1) identification of postoperative tissue changes on imaging for flap delineation, (2) understanding of tumor relapse risks and target volume definitions, (3) functional radiation-induced deterioration, (4) feasibility of flap avoidance., Results: Across the 4 domains, international consensus (median score ≥ 7/9) was achieved only for functional deterioration (73.3%); other consensus rates were 55.6% for poRT avoidance of flap structures, 41.2% for flap definition and 11.1% for tumor spread patterns. Radiation-induced flap fibrosis or atrophy and their functional impact was well recognized while flap necrosis was not, suggesting dose-volume adaptation for the former. Flap avoidance was recommended to minimize bone flap osteoradionecrosis but not soft-tissue toxicity. The need for identification (CT planning, fiducials, accurate operative report) and targeting of the junction area at risk between native tissues and flap was well recognized. Experts variably considered flaps as prone to tumor dissemination or not. Discrepancies in rating of 11 items among international reviewing participants are shown., Conclusion: International GORTEC and HNCIG-endorsed recommendations were generated for the management of flaps in head and neck radiotherapy. Considerable knowledge gaps hinder further consensus, in particular with respect to tumor spread patterns., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose of Review: Management of metastatic head and neck squamous cell cancers (HNSCC) can be challenging. This review gives an insight of current treatment options for patients with synchronous metastatic HNSCC and suggests a therapeutic algorithm., Recent Findings: With the rise of novel therapeutic techniques and medications, many treatment options for both locoregional and distant metastatic disease have become available. The evolving paradigm of metastatic disease now integrates the concept of oligometastatic disease. On top of systemic treatments, patients with low metastatic burden can benefit from curative approaches such as local therapies (surgery, radiotherapy) directed to either primary tumour and distant metastasis. However, data integrating these considerations in the management of metastatic HNSCC is still lacking. Based on this algorithm, we can provide a tailored treatment to each patient with synchronous metastatic HNSCC, according to their age, general condition and metastatic burden.

Target volume selection and delineation for both the primary tumor and the lymph nodes are critical steps in the treatment of head and neck tumors with Intensity Modulated Radiation therapy (IMRT). These steps should be based on a probabilistic approach, which is that selection and delineation will be considered as optimal when reaching the best compromise between a too tight volume that could be associated to an unacceptable rate of local recurrence, and a too large volume, which could be associated to an unacceptable rate of treatment morbidity. Failure to do so have been reported to be associated to a higher risk of loco-regional recurrences and/or morbidity after treatment. In this framework, groups of experts proposed sets of guidelines for the radiation oncology community, aiming at standardizing radiotherapy practices of head and neck cancer patients. Although in constant improvement, such guidelines have been shown to translate into more consistent treatment approaches. This review article summarizes the knowledge accumulated over the years on target volume selection and delineation and tries to reconcile the various schools of thoughts on the topic., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Few studies have reported large inter-observer variations in target volume selection and delineation in patients treated with radiotherapy for head and neck squamous cell carcinoma. Consensus guidelines have been published for the neck nodes (see Grégoire et al., 2003, 2014), but such recommendations are lacking for primary tumour delineation. For the latter, two main schools of thoughts are prevailing, one based on geometric expansion of the Gross Tumour Volume (GTV) as promoted by DAHANCA, and the other one based on anatomical expansion of the GTV using compartmentalization of head and neck anatomy., Method: For each anatomic location within the larynx, hypopharynx, oropharynx and oral cavity, and for each T-stage, the DAHANCA proposal has been comprehensively reviewed and edited to include anatomic knowledge into the geometric Clinical Target Volume (CTV) delineation concept. A first proposal was put forward by the leading authors of this publication (VG and CG) and discussed with opinion leaders in head and neck radiation oncology from Europe, Asia, Australia/New Zealand, North America and South America to reach a worldwide consensus., Results: This consensus proposes two CTVs for the primary tumour, the so called CTV-P1 and CVT-P2, corresponding to a high and lower tumour burden, and which should be associated with a high and a lower dose prescription, respectively., Conclusion: Implementation of these guidelines in the daily practice of radiation oncology should contribute to reduce treatment variations from clinicians to clinicians, facilitate the conduct of multi-institutional clinical trials, and contribute to improved care of patients with head and neck carcinoma., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials., Methods: For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival., Findings: Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90-0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3-4·9) and at 10 years of 1·2% (-0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74-0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (-0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05-1·42; p=0·0098), with absolute differences at 5 years of -5·8% (-11·9 to 0·3) and at 10 years of -5·1% (-13·0 to 2·8)., Interpretation: This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested., Funding: Institut National du Cancer; and Ligue Nationale Contre le Cancer., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To analyze the outcome of N3 patients treated with very accelerated radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT) within two phase III trials., Patients and Methods: Data of 179 patients with N3 HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients received either VART: 64.8Gy/3.5weeks or one of the 3 following CRT regimens: Conventional CRT: 70Gy/7weeks+3 cycles carboplatin-5FU; Moderately accelerated CRT: 70Gy/6weeks+2 cycles carboplatin-5FU; Strongly intensified CRT: 64Gy/5weeks+cisplatin (days 2, 16, 30) and 5 FU (days 1-5, 29-33) followed by 2 cycles adjuvant cisplatin-5FU., Results: Median follow-up was 13.3 and 5.2years for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS) was 13.8%. No significant difference was observed between CRT versus VART in terms of OS (hazard ratio [HR]: 0.93, p=0.68), loco-regional progression (HR: 0.70, p=0.13), or distant progression (HR: 0.86, p=0.53). OS was worse for patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p=0.015). In multivariate analysis, the oropharyngeal subsite presented a higher risk of distant metastasis (as first event 46.5% vs 19.2%, p<0.001),). A significant interaction between treatment modalities and subsites has been observed concerning loco-regional and distant failures., Conclusion: The outcome of N3 HNSCC was extremely poor despite treatment intensification and no difference between CRT and VART. Both distant metastases and loco-regional failures remain important treatment challenge., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this project was to define consensus guidelines for delineating organs at risk (OARs) for head and neck radiotherapy for routine daily practice and for research purposes., Methods: Consensus guidelines were formulated based on in-depth discussions of a panel of European, North American, Asian and Australian radiation oncologists., Results: Twenty-five OARs in the head and neck region were defined with a concise description of their main anatomic boundaries. The Supplemental material provides an atlas of the consensus guidelines, projected on 1mm axial slices. The atlas can also be obtained in DICOM-RT format on request., Conclusion: Consensus guidelines for head and neck OAR delineation were defined, aiming to decrease interobserver variability among clinicians and radiotherapy centers., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Introduction: One of the goals of Quality Assurance in Radiotherapy (QART) is to reduce the variability and uncertainties related to treatment planning and beam delivery. The purpose of this study was to assess the outcome impact and cost-effectiveness (CE) of various QART levels for a head and neck (H&N) cancer study., Materials and Methods: QART levels were defined as: basic QART with a dummy run (level 2), level 2 plus prospective Individual Case Reviews (ICRs) for 15% of patients (level 3) and level 2 plus prospective ICRs for all patients (level 4). The follow-up of patients was modeled using a multi-state model with parameters derived from EORTC, TROG and RTOG prospective studies. Individual patient data, linking QART results with outcome, were retrieved from the TROG database. Results for each QART level were expressed as percentage of mortality and local failure at 5 years., Results: Quality-of-life-adjusted and recurrence-free survival increased with increasing QART levels. The increase of all these metrics was more sizeable with an increased QART level from 2 or 3 to 4. The estimated quality-adjusted-life-years (QALYs) for an increase of QART levels of 3-4 and 2-4 were 0.09 and 0.15, respectively. The incremental CE ratio was €5525 and €3659 Euros per QALY for these QART levels. Compared to QART level 2 or 3, level 4 was cost-effective., Conclusions: Increasing QART levels resulted in better patient outcome in this simulated study. The increased complexity of the QART program was also cost-effective., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In 2003, a panel of experts published a set of consensus guidelines for the delineation of the neck node levels in node negative patients (Radiother Oncol, 69: 227-36, 2003). In 2006, these guidelines were extended to include the characteristics of the node positive and the post-operative neck (Radiother Oncol, 79: 15-20, 2006). These guidelines did not fully address all nodal regions and some of the anatomic descriptions were ambiguous, thereby limiting consistent use of the recommendations. In this framework, a task force comprising opinion leaders in the field of head and neck radiation oncology from European, Asian, Australia/New Zealand and North American clinical research organizations was formed to review and update the previously published guidelines on nodal level delineation. Based on the nomenclature proposed by the American Head and Neck Society and the American Academy of Otolaryngology-Head and Neck Surgery, and in alignment with the TNM atlas for lymph nodes in the neck, 10 node groups (some being divided into several levels) were defined with a concise description of their main anatomic boundaries, the normal structures juxtaposed to these nodes, and the main tumor sites at risk for harboring metastases in those levels. Emphasis was placed on those levels not adequately considered previously (or not addressed at all); these included the lower neck (e.g. supraclavicular nodes), the scalp (e.g. retroauricular and occipital nodes), and the face (e.g. buccal and parotid nodes). Lastly, peculiarities pertaining to the node-positive and the post-operative clinical scenarios were also discussed. In conclusion, implementation of these guidelines in the daily practice of radiation oncology should contribute to the reduction of treatment variations from clinician to clinician and facilitate the conduct of multi-institutional clinical trials., (Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Purpose: To propose an automatic atlas-based segmentation framework of the dental structures, called Dentalmaps, and to assess its accuracy and relevance to guide dental care in the context of intensity-modulated radiotherapy., Methods and Materials: A multi-atlas-based segmentation, less sensitive to artifacts than previously published head-and-neck segmentation methods, was used. The manual segmentations of a 21-patient database were first deformed onto the query using nonlinear registrations with the training images and then fused to estimate the consensus segmentation of the query., Results: The framework was evaluated with a leave-one-out protocol. The maximum doses estimated using manual contours were considered as ground truth and compared with the maximum doses estimated using automatic contours. The dose estimation error was within 2-Gy accuracy in 75% of cases (with a median of 0.9 Gy), whereas it was within 2-Gy accuracy in 30% of cases only with the visual estimation method without any contour, which is the routine practice procedure., Conclusions: Dose estimates using this framework were more accurate than visual estimates without dental contour. Dentalmaps represents a useful documentation and communication tool between radiation oncologists and dentists in routine practice. Prospective multicenter assessment is underway on patients extrinsic to the database., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Concomitant chemoradiotherapy and accelerated radiotherapy independently improve outcomes for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC). We aimed to assess the efficacy and safety of a combination of these approaches., Methods: In our open-label phase 3 randomised trial, we enrolled patients with locally advanced, stage III and IV (non-metastatic) HNSCC and an Eastern Cooperative Oncology Group performance status of 0-2. We randomly allocated patients centrally with a computer program (with centre, T stage, N stage, and localisation as minimisation factors) in a 1:1:1 ratio to receive conventional chemoradiotherapy (70 Gy in 7 weeks plus three cycles of 4 days' concomitant carboplatin-fluorouracil), accelerated radiotherapy-chemotherapy (70 Gy in 6 weeks plus two cycles of 5 days' concomitant carboplatin-fluorouracil), or very accelerated radiotherapy alone (64·8 Gy [1·8 Gy twice daily] in 3·5 weeks). The primary endpoint, progression-free survival (PFS), was assessed in all enrolled patients. This trial is completed. The trial is registered with ClinicalTrials.gov, number NCT00828386., Findings: Between Feb 29, 2000, and May 9, 2007, we randomly allocated 279 patients to receive conventional chemoradiotherapy, 280 to accelerated radiotherapy-chemotherapy, and 281 to very accelerated radiotherapy. Median follow-up was 5·2 years (IQR 4·9-6·2); rates of chemotherapy and radiotherapy compliance were good in all groups. Accelerated radiotherapy-chemotherapy offered no PFS benefit compared with conventional chemoradiotherapy (HR 1·02, 95% CI 0·84-1·23; p=0·88) or very accelerated radiotherapy (0·83, 0·69-1·01; p=0·060); conventional chemoradiotherapy improved PFS compared with very accelerated radiotherapy (0·82, 0·67-0·99; p=0·041). 3-year PFS was 37·6% (95% CI 32·1-43·4) after conventional chemoradiotherapy, 34·1% (28·7-39·8) after accelerated radiotherapy-chemotherapy, and 32·2% (27·0-37·9) after very accelerated radiotherapy. More patients in the very accelerated radiotherapy group had RTOG grade 3-4 acute mucosal toxicity (226 [84%] of 268 patients) compared with accelerated radiotherapy-chemotherapy (205 [76%] of 271 patients) or conventional chemoradiotherapy (180 [69%] of 262; p=0·0001). 158 (60%) of 265 patients in the conventional chemoradiotherapy group, 176 (64%) of 276 patients in the accelerated radiotherapy-chemotherapy group, and 190 (70%) of 272 patients in the very accelerated radiotherapy group were intubated with feeding tubes during treatment (p=0·045)., Interpretation: Chemotherapy has a substantial treatment effect given concomitantly with radiotherapy and acceleration of radiotherapy cannot compensate for the absence of chemotherapy. We noted the most favourable outcomes for conventional chemoradiotherapy, suggesting that acceleration of radiotherapy is probably not beneficial in concomitant chemoradiotherapy schedules., Funding: French Ministry of Health., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: This randomized phase III trial investigated the potential benefit of concurrent re-irradiation, fluorouracil and hydroxyurea versus methotrexate for patients treated with palliative intent for recurrent or second primary head and neck squamous cell carcinoma (HNSCC) in previously irradiated area., Patients and Methods: Patients with recurrent HNSCC or a second primary not amenable to curative-intent treatment were randomized to the R-RT arm (concurrent re-irradiation, fluorouracil and hydroxyurea) or to the Ch-T arm (methotrexate). The primary endpoint was overall survival (OS). Due to a very slow accrual, the trial was closed after inclusion of 57 patients., Results: Fifty-seven patients were included. All patients died in the two arms with a maximal follow-up of 5years. Although four complete responses were achieved in R-RT arm, (none in Ch-T arm) re-irradiation did not improve OS compared with methotrexate (23% versus 22% at 1year, NS). Sixteen patients experienced clinical grade ⩾3 late toxicities (>6months), 11 in R-RT arm and five in Ch-T arm., Conclusions: Premature discontinuation of the trial did not allow us to draw firm conclusions. However, there was no suggestion that concurrent re-irradiation, fluorouracil and hydroxyurea improved OS compared to methotrexate alone in patients treated with palliative intent for a recurrent or second primary HNSCC., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

PURPOSE To address the impact of positron emission tomography with [(18)F]fluorodeoxyglucose (PET-FDG) on the initial staging and management of patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS This multicenter, prospective study included 233 patients with newly diagnosed and untreated HNSCC. TNM stage and therapeutic decision were first determined based on the conventional work-up (including physical examination, computed tomography [CT]/magnetic resonance imaging of the head and neck region, and thoracic CT) and sealed in envelope 1. Whole-body PET-FDG was then performed, and subsequent TNM stage and therapeutic decision were written in envelope 2. Changes in TNM stages and in patient management as a result of PET-FDG imaging were recorded. Clinical outcome and histopathology were used as gold standards to validate the TNM stage. Conventional and PET stages were compared using the McNemar test. Results Conventional and PET stage were discordant in 100 (43%) of 233 patients. PET proved to be accurate in 47 patients and inaccurate in 13 patients. TNM status was left unconfirmed in 40 patients because no therapeutic change was expected from the stage difference. Conventional + PET TNM classification (envelope 2) was significantly more accurate than conventional classification (envelope 1; P < .0001, McNemar test). PET-FDG altered the therapeutic plan in 32 (13.7%) of 233 patients. CONCLUSION Adding whole-body PET-FDG to the pretherapeutic conventional staging of HNSCC improved the TNM classification of the disease and altered the management of 13.7% of patients. These findings support the implementation of PET-FDG in the routine imaging work-up of HNSCC.

Purpose: To analyse clinical and dosimetric characteristics with regard to clinical constraints in head and neck cancer patients treated with intensity-modulated radiotherapy (IMRT)., Materials and Methods: Between August 2001 and July 2005, 75 patients with non-metastatic head and neck cancers were treated with IMRT with curative intent. Dose-volume histograms (DVH) drawn up from inverse dosimetry were analysed and compared to the prescription according to the clinical presentation of the disease., Results: For bilateral irradiation, the mean doses delivered to the contralateral and ipsilateral parotid glands were, respectively, 28.1 and 26.3Gy. Dose constraints to the submandibular glands were only respected for the contralateral gland during unilateral irradiation. For tumors located in paranasal sinuses, the maximal dose to the contralateral and ipsilateral optic nerves remained significantly lower than the constraint doses while the constraints for the anterior part of the eyes could not be respected., Conclusions: Significant differences were observed concerning respect of the constraints applied to the parotid or to the submandibular glands for medial tumors. The respect of constraints for the organs at risk critically depends on the location and size of the primary tumor and on the definition of the CTV. The clinical impact has to be further evaluated.

Purpose: To assess the benefit of intensity-modulated radiotherapy (IMRT) compared with conventional RT for the quality of life (QOL) of head and neck cancer survivors., Methods and Materials: Cross-sectional QOL measures (European Organization for Research and Treatment of Cancer QOL questionnaire C30 and head and neck cancer module) were used with a French multicenter cohort of patients cured of head and neck cancer (follow-up > or = 1 year) who had received bilateral neck RT (> or = 45 Gy) as a part of their initial treatment. We compared the QOL mean scores regarding RT modality (conventional RT vs. IMRT). The patients of the two groups were matched (one to one) according to the delay between the end of RT and the timing of the QOL evaluation and the T stage. Each QOL item was divided into two relevant levels of severity: "not severe" (responses, "not at all" and "a little") vs. "severe" (responses "quite a bit" and "very much"). The association between the type of RT and the prevalence of severe symptoms was approximated, through multivariate analysis using the prevalence odds ratio., Results: Two comparable groups (67 pairs) were available. Better scores were observed on the head and neck cancer module QOL questionnaire for the IMRT group, especially for dry mouth and sticky saliva (p < 0.0001). Severe symptoms were more frequent with conventional RT concerning saliva modifications and oral discomfort. The adjusted prevalence odds ratios were 3.17 (p = 0.04) for dry mouth, 3.16 (p = 0.02) for sticky saliva, 3.58 (p = 0.02) for pain in the mouth, 3.35 (p = 0.04) for pain in the jaw, 2.60 (p = 0.02) for difficulties opening the mouth, 2.76 (p = 0.02) for difficulties with swallowing, and 2.68 (p = 0.03) for trouble with eating., Conclusion: The QOL assessment of head and neck cancer survivors demonstrated the benefit of IMRT, particularly in the areas of salivary dysfunction and oral discomfort.

Purpose: To retrospectively analyze a series of mucosal melanoma of the upper aerodigestive tract to determine the prognostic factors and contribute to understanding the role of radiotherapy in the therapeutic strategy., Methods and Materials: Seventy-four patients were analyzed. The most frequent locations were nasal and oral, in 31 patients (41.9%) and 12 patients (16.2%), respectively. Sixty-three patients (85.1%) were in Stage I, 5 (6.8%) in Stage II, and 6 (8.1%) in Stage III. Treatment consisted of surgery in 17 patients (23.0%), surgery and radiotherapy in 42 (56.8%), radiotherapy in 11 (14.9%), and chemo-immunotherapy in 4 (5.4%). Median follow-up was 20 months., Results: Local control at 3 years was 57% after surgery alone and 71% after surgery and radiotherapy. Overall and disease-free survival rates, respectively, were 41% and 31% at 3 years and 14% and 22% at 10 years. After univariate analysis, female gender, melanosis, tumor size

Background: We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer., Methods: After undergoing surgery with curative intent, 167 patients were randomly assigned to receive radiotherapy alone (66 Gy over a period of 6 1/2 weeks) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1, 22, and 43 of the radiotherapy regimen., Results: After a median follow-up of 60 months, the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P=0.04 by the log-rank test; hazard ratio for disease progression, 0.75; 95 percent confidence interval, 0.56 to 0.99), with 5-year Kaplan-Meier estimates of progression-free survival of 47 percent and 36 percent, respectively. The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group (P=0.02 by the log-rank test; hazard ratio for death, 0.70; 95 percent confidence interval, 0.52 to 0.95), with five-year Kaplan-Meier estimates of overall survival of 53 percent and 40 percent, respectively. The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group (P=0.007). The estimated five-year cumulative incidence of local or regional relapses (considering death from other causes as a competing risk) was 31 percent after radiotherapy and 18 percent after combined therapy. Severe (grade 3 or higher) adverse effects were more frequent after combined therapy (41 percent) than after radiotherapy (21 percent, P=0.001); the types of severe mucosal adverse effects were similar in the two groups, as was the incidence of late adverse effects., Conclusions: Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications., (Copyright 2004 Massachusetts Medical Society)

Intensity-modulated radiation therapy (IMRT) for head and neck (HN) tumors refers to a new approach to the whole treatment procedure from patient immobilization to beam delivery. Implementation of IMRT thus requires knowledge of setup uncertainties, adequate selection, and delineation of target volumes based on optimal imaging modalities, appropriate specification, and dose prescription regarding dose-volume constraints and ad hoc quality control of both the clinical and physical aspects of the whole procedure. A large number of issues still need to be resolved and/or further refined, such as the optimal selection and delineation of the target volume, in particular, with the introduction of functional imaging, and a better integration of improved dose distribution into the fractionation strategy. IMRT is associated with a potentially increased incidence of carcinogenesis, although in the HN area this risk is relative to the intrinsic risk of comorbidity and secondary cancer associated with the patient's lifestyle. Currently, the implementation of IMRT into routine clinical practice for HN cancers may not be a straightforward matter and should probably be restricted to selected institutions with adequate resources and experience. This review emphasizes these aspects and provides some recommendations for the future use of IMRT in patients with HN tumors.

Background and Purpose: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies., Materials and Methods: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck., Results and Conclusions: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described.