[Protontherapy : principles, advantages, limitations, indications, perspectives...and some Belgian peculiarities]. / La protonthérapie : principes, avantages, limitations, indications, perspectives...et quelques histoires belges.

Most radiotherapy treatments are nowadays delivered with linear accelerators producing photons. This robust radiation technique improved outstandingly during the last three decades, allowing treatments for most tumoural indications with an exquisite accuracy, a formidable effectiveness, a low toxicity, and a very low cost for the society. Therefore, the reasons for using and developing the more expensive hadron therapy and more particularly proton therapy may seem futile. In the current article targeting the general practitioners readership, we look at the principles of this innovative technique, its inherent advantages and limitations, the current and future indications, the challenges and perspectives for the future. We conclude with an overview of the Belgian landscape in terms of installation, operation, access and reimbursement procedures.

L'essentiel des traitements de radiothérapie sont délivrés à l'aide d'accélérateurs linéaires produisant des photons. La technique est robuste et a connu une évolution fulgurante ces trois dernières décennies, apportant une efficacité redoutable et une extrême précision dans de nombreuses indications tumorales, avec les avantages d'un risque de toxicité réduit et d'un coût sociétal extrêmement faible. Dès lors, quel intérêt y aurait-il à utiliser et développer des traitements de radiothérapie par hadrons, et plus particulièrement par protons, sachant que les coûts d'installation et de production sont, au bas mot, décuplés par rapport aux photons ? Dans cet article destiné en première intention aux praticiens de santé généralistes, nous abordons les principes de fonctionnement, les avantages et limitations inhérents à la technique, les indications actuelles et celles qui se profilent, les défis et perspectives à venir. Nous terminons, enfin, par un tour d'horizon du paysage belge en termes d'installation, de fonctionnement, d'accès et de modalités de remboursement.

Patterns and quality of care for head and neck cancer in Belgium: A population-based study.

OBJECTIVES: We evaluated the quality of care for patients with squamous cell carcinoma (SCC) of the oral cavity, oropharynx, hypopharynx or larynx in Belgium. METHODS: Data of the Belgian Cancer Registry were coupled with health insurance data and hospital discharge data. Quality of care and the association with hospital volume were evaluated based on six quality indicators. RESULTS: Half of the patients were treated with primary radiotherapy, with or without systemic therapy (49.7%) and 38.1% with surgery, with or without (neo)adjuvant therapy. Single-modality treatment was provided to 78.1% of early-disease patients. Of the patients with cN0 disease, 56.4% underwent neck dissection. Postoperative radiotherapy was completed timely in 48.5% of patients. Concomitant chemotherapy was administered to 58.2% of patients <70 years with locally advanced disease. Imaging of the neck after radiotherapy was performed appropriately in 32.7% of patients. Variability between centres was considerable. No clear relationship between hospital volume and results of the individual QIs was observed. CONCLUSIONS: Results show that for the measured QIs, targets are not met and variability between centres is considerable. Through individual feedback, centres are motivated to improve the quality of care for head and neck cancer patients in Belgium.

Feasibility of tongue strength measurements during (chemo)radiotherapy in head and neck cancer patients.

PURPOSE: The aim of this study was to investigate the feasibility of tongue strength measures (TSMs) and the influence of bulb location, sex, and self-perceived pain and mucositis in head and neck cancer (HNC) patients during chemoradiotherapy (CRT). METHODS: Twenty-six newly diagnosed HNC patients treated with CRT performed anterior and posterior maximal isometric tongue pressures by means of the Iowa Oral Performance Instrument (IOPI). The Oral Mucositis Weekly Questionnaire (OMWQ) and a Visual Analogue Scale (VAS) for pain during swallowing were completed weekly from baseline to 1 week post CRT. RESULTS: Feasibility of TSMs during CRT declines significantly from 96 to 100% at baseline to 46% after 6 weeks of CRT. But post-hoc analyses reveal only significant differences in feasibility between baseline and measurements after 4 weeks of treatment. No effect of gender or bulb location was established, but feasibility is influenced by pain and mucositis. CONCLUSIONS: Feasibility of TSMs declines during CRT and is influenced by mucositis and pain. For the majority of subjects, TSMs were feasible within the first 4 weeks, which provides a window of scientific and clinical opportunities in this patient population.

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial.

BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION: Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. FUNDING: Amgen.

Early prediction of response to cetuximab and radiotherapy by FDG-PET/CT for the treatment of a locoregionally advanced squamous cell carcinoma of the hypopharynx.

Cetuximab (CTX) is used for the concurrent treatment with radiotherapy (RT) in squamous cell carcinoma of head and neck (HNSCC). There are no reliable clinical predictive markers of effectiveness of CTX at yet. We describe the clinical case of patient who received a CTX/RT to cure locoregionally advanced hypopharyngeal SCC. 2-Deoxy-2-[(18)F]fluoro-d-glucose positron emission tomography and computed tomography ((18)FDG-PET/CT) was performed before the treatment and repeated 10 days after CTX induction dose. A repeated (18)FDG-PET/CT scan showed dramatic decrease of metabolic parameters. Patient had a complete response after treatment and is still alive and cured after 5 years.

A prospective randomized study comparing two frameless immobilization systems for cranial stereotactic radiotherapy.

Introduction: The Dual Shell Encompass Fibreplast™ System (DS-Encompass) by CQ Medical™ is validated for frameless immobilization in stereotactic brain radiotherapy. An alternative mask model has been proposed with the rear shell replaced by a Moldcare® cushion (M-Encompass). To validate the use of this model in our cranial stereotactic workflow method including HyperArc™, we performed a prospective randomized study comparing inter-and intrafractional motion and patients comfort between both masks. Materials & Methods: A prospective randomized study between DS-Encompass and M-Encompass was conducted involving 60 participants. Stratification between DS-Encompass and M-Encompass was carried out based on the fractionation scheme. Treatment plans were created with HyperArc™. During treatment, surface guidance was used for patient positioning and monitoring. A pre-treatment cone-beam CT (CBCT) was acquired to correct interfractional motion and a post-treatment CBCT was acquired to quantify the intrafractional motion. Patients reported comfort was analyzed with a Likert-scale at the end of the treatment. Unpaired t-tests were conducted to determine the level of significance. Results: No significant difference in interfractional translations is present. A significant difference is revealed in roll-axis rotation, where DS-Encompass allows for smaller deviations. Since interfractional motion can be corrected through daily CBCT-scans and 6D-couch corrections, they are clinically irrelevant. Intrafractional motion does not differ significantly and remains below 0.5 mm and 0.5° for both systems. There is no statistical difference in patient-reported comfort. Conclusion: We conclude that Encompass with Moldcare offers a safe alternative to Duall Shell Encompass for non-coplanar stereotactic brain radiotherapy. There is no significant difference in intrafractional motion nor difference in comfort levels.

Disease Control and Late Toxicity in Adaptive Dose Painting by Numbers Versus Nonadaptive Radiation Therapy for Head and Neck Cancer: A Randomized Controlled Phase 2 Trial.

PURPOSE: Local recurrence remains the main cause of death in stage III-IV nonmetastatic head and neck cancer (HNC), with relapse-prone regions within high 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)-signal gross tumor volume. We investigated if dose escalation within this subvolume combined with a 3-phase treatment adaptation could increase local (LC) and regional (RC) control at equal or minimized radiation-induced toxicity, by comparing adaptive 18F-FDG-PET voxel intensity-based dose painting by numbers (A-DPBN) with nonadaptive standard intensity modulated radiation therapy (S-IMRT). METHODS AND MATERIALS: This 2-center randomized controlled phase 2 trial assigned (1:1) patients to receive A-DPBN or S-IMRT (+/-chemotherapy). Eligibility: nonmetastatic HNC of oral cavity, oro-/hypopharynx, or larynx, needing radio(chemo)therapy; T1-4N0-3 (exception: T1-2N0 glottic); KPS ≥ 70; ≥18 years; and informed consent. PRIMARY OUTCOMES: 1-year LC and RC. The dose prescription for A-DPBN was intercurrently adapted in 2 steps to an absolute dose-volume limit (≤1.75 cm3 can receive >84 Gy and normalized isoeffective dose >96 Gy) as a safety measure during the study course after 4/7 A-DPBN patients developed ≥G3 mucosal ulcers. RESULTS: Ninety-five patients were randomized (A-DPBN, 47; S-IMRT, 48). Median follow-up was 31 months (IQR, 14-48 months); 29 patients died (17 of cancer progression). A-DPBN resulted in superior LC compared with S-IMRT, with 1- and 2-year LC of 91% and 88% versus 78% and 75%, respectively (hazard ratio, 3.13; 95% CI, 1.13-8.71; P = .021). RC and overall survival were comparable between arms, as was overall grade (G) ≥3 late toxicity (36% vs 20%; P = .1). More ≥G3 late mucosal ulcers were observed in active smokers (29% vs 3%; P = .005) and alcohol users (33% vs 13%; P = .02), independent of treatment arm. Similarly, in the A-DPBN arm, significantly more patients who smoked at diagnosis developed ≥G3 (46% vs 12%; P = .005) and ≥G4 (29% vs 8%; P = .048) mucosal ulcers. One arterial blowout occurred after a G5 mucosal toxicity. CONCLUSIONS: A-DPBN resulted in superior 1- and 2-year LC for HNC compared with S-IMRT. This supports further exploration in multicenter phase 3 trials. It will, however, be challenging to recruit a substantial patient sample for such trials, as concerns have arisen regarding the association of late mucosal ulcers when escalating the dose in continuing smokers.

Target volume delineation for radiotherapy of meningiomas: an ANOCEF consensus guideline.

PURPOSE: Radiotherapy is, with surgery, one of the main therapeutic treatment strategies for meningiomas. No prospective study has defined a consensus for the delineation of target volumes for meningioma radiotherapy. Therefore, target volume definition is mainly based on information from retrospective studies that include heterogeneous patient populations. The aim is to describe delineation guidelines for meningioma radiotherapy as an adjuvant or definitive treatment with intensity-modulated radiation therapy and stereotactic radiation therapy techniques. This guideline is based on a consensus endorsed by a multidisciplinary group of brain tumor experts, members of the Association of French-speaking Neuro-oncologists (ANOCEF). MATERIALS AND METHODS: A 3-step procedure was used. First, the steering group carried out a comprehensive review to identify divergent issues on meningiomas target volume delineation. Second, an 84-item web-questionnaire has been developed to precisely define meningioma target volume delineation in the most common clinical situations. Third, experts members of the ANOCEF were requested to answer. The first two rounds were completed online. A third round was carried out by videoconference to allow experts to debate and discuss the remaining uncertain questions. All questions remained in a consensus. RESULTS: Limits of the target volume were defined using visible landmarks on computed tomography and magnetic resonance imaging, considering the pathways of tumor extension. The purpose was to develop clear and precise recommendations on meningiomas target volumes. CONCLUSION: New recommendations for meningiomas delineation based on simple anatomic boundaries are proposed by the ANOCEF. Improvement in uniformity in target volume definition is expected.

Cervical squamous cell carcinoma of unknown primary: Oncological outcomes and prognostic factors.

Background/Objectives: Cervical squamous cell carcinoma of unknown primary (SCCUP) is a rare entity within head and neck cancer and both treatment regimens as well as identified potential predictors for oncological outcomes vary between published series. In this study, we evaluated oncological outcomes and identified potential prognostic factors for outcome. Patients and methods: This retrospective monocentric cohort study includes 82 SCCUP patients diagnosed and treated between January 2000 and June 2021. Overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and locoregional recurrence-free survival (LRFS) were evaluated. The Cox proportional hazards model was used to analyze the prognostic effect of patient and tumor characteristics on oncological outcomes. Results: Five year OS, DSS, DFS and LRFS were respectively 53.9%, 72.2%, 68.9% and 67.3%. The p16 status was evaluated in 55 patients with 40% being p16 positive. On univariable analysis, p16 negative SCCUPs had significantly worse survival and recurrence rates in the presence of clinical extranodal extension (cENE) (OS: p=0.0013, DSS: p=0.0099, DFS: p=0.0164, LRFS: p=0.0099) and radiological extranodal extension (rENE) (OS: p=0.0034, DSS: p=0.0137, DFS: p=0.0167, LRFS: p=0.0100). In p16 positive SCCUP patients, rENE had a significantly negative prognostic effect on DFS (p=0.0345) and LRFS (p=0.0367). Total group multivariate analysis identified rENE as an independent negative predictor for all oncological outcomes. The "number of positive lymph nodes" was a second independent predictor for DSS (p=0.0257) and DFS (p=0.0435). Conclusions: We report favorable oncological outcomes, comparable to previously published results. Although the presence of rENE seems associated with poor oncological outcomes, the differential effect of clinical, radiological and pathological ENE in both p16 positive and negative subgroups remain to be elucidated by further prospective research.

The individual risk of symptomatic radionecrosis after brain metastasis radiosurgery is predicted by a continuous function of the V12Gy.

INTRODUCTION: Brain metastases are frequently treated with stereotactic radiosurgery (SRS). Radionecrosis (RN) is the late side effect in up to 24% of patients, being symptomatic in 8-10%. Fixed values of the radiosurgical volume receiving 12 Gy or more (V12Gy) are used to roughly predict the global risk. The aim of this retrospective study is to fine-tune the model of individual risk prediction for symptomatic radionecrosis and identify modulating factors. MATERIALS AND METHODS: Data of patients treated with SRS for ≤3 BM of solid tumours at CHU-UCL-Namur were retrospectively reviewed. Doses ranging from 15 to 24 Gy were prescribed to the 70% isodose in function of the lesion diameter. Treatment was administered with a stereotactic linear accelerator. Follow-up magnetic resonance imaging was performed 3-monthly for 18 months and 6-monthly thereafter. RN was prospectively diagnosed and confirmed by the tumour board. V12Gy, previous or salvage whole-brain radiotherapy (WBRT), smoking history, diabetes, postoperative SRS, diagnosis-specific graded prognostic assessment score, cerebral lobe location and relative location (superficial versus deep) were retrieved. Univariate and multivariate analyses were performed to assess their predictive values and derive a model. RESULTS: 128 patients with 220 lesions were analysed. The risk of RN was predicted by a continuous function of the V12Gy (p = 0.005). No other factor had a significant impact, particularly WBRT that did not increase the risk. CONCLUSION: The risk of symptomatic RN is predicted on an individual basis by a model in function of the V12Gy and must be confirmed in a prospective study.

Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD.

PURPOSE: The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS: Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS: A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION: The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

Brachytherapy in Belgium in 2018. A national survey of the brachytherapy study group of the Belgian SocieTy for Radiotherapy and Oncology (BeSTRO).

PURPOSE: To explore the current practices patterns and evaluate the actual brachytherapy (BT) resources in Belgium. MATERIAL AND METHODS: In 2019, the Brachytherapy Study Group proposed to conduct a survey on behalf of the Belgian SocieTy of Radiation Oncology (BeSTRO) in order to identify current BT practice patterns. An electronic questionnaire was sent to all primary radiotherapy centers in Belgium. This questionnaire was based on the questionnaire that was used by the Italian Association of Radiation Oncology (AIRO) in 2016, asking for: (a) General information on the Radiation Oncology Centre; (b) BT equipment and human resources; (c) BT procedures; (d) BT assessment (number of patients treated annually, treated sites, and different modalities of treatments). RESULTS: All 24 radiation oncology centers (100% response rate) answered the questionnaire and gave also information on the performance of brachytherapy in their (eventual) satellite centers. Eighteen (18) BT afterloader units were installed and operational in 2018. Thirteen centers mentioned a prostate seed implant program, one center a prostate and eye plaque program and one center only an eye plaque program. Less than 50% of centers have the infrastructure to offer the full-range of BT in their own department. In 2018, 1486 patients received a BT-treatment, 28% of them were treated by prostate seed implant, 8% were treated by eye-(seed) BT and 64% by high dose rate (HDR)/pulsed dose rate (PDR) BT. Forty-five percent of HDR/PDR patients were treated by vaginal dome BT, 22% by intra-uterine BT, 11% by skin BT, 10% by breast BT (almost exclusively in one centre), 8% for benign pathology (keloid) and the remaining 4% were treated for prostate (as a boost or as salvage in one centre), anal, penile, lung or oesophageal cancer. CONCLUSIONS: Belgian radiotherapy departments often perform BT only in a (highly) selected group of pathologies, resulting in a limited number of patients treated by this technique despite the sufficient availability of BT equipment. Modern indications are often not covered, hence patients do not have regular access to recognized treatment options, possibly leading to inferior oncological outcome. BeSTRO will use the results of this survey to stimulate improvements in training, awareness, education, implementation, collaboration and cooperation in the field of brachytherapy.

Individualized Prophylactic Neck Irradiation in Patients with cN0 Head and Neck Cancer Based on Sentinel Lymph Node(s) Identification: Definitive Results of a Prospective Phase 1-2 Study.

PURPOSE: This prospective, nonrandomized, interventional phase 1-2 study investigated the individualization of elective node irradiation in clinically N0 head and neck squamous cell carcinoma by sentinel lymph node (SLN) mapping with single-photon emission computed tomography/computed tomography (SPECT/CT) and its impact on tumor control and radiation-related toxicity. METHODS AND MATERIALS: Forty-four patients with clinically N0 head and neck squamous cell carcinoma treated with definitive (chemo-)radiation therapy were imaged with SPECT/CT after 99mTc nanocolloid injection around the tumor. The neck levels containing up to the 4 hottest SLNs were selected for prophylactic irradiation. A comparative virtual planning was performed with the selection of neck levels based on the current international guidelines. Regional control was monitored as a function of the selected volume. Dosimetric data for the organs at risk were compared between the plans. Normal tissue complication probability (NTCP) rates were derived for xerostomia, dysphagia, and hypothyroidism to predict the clinical benefit and correlated to quality-of-life (QoL) assessments at 6 months. RESULTS: Sixteen percent of patients presented unpredicted lymphatic drainage, and 48% drained unilaterally. The nodal clinical target volume based on lymphoscintigraphy was smaller than the nodal clinical target volume based on international guidelines by a factor of 2 (P < .0001). After a median follow-up of 46 months, only 1 patient experienced a regional relapse in a nonirradiated area. Significant median dose reductions to organs at risk were observed, particularly to contralateral salivary glands in patients with unilateral drainage (14.6-28.1 Gy) and to the thyroid gland in all patients (22.4-48.9 Gy). Median NTCP reductions were observed for xerostomia (0.3% to 13.7%), dysphagia (1.7% to 10.8%), and hypothyroidism (14.0% to 36.1%). QoL at 6 months was improved, particularly in patients irradiated unilaterally. CONCLUSIONS: Neck SLN mapping with SPECT/CT individualizes and reduces the elective nodal target volumes without compromising the regional control. The NTCP rates were reduced and favorable QoL were observed in all patients, particularly in the case of unilateral irradiation.

Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome.

BACKGROUND AND PURPOSE: A multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck carcinoma reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. Here, we report on the long-term follow-up of the secondary endpoint (NCT01812486). MATERIALS AND METHODS: Two hundred patients treated with primary (chemo)radiotherapy (RT) were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose (EQD2) of 50 Gy and the experimental arm, irradiation to PTVelect up to EQD2 of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care, EQD2 70 Gy (PTVhigh). Regional recurrences (RR) were projected on the initial RT planning-CT to identify the recurrence localization. RESULTS: The 5-year (5Y) RR was 14.0% (CI95% 7.9; 21.8) in the 40 Gy arm versus 7.5% (CI95% 3.3; 14.0) in the 50 Gy arm (p = 0.10). Majority of RR in the 40 Gy arm (9/13) were projected in PTVhigh and 2 RR were seen outside the treated RT volume. Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect. The 5Y-overall survival (OS) was 56.5% (CI95% 45.7; 65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0; 59.2) in the 50 Gy arm (p = 0.56). CONCLUSION: At 5-years, no statistically significant differences regarding OS, local recurrence, RR nor distant metastases were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority. However, since in both arms only two RR in the PTVelect were observed, reducing the dose to PTVelect appears safe and should be further investigated.

Evolution of self-perceived swallowing function, tongue strength and swallow-related quality of life during radiotherapy in head and neck cancer patients.

BACKGROUND: Radiation-associated-dysphagia is a serious side effect of radiotherapy (RT) for head and neck cancer (HNC). METHODS: Seventy-six patients had a weekly prospective follow-up from baseline until one week post-RT. Combined mixed model analysis (n = 43) determined the evolution of self-perceived swallowing function, isometric tongue strength (MIP), tongue strength (TS) during swallowing (Pswal), and quality of life (QoL) in these patients during RT. RESULTS: Swallowing deteriorated from the third week on, resulting in an increase of tube dependency from 10% at baseline toward 31% post-RT. Both MIP and Pswal are reduced, with anterior MIP decreasing in 29% of patients and posterior MIP in 17%. Pswal decreases for saliva and a bolus swallow. All QoL subscales except "sleep" were affected during RT. CONCLUSIONS: Self-perceived swallowing function, TS and QoL decrease during RT for HNC. Current findings highlight the need for early monitoring of these parameters.

Radiotherapy induced dermatitis is a strong predictor for late fibrosis in head and neck cancer. The development of a predictive model for late fibrosis.

PURPOSE: To determine if the severity of radiodermatitis at the end of radio(chemo)therapy (R(C)T) for head and neck cancer (HNC) is a predictive factor for late fibrosis of the neck and to find a model to predict neck fibrosis grade⩾2 (fibrosis RTOG2-4) at 6months following R(C)T for HNC. MATERIAL/METHODS: 161 patients were prospectively included. We correlated radiodermatitis at the end of RCT, age, sex, T/N stage, tumor site, concomitant chemotherapy, upfront neck dissection, neo-adjuvant chemotherapy, accelerated RT, smoking, alcohol consumption, HPV status and the dose prescribed to the elective neck with fibrosis RTOG2-4 6months after the end of treatment. RESULTS: Radiodermatitis at the end of R(C)T ⩾grade 3 proved to be associated with the incidence of fibrosis RTOG2-4 at 6months (p<0.01). Furthermore, upfront neck dissection (p<0.01), increasing N stage (p<0.01) and tumor site (p=0.02) are significantly associated in univariate analysis with fibrosis RTOG2-4 at 6months of follow-up. Upfront neck dissection and radiodermatitis grade⩾3 at the end of R(C)T were identified by our multivariate model. Additionally, increasing N stage was selected as an independent predictor variable. The AUC for this model was 0.92. CONCLUSION: A model for the prediction of fibrosis RTOG2-4 following R(C)T for head and neck cancer is presented with an AUC of 0.92. Interestingly, radiodermatitis grade⩾3 at the end of R(C)T is associated with RTOG2-4 fibrosis at 6months.

Recurrence patterns after a decreased dose of 40Gy to the elective treated neck in head and neck cancer.

PURPOSE: To investigate the patterns of regional recurrences with emphasis on recurrences in the electively irradiated lymph node regions after dose de-escalation to 40Gy (EQD2Gy) in head and neck cancer. METHODS AND MATERIALS: Two hundred thirty-three patients treated with radio(chemo)therapy using 40Gy (EQD2Gy) to the elective lymph node regions were included. All regional recurrences were reconstructed and projected on the initial radiotherapy planning Computed Tomography studies to identify the localization of recurrence. Furthermore, patient and treatment characteristics were correlated with the regional recurrences to identify risk factors. RESULTS: The median follow-up in our study was 26months. Overall- and disease-specific survival at 2years were 71.2% (95% CI 65.3-77.1) and 64.2% (95% CI 59.2-69.3), respectively. Local, regional and distant control at 2years was 84.1% (95% CI 79.1-89.2), 89.2% (95% CI 84.3-94.1) and 83.2% (95% CI 76.3-90.1), respectively. Twenty-eight patients experienced a regional recurrence. Fourteen of these patients had a recurrence within the high dose volume (14 of 28). Nine had a recurrence in the electively irradiated lymph node regions (9 of 28) and 5 recurrences occurred outside the target volume. The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. No significant associations could be observed between recurrence in electively irradiated lymph node regions and age, gender, tumor site, stage, or the presence of human papillomavirus in oropharyngeal cancers. CONCLUSIONS: The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. This incidence is comparable to recurrence rates after standard dose of 50Gy, suggesting that lower doses to the elective neck do not result in higher regional recurrences.

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control.

BACKGROUND AND PURPOSE: A multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control. MATERIALS AND METHODS: Two hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2Gy fractions (NID2Gy) of 50Gy in the standard arm and of 40Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24months using the RTOG scoring system. RESULTS: We observed a trend toward less dysphagia at 6months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p=0.01) and 18months (p=0.03). After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40Gy arm vs 14.4% in the 50Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50Gy arm respectively). CONCLUSIONS: In our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18months in the 40Gy arm.

Impact of the type of imaging modality on target volumes delineation and dose distribution in pharyngo-laryngeal squamous cell carcinoma: comparison between pre- and per-treatment studies.

BACKGROUND AND PURPOSE: It has been shown that the use of pre-treatment FDG-PET impacted on the GTV delineation of pharyngo-laryngeal tumors. The goals of this study were to evaluate (1) the impact of FDG-PET GTV on dose distribution, and (2) the impact of per-treatment re-imaging on target volume delineation and dose distribution. MATERIALS AND METHODS: Eighteen patients with squamous cell carcinoma of the oropharynx or larynx/hypopharynx were treated with curative intent by forward planning IMRT. Prior to treatment and on average after a dose of 46 Gy, all patients underwent contrast-enhanced CT, MRI and FDG-PET. After coregistration, GTVs were delineated manually on CT and MRI and automatically on FDG-PET. From these volumes, CTVs and PTVs were derived using consistent guidelines. Planning was performed using conformal radiotherapy. RESULTS: GTVs, CTVs and PTVs based on pre-treatment FDG-PET were significantly smaller than those based on pre-treatment CT. Such difference in target volumes (TV) translated into a significant reduction in the irradiated volumes (reduction of 13 and 18% of the V50 and V95, respectively), Dmean to ipsilateral parotids (30.7 and 38.6% for FDG-PET and CT based plans, respectively) and to controlateral parotids (11.2 and 14.4% for FDG-PET and CT based plans, respectively). TVs based on per-treatment CT or MRI were also significantly smaller compared to those delineated from pre-treatment CT. Volumes delineated with MRI were significantly smaller than those delineated with CT. Due to radiotherapy-induced peri-tumoral inflammation, automatic delineation of FDG-PET GTV could not be performed. Such reductions in TVs translated into a reduction of the irradiated volumes compared to pre-treatment CT planning (reduction for V50 of 19 and 32%, and for V95 of 22 and 40%, for CT and MRI, respectively); Dmean to the ipsilateral parotids were also reduced (ipsilateral parotid Dmean of 20.4% for CT and of 20.1% for MRI compared to 24.7% for pre-treatment CT). CONCLUSIONS: The use of pre-treatment FDG-PET and per-treatment CT or MRI significantly impacts on the delineation of TVs in pharyngo-laryngeal SCC, translating into more normal tissue sparing after conformal radiotherapy planning.