OBJECTIVE: The purpose of this study was to assess if multicriteria optimization could limit interoperator variability in radiation therapy planning and assess if this method could contribute to target volume coverage and sparing of organ at risk for intensity-modulated curative radiation therapy of head and neck cancers.
METHODS: We performed a retrospective analysis on 20 patients treated for an oropharyngeal or oral cavity squamous cell carcinoma. We carried out a comparative dosimetric study of manual plans produced with Precision® software, compared with the plans proposed using the multicriteria optimization method (RayStation®). We assessed interoperator reproducibility on the first six patients, and dosimetric contribution in sparing organs at risk using the multicriteria optimization method.
RESULTS: Median age was 69 years, most lesions were oropharyngeal carcinoma (65%), and 35% lesions were stage T3. First, we obtained a high degree of similarity between the four operator measurements for each patient at the level of each organ. Intraclass correlation coefficients were greater than 0.85. Second, we observed a significant dosimetric benefit for contralateral parotid gland, homolateral and contralateral masseter muscles, homolateral and contralateral pterygoid muscles and for the larynx (P<0.05). For the contralateral parotid gland, the mean dose difference between the multicriteria optimization and manual plans was -2.0Gy (P=0.01). Regarding the larynx, the mean dose difference between the two plans was -4.6Gy (P<0.001).
CONCLUSIONS: Multicriteria optimization is a reproducible technique and faster than manual optimization. It allows dosimetric advantages on organs at risk, especially for those not usually taken into consideration in manual dosimetry. This may lead to improved quality of life.

The management of head and neck cancers is multidisciplinary, often relying on the use of combined treatments to maximize the chances of cure. Combined treatments are however also responsible for cumulative side effects. The aim of reconstructive surgery with a flap is to restore a function lost with the loss of substance from the tumor resection. However, changes in reconstructive surgery have impact of postoperative radiotherapy planning. The optimization of imaging protocols for radiotherapy planning should make it possible to identify postoperative changes and to distinguish flaps from surrounding native tissues to delineate the flaps and document the spontaneous evolution of these flaps or dose-effect relationships in case of radiotherapy. Such changes include atrophy, fibrosis of soft tissue flaps and osteoradionecrosis of bone flaps. Radiotherapy optimization also involves standardization of the definition of target volumes in situations where a flap is present, a situation that is increasingly common in routine care. This evolution of practice, beyond the essential multidisciplinary consultation meetings defining treatment indications, requires a close radio surgical collaboration with respect to technical aspects of the two disciplines. Doing so, anticipation of relapse and toxicity profiles could possibly lead to propose strategies for personalized de-escalation of multimodal treatments through interdisciplinary trials.

OBJECTIVE: Efforts have been made to reduce epidemiological indicators of osteoradionecrosis in patients with head and neck cancer over recent years. This umbrella review aims to synthesize the information of the systematic reviews/meta-analyses investigating the effect of radiotherapy in patients with head and neck cancer on the frequency of osteoradionecrosis and to identify and analyze the gaps in current scientific literature.
METHODS: A systematic review of systematic reviews with and without meta-analysis of intervention studies was conducted. Qualitative analysis of the reviews and their quality evaluation were performed.
RESULTS: A total of 152 articles were obtained, and ten of them were selected for the final analysis, where six were systematic reviews and four were meta-analysis. According to the guide Assessing the Methodological Quality of Systematic Reviews (Amstar), eight articles included were of high quality and two of medium quality. These descriptive systematic reviews/meta-analyses included a total of 25 randomized clinical trials, showing that radiotherapy has positive effects on the frequency of osteoradionecrosis. Even though a reduction in the incidence of osteoradionecrosis was observed back in the history, in systematic reviews with meta-analysis, overall effect estimators were not significant.
CONCLUSIONS: Differential findings are not enough to demonstrate that there is a significant reduction in the frequency of osteoradionecrosis in patients with head and neck cancer treated by radiation. Possible explanations are related to factors such as the type of studies analyzed, indicator of irradiated complication considered, and specific variables included in the analysis. Many systematic reviews did not address publication bias and did identify gaps in knowledge that require further clarification.

OBJECTIVE: Radiotherapy induces significant and prolonged lymphopenia in head and neck cancer patients with poorer outcomes and reduced survival. Irradiated volumes may be correlated with lymphopenia with a potential impact on immunotherapy efficacy. We assessed associations between volumes treated with radiotherapy and the nadir of the lymphocyte count in patients with head and neck cancer.
METHODS: We conducted a monocentric retrospective study in patients with head and neck cancer treated with radiation. Univariate analysis used regression analysis to model nadir lymphocyte count and radiotherapy volumes; multivariate analysis then modelled factors associated with nadir lymphocyte count.
RESULTS: Of the 77 included patients, 97% presented lymphopenia during radiotherapy with an average nadir of 431 cells/mm3 at a median of 40 days after the beginning of treatment. The volume of high-risk radiotherapy and gross tumour volume were correlated with nadir lymphocyte count with a Spearman coefficient of -0.267 (P=0.019) and -0.387 (P=0.001), respectively. After multivariate linear regression, high-risk radiotherapy was significantly associated with nadir lymphocyte count with a regression coefficient of -0.32 (per cubic centimetre) [95% CI=-0.60; -0.03] (P=0.028).
CONCLUSIONS: High-risk radiotherapy was significantly associated with nadir lymphocyte count in patients with head and neck cancer treated with radiation. Sparing lymphoid volumes from irradiation by elective nodal irradiation or proton therapy may limit lymphopenia and needs to be investigated in combination with immunotherapy.

The aim of the review was to present the current literature status about replanning regarding anatomical and dosimetric changes in the target and OARs in the head and neck region during radiotherapy, to discuss and to analyze factors influencing the decision for adaptive radiotherapy of head and neck cancer patients. Significant progress has been made in head and neck patients\' evaluation and qualification for adapted radiotherapy over the past ten years. Many factors leading to anatomical and dosimetric changes during treatment have been identified. Based on the literature, the most common factors triggering re-plan are weight loss, tumor and nodal changes, and parotid glands shrinkage. The fluctuations in dose distribution in the clinical area are significant predictive factors for patients\' quality of life and the possibility of recovery. It has been shown that re-planning influence clinical outcomes: local control, disease free survival and overall survival. Regarding literature studies, it seems that adaptive radiotherapy would be the most beneficial for tumors of immense volume or those in the nearest proximity of the OARs. All researchers agree that the timing of re-planning is a crucial challenge, and there are still no clear consensus guidelines for time or criteria of re-planning. Nowadays, thanks to significant technological progress, the decision is mostly made based on observation and supported with IGRT verification. Although further research is still needed, adaptive strategies are evolving and now became the state of the art of modern radiotherapy.

OBJECTIVE: To identify from the current literature when is the right time to replan and to assign thresholds for the optimum process of replanning. Nowadays, adaptive radiotherapy (ART) for head and neck cancer plays an exceptional role consisting of an evaluation procedure of the prominent anatomical and dosimetric variations. By performing complex radiotherapy methods, the credibility of the therapeutic result is crucial. Image guided radiotherapy (IGRT) was developed to ensure locoregional control and thus changes that might occur during radiotherapy be dealt with.
METHODS: An electronic research of articles published in PubMed/MEDLINE and Science Direct databases from January 2004 to October 2020 was performed. Among a total of 127 studies assessed for eligibility, 85 articles were ultimately retained for the review.
RESULTS: The most noticeable changes have been reported in the middle fraction of the treatment. Therefore, the suggested optimal time to replan is between the third and the fourth week. Anatomical deviations>1cm in the external contour, average weight loss>10%, violation in the dose coverage of the targets>5%, and violation in the dose of the peripherals were some of the thresholds that are currently used, and which lead to replanning.
CONCLUSIONS: ART may decrease toxicity and improve local-control. Whether it is beneficial or not, depends ultimately on each patient. However, more investigation of the changes should be performed in future prospective studies to obtain more accurate results.

OBJECTIVE: To explore the possibility of revising the spinal cord tolerance dose in Simultaneously Integrated Boost (SIB) intensity modulated treatment plan of locally advanced head and neck (H&N) cancer and assessment of achieved planning gain due to the revision. In SIB regimen, the Organ at Risk (OARs) tolerance dose is equally distributed throughout the treatment. Clinicians have usually considered the spinal cord tolerance to be the same as in conventional technique. However, in SIB fractionation regimen with intensity modulation treatment, the spinal cord may receive a physical dose of 45Gy, with much lesser dose per fraction than 2Gy per fraction. So when the dose of spinal cord is distributed throughout the treatment, the tolerance dose limit of physical dose can be considered higher than the usual conventional dose limits. In this study, an attempt has been made to explore the possibilities of dose escalation and treatment planning benefits while exploiting this \"Window of Opportunity (WoO)\" of increase in spinal cord and Planning Risk Volume (PRV) spinal cord tolerance dose.
METHODS: A total of 12 patients CT data set along with approved structure set of H&N cancer used for treatment planning in. Three independent SIB VMAT plans named as SPC, SPR and SPDE were generated for the 12 patients. First plan (SPC) was generated by considering standard spinal cord tissue constraint of maximum dose of 45Gy and PRV spinal cord maximum dose 50Gy as per QUANTEC summary and second plan (SPR) was generated considering spinal cord tissue constraint of maximum dose 52.50Gy and PRV spinal cord maximum dose 56.35Gy while optimization and dose calculation. The objectives for rest of the Organ at Risk (OAR) were kept same in both the plans during optimization and dose calculation. The SPC plan was copied for creation of third plan (SPDE) in which dose was escalated by increasing dose per fraction for target volumes such that dose to spinal cord reached a maximum dose of 52.50Gy and PRV spinal cord maximum dose of 56.35Gy. In this plan there have been changes to only dose per fraction, however dose optimization and dose calculation have not been performed. Radiobiological parameters TCP and NTCP were also calculated by using indigenously developed software.
RESULTS: Considering the increase of spinal cord tolerance dose as \"window of opportunity\", a sufficient escalation in physical dose, Biological Effective Dose (BED) and Tumor Control Probability (TCP) was observed for all target volumes with acceptable level of NTCP values.
CONCLUSIONS: Sufficient dose escalation and increased in TCP for target volumes or effective planning benefits can be achieved by revising the spinal cord tolerance dose in intensity modulated SIB treatment of locally advanced H&N cancers.

OBJECTIVE: To assess the efficacy and the tolerance of a split course hypofractionated (SCH) radiotherapy (RT) protocol in head and neck cancer (HNC) for eldery and/or unfit patients (pts).
METHODS: Pts with HNC treated by SCH-RT in two institutions were included retrospectively. The main SCH RT regimen was two courses of 30 grays (Gy)/10 fractions separated by 2-4 weeks, without any systemic therapy.
RESULTS: Between February 2012 and January 2019, 75 consecutive patients were analyzed. The median age was 80 years (range: 45.7-98.2) and 53 (70.7%) were men. Sixty-one (81.3%) pts had stage III/IV disease and 54 (72%) had at least two comorbidities. All of them were treated with intensity-modulated radiotherapy. Median follow-up was 10.6 months (range: 3.1-58.3). Local control at 12 and 24 months was 72.8% IC95%[62-85.5] and 51.7% IC95%[38.1-70.1] respectively. Progression free survival (PFS) at 12 and 24 months were 47.7% IC95%[37.4-60.8] and 41% IC95%[15-36.4] respectively, with a median of 11.5 months IC95%[8.9-17]. OS at 12 and 24 months were 60.4% IC95%[50-73.1] and 41% IC95%[30.6-54.9] respectively, with a median of 19.3 months IC95%[11.9-25.8]. Acute and late grade 3 or higher toxicities occurred for 6 (8%) and 3 (4%) pts.
CONCLUSIONS: The present SCH-RT regimen seems effective, well-tolerated and could represent an alternative to palliative strategies for pts deemed unfit for standard exclusive RT.

OBJECTIVE: Flaps are increasingly used during reconstructive surgery of head and neck cancers to improve functional outcomes. There are no guidelines as to whether the whole flap or its anastomotic border should be included in the primary tumour target volume of postoperative radiotherapy to prevent local relapses. Relapse and toxicity rates can increase substantially if the whole flap received full dose. Our aim was to determine whether flaps were included in the primary tumour target volume and to report the patterns of relapse and toxicity.
METHODS: Consecutive patients in 2014 through 2016, with or without a flap, receiving postoperative radiotherapy were selected in a retrospective monocentric control study. Flaps were homogenously delineated blind to treating radiation oncologists using a flap-specific atlas. Tumour recurrence, acute and late toxicity were evaluated using univariate and propensity score analyses.
RESULTS: A hundred patients were included; 54 with a flap. Median flap volume included in the tumour volume was 80.9%. Twelve patients experienced local recurrences: six with a flap, among whom two within their flap (3.7%). Patients with flaps had larger median tumour volumes to be irradiated (25cm3 versus 58cm3, p<0.001) and higher acute/late toxicity rates (p<0.001) even after adjustment on biases (more advanced T stage, oral cavity, active smoking in patients with flaps). Locoregional recurrence and survival rates were similar between patients with/without a flap.
CONCLUSIONS: Recurrences within a flap were rare in this series when including the whole flap body in the 60Gy-clinical target volume but inclusion of the flap in the primary tumour target volume increased toxicity. Multicentric studies are warranted.

OBJECTIVE: To report the results of Botulinum Toxin A (BTA) for radiation-induced head and neck pain.
METHODS: This single-center retrospective study included all the patients treated at our institution with botulinum toxin A injections for radiation-induced head and neck pain between 2006 and 2017. Pain was evaluated by each patient on a visual analogue scale (VAS) (between 0 and 10) before, and 1 month after the injection.
RESULTS: Sixteen patients were included in this series. The mean value of the pain was 8.5 before and 8 after the first injection. The difference was statistically significant (p<0.01). Major response occurred in 15 patients (VAS≤3 after BTA) and complete response in 11 patients (VAS=0 after BTA).
CONCLUSIONS: Botulinum toxin is an effective treatment for radiation-induced head and neck pain.