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Introduction: Technological and technical improvements allowed for significant advances in the field of radiation therapy (RT) of head and neck cancer (HNC). Several organ-sparing strategies have been investigated with the objective to decrease acute and long-term adverse effects and, subsequently, to assure a better quality of life in patients affected by HNC. In this context, intensity modulated irradiation and the use of multimodality-imaging could help clinicians to obtain a rapid dose fall off towards surrounding healthy tissues and a better delineation of targets volumes and organs at risk. Areas covered: A literature review was performed with the aim to offer an update on radiation therapy in HNC. Expert commentary: During these last years, radiation oncologists have observed a continuous changing regarding radiation treatment for HNC. The adoption of intensity-modulated RT (IMRT) and the use of multimodality-imaging for tumor volume definition and organs at risk or delineation have improved the clinical outcomes of HNC patients. In the future, a better integration of functional imaging for target volume delineation as well as adaptive delivery strategies will allow to further personalize radiation oncology in HNC. Furthermore, the latest breakthrough technologies, such as magnetic resonance imaging (MRI)-linacs and heavy particles technologies have a great potential to improve treatment-related quality of life in HNC. Future studies are needed to demonstrate the clinical advantages of these new RT technologies in HNC.

Aim: To analyze the impact of 18F-fluorodeoxyglucose-PET/CT (PET/CT) in the radiotherapy (RT) planning strategy in HNC, correlating CT-scan and PET/CT performances., Materials and Methods: Inclusion criteria were: age >18 years old, histologically proven head and neck cancer (HNC), patients candidate to definitive RT ± chemotherapy, stage of disease by means of PET/TC and CT-scan performed at our Cancer Care Center., Results: Sixty patients were analyzed. The following primary tumor sites were investigated: nasopharynx (13%), oropharynx (42%), oral cavity (32%) and larynx non-glottic (13%). Globally, PET/CT findings caused changes on nodal radiation treatment volumes in 10% of all the population of study. Specifically, in 5 cases out of 19 oral cavity tumors (26%), PET/CT detected neck-nodes positive (not detected at CT-scan). These findings have allowed to change the patients management, including PET/CT neck-nodes positive in the high-risk RT volumes., Conclusion: In the RT planning strategy, the present findings support the use of PET/CT to improve upfront regional staging of HNC disease, particularly for oral cavity tumors. Further investigations are advocated to evaluate if this strategy could impact on long-term outcomes in terms of local control and overall survival.

Purpose: The aim of the current analysis was to evaluate the effectiveness and tolerability of rapid onset opioid in a cohort of head and neck cancer (HNC) patients affected by painful mucositis influencing swallowing function during RT ± ChT with definitive or adjuvant intent., Methods: A retrospective analysis was conduct on HNC patients during RT ± ChT that received fentanyl pectin na sal spray (FPNS) for incidental BTP due to painful mucositis 13 min before the main meals. The period of observation has been 90 days starting from the beginning of RT ± ChT., Results: Forty HNC patients with incidental BTP due to painful mucositis treated with FPNS were analyzed. The mean NRS of untreated episodes of BTP was 5.73 ± 1.54 decreasing to 2.25 ± 2.45 with FPNS (median dose 100 mcg). During the pain treatment, the number of meals increased from 2.08 ± 0.35 to 2.868 ± 0.4 (p = 0.000), and the BMI remained stable (from 25.086 ± 3.292 to 25.034 ± 3.090; p = 0.448). The 94.9% of patients was satisfied or very satisfied for the rapidity of the effect, and 97.4% for the easiness and convenience in the use., Conclusions: FPNS showed an acceptable safety activity profile in predictable BTP due to painful mucositis in HNC patients during RT ± ChT. FPNS was also effective in reducing the mucositis sequelae and allowing the completion of RT scheduled scheme. Moreover, patients declared satisfaction in terms of ease of use.

The Jacobian of the deformation field of the registration between images taken during Radiotherapy is a measure of compression/expansion of the voxels within an organ. The Jacobian mean value was applied to investigate possible correlations between parotid deformation and anatomical, clinical and dosimetric parameters. Data of 84 patients were analyzed. Parotid deformation was evaluated through Jacobian maps of images taken at the start and at the end of the treatment. Several clinical, geometrical and dosimetric factors were considered. Correlation between Jacobian mean value and these parameters was assessed through Spearman's test. Univariate and multivariate logistic analyses were performed by considering as the end point the first quartile value of the Jacobian mean value. Parotid dose volume histograms were stratified according to gland deformation, assessing the most predictive dose-volume combination. At multivariate analysis, age (p = 0.02), overlap between tumor volume and parotid gland (p = 0.0006) and the parotid volume receiving more than 10 Gy (p = 0.02) were found as the best independent predictors, by considering Jacobian mean value fist quartile, the parotid volume receiving more than 10 Gy and 40 Gy were found as the most predictive dosimetric parameters. Parotid glands were divided in three different sub-groups (bad-, medium- and good dose volume histogram). The risk to have Jacobian means value lower than first quartile was 39.6% versus 19.6% versus 11.3% in these three groups. By including in the multivariate analysis this "dose volume grouping" parameter, age and bad dose volume histogram were found as the most predictive parameters for large shrinkage. The pattern of parotid deformation may be well predicted by some pre-treatment variables; a bad dose volume histogram seems the most important predictor., (© The Author(s) 2014.)

Objective: Dysphagia remains a side effect influencing the quality of life of patients with head and neck cancer (HNC) after radiotherapy. We evaluated the relationship between planned dose involvement and acute and late dysphagia in patients with HNC treated with intensity-modulated radiation therapy (IMRT), after a recontouring of constrictor muscles (PCs) and the cricopharyngeal muscle (CM)., Methods: Between December 2011 and December 2013, 56 patients with histologically proven HNC were treated with IMRT or volumetric-modulated arc therapy. The PCs and CM were recontoured. Correlations between acute and late toxicity and dosimetric parameters were evaluated. End points were analysed using univariate logistic regression., Results: An increasing risk to develop acute dysphagia was observed when constraints to the middle PCs were not respected [mean dose (Dmean) ≥50 Gy, maximum dose (Dmax) >60 Gy, V50 >70% with a p = 0.05]. The superior PC was not correlated with acute toxicity but only with late dysphagia. The inferior PC was not correlated with dysphagia; for the CM only, Dmax >60 Gy was correlated with acute dysphagia ≥ grade 2., Conclusion: According to our analysis, the superior PC has a major role, being correlated with dysphagia at 3 and 6 months after treatments; the middle PC maintains this correlation only at 3 months from the beginning of radiotherapy, but it does not have influence on late dysphagia. The inferior PC and CM have a minimum impact on swallowing symptoms., Advances in Knowledge: We used recent guidelines to define dose constraints of the PCs and CM. Two results emerge in the present analysis: the superior PC influences late dysphagia, while the middle PC influences acute dysphagia.

Purpose: To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer., Materials and Methods: Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients., Results: A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05)., Conclusions: Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Aims: To investigate dosimetric predictors of voice changes after whole-field intensity-modulated radiotherapy (IMRT)., Materials and Methods: Patients treated with whole-field IMRT for oropharyngeal/unknown primary tumours were selected for the present retrospective study having grossly uninvolved larynx at the time of radiotherapy and at least one follow-up visit. Voice changes were prospectively scored at each follow-up examination according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 scale and self-reported by two items (HN4 and HN10) of the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-HN) questionnaire. Predictors of toxicity were investigated at logistic regression, including various patient and tumour characteristics, as well as individual dosimetric data., Results: With a median follow-up of 18 months (range 3-46 months), peak CTCAE dysphonia was graded as 2 in 13 patients (10.5%), whereas 45 patients (36.3%) reported peak grade 0-1 voice changes according to FACT-HN4. Communication (FACT-HN10) was barely affected. At multivariate analysis, the mean laryngeal dose was an independent predictor of both grade 2 CTCAE dysphonia (odds ratio = 1.10, 95% confidence interval 1.01-1.20, P = 0.025) and grade 0-1 FACT-HN4 voice changes (odds ratio = 1.11, 95% confidence interval 1.04-1.18, P = 0.001). Further stratification optimised by a receiver operating characteristic (ROC) analysis showed that, to minimise the risk of grade 0-1 FACT-HN4 voice changes, the mean dose to the larynx has to be kept ≤ 49.4 Gy., Conclusion: Voice changes after whole-field IMRT are common, but mild, and are strictly correlated to the dose received by the uninvolved larynx; in order to minimise the risk of side-effects, the mean dose to the larynx should be kept ≤ 50 Gy., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: To assess volumetric changes of human papillomavirus (HPV)-related lymph nodes (LN) before, during, and after a course of intensity-modulated radiation therapy (IMRT) ± chemotherapy., Methods: Each "pathologic" LN (≥1 cm) was contoured on the available diagnostic/planning CTs before, during each week, and after treatment., Results: Seventy-nine LNs in 50 patients were identified. Beyond the first week of treatment, 3 patterns of LN change were recorded: consistently shrinking LN (n = 33; 41.8%), inconsistently shrinking LN with temporary enlargement limited to the first week (n = 14; 17.7%), or also during the subsequent weeks (n = 32; 40.5%). Nodal density at planning is highly predictive of group assignment, with a larger mean density for consistently over inconsistently shrinking LNs (p = .009). Also, this grouping predicts the response at the end of treatment., Conclusion: HPV-related LN behavior during IMRT is extremely variable but somewhat predictable on the basis of nodal density at planning., (Copyright © 2012 Wiley Periodicals, Inc.)

Purpose: Measuring parotid density changes in patients treated with IMRT for head-neck cancer (HNC) and assessing correlation with treatment-related parameters., Patients and Materials: Data of 84 patients treated with IMRT for different HNC were pooled from three institutions. Parotid deformation and average Hounsfield number changes (ΔHU) were evaluated through MVCT (with Helical Tomotherapy) or diagnostic kVCT images taken at the treatment start/end. Parotids were delineated in the first image and propagated to the last using a previously validated algorithm based on elastic registration. The correlation between ΔHU and several treatment-related parameters was tested; then, logistic uni- and multi-variate analyses taking "large" ΔHU as end-point were carried out. Due to the better image quality, analyses were repeated considering only kVCT data., Results: ΔHU was negative in 116/168 parotids (69%; for kVCT patients: 72/92, 78%). The average ΔHU was significantly different from zero (-7.3, 0.20-0.25 HU/fraction, p<0.001). Individual ΔHU was highly correlated with parotid deformation both in terms of volume change and mean value of the Jacobian of the deformation field (Jac&#95;mean), and with neck thickness variation; these correlations were much stronger for kVCT data. Logistic analyses considering ΔHU<-11 (quartile value) as the end-point showed a two-variable model including large deformation (Jac&#95;mean<0.68) and initial neck thickness to be the most predictive variables (p<0.0005, AUC=0.683; AUC=0.776 for kVCT); the odd ratio of large vs moderate/small parotid deformation was 3.8 and 8.0 for the whole and the kVCT population respectively., Conclusions: Parotid density reduced in most patients during IMRT and this phenomenon was highly correlated with parotid deformation. The individual assessment of density changes was highly reliable just with diagnostic KvCT. Density changes should be considered as an additional objective measurement of early parotid radiation-induced modifications; further research is warranted., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To propose a method of intensity-modulated radiotherapy (IMRT) planning that generates achievable dose-volume histogram (DVH) objectives using a database containing geometric and dosimetric information of previous patients., Methods and Materials: The overlap volume histogram (OVH) is used to compare the spatial relationships between the organs at risk and targets of a new patient with those of previous patients in a database. From the OVH analysis, the DVH objectives of the new patient were generated from the database and used as the initial planning goals. In a retrospective OVH-assisted planning demonstration, 15 patients were randomly selected from a database containing clinical plans (CPs) of 91 previous head-and-neck patients treated by a three-level IMRT-simultaneous integrated boost technique. OVH-assisted plans (OPs) were planned in a leave-one-out manner by a planner who had no knowledge of CPs. Thus, DVH objectives of an OP were generated from a subdatabase containing the information of the other 90 patients. Those DVH objectives were then used as the initial planning goals in IMRT optimization. Planning efficiency was evaluated by the number of clicks of the "Start Optimization" button in the course of planning. Although the Pinnacle(3) treatment planning system allows planners to interactively adjust the DVH parameters during optimization, planners in our institution have never used this function in planning., Results: The average clicks required for completing the CP and OP was 27.6 and 1.9, respectively (p <.00001); three OPs were finished within a single click. Ten more patient's cord + 4 mm reached the sparing goal D(0.1cc) <44 Gy (p <.0001), where D(0.1cc) represents the dose corresponding to 0.1 cc. For planning target volume uniformity, conformity, and other organ at risk sparing, the OPs were at least comparable with the CPs. Additionally, the averages of D(0.1cc) to the cord + 4 mm decreased by 6.9 Gy (p <.0001); averages of D(0.1cc) to the brainstem decreased by 7.7 Gy (p <.005). The averages of V(30 Gy) to the contralateral parotid decreased by 8.7% (p <.0001), where V(30 Gy) represents the percentage volume corresponding to 30 Gy., Conclusion: The method heralds the possibility of automated IMRT planning., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC)., Materials: Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (DeltaV) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between DeltaVcc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a DeltaVcc/% larger than the median value. Linear models of DeltaV (continuous variable) based on the most predictive variables found at the MVA were developed., Results: Median DeltaVcc/% were 6.95 cc and 26%, respectively. The most predictive independent variables of DeltaVcc at MVA were the initial parotid volume (IPV, OR: 1.100; p=0.0002) and Dmean (OR: 1.059; p=0.038). The main independent predictors of DeltaV% at MVA were age (OR: 0.968; p=0.041) and V40 (OR: 1.0338; p=0.013). DeltaVcc and DeltaV% may be well described by the equations: DeltaVcc=-2.44+0.076 Dmean (Gy)+0.279 IPV (cc) and DeltaV%=34.23+0.192 V40 (%)-0.2203 age (year). The predictive power of the DeltaVcc model is higher than that of the DeltaV% model., Conclusions: IPV/age and Dmean/V40 are the major dosimetric and clinical/anatomic predictors of DeltaVcc and DeltaV%. DeltaVcc and DeltaV% may be well described by bi-linear models including the above-mentioned variables., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)