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Background: To assess the risk of subclinical neck nodal involvement of levels IB, IV and V for early T-stage, node positive, human papilloma virus (HPV)-related oropharyngeal carcinoma., Material and Methods: We retrospectively identified the patients with clinically positive and un-violated neck that underwent upfront ipsilateral neck dissection for HPV-related oropharyngeal cancer between 1998 and 2010. From the pathology report we extracted the prevalence rate of involvement of each selected level and then estimated the risk that a level that does not contain any node larger than 10 mm at computed tomography (CT) harbors subclinical disease. Predictors of involvement were investigated as well., Results: Ninety-one patients were analyzed. The risk of subclinical disease in both levels IB and V is < 5%, while it is 6.5% (95% CI 3.1-9.9%) for level IV. Level IB subclinical involvement slightly exceeds 5% when 2 + ipsilateral levels besides IB are involved. The risk of occult disease in level IV tends to be < 5% when level III is not involved., Conclusion: These data support the exclusion from the elective nodal volume of level V and level IB but when 2 + other levels are involved. Level IV might also be spared when level III is negative. Clinical implementation within a prospective study is justified.

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.)

Purpose: To prospectively assess predictors of PEG dependence after IMRT with/without concomitant chemotherapy (CHT)., Methods and Materials: One-hundred-seventy-one patients were considered (exclusive RT: 58, RT+CHT: 113; 159/171 treated at a median dose of 70 Gy, 2 Gy/fr). Patients treated with RT+CHT underwent prophylactic PEG insertion; PEG was as needed for the others. A number of clinical factors and dose-volume information concerning oral mucosa (OM), constrictors, masticatory muscles, larynx, esophagus and parotids were available. The 25th/10th percentiles of the duration of PEG dependence were our end-points (respectively 3.3 and 7 months, PEG3/PEG7). Logistic uni and multi-variate (MVA) analyses were performed., Results: Concerning PEG3, the independent predictors at MVA were: CHT/PEG policy (OR: 6.8, p=0.001), V9.5G&#95;OMGy/week (OR: 1.017, p=0.01), larynx V50 (OR: 1.018, p=0.01) and superior constrictor (SC) D&#95;mean (OR: 1.002, p=0.005); the predictive value of the model (AUC) was 0.818 (95% CI: 0.751-0.873). The independent predictors of PEG7 were: larynx V50 (OR: 1.042, p=0.0005) and SC D&#95;mean (OR: 1.003, p=0.02), symptoms at diagnosis (yes vs no, OR: 3.6, p=0.08) and sex (male vs female, OR: 0.25, p=0.07); AUC was 0.897 (95% CI: 0.841-0.939)., Conclusions: OM V9.5 Gy/week and CHT/PEG&#95;policy modulate the risk of early PEG dependence. For longer PEG dependence, larynx V50 (or D&#95;mean) and SC D&#95;mean are highly predictive, suggesting that the fibrosis of constrictors and larynx is the main cause., (Copyright © 2013 Elsevier Ireland 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 define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer., Methods and Materials: 164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist. Ninety-three patients received concomitant chemotherapy (cCHT) and 14 received induction chemotherapy (iCHT). Individual information of the dose received by the oral mucosa (OM) was extracted as absolute cumulative dose-volume histogram (DVH), corrected for the elapsed treatment days and reported as weekly (w) DVH. Patients were seen weekly during treatment, and peak acute toxicity equal to or greater than confluent mucositis at any point during the course of IMRT was considered the endpoint., Results: Overall, 129 patients (78.7%) reached the endpoint. The regions that best discriminated between patients with/without Grade 3+ mucositis were found at 10.1 Gy/w (V10.1) and 21 cc (D21), along the x-axis and y-axis of the OM-wDVH, respectively. On multivariate analysis, D21 (odds ratio [OR] = 1.016, 95% confidence interval [CI], 1.009-1.023, p < 0.001) and cCHT (OR = 4.118, 95% CI, 1.659-10.217, p = 0.002) were the only independent predictors. However, V10.1 and D21 were highly correlated (rho = 0.954, p < 0.001) and mutually interchangeable. cCHT would correspond to 88.4 cGy/w to at least 21 cc of OM., Conclusions: Radiotherapy and chemotherapy act independently in determining acute mucosal toxicity; cCHT increases the risk of mucosal Grade 3 toxicity ≈4 times over radiation therapy alone, and it is equivalent to an extra ≈6.2 Gy to 21 cc of OM over a 7-week course., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To investigate the roles of volumetric modulated arc therapy with SmartArc (VMAT-S), intensity-modulated radiation therapy (IMRT), and helical tomotherapy (HT) for oropharyngeal cancer using a simultaneous integrated boost (SIB) approach., Methods and Materials: Eight patients treated with IMRT were selected at random. Plans were computed for both IMRT and VMAT-S (using Pinnacle TPS for an Elekta Infinity linac) along with HT. A three-dose level prescription was used to deliver 70 Gy, 63 Gy, and 58.1 Gy to regions of macroscopic, microscopic high-risk, and microscopic low-risk disease, respectively. All doses were given in 35 fractions. Comparisons were performed on dose-volume histogram data, monitor units per fraction (MU/fx), and delivery time., Results: VMAT-S target coverage was close to that achieved by IMRT, but inferior to HT. The conformity and homogeneity within the PTV were improved for HT over all strategies. Sparing of the organs at risk (OAR) was achieved with all modalities. VMAT-S (along with HT) shortened delivery time (mean, -38%) and reduced MU/fx (mean, -28%) compared with IMRT., Conclusion: VMAT-S represents an attractive solution because of the shorter delivery time and the lower number of MU/fx compared with IMRT. However, in this complex clinical setting, current VMAT-S does not appear to provide any distinct advantage compared with helical tomotherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Aims and Background: To retrospectively determine acute toxicity and local control in patients with recurrence after definitive radiotherapy for prostate, bladder and rectal carcinoma., Methods: Between September 2009 and March 2010, 4 patients with a prior history of pelvic radiotherapy were treated with helical tomotherapy. The prior course of radiotherapy was given for prostate cancer in 2 patients, bladder carcinoma in 1 patient and rectal carcinoma in 1 patient. The median prescribed dose of the prior course of radiotherapy was 6320 cGy (range, 5000-7600), and the median elapsed time between the first and second course was 17 months (range, 4-73). The total prescribed dose for tomotherapy retreatment was 60 Gy in 3 patients and 50 Gy in 1 patient. Hormone therapy was administered to 2 patients before and during radiation. No patient underwent surgical resection., Results: The cumulative mean dose to the rectum ranged from 3813 to 6058 cGy; cumulative rectal maximum dose to 1 cc ranged from 6475 to 8780 cGy. Regarding the bladder, the cumulative mean dose was between 4384 and 7612 cGy; cumulative maximum dose to 1 cc ranged from 7560 to 9790 cGy. All patients completed the re-irradiation course. Acute genitourinary toxicity (RTOG scale) was grade 0 in 3 patients and grade 1 in 1 patient; acute gastrointestinal toxicity was grade 0 in 3 patients and grade 1 in 1 patient. With a median follow-up of 9 months (range, 7-12), late toxicity was G0 in all patients. Three patients showed partial response with computed tomography or magnetic resonance imaging, and 1 had a PSA decrease., Conclusions: Re-irradiation with helical tomotherapy was well tolerated, with low rates of acute and late toxicity. It can be therefore considered a useful tool to improve local control in patients previously treated with radiotherapy. However, a larger number of patients and a longer follow-up are required to assess retreatment safety.

Purpose: To assess volumetric changes of selected organs at risk (OAR) during intensity-modulated radiotherapy (IMRT) for oropharyngeal carcinoma., Materials and Methods: Twenty-six consecutive patients that were treated with definitive IMRT ± chemotherapy between November 2007 and November 2008 were selected for the present study. As part of an internal quality assurances program, a repeat kilovolt (KV) computed tomography was planned weekly during the 7-week treatment course. On each available scan, a single observer contoured the parotid submandibular, and thyroid glands (PG/SMG/TG), larynx (L), and constrictor, masticatory, and sternocleidomastoid muscles (CM/MM/SCM) as appropriate. The volume at each scan was compared with the one at planning CT in a pair-wise fashion. p values <0.05 after correction for multiple testing were considered significant., Results: A total of 159 scans was obtained during treatment for a total of 185 scans, including the baseline imaging. All OARs showed statistically significant changes over baseline by week 5. At week 7, the PG showed the largest absolute change with an average reduction of ∼10 mL followed by both the SCM and MM (∼-5 mL). The largest (∼-30%) relative change was observed for the salivary glands. L and CM showed a ∼15% increase in volume during treatment., Conclusion: All selected OAR undergo significant volumetric changes during a course of IMRT for oropharyngeal squamous cell carcinoma., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: The aim of this investigation was to evaluate the feasibility of a shortened whole-breast irradiation schedule with a concomitant boost delivered to the tumor bed once-a-week in patients with early breast cancer submitted to conservative surgery., Patients and Methods: Patients with pT1 and pT2 M0 carcinoma of the breast were selected. The basic course consisted of 4600 cGy to the whole breast in 20 fractions, 4 times a week, for 5 weeks. Once a week, a concomitant boost of 120 cGy was delivered to the lumpectomy area., Results: From March 2007 to August 2008, we assessed this radiotherapy schedule in 377 patients. According to the RTOG/EORTC Toxicity Criteria, at treatment completion, 85% of patients showed G0-1, 12% G2 and 3% G3 skin toxicity. At 24 months, late toxicity was G0 in 92%, G1 in 7% and G2 in 1%; cosmesis was excellent or good in 95% of patients. To date, at a median follow-up of 33 months, no patient has yet experienced local relapse., Conclusion: A shortened whole-breast irradiation schedule with a weekly concomitant boost may be an alternative option with acceptable toxicity and excellent cosmesis.

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.)

Purpose: Intensity modulated radiation therapy (IMRT) treatment plan quality depends on the planner's level of experience and the amount of time the planner invests in developing the plan. Planners often unwittingly accept plans when further sparing of the organs at risk (OARs) is possible. The authors propose a method of IMRT treatment plan quality control that helps planners to evaluate the doses of the OARs upon completion of a new plan., Methods: It is achieved by comparing the geometric configurations of the OARs and targets of a new patient with those of prior patients, whose plans are maintained in a database. They introduce the concept of a shape relationship descriptor and, specifically, the overlap volume histogram (OVH) to describe the spatial configuration of an OAR with respect to a target. The OVH provides a way to infer the likely DVHs of the OARs by comparing the relative spatial configurations between patients. A database of prior patients is built to serve as an external reference. At the conclusion of a new plan, planners search through the database and identify related patients by comparing the OAR-target geometric relationships of the new patient with those of prior patients. The treatment plans of these related patients are retrieved from the database and guide planners in determining whether lower doses delivered to the OARs in the new plan are feasible., Results: Preliminary evaluation is promising. In this evaluation, they applied the analysis to the parotid DVHs of 32 prior head-and-neck patients, whose plans are maintained in a database. Each parotid was queried against the other 63 parotids to determine whether a lower dose was possible. The 17 parotids that promised the greatest reduction in D50 (DVH dose at 50% volume) were flagged. These 17 parotids came from 13 patients. The method also indicated that the doses of the other nine parotids of the 13 patients could not be reduced, so they were included in the replanning process as controls. Replanning with an effort to reduce D50 was conducted on these 26 parotids. After replanning, the average reductions for D50 of the 17 flagged parotids and nine unflagged parotids were 6.6 and 1.9 Gy, respectively. These results demonstrate that the quality control method has accurately identified not only the parotids that require dose reductions but also those for which dose reductions are marginal. Originally, 11 of out the 17 flagged parotids did not meet the Radiation Therapy Oncology Group sparing goal of V(30 Gy) < 50%. Replanning reduced them to three. Additionally, PTV coverage and OAR sparing of the original plans were compared to those of the replans by using pairwise Wilcoxon p test. The statistical comparisons show that replanning compromised neither PTV coverage nor OAR sparing., Conclusions: This method provides an effective quality control mechanism for evaluating the DVHs of the OARs. Adoption of such a method will advance the quality of current IMRT planning, providing better treatment plan consistency.