F. Ricchetti

Patient geometry-driven information retrieval for IMRT treatment plan quality control.

PURPOSE Intensity modulated radiation therapy (IMRT) treatment plan quality depends on the planners 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.

SmartArc-Based Volumetric Modulated Arc Therapy for Oropharyngeal Cancer: A Dosimetric Comparison With Both Intensity-Modulated Radiation Therapy and Helical Tomotherapy

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.

Effect of Radiotherapy and Chemotherapy on the Risk of Mucositis During Intensity-Modulated Radiation Therapy for Oropharyngeal Cancer

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.

Volumetric change of selected organs at risk during IMRT for oropharyngeal cancer.

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.

Dose–volume-related dysphagia after constrictor muscles definition in head and neck cancer intensity-modulated radiation treatment

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.

A two-variable linear model of parotid shrinkage during IMRT for head and neck cancer.

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.

Predictors of PEG dependence after IMRT ± chemotherapy for oropharyngeal cancer

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_OMGy/week (OR: 1.017, p=0.01), larynx V50 (OR: 1.018, p=0.01) and superior constrictor (SC) D_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_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_policy modulate the risk of early PEG dependence. For longer PEG dependence, larynx V50 (or D_mean) and SC D_mean are highly predictive, suggesting that the fibrosis of constrictors and larynx is the main cause.

Intensity modulated radiation therapy with simultaneous integrated boost in early breast cancer irradiation. Report of feasibility and preliminary toxicity.

PURPOSE To investigate the feasibility and tolerance in the use of adjuvant intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in patients with a diagnosis of breast cancer after breast-conserving surgery. PATIENTS AND METHODS Between September 2011 to February 2013, 112 women with a diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and simultaneous integrated boost after breast-conserving surgery in our institution. A dose of 50Gy in 25 fractions was prescribed to the whole breast and an additional dose of radiation was prescribed on the tumour bed. A dose prescription of 60Gy in 25 fractions to the tumour bed was used in patients with negative margins after surgery, whereas if the margins were close (<1mm) or positive (without a new surgical resection) a dose of 64Gy was prescribed. All patients were followed with periodic clinical evaluation. Acute and late toxicity were scored using the EORTC/RTOG radiation morbidity score system. Both patient and physician recorded cosmetic outcome evaluation with a subjective judgment scale at the time of scheduled follow-up. RESULTS The median follow-up was 28 months (range 24-40 months). The acute skin grade toxicity during the treatment was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%). No grade 3 or higher acute skin toxicity was observed. At 12 months, skin toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade 0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity or higher was registered. The pretreatment variables correlated with skin grade 2 acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume ≥700cm(3) (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability to develop late skin toxicity (P<0.0001). In the 98% of cases, patients were judged to have a good or excellent cosmetic outcome. The 2-year-overall survival and 2-year-local control were 100%. CONCLUSION These data support the feasibility and safety of IMRT with simultaneous integrated boost in patients with a diagnosis of early breast cancer following breast-conserving surgery with acceptable acute and late treatment-related toxicity. A longer follow-up is needed to define the efficacy on outcomes.

Pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy

OBJECTIVE To describe the pattern and predictors of volumetric change of parotid glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer. METHODS A cohort of patients undergoing weekly CT scans during dose-painted IMRT was considered. The parotid glands were contoured at the time of treatment planning (baseline) and on all subsequent scans. For a given patient, the parotid glands were labelled as higher (H) and lower (L), based on the mean dose at planning. The volume of each gland was determined for each scan and the percent change from baseline computed. Data were fit to both linear and quadratic functions. The role of selected covariates was assessed with both logistic regression and pair-wise comparison between the sides. The analyses were performed considering the whole treatment duration or each separate half. RESULTS 85 patients, 170 glands and 565 scans were analysed. For all parotids except one, the quadratic function provided a better fit than the linear one. Moreover, according to both the logistic regression and pair-wise comparison, the cumulative mean dose of radiation is independently correlated with the parotid shrinkage during the first but not the second half of the treatment. Conversely, age and weight loss are predictors of relative parotid shrinkage during the entire course of the treatment. CONCLUSION Parotid gland shrinkage during IMRT is not linear. Age, weight loss and radiation dose independently predict parotid shrinkage during a course of IMRT. ADVANCES IN KNOWLEDGE The present study adds to the pathophysiology of parotid shrinkage during radiotherapy.

Predictors of mucositis in oropharyngeal and oral cavity cancer in patients treated with volumetric modulated radiation treatment: A dose–volume analysis

The purpose of this study was to assess predictors of mucositis in oropharyngeal and oral cavity cancer after definitive or adjuvant volumetric modulated arc radiotherapy (VMAT) +/− chemotherapy.