Neck Intensity-modulated Radiation Therapy Research Articles

A reinforcement learning agent for head and neck intensity-modulated radiation therapy

Head and neck (HN) cancers pose a difficult problem in the planning of intensity-modulated radiation therapy (IMRT) treatment. The primary tumor can be large and asymmetrical, and multiple organs at risk (OARs) with varying dose-sparing goals lie close to the target volume. Currently, there is no systematic way of automating the generation of IMRT plans, and the manual options face planning quality and long planning time challenges. In this article, we present a reinforcement learning (RL) model for the purposes of providing automated treatment planning to reduce clinical workflow time as well as providing a better starting point for human planners to modify and build upon. Several models with progressing complexity are presented, including the relevant plan dosimetry analysis and model interpretations of the resulting strategies learned by the auto-planning agent. Models were trained on a set of 40 patients and validated on a set of 20 patients. The presented models are shown to be consistent with the requirements of an RL model to be underpinned by a Markov decision process (MDP). In-depth interpretability of the models is presented by examination of the decision space using action hyperplanes. The auto-planning agent was able to generate plans with superior reduction in the mean dose of the left and right parotid glands by approximately 7 Gy ± 2.5 Gy (p < 0.01) over a starting, static template plan with only pre-defined general prescription information. RL plans were comparable to a human expert’s clinical plans for the primary (44 Gy), boost (26 Gy) , and the summed plans (70 Gy) with p-values of 0.43, 0.72, and 0.67, respectively, for the dosimetric endpoints and uniform target coverage normalization. The RL planning agent was able to produce the plans used in validation in an average of 13.58 min, with a minimum and a maximum planning time of 2.27 and 44.82 min, respectively.

Changes in periapical status of root canal-treated teeth after head and neck IMRT: a retrospective study.

The objective of this retrospective study was to analyze the effect of the intensity modulated radiotherapy (IMRT) of the head and neck region on root canal-treated teeth and their periapical changes due to radiation. Patients undergoing IMRT of the head and neck region were evaluated. Different types of teeth (molars, premolars, incisors and canines) were compared. Panoramic and dental radiographs were used to assess the periapical region of root canal-treated teeth using the periapical index (PAI) before and after radiotherapy (RT) and put in relation to the radiation dose per tooth. Further parameters (patient-, therapy- and tooth-related factors) were included in this study. One hundred and twenty-four root canal-treated teeth (maxilla and mandible) of 51 patients were observed. A radiolucency in the periapical region was seen in 34.7% of the samples before IMRT and an increasing number of 46% after IMRT (p-value 0.092). Clinical or radiological signs of osteoradionecrosis could not be determined. The only statistically significant difference was detected in regions irradiated with less than 40 Gy (p-value 0.045). In regions irradiated with higher doses (>40 Gy), comparable pathologies increased in non-significant numbers. A statistically significant increase of periapical pathologies was detected in premolars of the maxilla. The observations reported here suggest that a high radiation dose during IMRT has no significant consequences on root canal-treated teeth. To compare the success of endodontic treatment before versus after IMRT, further research needs to be done.

Clinical target volume segmentation based on gross tumor volume using deep learning for head and neck cancer treatment.

Accurate clinical target volume (CTV) delineation is important for head and neck intensity-modulated radiation therapy. However, delineation is time-consuming and susceptible to interobserver variability (IOV). Based on a manual contouring process commonly used in clinical practice, we developed a deep learning (DL)-based method to delineate a low-risk CTV with computed tomography (CT) and gross tumor volume (GTV) input and compared it with a CT-only input. A total of 310 patients with oropharynx cancer were randomly divided into the training set (250) and test set (60). The low-risk CTV and primary GTV contours were used to generate label data for the input and ground truth. A 3D U-Net with a two-channel input of CT and GTV (U-NetGTV) was proposed and its performance was compared with a U-Net with only CT input (U-NetCT). The Dice similarity coefficient (DSC) and average Hausdorff distance (AHD) were evaluated. The time required to predict the CTV was 0.86 s per patient. U-NetGTV showed a significantly higher mean DSC value than U-NetCT (0.80 ± 0.03 and 0.76 ± 0.05) and a significantly lower mean AHD value (3.0 ± 0.5 mm vs 3.5 ± 0.7 mm). Compared to the existing DL method with only CT input, the proposed GTV-based segmentation using DL showed a more precise low-risk CTV segmentation for head and neck cancer. Our findings suggest that the proposed method could reduce the contouring time of a low-risk CTV, allowing the standardization of target delineations for head and neck cancer.

The Organs-at-Risk Dose Constraints in Head and Neck Intensity Modulated Radiation Therapy Using Data from a Multi-Institutional Clinical Trial (JCOG1015A1)

<h3>Purpose/Objective(s)</h3> The purpose of this study was to determine the organ specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from a multi-institutional clinical trial (JCOG1015). <h3>Materials/Methods</h3> Dose constraints used in the JCOG1015 were as follows; Spinal cord Dmax <50 Gy, Brain Dmax <70 Gy, Brainstem Dmax <54 Gy, Optic nerve Dmax <50 Gy, Eyeball Dmax <40 Gy, Lens Dmean <6 Gy, Parotid gland Dmean <26 Gy, pharyngeal constrictor muscle (PCM) Dmean <54 Gy, Larynx Dmean <54 Gy, Inner ear Dmean <45 Gy. Brain D1cc, brainstem D1cc, and thyroid Dmean were not stated but recorded. Patient data and dose-volume histograms (DVH) of organs-at-risk (OARs) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in the JCOG1015 trial. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. <h3>Results</h3> Estimated DVH cut-off values were brainstem D1cc:55.8 Gy for G1 myelitis, brain D1cc:72.1 Gy for ≥G1 central nerve necrosis, optic nerve Dmax:53.3 Gy for G2 vision impaired, eye-ball Dmax:36.6 Gy for G2 impaired, PCM Dmean:41.2 Gy for ≥G2 dysphagia, ipsilateral inner ear Dmean:44.0 Gy for ≥G2 hearing impaired, ipsilateral inner ear Dmean:51.5 Gy for ≥G2 middle ear inflammation, and thyroid Dmean: 45.6 Gy for G1 hypothyroidism. The 3- and 5-year cumulative incidence of late toxicity by dose metrics were shown in Table 1. The estimated cut-off values were similar to dose constraints criteria used in the JCOG1015 except for PCM. In patients who received higher dose than the dose constraints in brainstem and inner ear, incidence of myelitis and hearing impaired were notably high. <h3>Conclusion</h3> The dose constraints criteria of the JCO1015 were appropriate for most OARs, although more strict dose constraints might be necessary for PCM. Dose constraints for inner ear and brainstem should be archived with higher priority.

Commissioning of an Artificial Intelligence (AI) Tool for Automated Head and Neck Intensity Modulated Radiation Therapy (IMRT) Treatment Planning

<h3>Purpose/Objective(s)</h3> Radiation treatment planning for head and neck (HN) cancers is challenging due to complex anatomy and labor-intensive inverse optimization. Recently we developed an Artificial Intelligence (AI) tool to generate IMRT plans for bilateral planning target volumes (PTVs) with promising results in both plan quality and efficiency. In this study, we describe the clinical commissioning process of this tool. <h3>Materials/Methods</h3> The AI tool was interfaced to the commercial treatment planning system (TPS) in the clinical environment. Essential information about patient anatomy was collected through vendor-supported scripts and transmitted to a designated workstation. This workstation was configured to perform AI core functions to avoid modification and burden on TPS workstations. The AI-generated optimal fluence maps were then imported into TPS for leaf sequencing, dose calculation, and optional fine-tuning. Planners could examine the plan dose and make further adjustments as clinically needed. The workflow and performance were evaluated and validated by experienced physicians and physicists specializing in HN treatment. Training, validation, and testing datasets of the AI tool consisted of 200, 16, and 15 retrospective cases. The commissioning dataset of the AI tool used 36 recent cases of various disease sites in HN. The commissioning AI plans were evaluated based on the corresponding clinical plans regarding critical dose-volume endpoints and 3D dose distributions. All plans were normalized to 44Gy covering 95% of PTV. Wilcoxon signed-rank tests were performed with a significance level of 0.05. <h3>Results</h3> The average AI planning time was 10 to 15min per case with default settings from start to finish. The dose distributions were comparable to clinical plans with slightly better dose conformity and slightly worse but acceptable dose heterogeneity and maximum dose. OAR sparing was comparable. <h3>Conclusion</h3> The AI planning tool for HN was commissioned in our clinic. The commissioning process demonstrates outstanding performance and robustness of the AI tool and provides sufficient validation and confidence for clinical use. Table. Statistics of dosimetric endpoints (median ± std) of the 36 commissioning cases.

Chronic Dysphagia in Patients Treated with Head and Neck Intensity-Modulated Radiotherapy: Incidence, Risk Factors and Implications

<h3>Purpose/Objective(s)</h3> Late dysphagia after head and neck radiotherapy is an important driver of poor quality-of-life. We aimed to identify risk factors associated with long-term gastrostomy tube (g-tube) dependence in patients with head and neck squamous cell carcinoma treated with definitive or postoperative radiotherapy. <h3>Materials/Methods</h3> A retrospective cohort analysis of patients with head and neck squamous cell carcinoma treated with definitive or adjuvant intensity-modulated radiotherapy was performed. Patients with locoregional or distance recurrence were excluded from the analysis. G-tube dependence was used as a surrogate marker for late dysphagia, and its placement and removal from initial presentation to last follow-up was tracked. The risk of g-tube dependence from years one through five was calculated, and factors associated with 1- and 2-year g-tube use were analyzed with multivariable logistic regression. <h3>Results</h3> Our analytic cohort consisted of 421 survivors with head and neck squamous cell cancer treated from 2001 to 2018. A total of 210 patients required a g-tube with 80, 124, and 13 g-tubes placed before, during, and after radiotherapy, respectively. The median follow-up of the entire cohort was 4 years (IQR 3-5), with 314, 222, and 124 patients at-risk in years 3, 4 and 5. The Kaplan-Meier g-tube dependence rate at 1 and 2 years after radiotherapy were 11% and 6%, respectively, and 5%, 3% and 2% at three, four and five years, respectively. On multivariable regression analysis on 1-year g-tube dependence, history of depression or anxiety (odds ratio, OR, 95% confidence interval, CI, 3.86 [1.47, 10.3]), clinical T3/T4 stage (3.75 [1.60, 9.30]), clinical N2 or N3 stage (3.66 [1.03, 14.4]), baseline swallowing impairment to both solids and liquids (11.1 [3.22, 41.8]), and intra-treatment weight loss greater than 10% (3.75 [1.51, 9.81]) were significant predictors. A total of 390 patients had adequate follow-up data for the 2-year analysis. On multivariable analysis, age (1.06 [1.00, 1.14]), clinical N2/N3 stage (15.2 [1.72, 393]), and baseline swallowing impairment to both solids and liquids (95% confidence interval: 41.5 [5.59, 551]) were significantly associated with increased odds of 2-year g-tube dependence. Definitive vs. adjuvant treatment was not significantly associated with 1 or 2-year g-tube dependence. Out of 22 patients with g-tube dependence at two years after radiotherapy, only six (27%) patients had a known tube removal in the years to follow. <h3>Conclusion</h3> The overall incidence of prolonged g-tube dependence is low but not trivial, and the vast majority of patients with dependence at two years remained dependent permanently. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted since late removal becomes progressively more unlikely.

Examination of New Indicators in Adaptive Radiotherapy Using Machine Learning in Head and Neck Volumetric Modulated Arc Therapy

<h3>Purpose/Objective(s)</h3> During head and neck intensity-modulated radiotherapy treatment, a decrease in the patient's bodyweight and tumor size can often lead to inconsistencies in fixation and over- or under-dosage around the target. Treatment accuracy can be ensured by image-guided radiotherapy (IGRT). If substantial changes occur in the tumor volume or bodyweight, adaptive radiotherapy (ART) is performed. There is no clear guideline to initiate ART, and the decision is largely operator-driven. This study aimed to propose a new ART index using cone-beam computed tomography (CBCT) for existing patient data using machine learning. <h3>Materials/Methods</h3> The clinical target volume (CTV) and the parotid glands on the planning CT were automatically contoured to CBCT by deformable image registration (DIR), and the dice similarity coefficient (DSC) according to the number of fractions that were calculated from the original ROIs and DIR_ROIs. These DSCs were normalized by the maximum value and differentiated between patients who underwent ART (n = 416) and those who did not (n = 704). To determine the ART trigger from these DSCs, we devised a program that could guide the decision boundary by machine learning. The decision boundary was calculated using Python 3.7.6 with a support vector machine (SVM). T-test was performed to observe whether there was a difference in the slopes of the CTV and the parotid glands with and without replanning. We included the difference due to the slopes to the decision boundary and examined whether it is possible to classify areas as requiring ART or not. <h3>Results</h3> The accuracy rate using the test data was 0.66 for SVM. The decision boundary was shown by the following equation, where f(x) is the DSC and x is the number of fractions. f(x) = -0.0087x + 0.814 The p-values of the ART group and the non-implemented group of the slopes of CTV and the parotid glands were 0.005 and 4.195E-17, respectively, and a significant difference was confirmed (p < 0.05). Normal distribution was created from the slopes of each unimplemented group. The correct answer rate increased to 0.75, assuming that the slope larger than 1σ was an additional condition for ART. <h3>Conclusion</h3> We were able to derive the decision boundary f(x) using machine learning. If the DSC shows a value lower than the f(x) calculated for the same number of fractions, ART is indicated. However, in some cases, ART was performed even though it was not numerically necessary. In other cases, patients who did not undergo ART were judged numerically to require ART. These may be due to the DIR not working well because the tumor changes were intracranial, or due to the oncologist's preference not to perform ART despite large morphological changes. In this study, we proposed the need for ART to approximately 75% of patients. The findings suggest that machine learning may assist the operator with decision-making and replanning.

Organs-at-risk dose constraints in head and neck intensity-modulated radiation therapy using a dataset from a multi-institutional clinical trial (JCOG1015A1)

BackgroundJCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015.MethodsIndividual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities.ResultsThe 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less).ConclusionsThe dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Long-term opioid use in patients treated with head and neck intensity-modulated radiotherapy.

Acute and chronic pain during and after radiotherapy is an important driver of poor quality of life. We aimed to identify risk factors associated with increased chronic opioid use in head and neck squamous cell cancer survivors. We performed a retrospective cohort analysis on head and neck squamous cell cancer patients treated with definitive or adjuvant intensity-modulated radiotherapy. We tracked their oncologic opioid prescription profile from initial presentation to the last follow-up date. We determined the incidences of 1- and 2-year opioid use and performed multivariate logistic regression for both outcomes. Our analytic cohort consisted of 403 head and neck squamous cell cancer survivors. The numbers of patients requiring opioids at 3months, 6months, and 1year after treatment were 316 (78%), 203 (50%), and 102 (25%), respectively. On multivariate logistic regression, positive smoking history (95% CI 1.86 [1.03, 3.43], p = 0.04), unemployment (95% CI 2.33 [1.16, 4.67], p = 0.02), prior psychiatric illness (95% CI 2.15 [1.05, 4.40], p = 0.03), and opiate use before radiotherapy (95% CI 2.75 [1.49, 5.20], p = 0.01) were independently associated with significantly greater odds of opioid use at 1year. Our institutional analysis has shown that a substantial amount of head and neck cancer survivors are chronically dependent on opioids following radiotherapy. We have identified a cohort at highest risk for long-term use, for whom early interventions should be targeted.

Correlation between the \u03b3 passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer

BackgroundBoth patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer.MethodsTwenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms.ResultsThe γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone.ConclusionIn clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

Evaluation of treatment plan quality for head and neck IMRT: a multicenter study

Intensity-modulated radiotherapy (IMRT) treatment planning for head and neck cancer is challenging and complex due to many organs at risk (OAR) in this region. The experience and skills of planners may result in substantial variability of treatment plan quality. This study assessed the performance of IMRT planning in Malaysia and observed plan quality variation among participating centers. The computed tomography dataset containing contoured target volumes and OAR was provided to participating centers. This is to control variations in contouring the target volumes and OARs by oncologists. The planner at each center was instructed to complete the treatment plan based on clinical practice with a given prescription, and the plan was analyzed against the planning goals provided. The quality of completed treatment plans was analyzed using the plan quality index (PQI), in which a score of 0 indicated that all dose objectives and constraints were achieved. A total of 23 plans were received from all participating centers comprising 14 VMAT, 7 IMRT, and 2 tomotherapy plans. The PQI indexes of these plans ranged from 0 to 0.65, indicating a wide variation of plan quality nationwide. Results also reported 5 out of 21 plans achieved all dose objectives and constraints showing more professional training is needed for planners in Malaysia. Understanding of treatment planning system and computational physics could also help in improving the quality of treatment plans for IMRT delivery.

Prospective Phase 2 Study of Radiation Therapy Dose and Volume De-escalation for Elective Neck Treatment of Oropharyngeal and Laryngeal Cancer

The required elective nodal dose and volumes for head and neck intensity modulated radiation therapy have largely been extrapolated from conventional radiation therapy fields. In this prospective, dual-center, phase 2 study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma. Patients with newly diagnosed squamous cell carcinoma of the oropharynx and larynx were eligible for enrollment. Each lymph node was characterized as involved or suspicious based on imaging criteria. For oropharynx cancer, only involved and immediately adjacent stations were treated to 40 Gy in 20 fractions. In larynx patients, at least bilateral levels II and III were treated to 40 Gy, with level IV treated only if level III was involved. Involved and suspicious nodes were then boosted with 30 Gy and 24 Gy in 15 fractions, respectively. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was solitary elective volume recurrence, with secondary endpoints including patterns of failure and patient-reported outcomes. A total of 72 (51 oropharynx, 21 larynx) patients completed treatment on this trial from January 2017 through November 2018. The stages at presentations were 5, 17, and 50 stage I-II, III, and IV, respectively, with 90% treated with chemoradiation therapy. At a median follow-up of 24.7 months for surviving patients, there have been no solitary elective nodal recurrences. Seven patients developed a nodal recurrence, 5 of which were in-field and 2 were elective with synchronous in-field recurrence. Patient-reported outcomes assessment at 1 year showed superior or equivalent outcomes compared with baseline, except for saliva and taste measures. The results of this trial suggest that elective dose and volume reduction is oncologically sound for oropharyngeal and laryngeal cancer treated with intensity modulated radiation therapy, with promising quality-of-life outcomes.

Characterisation and use of OSLD for in vivo dosimetry in head and neck intensity-modulated radiation therapy

AbstractAim:This study reveals the characteristic nature and the use of optically stimulated luminescence dosimeters (OSLD) as an in vivo dosimetry tool for head and neck intensity-modulated radiation therapy (IMRT).Materials and methods:Calibration and characterisation of OSLD such as sensitivity, reproducibility, dose-rate dependence, beam quality dependence, output factor measurement and comparison of two bleaching techniques using halogen and compact fluorescent lamp (CFL) were initially performed. Later, eye dose measurements were performed for head and neck IMRT patients using OSLD and were compared with the corresponding dose calculated by the treatment planning system (TPS).Results:While the sensitivity was found to be within ±5%, the dose-rate dependence and reproducibility were found to be within ±3%. The OSLD showed an under-response of 3% for 15 MV and an increase in response by 5% for Co60 (1·25 MeV) when compared with the 6 MV X-ray beam. Therefore, a separate calibration for different beam energies is required. The percentage deviation of OSLD to that of TPS was found to be within ±2·77%. The OSLD has been successfully used for the in vivo dosimetry of patients who received IMRT. Hence, it is concluded that OSLDs can serve as effective dosimeters for in vivo dosimetry.

Deep learning-based metal artifact reduction using cycle-consistent adversarial network for intensity-modulated head and neck radiation therapy treatment planning

To develop a deep learning-based metal artifact reduction (DL-MAR) method using unpaired data and to evaluate its dosimetric impact in head and neck intensity-modulated radiation therapy (IMRT) compared with the water density override method. The data set comprised the data of 107 patients who underwent radiotherapy. Fifteen patients with dental fillings were used as the test data set. The computed tomography (CT) images of the remaining 92 patients were divided into two domains: the metal artifact and artifact-free domains. CycleGAN was used for domain translation. The artifact index of the DL-MAR images was compared with that of the original uncorrected (UC) CT images. The dose distributions of the DL-MAR and UC plans were created by comparing the reference clinical plan with the water density override method (water plan) in each dataset. Dosimetric deviation in the oral cavity from the water plan was evaluated. The artifact index of the DL-MAR images was significantly smaller than that of the UC images in all patients (13.2±4.3 vs. 267.3±113.7). Compared with the reference water plan, dose differences of the UC plans were greater than those of the DL-MAR plans. DL-MAR images provided dosimetric results that were more similar to those of the water plan than the UC plan. We developed a fast DL-MAR method using CycleGAN for head and neck IMRT. The proposed method could provide consistent dose calculation against metal artifact and improve the efficiency of the planning process by eliminating manual delineation.

A method for generating intensity-modulated radiation therapy fields for small animal irradiators utilizing 3D-printed compensator molds.

The purpose of this study was to investigate the feasibility of using fused deposition modeling (FDM) three-dimensional (3D) printer to generate radiation compensators for high-resolution (~1mm) intensity-modulated radiation therapy (IMRT) for small animal radiation treatment. We propose a novel method incorporating 3D-printed compensator molds filled with NaI powder. The inverse planning module of the computational environment for radiotherapy research (CERR) software was adapted to simulate the XRAD-225Cx irradiator, both geometry and kV beam quality (the latter using a phase space file provided for XRAD-225Cx). A nine-field IMRT treatment was created for a scaled-down version of the imaging and radiation oncology core (IROC) Head and Neck IMRT credentialing test, recreated on a 2.2-cm-diameter cylindrical phantom. Optimized fluence maps comprising nine fields and a total of 2564 beamlets were calculated at resolution of 1.25×1.25mm2 . A hollow compensator mold was created (using in-house software and algorithm) for each field using 3D printing with polylactic acid (PLA) filaments. The molds were then packed with sodium iodide powder (NaI, measured density ρNaI =2.062g/cm3 ). The mounted compensator mold thickness was limited to 13.8mm due to clearance issues with couch collision. At treatment delivery, each compensator was manually mounted to a customized block tray attached to the reference 40×40mm2 collimator. Compensator reproducibility among three repeated 3D-printed molds was measured with Radiochromic EBT2 film. The two-dimensional (2D) dose distributions of the nine fields were compared to calculated 2D doses from CERR using gamma comparisons with distance-to-agreement criteria of 0.5-0.25mm and dose difference criteria of 3-5%. Good reproducibility of 3D-printed compensator manufacture was observed with mean error of ±0.024Gy and relative dose error of ±4.2% within the modulated part of the beam. Within the limit of 13.8mm compensator height, a maximum radiation blocking efficiency of 91.5% was achieved. Per field, about 45.5g of NaI powder was used. Gamma analysis on each of the nine delivered IMRT fields using radiochromic films resulted in eight of nine treatment fields with >90% pass rate with 5%/0.5mm tolerances. However, low gamma passing rate of 49-66% (3%/0.25mm to 5%/0.5mm) was noted in one field, attributed to fabrication errors resulting in over-filling the mold. The nine-field treatment plan was delivered in under 30min with no mechanical or collisional issues. We show the feasibility of high spatial resolution IMRT treatment on a small animal irradiator utilizing 3D-printed compensator shells packed with NaI powder. Using the PLA mold with NaI powder was attractive due to the ease of 3D printing a PLA mold at high geometric resolution and the well-balanced attenuation properties of NaI powders that prevented the mold from becoming too bulky. IMRT fields with 1.25-mm resolution are capable with significant fluence modulation with relative dose accuracy of ±4.2%.

Dose to swallowing structures and dysphagia in head and neck Intensity Modulated Radiation Therapy - A long term prospective analysis.

To analyse the long term swallowing function in head and neck cancer patients and correlate with the dose to midline swallowing structures. The use of concurrent chemo radiation (CRT) as the present standard of care resulted in high rates of early and late toxicities. Dysphagia, aspiration, and xerostomia are early as well as late effects of radiation. Not many studies on the dysphagia scores during radiation and follow-up period have correlated dose to the swallowing structures, hence this study. Histologically proven head and neck cancer patients treated with intensity modulated radiation therapy were accrued in this study. The pharyngeal constrictors, larynx and cervical oesophagus were contoured and labelled as midline swallowing structures. The volume of the midline swallowing structures which were outside the PTV was delineated separately and was given a mean dose constraint of 45Gy. Dysphagia was assessed at baseline, weekly intervals during irradiation and follow-up at six years. The dose to the structures for swallowing was correlated with degree of dysphagia. There was a gradual increase in the dysphagia grade during the course of radiation. There was a significant recovery of late dysphagia compared to dysphagia during the completion of radiation therapy in patients who received <45Gy to the swallowing structures (p<0.0001). Giving a constraint to the swallowing structure and limiting it to <45Gy resulted in earlier recovery of swallowing function resulted in good physical, mental and social well being of the patients when compared to those who received >45Gy.

Recurrence and Quality-of-Life Following Elective Nodal Volume and Dose De-Escalation for Oropharyngeal and Laryngeal Cancer: Initial Results from the Infield Trial

The required elective nodal dose and volumes for head and neck intensity-modulated radiotherapy (IMRT) have largely been extrapolated from conventional radiotherapy fields. The combination of CT and PET-CT imaging with surgically established patterns-of-nodal-spread provides an opportunity to meaningfully reduce the elective dose and volume, with a significant gain in acute and long-term morbidity. In this prospective phase II study, we investigated the efficacy and tolerability of reduced elective nodal volume and dose in oropharyngeal and laryngeal squamous cell carcinoma. Patients with newly-diagnosed squamous cell carcinoma of the oropharynx and larynx were eligible for enrollment; only stage I-II glottic larynx were excluded. In collaboration with a nuclear radiologist, each lymph node was characterized as involved or suspicious based on anatomic and PET criteria. Lymph nodes whose cross-sectional diameter was at least 17 mm and/or nodes with FDG uptake greater than the adjacent blood pool were considered suspicious. For oropharynx cancer, only involved nodal stations plus one adjacent station (and retropharynx) were treated to 40 Gy in 20 fractions. In larynx patients, at least bilateral levels II and III were treated to 40 Gy, with level IV treated only if level III was involved. Involved and suspicious nodes were then boosted with 30 Gy and 24 Gy in 15 fractions, respectively. The primary gross tumor and clinical target volumes were irradiated to 70 and 64 Gy, respectively, in the same fractionation. Concurrent chemotherapy was required for stage T3N0-1 and IVA/B patients. The primary endpoint of the study was solitary elective volume recurrence, with secondary endpoints including patterns-of-failure and patient reported outcomes. A total of 72 patients completed treatment on this trial from January 2017 through November 2018. The study was composed of 19 larynx and 53 oropharyngeal patients, 77% of whom were p16-positive. The stages at presentations were 5, 17, and 50 stage I-II, III, and IV, respectively, with 8% and 92% treated with accelerated radiotherapy and chemoradiotherapy, respectively. Average contralateral mean parotid and SMG doses for non-N2c patients were 16.5 Gy and 36.7 Gy, respectively. With a median follow-up of 11.9 months for surviving patients, there have been no recurrences in the 40 Gy or untreated elective nodal stations. Gastrostomy was placed in 32 (44%), with median removal after 2.9 months for disease-free patients; only one disease-free patient is still dependent. At 3 months, the mean composite MDADI score was 79, and the mean EORTC HN35 dry mouth and sticky saliva scores were 59 and 40, respectively. Preliminary results suggest that elective dose and volume reduction is oncologically sound for oropharyngeal and laryngeal cancer treated with IMRT, with promising quality-of-life outcomes. Longer follow-up is needed to confirm these results.

Prospective observational study to estimate set-up errors and optimise PTV margins in patients undergoing IMRT for head and neck cancers from a Government cancer centre of Eastern India

AbstractBackground:The head and neck cancers as a whole are the most common cancers among males in India. Technological advancements have led to an improvement in radiation therapy (RT) techniques with subsequent reduction in normal tissue complications. To correct patient set-up errors, an off-line correction method like no action level (NAL) protocol may be used as a preferred protocol particularly for a busy department. The objectives of the study were to measure the translational set-up errors using kV cone-beam computed tomography (CBCT) in patients undergoing intensity modulated radiotherapy (IMRT) in head and neck cancers and also to optimise clinical target volume (CTV) to planning target volume (PTV) margin using NAL protocol.Material and methods:On the first 5 days of RT, patient’s position was verified by kV-CBCT and then weekly during the course of treatment. The comparison between the reference and kV-CBCT images was performed, and the shifts measured and recorded. The mean error from the initial five consecutive fractions was corrected on the sixth daily fraction. Displacements in all the directions were measured. The population systematic and random errors were determined and used to estimate PTV margins according to the van Herk formula.Results:A total of 322 images were analysed. Before correction, 15, 12 and 9% patients had systematic error ≥3 mm on X, Y and Z axes, but after correction this was reduced to 9, 0 and 0%. The total percentage of patients whose set-up margin was ≥5 mm before correction was 5, 6·25, 3·75%, but after correction it reduced to 1·88, 0, and 0·63%. The margins of total population were reduced to 63, 65 and 56% after correction on X, Y and Z axes, respectively.Conclusion:A simple off-line NAL protocol can correct the set-up errors without daily on-line imaging in patients undergoing IMRT and hence acting as a resource sparing alternative. Five millimetre margin to CTVs was adequate and safe to overcome the problem of set-up errors in head and neck IMRT.

Independent recalculation outperforms traditional measurement-based IMRT QA methods in detecting unacceptable plans.

To evaluate the performance of an independent recalculation and compare it against current measurement-based patient specific intensity-modulated radiation therapy (IMRT) quality assurance (QA) in predicting unacceptable phantom results as measured by the Imaging and Radiation Oncology Core (IROC). When institutions irradiate the IROC head and neck IMRT phantom, they are also asked to submit their internal IMRT QA results. Separately from this, IROC has previously created reference beam models on the Mobius3D platform to independently recalculate phantom results based on the institution's DICOM plan data. The ability of the institutions' IMRT QA to predict the IROC phantom result was compared against the independent recalculation for 339 phantom results collected since 2012. This was done to determine the ability of these systems to detect failing phantom results (i.e., large errors) as well as poor phantom results (i.e., modest errors). Sensitivity and specificity were evaluated using common clinical thresholds, and receiver operator characteristic (ROC) curves were used to compare across different thresholds. Overall, based on common clinical criteria, the independent recalculation was 12 times more sensitive at detecting unacceptable (failing) IROC phantom results than clinical measurement-based IMRT QA. The recalculation was superior, in head-to-head comparison, to the EPID, ArcCheck, and MapCheck devices. The superiority of the recalculation vs these array-based measurements persisted under ROC analysis as the recalculation curve had a greater area under it and was always above that for these measurement devices. For detecting modest errors (poor phantom results rather than failing phantom results), neither the recalculation nor measurement-based IMRT QA performed well. A simple recalculation outperformed current measurement-based IMRT QA methods at detecting unacceptable plans. These findings highlight the value of an independent recalculation, and raise further questions about the current standard of measurement-based IMRT QA.

Ipsilateral neck radiotherapy in N2b well-lateralized tonsil cancer - Approach with caution.

Treatment of the uninvolved neck in well-lateralized tonsillar squamous cell carcinoma is controversial. We became concerned after a number of contralateral neck recurrences (CNRs) in patients receiving ipsilateral radiotherapy (RT). This is a single center retrospective series including patients with well-lateralized tonsillar cancer treated with ipsilateral neck RT between 2004 and 2011. We identified 53 patients treated with ipsilateral neck RT during the study period. The rate of CNR was 7.5% (4 of 53). All four patients had p16-positive, T1, N2b, M0 tumors. The subgroup of patients with N2b disease (28 of 53) had a CNR of 14.3%. We subsequently switched to treat patients with N2b with bilateral neck RT. We analyzed the outcomes of 23 patients with N2b treated with bilateral neck intensity-modulated RT (IMRT) and observed no CNRs. We observed a higher than expected rate of CNR in the N2b population. Bilateral neck IMRT for these patients represents a safe alternative.