Anatomical and dosimetric variations during volumetric modulated arc therapy in patients with locally advanced nasopharyngeal carcinoma after induction therapy: Implications for adaptive radiation therapy.

Purpose: To investigate anatomical and dosimetric changes during volumetric modulated arc therapy (VMAT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) after induction therapy (IT) and explore characteristics of patients with notable variations. Materials and methods: From July 2021 to June 2023, 60 LA-NPC patients undergoing VMAT after IT were retrospectively recruited. Adaptive computed tomography (aCT), reconstructed from weekly cone-beam computed tomography(CBCT), facilitates recontouring and planning transplantation. Volume, dice similarity coefficients, and dose to target volumes and organs at risk(OARs) on planning CT(pCT) and aCT were compared to identify changing patterns. Multivariate logistic regression was used to investigate risk factors. Results: The volumes of PGTVnasopharynx (PGTVp), PGTVnode (PGTVn), ipsilateral and contralateral parotid glands decreased during VMAT, with reductions of 2.25 %, 6.98 %, 20.09 % and 18.00 %, respectively, at 30 fractions from baseline (P < 0.001). After 25 fractions, D99 and D95 of PGTVn decreased by 7.94 % and 4.18 % from baseline, respectively, while the Dmean of ipsilateral and contralateral parotid glands increased by 7.80 % and 6.50 %, marking the peak rates of dosimetric variations (P < 0.001). The dosimetric fluctuations in PGTVp, the brainstem, and the spinal cord remained within acceptable limits. Furthermore, an initial BMI ≥ 23.5 kg/m2 and not-achieving objective response (OR) after IT were regarded as risk factors for a remarkable PGTVn dose reduction in the later stages of VMAT. Conclusions: Replanning for post-IT LA-NPC patients appears reasonable at 25F during VMAT. Patients with an initial BMI ≥ 23.5 kg/m2 and not-achieving OR after IT should be considered for adaptive radiation therapy to stabilize the delivered dose.

Potential anatomical triggers for plan adaptation of cervical cancer external beam radiotherapy.

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.

Optimal timing of re-planning for head and neck adaptive radiotherapy.

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) relies on re-planning to correct treatment variations, but the optimal timing of re-planning to account for dose changes in head and neck organs at risk (OARs) is still under investigation. We aimed to find out the optimal timing of re-planning in head and neck ART. MATERIALS AND METHODS: A total of 110 head and neck cancer patients were retrospectively enrolled. A semi auto-segmentation method was applied to obtain the weekly mean dose (Dmean) to OARs. The K-nearest-neighbour method was used for missing data imputation of weekly Dmean. A dose deviation map was built using the planning Dmean and weekly Dmean values and then used to simulate different ART scenarios consisting of 1 to 6 re-plannings. The difference between accumulated Dmean and planning Dmean before re-planning (ΔDmean_acc_noART) and after re-planning (ΔDmean_acc_ART) were evaluated and compared. RESULTS: Among all the OARs, supraglottic showed the largest ΔDmean_acc_noART (1.23 ± 3.13 Gy) and most cases of ΔDmean_acc_noART > 3 Gy (26 patients). The 3rd week is suggested in the optimal timing of re-planning for 10 OARs. For all the organs except arytenoid, 2 re-plannings were able to guarantee the ΔDmean_acc_ART below 3 Gy while the average |ΔDmean_acc_ART| was below 1 Gy. ART scenarios of 2_4, 3_4, 3_5 (week of re-planning separated with "_") were able to guarantee ΔDmean_acc_ART of 99 % of patients below 3 Gy simultaneously for 19 OARs. CONCLUSIONS: The optimal timing of re-planning was suggested for different organs at risk in head and neck adaptive radiotherapy. Generic scenarios of timing and frequency for re-planning can be applied to guarantee the increase of accumulated mean dose within 3 Gy simultaneously for multiple organs.

Dosimetric Impact of Source Displacement in GammaTile Surgically Targeted Radiation Therapy for Gliomas.

Background This study aims to evaluate dosimetric changes that happened during the first month after GammaTile surgically targeted radiation therapy (STaRT) for gliomas due to Cesium-131 (Cs-131) seed displacement caused by cavity shrinkage in brain brachytherapy. Methodology In this study, 10 glioma patients had 4-11 GammaTiles placed along the resection bed after maximal safe resection during craniotomy. Each GammaTile is composed of four Cs-131 seeds embedded in a biodegradable collagen sponge to minimize seed movement and maintain seed-to-cavity surface distance. The Cs-131 seed positions were identified using VariSeed on day one. On day 30, post-implant computed tomography (CT) images and dosimetry parameters were calculated. An iterative closest point (ICP) algorithm was used to compute rigid transformation between the day one and day 30 seed clouds. The seed displacement was calculated after registration. The volume receiving 100% of the prescription dose (V100), the dose received by 90% of the planning target volume (D90_PTV), the planning target volume receiving 100% of the prescription dose (V100_PTV), and the dose to organs at risk (OARs) were calculated for both CT images to determine the dosimetric changes from any seed displacement. Results The mean seed displacement of 1.8 ± 1.0 mm for all patients was observed between day one and day 30. The maximum seed displacement for each patient ranged from 2.3 mm to 7.3 mm. The mean V100 difference between day one and day 30 was 2.5 cc (range = 0.5-6.5 cc). The mean D90_PTVs were 95.5% (range = 69.0%-131.0%) and 98.1% (range = 19.9%-149.0%) on day one and day 30, respectively. The mean V100_PTVs were 88.4% (range = 81.3%-99.1%) and 87.9% (range = 47.0%-99.7%) on day one and day 30, respectively. On day one, the brainstem dose was 63.5 Gy for one case and 28.1 Gy for another case; while on day 30, the brainstem dose was 55.8 Gy and 20.6 Gy for the same patients, contributing to 7.7 Gy (12.8%) and 7.5 Gy (12.5%) dose reductions to brainstem for these patients, respectively. Only two patients received a dose to the optic nerves (34.1 Gy and 5.2 Gy). There were small changes (1.8 Gy and 0.5 Gy, respectively) in the dose to optic nerves when comparing the dose calculated on day one and the dose calculated on day 30 CT images. The same two patients received 30.4 Gy and 6.8 Gy to the chiasm, respectively. Small changes in the dose to the chiasm (≤1.1 Gy) were noted between day one and day 30. Conclusions A maximum seed displacement of up to 7.3 mm and a mean seed displacement of 1.8 mm caused by cavity shrinkage were observed during the first month after GammaTile STaRT for gliomas. There were noticeable changes in dosimetry parameters. Changes in the doses to OARs, particularly the brainstem, were large (up to 12.8% of the prescription dose). These changes in dosimetry should be considered when evaluating treatment outcomes and planning future GammaTile treatments.

An efficient strategy to select head and neck cancer patients for adaptive radiotherapy.

BACKGROUND AND PURPOSE: Adaptive radiotherapy (ART) is workload intensive but only benefits a subgroup of patients. We aimed to develop an efficient strategy to select candidates for ART in the first two weeks of head and neck cancer (HNC) radiotherapy. MATERIALS AND METHODS: This study retrospectively enrolled 110 HNC patients who underwent modern photon radiotherapy with at least 5 weekly in-treatment re-scan CTs. A semi auto-segmentation method was applied to obtain the weekly mean dose (Dmean) to OARs. A comprehensive NTCP-profile was applied to obtain NTCP's. The difference between planning and actual values of Dmean (ΔDmean) and dichotomized difference of clinical relevance (BIOΔNTCP) were used for modelling to determine the cut-off maximum ΔDmean of OARs in week 1 and 2 (maxΔDmean_1 and maxΔDmean_2). Four strategies to select candidates for ART, using cut-off maxΔDmean were compared. RESULTS: The Spearman's rank correlation test showed significant positive correlation between maxΔDmean and BIOΔNTCP (p-value <0.001). For major BIOΔNTCP (>5%) of acute and late toxicity, 10.9% and 4.5% of the patients were true candidates for ART. Strategy C using both cut-off maxΔDmean_1 (3.01 and 5.14 Gy) and cut-off maxΔDmean_2 (3.41 and 5.30 Gy) showed the best sensitivity, specificity, positive and negative predictive values (0.92, 0.82, 0.38, 0.99 for acute toxicity and 1.00, 0.92, 0.38, 1.00 for late toxicity, respectively). CONCLUSIONS: We propose an efficient selection strategy for ART that is able to classify the subgroup of patients with >5% BIOΔNTCP for late toxicity using imaging in the first two treatment weeks.

Adaptive radiation therapy: When, how and what are the benefits that literature provides?

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

A novel semi auto-segmentation method for accurate dose and NTCP evaluation in adaptive head and neck radiotherapy.

BACKGROUND AND PURPOSE: Accurate segmentation of organs-at-risk (OARs) is crucial but tedious and time-consuming in adaptive radiotherapy (ART). The purpose of this work was to automate head and neck OAR-segmentation on repeat CT (rCT) by an optimal combination of human and auto-segmentation for accurate prediction of Normal Tissue Complication Probability (NTCP). MATERIALS AND METHODS: Human segmentation (HS) of 3 observers, deformable image registration (DIR) based contour propagation and deep learning contouring (DLC) were carried out to segment 15 OARs on 15 rCTs. The original treatment plan was re-calculated on rCT to obtain mean dose (Dmean) and consequent NTCP-predictions. The average Dmean and NTCP-predictions of the three observers were referred to as the gold standard to calculate the absolute difference of Dmean and NTCP-predictions (|ΔDmean| and |ΔNTCP|). RESULTS: The average |ΔDmean| of parotid glands in HS was 1.40 Gy, lower than that obtained with DIR and DLC (3.64 Gy, p < 0.001 and 3.72 Gy, p < 0.001, respectively). DLC showed the highest |ΔDmean| in middle Pharyngeal Constrictor Muscle (PCM) (5.13 Gy, p = 0.01). DIR showed second highest |ΔDmean| in the cricopharyngeal inlet (2.85 Gy, p = 0.01). The semi auto-segmentation (SAS) adopted HS, DIR and DLC for segmentation of parotid glands, PCM and all other OARs, respectively. The 90th percentile |ΔNTCP|was 2.19%, 2.24%, 1.10% and 1.50% for DIR, DLC, HS and SAS respectively. CONCLUSIONS: Human segmentation of the parotid glands remains necessary for accurate interpretation of mean dose and NTCP during ART. Proposed semi auto-segmentation allows NTCP-predictions within 1.5% accuracy for 90% of the cases.

An evaluation of adaptive planning by assessing the dosimetric impact of weight loss throughout the course of radiotherapy in bilateral treatment of head and neck cancer patients.

The purpose of this study was to investigate the dosimetric impact of weight loss in head and neck (H&N) patients and examine the effectiveness of adaptive planning. Data was collected from 22 H&N cancer patients who experienced weight loss during their course of radiotherapy. The robustness of Intensity Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) treatment plans were compared including the potential need for replanning. The dosimetric impact of weight loss was evaluated by calculating a verification plan for each patient on an assessment CT scan taken during the course of treatment. Using a regression analysis, significance was tested for the dosimetric change in target volumes and 10 specific organs at risk (OAR) using an anatomical separation difference in the H&N at corresponding levels. For both the IMRT and VMAT plans, a significant correlation was found for the dose to 5% of the high risk Planning Target Volume (PTV) (D5), dose to 95% of the intermediate risk PTV and Clinical Target Volume (CTV) (D95), and the percentage of the pharynx receiving 65 Gy. An independent t-test was also performed for each metric in the VMAT and IMRT plans showing the dose to 95% of the intermediate risk PTV as significant. No quantitative method for finding the threshold of anatomical separation difference requiring a replan was established. Based on the increase in dose to organs at risk and increased target coverage due to separation loss, it was concluded that adaptive radiotherapy may not always be necessary when alignment of bony anatomy and remaining soft tissue is within tolerance. Physician judgment and preference is needed in such situations.

The importance of mesorectum motion in determining PTV margins in rectal cancer patients treated with neoadjuvant radiotherapy.

New precision radiotherapy (RT) techniques reduce the uncertainties in localizing soft and moving tumors. However, there are still many uncontrollable internal organ movements. In our study, patients who underwent neoadjuvant chemoradiotherapy (NA-CRT) for rectal cancer were evaluated to determine inter-fraction mesorectum motion and dosimetric changes. Fourteen patients treated with NA-CRT for rectal cancer between 2014 and 2016 were included in the analysis. The mesorectum and clinical target volume (CTV) were delineated on planning computed tomography (CT) and cone-beam CT (CB-CT) scans. After planning with a volumetric modulated arc therapy (VMAT) plan, re-planning was performed on all CB-CTs. Finally, the volumetric and dosimetric changes of PTV and mesorectum were evaluated in all CB-CTs compared with the initial CT and VMAT plans. The geometrical center of mesorectum volume in CB-CTs had moved 1 (0.2-6.6), 1.6 (0.2-3.8) and 1.6 (0-4.9) mm in the x, y and z-axis respectively compared with the initial CT. The dosimetric parameters of PTV including D2, D95 and D98 on CB-CT showed a median 47.19 (46.70-47.80), 45.05 (44.18-45.68) and 44.69 (43.83-45.48) Gy and median 1% (1-2), 0% (0-2) and 1% (0-2) dosimetric change compared with the initial VMAT plan. In our study, we have shown that the mesorectum has moved up to 20 mm in the lateral and anterior-posterior direction and almost 10 mm in the superior/inferior direction during RT, causing a median of ~2% change in dosimetric parameters. Therefore, these movements must be considered in determining PTV margins to avoid dosimetric changes.

Incorporation of Dosimetric Gradients and Parotid Gland Migration Into Xerostomia Prediction.

Purpose: Due to the sharp gradients of intensity-modulated radiotherapy (IMRT) dose distributions, treatment uncertainties may induce substantial deviations from the planned dose during irradiation. Here, we investigate if the planned mean dose to parotid glands in combination with the dose gradient and information about anatomical changes during the treatment improves xerostomia prediction in head and neck cancer patients. Materials and methods: Eighty eight patients were retrospectively analyzed. Three features of the contralateral parotid gland were studied in terms of their association with the outcome, i.e., grade ≥ 2 (G2) xerostomia between 6 months and 2 years after radiotherapy (RT): planned mean dose (MD), average lateral dose gradient (GRADX), and parotid gland migration toward medial (PGM). PGM was estimated using daily megavoltage computed tomography (MVCT) images. Three logistic regression models where analyzed: based on (1) MD only, (2) MD and GRADX, and (3) MD, GRADX, and PGM. Additionally, the cohort was stratified based on the median value of GRADX, and a univariate analysis was performed to study the association of the MD with the outcome for patients in low- and high-GRADX domains. Results: The planned MD failed to recognize G2 xerostomia patients (AUC = 0.57). By adding the information of GRADX (second model), the model performance increased to AUC = 0.72. The addition of PGM (third model) led to further improvement in the recognition of the outcome (AUC = 0.79). Remarkably, xerostomia patients in the low-GRADX domain were successfully identified (AUC = 0.88) by the MD alone. Conclusions: Our results indicate that GRADX and PGM, which together serve as a proxy of dosimetric changes, provide valuable information for xerostomia prediction.

Adaptive intensity-modulated radiotherapy in head-and-neck cancer: A volumetric and dosimetric study.

INTRODUCTION AND OBJECTIVE: Anatomic and volumetric changes occur in head-and-neck cancer during fractionated radiotherapy (RT), and the actual dose received by patient is considerably different from the original plan. The purpose of this study is to evaluate volumetric and dosimetric changes occurring during radiation therapy. PATIENTS AND METHODS: Ten patients of locally advanced head-and-neck cancer, 6 oropharynx, 3 larynx, and 1 hypopharynx underwent computed tomography (CT) simulation before treatment and after 4 weeks during RT treatment. Original plan (OPLAN) was generated based on initial CT scan for the entire course of treatment. The initial plan is implemented on the second planning CT scan, and the dose distribution is recalculated. Beam configuration of OPLAN was applied onto the second CT scan and then hybrid plan (HPLAN30) was generated. RPLAN30 is the intensity-modulated RT replan generated on the second CT scan for the remaining 30 Gy. Dose and volume parameters between OPLAN30 (based on the first CT scan for the remaining 30 Gy), HPLAN30, and RPLAN30 were compared. RESULTS: The volume reduction of planning target volume (PTV), ipsilateral and contralateral parotid after 4 weeks of RT, was statistically significant (P < 0.05). D2% and V > 107% of PTV were higher in HPLAN than that of RPLAN (P < 0.05). Hybrid plans showed increase in delivered dose to spinal cord. Mid treatment replanning reduced doses to spinal cord (Dmax and D1%), which is statistically significant (P < 0.05). Mean doses to ipsilateral and contralateral parotid of RPLAN (21.4 Gy and 16.74 Gy, respectively) were reduced when compared to that of HPLAN (22.99 Gy and 22 Gy, respectively). CONCLUSION: Interim CT scanning and replanning (adaptive) improves target volume coverage and normal tissue sparing.

Selection of head and neck cancer patients for adaptive radiotherapy to decrease xerostomia.

BACKGROUND AND PURPOSE: The aim of this study was to develop and validate a method to select head and neck cancer patients for adaptive radiotherapy (ART) pre-treatment. Potential pre-treatment selection criteria presented in recent literature were included in the analysis. MATERIALS AND METHODS: Deviations from the planned parotid gland mean dose (PG ΔDmean) were estimated for 113 head and neck cancer patients by re-calculating plans on repeat CT scans. Uni- and multivariable linear regression analyses were performed to select pre-treatment parameters, and ROC curve analysis was used to determine cut off values, for selecting patients with a PG dose deviation larger than 3Gy. The patient selection method was validated in a second patient cohort of 43 patients. RESULTS: After multivariable analysis, the planned PG Dmean remained the only significant parameter for PG ΔDmean. A sensitivity of 91% and 80% could be obtained using a threshold of PG Dmean of 22.2Gy, for the development and validation cohorts, respectively. This would spare 38% (development cohort) and 24% (validation cohort) of patients from the labour-intensive ART procedure. CONCLUSIONS: The presented method to select patients for ART pre-treatment reduces the labour of ART, contributing to a more effective allocation of the department resources.

Identifying patients who may benefit from adaptive radiotherapy: Does the literature on anatomic and dosimetric changes in head and neck organs at risk during radiotherapy provide information to help?

In the last decade, many efforts have been made to characterize anatomic changes of head and neck organs at risk (OARs) and the dosimetric consequences during radiotherapy. This review was undertaken to provide an overview of the magnitude and frequency of these effects, and to investigate whether we could find criteria to identify head and neck cancer patients who may benefit from adaptive radiotherapy (ART). Possible relationships between anatomic and dosimetric changes and outcome were explicitly considered. A literature search according to PRISMA guidelines was performed in MEDLINE and EMBASE for studies concerning anatomic or dosimetric changes of head and neck OARs during radiotherapy. Fifty-one eligible studies were found. The majority of papers reported on parotid gland (PG) anatomic and dosimetric changes. In some patients, PG mean dose differences between planning CT and repeat CT scans up to 10 Gy were reported. In other studies, only minor dosimetric effects (i.e. <1 Gy difference in PG mean dose) were observed as a result of significant anatomic changes. Only a few studies reported on the clinical relevance of anatomic and dosimetric changes in terms of complications or quality of life. Numerous potential selection criteria for anatomic and dosimetric changes during radiotherapy were found and listed. The heterogeneity between studies prevented unambiguous conclusions on how to identify patients who may benefit from ART in head and neck cancer. Potential pre-treatment selection criteria identified from this review include tumour location (nasopharyngeal carcinoma), age, body mass index, planned dose to the parotid glands, the initial parotid gland volume, and the overlap volume of the parotid glands with the target volume. These criteria should be further explored in well-designed and well-powered prospective studies, in which possible relationships between anatomic and dosimetric changes and outcome need to be established.

Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5mm) and generated new external contours of head and neck. The volumes of reconstructed external contours were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from -2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary.