The dosimetric and clinical advantages of the GTV-CTV-PTV margins reduction by 6 mm in head and neck squamous cell carcinoma: Significant acute and late toxicity reduction.

PURPOSE: We aim to identify the dosimetric and clinical impact of reducing the total GTV-CTV-PTV margins in head-and-neck squamous cell carcinoma (HNSCC) treated with definitive (chemo)radiation. MATERIALS AND METHODS: The acute and late toxicity and outcomes of 155 consecutive patients treated between February 2017 and March 2019 with GTV-CTV-PTV margins of 9 mm were compared to those of 155 consecutive patients treated with total margin of 15 mm margin, before April 2015. All patients were treated with VMAT with daily-image guidance using CBCT. RESULTS: Reducing the GTV-CTV-PTV by 6 mm resulted in significant reduction of total irradiated volume (PTV-total) by a median of 28.1% and significant reduction of doses to all salivary glands (largest reduction ipsilateral parotid gland; median -9.6 Gy) and constrictor muscle (-6.1 Gy) with subsequent reduction of the incidence of overall acute grade 3 toxicity (47.7% for 9 mm and 66.5% for 15 mm groups, p = 0.001), grade 3 mucositis (18.1% vs. 35.5%, p < 0.001) and feeding tube-dependency at the end of treatment (24.5% vs. 40%, p = 0.005). The incidence of late grade ≥ 2 xerostomia and dysphagia were also significantly lower in the 9 mm group (31.7% vs. 58.6% p < 0.001, and 15.4% vs. 26.7%, p = 0.04). The 2-year rates of loco-regional control, disease-free and overall survival were 78.8% vs.75.8%, 70.9% vs. 64.4%, and 83.8% vs. 67.6%, (p > 0.05, all). CONCLUSION: Reduction of the total GTV-CTV-PTV margins from 15 to 9 mm in HNSCC significantly reduced the irradiated volumes and the dose to salivary glands and constrictor muscle with significant reduction of radiation-related toxicity. The loco-regional control rates of both groups were comparable.

An anomaly detector as a clinical decision support system for parotid gland delineations.

Purpose. Auto-contouring (AC) is rapidly becoming standard practice for OAR contouring. However, in clinical practice, clinicians still need to manually check and correct contours. Anomaly detection systems (ADS) can aid the clinical decision process by suggesting which structures require corrections or not, greatly enhancing the value of AC. The purpose of this work is to develop and evaluate a decision support system for detecting anomalies in the case of parotid gland delineations. METHODS: Head and neck parotid gland delineations (1037 right, 1038 left), were retrieved from the Netherlands Cancer Institute (NKI) database. Morphological and image-based features were extracted from each patient's CT and structure set. An isolation forest model was initially trained on 70% of the data, of which 10% had synthetically generated anomalies and validated on the remaining 30% of clinical data. The ADS was tested on an independent set of 250 patients (Normal: 174, Anomalies: 76) and on a clinical autocontouring software. RESULTS: Applied to the validation set, the ADS system resulted in area under the curve (AUC) values of 0.93 and 0.94 for the parotid left and right respectively. Image features appeared more important than morphological, but using all features resulted marginally in the best model. Applied to the test set the ADS system reached an accuracy level of 0.83 and 0.81 for the parotid left and right respectively. The ADS was particularly sensitive to uniform expansions/contractions, misplacements, extra/missing slices and anisotropic over-contouring. CONCLUSION: Anomaly detection can serve as a powerful contour quality assurance tool, especially for cases of organ misplacement and over-contouring.

First system for fully-automated multi-criterial treatment planning for a high-magnetic field MR-Linac applied to rectal cancer.

Background and purpose: In this study we developed a workflow for fully-automated generation of deliverable IMRT plans for a 1.5 T MR-Linac (MRL) based on contoured CT scans, and we evaluated automated MRL planning for rectal cancer.Methods: The Monte Carlo dose calculation engine used in the clinical MRL TPS (Monaco, Elekta AB, Stockholm, Sweden), suited for high accuracy dose calculations in a 1.5 T magnetic field, was coupled to our in-house developed Erasmus-iCycle optimizer. Clinically deliverable plans for 23 rectal cancer patients were automatically generated in a two-step process, i.e., multi-criterial fluence map optimization with Erasmus-iCycle followed by a conversion into a deliverable IMRT plan in the clinical TPS. Automatically generated plans (AUTOplans) were compared to plans that were manually generated with the clinical TPS (MANplans).Results: With AUTOplanning large reductions in planning time and workload were obtained; 4-6 h mainly hands-on planning for MANplans vs ∼1 h of mainly computer computation time for AUTOplans. For equal target coverage, the bladder and bowel bag Dmean was reduced in the AUTOplans by 1.3 Gy (6.9%) on average with a maximum reduction of 4.5 Gy (23.8%). Dosimetric measurements at the MRL demonstrated clinically acceptable delivery accuracy for the AUTOplans.Conclusions: A system for fully automated multi-criterial planning for a 1.5 T MR-Linac was developed and tested for rectal cancer patients. Automated planning resulted in major reductions in planning workload and time, while plan quality improved. Negative impact of the high magnetic field on the dose distributions could be avoided.

SPECT/CT-guided elective nodal irradiation for head and neck cancer is oncologically safe and less toxic: A potentially practice-changing approach.

BACKGROUND AND PURPOSE: Bilateral elective nodal irradiation (ENI) remains the standard treatment for head and neck squamous cell carcinoma (HNSCC). Unilateral ENI could reduce treatment toxicity and improve health-related quality-of-life (HRQOL). This prospective proof-of-principle trial (NCT02572661) investigated the feasibility, safety and clinical benefits of SPECT/CT-guided ENI of the node-negative contralateral neck. MATERIALS AND METHODS: Patients with lateralized T1-3N0-2bM0 HNSCC of the oropharynx, oral cavity, larynx and hypopharynx underwent SPECT/CT after peritumoral 99mTc-nanocolloid injection. Patients without contralateral lymph drainage received ipsilateral ENI only. If lymph drainage to only one contralateral hot spot was visible, ENI to the contralateral neck would be limited to only the level containing the hot spot. The primary endpoint was the incidence of contralateral regional failure (CRF) at 2 years. Toxicity and HRQOL were compared with a 1:1 matched historical cohort that received standard bilateral ENI (B-ENI) with identical planning and treatment techniques. RESULTS: Fifty patients were treated with SPECT/CT-guided ENI. After a median follow-up of 33 months (range 18-45), CRF was observed in one patient (2%; 95% confidence interval: 0-6%). Compared to the matched B-ENI group, patients treated with SPECT/CT-guided ENI had significantly lower incidences of grade ≥2 dysphagia (54% vs. 82%; p < 0.001), tube feeding (10% vs. 50%; p < 0.001) and late grade ≥2 xerostomia (9% vs. 54%; p < 0.001). Significant and clinically relevant HRQOL benefits of SPECT/CT-guided ENI were observed on the EORTC QLQ-C30 summary score, and QLQ-HN35 swallowing and dry mouth subscales. CONCLUSION: SPECT/CT-guided ENI is associated with a low risk of contralateral regional failure. Compared to B-ENI, SPECT/CT-guided ENI significantly reduces dysphagia, feeding tube placement, and late xerostomia and improves HRQOL.

SPECT/CT-guided elective nodal irradiation for head and neck cancer: Estimation of clinical benefits using NTCP models.

BACKGROUND AND PURPOSE: The great majority of patients with lateralized head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy routinely undergo bilateral elective nodal irradiation (ENI), even though the incidence of contralateral regional failure after unilateral ENI is low. Excluding the contralateral neck from elective irradiation could reduce radiation-related toxicity and improve quality-of-life. The current study investigated the dosimetric benefits of a novel approach using lymph drainage mapping by SPECT/CT to select patients for unilateral ENI. PATIENTS AND METHODS: Forty patients with lateralized cT1-3N0-2bM0 HNSCC underwent lymph drainage mapping. Two radiation plans were made; the real plan with which patients were actually treated (selective SPECT/CT-guided plan irradiating the ipsilateral neck ±â€¯any contralateral draining level); and the virtual plan (standard plan according to institutional guidelines, as if the same patient would have been treated bilaterally). Radiation doses to clinically important organs-at-risk were compared between the two plans. We used five normal tissue complication probability (NTCP) models to predict the clinical benefits of this approach. RESULTS: Median dose reductions to the contralateral parotid gland, contralateral submandibular gland, glottic larynx, supraglottic larynx, constrictor muscle and thyroid gland were 19.2, 27.3, 11.4, 9.7, 12.1 and 18.4 Gy, respectively. Median NTCP reductions for xerostomia, contralateral parotid function, dysphagia, hypothyroidism and laryngeal edema were 20%, 14%, 10%, 20% and 5% respectively. CONCLUSIONS: Selective SPECT/CT-guided ENI results in significant dose reductions to various organs-at-risk and corresponding NTCP values, and will subsequently reduce the incidence and severity of different troublesome radiation-related toxicities and improve quality-of-life.

Tumor Trailing for Liver SBRT on the MR-Linac.

PURPOSE: Tumor trailing is a treatment delivery technique that continuously adjusts the beam aperture according to the last available time-averaged position of the target. This study investigates whether tumor trailing on a magnetic resonance (MR) linear accelerator (linac) can improve target coverage in liver stereotactic body radiation therapy (SBRT) in the case of baseline motion. METHODS AND MATERIALS: For 17 patients with oligometastatic liver disease, midposition SBRT treatment plans (3 × 20 Gy, 11-beam intensity modulated radiotherapy) were created for the Elekta Unity MR-Linac. Treatment was simulated using an in-house-developed delivery emulator. Respiratory motion was modelled as the superposition of periodic motion (patient-specific amplitude, 4-second period) and the following baseline motion scenarios: a continuous linear drift (0.5 mm/min), (2) a single shift halfway through treatment (10 mm), (3) a periodic drift (amplitude: 5 mm, period: 5 minutes), or (4) MR imaging-measured baseline drifts. Delivered dose was calculated under full consideration of the patient and machine motion interplay. In addition, trailing was experimentally validated on the MR-Linac using a programmable motion phantom. RESULTS: The average simulated delivery and beam-on times were 15.9 and 8.7 minutes, respectively. An imaging frequency of ≥1 Hz was deemed necessary for trailing. Trailing increased the median gross tumor volume D98% dose by 1.9 Gy (linear drift), 1.2 Gy (single shift), 0.7 Gy (periodic drift), and 0.5 to 1.5 Gy (measured drifts) per fraction, compared with a conventional delivery. In the phantom experiments, the 3%/2 mm local gamma pass rate nearly doubled to 98% when using trailing. CONCLUSION: Tumor trailing on the MR-Linac restores target dose in liver SBRT in the case of baseline motion for the presented patient cohort.

Evaluation of plan quality in radiotherapy planning with an MR-linac.

BACKGROUND & PURPOSE: Clinical introduction of magnetic resonance (MR)-guided radiotherapy involves treatment planning while taking into account machine-specific characteristics. Our aim was to investigate the feasibility of high-quality MR-linac treatment planning for an MR-linac and to benchmark MR-linac plan quality (IMRT) against current clinical practice (VMAT). MATERIALS & METHODS: Data of eight rectal and eight prostate cancer patients, who received radiotherapy on a conventional CBCT-integrated linac, were selected. Clinically acquired CTs and associated delineations of target volumes and organs-at-risk (OARs) were used for MR-linac treatment planning in Monaco. To investigate treatment planning software bias 'quasi MR-linac plans' were generated in Pinnacle3 by mimicking MR-linac specific beam characteristics. MR-linac, quasi MR-linac, and clinical plans were compared and differences in target and OAR doses assessed. Differences in plan complexity were determined by the number of segments and monitor units. RESULTS: Compared to clinical plans, MR-linac plans showed a statistically significant decrease in plan homogeneity, an increase in PTV Dmean (prostate: 0.6 Gy; rectum: 0.8 Gy) and D1% (prostate: 1.9 Gy; rectum: 2.0 Gy), and increases in OAR dose. Quasi MR-linac plans were comparable to MR-linac plans with respect to OAR dose and plan homogeneity. For rectal cancer an increase was seen in PTV Dmean (0.12 Gy) and D1% (0.5 Gy) compared to regular MR-linac plans. All created plans were clinically equivalent to current clinical practice. CONCLUSIONS: This study demonstrates the feasibility of creating high-quality MR-linac treatment plans. The results supported the clinical introduction of an MR-linac.