R.G.J. Kierkels

Sparing the region of the salivary gland containing stem cells preserves saliva production after radiotherapy for head and neck cancer

Avoiding irradiation of the region of the parotid gland containing stem cells reduces the risk of xerostomia (dry mouth). Preserving saliva flow after radiotherapy Radiotherapy for head and neck cancer may damage the salivary glands, resulting in reduced salivation with consequent xerostomia (dry mouth). Xerostomia affects the quality of life of patients with head and neck cancer. van Luijk and co-workers reported the location of salivary (parotid) gland stem cells in the mouse, rat, and human. Next, they showed in rat and human that irradiation of the salivary gland region containing the highest number of stem cells resulted in the greatest loss of saliva production after treatment. Finally, the authors showed that it is possible to avoid irradiation of this specific area during therapy, which may reduce the patient’s risk of developing post-radiotherapy xerostomia. Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

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.

Multivariable normal tissue complication probability model-based treatment plan optimization for grade 2-4 dysphagia and tube feeding dependence in head and neck radiotherapy

BACKGROUND AND PURPOSE Radiotherapy of the head and neck is challenged by the relatively large number of organs-at-risk close to the tumor. Biologically-oriented objective functions (OF) could optimally distribute the dose among the organs-at-risk. We aimed to explore OFs based on multivariable normal tissue complication probability (NTCP) models for grade 2-4 dysphagia (DYS) and tube feeding dependence (TFD). MATERIALS AND METHODS One hundred head and neck cancer patients were studied. Additional to the clinical plan, two more plans (an OFDYS and OFTFD-plan) were optimized per patient. The NTCP models included up to four dose-volume parameters and other non-dosimetric factors. A fully automatic plan optimization framework was used to optimize the OFNTCP-based plans. RESULTS All OFNTCP-based plans were reviewed and classified as clinically acceptable. On average, the Δdose and ΔNTCP were small comparing the OFDYS-plan, OFTFD-plan, and clinical plan. For 5% of patients NTCPTFD reduced >5% using OFTFD-based planning compared to the OFDYS-plans. CONCLUSIONS Plan optimization using NTCPDYS- and NTCPTFD-based objective functions resulted in clinically acceptable plans. For patients with considerable risk factors of TFD, the OFTFD steered the optimizer to dose distributions which directly led to slightly lower predicted NTCPTFD values as compared to the other studied plans.

An automated, quantitative, and case-specific evaluation of deformable image registration in computed tomography images

A prerequisite for adaptive dose-tracking in radiotherapy is the assessment of the deformable image registration (DIR) quality. In this work, various metrics that quantify DIR uncertainties are investigated using realistic deformation fields of 26 head and neck and 12 lung cancer patients. Metrics related to the physiologically feasibility (the Jacobian determinant, harmonic energy (HE), and octahedral shear strain (OSS)) and numerically robustness of the deformation (the inverse consistency error (ICE), transitivity error (TE), and distance discordance metric (DDM)) were investigated. The deformable registrations were performed using a B-spline transformation model. The DIR error metrics were log-transformed and correlated (Pearson) against the log-transformed ground-truth error on a voxel level. Correlations of r  ⩾  0.5 were found for the DDM and HE. Given a DIR tolerance threshold of 2.0 mm and a negative predictive value of 0.90, the DDM and HE thresholds were 0.49 mm and 0.014, respectively. In conclusion, the log-transformed DDM and HE can be used to identify voxels at risk for large DIR errors with a large negative predictive value. The HE and/or DDM can therefore be used to perform automated quality assurance of each CT-based DIR for head and neck and lung cancer patients.

The effects of computed tomography image characteristics and knot spacing on the spatial accuracy of B-spline deformable image registration in the head and neck geometry

ObjectivesTo explore the effects of computed tomography (CT) image characteristics and B-spline knot spacing (BKS) on the spatial accuracy of a B-spline deformable image registration (DIR) in the head-and-neck geometry.MethodsThe effect of image feature content, image contrast, noise, and BKS on the spatial accuracy of a B-spline DIR was studied. Phantom images were created with varying feature content and varying contrast-to-noise ratio (CNR), and deformed using a known smooth B-spline deformation. Subsequently, the deformed images were repeatedly registered with the original images using different BKSs. The quality of the DIR was expressed as the mean residual displacement (MRD) between the known imposed deformation and the result of the B-spline DIR.Finally, for three patients, head-and-neck planning CT scans were deformed with a realistic deformation field derived from a rescan CT of the same patient, resulting in a simulated deformed image and an a-priori known deformation field. Hence, a B-spline DIR was performed between the simulated image and the planning CT at different BKSs. Similar to the phantom cases, the DIR accuracy was evaluated by means of MRD.ResultsIn total, 162 phantom registrations were performed with varying CNR and BKSs. MRD-values < 1.0 mm were observed with a BKS between 10–20 mm for image contrast ≥ ± 250 HU and noise < ± 200 HU. Decreasing the image feature content resulted in increased MRD-values at all BKSs. Using BKS = 15 mm for the three clinical cases resulted in an average MRD < 1.0 mm.ConclusionsFor synthetically generated phantoms and three real CT cases the highest DIR accuracy was obtained for a BKS between 10–20 mm. The accuracy decreased with decreasing image feature content, decreasing image contrast, and higher noise levels. Our results indicate that DIR accuracy in clinical CT images (typical noise levels < ± 100 HU) will not be effected by the amount of image noise.

External validation of a multifactorial normal tissue complication probability model for tube feeding dependence at 6 months after definitive radiotherapy for head and neck cancer

BACKGROUND AND PURPOSE The purpose of this study was to externally validate a previously published normal tissue complication probability (NTCP) model for tube feeding dependence at 6 months (TUBEM6) after completion of (chemo) radiotherapy. MATERIALS AND METHODS This study evaluated 122 head and neck cancer patients treated by definitive (chemo) radiotherapy. The closed testing procedure was used to select the appropriate method for updating the NTCP model. In this procedure, the likelihood ratio test was used to compare the updated model against the original model. RESULTS Mean predicted NTCP was 12.2% (95% CI: 9.9%-14.5%) when using the original NTCP model for TUBEM6. TUBEM6 at our institute was 5.7% (95% CI: 1.8-9.6%) for the 122 patients evaluated. The test for the model revision against the original NTCP model was statistically significant (p = 0.032). The test for the model revision against the model adjusting intercept only was not statistically significant (p = 0.240). According to the closed testing procedure, the model required adjusting the intercept only. CONCLUSIONS TUBEM6 at our institute was lower than that predicted by the original NTCP model. The closed testing procedure indicated that only an adjustment of the intercept was needed indicating the importance of external validation.

Reproducibility of the lung anatomy under active breathing coordinator control: Dosimetric consequences for scanned proton treatments

Purpose The treatment of moving targets with scanned proton beams is challenging. For motion mitigation, an Active Breathing Coordinator (ABC) can be used to assist breath‐holding. The delivery of pencil beam scanning fields often exceeds feasible breath‐hold durations, requiring high breath‐hold reproducibility. We evaluated the robustness of scanned proton therapy against anatomical uncertainties when treating nonsmall‐cell lung cancer (NSCLC) patients during ABC controlled breath‐hold. Methods Four subsequent MRIs of five healthy volunteers (3 male, 2 female, age: 25–58, BMI: 19–29) were acquired under ABC controlled breath‐hold during two simulated treatment fractions, providing both intrafractional and interfractional information about breath‐hold reproducibility. Deformation vector fields between these MRIs were used to deform CTs of five NSCLC patients. Per patient, four or five cases with different tumor locations were modeled, simulating a total of 23 NSCLC patients. Robustly optimized (3 and 5 mm setup uncertainty respectively and 3% density perturbation) intensity‐modulated proton plans (IMPT) were created and split into subplans of 20 s duration (assumed breath‐hold duration). A fully fractionated treatment was recalculated on the deformed CTs. For each treatment fraction the deformed CTs representing multiple breath‐hold geometries were alternated to simulate repeated ABC breath‐holding during irradiation. Also a worst‐case scenario was simulated by recalculating the complete treatment plan on the deformed CT scan showing the largest deviation with the first deformed CT scan, introducing a systematic error. Both the fractionated breath‐hold scenario and worst‐case scenario were dosimetrically evaluated. Results Looking at the deformation vector fields between the MRIs of the volunteers, up to 8 mm median intra‐ and interfraction displacements (without outliers) were found for all lung segments. The dosimetric evaluation showed a median difference in D98% between the planned and breath‐hold scenarios of −0.1 Gy (range: −4.1 Gy to 2.0 Gy). D98% target coverage was more than 57.0 Gy for 22/23 cases. The D1 cc of the CTV increased for 21/23 simulations, with a median difference of 0.9 Gy (range: −0.3 to 4.6 Gy). For 14/23 simulations the increment was beyond the allowed maximum dose of 63.0 Gy, though remained under 66.0 Gy (110% of the prescribed dose of 60.0 Gy). Organs at risk doses differed little compared to the planned doses (difference in mean doses <0.9 Gy for the heart and lungs, <1.4% difference in V35 [%] and V20 [%] to the esophagus and lung). Conclusions When treating under ABC controlled breath‐hold, robustly optimized IMPT plans show limited dosimetric consequences due to anatomical variations between repeated ABC breath‐holds for most cases. Thus, the combination of robustly optimized IMPT plans and the delivery under ABC controlled breath‐hold presents a safe approach for PBS lung treatments.

EP-1812: Adaptive VMAT for cT1-2aN0M0 laryngeal cancer: potential risk of target volume over dosage

ESTRO 35 2016 _____________________________________________________________________________________________________ Results: Figure 1 displays the mean differences of the dose metrics between repeated CT and CBCT, for Varian and Elekta CBCT scans. For Varian, a good agreement between the dose distributions recalculated on CBCT and repeated CT was observed when a thorax-specific HU-ED table was used. For Elekta, the dose metrics showed larger deviations with the thorax-specific HU-ED table, however, using a patientspecific HU-ED table resulted in similar accuracy as for Varian CBCT dose calculations. Differences between repeated CT and CBCT dose metrics were below 3% for both vendors.