Gerda M. Verduijn

Clinical integration of software tool VEDO for adaptive and quantitative application of phased array hyperthermia in the head and neck.

Abstract Background and purpose: In Rotterdam, patient-specific hyperthermia (HT) treatment planning (HTP) is applied for all deep head and neck (H&N) HT treatments. In this paper we introduce VEDO (the Visualisation Tool for Electromagnetic Dosimetry and Optimisation), the software tool required, and demonstrate its value for HTP-guided online complaint-adaptive (CA) steering based on specific absorption rate (SAR) optimisation during a H&N HT treatment. Materials and methods: VEDO integrates CA steering, visualisation of the SAR patterns and mean tumour SAR (SARtarget) optimisation in a single screen. The pre-calculated electromagnetic fields are loaded into VEDO. During treatment, VEDO shows the SAR pattern, overlaid on the patients’ CT-scan, corresponding to the actually applied power settings and it can (re-)optimise the SAR pattern to minimise SAR at regions where the patient senses discomfort while maintaining a high SARtarget. Results: The potential of the quantitative SAR steering approach using VEDO is demonstrated by analysis of the first treatment in which VEDO was used for two patients using the HYPERcollar. These cases show that VEDO allows response to power-related complaints of the patient and to quantify the change in absolute SAR: increasing either SARtarget from 96 to 178 W/kg (case 1); or show that the first SAR distribution was already optimum (case 2). Conclusion: This analysis shows that VEDO facilitates a quantitative treatment strategy allowing standardised application of HT by technicians of different HT centres, which will potentially lead to improved treatment quality and the possibility of tracking the effectiveness of different treatment strategies.

The impact of treatment modality and radiation technique on outcomes and toxicity of patients with locally advanced oropharyngeal cancer

To investigate the impact of treatment modality and radiation technique on oncologic outcomes and toxicity of patients with locally advanced oropharyngeal cancer (OPC).

CT-based patient modeling for head and neck hyperthermia treatment planning : manual versus automatic normal-tissue-segmentation

BACKGROUND AND PURPOSE Clinical trials have shown that hyperthermia, as adjuvant to radiotherapy and/or chemotherapy, improves treatment of patients with locally advanced or recurrent head and neck (H&N) carcinoma. Hyperthermia treatment planning (HTP) guided H&N hyperthermia is being investigated, which requires patient specific 3D patient models derived from Computed Tomography (CT)-images. To decide whether a recently developed automatic-segmentation algorithm can be introduced in the clinic, we compared the impact of manual- and automatic normal-tissue-segmentation variations on HTP quality. MATERIAL AND METHODS CT images of seven patients were segmented automatically and manually by four observers, to study inter-observer and intra-observer geometrical variation. To determine the impact of this variation on HTP quality, HTP was performed using the automatic and manual segmentation of each observer, for each patient. This impact was compared to other sources of patient model uncertainties, i.e. varying gridsizes and dielectric tissue properties. RESULTS Despite geometrical variations, manual and automatic generated 3D patient models resulted in an equal, i.e. 1%, variation in HTP quality. This variation was minor with respect to the total of other sources of patient model uncertainties, i.e. 11.7%. CONCLUSIONS Automatically generated 3D patient models can be introduced in the clinic for H&N HTP.

Accurate 3D temperature dosimetry during hyperthermia therapy by combining invasive measurements and patient-specific simulations

Abstract Purpose: Dosimetry during deep local hyperthermia treatments in the head and neck currently relies on a limited number of invasively placed temperature sensors. The purpose of this study was to assess the feasibility of 3D dosimetry based on patient-specific temperature simulations and sensory feedback. Materials and methods: The study includes 10 patients with invasive thermometry applied in at least two treatments. Based on their invasive thermometry, we optimised patient-group thermal conductivity and perfusion values for muscle, fat and tumour using a ‘leave-one-out’ approach. Next, we compared the accuracy of the predicted temperature (ΔT) and the hyperthermia treatment quality (ΔT50) of the optimisations based on the patient-group properties to those based on patient-specific properties, which were optimised using previous treatment measurements. As a robustness check, and to enable comparisons with previous studies, we optimised the parameters not only for an applicator efficiency factor of 40%, but also for 100% efficiency. Results: The accuracy of the predicted temperature (ΔT) improved significantly using patient-specific tissue properties, i.e. 1.0 °C (inter-quartile range (IQR) 0.8 °C) compared to 1.3 °C (IQR 0.7 °C) for patient-group averaged tissue properties for 100% applicator efficiency. A similar accuracy was found for optimisations using an applicator efficiency factor of 40%, indicating the robustness of the optimisation method. Moreover, in eight patients with repeated measurements in the target region, ΔT50 significantly improved, i.e. ΔT50 reduced from 0.9 °C (IQR 0.8 °C) to 0.4 °C (IQR 0.5 °C) using an applicator efficiency factor of 40%. Conclusion: This study shows that patient-specific temperature simulations combined with tissue property reconstruction from sensory data provides accurate minimally invasive 3D dosimetry during hyperthermia treatments: T50 in sessions without invasive measurements can be predicted with a median accuracy of 0.4 °C.

Status quo and directions in deep head and neck hyperthermia

The benefit of hyperthermia as a potent modifier of radiotherapy has been well established and more recently also the combination with chemotherapy was shown beneficial. Also for head and neck cancer, the impact of hyperthermia has been clinically demonstrated by a number of clinical trials. Unfortunately, the technology applied in these studies provided only limited thermal dose control, and the devices used only allowed treatment of target regions close to the skin. Over the last decade, we developed the technology for deep and controlled hyperthermia that allows treatment of the entire head and neck region. Our strategy involves focused microwave heating combined with 3D patient-specific electromagnetic and thermal simulations for conformal, reproducible and adaptive hyperthermia application. Validation of our strategy has been performed by 3D thermal dose assessment based on invasively placed temperature sensors combined with the 3D patient specific simulations. In this paper, we review the phase III clinical evidence for hyperthermia in head and neck tumors, as well as the heating and dosimetry technology applied in these studies. Next, we describe the development, clinical implementation and validation of 3D guided deep hyperthermia with the HYPERcollar, and its second generation, i.e. the HYPERcollar3D. Lastly, we discuss early clinical results and provide an outlook for this technology.

Single vocal cord irradiation: Image guided intensity modulated hypofractionated radiation therapy for T1a glottic cancer: Early clinical results

PURPOSE To report, from a retrospective analysis of prospectively collected data, on the feasibility, outcome, toxicity, and voice-handicap index (VHI) of patients with T1a glottic cancer treated by a novel intensity modulated radiation therapy technique developed at our institution to treat only the involved vocal cord: single vocal cord irradiation (SVCI). METHODS AND MATERIALS Thirty patients with T1a glottic cancer were treated by means of SVCI. Dose prescription was set to 16 × 3.63 Gy (total dose 58.08 Gy). The clinical target volume was the entire vocal cord. Setup verification was done by means of an online correction protocol using cone beam computed tomography. Data for voice quality assessment were collected prospectively at baseline, end of treatment, and 4, 6, and 12 weeks and 6, 12, and 18 months after treatment using VHI questionnaires. RESULTS After a median follow-up of 30 months (range, 7-50 months), the 2-year local control and overall survival rates were 100% and 90% because no single local recurrence was reported and 3 patients died because of comorbidity. All patients have completed the intended treatment schedule; no treatment interruptions and no grade 3 acute toxicity were reported. Grade 2 acute dermatitis or dysphagia was reported in only 5 patients (17%). No serious late toxicity was reported; only 1 patient developed temporary grade 2 laryngeal edema, and responded to a short-course of corticosteroid. The VHI improved significantly, from 33.5 at baseline to 9.5 and 10 at 6 weeks and 18 months, respectively (P<.001). The control group, treated to the whole larynx, had comparable local control rates (92.2% vs 100%, P=.24) but more acute toxicity (66% vs 17%, P<.0001) and higher VHI scores (23.8 and 16.7 at 6 weeks and 18 months, respectively, P<.0001). CONCLUSION Single vocal cord irradiation is feasible and resulted in maximal local control rate at 2 years. The deterioration in VHI scores was slight and temporary and subsequently improved to normal levels. Long-term follow-up is needed to consolidate these promising results.

Highly-conformal intensity-modulated radiotherapy reduced toxicity without jeopardizing outcome in patients with paranasal sinus cancer treated by surgery and radiotherapy or (chemo)radiation

OBJECTIVES To report oncologic outcomes of patients with paranasal sinus cancer (PNSC) treated by surgery and radiotherapy or (chemo)radiation and to investigate the impact of improving the radiation technique on outcomes and toxicity. MATERIALS AND METHODS Between 1999 and 2010, 82 consecutive patients with PNSC were treated by surgery and radiotherapy or by definitive (chemo)radiation. Three-dimensional conformal (3DCRT) or highly-conformal intensity-modulated RT (IMRT) was used. Endpoints were local control (LC), regional control (RC), disease-free (DFS), cause-specific (CSS), and overall survival (OS), late toxicity, and quality-of-life (QoL). RESULTS After median follow-up of 51 months, the 5-year actuarial rates of LC, RC, DFS, CSS, and OS were 74%, 94%, 56%, 64%, and 54%, respectively. Grade ≥ 2 late toxicity at 5-years was 28%. High T-stage and perineural invasion were significantly associated with poor LC and RT-technique with late toxicity. Late toxicity was significantly lowered using IMRT, compared to 3DCRT (17% vs. 52%, p<0.0001). Visual preservation were significantly improved using IMRT (88% and 65%, respectively, p=0.01). LC-rate was also improved by IMRT (80% vs. 64%, respectively, p=0.2). QoL-scores deteriorated during and shortly after treatment but returned in almost all scales to baseline levels within 3-12 months. CONCLUSIONS Surgery and radiotherapy or definitive (chemo)radiation resulted in good LC rates but with high rate of late side-effects. However, late toxicity and permanent visual impairment were significantly decreased by using highly-conformal IMRT without jeopardizing outcome. The improvements in the therapeutic ratio achieved by using IMRT would allow dose escalation of RT to further improve outcomes.

MRI integration into treatment planning of head and neck tumors: Can patient immobilization be avoided?

To assess whether deformable registration between CT and MR images can be used to avoid patient immobilization, we compared registration accuracy in various scenarios, with and without immobilization equipment. Whereas both deformable registration and the use of immobilization equipment improved the registration accuracy, the combination gave the best alignment.

Intralesional cryotherapy versus excision and corticosteroids or brachytherapy for keloid treatment: study protocol for a randomised controlled trial

BackgroundKeloids are a burden for patients due to physical, aesthetic and social complaints and treatment remains a challenge because of therapy resistance and high recurrence rates. The main goal of treatment is to improve the quality of life (QoL); this implies that, apart from surgical outcomes, patient-reported outcome measures (PROMs) need to be taken into account. Decision making in keloid treatment is difficult due to heterogeneity of the condition and the lack of comparative studies.Methods/DesignThis is a multicentre, randomised controlled open trial that compares 1) intralesional cryotherapy versus excision and corticosteroids for primary keloids, and 2) intralesional cryotherapy versus excision and brachytherapy for therapy-resistant keloids. The primary outcome is the Patient and Observer Scar Assessment Scale (POSAS), a 12-item scale (with score 12 indicating the best and 120 indicating the worst scar imaginable). A difference of six points on the total score is considered to be of clinical importance. Secondary outcomes are recurrence rates, volume reduction, Skindex-29 scores, SF-36 scores and complication rates. Primary and secondary outcome measurements are taken at baseline, and at 2, 12, 26 and 52 weeks postoperatively. For analysis, a linear mixed model is used. A total of 176 patients will be included over a period of 2.5 years. The protocol is approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam and follows good clinical practice guidelines.DiscussionThe outcomes of this study will improve evidence-based decision making for the treatment of keloids, as well as patient education.Trial registrationDutch Trial Register NTR4151.

Brachytherapy or stereotactic body radiotherapy boost for early-stage oropharyngeal cancer: comparable outcomes of two different approaches.

OBJECTIVES To compare outcome, toxicity and QoL of two boost modalities for T1-2 oropharyngeal carcinoma (OPC). MATERIALS AND METHODS Between 2000 and 2012, 250 consecutive patients with T1-2N0-3 were treated with 46-Gy of IMRT followed by boost using brachytherapy (BTB) or stereotactic body radiotherapy (CKB). Endpoints were local control (LC), disease-free survival (DFS), overall survival (OS), toxicity and prospective QoL-assessment. RESULTS The 3-year actuarial incidence of LC were 97% and 94% for the CKB and BTB, respectively (p=0.33). The figures for DFS were 92% and 86% (p=0.15) and for OS were 81% and 83% (p=0.82), respectively. The incidence of tube feeding were 17% and 20%, respectively (p=0.47). The figures for grade ⩾2 late dysphagia were 11% and 8% (p=0.34) and for xerostomia were 16% and 12% (p=0.28), respectively. For both modalities, clinically relevant deteriorations were seen on all scales at end of treatment but the scores returned to almost baseline levels within 6-12months, with exception of QLQ-H&N35-xerostomia. The difference on that scale was neither statistically significant nor clinically relevant between both modalities. CONCLUSION Comparable outcome, toxicity and QoL-scores were achieved with both modalities. In the light of the logistical hassle around the implantation, the need of dexterity, and the risk of anaesthesia and peri-operative complications associated with BTB, CKB might be regarded as the optimal option to boost early-stage OPC. However, in radiotherapy departments where no facilities are available for stereotactic radiotherapy, BTB is an elegant option to achieve excellent outcome with low toxicity profile and good QoL.