J. Crezee
University of Amsterdam, Radiation Oncology, Faculty Member
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Background: Irreversible electroporation (IRE) is an ablation technique based on the application of short, high-voltage pulses between needle electrodes (diameter: ~1.0 × 10−3 m). A Finite Difference-based software simulating IRE... more
Background: Irreversible electroporation (IRE) is an ablation technique based on the application of short, high-voltage pulses between needle electrodes (diameter: ~1.0 × 10−3 m). A Finite Difference-based software simulating IRE treatment generally uses rectangular grids, yielding discretization issues when modeling cylindrical electrodes and potentially affecting the validity of treatment planning simulations. Aim: Develop an Electric-Potential Estimation (EPE) method for accurate prediction of the electric-potential distribution in the vicinity of cylindrical electrodes. Methods: The electric-potential values in the voxels neighboring the cylindrical electrode voxels were corrected based on analytical solutions derived for coaxial/cylindrical electrodes. Simulations at varying grid resolutions were validated using analytical models. Low-resolution heterogeneous simulations at 2.0 × 10−3 m excluding/including EPE were compared with high-resolution results at 0.25 × 10−3 m. Results...
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Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and... more
Purpose The combination of hyperthermia (HT) with radio(chemo)therapy or chemotherapy (CT) is an established treatment strategy for specific indications. Its application in routine clinical practice in Europe depends on regulatory and local conditions. We conducted a survey among European clinical centers to determine current practice of HT. Methods A questionnaire with 22 questions was sent to 24 European HT centers. The questions were divided into two main categories. The first category assessed how many patients are treated with HT in combination with radio(chemo)therapy or CT for specific indications per year. The second category addressed which hyperthermia parameters are recorded. Analysis was performed using descriptive methods. Results The response rate was 71% (17/24) and 16 centers were included in this evaluation. Annually, these 16 centers treat approximately 637 patients using HT in combination with radio(chemo)therapy or CT. On average, 34% (range: 3–100%) of patients ...
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Abstract Background In patients with inoperable local regional recurrences of breast cancer in previously irradiated areas, local control is difficult to maintain and treatment options are limited. The Dutch standard treatment for such... more
Abstract Background In patients with inoperable local regional recurrences of breast cancer in previously irradiated areas, local control is difficult to maintain and treatment options are limited. The Dutch standard treatment for such recurrences is reirradiation combined with hyperthermia. Apart from enhancing the effect of reirradiation, hyperthermia is also known to improve local effects of chemotherapy like cisplatin. This randomized phase-II trial compares reirradiation and hyperthermia versus the same treatment combined with cisplatin. Patients and methods From December 2010 up to January 2019, 49 patients were randomized, 27 in the standard arm and 22 in the combined arm. A total of 32 Gy was given in eight fractions of 4 Gy in 4 weeks, at two fractions per week. After January 2015, the radiation schedule was changed to 46 Gy in 23 fractions of 2 Gy, at five fractions per week. Hyperthermia was added once a week after radiotherapy. The combined arm was treated with four cycles of weekly cisplatin 40 mg/m2. Results Complete response rate was 60.9% in the standard arm and 61.1% in the combined arm (p = 0.87). Partial response rate was 30.4% in the standard arm and 33.3% in the combined arm (p = 0.79). One-year overall survival was 63.4% in the standard arm and 57.4% in the combined arm. One-year local progression-free interval was 81.5% in the standard arm and 88.1% in the combined arm (p = 0.95). Twenty-five percentage of patients in the standard arm experienced grade 3 or 4 acute toxicity and 29% of patients in the combined arm (p = 0.79). Conclusion No potential benefit could be detected of adding cisplatin to reirradiation and hyperthermia in patients with recurrent breast cancer in a previously irradiated area. With or without cisplatin, most patients had subsequent local control until last follow-up or death.
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Treatment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is relatively ineffective and associated with morbidity. This raises the question whether we should focus on prevention of the development of PC. We determined... more
Treatment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is relatively ineffective and associated with morbidity. This raises the question whether we should focus on prevention of the development of PC. We determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in a short stay setting. A prospective single centre pilot study was conducted between January 2011 and July 2012. Ten patients at risk of developing PC of CRC origin were included. Laparoscopic HIPEC using Mitomycin-C (90 min; inflow temperature 42-43 °C) was performed within several weeks after primary resection of CRC and was considered feasible when postoperative hospital stay was three days or shorter in at least six patients, and if a maximum of one conversion and one re-admission within 30 days occurred. HIPEC was performed after a median of 6 weeks (range 3-9 weeks). Postoperatively, five patients were discharged at day one, four patients at day two an...
Research Interests: Medicine, Colorectal cancer, Prospective studies, Humans, Female, and 14 moreFeasibility Studies, Male, Length of Stay, Aged, Middle Aged, Carcinoma, Adult, Pilot Projects, Laparoscopy, Mitomycin, Cohort Studies, Colorectal Neoplasms, hyperthermic intraperitoneal chemotherapy, and Peritoneal Neoplasms
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Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40–43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby... more
Hyperthermia (HT) is a cancer treatment modality which targets malignant tissues by heating to 40–43 °C. In addition to its direct antitumor effects, HT potently sensitizes the tumor to radiotherapy (RT) and chemotherapy (CT), thereby enabling complete eradication of some tumor entities as shown in randomized clinical trials. Despite the proven efficacy of HT in combination with classic cancer treatments, there are limited international standards for the delivery of HT in the clinical setting. Consequently, there is a large variability in reported data on thermometric parameters, including the temperature obtained from multiple reference points, heating duration, thermal dose, time interval, and sequence between HT and other treatment modalities. Evidence from some clinical trials indicates that thermal dose, which correlates with heating time and temperature achieved, could be used as a predictive marker for treatment efficacy in future studies. Similarly, other thermometric parame...
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Purpose: Earlier work showed that IVIM-NET_orig, an unsupervised physics-informed deep neural network, was more accurate than other state-of-the-art intravoxel-incoherent motion (IVIM) fitting approaches to DWI. This study presents an... more
Purpose: Earlier work showed that IVIM-NET_orig, an unsupervised physics-informed deep neural network, was more accurate than other state-of-the-art intravoxel-incoherent motion (IVIM) fitting approaches to DWI. This study presents an improved version: IVIM-NET_optim, and characterizes its superior performance in pancreatic ductal adenocarcinoma (PDAC) patients. Method: In simulations (SNR=20), the accuracy, independence and consistency of IVIM-NET were evaluated for combinations of hyperparameters (fit S0, constraints, network architecture, # hidden layers, dropout, batch normalization, learning rate), by calculating the NRMSE, Spearman's ρ, and the coefficient of variation (CV_NET), respectively. The best performing network, IVIM-NET_optim was compared to least squares (LS) and a Bayesian approach at different SNRs. IVIM-NET_optim's performance was evaluated in 23 PDAC patients. 14 of the patients received no treatment between scan sessions and 9 received chemoradiotherapy...
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Hyperthermia therapy (40–44 °C) is a promising option to increase efficacy of radiotherapy/chemotherapy for brain tumours, in particular paediatric brain tumours. The Chalmers Hyperthermia Helmet is developed for this purpose.... more
Hyperthermia therapy (40–44 °C) is a promising option to increase efficacy of radiotherapy/chemotherapy for brain tumours, in particular paediatric brain tumours. The Chalmers Hyperthermia Helmet is developed for this purpose. Hyperthermia treatment planning is required for treatment optimisation, but current planning systems do not involve a physically correct model of cerebrospinal fluid (CSF). This study investigates the necessity of fluid modelling for treatment planning. We made treatments plans using the Helmet for both pre-operative and post-operative cases, comparing temperature distributions predicted with three CSF models: a convective “fluid” model, a non-convective “solid” CSF model, and CSF models with increased effective thermal conductivity (“high-k”). Treatment plans were evaluated by T90, T50 and T10 target temperatures and treatment-limiting hot spots. Adequate heating is possible with the helmet. In the pre-operative case, treatment plan quality was comparable for...
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PURPOSE Temperature measurement during superficial hyperthermia is limited by poor spatial resolution. We investigated two sheets to improve temperature monitoring of the skin surface. METHODS AND MATERIALS Two different sheets were... more
PURPOSE Temperature measurement during superficial hyperthermia is limited by poor spatial resolution. We investigated two sheets to improve temperature monitoring of the skin surface. METHODS AND MATERIALS Two different sheets were studied with a grid of temperature sensors with one sensor per ~5 cm2. The first was a matrix of multisensor thermocouple probes laced through a silicone sheet. The second sheet had rows of thermistors connected by meandering copper leads mounted on stretchable printed circuit board (SPCB). Accuracy, temperature resolution and two hour stability of both sheets were investigated. Furthermore, we determined the ability to follow body contours, thermal conduction errors and electromagnetic (EM) compatibility to clinically used 434 and 915 MHz hyperthermia applicators. RESULTS For both sheets the accuracy (≤0.2 °C), temperature resolution (≤0.03 °C) and stability (≤0.01°C hr-1) were adequate for clinical use. Thermal conduction errors ranged from 5.25 - 11.2...
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Experimental electric field and dielectric tissue property mapping using a regularized CSI-EPT reconstruction method Edmond Balidemaj, Johan Trinks, Rob F. Remis, Hans Crezee, Astrid van Lier, Aart J. Nederveen, and Cornelis A.T. van den... more
Experimental electric field and dielectric tissue property mapping using a regularized CSI-EPT reconstruction method Edmond Balidemaj, Johan Trinks, Rob F. Remis, Hans Crezee, Astrid van Lier, Aart J. Nederveen, and Cornelis A.T. van den Berg Radiotherapy, Academic Medical Center, Amsterdam, Netherlands, Technical University Delft, Delft, Netherlands, UMC Utrecht, Utrecht, Netherlands, Academic Medical Center, Amsterdam, Netherlands
Transperineal laser ablation (TPLA) treatment of prostate cancer allows for a minimal invasive treatment approach. However, a predictive dosimetry model for accurate treatment planning for prostate cancer is not yet available. Therefore,... more
Transperineal laser ablation (TPLA) treatment of prostate cancer allows for a minimal invasive treatment approach. However, a predictive dosimetry model for accurate treatment planning for prostate cancer is not yet available. Therefore, we simulated TPLA treatments on porcine liver and quantitatively evaluated thermal distribution and histology slides were made. Hereby, we determined the cumulative equivalent thermal isoeffect dose at 43°C (CEM43) that predicts cell death and led to the development of a dosimetry model.
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Research Interests: Engineering and Medicine
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Cancer treatments based on mild hyperthermia (39–43 °C, HT) are applied to a widening range of cancer types, but several factors limit their efficacy and slow down more widespread adoption. These factors include difficulties in adequate... more
Cancer treatments based on mild hyperthermia (39–43 °C, HT) are applied to a widening range of cancer types, but several factors limit their efficacy and slow down more widespread adoption. These factors include difficulties in adequate heat delivery, a short therapeutic window and the acquisition of thermotolerance by cancer cells. Here, we explore the biological effects of HT, the cellular responses to these effects and their clinically-relevant consequences. We then identify the heat stress response—the cellular defense mechanism that detects and counteracts the effects of heat—as one of the major forces limiting the efficacy of HT-based therapies and propose targeting this mechanism as a potentially universal strategy for improving their efficacy.
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Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature... more
Background: Accurate monitoring of skin surface temperatures is necessary to ensure treatment quality during superficial hyperthermia. A high-resolution thermal monitoring sheet (TMS) was developed to monitor the skin surface temperature distribution. The influence of the TMS on applicator performance was investigated, feasibility and ability to reliably monitor the temperature distribution were evaluated in a clinical study. Methods: Phantom experiments were performed to determine the influence of the TMS on power deposition patterns, applicator efficiency, and heat transfer of the water bolus for 434 and 915 MHz applicators. Clinical feasibility was evaluated in 10 women with locoregional recurrent breast cancer. Skin surface temperatures during consecutive treatments were monitored alternatingly with either standard Amsterdam UMC thermometry or TMS. Treatments were compared using (generalized) linear mixed models. Results: The TMS did not significantly affect power deposition pat...
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Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin... more
Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (T) and maximum (T) temperature, as well as T90 and T10. Eighty patients were included yielding a total of 400 hyperther...
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To investigate the relationship of thermal skin damage (TSD) to time-temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the... more
To investigate the relationship of thermal skin damage (TSD) to time-temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Sixty-eight patients (26%) developed 79 sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to act...
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Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of... more
Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted el...
Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or... more
Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence for the present standard treatment of transurethral resection of the bladder (TURB) followed by intravesical instillation of Mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). To decrease this high recurrence rate, alternative treatments are studied. Intravesical MMC combined with hyperthermia could be an interesting alternative active treatment for intermediate- and high-risk NMIBC, and has been investigated in the past years. Hyperthermia, raising tumour temperatures to 40-44 °C, can be achieved with several hyperthermia systems, based on three different techniques: 1) intravesical microwave induced heating, 2) conductive heating, and 3) loco-regional, using external radiofrequency antennas. In this review an overview is given of the available hyperthermia systems and the reported outcomes. Future directions are discussed. Optimal implementation of a combined regimen of MMC and hyperthermia ...
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Research Interests: Cancer and Power Control
Specific absorption rate (SAR) assessment is essential for safety purposes during MR acquisition. Online SAR assessment is not trivial and requires, in addition, knowledge of the electric tissue properties and the electric fields in the... more
Specific absorption rate (SAR) assessment is essential for safety purposes during MR acquisition. Online SAR assessment is not trivial and requires, in addition, knowledge of the electric tissue properties and the electric fields in the human anatomy. In this study, the potential of the recently developed CSI-EPT method to reconstruct SAR distributions is investigated. This method is based on integral representations for the electromagnetic field and attempts to reconstruct the tissue parameters and the electric field strength based on [Formula: see text] field data only. Full three-dimensional FDTD simulations using a female pelvis model are used to validate two-dimensional CSI reconstruction results in the central transverse plane of a 3T body coil. Numerical experiments demonstrate that the reconstructed SAR distributions are in good agreement with the SAR distributions as determined via 3D FDTD simulations and show that these distributions can be computed very efficiently in the...
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Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate... more
Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment deliv...
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Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45°C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients... more
Treatment options for irresectable locoregional recurrent breast cancer in previously irradiated area are limited. Hyperthermia, elevating tumor temperature to 40-45°C, sensitizes radio-and-chemotherapy. Four hundred and fourteen patients treated with reirradiation+hyperthermia (reRT+HT) in the AMC(n=301) and the BVI(n=113), from 1982 to 2005 were retrospectively analyzed for treatment response, locoregional control (LC) and prognostic factors for LC and toxicity. All patients received previous irradiation (median 50Gy). reRT consisted of 8×4Gy-2/week (AMC) or 12×3Gy-4/week (BVI). Hyperthermia was added once (AMC)/twice (BVI) a week. Overall clinical response rate was 86%. The 3-year LC rate was 25%. The number of recurrence episodes, distant metastases (DM), tumor site, tumor size, time to recurrence and treatment year were significant for LC. Acute ⩾grade 3 toxicity occurred in 24% of patients. Actuarial late ⩾grade 3 toxicity was 23% at 3-years. In multivariable analysis reRT fraction dose was significantly related to late ⩾grade 3 toxicity. reRT+HT is an effective curative and palliative treatment option for patients with irresectable locoregional recurrent breast cancer in previously irradiated area. Early referral, treatment of chest wall recurrences ⩽5cm in the absence of distant metastases, provided the highest local control rates. The cumulative effects of past and present treatments should be accounted for by adjusting treatment protocol to minimize toxicity.
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Purpose: The use of patient-specific radiofrequency (RF) shim sets to mitigate B 1 + inhomogeneity in high-field MRI requires on-line, patient-specific monitoring of the specific absorption rate (SAR). Numerical simulation is currently... more
Purpose: The use of patient-specific radiofrequency (RF) shim sets to mitigate B 1 + inhomogeneity in high-field MRI requires on-line, patient-specific monitoring of the specific absorption rate (SAR). Numerical simulation is currently the most effective way to do so as the electric fields required for this evaluation cannot be measured directly. These simulations however require a dielectric model of the patient, which largely complicates the clinical work-flow if this needs to be done on an individual basis. For this reason, generality in the SAR distribution during MRI of the head is investigated to evaluate whether a generic model can be used as a practical alternative. Methods: Electric and magnetic fields were simulated for an 8 channel parallel transmit array [1] with an in-house developed GPU implementation of the finite-difference time-domain algorithm. The array was loaded with 6 different voxel models of the head (2mm isotropic) constructed from detailed manual segmentati...
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Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. The records of 175,538... more
Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for hyperthermia or equivalent words. A total of 109 trials were identified in which hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional hyperthermia, 13 trials (12%) whole body hyperthermia, seven trials (6%) superf...