| 1. |
- Bakker, A., et al.
(author)
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Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments
- 2018
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 34:7, s. 910-917
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Journal article (peer-reviewed)abstract
- Purpose: 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. Methods: 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 cm2). 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 (Tmin) and maximum (Tmax) temperature, as well as T90 and T10. Results: Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was 50 sensors were used. Subsets of 50 sensors were used. Thermal profiles (8–21 probes) yielded a median ΔT < 0.01 °C for T90 and Tmax, with a 95%CI of −0.2 °C and 0.4 °C, respectively. The detection rate of Tmax≥43 °C is ≥85% while using >50 stationary sensors or thermal profiles. Conclusions: Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm2applicator. Thermal mapping is a valid alternative.
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| 2. |
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| 3. |
- Belgrano, Valerio, et al.
(author)
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BRAF status as a predictive factor for response in isolated limb perfusion.
- 2019
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In: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. - : Informa UK Limited. - 1464-5157. ; 36:1, s. 511-15
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Journal article (peer-reviewed)abstract
- Isolated limb perfusion (ILP) is a treatment option for unresectable in-transit melanoma metastases of the extremities. Approximately two-thirds of the patients have a complete response, and known predictive factors mainly regard tumor burden. In an attempt to identify subgroups with higher response rates, we retrospectively analyzed the predictive value of the BRAF V600E/K mutation for response at our institution.Between January 2012 and December 2017, 98 consecutive patients underwent first-time ILP with melphalan for melanoma in-transit metastases and were included in the study. Data was retrieved from our prospectively kept database. Tumor burden was assessed preoperatively as number of lesions and largest tumor diameter. BRAF status was determined according to clinical routine. Response rates were classified according to WHO criteria.Of the 98 patients included in the analysis, 32 patients had a BRAF V600E/K mutation (33%) and 66 patients were BRAF wild type (wt). There was no difference in age, sex or tumor burden between the groups. Comparing response between BRAF V600E/K mutation and BRAF wt, the overall response rate was 69% vs. 77% (p=.36) and the complete response rate was 47% vs. 52% (p=.67). There was no difference in survival, with a median survival of 47 months.In this consecutive series of patients, BRAF V600E/K mutation was not found to be a significant factor for response or survival following ILP.
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| 4. |
- Belgrano, Valerio, et al.
(author)
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Isolated limb perfusion as a treatment option for rare types of tumours
- 2016
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 32:6, s. 595-599
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Journal article (peer-reviewed)abstract
- Background: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. Methods: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. Results: The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). Conclusions: These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.
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| 5. |
- Ben-Shabat, Ilan, et al.
(author)
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The effect of perfusate buffering on toxicity and response in isolated hepatic perfusion for uveal melanoma liver metastases
- 2017
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 483-488
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Journal article (peer-reviewed)abstract
- Background: Isolated hepatic perfusion (IHP) is a treatment option for patients with liver metastases. Previous studies have found that liver toxicity is one of the limiting factors, and in an attempt to reduce the toxicity a buffering agent was added to the perfusate. The aim was to retrospectively analyse if this buffering reduced toxicity and complication rates.Methods: A retrospective review of 52 consecutive patients with uveal melanoma liver metastases treated with IHP between 2005 and 2013. Patients were followed by daily liver function tests (LFT). Toxicity was graded according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE; United States Department of Health & Human Services, Washington, D.C), complications according to Clavien-Dindo and response according to RECIST-criteria.Results: Thirty-six patients were treated with a buffered perfusate and 16 patients without buffer. There was no difference in age, gender, largest tumour size or number of tumours between the groups. There was a significantly lower mean in peak ALT, AST, PK (INR) and bilirubin when comparing buffer with no-buffer. There were five major complications without a significant difference between the groups (8.3 vs. 12.5%, p=0.33). There was a lower complete response (CR) rate (11 vs. 44%, p=0.023) and a trend for shorter time to local progression (9.2 vs. 17.6 months, p=0.096); however, not significant in multivariate analysis. There was no difference in survival (24.2 vs. 26.0 months, p=0.43) between the two groups.Conclusions: Adding buffer to the perfusate during IHP significantly reduces postoperative LFTs; however, without a reduced complication rate. Interestingly, buffering also seems to reduce the response rate; however, this did not translate into a survival difference. To address if buffering adds any clinical benefit to the patients concerning toxicity, a larger prospective trial is necessary.
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| 6. |
- Blad, B., et al.
(author)
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Quantitative assessment of impedance tomography for temperature measurements in hyperthermia
- 1992
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 8:1, s. 33-43
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Journal article (peer-reviewed)abstract
- The objective of this study is a non-invasive assessment of the thermal dose in hyperthermia. Electrical impedance tomography (EIT) has previously been given a first trial as a temperature monitoring method together with microwave-induced hyperthermia treatment, but it has not been thoroughly investigated. In the present work we have examined this method in order to investigate the correlation in vitro between the true spatial temperature distribution and the corresponding measured relative resistivity changes. Different hyperthermia techniques, such as interstitial water tubings, microwave-induced, laser-induced and ferromagnetic seeds have been used. The results show that it is possible to find a correlation between the measured temperature values and the tomographically measured relative resistivity changes in tissue-equivalent phantoms. But the uncertainty of the temperature coefficients, which has been observed, shows that the method has to be improved before it can be applied to clinical in vivo applications.
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| 7. |
- Carrapiço-Seabra, Carolina, et al.
(author)
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Application of the ESHO-QA guidelines for determining the performance of the LCA superficial hyperthermia heating system
- 2023
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In: International Journal of Hyperthermia. - 0265-6736 .- 1464-5157. ; 40:1
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Journal article (peer-reviewed)abstract
- Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility. Materials and methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging. Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS. Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.
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| 8. |
- Corderfeldt, Anna, et al.
(author)
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Is blood a necessary component of the perfusate during isolated limb perfusion - a randomized controlled trial
- 2019
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 36:1, s. 794-800
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Journal article (peer-reviewed)abstract
- Background: Isolated limb perfusion (ILP) is a treatment option for malignancies localized to an extremity and is performed by surgical isolation of the limb which is connected to an extracorporeal circulation system. A high concentration of a chemotherapeutic agent is perfused through the limb, while systemic toxicity is avoided. Currently, the use of packed red blood cells in the priming solution is the norm during ILP. The aim of this study was to investigate the possibility to replace an erythrocyte-based prime solution with a crystalloid-based prime solution while maintaining the regional metabolic oxygen demand during ILP. Methods: In a single-center, randomized controlled, non-blinded, non-inferiority clinical trial, 21 patients scheduled for treatment with ILP were included and randomized 1:1 to either an erythrocyte-based prime solution (control) or a crystalloid-based prime solution (intervention). Results: There was a significant difference in lactate level (mmol/L) during the perfusion between the intervention group and the control group (1.6 +/- 0.4 vs. 3.6 +/- 0.7, p = .001). No significant differences in oxygen extraction (%) (22 +/- 11 vs. 14 +/- 4, p = .06), oxygen delivery (ml/min) (90 +/- 49 vs. 108 +/- 38, p = .39), oxygen consumption (ml/min) (14 +/- 2 vs. 14 +/- 5, p = .85), regional central venous saturation (%) (83 +/- 10 vs. 91 +/- 4, p = .07) or INVOS (%) (76 +/- 14 vs. 81 +/- 11, p = .42) were found between the intervention group and the control group. Conclusion: This study showed no significant improvement with the addition of packed red blood cells into the prime solution in ensuring the metabolic oxygen demand in the treated extremity during ILP, and we, therefore, recommend that a crystalloid-based prime solution should be used.
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| 9. |
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| 10. |
- de Lazzari, Mattia, 1996, et al.
(author)
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Ethylcellulose-stabilized fat-tissue phantom for quality assurance in clinical hyperthermia
- 2023
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In: International Journal of Hyperthermia. - 0265-6736 .- 1464-5157. ; 40:1
-
Journal article (peer-reviewed)abstract
- Background: Phantoms accurately mimicking the electromagnetic and thermal properties of human tissues are essential for the development, characterization, and quality assurance (QA) of clinically used equipment for Hyperthermia Treatment (HT). Currently, a viable recipe for a fat equivalent phantom is not available, mainly due to challenges in the fabrication process and fast deterioration. Materials and methods: We propose to employ a glycerol-in-oil emulsion stabilized with ethylcellulose to develop a fat-mimicking material. The dielectric, rheological, and thermal properties of the phantom have been assessed by state-of-the-art measurement techniques. The full-size phantom was then verified in compliance with QA guidelines for superficial HT, both numerically and experimentally, considering the properties variability. Results: Dielectric and thermal properties were proven equivalent to fat tissue, with an acceptable variability, in the 8 MHz to 1 GHz range. The rheology measurements highlighted enhanced mechanical stability over a large temperature range. Both numerical and experimental evaluations proved the suitability of the phantom for QA procedures. The impact of the dielectric property variations on the temperature distribution has been numerically proven to be limited (around 5%), even if higher for capacitive devices (up to 20%). Conclusions: The proposed fat-mimicking phantom is a good candidate for hyperthermia technology assessment processes, adequately representing both dielectric and thermal properties of the human fat tissue while maintaining structural stability even at elevated temperatures. However, further experimental investigations on capacitive heating devices are necessary to better assess the impact of the low electrical conductivity values on the thermal distribution.
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| 11. |
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| 12. |
- Dobsicek Trefna, Hana, 1979, et al.
(author)
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Design of a wideband multi-channel system for time reversal hyperthermia
- 2012
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 28:2, s. 175-183
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Journal article (peer-reviewed)abstract
- Purpose: To design and test a wideband multi-channel amplifier system for time reversal (TR) microwave hyperthermia, operating in the frequency range 300 MHz-1 GHz, enabling operation in both pulsed and continuous wave regimes. This is to experimentally verify that adaptation of the heating pattern with respect to tumour size can be realised by varying the operating frequency of the antennas and potentially by using Ultra-wideband (UWB) pulse sequences instead of pure harmonic signals. Materials and methods: The proposed system consists of 12 identical channels driven by a common reference signal. The power and phase settings are applied with resolutions of 0.1W and 0.1 degrees, respectively. Using a calibration procedure, the measured output characteristics of each channel are interpolated using polynomial functions, which are then implemented into a system software algorithm driving the system feedback loop. Results: The maximum output power capability of the system varies with frequency, between 90 and 135W with a relative power error of +/- 6%. A phase error in the order of +/- 4 degrees has been achieved within the entire frequency band. Conclusions: The developed amplifier system prototype is capable of accurate power and phase delivery, over the entire frequency band of the system. The output power of the present system allows for an experimental verification of a recently developed TR-method on phantoms or animals. The system is suitable for further development for head and neck tumours, breast or extremity applications.
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| 13. |
- Dobsicek Trefna, Hana, 1979, et al.
(author)
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Evaluation of a patch antenna applicator for time reversal hyperthemia
- 2010
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 26:2, s. 185-197
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Journal article (peer-reviewed)abstract
- Purpose: To describe the design, analysis and evaluation of a new antenna array system for microwave hyperthermia. The proposed antenna array was evaluated by the focusing method based on the time-reversal principle. Materials and methods: Power absorption distributions in a cylindrical homogeneous and inhomogeneous phantom were calculated for the frequency range 500-900 MHz. Two set-ups with 12 and 16 antennas were analysed by comparing the changes in focusing areas enclosed by the 50%, 75% and 90% iso-SAR contours. For a more quantitative evaluation of the results the average power absorption ratio and remaining tissue maximum index were calculated. Results: The sharpest focusing area in the centre of the phantom, 151 mm
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| 14. |
- Dobsicek Trefna, Hana, 1979, et al.
(author)
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Quality assurance guidelines for interstitial hyperthermia
- 2019
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 36:1, s. 277-294
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Journal article (peer-reviewed)abstract
- Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40–44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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| 15. |
- Dobsicek Trefna, Hana, 1979, et al.
(author)
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Quality assurance guidelines for superficial hyperthermia clinical trials: I. Clinical requirements
- 2017
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 471-482
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Journal article (peer-reviewed)abstract
- Quality assurance guidelines are essential to provide uniform execution of clinical trials and treatment in the application of hyperthermia. This document provides definitions for a good hyperthermia treatment and identifies the clinical conditions where a certain hyperthermia system can or cannot adequately heat the tumour volume. It also provides brief description of the characteristics and performance of the current electromagnetic (radiative and capacitive), ultrasound and infra-red heating techniques. This information helps to select the appropriate heating technique for the specific tumour location and size, and appropriate settings of the water bolus and thermometry. Finally, requirements of staff training and documentation are provided. The guidelines in this document focus on the clinical application and are complemented with a second, more technical quality assurance document providing instructions and procedure to determine essential parameters that describe heating properties of the applicator for superficial hyperthermia. Both sets of guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.
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| 16. |
- Enblad, Malin, et al.
(author)
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Prognostic scores for colorectal cancer with peritoneal metastases treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
- 2018
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In: International Journal of Hyperthermia. - : TAYLOR & FRANCIS LTD. - 0265-6736 .- 1464-5157. ; 34:8, s. 1390-1395
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Journal article (peer-reviewed)abstract
- Background: Selecting colorectal patients for HIPEC-surgery needs improvement. The study aim was to improve the colorectal peritoneal score (COREP) and to compare it with three other scores: peritoneal-surface disease-severity score (PSDS), colorectal-peritoneal metastases prognostic-surgical-score (COMPASS), and the CEA/PCI ratio.Method: Twelve preoperative factors were chosen to evaluate for COREP score modification. Criteria from logistical analyses were set to qualify for the modified COREP score (mCOREP). Odds ratios were used to assign score points for the eligible factors with open/close laparotomy prediction as endpoint. mCOREP was applied internally and compared with the original COREP, PSDS, COMPASS, and CEA/PCI ratio. Odds ratios, hazard ratios, and Kaplan-Meier curves were used for comparison.Results: Seven factors qualified for mCOREP: CEA, CA 19-9, CA-125, C-reactive protein, albumin, platelet count and signet-cell histology. mCOREP was superior to the original COREP. mCOREP and COMPASS scores were the only scores with independent prognostic value. The mCOREP had the best discriminatory ability between its prognostic groupings. mCOREP 11+had 9months survival with half of patients being open/close surgery.Conclusion: The mCOREP has successfully been simplified while still improving its prognostic ability. The mCOREP and COMPASS scores have independent prognostic value. Patients with mCOREP 11+may not benefit from treatment.
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| 17. |
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| 18. |
- Liljemalm, Rickard, et al.
(author)
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Damage criteria for cerebral cortex cells subjected to hyperthermia
- 2016
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In: International Journal of Hyperthermia. - : Taylor & Francis. - 0265-6736 .- 1464-5157. ; 32:6, s. 704-712
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Journal article (peer-reviewed)abstract
- Temperatures above the normal physiological threshold may cause damage to cells and tissue. In this study, the response of a culture of dissociated cerebral cortex cells exposed to laser-induced temperature gradients was examined. The cellular response was evaluated using a fluorescent dye indicating metabolic activity. Furthermore, by using a finite element model of the heating during the pulsed laser application, threshold temperatures could be extracted for the cellular response at different laser pulse lengths. These threshold temperatures were used in an Arrhenius model to extract the kinetic parameters, i.e. the activation energy (E-a), and the frequency factor (A(c)), for the system. A damage signal ratio was defined and calculated to 5% for the cells to increase their metabolism as a response to the heat. Furthermore, efficient stimulation with 20-ms long laser pulses did not evoke changes in metabolism. Thus, 20 ms could be a potential pulse length for functional stimulation of neural cells.
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| 19. |
- Lindholm, C E, et al.
(author)
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Arterial rupture after microwave-induced hyperthermia and radiotherapy. With reference to two patients treated for recurrence in previously operated and irradiated areas
- 1990
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 6:3, s. 499-509
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Journal article (peer-reviewed)abstract
- Two patients who developed frank arterial bleeding after combined microwave-induced hyperthermia and radiotherapy are described. One patient received re-irradiation and hyperthermia for recurrent metastatic neck nodes of a mesopharyngeal carcinoma. Full course radiotherapy had been given 6 years previously and a right-sided radical neck node dissection had been performed 4 months earlier because of recurrent neck node metastases. Six weeks after the combined therapy for a second recurrence, which achieved complete remission, a fatal rupture of the carotid artery occurred. The other patient received re-irradiation and hyperthermia for a chest wall recurrence of a breast carcinoma, treated 5.5 years previously by sector resection and tangential beam radiotherapy, and treated again 2 years earlier with extensive surgery for a local recurrence. A frank arterial bleeding from the treated region was seen after 7 months, but could be arrested with surgery. This important complication in combined hyperthermia and radiotherapy does not seem to have been recognized before. Different explanations are discussed, such as the previous local treatment as well as high temperature and atherosclerosis per se.
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| 20. |
- Lindholm, Clas-Ebbe, et al.
(author)
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Microwave-induced hyperthermia and radiotherapy in human superficial tumours: clinical results with a comparative study of combined treatment versus radiotherapy alone
- 1987
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 3:5, s. 393-411
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Journal article (peer-reviewed)abstract
- Eighty-five evaluable superficial recurrent malignant tumours, mainly adenocarcinomas (78 per cent), in 38 patients were treated with either combined local hyperthermia (41-45 degrees C for four sessions) and low dose radiotherapy (30.0 Gy) or the same low dose radiotherapy alone. The treatment was given for two weeks. Hyperthermia was induced externally with 2450 MHz or 915 MHz microwaves. Totally 57 tumours were given combined treatment with a complete and partial response rate of 46 and 30 per cent, respectively (duration 1-38 months). In 18 patients with 2-10 superficial tumours each, 56 tumours were used in a comparative study, comparing the effect of combined hyperthermia and low dose radiotherapy versus the same low dose radiotherapy alone, the patients acting as their own controls. The total response rates were 89 and 50 per cent, respectively, in the two treatment modality groups. The difference in response rates is significant (p = 0.0039) in favour of the combined treatment, and this is also found when comparing complete remissions only (p = 0.0027). Local pain and normal tissue reactions presented problems during and after 2450 MHz microwave-induced hyperthermia treatment, performed without a coupling water bag system. Introduction of 915 MHz microwave-induced hyperthermia with a coupling deionized water bag system and refinement of microwave applicators, as well as the temperature control system considerably reduced these problems.
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| 21. |
- Lindholm, C-E, et al.
(author)
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Prognostic factors for tumour response and skin damage to combined radiotherapy and hyperthermia in superficial recurrent breast carcinomas
- 1995
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 11:3, s. 337-355
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Journal article (peer-reviewed)abstract
- Prognostic factors for complete tumour response and acute skin damage to combined hyperthermia and radiotherapy were analysed in material of patients with breast cancer, recurrent in previously irradiated areas. Radiotherapy was given daily to a total absorbed dose of 30.0 Gy in 2 weeks or 34.5 Gy in 3 weeks. The first radiotherapy schedule was combined with heat twice weekly, a total of four heat treatments (schedule A). The second radiotherapy schedule was combined with heat either once or twice a week resulting in a total of three (schedule B) or six (schedule C) heat treatments. Heat was induced with microwaves (2450, 915 or 434 MHz) via external applicators and always given after the radiotherapy fraction. The complete response (CR) rate in evaluable patients was 71% (49/69). There was no significant difference in CR rate between the three different hyperthermia schedules. The CR rates were 74% (14/19), 65% (15/23) and 74% (20/27) for schedules A, B and C respectively. The only factor predicting CR, evaluated both uni- and multivariately, was the CRE-value for the present radiotherapy dose (p = 0.02). If only tumours treated with 915 MHz were taken into account, however, then the highest minimum temperature at a given heat session predicted complete response (p = 0.03). This was true also in a multivariate analysis of this subgroup of tumours. A Kaplan-Meier analysis (log rank test) showed no significant difference in duration of CR between the different treatment schedules. Cox's proportional hazards method revealed three significant factors: tumour size (negatively correlated, p = 0.007), the time interval between the diagnosis of the primary tumour and the present treatment (p = 0.02) and the average temperature (0.03). Maximum acute skin reactions in the treatment field were scored according to an ordinal scale of 0-8, modified after WHO 1979. Twenty-six treatment areas (32%) expressed more severe skin damage (score > or = 5) in terms of desquamation with blisters (14%) and necrosis or ulceration (19%). Factors correlated with skin damage were the size of the lesion area (p = 0.011), the highest average maximum temperature during a given heat session (p = 0.03) and the fractionation schedule of hyperthermia (p = 0.05). The extent of previous radiotherapy absorbed dose, previous surgery in the treated area or previous chemotherapy had no significant influence on the acute skin reactions.
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| 22. |
- Möller, P. H., et al.
(author)
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Temperature control and light penetration in a feedback interstitial laser thermotherapy system
- 1996
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 12:1, s. 49-63
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Journal article (peer-reviewed)abstract
- The aim of this study was to describe the performance of a closed loop interstitial laser thermotherapy system in processed liver and to demonstrate its suitability for treating a vascularized tumour in vivo. The thermotherapy system consisted of an Nd:YAG laser and a temperature feedback circuit including an automatic thermometry system and thermistor probes. Experiments in processed liver were performed with a sapphire probe and temperature control at a distance of 10 mm. In most experiments at 1-2 W, and in half of the experiments at 3 W, there was no carbonization, a moderate change in the light penetration and excellent control of the temperature. In experiments with output powers of 4-5 W there was carbonization with rapid deterioration of light penetration and impaired control of the temperature. Carbonization affected the distribution of temperatures, which were lower below, and higher above, the laser tip in experiments with carbonization as compared to experiments without carbonization. Treatment of an adenocarcinoma implanted into rat liver was performed at 2 W with a bare fibre and without blood inflow occlusion. The feedback thermistor probe was placed 3 mm outside the margin of the tumour (largest diameter 9.5 ± 0.3 mm (mean ± SEM)). Temperature control and light penetration characteristics were similar to those found in vitro. No tumour could be demonstrated at sacrifice 6 days later. It is concluded that a closed loop feedback system can produce stable and reproducible local hyperthermia, that it performs better when carbonization is avoided and light penetration is preserved and that it has a great potential for interstitial thermotherapy of malignant tumours.
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| 23. |
- Nilsson, P., et al.
(author)
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Absorbed power distributions from two tilted waveguide applicators
- 1985
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 1:1, s. 29-43
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Journal article (peer-reviewed)abstract
- One major problem in microwave-induced clinical hyperthermia treatment of superficial tumours is to obtain therapeutic temperatures at the tumour periphery and adequate deep heating when using a single applicator. The use of multiple applicators has therefore been investigated in order to improve the power distribution. Anatomical surface topography often permits the application of two tilted applicators, e.g. in the head and neck area, on extremities and on large protruding tumours. Theoretical calculations of the absorbed power distribution from such an applicator configuration were performed in a homogeneous muscle equivalent medium. The power distribution from two conventional radiative apertures (TE10) was studied at different frequencies, aperture sizes, tilting angles and non-coherent or coherent fields in phase, both theoretically and with phantom experiments using a thermographic camera. With controlled phase relations between two tilted applicators excited at the lower microwave or upper radiofrequency band, the absorbed power distribution can be varied in a wide range. The theoretical calculations and thermographic phantom experiments in simple geometries give valuable information on absorbed power distributions and guidance for the location of temperature probes in clinical hyperthermia.
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| 24. |
- Olofsson Bagge, Roger, 1978, et al.
(author)
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Minimally invasive isolated limb perfusion - technical details and initial outcome of a new treatment method for limb malignancies
- 2019
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 35:1, s. 667-673
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Journal article (peer-reviewed)abstract
- Objective: Isolated limb perfusion (ILP) and isolated limb infusion (ILI) are treatment options for patients with locally advanced melanomas and sarcomas of the extremities. ILP potentially have higher response rates, but requires open surgery for vascular access, whereas ILI is minimally invasive and easier to perform. We now present the technical details and outcome of a new approach to ILP by a minimally invasive vascular access (MI-ILP). Methods: Six patients, five with melanoma in-transit metastases and one with squamous cell carcinoma, were included in a phase I feasibility trial. Percutaneous vascular access of the extremity vessels was performed and the inserted catheters were then connected to a perfusion system. Results: All six treated patients underwent the procedure without the need for conversion to open surgery. The median operating time was 164 min and the median leakage rate was 0.1%. The complete response rate was 67%. Four patients (67%) had a Wieberdink grade II reaction and two patients (33%) had a grade III reaction. Conclusions: MI-ILP is feasible and gives the same treatment characteristics as open ILP, but with the advantage of a minimally invasive vascular access.
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| 25. |
- Olofsson Bagge, Roger, 1978, et al.
(author)
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Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities - Long-term follow-up of a randomised trial
- 2014
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 30:5, s. 295-298
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Journal article (peer-reviewed)abstract
- Introduction: Isolated limb perfusion (ILP) is a treatment option most commonly used in the treatment of melanoma in-transit metastases of the extremities. The principle idea is to surgically isolate a region of the body and then deliver a high concentration of a chemotherapeutic agent together with hyperthermia. There have been three randomised trials exploring whether adjuvant ILP to patients with recurrent or high-risk primary melanomas increases survival; one of these trials has now been updated with a 25-year follow-up. Methods: The original study randomised 69 patients (between 1981 and 1989) with their first satellite or in-transit recurrence to either wide excision (WE group, n=36 patients) or to WE and adjuvant ILP (WE + ILP group, n=33 patients). Follow-up data 25 years later concerning survival and cause of death was retrieved from the Swedish National Cause of Death Register. Results: In the WE + ILP group there were 20 deaths (61%) due to melanoma compared with 26 deaths (72%) in the WE group (p=0.31). Median melanoma-specific survival was 95 months for WE + ILP compared to 38 months for the WE group, an almost 5 year benefit without statistical significance (p=0.24). Discussion: There is no evidence that adjuvant ILP prolongs survival in patients with high-risk or recurrent melanoma; however, the existing randomised trials are largely underpowered to detect such a difference. New studies are exploring systemic immunological effects of ILP, and a combination of regional therapy and immunotherapy may serve as a rationale for new trials using ILP in the future.
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| 26. |
- Olofsson, Roger, 1978, et al.
(author)
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Long-term follow-up of 163 consecutive patients treated with isolated limb perfusion for in-transit metastases of malignant melanoma.
- 2013
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In: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. - : Informa UK Limited. - 1464-5157. ; 29:6, s. 551-7
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Journal article (peer-reviewed)abstract
- Abstract Purpose: The aim of the present study is to describe our experience with isolated limb perfusion (ILP) in the treatment of in-transit metastases of malignant melanoma and to determine prognostic factors for response, local progression, survival and toxicity. Materials and methods: A retrospective follow-up of all patients (n=163) treated between January 1984 and December 2008 using data collected from individual patient records and the Swedish National Patient Register. Results: Clinical response was evaluable in 155 patients, 65% had a complete response (CR) and 20% had a partial response (PR). Local progression occurred in 63% of the patients after a median time of 16 months. Negative prognostic factors in univariate analyses were proximal location of the primary tumour, >10 in-transit metastases and if there was no CR after ILP. In multivariate analysis, proximal location of the primary tumour and no CR after ILP were significant prognostic factors. Median cancer-specific survival was 30 months, and negative prognostic factors in univariate analyses were male gender, positive lymph node status, systemic metastases, bulky tumour, >10 in-transit metastases and if there was no CR after ILP. In multivariate analysis, positive lymph node status, bulky tumour and no CR after ILP were significant prognostic factors. A majority (97%) of the patients had a Wieberdink grade II-III local toxicity. Four patients underwent limb amputation after a median of 19 months, none because of toxicity. Conclusion: We found that ILP is a safe method with a high response rate for the treatment of patients with in-transit metastases of malignant melanoma.
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| 27. |
- Olofsson, Roger, 1978, et al.
(author)
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Melan-A specific CD8+ T lymphocytes after hyperthermic isolated limb perfusion : A pilot study in patients with in-transit metastases of malignant melanoma
- 2013
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 29:3, s. 234-238
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Journal article (peer-reviewed)abstract
- Purpose: Isolated limb perfusion (ILP) with hyperthermia is an effective treatment for in-transit metastases of malignant melanoma in the extremities. Preclinical studies have shown that hyperthermia may induce an immunogenic death of tumour cells. We therefore decided to study whether ILP may induce tumour-specific immune responses in the clinical setting. Method: The number of Melan-A/Mart-1 specific CD8+ T cells, as well as other phenotypically different immune cells, was recorded in peripheral blood in 12 HLA-A2+ patients with in-transit metastases undergoing hyperthermic ILP with melphalan. Results: All patients underwent ILP without any complication and with an overall response rate of 83%. No substantial changes in the number of circulating T-cells, B-cells, NK-cells or monocytes were observed during follow-up. Four out of 12 patients showed an elevation of Melan-A+ CD8+ T-cells 4 weeks after ILP. Conclusion: We here report our preliminary observations that a small increase in tumour-specific T-cells could be seen in a subpopulation of patients after ILP. However, much more work is necessary to fully delineate the systemic immune response to hyperthermic ILP.
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| 28. |
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| 29. |
- Paulides, M. M., et al.
(author)
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ESHO benchmarks for computational modeling and optimization in hyperthermia therapy
- 2021
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 38:1, s. 1425-1442
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Journal article (peer-reviewed)abstract
- Background: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance. Materials and methods: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes. Results and discussion: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/). Conclusion: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included.
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| 30. |
- Paulides, M. M., et al.
(author)
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Introduction to computational modeling in hyperthermia
- 2022
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 39:1, s. 1358-1359
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Journal article (other academic/artistic)abstract
- Over the past two decades, computational modeling has gained a prominent role in hyperthermia research and its role for guiding treatments is expanding. Computational modeling serves e.g., to design new applicators, in silico testing of novel treatment approaches and providing insight in treatment safety. Hyperthermia treatment modeling and optimization (HTM&O), also known as hyperthermia treatment planning (HTP), is the process in which the multidisciplinary hyperthermia team defines the optimal treatment plan for a specific cancer patient using the available hyperthermia treatment resources. HTM&O includes computational modeling approaches for pretreatment HTP and online treatment guidance.
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| 31. |
- Sharma, Har Shanker
(author)
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Hyperthermia induced pathophysiology of the central nervous system
- 2003
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 19:Number 3 / May 2003, s. 325-354
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Journal article (peer-reviewed)abstract
- This review is focused on the pathophysiology of the central nervous system (CNS) associated with mild-to-moderate hyperthermia (body temperature > 37°C but <40°C) induced thermal stress in Human cases as well as whole body hyperthermia (WBH) in animal studies. Pathological changes can be observed in the nerve cells and glial cells in Humans following mild-to-moderate thermal exposure. On the other hand, morphological changes in the axons, nerve cells, glial cells and vascular endothelium is seen at the cellular and the molecular levels in rats subjected to heat exposure at 38°C for 4 h (body temperature > 40°C but <42°C). This effect depends on the age of the animals and their prior thermal experiences. Taken together, heat stress induced hyperthermia, once believed to be non-toxic in the mammalian CNS, do produce specific alterations in the CNS that may have long-term behavioural, physiological and neuropathological consequences. The probable mechanism(s) underlying hyperthermia induced brain pathology is discussed.
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| 32. |
- Takook, Pegah, 1982, et al.
(author)
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Compact self-grounded Bow-Tie antenna design for an UWB phased-array hyperthermia applicator
- 2017
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:4, s. 387-400
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Journal article (peer-reviewed)abstract
- Using UWB hyperthermia systems has the potential to improve the heat delivery to deep seated tumours. In this paper, we present a novel self-grounded Bow–Tie antenna design which is to serve as the basis element in a phased-array applicator. The UWB operation in the frequency range of 0.43–1 GHz is achieved by immersing the antenna in a water bolus. The radiation characteristics are improved by appropriate shaping the water bolus and by inclusion of dielectric layers on the top of the radiating arms of the antenna. In order to find the most appropriate design, we use a combination of performance indicators representing the most important attributes of the antenna. These are the UWB impedance matching, the transmission capability and the effective field size. The antenna was constructed and experimentally validated on muscle-like phantom. The measured reflection and transmission coefficients as well as radiation characteristics are in excellent agreement with the simulated results. MR image acquisitions with antenna located inside MR bore indicate a negligible distortion of the images by the antenna itself, which indicates MR compatibility.
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| 33. |
- Verwaal, Victor J., et al.
(author)
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Registries on peritoneal surface malignancies throughout the world, their use and their options
- 2017
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:5, s. 528-533
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Journal article (peer-reviewed)abstract
- Aim: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries. Methods: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected. Results: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year. Conclusions: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.
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| 34. |
- Wendt Nyström, Andreas, 1981, et al.
(author)
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Myoglobin does not predict local toxicity in isolated limb perfusion
- 2017
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 33:6, s. 679-683
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Journal article (peer-reviewed)abstract
- Introduction: Isolated limb perfusion (ILP) is a treatment option for patients with in-transit metastases of malignant melanoma in the extremities, as well as locally advanced sarcoma. ILP allows for a delivery of high-dose chemotherapy to an isolated extremity with minimal systemic toxicity. However, local toxicity like oedema, blistering, nerve damage and compartment syndrome can occur. Myoglobin measurements have been used as a screening method to predict the most severe cases of local toxicity. The aim was to investigate if myoglobin is a predictive factor for local toxicity after ILP in patients with melanoma in-transit metastases. Methods: One hundred and ninety-three patients were treated for the first time with ILP for in-transit metastases between 2001 and 2015. Myoglobin was measured once the first hours after the perfusion (POD0), and for the first five post-operative days (POD1-5). Local toxicity was graded according to Wieberdink, and grouped in mild (I and II), moderate (III), and severe (IV and V). Wieberdink-groups were compared with myoglobin measurements, and myoglobin measurements were compared between gender, perfusion time, perfusion temperature and cannulated vessels. Results: There is no statistically significant difference in myoglobin serum levels during the first five days post perfusion between patients suffering from mild, moderate or severe local toxicity. There is no difference between toxicity groups when it comes to distribution of sex, tumour size, or tumour numbers. Conclusion: Levels of myoglobin do not predict local toxicity for patients with melanoma in-transit metastases treated with ILP when measured during the first five post-operative days.
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| 35. |
- Wren, Joakim, 1973-, et al.
(author)
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A hybrid equation for simulation of perfused tissue during thermal treatment
- 2001
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 17:6, s. 483-498
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Journal article (peer-reviewed)abstract
- Bio-heat equations (BHEs) are necessary for predicting tissue temperature during thermal treatment. For some applications, however, existing BHEs describe the convective heat transfer by the blood perfusion in an unsatisfactory way. The two most frequently used equations, the BHE of Pennes and the keff equation, use for instance either a heat sink or an increased thermal conductivity in order to account for the blood perfusion. Both these methods introduce modelling inaccuracies when applied to an ordinary tissue continuum with a variety of vessel sizes. In this study, a hybrid equation that includes both an increased thermal conductivity and a heat sink is proposed. The equation relies on the different thermal characteristics associated with small, intermediate and large sized vessels together with the possibilities of modelling these vessels using an effective thermal conductivity in combination with a heat sink. The relative importance of these two terms is accounted for by a coefficient ▀. For ▀ = 0 and ▀ = 1, the hybrid equation coincides with the BHE of Pennes and the keff equation, respectively. The hybrid equation is used here in order to simulate temperature fields for two tissue models. The temperature field is greatly affected by ▀, and the effect is dependent on, e.g. the boundary conditions and the power supply. Since the BHE of Pennes and the keff equation are included in the hybrid equation, this equation can also be useful for evaluation of the included equations. Both these heat transfer modes are included in the proposed equation, which enables implementation in standard thermal simulation programmes.
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| 36. |
- Wren, Joakim, 1973-
(author)
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Evaluation of three temperature measurement methods used during microwave thermotherapy of prostatic enlargement
- 2004
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 20:3, s. 300-316
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Journal article (peer-reviewed)abstract
- Three temperature measurement methods used during microwave thermotherapy of prostatic enlargement are analysed and evaluated using a phantom model. A commercial transurethral microwave thermotherapy (TUMT) system that uses a radiometric thermometer for temperature control was used to heat the phantom. The transient temperature distribution was obtained by using both fibreoptic (which is considered as gold standard) and thermocouple measurements. Both methods are subject to potential measurement errors caused by electro-magnetic and/or thermal interference. The error sources are analysed and the measurement methods evaluated. The radiometric temperature and especially its relation to the transient temperature distribution was evaluated based on the fibreoptic and thermocouple measurements. These measurements in principle gave equivalent temperature distributions, and thermal interference was concluded to be the largest source of measurement error. The radiometric measurement method gave qualitative rather than quantitative readings of the temperature, and an underestimation of more than 10°C was obtained for some parts of the heated area. The area that gives most of the radiometric signal was relatively close to the catheter in contrast to previously published results.
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| 37. |
- Zanoli, Massimiliano, 1989, et al.
(author)
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The hot-to-cold spot quotient for SAR-based treatment planning in deep microwave hyperthermia
- 2022
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In: International Journal of Hyperthermia. - : Informa UK Limited. - 0265-6736 .- 1464-5157. ; 39:1, s. 1421-1439
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Journal article (peer-reviewed)abstract
- BACKGROUND: A necessary precondition for a successful microwave hyperthermia (HT) treatment delivered by phased arrays is the ability of the HT applicator to selectively raise the temperature of the entire tumor volume. SAR-based treatment plan (HTP) optimization methods exploit the correlation between specific absorption rate (SAR) and temperature increase in order to determine the set of steering parameters for optimal focusing, while allowing for lower model complexity. Several cost functions have been suggested in the past for this optimization problem. However, their correlation with high and homogeneous tumor temperatures remains sub-optimal in many cases. Previously, we proposed the hot-to-cold spot quotient (HCQ) as a novel cost function for SAR-based HTP optimization and showed its potential to address these issues. MATERIALS AND METHODS: In this work, we validate the HCQ on a standard ESHO patient repository within single and multi-frequency contexts. We verify its correlation with clinical SAR and temperature indexes, and compare it to HTPs obtained using a commonly accepted cost-function for SAR-based HTP (hot-spot to target quotient, HTQ). RESULTS AND DISCUSSION: The results show that low HCQ values produce better SAR (TC50, TC75) and temperature metrics (T50, T90) than HTQ in most patient models and frequency settings. For the deep-seated tumors, the correlation between the clinical indicators and 1/HCQ is more favorable than the correlation exhibited by 1/HTQ. CONCLUSION: The validation confirms the ability of HCQ to promote target coverage and hot-spot suppression in SAR-based HTP optimization, resulting in higher SAR and temperature indexes for deep-seated tumors.
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