Intraoperative interstitial microwave-induced hyperthermia and brachytherapy

Intra-operative placement of 11-gauge nylon catheters into deep-seated unresectable tumors for interstitial brachytherapy permits localized heating of tumors (hyperthermia) using microwave (915 MHz) antennas which are inserted into these catheters. Four preliminary cases are described where epithelial tumors at various sites were implanted with an antenna array and heated for 1 hour, both before and after the iridium-192 brachytherapy. Temperatures were monitored in catheters required for the appropriate radiation dosimetry but not required for the interstitial microwave antenna array hyperthermia (IMAAH) system. Additional thermometry was obtained using nonperturbed fiberoptic thermometry probes inserted into the catheters' housing antennas. No significant complications, such as bleeding or infection, were observed. This approach to cancer therapy is shown to be feasible and it produces controlled, localized hyperthermia, with temperatures of 50 degrees C or more in tumors. This technique may offer a therapeutic option for pelvic, intra-abdominal and head and neck tumors.     

CT fluoroscopy-guided closed-tip catheter placement before regional hyperthermia treatment of soft tissue sarcomas: 5-Year experience in 35 consecutive patients

Purpose: This study was designed to assess technical success and complications in patients with high-risk soft tissue sarcomas undergoing CT fluoroscopy-guided closed-tip catheter placement before treatment with combined chemotherapy and regional hyperthermia. Materials and methods: This retrospective study comprised all patients referred for insertion of closed-tip catheters for the introduction of thermometry probes before regional hyperthermia treatment at a single university centre from 2010 to 2015. Catheter placements were performed under local anaesthesia and intermittent CT fluoroscopy guidance. Technical success, complication rate, duration of catheter insertion and dose–length product (DLP) were analysed. Technical success was defined as intratumoural catheter placement suitable for subsequent thermometry. Results: A total of 35 procedures were performed on 35 patients (22 men, 13 women). In 34 out of 35 interventions catheters were inserted successfully; in one patient catheter placement was not feasible. No intra-interventional complications occurred. In six patients post-interventional complications were observed – two major (one abscess formation and one severe catheter dislocation) and four minor complications. Technical failure was observed in 11.4% of patients, especially catheter kinking. A total of 55 catheters were placed, with a mean number of 1.7?±?0.7 per patient. Mean total DLP was 723.2?±?355.9 mGy*cm. Conclusion: CT fluoroscopy-guided closed-tip catheter placement into high-risk soft tissue sarcomas was characterised by high technical success and relatively low complication rate. While major complications were rarely observed, catheter-kinking preventing successful thermometry represented the most frequent technical failure.     

Rationale for using invasive thermometry for regional hyperthermia of pelvic tumors

Purpose: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and risky for the patient. We tried to estimate the benefit/cost ratio of invasive thermometry in regional hyperthermia using the radiofrequency system BSD-2000.

Methods and Materials: We evaluated 182 patients with locally advanced pelvic tumors that underwent regional hyperthermia. In every patient a tumor-related temperature measurement point was obtained either by invasive or minimally invasive catheter measurement tracks. In the earlier period for every patient an intratumoral measurement point was decided as obligatory and intratumoral catheters were implanted intraoperatively, CT guided, or under fluoroscopy. In the later period, invasive thermometry often was avoided, if a measurement point in or near the tumor was reached by an endoluminally inserted catheter (rectal, vaginal, cervical, urethral, or vesical). For every patient side effects and complications referred to thermometry were evaluated and compared with the potential benefit of the invasively achieved temperature data. The suitability of endolumimally registered temperatures is analyzed to estimate local feasibility (specific absorption rate achieved) and local effectiveness (thermal parameters correlated with response).

Results: In 74 of 182 patients invasive thermometry was performed, at most CT-guided for soft tissue sarcomas and rectal recurrences. In 14 of 74 (19%) side effects such as local inflammation, pain, or abscess formation occurred that enforced removal of the catheter. However, local problems were strongly correlated with the dwell time of the catheter and nearly never occurred for dwell times less than 5 days. Fortunately, no fatal complications (e.g., bleeding or perforation) occurred during or after implantation which could be attributed to the invasive thermometry procedure. Endoluminal tumor-related temperature rises per time unit (to estimate power density) were correlated with intratumoral rises at the same patients (where both measurements were available). For a subgroup of patients pooled in two Phase II studies with rectal (n = 37) and cervical (n = 18) carcinomas thermal parameters derived from endoluminal measurements were correlated with response or local control, resp.

Conclusions: If a tumor-related endoluminal temperature measurement point is available, additional invasive thermometry gives no further information to improve the power deposition pattern. For primary rectal and cervical cancer, and probably as well for prostate, bladder and anal cancer, endoluminal measurements are suitable to estimate local feasibility and effectiveness. Therefore, invasive thermometry is dispensable in the majority of patients. In some selected cases, temperature measurement in the tumor center is required to estimate the maximum temperature. In those cases, dwell time of catheters should be minimized—and it should be considered to perform invasive thermometry at the beginning (one or two heat treatments).     

A phase I and II clinical trial of a newly developed ultrasound hyperthermia system with an improved planar transducer

: The clinical usefulness of a newly developed ultrasound hyperthermia system was evaluated.

: The hyperthermia system uses a modified planer transducer operated at frequencies of 0.5, 1.0, and 1.5 MHz. The transducer has a nonvibrating part at the center to reduce the central hot spot. Frequency sweeping technique is also used to eliminate the annular hot spot around the center. Thirty-eight tumors in 29 patients were examined in this study. In 35 tumors, hyperthermia was given in conjunction with irradiation and/or chemotherapy, and in the remaining 3 tumors, hyperthermia alone was given. In all, a total of 153 hyperthermia sessions were performed.

: The number of hyperthermia sessions per tumor ranged from 1 to 7 (mean, 4.0 ± 1.3). The number of intratumor thermometr points per session ranged from 1 to 8 (mean, 4.3 ± 1.5). The average intratumor temperature for tumors with a maximum depth of <3 cm, 3–6 cm, and >6 cm was 42.1 ± 1.2, 41.7 ± 1.4, and 39.9 ± 2.0°C, respectively. The percentage of monitored intratumor points with temperature exceeding 42°C was 56 ± 31%, 43 ± 34%, and 21 ± 24%, respectively. Of the 30 evaluable tumors treated with combined irradiation, 12 showed complete response, 14 partial response, and 4 no change. Observed complications included pain at the treatment site in 13 of the 153 treatment sessions and vesicle formation in 3 of the 38 treatment sites. No serious complication was seen.

: These results indicate that the newly developed ultrasound hyperthermia system is clinically useful for the treatment of localized superficial and subsurface tumors with a maximum tumor depth of no more than 6 cm.     

The use of implanted closed-tip catheters for the introduction of thermometry probes during local hyperthermia treatment series

In the past two and a half years custom-made closed-tip catheters have been used to allow extensive temperature monitoring with multi-junction thermocouple probes during local hyperthermia. Data from animal experiments indicate that the use of thermometry probes within such a catheter provides reliable temperature measurements. In order to reduce stress to the patient the catheters were fixed so that they could stay in place during the total treatment series. The catheters, outer diameter 1.22 mm, were introduced through hollow needles under sterile conditions before the first hyperthermia session, and fixed using Histo-acryl (tissue adhesive) and Tegaderm (transparent adhesive). Recently, the data concerning the first 180 catheters placed in 74 treatment areas were evaluated. In one patient, an abscess developed 10 days after removal of the (3) catheters, which required surgical intervention, but it was not clear whether these problems had developed as a result of catheter placement. There were no problems with 139 of the remaining 177 catheters (79 per cent) and in 50 treatment fields (68 per cent), respectively, for a duration of 9-55 (mean 23) days. Ten catheters (6 per cent) were lost during the treatment series after 1-22 (mean 10) days. With 28 catheters (16 per cent) infection was observed, 14-27 (mean 19) days after insertion, which necessitated catheter removal before the last treatment session in 11 cases (6 per cent). The complication rate decreased with increasing experience; from 29 per cent (25/85) in the early period to 14 per cent (13/92) in the later period. We conclude that the use of closed-tip catheters under proper control generally causes few, if any, problems. This results in the acquisition of a substantial amount of reliable temperature data at reproducible sites, and it is well tolerated by the patient.     

热疗加放疗治疗盆腔恶性肿瘤的临床热剂量学研究

目的采用温度当量分(TEM42．5℃)作为热剂量单位,评价其与肿瘤缓解率之间的关系,找出适合临床应用的热剂量单位。方法对49例复发或转移的盆腔恶性肿瘤患者采用热疗(放疗后30min热疗,每次热疗40～60min,2次／周)联合放疗(1．8～2．OGy／次,1次／d,5次／周),并用高电阻铅测温针在肿瘤中心部位单点连续测温。以TEM42．5℃作为热剂量单位。结果49例患者中,完全缓解(CR)14例,部分缓解(PR)21例,无缓解(NR)14例。肿瘤缓解(CR PR)率和TEM42．5℃,放疗剂量呈明显正相关;肿瘤体积和热疗次数,与肿瘤缓解率无相关性。结论TEM42．5℃和放疗剂量,与肿瘤缓解率呈明显正相关,可作为肿瘤热疗联合放疗时的热剂量单位。     

Three-dimensional controlled interstitial hyperthermia combined with radiotherapy for locally advanced prostate carcinoma--a feasibility study

PURPOSE: To perform a feasibility study of three-dimensional spatially controlled interstitial hyperthermia for locally advanced prostate cancer. METHODS AND MATERIALS: Twelve patients with prostate cancer (T3NxM0) were treated with conventional external beam radiotherapy and one interstitial hyperthermia treatment. Hyperthermia was delivered with the 27-MHz multielectrode current source (MECS) interstitial hyperthermia technique on an outpatient basis. Guided by transrectal ultrasonography, 12 catheters (range 7-16) were placed in the prostate through a template. Two electrodes per probe were inserted. Thermometry (average 100 sensors) was performed from within the probes for online temperature control. Additional thermometry was done in the prostate, rectum, urethra, and bladder. Reconstruction was done by sonography. Prostate perfusion was estimated from the thermal decay at the end of treatment. The full three-dimensional temperature distribution was calculated. RESULTS: No toxicities greater than Grade 2 were recorded. A learning curve for implantation, position verification, reconstruction, and temperature simulation was experienced. Perfusion was 47 mL/100 g/min (range 30-65). The average measured temperature was T(90) (90% of the prostate reached a temperature of at least:) 39.9 degrees C and T(50) 44.1 degrees C. The average calculated temperatures were lower: T(90), 39.4 degrees C and T(50), 41.8 degrees C, because the entire prostate was taken into account. The tumor temperatures were T(90), 40.7 degrees C and T(50), 43.0 degrees C. The bladder and rectal temperatures were below the safety limits. CONCLUSION: Multielectrode-current-source interstitial hyperthermia is technically feasible and well tolerated. It was not possible to achieve the goal temperature of 42-43 degrees C because of high perfusion and implantation limitations.     

Interstitial thermoradiotherapy of brain tumors: preliminary results of a phase I clinical trial

A Phase I clinical trial has been initiated to determine the feasibility, tolerance, and toxicity of interstitial thermoradiotherapy in the treatment of high-grade supratentorial brain gliomas. Hyperthermia was delivered by means of thermally-regulating ferromagnetic implants afterloaded into stereotactically placed plastic catheters. Heat treatments were given immediately before interstitial irradiation; in addition, five patients received a second heat treatment at the completion of brachytherapy. The desired target temperature for the 60-minute hyperthermia session was between 42 degrees C and 45 degrees C. Following hyperthermia, the catheters were afterloaded with Ir-192, which delivered a variable radiation dose of 14-50 Gy depending on the clinical situation. Interstitial irradiation was supplemented with external beam radiotherapy (40-41.4 Gy) in patients with previously untreated tumors. A total of 14 patients (4 males, 10 females) have been treated to date on this protocol. Eleven of the patients had a diagnosis of glioblastoma multiforme, whereas three had anaplastic astrocytoma. The mean implant volume was 61.5 cm3 (range: 9-119 cm3); the median number of interstitial treatment catheters implanted was 19 (range: 7-33). Continuous temperature monitoring was performed by means of multisensor thermocouple probes inserted in the center as well as in the periphery of the tumor. Of the 175 monitored intratumoral points, 83 (47%) had time-averaged mean temperatures of greater than 42 degrees C, and only 12 sensors (7%) exceeded a temperature of 45 degrees C. Among the 19 heat treatments attempted, there have been four minor acute toxicities, all of which resolved with conservative medical management and one major complication resulting in the demise of a patient. These preliminary results indicate that ferromagnetic implants offer a promising new approach to treating brain tumors with hyperthermia.     

Safety and efficacy of concurrent interstitial radiation and hyperthermia in the treatment of progressive malignant brain tumors

High activity 125I brachytherapy has efficacy in selected recurrent malignant brain tumors, but limited efficacy and risk of radiation necrosis have prompted investigation of additional adjunctive therapies. This study aims to assess the toxicity of interstitial conductive hyperthermia used concurrently with 125I brachytherapy for the treatment of recurrent brain malignancies. Twelve patients with recurrent malignant brain tumors were implanted using afterloading catheters intended to deliver 50 Gy at the isodose line encompassing the enhancing tumor with a 5-mm margin and heated to 41.5 degrees C for 48 h. The average implant volume was 18 cc with 5.3 catheters containing 9.4 sources with a total activity of 265 mCi. Serious toxicities included 8 motor deficits, 2 mood alterations, 4 seizures and 2 catheter wound cerebrospinal fluid leaks. Median survival was 10.35 months with the best responses being 6 with stable disease and 2 with partial responses. Reoperation rate for radiation necrosis was 33%. Concurrent conductive thermoradiotherapy is feasible but is associated with serious toxicity. There is no suggestion of improved survival with thermoradiotherapy over brachytherapy alone. Given the degree of toxicity observed, alternative approaches to improving local control of these tumors are being explored.     

Risk of tumour growth along thermometry catheter trace: a case report

A patient with recurrent rectal cancer was treated with the combination of radiotherapy plus hyperthermia. Intratumoral thermometry probes were introduced within closed-tip catheters, inserted through the buttocks under computed tomography (CT) control. Catheters were fixed to the skin to stay in place during the whole treatment series. At the end of the radiotherapy series, tumour progression was apparent. Seven months following treatment, tumour growth was visible at the insertion site of one of the catheters. This finding indicates that catheters should not be placed outside the treatment volume involved in any locally curative treatment.     

Risk of tumour growth along thermometry catheter trace: a case report.

A patient with recurrent rectal cancer was treated with the combination of radiotherapy plus hyperthermia. Intratumoral thermometry probes were introduced within closed-tip catheters, inserted through the buttocks under computed tomography (CT) control. Catheters were fixed to the skin to stay in place during the whole treatment series. At the end of the radiotherapy series, tumour progression was apparent. Seven months following treatment, tumour growth was visible at the insertion site of one of the catheters. This finding indicates that catheters should not be placed outside the treatment volume involved in any locally curative treatment.     

Deep hyperthermia with the HYPERcollar system combined with irradiation for advanced head and neck carcinoma – a feasibility study

Purpose: Radiotherapy (RT) treatment of locally-advanced and recurrent head and neck carcinoma (HNC) results in disappointing outcomes. Combination of RT with cisplatin or cetuximab improves survival but the increased toxicity and patient's comorbidity warrant the need for a less-toxic radiosensitizer. Stimulated by several randomized studies demonstrating the radio-sensitizing effect of hyperthermia, we developed the HYPERcollar. Here, we report early experience and toxicity in patients with advanced HNC.

Methods and materials: 119 hyperthermia treatments given to 27 patients were analyzed. Hyperthermia was applied once a week by the HYPERcollar aimed at achieving 39–43?°C in the target area, up to patients’ tolerance. Pre-treatment planning was used to optimize treatment settings. When possible, invasive thermometry catheters were placed.

Results: Mean power applied during the 119 hyperthermia treatments ranged from 120 to 1007?W (median 543?W). 15 (13%) hyperthermia treatments were not fully completed due to: pain allocated to hyperthermia (6/15), dyspnea from sticky saliva associated with irradiation (2/15) and unknown reasons (7/15). No severe complications or enhanced thermal or mucosal toxicities were observed. Excluding post-operative treatment, response rates after 3?months were 46% (complete) and 7% (partial).

Conclusion: Hyperthermia with the HYPERcollar proved to be safe and feasible with good compliance and promising outcome.     

Blood perfusion measurements in human tumours: evaluation of laser Doppler methods

Laser Doppler flowmetry is a simple method of determining, directly and continuously, tissue blood flow. However, its applicability to monitoring tumour blood flow interstitially during hyperthermia treatments is still being evaluated. The purposes of this study were to physically characterize the measurement probes, to evaluate potential sources of artifact with the interstitial use of the probes during hyperthermia treatment, and to obtain measurements in human tumours during hyperthermia sessions. The accuracy of the method in quantifying blood flow, velocity and volume during hyperthermia was found to be unaffected by heating the measurement probe to 42-46 degrees C or by exposing it to various intensities of 915 MHz microwave fields (10-40 W), or 1 MHz ultrasound fields. Catheter insertion methods were developed to place the flow probes interstitially in tumours. Tissue damage was confined to a distance of no greater than 0.12 mm away from the catheter tract, and physical evidence of vascular disruption was within a distance of 0.05 mm as measured in a rat tumour model. This degree of damage/disruption is unlikely to affect LDF measurements which represent blood flow averaged over a 1.0-1.5 mm radius from the probe tip. Concurrently, the device was used to monitor tumour blood flow parameters interstitially in human subjects during hyperthermia treatments given in combination with conventional radiotherapy. Blood-flow data from multiple sites of measurement showed marked heterogeneity within individual tumours (up to 55-fold differences) and between different tumours (greater than 100-fold differences). Measurements made by translating the probe along a tumour radius, beginning at the tumour core and advancing to the tumour edge, were consistent with a two-component tumour perfusion model (shell and core). Data are presented from one patient illustrating a persistent change in perfusion distribution during the hyperthermia treatment course, which occurred concomitantly with increases in thermal data. These results suggest that the technique might be of value in monitoring change in flow between treatments. Responses during hyperthermia treatment sessions were also investigated. Four temporal patterns of flow were observed, ranging from a steady increase in flow to a plateau level to a steady drop in flow during heating. These patterns were not well correlated with average temperature recorded at the site of flow measurement. Further study is needed to determine if this LDF technique is to be useful for evaluation of heat transfer by blood perfusion.     

Intra-luminal thermometry: is tissue type assignment a necessity for thermal analysis?

INTRODUCTION: Tissue type assignment, i.e. differentiation tumour from normal tissue, is a normal procedure for interstitial thermometry. In our department, thermometry in patients with a tumour in the lower pelvis is usually restricted to the intra-luminal tracks. It is unknown whether discrimination between normal and tumour tissue is relevant for deep regional hyperthermia thermal dosimetry using only intra-luminal tumour contact and tumour adjacent thermometry. This study has analysed the acquired temperature data in order to answer this question. PATIENTS AND METHODS: Seventy-five patients with locally advanced cervical carcinoma were selected randomly. Patients were treated with a two or three modality combination, i.e. radiotherapy +hyperthermia or radiotherapy + hyperthermia + chemotherapy from October 1997 to September 2003. The first 100 hyperthermia treatments fulfilling the only selection criterion: no displacement of the thermometry catheter along the insertion length during the treatment, were included in the study, resulting in 43 patients with one-to-five treatments/patient (median 2). Using RHyThM (Rotterdam Hyperthermia Thermal Modulator), for each single treatment tissue type, was defined on the basis of information given by a CT scan in radiotherapy position. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the catheter. RESULTS: The average T50 (median temperature) in bladder tumour indicative, vagina tumour contact and rectum tumour indicative was 40.9 +/- 0.9 degrees C, 39.7 +/- 0.9 degrees C and 40.6 +/- 0.8 degrees C, respectively. The average normal tissue T50 in bladder, vagina and rectum was 40.8 +/- 0.9 degrees C, 40.1 +/- 0.9 degrees C and 40.7 +/- 0.8 degrees C, respectively. The differences between bladder tumour indicative T50 and bladder normal tissue T50 and also between vagina tumour contact T50 and vagina normal tissue T50 were significant ( p = 0.0001). No statistical difference was found between rectum tumour indicative t50 and rectum normal tissue T50. CONCLUSION: At present the cause of the temperature difference is not known. However, as the difference between tumour (indicative/contact) and normal tissue is very small and considering also the inaccuracy in the tissue type assignment it can be stated that this study does not provide sufficient evidence to conclude that the statistical difference has clinical relevance. Therefore, it was concluded that at this time there is no need to differentiate between normal and tumour tissue in intra-luminal thermometry.     

On verification of hyperthermia treatment planning for cervical carcinoma patients.

PURPOSE: The aim of this study was to verify hyperthermia treatment planning calculations by means of measurements performed during hyperthermia treatments. The calculated specific absorption rate (SAR(calc)) was compared with clinically measured SAR values, during 11 treatments in seven cervical carcinoma patients. METHODS: Hyperthermia treatments were performed using the 70 MHz AMC-4 waveguide system. Temperatures were measured using multisensor thermocouple probes. One invasive thermometry catheter in the cervical tumour and two non-invasive catheters in the vagina were used. For optimal tissue contact and fixation of the catheters, a gynaecological tampon was inserted, moisturized with distilled water (4 treatments), or saline (6 treatments) for better thermal contact. During one treatment no tampon was used. At the start of treatment the temperature rise (DeltaT(meas)) after a short power pulse was measured, which is proportional to SAR(meas). The SAR(calc) along the catheter tracks was extracted from the calculated SAR distribution and compared with the DeltaT(meas)-profiles. RESULTS: The correlation between DeltaT(meas) and SAR(calc) was on average R = 0.56 +/- 0.28, but appeared highly dependent on the wetness of the tampon (preferably with saline) and the tissue contact of the catheters. Correlations were strong (R approximately 0.85-0.93) when thermal contact was good, but much weaker (R approximately 0.14-0.48) for cases with poor thermal contact. CONCLUSION: Good correlations between measurements and calculations were found when tissue contact of the catheters was good. The main difficulties for accurate verification were of clinical nature, arising from improper use of the gynaecological tampon. Poor thermal contact between thermocouples and tissue caused measurement artefacts that were difficult to correlate with calculations.     

Synergistic effects of intratumor administration of cis-diamminedichloroplatinum(II) combined with local hyperthermia in melanoma bearing mice.

The synergistic effect of local hyperthermia (LHT) with intratumor injection (i.t.) of cis-diamminedichloroplatinum (II) (DDP) was studied using a rodent model with implanted B16 melanoma tumors. The hindfoot of the C57BL/6 mouse bearing the tumor was placed in a water bath at 42.5 +/- 0.2 degrees C (intratumor temperature was at 42.3 +/- 0.1 degrees C) for 30 minutes just after local (i.t.) or systemic (intraperitoneal;i.p.) administration of DDP (1-3 mg/kg once in experiment I and 1-3 mg/kg three times in experiment II). The tumor growth ratio (TGR) at 7 days after treatment in the group given DDP 3 mg/kg (i.t.) with LHT was 1.1 in experiment I and 0.5 in experiment II, and there was a statistically significant difference in both experiments compared to findings in other groups (P < 0.01). The mean survival time was 42.1 days in experiment I and 50.2 days in experiment II, with a significant difference in the latter (P < 0.001). Thus regional injection chemotherapy given concomitantly with local hyperthermia promotes the anticancer effects and improves the prognosis without either severe renal injury or the promotion of hematogenic metastasis.     

Accuracy and precision of computer-simulated tissue temperatures in individual human intracranial tumours treated with interstitial hyperthermia

Accurate knowledge of tissue temperature is necessary for effective delivery of clinical hyperthermia in the treatment of malignant tumours. This report compares computer-predicted versus measured intratumoral temperatures in 11 human subjects with intracranial tumours, treated with a conceptually simple ‘conductive’ interstitial hyperthermia system. Interstitial hyperthermia was achieved by the use of parallel arrays of implanted, electrically heated catheters. The tissue was warmed by thermal conduction and blood convection. Simulation of intratumoral temperatures was achieved by solving a modified bioheat transfer equation on a digital computer using a finite difference method. Comparison of intratumoral temperatures from simulations and measured values differed by about ±0?75°C. Further analysis of computed temperature distributions between catheters revealed a rapidly computable relationship between the local minimum tumour temperature and nearby catheter power and temperature that accounts for effects of varying blood flow. These findings suggest that ‘on-line’ prediction and control of local minimum tumour temperatures are feasible with the conductive interstitial technique.     

Radiofrequency capacitive hyperthermia for deep-seated tumors. I. Studies on thermometry

The thermometry results of radiofrequency (RF) capacitive hyperthermia for 60 deep-seated tumors in 59 patients are reported. Hyperthermia was administered regionally using two RF capacitive heating equipments which the authors have developed in cooperation with Yamamoto Vinyter Company Ltd., (Osaka, Japan). Intratumor temperatures were measured by thermocouples inserted through angiocatheters which were placed 5 cm to 12 cm deep into the tissues. Tumor center temperatures were measured for 307 treatments in all tumors; thermal distributions within tumors and surrounding normal tissues were obtained for 266 treatments of 53 tumors by microthermocouples. Thermometry results obtained were summarized as follows. A maximum tumor center temperature greater than 43 degrees C and 42 degrees C to 43 degrees C was obtained in 23 (38%) and 14 (23%) of the 60 tumors respectively. The time required to reach 43 degrees C in the tumor center was within 20 minutes after the start of hyperthermia in 87% of tumors heated to more than 43 degrees C. Temperature variations within a tumor exceeded 2 degrees C in 81% of tumors heated to more than 43 degrees C. The lowest tumor temperature greater than 42 degrees C was achieved in six of the 53 tumors (11%). Of 42 tumors in which temperatures of the subcutaneous fat, surrounding normal tissues, and the tumor center were compared, 24 (57%) showed the highest temperature in the tumor center and ten (24%) in the subcutaneous fat. When the heating efficacy was assessed in terms of a maximum tumor center, it great deal depended on the treatment site, tumor size, thickness of subcutaneous fat, and tumor type. Tumors in the head and neck, thorax, lower abdomen, and pelvis could be heated better than tumors in the upper abdomen. Greater heating efficacy was shown in patients with large, hypovascular tumors, and with the subcutaneous fat measuring less than 15 mm thick. The predominant limiting factor for power elevation was pain associated with heating. Systemic signs including increases in pulse rate and body temperature were not serious and seldom became limiting factors for power elevation. Our thermometry results indicate that the advantages of deep RF capacitive heating are its applicability to various anatomic sites and negligible systemic effects. The disadvantages are that its primary usefulness is limited to patients with thin subcutaneous fat and with large or hypovascular tumors.     

Accuracy and precision of computer-simulated tissue temperatures in individual human intracranial tumours treated with interstitial hyperthermia

Accurate knowledge of tissue temperature is necessary for effective delivery of clinical hyperthermia in the treatment of malignant tumours. This report compares computer-predicted versus measured intratumoral temperatures in 11 human subjects with intracranial tumours, treated with a conceptually simple 'conductive' interstitial hyperthermia system. Interstitial hyperthermia was achieved by the use of parallel arrays of implanted, electrically heated catheters. The tissue was warmed by thermal conduction and blood convection. Simulation of intratumoral temperatures was achieved by solving a modified bioheat transfer equation on a digital computer using a finite difference method. Comparison of intratumoral temperatures from simulations and measured values differed by about +/- 0.75 degrees C. Further analysis of computed temperature distributions between catheters revealed a rapidly computable relationship between the local minimum tumour temperature and nearby catheter power and temperature that accounts for effects of varying blood flow. These findings suggest that 'on-line' prediction and control of local minimum tumour temperatures are feasible with the conductive interstitial technique.