Superficial Human Tumors Research Articles

Laser-Induced Thermal Treatment of Superficial Human Tumors: An Advanced Heating Strategy and Non-Arrhenius Law for Living Tissues

The most interesting, but insufficiently known results obtained by the author in modeling laser-induced hyperthermia of human tumors are discussed. It is important that the traditional equation for the local bio-heat transfer does not work in superficial layers of the body. It is shown also that the classical Arrhenius law is not applicable to living tissues because of the tissue regeneration due to oxygen supplied by the arterial blood. The latter is one of the main reasons of the suggested strategy of laser heating of tumors in the therapeutic window of semitransparency when the tumor asphyxiation is considered as one of important weapons against the cancer. The other advantages of this advanced strategy of a soft thermal treatment (in few of sessions), which is painless for patients, are discussed as well. Some features of modeling various heat transfer modes are also considered. The best choice between the simplest differential models for the radiative transfer calculations is dependent of the particular problem statement. The known finite-difference or finite element algorithms can be preferable in solving transient heat transfer problems. As a rule, it depends on the shape of the computational region. It is expected that this paper will help the colleagues to overcome some typical weaknesses of computational modeling of infrared photothermal treatment of superficial tumors.

Hyperthermia improves the complete response rate for superficial tumors treated with radiation: results of a prospective randomized trial testing the thermal dose parameter CEM 43°T 90

Purpose/Objective: To test the effectiveness of local hyperthermia and radiotherapy in superficial human tumors in a prospective randomized trial that compares a low vs. high dose of local hyperthermia (HT) and radiotherapy, utilizing the parameter CEM 43° T90 (the number of equivalent minutes at 43° for 90% of monitored points within the tumor) as a measure of thermal dose.

Superficial hyperthermia in combination with radiotherapy and chemotherapy

Prospects for improved control of superficial human tumors by combining hyperthermia and radiation are reviewed.

Blood flow in human tumors during local hyperthermia

The response of tumor blood flow during local hyperthermia was studied at 40 different points in 15 superficial human tumors. Hyperthermia was administered for 60 minutes by use of 915 MHz microwaves. Blood flow was determined from the rate of thermal clearance by use of the bioheat equation. The rate of thermal clearance was sampled at 10–15 minutes intervals by turning the applied power off for 30 seconds. A correction was made for thermal conduction from orthogonal profiles of the tumor temperature. No measurements were made during the first 10–15 minutes of heating. The response of tumor blood flow was found to be independent of temperature in the range of 40–44°C. The mean blood flow rate increased 10–15% between 15 and 30 minutes, but remained nearly constant thereafter. The coefficient of variation in this pattern is 15–20%. No evidence of a sharp reduction in flow was observed. Furthermore, the mean temperature elevation, net forward power, and rate of thermal conduction all remained nearly constant with time, providing further evidence of stability in the blood flow rate. Data obtained in one tumor suggest that a reduction in flow may occur at temperatures above 44°C. The mean blood flow rates obtained in this study range from 0–34 ml/100g/min with an average value of 15 ml/1008/min.

P-31 spectroscopy study of response of superficial human tumors to therapy.

Studies were performed to characterize phosphorus-31 magnetic resonance (MR) spectra obtained from 10 superficial human tumors outside the brain and to determine whether P-31 MR spectroscopy could allow detection of a response to therapy before a change in tumor size was measured. The ratio of phosphomonoester to adenosine triphosphate peak intensities (PME/ATP) was unusually large in all tumors studied. The average PME/ATP in lymphomas (1.8 +/- 0.5) was greater than in nonlymphoma cancers (1.1 +/- 0.15). The average PME/ATP for all tumors studied (1.4 +/- 0.5) was much greater than that of underlying skeletal muscle (0.23 +/- .09). Eight of the tumors were studied before and after therapy. Responders were distinguished from nonresponders on the basis of changes in tumor size. PME/ATP decreased during therapy in three lymphomas that responded to therapy. In an adenocarcinoma and Ewing sarcoma that did not respond to therapy, PME/ATP increased. PME/ATP remained constant in two squamous cell carcinomas that responded to therapy and decreased in one squamous cell carcinoma that decreased in size by 40% but was classified as a nonresponder. Changes in PME/ATP did not always parallel changes in tumor size during therapy. In two patients, a decrease in PME/ATP preceded a decrease in tumor size. In four patients, PME/ATP increased transiently during periods when tumor size remained constant.

Proton magnetic resonance spectroscopy of small regions (1 mL) localized inside superficial human tumors. A clinical feasibility study

It is demonstrated that the stimulated echo technique for proton magnetic resonance spectroscopy (MRS) can be used to study metabolites in volumes of interest (VOIs) as small as 1 mL localized within superficial human tumors. Access to these small VOIs is important for characterization of tissue regions within a tumor, before, during and after treatment. Spectral appearance resembles that from studies on extracts, and cell suspensions and perfused cells of several tumor types. For the first time proton MRS was used to study cancer treatment in vivo in humans, for a case of radiation treatment of squamous cell carcinoma. No spectral evidence of changed metabolism prior to reduction in tumor size was found. However, after the first period of radiation (39 Gy, 4 weeks), complete disappearance of the metabolite resonances from the spectrum was observed, while a considerable mass still remained, suggesting effective cell destruction upon treatment. Needle aspiration cytology of this mass showed absence of malignant cells, supporting this result.

Response of tumors to therapy studied by 31P magnetic resonance spectroscopy.

Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.

Regional hyperthermia combined with systemic chemotherapy in advanced abdominal and pelvic tumors: first results of a pilot study employing an annular phased array applicator.

The clinical use of an annular phased array system of electromagnetic wave applicators for regional heating of deep-seated tumors has been previously reported (Sapozink et al. 1984,1986; Emami et al. 1984; Gibbs et al. 1984; Howard et al. 1986). In these studies the patients received regional hyperthermia combined with radiotherapy. The rationale for this combined treatment modality is based on biological data in vitro and in vivo indicating a synergistic interaction between heat and radiation (Dewey 1984). In clinical studies on superficial human tumors, combined hyperthermia and radiotherapy has been shown to be superior to either modality alone in achieving complete responses (Overgaard 1985).

Capacitive heating of phantom and human tumors with an 8 MHz radiofrequency applicator (thermotron RF-8)

The thermal profile was investigated in agar phantoms and in human tumors heated capacitively with 8 MHz RF. Deep and homogeneous heating could be achieved in a large homogeneous phantom of 25 cm diameter and 24 cm thick when heated with a pair of 25 cm diameter electrodes, coupled to both bases of the phantom. When the size of the two electrodes was not the same, the region near the smaller electrode was preferentially heated. It was, therefore, possible to control the depth of heating by choosing properly sized electrodes. Therapeutic temperature (>42°C) could be obtained in 7 out of 9 small, as well as, bulky superficial human tumors as large as 8 × 8 × 10 cm. Indications are that heating of some deep-seated human tumors might be achieved by the capacitive method, provided that subcutaneous fat layer is cooled by temperature controlled bolus and large electrodes are used. The effect of the anatomical structure on the power deposition in the human body during capacitive heating should be further investigated.

Ultrasound-induced hyperthermia for the treatment of human superficial tumors

Ultrasonic systems were developed for the treatment of superficial human tumors, generating local tumor hyperthermia at tumor center temperatures ranging from 43°to 50°. Twenty-eight patients with disease of varying histology were evaluable for response, and demonstrated an overall response rate of 57 % with a complete response rate of 18 %. In 11 patients who had received definitive radiation therapy to the heat treated area, the response rate was 81 %; there were no toxicities other than those noted for the overall study. As temperature was escalated a marked increase was observed both in response rates (from 53% (43–44°C) to 83% (48–50°C) and in duration of response (from 29 to 250 days for the same temperatures). Toxicities were minimal, consisting of superficial blistering in four patients and pain in six patients. Pain was usually associated with tumor involvement in the periostium.

Combined radiation and hyperthermia in superficial human tumors.

Hyperthermia (42--43 C) appears to potentiate the effects of radiation therapy in experimental tumor models. In addition, some studies indicate that tumors may be sensitized to a greater extent than normal tissue. This study was designed to test whether the effectiveness of irradiating human tumors was enchanced significantly by concomitant heating. We also examined skin to see if heating enhanced the response to radiation of normal tissues. Nineteen patients with multiple metastatic superficial tumor masses of various histologies were studied. All were considered incurable and an independent clinical decision had been made to irradiate for palliation. Two or more masses in the same patient were matched for size and location, so that one of the patient's own tumors was a control to monitor the effect of irradiation alone. On each patient the tumors were treated with identical fractions and to the same total dose of radiation. One of the matched nodules was given hyperthermia (43 C) for 15 minutes before and 30 minutes after each radiation fraction. The response of the tumor that received radiation alone was compared with that of the tumor receiving hyperthermia and radiation. In seven of 15 evaluable patients the tumor that received heat in addition to radiation had a greater objective response than the tumor receiving radiation alone (P < .065). Of the remaining eight patients, four had complete tumor regression in both areas without later regrowth, two failed to respond in either area, and two partially responded in both areas. Two patients had increased cutaneous reaction to radiation in the heated area; one of these was a severe desquamative reaction, which conformed to the size and shape of the ultrasound field. These results suggest that hyperthermia improves the objective response to radiation in some human tumors; in two cases it appeared to sensitize skin as well.