0180_CHANGES IN TUMOR TISSUE OXYGENATION DURING MICROWAVE HYPERTHERMIA - 02.pdf

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    CHANGES IN TUMOR TISSUE OXYGENATION DURING MICROWAVE HYPERTHEP~MIACLINICAL RELEVANCE

    Haim I. Bicher, M.D. and Nodar P. Mitagvaria~ Ph.D.*, Valley CancerInstitute, 6917 Valjean Avenue Van Nuys, CA, USA, *Institute of PhysiologyGeorgian Academy of Sciences, Tbilisi, USSR

    ccepted for publication4th International Symposi~imHyperthermic OncologyAarhus, Denmark, July ]984

    STR CT

    A~ previously described (Bicher 1981) Tp02 and blood flow increase intumor as temperature increases until 41C and decrease thereafter(mlcrocirculation "breaking point"). In the present clinical study using02 microelectrodes this response was reproduced in over 54 treatmentsessions. However, it was found that as treatment progresses (patientsare treated for one hour I0 times, twice weekly, and concomitantly receive4000 rads of ionizing radiation) the initial increase of blood flow andTpO2 is reduced and there is immediate decrease in tissue oxygenation.-A correlation between microvascular tumor physio ogical changes and tumortreatment responses is >~ing developed.

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    for each of the 10 sequential heat fractions usually administeredpatient.

    to each

    2. METHODS

    Microthermocouples: Tissue temperatures were d~termined usingcopper-conatantan clinical microthermocouples manufactured by PDM, 6917Valjean Avenue, Van Nuys, CAo Each 75 micron wire of the thermocouple pairis insulated by teflon and the sensor is mounted in a triple suture whichcarries it in place when introduced using a miniature needle system.Through~ut treatment, temperature readings were taken at 5-min intervalsunder "power off" conditions. Temperatures were recorded using a modifiedmicroprocessor with a special interface controlling the microwave "on-off"cycle. A minimum of 4 probes were used in each treatment.

    Oxygen microelectrodes: A 25 micron gold wire, insulated in teflon,was prepared for use as an oxygen mlcroelectrodes by forming a "Rhoplex-Formvar membrane over the exposed tip as described in previouspublications (Bicher 1980). These electrodes are activated according topolarographic pminciples and recorded through appropriate activatorsmicroprocessors and A-D converters to the same~computer system describedabove; Oxygen readings were performed under "power off" conditions in the

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    3. RESULTS

    The typical changes of tumor oxygen levels during a heating period ared~vided into three phases. First there is an increase in TpO

    2to more

    than double its original value. Thereafter the "critical point" isreached, about 10-30 minutes into the treatment, and the oxygen levelsbegin to decrease. The third phase is one of stabilization, which usuallyoccurs above the original baseline in previously untreated patients.Thesetrlphaslc responses have been~descrlbed in previous publications(Bicher 1978, 1980) and was confirmed in the present series, in all cases

    ~ during the first treatment (see Figure IA and Table I)~As additional hyperthermla fractions are given there is a marked change

    in the trlphaslc TpO2 hyperthermlc response. The initial TpO2increase gradually disappears and the stabilization occurs below theinitial TpO2 baseline. (Figure I, B and C and Table I). By the 10thtreatment the initial size is always absent and the stabilization occursbelow the initial level.

    T p O ; O I A N B E S D U R I N G H Y P E R T H E P ~ I A H U , " , A N I U ~ O R S

    ~ o . O F T RF A T ~ E ~ T S ~15T 2 5Tff

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    decrease in tissue pH which is of long duration. (Bicher 1980, Song1980). The pH changes have considerable effect on hyperthermla cellkilling, which is increased fivefold at low pH values (Gerweck 1974). Thepresent results clearly indicate that fundamental changes in themlcrocirculation ability to perfuse tumors occur during the multifractionradiation-hyperthermia treatments.

    As the series progresses the initial 02 increase, an obvious activecompensating physiological response, is obliterated. Also, the fact thatpO2 levels decrease during the treatment to below the initial levelsindicates that the microcirculation is unable to compensate for increased02 demand due to increased metabolic activity probably induced by theraised tissue temperatures

    In this respect, routine TpO2 monitoring during treatment c~uld ~e ofclinical value.

    BErber, B.. Betzel. F. and DAgostino.L., 1977, Changes n tu~or tissue Oxygenation induced by microwavehyperthemie. Internatlonal Journal Radiation Oncolo~ Biology Ph~slcs~ 2, 157.

    Bicher, H.. 1978, Increase in brain rissue oxygen availability induced by localized mlcrovave hyperrhermla.In Silver Ernclnska and Bicher, Oxygen transport to tissue; Vol. flip ~7-353, NY,

    gicher, H., et el~ 1980, Effects o[ hypertherm[a o~ normal end tumor microenvlro~en~. R~dlarlon ~7,52~ 5~0

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