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Over the course of 3 years, tumours of 19 patients were heated with ultrasound in the operating room during surgical resection. Immediately following intraoperative radiation therapy, thermocouples were inserted into tumour and adjacent normal structures. Patients were then given a 60-min heat treatment with ultrasound after a 10-15-min heatup period. Temperatures were measured at a total of 133 fixed locations for the 19 patient series. Temperature mapping was done in the tumour volume when logistically feasible. Treatment sites included colorectal (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3), sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating system was utilized to control surface temperatures. Three generations of completely immersible transducers were designed over the course of this study with a 4-cm height specification. Since the ultrasound transducer was assembled on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic field to the tumour size. Average of the maximum temperatures attained was 46.6 degrees C. Temperature with which 90% of all measured points equalled or exceeded (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient clinic series, in which superficial tumours were treated with a similar external applicator, and patient tolerance was often a treatment limitation.

A rationale for coordinating the administration of carboplatin with radiation to achieve enhancement of cancer therapy is developed. This approach is based upon a review of the reports of effects in a variety of systems, effects attributed to interactions between cisplatin or other platinum analogs and radiation. Two major effects include radiosensitization (RS) of hypoxic cells with platinum present during irradiation and potentiation of cell kill with platinum complexes administered after irradiation. Both these effects are expected to result in an improved therapeutic ratio. The latter effect may include inhibition of recovery from radiation-induced potentially lethal damage (PLD) and sublethal damage (SLD). Evidence for RS by carboplatin with an enhancement ratio (ER) of 1.8 is presented in Chinese hamster lung cells (V79) irradiated in culture under hypoxic conditions. Potentiation of radiation therapy in mice bearing a transplanted mouse mammary tumor (MTG-B) is reported as a supra-additive tumor growth delay when 60 mg/kg carboplatin is administered either 30 minutes before or immediately after 20 Gy of X-irradiation. Improved efficacy resulting from ongoing clinical trials coordinating cisplatin with radiation should support the role for carboplatin as a potentiator of radiation therapy since this second generation complex of platinum also interacts with radiation and larger concentrations of platinum should be attainable in tumors using the new drug.

The important chemotherapeutic agent cisplatin is currently being combined with radiation therapy (RT) in clinical protocols intended to exploit the potential for this drug to potentiate radiation-induced tumor cell kill. This paper reviews the reports from preclinical studies leading to the design of combined modality protocols and describes the effects produced when platinum complexes are combined with RT. Two interactions that are receiving considerable attention since they might produce an improved therapeutic ratio are the radiosensitization of hypoxic cells and post-RT potentiation of cell kill. This latter effect might include the inhibition of recovery from RT-induced potentially lethal or sublethal damage. However, platinum-radiation interactions are complex and probably include several mechanisms that are unknown at this time. The potential for platinum complexes will be especially promising if results of ongoing phase III combined modality trials show them to be efficacious, since it is unlikely that current protocol designs are optimal. Furthermore, second-generation platinum analogs or other metal complexes designed as potentiators of RT may prove to be more interactive with RT.

Hyperthermia has emerged as a promising alternative or adjunct to other forms of cancer therapy. In order to utilize hyperthermia in very localized volumes immersed in regions of vital normal tissue, an invasive microwave coaxial monopole antenna has been developed. An experimental approach has been taken to characterize and optimize the electromagnetic properties and heating capabilities of bare and insulated antennas imbedded in tissue equivalent phantoms and dog brain. Four methods have been used to visualize the thermal profiles of the microwave probes: the liquid crystal technique, the gelatin technique, and the direct measurement of temperature with thermistor probes in phantom and dog brain. Among the parameters studied are: antenna impedance, insertion depth, antenna insulation (dielectric constant and thickness), shaft insulation, and frequency.

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.