Taljit S. Sandhu

Hyperthermia and radiation in combination: A clinical fractionation regime☆☆☆

Abstract A fractionation regime has been devised and clinically tested to use a combination of hyperthermia and low dose radiation therapy to treat tumors with a curative intent. Hyperthermia is induced using microwaves delivered to a defined tissue volume through specially designed applicators. Frequencies of 2450, 915 or 300 MHz are used according to the desired penetration depth. Each treatment lasts for 90 minutes. The skin is cooled by an air jet. Tissue temperature is kept at 45°C when hyperthermia alone is used and at 42°C in combination with radiation. Patients are treated twice a week with 72 hour intervals between treatments. The regime consists of 4 treatments of hyperthermia alone followed by a week of rest. Thereafter each hyperthermia treatment is preceded by a 400 rad fraction of x-irradiation delivered in 4 combined treatments to a total of 1600 rad. This low total radiation dose allows retreatment of previously irradiated areas or organs. No toxicity induced by this combination has been detected, even in areas previously radiated to high doses. Twenty-three patients have been entered into the protocol that encompasses 37 treatment fields. Most tumors respond to treatment, many of these with total disappearance; skin, brain, breast and spinal cord are among the treated areas. Melanomas and lymphomas are the most sensitive tumors, sarcomas the most resistant; adeno and squamous cell carcinoma in between.

Once-Weekly, High-Dose Stereotactic Body Radiotherapy for Lung Cancer: 6-Year Analysis of 60 Early-Stage, 42 Locally Advanced, and 7 Metastatic Lung Cancers

PURPOSE To explore once-weekly stereotactic body radiotherapy (SBRT) in nonoperable patients with localized, locally advanced, or metastatic lung cancer. METHODS AND MATERIALS A total of 102 primary (89 untreated plus 13 recurrent) and 7 metastatic tumors were studied. The median follow-up was 38 months, the average patient age was 75 years. Of the 109 tumors studied, 60 were Stage I (45 IA and 15 IB), 9 were Stage II, 30 were Stage III, 3 were Stage IV, and 7 were metastases. SBRT only was given in 73% (40 Gy in four fractions to the planning target volume to a total dose of 53 Gy to the isocenter for a biologically effective dose of 120 Gy(10)). SBRT was given as a boost in 27% (22.5 Gy in three fractions once weekly for a dose of 32 Gy at the isocenter) after 45 Gy in 25 fractions to the primary plus the mediastinum. The total biologically effective dose was 120 Gy(10). Respiration gating was used in 46%. RESULTS The overall response rate was 75%; 33% had a complete response. The overall response rate was 89% for Stage IA patients (40% had a complete response). The local control rate was 82%; it was 100% and 93% for Stage IA and IB patients, respectively. The failure rate was 37%, with 17% within the planning target volume. No Grade 3-4 acute toxicities developed in any patient; 12% and 7% of patients developed Grade 1 and 2 toxicities, respectively. Late toxicity, all Grade 2, developed in 3% of patients. The 5-year cause-specific survival rate for Stage I was 70% and was 74% and 64% for Stage IA and IB patients, respectively. The 3-year Stage III cause-specific survival rate was 30%. The patients with metastatic lung cancer had a 57% response rate, a 27% complete response rate, an 86% local control rate, a median survival time of 19 months, and 23% 3-year survival rate. CONCLUSIONS SBRT is noninvasive, convenient, fast, and economically attractive; it achieves results similar to surgery for early or metastatic lung cancer patients who are older, debilitated, and with comorbidities. Elderly patients and/or patients medically unfit for combined modality therapy with locally advanced disease can find an effective palliative alternative in SBRT.

A pilot study to investigate skin and tumor thermal enhancement ratios of 41.5–42.0°c hyperthermia with radiation☆

This article reports the clinical results of the combined treatment of radiation and localized microwave hyperthermia to treat multiple metastatic melanoma tumors. The response of normal skin to the treatment was measured by evaluating the degree of erythema using a numerical scoring system. Tumor response to the treatment was assessed by measuring tumor diameter at follow-up visits. Whenever possible, thermal enhancement ratios for normal skin and tumor tissue were evaluated. The manuscript discusses problems associated with obtaining useful clinical data.

The development of microwave hyperthermia applicators

Abstract Two direct-contact microwave (915 MHz and 2450 MHz) applicators were designed and fabricated for localized hyperthermia treatments of solid tumors. The 2.45 GHz applicator can be attached to an X-ray machine head and used as a cone to deliver X-rays and microwaves simultaneously. The 915 MHz applicator has the capability of cooling the skin surface by circulating a dielectric liquid through a bag attached to the application end of the applicator. The temperature and the flow of the liquid can be controlled to achieve the desired skin temperature. The temperatures of the incoming and outgoing liquid through the bag were measured to determine the energy lost. Temperature distributions were obtained using a pig in vivo system with liquid crystal and thermocouple probes. Using the 2.45 GHz applicator the skin surface remained at the highest temperature and a very steep temperature drop was observed (3.5°C drop at a depth of 3 cm). Temperature distribution improved when the 915 MHz applicator was employed. The skin surface remained at a temperature 0.5° C lower than that of the tissue at 1 cm depth. A temperature drop of only 1°C was observed at a depth of 3 cm. An even better distribution was obtained when skin surface was cooled. Skin surface and tissue at a depth of 3 cm were elevated to the same temperature while the tissue at depth of 2 cm was raised to a temperature 1°C higher.

Measurement of blood flow using temperature decay: Effect of thermal conduction

Within the framework of the bioheat equation, we studied the effect of conduction on the thermal washout curve for a model tissue configuration subjected to a thermal perturbation such as hyperthermia treatment. In particular, we studied the implications of the assumption made by many investigators to neglect the effect of thermal conduction while analyzing the temperature decay curve for measuring blood perfusion. The present analysis suggests that during the localized hyperthermia treatments, this assumption can lead to inaccurate values for the blood perfusion parameter. This is particularly so under non-steady state conditions when the temperature distribution is changing. In addition to the value of blood flow, the shape of the temperature decay curve depends on the temperature distribution at the start of temperature decay.

Results of a Phase I/II Clinical Trial of Fractionated Hyperthermia in Combination with Low Dose Ionizing Radiation

This paper addresses, in part, the current status of hyperthermia as a new clinical modality and reports the results of a large, prospective clinical trial employing microwave hyperthermia in combination with low doses of ionizing radiation. In the protocol employed, each treated area received 8 hyperthermia treatments of 1.5 hour combined with 1600 rad over a total period of 5 weeks. Patients were heated with microwaves of 915 or 300 MHz employing external applicators or internal intracavitary antennas. The results of this fractionation scheme are encouraging since in 121 fields that were treated completely according to protocol and were available for follow-up for at least 2 months, complete responses were observed in 65% of all cases, partial response in 30% and no response in only 5%. It is also important to note that toxicity was minimal throughout the study.