L. Leybovich

TUMOR CONTROL IN LONG-TERM SURVIVORS FOLLOWING SUPERFICIAL HYPERTHERMIA

Sixty tumors with a minimum of 1-year follow-up were treated with radiation and superficial microwave hyperthermia (915 MHz). The overall local control rate was 50% (30/60). The most important factor in outcome was appropriateness of the hyperthermia applicator. Tumors covered by at least the 25% iso-SAR contour achieved 65% local control versus 21% local control with less than 25% SAR coverage (p less than 0.01). Several measures of adequate minimum monitored tumor temperature and duration were considered. The measure best correlated with outcome was best single session time at or above 43 degrees C (t43). If each monitored tumor catheter achieved t43 greater than or equal to 30 minutes in at least one session, then tumor control was significantly (p less than 0.01) improved (63% with Min t43 greater than or equal to 30 versus 25% with Min t43 less than 30). Although there was considerable overlap between tumors with SAR greater than or equal to 25% and those achieving Min t43 greater than or equal to 30, a statistically significant (p = 0.02) difference could be demonstrated between the group meeting both the SAR and the minimum tumor time/duration standards as opposed to those meeting only one standard. The actuarial local progression-free survival for tumors most likely to have had adequate hyperthermia (defined as SAR greater than or equal to 25% and Min t43 greater than or equal to 30) and all other tumors did not begin to separate significantly until 8 to 12 months after treatment. Implications for future randomized studies are discussed.

Interstitial thermoradiotherapy in treatment of malignant tumours

From October 1981 to October 1985, 48 recurrent/persistent tumours (46 patients) were treated with a combination of interstitial hyperthermia and interstitial radiation therapy. All patients had failed other conventional treatment modalities. Radiation was administered using 192Ir with doses varying from 2000 to 6000 rad, depending on the dose of previous irradiation. Hyperthermia was administered with either localized current fields (LCF) or microwaves, two sessions each, minimum tumour temperature of 42.5 degrees C for 60 min. Of 37 lesions treated with at least one satisfactory hyperthermia session, there were 26 of 37 (70 per cent) complete responses and 11 of 37 (29.7 per cent) partial responses. Of 11 lesions with no sessions of satisfactory hyperthermia, there were no complete responses and only five partial responses. The detailed results are presented.

Thermoradiotherapy of malignant melanoma

From 1978 through February 1986, 49 measurable lesions in 18 patients with recurrent primary or metastatic malignant melanomas were treated with a combination of radiation therapy and hyperthermia. The primary sites were head and neck (eight), chest wall (two), pelvis (one), upper extremities (three), and lower extremities (35). Because of the length of the study, the dose and fractionation of radiation therapy varied (dose per fraction from less than 400 cGy to 800 cGy and a total dose of 2000 cGy to 6000 cGy). This variation was mostly dependent on the prior course of radiation therapy of these lesions. The hyperthermia technique used in these patients was superficial local microwave hyperthermia; a minority of patients were treated with ultrasound. Complete response was achieved in 29 lesions (59.2 per cent) and partial response in six lesions (12 per cent). In a separate analysis of 67 lesions with superficial malignant melanoma who were treated by radiation therapy alone, a 24 per cent complete response and a 34 per cent partial response were achieved. Detailed analyses are presented in regard to dose per fraction, total radiation dose, and the size of lesions.

Combined hyperthermia and irradiation in the treatment of superficial tumors: results of a prospective randomized trial of hyperthermia fractionation (1/wk vs 2/wk)☆

From December 1984 to December 1989, 240 superficially located recurrent/metastatic malignant lesions (173 patients) were enrolled in a prospective randomized study of one versus two hyperthermia fractions per week. In the majority of patients, the dose of radiation therapy was less than 4000 cGy over 4 to 5 weeks. Stratification was by tumor size, site, and histology. The goal of the hyperthermia sessions were 42.5 degrees C for 45-60 min minimum intra-tumor measured temperature. Hyperthermia was given after radiation within 30-60 min. External applicators, both microwave (over 90% of treatments) and ultrasound, were used. Overall, complete response rate in 222 evaluable lesions was 56.3% (125/222) with a minimum follow-up of 6 months and a maximum follow-up of 52 months. The complete response rate for once a week versus twice a week hyperthermia group was 54.7% and 57.8%, respectively. The severe complication rate was 18% (41/222). There was no difference between the two treatment arms. Cox regression analyses were performed to study the prognostic significance of patient characteristics, tumor characteristics, and treatment parameters. Detailed analysis and results are presented.

Interstitial thermoradiotherapy in the treatment of recurrent/residual malignant tumors

From October 1981-November 1983, a total of 31 recurrent and/or persistent tumors in 29 patients were treated with interstitial radiotherapy in combination with interstitial hyperthermia. All patients had undergone extensive previous treatments by surgery and/or radiation therapy. In the present series, radiation used was administered by iridium 192 implant, with doses varying from 4000–6000 cGy, delivered at the rate of 1000 cGy ± 10%/day. Hyperthermia was delivered by radiofrequency (8 lesions) and microwave (25 lesions) in two sessions, each raising tumor temperature to a minimum of 42°C over 60 minutes. Of 26 lesions with at least one satisfactory heating session, there were 18 (69%) complete responses, five (19%) partial responses, and three with less than 50% regression. None of the five lesions with unsatisfactory heating resulted in complete response. Of the total group, two patients developed a cutaneous sinus and one patient developed a fistula. The detailed methodology and results are presented and recommendations for future improvements are discussed.

Equilibrium temperature distributions in uniform phantoms for superficial microwave applicators: Implications for temperature-based standards of applicator adequacy

Equilibrium temperature distributions are computed using measured SAR distributions for five different superficial microwave (915 MHz) applicators. We assume a model with uniform conduction and blood flow. A Greens function approach is used to calculate equilibrium solutions which identically obey boundary conditions at the surface of the phantom and at infinite depth. The equilibrium solutions are categorized by surface temperature (TS), maximum allowed temperature (TM), and by a parameter (referred to as the diffusion length, lambda) which characterizes the contributions of thermal conduction relative to blood flow. The computed equilibrium temperature distribution at depths of 2 and 3 cm is strongly dependent on lambda and on TM. It is not strongly dependent on surface temperature for TS below 35 degrees C. In previous work we compared the SAR distribution with local control of 53 superficial tumours with over 1 year of follow-up. As an alternative to an SAR-based description of applicator adequacy we consider a temperature-based standard. Tumours are categorized by the minimum value of lambda that would allow full coverage of the tumour volume by the 42 degrees C contour, assuming a TM of 47.5 degrees C and a TS of 35 degrees C. Eighteen of 27 lesions (67%) were locally controlled for lambda less than 1 cm. The local control in 26 lesions with lambda greater than or equal to 1 cm was 31% (p = 0.016). The lesions with the best results were those with both good coverage in theory (lambda less than 1 cm) and with all monitored catheter tracks achieving at least one session with 30 min at or above 43 degrees C. We found that the temperature-based standard of applicator adequacy was not independent of an SAR-based standard, and in this cohort of patients either a minimum SAR criterion or a maximum diffusion length criterion would serve equally well as a screen for inappropriate applicators.

Characteristics of improved microwave interstitial antennas for local hyperthermia

The heating potentials of two newly-developed microwave interstitial antennas are reported in this paper. The longitudinal (parallel to the antenna) and transverse (over a plane perpendicular to the antenna) specific absorption rate (SAR) distributions of single and an array of four parallel antennas were measured in a muscle equivalent phantom and their performance characterized at 915 MHz in terms of the following parameters: peak depth (location of the profile peak with respect to the surface), 50% HL (effective heating length over which SAR greater than 50% of the peak normalized SAR), dead length (axial length at the antenna tip with SAR less than 50% of peak normalized SAR), and the variations of the specific absorption rate pattern relative to the depth of insertion. The results are analyzed and discussed in terms of these parameters and other factors important in the clinical use of these antennas for effective interstitial hyperthermia.

Physical predictors of adequate hyperthermia with the annular phased array

One hundred and fifty-two hyperthermia sessions in 36 consecutive patients treated with the BSD 1000 annular phased array system (APAS) are reviewed with regard to physical predictors of quality of hyperthermia. Although central tumour temperatures exceeding 42 degrees C were momentarily obtained in 62% of the sessions, it frequently proved difficult to maintain the patient at temperature for prolonged periods of time. The time to reach target temperature was negatively associated with quality of hyperthermia. Thus, of 25 sessions which required over 25 min to attain a temperature of 42 degrees C, only one was adequate (defined as central tumour temperature greater than or equal to 42 degrees C maintained for at least 30 min) as opposed to 28/69 adequate sessions when 42 degrees C was reached in less than 25 min. Physical parameters measured in the first 3 min of the session found to be associated with adequate hyperthermia include an initial rate of temperature rise at the tumour site exceeding 0.4 degrees C/min achieved with a net forward power less than 1500 W. Only three of 57 sessions not meeting these criteria were adequate. Treatment policy recommendations and recommendations for future research are made.

Dual-antenna applicator for hyperthermia of tumours at intermediate depth

A dual-antenna applicator with 21 x 26 cm2 aperture, that is fully loaded and operates at 74 MHz, was developed at the Mallinckrodt Institute of Radiology. By placing two antennas into an applicator capable of propagating TE10 mode, a significant enlargement of heating pattern was achieved without an increase in applicator dimensions. When antennas are placed symmetrically about a parallel to the antenna axis of symmetry, the sensitivity of the applicator input impedance to variations of load impedance reduces. Stable coupling of the RF power to the treatment area may be provided. Twenty patients with eccentrically located tumours were treated using this device.

A practical, modular hyperthermia phantom

A catheterized, three-component slab phantom has been fabricated for use in mapping specific absorption rate (SAR) distributions from hyperthermia applicators. A planar array of 21 closely spaced catheters, located at one surface of the 1-cm-thick slab, can be positioned at depths of 0-7 cm below the phantom surface, in 1-cm steps, through appropriate placement and orientation of this slab within the three-slab set. Owing to its modular design, the phantom can be prepared, and also purged of degraded material rapidly and without damage to the catheter tracks.