Parameters predictive for complications of treatment with combined hyperthermia and radiation therapy

Abstract

Pretreatment and treatment related factors were reviewed for 996 hyperthermia sessions involving 268 separate treatment fields in 131 patients managed with hyperthermia for biopsy confirmed local-regionally advanced or recurrent malignancies to ascertain parameters associated with the development of complications. A subset of 249 fields were identified in which multipoint or mapped temperature data were available for at least one treatment session per field. A total of 198 fields involved superficially located tumors (≤ 3 cm from the surface), whereas 51 fields involved more deeply located tumors. Most of these patients had received extensive prior therapy: 77% had surgery, 75% chemotherapy, 65% radiation therapy and 28% hormonal therapy. They were treated with hyperthermia in conjunction with radiation therapy (244 fields) or hyperthermia alone (5 fields). The hyperthermia treatment objectives were to elevate intratumoral temperatures to a minimum of 43.0°C for 45 minutes while maintaining maximum normal tissue temperatures to ≤ 43°C and maximum intratumoral temperatures to ≤ 50°C. The hyperthermia was given within 30 to 60 minutes following radiation therapy without the administration of additional analgesics. Hyperthermia treatment regimens using radiative electromagnetic, ultrasound, or radiofrequency interstitial techniques were individualized, with 3 to 4 days between hyperthermia treatments and an average of 3.6 treatments (range 1–14; standard deviation 2.2) utilized per field. A total of 38 complications in 33 treatment fields were noted; an incidence of 27 198 (13.6%) for fields with superficially located tumors, and 6 51 (11.8%) in fields with more deeply located tumors. Univariate analyses demonstrated statistically significant correlations between the maximum tumor temperature ( p = 0.0005), average of the maximum tumor temperatures ( p = 0.0006), the average of the % tumor temperatures > 43.5°C ( p = 0.0071), and the average number of hyperthermia treatments ( p = 0.033), with the development of complications. The average of the maximum measured tumor temperature for fields without complications was 44.6°C compared with 45.9°C for fields with complications. The complication rate increased from 7.5% ( 9 120 ) in fields that received one or two hyperthermia treatments to 18.6% ( 24 129 ) in fields that received greater than two hyperthermia treatments. Multivariate logistic regression analyses revealed the best bivariate model predictive of the development of complications included average of the maximum tumor temperature and the number of treatments per field ( p = 0.00012 for the bivariate model). Using the results of the logistic model, isocomplication curves have been generated indicating the risk of the development of complications as a function of maximum intratumoral temperatures and number of hyperthermia treatments. Hopefully, these will aid in the design and analysis of future hyperthermia-radiation therapy clinical trials.