Prospective assessment of quality of life in ovarian cancer patients receiving whole abdomen hyperthermia and liposomal doxorubicin.

PURPOSE: Prospective assessment of quality of life (QoL) in patients with refractory, residual or recurrent ovarian cancer receiving whole abdomen hyperthermia and intravenous liposomal doxorubicin chemotherapy. METHODS: Treatment consisted of six cycles of intravenous liposomal doxorubicin at 40 mg m2 followed by whole abdomen hyperthermia with each cycle delivered every 4 weeks. QoL assessment was performed at baseline, prior to each cycle of chemotherapy and every 3 months during follow-up using self-administered questionnaires. Global QoL was rated on a seven-point scale and specific domains of QoL, disease related symptoms and treatment related toxicity were rated on a four-point scale. RESULTS: Thirty-two patients were enrolled on the study and 129 QoL questionnaires were completed. Average age was 57.9 (range 45-76); nine patients had persistent and 23 recurrent disease. Ten patients completed six cycles of therapy. Three patients returned follow-up surveys. Subjects rated their overall QoL and health at baseline as above average with mean scores 5.10 (95% CI=4.62-5.58) and 4.66 (95% CI=4.23-5.08), respectively. No significant change in overall QoL was found between baseline and cycles 4-6 of therapy. Mean ratings of overall health and subject reported differences in QoL between cycles were not significantly changed during therapy. Limited follow-up data were available, but scores suggest possible improvement in QoL for patients completing all therapy. Subjects rated the greatest negative impact on QoL in areas of role functioning and social functioning, where the mean (SD) over all cycles was 2.00 (0.67) and 1.98 (0.70), respectively. For physical symptoms, fatigue and sleep disturbance had the most negative impact on QoL with means (SD) of 2.26 (0.62) and 1.91 (0.70). The moderate treatment related toxicity seen in this study did not significantly impact patients reported QoL. CONCLUSIONS: Patients with unfavourable ovarian cancer responding to intravenous liposomal doxorubicin and whole abdomen hyperthermia maintained above average QoL during therapy. Limited data on patients completing protocol therapy demonstrated possible improvement in QoL.

Hyperthermia treatment planning and temperature distribution reconstruction: a case study.

While a great deal of effort has been applied toward solving the technical problems associated with modelling clinical hyperthermia treatments, much of that effort has focused on only estimating the power deposition. Little effort has been applied toward using the modelled power depositions (either electromagnetic (EM) or ultrasonic) as inputs to estimate the hyperthermia induced three-dimensional temperature distributions. This paper presents a case report of a patient treated with hyperthermia at the Duke University Medical Center where numerical modelling of the EM power deposition was used to prospectively plan the treatment. Additionally, the modelled power was used as input to retrospectively reconstruct the transient three-dimensional temperature distribution. The modelled power deposition indicated the existence of an undesirable region of high power in the normal tissue. Based upon this result, amplitudes and phases for driving the hyperthermia applicator were determined that eliminated the region of high power and subsequent measurements confirmed this. The steady-state and transient three-dimensional temperature distributions were reconstructed for four out of the seven treatments. The reconstructed steady-state temperatures agreed with the measured temperatures; root-mean-square error ranged from 0.45 to 1.21 degrees C. The transient three-dimensional tumour temperature was estimated assuming that the perfusion was constant throughout the treatment. Using the computed three-dimensional transient temperature distribution, the hyperthermia thermal dose was computed. The equivalent minutes at 43 degrees C achieved by 50% (T50Eq43) of the tumour volume was computed from the measured data and the three-dimensional reconstructed distribution yielding T50Eq43 = 40.6 and 19.8 min respectively.

Anaphylactoid reactions with intraperitoneal cisplatin.

OBJECTIVE: To report the occurrence of anaphylactoid reactions to intraperitoneal cisplatin in 3 patients. CASE SUMMARIES: While conducting a protocol evaluating the efficacy of intraperitoneal cisplatin and hyperthermia in the treatment of recurrent ovarian cancer, 3 patients were noted to exhibit anaphylactoid reactions. A 43-year-old woman received cisplatin 60 mg/m2 in 15 minutes during her sixth cycle of therapy. She developed pruritus, edema, and urticaria over both hands. The reaction subsided after treatment with diphenhydramine and dexamethasone. A 57-year-old woman received 400 mL (62.4 mg) of a cisplatin solution concentrated to deliver cisplatin 100 mg/m2 during her first attempted therapy. At this point, she developed whole body urticaria and pruritus with edema of the extremities. The reaction was aborted with diphenhydramine and dexamethasone. Despite premedication with dexamethasone prior to a second attempt at therapy, she again experienced similar symptoms after receiving 500 mL (78 mg) of cisplatin solution. A 55-year-old woman received 2 cycles of therapy with cisplatin 100 mg/m2 without difficulty. During her third cycle, she again received cisplatin 100 mg/m2 over 30 minutes and developed palmar pruritus, urticaria, and edema. Symptomatology resolved with diphenhydramine. Despite premedication with diphenhydramine and dexamethasone, she experienced generalized pruritus and urticaria, as well as headache and chest pain/tightness, after her next infusion. For both the second and third patients, symptomatology failed to resolve until the intraperitoneal cisplatin solution was withdrawn. DISCUSSION: Anaphylactoid reactions have been described previously with cisplatin administration. No dose-rate effect has been reported, however. We observed 5 reactions in 3 patients that appear to be related to a high dose-infusion time ratio, indicating that dose and rate of infusion may be important factors in precipitating anaphylactoid reactions with cisplatin. CONCLUSIONS: We conclude that a high dose combined with a short infusion time increases the risk of anaphylactoid reactions with the administration of intraperitoneal cisplatin. There was no indication that the increase in anaphylactoid reactions was associated with the use of hyperthermia.

Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.

PURPOSE: To review the theoretical basis and results of a Phase I study of concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian carcinoma. METHODS AND MATERIALS: Previously treated patients with epithelial ovarian carcinoma received intraperitoneal instillation of cisplatin and 60 minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C. Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies with and without hyperthermia were performed. RESULTS: Fifteen patients receiving 17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in all but one course. The median intraperitoneal temperature was 40.7 degrees C; the majority of treatments in which the goal temperature was not reached had power limited by patient discomfort. No major toxicities attributable to hyperthermia were noted. Pharmacokinetic studies noted no significant differences between treatments with vs. without hyperthermia, with intraperitoneal to plasma area under the curve ratios being 30-35. Ten patients had a decline in their CA-125 count during treatment, although in only two patients did this response persist beyond their course of treatment. CONCLUSION: Intraperitoneal cisplatin and regional hyperthermia can be performed with reasonable toxicity. The maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar to those reported with cisplatin alone) and median intraperitoneal temperatures of 40.7 degrees C, however, are felt to be too low to be efficacious in a significant percentage of women with bulky recurrent disease. Further study using intravenous thiosulfate and controlled analgesia is being performed.

Cumulative minutes with T90 greater than Tempindex is predictive of response of superficial malignancies to hyperthermia and radiation.

PURPOSE: To better define thermal parameters related to tumor response in superficial malignancies treated with combined hyperthermia and radiation therapy. METHODS AND MATERIALS: Patients were randomized to receive one or two hyperthermia treatments per week with hyperthermia given during each week of irradiation. Hyperthermia was given for 60 min with treatments begun within 1 hr following irradiation. Power was increased to patient tolerance or normal tissue temperature of 43.0 degrees C. Irradiation was generally given 5 times per week with doses prescribed to normal tissue tolerance (generally 24-70 Gy at 1.8-2.5 Gy per fraction). Multipoint thermometry was used with temperatures obtained every 5 min. RESULTS: One hundred eleven individual treatment fields containing 1 or more tumor nodules were completely evaluable. The complete and overall response rates were 46% and 80%, respectively. Forty-one percent of all treatment fields (51% of responding lesions) remained controlled at 2 years. Multivariate analysis revealed that the cumulative minutes that the temperature achieved by 90% of the measured tumor sites (T90) was > or = 40.0 degrees C, tumor histology, tumor volume, and radiation dose were significantly associated with complete tumor response. The complete response rate was not significantly affected by the number of hyperthermia treatments given per week. The incidence of clinically significant complications was low. CONCLUSIONS: These results support the usefulness of the cumulative minute system in describing time-temperature relationships. The significance of thermal variables with regard to tumor response strongly supports the contention that hyperthermia can be a useful adjunct to irradiation for the local control of cancer.

Clinical experience with a multi-element ultrasonic hyperthermia system: analysis of treatment temperatures.

A summary of tumour temperature data obtained from 31 patients who underwent 147 hyperthermia treatments with the Sonotherm 1000 ultrasonic system is presented. The treatment goal was to achieve a minimum of 42.0 degrees C in tumour for 60 min duration with normal tissues remaining below 43.0 degrees C. In 83% of treatments at least one measured tumour temperature reached or exceeded 42.0 degrees C at some time during the treatment. Nineteen per cent of these treatments had a time- and spatial-averaged temperature (measured in tumour) greater than or equal to 42.0 degrees C. A variety of anatomical sites were treated and these were grouped into four categories: groin/trunk, axilla, breast/chest wall and head/neck. Measured temperatures in tumours located in the groin and trunk sites were significantly higher (22% greater than or equal to 42 degrees C) than other locations. The head and neck treatment temperatures were significantly lower (8% of measured points greater than or equal to 42 degrees C.