Serum concentration: effects on cycle and x-ray sensitivity of mammalian cells.

If the content of serum in the culture medium of exponentially growing Chinese hamster cells is below optimum (15 percent), the doubling time and the resistance to x-irradiation of the cells are increased. In synchronously dividing populations the increase in doubling time is primarily caused by increase in duration of the postmitotic (G(1)) phase of the cells; this phase is relatively radiation resistant. The response of the cells growing synchronously is related quantitatively to the response of the cells dividing randomly.

Anatomical site-specific modalities for hyperthermia.

The clinical application of hyperthermia in the treatment of deep-seated tumors remains an empirical science. The pleomorphic nature of the neoplasms and the great diversity in the anatomy and physiology of the individual tumor locations make the treatment of nearly every neoplasm a unique challenge. A wide variety of devices is required, both for the administration of hyperthermia and for the measurement of the temperatures achieved. At Stanford University, these include the BSD Medical Corp. annular phased array system, an isospherical ultrasound device, and interstitial radiofrequency for deep heating. Ultrasound transducers and a variety of microwave applicators are used for superficial hyperthermia. Six illustrative case studies, selected from the 91 patients treated in our program since October 1981, are presented, with discussion and comparison of treatment devices. Difficulties in deep heating were encountered in several instances, believed secondary to the thickness of the s.c. fat, the relatively high heat-induced tumor blood flow, and the presence of adjacent bone. It is suggested that ultimate improvement in clinical results will be possible once a better understanding is achieved of such anatomical and physiological factors.

Postoperative radiation therapy for epithelial ovarian cancer: the curative role based on a 24-year experience.

We updated 152 cases of epithelial ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stages I through III, treated at the Stanford Medical Center (Stanford, Calif) with irradiation as the only postoperative therapy. In 133 patients, radiation was directed only to those regions of known disease, while it was delivered to the whole abdomen and pelvis by the Martinez technique in 19 patients. Mean follow-up time was 6.8 years. The results were analyzed as freedom from relapse (FFR) at 15 years; overall, FFR constituted 44% of the patients. Statistically significant differences of FFR appeared between stages II (60%) and III (16%); among the histopathologic variants endometrioid (64%), serous papillary (45%), and undifferentiated (7%); between pathologic grades 2 (68%) and 3 (20%); between amounts of postoperative residual disease less than 2 cm (48%) and greater than 2 cm (16%); and between ages less than 40 (80%) and greater than or equal to 40 (38%). Considering all stages and grades together, FFR in the 54 cases with unfavorable residuum (greater than 2 cm) was 14%. Among the 98 with favorable residuum (none, or less than 2 cm) FFR was 62%; and 14 (39%) of the 36 relapses were in the untreated upper abdomen. Results in the favorable group support effectiveness of irradiation as postoperative therapy. These patterns of relapse suggest that whole-abdominopelvic irradiation would further increase FFR. We believe that, for favorable disease as defined such radiotherapy should be the standard for comparison.

Current conflicts in the management of prostatic cancer.

In summary, 5-, 10-, and 15-year actuarial survival can be achieved in 81, 60, and 35% of patients with disease limited to the prostate and in 61, 36, and 18% of those with extracapsular extension. In various subgroups of patients with nodular disease who were selected by the same criteria applied in the selection for surgical resection, survival of 60% can be achieved. Conversely, local control may not be achieved following irradiation because of cell survival within the target volume. More sophisticated boost therapy using interstitial implants, high energy particles, radiosensitizers, and/or hyperthermia may improve local control and hence longer term survival. Local control may not be achieved following surgical resection because of transection of tumor at the surgical margin. Case selection for surgery might be improved by pre-operative transrectal ultrasonography or MRI examination. In situations in which pathologic examination demonstrates frank tumor transection, local control still may be achieved by prompt and judicious salvage by X-ray therapy.

Secondary external-beam radiotherapy and hyperthermia for local recurrence after 125-iodine implantation in adenocarcinoma of the prostate.

At Stanford, six patients underwent a course of external radiotherapy after local recurrence following 125-iodine implantation. Four of the six patients also received concomitant hyperthermia. Four patients were initially managed with hormonal manipulation at time of local relapse and subsequently received external beam radiotherapy with or without hyperthermia. The hyperthermia was non-invasively induced using an annular phased array radiative electromagnetic system. Treatment was well tolerated, and none of the patients experienced severe rectal or bladder complications. Three patients are free from disease; one patient experience local-regional recurrence based on biopsy; one recurred in the bladder, was treated with cystoprostatectomy and subsequently succumbed to metastatic disease; and one patient died of presumed metastatic disease. External-beam irradiation with concurrent hyperthermia can be safely delivered to treat locally recurrent prostatic carcinoma after 125-iodine implantation.

Predictors of survival after a positive post-irradiation prostate biopsy.

PURPOSE: Considerable debate persists in the urologic oncology literature with regard to the optimum management of patients with a positive post-irradiation prostate biopsy. This analysis characterizes a group of such patients who have had a favorable course without intervention. METHODS AND MATERIALS: Between 1956 and 1991, 116 patients have had a positive prostate biopsy 12 or more months post-irradiation without hormonal intervention or evidence of distant relapse. The population had an age range of 42 to 82 years (median - 61). American Joint Committee on Cancer stages included 1 T1, 70 T2, 44 T3, and 1 T4. Median actuarial survival for the entire population was 14.4 years (range = 2.2-21.5 years) from presentation and 5.2 years from re-biopsy. RESULTS: Fifty-one of the 116 patients developed metastases subsequent to re-biopsy and 65 remain free from distant relapse. Among these 65 patients, 50 remain alive and otherwise well, 11 have died of other causes, and only four have succumbed to their local disease. The best predictor of distant relapse subsequent to re-biopsy was digital rectal exam. Forty-one of the 51 patients later developing metastases had an abnormal digital rectal exam compared to 37 of 65 with sustained distant control (p = .01). CONCLUSION: These data demonstrate that long-term, disease-free (other than re-biopsy) survival is common following a "positive" post-irradiation biopsy without intervention especially among patients with a normal digital rectal exam. Therefore, routine re-biopsy without clinical indications is not a useful practice.

Reduction of spinal metastases after preemptive irradiation in prostatic cancer.

For this study, 136 patients treated at Stanford University Hospital for prostatic cancer between 1971 and 1980 were selected for review. The patients had received no prior therapy, and had no evidence of bone metastases at time of radiation treatment based on radiographic studies and bone scan. Of this group, 71 patients received extended-field irradiation (paraaortic and pelvic fields), and 65 patients received pelvic irradiation. The pelvic field was treated to 50 Gy and the paraaortic field received 45 Gy to 60 Gy. All patients subsequently underwent routine follow-up examinations and studies at Stanford University Hospital: 1,513 follow-up X rays, bone scans, and CT-scans were analyzed for site-specific recurrence. The follow-up ranged from 14 months to 16 yrs from the time of initial treatment, with a mean follow-up of 7 yrs. Lower extremities and ribs were found to be the most common sites of bone metastases. Irradiation of the lumbar spine to a dose of 35 to 60 Gy, coincidental to irradiation of the paraaortic lymph nodes prevented or delayed the development of lumbar spine metastases. The potential mechanism and clinical implications are discussed.

The clinical significance of a positive post-irradiation prostatic biopsy without metastases.

To define the prognostic value of a post-irradiation prostatic biopsy, the outcome of 203 previously irradiated patients who underwent post-treatment biopsy was analyzed. The majority of patients were selected for biopsy based on an abnormal digital rectal exam or elevated prostate specific antigen. Patients with distant metastases found at the time of biopsy were excluded from further analysis. One hundred thirty-nine (139) of these had a positive biopsy and 64 were negative. Those with a positive biopsy tended to present with more locally-advanced (Stage B2/C) tumors (61%) compared to those with negative biopsies (42%). The 10- and 15-year survival and cause-specific survival from the time of initial presentation were similar for both groups. However, those with a negative biopsy had a more favorable survival and cause-specific survival from the time of post-treatment biopsy and were less likely to develop distant metastases than the positive biopsy group. These data suggest that a positive prostatic biopsy is associated with a greater likelihood of subsequent distant relapse and decreased survival following biopsy relative to patients with negative biopsies. Since a positive post-treatment biopsy is more likely among patients presenting with locally-advanced disease, perhaps more aggressive initial therapy (i.e., interstitial boost or hyperthermia) would benefit this subgroup.

Prostate-specific antigen kinetics after external beam irradiation for carcinoma of the prostate.

PURPOSE: A mathematical model that describes the kinetics of prostate-specific antigen measured in patients who received therapeutic doses of radiation therapy is presented. The clinical implications of the model are also investigated. METHODS AND MATERIALS: Data from 122 patients treated at Stanford University between December 1985 and December 1990 were used. The general form of the model contains five parameters, two associated with a decreasing exponential, two with a rising exponential and one additional constant. A nonlinear steepest-descent procedure that minimized chi-squared was used to determine the parameters producing the best fit to a patient's data. The correlation of the model parameters with clinical findings was investigated using standard statistical techniques including multivariate life-table and logistic regression. RESULTS: The data for all patients could be fit with either a decreasing exponential with or without the additional constant (nonrelapsing pattern with two or three parameters) or with a decreasing plus rising exponential (relapsing pattern with three or four parameters). In no instance were all five parameters of the general model required to describe a patient's data. Three of 61 patients with nonrelapsing patterns experienced clinical relapse, whereas 36 of 61 patients with relapsing patterns did. The logarithm of the initial prostate-specific antigen level and the corresponding model parameter correlated with T-stage and Gleason score. Among the patients with relapsing patterns, the nadir in antigen level occurred within 2 years of the start of treatment and the time to nadir, as calculated from the model parameters, was associated with the probability of clinical relapse. In no instance was the rate of initial decline ever exceeded by the rate of subsequent rise. CONCLUSION: The model is capable of describing the kinetics of prostate-specific antigen levels found in patients after receiving radiation therapy. The parameters derived from the model are strong correlates with clinical findings and patient outcome.

Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer.

PURPOSE: To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence. METHODS AND MATERIALS: Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml. RESULTS: At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure. CONCLUSION: This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.

Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma.

Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients--of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

Long-term results of pion therapy at Los Alamos.

Two hundred twenty-eight patients were treated at the Los Alamos Meson Physics Facility (LAMPF) with negative pi-mesons (pions) between 1974 and 1981. Of these, 19 patients with metastatic disease were treated in pilot studies. Following the clinical determination of relative biological effectiveness (RBE) of pions, 209 patients were treated in site and dose searching studies beginning in 1977. Advanced but regionally localized cancers that were considered poorly responsive to conventional therapy were selected for treatment. A wide range of treatment fractions (22 to 45) and of total dose (1800 to 4200 cGy at the 80% isodose level) to the prescribed target volumes was explored. A follow-up observation period of between 4.5 and 9 years has been completed. The analysis focuses on 129 patients receiving pion therapy alone. Thirty-six (28%) had persisting local tumor control of which 12 (9%) suffered complications of treatment. The results varied among treatment sites, for example: prostate cancer, 18/21 (86%) locally controlled, 6/21 (29%) complications; head and neck, 8/31 (26%) locally controlled, 1/31 (3%) complications; and pancreas, none controlled and no complications. Analysis of dose-fraction response suggests a steep rising curve of complications beyond the dose level of 3750 cGy minimum, 4700 cGy maximum, in 38 fractions. The tumor control response has a broader and ill-defined curve possibly due to the heterogeneity of tumor types. The RBE for late effects in normal tissues appeared to be higher than that for acute effects although the mixture of tumor types, sites, dose, and fractionation made this estimate highly uncertain. No late secondary neoplastic changes in pion irradiated tissues were seen. It is concluded that pions can locally ablate some advanced cancers, often without significant sequelae, but that the optimum therapeutic range is critical. The Los Alamos data may be of use to ongoing pion studies in Canada and Switzerland.

External beam radiotherapy for incidental adenocarcinoma of the prostate discovered at transurethral resection.

This paper updates the results of 89 patients treated between 1967 and 1989 for incidental carcinoma discovered at transurethral resection of the prostate (Stanford stage T0 or AJC-UICC stage T1) with external beam irradiation. Twenty-two patients had Stanford T0 focal (less than 5% involvement of the prostatic chips) and 67 presented with Stanford T0 diffuse (5% or more involvement). Follow-up ranges from 4 months to 25.1 years, with a mean follow-up of 9.8 years. The actuarial local control for Stanford T0 focal is 100%, and 70% for Stanford T0 diffuse at 15 years. There was no difference in survival between Stanford T0 diffuse and T0 focal and the expected survival of an age-matched control population. Patients who were treated when younger than 65 had a similar local control and distant relapse when compared to those treated when 65 or older. There was no difference in local control, freedom from relapse, or disease-specific survival when the 38 patients who received irradiation to the prostate only are compared with the 29 who also received pelvic irradiation for Stanford T0 diffuse carcinoma. Patients with a Gleason score of 6 or more, when compared with those with a score of 5 or less, experienced more distant relapses and similar local control, suggesting that patients with a high grade tumor have occult metastases at presentation.

The influence of initial hemoglobin and blood pressure levels on results of radiation therapy for carcinoma of the prostate.

A group of 914 patients with carcinoma of the prostate treated by definitive radiotherapy at Stanford between 1956 and 1985 was studied. Of these, the initial hemoglobin level was recorded in 656 cases and the initial blood pressure in 760 cases. End-points studied in actuarial analyses were survival, disease-specific survival, local control, freedom from distant relapse, and occurrence of late intestinal complications. Although the anemic group (Hb less than 13.5 g/dl) was correlated negatively with survival (p = 0.02), there was no correlation with disease-specific survival or local control. The conclusion was that anemia per se did not affect the outcome of radiation therapy. A pulse pressure greater than or equal to 60 mm Hg was significantly correlated with worse survival (p = 0.01) and local control (p = 0.04), but no correlation was found between systolic and diastolic blood pressure and the end-points measured. Neither anemia nor hypertension were significantly correlated with late intestinal complications.

Aggressive management of second primary tumors in survivors of hereditary retinoblastoma.

Survivors of hereditary retinoblastoma are at increased risk for the development of second primary tumors, most commonly osteosarcoma. Recent molecular genetic data demonstrate that a pleiotrophic effect of the retinoblastoma gene may be responsible for the development of these sarcomas. This report describes the incidence of second nonocular malignancies among 53 infants seen at Stanford University Medical Center who have been followed a median of 11.7 years. Of these, 42 initially had bilateral disease and eleven had unilateral disease. Of 53 infants, 50 received irradiation either as part of the initial therapy or as treatment for recurrent disease. The actuarial survival for the entire group is 67% at 30 year follow-up with a median survival of 79% at 11.7 years. Eight patients developed eleven second primary tumors. All occurred in the group having hereditary retinoblastoma. Eight were within the previously irradiated field and three were at distant sites. The second tumors included seven osteosarcomas, one angiosarcoma, one rhabdomyosarcoma, one malignant fibrous histiocytoma, and one unclassifiable round blue cell tumor. The actuarial incidence of the development of a second primary malignancy was 6% at 10 years, 19% at 20 years, and 38% at 30 years. The latent period from treatment of retinoblastoma to the diagnosis of malignancy ranged from 5.2 years to 36.2 years (median 16 years). An aggressive approach with combined modality therapy including radical resection, re-irradiation and/or chemotherapy was used to treat these second primary tumors in five of eight patients. In four of the five, there was no evidence of disease at 22-72 months following treatment. In the three patients who did not receive aggressive combined treatment, there were no survivors. These data confirm the previously reported risk of developing a second primary tumor among survivors with hereditary retinoblastoma. Careful long-term follow-up for this genetically susceptible group is essential for early detection and implementation of curative therapy.

Stereotaxic radiosurgery for brain metastases: the importance of adjuvant whole brain irradiation.

Stereotaxic radiosurgery delivered from a modified 4 MV linear accelerator was used to treat 47 brain metastases in 27 patients at Stanford. Response was assessed in 41 lesions. Histopathologies included adenocarcinoma (24 lesions), renal cell carcinoma (9 lesions), melanoma (6 lesions), and squamous cell carcinoma (2 lesions). Follow-up ranged from 1.0-16.5 months, with a median of 5.0 months. Radiographic local control was achieved in 88% of the lesions. Three patients developed enlarging contrast-enhancing lesions in the radiosurgical field; one of these was biopsied and revealed necrosis with no viable tumor. Adjuvant whole brain irradiation (10 patients) was associated with regional intracranial control in 80% of patients. This was statistically superior (p = 0.0007) to the regional intracranial control rate achieved when radiosurgery alone was employed (6 patients). Most patients reported resolution of their neurologic symptoms, and were able to discontinue dexamethasone without impairment of neurologic function.

Definitive radiotherapy in resectable (stage A2 and B) carcinoma of the prostate--results of a nationwide overview.

To evaluate the efficacy of definitive radiotherapy in a population of patients with carcinoma of the prostate who satisfy the customary selection criteria for radical prostatectomy, a nation-wide search was conducted. The assessed population consists of patients with clinical Stage A2 and B carcinoma of the prostate, negative staging lymphadenectomy, negative bone scan, and normal serum acid phosphatase. The search included patients from Stanford University, Washington University in St. Louis, those participating in the Radiation Therapy Oncology Group and a broad range of radiotherapy practices surveyed by the PCS (Patterns of Care Study). A total of 209 patients satisfying the selection criteria received definitive radiotherapy during the surveyed period. The end-point of analysis was the time to progression (distant metastases). The results of the analysis indicate a very low (less than 10%) probability of progression within the first 5 years after completion of treatment. Contrary to the recent report from the VA Uro-Oncology Group the study demonstrates a comparable outcome in radiotherapeutically and surgically treated patients.

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

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 (less than or equal to 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 degrees C for 45 minutes while maintaining maximum normal tissue temperatures to less than or equal to 43 degrees C and maximum intratumoral temperatures to less than or equal to 50 degrees 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 greater than 43.5 degrees 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 degrees C compared with 45.9 degrees 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).(ABSTRACT TRUNCATED AT 400 WORDS)

Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy for the treatment of carcinoma of the prostate.

PURPOSE: Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study. METHODS AND MATERIALS: From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures. RESULTS: Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively. CONCLUSION: From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.

Two or six hyperthermia treatments as an adjunct to radiation therapy yield similar tumor responses: results of a randomized trial.

From March 1984 to February 1988, 70 patients with 179 separate treatment fields containing superficially located (less than 3 cm from surface) recurrent or metastatic malignancies were stratified based on tumor size, histology, and prior radiation therapy and enrolled in prospective randomized trials comparing two versus six hyperthermia treatments as an adjunct to standardized courses of radiation therapy. A total of 165 fields completed the combined hyperthermia-radiation therapy protocols and were evaluable for response. No statistically significant differences were observed between the two treatment arms with respect to tumor location; histology; initial tumor volume; patient age and pretreatment performance status; extent of prior radiation therapy, chemotherapy, hormonal therapy, or immunotherapy; or concurrent radiation therapy. The means for all fields of the averaged minimum, maximum, and average measured intratumoral temperatures were 40.2 degrees C, 44.8 degrees C, 42.5 degrees C, respectively, and did not differ significantly between the fields randomized to two or six hyperthermia treatments. The treatment was well tolerated with an acceptable level of complications. At 3 weeks after completion of therapy, complete disappearance of all measurable tumor was noted in 52% of the fields, greater than or equal to 50% tumor reduction was noted in 7% of the fields, less than 50% tumor reduction was noted in 21% of the fields, and continuing regression (monotonic regression to less than 50% of initial volume) was noted in 20% of the fields. No significant differences were noted in tumor responses at 3 weeks for fields randomized to two versus six hyperthermia treatments (p = 0.89). Cox regression analyses were performed to identify pretreatment or treatment parameters that correlated with duration of local control. Tumor histology, concurrent radiation doses, and tumor volume all correlated with duration of local control. The mean of the minimum intratumoral temperatures (less than 41 degrees C vs. greater than or equal to 41 degrees C) was of borderline prognostic significance in the univariate analysis, and added to the power of the best three covariate model. Neither the actual number of hyperthermia treatments administered nor the hyperthermia protocol group (two versus six treatments) correlated with duration of local control. The development of thermotolerance is postulated to be, at least in part, responsible for limiting the effectiveness of multiple closely spaced hyperthermia treatments.