William N. Brand

The role of adjuvant irradiation following primary prostatectomy, based on histopathologic extent of tumor

One hundred twenty-three patients who underwent primary prostatectomy at Northwestern Memorial Hospital during the-years 1976 to 1985 are reviewed. The patients were divided into three groups: Group 1 (50 patients) comprises patients with tumor well-contained within the prostate and without perineural, perivascular, or lymphatic (NVL) invasion; Group 2 (57 patients) comprises patients with more extensive tumor extending through or to the prostatic capsule, extending to or near the surgical margin, involving seminal vesicles, or having NVL invasion; Group 3 (16 patients) comprises those patients who received immediate postoperative irradiation. The actuarial 10-year local control rates of Group 1 (88%) and Group 3 (100%) were statistically superior to that of Group 2 (72%), p less than 0.05. The actuarial 10-year disease-free survival rate of Group 1 (72%) is statistically superior to that of Group 2 (56%), p less than 0.01; the difference in 10-year disease-free survival between Group 2 (56%) and Group 3 (64%) did not reach statistical significance. Ten-year actuarial survival statistics are 64%, 80%, and 76% for Groups 1, 2, and 3 respectively. There was no statistically significant difference in actuarial survival among any of the groups. Patients with tumor extending to or through the prostatic capsule, extending to or near the surgical margins, involving the seminal vesicles, or having NVL invasion all may benefit from adjuvant irradiation in the immediate perioperative period.

Evaluation of an ingestible telemetric temperature sensor for deep hyperthermia applications

We have investigated the potential of an ingestible thermometric system (ITS) for use with a deep heating system. The ingestible sensor contains a temperature-sensitive quartz crystal oscillator. The telemetered signal is inductively coupled by a radiofrequency coil system to an external receiver. The sensors, covered with a protective silicon coating, are 10 mm in diameter and 20 mm long and are energized by an internal silver-oxide battery. Experimental studies were carried out to investigate the accuracy of the system and the extent of reliable operation of these sensors in an electromagnetic environment. Different measurements were repeated for five sensors. Calibration accuracy was verified by comparison with a Bowman probe in the temperature range 30 degrees C to 55 degrees C. Linear regression analysis of individual pill readings indicated a correlation within +/- 0.4 degrees C at 95% prediction intervals in the clinical temperature range of 35 degrees C to 50 degrees C. Further work is required to improve this accuracy to meet the quality assurance guidelines of +/- 0.2 degrees C suggested by the Hyperthermia Physics Center. Response times were determined by the exponential fit of heat-up and cool-down curves for each pill. All curves had correlation coefficients greater than 0.98. Time (mean +/- SE) to achieve 90% response during heat-up was 115 +/- sec. Time to cool-down to 10% of initial temperature was 114 +/- 4 sec. The effect of the external antenna and sensor spacing and the angle of orientation of the sensor relative to the antenna plane were also studied. Electromagnetic interference effects were studied by placing the sensor with a Bowman probe in a cylindrical saline phantom for the tests in an annular phase array applicator. Different power levels at three frequencies--80, 100, and 120 MHz--were used. Accurate temperature readings could not be obtained when the electromagnetic power was on because of interference effects with the receiver. However, the temperatures read with the ITS immediately after the electromagnetic power was switched off correlated well with the Bowman probe readings across the power categories and the three frequencies used. The phantom was heated to steady state, with a Bowman probe placed at the central axis of the cylinder used as control. During the heat-up period and the steady state, the mean difference (+/- SE) between the ITS and Bowman probe was 0.12 degrees C (+/- 0.05 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)

Role of radiation therapy in the management of carcinoma in situ of the larynx

Twenty-one patients with carcinoma in situ of the larynx were treated with definitive irradiation from 1959 to 1987. The in situ changes were limited to 1 vocal cord in 19 patients, and to both vocal cords in 1 patient. One patient demonstrated extensive in situ changes involving the vocal cords bilaterally, as well as the anterior commissure, with both supraglottic and infraglottic extension. The mean follow-up from completion of treatment was 6.2 years, with a median of 50 months. Definitive irradiation resulted in a local control rate of 95%. The patient with extraglottic spread of in situ changes experienced a local failure 7 months after completion of treatment and, despite surgical salvage, died of local recurrence. This patient represents the only recurrence in our series. Our data suggest that radiation therapy can provide excellent control in carcinoma in situ limited to the true vocal cord.

Optic Glioma in Children

From 1967 to 1975, 16 consecutive children with optic-tract glioma were treated with postoperative irradiation. Clinical, surgical and pathologic findings have been summarized. Doses ranged from 4,000

Hyperfractionated Craniospinal Radiation in Medulloblastoma

From 1986 to 1991, 13 patients at Northwestern Memorial Hospital were entered onto a pilot study designed to test the feasibility of treating children with medulloblastoma (11 patients) or primitive neuroectodermal tumors of the cerebral hemispheres (2 patients) with hyperfractionated craniospinal radiotherapy (HFxRT). Follow-up times ranged from 10 to 96 months with a median of 53 months. The patients were prospectively divided among three treatment arms depending on prior treatment history, if any, and degree of surgical resection. The 3 patients in group I had undergone gross total resection of the primary site, receiving 64.8 Gy to the primary site and 31.2 Gy directed to the craniospinal axis (CSA). Of these 3 patients, patient 1 had residual disease in the thoracic spine at T-10. The 8 patients in group II, who had gross residual disease remaining at the primary site, received 72 Gy to the primary site and 34 Gy to the CSA. Five of these eight patients in group II also received 8-in-1 chemotherapy. The 2 patients in group III had already failed chemotherapy and were then treated with 60 Gy to the primary site and 26 Gy to the CSA. Of the 11 patients in groups I and II, 7 of the 11 (64%) have never recurred. Two of the three group-I patients have not recurred, and 5 of the 7 group-II patients have not recurred. In addition, patient 7 (group II) remains alive after salvage with bone marrow transplant, following a local failure bordering the tentorium. Unfortunately, neither of the group-III patients could be salvaged with HFxRT. Acute/subacute toxicities included 7 cases of external auditory canal or skin desquamation, 2 cases of postradiation somnolence, and 1 case each of poor wound healing and neutropenia. Chronic toxicities included hypothyroidism in 2 patients and growth problems in 2 patients. Neuropsychologic complications affected only the 3 youngest patients in the study. Three patients developed neurologic sequelae attributed to radiation, including 1 with progressive urinary incontinence, 1 who developed a transient ischemic attack, and 1 who became progressively ataxic. Our research, although based on a small number of patients, suggests that hyperfractionated radiation therapy to craniospinal access is feasible and that the survival results are favorable. This treatment strategy should be further explored in a phase-III randomized trial.

The Effect of Testicular Irradiation on Established BPH in the Dog: Evidence of a Non-Steroidal Testicular Factor for BPH Maintenance

Irradiation of the testes of four to 13-year-old male beagles with benign prostatic hyperplasia (BPH) was undertaken to attempt to evaluate the possibility that the testes secrete a non-androgenic accessory sex gland-stimulating substance that may have a critical role in the development of BPH. Available evidence indicates that development of prostatic hyperplasia in dog and man is dependent on testicular secretions and that testes irradiation is unlikely to alter testosterone secretion appreciably but does produce profound effects on the seminiferous tubules. Thirteen non-irradiated and shoulder irradiated control and 16 beagles subjected to 1500 to 2200 rads single dose testis irradiation had pre-irradiation, interval post-irradiation and terminal caliper measurements of prostatic length, width and depth, prostatic and testicular biopsies, and determination of serum testosterone and estradiol levels. Four beagles survived in a group observed for 109 weeks post testis irradiation, 12 in a group observed for 51 and 10 in a group observed for 59 weeks. The wet weight of the prostate was determined at sacrifice. Ratios of the final/initial length and width and final actual/initial calculated weight of the prostate were significantly decreased in testis-irradiated as compared to control beagles. Histologic evaluation also demonstrated a significant difference in degree of prostatic stimulation in control and testis-irradiated groups. The serum testosterone and estradiol levels were not significantly different in the testis-irradiated and control beagles. These observations indicate that irradiation of the testes of beagles with BPH alters the size, weight and histology to suggest decreased stimulation of the prostate without producing an identifiable change in the serum levels of the steroid hormones studied. The data support the hypothesis that the testis of the aging beagle secretes a non-androgenic and probably non-steroidal prostatic stimulating substance which is affected by irradiation of the testis.

Results of small-field irradiation of apparent solitary metastasis from Wilms's tumor.

Small-field irradiation combined with dactinomycin therapy in the treatment of solitary lung metastasis from Wilmss tumor was analyzed. Of the 13 children treated for roentgenologic solitary lung metastasis, 5 survived, the remaining 8 having occult multiple metastases. This is in agreement with the 35% incidence of true solitary lung metastasis recorded in the literature. Since, at the present time, there is no way to recognize the true solitary metastasis, whole-lung irradiation is recommended in all cases. Current techniques employ whole-lung irradiation to a dose of 1,400 rads delivered at the rate of 1,000 rads per week.

Effect of Lymphangiography on Metastasis

Complications related to lymphangiography have been minor and easily treated in most instances. The possibility exists, however, that the passage of contrast material through cancerous lymph nodes may facilitate metastasis. This possibility became apparent to us after we viewed histologic preparations of lymph nodes removed from patients subjected to lymphangiography. The histopathology of these nodes revealed marked inflammatory changes, acute and chronic; replacement of portions of lymph node parenchyma by oil droplets; and decreased number of germinal centers (Figs. 1 and 2). Similar findings have been reported by Ravel (4), who studied a large series of nodes removed at varying intervals following lymphangiography. Our study was undertaken to determine whether lymphangiography affected tumor metastasis by any one or a combination of the following factors: (a) facilitation of metastasis from the marked alteration in lymph node architecture, (b) increase in blood-borne metastasis through lymphovenous sh...

Management of early-stage Hodgkin's lymphoma. The radiation oncology experience at Northwestern University/Northwestern Memorial Hospital.

Early-stage Hodgkins lymphoma patients treated with radiotherapy alone or combined modality therapy were retrospectively analyzed for survival, patterns of failure, salvage, and toxicity. Of 75 evaluable patients, 47 were given radiotherapy alone and 28 were given combination radiotherapy and chemotherapy. Of the patients studied, 26 were clinical stage I and 49 were clinical stage II, with nine patients upstaged at laparotomy. Minimum follow-up was 2 years, with a median of 81 months. Complete response rate was 95%. Relapse-free survival and overall survival were 89% and 96%, respectively, at 2 years; 78% and 86% at 5 years; and 76% and 82% at 10 years. Of 16 patients who relapsed (21%), 13/47 patients were treated with radiotherapy and 3/28 were treated with combined modality therapy. Salvage rates were higher in those treated with radiotherapy alone. There were 13 deaths: six from disease, two from treatment-related complications, and five from second primary malignancies. There was a higher incidence of second malignancies and deaths due to complication in patients treated with combined modality therapy. Radiotherapy alone or with chemotherapy is an effective modality in the treatment of Hodgkins lymphoma. Treatment should be selected properly to optimize results and decrease complications.

A new radioisotope technique of splenic localization for radiation treatment

A new technique of splenic localization, before initiating radiation therapy in patients with Hodgkins disease, is described. We find this method of splenic localization economical and accurate.