Gestational trophoblastic disease metastatic to the brain.

PURPOSE: To evaluate clinical characteristics, treatment technique, and results in patients with gestational trophoblastic disease metastatic to the brain. MATERIALS AND METHODS: From 1962 to 1994, 26 (4.1%) of 631 patients who underwent treatment for trophoblastic disease had or developed evidence of brain metastases (patients were aged 14-43 years). All patients received multiagent systemic chemotherapy and whole-brain irradiation. Total doses of radiation were 2,386-4,000 cGy (200-300 cGy per fraction). No patient received intrathecal chemotherapy. Patients were divided into three groups: group A, symptomatic brain metastases at presentation; group B, asymptomatic or minimally symptomatic brain disease at presentation; and group C, development of brain metastases during systemic chemotherapy. RESULTS: The overall 5-year actuarial survival rate was 51%. Multivariate analysis findings indicated that age, preceding pregnancy event, human chorionic gonadotropin level, World Health Organization score, performance of craniotomy, and number of brain metastases did not influence survival. The difference in the 5-year overall survival rates between groups A (39%) and B (100%) was significant (P = .03). CONCLUSION: Gestational trophoblastic disease metastatic to the brain is curable with systemic chemotherapy and whole-brain irradiation. The authors suggest treatment with steroids, chemotherapy (etoposide, high-dose methotrexate [1 g/m2], dactinomycin, cyclophosphamide, and vincristine sulfate), and concurrent whole-brain irradiation (3,000 cGy in 200-cGy fractions).

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

Early-stage Hodgkin's 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 Hodgkin's lymphoma. Treatment should be selected properly to optimize results and decrease complications.

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.

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.

Results of radiation therapy in early glottic carcinoma: multivariate analysis of prognostic and radiation therapy variables.

A detailed retrospective analysis was performed with 103 patients who had T1 carcinoma of the glottic larynx and underwent radiation therapy between 1960 and 1987. Prognostic and radiation therapy variables were analyzed including sex; age; staging procedures; mucosal extent; histologic grading of tumor; field size; use of wedges; treatment of alternate fields versus both fields every day; nominal standard dose; time, dose, and fraction; dose per fraction; total radiation dose per fraction; total radiation doses; and the impact of cord stripping. Initial local control was 89%, and ultimate control after surgical salvage was 97%, with a 5- and 10-year adjusted survival of 98%. Univariate analysis indicated that larger field size (P = .04), histologic grade (P = .02), and treatment strategy (P = .08) were of some value in predicting recurrence. Multivariate analysis indicated that field size (P = .03) was the only significant variable in predicting local recurrence. These data confirm that radiation is highly effective in the treatment of early laryngeal cancer.

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)

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.

A new radioisotope technique of splenic localization for radiation treatment.

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

Benign ependymomas of the posterior fossa in childhood.

A series of 22 infants and children with posterior fossa benign ependymomas treated surgically during the past 12 years is presented. All patients were operated on with posterior fossa craniotomy: visible total resection in 10, subtotal resection in 9, partial resection in 2 and biopsy only in 1. One patient (4.5%) died shortly after surgery. Only 5 patients had documented infiltration of the floor of the fourth ventricle. Postoperative radiotherapy was administered with variable radiation fields and doses. Two out of six patients who had total resection and postoperative radiation therapy did not show recurrence during at least 26 months follow-up period. However, patients with incomplete tumor resection almost invariably developed recurrence. An attempt should be made to remove posterior fossa ependymomas totally at the initial craniotomy. The risk periods for recurrence were between 1 and 2 years after subtotal resection and between 2 and 3 years after total resection. In our experience, gross recurrent tumors appear to be resistant to chemotherapy, and a combination of surgery and radiation therapy does not necessarily prevent recurrence. Newer agents or protocols of adjuvant chemotherapy are needed to explore.

Long-term results of a pilot study of low dose cranial-spinal irradiation for cerebellar medulloblastoma.

Between May 1974 and March 1983, 44 children with histologically verified cerebellar medulloblastoma were seen for post-operative cranial-spinal irradiation following attempted total tumor removal. Six patients were excluded from review because they received all or part of their treatment at another institution (3 patients) or did not complete the planned course of irradiation (3 patients). All of the 38 remaining patients were treated by a previously described technique on a 4 MeV Linear Accelerator with 55 Gy delivered to the primary tumor site. Prior to December 1978, 19 consecutive children (Group A) had spinal prophylactic doses of 30-40 Gy and brain prophylactic doses of 40-50 Gy. After the date, 25 Gy was given to the cranial-spinal axis of 19 consecutive children (Group B). This lower dose was arbitrarily selected with the hope of reducing morbidity in treated survivors and achieving the same tumor control. Risk factors that define good and poor prognosis were evaluated for each group, and there were no differences noted. Myelography and CSF cytology were not routinely performed. Follow-up for the 38 patients ranges from 20 months to 124 months. For the low risk patients, survival (12/15 or 80%) was independent of cranial-spinal radiation dose (Group A 6/8, Group B 6/7). For the high risk patients survival was poor (9/23 or 39%), not dependent on cranial-spinal radiation dose (Group A 5/11, Group B 4/12), and associated with failure at the primary site (10/14), often with CSF seeding (8/10). The other 4 failures include 2 who had moved outside the United States (details of failure are unknown), 1 with supratentorial, CSF seeding and distant metastases, and 1 with distant metastasis only. There were no isolated spinal failures. This pilot study shows that the prophylactic radiation dose to the cranial-spinal axis can be decreased to 25 Gy without jeopardizing control rate and survival in patients with medulloblastoma.

Analysis of complete responders after initial treatment with chemotherapy in head and neck cancer.

We treated 60 patients with cisplatin-based combination chemotherapy before definitive surgery and/or radiation. All had squamous cell tumors of the head and neck, stages II to IV, M0. Twelve patients (20%) achieved a complete remission after chemotherapy. Eight of these patients showed no histologic evidence of residual disease after biopsy or surgery. Definitive local therapy with surgery and/or radiation was carried out on almost all patients regardless of the extent of the response to preceding chemotherapy. Chemotherapy-induced complete responders have had an improved survival rate in comparison with patients achieving a partial response or less. The extent of primary tumor correlates inversely with a complete response to chemotherapy.

Sequential bilateral germ cell testicular tumors of different cell types.

A case of bilateral successive testicular cancer of different cell types (seminoma and embryonal carcinoma) is presented. The time interval between the two tumors was 30 months. Previous reports in English of bilateral testicular tumors are briefly reviewed.

Optic glioma in children. Review of 16 cases given megavoltage radiation therapy.

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 to 6,000 rad. As of 1976, follow-up had been obtained in 13 of 16 children. 9 of 13 survived and 3 were lost to follow-up. We have been unable to relate survival to age, sex, pathologic grade, radiation dose of field size. Although all patients in our series were irradiated, it appears that survival is excellent for those with gliomas that are confined to the optic nerve or chiasm without hydrocephalus even if postoperative irradiation is not given. In patients with extension beyond the chiasm or with hydrocephalus, survival may be improved by the addition of irradiation. A staging system is proposed.