W. John Simpson

The Effects of Surgery, Radioiodine, and External Radiation Therapy on the Clinical Outcome of Patients with Differentiated Thyroid Carcinoma

The aim of this study was to determine the prognostic factors for local failure and cause specific survival in differentiated thyroid carcinoma and the impact of surgery, radioiodine, and external beam radiation therapy (RT) when used as part of the initial management.

Radiation therapy in the management of primary malignant lymphoma of the brain

Abstract This study reviewed 21 patients with primary malignant lymphoma of the brain. A rapid onset of symptoms was observed in most patients with a median interval of 10 weeks between first symptom and diagnosis. All received cranial irradiation following either gross total removal of tumor (9 patients), biopsy alone (1l patients) or no surgery (1 patient). Two patients received short courses of chemotherapy. Early clinical improvement was commonly observed following commencement of radiation but this was not sustained. Overall survival from diagnosis was 47 % at one year and 16 % at two years. Analysis of treatment parameters failed to indicate any well-defined factors which may have resulted in an improved survival. There was a suggestion that males fared better than females sad that irradiation of the entire brain to a minimum dose of 5000 rad was associated with longer survival.

RADIATION THERAPY OF CEREBRAL METASTASES: A RANDOMIZED PROSPECTIVE CLINICAL TRIAL?

Abstract A randomized prospective clinical trial compared doses of 3000 rad in 2 weeks whole brain irradiation with a single dose of 1000 rad. In the 101 patients analyzed, no statistical difference between the two fractionation schemes was demonstrated in terms of survival, frequency or degree of respone to treatment, complication rate or local control rate. The results are compared to similar retrospective and prospective series, leading to the conclusion that a single dose of 1000 rad provided as good palliation as fractionated schedules. The advantages of the short treatment are discussed. The factors which influenced survival included the site of the primary tumor and the functional level at the time of cranial radiation. Factors which did not affect the prognosis included papilledema and complications of the treatment. The predominant cause of death in these patients was recurrence of the cerebral metastases.

Malignant astrocytoma: hyperfractionated and standard radiotherapy with chemotherapy in a randomized prospective clinical trial.

A prospective randomized trial of 157 patients with malignant astrocytoma (Grade III or IV) was carried out at a single institution. The minimization technique ensured balanced distribution of prognostic factors between the treatment groups. All received oral lomustine (CCNU, 80 mg/m2) six weekly and hydroxyurea (HU, 3.5 gm/m2 over 5 days) three weekly, for one year or until recurrence, with doses adjusted for myelosuppression. Patients were randomized to daily (5000 rad in 25 fractions (fr) in 5 weeks) or Q3h (every 3 hours) Cobalt 60 irradiation (3600–4000 rad in 36–40 fr of 100 rad each, given 4 fr per day at 3‐hour intervals over two weeks) Steroid therapy (up to 16 mg day dexamethasone) was permitted. Complications were moderate and equivalent in the two groups. No significant survival or toxicity differences were seen between the two groups. Age, initial performance status, and extent of surgical resection were found to be significant (P < 0.01) prognostic factors for survival. Median survival of the whole group was 48 weeks with a minimum follow‐up of one year. There was no advantage to large radiation fields. The hyperfractionation and daily regimes had similar efficacy and toxicity. Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease.

Spinal cord ependymomas: a retrospective analysis of 59 cases

PURPOSE To determine the outcome of patients with primary spinal ependymoma treated with postoperative radiotherapy and to identify clinical and treatment variables predictive of outcome. METHODS AND MATERIALS A retrospective chart review was undertaken of 59 spinal ependymoma patients referred to the Princess Margaret Hospital between 1958 and 1987. All patients were treated with radiation therapy to either the site of the primary tumor or the craniospinal axis. There were 23 female and 36 male patients with a median age of 37 years (range: 8-66 years). Median follow-up was 130 months (range: 1-371 months). Clinical variables including age, sex, length of symptoms, functional status, tumor location, and grade as well as treatment variables including extent of surgery, radiation dose and treatment volume were analyzed for influence on outcome. RESULTS Treatment was well-tolerated with no cases of radiation myelopathy identified. Overall actuarial survival at 5 and 10 years was 83% and 75%, respectively. Eleven patients had recurrent tumor with the 9/11 having a component of their recurrence within the treatment field. Median time to recurrence was 2 years with 9 of the 11 recurrences within the first 3 years. Tumor grade was the only independent variable identified as predictive of outcome. Patients with well differentiated tumors had a 5-year cause-specific survival of 97% compared to 71% for those with intermediate or poorly differentiated tumors (p = 0.005). CONCLUSION We conclude that postoperative irradiation for patients with spinal ependymomas is associated with a favorable outcome and that tumor grade is a major prognostic factor. Based on results of this series and a review of the literature, specific management recommendations are made for this rare tumor.

Malignant lymphoma of the thyroid gland

Abstract We reviewed the records of 20 patients with malignant lymphoma presenting in the thyroid gland who were seen at The Princess Margaret Hospital between 1958 and 1977. The disease predominantly affected females of an older age group and clinically was characterized by a rapidly enlarging neck mass associated with obstructive symptoms. Seventeen of the patients (85 %) had histiocytic lymphoma. Eighteen patients (90 %) either were clinically Stage IE or Stage HE disease (Ann Arbor classification). All patients were treated with radiotherapy. Adjuvant chemotherapy was used in only three patients. Overall survival rate at 5 years was 35%. All recurrences but one occurred within 6 months. Survival rate at 5 years from time of recurrence was 7%. Postmortem examination of eight patients showed widespread lymphoma in all; the lung, G.I. tract, liver and kidney were the most frequently affected distant sites. The long term survival group (A) was composed of three patients with Stage I and four with Stage II disease. The failure group (B) included live patients with Stage I, six with Stage II and two with Stage IV disease. Group A patients had “localized” disease and all but two patients received radiation treatment to the neck and mediastinum. Group B patients with Stage I disease received radiation to the neck only and none survived 5 years. All six Stage II patients in group B (five patients with “extensive” disease and one with “localized” disease) received radiation to the neck only; none survived 5 years. We conclude that radiotherapy to the neck and mediastinum is an adequate form of treatment in patients with lymphoma of the thyroid gland with Stage I or localized Stage II disease. More advanced disease should be managed with radiation and chemotherapy.

Squamous cell carcinoma of the thyroid gland.

We present the clinical manifestations and details of treatment and outcome for eight patients with squamous cell cancer arising in the thyroid gland, which is a rare entity. All patients had advanced disease, with primary tumors invading adjacent structures (the trachea, esophagus, and major vessels). In two patients, pulmonary metastases were also present. Six patients died 6 months or less after diagnosis, five from the effects of local disease. Transient palliation was obtained in four patients who underwent partial excision (three patients) and radical radiotherapy (one patient). Two patients remained free of disease at last follow-up more than 4 years after gross total tumor resection and radical radiotherapy and were presumably cured. One patient treated by partial resection and radical radiotherapy died from other causes 17 months later. His disease status was unknown. Complete excision with postoperative radiotherapy may be curative, and debulking followed by external irradiation may provide short-term palliation. Patients with unresectable tumors are best managed by supportive measures only unless a truly effective chemotherapeutic regimen is developed for squamous cell cancer of the head and neck.

Oligodendroglioma. The princess margaret hospital experience (1958–1984)

Background. Oligodendrogliomas are rare central nervous system (CNS) tumors. Although surgery remains the primary treatment, the role of postoperative radiation treatment remains a matter of controversy. This study assesses whether postoperative radiation improves survival and local tumor control when compared with surgical treatment alone.

The role of external radiation in the management of papillary and follicular thyroid cancer.

Review of 137 patients with differentiated thryroid carcinoma (82 papillary and 55 follicular) demonstrates that external radiation in moderate dosage eradicates microscopic disease. Its use could lead to a decrease in surgical complications by avoiding unnecessarily radical attempts at removing all potential microscopic disease. Gross tumor also responds favorably to external radiation, but its very slow regression rate has led to the misconception that external radiation is ineffective in the treatment of these cancers. Both radioiodine and thyroid hormone play an important role in the management of differentiated thyroid cancers, but their effectiveness should not be overestimated.

Review of 154 patients with non-functioning pituitary tumors

Abstract A retrospective review was carried out on the charts of 154 patients with pituitary tumors that were not associated with Cushings Disease or acromegaly. Patients were divided into three treatment groups: (1) surgery + post-operative radiation (S+R); (2) radiotherapy (R); and (3) surgery followed by radiation at the time of recurrence (S). Pretreatment evaluation revealed that patients in (S+R) had significantly larger tumors than patients in (R). However, there was no difference in the endocrinological status of patients prior to therapy in all treatment groups. The results of treatment were similar in the (S+R) and (R) treatment groups. This suggests that patients with small pituitary tumors may be treated successfully with radiation alone. Analysis of the recurrences revealed several reasons for failure of initial therapy, chiefly very large or locally aggressive tumors. Patients had recurrences up to 15 years after initial therapy. Therefore, follow-up of these patients should continue over a long period of time. Complications of each form of therapy were evaluated. Only one case of vascular occlusion was felt to be radiation-related. Long term steroid replacement therapy also was associated with complications. These included avascular necrosis of the femoral heads, gram negative sepsis and Addisonian crisis. The role of surgery as a single modality could not be assessed.