Immunohistochemistry as a predictor of clinical outcome in patients given postoperative radiation for subtotally resected pituitary adenomas.

There is general agreement that postoperative radiation therapy is beneficial for patients with subtotally resected pituitary adenomas. We have identified 41 such patients treated during a 20-year period who received postoperative irradiation for a pituitary adenoma. The usual dose was 5040 cGy in 28 fractions. The mean follow-up time was 10.3 years. On routine hematoxylin and eosin (H&E) staining, there were thirty-three chromophobe, seven eosinophilic, and one basophilic adenoma. Tissue blocks were stained for growth hormone (GH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin (PRL), and/or adrenocorticotropin (ACTH) using the peroxidase-antiperoxidase immunohistochemistry (IHC) method. Routine H&E staining was a poor predictor of the IHC stain. While most patients with a known clinical endocrine syndrome stained positive on IHC for the suspected offending hormone, many patients without a clinical syndrome also stained positive indicating the presence of hormonally occult adenomas in this locally invasive group. The IHC stain results were compared to clinical outcome. The presence of positive GH IHC staining decreased the 15-year progression-free survival (PFS) from 100% to 64% compared to GH negative adenomas (p = 0.06). There was a trend toward decreased 15-year PFS in patients who did not stain for LH. Positive staining for prolactin, ACTH, or TSH had no influence on the progression-free survival. We conclude that additional prognostic information can be obtained in this subset of patients (by performing IHC analysis) that is not known by the clinical presentation or appearance on H&E stain.

Carcinoma of the hard palate.

Thirteen patients with primary carcinoma of the hard palate were seen over an 18-year period at the Mallinckrodt Institute of Radiology. Nine patients had adenoid cystic carcinoma, three had squamous cell carcinoma, and one patient had mucoepidermoid carcinoma. The median tumor size was 3 cm3. The patients were clinically staged: T = 1, T2 = 5, T3 = 3, T4 = 4. All were N0M0. Ten patients underwent excision and postoperative irradiation. The remaining three patients were treated definitively with radiotherapy. The 10-year disease-free survival is 77% with an actuarial local control rate of 92%. Patients with negative surgical margins had an improved local control and disease-free survival. Duration of radiation therapy, total tumor dose or histology had no impact on outcome. We conclude that combined surgery and irradiation gives good 10-year local control and disease-free survival rates in patients with this disease.

Intracranial ependymoma long term outcome, patterns of failure.

We analyzed 31 patients with intracranial ependymoma, all verified by secondary neuropathology review. There were 12 patients with ependymomas and 19 patients with anaplastic ependymoma by the WHO classification. Eight patients received craniospinal irradiation, 22 patients received cranial irradiation alone, and one patient was treated with chemotherapy alone. The median follow-up time was 11 years. The 5- and 10-year progression-free survivals (PFS) were 60% and 48%. Those with anaplastic tumors had a decreased 10 year PFS over those with low grade lesions: 26% vs. 55% (p = 0.02). Delivering spinal irradiation in addition to cranial irradiation did not improve outcome. There were relapses in 16 patients. All patients relapsed at the primary intracranial sites with no spinal failures. Patients treated with whole brain irradiation had decreased 10 year PFS over those treated with local fields: 19% vs. 64% (p = 0.006). Those patients treated to > or = 50 Gy had an improved long-term PFS (p = 0.04). Multivariate analysis was undertaken with the following variables: extent of cranial irradiation, pathology, anatomic site of ependymoma, cranial irradiation dose, extent of surgery, and whether spinal irradiation was given. With PFS as the endpoint, only extent of cranial irradiation (favoring local fields) and pathology (favoring low grade ependymoma) were significant prognosticators. We conclude that carefully outlined local field irradiation is the therapy of choice, and elective spinal irradiation is of questionable benefit.

The effect of volume of disease in patients with carcinoma of the uterine cervix.

This is a retrospective study of 635 consecutively treated patients with FIGO Stage IIB or IIIB carcinoma of the uterine cervix. All patients were treated definitively with radiation therapy. The effect of volume of disease on outcome was studied. The 5-, 10-, and 15-year disease-free survivals (DFS) for the 346 Stage IIB patients were 64%, 61%, and 58%, respectively. Corresponding DFS for the 289 Stage IIIB patients were 40%, 38%, and 34%, respectively. The presence of bilateral parametrial invasion did not alter the 10-year DFS in Stage IIB patients (61% vs 64%, p = 0.60) but did decrease it in Stage IIIB patients (34% vs 50%, p = 0.006). Patients with both Stage IIB and IIIB cancers and central bulky disease (greater than or equal to 5 cm in diameter) had decreased DFS when compared to those without central bulky disease. Stage IIB patients with the lateral half of the parametrium involved had a decreased 10-year DFS in comparison with medial half involvement (52% vs 68%, p = 0.004). The total pelvic failure rate was 23% for Stage IIB and 41% for Stage IIIB patients. Central bulkiness increased the pelvic failure rate by about 11% for all patients. Bilateral parametrial disease increased the pelvic failure rate in Stage IIIB patients but not in patients with Stage IIB disease. The total pelvic failure rate for Stage IIB patients was greater in those whose disease extended into the lateral parametrium. Multivariate analysis was done using stage, lateral pelvic wall dose, parametrial disease, central bulkiness, age, and total dose to point A as variables. With local control as the endpoint, only stage (IIB vs IIIB) was significant (p = 0.008). Using DFS as the endpoint, stage (p = 0.0001) and central bulkiness of tumor (p = 0.026) were significant. Complications were not increased in patients with bulky or bilateral disease. We conclude that there is justification for subdividing FIGO Stage IIIB patients into those with unilateral or bilateral disease; however, these data do not support such a division for FIGO Stage IIB patients. These latter patients would be better analyzed with reference to medial versus lateral parametrial extension because of the difference in pelvic control and survival.

Cervical stump carcinoma.

Although supracervical hysterectomy is becoming a vanishingly rare procedure, there are still many women with a retained cervical stump. We have reviewed 70 patients treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology for carcinoma of the cervical stump. The average time between the hysterectomy and the diagnosis of cancer in the stump was 26.6 years. The median age at diagnosis of 63.5 years is 8.5 years older than the median age at diagnosis of patients with cancer of the cervix with an intact uterus. Patients were treated with external beam radiation and/or intracavitary implants. Sixteen patients underwent surgery as well. The 5- and 10-year overall actuarial survival for all patients was 60% and 40%, respectively. The 5- and 10-year progression-free survival for all patients was 77% and 70%, respectively. Ten-year progression-free survival by stage was: 0--100%, 1A--100%, 1B--79%, 2A--100%, 2B--66%, and 3B--39%. Poor histologic differentiation correlated with a decreased long-term progression-free survival. Black patients, and those receiving prolonged courses of external beam irradiation, had a trend toward a worse prognosis. Neither non-squamous histology nor gross appearance affected outcome. With a median follow-up time of 12.9 years, there were only three isolated local failures and four combined with distant metastases. Complications were few, with twice as many occurring in the gastrointestinal system as in the genitourinary tract. We conclude that carcinoma of the cervical stump effectively treated by radiation therapy yields results equivalent to those seen in patients with an intact uterus.

Hepatocellular carcinoma as second malignant neoplasms in successfully treated Wilms' tumor patients. A National Wilms' Tumor Study report.

Although rare, second malignant neoplasms (SMN) after treatment for Wilms' tumor are deadly. A recent National Wilms' Tumor Study (NWTS) report identified 15 patients with second malignancies discovered over 14,381 person-years of observation. This report described four patients with secondary hepatocellular carcinoma in greater detail. These patients were strikingly similar in that all had right-sided tumors and each one had received right upper-quadrant irradiation. All patients died shortly after diagnosis of the SMN.

The relationship of clinical factors and radiation exposure rates from iodine-131 treated thyroid carcinoma patients.

Iodine-131 (I-131) was administered orally 58 times over a 31-month period to patients with thyroid carcinoma. Federal regulations (10 CFR 35) require that a patient remain hospitalized until total body activity is less than 30 mCi. This mandated a hospitalization of more than 48 hours in 10 of 58 patients (17%), and greater than 72 hours in 1 of 58 patients (2%). During each administration of I-131 exposure rates were periodically measured throughout the hospitalization at the surface of the neck, 1 meter from the neck surface, the surface of the abdomen, 1 meter from the anterior abdominal surface, and 1 meter from the lateral abdominal surface. Semi-log regression curves were generated for exposure rate versus time for various parameters, including tumor histology, extent of surgery, gender, age, TSH, site of measurement, and administered activity. The endpoint evaluated was the regressed time to reduce the exposure rate to 10% of the initial value. None of the clinical characteristics tested revealed any differences in decay times. The measurements taken 1 meter anterior to the stomach and neck surface were found to correlate best with decay time. We conclude that exposure rate assessments for the purpose of hospital discharge should be made at 1 meter anterior to the stomach or neck, and that individual patient measurements are necessary because none of the clinical parameters were predictive of I-131 elimination.

Recurrent pituitary adenomas after surgical resection: the role of radiation therapy.

Postoperative radiation therapy for pituitary adenomas is usually reserved for extensive lesions or those that are incompletely resected. Nineteen patients who received external beam radiation as a salvage procedure after recurrence following surgery alone for pituitary adenomas were studied. At recurrence, nine patients underwent reexcision. All 19 patients underwent external beam irradiation for salvage. Within a median follow-up time of 11.8 years from the time of surgical failure, two patients have died of progressive adenoma, two are alive with disease progression, eight are alive without disease progression, and seven have died of intercurrent disease. The 5-, 10-, 15-, and 20-year overall actuarial (and progression-free) survival rates were 79% (90%), 62% (90%), 44% (80%), and 44% (53%), respectively. Dose of radiation, suprasellar extension at the time of surgical failure, and histologic findings had no bearing on prognosis. One patient developed a radiation-induced brain necrosis that was successfully resected. Radiation therapy can be an effective salvage modality for recurrent pituitary adenomas after surgical failure.

Radiation therapy for gliomas of the optic nerve and chiasm.

Thirty-three patients with optic glioma seen over a 30-year period were reviewed. Five patients (15%) had tumor confined to the optic nerve, 8 patients (24%) had optic nerve and chiasmal involvement, and the remaining 20 patients (61%) had invasion of contiguous structures as well as chiasmal involvement. Eleven patients (33%) had a history of neurofibromatosis. Two-thirds of the patients had either a biopsy or a partial resection of the tumor, with the remaining one-third being clinically diagnosed. All patients received irradiation to local fields. The median dose was 5040 cGy in 160 cGy fractions. Of patients alive at last follow-up, the median time of follow-up was 12.3 years. The 5-, 10-, and 15-year overall actuarial survivals were 94, 81, and 74%, respectively. Univariate and multivariate analysis were performed on the following clinical variables: extent of primary tumor, extent of surgery, dose of radiation, gender, race, age, and presence or absence of neurofibromatosis. Extension of the primary lesion to the optic chiasm and age less than or equal to 15 years were the only two variables to have statistically significantly inferior 15-year progression free survivals by multivariate analysis. Eighteen (55%) patients had treatment related complications with most involving the pituitary gland. We conclude that postoperative radiotherapy is beneficial in patients with chiasmal involvement and those with incomplete resections. A minimum tumor dose of 4000 cGy is recommended.

Radiation therapy following keloidectomy: a 20-year experience.

Radiation therapy following excision for keloids has been shown to decrease the recurrence rate by about 50%. We followed 75 patients with 113 keloids for a mean time of 9.75 years. Seventy-four percent of the lesions involved the earlobe. Superficial X ray therapy was used in 89% of the cases. The most frequent dose schedule was 12 Gy in three fractions over 3 days. The overall control rate was 73%. There was no advantage to starting radiation within 1 day of surgery. Keloids greater than 2 cm in size, those that had previous therapy, and those occurring in men were found to indicate a high likelihood of recurrence. The mean time to recurrence was 12.8 months. There were no complications from this low dose treatment. Radiotherapy following excision is an effective and safe adjuvant treatment for keloids.

Endocavitary irradiation for rectal cancer and villous adenomas.

Endocavitary irradiation has been used for rectal adenocarcinoma and villous adenoma at St. Joseph's Hospital, Milwaukee, Wisconsin since 1978. The 52 patients treated since that time include 32 patients with adenocarcinoma, 19 patients with villous adenoma, and 1 patient with an adenomatous polyp and associated atypia. The average age of these patients (70.5 years) was a full decade older than the average age of all rectal cancer patients. The treatment was administered by a superficial contact machine with most patients receiving 80 Gy over four treatments in a period of 1.5 months. The overall local recurrence rate was 24% in the cancer group and 32% in the villous adenoma group. The 1-, 2-, and 3-year determinate disease-free survival rates were 90.4%, 78.6%, 74.2% and 80.4%; 60.3%, 45.2% for invasive adenocarcinoma and villous adenoma patients, respectively. There was no mortality and very little morbidity associated with the treatment. It is concluded that endocavitary irradiation is an effective alternative to surgery for the treatment of rectal cancer in selected cases. However, villous adenomas do not respond as well. Better results may be obtained for this group of patients by higher doses than were used in this study.