Spinal cord ependymomas treated with surgery and radiation therapy. A review of 11 cases.

Between 1971 and 1990, 11 patients with primary spinal cord ependymomas were treated with surgery and postoperative irradiation or surgery alone at the University of Colorado Health Sciences Center. Of the 11 patients, 6 (54%) were subclassified with myxopapillary ependymomas that were located in the lumbosacral region of the spinal cord: 2 patients underwent complete resections, 8 had subtotal resections, and 1 had a biopsy only; 8 patients received postoperative irradiation (range: 4,500-5,482 cGy) with 7 of 8 patients treated to involved spinal fields. With a mean follow-up of 7.4 years, 3 patients (27%) have developed recurrent disease, 2 in the combined treatment group, and 1 in the surgery alone group. The 5- and 10-year actuarial survival rates were 100% and 80%, respectively. Eight of nine patients (89%) demonstrated clinical improvement after postoperative irradiation which suggests that the irradiation may have contributed to the improvement. The present study supports the long-term survival of patients with spinal cord ependymomas. Results from this series and a review of the literature indicate that complete surgical resection is only possible in about one-quarter of cases. Local spinal irradiation should continue to be utilized when surgery is incomplete.

Multiple brain metastases are associated with poor survival in patients treated with surgery and radiotherapy.

PURPOSE: A retrospective analysis was performed to evaluate the role of surgery in the management of patients with solitary and multiple brain metastases. PATIENTS AND METHODS: Between 1980 and 1990, 46 patients underwent surgical resection of brain metastases at the University of Colorado Health Sciences Center. All but two patients received postoperative whole-brain radiotherapy to a median total dose of 30 Gy (range, 11.4 Gy to 50.0 Gy). Lung was the most common (56%) primary site and adenocarcinoma was the most common (46%) tumor histology. Twenty-eight of 46 patients (61%) had solitary metastases, while the remaining 18 patients had two or more foci. RESULTS: The median survival of all 46 patients was 11 months, and the 1- and 2-year survival rates were 40% and 12%, respectively. Moderately severe to severe neurologic impairment at the time of diagnosis and the presence of multiple brain metastases were associated with a significantly poorer survival. In patients with solitary metastasis, gross total resection and adenocarcinoma tumor histology significantly prolonged survival, whereas primary tumor site, the presence of active extracranial disease, and radiation dose had no significant effect on survival. CONCLUSION: These results are consistent with a recent randomized study supporting the role of surgery and whole-brain radiation therapy in the management of patients with solitary brain metastases. We would caution against the generalization of this concept to patients with two or more brain metastases.

Prostatic thermoluminescent dosimeter analysis in a patient treated with 18 MV X rays through a prosthetic hip.

External beam radiation therapy with high energy photon beams through hip prostheses has been shown to cause dose inhomogeneities for target volumes in the pelvis. In this work, measurements of dose using thermoluminescent dosimetry were compared with dose calculations from a computerized treatment planning system in a patient with prostatic carcinoma and a cobalt-chromium-molybdenum hip prosthesis. A 39% decrement in dose at isocenter was demonstrated for an 18 MV photon beam passing through the prosthesis. A discrepancy of only 3.1% was shown between measured and calculated dose when the tissue-maximum ratio (TMR) method of heterogeneity correction was used. However, it is recognized that several sources of error are possible when heterogeneity corrections are performed for high density prostheses and these are discussed below. The results of this work stress the importance of accurate data for use with the "ratio of TMR's" algorithm in order that accurate treatment planning can be performed.

Survival results in adult patients treated for medulloblastoma.

The records of all 27 adult patients (age, greater than or equal to 16 years) diagnosed with cerebellar medulloblastoma between 1968 and 1986 were reviewed. Twenty-four patients (89%) were treated with postoperative megavoltage irradiation. Twenty of these patients underwent craniospinal irradiation. Sixteen patients received greater than 5000 cGy to the posterior fossa (range, 2340 to 6600 cGy; median, 5490 cGy). Forty-eight percent of patients also received adjuvant chemotherapy. A 5-year and 10-year actuarial survival rate of 48% was achieved. The use of adjuvant chemotherapy did not improve survival in this series. All relapses occurred within 35 months of diagnosis (median time to relapse, 23.5 months), except one patient who had a recurrence in the posterior fossa at 140 months. The posterior fossa was the most common site of treatment failure and represented 50% of all initial relapses. All survivors had no sequelae, except one in whom leukoencephalopathy developed after craniospinal irradiation and intrathecal methotrexate administration. The survival results obtained in this series compare favorably with other reported modern adult medulloblastoma series.

AIDS-related non-Hodgkin's lymphoma: the outcome and efficacy of radiation therapy.

The records of all 16 patients with AIDS-related lymphoma treated with radiation therapy at our institutions were reviewed. All patients were male with a median age of 32 years, and all but one had biopsy proven high-grade NHL. Eleven had lymphoma involving the central nervous system and five had lymphoma involving other sites. Seven of the 11 patients with CNS involvement had primary CNS lymphoma. All patients were treated with megavoltage X rays to doses ranging from 1050 cGy in 1 1/2 weeks to 5037 cGy in 6 weeks. Of those patients with CNS lymphoma, only one responded completely and four responded partially to irradiation. All patients died within a range of 0.2 to 5.3 months (median survival = 2.2 months) from starting radiation therapy. In contrast, 3 of 5 patients (60%) with NHL outside the CNS responded completely and 1 responded partially to involved-field irradiation. These patients survived a median of 12.6 months with one achieving long-term lymphoma-free survival at 40 months. This long-term survivor presented with Stage IE lymphoma as his only manifestation of AIDS. We conclude that AIDS-related lymphomas respond less favorably to radiation therapy than lymphomas in non-immunosuppressed patients. Furthermore, CNS lymphomatous involvement is an ominous occurrence in the AIDS patient. In our experience, cranial irradiation failed to provide significant palliation or survival prolongation in this group of patients. Instead, long-term survival is possible in AIDS patients with limited NHL outside the CNS, and it is in these patients that combination chemotherapy plus involved-field radiation therapy may play a curative role.

Beta-carotene induces morphological differentiation and decreases adenylate cyclase activity in melanoma cells in culture.

Several studies suggest that beta-carotene reduces the risk of some cancers. Except for its function as an antioxidant, the effect of this vitamin on mammalian cells remains poorly defined. This study was performed to show whether beta-carotene treatment of murine B-16 melanoma cells in culture induces differentiation and alters the adenylate cyclase (AC) system. The AC system mediates the action of agents which regulate cell differentiation and transformation. Results showed that beta-carotene treatment for a period of 24 hours or more caused morphological differentiation without changing the level of melanin, and reduced basal and melanocyte-stimulated hormone (MSH)-, sodium fluoride (NaF)-, and forskolin-stimulated AC activity in vitro. Retinol, a metabolite of beta-carotene, inhibited growth without morphological differentiation and reduced basal and MSH- and NaF-stimulated AC activity. However, butylated hydroxyanisole, a lipid-soluble antioxidant, also reduced growth without morphological differentiation, but it failed to alter basal or MSH-stimulated AC activity. The present and previous studies show that the AC system represents a common site where some antitumor-promoting vitamins (beta-carotene, retinol, retinoic acid, and alpha-tocopheryl succinate) act.

Hyperfractionated radiation and chemotherapy for unresectable localized adenocarcinoma of the pancreas. The Gastrointestinal Tumor Study Group experience.

Eighteen patients with unresectable localized adenocarcinoma of the pancreas were treated by a combination of chemotherapy plus hyperfractionated radiation therapy to the pancreas for 4080 cGy with an additional 960 cGy to the pancreatic tumor and a surrounding margin. One hundred and twenty cGy were given twice daily 4 to 6 hours apart. High-energy photon or electron beams were used with treatment planning based on computed tomographic (CT) scans. Patients were given chemotherapy in the form of 5-fluorouracil (5-FU) at 350 mg/m2 on the first 3 and last 3 days of radiation therapy. On day 53, chemotherapy was given that included 600 mg/m2 IV of 5-FU, 1 gm/m2 of streptozotocin, and 10 mg/m2 IV of mitomycin C. The 5-FU and streptozotocin were repeated on days 60, 81, and 88, and the stretozotocin and mitomycin (SMF) cycles were repeated every 8 weeks until progression. Radiation toxicity was generally tolerable with one of 18 evaluable patients having severe nausea and vomiting and two of 18 patients having severe diarrhea. One patient had total liver failure and died 3 months after initiation of therapy. Six patients had severe hematopoietic toxicity during chemotherapy. Overall, the severe toxicity rate was higher (67%) than in previous studies. Median survival was 35 weeks, the 1-year survival rate was 39%, and the patient who survived the longest died at 68 months. Although this schedule of hyperfractionated radiation and chemotherapy was disappointing, combined experimental radiation approaches plus chemotherapy for localized unresectable adenocarcinoma of the pancreas deserve additional research.

Treatment-related central nervous system toxicity: MR imaging evaluation with CT and clinical correlation.

Thirteen patients with abnormal brain MR scans attributable to treatment-induced injury were retrospectively reviewed. All patients were treated with radiation therapy and 62% received chemotherapy. Five patients were graded as having severe white matter (WM) changes, four had moderate WM changes, and four had mild WM changes. CT was generally equivalent to MR in evaluation of severe and moderate WM abnormalities, whereas MR was superior to CT in detection of mild WM abnormalities. In general, the severity of changes depicted by MR/CT correlated with the extent of neurologic dysfunction. The most severe changes were seen in those patients treated with combination irradiation and chemotherapy.

Brain metastases: results and effects of re-irradiation.

Re-irradiation for recurrent manifestations of brain metastases has been reported to be of benefit by either increasing the duration of survival or improving the quality of life. The records of 455 patients with brain metastases treated by radiation therapy at the University of Colorado Health Sciences Center from 1975 through 1986 were reviewed. Of these, 44 patients (9.7%) were re-irradiated because of suggestive neurological findings and/or imaging studies diagnostic of recurrent disease. The primary site distribution was as follows: lung (non-small cell)--15 (34%), lung (small cell)--9 (20%), melanoma--5 (11%), breast--4 (9%), genitourinary--4 (9%), unknown--4 (9%), lymphoma--2 (4%), and endometrium--1 (2%). Retreated patients received at least two courses of irradiation and one received three. The median interval between the first and second courses was 34 weeks (7.8 months). For the initial course of treatment, all patients were treated to the whole-brain with megavoltage X rays to a dose of 30-36 Gy (median 30 Gy) at 1.5 to 4.0 Gy/fraction (median 3.0 Gy/fraction). Retreatment also consisted of whole-brain irradiation (37/42 patients) to additional doses of 6-36 Gy (median 25 Gy) at 2.0 to 4.0 Gy/fraction (median 3.0 Gy/fraction). The total cumulative doses to the brain, therefore, varied from 38-75 Gy with a median of 60 Gy. Survival data were available for 42 of 44 patients retreated. All patients died with disease. The overall median survival following the initial course of irradiation was 40 weeks (9.2 months) with 10 patients (24%) living beyond 1 year. The median survival following retreatment, however, was only 8 weeks with one patient surviving greater than 1 year. Only 12 patients (27%) showed partial neurological improvement with re-irradiation and over one-half (55%) either failed to respond or deteriorated during or soon following retreatment. Brain necropsies were performed in 8 patients. Three of these had developed brain necrosis and two most likely died as a direct consequence. It is concluded that retreatment of brain metastases is seldom worthwhile. Survival is usually short and most importantly, the quality of survival frequently is not improved.

Hip prostheses during pelvic irradiation: effects and corrections.

Treatment of pelvic malignancies frequently includes the use of lateral, arc, or rotational fields. The presence of hip prostheses in these treatment fields will perturb the dose distribution. Correction factors for metal-based alloys used in artificial hips have not previously been reported. Prostheses constructed from frequently used alloys were obtained and measurements were made of the transmission of 4MV and 10MV photons. These measured data were compared with computed correction factors. The computer uses the "ratio of tissue-maximum ratios (TMR's)" method of heterogeneity correction. The computer was provided with both the physical density and the relative electron density of each prosthesis for comparison purposes, since electron densities for hip prostheses are not widely known. Correction factors determined from electron densities demonstrated better agreement with measured data. The "ratio of TMR's" correction algorithm does not consider the contribution of scattered radiation in the dose computations. Consequently, a small adjustment to the relative electron density of the prosthetic hip was required at lower X ray beam energies. Agreement was satisfactory for higher energy X rays, and thus no adjustment was necessary. Relative electron densities and adjusted electron densities for alloys used in artificial hips are provided for computer-aided treatment planning. Recommendations for incorporating the hip prosthesis into the treatment planning process are also provided.

Response to radiotherapy of head and neck tumors in AIDS patients.

Initial manifestations of AIDS in the head and neck area occur frequently. In fact, up to 40 percent of patients may have involvement of the head and neck. The most common malignancies are Kaposi's sarcoma and non-Hodgkin's lymphoma. Since AIDS-related malignancies are a relatively new problem for radiation oncologists, optimal therapy for these neoplasms is unknown. A retrospective review of AIDS patients treated with radiotherapy has been performed. Fourteen patients were identified. Of these, five were treated for head and neck tumors (four for Kaposi's sarcoma and one for non-Hodgkin's lymphoma). Epidemic Kaposi's sarcoma, as well as non-Hodgkin's lymphoma, were seen to be as radioresponsive as the classical forms, but local control was difficult to achieve. Kaposi's sarcoma tended to recur marginally and within the field. Nonetheless, we believe radiotherapy can offer significant palliation for AIDS patients with head and neck tumors. It is of utmost importance that the head and neck surgeon must be acutely aware of the common patterns of presentation of this disease.

Perineal effects of postoperative treatment for adenocarcinoma of the rectum.

Nine (4%) first recurrences that involved the perineum were identified in a randomized study of 202 patients treated by no further therapy, chemotherapy only, radiotherapy only, combined radiotherapy and chemotherapy, following complete surgical excision of adenocarcinoma of the rectum. Six of these were in unirradiated patients and in two of the three irradiated patients the perineum was included in the treatment volume. Eight of the nine patients were male and all nine had received abdominoperineal resection (APR). Our quality assurance procedures identified 22 of 96 irradiated patients in whom the perineum was grossly outside the fields. Sixteen of these had undergone APR. As only one of these 16 relapsed in the perineum no definite effect of the surgical procedure on the likelihood of perineal recurrence could be demonstrated. Examination of the pathology reports revealed that 28 patients undergoing APR had tumors within 2 cm of the anorectal junction (pectinate line). Five (17.8%) developed perineal recurrence compared with 4 (3.6%) of 110 patients whose tumors were more than 2 cm from the anus (p less than 0.02-Fisher exact test). No survival differences could be demonstrated between those receiving perineal irradiation and those not but perineal irradiation was associated with toxicity with at least nine (12.2%) out of 74 developing severe complications directly related to the perineum. The routine inclusion of the perineum in postoperative pelvic irradiation fields for all cases of adenocarcinoma of the rectum is questioned. Our current policy following APR includes optional coverage of the perineum for those tumors more than 5 cm from the anorectal junction.

Double and multiple primary cancers in an adult head and neck radiation therapy clinic.

The records of 321 consecutive patients referred to the Radiation Oncology Center between January 1, 1980, and December 30, 1982, for head and neck cancers were reviewed to determine the incidence of other cancers. Two hundred sixty-two patients have had a single primary cancer in the head and neck region. Fifty-nine patients (18%) have had more than one cancer. These 59 patients have had 68 other cancers. While other head and neck cancers lead the list of second primaries, second cancers also occurred in the esophagus, lung, genitourinary system and elsewhere. Twenty cancers had occurred prior to the patient developing head and neck cancer. Thirty-two cancers were synchronous with the head and neck cancer; 16 have been metachronous. These numbers emphasize that patients with head and neck cancers are in a cancer-prone group that develops a variety of other cancers. These findings have important implications in work-up, radiation treatment planning, treatment goals and follow-up programs.

Patterns of care study: Hodgkin's disease relapse rates and adequacy of portals.

The Patterns of Care Study (PCS) has noted differences in stage adjusted relative relapse rates for Hodgkin's disease in four large facilities; the rates vary from 0% to 11% for infield or marginal recurrence (P = 0.003), and from 10% to 39% for any relapse (P = 0.0006) among these facilities. These differences in outcome were not attributable to variation in patient workup, treatment method, or radiation dose. A resurvey of 181 of these records of patients treated with radiation therapy for cure, in which portal films were available for review, indicates that treatment portal films did not encompass the disease adequately in 66 patients. When this occurred, there was a 50% overall relapse rate with 32% recurrence either infield or marginal. Chemotherapy tended to obscure the effect of inadequate technology, and when the 26 patients receiving chemotherapy as part of their initial treatment were excluded, inadequate margins were followed by even higher rates of relapse. For the subgroup of patients treated with radiation therapy alone, inadequate margins were associated with a 54% overall relapse rate, of which 33% were infield or marginal recurrence. When the portal films for patients treated with radiation therapy only were judged to be adequate, the total rate of any relapse was 14%, with 7% infield or marginal recurrence. PCS data indicate there is a critical need for accurate inclusion of Hodgkin's disease in the treatment portals; that marked facility differences exist in this technical process; and that skilled independent observers can reliably identify inaccurate technical performance.

Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal.

Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Patterns of care outcome studies. Results of the national practice in Hodgkin's disease.

The outcome of treatment for Hodgkin's disease has been determined for 407 patients treated in 1973. A two-level random sampling assures that these results are representative of the national practice. Actuarial analysis of recurrence-free survival at four years is: Stage IA, 80%; Stage IIA, 75%; Stage IIIA, 60%; combined Stages IB, IIB, and IIIB, 50%. Factors significantly associated with recurrence include stage, histology, age, chemotherapy, new patient load, part-time practice, treatment technique, treatment machine, treatment simulation, work up score, treatment score, and facility of treatment. Major treatment complications by stage ranged from 4-12%; complications are significantly associated with disease location, patient age, and the presence of coexisting disease.

Patterns of care outcome studies in Hodgkin's disease: results of the national practice and implications for management.

In a statistically valid random sample of 387 patients selected from the national practice and treated with radiation therapy in 1973 for Hodgkin's disease, the 4-year recurrence-free survival was: stage IA, 82%; stage IIA, 75%; stage IIIA. 60%; and combined stages IB-IIIB, 50%. Observations of in-field recurrence in 996 separate lymph node areas show no dose-response relationship between 3000 and 5000 rad. The use of chemotherapy in stage IIIA Hodgkin's disease in the national practice is associated with a significant improvement in recurrence-free survival (P = 0.01). A group of 51 patients with stages IA-IIIA Hodgkin's disease, aged 5-15, treated with radiation therapy alone, has a 92% recurrence-free rate at 3 years with no major complications.

Diffuse histiocytic lymphoma with sclerosis: a clinicopathologic entity frequently causing superior venacaval obstruction.

Of 107 patients with diffuse histiocytic lymphoma (DHL) seen at the University of Chicago, 14 (13%) were classified as having moderate to marked sclerosis. Three of the 14 (21%) had predominantly retroperitoneal masses. Fifty percent of our group, however, had bulky disease seen predominantly or exclusively in the mediastinum, and all of these individuals had superior venacaval (SVC) obstruction. Of the seven patients with SVC syndrome, three were in Pathologic Stage IIA, three were in Clinical Stage II, and only one was in Clinical Stage IIIA. No other patients with DHL displayed SVC obstruction or predominantly mediastinal disease. Five of seven patients with SVC syndrome had large cleaved cell histology. In spite of an apparently favorable histopathologic subtype and a tendency to localized involvement, patients with DHL and sclerosis who have bulky or disseminated disease appear to be resistant to megavoltage radiotherapy alone and relatively resistant to combination chemotherapy.

Necrotizing myelopathy complicating Hodgkin's disease.

A case of necrotizing myelopathy is presented as a complication of Hodgkin's disease. The distinctive pathologic feature of this case was severe acute vasculitis involving only the vessels of the spinal cord that was considered to have been the cause of the segmental necrosis.