The role of radiation therapy in the treatment of astrocytomas.

One hundred forty-seven patients with astrocytoma were treated between 1942 and 1967.There were 25 postoperative deaths. The 14 patients in whom the tumor was thought tohave been completely removed were not irradiated and all survived 5 years or longer. Seventy-one of the 108 patients with imcompletely excised lesions received radiation therapy. The 5-year survival rate for those with imcomplete resection alone was 19%, compared to 46% when irradiation was given. Based on observations up to 20 years, after incomplete removal postoperative irradiation significally prolonged useful life and may have lead to permanent control in some. There was no evidence of radiation damage. Most of these tumors were fibrillary astrocytomas, and the results apply particularly to this histologic type. Only 1 of 11 patients with gemistocytic astrocytoma survivied 5 years. The survival rate for Grade i tumors was appreciably greater than for Grade iilesions; in both grades, it was improved by irradiation.     

The value of radiation therapy as an adjuvant to surgery in intracranial meningiomas

Our experience with benign and malignant intracranial meningiomas between 1970 and 1983 is reported. Fourteen cases were treated after surgery, 10 benign and four malignant, following complete or incomplete resection or recurrence after resection. Two of 10 benign meningiomas have recurred and one of the two has been controlled by reoperation. None of the malignant meningiomas have been cured, but disease-free intervals up to 4 years were noted. The mean radiation dose was 5,400 rad, given with complex fields and shrinking field technique with no major complications. Adjuvant radiation after resection of meningiomas results in frequent cure of benign meningioma and may extend the interval of recurrence in malignant variants.     

Treatment of low-grade diffuse astrocytomas by surgery and human fibroblast interferon without radiation therapy

Low-grade diffuse astrocytomas are slowly growing tumors with a relatively long overall survival. However, a substantial proportion undergoes dedifferentiation to a more malignant phenotype. Considerable controversy exists as to the best therapeutic management for patients with such tumors. Over the past decade, we have applied human fibroblast interferon (HFIF) therapy without radiation therapy to low-grade astrocytomas. We investigated 28 patients with WHO grade II astrocytomas of the cerebral hemispheres treated by surgery plus HFIF therapy. The overall response rate to the HFIF therapy was 36%. All side-effects of HFIF were transient, tolerable and manageable. The 5-year progression free survival and overall survival probabilities were 65% and 96%, respectively. Although our data from small cohort of patients may have modest value, our results suggest that HFIF may be useful in treating low-grade diffuse astrocytomas.     

Chemotherapy in recurrent noncystic low-grade astrocytomas of the cerebrum in children

Six children with grade II astrocytomas were treated with combination chemotherapy consisting of 1,3 bis(2-chloroethyl) 1-nitrosourea (BCNU). Vincristine (VCR), intrathecal Methotrexate (i.t. MTX), and Dexamethasone. Of the children, 3 showed a partial remission, and 1 other showed clinical improvement. Our data suggest that chemotherapy is effective in low-grade astrocytomas, and there is now a need for larger trials in low-grade astrocytomas to document the role of chemotherapy accurately in these tumors. It is suggested that trials of chemotherapy as adjuvant to surgery and radiotherapy should be initiated.     

Anaplastic astrocytoma of the adult cerebrum. Prognostic value of histologic features

Initial biopsy and resection specimens from 78 cerebral astrocytomas with anaplastic foci occurring in adults were examined for the presence of five specific histologic features traditionally considered indicative of anaplasia. Anaplastic astrocytomas with foci of tumor necrosis had been classified as glioblastoma multiforme and excluded from this analysis. Median actuarial survival was shorter for patients whose tumors contained vascular endothelial proliferation (3.5 years versus 5.5 years) or greater than 1 mitosis per 10 high power microscopic fields (1 year versus 5.5 years). No correlation with survival was found for estimation of nuclear pleomorphism and cell density or the presence of secondary structures. Vascular endothelial proliferation and increased mitotic activity may serve as prognostically significant histologic markers in cerebral astrocytomas of intermediate malignancy.     

The value of mammography after limited breast surgery and before definitive radiation therapy.

One hundred twenty consecutive patients who had breast-conserving surgery for cancer and were referred for definitive radiation therapy (RT) had a mammogram performed before starting RT. This was done to determine the presence of residual neoplasm or other abnormalities that may alter or delay the planned RT and are undetected by other means. It also was performed to provide a baseline for the diagnosis of postoperative changes and recurrence of disease on follow-up studies. In six (5%) patients, calcifications or masses were found that proved to be residual tumors. This led to reexcision in two, mastectomies in two, and a higher radiation booster dose to the tumor bed in two. Eight (6.6%) patients had postoperative hematomas larger than 4 cm in diameter, which delayed the start of RT by 2 to 3 weeks. In 39 (32%) patients, the pre-RT mammogram provided information considered to be helpful for the interpretation of post-RT mammograms. Such information may lead to a decrease in the number of diagnostic biopsies based on indeterminate mammographic findings. Therefore, a routine mammogram is recommended before RT is started.     

The role of whole-brain radiation therapy after stereotactic radiation surgery for brain metastases

The benefit of whole-brain radiation therapy (WBRT) following stereotactic radiation surgery (SRS) for brain metastases is controversial. We conducted a systematic analysis of published literature to explore the outcome of brain metastases treated with SRS and WBRT versus SRS alone using PubMed and MEDLINE. Outcomes including survival, control, salvage therapy, and other quality of life measures were reported. Three randomized controlled trials involving 389 patients with 1 to 4 brain metastases were selected. In 2 of these trials (n = 190), the mean 1-year survival was 33.2% for SRS + WBRT and 38.7% for SRS alone (P = .5233); 1-year local control was 89% for SRS + WBRT and 71% for SRS alone (P < .001). Mean crude distant recurrence rate for SRS + WBRT was 36.6% and 54% for SRS alone (P < .001). Patients without WBRT were over 3 times more likely to require salvage therapy (P < .001). The addition of WBRT was associated with a decreased health-related quality of life assessment, mini mental status exam, and Hopkins Verbal Learning Test (P < .05). Five retrospective studies (n = 1122) were also included in a separate analysis and yielded findings that supported results from the randomized trials. Our systematic analysis demonstrates that adjuvant WBRT following SRS for the treatment of oligometastases in the brain is more effective at controlling local and distant recurrence than SRS alone, but there is no apparent benefit for survival or symptomology. The proven cognitive decline and neurotoxicity present with WBRT should be weighed against the benefit of local control. Prognosis of brain metastasis is poor regardless of current treatment and further exploration for alternative adjuvant treatment for SRS is warranted.     

The value of extended field radiation therapy in carcinoma of the prostate

Since 1970, a total of 342 patients have received radical radiation therapy for carcinoma of the prostate. The estimated 5 year survival of 78% and 5 year disease-free survival of 67% remains unchanged. Initially, all patients received radiation therapy to the prostate. Recently, patients with more advanced disease as well as a selected group of patients with less extensive disease received extended field radiation to the pelvis. comparison of these two groups of patients shows no advantage for extended field radiation in early stage disease. However, in more advanced disease [patients with involvement of more than one lobe or extraprostatic extension], there is evidence that extended field radiation improves the disease-free survival of these patients [63% for 5 year disease free for extended field radiation versus 35% for localized radiation]. This difference persists irrespective of method of diagnosis. While this study is non-randomized, the results were obtained during a period when there has been no other change in treatment philosophy. The results will require confirmation on a randomized trial basis.     

The treatment of adult supratentorial high grade astrocytomas

Summary From 1 January, 1982 until 31 December, 1987 260 adult patients were referred to the Cancer Control Agency of B.C. with high grade supratentorial astrocytomas. Multifocal disease on presentation was present in 17 cases (6.5%). Their survival is poor and whole brain radiotherapy is required. All other cases had unifocal disease, but eight did not receive radiotherapy. The 235 cases who received radiotherapy were subject to univariate and multivariate analyses according to extent of surgery, age, Kernohan and WHO grading, Karnofsky performance status, whole brain treatment, partial brain treatment, total dose and neuroret. Age is an extremely important predictor of survival (P = 0). The pathologic appearance of glioblastoma (WHO grade) as well as the Karnofsky performance status were also important independent factors in predicting survival (P = 0.016, 0.027 respectively) on Cox multivariate analysis. Dose and neurorets were significant factors only in cases where the performance status was not recorded, suggesting that dose was selected according to the patient's condition and age. In this analysis it was found that localized radiation fields may be used rather than whole brain without jeopardizing survival.     

The value of radiation therapy in the management of aggressive non-Hodgkin's lymphomas

Even though chemotherapy plays a major role in the treatment of aggressive non-Hodgkin's lymphomas, the high radiosensitivity of the lymphatic lesions has established radiotherapy as an important component in the management of the disease in localized stages. Nevertheless, the treatment strategies with regard to the stage-adopted indications for radiotherapy, the treatment volume, and the dose remain controversial. This article reviews the available data concerning combined-modality treatment in localized stages and treatment of bulky lesions and residual lymphomas after chemotherapy with emphasis on the role of radiation therapy.     

Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy

Of 77 patients with supratentorial Grades I and II astrocytoma diagnosed from January 1975 to December 1984, 66 were treated with postoperative radiation therapy. The patients received a tumor dose of 5000 to 5500 cGy in 180 cGy fractions, five fractions per week, over 5.5 to 6 weeks. Overall actuarial survival at 2, 5, and 10 years was 71%, 55%, and 43%, respectively. Progression-free survival at 2, 5, and 10 years was 69%, 50%, and 39%, respectively. Survival for patients receiving postoperative radiation therapy in the range of 4500 to 5900 cGy was 78% and 66% at 2 and 5 years, respectively. Quality of life was determined at two points in time: 1 to 2 years postoperatively, and at last follow-up (2-12 years postoperatively). The occurrence of mental retardation was specifically addressed in long-term survivors, and was observed in 50% of children. Overall, however, 80% of short-term survivors and 67% of long-term survivors were intellectually and physically intact, without major neurologic deficit. Specific prognostic factors were assessed by multivariate analysis. Improved survival was observed with young patients, females, normal preoperative mental status, surgical resection (versus biopsy alone), involvement of only one lobe with tumor, and a history of preoperative seizures. A weighted prognostic factor score derived from these observations permits a clinically useful assessment of risk for individual patients.     

Prospective single-arm study of 72 Gy hyperfractionated radiation therapy and combination chemotherapy for anaplastic astrocytomas

Background  

Despite intensive multimodal treatment, outcome of patients with malignant glioma remains poor, and a standard dose of radiotherapy for anaplastic astrocytoma has not been defined. In the past RTOG study (83-02), the arm of 72 Gy hyperfractionated radiotherapy (HFRT) for malignant gliomas showed better outcome than the arms of higher doses (76.8 – 81.6 Gy) and the arms of lower doses (48 – 54.4 Gy). The purpose of this study is to verify the efficacy of this protocol.     

The role of radiation therapy in the treatment of recurrent adult laryngeal papillomatosis

Laryngeal papillomatosis is an uncommon condition in the adult, but it can be severe enough to require tracheostomy for obstructive changes following multiple recurrences, despite surgical local excisions and medical therapies. Few satisfactory treatments are available for such cases to restore both airway function and speech. Some patients may require laryngectomy for progressive dysfunction. The role of radiation therapy has been controversial, with some reports of malignant transformation following treatment. The authors describe two cases treated with irradiation, resulting in complete clearance of the lesions and return of airway and vocal function. Follow-up is given, and the available literature is reviewed.     

A pilot study of cis-diamminedichloroplatinum and radiation therapy in patients with high grade astrocytomas

A pilot study was performed combining cis-diamminedichloroplatinum (CDDP) and radiation therapy to treat patients with high-grade astrocytomas. CDDP at a dose of 40 mg/m2/week intravenously was given during the course of cranial irradiation. Following irradiation, CDDP was given every three weeks on a schedule of 35-40 mg/m2/day for three days until toxicity became unacceptable or until tumor progression occurred. Radiation therapy consisted of 6 000 rads over a seven week period or 5 000 rads followed by an additional 1 500 rads to the tumor site. Patients were followed by computerized axial tomography (CT) scan and neurologic examination. Thirty patients were entered onto the study; 22 were considered evaluable. The median survival was 53 weeks and the median time to progression was 21 weeks. Toxicity was generally tolerable; however, ototoxicity may be enhanced by this treatment. CDDP combined with cranial irradiation is tolerable and feasible, although close follow-up is recommended in case CDDP has to be temporarily interrupted.     

Strategy of surgery and radiation therapy for brain metastases

Cancer patients with brain metastases have poor prognoses and their median survival time is about 1 year. Surgery with whole-brain radiation therapy (WBRT) has been used in the treatment of single brain metastasis measuring 3 cm or more. Stereotactic radiosurgery (SRS) including the use of the Gamma knife and Cyberknife is widely used for the treatment of small and multiple brain metastases; however, recent clinical studies have revealed that SRS + WBRT is superior to WBRT or SRS alone in terms of survival time and local tumor control rates. Here, surgical indications and the strategy of surgery and radiation therapy are discussed, based on many clinical trials of treatments for brain metastases. To improve the survival rate and quality of life for these cancer patients with brain metastases, it is necessary to choose the most suitable mode of surgery and radiotherapy with the close cooperation of physicians, surgeons, radiologists, and neurosurgeons, based on accumulated evidence.     

Anaplastic ependymoma simulating glioblastoma in the cerebrum of an adult

A case of anaplastic ependymoma of the cerebral hemisphere in which the histopathological features closely simulated those of glioblastoma is reported. The patient was a 72-year-old woman with a large, well-demarcated tumor in the left temporal lobe. The tumor was totally extirpated, but recurred 18 months later, and the patient died after 4 months. The extirpated tumor was well circumscribed from the surrounding brain tissue and consisted of a sheet-like, dense proliferation of atypical, short spindle or polygonal cells. Extensive geographic necrosis with nuclear pseudopalisading was seen. Although perivascular pseudorosettes were observed in many areas, true ependymal rosettes were absent. Immunohistochemistry for glial fibrillary acidic protein and epithelial membrane antigen and ultrastructural study confirmed the ependymal nature of tumor cells. The histopathological spectrum of anaplastic ependymoma is very wide and reflects the basically dual characteristics of ependymal cells: epithelial and glial phenotypes. The present case indicates that some anaplastic ependymomas strongly express the glial phenotype and also show remarkable anaplastic cytological features, thus closely simulating glioblastoma. The diagnostic criteria for anaplastic ependymoma, and the nosological position of highly anaplastic ependymoma and its possible clinical implications, are briefly discussed.