A histopathological contribution to supratentorial glioma grading, definition of mixed gliomas and recognition of low grade glioma with Rosenthal fibers.

BACKGROUND: Previous glioma studies have described separate grading systems for oligodendrogliomas and astrocytomas. Many of these gliomas contain mixtures of neoplastic astrocytes and oligodendrocytes. Prognosis may be related to the percentages of these neoplastic components. Previous survival/grading studies have been limited to histopathological features but have not evaluated the importance of percentages of neoplastic components. This study attempted to perceive the relative importance of percentages of neoplastic astrocytes and oligodendrocytes for definition of astroglial, oligodendroglial and mixed oligoastroglial tumors. After determination of these limits we explored the possibility to develop a grading system for common supratentorial gliomas based on reproducible histopathological features. METHODS: A retrospective study was performed of 362 cases of unselected supratentorial glioma. One hundred and thirty-eight binary and nine continuous histopathological variables, amongst which percentages of neoplastic astrocytes and oligodendrocytes, were scored and related to survival. Only well reproducible histological features were accepted in Cox regression to define glioma grades. RESULTS AND CONCLUSIONS: Supratentorial gliomas appeared to be composed of variable percentages of neoplastic oligodendrocytes and astrocytes, but this spectrum did not correspond to a continuous change in prognosis. Gliomas containing 30% or more neoplastic oligodendrocytes had a slightly better outcome (p < 0.0432) but higher percentages did not further improve prognosis. Percentages of neoplastic astrocytes were not correlated to survival. We therefore propose to designate gliomas containing 30% or more neoplastic oligodendrocytes as oligodendroglial tumors, and others as astroglial tumors. From a prognostic point of view there is no need to recognize mixed oligoastrocytomas. An interesting finding was the recognition of a low grade glioma group with Rosenthal fibers, which had the longest postoperative survival. Another prognosticator of interest concerns the mitotic rate as a continuous variable. Atypical mitoses indicated the worst survival, after necrosis. It was possible to develop a grading system for all supratentorial gliomas using six reproducible histological parameters: necrosis, atypical mitoses, the mitotic rate, endothelial proliferative activity, percentage of neoplastic oligodendrocytes and Rosenthal fibers. This resulted in four grades for astroglial tumors (p < 0.002) and three grades for oligodendroglial tumors (p < 0.008) which differed significantly within each group with respect to survival.

[Stereotactic radiosurgery with adjusted linear accelerator for cerebral arteriovenous malformations: preliminary results in the Netherlands]. / Stereotactische radiochirurgie met aangepaste lineaire versneller voor cerebrale arterioveneuze malformaties: eerste ervaringen in Nederland.

OBJECTIVE: To assess the effects of stereotactic radiosurgery of a cerebral arteriovenous malformation (AVM). DESIGN: Prospective. METHOD: In November 1991-December 1995 linear acceleration radiosurgery was performed on 29 patients for their 30 cerebral AVMs in the University Hospital Vrije Universiteit, Amsterdam, the Netherlands. There were 15 females and 14 males with a mean age of 37.1 years (range: 13-58). Generally one isocentre was used and 15 Gy was given to the margins of the AVM at the 80% isodose. The mean target volume was 2.4 ml (range; 0.5-8.2). After 6 months, one year and thereafter every year, neurological and MRI-controls took place, in the outpatient ward. Angiography was performed after an average of 35 months (range: 24-70) to check if the AVM had obliterated. RESULTS: Angiographic post-treatment results were available in 27 patients and MRI information in one. Angiographic obliteration occurred in 20 patients (71%). No permanent radiation-induced neurological deficit was seen, nor did any hemorrhage occur during the interval between irradiation and obliteration.

Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma.

In cerebral glioma combination chemotherapy with procabazine, CCNU and vincristine (PCV) is used as adjuvant therapy in cases of recurrence. Standard PCV is usually well tolerated, but intensive PCV (CCNU 130 mg/m2 on day 1, procarbazine 75 mg/m2 on day 8-21, vincristine 1.4 mg/m2 on day 8 and 29; 6 courses every 6 weeks) is less well tolerated. We observed central neurotoxic side effects (focal neurological deficit, cognitive disturbances, slowing of EEG background activity, atrophy on cerebral MR) in combination with hematological and hepatic toxicity in four of 26 PCV treated patients with recurrent glioma. Prolonged myelo-suppression and/or ongoing (partial reversible in two patients) neurological deficit still influence daily life in three of four patients months after discontinuation of chemotherapy. Despite the fact that all four patients used anticonvulsants and have been treated with radiotherapy in the past, we have the strong impression that central neurotoxic side effects are related to intensive PCV therapy. We advocate to use the standard PCV regimen in patients with recurrent glioma, because of this potential toxicity and the lack of evidence that intensive PCV leads to better tumor control than standard PCV in cerebral glioma.

Hypofractionated radiation therapy in patients with glioblastoma multiforme: results of treatment and impact of prognostic factors.

PURPOSE: Median survival of patients with glioblastoma multiforme (GBM) is only about 4 months with surgery and about 9 months for surgery followed by radiotherapy. Prolonged treatment is futile for many patients and the time of treatment and hospitalization should be minimized. METHODS AND MATERIALS: This was a prospective, nonrandomized study of 30 patients treated with a hypofractionated radiation scheme (42 Gy in 14 fractions). RESULTS: Median survival was 36 weeks. Age, Karnofsky performance status (KPS) and extent of surgery were strongly interrelated and all correlated with survival (p < 0.05). Three prognostic groups were identified. Patients with three favorable prognostic factors (age <50, KPS 80-100, and > or = 75% of the tumor removed) had the best prognosis (median survival 50 weeks). Patients with no favorable prognostic factors (age > or = 50, KPS < or = 70, and < 75% of the tumor removed) had the worst prognosis (median survival 25 weeks). Median survival of the intermediate group (with one or two favorable prognostic factors) was 38 weeks. No severe acute or late toxicity was observed. CONCLUSION: The treatment results are comparable to those achieved with conventional radiotherapy schemes. Based on the number of favorable prognostic factors (age < 50, KPS 80-100 and > or = 75% of tumor resected) the radiation schedule should be selected.

Surgery and postoperative radiotherapy and radiotherapy alone in T3-T4 cancers of the pyriform sinus. Treatment results and patterns of failure.

Fifty-four patients with T3-T4 squamous cell carcinomas of the pyriform sinus were treated between 1976 and 1990. Surgery with postoperative radiotherapy (n = 32) was the treatment of choice. Radical radiotherapy was used in patients with contraindications for surgery or with inoperable tumors and in patients who refused surgery. The local control rate was significantly higher in the combined treatment group (31/32; 97%) than in the group treated with radical radiotherapy (14/22; 64%) which consisted of more advanced cases. In patients who received radical radiotherapy, the highest local control rates were recorded with doses of 70 Gy and above and with the use of 2 fractions per day. There was no significant difference in regional control and survival rates between the treatment groups. New approaches are indicated to improve the prognosis of hypopharyngeal cancer.

Radiation retino- and opticopathy. A prospective study.

This is a report of a prospective study of irradiation pathology of retina and optic nerve following radiotherapy for malignant tumors in the region of the nose, pharynx, nasopharynx, and sinuses. The eyes, optic nerves or supplying blood vessels were situated in or near the radiation field. In 16.7% of the cases after an average of 2 1/4 years interval pathology of retina and optic nerve did occur.

Ethmoid and upper nasal cavity carcinoma: treatment, results and complications.

From 1970 to 1985, 45 patients with carcinoma of the upper nasal cavity and ethmoid sinuses were radically treated. The tumor parameters, treatment strategy, radiotherapy technique and the results of treatment of these patients are retrospectively analysed in this study with particular reference to complete blindness as a major complication. In most cases tumor was removed by meticulous surgical dissection, and thereafter quality-controlled radiation therapy (external therapy: mean dose 65 Gy in about 7 weeks, or external therapy with brachytherapy boost: mean dose 82 Gy in about 10 weeks) was used for this group of patients. The results show 68% recurrence-free survival at 5 years, adjusted for intercurrent deaths. Complications of treatment were seen in seven patients (16%) who developed eye damage with some loss of visual acuity, none however leading per se to complete blindness. It may be concluded that blindness may be avoided to a major extent while treating carcinomas in the nose-ethmoid areas without compromising loco-regional control.

A critical look at the TNM classification for laryngeal carcinoma.

A total number of 564 patients with glottic (427) and supraglottic (137) laryngeal carcinoma was prospectively staged clinicoendoscopically (CS) and radiologically (RS). These patients were treated from 1974 to 1985 with quality-controlled high-dose radiation therapy. The validity of CS versus RS was checked in this study with the parameter of recurrence-free adjusted survival (RFADS) at 3 and at 5 years. It appears that RS is more valid and has therapeutic implications in planning the target volume for irradiation. The CS should be regarded as inadequate for radiotherapeutic considerations. The International Union Against Cancer (UICC) 1987 norms for staging laryngeal carcinoma (clinical, endoscopic, and imaging) should be strictly followed.

Radiation therapy for advanced (T3T4N0-N3M0) laryngeal carcinoma: the need for a change of strategy: a radiotherapeutic viewpoint.

Since 1974 through 1984, 137 selected patients with loco-regionally advanced carcinoma of the larynx (T3T4 N0-N3) were treated primarily with quality controlled high dose megavoltage radiation therapy with salvage surgery in reserve. This policy of treatment has yielded 67% loco-regional control probability with primary radiotherapy and 85% with salvage surgery at 3 years. Fourteen patients (14/38) had moderate to severe complications after salvage surgery. The quality of life of the patients successfully treated by radiation therapy is obviously and unquestionably better. Primary radiotherapy with salvage surgery in reserve should be accepted as the strategy of choice in at least a selected group of patients with advanced laryngeal carcinoma.

Heterogeneity of stage II glottic carcinoma and its therapeutic implications.

The heterogeneity of glottic carcinoma results in variable loco-regional control probabilities from 40 to 80%. These widely different results may be due to two prognostic parameters of the tumor: the mobility of the vocal cord and the volume of the tumor. On the other hand radiation dose and technique may influence the treatment results. Stringent work-up has been prospectively undertaken in 156 patients with Stage II glottic carcinoma since 1974 through 1983 in the Academic Hospital of the Free University in Amsterdam. Several subgroups were defined from the beginning to indicate one or both of these prognostic factors. All were treated with a high quality accurate radiation therapy program delivering high dose to all patients with worse prognostic factors and even higher dosages to voluminous tumors with impaired mobility of a cord or slowly regressing tumors. The latter was individually judged for each patient towards the end of the treatment period. The loco-regional control probability of around 80% for all the subgroups irrespective of the prognostic factors indicate that the heterogeneity of Stage II glottic cancer may be influenced by high dosages of quality controlled radiotherapy. Thus results hitherto reported in literature may be further improved by the dose-schedules outlined here.