Surgical Results and Complications

The length and quality of postoperative survival are the most important indicators by which one can evaluate the results of any treatment for supratentorial brain tumors, The inherent risk of surgery as a treatment modality requires that some analysis also be made of perioperative morbidity and mortality. The 30-day operative mortality for glioma surgery remained in the range of 20 to 40 percent until the advent of corticosteroids and modern neuroanesthesia in the early 1960s, Since then there has been a steady decline in surgical risk, and the authors of several published series have achieved mortality rates of less than 3 percent. Recent attention to the details of surgical technique have also probably contributed to this steady improvement. It is the general opinion of experienced operators that limited biopsy at open surgery poses a greater risk to the patient than either radical excision or a stereotactic procedure, and this is borne out by a retrospective analysis of the available survival data. The selection bias in these data is quite strong, because there is a tendency for older and sicker patients to receive more limited surgical procedures. Nevertheless, the analysis is based on 603 patients drawn from the literature who did not receive postoperative radiation for glioblastoma, and it is quite unlikely that any better data will ever be accrued on the effects of surgery uncontaminated by the influence of other concomitant therapies. Because the extent of surgical resection for cancers else­where in the body can also be correlated with the length of postoperative survival, the general principle that radical excision is preferable to either partial removal or simple biopsy is adequately supported. The operating microscope and the carbon dioxide laser facilitate the performance of a more radical tumor removal in greater numbers of patients and with correspondingly less operative morbidity and mortality. Somewhat surprisingly, relatively little attention has been paid to postoperative morbidity, because survival was the prime issue of importance in the early series. Davis and his associates did provide several anecdotal reports of patients retaining the ability to fulfil their economic and social obligations but made no statistical analysis. In 44 patients surviving more than 3 months after surgery for glioblastoma, Hitchcock and Sato found that 76 percent had a "useful" survival of at least 6 months but that only 28 percent were able to return to work. Of course, the failure of patients to return to work is subject to many factors other than the postoperative neurological condition; among these are familial, social, psychological, and economic influences. Up to 40 percent of postoperative survivors are neurologically normal or suffer from minimal deficits such as facial weakness and quadrantanopsia; another 26 percent suffer from more severe deficits, including hemiparesis, but remain ambulatory and able to care for themselves, Patients undergoing extensive resections have the greatest likelihood of improving their preoperative condition and achieving some degree of independent existence. Resection of neuroectodermal tumors is more likely to alleviate existing symptoms than to produce additional ones. Beneficial changes in cerebral metabolism and blood flow may underlie some of these functional improvements.

Radiation :It is common practice to give postoperative irradiation to patients with glioblastoma but it is not equally appreciated that a similar policy should be adopted in regard to all grades of supratentorial astrocytoma. The 5-year survival rate for patients with grade 1 and grade 2 astrocytomas is only 19 percent after incomplete resection but is 46 percent when postoperative irradiation is added. In some series, the magnitude of the beneficial effect of irradiation for low-grade tumors has even been independent of the extent of the resection. Patients with oligodendroglioma also appear to benefit from combined-modality therapy, In a series of 35 patients evaluated at more than 5 years after surgery, the 5-year survival rate for surgery alone was 82 percent and the recurrence rate (including deaths) was 36 percent; in contrast, the 5-year survival rate after both surgery and irradiation was 100 percent, and there were no clinical or radiographic recurrences. An important consideration, in this regard, is the theoretical necessity of providing maximal therapy at the earliest possible juncture in the clinical course, since recurrence is almost invariably fatal. Two-thirds of all astrocytomas are of a more malignant grade at the time of first recurrence, with nearly one-third of grade 1 tumors and nearly one-half of grade 2 tumors having become frank glioblastomas. Similarly, 50 percent of recurrent oligodendrogliomas appear to be histologically more malignant at reoperation, and nearly 20 percent recur as glioblastomas. Hence it is recommended that all adult patients with a supratentorial astrocytoma or oligodendroglioma undergo postoperative irradiation.

Without radiation, the median postoperative survival for patients with glioblastoma is only 4 months, even if all cases with limited resections or simple biopsies are excluded. The addition of postoperative irradiation increases this figure to 9.25 months and improves the 2-year survival rate from 3 to 11 percent. Although the use of postoperative irradiation increases the proportion of patients surviving at all intermediate points in the first 18 months following surgery, the natural course of the disease is such that all survival curves, irrespective of the mode of treatment, appear to converge at 18 to 24 months after diagnosis. Nevertheless, the value of irradiation is unequivocal, because virtually all study groups that have reported a zero percent 2-year survival rate also failed to irradiate their patients. Unfortunately, the amount of external irradiation that can be safely delivered is limited by the sensitivity of the brain and its blood vessels to the detrimental effects of ionizing radiation.

Interstitial brachytherapy has been shown to be the most effective rescue therapy for patients with recurrent high-grade tumors. Median additional survival times of more than 50 and 80 weeks have been reported in patients with glioblastoma and malignant astrocytoma, respectively, who were stereotactically implanted with iodine-125 seeds. The longest survivals were observed in those patients who required reoperation for radiation necrosis. Clinical trials are presently underway to study the use of this tech­nique in combination with hyperthermia and chemotherapy, as well as in the initial treatment of gliomas in which brachytherapy can be used as the focal boost to conventional external irradiation. Unfortunately, only 20 to 30 percent of patients with recurrent tumors are eligible for brachytherapy, because of either the size and site of the tumor, or the performance status of the patient.

Chemotherapy: Further small increments in the length of postoperative survival can be obtained through the use of nitrosourea chemotherapy; the number of long-term survivors is increased in randomized studies, and the median survival in a retrospective analysis of maximally operated patients rises to almost 10 months. Nevertheless, the beneficial effect of chemotherapy is so modest that it is easily obscured by the impact of such major prognostic variables as age, tumor histology, and performance status; in addition, chemotherapy does not appear to influence the shape of the survival curve or the likelihood of cure in the majority of patients. Some tumors in young patients are inherently more sensitive to nitrosourea than virtually any tumors in older patients, thus contributing to the marked dependency of survival statistics on the patient's age at diagnosis.37,43 The end result of this and other biological factors is an inability to extend either the median survival beyond 15 months or the 2-year survival rate beyond 40 percent in patients with malignant astrocytoma, even when they are subjected to an extremely aggressive combination of radical resection, maximum radiation, high-dose chemotherapy, and frequent reoperation. It is conceivable that therapeutic failures are rooted in the cellular heterogeneity of most solid tumors and the tendency to deliver treatments sequentially in isolation rather than in combination