Joseph H. Galicich

Patterns of failure following treatment for glioblastoma multiforme and anaplastic astrocytoma

Recurrence patterns of glioblastoma multiforme (25) and anaplastic astrocytoma (9) were studied using CT scans of 34 patients who received all or a portion of their surgical treatment at Memorial Sloan-Kettering Cancer Center from January 1983 through February 1987. Thirty-two patients presented with unifocal tumors and two with multifocal tumors. All patients received radiation therapy following initial surgery. Eighteen patients who underwent re-operation following CT evidence of recurrence had histologic verification of recurrent tumor; sixteen patients had radiographic evidence of recurrence only. Seventy-eight percent (25/32) of unifocal tumors recurred within 2.0 cm of the pre-surgical, initial tumor margin, defined as the enhancing edge of the tumor on CT scan. Fifty-six percent (18/32) of tumors recurred within 1.0 cm of the initial tumor margin. Tumors for which a gross total resection was accomplished tended to recur closer to the initial tumor margin than did subtotally resected tumors (p greater than 0.1). Extensive pre-operative edema was associated with a decreased distance between initial and recurrent tumor margins. Large tumors were generally not more likely to recur further from the initial tumor margin than were smaller tumors. No unifocal tumor recurred as a multifocal tumor. Only one tumor (initially near the midline) recurred in the contralateral hemisphere. The findings support the use of partial brain irradiation for post-operative treatment of glioblastoma multiforme and anaplastic astrocytomas, and may help to determine the most appropriate treatment volume for interstitial irradiation.

The role of postoperative radiotherapy after resection of single brain metastases

To assess the value of whole brain radiotherapy (WBRT) after complete resection of a single brain metastasis we reviewed the records of 98 patients who had elective craniotomy between 1978 and 1985. Seventy-nine patients received postoperative WBRT (Group A) and 19 patients no radiotherapy (RT) (Group B). Neurological relapse was designated as local (i.e., at the site of the original metastasis) or distant (i.e., elsewhere in the brain). Postoperative WBRT significantly prolonged the time to any neurological relapse (P = 0.034) with a 1-year recurrence rate of 22% in Group A and 46% in Group B patients; however, it did not specifically control either local or distant cerebral recurrence. Recurrence of metastatic brain disease was not affected by location of the original lesion; however, meningeal relapse occurred in 38% of cerebellar lesions, but only in 4.7% of supratentorial metastases (P = 0.003). The total radiation dose or fractionation scheme of RT did not affect survival nor time to neurological relapse. The median survival was 20.6 and 14.4 months for Groups A and B, respectively (not statistically different). Forty-eight percent of Group A and 47% of Group B patients survived for 1 year or longer; however, 11% of patients who had received RT and survived 1 year developed severe radiation-induced dementia. All patients with radiation-related cerebral damage received hypo-fractionated RT with high daily fractions as commonly designed for rapid palliation of macroscopic brain metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Reoperation in the Treatment of Recurrent Intracranial Malignant Gliomas

Fifty-five consecutive patients with recurrent intracranial malignant gliomas were reoperated at Memorial Sloan-Kettering Cancer Center from 1972 to 1983. The patients were 10 to 70 years old (median, 48 years). Thirty-five patients (64%) had glioblastoma multiforme, and 20 (36%) had anaplastic astrocytoma. The median interval between the first operation and reoperation was 43 weeks. The Karnofsky rating before reoperation ranged from 40 to 90 (median, 70). Eleven patients (20%) had more than one reoperation. The mortality rate was 1.4% per procedure, and the morbidity rate was 16% per procedure. After reoperation, 41 patients (75%) had chemotherapy and/or radiation therapy. The median survival for all patients was 92 weeks. The median survival after reoperation was 36 weeks. Patients with Karnofsky ratings of greater than or equal to 70, with anaplastic astrocytomas, or in whom gross total removal of the tumor was undertaken lived longer than their respective counterparts (P less than 0.05). Prereoperation Karnofsky rating and extent of surgical resection were the most important independent factors related to survival after reoperation according to multivariate analysis (P less than 0.01 and P less than 0.05, respectively). Twenty-five patients (45%) had improved Karnofsky ratings after reoperation, and the 32 patients (58%) who were independent after reoperation were able to stay so for more than 6 months of their survival time (median value). Reoperation is feasible and can be accomplished with acceptable mortality and morbidity. When intracranial malignant gliomas recur, the combined use of reoperation and adjuvant therapy prolongs good quality life.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal metastases from solid tumors. Analysis of factors affecting survival

Background. Factors affecting survival were determined for 109 patients with thoracic spine metastases and cord compression. Lung, prostate, and breast were the most common primary sites (78%). All patients had surgical decompression of the spinal cord, and 99% received radiotherapy.

Radiation Therapy for Spinal Epidural Metastases with Complete Block

Myelography was performed in 535 patients at the Memorial Sloan-Kettering Hospital from January 1979 to December 1979. In 110 cases a complete block was demonstrated and of these, 78 had epidural metastases. A uniform treatment was applied using radiation therapy and high dose steroid. The neurologic outcome for each patient was evaluated, correlating pre-treatment neurologic status, pathologic type, nature of block (level, structural versus tumoral), and result of repeat fluoromyelography. Only 2 patients improved, but 11 became completely paraplegic. The survival was influenced by the ambulatory status after treatment (median survival: 52.7 weeks in the ambulatory group and 4.6 weeks in the paraplegic). Based on this series, rational approach and management of complete block secondary to spinal epidural metastases are discussed.

Surgical treatment of brain metastases. Clinical and computerized tomography evaluation of the results of treatment

The results of treatment of brain metastases in a series of 125 patients who underwent surgery with or without postoperative radiation from 1978 through 1982 were analyzed. The major sites of primary tumor included the lung (40%), melanoma‐skin (11%), kidney (11%), colon (8%), soft tissue sarcoma (8%), breast (6%), and a variety of others (15%). At the time of craniotomy, disease was considered limited to the central nervous system in 63 patients (50%). After surgery, 83 patients (66%) were neurologically improved, and 26 (21%) had their deficits stabilized. The overall median survival was 12 months, and 25% lived 2 years. Eight patients (12%) are alive 5 years or more following surgery. Survival varied with site of primary tumor, location of brain metastasis, extent of systemic disease, and neurologic deficit at time of craniotomy. Over a follow‐up period ranging from 18 months to 6 years, 42 patients (34%) developed either local recurrences or other sites of brain metastases. These data suggest that although craniotomy followed by radiation is highly effective in the initial treatment of selected patients with brain metastases, alternate therapies require investigation in view of the high central nervous system relapse rate in long‐term survivors. Cancer 55:1382‐1388, 1985.

Surgical resection of brain metastases from renal cell carcinoma in 50 patients

OBJECTIVESnMetastases are frequently diagnosed among patients with renal cell carcinoma (RCC). Of 709 patients with brain metastases (BMET) who were operated on at our institution between 1974 and 1993, 50 (7%) were of renal origin.nnnMETHODSnMedical records were reviewed retrospectively. Survival time was calculated by the Kaplan-Meier method and Cox proportional hazards model.nnnRESULTSnThere were 38 men and 12 women. The median age was 60 years. The primary RCC was resected in 47 patients. Forty patients had a metachronous diagnosis of RCC and BMET. Median interval between the diagnosis of RCC and BMET was 17 months. In all 50 patients overall median survival (MS) from diagnosis of primary RCC was 31.4 months and from craniotomy was 12.6 months. Postoperative mortality was 10% (5 patients). In patients with primary RCC in the left kidney (n=25) versus right kidney (n=25) median survival from craniotomy was longer; 21.3 versus 7.4 months (P<0.014). Twenty-three patients (46%) had intratumoral hemorrhage. Eight patients had cerebellar metastasis (MS, 3.0 months) and 9 had multiple metastases resected (MS, 7.6 months). Thirty-eight patients had both brain and pulmonary metastases, and 16 of them had pulmonary resection (MS, 18.6 versus 8.0 months; P<0.03). Twenty-two patients received whole-brain radiation therapy (WBRT) after craniotomy and 18 did not receive WBRT (MS, 13.3 versus 14.5 months; P<0.62). The 1-year, 2-year, 3-year, and 5-year survival was 51%, 24%, 22%, and 8.5% respectively.nnnCONCLUSIONSnOnly the resection of lung metastasis, supratentorial location of BMET, left-sided localization of primary RCC, and lack of neurologic deficit before craniotomy were statistically significant prognostic factors in Cox regression analysis. In the absence of effective systemic treatment, we suggest that patients with BMET from RCC be considered for operative resection for treatment and palliation.

Surgical treatment of single brain metastasis: Factors associated with survival

The results of surgical excision of solitary intracerebral metastases followed by whole‐brain radiation therapy between 1972 and 1978 in a series of 78 patients were analyzed. The overall median survival of the series was 6 months with a 1‐year survival rate of 29%. Statistical analyses of the data revealed that patients who presented with a cerebral metastasis 1 year or more after diagnosis of the primary cancer had a significantly longer survival than those in whom the metastasis was detected within 1 year (P <.04). Patients with mild or no neurological deficits at time of craniotomy had a longer median survival and a 1‐year survival of 44% (P <.01). The presence of metastases at one or two other sites did not significantly affect overall survival except in those patients in whom the brain metastasis was detected more than 1 year after diagnosis of the primary tumor. Factors found to affect survival in this study may be useful in predicting survival of future patients similarly treated.

Vertebral body resection in the treatment of cancer involving the spine

Results of radical spinal surgery with vertebral body resection in of 51 patients with primary and metastatic cancer of the spine were analyzed. Seven patients had primary spine tumors, 16 had paravertebral tumors that involved the spine by direct extension, and 28 had blood—borne metastases to the spine. Thirty‐five patients (68%) had prior therapy directed to the spine: 4 had undergone previous surgery, 9 had surgery and radiation, and 22 had radiation alone. Forty‐five patients (90%) had intractable pain, and 25 patients (48%) were nonambulatory. Myelography revealed high‐grade or complete block in 39 patients (76%). Following surgery, 38 of 45 (84%) had pain relief, and 40/58 (78%) were ambulatory at discharge. Of the 25 patients who were unable to walk prior to surgery, 15 (60%) improved to fully ambulatory status. The surgical mortality was low (4%), and complications were few (10%). These results are superior to those reported following treatment by radiation and steroid therapy. In selected patients who have actual or potential neural compression resulting from tumor within the vertebral body, such surgery should be considered as initial therapy. Cancer 53:1393‐1396, 1984.

Sufentanil, alfentanil, and fentanyl: impact on cerebrospinal fluid pressure in patients with brain tumors.

Summary In order to evaluate the safety of the new synthetic opioids, alfentanil and sufentanil, in neurosurgical patients, we administered sufentanil 1 μg/kg i.v., alfentanil 50 μg/kg i.v. followed by an infusion of 1 μg/kg/min, or fentanyl 5 μg/kg i.v. to 30 patients with supratentorial tumors anesthetized with nitrous oxide (N2O), 60% in O2. Lumbar cerebrospinal fluid pressure (CSFP) and mean arterial pressure (MAP) responses were recorded for 10 min thereafter, while ventilation was held constant [mean PaCO2 = 36.1 ± 1.0 mm Hg (SEM)]. There was no change in CSFP after fentanyl. In contrast, both sufentanil and alfentanil caused increases in CSFP, equal to 89 ± 31 % SE (p < 0.05) and 22 ± 5% (p < 0.05), respectively. MAP decreased after administration of each opioid. Peak decreases in cerebral perfusion pressure (MAP - CSFP) were 14 ± 3% after fentanyl, 25 ± 5% after sufentanil, and 37 ± 3% after alfentanil. It is concluded that because sufentanil increased CSFP in patients who have brain tumors, it also may be contraindicated in other neurosurgical patients at risk for intracranial hypertension. Alfentanil may share this propensity, since CSFP increased despite a profound reduction in MAP. Among the three opioids evaluated, only fentanyl appears to be appropriate for supplementing N2O-2 anesthesia in patients who have compromised intracranial compliance.