Terrence L. Cascino

Differential diagnosis between radiation and tumor plexopathy of the pelvis

We studied 20 patients with lumbosacral radiculoplexopathy from radiation treatment and 30 patients with plexus damage from pelvic malignancy. Indolent leg weakness occurred early in radiation disease, whereas pain marked the onset of tumor plexopathy. Eventually, all radiation cases had weakness, which was bilateral in most of them and painless in one-half of them. Tumor patients typically had unilateral weakness, which was painful in all of them. Radiation disease often resulted in serious neurologic disability. Of the tumor patients, 86% were dead within 31/2 years after onset of neurologic symptoms.

Comprehensive study of diagnosis and treatment of trigeminal neuralgia secondary to tumors

Among 5,058 patients seen at the Mayo Clinic from 1976 through 1990 for face pain, we diagnosed trigeminal neuralgia in 2,972. Tumors were causing the face pain in 296 patients. Sex and pain distributions paralleled those in idiopathic trigeminal neuralgia; however, patients with tumors causing trigeminal neuralgia were younger than those with idiopathic pain. Meningiomas and posterior fossa tumors were the most common. Neurologic deficits developed on follow-up evaluation in 47% of the patients, often precipitating further study and eventual diagnosis of the tumor. Delay in tumor diagnosis averaged 6.3 years. CT with contrast was the most frequently used initial diagnostic radiographic technique, detecting a tumor in 40 of 43 examinations. MRI was subsequently used to confirm and better delineate the tumor in five of five cases. Carbamazepine was the most effective drug for relieving trigeminal neuralgia, but relief was usually temporary. Of the surgical treatment options, total removal of the tumor was the most effective in completely relieving tic pain. In patients at high surgical risk, however, temporarily or permanently blocking afferent impulses with radiofrequency ablation, glycerol rhizotomy, or alcohol blocks was a good alternative to craniotomy.

Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients.

PURPOSE A minority of cancer survivors develops long-term postsurgical neuropathic pain. Based on evidence that capsaicin, the pungent ingredient in hot chili peppers, might be useful for treating neuropathic pain, we developed the present clinical trial. PATIENTS AND METHODS Ninety-nine assessable patients with postsurgical neuropathic pain were entered onto this study. After stratification, patients were to receive 8 weeks of a 0.075% capsaicin cream followed by 8 weeks of an identical-appearing placebo cream, or vice versa. A capsaicin/placebo cream was to be applied to the painful site four times daily. Treatment evaluation was performed by patient-completed weekly questionnaires. RESULTS During the first 8-week study period, the capsaicin-cream arm was associated with substantially more skin burning, skin redness, and coughing (P < .0001 for each). Nonetheless, treatment was stopped for patient refusal or toxicity just as often while patients were receiving the placebo as compared with the capsaicin. The capsaicin cream arm had substantially more pain relief (P = .01) after the first 8 weeks, with an average pain reduction of 53% versus 17%. On completion of the 16-week study period, patients were asked which treatment period was most beneficial. Of the responding patients, 60% chose the capsaicin arm, 18% chose the placebo arm, and 22% chose neither (P = .001). CONCLUSION A topical capsaicin cream decreases postsurgical neuropathic pain and, despite some toxicities, is preferred by patients over a placebo by a three-to-one margin among those expressing a preference.

Distinction between neo plastic and radiation‐induced brachial plexopathy, with emphasis on the role of EMG

results of clinical, radiologic, and electro physiologic studies are retrospectively reviewed for 55 patients with neo plastic and 35 patients with radiation-induced brachial plexopathy. The presence or absence of pain as the presenting symptom, temporal profile of the illness, presence of a discrete mass on CT of the plexus, and presence of myokymic discharges on EMG contributed significantly to the prediction of the underlying caw of the brachial plexopathy. The distribution of weakness and the results of nerve conduction studies were of no help in distinguishing neo plastic from radiation-induced brachial plexopathy.

Radiation-associated atheromatous disease of the cervical carotid artery: report of seven cases and review of the literature

The natural history of postirradiation extracranial cerebrovascular disease is uncertain. Previous reported cases spanning 20 years of carotid surgery are difficult to evaluate, because patients may sometimes have unspecified symptoms, physical examinations, postoperative results, and follow-up. Also, the evolution of carotid surgery over the past two decades makes it impossible to compare earlier operative technique with the state-of-the-art technique of today. Our series of 7 patients underwent 9 carotid endarterectomies with an average follow-up period of 46 months. The number of patients is small, and although technically this is a more difficult operation, we feel the results are favorable and may be comparable with endarteerctomy procedures in nonirradiated patients. These patients should be approached as if radiation changes are not a major factor when they are considered for reconstructive arterial surgery.

Effects of radiation and chemotherapy on cognitive function in patients with high-grade glioma.

PURPOSE The effect of radiotherapy on the long-term cognitive performance of patients treated for intracranial neoplasm is a major concern to clinicians and patients, particularly as long-term survival or cure is possible for a small minority of patients. To assess the effects of cranial radiotherapy and chemotherapy on the cognitive performance of high-grade glioma patients, we analyzed cognitive performance data collected in a series of prospective clinical trials. METHODS We studied 701 high-grade brain tumor patients entered onto two consecutive North Central Cancer Treatment Group (NCCTG) randomized treatment trials designed to compare radiotherapy and carmustine (BCNU) versus radiotherapy and 1-(2-chloroethyl)-3(2,6 dioxo-l-piperidyl)-1-nitrosource a (PCNU) (first trial) and radiotherapy and BCNU and interferon alfa (IFN) versus radiotherapy and BCNU (second trial). Folstein Mini-Mental Status Exam (MMSE) score and Eastern Cooperative Oncology Group (ECOG) performance score (PS) recorded at baseline and 6, 12, 18, and 24 months were analyzed to assess cognitive and physical function over time. Patients who did not demonstrate tumor progression within 60 days of the assessment time were considered nonprogressors at that evaluation. A loss of greater than 3 points on the MMSE was considered significant deterioration. RESULTS The number of patients who experienced a greater than 3-point decrease in MMSE from baseline was 13 of 119 nonprogressors (10.9%; 95% confidence interval [CI], 6.3% to 18.9%) at 6 months, three of 54 nonprogressors (5.5%; 95% CI, 0.5% to 12.8%) at 12 months, three of 30 nonprogressors (10%; 95% CI, 2.1% to 26.5%) at 18 months, and four of 22 nonprogressors (18.2%; 95% CI, 5.2% to 40.3%) at 24 months. The CIs at all times overlapped, which indicates no statistically significant increase in the percentage of patients who experienced a significant decrease in their MMSE score. Patients who demonstrated a significant decrease in their MMSE score were significantly older than those who did not (P = .0017) at 6 months and remained so throughout follow-up; moreover, they had a significantly shorter time to progression and death. ECOG PS was strongly negatively correlated with MMSE score throughout the study, and MMSE score at all time intervals was correlated with baseline PS. CONCLUSION In this population of glioma patients who received radiotherapy, there is no clear trend to cognitive worsening. Factors such as older age, poorer PS, and subclinical tumor progression may be more significant factors in those patients who did demonstrate a significant cognitive decline.

A phase 3 randomized study of radiotherapy plus procarbazine, CCNU, and vincristine (PCV) with or without BUdR for the treatment of anaplastic astrocytoma: a preliminary report of RTOG 9404.

PURPOSE This study was an open label, randomized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine, CCNU, and vincristine (PCV) chemotherapy with or without bromodeoxyuridine (BUdR) given as a 96-hour infusion each week of radiotherapy. METHODS AND MATERIALS Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible; central pathology review was accomplished, but was not mandated prior to registration. The study had initially opened as a Northern California Oncology Group (NCOG) trial in 1991, becoming an Intergroup RTOG, SWOG, and NCCTG study in July 1994. Total accrual of 293 patients was planned as the sample size, using survival and time to tumor progression as the primary endpoints. The experiment arm (RT/BUdR plus PCV) was to be compared to the control arm (RT plus PCV) using an alpha = 0.05, one-tailed, with a power of 85% for detecting an increase in median survival from 160 to 240 weeks, assuming a 3-year follow-up after completion of enrollment. RESULTS As of July 1996, 281 patients had been randomized; 53 (20%) were ineligible, primarily based upon central pathology review, and another 39 cases were canceled. In total, 30% of cases were excluded from analysis. The treatment arms were well balanced despite this rate of exclusion. The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival. In February 1997, the study was closed prior to full enrollment. At that time, the 1-year survival estimates were 82% versus 68% for RT plus PCV and RT/BUdR plus PCV respectively (one-sided, p = 0.96). The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01%. The differences in the two arms seem to be due to early deaths in the BUdR arm, not related to toxicity of the treatment. CONCLUSIONS Despite encouraging Phase 2 results with BUdR, it is unlikely that a survival benefit will be seen. A final study analysis will not be done for at least 3 more years.

Magnetic Resonance Imaging in Brachial Plexopathy of Cancer

Article abstract-We retrospectively reviewed the clinical records of all patients with cancer and brachial plexopathy who had an MRI of the brachial plexus between 1984 and 1993 (71 patients). The MRIs were reevaluated in a blinded fashion. The presence of a mass adjacent to the brachial plexus on MRI was highly predictive of tumor infiltration as determined by clinicopathologic criteria and was the most useful feature in distinguishing radiation plexopathy from tumor infiltration. Increased T2 signal in or near the brachial plexus was commonly seen in both groups and was not useful in this distinction. MRI was very sensitive for brachial plexus abnormalities in this condition, and limited comparison with CT suggested that MRI is superior to CT as an imaging modality. CT performed sufficiently well, however, to suggest that a prospective comparison study of the cost effectiveness and clinical utility of the two imaging modalities in this clinical setting is warranted. NEUROLOGY 1995;45: 421-427

Brain metastasis in hypernephroma

Of 926 patients with hypernephroma, 36 (3.9%) had metastasis to the brain. The median age at presentation was 61 years (range, 34 to 82). Nineteen patients had a single lesion metastatic to the brain, and 16 of these lesions were supratentorial. In 28% of the patients, computed tomography showed hyperdense lesions before contrast material was injected. All patients, except 2 with incomplete records, had evidence of widespread disease involving bone, liver, or lung. The median time interval between the initial diagnosis and the discovery of brain metastasis was 65.5 weeks (range, 0 to 462), with only 2 patients initially presenting with brain metastasis. Twenty-five of the patients who received only radiation therapy had a median survival of 13 weeks (range, 4 to 146), while 7 selected patients who underwent surgical resection and postoperative radiation had a median survival of 66 weeks (range, 18 to 260). In 5 of the 7 patients, scans demonstrated recurrent tumor from 6 to 23 weeks postoperatively. One patient had a pronounced reduction in the size of the tumor after radiation therapy only. This study shows that brain metastasis is usually a late complication of hypernephroma and is associated with a poor prognosis.

Magnetic Resonance Imaging in Cancer-Related Lumbosacral Plexopathy

OBJECTIVE To study the relative utility of computed tomography (CT) and magnetic resonance imaging (MRI) of the lumbosacral plexus in patients with systemic cancer and plexopathy. DESIGN In a retrospective study, we identified all patients encountered at Mayo Clinic Rochester between 1987 and 1993 with a diagnosis of lumbosacral plexopathy, and we selected for analysis those with MRI scans of the plexus (an abnormal finding was not necessary for inclusion) and a clinical and electrophysiologic appearance consistent with a diagnosis of metastatic lumbosacral plexopathy. MATERIAL AND METHODS The study group consisted of 31 patients (20 men and 11 women). The types of tumor were as follows: prostatic, 10 patients; colorectal, 7; bladder, 3; cervical, 3; and other, 8. Eighteen patients had received pelvic radiotherapy before diagnosis of lumbosacral plexopathy. All available MRI scans (in 27 patients) were reviewed blinded; the initial imaging report was used if the actual scans were unavailable (in 4). CT had been done in 22 patients, and results for 16 were available for blinded review. Original reports were available for the other six. RESULTS Direct involvement of the lumbosacral plexus by tumor was evident on 23 MRI studies, and 6 others showed widespread metastatic disease in the region of the plexus. On 13 CT examinations, direct involvement of the lumbosacral plexus by tumor was noted. In four patients, MRI findings were abnormal and CT findings were normal. No patient had abnormal CT findings and normal MRI findings. CONCLUSION In this retrospective review, MRI was more sensitive than CT for diagnosing cancer-induced lumbosacral plexopathy. Thus, use of MRI should be considered in the diagnostic work-up of patients with clinical and electrophysiologic evidence of plexopathy and suspected systemic cancer.