Correspondence 1005

spectively, to differentiate false-negative frozen-section pa- tients (microscopic lymph node disease) from true positive patients (unpublished data). Only at the extremes of PSA and grade can we predict lymph node metastases with greater efficiency than by frozen section and, for the major- ity of our patients, there is no relationship between PSA and biopsy grade, and size of the metastasis. Metastasis does not necessarily result in lymph node enlargement.

As prostate cancer is diagnosed “earlier,” I anticipate that a greater proportion of metastases will be occult,’ for the diagnosis of which current routine clinical laboratory tests and imaging are inadequate. The application of new diagnostic technology (such as polymerase chain reaction amplification” for the detection of currently occult can- cer cells in the blood stream or tissues obtained with minimally or noninvasive techniques with imaging local- ization) is needed for the accurate and cost-effective stag- ing and treatment of prostate cancer.

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Rifkin MD, Zerhouni EA, Gatsonis CA, Quint LE, Paushter DM, Epstein JI, et al. Comparison of magnetic resonance imaging and ultrasonography in staging early prostate can- cer. N Engl J Med 1990;323:39-45. Davis GL. Sensitivity of frozen section examination of pelvic lymph nodes for metastatic prostate carcinoma. Cancer

Campbell SC, Klein EA, Levin HC, Piedemonte MR. Open pelvic lymph node dissection for prostate cancer: a reassess- ment. Urology 1995;46:353-5. Blute ML. Refining the early detection and staging of pros- tate cancer [editorial]. J Urol 1995; 154:1401-2. Flanigan RC. Prostate cancer [editorial]. J Urol 1995; 154: 1084. Narayan P, Fournier G, Gajendran V, Leidich R, Lo R, Wolf JS, et al. Utility of preoperative serum prostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer. Urology

Van Poppel H, AMeye F, Oyen R, Van de Voorde W, Baert L. Accuracy of combined computerized tomography and fine needle aspiration cytology in lymph node staging of local- ized prostatic carcinoma. J Urol 1994; 151:1310-4. Wolf JS, Cher M, Dall’Era M, Presti JC Jr, Hricak H, Carroll PR. The use and accuracy of cross-sectional imaging and fine needle aspiration cytology for detection of pelvic lymph node metastases before radical prostatectomy. j Urol

Bretton PR, Melamed MR, Fair WR, Cote RJ. Detection of occult micrometastases in the bone marrow of patients with prostate cancer. Prostare 1994;25:108-14. Foss AJE, Guille MJ, Occleston NL, Hykin PG, Hungerford JL, Lightman S. The detection of melanoma cells in peripheral blood by reverse transcription-polymerase chain reaction. Br J Cancer 1995;72:155-9.

1995;76:661-8.

1994; 44:519-24.

1995; 153:993-9.

Gustave L. Davis, M.D. Department of Pathology and Laboratory Medicine

Bridgeport Hospital Bridgeport, CT

Cost Effectiveness and Outcome Assessment of Magnetic Resonance Imaging in Diagnosing Cord Compression

read with interest the recent article of Jordan et al., I [“Cost Effectiveness and Outcome Assessment of Mag- netic Resonances Imaging in Diagnosing Cord Compres- sion”] regarding cost-effectiveness of magnetic reso- nance imaging (MRI) versus myelography for diagnosing malignant epidural spinal cord compression. I would like to raise some issues that might influence their model.

First, the authors do not address the issue of how much of the spinal column was imaged in the MRI versus the myelography group. When myelography is utilized to diagnose cord compression, the standard of care has been a complete myelogram.’ If high-grade block is present, this may require a second injection of dye above the level of the block. In contrast, the mean cost of $2283 for MRI patients in Jordan’s study suggests that, on average, fewer than two of three spinal segments (cervical, thoracic, and lumbosacral) were imaged. Therefore, patients receiving myelograms were more likely to have complete spinal imaging. Although more expensive, myelography might actually result in a better neurologic outcome, since 10% to 30% of patients with epidural disease at one spinal site will have epidural disease at a remote site that might be missed by subtotal spine MRL2.”‘ Costs in Jordan’s two groups might have been quite similar had each group had the entire neuraxis imaged. From the neuro-oncologic viewpoint, imaging the entire spine is preferable to im- aging only the segment clinically suspected of harboring epidural tumor.

Second, the authors state that the cost of a false positive neuroimaging study includes the cost of radiation followed by the cost of surgery, implying that standard treatment consists of this combination. They admit that, “radiation will not be followed by surgery in all cases.” In fact, treat- ment for spinal cord compression generally consists of radi- ation therapy alone. Surgery is sometimes employed as ini- tial therapy in patients requiring a tissue diagnosis, patients with radioresistant tumors, and patients with spinal insta- bility. Radiation followed by surgery is not standard treat- ment for spinal cord compression, although this sequence of events may occur in patients who deteriorate during radi- ation, or in patients who eventually relapse following an initial response to radiation.

Finally, although spinal cord compression is indeed a neurologic emergency, and although pretreatment neu- rologic status is the most important predictor of treat- ment o ~ t c o m e , ~ , ~ , ~ , * ~ ’ I am aware of no data which sup- ports the authors’ hypothesis that a 16-hour average delay

1006 CANCER March 1,1996 / Volume 77 / Number 5

in diagnosis because of difficulty in arranging myelogram would increase the percentage of patients ultimately non- ambulatory from 32% to 64%. Spinal cord dysfunction from malignant epidural disease rarely develops without warning; most patients have had symptoms [particularly pain) for weeks to months before the diagnosis is consid- ered."" Certainly it is important to minimize delays in obtaining the MRI scan or myelogram once epidural cord compression has been considered. However, educating the cancer patient and caregivers on the importance of expeditious medical attention for symptoms of epidural disease is likely to be far more important in reducing the numbers of patients with poor outcomes.

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Posner JB. Neurologic complications of cancer. Philadel- phia: F.A. Davis, 1995:128. Loeffler JS, Glicksman AS, Tefft M, Gelch M. Treatment of spinal cord compression: A retrospective analysis. Med Pedi- atr Orzcoll983; 11:347-351. van der Sande JJ, Kroger R, Boogerd W. Multiple spinal epi- dural metastases; an unexpectedly frequent finding. J Neurol Neurosurg Psychiatry 1990; 53:lOOl-3. Ruff RL, Lanska DJ. Epidural metastases in prospectively evaluated veterans with cancer and back pain. Cancer

Gilbert RW, Kim JH, Posner JB. Epidural spinal cord com- pression from metastatic tumor: Diagnosis and treatment. Ann Neurol 1978;3:40-51. Greenberg HS, Kim JH, Posner JB. Epidural spinal cord com- pression from metastatic tumor: Results with a new treat- ment protocol. Ann Neurol 1980; 8:361-366. Maranzano E, Latini P, Checcaglini F, Ricci S, Panizzo BM, Aristei C, et al. Radiation therapy in metastatic spinal cord compression. Cancer 1991; 67: 131 1- 1317. Findlay GFG. Adverse effects of the management of malig- nant spinal cord compression. J Neurol Neurosurg Psychiatry

Zevallos M, Chan PYM, Munoz L, Wagner J, Kagan AR. Epi- dural spinal cord compression from metastatic tumor. lnt J Radiat Oncol Biol Phys 1987; 13:875-878. Helweg-Larsen S, Sorensen PS. Symptoms and signs in met- astatic spinal cord compression: a study of progression from first symptom until diagnosis in 153 patients. Eur J Cancer

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David Schiff, M.D. Department of Neurology

Mayo Clinic Rochester, Minnesota

What Is the Etiology of Human Brain Tumors?

here is an increasing incidence of human brain tu- T mors, especially among the elderly, in the western

world.' The First Lebow Conference discussed, among other things, exposure to electromagnetic fields as a risk factor for human brain tumors as well as a potential asso- ciation.' Because we have recently evaluated epidemio- logic and experimental findings regarding exposure to extremely low frequency electromagnetic fields (EMF) and the risk for malignant diseases3 we would like to make some additional comments on this topic. In this review, we have scrutinized all available peer-reviewed articles according to bibliographic services and reference lists.

Residential exposure to EMF (mainly overhead power lines) in relation to central nervous system tumors in children was analyzed in six ~ t u d i e s ~ - ~ and in three studies for tumors in Five of these studies had measured and/or estimated exposure in microTesla (pT). We concluded that when considering all later studies to- gether, there was no support for the hypothesis of an association between EMF exposure and central nervous system tumors in children and adults as initially postu- lated by Wertheimer and Lee~er .~ ,"

Results regarding childhood central nervous system tumors and parental exposure to EMF were given in five

All were of the hypothesis-generating type with no assessment of measured or evaluated exposure to magnetic fields, or control for other potential risk fac- tors for these tumor types. Although most odds ratios were above unity, no conclusion could be drawn. More- over, in light of the lack of evidence of genotoxicity of

it is presently difficult to imagine how paternal exposure could influence cancer risk in offspring."

We divided the results for occupational exposure to EMF and central nervous system tumors according the International Classification of Diseases (ICD) of the World Health Organization code or histopathology in the pub- lished papers if such results were available. Eleven studies gave results for central nervous system tumors as a whole group. Evaluated exposure in pT was given in one study,21 but the rest used occupational codes as a surrogate for exposure to Brain tumors were studied in 12 pub l i~a t ions~*-~~ with group level measurements of expo- sure to EMF based on job titles in Z.4',43 Five studies dis- cussed glioma but none presented exposure in pT.44-4H Six studies gave results for a~trocytoma,~'"'"-"' two with measured and estimated exposure in pT.50*s2 Based on the results from all these studies, we concluded that there seemed to be a consistent pattern of increased risk for central nervous system tumors (including brain tumors) among workers in occupations involving the design, manufacture, installation, or maintenance of electronic or electrical equipment. Factors such as solvents, poly- chlorinated biphenyls, plasticizers, soldering fumes, or other agents prevalent in these occupations should be considered further. We did not find a consistent pattern