Journal of Neuro-Oncology 8: 275-280, 1990. © 1990 Kluwer Academic Publishers. Printed in the Netherlands.

Clinical Study

Decompression of epidural metastases from germ cell tumors with chemotherapy

Karen Cooper, Dean Bajorin, William Shapiro, George Krol, Gordon Sze and George J. Bosl The Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, the Department of Neurology, and the Department of Medical Imaging, Memorial Sloan-Kettering Cancer Center, New York, New York and the Departments of Medicine and Neurology, Cornell University Medical College, New York, New York, USA

Key words: cord compression, germ cell tumors, cisplatin-based chemotherapy

Summary

Epidural cord compression from germ cell tumor metastases is not common. Treatment usually requires high dose corticosteroids with radiation therapy and/or surgical decompression. Three patients with epidural germ cell tumor metastases were treated with cisplatin-based chemotherapy and all three had complete neurologic recovery. Systemic chemotherapy should be considered as initial therapy with corticosteroids for epidural cord compression from metastatic germ cell tumor.

Abbreviations: DOX - Doxorubicin, CYC - Cyclophosphamide, CDDP - Cisplatin, BLEO - Bleomycin, VBL - Vinblastine, ETO - Etoposide, IFOS - Ifosfamide, PROC - Procarbazine, VINC - Vincristine, ACT D - Actinomycin D. Adapted from Friedman [16].

Introduction

Epidural cord compression usually requires high dose corticosteroids with radiation therapy and/or surgical decompression in order to minimize the neurological sequelae. Chemotherapy has only rarely been used. However, the treatment of meta- static germ cell tumors (GCT) has become increas- ingly successful with cisplatin-based combination chemotherapy and most patients respond to ther- apy [1, 2]. Recently, three consecutive advanced stage III GCT (two with embryonal carcinoma (EC), and one with seminoma (S)) with metastatic epidural disease were treated with cisplatin-based chemotherapy. All three patients presented with symptoms of spinal cord compression that was doc- umented radiographically. Each was treated with systemic chemotherapy as their first mode of in-

tervention. Immediate pain relief and complete neurological recovery was observed in all three patients without radiation therapy or surgical de- compression.

Case reports

Case 1

A 30 year old white male presented in April 1986 with cough, chest pain and a chest x-ray showing a mediastinal mass. He underwent bronchoscopy and mediastinoscopy and an embryonal carcinoma was found pathologically. He was treated with car- boplatin, etoposide, and bleomycin between June and October 1986. A residual mass was resected and revealed viable tumor. New pulmonary nodu-

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Fig. 1. Case l - Top: Myelogram showing destruction of L3 with a ventral epidural mass (arrow) and obstruction extending to L4. Bottom: Follow-up exam performed after chemotherapy shows no evidence of obstruction.

les and an increased H C G were found in November 1986. He was treated with three cycles of vinblas- tine, actinomycin D, bleomycin, cisplatin and cy- clophosphamide (VAB-6) [1] with a partial re- sponse. In March 1987 the patient progressed with new pulmonary nodules and an investigational drug was initiated. In June 1987 the patient pre- sented with leg weakness, difficulty walking down stairs and diffuse lower back pain. A myelogram and CT scan revealed destruction of L3 with a ventral epidural mass extending to L4 with a partial epidural compression. He was immediately begun on dexamethasone 24 mg every six hours and sal- vage chemotherapy with cisplatin, etoposide, ifos- famide, and mesna [3]. Four cycles of chemother- apy were administered. Steroids were tapered over two weeks. Resolution of all neurological symp- toms occurred and complete regression of the epid-

ural mass was documented by myelogram (Fig. 1) and CT scan (Fig. 2) and a 50% decrease in pulmo- nary nodules and mediastinal mass was noted. Sub- sequently, the patient developed brain metastases and died from progression of his disease in Novem- ber 1987.

Case 2

A 30 year old white male presented in August 1985 with a testicular mass and increased AFP. A left inguinal orchiectomy was done followed by a retro- peritoneal lymph node disection for a persistently elevated AFP and the pathology of both specimens revealed EC. In November 1985 the patient had an elevated AFP. An evaluation failed to reveal a specific site of disease and he was treated with four

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Fig. 2. Case 2 - Top: Myelogram showing complete block at T7-T8 (arrow). Bottom: Refluoro-myelogram performed after chemother- apy shows complete passage of contrast through T7-T8.

cycles of cisplatin and etoposide [1] with normal- ization of the AFP. In September 1986 an elevated AFP was detected and an evaluation failed to re- veal the site of metastases. He was treated with VAB-6 for three cycles with response. In April 1987 an elevated AFP and a positive bone scan were found. A resection of the left 8th rib was positive for EC and surgery resulted in normal- ization of the AFP. In September 1987 the patient developed an increased AFP and back pain but chose to delay treatment until October 1987 when he presented with leg weakness and difficulty walk- ing. A C T scan, myelogram and MRI revealed a complete block at T7-8 and a partial block at T6 consistent with an epidural mass from T6 to T8. He was started on dexamethasone 24mg every six hours and salvage chemotherapy with cisplatin, etoposide, ifosfamide, and mesna. Four cycles of

therapy were given and the patient had a complete neurologic recovery. A myelogram documented free passage of dye (Fig. 3) and an MRI (not shown) demonstrated complete disappearance of the epidural mass. The patient has no evidence of disease at present, 17 months from treatment.

Case 3

A 38 year old white male presented in November 1985 with a left testicular mass and underwent an inguinal orchiectomy, the pathology of which was seminoma. Stage I disease was present and he was treated with infradiaphragmatic radiation therapy. In February 1986 the patient presented with sternal chest pain and an anterior mediastinal soft tissue mass and a positive bone scan at the 7th left rib and

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100 mg bolus followed by 24 mg every six hours and salvage chemotherapy with cisplatin, etoposide, ifosfamide and mesna. The patient received four cycles of chemotherapy with complete neurologic recovery and complete resolution of the epidural mass documented by myelogram (Fig. 3). The pa- tient has no evidence of disease at present, 14 months from treatment; however, he has devel- oped osteonecrosis of both femoral heads second- ary to radiation therapy.

Discussion

Fig. 3. Case 3 - Left: Myelogram with needle placed between L4-L5 showing complete block at L5-$1. Right: Follow-up exam after chemotherapy shows no evidence of obstruction.

sternum. A rib biopsy revealed seminoma. Be- tween June and September 1986 he was treated with four cycles of VAB-6. In January 1987 he developed a mass over the sternum with a positive bone scan. A biopsy was positive for seminoma. He was treated with four cycles of cisplatin and etopo- side and subsequent radiation therapy to the ster- num for residual disease. In January 1988 the pa- tient presented with lower back pain, urinary and fecal incontinence and leg weakness. A myelogram and CT scan revealed a complete block at L5-$I. He was immediately started on dexamethasone

The treatment of epidural metastases from GCT with cisplatin-based chemotherapy as a first-line modality is indicated in patients who are previously untreated or who have previously responded to chemotherapy. Early diagnosis and aggressive management are essential for a successful outcome to this oncologic emergency. Patients will present with classical signs and symptoms of spinal cord compression and then a treatment decision must be made. Cisplatin-based chemotherapy should be considered as the first therapy for epidural metas- tasis from GCT. Initiating chemotherapy along with steroids will not only treat the area of epidural disease, but other metastatic sites.

Historically, the primary mode of treatment for patients with epidural metastasis was decompres- sive laminectomy. Outcome was measured in terms of ambulation. Corticosteroids were usually begun prior to surgery since they were shown to decrease edema in patients with brain tumors and thus thought would do the same for lesions of the spinal cord [4]. Surgery was then followed by RT in most cases. Two series retrospectively compared pa- tients treated with surgery alone versus patients treated with surgery and RT [5, 6]. Both studies demonstrated that patients treated with postoper- ative RT had a much higher response rate than those treated with surgery alone.

Several series retrospectively reviewed the re- sults of treatment with RT alone. Of 130 cases of spinal cord compression seen at MSKCC between 1974-1976 and another 105 patients previously re- ported between 1964-1970, 65 patients were treat-

ed with surgery and RT and 170 with RT alone [7, 8]. There was no difference in outcome in the two groups; 46% were ambulatory with the combined modality and 49 % with radiation therapy. The best outcome was achieved in those patients who were ambulating at the onset of symptoms. Those pa- tients with paraplegia did poorly regardless of treatment modality. Patients with radiosensitive tumors again fared better. Two other studies failed to demonstrate the value of surgery in addition to RT in patients with cord compression secondary to metastatic disease [9, 10].

Chemotherapy has rarely been used as initial treatment. The use of corticosteroids alone must not be underestimated. In a rat model dexametha- sone caused significant although transient resolu- tion of neurologic dysfunction from epidural spinal cord metastases [11]. Posner described the 'onco- lytic effect of glucocorticoids' in four patients with lymphoma, seminoma, thymoma and Ewing's sar- coma [4]. Two were treated with steroids only (thy- moma and lymphoma) and the other two with a combination of steroids and chemotherapy. All four patients had rapid relief of their symptoms with marked tumor shrinkage. The benefit of ste- roids alone or in conjunction with chemotherapy has been reported in a small number of cases (Ta- ble 1). The largest series of patients treated with chemotherapy is in the treatment of neuroblastoma and Ewing's sarcoma [12]. Fourteen patients were treated with chemotherapy, five of whom had un- dergone prior laminectomy. All patients had

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prompt neurologic recovery after chemotherapy. The five patients who underwent an initial laminec- tomy did poorly until they received chemotherapy. Neuroblastoma and Ewing's sarcoma are chemore- sponsive tumors which are more likely to show benefit from initial definitive treatment with che- motherapy. A retrospective review of the Memo- rial Sloan-Kettering Cancer Center (MSKCC) ex- perience with RT and chemotherapy revealed that 14/41 (34%) patients became ambulatory and in half there was radiographic documentation of re- sponse [13]. Patients with radiosensitive and che- mosensitive tumors such as lymphoma, Ewing's sarcoma, and neuroblastoma fared better than those with more resistant malignancies.

These three GCT patients presented with classi- cal symptoms of epidural metastasis causing spinal cord compression. A myelogram was done in all patients prior to starting therapy along with CT scan and MRI in some cases. Steroids were initi- ated on the day of presentation with chemotherapy starting 24 hours thereafter. Since all the patients had had more than one relapse from a complete remission each was treated with a third-line treat- ment program. It is important to note that all three patients had previously responded to chemother- apy which had included cisplatin; each responded to a third cisplatin-containing regimen. All patients had prompt relief of their neurologic dysfunction after completing the first five-day cycle.

Myelograms performed before and after chemo- therapy were done demonstrating complete disap-

Table 1. Treatment of spinal cord compression with chemotherapy and/or corticosteroids

Treatment # Pts Type of tumor Response (Pts) Reference

Dexamethasone - 96 mg/daily 2 Lymphoma 2 Dexamethasone - 96 mg/daily 1 Lymphoma 1 Dexamethasone - 96 mg/daily 1 Thymoma 1 Dexamethasone - 160 mg/daily 2 Breast 2 DOX/CYC 2 Ewing 2 DOX/CYC/CDDP 6 Neuroblastoma 6 CDDP/BLEO/VLB 1 GCT 1 Dexamethasone (96 mg/daily)/CDDP/ETO/IFOS/MESNA 3 GCT 3 Dexamethasone (160 mg/daily)/VINC/PROC 1 Hodgkin's 1 Dexamethasone (96 mg/daily)/CDDP 1 GCT 1 Dexamethasone (96 mg/daily)/CYC/ACT D/BLEO 1 Ewing's 1

14 4 4

14 12 12 15 present 14 4 4

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pearance of the original metastases. In some in- stances MR/and/or CT scans were also performed. There is no indication to perform repeatedly all three modes of radiographic documentation. One is sufficient to follow patients long term. MRI alone is probably satisfactory. The absence of a prior response to a cisplatin-based regimen pre- cludes a chemotherapy approach to epidural dis- ease from GCT.

Conclusion

In the treatment of epidural spinal cord compres- sion, one must consider all modalities of therapy. In those tumors known to be chemoresponsive (e.g. GCT, lymphoma, neuroblastoma, Ewing's sarcoma) chemotherapy should be considered as first-line treatment once steroids have been initi- ated and radiographic documentation is complete. This approach can result in the resolution of neur- ologic dysfunction due to epidural metastases as well as address all sites of metastatic disease. Spe- cifically in GCT, initial cisplatin-containing chemo- therapy is excellent initial therapy in previously untreated or previously responding patients with epidural spinal cord compression. RT and/or sur- gery should be considered when the disease is not chemotherapy responsive or when the diagnosis is in doubt.

Acknowledgements

Supported in part by grants CA 07337, CA 05826, and CA 09207 from the National Cancer Institute and the Brian Piccolo Cancer Research Fund.

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Address for offprints: G.J. Bosl, Memorial Hospital, 1275 York Avenue, New York, New York 10021, USA