Ten-Year Follow-Up of a Patient with Metastatic Ewing's Sarcoma of the Pelvis
Ten-Year Follow-Up of a Patient with Metastatic Ewing's Sarcoma of the Pelvis
Ashford, Robert U.;McCloskey, Eugene V.;Purohit, O. Prakash;Ingram, Christine E.;Grimer, Robert J.;Coleman, Robert E.
2002-01-01 00:00:00
Patient: We report a 32-year-old women with a pelvic Ewing’s sarcoma, who developed skeletal metastases within 20 months of diagnosis but following treatment remains disease-free at 10 years. Discussion: Ewing’s sarcoma is a highly malignant tumour of bone. Presentation of a pelvic tumour over the age of 30 years is extremely rare and associated with a poor prognosis. Early recurrence is also associated with an extremely grave prog- nosis. In our patient there was little or no response to salvage chemotherapy, but, against the odds, remission was induced with pamidronate and palliative radiotherapy to some but not all sites of disease. This remission has been maintained without additional therapy for a further 5 years. Key words: Ewing’s sarcoma, pelvis, bisphosphonates, metastases Introduction Eight months after completion of chemotherapy (20 months after surgery), she experienced discom- Metastatic Ewing’s sarcoma of the pelvis has an fort in the chest, and a chest radiograph revealed extremely poor prognosis in adult patients. We multiple lytic metastases in the ribs (Fig. 2). CT report the case of a woman aged 32 years at diag- scanning demonstrated no soft tissue extension of nosis, who developed skeletal metastases within 20 these lesions. A 99-technetium isotope bone scan months of diagnosis but following treatment remains revealed areas of increased uptake in the pelvis, ribs, disease-free at 10 years. spine and sternum, consistent with multiple metas- tases (Fig. 3, left). Her full blood count was normal. Case report Given the typical appearances of metastases both A 32-year-old woman was referred to Weston Park radiologically and on isotope bone scanning, con r- Hospital in 1990 with a Ewing’s sarcoma of the right matory biopsy was not performed. She was subse- superior pubic ramus (Fig. 1a,b). Following three quently treated with ve cycles of carboplatin and cycles of pre-operative chemotherapy with ifosfamide methotrexate. A further cycle of chemotherapy was vincristine and doxorubicin (IVAD), she underwent a not given because of deterioration in her renal two-stage tumour excision and endoprosthesis with a function as assessed by both creatinine clearance titanium hemipelvic replacement. She then received (Table 1) and by an increase in creatinine from 90 m m post-operative chemotherapy with the same agents, mol/l (pre-chemotherapy) to 250 mol/l. The chest substituting actinomycin D for doxorubicin after a pain persisted and required radiotherapy (single frac- total of six cycles of IVAD during which time her tion of 600cGy) to the left lateral ribs and the left hip renal function deteriorated (Table 1). Her endopros- (2000 cGy in ve fractions). In addition, three cycles thetic surgery was complicated by a streptococcal of intravenous pamidronate (120 mg per cycle) were wound infection and subsequently dislocation of also given for the bone pain, with good, but tempo- her prosthesis. rary, symptomatic relief. Correspondence to: Mr Robert U. Ashford MRCS (Glasg.), Rose Cottage, Crooked Lane, Kirk Hammerton, York YO26 8DG, UK. Tel.: +44-1423-339361; E-mail: robert.ashford@virgin.net ISSN 1357–714X print/ISSN 1369–1643 online/02/0200131–04 © Taylor & Francis Ltd DOI: 10.1080/1357714021000022140 132 Ashford et al. Table 1. Creatinine clearance in this patient over time Date Notes Creatinine clearance (ml/min) 1990 Pre-chemotherapy 90 January 1991 Post IVAD 70 December 1991 After recurrence 50 Late 1992 After salvage chemotherapy 30 All subsequent measurements 30–35 Fig. 1. (a) Radiograph of the pelvis demonstrating a tumour of the right superior pubic ramus. (b) Histology (H&E) characteristic of Ewing’s sarcoma. Discussion Six months later (late 1992), a further 6-week course of low-dose weekly palliative chemotherapy Ewing’s sarcoma is a highly malignant round-cell with vincristine, epirubicin and cyclophosphamide tumour of bone that occurs most commonly between was administered. This did not produce any signi - the ages of 10 and 25 years. Presentation over the age cant symptomatic improvement and was followed by of 30 years, as in our patient, is extremely rare and is palliative radiotherapy to the left shoulder (800 cGy associated with a poor prognosis. The pelvis is the in a single fraction) and again to the left hip (800 cGy most commonly affected site and carries an espe- in a single fraction). Intermittent infusions of cially poor prognosis with high rates of both local 1–4 pamidronate 120 mg were continued every 4 to 12 recurrence and distant metastases. Surgical resec- weeks as required for pain with good symptomatic tion in combination with chemotherapy has improved 1–4 improvement. A further course of fractionated radio- the prognosis of pelvic Ewing’s sarcoma, but the therapy (1250 cGy in ve fractions) for a recurrence outlook remains poor in those patients who develop of severe bone pain in her lower ribs was required in skeletal metastases. Of the seven patients over the age late 1993. Isotope bone scanning at this stage demon- of 20 years managed at UCLA, who developed bone strated further increased uptake in the pubic rami and persistence of the other skeletal lesions. In 1994, she suffered insuf ciency fractures of both left pubic rami and underwent investigations of bone metabolism. These revealed normal calcium, vitamin D and parathyroid hormone but grossly elevated hydroxyproline and pyridinoline. A unicor- tical, double-labelled iliac crest bone biopsy revealed renal osteodystrophy with signs of hyperparathy- roidism and no evidence of osteomalacia. Treatment with calcitriol corrected her abnormal bone biochemistry. Isotope bone scanning at that stage (1995) revealed no evidence of skeletal metastases, and the focal increased uptake in the ribs had disap- peared (Fig. 3, right). Since 1995, the patient has remained in remission with a recent assessment revealing no evidence of metastatic disease. Serial isotope bone scans remain Fig. 2. Radiograph of ribs demonstrating destructive osteolytic lesions affecting ribs 3 and 4. unchanged from 1995. Metastatic Ewing’s sarcoma of the pelvis 133 Fig. 3. 99-Tc isotope bone scans. (Left) pre-therapy with multiple metastases and (right) post-therapy with resolution and remission induced. metastases, the median survival from date of primary tumour cells. Whether this remarkable response is diagnosis was 21 months (range 6–56 months). related to these phenomena is impossible to Similarly, in two patients of the same age group in the conclude, but the possibility is intriguing and further Mayo Clinic, death occurred within a year of diag- in vivo evaluation of the ‘antitumour effects’ of nosis. Early recurrence can therefore be seen to be bisphosphonates is required. associated with an extremely grave prognosis. This is a complex case and no one intervention is This patient had widespread lytic skeletal metas- responsible for the prolonged survival in this patient. tases, which developed within 2 years of the primary tumour, treated by a combination of chemotherapy, Acknowledgements radiotherapy and bisphosphonates.There was little or no response to salvage chemotherapy, but, against the The authors wish to thank Dr Charles Mangham, odds, remission was induced with pamidronate and Department of Musculo-Skeletal Pathology, Selly palliative radiotherapy to some but not all sites of Oak Hospital, Birmingham, for providing the disease. This remission has been maintained without histology slides. additional therapy for a further 5 years. It is unlikely that radiotherapy played a major role against the References disease given the disseminated nature of the skeletal changes on isotope bone scanning. It may, however, 1. Baldini EH, Demetri GD, Fletcher CDM, Foran J, be that salvage chemotherapy in 1991 and 1992 was Marcus KC, Singer S. Adults with Ewing’s sarcoma/ more effective than we estimated. What goes against primitive neuroectodermal tumor: adverse effect of older age and primary extraosseous disease on this is that prolonged survival with salvage outcome. Ann Surg 1999; 230(1): 79–86. chemotherapy in metastatic Ewing’s disease is 2. Hoffman C, Ahrens S, Dunst J, et al. Pelvic Ewing extremely rare. sarcoma: a retrospective analysis of 241 cases. Cancer The major determinant of a lack of response in this 1999; 85(4): 869–77. case is persisting pain and poor mobility. However, 3. Yang R-S, Eckhardt JJ, Eilber FR, et al. Surgical indi- cations for Ewing’s sarcoma of the pelvis. Cancer 1995; follow-up X-rays failed to demonstrate healing of the 76(8): 1388–97. bone lesions during chemotherapy. Additionally, 4. Frassica FJ, Frassica DA, Pritchard DJ, Schomberg PJ, bone scanning only began to show fading of the hot Wold LE, Sim FH. Ewing sarcoma of the pelvis. spots from 1995. Clinicopathological features and treatment. J Bone Jt Bisphosphonates have potent effects on bone Surg 1993; 75A(10): 1457–65. 5. Jagdev S, Coleman RE, Shipman CM, Amin Rostami- metabolism and the bone marrow microenviron- H, Croucher PI. The bisphosphonate zoledronic acid ment. There are also in vitro data that suggest that induces apoptosis of breast cancer cells: evidence for high concentrations of bisphosphonates may inhibit synergy with paclitaxel. Br J Cancer 2001; 84(8): tumour cell proliferation and promote apoptosis of 1126–34. 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