nodular sclerosis type, stage Ill Bb. He received 6 courses of. ABVD-MOPP, with a total dose of 3 600 mg prednisone (Delta- cortene), followed by radiotherapy ...
Acta Oncologica Vol. 31, No. I, pp. 64-65, 1992
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Correspondence and Short Communications Comments on published articles, short communications 01a preliminary nature, case reports, technical notes and the like are accepted under this heading. The articles should be short and concise and contain a minimum af flgures, tables and references.
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AVASCULAR NECROSIS OF THE FEMORAL HEAD AFTER TREATMENT OF HODGKIN’S DISEASE Advances in the treatment of Hodgkin’s disease have resulted in an increased proportion of long-term survivors, but have also induced various iatrogenic problems. In the present study we have analysed the incidence and possible cause of avascular femoral head necrosis as a complication of therapy for Hodgkin’s disease. During the last 15 years, 950 patients with Hodgkin’s disease were treated at the Radiology Institute and Human Biopathology Department, hematology section of the ‘La Sapienza’ University in Rome. Among these patients 157 received only superdiaphragmatic radiotherapy or, in some cases, subdiaphragmatic irradiation of the lumbo-aortic lymph node regions. Among the remaining 793 patients, four developed osteonecrosis of the femoral head; all these patients had at presentation stage Ill disease. Depending upon the stage of the disease our patients had also received different types of multiple drug chemotherapy (1). Three of the four patients, who developed avascular necrosis had received MOPP-ABVD with alternating courses; the fourth patient had got MOPP only. All the ABVD and MOPP courses given included prednisone. Three of the four patients had received radiotherapy with the femoral heads included in the treated volume. Case I . A 16-year-old male farmer with Hodgkin’s disease, nodular sclerosis type, stage Ill Bb. He received 6 courses of ABVD-MOPP, with a total dose of 3 600 mg prednisone (Deltacortene), followed by radiotherapy with 25 Gy against the superdiaphragmatic lymph node regions and a subdiaphragmatic inverted Y-field. A partial remission was achieved and the patient then received additional treatment with 800.5 mg prednisone in 10.5 months. The total quantity of prednisone was 4 400.5 mg. The patient got pains in the right coxofemoral region, starting 33 months after admission and during the last two months of prednisone treatment. Radiography showed an area of moderately increased density in the right femoral head. The diagnosis of bone necrosis was established two months after the initial symptoms. Case 2. A 26-year-old male electrician, with Hodgkin’s disease stage 111 Ab, nodular sclerosis type. He was given radiotherapy with a total of 44Gy in the superdiaphragmatic lymph node regions and a total of 36 Gy in the lumbo-aortic, inguinal-iliac and inguinal-femoral lymph node regions. After completion of radiotherapy the patient was considered to be in partial remission (PR) and was then treated with 7 courses of MOPP-ABVD, including a total amount of 4 440 mg prednisone ( Delta-cortene). Fifty-three months after the start of the disease and one month before the completion of therapy, while still considered in PR, the patient started to complain of pain in the right leg. X-ray examination showed a small area of bony rarefaction at the level of the right acetabular roof, limited by a narrow strip of bone sclerosis. Bone scintigraphy confirmed the existence of an injured area with increased tracer uptake in both hip joints, and higher uptake on the right side. Later on the pains extended also to the left hip. Six months later radiography showed evident deformity of both femoral heads with asymmetry of the joint cavities and bony sclerosis. The
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diagnosis bilateral femoral head necrosis was established 18 months after the start of the symptoms. Case 3. A 31-year-old housewife with Hodgkin’s disease-stage 111 Bb, nodular sclerosis type. She received 6 courses of MOPP during a 6-month period, including a total dose of 5400mg prednisone. At the end of therapy the patient was considered to be in complete remission (CR), but a lymph node relapse was found in the left axilla 12 months later. She then received 2 courses of MOPP with a total dose of 1 800 mg prednisone, followed by local radiotherapy with 44 Gy. The total amount of prednisone was 7 200 mg. By the end of the therapy, 25 months after the start of the disease, the patient complained of pain in the left hip joint. X-ray examination showed a deformed rima in the left hip joint and a sclerotic area in the upper part of the femoral head, surrounded by a rarefaction. Bone scintigraphy showed increased tracer uptake corresponding to the left acetabular cavity. At orthopedic evaluation the diagnosis of left-side femoral head necrosis was established 8 months after the first symptoms of the injury. Case 4. A 28-year-old male municipal employee with Hodgkin’s disease, stage 111 Bb, mixed cellularity type. He received 8 alternating courses of MOPP-ABVD with a total of 4 560 prednisone (Delta-cortene). At the end of the therapy the patient was considered to be in CR. He then received radiotherapy against a subdiaphragmatic, inverted Y-field also including the spleen with 20-22 Gy. The irradiation was interrupted due to thrombocytopenia. Twenty-five months after the start of the disease and 10 months after the end of the radiotherapy, the patient started to complain of pronounced pain and paresthesia in the left leg. X-ray examination of pelvis showed areas with osteolysis in the left femoral head. Bone scintigraphy showed increased tracer uptake in the left hip region, especially in the inferior 2/3 of the femoral head. Nine months after the initial pain a diagnosis of necrosis in the left femoral head was established. Discussion. Both radiotherapy and corticosteroid drugs are considered as risk factors of avascular necrosis (AVN) of the bone. The most frequent localization of AVN is the femoral head and all our cases had this location. Three patients received a prolonged corticotherapy (one for early relapse, two for partial remission). Only one of the four patients had received radiotherapy with a dose exceeding 25 Gy in the femoral head. None of our four patients worked in professions especially exposed to traumatic events in the region, or had previous fractures, collagen disease, alchoholism, or pancreatic disease. The main risk factor emerging from our study seems to be the corticosteroid therapy. The low incidence of AVN that we observed (0.8%) compared to a range of 1.3-10”h found in other studies (2-5) may be explained by the fairly small number of chemotherapy courses, which our patients were exposed to: 8 MOPP-ABVD or 6 MOPP ( I ) . The average latency in our patients from the beginning of therapy to the onset of clinical signs or symptoms was 27 months. The average time from the onset of signs or symptoms to diagnosis of AVN was 8 months (range 2-18 months). AVN of the femoral head is a rare complication of therapy for Hodgkin’s disease but can be suspected especially in patients who have received corticosteroids for extensive time and at high dosage. It is important to get an early diagnosis and to treat the condition adequately before severe anatomical abnormality and functional disability develop. V. TOMBOLINI A. CAPUA E. POMPILI August 1991
Radiology Institute Institute ‘Umberto I Polyclinic’ ‘La Sapienza’ University in Rome Rome, Italy
Acta Oncologica Vol. 31, No. 1, 1992
Correspondence to: Dr Eleonora Pompili, Via Garibaldi 43, 1-04100 Latina, Italy.
REFERENCES 1. Mandelli F, Anselmo AP, Cartoni C, Cimino G, Maurizi
Enrici R, Biagini C. Evaluation of therapeutic modalities in the control of Hodgkin's Disease. Radiat Oncol Ther Phys Biol 1986; 12: 1617-20. 2. Cruess RL, Ross D, Crawshaw E. The etiology of steroidinduced avascular necrosis of bone. Clin Orthop 1975; 1 1 3: 178-83. 3. lnde DC, De Vita VT.Osteonecrosis of the femoral head in patients with lymphoma treated with intermittent combination chemotherapy (including corticosteroids). Cancer 1795; 36: Acta Oncol Downloaded from informahealthcare.com by 190.202.247.181 on 05/20/14 For personal use only.
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1585-8. 4. Rossleigh MA, Smith J, Straws DJ, Engel IA. Osteonecrosis in patients with malignant lymphoma. Cancer 1986; 58: 1 1 12-6. 5. Timothy AR, Tucker AK, Park WN, Cannell LB. Osteonecrosis in Hodgkin's disease. Br J Radiol 1978; 51: 328-32.
LEUKEMIA AFTER 1311 TREATMENT OF THYROID CANCER-COMMENTS O N T H E ARTICLE 'SECOND CANCER FOLLOWING CHEMOTHERAPY A N D RADIOTHERAPY -AN EPIDEMIOLOGICAL PERSPECTIVE' BY J. KALDOR We read with interest the article 'Second cancer following chemotherapy and radiotherapy-an epidemiological perspective' by J. Kaldor (1). The author has highlighted the role of chemotherapy and radiotherapy which often are combined for optimal management of various cancers and sometimes produce favorable results with long-term survivals. The emergence of second malignancies following chemo-radiotherapy is, however, undesirable and has been dealt with in depth in the above mentioned article. We would like to point out the leukemogenic potential of one type of radiotherapy not mentioned by the author, namely radioactive iodine ( '"I) when used in large activities for the management of thyroid cancer. Pochin (2) reported the incidence of leukemia to be around 2.0% following radioactive iodine therapy for thyroid cancer. Brincker et al. (3) reported 13 cases of leukemia to have developed after such treatment. The majority of these leukemias have represented acute myeloid leukemia. Recently we have reported a case of Ph' positive chronic myeloid leukemia developing in a middle-aged female 7 years after radioactive iodine therapy of thyroid cancer (in press). The cases reported in the literature have occurred after various, but as a rule very large, activities of I3'l while our patients had received only 3 810 MBq (103 mCi) I3'I which, to our knowledge, is the
smallest activity of '"I reported to have been followed by the development of leukemia (3). No activity of 13'1, however, is probably without risk of causing leukemia, as it could produce sublethal damage in a bone marrow cell producing chromosomal abberations, oncogene activation and thereby malignant transformation (4). Identification of the leukemogenic potential of I3'I and the dose-response relation need cohort studies with long-term followup of patients receiving such therapy. Investigations at cytogenetic, molecular biologic, and cell kinetic level could also provide a better insight into the pathogenesis of leukemia. S. H. ADVANI U. P. HEGE
Tata Memorial Hospital Dr Ernest Borges Marg Pare1 Bombay 400 012 India
September 1991 Correspondence ro: Dr. S . H. Advani (address as above).
REFERENCES I . J. Kaldor. Second cancer following chemotherapy and radiotherapy-An epidemiological perspective. Acta Oncol 1990; 29: 647-55. 2. Pochin EE. Prospects from the treatment of thyroid carcinoma with radioiodine. Clin Radiol 1967; 18: 113-35. 3. Brincker H, Hansen HS, Anderson AP. Induction of leukemia by I3'l treatment of thyroid carcinoma. Br J Cancer 1973; 28: 232-7. 4. Weinburg RA. The action of oncogenes in the cytoplasm and nucleus. 1985; 2 3 0 770-6.
Editor's comments
It was not Dr. Kaldor's intention to give a complete review of all radiotherapeutic procedures that include a carcinogenic riskthe literature in this field is enormous. The aim was instead to stress the importance of an epidemiological approach, which makes it possible to study relative risks and dose-response relations. We are grateful for Dr. Advani's and Dr. Hege's comments concerning leukemia after I3'l therapy of thyroid cancer. As pointed out, most cases have occurred after very high cumulative activities of '3'I-usually 40 000 MBq or more. Activities of this order of magnitude give bone marrow doses in the Gy-level, i.e. comparable with the more heavily exposed Japanese A-bomb survivors. The patient mentioned by Advani & Hege had received a remarkably low activity of I 3 ' L The likelihood of an incidental 'spontaneous' CML might perhaps be quite as great as that of a radiation-induced leukemia. With sufficient epidemiological data these likelihoods might be given numerical values. LARS-GUNNAR LARSSON
