Australasian Radiology (1 996) 40, 43-44

Secondary tumours after prophylactic cranial irradiation John Leung’ and Michael Guiney2 ‘Department of Radiation Oncology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales and 2Department of Radiation Oncology, Peter MacCallum Institute, East Melbourne, Victoria, Australia

SUMMARY

A 22 year old woman, who at the age of 6 years had prophylactic cranial irradiation for acute lymphoblastic leukaemia, presented with both astrocytoma of the brain and breast carcinoma. The link between the two solid tumours and previous cranial irradiation is discussed.

Key words: cranial irradiation; lymphoblastic leukaemia.

INTRODUCTION In the past several decades, the treatment of acute lympho- blastic leukaemia has undergone considerable advances. The increased number of survivors has led to the development and recognition of some important late consequences of the dis- ease and its treatment. Previous reports demonstrate that the incidence of brain tumours is increased after radiation treat- ment of the central nervous system (CNS) in patients with acute lymphoblastic leukaemia (ALL).’-’ More difficult to evaluate is the incidence of other tumours related to CNS therapy.

We report a case of a 22 year old woman developing a breast carcinoma and a glioma many years after her treatment for ALL.

CASE REPORT In February 1973 a 6 year old girl presented with a 1 month history of tiredness, loss of weight, sore throat and swollen glands in the neck. She was diagnosed as having acute lymphoblastic leukaemia. She received cytotoxic chemo- therapy including intrathecal methotrexate. She presented for prophylactic cranial irradiation. She received a total of 16 Gy in eight fractions using 4 MeV photons.

The radiotherapy was delivered with right and left lateral cranial fields and was given during the period of 22 February 1973 to 12 March 1973. She remained well without evidence of disease for a number of years.

In April 1988, at the age of 21, she noticed a mass in the right breast. She underwent mastectomy and axillary clear- ance. She was found to have an infiltrating ductal carcinoma

of the breast. She was found to have 14 axillary lymph nodes out of the 19 sampled involved with carcinoma. The primary was said to be extensive and it was felt she had a locally advanced carcinoma of the breast which was oestrogen and progesterone receptor positive. Subsequently, she underwent three cycles of adjuvant chemotherapy with adriamycin and cyclophosphamide. She was then given a course of radio- therapy to the chest with 50Gy in 25 fractions using medial and lateral tangents with an additional boost of 15 Gy in five fractions to the surgical bed using 7 MeV electrons. The supra- clavicular nodes were treated with 45 Gy in 20 fractions. The treatment was carried out from 14 July 1988 to 24 August 1988. She then had two more courses of adriamycin and cyclophosphamide, but refused her sixth course. She remained well for several months.

In January 1988, she complained of frontal headaches and a computed tomography (CT) scan revealed a left frontal lesion. Craniotomy exicision of the mass revealed an astrocytoma which was Grade 3 (Kernohan’s classification). Adjuvant irra- diation was offered but declined at the time.

In August 1989, the patient presented with recurring head- aches and a repeat CT scan showed extensive oedema and tumour recurrence in the left frontal lobe. Further biopsy and debulking of the tumour revealed Grade 3 astrocytorna. She received 45 Gy in 20 fractions to the whole brain using parallel opposed lateral fields at 4 MV photons.

Following radiotherapy she developed somnolence and irritability, but otherwise recovered quite well from her radiotherapy.

J Leung FRACR; M Gulney FRACR, FRACP. Correspondence: Dr John Leung. 3 Sutherland Road, Armadale, Victoria 31 43, Australia. Submitted 5 December 1994; accepted 3 March 1995.

44 J LEUNG AND M GUINEY

In February 1991, she developed an extensive local recur- rence from her breast cancer involving the previous mastec- tomy site, bilateral axillary and supraclavicular regions. She was offered chemotherapy, but declined and was commenced on tamoxifen. After extensive discussions with her family, she was persuaded to have chemotherapy. She was prescribed CMFP chemotherapy for two courses and assessment was made after these courses. Due to the poor response of chemotherapy on the local site and the development of distant metastatic disease, it was elected to cease treatment. The patient died on 9 August 1991.

DISCUSSION Prophylactic cranial irradiation in patients with acute lympho- blastic leukaemia has been extensively used since the early 1970s.’ The combination of chemotherapy (intrathecal metho- trexate) and radiation greatly reduces the probability of CNS recurrence from ALL. While ALL patients are treated with rela- tively low radiation doses, they receive total cranial irradiation. This patient was unusual in that she developed two tumours after cranial irradiation.

The link between cerebral astrocytoma and cranial irradia- tion for ALL is well Some specific criteria have been laid down for the attribution of CNS tumours to radia- t i ~ n . ~ , ~ First, the lesion must arise in the field of previous radia- tion treatment; second, it must be histologically different from the lesion for which treatment was given; third, a sufficient latency period must elapse between the commencement of irradiation and the clinical onset of the tumour; and last, con- ditions that facilitate neoplastic growth such as Von Reckling- housen’s disease, xeroderma pigmentosum, retinoblastoma and immunodeficiency syndromes, must be excIuded.8~g

Our patient had a latent period of 16 years before the development of her astrocytoma. Salvati et aL8 reviewed the literature and found the first two reported cases of post radia- tion glioma dating back to 196O.’OJ1 Since that time, another 70 cases have been reported in the literature. These patients had a mean age of onset of 22 years, a mean latency period of 9 years and a mean radiation dose of 36.7 G Y . ~

More difficult to evaluate is the aetiology of the breast car- cinoma. It is difficult to evaluate retrospectively the dose the breast would have received but our physicists calculate the maximum scatter dose at being 1%. There have been reports of increased risk of breast cancer after low dose irradiation.12 Moden et a/.12 reported a significant increase in the risk of breast cancer in the long term follow up of children subjected to scalp irradiation. This increased risk, like that of our patient, was found in patients aged 5 to 9 years at the time of expo- sure.12 The breast had been exposed to doses as low as 16mGy12 and it was postulated that two mechanisms may have been responsible. First, the young breast might be more radio-

sensitive than presently thought.13 Second, the cranial dose may have altered endocrine homeostasis causing impaired growth hormone secretion, neutralization of prolactin inhibiting factor and excess prolactin ~ecretion.’~ Mammary tumours have been induced by cranial irradiation of rats.14

In conclusion, the glioma certainly may have been induced by previous cranial irradiation. It may also be reasonable to assume that the low dose irradiation to the breast may have been responsible for the development of the breast carci- noma. The risk of a second malignancy in patients previously treated for cancer is an important reason for following patients long term, even long after the period of risk for relapse of the original primary has passed.

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