Patricia H. Morris Jones

Endocrine function following the treatment of acute leukemia in childhood.

Pituitary function has been studied in 25 children after treatment of acute leukemia. Impaired growth hormone responses both to hypoglycemia and to Bovril were found in 11 subjects. Elevated basal thyroid-stimulating hormone levels were seen in five children, three of whom had an augmented TSH response to thyrotrophin-releasing hormone. Radiation-induced damage to the hypothalamic-pituitary region is thought to be the cause of these abnormalities in growth hormone and in secretion of TSH. The peak cortisol response to hypoglycaemia is significantly decreased in the group of subjects who received the higher dose of cranial radiation therapy, but no individual child is hypothyroid or shows impaired adrenal function, clinically or biochemically. Three prepubertal girls studied have biochemical evidence of ovarian failure following the use of combination chemotherapy.

Thyroid dysfunction following external irradiation to the neck for Hodgkin's disease in childhood.

Thyroid function was studied in 32 patients who had received neck irradiation during childhood for Hodgkins disease. All except one patient received a dose of 2500-3000 rad over a period of 19-25 days. In 12 patients lymphangiography was performed. Clinically all patients were considered euthyroid. One had a thyroid swelling which was cystic in nature. Five (16%) patients were biochemically hypothyroid, 17 (53%) were euthyroid with an elevated basal serum TSH concentration and a further seven (22%) were euthyroid with a normal basal serum TSH level but an augmented thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH). Only three (9%) patients had completely normal thyroid function tests. The basal serum TSH concentration and the peak serum TSH response to TRH were significantly greater in the patients who received neck irradiation and lymphangiography than in those who received neck irradiation alone. In addition the free thyroxine index decreased significantly as the time interval between treatment and study increased in the lymphangiography group. These data demonstrate that the normal thyroid gland is vulnerable to the damaging effects of external irradiation, and that the combination of neck irradiation and lymphangiography is more likely to result in thyroid dysfunction than is neck irradiation alone. Furthermore, in view of the deterioration in thyroid function with time, periodic clinical and biochemical assessment of thyroid function is clearly indicated.

Carcinoma of the Adrenal Gland in Children

Abstract Five cases of functioning adrenocortical carcinoma in children aged 8 mo to 11 yr have been treated in Manchester since 1953. Their endocrine signs and symptoms were those of either Cushings syndrome or virilization or both. Differentiation of these patients from those with adrenocortical carcinoma was best accomplished by means of measurement of the 24-hr urinary steroid excretion and its response to dexamethazone infusion as well as by the use of an intravenous pyelogram and an angiogram. All children were treated by surgical removal of the tumor and postoperative irradiation with careful management of their steroid balance before, during, and after operation. Four of the five are living and free of recurrence for from 1 to 12 yr after operation.

Cancer in the families of children with soft tissue sarcoma

The cancer experience among 754 first‐degree relatives (mothers, fathers, and siblings) of a population‐based series of 177 children with soft tissue sarcoma is reported. the current study represents an extension of our earlier work in which the authors found an excess of breast cancer in the mothers of 143 of these children. There were 40 cancers among all first‐degree relatives, compared with 24.82 expected (relative risk [RR] 1.61, P = 0.006). There was no excess in fathers, but an excess of borderline significance was seen in mothers (RR 1.67, P = 0.0545), and a significant excess in siblings (RR 4.55, P = 0.0002), mainly due to carcinoma of the breast and pediatric tumors. Results of a step forward Cox multivariate analysis identified three variables in the index child which were independently associated with high cancer risk in relatives, as follows: age younger than 24 months at diagnosis; histologic type, embryonal rhabdomyosarcoma or other and unspecified soft tissue sarcoma; and male sex. It was possible, therefore, to identify a subgroup of children whose relatives are at high risk of early onset cancer (RR in this group 10.14). the pattern of cancers is consistent with the Li‐Fraumeni syndrome. the authors conclude that a marked proportion of childhood soft tissue sarcoma has a genetic basis.

Patterns of cancer in the families of children with soft tissue sarcoma

Background. Childhood soft tissue sarcomas are known to occur in a number of genetic syndromes. This study assesses the proportion of soft tissue sarcoma diagnosed in childhood associated with genetic predisposition to cancer.

Ascending myelitis after intensive chemotherapy and radiation therapy in children with cranial parameningeal sarcoma

In 1977, a program of early, wide‐field radiation therapy (RT) to the central nervous system and repeated lumbar intrathecal (IT) medications along with systemic chemotherapy was begun by the Intergroup Rhabdomyosarcoma Study (IRS) for patients younger than 21 years of age with cranial parameningeal sarcoma and a high risk of meningeal extension. From 1977 until 1987, 149 eligible patients with high‐risk cranial parameningeal sarcoma were enrolled in IRS trials. None had evidence of lower extremity or sphincter impairment at diagnosis. Five of the 149 (3.4%) had ascending myelitis at 5.5 to 9 months after the initiation of therapy, with loss of sphincter control and inability to walk; this progressed to severe flaccid quadriparesis and necessitated longterm ventilatory support in 4. All five had received vincristine, dactinomycin, cyclophosphamide, and doxorubicin; four also had received cisplatin and three also had received etoposide. All patients received 4770 to 5500 cGy to the primary tumor, and four patients received 3000 cGy of cranial RT. Three patients received cervical RT and two received spinal RT. The patients also received four to seven courses of IT methotrexate, hydrocortisone, and cytosine arabinoside. Three patients died: one after local tumor recurrence with central nervous system extension and two without known recurrence. In one of the latter patients, the results of an autopsy showed necrosis of the cervical spinal cord and caudal medulla. Although the exact cause of this complication is unclear, no additional cases have been reported to the IRS since the protocol was revised in 1987 to reduce the doses of the IT drugs and to limit them to four courses each. Cancer 1992; 69:1498‐1506.

Ewing's sarcoma, adjuvant chemotherapy and pathologic fracture.

Abstract Between 1970 and 1975, 19 patients under age 15 with Ewings sarcoma have been treated with adjuvant chemotherapy in addition to radiotherapy to the primary tumour. The chemotherapy regimen of vincristine and cyclophosphamide was not rigorously structured and evolved over the six years. The two most recent patients have also had adriamycin. The median survival of 45 months is statistically better than the 18 months experienced by the 31 children treated without adjuvant chemotherapy from 1956 to 1969 . Eight pathologic fractures have occurred in 6 of the 19 patients on adjuvant chemotherapy. Only one of the fractures was at diagnosis. The other 7 fractures occurred from 3 to 72 months following diagnosis with a median of 6 months. There were only 3 pathologic fractures in the 31 patients treated without adjuvant chemotherapy—two were at diagnosis and one was at a metastatic site. The increased risk of pathologic fractures appears to be related to the adjuvant chemotherapy.

Sarcomas in Three Generations of a Family with Neurofibromatosis

The development of sarcomas in three generations of a family with neurofibromatosis (NF) is described. A 7-month-old boy developed a prostatic rhabdomyosarcoma. Family history revealed that his maternal grandmother had died of a malignant peripheral nerve sheath tumor at age 37 years and had been affected with neurofibromatosis. His mother (aged 36 years) has also developed a malignant peripheral nerve sheath tumor and NF has been confirmed in both mother and son. This family illustrates a cluster of sarcomas associated with NF and shows the importance of thorough investigation of reported family illnesses.