Mary Jean Klein

Late complications of therapy in 213 children with localized, nonorbital soft-tissue sarcoma of the head and neck : A descriptive report from the intergroup rhabdomyosarcoma studies (IRS)-II and - III

Background. This review of children and adolescents with nonorbital soft-tissue sarcoma of the head and neck was undertaken to describe late sequelae of treatment, as manifested primarily by problems with statural growth, facial and nuchal symmetry, dentition, vision and hearing, and school performance, Procedure. Four hundred sixty-nine patients entered the IRS-II and -III protocols with localized, nonorbital soft-tissue sarcomas of the head and neck from 1978 through 1987, Their overall survival rate was 53% (250/469) at 5 years. Two hundred thirteen patients were surviving relapse free 5 or more years after diagnosis, for whom there were serial height measurements at 2 or more years after initiation of therapy. Their me dian age at diagnosis was 5 years; the median length of follow-up was 7 years. All received multiple-agent chemotherapy, and all but 3 received irradiation to the primary tumor volume Sixty-eight percent of the tumors arose in cranial parameningeal sites, 22% in nonparameningeal sites, and 10% in the neck. We reviewed flow sheets submitted to the IRS Group Statisti cal Office to ascertain which late sequelae were recorded. Results. One hundred sixty-four patients (77%) had one or more problems recorded. One hundred ninety of the two hundred thirteen patients (89%) were under 15 years of age at study entry, and at follow-up 92 (48%) had failed to maintain their initial height velocity, which had decreased by more than 25 percentile points from the original value. Thirty-six of the one hundred ninety patients (19%) were receiving growth hormone injections.

Pulmonary metastases in children and young adults with differentiated thyroid cancer

Background. The prognostic significance and optimal care of children with differentiated thyroid cancer and pulmonary metastases are not well established.

Late effects of therapy in 94 patients with localized rhabdomyosarcoma of the orbit: Report from the Intergroup Rhabdomyosarcoma Study (IRS)-III, 1984-1991

BACKGROUND We reviewed the late complications of therapy in 94 patients with localized, primary rhabdomyosarcoma of the orbit treated on the Intergroup Rhabdomyosarcoma Study (IRS)-III protocol (1984-1991). PROCEDURE A questionnaire was sent to the institutions that had registered 106 patients with orbital RMS on the IRS-III protocol, seeking information about vision, periocular structures, and growth and development of the 102 survivors. RESULTS Ninety-four questionnaires were returned. The median follow-up interval was 7.6 years. The affected eye was removed from 13 patients because of local recurrence (N = 10) or other causes (N = 3). Seventy-nine of the eighty-one remaining patients had received radiation therapy. Sixty-five of these seventy-nine patients (82%) developed a cataract, and 43 of them (66%) underwent cataract surgery. Fifty-five patients (70%) had decreased visual acuity. Twenty-four patients had a dry eye, and 22 had chronic keratitis, conjunctivitis, or corneal changes. Strabismus, diplopia, retinopathy, and uveitis were uncommon. The orbit was hypoplastic in 48 of 82 patients assessed (59%). Ptosis and enophthalmos were reported in 22 patients. Decreased statural growth was noted in 13 of the 53 irradiated patients aged 3-14 years at diagnosis with sufficient data (24%). CONCLUSIONS The overall survival rate was 96% (102/106). The eye was preserved in 86% of the patients, but vision was impaired in 70% of them. Other frequent complications were cataract, orbital hypoplasia, keratoconjunctivitis, and ptosis/enophthalmos. The current IRS-V study recommends decreasing the dose of irradiation and using conformal techniques in an attempt to minimize these complications.

Estrogen Replacement Therapy After Localized Breast Cancer: Clinical Outcome of 319 Women Followed Prospectively

PURPOSE To determine whether estrogen replacement therapy (ERT) alters the development of new or recurrent breast cancer in women previously treated for localized breast cancer. PATIENTS AND METHODS Potential participants (n = 319) in a trial of ERT after breast cancer were observed prospectively for at least 2 years whether they enrolled onto the randomized trial or not. Of 319 women, 39 were given estrogen and 280 were not given hormones. Tumor size, number of lymph nodes, estrogen receptors, menopausal status at diagnosis, and disease-free interval at the initiation of the observation period were comparable for the trial participants (n = 62) versus nonparticipants (n = 257) and for women on ERT (n = 39) versus controls (n = 280). Cancer events were ascertained for both groups. RESULTS Patient and disease characteristics were comparable for the trial participants versus nonparticipants, as well as for the women on ERT versus the controls. One patient in the ERT group developed a new lobular estrogen receptor-positive breast cancer 72 months after the diagnosis of a ductal estrogen receptor-negative breast cancer and 27 months after initiation of ERT. In the control group, there were 20 cancer events: 14 patients developed new or recurrent breast cancer at a median time of 139.5 months after diagnosis and six patients developed other cancers at a median time of 122 months. CONCLUSION ERT does not seem to increase breast cancer events in this subset of patients previously treated for localized breast cancer. Results of randomized trials are needed before any changes in current standards of care can be proposed.

Estrogen replacement therapy after treatment for localized breast carcinoma. Patient responses and opinions.

Women who reach menopause after receiving treatment for breast carcinoma have been advised to avoid estrogen replacement therapy (ERT), but the validity of this practice is being reappraised and the need for prospective studies is discussed. The likely response of potential participants to the tangible rather than theoretic option for ERT provides not only useful information for planning such studies but also important insights into the attitudes and expectations of breast cancer survivors.

Growth hormone deficiency in children with neurofibromatosis type 1 without suprasellar lesions

Risk factors for shortness of stature in children with neurofibromatosis type 1 (NF-1) include suprasellar lesions, which can lead to growth hormone deficiency (GHD), skeletal deformities, nutritional insufficiency, and methylphenidate use. At our Neurofibromatosis Clinic, we have observed short children growing poorly without these risk factors. This study investigated whether GHD occurs in children with NF-1 in the absence of suprasellar lesions. Of 251 children with NF-1, 112 were at or below the 25th percentile for height (68 were at or below the 10th). Of these, 51 children, 5-16 years of age were short, growing poorly, and without medical or radiologic findings to explain the poor growth. In 19 of 51, we evaluated GH secretion; 15 of 19 had GHD (peak GH level less than 5 ng/mL in most cases). These findings suggest that GHD may be relatively common in short children with NF-1 without suprasellar abnormalities, suggesting an association with NF-1 independent of organic, pituitary damage. Larger cohorts of NF-1 children should be evaluated to clarify whether NF-1 represents a novel etiology of GHD. Also, a careful assessment of GH secretion in children with NF-1 who are growing poorly in the absence of another clinical explanation is warranted.

Efficacy of Growth Hormone Replacement Therapy in Children with Organic Growth Hormone Deficiency after Cranial Irradiation

We evaluated the growth response of 20 childhood cancer survivors who received growth hormone (GH) replacement therapy (0.3 mg/kg/week) for at least 12 months. In all subjects, GH deficiency was associated with cranial irradiation and was documented with growth charts, bone age, and somatomedin C levels; at least one GH stimulation test was available for 14 children. Pretreatment overall growth velocity was 3.3 +/- 0.5 cm/year (mean +/- SE) over a 3-year period. After GH replacement, growth velocity was 8.6 +/- 0.6 cm/year during the first year (n = 20), 7.2 +/- 0.5 cm/year during the second year (n = 17), 5.9 +/- 0.6 cm/year during the third year (n = 11), and (6.1 +/- 0.6 cm/year during the fourth year (n = 7). Growth response, tabulated by age at onset of GH replacement, was compared with the response in GH-naive children with idiopathic GH deficiency (data obtained through the Genentech Inc. National Cooperative Growth Study Summary, September 1991); the growth velocity fell within the range described for idiopathic GH deficiency adjusted for either chronological or bone age. We conclude that children with GH deficiency after cranial irradiation for neoplastic diseases respond to GH replacement therapy as well as children with idiopathic GH deficiency.