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C Sklar

Publications and source records attributed to C Sklar.

At least 19 recordsLinked to original sources
PubMed1999

Gonadal function in young patients successfully treated for Hodgkin disease.

BACKGROUND: Gonadal function in pediatric and young adult survivors of Hodgkin disease is not very well defined. This study evaluates the outcome following the Multiple Drug Protocol (MDP) and the results are compared to the published experience. PROCEDURE: Ovarian and testicular function was assessed in 65 patients (36 males) with Hodgkin disease in first or second complete remission after treatment with either radiation (RT, n = 13), chemotherapy (CT, n = 9), or both (n = 43). Chemotherapy consisted of six cycles of the MDP (doxorubicin, procarbazine, prednisone, vincristine, and cyclophosphamide). Median age at diagnosis was 13.1 years (range, 2.4-22.6) and median age at evaluation was 22.6 years (range, 15.1-33.7), which was 6.7 years (range, 2.0-19.8) after the completion of all treatments. For the purpose of analysis, patients were divided into three groups: group A, patients who received only RT that did not include the pelvis (8 females, 5 males); group B, patients who received CT but no pelvic RT (15 females, 25 males); and group C, patients who received CT plus pelvic RT (6 females, 6 males). RESULTS: All patients progressed spontaneously through puberty and evaluable patients were found to be sexually mature (Tanner stage IV and V). Serum follicle stimulating hormone (FSH) was increased in 0/5, 13/25, and 5/6 and testicular volume was decreased in 1/3, 4/11, and 2/3 group A, B, and C male patients, respectively. Leydig cell dysfunction was uncommon; 91% and 88% of males had normal serum concentrations of luteinizing hormone (LH) and testosterone, respectively. FSH and LH were increased in 0/8, 3/15, and 2/6 group A, B, and C female patients, respectively, at last follow-up, indicating a 17% prevalence of ovarian dysfunction. Serial data in seven females whose initial levels of FSH/LH were elevated revealed normalization in four. Six females delivered eight normal children. CONCLUSIONS: The majority of males who received CT +/- RT have evidence of germ cell dysfunction, while Leydig cell function is unaffected in most. In females, although abnormal function early after the end of treatment was observed, ovarian function remained or returned to normal in most young women. Thus, in females the results of hormone testing performed early after treatment may not be predictive of their eventual reproductive potential.

Adolescent↗
PubMed1998

Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group.

OBJECTIVE: This study was done to define the extent of disease and evaluate the effect of staging and treatment variables on progression-free survival in patients with differentiated thyroid carcinoma who were less than 21 years of age at diagnosis. SUMMARY BACKGROUND DATA: Differentiated thyroid cancer in young patients is associated with early regional lymph node involvement and distant parenchymal metastases. Despite this, the overall long-term survival rate is greater than 90%, which suggests that biologic rather than treatment factors have a greater effect on outcome. METHODS: Variables analyzed for their impact on progression-free survival in a multi-institutional cohort of 329 patients included age, antecedent thyroid irradiation, extrathyroidal tumor extension, size, nodal involvement, distant metastases, technique of thyroid surgery and lymphatic dissection, initial treatment with 131Iodine, residual cervical disease, and histopathologic subtype. Surgical complications were correlated with the specific procedures completed on the thyroid gland or cervical lymphatics. RESULTS: The overall progression-free survival rate was 67% (95%, CI: 61%-73%) at 10 years with 2 disease-related deaths. Regional lymph node and distant metastases were present in 74% and 25% of patients, respectively. Progression-free survival was less in younger patients (p = 0.009) and those with residual cervical disease after thyroid surgery (p = 0.001). Permanent hypocalcemia was more frequent after total or subtotal thyroidectomy (p = 0.001) while wound complications increased after radical neck dissections (p < 0.00001). CONCLUSIONS: The progression-free survival rate was better after a complete resection and in older patients. Progression-free survival rate was the same after lobectomy or more extensive thyroid procedures, but comparison was confounded by the increased use of total or subtotal thyroidectomy in patients with advanced disease. The risk of permanent hypocalcemia increased when total or subtotal thyroidectomy was done. Thyroid lobectomy alone may be appropriate for patients with small localized lesions while total or subtotal thyroidectomy should be considered for more extensive tumors.

Adolescent↗
PubMed1997

Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/primitive neuroectodermal tumors: a comparison of hyperfractionated versus conventional radiotherapy.

BACKGROUND: Primary hypothyroidism is a common sequela of craniospinal radiotherapy in the treatment of pediatric brain tumors. METHODS: The authors compared the incidence of primary hypothyroidism after hyperfractionated radiotherapy (HFRT) (n = 14 patients) versus conventionally fractionated radiotherapy (CRT) (n = 34 patients) in a group of pediatric patients with medulloblastoma/primitive neuroectodermal tumors (MB/PNET). RESULTS: The mean age at the time of tumor diagnosis was 7.9 years in the HFRT group and 8.4 years in the CRT group. The patients were followed for a mean of 4.6 years (HFRT) and 8.3 years (CRT) after diagnosis. Mean radiation doses to the thyroid were similar in both radiotherapy groups (29 gray [Gy] [HFRT] vs. 24 Gy [CRT]). Approximately 14% of the HFRT and 62% of the CRT patients developed primary hypothyroidism within a similar period after irradiation (3.2 years [HFRT] vs. 3.0 years [CRT]). Analysis by cumulative incidence function demonstrated a significant difference in the risk of developing thyroid dysfunction between these two groups of patients (P = 0.02). CONCLUSIONS: The current study findings suggest that the use of HFRT in the treatment of pediatric patients with MB/PNET is associated with a lower risk of these patients developing primary hypothyroidism.

Adolescent↗
PubMed1997

Endocrine late effects of childhood cancers.

Long-term survival in children with cancer has increased markedly in the past 15 years. However, impaired linear growth and thyroid dysfunction that vary according to the age at diagnosis and treatment and to the dose and duration of radiation and chemotherapy have been described in these patients. The impact of cranial irradiation on the hypothalamic-pituitary-adrenal axis and on pubertal maturation has been less well studied. A positive correlation between the age at diagnosis and the age at onset of puberty in children who have been treated with high-dose cranial radiation therapy for central nervous system (CNS) tumors has been found recently. Frank adrenal insufficiency is uncommon after high-dose CNS irradiation, but alterations in the hypothalamic-pituitary-adrenal axis do occur. Assessments of the effects of newer modes of radiation therapy such as hyperfractionated craniospinal radiation suggest a lower incidence of primary hypothyroidism in the long term.

Adolescent↗
PubMed1997

Gonadal function after bone marrow transplantation for acute leukemia during childhood.

OBJECTIVE: To examine the impact of bone marrow transplantation (BMT), using high-dose chemotherapy and hyperfractionated total body irradiation, on gonadal function in survivors of acute leukemia treated during childhood. STUDY DESIGN: We conducted a retrospective study of 33 subjects (17 boys) who underwent a BMT for acute leukemia (acute lymphoblastic leukemia, n = 20; acute myelogenous leukemia, n = 13) at a single institution. All patients were prepubertal at the time of BMT (median age, 7.1 years (3.7 to 11.6 years)); at the time of their last examination the boys were a median of 14 years (10.4 to 17.1 years) of age and the girls were a median of 16.9 years (9.5 to 21.9 years) of age. RESULTS: Of 17 boys, 14 (82%) entered puberty spontaneously and 13 demonstrated age-appropriate plasma concentrations of testosterone. Two boys (aged 10.5 and 11 years) remain clinically and hormonally prepubertal, and one boy has overt Leydig cell failure requiring androgen replacement therapy. Thirty-six percent of pubertal boys have elevated plasma concentrations of luteinizing hormone and 64% have raised levels of follicle-stimulating hormone. Boys with increased levels of luteinizing hormone were significantly younger at BMT (5.4 +/- 0.8 vs 7.8 +/- 0.8 years; p = 0.024). Of 16 girls, 9 (56%) had spontaneous puberty with onset of menarche at a median age of 13 years (9.5 to 15.8 years). Though six (67%) of these nine girls have had increased plasma concentrations of luteinizing and follicle-stimulating hormones, normalization has occurred in two during a period of 4 to 7 years. The remaining seven subjects required hormone replacement because of clinical and biochemical evidence of ovarian failure. One of these subjects has recovered ovarian function after 5 1/2 years. Female patients with ovarian failure were significantly older at BMT compared with female patients with spontaneous puberty/menarche (8.6 +/- 23 years vs 6.1 +/- 1.8; p = 0.03). CONCLUSION: Our results indicate that most prepubertal boys undergoing BMT with chemotherapy and hyperfractionated total body irradiation can expect to enter and progress normally through puberty. For prepubertal girls treated with these regimens, at least 50% retain adequate ovarian function to enter puberty and menstruate regularly.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[Late effects of radiotherapy on the neuroendocrine system].

When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50% reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulating hormone, and adrenocorticotropin can be found. Following high-dose radiotherapy (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done.

Adult↗
PubMed1997

Hypothalamic-pituitary-adrenal function following cranial irradiation.

We assessed the effect of cranial irradiation on hypothalamic-pituitary (HP)-adrenal function in 17 patients (12 females, 5 males) treated with cranial/ craniospinal irradiation for acute leukemia (2 patients) or tumors distant from the hypothalamus and pituitary (8 medulloblastoma, 3 astrocytoma, 3 rhabdomyosarcoma, 1 ependymoma). Estimated doses of radiation (RT) to the HP region ranged from 18 to 72 Gy. Thirteen of seventeen patients were also treated with chemotherapy. Patients were a median of 3.75 years of age (1.5-19 years) at diagnosis and were studied at a median of 5 years (0.1-20 years) after RT. Patients received corticotropin-releasing factor (oCRF, 1 microgram/kg i.v.), and sampling for cortisol and ACTH levels was performed at -15, 0, 15, 30, 60, 90 and 120 min. The-5- and 0-min levels were combined for a standardized baseline value (Base). Cortisol levels at 0, Base, 30 and 120 min, as well as the peak cortisol response, were significantly lower in the patients. Twelve of seventeen patients' peak cortisol levels fell below the normal range. The patients' mean integrated values for cortisol (area under the curve) were not, however, different from controls. The ACTH responses to oCRF did not differ between patients and controls. No relationship was observed between ACTH or cortisol responses and the time elapsed from treatment or dose of HP RT. Further, in 10 of 12 patients, 0-min dehydroepiandrosterone sulfate levels were lower than the expected normal mean levels for age, sex and pubertal status, and in 4 of these 10 patients the values were below the normal range. These data suggest that some patients treated with HP RT may be at risk for adrenal insufficiency.

Adolescent↗
PubMed1996

Pulmonary function in children treated for rhabdomyosarcoma.

Chemotherapy, radiation therapy, and surgical intervention have markedly improved the survival of patients treated for rhabdomyosarcoma. Unfortunately, the therapy may have deleterious effects on the lung. Pulmonary functions tests were obtained from 17 patients treated for rhabdomyosarcoma because of our concern regarding potential pulmonary dysfunction in this group of patients who had received bleomycin, which is known to be associated with lung injury. Mean age at the time of the diagnosis of rhabdomyosarcoma was 10.1 (+/- 7.2) years (range 0.01-23.5 years). The mean age at the time of pulmonary function testing was 17.0 (+/- 7.5) years (range 5.8-34.0 years). Study patients reportedly had no pulmonary symptoms. Approximately 87% of study patients had a restrictive ventilatory impairment on pulmonary function testing as measured by total lung capacity (TLC) values less than the lower limit of normal. Approximately 70% of study patients had carbon monoxide diffusing capacity (DLCO) values less than the lower limit of normal. There were no significant differences in pulmonary function parameters when male study patients were compared to female study patients. There was a statistically significant lower forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio (P=0.03) and percent predicted forced expiratory flow at 25-75% of the FVC (FEF25-75; P=0.03) in the group of patients diagnosed with rhabdomyosarcoma over 8 years of age as compared to those individuals diagnosed under 8 years of age. In addition, there were no statistically significant differences in pulmonary function when the variables of sex and age at diagnosis (as outlined above) were studied in combination. In summary, we identified a high incidence of restrictive ventilatory abnormalities in a group of individuals (predominantly children) treated for rhabdomyosarcoma as well as a significantly lower FEV1/FVC ratio and percent predicted FEF25-75 in the group of patients diagnosed with the neoplasm over 8 years of age. Individuals caring for such patients are encouraged to obtain pre- and sequential posttreatment pulmonary function tests.

Adolescent↗
PubMed1996

Growth and final height after treatment for childhood Hodgkin disease.

PURPOSE: To evaluate in children the impact of contemporary treatment for Hodgkin disease on the pattern of growth and final height. PATIENTS AND METHODS: We studied 80 patients (54 males) aged <14 years at diagnosis, with newly diagnosed, pathologically confirmed Hodgkin disease, treated at a single institution. Forty six patients received chemotherapy (CT) + radiotherapy (RT), 23 patients received RT alone, and 11 patients received CT alone. Heights were obtained at diagnosis, at the end of treatment, 1, 2, and 3 years after the end of treatment and at attainment of final height. Heights were converted to age- and sex-adjusted SD scores (SDS). RESULTS: There was a significant change in height SDS at the end of treatment compared to height SDS at diagnosis for all three groups (CT + RT: -0.33, p<0.001; RT: +0.09, p=0.027; CT: -0.24, p=0.012). Over the 3 years following treatment, the rate of change of height SDS was not statistically different between the three treatment groups. Final height SDS was decreased for patients receiving RT + CT (-0.41 SDS, p=0.02; n=31). The change in final height SDS for patients receiving RT or CT only was -0.36 (n=14) and +0.42 (n=4), respectively. Loss of final height SDS correlated with younger age at diagnosis (p=0.005). Patients receiving higher RT doses tended to fare worse (p=0.08). CONCLUSIONS: Pediatric patients treated for Hodgkin disease with the combination of RT and CT suffer a small but significant decrease in their final height SDS. Younger patients and those treated with higher RT doses appear to experience the greatest loss of height potential.

Adolescent↗
PubMed1995

Growth in children after bone marrow transplantation for acute leukemia.

We evaluated the growth of children with acute leukemia who received a bone marrow transplant (BMT) after preparation with hyperfractionated total body irradiation (TBI). Seventy-two patients (27 female and 45 male patients) with acute lymphoblastic leukemia (ALL; n = 39) or acute myelogenous leukemia (AML; n = 33) who were less than 14 years of age at BMT were studied. Before BMT all had received multiagent chemotherapy and 31 had received cranial irradiation (RT). Preparation for BMT included total body irradiation (1,375 cGy [n = 37] or 1,500 cGy [n = 35]). Heights, expressed as standard deviation scores (SDS), were studied up to 4 years post-BMT. The estimated height SDS for the entire group at the time of BMT was -0.28 +/- 0.05 and decreased to -1.11 +/- 0.22 at 4 years post-BMT (P < .0001). Using a growth curve model to compare covariate groups over the period of study, we found that the loss in height SDS was most significant in those patients who received cranial RT before BMT (P = .005). The estimated height SDS for patients treated with cranial RT went from -0.52 +/- 0.20 at transplantation to -1.83 +/- 0.23 4 years later. In contrast, patients who did not receive cranial RT before BMT showed a smaller decrease in height SDS over the 4-year observation period, ie, -0.11 +/- 0.20 decreasing to -0.73 +/- 0.21. Similarly, patients with a diagnosis of ALL had a greater loss of height SDS than those with AML (P = .033). Fifteen of 18 patients tested were found to be growth hormone (GH) deficient; 9 patients were treated with GH and all showed an improvement in growth velocity (P < .0001). We conclude that (1) children with acute leukemia who have received cranial RT and subsequently undergo BMT, primarily those with ALL, are at high risk for growth failure and GH deficiency, and (2) that fractionation of TBI may have a relative sparing effect on growth.

Acute Disease↗
PubMed1995

Thyroid dysfunction following bone marrow transplantation using hyperfractionated radiation.

Thyroid dysfunction has been reported following single dose and fractionated radiation in the context of bone marrow transplantation (BMT). Limited data are available regarding this complication following hyperfractionated radiation. We undertook a retrospective analysis of thyroid function in 150 patients who received BMT at our institution, and who were alive and disease-free for at least 1 year after transplant. There were 100 pediatric patients and 50 adult patients, with a median follow-up of 6.2 years for the whole group. These patients had acute (n = 91) or chronic leukemias (n = 36), severe aplastic anemia (n = 18) or immunodeficiency disorders (n = 5). The majority of the patients received radiation-based cytoreductive regimens including 129 patients who received hyperfractionated total body irradiation (TBI) to a total dose of 1375 cGy or 1500 cGy and 10 patients who received total lymphoid irradiation (TLI) to a total dose of 600 cGy. Twenty two patients of the cohort of 150 patients (14.7%) and 21 of the 139 patients (15.1%) who received hyperfractionated radiation were found to have developed hypothyroidism, 11-88 months after transplant (median 49 months). Eight patients had received 1375 cGy and 12 patients 1500 cGy TBI, while one patient was treated with 600 cGy TLI and one patient was treated with chemotherapy only (busulfan and cyclophosphamide). Three patients had primary thyroid failure with an elevated TSH and a low T4 index, while 19 patients had compensated hypothyroidism with an elevated TSH but a normal T4 index. Six of eight patients with untreated compensated hypothyroidism recovered spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Prolactin-secreting macroadenomas in adolescents. Response to bromocriptine therapy.

OBJECTIVE: To report five cases of prolactin (PRL)-secreting macroadenomas in adolescents, including their presentations and responses to bromocriptine mesylate treatment. PATIENTS: Five adolescents (three females and two males) aged between 12.5 and 17 years were diagnosed as having PRL-secreting macroadenomas at the pediatric endocrine service at New York University Medical Center between 1987 and 1989. Presenting complaints included visual field deficits, gynecomastia, and amenorrhea, both primary and secondary. All patients demonstrated some feature of hypogonadism or pubertal arrest. Diagnostic criteria included an elevated serum PRL level (mean, 1670 micrograms/L; range, 610 to 3700 micrograms/L) and visualization of a pituitary tumor that measured greater than 1 cm by either a computed tomographic scan or magnetic resonance imaging (mean size, 2.7 cm; range, 1.4 to 4 cm). INTERVENTIONS: Each patient was treated with bromocriptine mesylate at an oral dose of 7.5 mg/d. The patients continued with that treatment for the duration of the study period. MEASUREMENTS AND RESULTS: Anterior pituitary function was evaluated in four of five patients before treatment. All four were growth hormone deficient. Three patients were also gonadotropin deficient. Thyrotropin (thyroid-stimulating hormone) and corticotropin (adrenocorticotropic hormone) deficiencies were demonstrated in three patients who had multiple pituitary deficits. Follow-up testing included serial PRL measurements and radiographic imaging of tumor size. All patients demonstrated a marked decrease in PRL levels, as well as in tumor size (mean shrinkage, 70%). The three patients who initially had visual field deficits showed significant improvement of vision with bromocriptine therapy. Follow-up study of anterior pituitary function showed significant improvement with bromocriptine treatment in three patients. CONCLUSIONS: Bromocriptine was quite effective in the shrinkage of PRL-secreting macroadenomas in all our patients. It is a noninvasive treatment that can preserve and restore vision, as well as pituitary function, which is integral to continued growth and sexual maturation of the adolescent. Bromocriptine is preferable to surgery or radiation in the treatment of PRL-secreting macroadenomas in the adolescent.

Adolescent↗
PubMed1993

Final height after treatment for childhood acute lymphoblastic leukemia: comparison of no cranial irradiation with 1800 and 2400 centigrays of cranial irradiation.

We analyzed growth and final heights in 127 patients (68 female patients) treated for childhood acute lymphoblastic leukemia. Central nervous system prophylaxis included either no cranial radiation therapy (CRT) (n = 38), irradiation with 1800 centigrays (cGy) (n = 36), or irradiation with 2400 cGy (n = 53). None of the patients received spinal irradiation. Mean (+/- SEM) age at diagnosis was 6.4 +/- 0.25 years, mean height standard deviation score (SDS) at diagnosis was 0.28 +/- 0.12, and mean age at final height was 18.26 +/- 0.19 years. The change in height SDS between diagnosis and achievement of final height was significant for all treatment groups: -0.49 +/- 0.14, no CRT; -0.65 +/- 0.15, 1800 cGy; and -1.38 +/- 0.16, 2400 cGy. Irradiated patients had a greater loss in height SDS compared with the nonirradiated patients (p < 0.01), and those treated with 2400 cGy CRT had a greater decrease in final height SDS than the patients treated with 1800 cGy (p < 0.01). Both younger age and female sex were significantly associated with a greater decrease in height SDS in the patients treated with CRT; girls < or = 4 years of age at diagnosis had a mean loss in height SDS that was more than twice that observed for others treated with the same dose of CRT. Thus, although modern regimens for acute lymphoblastic leukemia (no CRT or 1800 cGy CRT) appear overall to have only a modest impact on final height, patients, especially girls, treated with 1800 cGy CRT at a young age remain at risk for clinically significant growth failure.

Age Factors↗