Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: a report from the Children Cancer Study Group

Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.     

Gonadal function in patients treated for leukemia in childhood

Ovarian and testicular function were assessed in 67 long-term survivors (37 females, 30 males) treated for leukemia between 1973 and 1992. At diagnosis they were 1 - 16 (median 5) years old and had evaluation of gonadal function 4 - 25 (median 13) years later at the age of 13 - 31 (median 19). All had been treated with various combinations of chemotherapy (ChT) (including cyclophosphamide (CYC) and cytarabine in 32 patients), 62 patients had received prophylactic cranial irradiation with 12 - 49 (median 18) Gy, 2 patients had had craniospinal irradiation with 24 and 10 Gy respectively. Nine patients were treated for relapse; 2 boys had testicular irradiation (RT) with 12 Gy in 3 fractions and 1 girl whole-abdomen RT with 20 Gy as a part of this treatment. Three patients were treated for second malignancies. Gonadal function was assessed by clinical examination and measurement of serum concentrations of estradiol and testosterone. Serum levels of LH and FSH were determined in basal state and after stimulation. Primary hypogonadism was found in 6 (9%) patients. Five (16,5%) males had primary hypogonadism with evidence of damage to the germinal epithelium, 2 of them, treated with testicular RT, had evidence of damage to the Leydig cells and 2 had evidence of dysfunction of Leydig cells as well. Primary hypogonadism was found in 1 female, who was heavily treated for relapse (ChT containing CYC, abdominal RT and craniospinal RT). She was amenorrhoic and needed substitutional estrogen therapy but delivered a child anyway. Five females had early puberty after cranial RT. One female had secondary hypogonadism and hyposomatotropism after cranial RT with 30 Gy, one male had hyposomatotropism after receiving cranial RT twice (49 Gy total). Primary treatment for leukemia does not produce primary hypogonadism in girls, but it does in boys. Alkylating agents and gonadal RT are the most damaging factors. Not only RT to gonads but also alkylating agents alone cause dysfunction of Leydig cells.     

Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation

With the aim of evaluating the effect of high dose irradiation (6,500 cGy/36 fractions or higher) to pituitary fossa, a prospective study was carried out in patients with nasopharyngeal cancer by a serial determination of several hormones in the serum, before and after the course of radiation therapy (RT). The radiation treatment field was at least 1 cm above the skull base with bilateral parallel opposing fields. Hormone assays were performed three times on each patient: (1) prior to, (2) one month after, (3) 15-18 months after radiation therapy. The study included determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), cortisol, growth hormone (GH) and prolactin concentrations and LH-releasing hormone, thyrotrophin-releasing hormone stimulation and insulin tolerance tests were also carried out. Complete profiles were obtained in 24 patients (16 males and 8 females), aged 16-67 years. The results showed a significant decrease in the level of serum peak value of LH in males 18 months after therapy, and also in GH both one month and 18 months after therapy. A significant increase in the peak value of serum TSH observed after therapy. Decreased serum FSH, cortisol and prolactin levels were noted, but these did not reach statistical significance. The decrease in GH level appeared earlier and was more sensitive than that found for the other hormones, and could prove to be a useful parameter for clinical evaluation. None of the patients showed any clinically recognizable symptoms or signs of hormone deficiency in the 18-33 months following completion of the radiation therapy.     

Radiation therapy induced changes in male sex hormone levels in rectal cancer patients.

BACKGROUND AND PURPOSE: To determine the effect of curative radiation therapy (46-50 Gy) on the sex hormone levels in male rectal cancer patients. MATERIALS AND METHODS: Twenty-five male rectal cancer patients (mean age 65 years), receiving pelvic radiation therapy (2 Gyx23-25 fractions in 5 weeks) were included. Serum testosterone, FSH and LH were determined before start of treatment, at the 10th and 25th fractions, and 4-6 weeks after completed radiotherapy. The testicular dose was determined by thermoluminescent dosimetry. RESULTS: Five weeks of radiation therapy (46-50 Gy) resulted in a 100% increase in serum FSH, a 70% increase in LH, and a 25% reduction in testosterone levels. After treatment, 35% of the patients had serum testosterone levels below lower limit of reference. The mean radiation dose to the testicles was 8.4 Gy. A reduction in testosterone values was observed already after a mean dose of 3.3 Gy (10th fraction). CONCLUSION: Radiation therapy (46-50 Gy) for rectal cancer resulted in a significant increase in serum FSH and LH and a significant decrease in testosterone levels, indicating that sex hormone production is sensitive to radiation exposure in patients with a mean age of 65 years.     

The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence

Testicular function was evaluated in 75 boys after treatment for Hodgkin's disease with involved-field or extended-field irradiation and stage-dependent chemotherapy (vincristine, prednisone, procarbazine, Adriamycin [doxorubicin], and cyclophosphamide [OPPA/COPP]). Although pubertal development and testosterone levels were normal in all patients, 18 of 75 (24.0%) had elevated basal and 65/74 (87.8%) elevated stimulated luteinizing hormone (LH) levels, demonstrating chemotherapy-induced Leydig cell damage. In addition, there was a 40.5% and 53.4% incidence of elevated basal and stimulated FSH values, respectively, indicating severe impairment of spermatogenesis as confirmed by azoospermia in four patients. Testicular dysfunction was observed in patients treated before as well as during puberty. The incidence of elevated basal follicle stimulating hormone (FSH) and LH values was significantly higher in patients who had received higher cumulative doses of chemotherapy, i.e., 28.9% and 13.2% with two OPPA, 45.5% and 36.4% with two OPPA/two COPP, and 62.5% and 43.8% with two OPPA/four to six COPP, respectively. Chemotherapy for Hodgkin's disease causes a high and apparently dose-related incidence of testicular dysfunction in prepubertal as well as in pubertal boys affecting Leydig cell function as well as spermatogenesis. Circumstantial evidence indicates that procarbazine is the major gonadotoxic agent involved.     

Dentofacial development in long-term survivors of acute lymphoblastic leukemia. A comparison of three treatment modalities

Ninety-seven children who were diagnosed with acute lymphoblastic leukemia before 10 years of age and treated with chemotherapy alone, chemotherapy plus 1800-cGy cranial irradiation (RT), or chemotherapy plus 2400-cGy RT were evaluated for effects of therapy on dentofacial development. All patients were seen at least 5 years postdiagnosis. Dental abnormalities were determined from panoramic radiographs, and craniofacial evaluations were made from lateral cephalometric radiographs. Ninety-one (94%) of all patients and 41 (100%) of patients younger than 5 years of age at diagnosis had abnormal dental development. The severity of these abnormalities was greater in children who received treatment before 5 years of age and in those who received RT. Observed dental abnormalities included tooth agenesis, arrested root development, microdontia, and enamel dysplasias. Craniofacial abnormalities occurred in 18 of 20 (90%) of those patients who received chemotherapy plus 2400-cGy RT before 5 years of age. Mean cephalometric values of this group showed significant deficient mandibular development. The results of this study suggest that the severity of dentofacial-developmental abnormalities secondary to antileukemia therapy are related to the age of the patient at the initiation of treatment and the use of cranial RT.     

Hypothalamic-pituitary function of children with acute lymphocytic leukemia after three forms of central nervous system prophylaxis. A retrospective study

The hypothalamic-pituitary function of 93 children, who had received central nervous system (CNS) prophylaxis as part of their therapy for acute lymphocytic leukemia (ALL), and who remained in continuous complete remission, was evaluated retrospectively. Treatment regimens included--Group I: 31 subjects, intrathecal methotrexate (IT MTX); Group II: 31 subjects, IT MTX plus 2400 rad cranial irradiation; and Group III: 31 subjects, IT MTX and intravenous intermediate-dose methotrexate. Serum thyroid-stimulating hormone (TSH) and T4 levels were normal. All participants had normal adrenocorticotropic hormone (ACTH) secretion as assessed by plasma cortisol responses to insulin hypoglycemia. Urinary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) excretion of pubertal and postpubertal patients (N = 37) was appropriate, except for one subject from Group I who had an abnormally high output of gonadotropins, and one from Group II who had abnormally low levels. Growth hormone (GH) responses were subnormal after sequential arginine-insulin stimulation as follows--Group 1: 3 of 31 patients; Group II: 6 of 25 patients; and Group III: 2 of 29 patients. Nevertheless, all children had normal linear growth. It was concluded that the three forms of CNS prophylaxis evaluated had no long-term adverse effect on TSH and ACTH secretion. FSH-LH production appears to be normal, but final judgment must await follow-up studies because 60% of the patients were prepuberteral or still receiving chemotherapy. Eleven patients had subnormal GH responses after pharmacologic stimulation of the pituitary, but long-term linear growth was unaffected.     

Improved survival of children with isolated CNS relapse of acute lymphoblastic leukemia: a pediatric oncology group study .

PURPOSE: Isolated meningeal relapse in children with acute lymphoblastic leukemia (ALL) usually has been followed by bone marrow relapse and limited survival. The purpose of this study was to prevent marrow relapse by administering intensive therapy before delayed craniospinal radiation. PATIENTS AND METHODS: Eighty-three patients with ALL in first bone marrow remission with an isolated CNS relapse were treated with systemic chemotherapy known to enter into the CSF and intrathecal chemotherapy for 6 months. Craniospinal irradiation (24 Gy cranial/15 Gy spinal) was then administered, followed by 1.5 years of maintenance chemotherapy. RESULTS: All 83 patients achieved a second remission. The 4-year event-free survival (EFS) rate was 71.1% +/- 5.3%. There was a fourfold increased risk of relapse for children whose initial remission was less than 18 months. The 4-year EFS rate for patients with a first complete remission >/= 18 months was 83.3% +/- 5.3%, and for those with a first complete remission less than 18 months, it was 46.2% +/- 10.2% (P =.0002.) There was a low incidence of neurologic toxicity and an unexpectedly high rate of allergic reactions to L-asparaginase. Five patients developed secondary malignancies: two with acute nonlymphoblastic leukemia during therapy, one with myelodysplasia after therapy, and two with brain tumors 1.5 to 2 years after cessation of therapy. CONCLUSION: For children with ALL and an isolated CNS relapse, treatment that delays definitive craniospinal irradiation by 6 months to allow for more intensive systemic and intrathecal chemotherapy results in better EFS than has been previously reported. Using this approach, the long-term prognosis for children with first complete remission >/= 18 months is comparable to that at the time of original diagnosis of ALL.     

RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database.

PURPOSE: This phase II, open-label, multicenter study assessed the efficacy and safety of the potential radiation enhancer RSR13 plus cranial radiation therapy (RT) in patients with brain metastases. The primary end point was patient survival in comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database (RTOG RPA BMD). PATIENTS AND METHODS: Eligibility criteria were age > or = 18 years, Karnofsky performance score > or = 70, and brain metastases with solid tumor histology. Patients received cranial RT, 30 Gy in 10 fractions of 3 Gy each, preceded by RSR13, 50 to 100 mg/kg intravenously over 30 minutes. Univariate and multivariate comparisons of survival and cause of death were made between class II study patients and RTOG BMD patients. RESULTS: Fifty-seven RPA class II patients were enrolled. With a minimum follow-up of 24 months, the median survival time and 1- and 2-year survival rates were 6.4 months, 23%, and 11% for the RSR13-treated patients compared with 4.1 months, 15%, and 3% for the RTOG BMD patients (P =.0174). In an exact-matched case analysis (n = 38), median survival time for RSR13 patients was 7.3 months versus 3.4 months for the RTOG BMD patients (P =.006). There was a 54% reduction in the risk of death for RSR13 patients (P =.0267). RSR13-related adverse events of greater than or equal to grade 3 toxicity that occurred in more than one patient included hypoxia, headache, anemia, fatigue, hypertension, and intracranial hypertension. CONCLUSION: RSR13 plus cranial RT resulted in a significant improvement in survival, as well as a reduction in death due to brain metastases, compared with class II patients in the RTOG BMD.     

72例标危型髓母细胞瘤放疗剂量对生存的影响

目的 回顾分析标危型髓母细胞瘤采用全脑全脊髓放疗剂量≤24 Gy和>24 Gy对预后的影响。方法 标危型髓母细胞瘤定义为年龄>3岁、未发生转移、肿瘤全切或近全切(残留≤1.5 cm³)。2003—2013年共入组72例初治儿童、青少年标危型髓母细胞瘤患者。患者术后接受全脑全脊髓+局部瘤床放疗和8个疗程辅助化疗,化疗方案为顺铂、司莫司汀或卡莫司汀联合长春新碱。按放疗剂量≤24 Gy和>24 Gy分为A、B组(20、52例),比较两组患者复发率和生存率。Kaplan-Meier法计算复发率和生存率并Logrank法检验组间差异。结果 A组接受全脑全脊髓放疗19.2~24.0 Gy,B组接受全脑全脊髓放疗24.1~30.6 Gy。放疗后66例(92%)患者完成全部辅助化疗。共11例患者复发。随访满3年患者48例,其中复发11例,死亡7例。全组3年EFS率为83%,3年OS率为86%。A组和B组患者3年EFS率分别为84%和83%(P=0.609), 3年OS率分别为85%和87%(P=0.963)。结论 标危型髓母细胞瘤经规范综合治疗效果较好,其中全脑全脊髓放疗剂量减少至19.2~24.0 Gy未影响疗效。     

The influence of different intensity of treatment on hormonal markers of gonadal function in acute lymphoblastic leukemia survivors

Anti‐cancer treatment in children can deteriorate gonadal function and affect future fertility. We analyzed the hormonal markers of gonadal function in adolescent leukemia survivors, treated in childhood with different levels of aggressiveness. We analyzed hormone levels in 69 adolescents and young adults, leukemia survivors stratified into standard (SR), intermediate (IR), and high (HR) risk groups, and in 80 healthy controls (38 men) at a similar age. We assessed follicular stimulating hormone (FSH), luteinizing hormone (LH), and inhibin B in the whole group, testosterone in males, and E2 and anti‐Müllerian hormone (AMH) in females. Males classified into HR group presented, in comparison to control, higher levels of FSH, LH, lower inhibin B, and normal testosterone, whereas in SR and IR group, the hormonal values were comparable to the control. In females, in all risk groups, the levels of FSH, LH, E2, and inhibin B were comparable with the control, but the mean AMH levels were slightly lowered. We did not observe the effect of prophylactic cranial irradiation (12 or 18 Gy) or the time of treatment (before vs. during puberty) on hormone levels. In females, a positive correlation was found between the time interval after the end of treatment and AMH levels. Male leukemia survivors having undergone more intensive chemotherapy show the symptoms of disturbed spermatogenesis and need to be followed‐up in the future. Women, irrespective of the risk group, can develop the signs of preterm ovarian insufficiency. They should be informed about the impact of the treatment on gonadal function.     

Leydig cell function in the pubertal rat following local testicular irradiation

Dose- and time-response relationships were measured after irradiation of the pubertal rat testis with between 1 and 20 Gy of 300 kVp X-rays. The threshold dose for Leydig cell dysfunction was about 5 Gy. Dysfunction after higher doses was observed by 2 weeks post-irradiation as a dose-dependent decrease in serum testosterone (T) concentrations, and the levels were undetectable after 15 or 20 Gy. Despite the recovery of serum T by 24 and 36 weeks, dysfunction of the Leydig cell population was still observed as an increase in luteinizing hormone (LH) secretion (1.5 to 2-fold increase after 15 or 20 Gy at 24 weeks; 2 to 3-fold increase after 10 or 20 Gy at 36 weeks). The endocrine changes were probably due to the observed loss of Leydig cells following irradiation. These results indicate that the Leydig cells of pubertal rats are more radioresponsive than those of the adult.     

Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer

PURPOSE: This Phase III study was performed to determine whether twice-daily (b.i.d.) radiotherapy (RT) resulted in better survival than once-daily (q.d.) RT for patients with limited-stage small-cell lung cancer (LD-SCLC). METHODS AND MATERIALS: A total of 310 patients with LD-SCLC initially received three cycles of etoposide and cisplatin. Subsequently, the 261 patients without significant progression were randomized to two cycles of etoposide and cisplatin plus either q.d. RT (50.4 Gy in 28 fractions) or split-course b.i.d. RT (24 Gy in 16 fractions, a 2.5-week break, and 24 Gy in 16 fractions) to the chest. Patients then received a sixth cycle of etoposide and cisplatin followed by prophylactic cranial RT. RESULTS: Follow-up ranged from 4.6 to 11.9 years (median, 7.4 years). The median survival and 5-year survival rate from randomization was 20.6 months and 21% for patients who received q.d. RT compared with 20.6 months and 22% for those who received b.i.d. RT (p = 0.68), respectively. No statistically significant differences were found in the rates of progression (p = 0.68), intrathoracic failure (p = 0.45), in-field failure (p = 0.62), or distant failure (p = 0.82) between the two treatment arms. No statistically significant difference was found in the overall rate of Grade 3 or worse (p = 0.83) or Grade 4 or worse toxicity (p = 0.95). Grade 3 or worse esophagitis (p = 0.05) was more common in the b.i.d. arm. Grade 5 toxicity occurred in 4 (3%) of 130 patients who received b.i.d. RT compared with 0 (0%) of 131 who received q.d. RT (p = 0.04). CONCLUSION: Although this study did not demonstrate an advantage to split-course b.i.d. RT, the long-term survival was favorable, likely reflecting the positive influences of concurrent combined modality therapy and prophylactic cranial RT.     

Long-term outcomes of 60 Gy conventional radiotherapy combined with androgen deprivation for localized or locally advanced prostate cancer

BACKGROUND: Until 1998 in Japan, very few institutions were treating prostate cancer solely with radiotherapy (RT) >70 Gy and most were using < or =65 Gy in combination with hormone therapy. The present study reports the long-term results of RT combined with hormone therapy for localized and locally advanced prostate cancer. METHODS: We investigated 57 patients who were treated by external beam RT plus hormone therapy (median age 79 years, median prostate-specific antigen concentration 15.0 ng/ml) between 1992 and 1998. Patients received 40 Gy of radiation to the pelvis and an additional 20 Gy as a prostatic boost. Hormone therapy was begun on the first day of irradiation and continued thereafter. RESULTS: The median follow-up was 93.3 months and the 5 and 10 year actual overall survival rates were 67.8 and 32.6%, respectively, with 5 and 10 year cause-specific survival rates of 97.9 and 95.0%, respectively. The expected survival rate was 66.2% at 5 years, and overall survival was above expected survival. Only one patient developed severe proctitis (Grade 3). The 5 year occurrence of Grade 1/2 genitourinary toxicity was 23.2%. CONCLUSIONS: Combined RT and hormone therapy has a good long-term outcome without severe adverse events. The overall survival rate compares well with the expected survival rate.     

Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease

Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation. During conventionally fractionated radiation therapy, the testicular dose ranged from 6 to 70 cGy. Testicular function was measured in a prospective fashion by repeated analyses (every 6 to 12 months) of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Patients were also followed by serial semen analyses and by a questionnaire on fertility. The follow-up period ranged from 3 to 7 years after completion of radiation therapy. In patients receiving greater than or equal to 20 cGy, there was a dose-dependent increase in serum FSH values following irradiation, with the maximum difference at 6 months compared with pretreatment levels. All patients showed a return to normal FSH values within 12 to 24 months following irradiation. No significant changes in LH and testosterone were observed in this patient group. Eight patients with a normal pretreatment semen analysis provided serial semen samples and two patients showed transient oligospermia with complete recovery by 18 months following treatment. Four patients have fathered normal offspring following radiation therapy. We conclude that low doses (greater than 20 cGy) of scatter irradiation during treatment for Hodgkin's disease can result in transient injury to the seminiferous tubule as manifested by elevations of FSH for 6 to 24 months following treatment. Below 20 cGy, FSH values remained in the normal range. No evidence of Leydig cell injury (using LH and testosterone) was seen in this dose range (up to 70 cGy). Thus, patients with early-stage Hodgkin's disease can be treated with radiation therapy with little to no risk of irreversible testicular injury. Radiation treatment techniques to shield the testes are discussed.     

Gonadal dysfunction in patients treated for metastatic germ-cell tumors

The effects of chemotherapy on endocrine function were assessed in 22 previously treated patients with germ-cell tumors and compared with the endocrine function of six previously untreated patients. Baseline and stimulated serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, thyroid-stimulating hormone (TSH), prolactin, and thyroxine (T4) were obtained. Baseline LH levels were elevated in both groups of patients, whereas basal FSH levels were significantly elevated only in treated patients (P less than .001). Following gonadotropin-releasing hormone (GnRH), levels of LH (P = .051) and FSH (P = .003) were greater in treated patients than in untreated control patients. No abnormalities of thyroid function or prolactin responsiveness were observed. Patients younger than 25 years of age at the time of treatment had lower serum levels of LH and FSH following chemotherapy than patients older than 25. Evidence for partial recovery of gonadal function was present with patients treated more than 18 months before study having lower levels of LH and FSH than those patients studied less than 18 months after treatment. These data demonstrate that frequent gonadal dysfunction exists in untreated patients with germ-cell tumors and that chemotherapy induces additional injury to both Leydig cells and the germinal epithelium. Further studies with long-term follow-up are necessary to define the pattern of gonadal recovery and to assess the potential sequelae of endogenous gonadotropin hypersecretion.     

Evaluation of results of radiotherapy alone vs combined surgery and postoperative radiotherapy in carcinoma external auditory canal—10 years review

Forty-one patients of external auditory canal (EAC) cancer attended the Department of Radiotherapy (RT), Medical College Hospital, Kolkata during the period from 1987 to 1996. Majority were above 50 years of age with slight female preponderance. Out of 41 patients 36 patients completed the full course of treatment of which 12 patients underwent combined modality treatment (RT 50–55 Gy plus surgery) and 24 patients received primary RT alone (55–60 Gy). Radiation therapy was given in standard fractionation schedule. Retrospective analysis revealed complete response in 8/12 (66.7%) in combined modality treatment group and in 3/24 (12.5%) in RT alone group. The actuarial 2 year survival was 19%. following RT alone, 85% following combined modality, 70% in early lesions and 18% in advanced lesions. The study suggests, surgical resection followed by postoperative irradiation is an effective method and better treatment option than RT alone as primary treatment modality for carcinoma of EAC.     

Seminiferous epithelial function in the pubertal rat following local testicular irradiation

The dose- and time-related responses of the irradiated seminiferous epithelium in the pubertal rat have been investigated. The threshold dose for Sertoli cell dysfunction, as assessed by serum androgen binding protein (ABP) concentrations, was estimated to be 5 Gy. A significant reduction (to less than 50% of control levels) in serum ABP was observed at 8 weeks post-irradiation, with further reductions at later times (24 and 36 weeks). Serum follicle-stimulating hormone (FSH) was elevated to between 130 and 175% of control at only 2 weeks post-irradiation, but recovered with time. Normal FSH levels seemed to be related to recovery of spermatogenesis, as assessed by counts of regenerating tubule cross-sections. The results indicate that the clonogenic spermatogonia and Sertoli cells of the pubertal rat testis are less sensitive to radiation than those of the adult.     

The local field in infratentorial ependymoma: does the entire posterior fossa need to be treated?

INTRODUCTION: In the past decade, there have been multiple reports indicating that the predominant problem in the curative treatment of intracranial ependymoma is local failure. As a result, many have recommended local field radiotherapy. For infratentorial ependymoma, there is controversy regarding what constitutes the local field. Some radiation oncologists advocate coverage of the entire posterior fossa, whereas others recommend radiotherapy to the tumor bed and a safety margin. METHODS AND MATERIALS: From 1984 to 1998, 28 patients with posterior fossa ependymoma were diagnosed at our institution. There were 18 males and 10 females with a median age of 12 years (range, 2-81 years). Four patients (14%) had high-grade ependymoma and 3 (11%) had M+ disease at initial diagnosis. Gross total resection was achieved in 17 (61%) and postoperative radiotherapy (RT) was given to 22 (77%). Radiotherapy fields were craniospinal in 10, whole brain in 1, posterior fossa in 2, and tumor bed with a 2-cm. margin in 9. Median dose to the primary site was 54 Gy (range, 45-55 Gy). All 4 patients with high-grade ependymoma received craniospinal RT. Six patients did not receive RT after surgery. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the brain at initial diagnosis were compared to MRI or CT scans of patients at relapse to determine if the local relapse was in the tumor bed or nontumor bed posterior fossa. Median follow-up was 127 months (range, 14-188 months). RESULTS: Six patients have relapsed. For the 11 patients who had craniospinal or whole brain radiotherapy (RT), 3 recurred (tumor bed 1, spine 1, nontumor bed posterior fossa + spine 1). Both patients who failed in the spine had high-grade tumors. Neither of the 2 treated with posterior fossa fields relapsed. For the 9 patients who had tumor bed RT alone and the 6 who did not receive RT, there were 3 relapses; all were in the tumor bed. There were no relapses in the nontumor bed posterior fossa. CONCLUSION: For nondisseminated, low-grade infratentorial ependymoma, the radiotherapy volume does not need to include the entire posterior fossa. This information can be used to minimize late effects of RT in the era of three-dimensional (conformal) radiotherapy. No conclusion can be reached regarding the appropriate local field for high-grade infratentorial ependymoma because of the small number of patients.     

False elevations of human chorionic gonadotropin associated to iatrogenic hypogonadism in gonadal germ cell tumors

Radioimmunoassay (RIA) for fraction beta of the chorionic gonadotropin hormone (HCG-beta subunit) has a clinical value in the management of patients with gonadal germ cell tumors (GCT). Treatment of disease causes temporary or permanent iatrogenic hypogonadism and secondary plasmatic elevations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Small but significant cross-reactions with LH have been observed, resulting in spurious elevations of HCG, as result, also in part, of the lack of specificity of the RIA. Twelve patients with complete response showed high HCG follow-up levels between 1.7 and 7.8 mIU/ml; simultaneous determination of LH and FSH resulted, also, in high levels: 79.9 to 24.9 mIU/ml and 80 to 19.2 mIU/ml, respectively, in females, and 78 to 18 mIU/ml and 65.1 to 5 mIU/ml, respectively, in males. Administration of exogenous hormones resulted in all cases in reduction of LH and FSH values and normalization of HCG. Therefore, relationship between spurious elevations of HCG and the iatrogenic hypogonadism is clarified through this simple technique that is of most importance as regards the adoption of the appropriate therapy.