Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease.

OBJECTIVE: We assessed the gonadal function in boys with a newly diagnosed neoplastic disease prior to chemotherapy. Eighty-four boys (48 prepubertal and 36 pubertal) were evaluated, including 50 with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL), 10 with Hodgkin lymphoma (HL), and 24 with solid tumors. The control group consisted of 24 healthy prepubertal and 24 pubertal boys. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, and testosterone were determined, and testicular volumes were measured. RESULTS: Patients in prepuberty and early puberty (Tanner stages 1-3) diagnosed with ALL/NHL or solid tumor presented normal serum reproductive hormone levels, whereas in ALL/NHL patients in Tanner stages 4-5, the mean values of inhibin B were significantly lower (45.18 +/- 33.85 vs. 153.57 +/- 71.44 ng/L, p = 0.0027). In patients with HL in Tanner stages 4-5, a statistically significant lower mean inhibin B level (100.44 +/- 67.45 versus 153.57 +/-71.44 ng/L, p = 0.0027), higher mean FSH level (6.3 +/- 3.6 versus 4.6 +/- 2.2 mIU/mL, p = 0.05), and higher mean LH level (5.9 +/- 4.0 versus 3.6 +/- 1.8 mIU/mL, p = 0.05) were observed. No statistically significant differences were noted in assessed hormones in patients with solid tumors, independently of Tanner stage. CONCLUSION: Our analysis indicates that adolescents with ALL/NHL and HL prior to treatment, exhibit reduced levels of inhibin B, which indirectly suggests the possibility of spermatogenesis dysfunction.

Factors predicting survival in childhood malignant and intermediate vascular tumors : retrospective analysis of the Polish and German cooperative paediatric soft tissue sarcoma study groups and review of the literature.

BACKGROUND: The rarity of malignant and intermediate vascular tumors in children means that little is known about their clinical course, optimal treatment, and variables predicting survival. METHODS: A total of 32 children with malignant vascular tumors (14 angiosarcomas [AS], 5 epithelioid hemangioendotheliomas, and 13 intermediate vascular tumors, including other hemangioendotheliomas plus adult-type hemangiopericytomas), registered in the German and Polish Paediatric Soft Tissue Sarcomas Study Groups, were treated following the Cooperative Weichteilsarkom Studiengruppe (CWS)-81, -86, -91, and -96 protocols. RESULTS: Male sex, AS histology, tumor size >5 cm, and T2 invasiveness were independent predictors of inferior 5-year overall survival, while AS histology and T2 invasiveness were predictors of inferior 5-year event-free survival. AS histology was the most important negative prognostic factor for overall survival and event-free survival. Completeness of primary tumor excision was a good prognostic factor for survival in univariate, but not multivariate, analysis. Local therapy (radiotherapy and delayed surgery) were provided to the minority of patients (28% and 38%, respectively) late in the course of disease (after a mean of 9 and 6 months, respectively) and did not prevent local relapses. Response to systemic treatment was poor (44%) and did not prevent local and distant relapses. CONCLUSIONS: The clinical course and outcome in childhood epithelioid HE seems to be similar to intravascular tumors and less aggressive than AS. RTX and delayed surgery should be performed more frequently and earlier in the disease course. An urgent need for modification of systemic therapy is needed because of the development of many metastatic and/or combined relapses and poor response to classic chemotherapy. The problem of effective therapy for childhood AS is the most appaling: 13 of 14 patients died of progression despite multimodal treatment.

Testicular function after treatment for acute lymphoblastic leukemia (all) in prepubertal and pubertal boys.

Testicular function was evaluated in 59 male (27 prepubertal and 32 pubertal) survivors treated for ALL according to two different protocols. Serum inhibin B, FSH, testosterone, LH, and testicular volume were measured. In both groups the mean values of inhibin B were lower than control, whereas the other analyzed parameters were comparable. The inhibin B-to-FSH ratio was reduced as compared to the control. Testicular volume was lower than in healthy pubertal patients. The results show that treatment for ALL has a negative effect on spermatogenesis, regardless of the age at treatment and type of therapy.

[Progress in the treatment of non-Hodgkin's lymphoma (NHL) in children. The report of Polish Pediatric Leukaemia/lymphoma Study Group (PPLLSG)]. / Postep w leczeniu nieziarniczych chloniaków zlosliwych (NHL) u dzieci. Raport Polskiej Pediatrycznej Grupy ds. Leczenia Bialaczek i Chloniaków u Dzieci (PPGLBC).

Treatment results of non-Hodgkin lymphoma (NHL) in children has been shown in this study. From 1979 to 2003 children were registered with the diagnosis of NHL in oncology centers of Polish Pediatric Leukaemia/Lymphoma Study Group, a group of 397 patients with NHL B, 222 pts with NHL T and 54 pts with anaplastic large cell lymphoma (ALCL). The pts with NHL T have been treated according to BFM-90 protocol. The predominant primary site of disease was mediastinum (59.3%). Complete remission (CR) was achieved by 87%. EFS for all NHL T pts was 65% and 56% for pts with extensive tumours and 73% for pts with tumours < 10 cm. Patients with NHL B were treated according to the adopted LMB-89 protocol. The majority were Burkitts type and presented abdominal location (50%). 80% with disseminated disease. CR was achieved by 89% patients, but 94% with LDH < 500 IU/L and 73% with LDH > 500 IU. The median time of follow up was 53 months. EFS was 73% for all patients. The patients with ALCL were treated according to several protocols. Peripheral nodes were the most often primary location (40%), than mediastinum (24%) and abdomen (21%). EFS for all pts was 63%. Despite great progress in the therapy of NHL in children during 20 years of observation, the results are not satisfactory in disseminated stages. It is necessary to look for new prognostic markers which make it possible to improve classification of patients. Major surgery in advanced stages is not recommended since it delays chemotherapy and fails to improve overall survival. Early detection of neoplasm is one of the most important efforts to improve therapy success.

[Gonadal function in young men after the treatment for Hodgkin lymphoma]. / Czynnosc gonady meskiej u mlodocianych po leczeniu choroby Hodgkina.

INTRODUCTION: The survival rate after the treatment for Hodgkin lymphoma improved in the last three decades and the late effects of anticancer therapy, particularly gonadal toxicity, became an important problem. THE AIM OF WORK: Assessment of the influence of chemo- and radiotherapy on gonadal function in young male survivors after the treatment for Hodgkin lymphoma (HL). MATERIAL AND METHODS: Levels of inhibin B, testosterone, FSH, LH and testicular volume were measured in 26 HL survivors aged from 15.6 to 25.2, who had been treated for HL in prepubertal (n=8) or pubertal (n=18) period. RESULTS: 1. In all groups, comparing to control one, we found higher FSH concentration (15.2+/-12.3 IU/l vs. 3.3+/-1.2 IU/l); p=0.0004, lower inhibin B (60.9+/-44.5 ng/l vs. 198.1+/-58.1 ng/l); p=0.0001, lower testicular volume (18.2+/-2.6ml vs. 21.3 +/-5.1ml) p=0.01 and normal LH as well as testosterone values. 2. Higher >+2SD FSH and LH were found in 62% and 23%, respectively, and lower <-2SD inhibin B - in 72% of survivors. 3. We did not observe the differences between the patients: a) treated before and during puberty and b) the patients in different stages of disease. 4. Persistently lowered inhibin B concentration and higher, but gradually normalized values of FSH were found >6 years after the end of therapy, 5. Azoospermia was observed in 4/10 patients, oligospermia - in 4/10 and normospermia - only in 2/10. CONCLUSIONS: Anticancer treatment for HL, independently of the age at diagnosis and clinical stage, leads to serious and persistent gonadal dysfunction. The patients should be informed about the problem of gonadal toxicity and possibility of fertility preservation at the moment of diagnosis.

[Gonadal function in boys prior to treatment for acute lymphoblastic leukaemia]. / Ocena czynnosci gonad u chlopców przed leczeniem ostrej bialaczki limfoblastycznej.

UNLABELLED: The aim of this study was to evaluate the gonadal function in boys with newly-diagnosed acute lymphoblastic leukaemia, prior to therapy. PATIENTS AND METHODS: The analysis was evaluated in 48 boys with acute lymphoblastic leukaemia, at the time of diagnosis; 34 boys were prepubertal - Tanner stage of sexual maturation 1 (group I) and 14 - pubertal - Tanner stage 3-5 (group II). Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B, testosterone and testicular volume were determined. RESULTS: In group I no alteration in hormonal status was observed, whereas in group II lower inhibin B was found (68.09 ng/l+/-54.87 vs 152.66 ng/l+/-72.09, p=0.0002). The levels of FSH, LH, testosterone and testicular volume did not differ from healthy adolescents. We did not observe a correlation between inhibin B and FSH concentrations. We did not find the influence of immunophenotype of leukaemic cells, leukocytosis, haemoglobin, platelets levels as well as LDH activity on the values of analyzed hormones. CONCLUSION: In adolescent boys with newly diagnosed leukaemia, lowered inhibin B values may suggest the damage of spermatogenesis even before the start of chemo- and radiotherapy. The small number of examined children requires confirmation on a larger group of patients.

[Testicular function in young men treated in prepubertal period for childhood malignancy]. / Czynnosc gonad u chlopców i mlodych mezczyzn leczonych przed pokwitaniem z powodu choroby nowotworowej.

INTRODUCTION: A complex anticancer treatment leads to different late effects e.g. gonadal damage in adulthood. The information about gonadal function (steroido- and spermatogenesis) after the treatment in prepubertal period are ambiguous. THE AIM OF STUDY: was to evaluate testicular function in young men (Tanner puberty stages IV and V) treated in prepubertal period for childhood malignancies. MATERIAL AND METHODS: In thirty-two pubertal and postpubertal male survivors of childhood cancer (acute lymphoblastic leukemia, ALL - 14, non-Hodgkin lymphoma, NHL - 6, Hodgkin lymphoma, HL and solid tumors - 4) testicular volume and serum FSH, LH, testosterone, inhibin B and calculated quotient inhibin B:FSH were measured. Controls were 15 healthy boys matched by age and Tanner stage. RESULTS: In the whole studied group the mean values of FSH, LH and testosterone did not differ from control, while inhibin B was lower (87.5+/-96.3 vs. 196.5+/-66.8 ng/l; p<0,0003). The lowest values of inhibin B were found in HL (46,15+/-35,12 ng/l) and after ALL treatment (71,1+/-39,8 ng/l). We did not observe differences in hormonal parameters after NHL treatment. The inhibin B-to-FSH ratio was lower, especially after treatment for HL. CONCLUSIONS: Inhibin B is a sensitive marker of gonadal damage. Anticancer therapy in prepubertal period may lead to disturbances in spermatogenesis.

[Gonadal and thyroid function after treatment for Hodgkin's lymphoma in adolescents]. / Ocena wybranych funkcji endokrynnych po leczeniu ziarnicy zlosliwej.

PURPOSE: Complete treatment for Hodgkin's lymphoma (HL) may disturb functioning of different organs leading to deteriorated quality of future life. Endocrine complications are one of the most common and may be the result of radiotherapy of neck, mediastinal and infradiaphragmatic regions, as well as chemotherapy, especially with alkylating agents. The aim of our study was to analyse gonadal and thyroid disturbances in young adults after the treatment for HL in childhood. MATERIAL AND METHOD: In 36 adolescents and young adults (19 males; mean age 20.5+/-3.1) 5.9+/-3.4 years after treatment for HL, we have examined the thyroid function (TSH, thyroxine-T4, tri-iodothyronine-T3, ultrasound) as well as gonadal function in males: FSH, LH, testosterone, inhibin B and in females: FSH,LH, estradiol, inhibin B and anti-müllerian hormone (AMH). Radiotherapy of supradiaphragmatic region was used in 34/36 patients and for infradiaphragmatic region in 17 patients (7 males). Chemotherapy was composed of B-DOPA and MVPP protocols. RESULTS: 1. Signs of subclinical hypothyroidism (elevated TSH) were found in three survivors (irradiated on upper mediastinum). Ultrasonic abnormalities (simple nodules) were found in three patients after mantle radiotherapy. 2. In males the mean values of FSH were higher than in healthy boys (16.0 mIU/ml+/-13.0 vs 3.9 mIU/ml+/-2.0) p=0.0004, inhibin B- lower (50.1 ng/L +/- 43.5 vs.68.1 ng/L +/- 77.2) p = 0.0001, and testicular volume lower (17,3 ml+/-3.8 vs 18.5 ml+/-4.8) p = 0.05. The mean values of LH and testosterone were normal. Inhibin B<2SD and FSH>2SD in 6/19 males, LH>2SD in 4 cases (irradiated infradiaphragmatically) were found. 3. In females, we observed higher FSH values (8.53 mIU/ml+/-3.25 vs 5.8 mIU/ml+/-2.03) p=0.045; lower AMH (17.19 pmol/L+/-14.84 vs 29.40 pmol/L+/-13.2) p=0.05 and tendency to lower inhibin B (31.47 ng/L+/-18.83 vs 47.9 ng/L+/-26.39) p=0.08 than in control group. LH and estradiol concentrations did not differ in between groups. FSH>2SD, inhibin B and AMH<2SD were found in 5 girls (infradiaphragmatic irradiations in 4 cases). CONCLUSIONS: Our observations show the possibility of different endocrine disturbances after combined treatment for HL, especially gonadal function disturbances. Considering these long-term complications, further follow-up is needed, even in the absence of clinical symptoms.

[Spermato- and steroidogenesis in young men treated for non-Hodgkin's and Hodgkin's lymphoma during childhood]. / Ocena funkcji spermatogenezy i steroidogenezy u mlodych mezczyzn leczonych w dziecinstwie z powodu chloniaków nieziarniczych i ziarnicy zlosliwej.

INTRODUCTION: Chemo- and radiotherapy induce testicular damage leading to long-time or irreversible infertility. AIM: To investigate testicular function (spermato- and steroidogenesis) in adolescents and young men cured of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: In thirty one patients cured of HL 5.9 +/-3.3 years ago and sixteen--cured of NHL before 5.44y +/-2.9 and in twenty one healthy men, we measured serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone using immunoenzymatic methods and inhibin B (RIA method). In ten patients, examination of semen was made. RESULTS: 1. Patients with NHL and HL in clinical stage I and IIb, presented normal values of all analyzed parameters. 2. The treatment for HL in IIb, IIIb, IV clinical stage with increasing number of therapeutic protocols, especially together with radiotherapy, led to gonadal dysfunction (increase of FSH, decrease of inhibin B values). 3. The values of testosterone were normal in all patients, whereas LH was elevated in patients treated for HL (stages IIIb and IV). CONCLUSION: 1. Treatment for HL of higher clinical stage leads to gonadal dysfunction, especially of spermatogenesis. 2. The treatment for NHL essentially does not have a gonadotoxic effect. 3. The cryopreservation of sperm before starting the treatment should be especially offered to young men with HL. 4. Overall, attempts must be made to design cytostatics protocols less gonadotoxic than at present.

[Genitourinary soft tissue sarcomas located outside bladder and prostate in children treated according to the CWS-96 protocol--report from the Polish Paediatric Solid Tumours Study Group]. / Przebieg i powiklania terapii u dzieci z miesakami ukladu moczowo-plciowego z wylaczeniem pekcherza moczowego i prostaty leczonych wedlug schematu CWS-96.

AIM: Analysis of therapy efficacy in non-bladder/prostate genitourinary sarcomas in children treated from I'1997 to VI'2003 with CWS-96 protocol in Poland. MATERIAL AND METHODS: 19 children (M/F: 15/4, age: 3m-17,5y; median 7,2y). Histopathology: RMS - 15pts (RME-13), non-RMS- 4. RESULTS: Primary site: testes - 9 patients, paratesticular region - 6, uterus - 2, vagina and ovary-1 of each. 63% presented with low stage neoplasm (I - 7, II - 5). Primary tumour exceeded 5cm and/or invaded surrounding tissues in 7 patients (37%). 3 patients had regional, 2 patients--distant lymph nodes metastases. Primary excision: complete in 7 patients, incomplete - 12 (microscopically - 5, macroscopically - 7). Six of 7 patients with macroscopic tumour residues responded to chemotherapy (CR-4, GR-2). One patient (stage III triton tumour of uterus) did not, respond but obtained complete remission after mutilating delayed surgery. No other patient required delayed tumour resection. Radiotherapy (23,5-54 Gy) was given to 8 patients. 3 children developed local relapse, 3 patients died (16%): 2 due to neoplasm progression, 1 of neutropenia-related sepsis. 16 patients are alive (84%) with mean follow-up 48 months. The only permanent complications result from mutilating surgery. CONCLUSIONS: 1) prognosis in children with non-bladder/prostate genitourinary sarcomas is favourable despite incomplete primary excision of the neoplasm. 2) chemotherapy and radiotherapy were accompanied by severe but transient myelosupression in the HR group.

[Effect of anticancer treatment on leptin level, fat body mass (FM) and lean body mass (LBM)]. / Wplyw leczenia przeciwnowotworowego na wartosci leptyny w surowicy, wskaznik masy ciala oraz zawartosc masy tluszczowej i beztluszczowej.

UNLABELLED: Leptin plays an important role in the metabolism of adipose tissue. Considering that malignancy and its treatment cans affect normal development in childhood. We analysed the correlations between serum leptin levels and body composition after anticancer treatment. We studied 33 survivors (24 boys and 9 girls) who before our study, have been treated for acute lymphoblastic leukaemia (ALL) (n=23) and Hodgkin disease (n=10) after 7.15+/-3.5 years. Sixteen patients with ALL received cranial irradiation (12Gy). We measured body mass index (BM1) fat mass (FM) and lean body mass (LBM) using dual energy x-ray absorptiometry (DXA). We compared these results to the results obtained from reference values (SD score). Leptin levels were measured with the RIA method. RESULTS: 1. Mean leptin levels were higher in girls after puberty (10.93 ng/mL+/-8.9) than in boys (3.73 ng/mL+/-3. 7). In boys no differences were found in leptin levels between T2-4 and T5 stages. In girls the leptin values increased after puberty. Leptin SD score levels were higher in boys during (1.55 +/-1.0) and after puberty (1.46+/-0.75) and in girls - after puberty (1.19 +/-1.51). We did not find any influence of cranial irradiation (12Gy) or various methotrexate doses (5 g/m(2) vs. 19/m(2)) leptin values. 2. No difference in BMI SD score was found within the whole study group. 3. FM did not change ill boys during and after puberty, although FM SD score were higher during puberty (2.98 +/-4.8). In girls FM and FM SD score were higher after puberty. In boys and girls LBM augmented with pubertal development but LBM SD score in boys were lower after puberty (-1.67 +/-1.7) in comparison to puberty (0.2 +/-1.7). No differences were found between LBM SD score in girls during and after puberty. 4. We found a correlation between leptin levels and BMI (r=0.59 p=0.001) and FM (r=0.77 p=0.0001). 5. Relation of FM to LBM in boys remained unchanged, however in girls it increased within pubertal development. CONCLUSION: l. Anticancer treatment during childhood shows no influence on body mass index although the tendency to higher fat mass in pubertal boys and in post pubertal girls is observed. 2. Leptin values depend on fat mass and do not relate directly to the pubertal stage.