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Title: Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology

Abstract

Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver, kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is themore » risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.« less

Authors:
 [1];  [2];  [3];  [4];  [5];  [6];  [7];  [4];  [3];  [8];  [8];  [9]
  1. Department of Radiation Oncology, Centre Leon Berard, Lyon (France)
  2. (France)
  3. Department of Pediatrics, Institut Gustave Roussy, Villejuif (France)
  4. Department of Pediatrics, Institut Curie, Paris (France)
  5. Mater Hospitals, Brisbane (Australia)
  6. Department of Pediatrics, Hopital La Timone, Marseille (France)
  7. Department of Pediatrics, Hopital Nord C.H.U. Saint Etienne, Saint Priest-En-Jarez (France)
  8. Department of Pediatrics, Centre Leon Berard, Lyon (France)
  9. Department of Radiation Oncology, Centre Leon Berard, Lyon (France). E-mail: carrie@lyon.fnclcc.fr
Publication Date:
OSTI Identifier:
20793428
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.10.020; PII: S0360-3016(05)02832-4; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; AUDITORY ORGANS; BONE MARROW; CATARACTS; CHEMOTHERAPY; CHILDREN; HEART; KIDNEYS; LIVER; NEOPLASMS; PATIENTS; SIDE EFFECTS; STH; THYROID; TOXICITY; WHOLE-BODY IRRADIATION

Citation Formats

Flandin, Isabelle, Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon, Hartmann, Olivier, Michon, Jean, Pinkerton, Ross, Coze, Carole, Stephan, Jean Louis, Fourquet, Bernard, Valteau-Couanet, Dominique, Bergeron, Christophe, Philip, Thierry, and Carrie, Christian. Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.1.
Flandin, Isabelle, Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon, Hartmann, Olivier, Michon, Jean, Pinkerton, Ross, Coze, Carole, Stephan, Jean Louis, Fourquet, Bernard, Valteau-Couanet, Dominique, Bergeron, Christophe, Philip, Thierry, & Carrie, Christian. Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology. United States. doi:10.1016/J.IJROBP.2005.1.
Flandin, Isabelle, Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon, Hartmann, Olivier, Michon, Jean, Pinkerton, Ross, Coze, Carole, Stephan, Jean Louis, Fourquet, Bernard, Valteau-Couanet, Dominique, Bergeron, Christophe, Philip, Thierry, and Carrie, Christian. Sat . "Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology". United States. doi:10.1016/J.IJROBP.2005.1.
@article{osti_20793428,
title = {Impact of TBI on late effects in children treated by megatherapy for Stage IV neuroblastoma. A study of the French Society of Pediatric oncology},
author = {Flandin, Isabelle and Department of Radiotherapy/Oncology, Hospital Lyon Sud, Lyon and Hartmann, Olivier and Michon, Jean and Pinkerton, Ross and Coze, Carole and Stephan, Jean Louis and Fourquet, Bernard and Valteau-Couanet, Dominique and Bergeron, Christophe and Philip, Thierry and Carrie, Christian},
abstractNote = {Purpose: To determine the contribution of total body irradiation (TBI) to late sequelae in children treated with high-dose chemotherapy and autologous bone marrow transplantation for Stage IV neuroblastoma. Patients and Methods: We compared two populations that were similar with regard to age, stage, pre-autologous bone marrow transplantation chemotherapy (CT) regimen, period of treatment, and follow-up (12 years). The TBI group (n = 32) received TBI as part of the megatherapy procedure (1982-1993), whereas the CT group (n 30) received conditioning without TBI (1985-1992). Analysis 12 years later focused on growth, weight and corpulence (body mass index) delay; hormonal deficiencies; liver, kidney, heart, ear, eye, and dental sequelae; school performance; and the incidence of secondary tumors. Results: Impact of TBI was most marked in relation to growth and weight delay, although the mean delay was not severe, probably because of treatment with growth hormones. Other consequences of TBI were thyroid insufficiency, cataracts, and a high incidence of secondary tumors. Hearing loss and dental agenesis were more prominent in the group treated with CT alone. No differences were observed in school performance. Conclusion: The most frequent side effects of TBI were cataracts, thyroid insufficiency, and growth delay, but more worrying is the risk of secondary tumors. Because of the young mean age of patients and the toxicity of TBI regimens without any survival advantage, regimens without TBI are preferable in the management of Stage IV neuroblastoma.},
doi = {10.1016/J.IJROBP.2005.1},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 64,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 2006},
month = {Sat Apr 01 00:00:00 EST 2006}
}
  • Purpose: Radiation therapy is important for local control in neuroblastoma. This study reviewed the compliance of plans with the radiation therapy guidelines of the International Society of Paediatric Oncology (Europe) Neuroblastoma Group (SIOPEN) High-Risk Trial protocol. Methods and Materials: The SIOPEN trial central electronic database has sections to record diagnostic imaging and radiation therapy planning data. Individual centers may upload data remotely, but not all centers involved in the trial chose to use this system. A quality scoring system was devised based on how well the radiation therapy plan matched the protocol guidelines, to what extent deviations were justified, andmore » whether adverse effects may result. Central review of radiation therapy planning was undertaken retrospectively in 100 patients for whom complete diagnostic and treatment sets were available. Data were reviewed and compared against protocol guidelines by an international team of radiation oncologists and radiologists. For each patient in the sample, the central review team assigned a quality assurance score. Results: It was found that in 48% of patients there was full compliance with protocol requirements. In 29%, there were deviations for justifiable reasons with no likely long-term adverse effects resulting. In 5%, deviations had occurred for justifiable reasons, but that might result in adverse effects. In 1%, there was a deviation with no discernible justification, which would not lead to long-term adverse events. In 17%, unjustified deviations were noted, with a risk of an adverse outcome resulting. Conclusions: Owing to concern over the proportion of patients in whom unjustified deviations were observed, a protocol amendment has been issued. This offers the opportunity for central review of radiation therapy plans before the start of treatment and the treating clinician a chance to modify plans.« less
  • Purpose: To prospectively investigate the role of local hyperfractionated radiotherapy (RT) after surgical resection in the treatment of intracranial ependymomas in children. Patients and Methods: Postoperative local hyperfractionated RT was proposed for every child (>5 years old at diagnosis) with localized intracranial ependymoma. The planned dose was 60 Gy after complete resection (CR) and 66 Gy after partial resection, delivered in two daily fractions of 1 Gy, according to the early postoperative imaging findings. Results: Between November 1996 and December 2002, 24 children with infratentorial (n = 20) or supratentorial (n = 4) intracranial ependymoma were included. The median agemore » was 8.6 years (range, 5-17). The World Health Organization grade was anaplastic in 10 of the 24 patients (not assessable in 1). After a retrospective central review, a CR was reported in 16 patients, partial resection in 4, and doubtful resection in 4. The radiation dose was 60 Gy in 18 cases (one partial resection), 66 Gy in 5 cases (one CR), and 54 Gy in 1 case (CR). The 5-year overall survival rate was 74.8%, and the progression-free survival rate was 54.2%. Of the 24 patients, 11 developed a relapse: 7 local only and 4 metastatic and local. The histological grade and extent of resection were not prognostic factors. More than 3 in 4 children had no sequelae of RT at a median follow-up of 7 years (95% confidence interval, 66.4-90.0 months). Conclusion: The results of our study have shown that hyperfractionated RT is safe but provides no outcome benefit compared with other strategies of RT such as standard fractionated regimens.« less
  • The efficacy of intrathecal (i.t.) chemoprophylaxis was compared with cranial radiotherapy plus i.t. methotrexate (MTX) in a Southwest Oncology Group (SWOG) study accessing 408 patients from September 10, 1974, to October 29, 1976. Randomization was stratified by prognostic groups (PGs) based on age and white blood cell count at diagnosis. All received induction therapy with vincristine and prednisone (Pred); maintenance therapy consisted of daily 6-mercaptopurine and weekly MTX. Consolidation for arm 1 employed cyclophosphamide and L-asparaginase followed by biwekly 5-day courses of parenteral MTX. The first dose of each course of MTX was given i.t. in triple chemoprophylaxis (MTX, hydrocortisone,more » and cytosine arabinoside). During maintenance, i.t. chemoprophylaxis was bimonthly and 28-day Pred ''pulses'' were given every 3 mo. Arm 2 i.t. chemoprophylaxis was initiated on achievement of remission, and arm 3 i.t. on treatment day 1; both continued 1 yr. Arm 4 induction included two doses of L-asparaginase. On achievement of remission, CNS prophylaxis (radiotherapy, 2400 rad plus i.t. MTX) was given. For all, therapy was discontinued after 3 yr of continuous complete remission. Survival and the incidence of extramedullary relapse were similar for the treatment employing either i.t. chemoprophylaxis or radiotherapy plus i.t. MTX upon achievement of remission. The study indicates that i.t. chemoprophylaxis may be substituted for cranial radiotherapy when utilizing effective systemic regimens. Additionally, chemoprophylaxis may be reduced from 3 to 1 yr in patients with good prognostic factors. (JMT)« less
  • Our experience in scintigraphic diagnosis using /sup 123/I//sup 131/I-metaiodobenzylguanidine (MIBG) on 37 children with neuroblastomas stage III-IV is reported and discussed, together with the results obtained by other authors on MIBG diagnosis at the International Workshop of Pediatric Oncology held in Rome in September 1986. In our own investigation, 49 examinations were undertaken with /sup 123/I-MIBG and 66 with /sup 131/I-MIBG partly under therapy conditions with high-activity doses of /sup 131/I-MIBG. There were 29 neuroblastomas, 3 ganglioneuromas, and 3 ganglioneuroblastomas. The localization of all primary tumors was over 90%; for neuroblastomas with a high level of catecholamine excretion, over 95%.more » The specificity was about 100%. The sensitivity with respect to tumor relapse and all localization of metastasis and bone-marrow tumor infiltration in the follow-up-phase approaches was 70% during or after therapy. What emerges from the experience of most investigators is that /sup 123/I-MIBG is the agent best suited to detect tumor relapse and metastasis, especially in the bone marrow. MIBG examinations are of great value in follow-up studies for detecting tumor relapse and bone marrow infiltrations, especially before the onset of clinical symptoms and other indications. 16 references.« less
  • Purpose: To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. Methods and Materials: A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, andmore » 18.4 years at most recent follow-up. Results: Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). Conclusions: This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling on family planning.« less