Radiobiological risk estimates of adverse events and secondary cancer for proton and photon radiation therapy of pediatric medulloblastoma

Abstract Introduction. The aim of this model study was to estimate and compare the risk of radiation-induced adverse late effects in pediatric patients with medulloblastoma (MB) treated with either three-dimensional conformal radiotherapy (3D CRT), inversely-optimized arc therapy (RapidArc® (RA)) or spot-scanned intensity-modulated proton therapy (IMPT). The aim was also to find dose-volume toxicity parameters relevant to children undergoing RT to be used in the inverse planning of RA and IMPT, and to use in the risk estimations. Material and methods. Treatment plans were created for all three techniques on 10 pediatric patients that have been treated with craniospinal irradiation (CSI) at our institution in 2007–2009. Plans were generated for two prescription CSI doses, 23.4 Gy and 36 Gy. Risk estimates were based on childhood cancer survivor data when available and secondary cancer (SC) risks were estimated as a function of age at exposure and attained age according to the organ-equivalent dose (OED) concept. Results. Estimates of SC risk was higher for the RA plans and differentiable from the estimates for 3D CRT at attained ages above 40 years. The risk of developing heart failure, hearing loss, hypothyroidism and xerostomia was highest for the 3D CRT plans. The risks of all adverse effects were estimated as lowest for the IMPT plans, even when including secondary neutron (SN) irradiation with high values of the neutron radiation weighting factors (WRneutron). Conclusions. When comparing RA and 3D CRT treatment for pediatric MB it is a matter of comparing higher SC risk against higher risks of non-cancer adverse events. Considering time until onset of the different complications is necessary to fully assess patient benefit in such a comparison. The IMPT plans, including SN dose contribution, compared favorably to the photon techniques in terms of all radiobiological risk estimates.

[1]  S. Hancock,et al.  Thyroid abnormalities after therapeutic external radiation. , 1995, International journal of radiation oncology, biology, physics.

[2]  E. Somers.  International Agency for Research on Cancer. , 1985, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[3]  J. Stockman.  Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort , 2011 .

[4]  D. Green,et al.  Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  Se Byeong Lee,et al.  Craniospinal irradiation techniques: a dosimetric comparison of proton beams with standard and advanced photon radiotherapy. , 2011, International journal of radiation oncology, biology, physics.

[6]  R. Mohan,et al.  The risk of developing a second cancer after receiving craniospinal proton irradiation , 2009, Physics in medicine and biology.

[7]  M. Goitein,et al.  Fitting of normal tissue tolerance data to an analytic function. , 1991, International journal of radiation oncology, biology, physics.

[8]  I. Toma-Dasu,et al.  The use of risk estimation models for the induction of secondary cancers following radiotherapy , 2005, Acta oncologica.

[9]  N. Willich,et al.  Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91. , 2000, International journal of radiation oncology, biology, physics.

[10]  A. Skowrońska‐Gardas.  A literature review of the recent radiotherapy clinical trials in pediatric brain tumors. , 2009, Reviews on recent clinical trials.

[11]  Randall K Ten Haken,et al.  A comparison of dose-response models for the parotid gland in a large group of head-and-neck cancer patients. , 2010, International journal of radiation oncology, biology, physics.

[12]  Barbara Kaser-Hotz,et al.  Estimation of radiation-induced cancer from three-dimensional dose distributions: Concept of organ equivalent dose. , 2005, International journal of radiation oncology, biology, physics.

[13]  A. Maity,et al.  Pulmonary function abnormalities in children treated with whole lung irradiation , 2006, Pediatric blood & cancer.

[14]  D. Kuban,et al.  The calculated risk of fatal secondary malignancies from intensity-modulated radiation therapy. , 2005, International journal of radiation oncology, biology, physics.

[15]  D. Parkin,et al.  International Incidence of Childhood Cancer, Vol. II. , 1998, IARC scientific publications.

[16]  Kayla L. Stratton,et al.  Ocular late effects in childhood and adolescent cancer survivors: A report from the childhood cancer survivor study , 2010, Pediatric blood & cancer.

[17]  A. Ng,et al.  Secondary malignancies across the age spectrum. , 2010, Seminars in radiation oncology.

[18]  T. Björk-Eriksson,et al.  Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study , 2005, Acta oncologica.

[19]  L. Robison,et al.  Pulmonary complications in survivors of childhood and adolescent cancer , 2002, Cancer.

[20]  U. Schneider,et al.  Cancer risk estimates from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy , 2008, Radiation and environmental biophysics.

[21]  P. Merlet,et al.  Radiation dose and long term risk of cardiac pathology following radiotherapy and anthracyclin for a childhood cancer. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  S. Donaldson,et al.  Response of growing bone to irradiation: a proposed late effects scoring system. , 1995, International journal of radiation oncology, biology, physics.

[23]  H. Kal,et al.  Induction of severe cataract and late renal dysfunction following total body irradiation: dose-effect relationships. , 2009, Anticancer research.

[24]  U. Schneider,et al.  Site-specific dose-response relationships for cancer induction from the combined Japanese A-bomb and Hodgkin cohorts for doses relevant to radiotherapy , 2011, Theoretical Biology and Medical Modelling.

[25]  Marilyn Stovall,et al.  Second neoplasms in survivors of childhood cancer: findings from the Childhood Cancer Survivor Study cohort. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Uwe Schneider,et al.  Potential reduction of the incidence of radiation-induced second cancers by using proton beams in the treatment of pediatric tumors. , 2002, International journal of radiation oncology, biology, physics.

[27]  T. Merchant,et al.  Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. , 2006, The Lancet. Oncology.

[28]  L. Rorke,et al.  Metastasis stage, adjuvant treatment, and residual tumor are prognostic factors for medulloblastoma in children: conclusions from the Children's Cancer Group 921 randomized phase III study. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  Bingshu E. Chen,et al.  Second cancers among 104,760 survivors of cervical cancer: evaluation of long-term risk. , 2007, Journal of the National Cancer Institute.

[30]  E. Fliers,et al.  Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma. , 1998, European journal of cancer.

[31]  Radhe Mohan,et al.  Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams , 2009, Physics in medicine and biology.

[32]  I. Paddick.  A simple scoring ratio to index the conformity of radiosurgical treatment plans. Technical note. , 2000, Journal of neurosurgery.

[33]  M. Stovall,et al.  Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease. , 2003, JAMA.

[34]  A M Kellerer,et al.  On the conversion of solid cancer excess relative risk into lifetime attributable risk , 2001, Radiation and environmental biophysics.

[35]  J. Stockman.  Geographical Patterns and Time Trends of Cancer Incidence and Survival Among Children and Adolescents in Europe Since the 1970s (the ACCIS Project): An Epidemiological Study , 2006 .

[36]  M. Martel,et al.  Radiation dose-volume effects in the lung. , 2010, International journal of radiation oncology, biology, physics.

[37]  A. Mertens,et al.  A Model-Based Estimate of Cumulative Excess Mortality in Survivors of Childhood Cancer , 2010, Annals of Internal Medicine.

[38]  D. Lefkopoulos,et al.  Role of radiation dose in the risk of secondary leukemia after a solid tumor in childhood treated between 1980 and 1999. , 2010, International journal of radiation oncology, biology, physics.

[39]  Jack Valentin,et al.  Relative biological effectiveness (RBE), quality factor (Q), and radiation weighting factor (wR) , 2003 .

[40]  U. Schneider,et al.  Radiation risk estimates after radiotherapy: application of the organ equivalent dose concept to plateau dose–response relationships , 2005, Radiation and environmental biophysics.

[41]  D. Green,et al.  Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  E Brian Butler,et al.  Intensity-modulated radiation therapy for pediatric medulloblastoma: early report on the reduction of ototoxicity. , 2002, International journal of radiation oncology, biology, physics.

[43]  R. Mulhern,et al.  Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma. , 2006, International journal of radiation oncology, biology, physics.

[44]  D. Tait,et al.  Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  Bhatia,et al.  Thyroid Abnormalities after Therapy for Hodgkin's Disease in Childhood. , 1996, The oncologist.

[46]  Carmen L. Wilson,et al.  A report from the Childhood Cancer Survivor Study (CCSS): cancer related posttraumatic stress symptoms, depression, anxiety, and chronic pain in adult childhood cancer survivors , 2009 .