Neuroblastoma, Childhood Cancer Survivorship, and Reducing the Consequences of Cure

PERSPECTIVE Neuroblastoma, childhood cancer survivorship, and reducing the consequences of cure

Bone Marrow Transplantation (2007) 40, 721–722; and act upon, but of enormous importance to parents doi:10.1038/sj.bmt.1705815 and their children. As is clear from this study and others, radiation, particularly total body irradiation (TBI), is a bad actor Few would dispute the strategy that every reasonable, if not from a late effects standpoint. Hopefully, several of the conceivable, effort must be made to save the life of a child more onerous long-term adverse effects of neuroblastoma with cancer. In fact, the industrialized world has made truly will in the future be circumvented now that the current remarkable progress in pediatric multimodal, risk-adapted standard of care in the United States and Europe for cancer treatment, resultingin long-termsurvival rates for autologous stem cell transplantation avoids inclusion of most childhood malignant diseases that were unimaginable TBI as a preparatory agent. However, local irradiation, a few decades ago.1 Unfortunately, skirtingthis trend, high- myeloablative therapies includingcytotoxic alkylating risk neuroblastoma tumors have proven to be quite agents and platinum drugs, and surgical intervention are obstinate in the face of modern therapy and, even today, not going away in the foreseeable future, so the importance children with this form of cancer do not generally fare of understanding, monitoring and treating long-term effects well.2,3 As evidenced by the case series presented by Trahair of high-risk neuroblastoma (and other pediatric cancers et al.,4 in this issue of Bone Marrow Transplantation, those treated with stem cell transplantation) are also here to stay. who are fortunate enough to survive their disease confront This begs the question: who provides this specialized yet many serious long-term adverse effects from neuro- heterogeneous ‘survivorship’ care? One answer, of course, blastoma and its treatment. is multi-disciplinary long-term cancer follow-up clinics.17 Concerted study of the ‘consequences of cure’ from Such clinics, however, are still not equipped with proven cancer treatment has only recently emerged as a scientific standardized care guidelines or available in most settings, discipline within clinical and epidemiological research although they are slowly becoming more accepted as an arenas.5–7 Such survivorship research in the pediatric important clinical means for helpingpatients and families settinghas focused primarily on the more common identify, treat and navigate the constellation of symptoms malignancies, such as acute lymphoblastic leukemia and and conditions that not only linger after the completion of Hodgkin’s lymphoma, with very little systematic study on treatment, but newly surface many years after the disease is late effects of neuroblastoma, perhaps with the exception of defeated. The need for specialized treatment for physical documentingthe permanent ototoxic effects of cisplatin impairments, hearingloss, gonadaldysfunction, subtle and carboplatin.8–12 neurocognitive deficiencies, and psychological distress, From the present study4 and similar clinical follow- amongmany other sequelae, will differ dependingon the up work by Laverdie` re et al.13 and others,14 we can reach a developmental milestone that the child or adolescent or brief understandingof the risks for multi-organsequelae youngadult is negotiatingatthat point in time. Very few amongsurvivors of advanced stageneuroblastoma. cancer centers have programs to transition primary care The most prominent are endocrine impairments, including from childhood to adulthood; yet adult primary care short stature, hypothyroidism and ovarian and testicular physicians are not often exposed to these cases and are not dysfunction; musculoskeletal complications, including familiar enough with the toxic therapies to understand the kyphosis and scoliosis, significant dental abnormalities, complexity of the adverse consequences that may arise. slipped capital femoral epiphysis, fractures, fibrosis and Additionally, parents and childhood cancer survivors, who hypoplasia; major organ system impairment, most notably need to take the lead in self-care management, often are not serious renal dysfunction, but also cardiac toxicity and reliable historians of their disease or treatment.18,19 lungfibrosis or other pulmonary problems; neurological What are the oncologists and transplant team to do? disorders, includingopsoclonus myoclonus (opsoclonus Aside from the need for evidence-based clinical guidelines, ataxia), neurogenic bladder, and paresis and paraplegia; which has recently been taken on by the United Kingdom and sensory impairments, includingchronic pain, Children’s Cancer Study Group, the Scottish Intercollegi- parasthesia, cataracts and neurosensory hearingloss. ate Guidelines Network and the Children’s Oncology And of course, the effect that many parents fear the Group,19,20 careful and repeated education and support of most (perhaps after that of recurrence) is a sub- the parents to better understand, monitor, document and sequent primary malignancy. How these conditions act upon late effects is the most obvious and practical affect health-related quality of life of the patient,9,15,16 approach. The current paradigm is that survivorship and the well-beingof the family, is very difficult to measure trainingstarts when the disease is diagnosedand ‘treatment Perspective 722 with intent to cure’ begins, not five years after treatment is 8 Gilmer-Knight KR, Kraemer DF, Neuwelt EA. Ototoxicity completed.5 A patient care plan, focused on survivorship, in children receivingplatinum chemotherapy: underesti- needs to be implemented from day 1. Next, encouraging matinga commonly occurringtoxicity that may influence development of childhood cancer follow-up clinics that academic and social development. J Clin Oncol 2005; 23: readily serve the complex needs of the child as he or she 8588–8596. progresses through their developmental stages, physically 9 Gurney JG, Tersak JM, Ness KK, Landier W, Matthay KK, Schmidt ML. Hearingloss, quality of life, and academic and emotionally, would be of enormous help. Additionally, problems in long-term neuroblastoma survivors—a report trainingand supportingMed/Peds physicians in long-term from the Children’s Oncology Group. Pediatrics (in press). care of childhood cancer patients who could serve 10 Kushner BH, Budnick AS, Kramer K, Modak S, adolescents into their adulthood would be very valuable. CheungNKV. Ototoxicity from high-doseuse of platinum And finally, encouraging and supporting integrated train- compounds in patients with neuroblastoma. Cancer 2006; 107: ingin long-termcancer care and clinical outcomes research 417–422. in medical teaching settings, for oncologists and nurse 11 Parsons SK, Neault MW, Lehmann LE, Brennan LL, Eickhoff practitioners, but also for the many subspecialties, such as CE, Kretschmar CS et al. Severe ototoxicity following endocrinology, neurology, OB/GYN and psychology, is carboplatin-containing conditioning regimen for autologous Bone Marrow essential if quality of care is to improve and progress. We marrow transplantation for neuroblastoma. Transplant 1998; 22: 669–674. owe it to the kids and their families to advocate for these 12 Punnett A, Bliss B, Dupuis LL, Abdolell M, Doyle J, SungL. essential comprehensive services. Ototoxicity followingpediatric hematopoietic stem cell trans- JG Gurney plantation: a prospective cohort study. Pediatr Blood Cancer Child Health Evaluation and Research Unit, Department 2004; 42: 598–603. 13 Laverdiere C, CheungNK, Kushner BH, Kramer K, Modak of Pediatrics, University of Michigan Medical School, S, LaQuaglia MP et al. Long-term complications in survivors Ann Arbor, MI, USA of advanced stage neuroblastoma. Pediatr Blood Cancer 2005; E-mail: [email protected] 45: 324–332. 14 Laverdiere C, Gurney JG, Sklar CA. Late effects of treatment. In: CheungNK, Cohn SL (eds). Neuroblastoma. Springer: References Berlin, 2005, pp 277–288. 15 Barr RD, Chalmers D, De Pauw S, FurlongW, Weitzman S, 1 Reaman GH. Pediatric cancer research from past successes Feeny D. Health-related quality of life in survivors of Wilms’ through collaboration to future transdisciplinary research. tumor and advanced neuroblastoma: a cross-sectional study. J Pediatr Oncol Nurs 2004; 21: 123–127. J Clin Oncol 2000; 18: 3280–3287. 2 Matthay KK, CheungNK. Highrisk neuroblastoma. In: 16 Nathan PC, Ness KK, GreenbergML, Hudson M, Wolden S, CheungNK, Cohn SL (eds). Neuroblastoma. Springer: Berlin, Davidoff A et al. Health-related quality of life in adult 2005, pp 138–149. survivors of childhood Wilms tumor or neuroblastoma: a 3 Matthay KK, Villablanca JG, Seeger RC, Stram DO, Harris report from the Childhood Cancer Survivor Study. Pediatr RE, Ramsay NK et al. Treatment of high-risk neuroblastoma Blood Cancer 2006 (July 7, E-pub ahead of print). with intensive chemotherapy, radiotherapy, autologous bone 17 Friedman DL, Freyer DR, Levitt GA. Models of care for marrow transplantation, and 13-cis-retinoic acid. Children’s survivors of childhood cancer. Pediatr Blood Cancer 2006; 46: Cancer Group. N Engl J Med 1999; 341: 1165–1173. 159–168. 4 Trahair TN, Vowels MR, Johnston K, Cohn RJ, Russell SJ, 18 Kadan-Lottick NS, Robison LL, Gurney JG, Neglia JP, Yasui Neville KA et al. Long-term outcomes in children with high- Y, Hayashi R et al. Childhood cancer survivors’ knowledge risk neuroblastoma treated with autologous stem cell trans- about their past diagnosis and treatment: Childhood Cancer plantation. Bone Marrow Transplant 2007; 40: 741–746. Survivor study. JAMA 2002; 287: 1832–1839. 5 Hewitt M, Greenfield S, Stovall E, and the Institute of 19 Landier W, Wallace WH, Hudson MM. Long-term follow-up Medicine’s Committee on Cancer Survivorship (eds). From of pediatric cancer survivors: education, surveillance, and Cancer Patient to Cancer Survivor: Lost in Transition. The screening. Pediatr Blood Cancer 2006; 46: 149–158. National Academies Press: Washington, DC, 2005. 20 Landier W, Bhatia S, Eshelman DA, Forte KJ, Sweeney T, 6 Ness KK, Gurney JG. Adverse late effects of childhood cancer Hester AL et al. Development of risk-based guidelines for and its treatment on health and performance. Annu Rev Public pediatric cancer survivors: the Children’s Oncology Group Health 2007; 28: 279–302. Long-Term Follow-Up Guidelines from the Children’s Onco- 7 Meadows AT. Pediatric cancer survivorship: research and logy Group Late Effects Committee and Nursing Discipline. clinical care. J Clin Oncol 2006; 24: 5160–5165. J Clin Oncol 2004; 22: 4979–4990.

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