Hepatitis Major Organ Infl ammation

Pan et al. 2010 . Classic RT-induced liver toxic- ity presents with anicteric hepatomegaly and ascites, with onset usually occurring months after the completion of RT although it can occur more rapidly Chopra and Bogart 2009 ; Pan et al. 2010 . Elevated alkaline phosphatase 2× the upper limit of normal ULN is a commonly reported fi nding; pathologic fi ndings are similar to veno- occlusive diseasesinusoidal obstructive syndrome VODSOS Lawrence et al. 1995 ; Chopra and Bogart 2009 ; Pan et al. 2010 . Nonclassic presentations are usually seen in the setting of hepatocellular carcinoma with ele- vated liver transaminases 5× ULN Pan et al. 2010 . Other potential signs of liver toxicity include thrombocytopenia and coagulopathy. Cumulative radiation doses to the liver should be 28–32 Gy to decrease the risk of liver toxic- ity Pan et al. 2010 . Concurrent hepatic disease, secondary to hepatitis B, hepatitis C or the under- lying malignancy, is a potential risk factor for RT-induced hepatitis Pan et al. 2010 . Synergistic risk secondary to concomitant chemotherapy is likely but poorly defi ned. Infectious etiologies, metastases, and drug-induced hepatitis must be considered and ruled out Chopra and Bogart 2009 . Treatment includes diuretics as needed. The use of steroids and anticoagulants has been suggested; since the underlying pathology is sim- ilar to VODSOS, an analogous treatment strat- egy could be considered although this is not evidence-based. Liver failure is often irreversible in adult patients Pan et al. 2010 . Pediatric data are lacking. The presence of focal nodular hyper- plasia has been noted as a late effect after liver RT Bouyn et al. 2003 .

13.7.4 Nephropathy

Acute RT-induced kidney injury is usually sub- clinical with signs and symptoms such as decreased glomerular fi ltration rate and protein- uria occurring in the subacute time period Dawson et al. 2010 . Chronic injury occurs with a long latency and the development of hyperten- sion, elevated creatinine and renal failure, although the risk in the pediatric population receiving multimodal chemoradiotherapy appears low Dawson et al. 2010 ; Bölling et al. 2011 . Acute injury can rarely present with a hemolytic- uremic type syndrome or an increased creatinine, with the total RT dose to the kidney being the most important risk factor Dawson et al. 2010 . Data on incidence in children are lacking. In their review, Dawson et al. 2010 recommend a mean kidney dose of 10 Gy with TBI and 18 Gy with bilateral partial kidney irradiation. Although multiple factors can infl uence kidney function after HSCT, in their review of 92 children after TBI and HSCT, Gerstein et al. 2009 found a very low incidence of persistent renal dysfunc- tion with cumulative fractionated RT doses 12 Gy. Treatment may include low-protein diet, fl uid and salt restriction, use of antihypertensives and diuretics as needed, treatment of anemia, and, if necessary, dialysis Cassady 1995 .

13.7.5 Cystitis

RT to the bladder and urethra can acutely lead to urinary frequency, urgency and dysuria; inconti- nence is rarely seen in the acute period Marks et al. 1995 ; Chopra and Bogart 2009 . The mecha- nism for acute symptoms is unclear; smooth mus- cle edema as well as infl ammation and injury to the epithelial cell layer are proposed mechanisms Marks et al. 1995 . Bladder toxicity is unlikely to occur with cumulative fractionated RT doses 40–50 Gy Viswanathan et al. 2010 . Concurrent chemotherapy, especially with cyclophospha- mide, ifosfamide or busulfan, is an additional potential risk factor Payne et al. 2013 . Anesthetic agents e.g., pyridium and antispasmodics e.g., oxybutynin can be used symptomatically Chopra and Bogart 2009 . Pediatric data on acute RT-induced cystitis are lacking but is a potential complication in the treatment of pelvic tumors. Urinary tract infections should be considered and ruled out Chopra and Bogart 2009 . Hematuria is an unlikely early complication but should be treated with two-way Foley catheter insertion for copious bladder irrigation. Patients who are refractory to such therapy may benefi t from HBO or intravesical therapy Payne et al. 2013 .

13.8 Summary

Radiation-induced toxicity is a real possibility that is likely underrecognized in the pediatric population. The pediatric oncologist must be aware of potential RT-induced complications based on the radiation fi eld, RT dose, fraction- ation, concurrent chemotherapy and potential underlying patient morbidities. A multidisci- plinary approach is often required to plan for and treat any potential complications. Although evi- dence-based prevention and treatment strategies are generally lacking in the pediatric literature, the adult literature, through both evidence and consensus guidelines, provides an excellent resource from which to extrapolate reasonable management plans. References Abid SY, Malhotra V, Perry MC 2001 Radiation-induced and chemotherapy-induced pulmonary injury. Curr Opin Oncol 13:242–248 Abramoff MM, Lopes NN, Lopes LA et al 2008 Low- level laser therapy in the prevention and treatment of chemotherapy-induced oral mucositis in young patients. Photomed Laser Surg 26:393–400 Allen G, Logan R, Gue S 2010 Oral manifestations of cancer treatment in children: a review of the literature. Clin J Oncol Nurs 14:481–490 Archambeau JO, Pezner R, Wasserman T 1995 Pathophysiology of irradiated skin and breast. Int J Radiat Oncol Biol Phys 31:1171–1185 Barbería E, Hernandez C, Miralles V et al 2008 Paediatric patients receiving oncology therapy: review of the literature and management guidelines. Eur J Paediatr Dent 9:188–194 Basch E, Prestrud AA, Hesketh PJ et al 2011 Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29: 4189–4198 Basciano PA, Bussel JB 2012 Thrombopoietin-receptor agonists. Curr Opin Hematol 19:392–398 Becker-Schiebe M, Mengs U, Schaefer M et al 2011 Topical use of a silymarin-based preparation to pre- vent radiodermatitis. Strahlenther Onkol 187: 485–491 Bennett CL, Silver SM, Djulbegovic B et al 2008 Venous thromboembolism and mortality associated with recombinant erythropoietin and darbopoietin administration for the treatment of cancer-associated anemia. JAMA 299:914–924 Bensadoun RJ, Patton LL, Lalla RV et al 2011 Oropharyngeal candidiasis in head and neck cancer patients treated with radiation: update 2011. Support Care Cancer 19:737–744 Berg RA, Ch’ien LT, Lancaster W et al 1983 Neuropsychological sequelae of postradiation somnolence syndrome. J Dev Behav Pediatr 4: 103–107 Bernier J, Bonner J, Vermorken JB et al 2008 Consensus guidelines for the management of radiation dermatitis and coexisting acne-like rash in patients receiving radiotherapy plus EGFR inhibitors for the treatment of squamous cell carcinoma of the head and neck. Ann Oncol 19:142–149 Bleyer A, Choi M, Wang SJ et al 2009 Increased vulner- ability of the spinal cord to radiation or intrathecal chemotherapy during adolescence: a report from the Children’s Oncology Group. Pediatr Blood Cancer 53:1205–1210 Bohlius J, Wilson J, Seidenfeld J et al 2006 Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 98:708–714 Bolderston A, Lloyd NS, Wong RK et al 2006 The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guidelines. Support Care Cancer 14:802–817 Bölling T, Ernst I, Pape H et al 2011 Dose-volume anal- ysis of radiation nephropathy in children: preliminary report of the risk consortium. Int J Radiat Oncol Biol Phys 80:840–844 Bouyn CI, Leclere J, Raimondo G et al 2003 Hepatic focal nodular hyperplasia in children previously treated for a solid tumor. Incidence, risk factors, and outcome. Cancer 97:3107–3113 Bradley J, Movsas B 2004 Radiation esophagitis: pre- dictive factors and preventive strategies. Semin Radiat Oncol 14:280–286 Brizel DM, Dodge RK, Clough RW et al 1999 Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol 53:113–117 Budach W, Bölke E, Homey B 2007 Severe cutaneous reaction during radiation therapy with concurrent cetuximab. N Engl J Med 357:514–515 Bunn PA Jr, Crowley J, Kelly K et al 1995 Chemoradiotherapy with or without granulocyte- macrophage colony stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol 13:1632–1641 Burris HA 3rd, Hurtig J 2010 Radiation recall with anticancer agents. Oncologist 15:1227–1237 Bussel JB, Kuter DJ, George JN et al 2006 AMG 531, a thrombopoiesis-stimulating protein for chronic ITP. N Engl J Med 355:1672–1681 Butler JM, Rapp SR, Shaw EG 2006 Managing the cog- nitive effects of brain tumor radiation therapy. Curr Treat Options Oncol 7:517–523 Cassady JR 1995 Clinical radiation nephropathy. Int J Radiat Oncol Biol Phys 31:1249–1256