Nausea, Vomiting and Anorexia

and use of concurrent chemotherapy Feyer et al. 2011 . MASCCISOO and ASCO have created clinical practice guidelines for antiemetics with RINV and have devised an RT emetogenic risk stratifi cation, with high risk in those receiving TBI, moderate risk with RT to the upper abdo- men, low risk for cranial, craniospinal, head and neck, lower thorax, and pelvic RT, and minimal risk with extremity and breast RT Basch et al. 2011 ; Feyer et al. 2011 . Emetic prophylaxis should be per the chemotherapy- related anti- emetic schedule unless the risk of emesis is higher with RT Basch et al. 2011 ; Feyer et al. 2011 . Pediatric guidelines for RINV are lacking. Chap. 10 has a more extensive discussion of antiemetics in relation to chemotherapy- induced nausea and vomiting in children. MASCCISOO and ASCO guidelines both recommend prophylaxis with a 5-HT 3 receptor antagonist in the high- and moderate-risk groups with prophylactic dexamethasone in the high- risk group and optional dexamethasone in the moderate-risk group. MASCCISOO guidelines recommend prophylaxis or rescue with a 5-HT 3 receptor antagonist in the low-risk group while ASCO guidelines recommend no prophylaxis in this cohort. Finally, both guidelines advise res- cue only with either a 5-HT 3 receptor antagonist or dopamine antagonist in the minimal-risk group Basch et al. 2011 ; Feyer et al. 2011 . ASCO guidelines recommend a 5-HT 3 receptor antagonist prior to each fraction with 5 days of dexamethasone; MASCCISOO guidelines make no particular recommendation in regard to duration of prophylaxis Basch et al. 2011 ; Feyer et al. 2011 . Gastric protection should be consid- ered with repeated or prolonged dexamethasone therapy.

13.6.3 Enteritis

Abdominopelvic radiation can cause acute injury to the small bowel mucosa leading to enteritis GI mucositis with cramping, diarrhea, and malabsorptive symptoms, potentially exacer- bated by concomitant chemotherapy administra- tion Chopra and Bogart 2009 . Basic bowel care is recommended including maintenance of ade- quate hydration and consideration for possible lactose intolerance and bacterial pathogens Keefe et al. 2007 ; Peterson et al. 2011 . Symptoms of radiation-induced enteritis have traditionally been managed with moderate bowel rest, such as institution of a low-residue, low-fat and low-lactose diet. For severe diarrhea, anti- motility agents such as loperamide or atropine may be utilized. Due to the risk of bacterial pathogens, treatable causes such as Clostridium diffi cile should be ruled out. A recent systematic review by MASCCISOO suggests the prophy- lactic use of probiotics with Lactobacillus spp. and sulfasalazine, 500 mg twice daily, to prevent RT-induced enteritis for adult patients with pel- vic tumors Gibson et al. 2013 . The recommen- dation for sulfasalazine is specifi cally for patients receiving pelvic EBRT. Additionally the guidelines recommend octreotide in patients after HSCT with chemotherapy conditioning that fail loperamide for control of diarrhea Gibson et al. 2013 . Patients undergoing RT are not included in this recommendation. Agents that have not shown benefi t and should not be utilized include amifostine, 5-ASA and related compounds, and sucralfate Peterson et al. 2011 ; Gibson et al. 2013 . Pediatric data are lacking.

13.6.4 Proctitis

Adult patients receiving radiation for anal cancer are at risk for the development of radiation proc- titis which is usually self-limited and leads to softer or diarrhea-like stools, pain, a sense of rec- tal distension with cramping, urgency, increased frequency, and rarely bleeding Chopra and Bogart 2009 ; Michalski et al. 2010 . A potential example in pediatric patients could be perineal sarcoma; evidence is lacking. RT doses to the rectum 45 Gy increase the risk for proctitis Michalski et al. 2010 . Recent guidelines by MASCCISOO and ESMO suggest the use of IV intrarectal amifostine prior to RT as well as HBO and sucralfate enemas for the treatment of procti- tis and recommend against misoprostol supposi- tories Peterson et al. 2011 ; Gibson et al. 2013 .

13.7 Major Organ Infl ammation

Acute and long-term toxicity to organs within the radiation fi eld is directly related to RT dose, frac- tionation, concomitant chemotherapy and any underlying morbidities. The lungs and kidneys are particularly sensitive to RT and the kidneys specifi cally are the dose-limiting organ with TBI Dawson et al. 2010 . Acute organ toxicity is often poorly defi ned in the pediatric population, but the practitioner must be cognizant of this potential complication which is often a risk factor for the development of chronic complaints.

13.7.1 Pneumonitis

Lung tissue is extremely sensitive to radiation with histologic effects seen in all patients, even those receiving only a few hundred cGy McDonald et al. 1995 . The risk of long-term damage is increased with fractionated lung irra- diation 20 Gy Marks et al. 2010 . Chemotherapeutic agents including bleomycin, methotrexate, alkylating agents, dactinomycin, anthracyclines and vinca alkaloids can synergis- tically add to lung injury McDonald et al. 1995 ; Abid et al. 2001 . Pathologic exudative changes, directly related to the dose and volume of lung tissue irradiated, can lead to acute radiation pneu- monitis which can be followed by healing over weeks to months. Late lung injury with chronic pneumonitis, fi brosis and bronchiolitis obliterans can also result McDonald et al. 1995 ; Abid et al. 2001 . Pneumonitis is usually seen 1–3 months after completion of RT although can be seen more acutely, with 5–15 incidence in adult patients receiving mediastinal EBRT for lung and breast cancer and lymphoma; recent data show a decreased risk with IMRT McDonald et al. 1995 ; Marks et al. 2010 . Data on acute incidence of radiation pneumonitis in pediatric patients are lacking. Weiner et al. 2006 noted in a small cohort of pediatric patients who received whole lung irradiation median 12 Gy that the majority had long-term reductions in total lung capacity and diffusion capacity although most had also received doxorubicin. Common symptoms of acute radiation pneu- monitis include cough, dyspnea, low-grade fever, and pleuritic chest pain, with minimal physical signs although moist rales and pleural friction rub have been noted McDonald et al. 1995 ; Abid et al. 2001 . Early chest radiograph fi ndings include diffuse haziness with interstitial mark- ings or ground-glass opacifi cation in the radia- tion fi eld; the chest radiograph may also be normal McDonald et al. 1995 ; Abid et al. 2001 . Computed tomography is a more sensitive test for the diagnosis of acute radiation pneumonitis McDonald et al. 1995 . Acute radiation pneu- monitis is a risk factor for the development of chronic changes and patients should be followed clinically and with serial pulmonary function testing. Treatment for acute radiation pneumoni- tis is empirical; steroids at a dose of 1–2 mgkg day for several weeks followed by a slow taper have been shown benefi cial although randomized controlled trial data are lacking Abid et al. 2001 . Other potential etiologies including infec- tion, pulmonary embolism, and tumor recurrence should be considered and ruled out Chopra and Bogart 2009 .

13.7.2 Pericarditis

Acute pericarditis is an unlikely toxicity, espe- cially with conformal RT, but can be seen with RT to a substantial volume of the entire heart such as in patients with Hodgkin lymphoma Chopra and Bogart 2009 ; Gagliardi et al. 2010 . Treatment includes utilization of diuretics and cardiac inotropic support as needed. Synergistic acute risk with anthracycline therapy has not been defi ned. Long-term effects including coro- nary artery disease, cardiomyopathy, valvular damage, dysrhythmias and cardiac fi brosis are more likely with whole heart doses 30 Gy Gagliardi et al. 2010 .

13.7.3 Hepatitis

RT-induced liver disease in adults is split between classic and nonclassic presentations