Management of Thrombocytopenia Hematologic Toxicity

cancers. Nordsmark et al. 2005 showed that tumor hypoxia, independent of hemoglobin con- centration, was singularly associated with poor outcomes in adult patients with head and neck cancers. Multiple xenograft studies have shown a potential benefi t with the use of erythropoietin EPO-stimulating agents ESAs to increase tumor radiosensitivity and potentially improve patient outcomes Pinel et al. 2003 ; Stüben et al. 2003 ; Ning et al. 2005 . Yet, clinical studies with uterine cervix and head and neck cancers and a recent Cochrane review of adult patients with head and neck cancers have failed to show a ben- efi t in outcome with ESAs concurrent with RT Thomas et al. 2008 ; Hoskin et al. 2009 ; Lambin et al. 2009 . Additionally, meta-analyses of ESA usage in adult patients are troubling due to increased risk of thromboembolism and possible increased mortality Bohlius et al. 2006 ; Bennett et al. 2008 . Pediatric data are lacking. Recently updated American Society of Hematology ASH and ASCO guidelines by Rizzo et al. 2010 rec- ommend ESAs with caution for adult patients with chemotherapy-induced anemia and hemo- globin hgb 10 gdL. No mention is made of ESA usage for treatment of radiation-induced anemia. Pediatric consensus guidelines by the French National Cancer Institute recommend avoiding systematic administration of ESAs in pediatric cancer patients with anemia Marec- Berard et al. 2009 . Without any pediatric data, it is diffi cult to imply what potential benefi t transfusion may impart to solid tumor patients, such as patients with soft tissue sarcomas, undergoing radiother- apy. Patients with leukemia, lymphoma and germ cell tumors will likely not benefi t due to the inherent radiosensitivity of such tumor types. Additionally, it is unclear what level of hemoglo- bin would be optimal for radiosensitization. In the adult head and neck cancer studies, hgb 13 gdL was prognostic although again transfu- sion did not prove useful in altering outcomes Dunst et al. 2003 ; Prosnitz et al. 2005 . The cer- vical cancer studies, on the other hand, showed benefi t of transfusion, keeping the hgb ≥12 gdL Grogan et al. 1999 ; Thomas 2001 . Survey of pediatric oncologists’ blood transfusion practice with concurrent radiotherapy showed a bimodal distribution, with 47 of respondents transfus- ing for hgb 9 gdL Wong et al. 2005 . This again underscores the lack of clear evidence- based guidelines to provide for a more uniform treatment strategy, with data to date not support- ing transfusion.

13.3 Central Nervous System

Complications Risk factors for radiation-induced brain and spinal injury include higher total radiation dose, increased dose fractions e.g., 180–200 cGy dose, extended radiation fi eld volume and concomitant usage of central nervous system CNS toxic drugs such as intrathecal methotrex- ate New 2001 ; Butler et al. 2006 ; Chopra and Bogart 2009 ; Rinne et al. 2012 . The developed brain is able to tolerate high total RT doses with a 5 chance of radiation necrosis with daily frac- tionated doses to a total effective dose of 120 Gy Lawrence et al. 2010 . In comparison, the adult brain stem and spinal cord can tolerate effective doses of 54 Gy Kirkpatrick et al. 2010 ; Mayo et al. 2010 . Maximum standard of care doses are generally below these threshold levels. Acute neurologic complications include par- esthesias, seizures, encephalopathy, myelopathy, paralysis and coma and are most likely secondary to underlying brain and spinal pathology and the resulting alteration in the blood-brain barrier and tumor edema and potential mass effect which occurs with RT Keime-Guibert et al. 1998 ; Chopra and Bogart 2009 ; Soussain et al. 2009 ; Rinne et al. 2012 . Management of these symp- toms may require hospitalization as well as medi- cations such as anticonvulsants and steroids e.g., dexamethasone to reduce symptomatic edema. Unlike adults, radiation fatigue has not been reported in pediatric patients and is likely quite rare in this population. Methylphenidate can be used to treat fatigue as in adults if present Butler et al. 2006 . Somnolence syndrome, a subacute toxicity, has been reported in pediatric patients undergoing CNS irradiation Sect. 13.3.1 .