Height and Weight Indices After 12 Gy Versus 18 Gy Cranial Irradiation in Children With Acute Lymphoblastic Leukemia

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International Journal of Radiation Oncology  Biology  Physics

Author Disclosure: K. Kainz: None. E. Dalah: None. J.R. Robbins: None. B.A. Erickson: None. A. Li: None.

Purpose/Objective(s): To examine and describe developmental and behavioral functioning in pediatric brain tumor survivors treated at 3 years of age or younger with proton radiation therapy (PRT). Materials/Methods: Thirty-five patients were evaluated at initiation of PRT (baseline [BL]) and at follow-up (FU). Patients had no prior radiation and received BL and FU testing. Intelligence, adaptive skills, emotional/ behavioral and executive functioning were assessed with age-appropriate standardized measures. Treatment consisted of either craniospinal irradiation (CSI) or partial-brain PRT with or without chemotherapy. Results: Subjects were 63% female and 97% white. Mean household income was $81,689. Mean age at BL was 2.5 years (S.D. Z 0.9, range 1.0e3.8) and mean BL/FU interval was 2.1 years (SD Z 1.4, range 1.0 e 6.7). At diagnosis, 63% had hydrocephalus. Histology was 51% ependymoma, 23% medulloblastoma, 9% craniopharyngioma, 11% other, and 6% glial. Most patients received partial-brain radiation (80%), chemotherapy (66%), surgical resection (97%), and had infratentorial tumors (69%). At FU, 66% had a sensory deficit (hearing; motor). Mean Bayley Mental Development Index (MDI)/Wechsler Full Scale Intelligence Quotient (IQ) and mean Scales of Independent Behavior-Revised Broad Independence (BI) standard scores (SS) were in the Average range at BL (MDI/IQ Z 103.9, S.D. Z 15.5; BI Z 97.3, S.D. Z 15.3) and FU (MDI/IQ Z 107.3, S.D. Z 16.4; BI Z 96.0, S.D. Z 17.7), with no significant change in MDI/ IQ or BI seen at FU. Gender, income, chemotherapy, hydrocephalus, resection, tumor location, and sensory deficits were not related to mean change in MDI/IQ or BI. Extent of radiation was not related to mean change in BI, but was significantly related to change in MDI/IQ (CSI -12.6 SS points) versus partial-brain (+8.5 SS points) (P Z .02). At FU, there were no concerns with attention problems, emotional/behavioral or executive functioning; however, social withdrawal was reported in 21% of the total sample. This finding was not related to gender, extent of treatment, histology, hydrocephalus or sensory deficits at FU. Functional communication skills were significantly lower in the CSI group compared to the partial-brain group at follow-up (P Z .03). Conclusion: At 2 years after PRT, adaptive skills, emotional/behavioral functioning, and executive functioning skills were intact in these very young children. Patients treated with partial-brain radiation fared best in terms of intelligence and communication skills. Although significant declines were seen in intelligence and communication skills in those treated with CSI, scores remained in the developmentally appropriate range. Proton radiation therapy shows promise as a treatment for very young brain tumor patients. Author Disclosure: J. Grieco: None. B.R. Eaton: None. B. Pulsifer: None. C. Evans: None. K. Kuhlthau: None. S. MacDonald: None. N.J. Tarbell: Stock; PROCURE. T.I. Yock: None. M. Pulsifer: None.

1090 Factors Influencing Non-Infectious Interstitial Pneumonia in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation Based Myeloablative Conditioning Mustafa Abugideiri, MD,1 Ronica H. Nanda, MD,1 Charlotte Butker,2 Kuang-Yueh Chiang, MD,3 Elizabeth Butker, MS,1 Mohammad K. Khan, MD, PhD,1 Sungjin Kim, MS,4 Zhengjia Chen, PhD,5 Ann E. Haight, MD,3 and Natia Esiashvili, MD2; 1 Dept. of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia, 2Emory University, Atlanta, GA, 3Aflac Cancer Center and Blood Disorders Center, Children’s Healthcare of Atlanta and Emory University Pediatric Hematology, Oncology, Bone Marrow Transplant, Atlanta, GA, 4Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, CA, 5Dept. of Biostatistics, Winship Cancer Institute, Atlanta, GA Purpose/Objective(s): To evaluate factors associated with increased risk of non-infectious interstitial pneumonia (NIP) in pediatric patients after myeloablative conditioning using total-body irradiation (TBI) followed by allogeneic hematopoietic stem cell transplantation (HSCT). Materials/Methods: The records of 129 consecutive pediatric patients (range, 1-21 years) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution from January 2003 through May 2014 were reviewed. Although total TBI dose ranged from 10.5 to 14 Gy, lung doses were reduced to 10 Gy with partial transmission blocks. The TBI dose rate ranged from 5.57 cGy/min to 20.85 cGy/min. Results: NIP was classified using clinical symptoms, radiographic evidence, and ventilatory defects as noted on pulmonary function tests (PFT), for patients demonstrating no signs of infection throughout the follow-up period. NIP developed in 23.3% of patients (NZ30), but was not associated with an increased incidence of transplant-related mortality (PZ0.59). There was no significant difference in the incidence of NIP between the different types of hematologic malignancies that were treated (PZ0.32). The use of chemotherapeutic agents Cytarabine (PZ0.91) and Etoposide (PZ0.45) in combination with TBI did not influence the development of NIP. The incidence of NIP was not affected by the presence of acute graftversus-host-disease (PZ0.94), nor its severity (PZ0.39); likewise, neither TBI total dose (PZ0.87) nor dose per fraction (PZ0.14) influenced the probability of developing NIP. The TBI dose rate was the one factor to significantly influence NIP (PZ0.001). Overall survival was not significantly affected in patients who developed NIP (PZ0.540). Conclusion: TBI total dose and dose per fraction did not influence the development of NIP in patients treated with a uniform lung dose reduction to 10Gy. The only factor that significantly increased the risk of NIP was the use of a TBI dose rate 15cGy/min. In order to decrease NIP and the potential for late pulmonary toxicity, further reduction of lung dose and dose rate during TBI administration should be considered in children undergoing HSCT. Author Disclosure: M. Abugideiri: None. R.H. Nanda: None. C. Butker: None. K. Chiang: None. E.K. Butker: None. M.K. Khan: None. S. Kim: None. Z. Chen: None. A.E. Haight: None. N. Esiashvili: None.

1091 Developmental and Behavioral Functioning in Very Young Children Following Proton Radiation Therapy for Brain Tumors J. Grieco,1 B.R. Eaton,1 B. Pulsifer,1 C. Evans,1 K. Kuhlthau,1 S. MacDonald,1 N.J. Tarbell,2 T.I. Yock,1 and M. Pulsifer1; 1Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA

1092 Height and Weight Indices After 12 Gy Versus 18 Gy Cranial Irradiation in Children With Acute Lymphoblastic Leukemia A.C. Chen,1 M.F. Okcu,2 Z.E. Dreyer,3 K.Y. Kamdar,3 R.Y. Sonabend,3 H.S. Suzawa,3 and A.C. Paulino4; 1Baylor College of Medicine, Houston, TX, 2Texas Children’s Cancer Center, Houston, TX, 3Texas Children’s Hospital, Houston, TX, 4MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): To determine if there is a difference in height and weight indices among children with acute lymphoblastic leukemia (ALL) treated with 12 Gy versus 18 Gy cranial irradiation (RT). Materials/Methods: Records of children 14-years-old at time of RT with ALL treated at one institution from 2000-2011 were retrospectively reviewed. Patients were excluded if they received prior spinal RT or total body irradiation, had Trisomy 21, were postmenarchal, had not grown >2 cm in the past year, or had <2 years follow-up since RT. Patients’ height, weight, and body mass index (BMI) were converted into z-scores using Centers for Disease Control growth charts to normalize to number of standard deviations from the mean. These values were measured at the preRT clinic visit, and subsequent, yearly intervals. The z-scores of the growth

Volume 93  Number 3S  Supplement 2015 indices were compared based on RT dose, age at RT, and gender using t-tests. Results: A total of 52 patients met the study criteria, with 36 boys and 16 girls. The median age at radiation treatment was 9 years old [range, 2 to 14]. Patients were separated into two dose groups, 12 Gy (n Z 34) and 18 Gy (n Z 18). Median follow-up was 3.9 years [range, 2.0 to 10.9] and 5.67 years [range, 2.7 to 10.5], while the median pre-RT height z-scores were -0.2 [range, -2.2 to 1.4] and -0.9 [range, -3.1 to 0.8] for the two groups, respectively. The change in height indices between pre-RT and at 3 years post-RT was -0.04  0.57 [12 Gy] versus -0.37  0.45 [18 Gy] (P Z .037) and at last follow-up was -0.004  0.60 [12 Gy] versus -0.47  0.74 [18 Gy] for height (P Z .049). No significant change was seen in weight index or BMI. When using 9-years old at RT as the cutoff, there was no difference in height and weight indices between age groups. In girls, there was a significant difference between dose groups in the change in height-indices at 2 years (0.02  0.52 [12 Gy] versus -0.52  0.35 [18 Gy], P Z .028), and 3 years post-RT (0.30  0.48 vs -0.63  0.32, P Z .0009), but this was not significant at last follow-up (0.1  0.54 vs -0.88  1.04, P Z .16). Conclusion: At last follow-up, children with ALL receiving 12 Gy of cranial RT have less height impairment compared to those receiving 18 Gy. This study suggests that height may be affected more in girls than boys when receiving 18 Gy. Radiation therapy dose had no effect on weight or BMI. Author Disclosure: A.C. Chen: None. M.F. Okcu: None. Z.E. Dreyer: None. K.Y. Kamdar: None. R.Y. Sonabend: None. H.S. Suzawa: None. A.C. Paulino: None.

1093 Dose Sculpting Intensity Modulated Radiation Therapy for Vertebral Body Sparing in Treatment of Neuroblastoma L. Ng,1 K. Wong,2 and A.J. Olch3; 1University of Southern California Keck School of Medicine, Los Angeles, CA, 2Children’s Hospital Los Angeles / University of Southern California, Los Angeles, CA, 3Children’s Hospital Los Angeles, Los Angeles, CA Purpose/Objective(s): Long-term survivors of neuroblastoma have an increased cumulative incidence of musculoskeletal anomalies. Historically, for high-risk neuroblastoma, the radiation field to the primary site was designed to cover the full width of adjacent vertebral bodies to avoid growth deformities. With intensity modulated radiation (IMRT), one can shape dose distributions to spare vertebral body levels, possibly limiting growth inhibition without sacrificing tumor coverage. We reviewed our single institution experience with dose sculpting IMRT to assess its effect on vertebral body growth. Materials/Methods: Eighty-eight children with neuroblastoma underwent radiation at our institution from 2000 to 2011. Of these, 47 had a median follow up of 5.3 years with posttreatment thoracolumbar imaging (range, 3.1-9.9 years; 30 boys and 17 girls). Median age at start of radiation was 4 years; all had prior high-dose chemotherapy with stem cell rescue. If vertebral bodies could not be spared, we aimed to cover these “target” vertebral bodies with at least 18 Gy. Thoracic and lumbar vertebral body heights were assessed separately, due to reported differences in growth rates both before and during puberty. In each child’s pretreatment imaging, craniocaudal height was measured en-bloc for target versus spared vertebral bodies. An internal control group of out-of-field vertebral bodies was measured, if available. Craniocaudal heights of target, spared, and control vertebral bodies were similarly measured on follow-up imaging. Dose data for target versus spared vertebral bodies were extracted and correlated to vertebral body growth. Results: On an initial analysis of children from 2002 to 2008, treated to at least 21.6 Gy to paravertebral primary sites, target vertebral bodies received a mean dose of 21.4 Gy (SD 1.14), with V18 over 85% in all but one case. Spared vertebral bodies received a mean dose of 12.3 Gy (SD 1.34). The mean normalized growth rates of target, spared, and control

ePoster Sessions S195 thoracic vertebral bodies, in mm/body/year, were 0.25, 0.28, and 0.44, respectively. For the lumbar spine, mean normalized growth rates in mm/ body/year were 0.13, 0.53, and 0.98 for target, spared, and control vertebral bodies, respectively. The average normalized growth rates of control vertebral bodies, as well as T1-T12 and L1-L5, were lower than published normal rates. Conclusion: Vertebral body sparing was more effective in preserving craniocaudal growth rate in the lumbar spine than in the thoracic spine, both per patient and compared to published normal growth rates. The lower growth rate of control vertebral bodies is consistent with the reported growth delay in neuroblastoma survivors. While the trend in growth rates after dose sculpting IMRT is promising, further analysis and follow up of all cases is underway to develop a robust statistical model for assessing the relationship between dose and growth effects. Author Disclosure: L. Ng: None. K. Wong: None. A.J. Olch: None.

1094 Patterns of IFRT Protocol Deviations in Pediatric Versus Adolescent and Young Adults With Hodgkin Lymphoma Treated With a Pediatric Approach A.S. Parzuchowski,1 D.L. Friedman,2 T. Fitzgerald,3 S.L. Wolden,4 K.V. Dharmarajan,5 L.S. Constine,6 F. Laurie,7 S.K. Kessel,7 B. Appel,8 K. Fernandez,9 A. Punnett,10 and S.A. Terezakis11; 1Johns Hopkins University School of Medicine, Baltimore, MD, 2Vanderbilt University School of Medicine, Nashville, TN, 3University of Massachusetts Medical Center, Worcester, MA, 4Memorial Sloan Kettering Cancer Center, New York, NY, 5Icahn School of Medicine at Mount Sinai, New York City, NY, 6 University of Rochester, Rochester, NY, 7Quality Assurance Review Center, Lincoln, RI, 8Hackensack University Medical Center, Hackensack, NJ, 9University of Illinois College of Medicine at Peoria, Peoria, IL, 10 University of Toronto, Toronto, ON, Canada, 11Johns Hopkins University, Baltimore, MD Purpose/Objective(s): AHOD0031 protocol for Intermediate Hodgkin lymphoma (IRHL) evaluated the use of dose intensive regimen (ABVEPC) with response-based therapy augmentation (addition of DECA) or therapy reduction (elimination of radiation). Central review of diagnostic imaging to validate eligibility and response, and QA of the radiation was performed at the Quality Assurance Review Center (QARC). We examined patterns of radiation protocol deviation (RPD) and relapse between the pediatric (<15) and adolescent and young adult (AYA) (>15-21) patient cohorts. Materials/Methods: Review of IFRT treatment planning was required prior to the start of treatment and a review of the completed treatment was performed at the end of therapy. Records were reviewed by studyaffiliated or QARC-affiliated radiation oncologists to identify dose and volume RPD. Radiation protocol deviations were classified according to dose (DD), volume (VD), undertreatment, and overtreatment. A DD was called minor if there was a 6-10% deviation from protocol-specification, or major if >10%. A VD was called “minor” if volume margins were less than protocol specification, or major if fields transected disease-bearing areas. Undertreatment was defined as less than specified dose or volume and overtreatment as more than specified dose or volume. Proportions of RPD between pediatric and AYA groups were compared; additionally, the association between RPD and relapse was assessed. Results: Of the 1,712 patients enrolled, 1,173 received IFRT, 212 (18%) had RPD; DD and VD patterns were similar between pediatric and AYA groups [16% (77/475) vs 19% (135/698); P Z .19]. Minor VD was the most common type with no statistical difference between pediatric and AYA patients [(57% (44/77) vs 61% (82/135) (P Z .66). Undertreatment RPD accounted for 70% (54/77) in the pediatric group and 75% (101/135) in the AYA group. Thirty patients with RPD had disease relapse; 83% (25/30) of relapses occurred in patients that had an undertreatment RPD. There was no difference in relapse between patients