Predictors of Setup Accuracy in Image Guided CNS Radiation Therapy: Final Analysis From a Prospective Low-Dose Cone Beam CT Protocol From a Multinational Pediatrics Consortium

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International Journal of Radiation Oncology  Biology  Physics

that had RPD 14% (30/212) and those without RPD 13% (123/961) (P Z .57). There was no difference in RPD relapse between pediatric and AYA groups, 15% (12/77) versus 13% (18/135) respectively, (P Z .68). Conclusion: Radiation protocol deviation occurred in 18% of pediatric patients with IRHL undergoing IFRT with a pediatric approach. The majority of RPD were minor and were related to undertreatment. There was no observed difference in RPD between the pediatric and AYA cohorts demonstrating that the QA process was consistent regardless of age. Whether maximization of protocol RT treatment specification has an impact in the outcome of AYA group needs to be assessed in a larger cohort of patients. Author Disclosure: A.S. Parzuchowski: Research Grant; ASTRO Minority Summer Fellowship Award. D.L. Friedman: None. T. Fitzgerald: None. S.L. Wolden: None. K.V. Dharmarajan: None. L.S. Constine: None. F. Laurie: None. S.K. Kessel: None. B. Appel: None. K. Fernandez: None. A. Punnett: None. S.A. Terezakis: None.

disease progression following 131I-MIBG treatment of relapsed or refractory neuroblastoma. Author Disclosure: R. Fishel Ben Kenan: None. A.L. Polishchuk: Employee; Peninsula Orthopedic Associates. Research Grant; Lung Cancer Research Foundation. R.A. Hawkins: None. S.E. Braunstein: None. K.K. Matthay: None. S.G. DuBois: None. D.A. Haas-Kogan: None.

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Anatomic Patterns of Relapse and Progression Following Treatment With 131I-MIBG in Metastatic Neuroblastoma R. Fishel Ben Kenan, A.L. Polishchuk, R.A. Hawkins, S.E. Braunstein, K.K. Matthay, S.G. DuBois, and D.A. Haas-Kogan; University of California, San Francisco, San Francisco, CA

Predictors of Setup Accuracy in Image Guided CNS Radiation Therapy: Final Analysis From a Prospective Low-Dose Cone Beam CT Protocol From a Multinational Pediatrics Consortium S.R. Alcorn,1 C. Bojechko,2 R.A. Rubo,3 M.J. Chen,4 K. Dieckmann,5 R.P. Ermoian,6 E.C. Ford,2 S. MacDonald,7 T.R. McNutt,1 A. Nechesnyuk,8 K. Nilsson,9 H.C. Sjoestrand,9 K.S. Smith,10 E.J. Tryggestad,11 R.C. Villar,3 B. Winey,12 and S.A. Terezakis1; 1Johns Hopkins University, Baltimore, MD, 2University of Washington, Seattle, WA, 3Centro Infantil Boldrini, Campinas, Brazil, 4A. C. Camargo Cancer Center, Sa˜o Paulo, Brazil, 5Universita¨t Klinik Fu¨r Strahlentherapie und Strahlenbiologie, Vienna, Austria, 6University of Washington Medical Center, Seattle, WA, 7Massachusetts General Hospital, Boston, MA, 8 Federal Scientific Clinical Center of Children’s Hematology, Oncology and Immunology, Moscow, Russia, 9Akademiska Sjukhuset, Uppsala, Sweden, 10Johns Hopkins Hospital, Baltimore, MD, 11Mayo Clinic, Eau Claire, WI, 12Harvard Medical School, Boston, MA

Purpose/Objective(s): Neuroblastoma is the most common pediatric extracranial solid tumor. Patients with MIBG-avid relapsed or refractory neuroblastoma after up front therapy may exhibit significant, but often transient, responses to salvage treatment with 131I-MIBG. It is not known whether disease progression following 131I-MIBG treatment occurs in previously involved versus new anatomic sites of disease. Understanding this pattern of relapse may inform the use of consolidative external beam radiation therapy following 131I-MIBG administration. Materials/Methods: Patients with relapsed or refractory metastatic MIBGavid neuroblastoma or ganglioneuroblastoma who received single-agent 131 I-MIBG on phase 2 and compassionate access protocols at a singleinstitution were included if they had 1) stable or responding disease 6-8 weeks following 131I-MIBG infusion, but subsequently experienced disease progression and 2) had serial diagnostic MIBG scans available from protocol enrollment through first progression. Scans were reviewed to establish anatomic locations and temporal evolution of MIBG-avid disease. Progression was defined as development of MIBG-avid disease in a previously uninvolved anatomic location, or as recurrence of MIBG avidity in a previously involved site that had fully cleared following MIBG treatment. Results: A total of 142 MIBG-avid metastatic sites were identified immediately prior to MIBG therapy in a cohort of 15 patients (seven male, eight female). Median age at first 131I-MIBG treatment was 9.6 years (range, 4.3-51.2). Following first 131I-MIBG infusion, and prior to disease progression, five patients received additional 131I-MIBG treatments, but none received external beam radiation therapy. Median time to progression after first 131I-MIBG treatment was 0.6 years (range, 0.22.5). At first progression, a total of 140 MIBG-avid sites were identified, of which 103 (74%) overlapped with pretreatment disease sites, while 37 (26%) represented anatomically new disease areas. Nine of 15 patients had one or more new MIBG avid site at first progression. Of the 103 involved sites at progression that overlapped with pretreatment disease, 19 represented relapsed sites that had cleared following MIBG therapy, 19 were persistent but increasingly MIBG-avid, and 65 were stably persistent. Conclusion: Previously involved anatomic disease sites predominate at disease progression following 131I-MIBG treatment; nevertheless, the majority of patients progressed in at least one new anatomic disease site. This observation suggests that consolidative focal therapies targeting residual disease sites may be of limited benefit in preventing systemic

Purpose/Objective(s): Parameters and predictors of setup accuracy associated with lower dose cone beam CT (CBCT) protocols have not been well described for pediatric image guided radiation therapy (IGRT); yet, such protocols may allow for adequate target localization while minimizing radiation exposure, which is particularly important in the pediatric population. We describe updated results of a prospective evaluation of a low-dose CBCT protocol for central nervous system (CNS) IGRT across a multinational pediatrics consortium. Materials/Methods: Providers from nine international institutions participated in prospective data collection for CNS IGRT practices in patients  21 years. A low-dose CBCT protocol with skin dose of 0.1 cGy/scan was employed across sites. Treatment table shifts between setup with surface lasers versus CBCT in x (transverse), y (superiorinferior), and z (anterior-posterior) translational directions were used to approximate setup accuracy, and vector magnitudes [VM Z O( x2 + y2 + z2)] for these shifts were determined. Setup parameters were calculated, including 1) VM group mean error; 2) systematic error, as estimated by the standard deviation (SD) of mean VM; and 3) random error, as estimated by the root mean square (RMS) of SD. Predictor variables were collected prospectively and retrospectively and evaluated by general linear regression. Results: For 96 patients, 2 179 pretreatment CBCT were evaluated. Median patient age was 9 years (range, 1-20), and median baseline Karnofsky performance status (KPS) was 80 (range, 40-100). Tumors were most commonly gliomas (46%), and IGRT site was 43% supratentorial, 28% infratentorial, and 29% other (including craniospinal radiation). Median radiation therapy dose was 54 Gy (range, 24-59.4). Immobilization was achieved by short (67%) versus long (33%) thermoplastic masks. Anesthesia was used in 32% of cases, and baseline steroids were reported for 48% of patients. For the x, y, and z directions, respectively, group mean (SD) tables shifts were 0.20 mm (1.41), 0.13 mm (1.42), and -0.44 mm (1.72); group mean VM was 3.32 mm (1.24). Root mean squares of SD were 1.65, 1.60, 1.62, and 1.50, respectively. On multivariable linear regression, VM was significantly lower for patients with higher KPS, no baseline steroids requirement, and long mask immobilization. Use of anesthesia and patient age were not independent predictors of VM. Conclusion: A protocol for low-dose CBCT was successfully employed across a multinational pediatrics consortium, demonstrating setup with table shift VMs that approximate CTV-PTV expansions frequently used

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Volume 93  Number 3S  Supplement 2015 in CNS radiation therapy. Predictors of setup accuracy included baseline KPS, steroid requirement, and immobilization technique, suggesting that subpopulations that may benefit from more frequent pretreatment imaging. Author Disclosure: S.R. Alcorn: Research Grant; Elekta AB. C. Bojechko: Research Grant; Elekta AB. R. Rubo: Research Grant; Elekta AB. M.J. Chen: Research Grant; Elekta AB. K. Dieckmann: Research Grant; Elekta AB. R.P. Ermoian: Employee; Neighborcare. Volunteer Faculty; University of Washington. Research Grant; Elekta AB. E.C. Ford: Research Grant; Elekta AB. S. MacDonald: Research Grant; Elekta AB. T.R. McNutt: Research Grant; Elekta AB. A. Nechesnyuk: Research Grant; Elekta AB. K. Nilsson: Research Grant; Elekta AB. H.C. Sjoestrand: Research Grant; Elekta AB. K.S. Smith: Research Grant; Elekta AB. E.J. Tryggestad: Research Grant; Elekta AB. R.C. Villar: Research Grant; Elekta AB. B. Winey: Research Grant; Elekta AB. S.A. Terezakis: Research Grant; Elekta AB.

ePoster Sessions S197 ePoster Abstracts 1097; Table 1 Target Plan D95 A B C D

51.4 52.5 52.5 52.6

BS Dmean

BS Dmax

BS V50 Gy

BS LETmean

BS Dmean (Variable RBE)

BS Dmax (Variable RBE)

36.3 49.9 52.4 52.3

55.8 54.9 55.2 54.7

42.1 71.7 91.8 91.4

4.9 3.1 3.2 3.3

44.7 56.2 59.2 59.6

64.2 62.3 64.4 65.1

[1] Carabe et al. 2013 [2] Buchsbaum et al. 2014 [3] Indelicato et al. 2014 Author Disclosure: D. Giantsoudi: None. V. Kim: None. J.A. Adams: None. S. MacDonald: None. H. Paganetti: None.

1098 1097 LET Versus Dose-Sparing of the Brainstem in Proton Radiation Therapy: Treatment Technique Comparison for Posterior Fossa Tumors Based on Variable RBE D. Giantsoudi,1 V. Kim,2 J.A. Adams,2 S. MacDonald,2 and H. Paganetti1; 1 Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2 Massachusetts General Hospital, Boston, MA Purpose/Objective(s): Consideration of brainstem (BS) toxicity is crucial in proton radiation therapy (PRT) of posterior fossa tumors due to the target proximity. To spare the cochlea and other sensitive structures, ideal beam geometry requires placing the distal end of the treatment field towards or within the BS, emphasizing the significance of the calculation accuracy of the radiobiologically effective proton range. Several centers employ techniques to include the BS within the treatment field, placing the high linear energy transfer (LET) region beyond it to avoid potentially high RBE values within this sensitive structure. We examine the dosimetric efficacy of such techniques, when accounting for LET and dose-dependent variable RBE distribution [1]. Materials/Methods: Four planning techniques were applied in ependymoma cases: A) one posterior anterior (PA) and two lateral beams, covering only the target with margins extending into the BS, with two last fractions delivered by modified lateral beams to fully spare the BS; B) a PA and two posterior oblique (PAO) fields (60 from PA direction), including the whole-BS in the treatment volume; C) two PAO fields (25 from PA direction), including the whole-BS in the treatment volume; and D) same as C) with beam splitting and end or range shaping according to [2]. Monte Carlo (TOPAS) calculated dose, LET and RBE weighted dose distributions were compared among the different techniques in terms of target coverage and BS inclusion. Results: Table 1 presents dosimetric indexes of target coverage (D95) and BS inclusion (Dmean(constant RBE), V50 Gy, LETmean, Dmean(variable RBE)) for one case. The highest BS LET was observed for technique A; however, due to significantly lower physical dose, it still led to more beneficial variable RBE-weighted dose among all four techniques. Although technique D aimed to reduce the LET in the BS compared to technique C, our results showed a small increase instead (3.3 vs 3.2 keV/mm). For all “shoot through” techniques B-D, more than 61.7% of the BS volume received doses higher than 50 Gy (RBE), a dosimetric variable potentially associated with BS toxicity [3]. Conclusion: Restricting the prescription dose to the target leads to favorable variable RBE weighted doses, despite increased LET in the brainstem. Further research is warranted to determine the impact of LET for proton planning; however, concerns regarding LET should not waive the importance of previously documented dose/volume parameters and dosimetric benefit of techniques limiting brainstem dose over full inclusion of the brainstem structure in the treatment volume.

Subtotal Lymphoid Irradiation in the Treatment and Prevention of Pediatric Cardiac Allograft Rejection: A 17-year Experience S.X. Yan,1 A.K. Jain,2 S. Crockford,1 D.P. Horowitz,3 T.J. Wang,3 E.P. Connolly,3 L.J. Addonizio,3 and S.K. Cheng3; 1Columbia University College of Physicians and Surgeons, New York, NY, 2Ashland Bellefonte Cancer Center, Ashland, NY, 3Columbia University Medical Center, New York, NY Purpose/Objective(s): Allograft rejection continues to remain a leading cause of morbidity and mortality for pediatric heart transplant patients despite use of more efficacious immunosuppressive agents. A few small studies have shown the efficacy of total lymphoid irradiation (TLI) in treating recurrent rejections in pediatric cardiac allograft recipients. At our institution, we employed subtotal lymphoid irradiation (STLI) not only for treatment of allograft rejection but also as prophylactic therapy for prevention of rejection in a re-transplant graft in pediatric patients. We retrospectively reviewed pediatric heart transplant patients who received STLI for both rejection treatment and prevention. We reported the efficacy and safety data of STLI at our institution. Materials/Methods: From 1996 through 2011, pediatric heart transplant patients received STLI for treatment of recurrent rejections (n Z 11) or prophylactically for rejection prevention (n Z 11). Treatment consisted of 8 Gy in 10 fractions delivered twice a week to mantle and para-aortic/ spleen fields. Rejection was defined as  grade 1B on endomyocardial biopsy by ISHLT criteria. Median follow-up was 9.1 years, ranging from 6 months to 17 years. Results: Twenty-one patients completed treatment of 8 Gy over a median of 36 days despite relative leukopenia during STLI; treatment was truncated in one patient due to cholangitis. In the cohort treated for rejection, the number of rejections per patient dropped from 3.72 before treatment to 1.90 after treatment (P Z .04). Three out of 11 patients were rejection-free after STLI. Percentage of patients experiencing rejection one year before treatment was 81.8% compared to 54.5% one year after STLI. Mean time to developing a new rejection after STLI was 789.9 days compared to time to develop the first rejection after transplant (121.3 days, P Z .07). In patients who received STLI prophylactically, the number of rejections was 2.4 for the first graft versus 2.1 for the second graft (P Z .72). Mean time to the development of the first rejection was 566.7 days compared to 962.8 days (P Z .73). Five-year graft survival rose from 50.0% to 85.7%; 10-year graft survival rose from 10% to 66.7%. In all patients, there was no incident of hematological malignancies or blood dyscrasia during long-term follow-up as noted by other groups. Conclusion: Subtotal lymphoid irradiation may affect transplant grafts through multiple biological processes that are not fully understood. It is effective for treating recurrent rejections in pediatric cardiac allograft recipients. While it did not prevent rejection occurrences in re-