Low-Dose Cranial Boost in High-Risk Adult Leukemia Patients Undergoing Bone Marrow Transplant

Volume 96  Number 2S  Supplement 2016

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planning target volumes (PTVs), with differences of up to 366 cm3 for case 1 and 268 cm3for case 2. DSC values were generally high (>0.7), and the Hausdorff distances were < 5 mm, except for observer 8 (case 1), where the CTV was drawn as small “islands.” However, this did not lead to a smaller PTV size than for other observers. The standard deviations between all observer contours ranged from 1.9 to 3.8 mm (median: 3.2 mm). All plans satisfied the PTV coverage criterion. For case 1, variations in mean dose were under 0.2 Gy for the heart and 1.2 Gy for the lungs, considering both treatment modalities. For case 2, mean heart dose variations were under 0.4 Gy, except for observer 7 where the CTV encompassed more tissue in the inferior direction which led to a higher dose to the heart (both modalities) and lungs (IMRT). Conclusion: The standard deviation of the CTV contour is a first step towards calculating an evidence-based PTV margin for INRT in HL. Although large differences existed within this expert group, the systematic delineation uncertainty was around 3 mm which is comparable to that reported in other tumor sites. The impact of this variability on the dose to organs at risk was mitigated by the generation of the PTV, regardless of treatment modality. Author Disclosure: M.C. Aznar: None. M.V. Maraldo: None. T. Girinski: None. A. Kiil Berthelsen: None. B. Aleman: None. M. Beijert: None. M. Hutchings: None. Y. Lievens: None. P.J. Meijnders: None. P.M. Petersen: None. D. Schut: None. R. van der Maazen: None. L. Specht: None.

respectively (difference +16cm3, +5.6%). Mean lung volume was 2672.4 & 4272.5cm3 for FB & DIBH (difference +1600.2cm3, +63.1%) and mean heart volume was 661.5 & 598.1cm3 for FB & DIBH (- 63.3cm3, -10.6%) PTV coverage was similar for DIBH & FB. There was a statistically significant benefit in all the parameters examined for heart & lung doses (see table) & the magnitude of benefit was clinically significant in most patients. There was a trend for small benefit in breast doses. There was a significant association between reduction in MHD and MLD (PZ0.008). Patients with greater lung expansion achieved greater reductions in MLD and V20. Mean reductions in MLD and V20 in those with expansion of <1.5L were 1Gy and 2.2%, compared to 2.2Gy and 8.1% with expansion >1.5L. Similar effect was observed for MHD benefit. A lung expansion cut-off of 1.245L seems to predict most benefit. Patients with expansion 1.245L showed MHD benefit >1Gy (6/7), MLD benefit >1Gy (7/7) and lung V20 benefit >3% (6/7) compared to 2/4, 1/4, 0/4 in patients with less expansion (PZ0.002). Conclusion: Our early experience indicates that DIBH produces clinically significant benefit in most patients. The degree of lung expansion correlates well with degree of dosimetric benefit Author Disclosure: J.L. Brady: None. R. Begum: None. C. Hartill: None. A.G. Greener: Lead physicist; Guy’s and St Thomas’ hospital. N.G. Mikhaeel: Lead Clinician; Guy’s and St Thomas’ Hospital.

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3206 Analysis of Factors Affecting Benefit from Deep Inspiration Breath Hold Technique in Mediastinal Radiation Therapy for Lymphoma J.L. Brady,1,2 R. Begum,3 C. Hartill,4 A.G. Greener,5 and N.G. Mikhaeel1,2; 1King’s Health Partners, Academic Health Sciences Centre, London, United Kingdom, 2Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom, 3Department of Medical Physics, Guy’s and St Thomas’ Hospital, London, United Kingdom, 4Department of Radiotherapy, Guy’s and St Thomas’ Hospital, London, United Kingdom, 5 Department of Medical Physics, Guy’s and St Thomas’ Hospital, London, United Kingdom Purpose/Objective(s): Deep inspiration breath hold (DIBH) technique may reduce radiation dose to heart & lungs during mediastinal radiotherapy (RT) for lymphoma. Initial reports have shown that some patients gain more than others from the technique. In this prospective study we assessed dosimetric benefits of DIBH compared to free breathing (FB) RT & analyzed factors that may predict a greater benefit from the DIBH. Materials/Methods: Patients due to receive RT to the mediastinum for Hodgkin or high-grade non-Hodgkin lymphoma were included. DIBH was performed using an optical surface tracking system. FB & BH CT scans were performed & 3D conformal plans were produced for FB & DIBH volumes and compared in terms of PTV coverage (V95, D95), cardiac doses (MHD, V15), lung doses (MLD, V20, and V5), spinal cord max dose and breast doses in females (mean, V10,V5). The optimal plan was selected for treatment. We analyzed factors that could potentially predict benefit including CTV volume, position of CTV in the mediastinum, degree of diaphragmatic excursion, change in lung & heart volume with deep inspiration, & level of upper border of the heart. Results: Between March 2015 and January 2016 11 patients were eligible for DIBH RT. Prescribed dose was 30.6Gy/ 17 # for 10 patients and 36Gy/ 20# for 1. Mean CTV volume was 283.7 & 299.7cm3 for FB & DIBH

Low-Dose Cranial Boost in High-Risk Adult Leukemia Patients Undergoing Bone Marrow Transplant W. Su, M.R. Thompson, L. Isola, A.S. Steinberg, and R.L. Bakst; Icahn School of Medicine at Mount Sinai, New York, NY Purpose/Objective(s): In cases of high risk or relapsed leukemia undergoing a stem cell transplant, TBI is often utilized as part of the pre-conditioning regimen. In the past, a cranial boost (CB) of 12 Gy was given for those at risk of CNS relapse, but these fell out of favor because of significant toxicity. For adult patients at risk of CNS relapse, we have utilized lower 6 Gy CB. Here we analyze its efficacy and toxicity to determine its role in the management of high risk or relapsed disease. Materials/Methods: We identified all high risk and relapsed leukemia patients undergoing 6 Gy CB at our institution (43 patients) as part of their conditioning regimen. We also identified a cohort of high risk acute lymphoblastic leukemia (ALL) patients that did not receive CB for comparison (19 patients). All patients received TBI (median 12 Gy) prior to transplant. Their charts (62 total) were reviewed for CNS relapse, toxicity, and survival endpoints. The Kaplan-Meier method was used to estimate survival. IRB approval was obtained. Results: Baseline patient characteristics can be found in Table 1. In patients undergoing CB, the 3-year CNS disease free survival and overall survival were 90.7% (95% CI, 79.2-100) and 58.9% (95% CI, 44.7-77.7) respectively. By contrast, in those not undergoing CBs, the survivals were 81.8% (95% CI, 61.9-100) and 51.5% (95% CI, 32.9-80.5). Notably, in CB group, 11 had prior CNS involvement and 2 (18.2%) of these patients had post-transplant CNS relapse. For cohort without CB, 3 had prior CNS involvement. There were 2 cases of post-transplant CNS relapse in group without CB, neither of which had prior CNS involvement. In the CB cohort, the only notable acute toxicity was parotitis (2.3%). Late toxicity in the CB cohort included instances of cataracts (4.7%) without any cognitive complaints or radiation related secondary malignancy.

Abstract 3206; Table 1. FB (n[11) PTVV95 (%) D95 (Gy) LungMLD (Gy) V20 (%) V5 (%) HeartMHD (Gy) V15 (%) Breast (n[6) Mean dose (Gy) Breast V5 (%)

96.4 10.5 12.5 4.5

29.6 21.1 58.6 39.7 17.2

DIBH (n[11) 97.3 8.9 10.3 4.2

29.8 15.7 52.9 31.0 15.4

Difference 0.9 - 1.6 -2.2 -0.3

0.2 -5.4 -5.7 - 8.7 -1.8

P value (95% CI) (2 sided paired t test) 0.02 (0.2 to 1.7) 0.05 (-0.002 to 0.3) 0.0003 (-2.3 to -0.9) 0.006 (-8.9 to -1.9) 0.002 (-8.8 to -2.6) 0.002 (-3.3 to -1.1) 0.0005 (-12.6 to -4.9) 0.17 (-0.9 to 0.2) 0.10 (-4.1 to 0.5)

International Journal of Radiation Oncology  Biology  Physics

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Abstract 3207; Table 1. Category Median Follow-up Median Age at Transplant Intrathecal Chemotherapy Received Prior CNS Involvement Post-Transplant CNS Relapse Median Survival

Cranial Boost

No Cranial Boost

20.5 months 35 years (SD 12.4)

11.6 months 35 years (SD 17.7)

28 (65.1%)

14 (73.7%)

11 (25.6%) 2 (4.7%) [both with prior CNS involvement] 24.0 months

3 (15.8%) 2 (10.5%) [no prior CNS involvement] 19.3 months

Conclusion: A 6 Gy CB is well tolerated in the adult leukemia population as part of a radiation-based conditioning regimen. Low dose CB may be considered in adult patients with high risk leukemia without prior CNS involvement to reduce the risk of recurrence. Author Disclosure: W. Su: None. M.R. Thompson: None. L. Isola: None. A.S. Steinberg: None. R.L. Bakst: None.

3208 Single-Fraction Radiation Therapy Provides Highly Effective Palliation for Cutaneous T-cell Lymphoma A. Modh, C.A. McHargue, H. Lim, and F. Siddiqui; Henry Ford Health System, Detroit, MI Purpose/Objective(s): A variety of dose fractionation schemes and techniques have been reported when treating cutaneous T-cell lymphoma (CTCL) lesions for palliation. We sought to report our experience with single-fraction palliative radiation therapy. Materials/Methods: We reviewed 59 lesions in 17 patients with CTCL treated with a single fraction for palliative intent. Tumor characteristics, treatment approach, response to treatment, and toxicity were reviewed. Clinical response to treatment was defined as complete response (CR, 100% reduction), partial response (PR, >50% but <100%), and no response (NR). Results: All lesions were treated to a dose of 8 Gy, with a mean followup for all patients of 8 months (range 1-21 months). One lesion on the left knee was treated with high-dose-rate (HDR) iridium-192 brachytherapy because of its location, depth, irregular shape, and body contour. Another deeper lesion was treated with 6 MV photons, using a 3D plan with a 0.5 cm bolus. All remaining lesions (57) were treated with 6-12 MeV electrons prescribed to the 90% isodose line, using an en face technique with a 0.5 cm bolus. There was a CR in 56 (94.9%) lesions. Three lesions (5.1%) had an initial PR and were re-treated to a dose of 8Gy in 1 fraction. These lesions went on to have a CR. The time interval between first and second fraction in lesions with PR ranged from 1-4 months. Lesions that had a PR were large (>14 cm) and involved the anterior thigh, posterior thigh, and left buttock region. The thickness of the lesions did not predict for response. Tumor stage lesions responded equally well as plaque or patch lesions. Twelve of these lesions in 3 patients were those that were persistent after total skin electron therapy (TSET) to a dose of 36Gy in 24 fractions. These lesions were in areas of skin folds and were treated 6-8 weeks after completion of TSET. CR was achieved in all these residual lesions with an additional single fraction dose of 8Gy. No treatment related toxicity was observed in any of the patients. Conclusion: This study demonstrates a highly effective palliative approach for treating CTCL lesions with minimal toxicity. Larger lesions may need re-treatment. Treatment after total skin electron therapy is safe and well tolerated. Author Disclosure: A. Modh: None. C.A. McHargue: None. H. Lim: None. F. Siddiqui: None.

Low-Dose Splenic Irradiation in MyelofibrosisdA Safe Adjunct to Hematopoietic Cell Transplantation N.S. Kalman, N.D. Mukhopadhyay, C. Roberts, H.M. Chung, W. Clark, J.M. McCarty, A.A. Toor, and S. Song; Virginia Commonwealth University, Richmond, VA Purpose/Objective(s): For patients with myelofibrosis undergoing hematopoietic cell transplantation (HCT), hypersplenism can lead to delayed engraftment and a protracted post-transplant course. We evaluated the use of pre-transplant low dose splenic irradiation (LDSI) in improving posttransplant blood count recovery. Materials/Methods: Between January 2005 and December 2015, 20 patients underwent HCT for myelofibrosis; of these patients, 8 received LDSI prior to transplantation. Overall, 55% of patients had HLA matched related donors. No patient received total body irradiation. Median radiation prescription for LDSI patients was 4.5 Gy (range 3-6) delivered in 3 fractions (range 3-6) over 6 days (range 3-9). Clinical target volume (CTV) consisted of the entire spleen. Prescription dose utilizing 3D-conformal radiation technique covered at least 90% of the CTV. Results: Median age and Karnofsky performance score in the LDSI group were 60 years and 80, respectively, versus 50 years and 90 for the nonirradiated group. Median follow up was 10.4 months in LDSI patients and 12.8 months in non-irradiated patients. Median times to neutrophil and platelet engraftment were 13 and 19 days, respectively. Median absolute lymphocyte count at 30 days post-transplant was 0.4 x 109/L with interquartile range (IQR) of 0.3 - 0.7. No statistically significant difference was observed between the LDSI and non-irradiated patients. Median platelet and red blood cell transfusion requirements at 30 days in the LDSI group were 21 units (IQR 17 - 51) and 8.5 units (IQR 6 - 11), respectively, versus 10.5 units (IQR 9 - 20) and 7.5 units (IQR 5 - 11) in the non-irradiated group (P>0.1). No statistically significant difference in post-transplant infection rates were observed between groups. Median length of hospital stay was 22.5 days versus 19.5 days for the LDSI and non-irradiated groups (P>0.1). At last follow up, 75% of LDSI and 50% of non-irradiated patients were alive; only 2 patients (1 in each cohort) had relapsed. In LDSI patients, acute treatment toxicity was mild (2 patients with grade 1 and 2 patients with grade 2 nausea); no grade 3 toxicities were observed. Conclusion: This analysis is the first published evaluation of LDSI in patients with myelofibrosis undergoing HCT. In this group, LDSI was found to be technically feasible and safe. Prospective study in a larger cohort of patients is required to assess the optimal dose and efficacy of LDSI in this setting. Author Disclosure: N.S. Kalman: None. N.D. Mukhopadhyay: None. C. Roberts: None. H.M. Chung: None. W. Clark: None. J.M. McCarty: None. A.A. Toor: None. S. Song: None.

3210 Abrogation of JAK/STAT Pathway in Radiosensitization of NK/T Cell Lymphoma S. Lie,1 C.K. Ong,1 J. Tan,1 D. Huang,1 M.L. Nairisma¨gi,1 S.T. Lim,1 S.Y. Tan,2 B.T. Teh,1 and K.W. Yeoh1; 1National Cancer Centre Singapore, Singapore, Singapore, 2Singapore General Hospital, Singapore, Singapore Purpose/Objective(s): NK/T Cell Lymphoma (NKTCL) is an aggressive lymphoma, predominantly localized, requiring relatively high doses of radiotherapy (50-65 Gy) for effective treatment, usually in combination with multi-agent chemotherapy. This is associated with toxicity and suboptimal long term outcome. The JAK-STAT pathway has been identified to be dysregulated in lymphomagenesis and our group previously showed that 35.4% of cases had activating JAK3 mutations. We hypothesized that abrogating this pro-survival pathway could increase radiotherapy induced tumor cell death. Materials/Methods: Two NKTCL cell lines were investigated; SNK6 (JAK3 wildtype) and NKS1 (activating JAK3 mutant). We performed luminescent cell viability assays after treatment with tofacitinib (CP-