More Chemotherapy Does Not Obviate the Need for Radiation Therapy (RT): Treatment for Early-Stage Favorable Hodgkin Lymphoma According to the HD10 Trial Compared With Chemotherapy Alone

Volume 96  Number 2S  Supplement 2016

3201 Treatment Outcome for Patients With Stage II Extranodal NasalType NK/T-Cell Lymphoma: A Multicenter Study Q.L. Rong,1 Y.X. Li,2 Y. Zhu,3 J. Cao,4 Y.J. Zhang,5 L.M. Xu,6 Z.Y. Yuan,6 J. Wu,7 W. Wang,7 T. Wu,8 B. LU,9 S.Y. Zhu,10 L.T. Qian,11 F.Q. Zhang,12 and X.R. Hou12; 1Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 2Cancer Hospital and Institute, Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS), Beijing, China, 3Zhejiang Provincial Cancer Hospital, Hangzhou, China, 4 Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, TaiYuan, China, 5Sun Yat-sen University Cancer Center, Guangzhou, China, 6Cancer Hospital, Tianjin Medical University, Tianjin, China, 7Fujian Provincial Cancer Hospital, Fuzhou, China, 8 Guizhou Cancer Hospital, Guiyang, China, 9Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, and Guizhou Cancer Hospital, Guiyang, China, 10Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 11The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China, 12Peking Union Medical College Hospital, CAMS and PUMC, Beijing, China Purpose/Objective(s): The prognosis and optimal therapeutic strategy for patients with stage II extranodal nasal-type NK/T-cell lymphoma (NKTCL) are not well defined. The aim of this study was to evaluate the prognostic factors and treatment outcomes of patients with stage II NKTCL. Materials/Methods: A total of 345 patients with stage II NKTCL from 10 Chinese institutions were reviewed. Fifty-two patients were treated with radiation therapy (RT) alone, 63 patients with chemotherapy (CT) alone, and 230 patients with a combination of CT and RT (CMT). Patients were subclassified as low-, intermediate-, and high-risk groups according to prognostic nomogram score, as described in our previous study (Leukemia, 2015). A comprehensive comparative study was performed using multivariable and propensity score-matched (PSM) analyses. Results: The 5-year overall survival (OS) and progression-free survival (PFS) for all patients were 52.0% and 44.8%, respectively. On univariate analysis, only ECOG score  2 was associated with poor OS and PFS, whereas on multivariate analyses, ECOG score  2 and presence of primary tumor invasion (PTI) were independent prognostic factors. Patients at low-risk (48), intermediate-risk (49-100), and high-risk (>100) groups, as defined by nomogram score, had significantly different OS (P Z 0.002) and PFS (P Z 0.015). There was no significant difference in 5-year OS (45.2% versus 26.2%, P Z 0.211) or PFS (40.0% versus 15.0%, P Z 0.062) between RT alone and CT alone groups. However, compared with single modality therapy, CMT significantly improved survivals. The 5-year OS and PFS rates were 59.4% and 53.6% for CMT, compared with 35.1% (P < 0.001) and 25.8% (P < 0.001) for single modality therapy. After adjustment with PSM, similar significant survival differences were still observed between CMT and single modality therapy. One hundred and eighty-four patients experienced disease progression or relapse. The 5-year cumulative incidences of locoregional and systemic failure were 22.4% and 47.5%, respectively. Conclusion: Patients with stage II NKTCL had an unfavorable prognosis. CMT were proved to be more effective in terms of OS and PFS than CT or RT alone. Further study needs to focus on innovative systematic therapy and optimizing sequence of RT and CT. Author Disclosure: Q. Rong: None. Y. Li: None. Y. Zhu: None. J. Cao: None. Y. Zhang: None. L. Xu: None. Z. Yuan: None. J. Wu: None. W. Wang: None. T. Wu: None. B. LU: None. S. Zhu: None. L. Qian: None. F. Zhang: None. X. Hou: None.

3202 Primary Tumor Invasion as a Principal Prognostic Factor in Extranodal Nasal-type NK/T-Cell Lymphoma: A Multicenter Database Analysis S. Qi,1 S. Lan,2 X. Li-ming,3 J. Cao,4 Z. Yuan,5 J. Wu,6 T. Wu,7 S.Y. Zhu,8 L.T. Qian,9 X.R. Hou,10 J. Qiu,11,12 Y. Zhang,13 Y. Zhu,14 Y. Yang,1

Poster Viewing E489 and Y.X. Li15; 1Cancer Hospital and Institute, Peking Union Medical College (PUMC) and Chinese Academy of Medical Sciences (CAMS), Beijing, China, 2Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, TaiYuan, China, 3Cancer Hospital, Tianjin Medical University, TianJin, China, 4The Cancer Institute of Shanxi Province, Taiyuan, China, 5Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China, 6Fujian Provincial Cancer Hospital, Fuzhou, China, 7 Guizhou Cancer Hospital, Guiyang, China, 8Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Changsha, China, 9The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China, 10Peking Union Medical College Hospital, CAMS and PUMC, Beijing, China, 11Peking Union Medical College Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 12Peking Union Medical College Hospital, Beijing, China, 13Sun Yat-sen University Cancer Center, Guangzhou, China, 14Zhejiang Provincial Cancer Hospital, Hangzhou, China, 15Cancer Hospital and Institute, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China Purpose/Objective(s): Clinical prognostic factors for predicting outcomes and guiding treatments in extranodal NK/T-cell lymphoma, nasal type (NKTCL) are suboptimal. The current study sought to define the distribution features and prognostic role of primary tumor invasion (PTI) in a large patient cohort. Materials/Methods: A cohort of 1383 patients was recruited, including 947 (68.5%) stage I patients, 326 (23.6%) stage II patients, and 110 (8.0%) stage IIIIV patients. Seven hundred and fifty-one (54.3%) patients presented with PTI. Results: The presence of PTI was associated with disease aggressiveness, including a higher frequency of B symptoms, advanced-stage disease, regional lymph node involvement, lactate dehydrogenase elevation, a higher Eastern Cooperative Oncology Group performance status, and International prognostic index score. Overall survival (OS) was significantly or borderline higher in the PTI negative group than the PTI positive group in the entire cohort (5-year OS, 72.1% vs. 50.2%, p < 0.001) as well as in different Ann Arbor stage group (stage I-II, 75.9% vs. 53.0%, p < 0.001; stage III-IV, 20.3% vs. 16.8%, p Z 0.065). PTI was associated with significantly higher locoregional failure (LRF) in early-stage patients, with a 5-year LRF of 15.1% in the PTI negative group and 28.1% in the PTI positive group (p< 0.001). Conclusion: PTI was associated with multiple adverse clinical features in NKTCL, and was an independent indicator for inferior prognosis. Author Disclosure: S. Qi: None. S. Lan: None. X. Li-ming: None. J. Cao: None. Z. Yuan: None. J. Wu: None. T. Wu: None. S. Zhu: None. L. Qian: None. X. Hou: None. J. Qiu: None. Y. Zhang: None. Y. Zhu: None. Y. Yang: None. Y. Li: None.

3203 More Chemotherapy Does Not Obviate the Need for Radiation Therapy (RT): Treatment for Early-Stage Favorable Hodgkin Lymphoma According to the HD10 Trial Compared With Chemotherapy Alone C.C. Pinnix,1 Z. Abou Yehia,1 G.L. Smith,1 S.A. Milgrom,1 J.C. Ho,1 J. Reddy,1 J.R. Gunther,2 M. Akhtari,1 E.M. Osborne,1 L.J. Medeiros,1 M. Fanale,3 and B. Dabaja1; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2The University of Texas MD Anderson Cancer Center, Division of Radiation Oncology, Houston, TX, 3MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): The German Hodgkin Study Group (GHSG) HD10 trial established 2 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) and 20 Gy of consolidative RT as efficacious treatment for early stage favorable (ESF) Hodgkin lymphoma (HL). However, controversy remains regarding the safety of RT delivery, with some patients being offered ABVD alone to avoid presumed late RT morbidity. We sought to compare the efficacy of chemotherapy alone vs. the combined modality (CM) approach of HD10. Limited follow up precluded analysis of late RT-

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International Journal of Radiation Oncology  Biology  Physics

related morbidity; therefore we collected dosimetric data regarding doses to organs at risk (OAR) to access the risk of toxicity with modern involved site RT (ISRT) to 20 Gy. Materials/Methods: Patients with ESF HL by GHSG criteria who were treated with ABVD alone or CM therapy as per HD10 trial between 2003 and 2015 at a single institution were included. Patients scheduled to receive CM but failed to achieve complete response after chemotherapy were excluded. Survival was estimated using the Kaplan-Meier method. OAR were delineated according to a contouring atlas on restored CT-based RT plans and dosimetric data were collected. Results: Forty-three patients met the inclusion criteria; the median follow up time was 35.7 months (range 6.5-120.0). Sixteen patients (37.2%) had stage I disease. ABVD alone was given to 21 patients (48.8%) with a median number of 6 cycles (range 2-6). CM treatment was given to 22 patients with a median RT dose of 20 Gy (19.8-21.6 Gy). Three patients had relapsed disease after 6 cycles of ABVD alone at 4, 11 and 22 months upon completion of chemotherapy. Two of 3 relapses were isolated to sites of initial involvement. The third patient relapsed in initial and non-initial sites of involvement. All 3 patients received salvage chemotherapy, underwent autologous stem cell transplant and remain alive without disease. One patient died in a motor vehicle accident after ABVD alone without signs of disease. The 3 year PFS was 100% vs 78% (PZ0.62) for patients treated with and without RT. The 3 yr OS was 100% vs 94% (PZ0.346). The median doses of the OAR are listed in Table 1 for patients treated with ISRT. Of the 8 patients treated to the mediastinum the mean heart dose was < 5 Gy in all patients. The mean breast dose was  1 Gy in all 7 female patients treated to the mediastinum. Conclusion: The use of more chemotherapy does not obviate the need for RT. CM therapy with 2 cycles of ABVD and 20 Gy of RT seems to be highly effective while offering favorable dosimetric profiles expected to result in limited long-term toxicity.

vincristine), RT, and high-dose cytarabine. Clinical information was collected from the electronic medical record. Results: The median age was 66 years (range 48-72). Two patients had diabetes; 1 had unilateral grade 1 diabetic retinopathy at presentation. RT targeted the bilateral orbits to a median dose of 36 Gy (range 30.6-39.6 Gy) with opposed tangential 6 MV photon beams (18%), intensity modulated RT (27%), or appositional 12-16 MeV electron beams with custom skin collimation (55%). A multidisciplinary team, including an ocular oncologist, followed patients for a median of 42 months after RT (range 8-94). Common adverse events included dermatitis (100%), conjunctivitis (82%), exophthalmia (64%), and keratopathy (45%). All phakic eyes developed cataracts (100%); cases that underwent subsequent cataract extraction maintained good visual acuity. New, visually significant retinopathy was observed in only 1 eye (<5%) and affected the only patient with pre-existing diabetic retinopathy. There was no case of radiationinduced optic neuropathy. At diagnosis, visual acuity was 20/40 or better in 15/22 eyes (68%). In the patients who did not experience an intraocular disease relapse, visual acuity at last follow-up was 20/40 or better in 9/16 eyes (56%); of note, poor vision at last follow-up was attributed to uncorrected cataracts in 4 eyes and therefore was considered correctable. Conclusion: This report suggests that severe, vision-threatening complications are uncommon following orbital RT and chemo-immunotherapy for PIOL. In the absence of comorbidities, orbital RT should not be withheld due to fear of vision-threatening toxicity. The risk of toxicity may be augmented by comorbidities, so an individualized approach is recommended. Author Disclosure: S.A. Milgrom: None. C. Cheah: None. C.C. Pinnix: None. G.L. Smith: None. B. Dabaja: None. P. Horace: None. P. ChevezBarrios: None. N.H. Fowler: None. D.S. Gombos: None.

3205 Abstract 3203; Table 1. OAR Parameter (# pts at risk) Mean Mean Mean Mean Mean Mean Mean Mean Mean

Total Total Total Total Total Total Total Total Total

Lung (n[8) Left Breast (n[7) Right Breast (n[7) Heart (n[8) Left Main/LAD Coronary (n[8) Right Coronary Right Parotid (n[18) Left Parotid (n[18) Thyroid (n[20)

Median Value (Gy) Range (Gy) 3.9 0.17 0.17 3.4 3.7 0.66 2.9 1.1 10.3

1.0-5.8 0.07-1.0 0.12-0.91 0.09-4.8 0.07-8.0 0-4.6 0.07-16.8 0.04-15.6 0.14-15.1

Author Disclosure: C.C. Pinnix: None. Z. Abou Yehia: None. G.L. Smith: None. S.A. Milgrom: None. J.C. Ho: None. J. Reddy: None. J.R. Gunther: None. M. Akhtari: None. E.M. Osborne: None. L. Medeiros: None. M. Fanale: None. B. Dabaja: None.

3204 Acute and Late Toxicity of Bilateral Orbital Irradiation in the Management of Primary Intraocular Lymphoma S.A. Milgrom,1 C. Cheah,2 C.C. Pinnix,1 G.L. Smith,1 B. Dabaja,1 P. Horace,3 P. Chevez-Barrios,3 N.H. Fowler,1 and D.S. Gombos3; 1The University of Texas MD Anderson Cancer Center, Houston, TX, 2Peter MacCallum Cancer Centre, Melbourne 8006, Australia, 3MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Primary intraocular lymphoma (PIOL) is a rare malignancy with poor outcomes. Data suggest that a combination of chemotherapy and orbital radiation therapy (RT) results in better ocular disease control and improved survival, compared to treatment with either modality alone. However, some clinicians withhold RT out of concern for toxicity, particularly vision-threatening retinopathy. We aimed to quantify the ocular toxicity of RT in PIOL patients treated uniformly with chemoimmunotherapy and RT. We hypothesized that vision-threatening complications would be rare. Materials/Methods: Eleven patients were identified who received sequential R-MPV (rituximab, methotrexate, procarbazine, and

Interobserver Delineation Uncertainty in Involved Node Therapy for Early-Stage Hodgkin Lymphoma M.C. Aznar,1 M.V. Maraldo,1 T. Girinski,2 A. Kiil Berthelsen,1 B. Aleman,3 M. Beijert,4 M. Hutchings,1 Y. Lievens,5 P.J. Meijnders,6 P.M. Petersen,1 D. Schut,1 R. van der Maazen,7 and L. Specht1; 1 Rigshospitalet, Copenhagen, Denmark, 2Institute Gustave Roussy, Paris, France, 3The Netherlands Cancer Institute (NKI-AVL), Amsterdam, Netherlands, 4University Medical Center Groningen, Groningen, Netherlands, 5Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium, 6GZA St Augustinus/Iridium Cancer Network, Antwerp, Belgium, 7University Hospital Nijmegen, Nijmegen, Netherlands Purpose/Objective(s): In Hodgkin lymphoma (HL) precise target definition is challenging due to differences in anatomical disease localization among patients and the difficulty of defining the initially involved volume on a post-chemotherapy CT-scan. Here, we report on the inter-observer variability in target volume definition among members of the EORTC Lymphoma Group. The impact of this variability on the resulting treatment plans is also investigated. Materials/Methods: Two representative cases were selected (1: male with stage IB disease in the left axilla; 2: female with stage IIB disease in the mediastinum and bilateral neck). For each case, 8 experienced radiation oncologists individually defined the clinical target volume (CTV) using the involved node radiotherapy (INRT)-concept. A consensus contour was generated and the standard deviation computed. Overlap between observer and consensus contour was investigated with the dice similarity coefficient (DSC) while the magnitude of deviations between the contour surfaces was reported with the Hausdorff distance. A 3D-conformal (3D-CRT) and an intensity modulated radiotherapy (IMRT) plan were calculated for each contour (2x2x8 treatment plans) to a prescribed dose of 30.6 Gy, 17 fractions per week. Similar target coverage was enforced for all plans, and the mean dose to organs at risk was extracted. Results: The range in CTV was 21 to 215 cm3 (median: 120 cm3) for case 1, and 141 to 370 cm3 (median: 255 cm3) for case 2. Compared to the consensus contours, this represented variations of -155% to 39% for case 1 and -157% to 72% for case 2. These variations were carried on to the