Evaluation of Post-esophagectomy Adverse Events in Patients Who Underwent Neoadjuvant Concurrent Chemoradiation

E182

International Journal of Radiation Oncology  Biology  Physics

Purpose/Objective(s): The UK led PersonaLising Anal cancer radioTherapy dOse (PLATO) is a complex integrated protocol, consisting of 3 distinct anal cancer trials. Anal cancer IMRT contouring is challenging as there are several nodal areas that are electively irradiated and the primary tumour is not well visualised on CT. We identified FALCON, an ESTRO supported multifunctional online contouring platform (EduCase), aimed at reducing contouring variability, as a method to streamline pre-trial radiotherapy (RT) quality assurance (QA). Investigators contoured a benchmark case using FALCON prior to attending workshops aimed at evaluating contouring variation and refining the trial RT protocol. We present qualitative feedback received from workshop participants. We also present conformity analysis of contours compared with a reference contour. Materials/Methods: A T2N1 female case was selected. Clinical information was provided and PET/MRI imaging fused (rigid co-registration) to the planning CT to aid delineation. The trial RT protocol was used for target and OAR delineation. Conformity analysis of target structures (GTVA-primary, GTVN-positive node, and CTVE-elective nodes) in FALCON consisted of the Jaccard coefficient, Dice coefficient and Recall. Recall was defined as the fraction of volume overlapping with the reference volume. Jaccard and Dice were defined as below. Jaccard Coefficient Z AXB/AyB Dice Coefficient Z 2x(AXB)/ (A+B) Where A was the reference volume contoured by lead trial clinicians and B that of an investigator. Results: 20 sets of contours were analyzed through FALCON. Average DICE was highest in GTVN and CTVE; 0.77 (0.6-0.94) and 0.76 (0.470.85) respectively, and lowest in GTVA, 0.7 (0.42-0.85). Average Jaccard was also highest in GTVN and CTVE; 0.63 (0.49-0.80) and 0.64 (0.330.74) respectively, and lowest in GTVA, 0.58 (0.34-0.76). Whilst higher conformity metrics were seen on average in GTVN and CTVE a lower range of values was seen in CTVE. Subsequently changes were made to clarify CTVE contouring in the RT protocol. Changes were also made to clarify GTVA contouring, primarily stating the whole lumen is not to be included. Recall was generally consistent across GTVA, GTVN and CTVE; averaging 0.76 (0.35-0.99), 0.75 (0.55-0.97) and 0.73 (0.34-0.89) respectively, again a lower range of values were seen in GTVA and CTVE. More than 75% of the workshop participants (nZ42) found FALCON to provide good to excellent help in contouring.

Purpose/Objective(s): Local therapy options for patients with hepatocellular carcinoma (HCC) are frequently limited by medical co-morbidities including concurrent liver disease. Several non-operative local therapies exist, including intra-arterial embolization with yttrium-90 (Y90) microspheres, although outcomes data are limited. We report clinical outcomes of patients treated with Y90 intra-arterial radioembolization at our institution. Materials/Methods: We conducted a retrospective review of patients with HCC treated at our institution from 2005-2014. Clinical and treatmentrelated characteristics were recorded, including: age, stage, performance status, Child Pugh class, MELD score, liver mass/volume treated, prescription dose, lung shunt fraction, prior therapy, basic labs, and imaging characteristics (infiltrative or bulky disease). Acute and late toxicity were scored using the Common Toxicity Criteria v4.03. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for severe toxicity (any  Grade 3-5), local control (LC), and overall survival (OS) following Y90 therapy. Results: 43 patients and 118 distinct tumors treated with Y90 were identified. Median prescription dose was 97 Gy (range 60-157 Gy) and pulmonary shunt fraction was 5.9% (range 0-19.7%). Patients were stage I-IVB with the most frequent stage being II and IIIB (32.6% and 18.6% patients, respectively). 29 patients (67.4%) were Child-Pugh A and 14 (32.6%) were Child-Pugh B. Median OS among all patients was 8.5 months following Y90 (or their first lobe procedure, if multiple). The LC rate of all treated lesions was 83% and 68% at 6 and 12 months, respectively. Of the 28 patients with progressive disease after their first Y90, regional liver progression was more frequent than local or distant progression (18, 5, and 5 patients, respectively). 26 (60.4%) and 12 (27.9%) patients developed severe acute or late toxicity. The most common acute toxicity was a rise in baseline lab values (i.e. bilirubin or transaminases). On UVA, portal vein invasion, recurrent disease, prior therapy, and prescription dose were significant prognostic factors for LC. Only prescription dose remained significant on MVA (p Z 0.001, HR 0.806 [0.708-0.916]). There were no significant prognostic factors identified for toxicity or OS. Conclusion: Y90 radioembolization has modest efficacy in this population of patients with HCC with limited local therapy options. Prescription dose appears to be the only prognostic factor for LC. Patient selection is critical to identifying those who will potentially benefit from this therapy. Future studies will continue to assess dose distribution on an individual basis and to further clarify the role of Y90 in the management of HCC. Author Disclosure: K. Romano: None. A. Emery: None. D.M. Trifiletti: ARRO. T. Huber: None. B. Contrella: None. E. Janowski: None. P.W. Read: Research Grant; CMMS. see above.; University of Virginia. T.N. Showalter: Honoraria; Varian Medical Systems.

Abstract 2438; Table 1 Answers to the question: “How useful do you think FALCON was in completing the contouring exercises?” Excellent

Good

7 (17%)

25 (60%)

Satisfactory 7 (17%)

Poor 3 (7%)

Conclusion: Use of the FALCON has streamlined the pre-trial QA exercise and was seen as an enhanced learning tool/environment for clinical contouring in the PLATO trial. Generation of conformity metrics has also been a useful tool in online quantitative QA review and revising trial guidelines. We would like to acknowledge FALCON Group and RadOnc eLearning Center for the use of EduCase Author Disclosure: M. Robinson: None. D. Christophides: None. N. Abbott: None. S. Bell: None. A. Langley: None. M. Harrison: None. R. Adams: None. R. Muirhead: None. D. Sebag-Montefiore: None. M.A. Hawkins: None.

2439 Clinical Outcomes of Y90 Radioembolization for Hepatocellular Carcinoma K. Romano,1 A. Emery,2 D.M. Trifiletti,1 T. Huber,3 B. Contrella,3 E.M. Janowski,1 P.W. Read,1 and T.N. Showalter1; 1Department of Radiation Oncology, University of Virginia, Charlottesville, VA, 2 University of Virginia, Charlottesville, VA, 3Department of Radiology, University of Virginia, Charlottesville, VA

2440 Evaluation of Post-esophagectomy Adverse Events in Patients Who Underwent Neoadjuvant Concurrent Chemoradiation D. Rooke,1 P.K. Stumpf,2 T. Schefter,2 and K.A. Goodman2; 1University of Colorado, Aurora, CO, 2Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO Purpose/Objective(s): Neoadjuvant chemoradiation is standard of care for patients with Stage II-III esophageal and GE junction cancers. However, this trimodality therapy carries significant risk of morbidity and mortality, particularly in the post-operative setting with complication rates of around 60%. In practice, different radiation modalities, doses, and chemotherapy regimens are employed, however, the impact of these factors on the incidence and severity of post-esophagectomy adverse events is not well established. Recently, the CROSS study group reported the use of the Comprehensive Complication Index (CCI) to assess adverse events for those enrolled in the CROSS trial, finding 85% of patients experienced post-operative complications. We retrospectively

Volume 99  Number 2S  Supplement 2017 evaluated post-operative complications and the correlation with treatment factors using the CCI. Materials/Methods: Eighty-three patients with mid to distal esophageal cancer were treated with nCRT followed by resection between 2004 and 2016. 94% had adenocarcinoma. Almost all patients had a KPS  80 at onset of treatment (99%). Total doses ranged from 39.6 to 52.5 Gy. Treatment was planned using IMRT (41%), 3D-CRT (47%) and tomoIMRT (12%). There were 29 patients who had VMAT. Concurrent chemotherapy regimens were carboplatin/taxol (59%), cisplatin/5-FU (17%), or other (24%). Resection was performed at a median of 9 weeks, generally by Ivor-Lewis (67%), esophagogastrectomy (14%), or trans-hiatal (11%). Complications were evaluated at 30, 60, and 90 day after surgery. Pulmonary, cardiac, gastrointestinal, infectious, and nervous system complications were retrospectively reviewed and graded using the Clavien-Dindo scale. CCI scores were calculated with a web-based calculator at AssessSurgery.com and means were evaluated using ANOVA. Results: Among the 83 patients, 47 experienced post-operative complications (57%). There were a total of 5 post-operative deaths (6%). There were 3 deaths in the cohort receiving up to 45 Gy of total radiation (12%), 2 deaths between >45 and <50 Gy (10%), and zero deaths in the group who received 50.4 Gy or more. The mean CCI scores for all complications within 60 days were 25.1 (< or Z to 45 Gy), 28.2 (>45 and <50.4 Gy), and 19.4 (> or Z to 50.4), with the majority initiating within 30 days. The mean CCI for IMRT and 3D-CRT was 27.4 and 21.8, respectively. Patients who received concurrent carboplatin/taxol had a mean CCI of 26.2, and those who received concurrent cisplatin/5-FU had a mean CCI of 28.3. No statistical significance was found when mean CCI scores were compared for total radiation doses or when comparing chemotherapy regimens. Conclusion: There did not appear to be a difference in the severity of postoperative complications as measured by the CCI when comparing total radiation dose or concurrent chemotherapy agents. Additional studies are needed to further elucidate the optimal radiation dose combined with systemic agents with the goal of improving disease outcomes and minimizing toxicity. Author Disclosure: D. Rooke: None. P.K. Stumpf: None. T. Schefter: Honoraria; Sirtex. Travel Expenses; Sirtex. K.A. Goodman: None.

2441 Evaluation of Neutrophil-to-Lymphocyte Ratio and Clinical Outcomes for Esophagus Cancer Patients Undergoing Trimodality Therapy D.M. Routman,1 S.C. Lester,1 A.L.H. Arnett,1 R.K. Funk,1 W.S. Harmsen,2 M.A. Neben-Wittich,1 M.G. Haddock,3 C.L. Hallemeier,1 and K.W. Merrell3; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, 3Mayo Clinic, Rochester, MN Purpose/Objective(s): A high ratio of neutrophils-to-lymphocytes (NLR) in peripheral blood may represent immune dysfunction. Some reports suggest decreased survival in solid tumors for patients with a high NLR, although results are conflicting for esophagus cancer (EC). We investigated the impact of elevated NLR for patients with EC who received trimodality therapy. Materials/Methods: Between 2007 and 2012, 188 patients received trimodality therapy for EC at our institution. Of these, 176 had complete blood counts available and were included in this retrospective review. Pre-chemoradiation (CRT) NLR was determined from lab testing that occurred immediately before or within 7 days after initiation of CRT. Preoperative NLR was determined from the most recent timepoint prior to surgery and after pre-CRT baseline. The temporal change in NLR was defined as difference between baseline and preoperative NLR and was

Poster Viewing Abstracts E183 calculated as an absolute value. Potential association between NLR and clinical outcomes was analyzed as a continuous and dichotomized variable (< or 5.0). A univariate Cox proportional hazard model was performed for overall survival (OS). Fine and Grays extension of the Cox model incorporating death as a competing risk was performed for additional outcomes including disease free survival (DFS) and perioperative morbidity. Results: The median follow up was 3.3 years (range, 8 days to 7.4 years). Tumor histology was adenocarcinoma (89%) and squamous cell carcinoma (11%). NLR was  5 in 15% of patients prior to CRT and  5 in 64% of patients at the preoperative timepoint. Male gender was the only baseline characteristic associated with NLR >Z 5 (pZ0.01). The median OS was 39.3 months with 5 year OS of 41.3%. On univariable analysis, the only factor found to be associated with OS was patient age (HR 1.5 per 10 years, pZ.001). Baseline pre-CRT, pre-operative, and change in NLR when analyzed as a dichotomized and continuous variable were not associated with OS, DFS, perioperative morbidity/mortality, or pathologic response. Conclusion: In this single institutional analysis of patients with EC who received trimodality therapy, we did not observe an association between NLR and clinical outcomes. This is in contrast to other studies which observed poorer outcomes in patients with a high NLR. Further investigation in a prospective manner is warranted. Author Disclosure: D.M. Routman: None. S.C. Lester: None. A.L. Arnett: None. R.K. Funk: None. W.S. Harmsen: None. M.A. NebenWittich: None. M.G. Haddock: ; ISIORT. C.L. Hallemeier: Research Grant; Mayo Clinic. K.W. Merrell: None.

2442 Clinical Experience and Long Follow-Up of Patients With Liver and Lung Metastasis Treated with Stereotactic Body Radiation Therapy with Intrafraction Control of Tumor Motion Guided By Internal Fiducials and a Gating Technique C. Rubio,1 O. Hernando,2 E. Sanchez,2 X. Chen,2 J.J. Valero,2 R. Ciervide,2 M. Garcia Aranda,2 D. Zucca,3 J. Garcia Ruiz Zorrilla,2 M. Lopez,2 J. M. Perez Moreno,2 E. Vicente,2 Y. Quijano,2 A. Cubillo,2 B. Alvarez,3 L. Madrigal,2 P. Fernandez Leton,3 M. Allona,2 M.I. Torres,2 and M. Fernandez Velilla2; 1Hospital Universitario HM Sanchinarro, Madrid, Spain, 2Hospital Universitario HM Sanchinarro, Madrid, Spain, 3 Hospital Universitario HM Sanchinarro, Madrid, Spain Purpose/Objective(s): To report the outcome and toxicity of SBRT for patients with liver and lung oligometastases treated with intrafraction control of tumor motion guided by internal fiducials and a Gating Technique. Materials/Methods: This is a retrospective study of 132 patients with liver and lung metastases treated with SBRT at our institution, previously selected in a multidisciplinary committee. Prior to treatment, fiducial internal markers were implanted into the lung or the liver, guided by CT scan. The PTV included GTV and 5 mm margin. No ITV was defined. Daily IGRT with Stereoscopic X-Rays localized the internal markers and quantified the tumor movement, defining a “Gating beam on area” of irradiation with the Exactrac Adaptive Gating of a Novalis LINAC. Intrafraction verification of the internal marker position was verified in real time with X-Rays. Doses prescribed for liver and peripheral lung lesions were 50-60 Gy in 3-5 fractions and for central lung lesions 50 Gy in 5 fractions. Actuarial LC and OS curves were generated by using the Kaplan-Meier method and Log Rank Test was used for the univariate comparatives. Results: From July 2008 to December 2013, 132 patients and a total of 262 metastases were treated with SBRT. 64 patients were treated of 156 liver metastases (32.8% with 3 lesions); median follow-up 22 months