Efficacy of Radioembolization Treatments With Yttrium-90 Microspheres for Hepatocellular Carcinoma and Liver Metastases

Volume 84  Number 3S  Supplement 2012

Poster Viewing Abstracts S339

Author Disclosure: S. Cherian: None. T. Djemil: None. M. Abdel-Wahab: None. J. Greskovich: None. J. Fung: None. F. Aucejo: None. C. Miller: None. J. Sanabria: None. N. Menon: None. K. Stephan: None.

Author Disclosure: H. Yoon: None. D. Oh: None. H. Park: None. S. Kang: None. S. Park: None. Y. Han: None.

2322 2321 Dosimetric Analysis of Gastroduodenal Toxicity by Endoscopy in Cirrhotic Patients After Radiation Therapy for Hepatocellular Carcinoma H. Yoon,1 D. Oh,2 H. Park,3 S. Kang,4 S. Park,2,4 and Y. Han3; 1 Sungkyunkwan University, Seoul, Korea, Republic of Korea, 2Samsung Medical Center, Seoul, Korea, Republic of Korea, 3Samsung Medical Center, Sungkyunkwan University, Seoul, Korea, Republic of Korea, 4 Korea University, Seoul, Korea, Republic of Korea Purpose: To identify the dosimetric parameters associated with endoscopic gastroduodenal (GD) toxicity in patients with hepatocellular carcinoma (HCC) treated by radiation therapy (RT). Materials and Methods: We performed esophagogastroduodenoscopy (EGD) before the start of RT and 1 month after the completion of RT when target volume is in close proximity to gastroduodenum as institutional protocol. An additional EGD was performed thereafter, if patients complain of GD symptoms. GD toxicity was evaluated at 6 months after RT by Common Terminology Criteria for Adverse Events (CTCAE 3.0) and the event was defined as grade 2 or higher toxicity. All patients performed 4-dimensional computed tomography (4D-CT) for RT planning. Stomach and duodenum on each respiratory phase were delineated separately and merged together for dosimetric analysis of planning organ at risk volume (PRV) of stomach (S-PRV), and duodenum (D-PRV). The percentage of volume (Vdose) and absolute volume (aVdose) receiving more than the indicated dose were calculated. The receiver operating characteristic (ROC) curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best dosimetric parameter to predict for GD toxicity. Results: A total of 50 patients were enrolled in the current analysis between October 2008 and December 2010. RT was delivered with a median dose of 35 Gy (range, 30- 50 Gy) in 10 fractions. At 6 months, 14 patients (28.0%) experienced grade 2 GD toxicity and 7 patients (14.0%) experienced grade 3 GD toxicity. For duodenumV30 and aV30 were the most predictive factors. Duodenal toxicity rate at 6 months was 15.2% vs. 64.7% for V30 26% and V30 > 26% and 13.8% vs. 57.14% for aV30 11 cc and aV30 > 11 cc, respectively. For stomach, V25 and aV25 were the most predictive factors. Gastric toxicity rate at 6 months was 5.4% vs. 84.6% for V25 6.5% and V25 > 6.5% and 0% vs. 61.9% for aV25 6 cc and aV25 > 6 cc, respectively (Table). Conclusion: V30 for duodenum and V25 for stomach can be predictive factors for endoscopic GD toxicity in cirrhotic patients with HCC treated by RT.

Poster Viewing Abstract 2321; Table operating characteristic (ROC) curve

Dosimetric analysis by the receiver

S-PRV Cutoff Parameter point V15 V20 V25 V30 aV15 aV20 aV25 aV30

4.06 9.31 6.45 1.38 11.9 13.5 5.97 3.47

100/70.3 84.6/89.2 84.6/94.6 92.3/86.5 100/67.6 92.3/78.4 100/78.4 92.3/83.8

0.892 0.906 0.946 0.92 0.873 0.898 0.942 0.923

0.003 0.003 0.003 0.054 0.007 0.004 0.003 0.068

24.57 26.53 14.19 11.97 22.66 20.28 14.48 11.15

Sensitivity/ p specificity AUC value 87.5/52.9 81.2/67.6 81.2/64.7 81.2/73.5 81.2/55.9 81.2/64.7 81.2/64.7 75.0/76.5

Purpose/Objective(s): To investigate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) with real-time respiratory motion tracking for primary or metastatic liver tumors. Materials/Methods: Seventeen patients, who underwent SBRT between April 2010 and February 2012 using robotic radiosurgery, were followed up. In the selected patients, 14 patients (16 lesions) were diagnosed with primary liver tumors, and other 3 patients (4 lesions) with metastatic liver tumors. All the patients were received tumor-tracking SBRT treatments under the effectively same treatment condition. The patients treatment plans were designed with four-dimensional dynamic dose delivery technique based on the four-dimensional CT dataset with proper respiration modeling. The 45 Gy prescribed dose were delivered to planned target volume (PTV) throughout 3 fractionations with every other day treatment scheme. The PTV was delineated with 5-mm extent from gross tumor volume, which was drawn based on fused CT and MR image sets. To achieve both adequate target coverage and normal tissue sparing, we carefully designed the treatment plan that the prescribed isodose line covered entire GTV and at least 95% of PTV volumes, respectively, whereas the normal liver volume receiving 19 Gy did not exceed 700 cc. Tumor response after irradiations was evaluated based on the RECIST criteria and treatment toxicity was estimated according to the Common Toxicity Criteria (CTC) guidelines version 3.0. Results: All patients were evaluated based on follow-up images with median follow-up period of 13 months (range, 1-21 months). We observed clear tumor response after SBRT in all patient group. That is, complete response was shown in 45% of treatment lesions (9/20 lesions), partial response was in 40% (8/20 lesions), and stable disease was shown in 15% (3/20 lesions). Three of 17 (17.7%) patients experienced acute toxicities including nausea in 1 and fatigue in 2 patients, respectively, but they were only limited in Grade 1. No higher grade acute toxicity was observed. Conclusions: Our clinical data of SBRT for small liver tumors showed relatively better local control probability with less occurring of acute toxicity. Therefore, although the long-term follow-up must be needed to firmly prove the clinical efficacy, the SBRT with real-time respiratory motion tracking could be considered as a strong alternative to surgical operation for small liver tumors. Author Disclosure: K. Kang: None. Y. Lim: None. H. Jeong: None. I. Ha: None. B. Jeong: None. H. Jang: None. B. Choi: None. G. Chai: None.

2323

D-PRV

Cutoff Sensitivity/ p specificity AUC value point

Preliminary Report of Stereotactic Body Radiation Therapy With Respiratory Motion Tracking for Liver Tumors K. Kang,1 Y. Lim,2 H. Jeong,1 I. Ha,1 B. Jeong,1 H. Jang,3 B. Choi,3 and G. Chai1; 1Gyeonsang National University Hospital, Jinju, Korea, Republic of Korea, 2National Cancer Center, Goyang, Korea, Republic of Korea, 3Seoul St Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Republic of Korea

0.686 0.710 0.746 0.820 0.676 0.719 0.741 0.805

0.003 0.003 0.003 0.054 0.007 0.004 0.003 0.068

Abbreviations: Vdose, the percentage of volume receiving more than the indicated dose (%); aVdose, absolute volume receiving more than the indicated dose (cc); PRV, planning organ at risk volume; S, Stomach; D, Duodenum, AUC; the area under the ROC curve

Efficacy of Radioembolization Treatments With Yttrium-90 Microspheres for Hepatocellular Carcinoma and Liver Metastases M.A. Ziegler,1 R. Kumar,1 A.T. Wild,1 T.M. Pawlik,2 I.R. Kamel,3 J.M. Herman,1 and J.H. Geschwind4; 1Department of Radiation Oncology & Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, 2Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, MD, 3Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Hospital, Baltimore, MD, 4Russell H. Morgan Department of Radiology and Radiological Sciences, Division of Vascular and Interventional Radiology, Johns Hopkins Hospital, Baltimore, MD

S340

International Journal of Radiation Oncology  Biology  Physics

Purpose/Objectives: Treatment efficacy and median overall survival (mOS) were studied for patients with hepatocellular carcinoma (HCC) and liver metastases who received radioembolization treatments with Yttrium90 microspheres. Materials/Methods: Data were gathered for patients receiving Yttrium-90 radioembolization from July 2001 to February 2012 (n Z 126 patients, 173 treatments). Sixty-seven percent of patients were male and the average age was 60 years. Twenty-two patients were diagnosed with HCC and 104 patients had metastases to the liver. There were no differences in patient characteristics between patient subsets. Kaplan-Meier estimates were used to determine mOS from time of first treatment, and the Cox regression model was used to perform cohort analyses. Results: The average administered activity was 2.98 GBq (SD 1.58 GBq, range 0.01-9.44 GBq). The number of patients per subgroup, mOS, and 95% confidence intervals (CI) are presented in the table below. Patients with liver metastases had a longer mOS when compared to HCC patients (HR 1.80, 95% CI 1.07-3.03, p Z 0.026). Patients with neuroendocrine carcinoid metastases had a longer mOS versus patients with non-neuroendocrine metastases (HR 2.30, 95% CI 1.32-3.99, p Z 0.003). Patients with pancreatic neuroendocrine metastases did not have had a longer mOS when compared to non-pancreatic neuroendocrine metastases (HR 1.02, 95% CI 0.20-5.12, p Z 0.98). Conclusion: Radioembolization with Yttrium-90 microspheres has been shown in previous studies to be a safe and effective treatment for HCC and metastases to the liver with some showing a survival benefit over other treatment modalities. Our data confirms the utility of this treatment method in multiple histologies, particularly neuroendocrine primary lesions. Additional prospective dosimetric studies are needed to determine how to optimally escalate Yttrium-90 microspheres in an attempt to further improve survival of these patients. Author Disclosure: M.A. Ziegler: None. R. Kumar: None. A.T. Wild: None. T.M. Pawlik: None. I.R. Kamel: None. J.M. Herman: None. J.H. Geschwind: None.

Results: Median KPS and MELD scores were 80 (range, 60-90) and 8 (range, 3-13), respectively. AJCC staging distribution was: 0 patients stage I (0%), 8 stage II (30%), 9 stage IIIA (33%), 6 stage IIIB (22%), 0 Stage IIIC (0%), 2 stage IVA (7%), and 1 stage IVB (4%). Median diameter of the largest hepatic mass was 4 cm (range, 1-13). Eleven patients (41%) had prior TACE, and 2 patients (7%) had prior RFA. Median AFP level was 263 ng/mL (range, 3.1 - 221,650). Nineteen patients (70%) had one Y-90 treatment; 8 patients (30%) had two treatments (i.e. to left and right lobes). Median follow-up time was 4.4 months (range, 0.7- 40.8). Initial treatment responses were: no patients had a complete response, 10 patients (37%) had a partial response, 4 patients (15%) had stable disease, and 13 patients (48%) had progression of disease by RECIST criteria. Loco-regional and distant control for the 18 assessable patients: 16 patients had a local failure (89%), and 2 patients (11%) had a distant failure (including 1 patient with both local and distant failure). Median survival of all 27 patients was 5.7 months (range, 1 - 41). Thirteen patients were high-risk by Goin’s criteria with a 4.0-month median survival (range, 1.0 e 12.0). Acute NCI grade  3 toxicities were seen in 24 patients and included: elevations of AST and bilirubin, nausea, fatigue, abdominal pain, and ascites. Of 15 patients who had follow-up of at least 4 months, chronic NCI grade  3 toxicities were seen in 10 patients and included the following: elevations of bilirubin and creatinine, abdominal pain, and ascites. Conclusion: Y-90 Therasphere treatment can result in partial responses and stable disease in half of patients but likely does not substantially improve survival of patients with advanced primary HCC. Author Disclosure: M.J. Lobo: None. M.B. Syed: None. S. Sharma: None. K.A. Reardon: None. P.W. Read: None.

2324 Retrospective Analysis of the Yttrium-90 Microspheres in Hepatocellular Carcinoma M.J. Lobo, M.B. Syed, S. Sharma, K.A. Reardon, and P.W. Read; University of Virginia, Charlottesville, VA Purpose/Objective(s): This is a retrospective analysis of survival, disease control, and toxicity outcomes for patients with primary hepatocellular carcinoma (HCC) treated with Yttrium-90 Theraspheres. Materials/Methods: From June 2007 to February 2012, we analyzed data from 27 patients with HCC treated with Y-90 Theraspheres with a median target dose 112 Gy (range, 50 - 138). Pre-treatment, treatment, and followup data were obtained. Factors assessed included tumor location/size, AJCC staging, TACE/radiofrequency ablation (RFA) schedules, liver mass/ volume, doses to liver/lungs, target dose, radiographic/clinical response, and MELD score. Follow-up criteria included initial response, local/distant failure, and time to failure (from treatment to last follow-up). Relevant acute (from treatment to 4 months post-treatment) and late ( 4 months post-treatment) toxicities were scored by version 4.0 NCI Common Toxicity Criteria.

Poster Viewing Abstract 2323; Table histologic group

Median overall survival based on

Histology

Median OS (months)

95% CI

Hepatocellular carcinoma (n Z 22) Liver metastases (n Z 104) Colorectal mets (n Z 50) Neuroendocrine mets (n Z 36) Non-neuroendocrine mets (n Z 68) Pancreatic neuroendocrine mets (n Z 12) Other neuroendocrine mets (n Z 24)

9.0 14.8 8.2 29.2 8.7 41.9 24.6

2.5-15.4 2.0-27.6 4.3-12.0 17.0-41.3 5.7-11.6 15.8-68.1 10.9-38.4

2325 Propensity Score Analysis of Anastomotic Leakage After Rectal Cancer Resection: Risk Factors and Radiation Effects J. Chang,1 K. Keum,1 N. Kim,2 K. Lee,2 J. Kim,1 H. Yoon,1 C. Lee,1 and W. Koom1; 1Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea, Republic of Korea, 2Department of Surgery, Yonsei University College of Medicine, Seoul, Korea, Republic of Korea Purpose/Objective(s): To identify risk factors and assess the radiation effect on anastomotic leakage (AL) after rectal cancer resection. Materials/Methods: We retrospectively reviewed 230 consecutive rectal cancer patients treated with chemoradiation therapy and anterior resection between 2008 and 2010. Based on proposal by the International Study Group of Rectal Cancer, we defined postoperative AL as a defect of the intestinal wall at the anastomotic site, which required active therapeutic intervention (Grade B), or re-laparotomy (Grade C) within 90 days after surgery. One hundred eighty-two patients (79.1%) were stage III, and 48 (20.9%) were stage II. The average tumor height and height of anastomotic line above anal verge were 7.5 cm and 4.5 cm, respectively. Fifty-three patients (23.0%) underwent open low anterior resection and 177 underwent either laparoscopic (33.9%) or robot-assisted (43.0%) surgery. Diverting ileostomy was performed in 99 patients (43%) at the time of resection. All patients received chemotherapy during radiation therapy (RT). The patients were divided into two treatment groups for analysis: (1) 114 patients who received 50.4 Gy preoperative radiation therapy (RT group) and (2) 116 patients who received postoperative RT (surgery group). Multivariate and propensity score analysis were used to compensate for the differences in some baseline characteristics. Results: Postoperative AL occurred in 32 patients (13.9%) and resulted in prolonged hospital stays and delayed ileostomy closure. By multivariate analysis, being male (hazard ratio [HR] Z 4.41, p Z 0.034) and receiving blood transfusion during surgery (HR Z 5.79, p Z 0.026) were identified as independent risk factors for AL. Significant differences were present between the RT and surgery groups regarding smoking, tumor height, clinical T, N stage, type of resection (low anterior resection vs. ultra-low anterior resection), height of anastomotic line, diverting ileostomy, length of proximal margin, and total anesthesia time. After stratification into four quartiles according to propensity scores, all potential confounding factors