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Multimodality Local Therapy Improves Survival Without Hastening Liver Failure in Patients With Locally Advanced Hepatocellular Carcinoma.
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Volume 99 Number 2S Supplement 2017 (constraint for treatment, <3 cc), and V15 decreased from 7.07 cc and 9.12 cc to 2.02 cc and 3.91 cc, respectively (constraint for treatment, <9 cc). PTV coverage improved or was comparable between the pre- and postinjection studies. Modeling studies analyzing the 42 plans across 7 different patients demonstrated that separation of 5 mm was sufficient to reduce V15, V20 and V33. No additional reduction in V33 was noted after 5 mm of separation. Conclusion: Dose-escalation may improve outcomes in BR/LAPC. However, current technology is limited due to the radiosensitive structures adjacent to the pancreas. This preliminary study demonstrates the feasibility of an injectable radiopaque hydrogel for separation of the HOP from the duodenum. Future studies will evaluate the safety of this separation technique. If accceptable, clinical trials should follow to explore this novel use of a hydrogel spacer to improve the safety and accessibility of doseescalated SBRT or IMRT for pancreatic cancer patients. Author Disclosure: A.D. Rao: Employee; Johns Hopkins Hospital. Z. Feng: None. E. Shin: None. J. He: None. K. Waters: None. S. Coquia: None. R. De Jong: None. L.M. Rosati: None. L. Su: None. D. Li: None. J. Jackson: None. S. Clark: None. J. Schultz: None. D. Hutchings: None. S. Kim: None. R. Hruban: None. J.W. Wong: Research Grant; Elekta, Xstrahl. Consultant; Xstrahl. Travel Expenses; Elekta, Xstrahl. Stock; Elekta. Royalty; Elekta. Patent/License Fees/Copyright; Elekta. A. Narang: None. J.M. Herman: None. K. Ding: None.
2436 Multimodality Local Therapy Improves Survival Without Hastening Liver Failure in Patients With Locally Advanced Hepatocellular Carcinoma. P. Renz,1 S. Hasan,1 S. Abel,1 T. Uemura,2 L. Machado,2 N. Thai,2 and A.V. Kirichenko1; 1Allegheny Health Network Division of Radiation Oncology, Pittsburgh, PA, 2Allegheny Health Network Division of Transplant Surgery, Pittsburgh, PA Purpose/Objective(s): Locally advanced hepatocellular carcinoma (HCC) patients not candidates for orthotopic liver transplantation (OLT) have poor survival and often succumb to disease progression prior to liver failure despite conventional therapy with transarterial chemoembolization (TACE) and Sorafenib. We hypothesize that survival is improved without hastening liver failure in patients, with introduction of stereotactic body radiotherapy (SBRT) or fractionated radiotherapy (3DRT) with concurrent capecitabine to the multidisciplinary management of patients with locally advanced HCC. Materials/Methods: Retrospective review of locally advanced HCC patients treated with multimodality local therapy was performed from 2008 to 2015 in this IRB approved study. Locally advanced disease was defined as a single bulky lesion >6cm or multifocal tumors. 73% percent were BCLC intermediate stage HCC ineligible for transplant per MILAN criteria. Nine patients were excluded for Child-Pugh C cirrhosis, ECOG >3, metastasis, and malignant portal vein thrombosis. Multimodality local therapy included any two or more of the following: SBRT, TACE, 3DRT with capecitabine, and partial liver resection. The median SBRT and 3DRT doses were 40 Gy in 5 fractions and 40 Gy in 15 fractions, respectively. Endpoints of survival and Child Pugh (CP) progression were recorded. Kaplan-Meier statistical analysis was performed via MedCalc. Results: Median age was 63 and 80% were male. 41 patients received 115 local treatments for 92 lesions (median size 2.9cm). The average aggregate HCC size per patient was 6.8 cm (2.7-16 cm). There were 47 (41%) SBRT, 45 (39%) TACE, and 18 (16%) 3DRT treatments. 31% (nZ20) of SBRT/ 3DRT treatments were as a boost to TACE for bulky lesions. 22% received Sorafenib at any time. 59% were CP-A and 41% were Child B. Median survival (MS) was 32 months (37 months in CP-A and 10 months in CP-B (PZ0.01)). Multimodal local therapy improved survival compared with historical BCLC intermediate stage controls (20 months). 12% died due to intra or extrahepatic cancer progression. Aggregate HCC size <5cm correlated with improved survival (OS) (pZ0.04). Local therapy for downstaging or bridge to transplant allowed seven patients to become eligible for OLT, 5 of whom were alive at last follow up (median 37 months). The 3 year OS for OLT patients was 100% (P < 0.01). There was
no difference in OS when stratified by treatment combinations. 31% died from progression of liver failure with a median time to CP progression of 25 months. The only factor correlated with CP progression was CP score prior to treatment. Conclusion: Multimodality local therapy improves overall survival without hastening liver failure in patients with locally advanced hepatocellular carcinoma who are not candidates for OLT. Additionally, aggressive multimodality local therapy may downstage/bridge patients allowing OLT and improved long term survival. Author Disclosure: P. Renz: None. S. Hasan: None. S. Abel: None. T. Uemura: None. L. Machado: None. N. Thai: None. A.V. Kirichenko: None.
2437 Compensatory Increase in Future Liver Remnant Volume After External Beam Radiation Therapy to Liver Tumors C.H. Rim,1 J.Y. Woo,2 S. Park,1 and J. Seong1; 1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 2Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South) Purpose/Objective(s): Radiation to the focal liver can induce compensating hypertrophy, which has been reported in radioembolization. In this study, we investigated whether external beam radiotherapy (EBRT) could induce compensated hypertrophy in liver volume as well as related clinical factors. Materials/Methods: A total of 82 consecutive patients were recruited who received radiotherapy for hepatocellular carcinoma (n Z 77) or cholangiocarcinoma (n Z 5) from April 2012 to June 2014. The patients were divided into two subgroups according to whether tumors were located in the right or left lobe. Left lateral and right lobe were considered to be unirradiated volumes in the former and the latter groups, respectively. Total liver volume (TLV), normal liver volume (NLV), left and right whole liver volume (LLWV and RLWV), V30 (volume of liver irradiated <30 Gy), Child-Pugh score, future liver remnant ratio (FLR) and percentage of FLR hypertrophy from baseline (%FLR hypertrophy) were assessed on pre- and post- EBRT CT scans. Results: In the right lobe group, %FLR hypertrophy and LLWV increased significantly at all follow-ups (p <0.001). Clinical factors associated with %FLR hypertrophy were tumor volume, tumor location, and treatment method. Post-radiotherapy (RT) treatment affected Child-Pugh scores, which were significantly lower than the baseline at the 2nd, 3rd, and 4th follow-ups. V30 and %FLR hypertrophy showed significant correlations at 1st and 2nd follow-up (p Z 0.033, 0.013, respectively). In the left lobe group, %FLR hypertrophy and RLWV showed no significant change during follow-ups. Conclusion: Significant compensatory hypertrophy was observed after EBRT for liver cancer in the right lobe. %FLR hypertrophy increased steadily until 4th follow-up (median 396 days). Author Disclosure: C. Rim: None. J. Woo: None. S. Park: None. J. Seong: None.
2438 A Novel Pretrial Contouring Exercise for the UK led PersonaLising Anal cancer radioTherapy dOse (PLATO) Trial M. Robinson,1 D. Christophides,2 N. Abbott,3 S. Bell,4 A. Langley,4 M. Harrison,5 R. Adams,3 R. Muirhead,1 D. Sebag-Montefiore,2 and M.A. Hawkins1; 1CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom, 2University of Leeds, Cancer Research UK Leeds Centre, St James’ University Hospital, Leeds, United Kingdom, 3Velindre Cancer Centre, Cardiff, United Kingdom, 4Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom, 5Mount Veron Cancer Centre, Northwood, United Kingdom
Volume 99 Number 2S Supplement 2017 (constraint for treatment, <3 cc), and V15 decreased from 7.07 cc and 9.12 cc to 2.02 cc and 3.91 cc, respectively (constraint for treatment, <9 cc). PTV coverage improved or was comparable between the pre- and postinjection studies. Modeling studies analyzing the 42 plans across 7 different patients demonstrated that separation of 5 mm was sufficient to reduce V15, V20 and V33. No additional reduction in V33 was noted after 5 mm of separation. Conclusion: Dose-escalation may improve outcomes in BR/LAPC. However, current technology is limited due to the radiosensitive structures adjacent to the pancreas. This preliminary study demonstrates the feasibility of an injectable radiopaque hydrogel for separation of the HOP from the duodenum. Future studies will evaluate the safety of this separation technique. If accceptable, clinical trials should follow to explore this novel use of a hydrogel spacer to improve the safety and accessibility of doseescalated SBRT or IMRT for pancreatic cancer patients. Author Disclosure: A.D. Rao: Employee; Johns Hopkins Hospital. Z. Feng: None. E. Shin: None. J. He: None. K. Waters: None. S. Coquia: None. R. De Jong: None. L.M. Rosati: None. L. Su: None. D. Li: None. J. Jackson: None. S. Clark: None. J. Schultz: None. D. Hutchings: None. S. Kim: None. R. Hruban: None. J.W. Wong: Research Grant; Elekta, Xstrahl. Consultant; Xstrahl. Travel Expenses; Elekta, Xstrahl. Stock; Elekta. Royalty; Elekta. Patent/License Fees/Copyright; Elekta. A. Narang: None. J.M. Herman: None. K. Ding: None.
2436 Multimodality Local Therapy Improves Survival Without Hastening Liver Failure in Patients With Locally Advanced Hepatocellular Carcinoma. P. Renz,1 S. Hasan,1 S. Abel,1 T. Uemura,2 L. Machado,2 N. Thai,2 and A.V. Kirichenko1; 1Allegheny Health Network Division of Radiation Oncology, Pittsburgh, PA, 2Allegheny Health Network Division of Transplant Surgery, Pittsburgh, PA Purpose/Objective(s): Locally advanced hepatocellular carcinoma (HCC) patients not candidates for orthotopic liver transplantation (OLT) have poor survival and often succumb to disease progression prior to liver failure despite conventional therapy with transarterial chemoembolization (TACE) and Sorafenib. We hypothesize that survival is improved without hastening liver failure in patients, with introduction of stereotactic body radiotherapy (SBRT) or fractionated radiotherapy (3DRT) with concurrent capecitabine to the multidisciplinary management of patients with locally advanced HCC. Materials/Methods: Retrospective review of locally advanced HCC patients treated with multimodality local therapy was performed from 2008 to 2015 in this IRB approved study. Locally advanced disease was defined as a single bulky lesion >6cm or multifocal tumors. 73% percent were BCLC intermediate stage HCC ineligible for transplant per MILAN criteria. Nine patients were excluded for Child-Pugh C cirrhosis, ECOG >3, metastasis, and malignant portal vein thrombosis. Multimodality local therapy included any two or more of the following: SBRT, TACE, 3DRT with capecitabine, and partial liver resection. The median SBRT and 3DRT doses were 40 Gy in 5 fractions and 40 Gy in 15 fractions, respectively. Endpoints of survival and Child Pugh (CP) progression were recorded. Kaplan-Meier statistical analysis was performed via MedCalc. Results: Median age was 63 and 80% were male. 41 patients received 115 local treatments for 92 lesions (median size 2.9cm). The average aggregate HCC size per patient was 6.8 cm (2.7-16 cm). There were 47 (41%) SBRT, 45 (39%) TACE, and 18 (16%) 3DRT treatments. 31% (nZ20) of SBRT/ 3DRT treatments were as a boost to TACE for bulky lesions. 22% received Sorafenib at any time. 59% were CP-A and 41% were Child B. Median survival (MS) was 32 months (37 months in CP-A and 10 months in CP-B (PZ0.01)). Multimodal local therapy improved survival compared with historical BCLC intermediate stage controls (20 months). 12% died due to intra or extrahepatic cancer progression. Aggregate HCC size <5cm correlated with improved survival (OS) (pZ0.04). Local therapy for downstaging or bridge to transplant allowed seven patients to become eligible for OLT, 5 of whom were alive at last follow up (median 37 months). The 3 year OS for OLT patients was 100% (P < 0.01). There was
no difference in OS when stratified by treatment combinations. 31% died from progression of liver failure with a median time to CP progression of 25 months. The only factor correlated with CP progression was CP score prior to treatment. Conclusion: Multimodality local therapy improves overall survival without hastening liver failure in patients with locally advanced hepatocellular carcinoma who are not candidates for OLT. Additionally, aggressive multimodality local therapy may downstage/bridge patients allowing OLT and improved long term survival. Author Disclosure: P. Renz: None. S. Hasan: None. S. Abel: None. T. Uemura: None. L. Machado: None. N. Thai: None. A.V. Kirichenko: None.
2437 Compensatory Increase in Future Liver Remnant Volume After External Beam Radiation Therapy to Liver Tumors C.H. Rim,1 J.Y. Woo,2 S. Park,1 and J. Seong1; 1Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea, Republic of (South), 2Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University Health System, Seoul, Korea, Republic of (South) Purpose/Objective(s): Radiation to the focal liver can induce compensating hypertrophy, which has been reported in radioembolization. In this study, we investigated whether external beam radiotherapy (EBRT) could induce compensated hypertrophy in liver volume as well as related clinical factors. Materials/Methods: A total of 82 consecutive patients were recruited who received radiotherapy for hepatocellular carcinoma (n Z 77) or cholangiocarcinoma (n Z 5) from April 2012 to June 2014. The patients were divided into two subgroups according to whether tumors were located in the right or left lobe. Left lateral and right lobe were considered to be unirradiated volumes in the former and the latter groups, respectively. Total liver volume (TLV), normal liver volume (NLV), left and right whole liver volume (LLWV and RLWV), V30 (volume of liver irradiated <30 Gy), Child-Pugh score, future liver remnant ratio (FLR) and percentage of FLR hypertrophy from baseline (%FLR hypertrophy) were assessed on pre- and post- EBRT CT scans. Results: In the right lobe group, %FLR hypertrophy and LLWV increased significantly at all follow-ups (p <0.001). Clinical factors associated with %FLR hypertrophy were tumor volume, tumor location, and treatment method. Post-radiotherapy (RT) treatment affected Child-Pugh scores, which were significantly lower than the baseline at the 2nd, 3rd, and 4th follow-ups. V30 and %FLR hypertrophy showed significant correlations at 1st and 2nd follow-up (p Z 0.033, 0.013, respectively). In the left lobe group, %FLR hypertrophy and RLWV showed no significant change during follow-ups. Conclusion: Significant compensatory hypertrophy was observed after EBRT for liver cancer in the right lobe. %FLR hypertrophy increased steadily until 4th follow-up (median 396 days). Author Disclosure: C. Rim: None. J. Woo: None. S. Park: None. J. Seong: None.
2438 A Novel Pretrial Contouring Exercise for the UK led PersonaLising Anal cancer radioTherapy dOse (PLATO) Trial M. Robinson,1 D. Christophides,2 N. Abbott,3 S. Bell,4 A. Langley,4 M. Harrison,5 R. Adams,3 R. Muirhead,1 D. Sebag-Montefiore,2 and M.A. Hawkins1; 1CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom, 2University of Leeds, Cancer Research UK Leeds Centre, St James’ University Hospital, Leeds, United Kingdom, 3Velindre Cancer Centre, Cardiff, United Kingdom, 4Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom, 5Mount Veron Cancer Centre, Northwood, United Kingdom