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Factors Associated With Overall Survival After Radiation Therapy in Patients With Hepatocellular Carcinoma
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Volume 99 Number 2S Supplement 2017 comorbidity score, and treatment at an academic facility were not different between groups. On MVA, OS was improved with receipt of the highest RT dose (cohort 4), younger age, lower Charlson-Deyo comorbidity score, higher income (All p < 0.05), and lower stage (p<0.01). MVA showed superior OS for cohort 4 compared to cohort 1 (HR 1.4 [95% confidence interval 1.04 e 1.94], pZ0.027). Conclusion: Practice patterns for the definitive management of CEC demonstrate considerable heterogeneity with regard to radiation dose. Compared to lower doses, radiation doses > 64 Gy are associated with superior OS. Author Disclosure: P.R. Patel: None. M.W. McDonald: ; Emory Proton Therapy Center. A. Aiello: None. Y. Liu: None. N.F. Saba: None. J.J. Beitler: None. K.A. Higgins: None.
2431 Factors Associated With Overall Survival After Radiation Therapy in Patients With Hepatocellular Carcinoma W. Pi,1 Y. Zang,2 H. Zhang,3 H. Yao,3 S. Ellsworth,1 D. Long,1 W. Wang,3 J.Y. Jin,3 R.C. Zellars,3 M. Maluccio,4 and F.M. Kong1; 1Indiana University Department of Radiation Oncology, Indianapolis, IN, 2Indiana University Department of Biostatistics, Indianapolis, IN, 3Indiana University Department of Radiation Oncology, indianapolis, IN, 4Indiana University Department of Surgery, indianapolis, IN Purpose/Objective(s): The role of radiation therapy (RT) is evolving in patients with unresectable and inoperable hepatocellular carcinoma (HCC). This study is to 1) evaluate the efficacy of RT for HCC patients, and 2) identify factors predictive of survival in patients treated with RT. Materials/Methods: HCC patients from 2000 to 2016 in our institution were collected from the cancer registry system and studied retrospectively. Patients with any form of external beam radiation including stereotactic body radiotherapy (SBRT) and 3D conformal Radiation therapy (3DCRT) were eligible. The commonly used SBRT regimens were 48Gy in 4 fractions, 50 Gy in 5 fractions and 60 Gy in 3 fractions. The median dose of 3DCRT was 38 Gy (range 20-60 Gy). Age, gender, race, tobacco history, alcohol history, primary insurance payer, marital status, tumor size, histology grade, AFP level, SEER stage, clinical stage and pathologic stage, total dose, integral dose of the total dose, gross tumor volume (GTV), mean dose of GTV, planning target volume (PTV) and mean dose of PTV, liver volume, number of fraction, tumor biologically effective dose (BED), mean liver dose, SBRT and 3DCRT were tested for their association with survival. The primary endpoint is overall survival which was calculated from the first time of treatment to the last time of contact. Results: A total of 184 patients received external beam RT were included in this analysis: 127 with SBRT and 57 with 3DCRT. The median age was 61 years and the median follow-up was 37 months (95% CI 31-60) respectively. The 2- and 5- year survival rates were 61% (95% CI 54-69%) and 40% (95% CI 32-50%) respectively. Under the univariate analysis, tobacco history (current cigarette smoker, HRZ3.9, pZ0.03), SEER summary stage (distant, HRZ8.3, pZ310-14), tumor size per 1 cm (HRZ1.1, pZ0.0006), total dose (HRZ0.96, pZ0.0006), integral dose (HRZ1.3, pZ110-4), PTV (HRZ1.3, pZ910-5), GTV(HRZ1.001, pZ4.27x10-6), mean liver dose (HRZ1.1, pZ0.01), number of fraction (HRZ1.1, pZ0.002), BED (HRZ1.008, pZ3x10-3) and 3DCRT (HR Z 2.3, p Z 9.6x10-5) were significant factors for overall survival. Under multivariate analysis, PTV (HRZ1.6, pZ0.021) remained significant. The number of fraction had a borderline significance (HRZ1.1, pZ0.06), mean liver dose and other variables were not (all p>0.1). Of all 184 patients, 15 patients received liver transplant after RT (10 SBRT, 5 3DCRT). The median OS was 33 months (95% CI 27-59) for patients without transplant and 35 months for patients with transplant (HRZ0.4, pZ0.05, patients without transplant as reference). Conclusion: Radiation therapy provides reasonable long term outcomes with 40% 5-year survival in this populations. Negative impact of PTV on survival suggests importance of diagnosing and treating smaller tumor and potential benefit of high technology to shrink the PTV margin.
Author Disclosure: W. Pi: None. Y. Zang: None. H. Zhang: None. H. Yao: None. S. Ellsworth: None. D. Long: None. W. Wang: None. J. Jin: None. R. Zellars: None. M. Maluccio: None. F.(. Kong: Research Grant; NCI/NIH, Varian. ; Sino-American Network for Therapeutic Radiology, American Association of Women Radiologists (AAWR), Association for Chinese Professors, Chinese-American Network for Hematology and Oncolo, Sino-American Network for Therapeutic Radiation On.
2432 Endoluminal High-Dose Rate Brachytherapy for Medically Inoperable Early Stage and Locally Recurrent Esophageal cancer: Implementation of a Novel Applicator and Updated Institutional Experience K. Pitter,1 A. Taggar,1 G. Cohen,1 P. Brady,1 M.A. Schattner,1 J.J. Cuaron,1 K.A. Goodman,2 and A.J. Wu1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO Purpose/Objective(s): Management of recurrent and primary esophageal cancer (EC) in medically inoperable patients is complex. Endoluminal brachytherapy may be the only local treatment option in such cases, but historically has yielded mixed results. Here, we examined our institutional experience with endoluminal high-dose rate brachytherapy (EHDRBT) for early stage primary and locally recurrent EC, with particular focus on recent patients treated with a novel balloon centering esophageal applicator (BCEA). Materials/Methods: We retrospectively identified 33 EHDRBT-treated patients from 8/2008-8/2016, including 5 patients since 2015 treated with a new BCEA (E-App, Bionix Medical) designed specifically for EHDRBT by utilizing multiple articulating balloons to distend the lumen and center the source. There were 19 (57%) patients with locally recurrent disease, 7 (21%) with residual disease after external beam radiation or local excision, and 7 (24%) with previously untreated early stage tumors. The median dose was 14 Gy in 3 weekly fractions using Ir-192 source, prescribed to a median depth of 7 mm and to a median length of 6 cm. Twenty-four patients (73%) received concurrent chemotherapy. Patients typically underwent endoscopy and biopsy 3 months after EHDRBT and then every 36 months thereafter. Results: Twenty-nine patients were available for assessment with a median followup of 17.3 months. We identified 13 (45%) patients with grade 1 toxicities and 11 (38%) patients with grade 2, most commonly dysphagia and esophagitis. One patient had grade 3 stenosis requiring a stent and also developed a tracheoesophageal fistula. Biopsy-proven complete response (CR) was achieved in 15/28 (54%) patients. For patients who achieved CR, the median time to failure was 18.8 months, with 6 patients remaining disease-free, 8 with local failure, and 1 distant-only failure. The median overall survival for all patients was 20.8 months from EHDRBT. We observed no significant differences in toxicity or local control with use of the novel BCEA. Dosimetrically, the median mucosal Dmax was 10.6 Gy (7.9 - 21.2 Gy) per fraction, and there was no significant differences based on the applicator type. The BCEA patients were amenable to dose-volume histogram analysis. For these patients, the median hotspot to non-target esophagus (defined as D0.3cc) was 5.6 Gy per fraction, and the median V100 to non-target esophagus was 0.5 cc. Conclusion: For medically inoperable patients with primary or recurrent esophageal cancer, EHDRBT is well tolerated with minimal grade 3 toxicity. This may be due to improved techniques to center the source within the esophageal lumen. However, durable local control remains a challenge with these doses. To our knowledge, the current study includes the first reported series of patients treated with this novel balloon centering esophageal applicator, which was designed to produce more favorable dosimetry. This could facilitate dose-escalation studies, which we hope may lead to improved EHDRBT outcomes. Author Disclosure: K. Pitter: None. A. Taggar: None. G. Cohen: Honoraria; Biocompatibles, Inc. ; ABS. P. Brady: None. M.A. Schattner: None. J.J. Cuaron: None. K.A. Goodman: None. A.J. Wu: None.
Volume 99 Number 2S Supplement 2017 comorbidity score, and treatment at an academic facility were not different between groups. On MVA, OS was improved with receipt of the highest RT dose (cohort 4), younger age, lower Charlson-Deyo comorbidity score, higher income (All p < 0.05), and lower stage (p<0.01). MVA showed superior OS for cohort 4 compared to cohort 1 (HR 1.4 [95% confidence interval 1.04 e 1.94], pZ0.027). Conclusion: Practice patterns for the definitive management of CEC demonstrate considerable heterogeneity with regard to radiation dose. Compared to lower doses, radiation doses > 64 Gy are associated with superior OS. Author Disclosure: P.R. Patel: None. M.W. McDonald: ; Emory Proton Therapy Center. A. Aiello: None. Y. Liu: None. N.F. Saba: None. J.J. Beitler: None. K.A. Higgins: None.
2431 Factors Associated With Overall Survival After Radiation Therapy in Patients With Hepatocellular Carcinoma W. Pi,1 Y. Zang,2 H. Zhang,3 H. Yao,3 S. Ellsworth,1 D. Long,1 W. Wang,3 J.Y. Jin,3 R.C. Zellars,3 M. Maluccio,4 and F.M. Kong1; 1Indiana University Department of Radiation Oncology, Indianapolis, IN, 2Indiana University Department of Biostatistics, Indianapolis, IN, 3Indiana University Department of Radiation Oncology, indianapolis, IN, 4Indiana University Department of Surgery, indianapolis, IN Purpose/Objective(s): The role of radiation therapy (RT) is evolving in patients with unresectable and inoperable hepatocellular carcinoma (HCC). This study is to 1) evaluate the efficacy of RT for HCC patients, and 2) identify factors predictive of survival in patients treated with RT. Materials/Methods: HCC patients from 2000 to 2016 in our institution were collected from the cancer registry system and studied retrospectively. Patients with any form of external beam radiation including stereotactic body radiotherapy (SBRT) and 3D conformal Radiation therapy (3DCRT) were eligible. The commonly used SBRT regimens were 48Gy in 4 fractions, 50 Gy in 5 fractions and 60 Gy in 3 fractions. The median dose of 3DCRT was 38 Gy (range 20-60 Gy). Age, gender, race, tobacco history, alcohol history, primary insurance payer, marital status, tumor size, histology grade, AFP level, SEER stage, clinical stage and pathologic stage, total dose, integral dose of the total dose, gross tumor volume (GTV), mean dose of GTV, planning target volume (PTV) and mean dose of PTV, liver volume, number of fraction, tumor biologically effective dose (BED), mean liver dose, SBRT and 3DCRT were tested for their association with survival. The primary endpoint is overall survival which was calculated from the first time of treatment to the last time of contact. Results: A total of 184 patients received external beam RT were included in this analysis: 127 with SBRT and 57 with 3DCRT. The median age was 61 years and the median follow-up was 37 months (95% CI 31-60) respectively. The 2- and 5- year survival rates were 61% (95% CI 54-69%) and 40% (95% CI 32-50%) respectively. Under the univariate analysis, tobacco history (current cigarette smoker, HRZ3.9, pZ0.03), SEER summary stage (distant, HRZ8.3, pZ310-14), tumor size per 1 cm (HRZ1.1, pZ0.0006), total dose (HRZ0.96, pZ0.0006), integral dose (HRZ1.3, pZ110-4), PTV (HRZ1.3, pZ910-5), GTV(HRZ1.001, pZ4.27x10-6), mean liver dose (HRZ1.1, pZ0.01), number of fraction (HRZ1.1, pZ0.002), BED (HRZ1.008, pZ3x10-3) and 3DCRT (HR Z 2.3, p Z 9.6x10-5) were significant factors for overall survival. Under multivariate analysis, PTV (HRZ1.6, pZ0.021) remained significant. The number of fraction had a borderline significance (HRZ1.1, pZ0.06), mean liver dose and other variables were not (all p>0.1). Of all 184 patients, 15 patients received liver transplant after RT (10 SBRT, 5 3DCRT). The median OS was 33 months (95% CI 27-59) for patients without transplant and 35 months for patients with transplant (HRZ0.4, pZ0.05, patients without transplant as reference). Conclusion: Radiation therapy provides reasonable long term outcomes with 40% 5-year survival in this populations. Negative impact of PTV on survival suggests importance of diagnosing and treating smaller tumor and potential benefit of high technology to shrink the PTV margin.
Author Disclosure: W. Pi: None. Y. Zang: None. H. Zhang: None. H. Yao: None. S. Ellsworth: None. D. Long: None. W. Wang: None. J. Jin: None. R. Zellars: None. M. Maluccio: None. F.(. Kong: Research Grant; NCI/NIH, Varian. ; Sino-American Network for Therapeutic Radiology, American Association of Women Radiologists (AAWR), Association for Chinese Professors, Chinese-American Network for Hematology and Oncolo, Sino-American Network for Therapeutic Radiation On.
2432 Endoluminal High-Dose Rate Brachytherapy for Medically Inoperable Early Stage and Locally Recurrent Esophageal cancer: Implementation of a Novel Applicator and Updated Institutional Experience K. Pitter,1 A. Taggar,1 G. Cohen,1 P. Brady,1 M.A. Schattner,1 J.J. Cuaron,1 K.A. Goodman,2 and A.J. Wu1; 1Memorial Sloan Kettering Cancer Center, New York, NY, 2Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, CO Purpose/Objective(s): Management of recurrent and primary esophageal cancer (EC) in medically inoperable patients is complex. Endoluminal brachytherapy may be the only local treatment option in such cases, but historically has yielded mixed results. Here, we examined our institutional experience with endoluminal high-dose rate brachytherapy (EHDRBT) for early stage primary and locally recurrent EC, with particular focus on recent patients treated with a novel balloon centering esophageal applicator (BCEA). Materials/Methods: We retrospectively identified 33 EHDRBT-treated patients from 8/2008-8/2016, including 5 patients since 2015 treated with a new BCEA (E-App, Bionix Medical) designed specifically for EHDRBT by utilizing multiple articulating balloons to distend the lumen and center the source. There were 19 (57%) patients with locally recurrent disease, 7 (21%) with residual disease after external beam radiation or local excision, and 7 (24%) with previously untreated early stage tumors. The median dose was 14 Gy in 3 weekly fractions using Ir-192 source, prescribed to a median depth of 7 mm and to a median length of 6 cm. Twenty-four patients (73%) received concurrent chemotherapy. Patients typically underwent endoscopy and biopsy 3 months after EHDRBT and then every 36 months thereafter. Results: Twenty-nine patients were available for assessment with a median followup of 17.3 months. We identified 13 (45%) patients with grade 1 toxicities and 11 (38%) patients with grade 2, most commonly dysphagia and esophagitis. One patient had grade 3 stenosis requiring a stent and also developed a tracheoesophageal fistula. Biopsy-proven complete response (CR) was achieved in 15/28 (54%) patients. For patients who achieved CR, the median time to failure was 18.8 months, with 6 patients remaining disease-free, 8 with local failure, and 1 distant-only failure. The median overall survival for all patients was 20.8 months from EHDRBT. We observed no significant differences in toxicity or local control with use of the novel BCEA. Dosimetrically, the median mucosal Dmax was 10.6 Gy (7.9 - 21.2 Gy) per fraction, and there was no significant differences based on the applicator type. The BCEA patients were amenable to dose-volume histogram analysis. For these patients, the median hotspot to non-target esophagus (defined as D0.3cc) was 5.6 Gy per fraction, and the median V100 to non-target esophagus was 0.5 cc. Conclusion: For medically inoperable patients with primary or recurrent esophageal cancer, EHDRBT is well tolerated with minimal grade 3 toxicity. This may be due to improved techniques to center the source within the esophageal lumen. However, durable local control remains a challenge with these doses. To our knowledge, the current study includes the first reported series of patients treated with this novel balloon centering esophageal applicator, which was designed to produce more favorable dosimetry. This could facilitate dose-escalation studies, which we hope may lead to improved EHDRBT outcomes. Author Disclosure: K. Pitter: None. A. Taggar: None. G. Cohen: Honoraria; Biocompatibles, Inc. ; ABS. P. Brady: None. M.A. Schattner: None. J.J. Cuaron: None. K.A. Goodman: None. A.J. Wu: None.