- Email: [email protected]
Locally Advanced Esophageal Chemoradiation Therapy Practice Patterns: Results From a National Survey of ASTRO Members
ePoster Sessions S219
Volume 93 Number 3S Supplement 2015 associated with early tumor recurrence. Moreover, lower expression of genes in the DNA damage repair pathways has been associated with better survival after CRT. We hypothesized that response to CRT in ESCC patients is associated with a differential gene expression profile. Materials/Methods: We first identified ten patients treated at our institution, six of whom had a good response to CRT and four of whom had a poor response as defined by pathology or PET/CT. The patients received chemotherapy (cisplatin + 5-FU or carboplatin + taxol) and radiation (50.4 to 55.8 Gy) with or without esophagectomy. No correlation between patient response and chemotherapy regimen, radiation dose or esophagectomy status was noted. We isolated total RNA from formalin-fixed, paraffin embedded (FFPE) initial endoscopic biopsy specimens obtained at the time of diagnosis, and measured gene expression using the Human Transcriptome Array 2.0 (HTA 2.0), which contains probes to exons and splicing junctions of >245,000 protein coding transcripts and >40,000 non-coding Link RNAs. Results: We identified 525 genes whose expression was significantly different between responders and non-responders (P < .05), including five upregulated (CAPNS2, PADI1, FMO2, CXCL17 and miR-422) and four downregulated (CDK4, LMAN1, IGKV3D-20 and Cyclin D2) genes altered at least 1.5 fold for expression in non-responders. These genes regulate chemoresistance (CXCL17 to cisplatin, miR-422 to 5-FU), tumor invasion and/or angiogenesis (pro-invasive/angiogenic for Calpain 2 and CXCL17, anti-angiogenic for LMAN1), and cell cycle progression (CDK4 and Cyclin D2). Pathway and network analyses revealed that among the differentially expressed genes, four (CDK4, Cyclin D2, E2F3 and miR422) favored G1/S checkpoint progression in responders. Conclusion: To summarize, we have successfully completed a pilot study examining differential gene expression using FFPE biopsy specimens from ESCC patients based on their response to CRT. Preliminary data indicate the importance of the G1/S checkpoint progression in tumor sensitivity to CRT. We are currently seeking to obtain a larger cohort of patient specimens to further validate our results and explore new capabilities of the HTA 2.0 platform, such as identification of splicing variants. Author Disclosure: X. Chen: None. M. Veigl: None. J. Barnholtz-Sloan: None. W. Xin: None. Y. Chen: None. J.A. Dorth: None.
1154 Clinical Outcomes of Endoscopic Submucosal Dissection With Chemoradiation Therapy for Early-Stage Superficial Esophageal Cancer Y. Kajiya and N. Uchiyma; Kagoshima Municipal Hospital, Department of Radiation Oncology, Kagoshima, Japan Purpose/Objective(s): Although surgical resection is a standard therapy for superficial esophageal cancer, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) could also be definitive therapies. As the tumor extends beyond the mucosa, the possibility of lymph node metastasis and/or local recurrence increases. Thus, adjuvant therapy such as chemoradiation therapy (CRT) is recommended. Although CRT shows good results for superficial esophageal cancer, it is inferior compared with surgery. Materials/Methods: Sixteen patients with T1N0M0 esophageal cancer (median age: 69.6 years, range: 48e86 years) were treated at our institution. Five were treated with ESD and adjuvant CRT (ACRT), six with concurrent CRT (CCRT), and five with radiation therapy (RT) alone. Chemotherapy consisted of one or two courses of 5-FU infusion (500 mg/ m2, days 1e5) and CDDP infusion (50 mg/m2, day 1), with a 3-week interval. All ESD cases were examined for tumor depth pathologically and all showed T1b. The median RT dose was 54.7 Gy (range: 41.4e67.5 Gy). Actuarial overall survival (OS) and disease-free survival (DFS) were calculated using the KaplaneMeier method. Results: The 2-year OS and DFS of all 16 patients were 80% and 70%, respectively. The 2-year survival for ESD with ACRT, CCRT, and CRT alone was 100%, 75% and 80%, respectively. The 2-year DFS for ESD with ACRT, CCRT, and RT alone was 100%, 75% and 60%, respectively. Conclusion: ESD with ACRT were superior compared with CCRT or RT alone for early-stage superficial esophageal cancer. Author Disclosure: Y. Kajiya: None. N. Uchiyma: None.
1155 Locally Advanced Esophageal Chemoradiation Therapy Practice Patterns: Results From a National Survey of ASTRO Members D.A. Elliott,1 N. Nabavizadeh,1 A.S. Kusano,2 J.C. Voss,2 P.J. Bremjit,3 J.M. Holland,1 and T. Mitin1; 1Oregon Health and Science University, Portland, OR, 2University of Washington, Seattle, WA, 3University of Washington, Seattle, WA Purpose/Objective(s): Chemoradiation therapy (CRT), definitively or in the neoadjuvant setting, is the North American standard of care for patients with locally advanced esophageal cancer. The INT 0123 trial established the radiation dose of 50.4 Gy as the standard of care with concurrent chemotherapy, while the recent CROSS trial has shifted the paradigm of CRT for resectable esophageal cancer by utilizing an alternate chemotherapy regimen (carboplatin and paclitaxel or “carbo/taxol”) and a lower dose of radiation therapy (41.4 Gy) than North American standards. The purpose of this survey was to examine North American patterns of clinical practice in the years following CROSS. Materials/Methods: Five thousand nine hundred seventy-nine anonymous surveys were emailed to the members of the American Society for Radiation Oncology (ASTRO). The survey consisted of 13 questions pertaining to clinical choices of CRT in the treatment of locally advanced esophageal cancer. Results: We thank all 284 responders who took their time to respond to our online survey. Among them, 10 were non-physician, resulting in 274 evaluable responses. The majority of respondents practiced in the United States (1 from Canada), were over 10 years from completion of residency (150, 55%), practiced in private practice groups (151, 55%) and treated greater than 6 esophageal patients with curative intent over the last year (165, 60%). Surgical candidates were treated most often with 50.4 Gy with concurrent carbo/taxol (132, 49%). Borderline surgical candidates were also treated most often with 50.4 Gy with carbo/taxol (145, 54%). Non-surgical candidates were treated most often with greater than 50.4 Gy with either chemotherapy agent (103, 38%) followed by 50.4 Gy with carbo/taxol (93, 34%), 50.4 Gy with cis/5FU (62, 23%), while no providers would treat with 41.4 Gy with carbo/taxol for unresectable patients, and only 4 (2%) would lower dose below 50.4 Gy depending on DVH parameters. The majority of respondents believed that 50.4 Gy would yield a higher pathologic complete response (pCR) rate (236, 86%) and increased R0 resection rates (185, 68%) while being more toxic (147, 54%) than 41.4 Gy. The majority of respondents (206, 76%) would feel comfortable enrolling operable patients on a randomized trial comparing 41.4 Gy versus 50.4 Gy with concurrent carbo/taxol. Conclusion: Despite results of the INT 0123 trial, North American radiation oncologists commonly treat patients with non-resectable esophageal cancer with doses greater than 50.4 Gy. Despite the results of the CROSS trial, the majority of physicians continue to treat locally advanced esophageal cancer with neoadjuvant CRT to radiation doses greater than 41.4 Gy, with hopes of improved pCR rates and R0 resections, while recognizing this may increase toxicity. Given the paucity of prospective data, a randomized trial comparing 41.4 Gy versus 50.4 Gy in the neoadjuvant setting is needed and supported by ASTRO membership. Author Disclosure: D.A. Elliott: None. N. Nabavizadeh: None. A.S. Kusano: None. J.C. Voss: None. P.J. Bremjit: None. J.M. Holland: None. T. Mitin: None.
1156 Pathologic Complete Response and Dose-Escalation With Preoperative Dose Painting IMRT Chemoradiation in Esophageal Cancer P.S. Venkat,1 R. Shridhar,2 A.O. Naghavi,1 Y.A. Abuodeh,1 J.M. Frakes,1 J.M. Pimiento,1 K. Almhanna,1 K. Meredith,3 J.P. Fontaine,1 and S.E. Hoffe1; 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 2Florida Hospital Cancer Institute, Orlando, FL, 3Sarasota Memorial Hospital, Sarasota, FL Purpose/Objective(s): To evaluate pathologic response, treatment toxicity, and clinical outcomes of preoperative dose painting IMRT (dp-IMRT) with dose-escalation compared to standard IMRT in esophageal cancer. Materials/Methods: We retrospectively evaluated patients with locally advanced esophageal adenocarcinoma and squamous cell carcinoma treated
Volume 93 Number 3S Supplement 2015 associated with early tumor recurrence. Moreover, lower expression of genes in the DNA damage repair pathways has been associated with better survival after CRT. We hypothesized that response to CRT in ESCC patients is associated with a differential gene expression profile. Materials/Methods: We first identified ten patients treated at our institution, six of whom had a good response to CRT and four of whom had a poor response as defined by pathology or PET/CT. The patients received chemotherapy (cisplatin + 5-FU or carboplatin + taxol) and radiation (50.4 to 55.8 Gy) with or without esophagectomy. No correlation between patient response and chemotherapy regimen, radiation dose or esophagectomy status was noted. We isolated total RNA from formalin-fixed, paraffin embedded (FFPE) initial endoscopic biopsy specimens obtained at the time of diagnosis, and measured gene expression using the Human Transcriptome Array 2.0 (HTA 2.0), which contains probes to exons and splicing junctions of >245,000 protein coding transcripts and >40,000 non-coding Link RNAs. Results: We identified 525 genes whose expression was significantly different between responders and non-responders (P < .05), including five upregulated (CAPNS2, PADI1, FMO2, CXCL17 and miR-422) and four downregulated (CDK4, LMAN1, IGKV3D-20 and Cyclin D2) genes altered at least 1.5 fold for expression in non-responders. These genes regulate chemoresistance (CXCL17 to cisplatin, miR-422 to 5-FU), tumor invasion and/or angiogenesis (pro-invasive/angiogenic for Calpain 2 and CXCL17, anti-angiogenic for LMAN1), and cell cycle progression (CDK4 and Cyclin D2). Pathway and network analyses revealed that among the differentially expressed genes, four (CDK4, Cyclin D2, E2F3 and miR422) favored G1/S checkpoint progression in responders. Conclusion: To summarize, we have successfully completed a pilot study examining differential gene expression using FFPE biopsy specimens from ESCC patients based on their response to CRT. Preliminary data indicate the importance of the G1/S checkpoint progression in tumor sensitivity to CRT. We are currently seeking to obtain a larger cohort of patient specimens to further validate our results and explore new capabilities of the HTA 2.0 platform, such as identification of splicing variants. Author Disclosure: X. Chen: None. M. Veigl: None. J. Barnholtz-Sloan: None. W. Xin: None. Y. Chen: None. J.A. Dorth: None.
1154 Clinical Outcomes of Endoscopic Submucosal Dissection With Chemoradiation Therapy for Early-Stage Superficial Esophageal Cancer Y. Kajiya and N. Uchiyma; Kagoshima Municipal Hospital, Department of Radiation Oncology, Kagoshima, Japan Purpose/Objective(s): Although surgical resection is a standard therapy for superficial esophageal cancer, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) could also be definitive therapies. As the tumor extends beyond the mucosa, the possibility of lymph node metastasis and/or local recurrence increases. Thus, adjuvant therapy such as chemoradiation therapy (CRT) is recommended. Although CRT shows good results for superficial esophageal cancer, it is inferior compared with surgery. Materials/Methods: Sixteen patients with T1N0M0 esophageal cancer (median age: 69.6 years, range: 48e86 years) were treated at our institution. Five were treated with ESD and adjuvant CRT (ACRT), six with concurrent CRT (CCRT), and five with radiation therapy (RT) alone. Chemotherapy consisted of one or two courses of 5-FU infusion (500 mg/ m2, days 1e5) and CDDP infusion (50 mg/m2, day 1), with a 3-week interval. All ESD cases were examined for tumor depth pathologically and all showed T1b. The median RT dose was 54.7 Gy (range: 41.4e67.5 Gy). Actuarial overall survival (OS) and disease-free survival (DFS) were calculated using the KaplaneMeier method. Results: The 2-year OS and DFS of all 16 patients were 80% and 70%, respectively. The 2-year survival for ESD with ACRT, CCRT, and CRT alone was 100%, 75% and 80%, respectively. The 2-year DFS for ESD with ACRT, CCRT, and RT alone was 100%, 75% and 60%, respectively. Conclusion: ESD with ACRT were superior compared with CCRT or RT alone for early-stage superficial esophageal cancer. Author Disclosure: Y. Kajiya: None. N. Uchiyma: None.
1155 Locally Advanced Esophageal Chemoradiation Therapy Practice Patterns: Results From a National Survey of ASTRO Members D.A. Elliott,1 N. Nabavizadeh,1 A.S. Kusano,2 J.C. Voss,2 P.J. Bremjit,3 J.M. Holland,1 and T. Mitin1; 1Oregon Health and Science University, Portland, OR, 2University of Washington, Seattle, WA, 3University of Washington, Seattle, WA Purpose/Objective(s): Chemoradiation therapy (CRT), definitively or in the neoadjuvant setting, is the North American standard of care for patients with locally advanced esophageal cancer. The INT 0123 trial established the radiation dose of 50.4 Gy as the standard of care with concurrent chemotherapy, while the recent CROSS trial has shifted the paradigm of CRT for resectable esophageal cancer by utilizing an alternate chemotherapy regimen (carboplatin and paclitaxel or “carbo/taxol”) and a lower dose of radiation therapy (41.4 Gy) than North American standards. The purpose of this survey was to examine North American patterns of clinical practice in the years following CROSS. Materials/Methods: Five thousand nine hundred seventy-nine anonymous surveys were emailed to the members of the American Society for Radiation Oncology (ASTRO). The survey consisted of 13 questions pertaining to clinical choices of CRT in the treatment of locally advanced esophageal cancer. Results: We thank all 284 responders who took their time to respond to our online survey. Among them, 10 were non-physician, resulting in 274 evaluable responses. The majority of respondents practiced in the United States (1 from Canada), were over 10 years from completion of residency (150, 55%), practiced in private practice groups (151, 55%) and treated greater than 6 esophageal patients with curative intent over the last year (165, 60%). Surgical candidates were treated most often with 50.4 Gy with concurrent carbo/taxol (132, 49%). Borderline surgical candidates were also treated most often with 50.4 Gy with carbo/taxol (145, 54%). Non-surgical candidates were treated most often with greater than 50.4 Gy with either chemotherapy agent (103, 38%) followed by 50.4 Gy with carbo/taxol (93, 34%), 50.4 Gy with cis/5FU (62, 23%), while no providers would treat with 41.4 Gy with carbo/taxol for unresectable patients, and only 4 (2%) would lower dose below 50.4 Gy depending on DVH parameters. The majority of respondents believed that 50.4 Gy would yield a higher pathologic complete response (pCR) rate (236, 86%) and increased R0 resection rates (185, 68%) while being more toxic (147, 54%) than 41.4 Gy. The majority of respondents (206, 76%) would feel comfortable enrolling operable patients on a randomized trial comparing 41.4 Gy versus 50.4 Gy with concurrent carbo/taxol. Conclusion: Despite results of the INT 0123 trial, North American radiation oncologists commonly treat patients with non-resectable esophageal cancer with doses greater than 50.4 Gy. Despite the results of the CROSS trial, the majority of physicians continue to treat locally advanced esophageal cancer with neoadjuvant CRT to radiation doses greater than 41.4 Gy, with hopes of improved pCR rates and R0 resections, while recognizing this may increase toxicity. Given the paucity of prospective data, a randomized trial comparing 41.4 Gy versus 50.4 Gy in the neoadjuvant setting is needed and supported by ASTRO membership. Author Disclosure: D.A. Elliott: None. N. Nabavizadeh: None. A.S. Kusano: None. J.C. Voss: None. P.J. Bremjit: None. J.M. Holland: None. T. Mitin: None.
1156 Pathologic Complete Response and Dose-Escalation With Preoperative Dose Painting IMRT Chemoradiation in Esophageal Cancer P.S. Venkat,1 R. Shridhar,2 A.O. Naghavi,1 Y.A. Abuodeh,1 J.M. Frakes,1 J.M. Pimiento,1 K. Almhanna,1 K. Meredith,3 J.P. Fontaine,1 and S.E. Hoffe1; 1H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 2Florida Hospital Cancer Institute, Orlando, FL, 3Sarasota Memorial Hospital, Sarasota, FL Purpose/Objective(s): To evaluate pathologic response, treatment toxicity, and clinical outcomes of preoperative dose painting IMRT (dp-IMRT) with dose-escalation compared to standard IMRT in esophageal cancer. Materials/Methods: We retrospectively evaluated patients with locally advanced esophageal adenocarcinoma and squamous cell carcinoma treated