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Preoperative Dose Painting IMRT Chemoradiation to 56 Gy in Esophageal Cancer Doubles Pathologic Complete Response Rate Without Increasing Toxicity
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International Journal of Radiation Oncology Biology Physics
was seen in pre-CRT tumor maximum SUV (p Z 0.88); however, postCRT tumor maximum SUV was significantly decreased in patients taking metformin (p Z 0.02). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p Z 0.04). Metformin use was also associated with decreased in-field loco-regional failure following radiation (p Z 0.05). Conclusions: The use of metformin is associated with increased response to CRT in esophageal cancer in a dose-dependent manner and may be a sensitizer to this therapy. Author Disclosure: H.D. Skinner: None. M. McCurdy: None. A. Echeverria: None. S. Lin: None. J. Welsh: None. M. O’Reilly: None. W. Hofstetter: None. J. Ajani: None. R. Komaki: None. T. Guerrero: None.
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104 WITHDRAWN
105 Preoperative Dose Painting IMRT Chemoradiation to 56 Gy in Esophageal Cancer Doubles Pathologic Complete Response Rate Without Increasing Toxicity R. Shridhar,1 M.D. Chuong,1 J. Weber,1 K. Almhanna,1 K.L. Meredith,1 A. Cruz,2 and S.E. Hoffe1; 1H. Lee Moffitt Cancer Center, Tampa, FL, 2 University of South Florida College of Medicine, Tampa, FL Purpose/Objective(s): To determine the pathologic complete response rate (pCR) of preoperative dose painting IMRT (dp-IMRT) in esophageal cancer. Materials/Methods: We evaluated esophageal cancer patients treated between 2006 and 2011 with preoperative IMRT chemoradiation followed by esophagectomy. All patients underwent 4D CT simulation; most underwent endoscopic fiducial marker placement above and below the tumor. Our institutional philosophy evolved from uniform delivery of 50.4 Gy in 1.8 Gy fractions to dose painting gross disease to 56 Gy in 2.0 Gy fractions while keeping the CTV dose schema at 50.4 Gy in 1.8 Gy fractions. For all patients, the GTV was modified to account for respiration to create a GITV; this was then expanded 3-4 cm craniocaudally and 3-5 mm circumferentially with modifications for respiration to create a CITV. Elective nodal sites for lower esophageal/GE junction tumors included the celiac, mesenteric, portal, splenic hilar, paraortic, and gastrohepatic nodes. Motion management was individualized with either compensators or abdominal compression and daily image guidance. All patients underwent a CITV expansion of 5-7 mm to create a PTV 50.4. For those patients treated with dp-IMRT, a second PTV 56 was created by expanding the GITV by 3-5 mm. Results: We identified 70 patients (50.4 Gy: n Z 43; 56 Gy: n Z 27). There were no differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (60.7% vs. 30.2%) and lower pathologic nonresponse rate (3.6% vs. 25.6%) compared to patients treated to 50.4 Gy (p Z 0.015). There were no differences in treatment related grade 3 toxicities, hospital admissions, feeding tube or esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative complications with a higher rate of atrial fibrillation in patients treated with 56 Gy (18.5% vs. 2.4%; p Z 0.031). There were 4 (9.3%) deaths within 60 days of surgery in patients treated with 50.4 Gy compared to 2 (7.4%) deaths in patients treated with 56 Gy (p Z NS). Conclusions: Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on survival in esophageal cancer. Author Disclosure: R. Shridhar: None. M.D. Chuong: None. J. Weber: None. K. Almhanna: None. K.L. Meredith: None. A. Cruz: None. S.E. Hoffe: None.
A Phase I/II Study of Capecitabine (Cape), Oxaliplatin (Ox), Panitumumab (Pmab), and External Beam Radiation Therapy (RT) for Patients With Esophagogastric Carcinoma (EC) B. Czito, C. Willett, M. Palta, P. Kennedy-Newton, and H. Uronis; Duke University Medical Center, Durham, NC Purpose/Objective(s): EC is commonly managed with concurrent chemoradiation therapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab. Materials/Methods: Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates. Results: Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR, and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Grade 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Grade 2 (fibrosis > gross disease) in 4 (20%) and Gr 3 (gross residual > fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement). Conclusions: Concurrent chemoradiation therapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic, and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted. Author Disclosure: B. Czito: E. Research Grant; Amgen. C. Willett: None. M. Palta: None. P. Kennedy-Newton: None. H. Uronis: None.
107 Impact of Guideline Changes in the Elderly With Early Breast Cancer (BC): Practice Patterns at NCCN Institutions B. McCormick,1 R. Ottesen,2 M. Hughes,3 S. Javid,4 S. Khan,5 J. Mortimer,2 J. Niland,2 J. Weeks,3 and S. Edge6; 1Memorial SloanKettering Cancer Center, New York, NY, 2City of Hope Comprehensive Cancer Center, Duarte, CA, 3Dana-Farber Cancer Institute, Boston, MA, 4 Fred Hutchinson Cancer Research Center, Seattle, WA, 5Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 6Roswell Park Cancer Institute, Buffalo, NY Purpose/Objective(s): Radiation therapy (RT) is a critical adjunct to breast conservation surgery (BCS) because it enhances both local control and survival of BC. However, a phase III CALGB trial published in 2004 demonstrated that women age 70 or older with estrogen receptor (ER) positive, T1, cN0 cancers derive no survival advantage and only a very limited benefit in local control from radiation when treated with BCS and adjuvant tamoxifen (endocrine therapy [ET]). Treatment with BCS + ET without RT was incorporated as a Category I option in the NCCN Guidelines in 2004 for this subset of women. This study examines factors associated with adoption of this practice across the NCCN (National Comprehensive Cancer Network) cancer centers.
International Journal of Radiation Oncology Biology Physics
was seen in pre-CRT tumor maximum SUV (p Z 0.88); however, postCRT tumor maximum SUV was significantly decreased in patients taking metformin (p Z 0.02). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p Z 0.04). Metformin use was also associated with decreased in-field loco-regional failure following radiation (p Z 0.05). Conclusions: The use of metformin is associated with increased response to CRT in esophageal cancer in a dose-dependent manner and may be a sensitizer to this therapy. Author Disclosure: H.D. Skinner: None. M. McCurdy: None. A. Echeverria: None. S. Lin: None. J. Welsh: None. M. O’Reilly: None. W. Hofstetter: None. J. Ajani: None. R. Komaki: None. T. Guerrero: None.
106
104 WITHDRAWN
105 Preoperative Dose Painting IMRT Chemoradiation to 56 Gy in Esophageal Cancer Doubles Pathologic Complete Response Rate Without Increasing Toxicity R. Shridhar,1 M.D. Chuong,1 J. Weber,1 K. Almhanna,1 K.L. Meredith,1 A. Cruz,2 and S.E. Hoffe1; 1H. Lee Moffitt Cancer Center, Tampa, FL, 2 University of South Florida College of Medicine, Tampa, FL Purpose/Objective(s): To determine the pathologic complete response rate (pCR) of preoperative dose painting IMRT (dp-IMRT) in esophageal cancer. Materials/Methods: We evaluated esophageal cancer patients treated between 2006 and 2011 with preoperative IMRT chemoradiation followed by esophagectomy. All patients underwent 4D CT simulation; most underwent endoscopic fiducial marker placement above and below the tumor. Our institutional philosophy evolved from uniform delivery of 50.4 Gy in 1.8 Gy fractions to dose painting gross disease to 56 Gy in 2.0 Gy fractions while keeping the CTV dose schema at 50.4 Gy in 1.8 Gy fractions. For all patients, the GTV was modified to account for respiration to create a GITV; this was then expanded 3-4 cm craniocaudally and 3-5 mm circumferentially with modifications for respiration to create a CITV. Elective nodal sites for lower esophageal/GE junction tumors included the celiac, mesenteric, portal, splenic hilar, paraortic, and gastrohepatic nodes. Motion management was individualized with either compensators or abdominal compression and daily image guidance. All patients underwent a CITV expansion of 5-7 mm to create a PTV 50.4. For those patients treated with dp-IMRT, a second PTV 56 was created by expanding the GITV by 3-5 mm. Results: We identified 70 patients (50.4 Gy: n Z 43; 56 Gy: n Z 27). There were no differences in tumor or patient characteristics. Patients treated with 56 Gy demonstrated a higher pCR rate (60.7% vs. 30.2%) and lower pathologic nonresponse rate (3.6% vs. 25.6%) compared to patients treated to 50.4 Gy (p Z 0.015). There were no differences in treatment related grade 3 toxicities, hospital admissions, feeding tube or esophageal stent placement, or dilation. There was, however, a statistically significant increase in postoperative complications with a higher rate of atrial fibrillation in patients treated with 56 Gy (18.5% vs. 2.4%; p Z 0.031). There were 4 (9.3%) deaths within 60 days of surgery in patients treated with 50.4 Gy compared to 2 (7.4%) deaths in patients treated with 56 Gy (p Z NS). Conclusions: Dose escalation to 56 Gy with dp-IMRT is safe and results in significantly higher pathologic response rates in esophageal cancer without an increase in treatment-related toxicity. Prospective trials using dp-IMRT are needed to address the role of dose escalation on survival in esophageal cancer. Author Disclosure: R. Shridhar: None. M.D. Chuong: None. J. Weber: None. K. Almhanna: None. K.L. Meredith: None. A. Cruz: None. S.E. Hoffe: None.
A Phase I/II Study of Capecitabine (Cape), Oxaliplatin (Ox), Panitumumab (Pmab), and External Beam Radiation Therapy (RT) for Patients With Esophagogastric Carcinoma (EC) B. Czito, C. Willett, M. Palta, P. Kennedy-Newton, and H. Uronis; Duke University Medical Center, Durham, NC Purpose/Objective(s): EC is commonly managed with concurrent chemoradiation therapy, with or without surgical resection. The optimal combination and dose of agents is the subject of continued investigation. This study examines chemotherapeutic agents with known efficacy in EC in combination with the EGFR inhibitor panitumumab. Materials/Methods: Eligible pts received RT (1.8 Gy qd to 50.4 Gy) combined with concurrent chemotherapy. Dose-level (DL) 1 was cape (625 mg/m2/bid RT days), ox (40 mg/m2 weekly X 6 weeks), and pmab (3.6 mg/kg, weeks 1, 3 and 5). Chemotherapy doses were escalated barring dose limiting toxicity (DLT). The primary endpoint was defining the maximally tolerated dose with this combination. Secondary endpoints included toxicity and radiographic/pathologic response rates. Results: Twenty-nine pts were enrolled. Twenty-five had adenocarcinoma, 24 (83%) were cN+ and 9 (31%) had M1a/b disease. DLT was not encountered in DL 1. Two of 6 patients at DL 2 (cape 825 mg/m2/bid RT days, ox 50 mg/m2 weekly, pmab 4.8 mg/kg, weeks 1, 3 and 5) developed DLT (one hospitalization due to dehydration; one with drug reaction requiring hospitalization). Twenty additional pts were enrolled at DL1. Primary toxicities were EGFR-rash, esophagitis, nausea/vomiting and fatigue. On repeat endoscopy, 16 (55%) had CR, 10 (35%) PR, and 2 (7%) SD. Using PERCIST criteria, 12 (41%), 11 (38%), 2 (7%) and 3 (10%) had CR, PR, SD and PD response on restaging PET, respectively. Twenty pts underwent esophagectomy, revealing Grade 0 response (no residual disease) in 9 (45%), Gr 1 (single/microscopic cells) in 3 (15%), Grade 2 (fibrosis > gross disease) in 4 (20%) and Gr 3 (gross residual > fibrosis or no evident response) in 4 (20%). Seven pts (35%) experienced anastomotic leak (2 requiring reoperation and 3 stent placement). Conclusions: Concurrent chemoradiation therapy utilizing capecitabine, oxaliplatin, panitumumab is reasonably well-tolerated and associated with high rates of radiographic, endoscopic, and pathologic response. Postoperative anastomotic leak rates were higher than expected. Further study of this regimen in the operative and nonoperative settings is warranted. Author Disclosure: B. Czito: E. Research Grant; Amgen. C. Willett: None. M. Palta: None. P. Kennedy-Newton: None. H. Uronis: None.
107 Impact of Guideline Changes in the Elderly With Early Breast Cancer (BC): Practice Patterns at NCCN Institutions B. McCormick,1 R. Ottesen,2 M. Hughes,3 S. Javid,4 S. Khan,5 J. Mortimer,2 J. Niland,2 J. Weeks,3 and S. Edge6; 1Memorial SloanKettering Cancer Center, New York, NY, 2City of Hope Comprehensive Cancer Center, Duarte, CA, 3Dana-Farber Cancer Institute, Boston, MA, 4 Fred Hutchinson Cancer Research Center, Seattle, WA, 5Robert H. Lurie Comprehensive Cancer Center, Chicago, IL, 6Roswell Park Cancer Institute, Buffalo, NY Purpose/Objective(s): Radiation therapy (RT) is a critical adjunct to breast conservation surgery (BCS) because it enhances both local control and survival of BC. However, a phase III CALGB trial published in 2004 demonstrated that women age 70 or older with estrogen receptor (ER) positive, T1, cN0 cancers derive no survival advantage and only a very limited benefit in local control from radiation when treated with BCS and adjuvant tamoxifen (endocrine therapy [ET]). Treatment with BCS + ET without RT was incorporated as a Category I option in the NCCN Guidelines in 2004 for this subset of women. This study examines factors associated with adoption of this practice across the NCCN (National Comprehensive Cancer Network) cancer centers.