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Evaluating the Impact of Histologic Grade on Survival in Gallbladder Cancer
E170
International Journal of Radiation Oncology Biology Physics
year of diagnosis, and absense of LVI predicted for pCR. Using PSM in the subset of patients with adenocarcinoma, the rate of pCR was higher with 50.4 Gy vs. 41.4 Gy (HR 2.1 [95% CI 1.2 e 3.7], pZ0.01).There was no difference in pCR by dose for SCC. No differences in OS were identified between dose cohorts. The median OS increased to 63 mo with pCR vs 33 mo without (p<0.01). Conclusion: Utilization of 41.4 Gy for neoadjuvant CRT increased following publication of the CROSS trial, although rates remain low. 50.4 Gy was associated with higher pCR rate for esophageal adenocarcinoma compared to 41.4 Gy. Prospective studies will be needed to elucidate the optimal radiation dose in this setting. Author Disclosure: N.A. Madden: None. K.A. Higgins: None. D. Zaenger: None. K. Cardona: None. J.C. Landry: None. M. Behera: None. Y. Liu: None. P.R. Patel: None.
disease at any stage, and this trend is more pronounced in men. These changes in anal carcinoma patterns may reflect improved HIV management, increased use of barrier protection for men, and efficacious screening and management of anal squamous intraepithelial lesions. Author Disclosure: A.R. Mahal: None. K.L. Johung: Partner; Gastroenterology Center of Connecticut. B.A. Mahal: None. P.L. Nguyen: Consultant; GI Windows, Infinity Pharmaceuticals, Nanobiotix. Advisory Board; Dendreon, Ferring, Genome DX, Medivation. ; Genitourinary Cancers Symposium. J.B. Yu: None.
2409 An Update to Changing Patterns of Anal Carcinoma in the United States A.R. Mahal,1 K.L. Johung,2 B.A. Mahal,3 P.L. Nguyen,4 and J.B. Yu5; 1 Yale School of Medicine, New Haven, CT, 2Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 3Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, 4 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 5 Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT Purpose/Objective(s): Approximately 8,200 new cases (2,950 males; 5,250 females) of anal carcinoma will be diagnosed in the United States in 2017. Specifically, anal squamous cell carcinoma accounts for about 70% of all anal cancers in the US and is associated with human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections. As cancer prevention and treatments have evolved over time, medical management of HIV has improved, and sexual behaviors have changed, anal carcinoma incidence rates may have also changed. Materials/Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify and determine incidence rates for 6,607 men and 5,729 women diagnosed with anal cancer from 1973-2013. Carcinoma in situ (CIS) and invasive disease (SCC), as defined by the SEER historical stage category, were analyzed separately. Joinpoint regression models identified time points at which histology-specific incidence trends changed. Age-adjusted incidence rate changes over time are expressed as annual percent changes (APC), which represent the logtransformed slopes across time. Joinpoint regression was performed using the Joinpoint software program (v4.3.1.0) and all other analyses were performed using SEER*Stat software (v8.3.2) and Stata/SE (v13.1). Results: Joinpoint analyses identified 1994 and 2011 as the inflection points at which combined anal CIS and SCC average annual incidence rates shifted most markedly among 12,336 patients from 1973-2013. The slope of incidence rates recently decreased (2011, 95% CI 2008-2011; APC -4.92, 95% CI -16.8 to 8.6). Separate joinpoint analyses were conducted for noninvasive disease (CIS) and invasive cancer (SCC). Although men and women were more likely to present with CIS (risk ratio [RR] 1.51, 95% CI 1.45-1.59) after 2011, the slope of incidence rates for CIS have statistically decreased (2010, 95% CI 2008-2011; APC -6.96, 95% CI -13.3 to -0.2), especially for men (2010, 95% CI 2007-2011, APC -9.25, 95% CI -16.0 to -1.9). Moreover, both men and women were less likely to present with localized (RR 0.81, 95% CI 0.76-0.87), regional (RR 0.69, 95% CI 0.63-0.76), and distant SCC (RR 0.89, 95% CI 0.75-1.06). During 2011-2013, men were more likely to present with CIS (RR 2.58, 95% CI 2.34-2.86) but less likely to present with localized (RR 0.46, 95% CI 0.41 0.53), regional (RR 0.41, 95% CI 0.34 - 0.49), and distant SCC (RR 0.37, 95% CI 0.26 - 0.51) compared to women. The later time period also included younger age at diagnosis. Conclusion: Anal cancer incidence rates have decreased since 2011. Moreover, patients are more likely to present with CIS than invasive
2410 Evaluating the Impact of Histologic Grade on Survival in Gallbladder Cancer J.A. Marascio,1 A.K. Misiura,2 N.A. Madden,3 D. Zaenger,4 and B.M. Rabatic5; 1Thomas Jefferson University, Philadelphia, PA, 2 Hahnemann University Hospital, Philadelphia, PA, 3Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 4Emory University, Atlanta, GA, 5University of North Carolina, Chapel Hill, NC Purpose/Objective(s): Gallbladder cancer is a rare aggressive malignancy for which adjuvant treatment options are not well studied. Recommendations are largely based on retrospective and often single institution studies. Current recommendations call for consideration of adjuvant treatments in the form of chemotherapy or chemotherapy and radiation in those with T2+ or node positive disease. Histologic grade has an important correlation with outcomes in other more well studied tumors. The purpose of this study was to evaluate the impact of histologic grade on cause specific survival (CSS) in gallbladder cancer. Materials/Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients with gallbladder cancer who underwent cholecystectomy and thus pathologic evaluation. Patients diagnosed between 2004-2013 were included. Patients with metastatic disease were excluded. Histologic grade was then formed into 2 groups; Low grade (grade I and II) and high grade (grade III and IV). CSS was then calculated for grade and compared across T and N staging. Results: 3,344 patients who met the above inclusion criteria were identified: 1,237 high grade and 2,107 low grade. The median age for both high and low grade cohorts was 71 years of age. Similarly, 71% were female in each group. T staging for high grade patients was 9.7%, 38.3%, 48.3% and 3.7% for T1 through T4 respectively. 65.6% were N0 at presentation while 34.4% were node positive. T staging for low grade patients was 24.5%, 46.6%, 27%, and 1.9% for T1 through T4 respectively. 80% of patients were N0 at presentation, while 20% were node positive. 3 year CSS was 27.4% (95% CI 24.5 e 30.4%) for high grade tumors and 51.9% (95% CI 49.3 e 54.4%) for low grade tumors. When evaluating only N0 patients this difference remained statistically significant across T1, T2, and T3 patients (calculated for 95% CI) with T4 showing a trend, but not reaching significance. 3 year CSS for high versus low grade tumors according to T stage was as follows: T1N0 - 42.5% (31.9 e 52.8) vs 72.5% (67.4 e 77), T2N0 - 43.6% (36.7 e 50.2) vs 64.5% (60.2 e 68.4), and T3N0 - 16.2% (12 e 20.9) vs 28% (22.6 -33.7). Conclusion: These findings demonstrate a significant discrepancy in CSS in low grade versus high grade gallbladder malignancy. In even the earliest stage patients (T1N0) the absolute difference in 3 year CSS is 30% when comparing high and low grade tumors. While the optimal adjuvant regimen is not well studied, patients with high grade disease represent a very high risk group that stand to benefit from treatment intensification. While prospective data is optimal, we feel our findings indicate that histologic grade should factor strongly into decision making regarding adjuvant therapy. In addition to including more advanced stages, future studies may consider including early stage patients with additional risk factors including high histologic grade when investigating adjuvant therapies. Author Disclosure: J.A. Marascio: None. A.K. Misiura: None. N.A. Madden: None. D. Zaenger: None. B.M. Rabatic: None.
International Journal of Radiation Oncology Biology Physics
year of diagnosis, and absense of LVI predicted for pCR. Using PSM in the subset of patients with adenocarcinoma, the rate of pCR was higher with 50.4 Gy vs. 41.4 Gy (HR 2.1 [95% CI 1.2 e 3.7], pZ0.01).There was no difference in pCR by dose for SCC. No differences in OS were identified between dose cohorts. The median OS increased to 63 mo with pCR vs 33 mo without (p<0.01). Conclusion: Utilization of 41.4 Gy for neoadjuvant CRT increased following publication of the CROSS trial, although rates remain low. 50.4 Gy was associated with higher pCR rate for esophageal adenocarcinoma compared to 41.4 Gy. Prospective studies will be needed to elucidate the optimal radiation dose in this setting. Author Disclosure: N.A. Madden: None. K.A. Higgins: None. D. Zaenger: None. K. Cardona: None. J.C. Landry: None. M. Behera: None. Y. Liu: None. P.R. Patel: None.
disease at any stage, and this trend is more pronounced in men. These changes in anal carcinoma patterns may reflect improved HIV management, increased use of barrier protection for men, and efficacious screening and management of anal squamous intraepithelial lesions. Author Disclosure: A.R. Mahal: None. K.L. Johung: Partner; Gastroenterology Center of Connecticut. B.A. Mahal: None. P.L. Nguyen: Consultant; GI Windows, Infinity Pharmaceuticals, Nanobiotix. Advisory Board; Dendreon, Ferring, Genome DX, Medivation. ; Genitourinary Cancers Symposium. J.B. Yu: None.
2409 An Update to Changing Patterns of Anal Carcinoma in the United States A.R. Mahal,1 K.L. Johung,2 B.A. Mahal,3 P.L. Nguyen,4 and J.B. Yu5; 1 Yale School of Medicine, New Haven, CT, 2Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 3Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, 4 Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 5 Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, CT Purpose/Objective(s): Approximately 8,200 new cases (2,950 males; 5,250 females) of anal carcinoma will be diagnosed in the United States in 2017. Specifically, anal squamous cell carcinoma accounts for about 70% of all anal cancers in the US and is associated with human papillomavirus (HPV) and human immunodeficiency virus (HIV) infections. As cancer prevention and treatments have evolved over time, medical management of HIV has improved, and sexual behaviors have changed, anal carcinoma incidence rates may have also changed. Materials/Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify and determine incidence rates for 6,607 men and 5,729 women diagnosed with anal cancer from 1973-2013. Carcinoma in situ (CIS) and invasive disease (SCC), as defined by the SEER historical stage category, were analyzed separately. Joinpoint regression models identified time points at which histology-specific incidence trends changed. Age-adjusted incidence rate changes over time are expressed as annual percent changes (APC), which represent the logtransformed slopes across time. Joinpoint regression was performed using the Joinpoint software program (v4.3.1.0) and all other analyses were performed using SEER*Stat software (v8.3.2) and Stata/SE (v13.1). Results: Joinpoint analyses identified 1994 and 2011 as the inflection points at which combined anal CIS and SCC average annual incidence rates shifted most markedly among 12,336 patients from 1973-2013. The slope of incidence rates recently decreased (2011, 95% CI 2008-2011; APC -4.92, 95% CI -16.8 to 8.6). Separate joinpoint analyses were conducted for noninvasive disease (CIS) and invasive cancer (SCC). Although men and women were more likely to present with CIS (risk ratio [RR] 1.51, 95% CI 1.45-1.59) after 2011, the slope of incidence rates for CIS have statistically decreased (2010, 95% CI 2008-2011; APC -6.96, 95% CI -13.3 to -0.2), especially for men (2010, 95% CI 2007-2011, APC -9.25, 95% CI -16.0 to -1.9). Moreover, both men and women were less likely to present with localized (RR 0.81, 95% CI 0.76-0.87), regional (RR 0.69, 95% CI 0.63-0.76), and distant SCC (RR 0.89, 95% CI 0.75-1.06). During 2011-2013, men were more likely to present with CIS (RR 2.58, 95% CI 2.34-2.86) but less likely to present with localized (RR 0.46, 95% CI 0.41 0.53), regional (RR 0.41, 95% CI 0.34 - 0.49), and distant SCC (RR 0.37, 95% CI 0.26 - 0.51) compared to women. The later time period also included younger age at diagnosis. Conclusion: Anal cancer incidence rates have decreased since 2011. Moreover, patients are more likely to present with CIS than invasive
2410 Evaluating the Impact of Histologic Grade on Survival in Gallbladder Cancer J.A. Marascio,1 A.K. Misiura,2 N.A. Madden,3 D. Zaenger,4 and B.M. Rabatic5; 1Thomas Jefferson University, Philadelphia, PA, 2 Hahnemann University Hospital, Philadelphia, PA, 3Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 4Emory University, Atlanta, GA, 5University of North Carolina, Chapel Hill, NC Purpose/Objective(s): Gallbladder cancer is a rare aggressive malignancy for which adjuvant treatment options are not well studied. Recommendations are largely based on retrospective and often single institution studies. Current recommendations call for consideration of adjuvant treatments in the form of chemotherapy or chemotherapy and radiation in those with T2+ or node positive disease. Histologic grade has an important correlation with outcomes in other more well studied tumors. The purpose of this study was to evaluate the impact of histologic grade on cause specific survival (CSS) in gallbladder cancer. Materials/Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients with gallbladder cancer who underwent cholecystectomy and thus pathologic evaluation. Patients diagnosed between 2004-2013 were included. Patients with metastatic disease were excluded. Histologic grade was then formed into 2 groups; Low grade (grade I and II) and high grade (grade III and IV). CSS was then calculated for grade and compared across T and N staging. Results: 3,344 patients who met the above inclusion criteria were identified: 1,237 high grade and 2,107 low grade. The median age for both high and low grade cohorts was 71 years of age. Similarly, 71% were female in each group. T staging for high grade patients was 9.7%, 38.3%, 48.3% and 3.7% for T1 through T4 respectively. 65.6% were N0 at presentation while 34.4% were node positive. T staging for low grade patients was 24.5%, 46.6%, 27%, and 1.9% for T1 through T4 respectively. 80% of patients were N0 at presentation, while 20% were node positive. 3 year CSS was 27.4% (95% CI 24.5 e 30.4%) for high grade tumors and 51.9% (95% CI 49.3 e 54.4%) for low grade tumors. When evaluating only N0 patients this difference remained statistically significant across T1, T2, and T3 patients (calculated for 95% CI) with T4 showing a trend, but not reaching significance. 3 year CSS for high versus low grade tumors according to T stage was as follows: T1N0 - 42.5% (31.9 e 52.8) vs 72.5% (67.4 e 77), T2N0 - 43.6% (36.7 e 50.2) vs 64.5% (60.2 e 68.4), and T3N0 - 16.2% (12 e 20.9) vs 28% (22.6 -33.7). Conclusion: These findings demonstrate a significant discrepancy in CSS in low grade versus high grade gallbladder malignancy. In even the earliest stage patients (T1N0) the absolute difference in 3 year CSS is 30% when comparing high and low grade tumors. While the optimal adjuvant regimen is not well studied, patients with high grade disease represent a very high risk group that stand to benefit from treatment intensification. While prospective data is optimal, we feel our findings indicate that histologic grade should factor strongly into decision making regarding adjuvant therapy. In addition to including more advanced stages, future studies may consider including early stage patients with additional risk factors including high histologic grade when investigating adjuvant therapies. Author Disclosure: J.A. Marascio: None. A.K. Misiura: None. N.A. Madden: None. D. Zaenger: None. B.M. Rabatic: None.