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Lymphocyte Trends During Neoadjuvant Chemoradiation Predict Pathologic Complete Response at Time of Surgical Resection of Locally Advanced Rectal Cancers
International Journal of Radiation Oncology Biology Physics
E202 5
Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada, 6Princess Margaret Cancer Center, Toronto, ON, Canada Purpose/Objective(s): Toxicity following SBRT for liver metastases (LM) appears low but dose/volumetric correlations have not clearly been established. We describe dosimetry and hepatic toxicity for patients with LM treated with SBRT. Materials/Methods: Cumulative dose volume histograms (DVHs) and dosimetric parameters for patients with LM treated on two sequential prospective trials of 6 fraction SBRT, were correlated with hepatic toxicity defined as an increase in Child Pugh (CP) score or CTCAEv3.0 grade in ALT, AST or ALP at 1 and 3 months. Patients with local progressive disease (PD) within 3 months of SBRT were excluded due to potential confounding effect. Dose to 700ml spared liver (calculated as dose at absolute volume minus 700cc) was analyzed as previous data has shown an association with liver toxicity. Univariate and multivariate binary logistic regression was performed to identify predictors of toxicity. Results: Eighty-eight patients were identified, with 18 excluded due to PD (4) or lacking dosimetric data (14). Patient characteristics included; median age 63 (30-90) years, 40 (57%) male, 49 (70%) colorectal carcinoma primary, one (1%) underlying untreated Hepatitis B, 41 (57%) extrahepatic disease, 44 (62%) prior chemotherapy, 20 (28%) previously treated with hepatic resection (13) and/or RFA (7), 67 (96%) baseline Child-Pugh A5, median number LM 2 (1-7), median GTV volume 50 (1-722) cc, median liver - GTV volume 1564 (8823029) cc, median SBRT prescription 42 (30-60) Gy median mean liver -GTV dose 16.2 (3-22.7) Gy, median Veffliver37% (5-80%), median physical and biologically normalized NTCP 15.8% (0-69%), and 0.07% (0-18.8%), median dose for all patients to 700cc of spared liver minus GTV 10.5 (0.2 e 38.2) Gy, with 58 patients (82.8%) meeting the Colorado dose sparing guideline e equivalent dose 19.5 Gy in 6 fractions (a/b 3). Two patients’ albumin decreased (CP score increase from A5 to A6) at 1 month, reversed at 3 months. Another developed a sustained decrease in albumin at 3 months. Liver enzyme toxicity up to 3 months post SBRT (Table 1) occurred in 43 patients (61%). There were no incidences of radiation induced liver disease. One patient had grade 3 ALP toxicity at 1 month that resolved at 3 months. On univariate analysis there was a trend to significance for dose to spared 700cc of liver and enzyme toxicity (P Z 0.08). On multivariate analysis dose to spared 700cc was statistically significant (P Z 0.025) and there was a trend to significance for prior liver surgery (P Z 0.29) or BioNTCP (P Z 0.21) and toxicity. No factors correlated with worsening of CP score. Conclusion: These results suggest that dose to 700cc of spared liver may be associated with acute liver enzyme abnormality. This dosimetric parameter has potential implications for future liver SBRT planning and ongoing clinical management.
Abstract 2494; Table 1. Liver enzyme toxicity
AST/ALT
ALP
Grade
Baseline Number of events
1 month Number of events
3 months Number of events
0 1 2 3 0 1 2 3
98 39 2 1 51 16 2 1
92 44 5 0 46 20 3 1
67 30 5 0 28 20 3 0
Author Disclosure: A.S. Barry: None. A.J. McPartlin: None. P.E. Lindsay: None. J. Brierley: None. J.J. Kim: None. J.G. Ringash: None. R. Wong: None. R. Dinniwell: None. B.J. Cummings: None. A.M. Brade: None. T. Craig: None. L.A. Dawson: Raysearch licensing agreement with institution; Raysearch.
2495 Lymphocyte Trends During Neoadjuvant Chemoradiation Predict Pathologic Complete Response at Time of Surgical Resection of Locally Advanced Rectal Cancers L. Dover, C. Dulaney, A. McDonald, and R. Jacob; University of Alabama at Birmingham, Birmingham, AL Purpose/Objective(s): While achieving complete pathologic tumor response (ypCR) following neoadjuvant chemoradiation (NCRT) is achievable in up to 25% of patients with locally-advanced rectal cancer, preoperative factors predicting which patients will achieve ypCR at time of definitive surgery are still poorly-elucidated. A number of studies have reported a correlation between peripheral lymphocyte counts and responses to various oncologic therapies and overall survival outcomes in patients with an array of malignancies including rectal cancer. The aim of this study is to determine whether lymphocyte trends at four weeks after initiation of NCRT are associated with complete treatment response in locally-advanced rectal cancers. Materials/Methods: Patient, tumor, and treatment data was abstracted on patients with T2 N1-2 and T3-4 N0-2 rectal cancers treated with NCRT and subsequent surgical resection at our institution from January 2009 through December 2013, allowing for two-year follow-up. Neoadjuvant chemoradiation for all patients consisted of completion of 4500 cGy to entire pelvis with boost to 5040 cGy to gross disease with concurrent 5-FU or capecitabine chemotherapy. Pathologic evaluation of final surgical specimens following NCRT was recorded as follows: complete response (ypCR), partial response (ypPR) or stable/progressive disease. Univariate analysis was performed to determine whether relative (%) lymphocyte counts at four weeks after initiation of NCRT (4wk RLC) and/or the ratio of 4wk total lymphocyte count (4wk TLC) to pre-treatment baseline total lymphocyte count (bTLC) were associated with the rates of ypCR. Frequencies were compared using the chisquare test. Results: Thirty-one patients were identified who underwent NCRT followed by surgical resection for locally-advanced rectal cancer during the specified time period. Of the 31 post-NCRT surgical specimens reviewed, ypCR was observed in 10 patients (32%) and ypPR was found in 18 patients (58%). When analyzed as a continuous variable, greater 4wk RLC was predictive of ypCR (OR Z 1.27, P Z 0.065). Area under the ROC curve as a predictor for ypCR for 4wk RLC was 0.71 and for 4wk TLC: bTLC ratio was 0.69. Of patients with 4wk RLC 9, 3/19 (16%) achieved ypCR compared to 7/12 (58%) with RLC > 9 (P Z 0.021). Of patients with 4wk TLC: bTLC 0.43, 3/17 (18%) achieved ypCR compared to 7/14 (50%) with 4wk TLC: bTLC > 0.43 (P Z 0.055). Conclusion: When assessing lymphocyte trends at four weeks after initiation of NCRT, both RLC as well as percent decrease of TLC from baseline were associated with tumor ypCR at time of definitive surgery in patients with locally-advanced rectal cancers. This study underlines the importance of understanding the role of the host immune response in rectal tumor control. Further work characterizing which tumors have the highest response to immune modulation may guide patient selection in future studies investigating immune checkpoint inhibitors. Author Disclosure: L. Dover: None. C. Dulaney: None. A. McDonald: None. R. Jacob: None.
2496 Effectiveness of Radiation Therapy for Low- to Intermediate-Grade Neuroendocrine Tumors J.N. Carter,1 S. Aggarwal,2 K. Radish,3 J.R. Allen,3 A.C. Koong,1 D.T. Chang,4 B.W. Loo, Jr,2 M. Diehn,2 P.L. Kunz,3 and M.F. Gensheimer4; 1Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, 2Stanford University Department of Radiation Oncology, Stanford, CA, 3Stanford University, Stanford, CA, 4 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA
E202 5
Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada, 6Princess Margaret Cancer Center, Toronto, ON, Canada Purpose/Objective(s): Toxicity following SBRT for liver metastases (LM) appears low but dose/volumetric correlations have not clearly been established. We describe dosimetry and hepatic toxicity for patients with LM treated with SBRT. Materials/Methods: Cumulative dose volume histograms (DVHs) and dosimetric parameters for patients with LM treated on two sequential prospective trials of 6 fraction SBRT, were correlated with hepatic toxicity defined as an increase in Child Pugh (CP) score or CTCAEv3.0 grade in ALT, AST or ALP at 1 and 3 months. Patients with local progressive disease (PD) within 3 months of SBRT were excluded due to potential confounding effect. Dose to 700ml spared liver (calculated as dose at absolute volume minus 700cc) was analyzed as previous data has shown an association with liver toxicity. Univariate and multivariate binary logistic regression was performed to identify predictors of toxicity. Results: Eighty-eight patients were identified, with 18 excluded due to PD (4) or lacking dosimetric data (14). Patient characteristics included; median age 63 (30-90) years, 40 (57%) male, 49 (70%) colorectal carcinoma primary, one (1%) underlying untreated Hepatitis B, 41 (57%) extrahepatic disease, 44 (62%) prior chemotherapy, 20 (28%) previously treated with hepatic resection (13) and/or RFA (7), 67 (96%) baseline Child-Pugh A5, median number LM 2 (1-7), median GTV volume 50 (1-722) cc, median liver - GTV volume 1564 (8823029) cc, median SBRT prescription 42 (30-60) Gy median mean liver -GTV dose 16.2 (3-22.7) Gy, median Veffliver37% (5-80%), median physical and biologically normalized NTCP 15.8% (0-69%), and 0.07% (0-18.8%), median dose for all patients to 700cc of spared liver minus GTV 10.5 (0.2 e 38.2) Gy, with 58 patients (82.8%) meeting the Colorado dose sparing guideline e equivalent dose 19.5 Gy in 6 fractions (a/b 3). Two patients’ albumin decreased (CP score increase from A5 to A6) at 1 month, reversed at 3 months. Another developed a sustained decrease in albumin at 3 months. Liver enzyme toxicity up to 3 months post SBRT (Table 1) occurred in 43 patients (61%). There were no incidences of radiation induced liver disease. One patient had grade 3 ALP toxicity at 1 month that resolved at 3 months. On univariate analysis there was a trend to significance for dose to spared 700cc of liver and enzyme toxicity (P Z 0.08). On multivariate analysis dose to spared 700cc was statistically significant (P Z 0.025) and there was a trend to significance for prior liver surgery (P Z 0.29) or BioNTCP (P Z 0.21) and toxicity. No factors correlated with worsening of CP score. Conclusion: These results suggest that dose to 700cc of spared liver may be associated with acute liver enzyme abnormality. This dosimetric parameter has potential implications for future liver SBRT planning and ongoing clinical management.
Abstract 2494; Table 1. Liver enzyme toxicity
AST/ALT
ALP
Grade
Baseline Number of events
1 month Number of events
3 months Number of events
0 1 2 3 0 1 2 3
98 39 2 1 51 16 2 1
92 44 5 0 46 20 3 1
67 30 5 0 28 20 3 0
Author Disclosure: A.S. Barry: None. A.J. McPartlin: None. P.E. Lindsay: None. J. Brierley: None. J.J. Kim: None. J.G. Ringash: None. R. Wong: None. R. Dinniwell: None. B.J. Cummings: None. A.M. Brade: None. T. Craig: None. L.A. Dawson: Raysearch licensing agreement with institution; Raysearch.
2495 Lymphocyte Trends During Neoadjuvant Chemoradiation Predict Pathologic Complete Response at Time of Surgical Resection of Locally Advanced Rectal Cancers L. Dover, C. Dulaney, A. McDonald, and R. Jacob; University of Alabama at Birmingham, Birmingham, AL Purpose/Objective(s): While achieving complete pathologic tumor response (ypCR) following neoadjuvant chemoradiation (NCRT) is achievable in up to 25% of patients with locally-advanced rectal cancer, preoperative factors predicting which patients will achieve ypCR at time of definitive surgery are still poorly-elucidated. A number of studies have reported a correlation between peripheral lymphocyte counts and responses to various oncologic therapies and overall survival outcomes in patients with an array of malignancies including rectal cancer. The aim of this study is to determine whether lymphocyte trends at four weeks after initiation of NCRT are associated with complete treatment response in locally-advanced rectal cancers. Materials/Methods: Patient, tumor, and treatment data was abstracted on patients with T2 N1-2 and T3-4 N0-2 rectal cancers treated with NCRT and subsequent surgical resection at our institution from January 2009 through December 2013, allowing for two-year follow-up. Neoadjuvant chemoradiation for all patients consisted of completion of 4500 cGy to entire pelvis with boost to 5040 cGy to gross disease with concurrent 5-FU or capecitabine chemotherapy. Pathologic evaluation of final surgical specimens following NCRT was recorded as follows: complete response (ypCR), partial response (ypPR) or stable/progressive disease. Univariate analysis was performed to determine whether relative (%) lymphocyte counts at four weeks after initiation of NCRT (4wk RLC) and/or the ratio of 4wk total lymphocyte count (4wk TLC) to pre-treatment baseline total lymphocyte count (bTLC) were associated with the rates of ypCR. Frequencies were compared using the chisquare test. Results: Thirty-one patients were identified who underwent NCRT followed by surgical resection for locally-advanced rectal cancer during the specified time period. Of the 31 post-NCRT surgical specimens reviewed, ypCR was observed in 10 patients (32%) and ypPR was found in 18 patients (58%). When analyzed as a continuous variable, greater 4wk RLC was predictive of ypCR (OR Z 1.27, P Z 0.065). Area under the ROC curve as a predictor for ypCR for 4wk RLC was 0.71 and for 4wk TLC: bTLC ratio was 0.69. Of patients with 4wk RLC 9, 3/19 (16%) achieved ypCR compared to 7/12 (58%) with RLC > 9 (P Z 0.021). Of patients with 4wk TLC: bTLC 0.43, 3/17 (18%) achieved ypCR compared to 7/14 (50%) with 4wk TLC: bTLC > 0.43 (P Z 0.055). Conclusion: When assessing lymphocyte trends at four weeks after initiation of NCRT, both RLC as well as percent decrease of TLC from baseline were associated with tumor ypCR at time of definitive surgery in patients with locally-advanced rectal cancers. This study underlines the importance of understanding the role of the host immune response in rectal tumor control. Further work characterizing which tumors have the highest response to immune modulation may guide patient selection in future studies investigating immune checkpoint inhibitors. Author Disclosure: L. Dover: None. C. Dulaney: None. A. McDonald: None. R. Jacob: None.
2496 Effectiveness of Radiation Therapy for Low- to Intermediate-Grade Neuroendocrine Tumors J.N. Carter,1 S. Aggarwal,2 K. Radish,3 J.R. Allen,3 A.C. Koong,1 D.T. Chang,4 B.W. Loo, Jr,2 M. Diehn,2 P.L. Kunz,3 and M.F. Gensheimer4; 1Department of Radiation Oncology, Stanford Cancer Institute, Stanford, CA, 2Stanford University Department of Radiation Oncology, Stanford, CA, 3Stanford University, Stanford, CA, 4 Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA