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Vertebral Bone Marrow Irradiation Contributes to Hematologic Toxicity During Chemoradiation Therapy for Esophageal Cancer
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Volume 99 Number 2S Supplement 2017 reasonable dose for them. Long-term OS can be expected once better tumor response is obtained for patients with upper EC, shorter tumor length and better tumor response to RT. These prognostic factors may improve clinicians’ abilities to predict individualized survival and to make treatment recommendations for elderly EC patients. Author Disclosure: T. Zhai: None. R. Huang: None. L. Xu: None. Y. Yu: None. L. Guo: None. J. Chen: None. Z. Zhong: None. C. Su: None. D. Li: None. C. Chen: None.
2491 Nimotuzumab Combined With Concurrent Chemoradiation Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma Y.R. Zhai,1 Z. Hui,2 X. Wang,3 J. Liang,3 W. Wang,3 Q. Feng,3 Z. Zhou,2 X. Wang,3 Z. Xiao,4 N. Bi,3 and L. Wang5; 1National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Department of Radiation Oncology, National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China, 3 Cancer Hospital and Institute, National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 4Department of Radiation Oncology, Cancer Hospital/ Institute, Chinese Academy of Medical Science, Beijing, China, 5National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China Purpose/Objective(s): Concurrent chemoradiotherapy is the standard care in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC) with unsatisfied outcomes. Epidermal growth factor receptor (EGFR) overexpression occurred in 30-90% of esophageal cancers. Nimotuzumab, an inhibitor of EGFR, was effective in treating ESCC with mild toxicities in previous studies. To investigate the feasibility and efficacy of Nimotuzumab combined with concurrent chemoradiotherapy in unresectable locally advanced ESCC, we designed this study. Materials/Methods: The enrollment criteria included pathologically or cytologically diagnosed as ESCC, with untreated stage III disease according to AJCC 6thstaging system, ECOG performance score 0-2, unresectable disease. All of the enrolled patients received thoracic radiation with dose of 50-70Gy, Nimotuzumab 200mg per week and platinum/fluorouracil based chemotherapy, concurrently. The overall survival (OS), progression free survival (PFS) and local-regional free survival (LRFS) were calculated using the Kaplan-Meier method. Toxicities were evaluated according to the NCI-CTC 3.0. Response was assessed 1 month after treatment, according to Response Evaluation Criteria in Solid Tumors 1.0. Results: From May 2011 to March 2015, 26 patients were enrolled. Twenty-three were male and 3 were female. The median age was 55.5 years. The disease was stage II, III, IV in 5, 14 and 7 patients , respectively. All patients were treated with concurrent chemoradiotherapy and Nimotuzumab. The median dose of radiotherapy was 60Gy (42-70Gy). Platinum plus paclitaxel, fluorouracil plus platinum, platinum alone and fluorouracil alone were given in 16 patients , 5 patients, 4 patients and 1 patients , respecitively. The median total dose of Nimotuzumab was 1200mg (200mg/week * 6weeks). At one month post-radiotherapy, there were 20 (76.9%) partial response, 4 (15.4%) stable disease and 2 (7.7%) progression disease. The median follow up time was 30.5 months. The median survival time was 28.7 months. Two- year and 3- year OS were 53.4% and 38.2%, LRFS were 73.3% and 62.8%, PFS were 46.2% and 33.3%. The incidence of grade 3-4 esophagitis, grade 3-4 digestive toxicities, grade 3-4 hematological toxicities, grade 3 skin dermitis and grade 2 pneumonitis were 61.5%, 7.7%, 26.9%,11.5% and 7.7%, respectively. Conclusion: Concurrent Nimotuzumab and chemoradiotherapy is effective and tolerable in locally advanced ESCC patients who are unfit for operation. Further evaluation based on larger cases is needed. Author Disclosure: Y. Zhai: None. Z. Hui: None. X. Wang: None. J. Liang: None. W. Wang: None. Q. Feng: None. Z. Zhou: None. X. Wang: None. Z. Xiao: None. N. Bi: None. L. Wang: None.
2492 Vertebral Bone Marrow Irradiation Contributes to Hematologic Toxicity During Chemoradiation Therapy for Esophageal Cancer A. Zhang,1 M.P. Deek,1 S. Kim,1 A. Grann,2 R.T. Wagman,2 U. Malhotra,1 E. Poplin,1 D. August,1 and S.K. Jabbour1; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2Robert Wood Johnson Barnabas Health, Livingston, NJ Purpose/Objective(s): Hematological toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer, with both modalities contributing to the decline in blood counts. Since leukopenia commonly precludes chemotherapy delivery, we sought to determine the dose volume histogram (DVH) constraints that correlate with decline in leukocyte counts due to comprehensive vertebra (CV) irradiation during CRT. Materials/Methods: 32 esophageal cancer patients treated with weekly neoadjuvant CRT were selected to be in the study. The typical chemotherapy regimen consisted of weekly intravenous carboplatin (area under the curve Z 2) and paclitaxel (50 mg/m2). Radiation therapy (RT) was delivered using 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT). Patients who missed CRT for reasons other than neutropenia or received colony-stimulating factors were excluded. HT was scored using the Common Terminology Criteria for Adverse Events version 4.0. CV were contoured from C2 to L2 vertebra on 4DCT simulation scans. DVH data in both percentages and cubic centimeters was collected for CV V10-V60 (CVV) in increments of 10s. CVV5 and mean vertebral dose (MVD) were included as well. A DVH parameter of Vx was defined as either the percentage or volume in cubic centimeters of organ receiving at least x Gy of radiation. Univariate linear regression was performed to identify associations between leukopenia nadirs and DVH parameters. b represents the change in blood counts in k/ mL for every 1 unit increase in DVH parameter. Receiver operator curves demonstrate cutoffs to avoid grade 3 leukopenia. Results: Of the 32 esophageal patients, 6 patients developed grade 1 leukopenia, 12 developed grade 2 leukopenia, 8 developed grade 3 leukopenia, and 3 developed grade 4 leukopenia. CVV30, CVV20, CVV10, and MVD were significantly associated with decreasing WBC when calculated either as a percentage or by volume of the organ on univariate analysis. CVV5 was significantly associated with decreasing WBC counts only when calculated as a percentage of the volume and not as volume by cubic centimers. Associations with leukopenia were not seen with higher DVH values. CVV60, CVV50, and CVV40 did not significantly influence WBC levels during CRT. Cutoffs to avoid grade 3 leukopenia were CVV20 < 44.3%, CVV10 < 54.2%, CVV20 < 225 cc, CVV10 < 260 cc, and MVD < 18.8 Gy.< table classZ”abstracttable>< tbody>< tr> CVV30 CVV20 CVV10 CVV5 MVD WBC (DVH by %) b p-value . -0.00528 0.0154 . -0.00767 0.0016 . -0.00826 0.0005 . -0.00828 0.0005 . -0.00014 0.0125 WBC (DVH by cc) . . . . . b p-value -0.00111 0.022 -0.00109 0.0269 -0.00107 0.0268 -0.000804 0.0577 -0.00014 0.0125 Conclusion: Leukopenia is associated with higher RT doses to the CVV30, CVV20, CVV10, CVV5, and MVD during CRT for esophageal cancer patients. Improved low dose radiation sparing of the CV may decrease HT. Author Disclosure: A. Zhang: None. M.P. Deek: None. S. Kim: None. A. Grann: None. R.T. Wagman: None. U. Malhotra: None. E. Poplin: None. D. August: None. S.K. Jabbour: Research Grant; Merck.
2493 Radiotherapy Alone or Concurrent Chemoradiation for Esophageal Squamous Cell Carcinoma in Elderly Patients L. Zhao,1 Y.C. Zhou,1 H. Pan,2 Y. Yin,1 S.H. Lin,3 and M. Shi1; 1 Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi ’an, China, 2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Volume 99 Number 2S Supplement 2017 reasonable dose for them. Long-term OS can be expected once better tumor response is obtained for patients with upper EC, shorter tumor length and better tumor response to RT. These prognostic factors may improve clinicians’ abilities to predict individualized survival and to make treatment recommendations for elderly EC patients. Author Disclosure: T. Zhai: None. R. Huang: None. L. Xu: None. Y. Yu: None. L. Guo: None. J. Chen: None. Z. Zhong: None. C. Su: None. D. Li: None. C. Chen: None.
2491 Nimotuzumab Combined With Concurrent Chemoradiation Therapy in Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma Y.R. Zhai,1 Z. Hui,2 X. Wang,3 J. Liang,3 W. Wang,3 Q. Feng,3 Z. Zhou,2 X. Wang,3 Z. Xiao,4 N. Bi,3 and L. Wang5; 1National Cancer Center/ Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China, 2Department of Radiation Oncology, National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China, 3 Cancer Hospital and Institute, National Cancer Center, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, 4Department of Radiation Oncology, Cancer Hospital/ Institute, Chinese Academy of Medical Science, Beijing, China, 5National Cancer Center / Cancer Institute & Hospital, Chinese Academic of Medical Sciences, Peking Union Medical College, Beijing, China Purpose/Objective(s): Concurrent chemoradiotherapy is the standard care in the treatment of patients with locally advanced esophageal squamous cell carcinoma (ESCC) with unsatisfied outcomes. Epidermal growth factor receptor (EGFR) overexpression occurred in 30-90% of esophageal cancers. Nimotuzumab, an inhibitor of EGFR, was effective in treating ESCC with mild toxicities in previous studies. To investigate the feasibility and efficacy of Nimotuzumab combined with concurrent chemoradiotherapy in unresectable locally advanced ESCC, we designed this study. Materials/Methods: The enrollment criteria included pathologically or cytologically diagnosed as ESCC, with untreated stage III disease according to AJCC 6thstaging system, ECOG performance score 0-2, unresectable disease. All of the enrolled patients received thoracic radiation with dose of 50-70Gy, Nimotuzumab 200mg per week and platinum/fluorouracil based chemotherapy, concurrently. The overall survival (OS), progression free survival (PFS) and local-regional free survival (LRFS) were calculated using the Kaplan-Meier method. Toxicities were evaluated according to the NCI-CTC 3.0. Response was assessed 1 month after treatment, according to Response Evaluation Criteria in Solid Tumors 1.0. Results: From May 2011 to March 2015, 26 patients were enrolled. Twenty-three were male and 3 were female. The median age was 55.5 years. The disease was stage II, III, IV in 5, 14 and 7 patients , respectively. All patients were treated with concurrent chemoradiotherapy and Nimotuzumab. The median dose of radiotherapy was 60Gy (42-70Gy). Platinum plus paclitaxel, fluorouracil plus platinum, platinum alone and fluorouracil alone were given in 16 patients , 5 patients, 4 patients and 1 patients , respecitively. The median total dose of Nimotuzumab was 1200mg (200mg/week * 6weeks). At one month post-radiotherapy, there were 20 (76.9%) partial response, 4 (15.4%) stable disease and 2 (7.7%) progression disease. The median follow up time was 30.5 months. The median survival time was 28.7 months. Two- year and 3- year OS were 53.4% and 38.2%, LRFS were 73.3% and 62.8%, PFS were 46.2% and 33.3%. The incidence of grade 3-4 esophagitis, grade 3-4 digestive toxicities, grade 3-4 hematological toxicities, grade 3 skin dermitis and grade 2 pneumonitis were 61.5%, 7.7%, 26.9%,11.5% and 7.7%, respectively. Conclusion: Concurrent Nimotuzumab and chemoradiotherapy is effective and tolerable in locally advanced ESCC patients who are unfit for operation. Further evaluation based on larger cases is needed. Author Disclosure: Y. Zhai: None. Z. Hui: None. X. Wang: None. J. Liang: None. W. Wang: None. Q. Feng: None. Z. Zhou: None. X. Wang: None. Z. Xiao: None. N. Bi: None. L. Wang: None.
2492 Vertebral Bone Marrow Irradiation Contributes to Hematologic Toxicity During Chemoradiation Therapy for Esophageal Cancer A. Zhang,1 M.P. Deek,1 S. Kim,1 A. Grann,2 R.T. Wagman,2 U. Malhotra,1 E. Poplin,1 D. August,1 and S.K. Jabbour1; 1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 2Robert Wood Johnson Barnabas Health, Livingston, NJ Purpose/Objective(s): Hematological toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer, with both modalities contributing to the decline in blood counts. Since leukopenia commonly precludes chemotherapy delivery, we sought to determine the dose volume histogram (DVH) constraints that correlate with decline in leukocyte counts due to comprehensive vertebra (CV) irradiation during CRT. Materials/Methods: 32 esophageal cancer patients treated with weekly neoadjuvant CRT were selected to be in the study. The typical chemotherapy regimen consisted of weekly intravenous carboplatin (area under the curve Z 2) and paclitaxel (50 mg/m2). Radiation therapy (RT) was delivered using 3-dimensional conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT). Patients who missed CRT for reasons other than neutropenia or received colony-stimulating factors were excluded. HT was scored using the Common Terminology Criteria for Adverse Events version 4.0. CV were contoured from C2 to L2 vertebra on 4DCT simulation scans. DVH data in both percentages and cubic centimeters was collected for CV V10-V60 (CVV) in increments of 10s. CVV5 and mean vertebral dose (MVD) were included as well. A DVH parameter of Vx was defined as either the percentage or volume in cubic centimeters of organ receiving at least x Gy of radiation. Univariate linear regression was performed to identify associations between leukopenia nadirs and DVH parameters. b represents the change in blood counts in k/ mL for every 1 unit increase in DVH parameter. Receiver operator curves demonstrate cutoffs to avoid grade 3 leukopenia. Results: Of the 32 esophageal patients, 6 patients developed grade 1 leukopenia, 12 developed grade 2 leukopenia, 8 developed grade 3 leukopenia, and 3 developed grade 4 leukopenia. CVV30, CVV20, CVV10, and MVD were significantly associated with decreasing WBC when calculated either as a percentage or by volume of the organ on univariate analysis. CVV5 was significantly associated with decreasing WBC counts only when calculated as a percentage of the volume and not as volume by cubic centimers. Associations with leukopenia were not seen with higher DVH values. CVV60, CVV50, and CVV40 did not significantly influence WBC levels during CRT. Cutoffs to avoid grade 3 leukopenia were CVV20 < 44.3%, CVV10 < 54.2%, CVV20 < 225 cc, CVV10 < 260 cc, and MVD < 18.8 Gy.< table classZ”abstracttable>< tbody>< tr> CVV30 CVV20 CVV10 CVV5 MVD WBC (DVH by %) b p-value . -0.00528 0.0154 . -0.00767 0.0016 . -0.00826 0.0005 . -0.00828 0.0005 . -0.00014 0.0125 WBC (DVH by cc) . . . . . b p-value -0.00111 0.022 -0.00109 0.0269 -0.00107 0.0268 -0.000804 0.0577 -0.00014 0.0125 Conclusion: Leukopenia is associated with higher RT doses to the CVV30, CVV20, CVV10, CVV5, and MVD during CRT for esophageal cancer patients. Improved low dose radiation sparing of the CV may decrease HT. Author Disclosure: A. Zhang: None. M.P. Deek: None. S. Kim: None. A. Grann: None. R.T. Wagman: None. U. Malhotra: None. E. Poplin: None. D. August: None. S.K. Jabbour: Research Grant; Merck.
2493 Radiotherapy Alone or Concurrent Chemoradiation for Esophageal Squamous Cell Carcinoma in Elderly Patients L. Zhao,1 Y.C. Zhou,1 H. Pan,2 Y. Yin,1 S.H. Lin,3 and M. Shi1; 1 Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi ’an, China, 2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 3 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX