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Phase 2 Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma
Oral Scientific Sessions S139
Volume 99 Number 2S Supplement 2017 MA, United States, 3Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, 5Beth Israel Deaconess Medical Center, Boston, MA, United States, 6Harvard Medical School, Boston, MA, 7Brigham and Women’s Hospital, Boston, MA Purpose/Objective(s): Prior studies have shown a significantly reduced second-cancer risk in Hodgkin lymphoma (HL) survivors treated with more limited-field radiation therapy (RT), although the impact of RT field size reduction on long-term overall survival (OS) has been unclear. The purpose of this study is to analyze long-term OS by field size. Materials/Methods: An institutional review board-approved retrospective study was conducted using a multi-institutional database of stage I and II HL patients treated 1967-2007 with RT with or without chemotherapy. Statistical analysis was conducted using SAS 9.3 (SAS Institute, Inc., Cary, NC) and Stata 14 (StataCorp LP, College Station, TX). Covariates included age, gender, year of treatment, histology, number of sites, B symptoms, favorable versus unfavorable prognostic group, chemotherapy regimen, RT field, and mediastinal RT dose. The Kaplan-Meier method was used for estimates of OS and the logrank test was used to test for significance of univariate differences. A Cox proportional hazards model was constructed based on an established method to evaluate for factors associated with all-cause mortality. Results: A total of 1,541 clinical stage I and II HL patients were included. The overall median follow-up time was 15.2 years, with 35% of patients having >20 years of follow-up. The 10-, 15- and 20-year OS rates were 89%, 83%, and 76%, respectively. There was an increasing percentage of patients treated with involved-field (IF) RT in more recent year-cohorts of treatment: 1967-1983 (2%), 1983-1993 (3%), and 19942007 (42.2%). On univariate analysis, younger age at diagnosis (P<0.01), favorable-prognosis disease (P<0.01), absence of B symptoms (P Z 0.04), classical or lymphocyte predominant histology (P<0.01) and more recent treatment era (P<0.01) were associated with longer OS. For the regression model (Table 1), follow-up time was restricted to the first 20 years of follow-up to ensure parity between treatment-era cohorts. Although correlated with RT field size, chemotherapy regimen fell out of the model due to lack of significance. After adjusting for covariates, IFRT, as compared to extended-field (EF) RT, was associated with significantly lower all-cause mortality, with a hazard ratio of 0.59 (P Z 0.038). Conclusion: Treatment with IFRT in early-stage Hodgkin lymphoma was associated with a 41% reduction in the risk of death compared to those treated with EFRT. These results support current efforts to reduce RT volume to involved sites and potential further volume reduction in selected patients. Abstract 297; Table 1
Hazard Ratios (HR) for All-Cause Mortality
HR Age at diagnosis
B symptoms Number of sites of disease Radiation Field
<21 years 21-30 31-40 > 40 Absent Present 3
ref. 1.22 1.54 6.21 ref. 1.29 ref.
4 EFRT IFRT
1.38 ref. 0.59
95% Confidence Interval
P value
0.84 1.02 4.40
1.78 2.32 8.78
0.296 0.041 <0.001
0.98
1.71
0.072
1.01
1.87
0.041
0.36
0.97
0.038
Author Disclosure: C. Patel: Research Grant; ASTRO. E. Michaelson: None. Y. Chen: None. B.J. Silver: None. K.J. Marcus: Member of Pediatric Oncology Editorial Board of NCI’s PDQ; PDQ. M. Stevenson: None. P.M. Mauch: Honoraria; UpToDate. A.K. Ng: None.
298 Phase 2 Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma C.R. Kelsey,1 A. Beaven,2 L. Diehl,3 G. Broadwater,4 and L.R. Prosnitz5; 1 Department of Radiation Oncology, Duke University, Durham, NC, 2duke University Medical Center, Durham, NC, 3Duke University Medical Center, Durham, NC, 4Duke University Medical Center, Durham, NC, 5 Duke University Medical Center, Durham, NC, United States Purpose/Objective(s): Combined modality therapy, consisting of chemotherapy (ChT) followed by radiation therapy (RT), is an established treatment paradigm for diffuse large B-cell lymphoma (DLBCL). A British National Lymphoma Investigation randomized trial demonstrated no difference in clinical outcomes, including local control, between 30 Gy and 40-45 Gy. Few patients in this study received rituximab or had PET-CT imaging to assessment ChT response. The hypothesis of this phase II study was that more effective systemic therapy (incorporation of rituximab) and optimal post-ChT response assessment (PET-CT), will allow the RT dose to be reduced from 30 Gy to 20 Gy while maintaining high rates of local control. Materials/Methods: Eligibility for this institutional review boardapproved, phase II prospective trial required histological documentation of DLBCL, receipt of 4 cycles of a rituximab/anthracycline-containing combination ChT regimen, and a negative post-chemotherapy PET-CT. Deauville criteria were adopted in 2013 with a negative scan defined as scores 1-3 (prior patients were scored retrospectively). Primary CNS lymphoma was excluded. Patients with stage I/II disease were treated comprehensively to all sites of original involvement; treatment fields for those with stage III/IV disease were individualized. RT field design followed principles of involved-site radiation therapy (ISRT). RT dose was 19.8-20 Gy in 1.8-2 Gy fractions. Primary endpoint: 5-year local recurrence-free survival. Secondary endpoints: 5-year progression-free survival (PFS) and overall survival (OS). PFS defined as time from initiation of RT to progression due to lymphoma or death, whichever occurred first and censored at last follow-up date. Kaplan Meier estimates were used to estimate PFS and OS. Results: From 2010-2015, 62 patients were enrolled (34 women, 28 men; median age: 58 years [range, 24-86 years]). Stage distribution: I (24, 39%), II (25, 40%), III (4, 6%), IV (9, 15%). Median largest tumor mass at diagnosis: 5.7 cm (range, 1-20). Bulky disease (defined as 7.5 cm or 10 cm) present in 23 (40%) and 16 (28%) of patients, respectively. ChT: RCHOP in 58 (94%) and R-EPOCH in 4 (6%). Number of ChT cycles: 4 (n Z 25, 40%); 5 (n Z 2, 3%); and 6 (n Z 35, 57%). Post-ChT Deauville scores: 1 (23, 37%), 2 (23, 37%), 3 (15, 24%), and 4 (1, 2%). Comprehensive RT administered to 4/4 patients with stage III and 6/9 patients with stage IV disease- 3 patient with stage IV disease received RT to only select sites. With a median follow-up of 34 months (range, 1-73), there were no local failures with LRFS of 100%. Systemic lymphoma progression developed in 4 patients with stage I/II disease and 1 with stage IV disease. There were 3 deaths (DLBCL, glioblastoma, unknown). PFS at 3 and 5 years: 92% (95% CI: 86-100%) and 78% (95% CI: 63-97%). OS at 3 and 5 years: 100% and 91% (95% CI: 79-100%). Conclusion: With more effective systemic therapy (R-CHOP) and more refined ChT response assessment (PET-CT), the dose of RT in combined modality treatment programs may be able to be further reduced to 20 Gy. Author Disclosure: C.R. Kelsey: None. A. Beaven: None. L. Diehl: None. G. Broadwater: None. L.R. Prosnitz: None.
299 Cardiac Disease and Lifestyle Risk Factors Following Hodgkin Lymphoma: An EORTC Lymphoma Group and GELA Follow-Up Study M.V. Maraldo,1 F. Giusti,2 M. van der Kaaij,3 M. Henry-Amar,4 B. Aleman,5 J. Raemaekers,6 P.J. Meijnders,7 E.C. Moser,8 H. KluinNelemans,9 M. Spina,10 C. Ferme,11 C. Fortpied,2 and L. Specht1; 1 Rigshospitalet, Copenhagen, Denmark, 2EORTC Headquarters, Brussels,
Volume 99 Number 2S Supplement 2017 MA, United States, 3Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 4Department of Radiation Oncology, Brigham and Women’s Hospital, Boston, MA, 5Beth Israel Deaconess Medical Center, Boston, MA, United States, 6Harvard Medical School, Boston, MA, 7Brigham and Women’s Hospital, Boston, MA Purpose/Objective(s): Prior studies have shown a significantly reduced second-cancer risk in Hodgkin lymphoma (HL) survivors treated with more limited-field radiation therapy (RT), although the impact of RT field size reduction on long-term overall survival (OS) has been unclear. The purpose of this study is to analyze long-term OS by field size. Materials/Methods: An institutional review board-approved retrospective study was conducted using a multi-institutional database of stage I and II HL patients treated 1967-2007 with RT with or without chemotherapy. Statistical analysis was conducted using SAS 9.3 (SAS Institute, Inc., Cary, NC) and Stata 14 (StataCorp LP, College Station, TX). Covariates included age, gender, year of treatment, histology, number of sites, B symptoms, favorable versus unfavorable prognostic group, chemotherapy regimen, RT field, and mediastinal RT dose. The Kaplan-Meier method was used for estimates of OS and the logrank test was used to test for significance of univariate differences. A Cox proportional hazards model was constructed based on an established method to evaluate for factors associated with all-cause mortality. Results: A total of 1,541 clinical stage I and II HL patients were included. The overall median follow-up time was 15.2 years, with 35% of patients having >20 years of follow-up. The 10-, 15- and 20-year OS rates were 89%, 83%, and 76%, respectively. There was an increasing percentage of patients treated with involved-field (IF) RT in more recent year-cohorts of treatment: 1967-1983 (2%), 1983-1993 (3%), and 19942007 (42.2%). On univariate analysis, younger age at diagnosis (P<0.01), favorable-prognosis disease (P<0.01), absence of B symptoms (P Z 0.04), classical or lymphocyte predominant histology (P<0.01) and more recent treatment era (P<0.01) were associated with longer OS. For the regression model (Table 1), follow-up time was restricted to the first 20 years of follow-up to ensure parity between treatment-era cohorts. Although correlated with RT field size, chemotherapy regimen fell out of the model due to lack of significance. After adjusting for covariates, IFRT, as compared to extended-field (EF) RT, was associated with significantly lower all-cause mortality, with a hazard ratio of 0.59 (P Z 0.038). Conclusion: Treatment with IFRT in early-stage Hodgkin lymphoma was associated with a 41% reduction in the risk of death compared to those treated with EFRT. These results support current efforts to reduce RT volume to involved sites and potential further volume reduction in selected patients. Abstract 297; Table 1
Hazard Ratios (HR) for All-Cause Mortality
HR Age at diagnosis
B symptoms Number of sites of disease Radiation Field
<21 years 21-30 31-40 > 40 Absent Present 3
ref. 1.22 1.54 6.21 ref. 1.29 ref.
4 EFRT IFRT
1.38 ref. 0.59
95% Confidence Interval
P value
0.84 1.02 4.40
1.78 2.32 8.78
0.296 0.041 <0.001
0.98
1.71
0.072
1.01
1.87
0.041
0.36
0.97
0.038
Author Disclosure: C. Patel: Research Grant; ASTRO. E. Michaelson: None. Y. Chen: None. B.J. Silver: None. K.J. Marcus: Member of Pediatric Oncology Editorial Board of NCI’s PDQ; PDQ. M. Stevenson: None. P.M. Mauch: Honoraria; UpToDate. A.K. Ng: None.
298 Phase 2 Study of Dose-Reduced Consolidation Radiation Therapy in Patients With Diffuse Large B-cell Lymphoma C.R. Kelsey,1 A. Beaven,2 L. Diehl,3 G. Broadwater,4 and L.R. Prosnitz5; 1 Department of Radiation Oncology, Duke University, Durham, NC, 2duke University Medical Center, Durham, NC, 3Duke University Medical Center, Durham, NC, 4Duke University Medical Center, Durham, NC, 5 Duke University Medical Center, Durham, NC, United States Purpose/Objective(s): Combined modality therapy, consisting of chemotherapy (ChT) followed by radiation therapy (RT), is an established treatment paradigm for diffuse large B-cell lymphoma (DLBCL). A British National Lymphoma Investigation randomized trial demonstrated no difference in clinical outcomes, including local control, between 30 Gy and 40-45 Gy. Few patients in this study received rituximab or had PET-CT imaging to assessment ChT response. The hypothesis of this phase II study was that more effective systemic therapy (incorporation of rituximab) and optimal post-ChT response assessment (PET-CT), will allow the RT dose to be reduced from 30 Gy to 20 Gy while maintaining high rates of local control. Materials/Methods: Eligibility for this institutional review boardapproved, phase II prospective trial required histological documentation of DLBCL, receipt of 4 cycles of a rituximab/anthracycline-containing combination ChT regimen, and a negative post-chemotherapy PET-CT. Deauville criteria were adopted in 2013 with a negative scan defined as scores 1-3 (prior patients were scored retrospectively). Primary CNS lymphoma was excluded. Patients with stage I/II disease were treated comprehensively to all sites of original involvement; treatment fields for those with stage III/IV disease were individualized. RT field design followed principles of involved-site radiation therapy (ISRT). RT dose was 19.8-20 Gy in 1.8-2 Gy fractions. Primary endpoint: 5-year local recurrence-free survival. Secondary endpoints: 5-year progression-free survival (PFS) and overall survival (OS). PFS defined as time from initiation of RT to progression due to lymphoma or death, whichever occurred first and censored at last follow-up date. Kaplan Meier estimates were used to estimate PFS and OS. Results: From 2010-2015, 62 patients were enrolled (34 women, 28 men; median age: 58 years [range, 24-86 years]). Stage distribution: I (24, 39%), II (25, 40%), III (4, 6%), IV (9, 15%). Median largest tumor mass at diagnosis: 5.7 cm (range, 1-20). Bulky disease (defined as 7.5 cm or 10 cm) present in 23 (40%) and 16 (28%) of patients, respectively. ChT: RCHOP in 58 (94%) and R-EPOCH in 4 (6%). Number of ChT cycles: 4 (n Z 25, 40%); 5 (n Z 2, 3%); and 6 (n Z 35, 57%). Post-ChT Deauville scores: 1 (23, 37%), 2 (23, 37%), 3 (15, 24%), and 4 (1, 2%). Comprehensive RT administered to 4/4 patients with stage III and 6/9 patients with stage IV disease- 3 patient with stage IV disease received RT to only select sites. With a median follow-up of 34 months (range, 1-73), there were no local failures with LRFS of 100%. Systemic lymphoma progression developed in 4 patients with stage I/II disease and 1 with stage IV disease. There were 3 deaths (DLBCL, glioblastoma, unknown). PFS at 3 and 5 years: 92% (95% CI: 86-100%) and 78% (95% CI: 63-97%). OS at 3 and 5 years: 100% and 91% (95% CI: 79-100%). Conclusion: With more effective systemic therapy (R-CHOP) and more refined ChT response assessment (PET-CT), the dose of RT in combined modality treatment programs may be able to be further reduced to 20 Gy. Author Disclosure: C.R. Kelsey: None. A. Beaven: None. L. Diehl: None. G. Broadwater: None. L.R. Prosnitz: None.
299 Cardiac Disease and Lifestyle Risk Factors Following Hodgkin Lymphoma: An EORTC Lymphoma Group and GELA Follow-Up Study M.V. Maraldo,1 F. Giusti,2 M. van der Kaaij,3 M. Henry-Amar,4 B. Aleman,5 J. Raemaekers,6 P.J. Meijnders,7 E.C. Moser,8 H. KluinNelemans,9 M. Spina,10 C. Ferme,11 C. Fortpied,2 and L. Specht1; 1 Rigshospitalet, Copenhagen, Denmark, 2EORTC Headquarters, Brussels,