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Comparison Between the German Hodgkin Study Group (GHSG) Involved Field Radiation Therapy (IF-RT) Versus the International Lymphoma Radiation Oncology Group (ILROG) Involved Site Radiation Therapy (IS-RT) for Patients with Hodgkin Lymphoma- Is ISRT the New Standard?
Oral Scientific Sessions S153
Volume 90 Number 1S Supplement 2014 fields), 15 with IMRT (4-9 fields), 5 with VMAT, and 1 with 3D conformal RT/IMRT. The variations in CTV-to-planning target volume (PTV) margins (1-1.5 cm), field arrangements, maximum tolerated dose, and plan conformity (conformity index Z V98%/PTV) were substantial. Five plans did not adhere to current ILROG guidelines. Estimated doses to OARs were comparable between centers. Dose estimates and plan parameters are presented in Table 1. Conclusions: RT planning for HL is challenging due to the heterogeneity in size and location of disease and, additionally, the variation in choice of treatment technique and field arrangements. Despite of the variation between 4 ILROG centers, there was an acceptable and comparable dose to the critical OARs. Adopting ILROG guidelines and implementing universal dose objectives could further standardize treatment techniques and contribute to lower the dose to the surrounding normal tissues. Author Disclosure: M.V. Maraldo: None. B. Dabaja: None. J. Garcia: None. J. Hadley: None. T. Illidge: None. P.M. Petersen: None. D.A. Schut: None. R. Tsang: None. L. Specht: None.
338 Comparison Between the German Hodgkin Study Group (GHSG) Involved Field Radiation Therapy (IF-RT) Versus the International Lymphoma Radiation Oncology Group (ILROG) Involved Site Radiation Therapy (IS-RT) for Patients with Hodgkin Lymphoma- Is ISRT the New Standard? J. Kriz, U. Haverkamp, S. Frick, and H.T. Eich; University of Muenster, Muenster, Germany Purpose/Objective(s): The present study addresses the role of IS-RT defined by the ILROG in comparison to the GHSG standard treatment IFRT for patients with Hodgkin Lymphoma (HL). Further we compared intensity-modulated radiation therapy (IMRT) in contrast to standard RT (APPA). Materials/Methods: For 44 patients with de novo HL treated with combined modality approach consisting of chemotherapy followed by 30 Gy IF-RT comparisons between the standard GHSG RT-volume IF-RT and the newly by the ILROG defined IS-RT were made. Further 60 treatment plans from 10 selected patients with APPA-treatment planning and virtually simulated IMRT-plans were evaluated. For the virtually simulated IMRT we used a sliding-window technique with 5 (IMRT-5F) and 7 (IMRT-7F) beam angles. For every patient 3 plans (APPA, IMRT-5F and IMRT7F) were calculated for the IF-RT and the IS-RT respectively. Following organs at risk (OAR) were analyzed: lung, heart, spinal cord, female breast and skin. We compared the different values with regard to dose volume histograms (DVH), conformity and homogeneity indices. Results: The average volume using IF-RT was 1642.53 cm3 and 919.24 cm3 for the IS-RT. With respect to the coverage of the planning target volume (PTV) the IMRT achieves a better conformity (95% CI Z 0.95 0.02 APPA; 0.97 0.03 IMRT-5F; 0.97 0.02 IMRT-7F) and homogeneity (HI: 0.24 0.05 APPA; 0.24 0.07 IMRT-5F; 0.26 0.05 IMRT7F) compared to the APPA. Regarding the Dmean for the lung the IMRT shows increased doses in contrast to the APPA. The IMRT (IMRT-5F > IMRT-7F) shows improved values for the Dmax concerning the dose applied to the spinal cord and to the heart. Due to the large amount of calculated values only the values regarding the heart are named exemplary in this abstract: ISRT: Dmean: (6.57 Gy APPA; 5.14 Gy IMRT-5F; 5.28 Gy IMRT-7F) IFRT: Dmean (17.6 Gy APPA; 15.3 Gy IMRT-5F; 15.62 Gy IMRT-7F). Regarding the Dmean of the female breast the APPA shows improved values. The ISRT spares significantly dose applied to the heart and the lungs as well as to the female breast. Conclusions: The IS-RT reduces significantly the treated volumes. IMRT shows advantages in the conformity of covering the PTV. The APPA shows reduction of dose applied to female breast and the lungs and the IMRT spares dose applied to the heart. We would recommend using IMRT or conventional APPA field arrangement on an individual patient adapted basis. Author Disclosure: J. Kriz: None. U. Haverkamp: None. S. Frick: None. H.T. Eich: None.
339 Identification of Gene Expression Signatures to Predict the Response of Low-Grade Lymphomas to Very Low Dose Radiation Therapy J.J. Cuaron,1 J. Yahalom,1 R. Sundaram,2 S. Katz,2 G. Wang,2 M. Sharma,3 P. Yau,3 and R.S. Bindra2; 1Memorial Sloan-Kettering Cancer Center, New York, NY, 2Yale School of Medicine, New Haven, CT, 3The Princess Margaret Genomics Centre, Toronto, ON, Canada Purpose/Objective(s): The response of low-grade lymphomas to very low dose radiation therapy is remarkably variable, and the molecular determinants of response currently are unknown. We performed a pilot study to identify gene expression patterns that predict the response of low grade, indolent lymphomas to very low dose RT (2 Gy x 2) in a cohort of patients treated at a single institution. Materials/Methods: Between 2006 and 2012, 90 sites in 68 patients with low-grade lymphomas were locally irradiated to a total dose of 4 Gy (2 Gy x 2). Histologies included follicular (68.9%), marginal zone (15.6%), mantle cell (6.7%), small lymphocytic (6.7%), mucosa-associated lymphoid tissue (1.1%) and cutaneous B-cell (1.1%). Initial responses were assessed by imaging or by physical examination and classified as a complete response (CR), partial response (PR) or no response (NR) based on NCCN response criteria. Local progression-free survival (LPFS) was estimated using the Kaplan-Meier method, and LPFS rates between response groups were compared using the log rank test. As an initial test of feasibility, formalin-fixed paraffin-embedded (FFPE) samples from 4 patients with follicular lymphoma (2 with CRs and 2 with NRs) were used for RNA extraction and transcriptome labeling with the Affymetrix FFPE kit. Microarray profiling was performed with Affymetrix GeneChip HTA 2.0 chips. Relative increases in gene expression patterns between CR and NR groups were compared via ANOVA. Genes were selected in with a threshold of > 1.5 fold changes between the CR and NR groups with < 0.05 p-values, and a subset of these gene expression changes were confirmed using NanoString arrays. Results: The median follow-up was 20.1 months. The 3-year LPFS for CR, PR and NR patients was 80.1%, 35.8%, and 16.7%, respectively (P < 0.001). The median time to local progression was 16.0 months, 8.5 months and 3.4 months, respectively. Gene expression patterns from the complete responders were compared to the non-responders, and approximately 400 unique mRNA transcripts were identified using this approach. Several of these genes were confirmed by NanoString Arrays. Selected genes were identified which were previously implicated in the cellular response to ionizing radiation. Conclusions: Initial response to very low dose RT was associated with significantly higher LPFS. Preliminary microarray profiling studies in a small group of patients showed statistically significant changes in relative gene expression patterns between CR and NR groups. These data highlight the feasibility of whole transcriptome profiling using FFPE tissue specimens from retrospective studies, with the potential for molecular stratification of treatment responses and the establishment of a gene expression signature that predicts the response to very low dose RT. Further studies are planned to perform gene expression profiling in a larger group of patients. Author Disclosure: J.J. Cuaron: None. J. Yahalom: None. R. Sundaram: None. S. Katz: None. G. Wang: None. M. Sharma: None. P. Yau: None. R.S. Bindra: None.
340 Characteristics and Outcomes of Patients With LymphocytePredominant Hodgkin Lymphoma Versus Classical Hodgkin Lymphoma: A Population-Based Analysis N. Gerber, C.L. Atoria, E.B. Elkin, and J. Yahalom; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Lymphocyte-predominant Hodgkin lymphoma (LPHL) is rare, comprising about 5% of all Hodgkin lymphoma (HL). Differences in clinical characteristics and outcomes between patients with
Volume 90 Number 1S Supplement 2014 fields), 15 with IMRT (4-9 fields), 5 with VMAT, and 1 with 3D conformal RT/IMRT. The variations in CTV-to-planning target volume (PTV) margins (1-1.5 cm), field arrangements, maximum tolerated dose, and plan conformity (conformity index Z V98%/PTV) were substantial. Five plans did not adhere to current ILROG guidelines. Estimated doses to OARs were comparable between centers. Dose estimates and plan parameters are presented in Table 1. Conclusions: RT planning for HL is challenging due to the heterogeneity in size and location of disease and, additionally, the variation in choice of treatment technique and field arrangements. Despite of the variation between 4 ILROG centers, there was an acceptable and comparable dose to the critical OARs. Adopting ILROG guidelines and implementing universal dose objectives could further standardize treatment techniques and contribute to lower the dose to the surrounding normal tissues. Author Disclosure: M.V. Maraldo: None. B. Dabaja: None. J. Garcia: None. J. Hadley: None. T. Illidge: None. P.M. Petersen: None. D.A. Schut: None. R. Tsang: None. L. Specht: None.
338 Comparison Between the German Hodgkin Study Group (GHSG) Involved Field Radiation Therapy (IF-RT) Versus the International Lymphoma Radiation Oncology Group (ILROG) Involved Site Radiation Therapy (IS-RT) for Patients with Hodgkin Lymphoma- Is ISRT the New Standard? J. Kriz, U. Haverkamp, S. Frick, and H.T. Eich; University of Muenster, Muenster, Germany Purpose/Objective(s): The present study addresses the role of IS-RT defined by the ILROG in comparison to the GHSG standard treatment IFRT for patients with Hodgkin Lymphoma (HL). Further we compared intensity-modulated radiation therapy (IMRT) in contrast to standard RT (APPA). Materials/Methods: For 44 patients with de novo HL treated with combined modality approach consisting of chemotherapy followed by 30 Gy IF-RT comparisons between the standard GHSG RT-volume IF-RT and the newly by the ILROG defined IS-RT were made. Further 60 treatment plans from 10 selected patients with APPA-treatment planning and virtually simulated IMRT-plans were evaluated. For the virtually simulated IMRT we used a sliding-window technique with 5 (IMRT-5F) and 7 (IMRT-7F) beam angles. For every patient 3 plans (APPA, IMRT-5F and IMRT7F) were calculated for the IF-RT and the IS-RT respectively. Following organs at risk (OAR) were analyzed: lung, heart, spinal cord, female breast and skin. We compared the different values with regard to dose volume histograms (DVH), conformity and homogeneity indices. Results: The average volume using IF-RT was 1642.53 cm3 and 919.24 cm3 for the IS-RT. With respect to the coverage of the planning target volume (PTV) the IMRT achieves a better conformity (95% CI Z 0.95 0.02 APPA; 0.97 0.03 IMRT-5F; 0.97 0.02 IMRT-7F) and homogeneity (HI: 0.24 0.05 APPA; 0.24 0.07 IMRT-5F; 0.26 0.05 IMRT7F) compared to the APPA. Regarding the Dmean for the lung the IMRT shows increased doses in contrast to the APPA. The IMRT (IMRT-5F > IMRT-7F) shows improved values for the Dmax concerning the dose applied to the spinal cord and to the heart. Due to the large amount of calculated values only the values regarding the heart are named exemplary in this abstract: ISRT: Dmean: (6.57 Gy APPA; 5.14 Gy IMRT-5F; 5.28 Gy IMRT-7F) IFRT: Dmean (17.6 Gy APPA; 15.3 Gy IMRT-5F; 15.62 Gy IMRT-7F). Regarding the Dmean of the female breast the APPA shows improved values. The ISRT spares significantly dose applied to the heart and the lungs as well as to the female breast. Conclusions: The IS-RT reduces significantly the treated volumes. IMRT shows advantages in the conformity of covering the PTV. The APPA shows reduction of dose applied to female breast and the lungs and the IMRT spares dose applied to the heart. We would recommend using IMRT or conventional APPA field arrangement on an individual patient adapted basis. Author Disclosure: J. Kriz: None. U. Haverkamp: None. S. Frick: None. H.T. Eich: None.
339 Identification of Gene Expression Signatures to Predict the Response of Low-Grade Lymphomas to Very Low Dose Radiation Therapy J.J. Cuaron,1 J. Yahalom,1 R. Sundaram,2 S. Katz,2 G. Wang,2 M. Sharma,3 P. Yau,3 and R.S. Bindra2; 1Memorial Sloan-Kettering Cancer Center, New York, NY, 2Yale School of Medicine, New Haven, CT, 3The Princess Margaret Genomics Centre, Toronto, ON, Canada Purpose/Objective(s): The response of low-grade lymphomas to very low dose radiation therapy is remarkably variable, and the molecular determinants of response currently are unknown. We performed a pilot study to identify gene expression patterns that predict the response of low grade, indolent lymphomas to very low dose RT (2 Gy x 2) in a cohort of patients treated at a single institution. Materials/Methods: Between 2006 and 2012, 90 sites in 68 patients with low-grade lymphomas were locally irradiated to a total dose of 4 Gy (2 Gy x 2). Histologies included follicular (68.9%), marginal zone (15.6%), mantle cell (6.7%), small lymphocytic (6.7%), mucosa-associated lymphoid tissue (1.1%) and cutaneous B-cell (1.1%). Initial responses were assessed by imaging or by physical examination and classified as a complete response (CR), partial response (PR) or no response (NR) based on NCCN response criteria. Local progression-free survival (LPFS) was estimated using the Kaplan-Meier method, and LPFS rates between response groups were compared using the log rank test. As an initial test of feasibility, formalin-fixed paraffin-embedded (FFPE) samples from 4 patients with follicular lymphoma (2 with CRs and 2 with NRs) were used for RNA extraction and transcriptome labeling with the Affymetrix FFPE kit. Microarray profiling was performed with Affymetrix GeneChip HTA 2.0 chips. Relative increases in gene expression patterns between CR and NR groups were compared via ANOVA. Genes were selected in with a threshold of > 1.5 fold changes between the CR and NR groups with < 0.05 p-values, and a subset of these gene expression changes were confirmed using NanoString arrays. Results: The median follow-up was 20.1 months. The 3-year LPFS for CR, PR and NR patients was 80.1%, 35.8%, and 16.7%, respectively (P < 0.001). The median time to local progression was 16.0 months, 8.5 months and 3.4 months, respectively. Gene expression patterns from the complete responders were compared to the non-responders, and approximately 400 unique mRNA transcripts were identified using this approach. Several of these genes were confirmed by NanoString Arrays. Selected genes were identified which were previously implicated in the cellular response to ionizing radiation. Conclusions: Initial response to very low dose RT was associated with significantly higher LPFS. Preliminary microarray profiling studies in a small group of patients showed statistically significant changes in relative gene expression patterns between CR and NR groups. These data highlight the feasibility of whole transcriptome profiling using FFPE tissue specimens from retrospective studies, with the potential for molecular stratification of treatment responses and the establishment of a gene expression signature that predicts the response to very low dose RT. Further studies are planned to perform gene expression profiling in a larger group of patients. Author Disclosure: J.J. Cuaron: None. J. Yahalom: None. R. Sundaram: None. S. Katz: None. G. Wang: None. M. Sharma: None. P. Yau: None. R.S. Bindra: None.
340 Characteristics and Outcomes of Patients With LymphocytePredominant Hodgkin Lymphoma Versus Classical Hodgkin Lymphoma: A Population-Based Analysis N. Gerber, C.L. Atoria, E.B. Elkin, and J. Yahalom; Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): Lymphocyte-predominant Hodgkin lymphoma (LPHL) is rare, comprising about 5% of all Hodgkin lymphoma (HL). Differences in clinical characteristics and outcomes between patients with