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Role of Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients with Primary CNS Lymphoma (PCNSL)
E424
International Journal of Radiation Oncology Biology Physics
associated with high response rates and decreased rates of neurotoxicity compared with higher dose WBRT. Our treatment policy for PCL patients with residual disease following chemotherapy is whole-brain irradiation to a total dose of 23.4 Gy in 13 fractions of 1.8 Gy followed by a sequential boost up to 45-50 Gy in 25 fractions of 1.8-2 Gy to the primary site/residual tumor. We propose a new methodology in order to limit the dose to the healthy brain to the prescribed dose by using composite planning (bias dose planning). Materials/Methods: We treated two patients with PCL and residual disease after chemotherapy using our methodology. First, we prepared a “standard plan”, where the WBRT dose was planned first for volumetric arc therapy (VMAT) using the Monoco TPS (Elekta), followed by the sequential boost dose plan; second, a “bias plan” where the sequential boost dose was planned first, and only thereafter the WBRT dose using the bias dose planning option with the Monaco TPS in order to have a final composite plan corresponding to the prescribed doses. Results: Treatment plans resulting from bias dose planning had a markedly reduced dose to the brain outside of the boost. The mean dose to the brain minus the boost volume was of 25.00 Gy 0.5 Gy (Bias plan) vs 30.00 0.6 Gy (standard plan). Conclusion: Composite planning of the boost first and only thereafter planning the dose to the brain taking the boost plan into account allows a reduction of 5 Gy to the healthy brain. To our knowledge, in lymphoma treatment, the total delivered dose is important, rather than the dose per fraction. We recommend this procedure for PCL radiations that have a sequential boost. Author Disclosure: F. Ahmad: None. A.-D. Durham: Employee; Incyte. M. Zeverino: None. J. Bourhis: None. M. Ozsahin: None.
could be controlled with focal radiotherapy. This pilot study suggests that adding HA-WBRT or focal radiation to chemotherapy could improve disease control while reducing treatment-related side effects. Author Disclosure: H. Wagner: None. A. Ali: None. M. Glantz: Honoraria; MundiPharma. A. Blakeley: None.
3006 Role of Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients with Primary CNS Lymphoma (PCNSL) H. Wagner, A. Ali, M. Glantz, and A. Blakeley; Penn State University, Hershey, PA Purpose/Objective(s): The mainstay of PCNSL treatment usually includes high-dose methotrexate and rituximab. Despite this therapy, most patients die from recurrence. WBRT delays local recurrence, but is associated with side effects including memory loss and dementia; thus, it is often not utilized in treatment. Reduction of the target volume to the region of imaged disease or reduction of the dose to the hippocampi are two techniques which might reduce this toxicity. This study evaluated patterns of failure in PCNSL in order to assess the suitability of focal radiotherapy or HA-WBRT as treatment options. Materials/Methods: We studied patients with PCNSL between 1998-2016. In patients treated with chemotherapy alone with a complete or nearcomplete response followed by recurrence, the original tumor, recurrence and hippocampi on the original MRI were contoured. Distances between the structures were recorded. A 5 mm distance was defined for hippocampal sparing. Results: We identified 97 patients with PCNSL. Fourteen patients underwent radiation during their initial treatment, 28 had progressive disease and died within a year, 8 were lost to follow-up, 7 never went into remission (or stable disease), 28 had no CNS recurrence and 2 patients did not have pre- or post imaging for review. Ten patients fulfilled eligibility criteria. Five recurred within the original tumor bed; 2 recurred >Z 5 mm from the hippocampi; 3 had tumors <5 mm from the hippocampi either at diagnosis or recurrence and could not have been controlled with HAWBRT. Median survival for all 10 patients was 27 months. Conclusion: We found that most (7 of 10) patients had tumors that recurred at least 5 mm from the hippocampi and thus had the potential to be controlled with HA-WBRT as an adjunct to primary treatment. Many PCNSL primaries (5 of 10) also recur within their original tumor bed and
3007 Circulating CD4:CD8 Ratio is Prognosticator of Response to Total Skin Electron Beam Radiation in Mycoses Fungoides Y. An,1 W. Jiang,2 T.Y. Andraos,3 C.C. Pinnix,3 S.A. Milgrom,3 S. Lloyd,4 L.D. Wilson,1 and B. Dabaja3; 1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX, 4University of Utah Huntsman Cancer Institute, Salt Lake City, UT Purpose/Objective(s): A lower proportion of CD8+ tumor infiltrating lymphocytes in mycoses fungoides (MF) patients is associated with poorer survival. However, whether circulating lymphocyte subsets, as reflected by circulating CD4:CD8 ratio, is a prognostic factor for radiotherapy response is not known. We hypothesized CD4:CD8 ratio is prognostic of outcomes in MF patients treated with total skin electron beam therapy (TSEBT) and performed multi-institutional retrospective analysis. Materials/Methods: We retrospectively examined 124 MF patients from MD Anderson Cancer Center (MDACC) and Yale Cancer Center (YCC) treated with TSEBT from 2001-2014. Circulating CD4:CD8 ratio (103/mL) was based on serum analysis obtained before TSEBT. TSEBT was delivered with 9mEV electrons from low (12 Gy) to conventional (12 Gy) doses. Cutaneous clinical treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of 75% was classified as near complete response (CR) and mSWAT decrease of <75% was considered as having a partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in discovery cohort. Multivariate logistic regression examined the association between CD4:CD8 and TSEBT response. Results: 71.8% and 28.2% of all patients achieved CR and PR to TSEBT, respectively. Higher CD4:CD8 ratio predicted poorer response: Median CD4:CD8 in patients with PR was 4.59 (interquartile range: 2.50-4.59) vs. 1.95 (1.10-3.09) in patients with CR (pZ0.002). A threshold CD4:CD8 value of 4.4 optimally discriminated patients with CR vs. PR (sensitivity 90% specificity 59% AUC Z0.71; PZ0.002). 34.5% of patients with CD4:CD8 4.4 (nZ29), achieved CR compared to 83.2% of patients with CD4:CD8 < 4.4 (nZ95). Among patients with low CD4:CD8 <4.4 (nZ73), 74% achieved CR with low dose TSEB vs. 93% with conventional dose TSEB (Chisquare PZ0.02); (Breslow Day PZ0.26 for the modifying effect of CD4:CD8 on TSEB dose). After adjusting for baseline mSWAT, stage, and TSEB dose, CD4:CD8 remained a significant predictor of TSEB response (ORZ0.113, 95% CI 0.04-0.31, p<0.001 for low vs. high CD4:CD8). Conclusion: For MF patients treated with TSEBT, CD4:CD8 ratio was an important prognostic factor of TSEBT treatment response at two high-volume academic centers. The potential for CD4:CD8 ratio’s modifying effect on the efficacy of low- vs. conventional-dose TSEBT warrants further investigation as a possible biomarker to inform radiation treatment decisions. Author Disclosure: Y. An: None. W. Jiang: None. T. Andraos: None. C.C. Pinnix: None. S.A. Milgrom: None. S. Lloyd: None. L.D. Wilson: Stock; Vertex, J and J, United Healthcare, UCAN, Pfizer. Board member; ABR, ASTRO. B. Dabaja: None.
3008 Mucositis Following HSCT With Myeloablative TBI Based on GVHD Prophylaxis Regimen J. Andrade, K. Wentzel, S. Yu, S.Y. Shi, A. Merchant, and L.K. Ballas; Keck School of Medicine of USC, Los Angeles, CA Purpose/Objective(s): Total body irradiation (TBI) is a commonly used preparative regimen for allogeneic hematopoietic stem cell transplantation
International Journal of Radiation Oncology Biology Physics
associated with high response rates and decreased rates of neurotoxicity compared with higher dose WBRT. Our treatment policy for PCL patients with residual disease following chemotherapy is whole-brain irradiation to a total dose of 23.4 Gy in 13 fractions of 1.8 Gy followed by a sequential boost up to 45-50 Gy in 25 fractions of 1.8-2 Gy to the primary site/residual tumor. We propose a new methodology in order to limit the dose to the healthy brain to the prescribed dose by using composite planning (bias dose planning). Materials/Methods: We treated two patients with PCL and residual disease after chemotherapy using our methodology. First, we prepared a “standard plan”, where the WBRT dose was planned first for volumetric arc therapy (VMAT) using the Monoco TPS (Elekta), followed by the sequential boost dose plan; second, a “bias plan” where the sequential boost dose was planned first, and only thereafter the WBRT dose using the bias dose planning option with the Monaco TPS in order to have a final composite plan corresponding to the prescribed doses. Results: Treatment plans resulting from bias dose planning had a markedly reduced dose to the brain outside of the boost. The mean dose to the brain minus the boost volume was of 25.00 Gy 0.5 Gy (Bias plan) vs 30.00 0.6 Gy (standard plan). Conclusion: Composite planning of the boost first and only thereafter planning the dose to the brain taking the boost plan into account allows a reduction of 5 Gy to the healthy brain. To our knowledge, in lymphoma treatment, the total delivered dose is important, rather than the dose per fraction. We recommend this procedure for PCL radiations that have a sequential boost. Author Disclosure: F. Ahmad: None. A.-D. Durham: Employee; Incyte. M. Zeverino: None. J. Bourhis: None. M. Ozsahin: None.
could be controlled with focal radiotherapy. This pilot study suggests that adding HA-WBRT or focal radiation to chemotherapy could improve disease control while reducing treatment-related side effects. Author Disclosure: H. Wagner: None. A. Ali: None. M. Glantz: Honoraria; MundiPharma. A. Blakeley: None.
3006 Role of Hippocampal-Avoidance Whole Brain Radiation Therapy (HA-WBRT) in Patients with Primary CNS Lymphoma (PCNSL) H. Wagner, A. Ali, M. Glantz, and A. Blakeley; Penn State University, Hershey, PA Purpose/Objective(s): The mainstay of PCNSL treatment usually includes high-dose methotrexate and rituximab. Despite this therapy, most patients die from recurrence. WBRT delays local recurrence, but is associated with side effects including memory loss and dementia; thus, it is often not utilized in treatment. Reduction of the target volume to the region of imaged disease or reduction of the dose to the hippocampi are two techniques which might reduce this toxicity. This study evaluated patterns of failure in PCNSL in order to assess the suitability of focal radiotherapy or HA-WBRT as treatment options. Materials/Methods: We studied patients with PCNSL between 1998-2016. In patients treated with chemotherapy alone with a complete or nearcomplete response followed by recurrence, the original tumor, recurrence and hippocampi on the original MRI were contoured. Distances between the structures were recorded. A 5 mm distance was defined for hippocampal sparing. Results: We identified 97 patients with PCNSL. Fourteen patients underwent radiation during their initial treatment, 28 had progressive disease and died within a year, 8 were lost to follow-up, 7 never went into remission (or stable disease), 28 had no CNS recurrence and 2 patients did not have pre- or post imaging for review. Ten patients fulfilled eligibility criteria. Five recurred within the original tumor bed; 2 recurred >Z 5 mm from the hippocampi; 3 had tumors <5 mm from the hippocampi either at diagnosis or recurrence and could not have been controlled with HAWBRT. Median survival for all 10 patients was 27 months. Conclusion: We found that most (7 of 10) patients had tumors that recurred at least 5 mm from the hippocampi and thus had the potential to be controlled with HA-WBRT as an adjunct to primary treatment. Many PCNSL primaries (5 of 10) also recur within their original tumor bed and
3007 Circulating CD4:CD8 Ratio is Prognosticator of Response to Total Skin Electron Beam Radiation in Mycoses Fungoides Y. An,1 W. Jiang,2 T.Y. Andraos,3 C.C. Pinnix,3 S.A. Milgrom,3 S. Lloyd,4 L.D. Wilson,1 and B. Dabaja3; 1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 3University of Texas MD Anderson Cancer Center, Houston, TX, 4University of Utah Huntsman Cancer Institute, Salt Lake City, UT Purpose/Objective(s): A lower proportion of CD8+ tumor infiltrating lymphocytes in mycoses fungoides (MF) patients is associated with poorer survival. However, whether circulating lymphocyte subsets, as reflected by circulating CD4:CD8 ratio, is a prognostic factor for radiotherapy response is not known. We hypothesized CD4:CD8 ratio is prognostic of outcomes in MF patients treated with total skin electron beam therapy (TSEBT) and performed multi-institutional retrospective analysis. Materials/Methods: We retrospectively examined 124 MF patients from MD Anderson Cancer Center (MDACC) and Yale Cancer Center (YCC) treated with TSEBT from 2001-2014. Circulating CD4:CD8 ratio (103/mL) was based on serum analysis obtained before TSEBT. TSEBT was delivered with 9mEV electrons from low (12 Gy) to conventional (12 Gy) doses. Cutaneous clinical treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of 75% was classified as near complete response (CR) and mSWAT decrease of <75% was considered as having a partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in discovery cohort. Multivariate logistic regression examined the association between CD4:CD8 and TSEBT response. Results: 71.8% and 28.2% of all patients achieved CR and PR to TSEBT, respectively. Higher CD4:CD8 ratio predicted poorer response: Median CD4:CD8 in patients with PR was 4.59 (interquartile range: 2.50-4.59) vs. 1.95 (1.10-3.09) in patients with CR (pZ0.002). A threshold CD4:CD8 value of 4.4 optimally discriminated patients with CR vs. PR (sensitivity 90% specificity 59% AUC Z0.71; PZ0.002). 34.5% of patients with CD4:CD8 4.4 (nZ29), achieved CR compared to 83.2% of patients with CD4:CD8 < 4.4 (nZ95). Among patients with low CD4:CD8 <4.4 (nZ73), 74% achieved CR with low dose TSEB vs. 93% with conventional dose TSEB (Chisquare PZ0.02); (Breslow Day PZ0.26 for the modifying effect of CD4:CD8 on TSEB dose). After adjusting for baseline mSWAT, stage, and TSEB dose, CD4:CD8 remained a significant predictor of TSEB response (ORZ0.113, 95% CI 0.04-0.31, p<0.001 for low vs. high CD4:CD8). Conclusion: For MF patients treated with TSEBT, CD4:CD8 ratio was an important prognostic factor of TSEBT treatment response at two high-volume academic centers. The potential for CD4:CD8 ratio’s modifying effect on the efficacy of low- vs. conventional-dose TSEBT warrants further investigation as a possible biomarker to inform radiation treatment decisions. Author Disclosure: Y. An: None. W. Jiang: None. T. Andraos: None. C.C. Pinnix: None. S.A. Milgrom: None. S. Lloyd: None. L.D. Wilson: Stock; Vertex, J and J, United Healthcare, UCAN, Pfizer. Board member; ABR, ASTRO. B. Dabaja: None.
3008 Mucositis Following HSCT With Myeloablative TBI Based on GVHD Prophylaxis Regimen J. Andrade, K. Wentzel, S. Yu, S.Y. Shi, A. Merchant, and L.K. Ballas; Keck School of Medicine of USC, Los Angeles, CA Purpose/Objective(s): Total body irradiation (TBI) is a commonly used preparative regimen for allogeneic hematopoietic stem cell transplantation