Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy

Vasu Tumati, Lakshya Trivedi, Hsiao Ching Li, Prapti Patel, Pier P. Scaglioni, Madhuri Vusirikala, Navid Sadeghi, Syed Rizvi, Weina Chen, Jason Wachsmann, Robert Collins, Neil B. Desai

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Abstract

Purpose: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). Methods and Materials: A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. Results: Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P =.04). Conclusions: DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.

Original languageEnglish (US)
Pages (from-to)1126-1132
Number of pages7
JournalInternational Journal of Radiation Oncology Biology Physics
Volume100
Issue number5
DOIs
StatePublished - Apr 1 2018

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radiation therapy
Lymphoma
Radiotherapy
chemotherapy
progressions
Disease-Free Survival
Lymphoma, Large B-Cell, Diffuse
Recurrence
Drug Therapy
refractories
Fluorescence In Situ Hybridization
Non-Hodgkin's Lymphoma
hazards
confidence
therapy
indication
screening
Immunohistochemistry
Confidence Intervals
proteins

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{8cc4a3e1a0564951b07274475bead7c8,
title = "Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy",
abstract = "Purpose: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). Methods and Materials: A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. Results: Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55{\%}) occurred at initially involved site(s), and 4 (36{\%}) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95{\%} confidence interval 0.02-0.94, P =.04). Conclusions: DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.",
author = "Vasu Tumati and Lakshya Trivedi and Li, {Hsiao Ching} and Prapti Patel and Scaglioni, {Pier P.} and Madhuri Vusirikala and Navid Sadeghi and Syed Rizvi and Weina Chen and Jason Wachsmann and Robert Collins and Desai, {Neil B.}",
year = "2018",
month = "4",
day = "1",
doi = "10.1016/j.ijrobp.2018.01.041",
language = "English (US)",
volume = "100",
pages = "1126--1132",
journal = "International Journal of Radiation Oncology Biology Physics",
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TY - JOUR

T1 - Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas

T2 - Implications for Radiation Therapy

AU - Tumati, Vasu

AU - Trivedi, Lakshya

AU - Li, Hsiao Ching

AU - Patel, Prapti

AU - Scaglioni, Pier P.

AU - Vusirikala, Madhuri

AU - Sadeghi, Navid

AU - Rizvi, Syed

AU - Chen, Weina

AU - Wachsmann, Jason

AU - Collins, Robert

AU - Desai, Neil B.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Purpose: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). Methods and Materials: A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. Results: Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P =.04). Conclusions: DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.

AB - Purpose: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL). Methods and Materials: A retrospective single-institution study of all patients with diagnoses of non-Hodgkin lymphoma between 2011 and 2015 was performed. DHL status was determined by fluorescence in-situ hybridization, and DEL status was determined by immunohistochemistry. Progression-free survival (PFS) was calculated from the end of chemotherapy using the Kaplan-Meier method. Cox modeling was used for multivariable analysis. Results: Screening of 275 DLBCL patients yielded a 53-patient cohort, including 32 patients with DHL, 10 with DEL, 9 with a triple rearrangement, and 2 triple expressors. Of the 26 patients whose disease progressed, 15 had primary refractory disease. The remaining 11 failures were relapses after complete response to initial chemotherapy. Of those failures, 6 (55%) occurred at initially involved site(s), and 4 (36%) were isolated initial site relapses. Consolidative radiation therapy was associated significantly with improved PFS on multivariable analysis (hazard ratio 0.17, 95% confidence interval 0.02-0.94, P =.04). Conclusions: DHL/DEL are associated with high relapse rates, which preferentially occur at initially involved sites. Among patients achieving complete response to chemotherapy, consolidative radiation therapy was associated with improved PFS. This provides a rationale for the continued role of radiation therapy in the treatment of DHL and DEL and requires validation in a larger cohort.

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DO - 10.1016/j.ijrobp.2018.01.041

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