Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era

www.nature.com/scientificreports OPEN Prognostic significance of interim PET/CT response for the treatment of advanced‑stage marginal zone lymphoma in the post‑rituximab era Ga‑Young Song1, Sang Eun Yoon4, Seok Jin Kim4, Jin Seok Kim5, Youngil Koh6, Joon‑Ho Moon7, Sung Yong Oh8, Ho Sup Lee9, Ho‑Jin Shin10, Young Rok Do11, Won Sik Lee12, Dae sik Kim13, Yong Park14, Ho‑Young Yhim2,3,15,17* & Deok‑Hwan Yang1,16,17* There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2–3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progressionfree survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1–2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1–2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071–4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era. The clinical significance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in the diagnosis or management of lymphoma is gradually becoming important1,2. 1 Chonnam National University Hwasun Hospital, Hwasun, Jeollanam‑do, Republic of Korea. 2Jeonbuk National University Medical School, Jeonju, Jeollabukdo, Republic of Korea. 3Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea. 4Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 5Yonsei University College of Medicine, Seoul, Republic of Korea. 6Seoul National University Hospital, Seoul, Republic of Korea. 7Department of Hematology/Oncology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea. 8Dong-A Medical Center, Busan, Republic of Korea. 9Kosin University Gospel Hospital, Busan, Republic of Korea. 10Division of Hematology‑Oncology, Department of Internal Medicine, Medical Research Institute, Pusan National University Hospital, Pusan, Republic of Korea. 11Keimyung University Dongsan Medical Center, Daegu, Republic of Korea. 12Busan Paik Hospital, Inje University, Busan, Republic of Korea. 13Korea University Guro Hospital, Seoul, Republic of Korea. 14Division of Hematology/Oncology, Department of Internal Medicine, Korea University School of Medicine Anam Hospital, Seoul, Republic of Korea. 15Department of Internal Medicine, Jeonbuk National University Medical School, 20 Geonji‑ro, Deokjin‑gu, Jeonju 54907, Republic of Korea. 16Department of Hematology/Oncology, Chonnam National University Hwasun Hospital, School of Medicine, Chonnam National University, 322 Seoyang‑ro, Hwasun‑eup,, Hwasun‑gun, Jeollanam‑do 58128, Republic of Korea. 17These authors contributed equally: Ho-Young Yhim and Deok-Hwan Yang. *email: ; Scientific Reports | (2020) 10:11649 | https://doi.org/10.1038/s41598-020-68310-w 1 Vol.:(0123456789) www.nature.com/scientificreports/ Although it remains controversial, several previous studies reported that the interim PET/CT response could predict long-term clinical outcomes in cases of Hodgkin lymphoma (HL), aggressive non-Hodgkin lymphoma (NHL), and follicular l ymphoma3–5. However, the role of 18F-FDG PET/CT assessment in indolent lymphomas other than follicular lymphoma is unclear due to variable 18F-FDG avidity6. Marginal zone lymphoma (MZL), which develops in the marginal zone or edge of the lymphoid tissue, comprises 7–8% of all B-cell NHL cases worldwide. In Korea, MZL is 2nd most common mature B-cell lymphoma (23.0%) because of the relatively lower incidence of follicular lymphoma and chronic lymphocytic leukemia/ small lymphocytic leukemia than those in the Western p opulation7,8. MZL has a heterogenous subgroup classified as extranodal, splenic and nodal. Extranodal MZL, also known as mucosa-associated lymphoid tissue (MALT), constitutes the majority (~ 70%) of MZL cases and has a variable clinical presentation depending on the involved sites9. There is no standard recommended treatment for MZL, but rituximab-containing immunochemotherapy is considered appropriate treatment for advanced-stage c ases10,11. The 18F-FDG avidity of MALT lymphoma, which is known 40–95%, varies according to the extranodal involvement sites, histologic features and morphologic features such as tumor size12–18. Several previous studies suggested potential clinical relevance of 18F-FDG PET/ CT in the diagnostic evaluation of M ZL12,19. In the latest National Comprehensive Cancer Network guidelines update, performing 18F-FDG PET/CT scan was essentially suggested in the initial staging work up of MZL regardless of s ubtypes20. However, evidence is still lacking regarding the use of PET/CT for treatment response assessments in cases of MZL. The prognostic significance of 18F-FDG PET/CT scan for patients with MZL has been suggested in a study by Kim and c olleagues21. In this study, patients who achieved complete response on the interim and/or posttreatment 18F-FDG PET/CT showed higher 5-year progression-free survival (PFS) rates than those with non-CR (post-treatment: 54.2% vs. 0.0%, P = 0.003; interim: 62.5% vs. 15.6%, P = 0.026)21. However, they assessed the PET scan using binary classification of metabolic response, but didn’t use current standard response assessment tool, Deauville criteria using 5-point scale (5-PS), or semi-quantitative assessment using SUVmax reduction rate (ΔSUVmax). Therefore, the present study aimed to evaluate the prognostic impact of interim 18F-FDG PET/CT assessment according to the Deauville 5-PS score (DS) and ΔSUVmax on survival outcomes of patients with MZL who were treated with rituximab-containing immunochemotherapy. Patients and methods Patients and study design. This multicenter, retrospective study was designed to evaluate the prognostic impact of interim 18F-FDG PET/CT response on the survival outcomes of patients with MZL. The clinical data of 178 adult (> 19 years of age) patients with newly diagnosed MZL from 13 independent institutions were initially analyzed between January 2008 and January 2018. Seven patients who were not administrated ri (...truncated)