Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging
Zheng Hao1, Yang Yong1, Qiu Yanyan2, Liao Siqin3, Huang Cheng1, Shi Guiqing1, Zhao Ruizhi1, Tang Tianlan1, Wang Shunyuan1, Chen Silin1, Liu Tingbo2, Xu Benhua1
1Department of Radiation Oncology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies), Fuzhou 350001, China; 2Department of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, China; 3Center of PET-CT, Fujian Medical University Union Hospital, Fuzhou 350001, China
Abstract:Objective To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging. Methods Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group (n=186) and PET-CT + bone marrow biopsy group (n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients (n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT (n=35) compared with their counterparts with the involvement of other organs (n=20) was 28.7% vs.42.0% (P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in (P=0.94). Conclusions Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.
Zheng Hao,Yang Yong,Qiu Yanyan et al. Diagnostic and prognostic value of bone marrow biopsy in patients with extranodal NK/T-cell lymphoma based on PET-CT staging[J]. Chinese Journal of Radiation Oncology, 2023, 32(4): 313-318.
[1] Vose J, Armitage J, Weisenburger D.International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes[J]. J Clin Oncol, 2008,26(25):4124-4130. DOI: 10.1200/JCO.2008. 16.4558. [2] Liu W, Ji X, Song Y, et al.Improving survival of 3760 patients with lymphoma: experience of an academic center over two decades[J]. Cancer Med, 2020,9(11):3765-3774. DOI: 10.1002/cam4.3037. [3] Qi SN, Li YX, Specht L, et al.Modern radiation therapy for extranodal nasal-type NK/T-cell lymphoma: risk-adapted therapy, target volume, and dose guidelines from the International Lymphoma Radiation Oncology Group[J]. Int J Radiat Oncol Biol Phys, 2021,110(4):1064-1081. DOI: 10.1016/j.ijrobp.2021.02.011. [4] Qi SN, Yang Y, Zhang YJ, et al.Risk-based, response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: a China Lymphoma Collaborative Group study[J]. Am J Hematol, 2020,95(9):1047-1056. DOI: 10.1002/ajh.25878. [5] Yang Y, Zhu Y, Cao JZ, et al. Risk-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma: analysis from a multicenter study[J]. Blood, 2015,126(12):1424-1432; quiz 1517. DOI: 10.1182/blood-2015-04- 639336. [6] Liu W, Yang Y, Qi S, et al.Treatment, survival, and prognosis of advanced-stage natural killer/T-cell lymphoma: an analysis from the China Lymphoma Collaborative Group[J]. Front Oncol, 2020,10:583050. DOI: 10.3389/fonc.2020.583050. [7] Fox CP, Civallero M, Ko YH, et al.Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project[J]. Lancet Haematol, 2020,7(4):e284-e294. DOI: 10.1016/S2352-3026(19)30283-2. [8] Cheson BD, Fisher RI, Barrington SF, et al.Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification[J]. J Clin Oncol, 2014,32(27):3059-3068. DOI: 10.1200/JCO.2013.54.8800. [9] El-Galaly TC, d'Amore F, Mylam KJ, et al. Routine bone marrow biopsy has little or no therapeutic consequence for positron emission tomography / computed tomography-staged treatment-naive patients with Hodgkin lymphoma[J]. J Clin Oncol, 2012,30(36):4508-4514. DOI: 10.1200/JCO.2012.42.4036. [10] d'Amore F, Gaulard P, Trümper L, et al. Peripheral T-cell lymphomas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2015,26 Suppl 5:v108-115. DOI: 10.1093/annonc/mdv201. [11] Horwitz SM, Ansell S, Ai WZ, et al.T-cell lymphomas, version 2.2022, NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Netw, 2022,20(3):285-308. DOI: 10.6004/jnccn.2022.0015. [12] Brunning RD, Bloomfield CD, McKenna RW, et al. Bilateral trephine bone marrow biopsies in lymphoma and other neoplastic diseases[J]. Ann Intern Med, 1975,82(3):365-366. DOI: 10.7326/0003-4819-82-3-365. [13] Salem P, Wolverson MK, Reimers HJ, et al.Complications of bone marrow biopsy[J]. Br J Haematol,2003,121(6):821. DOI:10.1046/j.1365-2141.2003.04328.x. [14] Li YX, Yao B, Jin J, et al.Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma[J]. J Clin Oncol, 2006,24(1):181-189. DOI: 10.1200/JCO.2005.03.2573. [15] Li YX, Fang H, Liu QF, et al.Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring[J]. Blood, 2008,112(8):3057-3064. DOI: 10.1182/blood-2008-05-160176. [16] Li YX, Wang H, Jin J, et al.Radiotherapy alone with curative intent in patients with stage I extranodal nasal-type NK/T-cell lymphoma[J]. Int J Radiat Oncol Biol Phys, 2012,82(5):1809-1815. DOI: 10.1016/j.ijrobp.2010. 10.040. [17] Zhang YC, Ma SY, Cai J, et al.Sequential P-GEMOX and radiotherapy for early-stage extranodal natural killer/T-cell lymphoma: a multicenter study[J]. Am J Hematol, 2021,96(11):1481-1490. DOI: 10.1002/ajh.26335. [18] Kim SJ, Yoon DH, Jaccard A, et al.A prognostic index for natural killer cell lymphoma after non- anthracycline-based treatment: a multicentre, retrospective analysis[J]. Lancet Oncol, 2016,17(3):389-400. DOI: 10.1016/S1470-2045(15)00533-1. [19] Yang Y, Zhang YJ, Zhu Y, et al.Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma, nasal-type: a multicenter study[J]. Leukemia, 2015,29(7):1571-1577. DOI: 10.1038/leu.2015.44. [20] Chen SY, Yang Y, Qi SN, et al.Validation of nomogram-revised risk index and comparison with other models for extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: indication for prognostication and clinical decision-making[J]. Leukemia, 2021,35(1):130-142. DOI: 10.1038/s41375- 020-0791-3. [21] Hong H, Li Y, Lim ST, et al.A proposal for a new staging system for extranodal natural killer T-cell lymphoma: a multicenter study from China and Asia Lymphoma Study Group[J]. Leukemia, 2020,34(8):2243-2248. DOI: 10.1038/s41375-020-0740-1. [22] Chen-Liang TH, Martin-Santos T, Jerez A, et al.The role of bone marrow biopsy and FDG-PET/CT in identifying bone marrow infiltration in the initial diagnosis of high grade non-Hodgkin B-cell lymphoma and Hodgkin lymphoma. Accuracy in a multicenter series of 372 patients[J]. Am J Hematol, 2015,90(8):686-690. DOI: 10.1002/ajh.24044. [23] Alzahrani M, El-Galaly TC, Hutchings M, et al.The value of routine bone marrow biopsy in patients with diffuse large B-cell lymphoma staged with PET/CT: a Danish-Canadian study[J]. Ann Oncol, 2016,27(6):1095-1099. DOI: 10.1093/annonc/mdw137. [24] Alderuccio JP, Isrow D, Reis IM, et al.Diagnostic bone marrow biopsy in patients with stage I EMZL treated with radiation therapy: needed or not?[J]. Blood, 2020,135(15):1299-1302. DOI: 10.1182/blood.201900 3236. [25] Fujiwara H, Maeda Y, Nawa Y, et al.The utility of positron emission tomography/computed tomography in the staging of extranodal natural killer/T-cell lymphoma[J]. Eur J Haematol, 2011,87(2):123-129. DOI: 10.1111/j.1600-0609.2011.01645.x. [26] Zhou ZY, Chen CY, Li X, et al.Evaluation of bone marrow involvement in extranodal NK/T cell lymphoma by FDG-PET/CT[J]. Ann Hematol, 2015,94(6):963-967. DOI: 10.1007/s00277-014-2289-4. [27] Wang YQ, Xie L, Tian R, et al.PET/CT-based bone-marrow assessment shows potential in replacing routine bone-marrow biopsy in part of patients newly diagnosed with extranodal natural killer/T-cell lymphoma[J]. J Cancer Res Clin Oncol, 2019,145(10):2529-2539. DOI: 10.1007/s00432-019-02957-5. [28] Kwong YL, Kim WS, Lim ST, et al.SMILE for natural killer/T-cell lymphoma: analysis of safety and efficacy from the Asia Lymphoma Study Group[J]. Blood, 2012,120(15):2973-2980. DOI: 10.1182/blood-2012-05-431460. [29] Jaccard A, Petit B, Girault S, et al.L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature[J]. Ann Oncol, 2009,20(1):110-116. DOI: 10.1093/annonc/mdn542. [30] Li X, Cui YY, Sun ZC, et al.DDGP versus SMILE in newly diagnosed advanced natural killer/T-cell lymphoma: a randomized controlled, multicenter, open-label study in China[J]. Clin Cancer Res, 2016,22(21):5223-5228. DOI: 10.1158/1078-0432.CCR-16-0153.