Multipl miyelomda metabolik tümör hacmi ve total lezyon glikolizinin prognostik etkisi

Öz

Amaç: 18F-2′-deoksi-2′-florodeoksiglukoz pozitron emisyon tomografisi (18F-FDG PET), multipl miyelomun (MM) tanısında kritik bir görüntüleme aracıdır ve tümör yükü ile hastalığın proliferatif kapasitesi hakkında kapsamlı bilgiler sunar. Bu çalışmada, tedavi öncesi 18F-FDG PET parametrelerinin MM hastalarında sağkalımı öngörmedeki rolü incelendi. Gereç ve yöntem: Ekim 2019 ile Mart 2024 tarihleri arasında, tedavi öncesi 18F-FDG PET incelemesi yapılan 41 MM hastası retrospektif olarak analiz edildi. Hastaların klinik özellikleri, tedavi yanıtları ve sağkalım verileri değerlendirildi. Bulgular: Medyan progresyonsuz sağkalım (PFS) 28,51±3,82 ay, medyan genel sağkalım (OS) ise 34,57±3,9 ay olarak hesaplandı. Ekstramedüller hastalık (EMD) varlığı, yüksek metabolik tümör hacmi (MTV) ve artmış total lezyon glikolizi (TLG), progresyon riskini anlamlı şekilde arttırken (p<0,05) PFS için olumsuz prognostik faktörler olarak belirlendi. Benzer şekilde, yüksek MTV, maksimum standart uptake değeri (SUVmax), ortalama standart uptake değeri (SUVmean) ve TLG ise mortalite riskini artırarak OS için olumsuz prognostik faktörler olarak saptandı (p<0,05). Çok değişkenli analizde, MTV ve TLG OS için bağımsız prognostik faktörler olarak doğrulandı ve MM’de prognostik önem taşıdıkları gösterildi. Sonuç: MTV ve TLG, multipl miyelomda önemli prognostik belirteçler olarak saptanmıştır. Bu parametreler tümörün hacimsel ve metabolik yükünü yansıttığından, Uluslararası Evreleme Sistemi’ne (ISS) entegre edilmeleri risk sınıflamasını ve prognostik değerlendirmeyi iyileştirebilir.

Anahtar Kelimeler

• Multipl miyelom
• prognoz
• ekstramedüller hastalık
• metabolic tümör hacmi
• total lezyon glikolizi

Prognostic impact of metabolic tumor volume and total lesion glycolysis in multiple myeloma

Abstract

Purpose: 18F-2′-deoxy-2′-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is a critical imaging tool for diagnosing multiple myeloma (MM), providing comprehensive insights into tumor burden and disease proliferation capacity. We evaluated the value of pretreatment 18F-FDG PET parameters in forecasting survival in patients with MM. Materials and methods: Between October 2019 and March 2024, a cohort of 41 patients with MM who received pretreatment 18F-FDG PET scans was retrospectively analyzed. Clinical characteristics, treatment response, and survival data were systematically evaluated. Results: The median progression-free survival (PFS) was 28.51±3.82 months, while the median overall survival (OS) was calculated as 34.57±3.9 months. The presence of extramedullary disease (EMD), high metabolic tumor volume (MTV), and elevated total lesion glycolysis (TLG) were significantly associated with an increased risk of progression (p<0.05), establishing them as poor prognostic factors for PFS. Similarly, high MTV, maximum standardized uptake value (SUVmax, SUVmean, and TLG were strongly correlated with an increased mortality risk (p<0.05) and were identified as adverse prognostic factors for overall survival. In multivariate analysis, MTV and TLG were confirmed to be independent prognostic factors for OS, supporting their role in predicting prognosis in MM. Conclusion: MTV and TLG were found to have important prognostic implications in multiple myeloma. Since these parameters reflect volumetric and metabolic tumor burden, their integration into the International Staging System (ISS) may improve risk stratification and prognosis assessment.

Keywords

• Multiple myeloma
• prognosis
• extramedullary disease
• metabolic tumor volume
• total lesion glycolysis

References

1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022;97(8):1086-1107. doi:10.1002/ajh.26590
2. Cavo M, Terpos E, Nanni C, et al. Role of 18F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group. Lancet Oncol. 2017;18(4):e206-e217. doi:10.1016/S1470-2045(17)30189-4
3. Greipp PR, San Miguel J, Durie BG, et al. International staging system for multiple myeloma. J Clin Oncol. 2005;23(15):3412-3420. doi:10.1200/JCO.2005.04.242
4. Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. Am Soc Clin Oncol Educ Book. 2016;35:e418-e423. doi:10.1200/EDBK_159009
5. Marchiori S, Cousin F, Papadopoulos I, et al. Prognostic value of visual IMPeTUs criteria and metabolic tumor burden at baseline [18F]FDG PET/CT in patients with newly diagnosed multiple myeloma. EJNMMI Res. 2024;14(1):51. doi:10.1186/s13550-024-01113-6
6. Tirumani SH, Sakellis C, Jacene H, et al. Role of FDG-PET/CT in Extramedullary Multiple Myeloma: Correlation of FDG-PET/CT Findings With Clinical Outcome. Clin Nucl Med. 2016;41(1):e7-e13. doi:10.1097/RLU.0000000000000902
7. Lapa C, Lückerath K, Malzahn U, et al. 18 FDG-PET/CT for prognostic stratification of patients with multiple myeloma relapse after stem cell transplantation. Oncotarget. 2014;5(17):7381-7391. doi:10.18632/oncotarget.2290
8. Haznedar R, Akı SZ, Akdemir OU, et al. Value of 18F-fluorodeoxyglucose uptake in positron emission tomography/computed tomography in predicting survival in multiple myeloma. Eur J Nucl Med Mol Imaging. 2011;38(6):1046-1053. doi:10.1007/s00259-011-1738-8

9. Zamagni E, Patriarca F, Nanni C, et al. Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma patients treated with up-front autologous transplantation. Blood. 2011;118(23):5989-5995. doi:10.1182/blood-2011-06-361386
10. McDonald JE, Kessler MM, Gardner MW, et al. Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma. Clin Cancer Res. 2017;23(8):1981-1987. doi:10.1158/1078-0432.CCR-16-0235
11. Kumar SK, Callander NS, Adekola K, et al. Multiple Myeloma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(12):1281-1301. doi:10.6004/jnccn.2023.0061
12. Sevindik ÖGHOK, Salihoğlu A, Iltar U. Türk Hematoloji Derneği Multiple Myelom Tanı ve Tedavi Klavuzu. 2020. https://doi.org/978-605-80353-4-8
13. Karam D, Kumar S. Post-Transplant Maintenance Treatment Options in Multiple Myeloma. Oncol Ther. 2021;9(1):69-88. doi:10.1007/s40487-021-00143-7
14. Terao T, Machida Y, Tsushima T, et al. Pre-treatment metabolic tumour volume and total lesion glycolysis are superior to conventional positron-emission tomography/computed tomography variables for outcome prediction in patients with newly diagnosed multiple myeloma in clinical practice. Br J Haematol. 2020;191(2):223-230. doi:10.1111/bjh.16633
15. Li Q, Hu L, Charwudzi A, Zhu W, Meng Y, Zhai Z. Prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography at diagnosis in untreated multiple myeloma patients: a systematic review and meta-analysis. Clin Exp Med. 2023;23(1):31-43. doi:10.1007/s10238-021-00775-z
16. Wan B, Zhang S, Wang P, Deng P, Dai W. Prognostic value of semi-quantitative parameters of 18F-FDG PET/CT in newly diagnosed multiple myeloma patients. Ann Nucl Med. 2023;37(3):155-165. doi:10.1007/s12149-022-01812-x
17. Kraeber Bodéré F, Zweegman S, Perrot A, et al. Prognostic value of positron emission tomography/computed tomography in transplant-eligible newly diagnosed multiple myeloma patients from CASSIOPEIA: the CASSIOPET study. Haematologica. 2023;108(2):621-626. doi:10.3324/haematol.2021.280051
18. Bezzi D, Ambrosini V, Nanni C. Clinical Value of FDG-PET/CT in Multiple Myeloma: An Update. Semin Nucl Med. 2023;53(3):352-370. doi:10.1053/j.semnuclmed.2022.10.008
19. Sundaram S, Driscoll J, Fernandez-Ulloa M, de Lima M, Malek E. FDG PET imaging in multiple myeloma: implications for response assessments in clinical trials. Am J Nucl Med Mol Imaging. 2018;8(6):421-427.
20. Nanni C, Zamagni E, Celli M, et al. The value of 18F-FDG PET/CT after autologous stem cell transplantation (ASCT) in patients affected by multiple myeloma (MM): experience with 77 patients. Clin Nucl Med. 2013;38(2):e74-e79. doi:10.1097/RLU.0b013e318266cee2
21. Waheed S, Mitchell A, Usmani S, et al. Standard and novel imaging methods for multiple myeloma: correlates with prognostic laboratory variables including gene expression profiling data. Haematologica. 2013;98(1):71-78. doi:10.3324/haematol.2012.066555
22. Nanni C. PET-FDG: Impetus. Cancers (Basel). 2020;12(4):1030. doi:10.3390/cancers12041030
23. Sachpekidis C, Merz M, Raab MS, et al. The prognostic significance of [18F]FDG PET/CT in multiple myeloma according to novel interpretation criteria (IMPeTUs). EJNMMI Res. 2021;11(1):100. doi:10.1186/s13550-021-00846-y
24. Nanni C, Versari A, Chauvie S, et al. Interpretation criteria for FDG PET/CT in multiple myeloma (IMPeTUs): final results. IMPeTUs (Italian myeloma criteria for PET USe). Eur J Nucl Med Mol Imaging. 2018;45(5):712-719. doi:10.1007/s00259-017-3909-8
25. Nanni C, Zamagni E, Versari A, et al. Image interpretation criteria for FDG PET/CT in multiple myeloma: a new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe). Eur J Nucl Med Mol Imaging. 2016;43(3):414-421. doi:10.1007/s00259-015-3200-9
26. Lee H, Hyun SH, Cho YS, et al. Semi-quantitative FDG parameters predict survival in multiple myeloma patients without autologous stem cell transplantation. Cancer Imaging. 2023;23(1):104. doi:10.1186/s40644-023-00625-z
27. Goksel S, Ilkkilic K, Bulbul O, Akdogan E. Relation of whole-body metabolic tumor volume and total lesion glycolysis on fluorodeoxyglucose PET/computed tomography with clinical and laboratory parameters in newly diagnosed multiple myeloma. Nucl Med Commun. 2022;43(10):1077-1083. doi:10.1097/MNM.0000000000001608
28. Terao T, Machida Y, Narita K, et al. Total diffusion volume in MRI vs. total lesion glycolysis in PET/CT for tumor volume evaluation of multiple myeloma. Eur Radiol. 2021;31(8):6136-6144. doi:10.1007/s00330-021-07687-2
29. Fonti R, Pellegrino S, Catalano L, Pane F, Del Vecchio S, Pace L. Visual and volumetric parameters by 18F-FDG-PET/CT: a head to head comparison for the prediction of outcome in patients with multiple myeloma. Ann Hematol. 2020;99(1):127-135. doi:10.1007/s00277-019-03852-2
30. Zirakchian Zadeh M, Ayubcha C, Raynor WY, Werner TJ, Alavi A. A review of different methods used for quantification and assessment of FDG-PET/CT in multiple myeloma. Nucl Med Commun. 2022;43(4):378-391. doi:10.1097/MNM.0000000000001528
31. Li J, Zhang X, Qin C, et al. A prognostication system based on clinical parameters and [18F]-FDG PET/CT in patients with newly diagnosed multiple myeloma. Eur J Nucl Med Mol Imaging. 2023;50(6):1665-1670. doi:10.1007/s00259-022-06088-x