Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.
Prospective Assessment of Tumour Burden and Bone Disease in Plasma Cell Dyscrasias Using DW-MRI and Exploratory Bone Biomarkers.
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DOI：
10.3390/cancers15010095
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发表时间：
2022-12-23
期刊：
影响因子：
5.2
通讯作者：
Ramasamy, Karthik
中科院分区：
文献类型：
--
作者：
Agarwal, Gaurav;Nador, Guido;Varghese, Sherin;Getu, Hiwot;Palmer, Charlotte;Watson, Edmund;Pereira, Claudio;Sallemi, Germana;Partington, Karen;Patel, Neel;Soundarajan, Rajkumar;Mills, Rebecca;Brouwer, Richard;Maritati, Marina;Shah, Aarti;Peppercorn, Delia;Oppermann, Udo;Edwards, Claire M.;Rodgers, Christopher T.;Javaid, Muhammad Kassim;Gooding, Sarah;Ramasamy, Karthik
虽然多发性骨髓瘤(MM)仍然无法治愈，但两个临床优先事项是延长缓解时间和减少并发症，其中脆性骨折是发病率的主要来源。为此，有必要开发能够准确跟踪肿瘤负担和骨丢失的生物标志物，以指导治疗决策。在这里，我们进行了一项初步的可行性研究，探索新的血清骨转换和血浆细胞负荷标志物和扩散加权磁共振成像(DW-MRI)在MM、意义不明的单克隆性伽马病(MGUS)和阴燃MM(SMM)患者的标准临床评估中的价值。我们发现血清Dkk1和BCMA可能与肿瘤负荷相关，而血清硬化素可能与骨密度相关。此外，我们验证了DW-MRI在肿瘤体积纵向评估中的作用。我们的研究强调了新出现的用于评估肿瘤负担和骨丢失的血清和放射生物标志物，需要在更大的队列中进行进一步研究，以验证这些发现并了解它们的临床应用。需要新的肿瘤负担和骨病生物标记物来指导浆细胞营养不良的临床治疗。最近，骨转换标志物(BTM)和弥散加权磁共振成像(DW-MRI)已经被探索，尽管它们在多发性骨髓瘤(MM)和未确定意义的单克隆性伽马病(MGUS)的前瞻性评估中的作用尚不清楚。在这里，我们进行了一项试验性观察性队列可行性研究，除了标准的临床评估外，还结合了血清BTM和DW-MRI。入选55例患者(MGUS 14例，阴燃MM 15例，新发MM 14例，复发MM 12例)，分别于基线和6个月随访行DW-MRI和血清标志物(P1NP、CTX-1、ALP、Dkk1、skerostin、RANKL：OPG和BCMA)检测。血清硬化素与骨密度呈正相关(r=0.40−0.5 4)。基线时，血清BCMA与血清副蛋白相关(r=0.42)，血清Dkk1与血清游离轻链相关(r=0.67)；在国际骨髓瘤工作组(IMWG)定义的应答者和无应答者之间，这两个生物标志物的纵向变化不同。连续DW-MRI的骨髓瘤反应评估和诊断系统(MY-RADS)评分与传统的IMWG反应标准相关，用于衡量肿瘤负荷的纵向变化。总体而言，我们的初步研究提出了MM/MGUS肿瘤负担和骨丢失的放射学和血清生物标志物候选指标，值得在更大规模的队列中进一步探索，以验证发现并更好地了解它们的临床应用。
Whilst multiple myeloma (MM) remains incurable, two clinical priorities are to prolong remission and reduce complications, of which fragility fractures are a major source of morbidity. To this end, there is the need to develop biomarkers that can accurately track tumour burden and bone loss to guide treatment decisions. Here, we conducted a pilot feasibility study exploring the value of novel serum bone turnover and plasma cell burden markers and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) when added to standard clinical assessment in patients with MM, monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM). We show serum DKK1 and BCMA as possible correlates of tumour burden, and that serum sclerostin may correlate with bone mineral density. Furthermore, we validate DW-MRI in longitudinal assessment of tumour volume. Our study highlights emerging serum and radiological biomarkers for assessment of tumour burden and bone loss, which require further study in larger cohorts to validate these findings and understand their clinical utility. Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40−0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility.
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影响因子：
12.8
作者：
Mateos MV;Kumar S;Dimopoulos MA;González-Calle V;Kastritis E;Hajek R;De Larrea CF;Morgan GJ;Merlini G;Goldschmidt H;Geraldes C;Gozzetti A;Kyriakou C;Garderet L;Hansson M;Zamagni E;Fantl D;Leleu X;Kim BS;Esteves G;Ludwig H;Usmani S;Min CK;Qi M;Ukropec J;Weiss BM;Rajkumar SV;Durie BGM;San-Miguel J
通讯作者：
San-Miguel J
影响因子：
2.6
作者：
Coban, Melahat;Okten, Sarper
通讯作者：
Okten, Sarper
影响因子：
4
作者：
Belotti A;Ribolla R;Cancelli V;Villanacci A;Angelini V;Chiarini M;Giustini V;Facchetti GV;Roccaro AM;Ferrari S;Peli A;Bottelli C;Cattaneo C;Crippa C;Micilotta M;Frittoli B;Grazioli L;Rossi G;Tucci A
通讯作者：
Tucci A
影响因子：
11.1
作者：
Hernández-Rivas JÁ;Ríos-Tamayo R;Encinas C;Alonso R;Lahuerta JJ
通讯作者：
Lahuerta JJ
影响因子：
3.1
作者：
Heider, Ulrike;Kaiser, Martin;Sezer, Orhan
通讯作者：
Sezer, Orhan