Backgrounds and Purpose — In indolent non-Hodgkin lymphoma, histological transformation is a dramatic event which reduces the prognosis significantly. SUVmax values from FDG-PET/CT help differentiate between aggressive and indolent lymphomas, and transformed indolent lymphomas also show an increased FDG uptake. Possibly FDG uptake increases early in the clinical course and could predict histological transformation. Our objective was to predict histological transformation in indolent lymphomas from initial staging FDG-PET/CT. Patients and Methods — A retrospective study was performed. Patients with biopsy-proven indolent lymphoma who had had initial staging FDG-PET/CT were included. Qualitative (foci compared with FDG uptake liver) and semiquantitative (SUVmax-value per focus) analyses were performed of all abnormal foci. Patient characteristics and outcome were evaluated. Results — We included 88 patients, 5 of whom developed a histological transformation. Semiquantitative analysis showed a relation between maximum standardized uptake value and histological transformation (odds ratio 1.25, 95% CI 1.024 - 1.513). Qualitative analysis showed a negative predictive relation of FDG uptake less than or equal to liver in the occurrence of histological transformation. Transformation - free survival was 100% over 30 months in those with FDG uptake lower than or equal to liver. More FDG uptake than liver showed transformation - free survival of 88% over 30 months. Conclusion — Qualitative analysis of staging FDG-PET/CT in indolent lymphomas could be useful to rule out transformation in the next 30 months. In our study , semiquantitative analysis was statistically significantly associated with histological transformation and maximum standardized uptake value. However, because of the small number of patients , cautious interpretation of the results is warranted. More studies are needed to investigate the role of staging PET/CT in patient with indolent non-Hodkin lymphoma in the prediction of transformation.
KeywordsIndolentLymphomaTransformationPET/CTPredictive Value
Y. Bastion, C. Sebban, F. Berger, P. Felman, G. Salles, C. Dumontet, et al., “Incidence, Predictive Factors, and Outcome of Lymphoma Transformation in Follicular Lymphoma Patients,” Journal of Clinical Oncology, Vol. 15, No. 4, 1997, pp. 1587-1594.
S. M. Hubbard, B. A. Chabner, V. T. DeVita, R. Simon, C. W. Berard. R. B. Jones, et al., “Histologic Progression in Non-Hodgkin’s Lymphoma,” Blood, Vol. 59, No. 2, 1982, pp. 258-264.
D. L. Oviatt, J. B. Cousar, R. D. Collins, J. M. Flexner and R. S. Stein, “Malignant Lymphomas of Follicular Center Cell Origin in Humans. V. Incidence, Clinical Features, and Prognostic Implications of Transformation of Small Cleaved Cell Nodular Lymphoma,” Cancer, Vol. 53, No. 5, 1984, pp. 1109-1114. http://dx.doi.org/10.1002/1097-0142(19840301)53:5 3.0.CO;2-O
A. G. Glass, L. H. Karnell and H. R. Menck, “The National Cancer Data Base Report on Non-Hodgkin’s Lymphoma,” Cancer, Vol. 80, No. 12, 1997, pp. 2311- 2320. http://dx.doi.org/10.1002/(SICI)1097-0142(19971215)80:12 3.0.CO;2-X
A. Smith, D. Howell, R. Patmore, A. Jack and E. Roman, “Incidence of Haematological Malignancy by Sub-Type: A Report from the Haematological Malignancy Research Network,” British Journal of Cancer, Vol. 105, No. 11, 2011, pp. 1684-1692. http://dx.doi.org/10.1038/bjc.2011.450
M. Sant, C. Allemani, C. Tereanu, R. De Angelis, R. Capocaccia, O. Visser, et al., “Incidence of Hematologic Malignancies in Europe by Morphologic Subtype: Results of the HAEMACARE Project,” Blood, Vol. 116, No. 19, 2010, pp. 3724-3734. http://dx.doi.org/10.1182/blood-2010-05-282632
K. M. Ardeshna, P. Smith, A. Norton, B. W. Hancock, P. J. Hoskin, K. A. MacLennan et al., “Long-Term Effect of a Watch and Wait Policy Versus Immediate Systemic Treatment for Asymptomatic Advanced-Stage Non-Hodgkin Lymphoma: A Randomised Controlled Trial,” Lancet, Vol. 362, No. 9383, 2003, pp. 516-522. http://dx.doi.org/10.1016/S0140-6736(03)14110-4
A. J. Al-Tourah, K. K. Gill, M. Chhanabhai, P. J. Hoskins, R. J. Klasa and K. J. Savage, “Population-Based Analysis of Incidence and Outcome of Transformed Non-Hodgkin’s Lymphoma,” Journal of Clinical Oncology, Vol. 26, No. 32, 2008, pp. 5165-5169. http://dx.doi.org/10.1200/JCO.2008.16.0283
S. Montoto, A.J. Davies, J. Matthews, M. Calaminici, A. J. Norton, J. Amess, “Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma,” Journal of Clinical Oncology, Vol. 25, No. 17, pp. 2426-2433. http://dx.doi.org/10.1200/JCO.2006.09.3260
A. Noy, H. Schoder, M. Gonen, M. Weissler, K. Ertelt and C. Cohler, “The Majority of Transformed Lymphomas Have High Standardized Uptake Values (SUVs) on Positron Emission Tomography (PET) Scanning Similar to Diffuse Large B-Cell Lymphoma (DLBCL),” Annals of Oncology, Vol. 20. No. 3, 2009, pp. 508-512. http://dx.doi.org/10.1093/annonc/mdn657
S. Montoto and J. Fitzgibbon, “Transformation of Indolent B-Cell Lymphomas,” Journal of Clinical Oncology. Vol. 29, No. 14, 2011, pp. 1827-1834. http://dx.doi.org/10.1200/JCO.2010.32.7577
A. Molica, “A Systematic Review on Richter Syndrome: What Is the Published Evidence?” Leuk Lymphoma, Vol. 51, No. 3, 2010, pp. 415-421. http://dx.doi.org/10.3109/10428190903515192
D. Rossi, M. Cerri, D. Capello, C. Deambrogi, F. M. Rossi, A. Zucchetto, et al., “Biological and Clinical Risk Factors of Chronic Lymphocytic Leukaemia Transformation to Richter Syndrome,” British Journal of Haematology, Vol. 142, No. 2, 2008, pp. 202-215. http://dx.doi.org/10.1111/j.1365-2141.2008.07166.x
P. Lin, A. Mansoor, C. Bueso-Ramos, S. Hao, R. Lai and L. J. Medeiros, “Diffuse Large B-cell Lymphoma Occurring in Patients with Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia. Clinicopathologic Features of 12 Cases,” American Journal of Clinical Pathology, Vol. 120, No. 2, 2003, pp. 246-253. http://dx.doi.org/10.1309/R01VXG46MFCDVNHL
M. Lapela, S. Leskinen, H. R. Minn, P. Lindholm, P. J. Klemi and K. O. Soderstrom, “Increased Glucose Metabolism in Untreated Non-Hodgkin’s Lymphoma: A Study with Positron Emission Tomography and Fluorine-18-Fluorodeoxyglucose,” Blood, Vol. 86, No. 9, 1995, pp. 3522-3527.
M. Rodriguez, S. Rehn, H. Ahlstrom, C. Sundstrom and B. Glimelius, “Predicting Malignancy Grade with PET in Non-Hodgkin’s Lymphoma,” Journal of Nuclear Medicine, Vol. 36, No. 10, 1995, pp. 1790-1796.
H. Schoder, A. Noy, M. Gonen, L. Weng, D. Green and Y. E. Erdi, “Intensity of 18 Fluorodeoxyglucose Uptake in Positron Emission Tomography Distinguishes between Indolent and Aggressive Non-Hodgkin’s Lymphoma,” Journal of Clinical Oncology, Vol. 23, No. 21, 2005, pp. 4643-4651. http://dx.doi.org/10.1200/JCO.2005.12.072
C. Bodet-Milin, F. Kraeber-Bodere, P. Moreau, L. Campion, B. Dupas and G. S. Le, “Investigation of FDG-PET/CT Imaging to Guide Biopsies in the Detection of Histological Transformation of Indolent Lymphoma,” Haematologica, Vol. 93, No. 3, pp. 471-472. http://dx.doi.org/10.3324/haematol.12013
M. Karam, P. J. Feustel, C. D. Vera and T. Nazeer, “Features of Large Cell Transformation of Indolent Lymphomas as Observed on Sequential PET/CT,” Nuclear Medicine Communications, Vol. 32, No. 3, 2011, pp. 177-185. http://dx.doi.org/10.1097/MNM.0b013e328342b9d2
N. L. Harris, E. S. Jaffe, J. Diebold, G. Flandrin, H. K. Muller-Hermelink, J. Vardiman, et al., “The World Health Organization Classification of Neoplastic Diseases of the Hematopoietic and Lymphoid Tissues. Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997,” Annals of Oncology, Vol. 10, No. 12, 1999, pp. 1419-1432. http://dx.doi.org/10.1023/A:1008375931236
N. L. Harris, E. S. Jaffe, J. Diebold, G. Flandrin, H. K. Muller-Hermelink, J. Vardiman, et al., “Lymphoma Classification—From Controversy to Consensus: The R.E.A. L. and WHO Classification of Lymphoid Neoplasms,” Annals of Oncology, Vol. 11, 2000, Suppl. 1, pp. 3-10. http://dx.doi.org/10.1093/annonc/11.suppl_1.S3
R. Boellaard, M. J. O’Doherty, W. A. Weber, F. M. Mottaghy, M. N. Lonsdale, S. G. Stroobants, et al., “FDG PET and PET/CT: EANM Procedure Guidelines for Tumour PET Imaging: Version 1.0,” European Journal of Nuclear Medicine and Molecular Imaging, Vol. 37, No. 1, 2010, pp. 181-200. http://dx.doi.org/10.1007/s00259-009-1297-4
S. F. Barrington, W. Qian, E. J. Somer, A. Franceschetto, B. Bagni, E. Brun, et al., “Concordance between Four European Centres of PET Reporting Criteria Designed for Use in Multicentre Trials in Hodgkin Lymphoma,” European Journal of Nuclear Medicine and Molecular Imaging, Vol. 37, No. 10, 2010, pp. 1824-1833. http://dx.doi.org/10.1007/s00259-010-1490-5
S. F. Barrington, J. E. MacKewn, P. Schleyer, P. K. Marsden, N. G. Mikhaeel, W. Qian et al., “Establishment of a UK-Wide Network to Facilitate the Acquisition of Quality Assured FDG-PET Data for Clinical Trials in Lymphoma,” Annals of Oncology, Vol. 22, No. 3, 2011, pp. 739-745. http://dx.doi.org/10.1093/annonc/mdq428
B. Tang, J. Malysz, V. Douglas-Nikitin, R. Zekman, R. H. Wong, I. Jaiyesimi, et al., “Correlating Metabolic Activity with Cellular Proliferation in Follicular Lymphomas,” Molecular Imaging and Biology, Vol. 11, No. 5, 2009, pp. 296-302. http://dx.doi.org/10.1007/s11307-009-0226-z
S. Zincirkeser, E. Sahin, M. Halac and S. Sager, “Standardized Uptake Values of Normal Organs on 18F-Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography Imaging,” Journal of International Medical Research, Vol. 35, No. 2, 2007, pp. 231- 236. http://dx.doi.org/10.1177/147323000703500207
M. Karam, L. Novak, J. Cyriac, A. Ali, T. Nazeer, F. Nugent, “Role of Fluorine-18 Fluoro-Deoxyglucose Positron Emission Tomography Scan in the Evaluation and Follow-Up of Patients with Low-Grade Lymphomas,” Cancer, Vol. 107, No. 1, 2006, pp. 175-183. http://dx.doi.org/10.1002/cncr.21967
T. Papajík, M. Myslivecek , Z. Sedová, E. Buriánková, V. Procházka, P. Koranda, et al., “Standardised Uptake Value of 18F-FDG on Staging PET/CT in Newly Diagnosed Patients with Different Subtypes of Non-Hodgkin’s Lymphoma,” European Journal of Haematology, Vol. 86, No. 1, 2011, pp. 32-37. http://dx.doi.org/10.1111/j.1600-0609.2010.01532.x
K. P. Beal, H. W. Yeung and J. Yahalom, “FDG-PET Scanning for Detection and Staging of Extranodal Marginal Zone Lymphomas of the MALT Type: A Report of 42 cAses,” Annals of Oncology, Vol. 16, No. 3, 2005, pp. 473-480.http://dx.doi.org/10.1093/annonc/mdi093
M. Hoffmann, S. Wohrer, A. Becherer, A. Chott, B. Streubel, K. Kletter, et al., “18F-Fluoro-Deoxy-Glucose Positron Emission Tomography in Lymphoma of Mucosa-Associated Lymphoid Tissue: Histology Makes the Difference,” Annals of Oncology, Vol. 17, No. 12, 2006, pp. 1761-1765. http://dx.doi.org/10.1093/annonc/mdl295
L. T. Tan and K. L. Ong, “Semi-Quantitative Measurements of Normal Organs with Variable Metabolic Activity on FDG PET Imaging,” ANNALS Academy of Medicine Singapore, Vol. 33, No. 2, 2004, pp. 183-185.