Opinion Statement
18 F-2-deoxy-d-glucose positron emission tomography (FDG-PET), combined with a multidetector helical CT (PET/CT) has emerged, in the past decade as one of the most important prognostic tool for lymphoma management. Besides proving as the only imaging technique able to recapitulate all the information yielded by the standard radiological staging and restaging, it provided new essential information for chemosensitivity assessment and radiotherapy planning. In lymphoma staging, functional imaging (FI) by PET/CT was shown to be more accurate than conventional radiological (anatomical) imaging to detect nodal and extranodal involvement, whereas in posttreatment restaging it showed a superior predictive value on treatment outcome. In Hodgkin lymphoma (HL), FI concurred to delineate a new paradigm of therapy in which PET is considered an essential tool to guide physician’s choice on treatment intensity and modality. In fact, PET proved very useful for: 1) assessing chemosensitivity early during treatment to predict final therapy outcome; 2) managing a residual mass, detected by CT scan in up to two thirds of patients at the end of chemotherapy; and 3) planning radiotherapy in early-stage disease when conformal radiotherapy fields are used to spare toxicity to adjacent tissues. The early chemosensitivity assessment is the underpinnings of a new therapeutic strategy in HL, aimed at minimizing treatment-related toxicity while maintaining treatment efficacy. Several clinical trials are currently underway to test this hypothesis. In diffuse, large, B-cell lymphoma (DLBCL), PET/CT proved very useful: 1) in lymphoma staging, leading to upward stage migration in one third of the patients; and 2) to identify patients benefiting from consolidation radiotherapy for FDG-avid, single mass or limited–extension disease. Different to HL, the role of interim PET in DLBCL remains controversial. In follicular lymphoma (FL) preliminary studies PET/CT proved useful, in baseline staging to predict time to treatment in patients in which a watchful observation without treatment (watch and wait) was chosen as therapeutic approach treatment. In FL end-of-treatment PET/CT proved the most powerful prognostic tool to predict long-term treatment outcome.
Similar content being viewed by others
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Warburg O. Über den Stoffwechsel der Tumoren: arbeiten aus dem Kaiser Wilhelm-Institut für Biologie, Berlin-Dahlem. Berlin: Springer; 1926.
Yamamoto T, Seino Y, Fukumoto H, Koh G, Yano H, Inagaki N, et al. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun. 1990;170(1):223–30.
Brown RS, Wahl RL. Overexpression of Glut-1 glucose transporter in human breast cancer. An immunohistochemical study. Cancer. 1993;72(10):2979–85.
Au KK, Liong E, Li JY, Li PS, Liew CC, Kwok TT, et al. Increases in mRNA levels of glucose transporters types 1 and 3 in Ehrlich ascites tumor cells during tumor development. J Cell Biochem. 1997;67(1):131–5.
Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M. Mazière BFDG accumulation and tumor biology. Nucl Med Biol. 1998;25(4):317–22.
Zhuang H, Pourdehnad M, Lambright ES, Yamamoto AJ, Lanuti M, Li P, et al. Alavi ADual time point 18 F-FDG PET imaging for differentiating malignant from inflammatory processes. J Nucl Med. 2001;42(9):1412–7.
Hartmann S, Agostinelli C, Diener J, Döring C, Fanti S, Zinzani PL, et al. Hansmann ML.GLUT1 expression patterns in different Hodgkin lymphoma subtypes and progressively transformed germinal centers. BMC Cancer. 2012;12:586.
Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T. Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med. 1992;33(11):1972–80.
Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL. Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: I. Are inflammatory cells important? J Nucl Med. 1995;36(10):1854–61.
Higashi K, Clavo AC, Wahl RL. Does FDG uptake measure proliferative activity of human cancer cells? In vitro comparison with DNA flow cytometry and tritiated thymidine uptake. J Nucl Med. 1993;34(3):414–9.
Brown RS, Leung JY, Fisher SJ, Frey KA, Ethier SP, Wahl RL. Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake. J Nucl Med. 1996;37(6):1042–7.
Wahl RL, Henry CA, Ethier SP. Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro-2-deoxy-D-glucose in rodents with mammary carcinoma. Radiology. 1992;183(3):643–7.
Clavo AC, Brown RS, Wahl RL. Fluorodeoxyglucose uptake in human cancer cell lines is increased by hypoxia. J Nucl Med. 1995;36(9):1625–32.
Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I, et al. Israel O (18)F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med. 2010;51(1):25–30.
Elstrom R, Guan L, Baker G, et al. Utility of FDG-PET scanning in lymphoma by WHO classification. Blood. 2003;101:3875–6.
Tsukamoto N, Kojima M, Hasegawa M, et al. The usefulness of 18Ffluorodeoxyglucose positron emission tomography (18 F-FDG-PET) and a comparison of 18 F-FDG-PET with 67gallium scintigraphy in the evaluation of lymphoma: relation to histologic subtypes based on the World Health Organization classification. Cancer. 2007;110:652–9.
Kwee TC, Kwee RM, Nievelstein RA. Imaging in staging of malignant lymphoma : a systematic review. Blood. 2008;111(2):504–16.
Munker R, Glass J, Griffeth LK, et al. Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin’s disease. Ann Oncol. 2004;15(11):1699–704.
Rigacci L, Vitolo U, Nassi L, et al. Positron emission tomography in the staging of patients with Hodgkin’s lymphoma. A prospective multicentric study by the intergruppo Italiano Linfomi. Ann Hematol. 2007;86(12):897–903.
Hutchings M, Loft A, Hansen M, et al. Position emission tomography with or without computed tomography in the primary staging of Hodgkin’s lymphoma. Haematologica. 2006;91(4):482–9.
Cheson BD. Role of Functional Imaging in the Management of Lymphoma. J Clin Oncol. 2011;29:1–11.
Rodriguez-Vigil B, Gomez-Leon N, Pinilla I, et al. PET/CT in lymphoma: Prospective study of enhanced full-dose PET/CT versus unenhanced low-dose PET/CT. J Nucl Med. 2006;47:1643–8.
Chalaye J, Luciani A, Meignan M, Enache C, Amraoui K, Beaussart P, et al. Clinical impact of contrast-enhanced computed tomography (CECT) combined with low-dose FDG PET/CT on lymphoma patient management. J Nucl Med. 2012;53:1369–75.
Pinilla I, Gomez-Leon N, Del Campo-Del VL, et al. Diagnostic value of CT, PET and combined PET/CT performed with low-dose unenhanced CT and full-dose enhanced CT in the initial staging of lymphoma. The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), Section of the Society of Radiopharmaceutical. Chem Biol. 2011;55:567–75.
Elstrom RL, Leonard JP, Coleman M, Brown RK. Combined PET and low-dose, non-contrast CT scanning obviates the need for additional diagnostic contrast-enhanced CT scans in patients undergoing staging or restaging for lymphoma. Ann Oncol. 2008;19(10):1770–3.
El-Galaly TC, D'Amore F, Mylan KJ, et al. Routine bone marrow biopsy has no little or no therapeutic consequence for positron emission tomography/computed tomography-staged treatment-naive patients with Hodgkin lymphoma. J Clin Oncol. 2012;30:4508–14. Role of PET scan to detect BM involvement by lymphoma.
Khan AB, Barrington SF, Mikhaeel NG, et al. PET-CT staging of DLBCL accurately identifies and provides new insight into the clinical significance of bone marrow involvement. Blood. 2013;122:61–7. Role of PET scan to detect BM involvement by lymphoma.
Abraham A. Staging DLBCL: bone marrow biopsy or PET-CT? Comment on Khan et al. Blood. 2013;122:61–7. Role of PET scan to detect BM involvement by lymphoma.
Le Dortz L et al. Diagnostic and prognostic impact of 18 F-FDG PET/CT in follicular lymphoma. Eur J Nucl Med Mol Imaging. 2010;37:2307–14.
Luminari S et al. The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi. Ann Oncol. 2013;24:2108–12.
Bodet-Milin et al. Prognostic impact of 18F-fluoro-deoxyglucose positron emission tomography in untreated mantle cell lymphoma: a retrospective study from the GOELAMS group. Eur J Nucl Med Mol Imaging. 2010;37:1633–42.
Karam M et al. FDG positron emission tomography/computed tomography scan may identify mantle cell lymphoma patients with unusually favourable outcome. Nucl Med Commun. 2009;30:770–8.
Barrington SF, Kostakoglu L, Hutchings M, Müller S, Schwarz LH, Meignan M, Biggi A, Mikhaeel NG. Proposed criteria for lymphoma staging and restaging. J Clin Oncol 2014; in press. Proposed criteria for interim and end-of-treatment PET scan interpretation.
Kostakoglu L, Goldsmith SJ, Leonard JP, Christos P, Furman RR, Atasever T, et al. FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease. Cancer. 2006;107:2678–87.
Hutchings M, Loft A, Hansen M, Pedersen LM, Buhl T, Jurlander J, et al. FDG-PET after two cycles of chemotherapy predicts treatment failure and progression-free survival in Hodgkin lymphoma. Blood. 2006;107:52–9.
Gallamini A, Rigacci L, Merli F, Nassi L, Bosi A, Capodanno I, et al. The predictive value of positronemission tomography scanning performed after two courses of standard therapy on treatment outcome in advanced stage Hodgkin’s disease. Haematologica. 2006;91:475–81.
Zinzani PL, Rigacci L, Stefoni V, Broccoli A, Puccini B, Castagnoli A, et al. Early interim 18 F-FDG PET in Hodgkin’s lymphoma: evaluation on 304 patients. Eur J Nucl Med Mol Imaging. 2012;39:4–12.
Cerci JJ, Pracchia LF, Linardi CC, et al. 18 F-FDG PET after 2 cycles of ABVD predicts event-free survival in early and advanced Hodgkin lymphoma. J Nucl Med. 2010;51:1337–43.
Hutchings M, Mikhaeel NG, Fields PA, Nunan T, Timothy AR. Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in Hodgkin lymphoma. Ann Oncol. 2005;16(7):1160–8.
Terasawa T, Lau J, Bardet S, Couturier O, Hotta T, Hutchings M, et al. Fluorine-18-fluorodeoxyglucose positron emission tomography for interim response assessment of advanced stage Hodgkin’s lymphoma and diffuse large B-cell lymphoma: a systematic review. J Clin Oncol. 2009;27:1906–14.
Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, et al. Early interim 2-[18 F]fluoro-2-deoxy-D glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25:3746–52.
Meignan M, Gallamini A, Haioun C. Report on the First International Workshop on interim-PET scan in lymphoma. Leuk Lymphoma. 2009;50(8):1257–60.
Gallamini A, Kostakoglu L. Interim FDG-PET in Hodgkin lymphoma: a compass for a safe navigation in clinical trials? Blood. 2012;120:4913–20. Ongoing interim PET response-adapted clinical trials in Hodgkin lymphoma.
Moskowitz CH, Schoder H, Teruya-Feldstein J, et al. Risk adapted dose-dense immunochemoterapy determined by interim FDG-PET in advanced stage diffuse large B-cell lymphoma. J Clin Oncol. 2010;28:1896–903.
Pregno P, Chiappella A, Bello M, et al. Interim 18-FDG-PET/CT failed to predict the outcome in diffuse large B-cell lymphoma patients treated at the diagnosis with rituximab-CHOP. Blood. 2012;119:2066–73.
Cashen AF, Dehdashti F, Luo J, Homb A, Siegel BA, Bartlett NL. 18-FDG-PET/CT for early response assessment in diffuse large B-cell lymphoma: poor predictive value of international harmonization project interpretation. J Nucl Med. 2011;52:386–92.
Dupuis J, Berriolo-Riedinger A, Julian A, Brice P, Tychyj-Pinel C, Tilly H, et al. Meignan M Impact of [(18)F]fluorodeoxyglucose positron emission tomography response evaluation in patients with high-tumor burden follicular lymphoma treated with immunochemotherapy: a prospective study from the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS. J Clin Oncol. 2012;30:4317–22. Prognostic role of End-of Treatment PET scan in follicular Lymphoma.
Pellegrini C,Casadei B,Derenzini E et al. The Role of Interim-PET and final-PET in the outcome of peripheral T-cell lymphoma (PTCL) treated at the diagnosis with CHOP. Blood 2012;120: Abstract 2721.
Meignan M, Gallamini A, Haioun C. Report on the first international workshop on interim-PET scan in Lymphoma. Leuk Lymphoma. 2009;50:1257–60.
Gallamini A, Fiore F, Sorasio P, Meignan M. Interim positron emission tomography scan in Hodgkin lymphoma: definitions, interpretation rules, and clinical validation. Leuk Lymphoma. 2009;50:1761–4.
Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, et al. International validation study for interim PET in ABVD-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54:683–90. International validation study of the prognostic role of interim PET in Hodgkin lymphoma.
Casasnovas RO, Meignan M, Berriolo-Riedinger A, Bardet S, Julian A, Thieblemont C, et al. SUVmax reduction improves early prognosis value of interim positron emission tomography scans in diffuse large B-cell lymphoma. Blood. 2011;118:37–43.
Zijlstra JM. Lindauer-van der Werf G, Hoekstra OS, Hooft L, Riphagen II, Huijgens PC. 18 F-fluoro-deoxyglucose positron emission tomography for post-treatment evaluation of malignant lymphoma: a systematic review. Haematologica. 2006;91:522–9.
Terasawa T, Nihashi T, Hotta T, Nagai H. 18 F-FDG PET for Posttherapy assessment of Hodgkin’s disease and aggressive non-Hodgkin’s lymphoma: a systematic review. J Nucl Med. 2008;49:13–21.
Radford JA, Cowan RA, Flanagan M, Dunn G, Crowther D, Johnson RJ, et al. The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin's disease. J Clin Oncol. 1988;6:940–6.
Surbone A, Longo DL, DeVita Jr VT, Ihde DC, Duffey PL, Jaffe ES, et al. Residual abdominal masses in aggressive non-Hodgkin's lymphoma after combination chemotherapy: significance and management. J Clin Oncol. 1988;6:1832–7.
Naumann R, Vaic A, Beuthien-Baumann B, Bredow J, Kropp J, Kittner T, et al. Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma. Br J Haematol. 2001;115:793–800.
Canellos GP. Residual mass in lymphoma may not be residual disease. J Clin Oncol. 1988;6:931–3.
Bonadonna G, Viviani S, Bonfante V, Gianni AM, Valagussa P. Survival in Hodgkin’s disease patients – Report of 25 years of experience at the Milan cancer Institute. Eur J Cancer. 2005;41:998–1006.
Engert A, Haverkamp H, Kobe C, Markova J, Renner C, Ho A, et al. Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 noninferiority trial. Lancet. 2012;379(9828):1791–9. End-of-therapy PET scan to guide consolidation radiotherapy in Hodgkin lymphoma.
Magagnoli M, Marzo K, Balzarotti M, Rodari M, Mazza R, Giordano L, et al. Dimension of Residual CT Scan Mass in Hodgkin's Lymphoma (HL) Is a Negative Prognostic Factor in Patients with PET Negative After Chemo+/− Radiotherapy. Blood. 2011; 118:93 [Abstract].
Savage KJ, Connors JM, Klasa RJ et al. The use of FDG-PET to guide consolidative radiotherapy in patients with advanced-stage Hodgkin lymphoma with residual abnormalities on CT scan following ABVD chemotherapy. J.Clin. Oncol. 2011; 29 (Suppl) 8034 [Abstract].
Sehn LH, Klasa R, Shenkier T et al. Long-term experience with PET-guided consolidative radiation therapy (XRT) in patients with advanced stage diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP. Oral presentation, Hematol Oncol 2013; 31 (Suppl.I): 96–150. [Abstract]. End-of-therapy PET scan to guide consolidation radiotherapy in aggressive B-cell lymphoma.
Brepoels L, Stroobants S, De Wever W, Spaepen K, Vandenberghe P, Thomas J, et al. Hodgkin lymphoma: Response assessment by Revised International Workshop Criteria. Leuk Lymphoma. 2007;48:1539–47.
Dupuis J, Itti E, Rahmouni A, Hemery F, Gisselbrecht C, Lin C, et al. Response assessment after an inductive CHOP or CHOP-like regimen with or without rituximab in 103 patients with diffuse large B-cell lymphoma: integrating 18fluorodeoxyglucose positron emission tomography to the International Workshop Criteria. Ann Oncol. 2009;20:503–7.
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, et al. Measurement of clinical and subclinical tumour response using [18 F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999;35:1773–82.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, and Diehl V. Revised Response Criteria for Malignant Lymphoma. J Clin Oncol. 2007;25:579–586.
Juweid ME, Cheson BD. Role of Positron Emission Tomography in Lymphoma. J Clin Oncol. 2005;23:4577–80.
Quddus F, Armitage JO. Salvage therapy for Hodgkin's lymphoma. Cancer. 2009;15:161–3.
Seshadri T, Kuruvilla J, Crump M, Keating A. Salvage therapy for relapsed/refractory diffuse large B cell lymphoma. Biol Blood Marrow Transplant. 2008;14(3):259–67.
Zinzani PL, Stefoni V, Tani M, Fanti S, Musuraca G, Castellucci P, et al. Role of [18 F]fluorodeoxyglucose positron emission tomography scan in the follow-up of lymphoma. J Clin Oncol. 2009;27:1781–7.
Canellos GP, Horwich A. Management of recurrent Hodgkin’s disease. In Hodgkin’s disease. Mauch P , Armitage J eds. Lippincott, William & Wilkins, 1999; p. 505–19.
Jerusalem G, Beguin Y, Fassotte MF, et al. Early detection of relapse by whole-body positron emission tomography in the follow-up of patients with Hodgkin's disease. Ann Oncol. 2003;14:123–30.
Liedtke M, Hamlin PA, Moskowitz CH, et al. Surveillance imaging during remission identifies a group of patients with more favorable aggressive NHL at time of relapse: a retrospective analysis of a uniformly-treated patient population. Ann Oncol. 2006;17:909–13.
Zinzani PL, Stefoni V, Tani M, et al. The role of FDG-PET scan in the follow-up of lymphoma: experience on 421 patients. J Clin Oncol. 2009;27:1781–7.
Armitage JO, Loberiza FR. Is there a place for routine imaging for patients in complete remission from aggressive lymphoma? Ann Oncol. 2006;17(6):883–4.
Radford JA, Eardley A, Woodman C, Crowther D. Follow up policy after treatment for Hodgkin's disease: too many clinic visits and routine test? A review of hospital records. Br Med J. 1997;314(7077):343–6.
Gallamini A, Kostakoglu L. Positron emission tomography/computed tomography surveillance in patients with lymphoma: a fox hunt? Haematologica. 2012;97:1–3. PET scan in surveillance of patients in RC after first-line therapy for lymphoma.
Petrausch U, Samaras P, Veit-Haibach P, Tschopp A, Soyka JD, Knuth A, et al. Hodgkin’s lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up? Ann Oncol. 2010;21:1053–7.
Liedtke M, Hamlin PA, Moskowitz CH, Zelenetz AD. Surveillance imaging during remission identifies a group of patients with more favorable aggressive NHL at time of relapse: a retrospective analysis of a uniformly treated patient population. Ann Oncol. 2006;17:909–13.
Weeks JC, Yeap BY, Canellos GP, Shipp MA. Value of follow-up procedures in patients with large-cell lymphoma who achieve a complete remission. J Clin Oncol. 1991;9:1196–203.
El-Galaly TC, Mylam KJ, Brown P, Specht L, Christiansen I, Munksgaard L, et al. Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs. Haematologica. 2012;97:931–6.
Song MK, Chung JS, Lee JJ, Jeong SY, Lee SM, Hong JS, et al. Metabolic tumor volume by positron emission tomography/computed tomography as a clinical parameter to determine therapeutic modality for early stage Hodgkin's lymphoma. Cancer Sci. 2013;104:1656–61.
Mikhaeel NG, Smith D, Dunn J, Phillips M, Fields P, Møller H, Barrington SF: Does quantitative PET-CT predict prognosis in Diffuse Large B-cell Lymphoma? 12-ICML, Lugano, 19 June 2013 Haematol Oncol 2013; 6 [Abstract]. Metabolic tumor volume in aggressive B-cell lymphoma.
Compliance with Ethics Guidelines
Conflict of Interest
Andrea Gallamini and Anna Borra declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gallamini, A., Borra, A. Role of PET in Lymphoma. Curr. Treat. Options in Oncol. 15, 248–261 (2014). https://doi.org/10.1007/s11864-014-0278-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11864-014-0278-4