Ceriani, Luca

Johnson, Peter W. M.

MARTELLI, Maurizio

Zucca, Emanuele

English

Luca Ceriani

Peter W.M. Johnson

Maurizio Martelli

Emanuele Zucca

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International Journal of Radiation Oncology*Biology*Physics

In Reply to Adams and Kwee

Archivio della ricerca- Università di Roma La Sapienza

Comments International Journal of Radiation Oncology  Biology  Physics870(3 of 88) rather than the discriminatory value of fluo-rodeoxyglucose positron emission tomography (FDG-PET).Even a test without any discriminatory value (which wouldclassify all patients as having a CMR) would have anexcellent NPVof 96.6% (85 of 88) in that scenario. Thus, theFDG-PET results have only minor additional value. Of note,in diffuse large B-cell lymphoma, which is known to have aworse prognosis than PMBCL, the NPVof end-of-treatmentFDG-PET diminishes drastically (3). One study even showedthat patients with high-risk diffuse large B-cell lymphomahave a very dismal progression-free survival of only 38.5%despite attaining a CMR (4, 5). The failure of FDG-PET toexclude residual disease results from its low spatial resolu-tion (6). Also, the positive predictive value in the study byCeriani et al (1) was only 30% (3 of 10) when the Luganocriteria were applied. Because biopsy confirmation beforesalvage therapy was not reported, even these 3 cases of re-sidual disease might be questionable. In addition, post-therapy FDG-PET scans have a high (biopsy-proven) false-positive rate (7), and death can result from erroneouslyinitiated toxic high-dose therapies rather than persistentlymphoma. However, despite early (presumed) identificationof refractory disease, 3 of 3 patients died, which confirms theresults of previous studies that early (asymptomatic) residualdisease detection does not improve outcomes (8).In conclusion, the NPV of post-therapy FDG-PET ishighly influenced by the low incidence of disease relapse inPMBCL. Furthermore, early detection of residual disease inPMBCL using the Lugano criteria is not feasible, consid-ering the low positive predictive value of FDG-PET in thissetting and that early residual disease detection does notimprove patient outcomes.Hugo J.A. Adams, MD, PhDDepartment of Radiology and Nuclear ImagingUniversity Medical Center UtrechtUtrecht, The NetherlandsThomas C. Kwee, MD, PhDDepartment of RadiologyNuclear Medicine and Molecular ImagingUniversity Medical Center GroningenGroningen, The Netherlandshttp://dx.doi.org/10.1016/j.ijrobp.2016.12.007Conflict of interest: none.References1. Ceriani L, Martelli M, Gospodarowicz MK, et al. Positron emissiontomography/computed tomography assessment after immunochemo-therapy and irradiation using the Lugano classification criteria in theIELSG-26 study of primary mediastinal B-cell lymphoma. Int J RadiatOncol Biol Phys 2017;97:42-49.2. Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging inthe staging and response assessment of lymphoma: Consensus of theInternational Conference on Malignant Lymphomas Imaging WorkingGroup. J Clin Oncol 2014;32:3048-3058.3. Adams HJ, Nievelstein RA, Kwee TC. Prognostic value of completeremission status at end-of-treatment FDG-PET in R-CHOP-treateddiffuse large B-cell lymphoma: Systematic review and meta-analysis.Br J Haematol 2015;170:185-191.4. Bishton MJ, Hughes S, Richardson F, et al. Delineating outcomes ofpatients with diffuse large B cell lymphoma using the NationalComprehensive Cancer Network-International Prognostic Index andpositron emission tomography-defined remission status: A population-based analysis. Br J Haematol 2016;172:246-254.5. Adams HJ, Kwee TC. Does end-of-treatment FDG-PET provide anyadditional prognostic value to the pre-treatment NCCN-IPI score? [e-pubahead of print].Br JHaematol 2016; http://dx.doi.org/10.1111/bjh.14050.6. Adams HJ, Kwee TC. A negative 18F-FDG-PET scan can neverexclude residual disease. Nucl Med Commun 2016;37:102-103.7. Adams HJ, Kwee TC. Proportion of false-positive lesions at interim andend-of-treatment FDG-PET in lymphoma as determined by histology:Systematic review and meta-analysis. Eur J Radiol 2016;85:1963-1970.8. El-Galaly TC, Jakobsen LH, Hutchings M, et al. Routine imaging fordiffuse large B-cell lymphoma in first complete remission does notimprove post-treatment survival: A Danish-Swedish population-basedstudy. J Clin Oncol 2015;33:3993-3998.In Reply to Adams and KweeTo the Editor: Biologic and clinical particularities to pri-mary mediastinal B-cell lymphoma (PMBCL) exist thatconfound the assertions in the letter from Adams andKwee (1, 2). They did not consider that nearly all patientswill have a bulky mediastinal mass at diagnosis andsimilarly will have significant residual lesions visible oncomputed tomography scans after therapy, whether suc-cessful or not. Moreover, despite the excellent outcomesfor most patients, the few who develop recurrent diseaseare extremely difficult to salvage with second-line therapy,making optimization of first-line therapy the dominantpriority.Although the high success rate of therapy results in a highnegative predictive value for fluoro-deoxyglucose positronemission tomography (FDG-PET), it remains the bestdiscriminator of the outcome and is certainly greatly supe-rior to computed tomography alone. The suggestion thatFDG-PET scanning cannot wholly exclude the presence ofresidual disease owing to its low resolution, although theo-retically possible, has simply not been borne out by our datafor PMBCL, which showed that the FDG-PET findings are avalid surrogate of long-term outcomes (1, 3, 4).The essential clinical need is to know whether thepost-treatment complete metabolic response predictslong-term remission. In this context, PET-computed to-mography will be superior to other imaging methods.Also, in PMBCL, owing to the intrinsic characteristics ofthe disease and the efficacy of available therapies, FDG-PET will perform much better than in other diffuse largeB-cell lymphomas.The assertion that early identification of relapse has noeffect on outcome is also flawed, because it was determinedVolume 97  Number 4  2017 Comments 871from data from patients with other types of diffuse largeB-cell lymphoma in complete remission. We would supportthe need for repeat biopsy wherever possible to confirm thetrue PET-positive findings. However, mediastinal biopsy ofsmall residual lesions can be technically difficult, and it isoften necessary to begin treatment of overt clinical andradiologic progression without delay.Of the 3 patients who died in our series, progressivedisease was confirmed by clinical and imaging follow-upstudies, and all the deaths were related to the lymphoma.Luca Ceriani, MDNuclear Medicine and PET-CT CentreOncology Institute of Southern SwitzerlandBellinzona, SwitzerlandPeter W.M. Johnson, MDCancer Research UK CentreUniversity of SouthamptonSouthampton, United KingdomMaurizio Martelli, MDDepartment of Cellular Biotechnologies and HematologySapienza UniversityRome, ItalyEmanuele Zucca, MDDepartment of OncologyOncology Institute of Southern SwitzerlandBellinzona, Switzerlandhttp://dx.doi.org/10.1016/j.ijrobp.2016.12.001References1. Ceriani L, Martelli M, Gospodarowicz MK, et al. Positron emissiontomography/computed tomography assessment after immunochemo-therapy and irradiation using the Lugano classification criteria in theIELSG-26 study of primary mediastinal B-cell lymphoma. Int J RadiatOncol Biol Phys 2017;97:42-49.2. Adams HJA, Kwee WC. In Regard to Cerani et al. Intl J Radiat OncolBiol Phys 2017;97:869-870.3. Martelli M, Ceriani L, Zucca E, et al. [18F]fluorodeoxyglucose positronemission tomography predicts survival after chemoimmunotherapy forprimary mediastinal large B-cell lymphoma: Results of the Interna-tional Extranodal Lymphoma Study Group IELSG-26 study. J ClinOncol 2014;32:1769-1775.4. Ceriani L, Martelli M, Zinzani PL, et al. Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primarymediastinal (thymic) large B-cell lymphoma. Blood 2015;126:950-956.

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