We thank Adams and colleagues for their interest in our research (1) on the prognostic value of baseline total metabolic tumor volume (TMTV) combined with molecular data in patients with diffuse large B-cell lymphoma (DLBCL). They give us the opportunity to discuss TMTV and clinical prognostic indices.

Adams and colleagues underlined the strong role of clinical indices, especially National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI), the new one developed for DLBCL since the introduction of rituximab. We agree with the importance of clinical indices, which have been established on large populations, but it does not reduce the potential interest of quantitative PET metrics and gene expression profiling, which are aimed to improve risk stratification for personalized medicine. In our study, we decided to adjust our results for the age-adjusted IPI (aaIPI) instead of NCCN-IPI because the latter was not yet included in the recent European Society of Medical Oncology (ESMO) recommendations. Moreover, we had tested this index in our population. It was predictive of progression-free survival (PFS) and overall survival (OS) even better than reported by Adams and colleagues (2): high NCCN-IPI (>3) was significantly associated with a lower PFS and OS (P = 0.0031 and P = 0.0194). However aaIPI > 1 was a better predictor (P = 0.0041 for PFS and P = 0.0075 for OS). Indeed, it is probably difficult to demonstrate the superiority of this important graded score, NCCN-IPI over aaIPI in small groups of patients.

The comments by Adams and colleagues led us to combine NCCN-IPI with TMTV, taking high NCCN-IPI and high TMTV as adverse factors. Interestingly, within patients with high NCCN-IPI, two groups of patients could be identified: a group with high TMTV, which had a very poor outcome (5-year PFS = 35%, 5-year OS = 42%), and a group with low TMTV, which had a much better outcome (5-year PFS = 64%, 5-year OS = 69%, P = 0.001 and P = 0.01, respectively). Patients with low NCCN-IPI had an excellent outcome irrespective of their TMTV (5-year PFS = 80%, 5-year OS = 77%; Fig. 1).

Figure 1.

Kaplan–Meier estimates of PFS and OS according to baseline TMTV combined with NCCN-IPI.

Figure 1.

Kaplan–Meier estimates of PFS and OS according to baseline TMTV combined with NCCN-IPI.

Close modal

Adams and colleagues stated that TMTV was not predictive of PFS and OS in DLBCL. However, using another method of TMTV measurement, Mikhaeel and colleagues (3) have recently shown that TMTV was a strong prognosticator of outcome, confirming the results of our group. Adams and colleagues could not demonstrate the prognostic value of TMTV in their study of 73 retrospectively included DLBCL patients (2). This is probably partly due to the small number of patients included in their series and to the shorter follow-up with fewer events than in our study. Moreover, their study revealed some difficulties to use the 41% SUVmax threshold method. Because of the software limitation, they could draw only spherical region of interest (ROI) around the lesion, which prevented the accurate delimitation of certain lesions, such as a diffuse splenic involvement. Adams and colleagues also explained that they placed ROI around conglomerates of lesions, which means that in a single ROI, they could have mixed lymph nodes with different SUVmax value and consequently underestimated the volume.

Adams and colleagues argue in their letter that early and end-of-treatment PET cannot be used as a reliable prognosticator and that we have “claimed” the opposite. It was not the scope of our study, and we only pointed out in the introduction that PET response could be used as a good prognosticator of outcome, as demonstrated by several recent well-conducted studies (3, 4). In the discussion, we reminded the reader that interim PET was not yet recommended by the ESMO, except in the setting of clinical trials. Indeed, the aim of our study was to investigate baseline PET and metabolic tumor volume as an earlier prognosticator and not to discuss the merits of early and end treatment PET in DLBCL.

By integrating NCCN-IPI in our study, we have underlined the strong prognostic potential of TMTV for risk stratification, which could be helpful for tailoring therapy. Our results are in agreement with the recently published study of Song and colleagues (5), who similarly have used the NCCN-IPI and TMTV in DLBCL patients with bone marrow involvement and shown that both had independent clinical impact.

See the original Letter to the Editor, p. 3413

No potential conflicts of interest were disclosed.

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