The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma

Abstract

The choice of a rituximab-based regimen and the prognostic significance of interim 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in primary mediastinal large B cell lymphoma (PMBCL) are debatable. We evaluated the clinical features and outcomes of 95 consecutive patients with PMBCL who were treated between 1985 and 2009. Forty-three patients received rituximab-based chemotherapy, R-VACOP-B (N = 30) or R-CHOP21 (N = 13), whereas 52 patients were treated with VACOP-B (N = 47) or CHOP21 (N = 5). Radiotherapy was not given. Patients who received rituximab had a 5-year progression-free survival (PFS) of 79 % and overall survival (OS) of 97 % compared with 58 % (p = 0.06) and 88 % (p = 0.2), respectively, without rituximab. Five-year PFS in patients treated with R-VACOP-B, R-CHOP21, VACOP-B, and CHOP21 were 83, 69, 62, and 20 %, respectively (p = 0.039). However, direct comparison showed that the difference between PFS rates in patients receiving R-VACOP-B compared to R-CHOP21 was not statistically significant (p = 0.3). None of the standard clinical risk factors predicted for PFS and OS in patients receiving rituximab (R)-chemotherapy. Mid-interim FDG-PET/CT scans were performed in 30/43 patients who received R-chemotherapy. The negative predictive values of mid-PET activity were high (100 % for R-VACOP-B and 86 % for R-CHOP21) while the positive predictive values (PPV) were relatively low (30 and 75 %, respectively). Despite the low PPV, the 5-year PFS for mid-PET-negative patients (N = 16) was significantly higher (94 %) than that for mid-PET-positive (N = 14) patients (57 %, p = 0.015). This retrospective analysis demonstrates that the superiority of VACOP-B over CHOP21 for treatment of PMBCL disappeared once rituximab was added. The potential benefit of using interim PET activity as a guide for continuing therapy in patients with PMBCL remains unclear due to the relatively low PPV.

Role of radiotherapy in the treatment of primary mediastinal large B-cell lymphoma

“…The current National Comprehensive Cancer Network 2013 guidelines recommended rituximab as the first-line treatment for PMLBCL. Rituximab combined with chemotherapy has been confirmed to be very effective and safe for PMLBCL in multiple studies (14,15,22), and the superiority of certain intensive regimens over CHOP for treatment of PMBCL disappeared once rituximab was added (23).…”

Role of FDG-PET/CT in staging and first-line treatment of Hodgkin and aggressive B-cell lymphomas

“…This observation may guide effective treatment modifications. Early response assessment has provided a major prognostic clue for patients with intermediate and advanced stage HL [52,53] as well as in DLBCL [54], while the results are controversial in PMLBCL [55,56]. However, even current recommendations do not propose the use of iPET to guide treatment decisions, because there is still no relevant evidence of survival benefit from randomized trials [2,3].…”

“…Data from two studies are conflicting [56,74]. In a study from Memorial Sloan Kettering Cancer Center, 51 patients with PMLBCL received four cycles of accelerated R-C 1000 HOP-14 and underwent iPET, which was negative in 27 and positive in 24 patients [74].…”

“…No difference in PFS emerged according to iPET result irrespective of the criterion used to define positivity. In a retrospective study, where the initial treatment regimen was continued irrespective of iPET result and RT was not given, 30 patients underwent iPET (19 after Rituximab, etoposide, adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin (R-VACOP-B and 11 after R-CHOP) [56]. A positive iPET was observed in 14/30 patients and the 3-year PFS was 94 % versus 57 % for iPET− and iPET+ cases (p= 0.015).…”

Primary mediastinal large B-cell lymphoma

“…Epidemiology PMBCL makes up 2-4% [8][9][10][11][12] of all non-Hodgkin's lymphomas (NHL) and 6-12% of all DLBCLs [10,[13][14][15]. It occurs predominantly during the third and fourth decades of life and is more common in women (46-78% cases) (Table 1) [10,16].…”