Metabolic tumor volume predicts outcome in patients with advanced stage follicular lymphoma from the RELEVANCE trial.

BACKGROUND: We investigated the prognostic value of baseline positron emission tomography (PET) parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase III RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R2) versus R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy. PATIENTS AND METHODS: Baseline characteristics of the entire PET-evaluable population (n = 406/1032) were well balanced between treatment arms. The maximal standard uptake value (SUVmax) and the standardized maximal distance between tow lesions (SDmax) were extracted, the standardized distance between two lesions the furthest apart, were extracted. The total metabolic tumor volume (TMTV) was computed using the 41% SUVmax method. RESULTS: With a median follow-up of 6.5 years, the 6-year progression-free survival (PFS) was 57.8%, the median TMTV was 284 cm3, SUVmax was 11.3 and SDmax was 0.32 m-1, with no significant difference between arms. High TMTV (>510 cm3) and FLIPI were associated with an inferior PFS (P = 0.013 and P = 0.006, respectively), whereas SUVmax and SDmax were not (P = 0.08 and P = 0.12, respectively). In multivariable analysis, follicular lymphoma international prognostic index (FLIPI) and TMTV remained significantly associated with PFS (P = 0.0119 and P = 0.0379, respectively). These two adverse factors combined stratified the overall population into three risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6-year PFS of 67.7%, 54.5%, and 41.0%, respectively. No significant interaction between treatment arms and TMTV or FLIPI (P = 0.31 or P = 0.59, respectively) was observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (P = 0.45) with a median PFS of 68.4% in the R-chemo arm versus 71.4% in the R2 arm. CONCLUSIONS: Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance.

Tandem versus single haematopoietic stem cell transplant and BV maintenance in relapsed/refractory Hodgkin lymphoma: A matched cohort analysis from the LYSA.

Autologous hematopoietic stem cell transplant (ASCT) is the standard curative treatment for patients with high-risk relapsed/refractory Hodgkin lymphoma (R/R HL). The AETHERA study showed survival gain with Brentuximab Vedotin (BV) maintenance after ASCT in BV-naive patients, which was recently confirmed in the retrospective AMAHRELIS cohort, including a majority of BV-exposed patients. However, this approach has not been compared to intensive tandem auto/auto or auto/allo transplant strategies, which were used before BV approval. Here, we matched BV maintenance (AMAHRELIS) and tandem SCT (HR2009) cohorts, and observed that BV maintenance was associated with better survival outcome in patients with HR R/R HL.

Risk stratification in diffuse large B-cell lymphoma using lesion dissemination and metabolic tumor burden calculated from baseline PET/CT†.

BACKGROUND: We analyzed the prognostic value of a new baseline positron emission tomography (PET) parameter reflecting the spread of the disease, the largest distance between two lesions (Dmax). We tested its complementarity to metabolic tumor volume (MTV) in a large cohort of diffuse large B-cell lymphoma (DLBCL) patients from the REMARC trial (NCT01122472). PATIENTS AND METHODS: MTVs were defined using the 41% maximum standardized uptake value threshold. From the three-dimensional coordinates, the centroid of each lesion was automatically obtained and considered as the lesion location. The distances between all pairs were calculated. Dmax was obtained for each patient and normalized with the body surface area [standardized Dmax (SDmax)]. RESULTS: From the REMARC trial, 290 patients aged 60-80 years were included: 91% had an advanced stage and 71% International Prognostic Index (IPI) ≥3. High versus low SDmax significantly impacted progression-free survival (PFS) (P < 0.0001) and overall survival (OS) (P = 0.0027). Patients with SDmax > 0.32 m-1 (n = 82) had a 4-year PFS and OS of 46% and 71%, respectively, against 77% and 87%, respectively, for patients with low SDmax. High SDmax and high MTV were independent prognostic factors of PFS (P = 0.0001 and P = 0.0010, respectively) and OS (P = 0.0028 and P = 0.0004, respectively). Combining MTV and SDmax yielded three risk groups with no (n = 109), one (n = 122) or two (n = 59) factors (P < 0.0001 for both PFS and OS). The 4-year PFS were 90%, 63%, 41%, respectively, and the 4-year OS were 95%, 79%, 66%, respectively. In addition, patients with at least two of the three factors including high SDmax, high MTV, Eastern Cooperative Oncology Group (ECOG) ≥2 had a higher number of central nervous system relapse (P = 0.017). CONCLUSIONS: SDmax is a simple feature that captures lymphoma dissemination, independent from MTV. These two PET metrics, SDmax and MTV, are complementary to characterize the disease, reflecting the tumor burden and its spread. This score appeared promising for DLBCL baseline risk stratification.

[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive]. / TEP/TDM et récidive biologique d'adénocarcinome prostatique : apport du 68Ga-PSMA-11 lorsque la 18F-fluorocholine n'est pas contributive.

INTRODUCTION: Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18F-fluorocholine (FCH) PET/CT was non-contributive. PATIENTS AND METHOD: Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. RESULTS: Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). CONCLUSION: 68Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. LEVEL OF EVIDENCE: 5.

Prognostic value of baseline total metabolic tumor volume (TMTV0) measured on FDG-PET/CT in patients with peripheral T-cell lymphoma (PTCL).

BACKGROUND: Most peripheral T-cell lymphoma (PTCL) patients have a poor outcome and the identification of prognostic factors at diagnosis is needed. PATIENTS AND METHODS: The prognostic impact of total metabolic tumor volume (TMTV0), measured on baseline [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography, was evaluated in a retrospective study including 108 PTCL patients (27 PTCL not otherwise specified, 43 angioimmunoblastic T-cell lymphomas and 38 anaplastic large-cell lymphomas). All received anthracycline-based chemotherapy. TMTV0 was computed with the 41% maximum standardized uptake value threshold method and an optimal cut-off point for binary outcomes was determined and compared with others prognostic factors. RESULTS: With a median follow-up of 23 months, 2-year progression-free survival (PFS) was 49% and 2-year overall survival (OS) was 67%. High TMTV0 was significantly associated with a worse prognosis. At 2 years, PFS was 26% in patients with a high TMTV0 (>230 cm(3), n = 53) versus 71% for those with a low TMTV0, [P < 0.0001, hazard ratio (HR) = 4], whereas OS was 50% versus 80%, respectively, (P = 0.0005, HR = 3.1). In multivariate analysis, TMTV0 was the only significant independent parameter for both PFS and OS. TMTV0, combined with PIT, discriminated even better than TMTV0 alone, patients with an adverse outcome (TMTV0 >230 cm(3) and PIT >1, n = 33,) from those with good prognosis (TMTV0 ≤230 cm(3) and PIT ≤1, n = 40): 19% versus 73% 2-year PFS (P < 0.0001) and 43% versus 81% 2-year OS, respectively (P = 0.0002). Thirty-one patients (other TMTV0-PIT combinations) had an intermediate outcome, 50% 2-year PFS and 68% 2-year OS. CONCLUSION: TMTV0 appears as an independent predictor of PTCL outcome. Combined with PIT, it could identify different risk categories at diagnosis and warrants further validation as a prognostic marker.

Long-term outcome in idiopathic granulomatous mastitis: a western multicentre study.

AIM: To investigate the presentation, disease course and long-term outcome of a western cohort of idiopathic granulomatous mastitis (IGM) and to analyse the impact of different therapeutic strategies. METHODS: Multicentre retrospective study of 23 women followed over an extended period. Patients were recruited in nine French internal medicine departments. RESULTS: The median follow-up was 6 years. IGM presented commonly as a single inflammatory unilateral extra-areolar lump of varying size. Clinical course was heterogeneous and frequently remitting/relapsing. Most patients had at least one recurrence (18/23, 78%). The mean number of recurrences was 1.3 ± 1.5. Seven women had a bilateral evolution. Twelve women received steroids (corticosteroids). Only two of these did not respond to corticosteroids, whereas six relapsed when dose was tapered off. Nine patients received colchicine and/or hydroxychloroquine. First-line treatment consisted of excisional surgery in eight cases. At the date of last interview, 91% of the patients declared to be healed, 15 being free of treatment. However, 12/21 (57%) reported significant sequelae (unsightly scars: eight and/or lasting pain: six). Unsightly scars were not more prevalent in patients who had received steroids whereas they tended to be more frequent after breast excisional surgery. In addition, we found that excisional surgery did not prevent recurrences more successfully than a conservative approach. CONCLUSIONS: Despite its retrospective nature, this Caucasian series provides novel information regarding long-term outcomes in IGM and argues in favour of conservative approaches. The value of immunomodulatory drugs such as colchicine or hydroxychloroquine deserves further investigation.

[Post-transfusion acute lung injury (Trali) after plasma infusion in a patient having a constitutional thrombotic microangiopathy]. / Syndrome d'oedème pulmonaire lésionnel aigu post-transfusionnel (Trali) après perfusion de plasma frais congelé au cours d'une microangiopathie thrombotique congénitale.

INTRODUCTION: Transfusion-related acute lung injury is a post-transfusion interstitial lung injury. CASE REPORT: We reported a post-transfusion acute lung injury in a 23-years old woman having a chronic thrombotic microangiopathy related to an ADAMTS 13 constitutional deficiency receiving monthly plasma infusion for six years. The temporal relationship between the lung injury and the infusion of fresh frozen plasma led to the diagnosis of transfusion-related acute lung injury. The finding in the donor of the transfused plasma of an anti-HLA class II antibody recognizing HLA-DR52 present on leucocytes of the recipient suggests a causal relationship between this antigen-antibody conflict and the triggering of the TRALI. This chronic pathologic state requiring monthly plasma transfusions for thrombotic accident prevention raises the question of the selection of plasma obtained from non-immunized donors. CONCLUSION: The occurrence of a post transfusion pulmonary edema without cardio-vascular overload, must lead to consider a TRALI especially in predisposing clinical situations. In the case reported the role of constitutional ADAMTS 13 deficiency in genesis of TRALI is considered.

[Transfusion-related acute lung injury]. / Oedème pulmonaire lésionnel aigu post-transfusionnel ou Trali.

OBJECTIVES: The transfusion-related acute lung injury frequency was for a long time underestimated since it lacked both a widely accepted clinical definition and a comprehensive etiologic description. Recent clinical and biological data have underlined its frequency and have allowed a better understanding of its mechanisms. CURRENT KNOWLEDGE AND KEY POINTS: Trali is an interstitial lung injury occurring within 6 hours after the beginning of a blood transfusion. This time relationship between blood injection and the occurrence of lung edema is sufficient for a positive diagnosis, if any other cause of interstitial lung edema have been excluded. The clinical definition relies on a desaturation of arterial blood associated to a lack of any cardiac failure or circulation overload. The link between transfusion and lung edema is not univocal and several categories of mechanisms have been discussed. At least 2 of them are well identified; the first one is an immune conflict, and the second one is an activation of neutrophils by injection of biological modifiers such as lipids or CD40 soluble ligand. Evidences exist for the occurrence of Trali only in predisposing condition that mostly consists of a preceding leucostase in lung capillaries. Trali is treated like other lung interstitial edema by oxygen therapy and mechanical ventilation. FUTURE PROJECTS: A better knowledge of Trali offers the opportunity of improving the understanding of the role of blood transfusion in lung edema occurring in complex situations and open the way for a better definition of at risk patient and at risk blood components.