Organ Infiltration and Patient Risk After Multivisceral Surgery for Primary Retroperitoneal Liposarcomas.

BACKGROUND: The extent of histological organ involvement (HOI) to organs and structures of a retroperitoneal liposarcoma may have prognostic implications. This study investigated incidence, characteristics, and risk association of HOI in these patients. PATIENTS AND METHODS: Data of patients who underwent multivisceral resection for primary liposarcoma (2009-2014) were retrospectively analyzed. HOI was the variable of interest and was classified into four degrees: absent (HOI-0), perivisceral (HOI-1), initial (HOI-2), and advanced (HOI-3). Primary endpoint was overall survival (OS). Secondary endpoint was disease-free survival (DFS). The prognostic value of HOI was adjusted for preoperative treatment and the Sarculator nomogram score. RESULTS: A total of 109 patients were included. HOI-0, HOI-1, HOI-2, and HOI-3 were detected in 9 (8.3%), 11 (10.1%), 43 (39.4%), and 46 (42.2%) patients. Median follow-up was 8.4 years [interquartile range (IQR) 7.2-9.6 years]. There were 68 recurrences and 50 patient deaths observed, resulting in a 10-year OS and DFS of 51.1% [95% confidence interval (CI) 41.9-62.1%] and 34.1% (95% CI 25.2-46.1%), respectively. Clinically relevant HOIs (HOI-2 and HOI-3) were found in 35/45 (77.8%) and 54/64 (84.4%) cases of well- and de-differentiated liposarcomas, respectively. On multivariable survival analysis, patients with HOI-3 had significantly shorter OS (HOI-3 vs HOI-0/HOI-1 HR 2.92; p = 0.012) and DFS (HOI-3 vs HOI-0/HOI-1 HR 2.23; p = 0.045), independently of the nomogram score (OS: HR 2.93; p < 0.001; DFS: HR 1.78; p = 0.003). CONCLUSIONS: Initial and advanced HOIs are frequently detected in both well-differentiated and de-differentiated liposarcomas, supporting that multivisceral resection may be needed. HOI stratifies the risk of patients with primary retroperitoneal liposarcoma.

Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse.

Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood-brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.