Rapid diagnosis and initiation of treatment has a crucial role in the prognosis of primary central nervous system lymphoma

Non peer reviewe

Survival of patients with mantle cell lymphoma in the rituximab era : Retrospective binational analysis between 2000 and 2020

Mantle cell lymphoma (MCL) is a rare peripheral B-cell lymphoma characterised by eventual relapse and progression towards a more aggressive disease biology. With the introduction of rituximab- and cytarabine-based immunochemotherapy regimens, the prognosis of the disease has changed dramatically over the last two decades. To assess the real-world survival of patients with MCL, we used a population-based cohort of 564 patients with MCL who were diagnosed and treated between 2000 and 2020. Patient data were collected from seven Finnish treatment centres and one Spanish treatment centre. For the entire patient population, we report a 2-year overall survival (OS) rate of 77%, a 5-year OS of 58%, and a 10-year OS of 32%. The estimated median OS was 80 months after diagnosis. MCL is associated with increased mortality across the entire patient population. Additionally, we assessed the survival of patients after MCL relapse with the aim of establishing a cut-off point of prognostic significance. Based on our statistical analysis of survival after the first relapse, disease progression within 24 months of the initial diagnosis should be considered as a strong indicator of poor prognosis.publishedVersionPeer reviewe

Real-world Data : MCL2 Protocol Demonstrates Excellent Treatment Results among Patients with Mantle Cell Lymphoma Not Fulfilling the Original Trial Inclusion Criteria

Non peer reviewe

Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events

Background: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. Methods: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Results: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively). Conclusions: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.Peer reviewe

The prognostic and predictive role of tumor-infiltrating lymphocytes (FoxP3 + and CD8 +) and tumor-associated macrophages in early HER2 + breast cancer

Purpose In HER2-positive (HER2 +) breast cancer, tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) may influence the efficacy of the HER2-antibody trastuzumab and the patient’s outcome. In this HER2 + patient cohort, our aim was to study the numbers of FoxP3 + regulatory TILs and CD8 + cytotoxic TILs, their correlations with CD68 + and CD163 + TAMs, and the prognostic and predictive value of the studied factors. Methods We evaluated 139 non-metastatic HER2 + breast cancer patients operated between 2001 and 2008. The FoxP3+TIL count (FoxP3+TILs) was assessed using the hotspot method, and the CD8 + TIL count (CD8+mTILs) utilizing a digital image analysis from invasive margin areas. The ratios between CD8+mTILs and FoxP3+TILs as well as CD8+mTILs and TAMs were calculated. Results FoxP3 + TILs and CD8 + mTILs correlated positively with each other (p<0.001). FoxP3+TILs had a positive correlation with CD68+and CD163+TAMs (p≤0.038), while CD8 + mTILs correlated only with CD68+TAMs (p<0.001). In the HER2 + and hormone receptor-positive Luminal B subgroup, high numbers of FoxP3+TILs were associated with shorter disease-free survival (DFS) (54% vs. 79%, p = 0.040). The benefit from adjuvant trastuzumab was extremely significant among patients with a high CD8 + mTILs/CD68 + TAMs ratio, with overall survival (OS) 84% vs. 33% (p = 0.003) and breast cancer-specific survival (BCSS) 88% vs. 48% (p = 0.009) among patients treated with or without trastuzumab, respectively. Conclusion In the HER2 + Luminal B subgroup, high FoxP3 + TILs were associated with shorter DFS. A high CD8 + mTILs/CD68 + TAMs ratio seems to associate with impressive efficacy of trastuzumab.peerReviewe

Primary central nervous system lymphoma high incidence and poor survival in Finnish population-based analysis

Abstract Background: We report here the first population-based incidence rates and prognosis of primary central nervous system lymphoma (PCNSL) in Finland. Methods: Finnish Cancer Registry data by histological diagnosis and tumor location (2007–2017) for cases with diffuse large B-cell lymphoma. Results: During 2007–2017, 392 new cases of PCNSL were reported (195 males, 197 females). The average age-adjusted incidence was 0.68/100,000 person-years. Incidence for males was 0.74/100,000 and for females 0.63/100,000, respectively. The incidence was highest, 2.93/100,000, among people aged 75–79 years. Concerning all cases in 2007–2017 the 2-year age-adjusted relative survival rate was 33% and the corresponding 5-year survival rate was 26%. Among patients under the age of 70, the age-adjusted 5-year relative survival rate increased from 36% in 2007–2012 to 43% for 2013–2017. Among patients aged 70+ the corresponding survival rates were poor, 7 and 9%. Conclusions: PCNSL incidence in Finland is among the highest reported in the world. The annual increase in incidence was 2.4%. The prognosis is still dismal, especially in elderly patients

Blood–Brain Barrier Disruption (BBBD)-Based Immunochemotherapy for Primary Central Nervous System Lymphoma (PCNSL), Early Results of a Phase II Study

Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood–brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood–brain barrier disruption treatment was initiated 3–4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood–brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood–brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile