Deep learning-based overall survival prediction model in patients with rare cancer: a case study for primary central nervous system lymphoma

Purpose Primary central nervous system lymphoma (PCNSL) is a rare, aggressive form of extranodal non-Hodgkin lymphoma. To predict the overall survival (OS) in advance is of utmost importance as it has the potential to aid clinical decision-making. Though radiomics-based machine learning (ML) has demonstrated the promising performance in PCNSL, it demands large amounts of manual feature extraction efforts from magnetic resonance images beforehand. deep learning (DL) overcomes this limitation.Methods In this paper, we tailored the 3D ResNet to predict the OS of patients with PCNSL. To overcome the limitation of data sparsity, we introduced data augmentation and transfer learning, and we evaluated the results using r stratified k-fold cross-validation. To explain the results of our model, gradient-weighted class activation mapping was applied.Results We obtained the best performance (the standard error) on post-contrast T1-weighted (T1Gd)-area under curve = 0.81(0.03), accuracy = 0.87(0.07), precision = 0.88(0.07), recall = 0.88(0.07) and F1-score = 0.87(0.07), while compared with ML-based models on clinical data and radiomics data, respectively, further confirming the stability of our model. Also, we observed that PCNSL is a whole-brain disease and in the cases where the OS is less than 1 year, it is more difficult to distinguish the tumor boundary from the normal part of the brain, which is consistent with the clinical outcome.Conclusions All these findings indicate that T1Gd can improve prognosis predictions of patients with PCNSL. To the best of our knowledge, this is the first time to use DL to explain model patterns in OS classification of patients with PCNSL. Future work would involve collecting more data of patients with PCNSL, or additional retrospective studies on different patient populations with rare diseases, to further promote the clinical role of our model

Diagnosis and Treatment Using Autologous Stem-Cell Transplantation in Primary Central Nervous System Lymphoma: A Systematic Review

Background: Consolidation therapy has improved the outcome of newly diagnosed PCNSL patients. Whole-brain radiotherapy (WBRT) was the first consolidation strategy used and represented the gold standard for many years, but at the expense of a high risk of neurotoxicity. Thus, alternative strategies are being investigated in order to improve disease outcomes and to spare the neurocognitive side effects due to WBRT. Methods: We reviewed published studies on PCNSL patients treated with HDC/ASCT, focusing on the efficacy and safety of the conditioning regimens. Prospective and retrospective studies, published in the English language from 1992 to 2022, in high-quality international journals were identified in PubMed. Results: Consolidation with HDC containing highly CNS-penetrating agents (thiotepa, busulfan or BCNU) followed by ASCT provided long-term disease control and survival in PCNSL patients. Two prospective randomized studies, comparing HDC/ASCT versus WBRT, reported similar progression-free survival (PFS) and similar results on the decline in neurocognitive functions in a substantial proportion of patients after WBRT but not after HDC-ASCT. A recent randomized study comparing HDC/ASCT versus non-myeloablative consolidation reported a longer PFS in transplanted patients. Conclusion: ASCT conditioned with regimens, including highly CNS-penetrating agents, represents, to date, the best choice among the available consolidation strategies for fit newly diagnosed PCNSL patients

Safety and efficacy of a dose-dense short-term therapy in patients with MYC-translocated aggressive lymphoma

Patients with aggressive B-cell lymphoma and MYC rearrangement at FISH exhibit poor outcome after R-CHOP. In the last decade, 68 patients with Burkitt lymphoma (BL; n=46) or high-grade B-cell lymphoma (single, double or triple hit; HGBCL; n=22) were treated with a dose-dense, short-term therapy termed "CARMEN regimen", at five Italian Centers. Forty-six (68%) patients were HIV-positive. CARMEN included a 36-day induction with sequsingle weekly doses of cyclophosphamide, vincristine, rituximab, methotrexate, etoposide, and doxorubicin plus intrathecal chemotherapy, followed by high-dose-cytarabine-based consolidation. Patients who did not achieve complete remission (CR) after induction received BEAM-conditioned ASCT after consolidation. Sixty-one (90%) patients completed induction and 59 (87%) completed consolidation. Seventeen patients received ASCT. Grade-4 hematological toxicity was common but did not cause treatment discontinuation; grade-4 non-hematological toxicity was recorded in 11 (16%) patients, with grade-4 infections in 6 (9%). Six (9%) patients died of toxicity (sepsis in four, COVID-19, ARDS). CR rate after the whole treatment was 73% (95%CI=55-91%) for HGBCL patients and 78% (95%CI=66-90%) for BL patients. At a median follow-up of 65 (IQR 40-109) months, 48 patients remain event-free, with a 5-year PFS of 63% (95%CI=58-68%) for HGBCL and 72% (95%CI=71-73%) for BL, with a 5-year OS of 63% (95%CI=58-68%) and 76% (95%CI=75-77%), respectively. HIV seropositivity had not a detrimental effect on outcome. This retrospective study shows that CARMEN is a safe and active regimen both in HIV-negative and -positive patients with MYC-rearranged lymphomas. Encouraging survival figures, attained with a single dose of doxorubicin and cyclophosphamide, deserve further investigation in HGBCL and other aggressive lymphomas