Search

Abstract: Patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBL-MYC/BCL2) respond poorly to immunochemotherapy compared with patients with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) without a MYC rearrangement. This suggests a negative impact of lymphoma-intrinsic MYC on the immune system. To investigate this, we compared circulating T cells and natural killer (NK) cells of patients with HGBL-MYC/BCL2 (n = 66), patients with DLBCL NOS (n = 53), and age-matched healthy donors (HDs; n = 16) by flow cytometry and performed proliferation, cytokine production, and cytotoxicity assays. Compared with HDs, both lymphoma subtypes displayed similar frequencies of CD8+ T cells but decreased CD4+ T cells. Regulatory T-cell (Treg) frequencies were reduced only in patients with DLBCL NOS. Activated (HLA-DR+/CD38+) T cells, PD-1+CD4+ T cells, and PD-1+Tregs were increased in both lymphoma subtypes, but PD-1+CD8+ T cells were increased only in HGBL-MYC/BCL2. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of senescent T cells than HDs. Functional assays showed no overt differences between both lymphoma groups and HDs. Deeper analyses revealed that PD-1+ T cells of patients with HGBL-MYC/BCL2 were exhausted with impaired cytokine production and degranulation. Patients with DLBCL NOS, but not patients with HGBL-MYC/BCL2, exhibited higher frequencies of NK cells expressing inhibiting receptor NKG2A. Both lymphoma subtypes exhibited lower TIM-3+- and DNAM-1+-expressing NK cells. Although NK cells of patients with HGBL-MYC/BCL2 showed less degranulation, they were not defective in cytotoxicity. In conclusion, our results demonstrate an increased exhaustion in circulating T cells of patients with HGBL-MYC/BCL2. Nonetheless, the overall intact peripheral T-cell and NK-cell functions in these patients emphasize the importance of investigating potential immune evasion in the microenvironment of MYC-rearranged lymphomas., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background and Purpose: In the BOOG 2013-08 trial (NCT02271828), cT1-2N0 breast cancer patients were randomized between breast conserving surgery with or without sentinel lymph node biopsy (SLNB) followed by whole breast radiotherapy (WBRT). While awaiting primary endpoint results (axillary recurrence rate), this study aims to perform a quality assurance analysis on protocol adherence and (incidental) axillary radiation therapy (RT) dose., Materials and Methods: Patients were enrolled between 2015 and 2022. Data on prescribed RT and (in 25% of included patients) planning target volumes (PTV) parameters were recorded for axillary levels I-IV and compared between treatment arms. Multivariable linear regression analysis was performed to determine prognostic variables for incidental axillary RT dose., Results: 1,439/1,461 included patients (98.5%) were treated according to protocol and 87 patients (5.9%) received regional RT (SLNB 10.9%, no-SLNB 1.5 %). In 326 patients included in the subgroup analysis, the mean incidental PTV dose at axilla level I was 59.5% of the prescribed breast RT dose. In 5 patients (1.5%) the mean PTV dose at level I was ≥95% of the prescribed breast dose. No statistically or clinically significant differences regarding incidental axillary RT dose were found between treatment arms. Tumour bed boost (yes/no) was associated with a higher incidental mean dose in level I (R 2  = 0.035, F(6, 263) = 1.532, p 0.168)., Conclusion: The results indicate that RT-protocol adherence was high, and that incidental axillary RT dose was low in the BOOG 2013-08 trial. Potential differences between treatmentarms regarding the primary endpoint can thus not be attributed to different axillary radiation doses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.

Purpose: Follow-up for breast cancer survivors consists of after care and surveillance. The benefits of routine surveillance visits remain debatable. In this study we compared the severity of locoregional recurrences (LRRs) and the subsequent risk of a distant metastasis (DM) between LRRs detected at routine and interval visits., Methods: Women diagnosed with early breast cancer between 2003 and 2008 in one of the 15 participating hospitals, and who developed a LRR as first event after primary treatment, were selected from the Netherlands Cancer Registry (Cohort A). Chi-squared tests were used to compare the severity of routine- and interval-detected local recurrences (LRs) and regional recurrences (RRs), using tumor size, tumor grade, and number of positive lymph nodes. Data on the development of a subsequent DM after a LRR were available for a subset of patients (Cohort B). Cohort B was used to estimate the association between way of LRR-detection and risk of a DM., Results: Cohort A consisted of 109 routine- and 113 interval-LRR patients. The severity of routine-detected LRs or RRs and interval-detected LRs or RRs did not significantly differ. Cohort B consisted of 66 routine- and 61 interval-LRR patients. Sixteen routine- (24%) and 17 (28%) interval-LRR patients developed a DM. After adjustment, way of LRR-detection was not significantly associated with the risk of a DM (hazard ratio: 1.22; 95% confidence interval: 0.49-3.06)., Conclusion: The current study showed that routine visits did not lead to less severe LRRs and did not decrease the risk of a subsequent DM., (© 2022. The Author(s).)

Background: Regular follow-up after treatment for breast cancer is crucial to detect potential recurrences and second contralateral breast cancer in an early stage. However, information about follow-up patterns in the Netherlands is scarce., Patients and Methods: Details concerning diagnostic procedures and policlinic visits in the first 5 years following a breast cancer diagnosis were gathered between 2009 and 2019 for 9916 patients from 4 large Dutch hospitals. This information was used to analyze the adherence of breast cancer surveillance to guidelines in the Netherlands. Multivariable logistic regression was used to relate the average number of a patient's imaging procedures to their demographics, tumor-treatment characteristics, and individual locoregional recurrence risk (LRR), estimated by a risk-prediction tool, called INFLUENCE., Results: The average number of policlinic contacts per patient decreased from 4.4 in the first to 2.0 in the fifth follow-up year. In each of the 5 follow-up years, the share of patients without imaging procedures was relatively high, ranging between 31.4% and 33.6%. Observed guidelines deviations were highly significant (P < .001). A higher age, lower UICC stage, and having undergone radio- or chemotherapy were significantly associated with a higher chance of receiving an imaging procedure. The estimated average LRR-risk was 3.5% in patients without any follow-up imaging compared with 2.3% in patients with the recommended number of 5 imagings., Conclusion: Compared to guidelines, more policlinic visits were made, although at inadequate intervals, and fewer imaging procedures were performed. The frequency of imaging procedures did not correlate with the patients' individual risk profiles for LRR., (© The Author(s) 2022. Published by Oxford University Press.)