Search Results (78)

Background: This work presents the procedures and application of the deep inspiration breath-hold (DIBH) technique for mediastinal lymphoma patients at a proton therapy (PT) center. It also discusses the implementation and validation of the surface-guided radiotherapy (SGRT) protocol in terms of positioning accuracy. Methods: This study included six lymphoma patients. Dedicated computed tomography (CT) protocols and a treatment workflow based on international guidelines were developed. Clinical data from the treatment planning system (TPS) were used to assess the difference between DIBH and free-breathing irradiation. Additionally, data from an optical patient positioning system and kilovoltage (kV) imaging system were used to estimate positioning shifts. The new CT protocol reduced the volume CT dose index by over six times compared with the standard protocol. Results: The DIBH method decreased the mean dose to the heart and lungs by up to 7.02 Gy(RBE) and 0.83 Gy(RBE), respectively. The median magnitude of patient setup errors and repeatability in DIBH positioning was 0.4 cm and 0.18 cm (mean for males and females) for the SGRT protocol. The kV imaging showed a setup error of over 0.3 cm for both groups. Conclusions: Despite the small size of the patient cohort, the relatively large number of individual positioning sessions enabled the detection of statistically significant differences (p < 0.05) in certain areas between male and female patients; however, no significant difference in the displacement vector magnitude was observed. DIBH treatment with SGRT offers high reproducibility for patient positioning. Full article

Purpose: This bi-centric pilot study investigates the predictive value of pre-treatment [¹⁸F]FDG PET/CT radiomics for assessing therapy response in primary mediastinal B-cell lymphoma (PMBCL). Methods: All PMBCL patients underwent PET/CT with [¹⁸F]FDG between January 2011 and January 2022 at Policlinico Tor Vergata University Hospital of Rome (70% training and 30% internal validation cohort) and Sant’Anna University Hospital of Ferrara (external validation cohort). The Deauville score (DS) was used as a predictor of therapy response (DS1-DS3 vs. DS4/DS5). A total of 121 quantitative radiomics features (RFts) were extracted from manually segmented volumes of interest (VOIs) in PET and CT images, according to IBSI. ComBat harmonization was applied to correct the center variability of features, followed by class balancing with SMOTE. Two machine learning (ML) prediction models, the PET model and the CT model, were independently developed using robust RFts. For each ML model, two different algorithms were trained (i.e., Random Forest, RF, and Support Vector Machine, SVM) using 10-fold cross validation, tested on the internal/external validation set. Receiver operating characteristic (ROC) curves, area under the curve (AUC), classification accuracy (CA), precision (Prec), sensitivity (Sen), specificity (Spec), true positive (TP) scores, and true negative (TN) scores were computed. Results: The entire dataset was composed of 29 samples for the Rome cohort (23 from D1–D3 and 6 from D4/D5) and 9 samples for the Ferrara cohort (4 from D1–D3 and 5 from D4/D5). A total of 27 RFts were identified as robust for each imaging modality. Both the CT and PET models effectively predicted the Deauville score. The performance metrics of the best classifier (SVM) for the CT and PET models in external validation were AUC = 0.75/0.80, CA = 0.85/0.77, Prec = 0.97/0.67, Sen = 0.60/0.80, Spec = 0.98/0.75, TP = 75.0%/66.7%, and TN = 77.8%/85.7%, respectively. Conclusions: ML models trained on [¹⁸F]FDG PET/CT radiomic features in PMBLC patients could predict the Deauville score. Full article

Background/Objectives: The National Cancer Institute introduced the intensified R-da-EPOCH regimen in primary mediastinal large B-cell lymphoma (PMLBCL) to improve outcomes while minimizing radiotherapy use. However, there is no randomized comparison of R-da-EPOCH vs. R-CHOP-21. The objective of this study was to compare R-da-EPOCH with R-CHOP-21 in consecutive patients with PMLBCL of a single, large referral center, where the R-da-EPOCH escalation schedule was strictly followed. Methods: We retrospectively analyzed all 35 consecutive patients who received R-da-EPOCH (2017–2022) compared to 35 consecutive patients treated with R-CHOP-21 arm at the same Department, starting from the most recent patient and going backwards (2005–2017). Results: R-da-EPOCH was given strictly in 33/35 (94%) patients. The 5-year freedom from progression (FFP) was 91% vs. 69% (p = 0.027). The 5-year event-free survival (EFS) was 84% vs. 69% (p = 0.124). The 5-year overall survival (OS) was 97% vs. 80% (p = 0.063). Among R-CHOP-21-responders, 20/29 (69%) received RT compared to 2/34 (6%) R-da-EPOCH-responders. In multivariate analysis, R-da-EPOCH remained better than R-CHOP-21 in terms of FFP [hazard ratios (HRs) 0.21–0.26, all p < 0.05] and was associated with very favorable HR for EFS and OS. Conclusions: Optimally delivered R-da-EPOCH minimized the use of RT in a real-life setting and provided superior outcomes than R-CHOP-21. Full article

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare and aggressive non-Hodgkin lymphoma (NHL), considered a specific entity with proper characteristics, therapies, and prognosis. First-line treatment is not unique, and subsequent strategies in case of disease persistence or relapse are the subject of debate and studies. In this scenario, [18F]FDG PET/CT plays a pivotal role both in characterizing the mediastinal mass, the main feature of PMLBCL, in staging, in restaging during therapy (interim PET), and at the end of treatment (EoT PET), to guide clinical management and give prognostic insights. The main issue with PMLBCL is distinguishing viable disease from residual fibrotic/inflammatory mass after therapy and, consequently, settling the next clinical strategy. Novel therapeutic approaches are ongoing and associated with the deepening of [18F]FDG PET/CT potentials as a principal tool in this context. In this review, we will explore PMLBCL from a Nuclear Medicine point of view to help clinicians in the management of these patients. Full article

Background: Lymphomas account for approximately 10% of cancers diagnosed during pregnancy, with Hodgkin’s lymphoma being the most common. However, non-Hodgkin lymphomas, including primary mediastinal large B-cell lymphoma (PMBCL), also represent a significant proportion. Both mediastinal lymphomas and pregnancy develop a hypercoagulable state, increasing the risk of venous thromboembolism and massive pulmonary embolism (PE), requiring extracorporeal membrane oxygenation (ECMO). Methods: Clinical data, blood test and imagings have been collected by the medical records of the patient. Results: We present a 25-year-old woman, at 32 weeks of gestation, who presented to the emergency department with progressive dyspnea and asthenia. Echocardiography revealed a hemodynamically significant pericardial effusion and severe right ventricular dysfunction. Given the severity of her condition, she underwent an emergency caesarean section and subsequently a pericardial drainage. A chest computed tomography scan revealed an incidental mediastinal mass along with a massive PE. Despite pericardial drainage, she remained hemodynamically unstable. Since thrombolysis was contraindicated for the recent cesarean section, venoarterial ECMO was initiated. Systemic anticoagulation was guaranteed by heparin, which shifted to argatroban for heparin resistance. The mediastinal mass was also biopsied, and the diagnosis of PMBCL carried out. Cytoreductive chemotherapy was initiated with the COMP-R regimen (i.e., cyclophosphamide, vincristine, methotrexate, prednisone, and rituximab), and the patient progressively improved up to ICU and hospital discharge. Conclusions: This case highlights the challenges in managing a complicated patient requiring early multidisciplinary intervention, which was crucial for stabilizing the patient and optimizing fetal and maternal prognosis. Full article

Multi-parametric flow cytometry is a powerful diagnostic tool that permits rapid assessment of cellular antigen expression to quickly provide immunophenotypic information suitable for disease classification. This chapter describes the classification of B-cell non-Hodgkin lymphoma (B-NHL) by flow cytometry suitable for the clinical and research environment. In addition to describing the immunophenotypic patterns of the most common B-NHL (including examples of common B-NHL), the effect of anti-CD19, -CD20, and -CD38 therapies on the evaluation of flow cytometric data is also discussed. Over the last 15 years, our laboratory has developed flow cytometry combinations that can immunophenotype classic Hodgkin lymphoma (CHL), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), and T-cell/histocyte-rich large B-cell lymphoma (THRLBCL) and the use of these assays will be presented. The CHL assay combination is also particularly well suited to immunophenotype primary mediastinal large B-cell lymphoma (PMLBCL) and our experience immunophenotyping PMLBCL by flow cytometry will be discussed. Finally, an approach to the evaluation of the reactive infiltrate of CHL, NLPHL, and THRLBCL that can provide diagnostic information will also be provided. Full article

Primary mediastinal large B-cell lymphoma (PMLBCL) is a rare, aggressive B-cell lymphoma, sharing common features with diffuse large B-cell lymphoma (DLBCL) and Hodgkin lymphoma (HL). PMLBCL is usually cured with single-hit immunochemotherapy in the first-line setting. Relapses tend to be aggressive and may be unresponsive to conventional chemotherapy. Autologous stem cell transplant (ASCT) remains a viable option for chemosensitive patients; nevertheless, targeted therapies appear to be highly promising. Checkpoint inhibitors (CPIs) have already transformed the course of relapse/refractory disease, while CD-19-directed Chimeric Antigen Receptor (CAR) T-cell therapy may produce remarkably favorable outcomes. The exact position of CAR T-cells and CPIs in the treatment algorithm, along with the role of radiotherapy and ASCT, remains to be precisely determined. In the current review, we aim to present the recent research on targeted agents in PMLBCL and define their sequencing within the treatment algorithm, mainly in the relapse/refractory setting. Full article

Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare form of aggressive B-cell lymphoma with a predominant onset in young patients. The minimization of potential (late) side effects is of cardinal interest for these patients. An anticipation of the individual risk profile is desirable to counsel the patient on the putative impact of radiotherapy (RT). Methods: RT plans for a cohort of 25 patients with PMBCL were prospectively designed. One plan with two parallel- opposing fields (APPA) and another with volume-modulated arc therapy (VMAT) technique with 40 Gy in 2 Gy fractions each. Normal The normal tissue complication probability (NTCP) was calculated using the Lyman-–Kutcher-–Burman model for heart, lung and oesophageal toxicity. Results: APPA planning resulted in lower median doses (Dmedian) for the heart and lungs, whereas all other dose metrics for heart, lungs and esophagus were lower in VMAT planning. A significant difference in the mean NTCPs when comparing the APPA to VMAT plans was seen for increased cardiac mortality, pneumonitis and esophagitis. PTV size correlated with increased cardiac mortality and esophagitis in both plan variations and with pneumonitis for VMAT plans. Dmean, Dmedian, and V20Gy correlated with the risk for pneumonitis, and Dmean, Dmedian, and V1% with the risk for esophagitis in both variants. Conclusions: We showed decreased risk of different NTCPs for VMAT and APPA planning for thoracic toxicities. The use of an IMRT technique like VMAT showed advantages for several DVH metrics in organs at risk and should therefore be recommended for radiation treatment of PMBCL. Full article

Background: CD79b is a B-cell-specific antigen that is crucial to the B-cell receptor and is considered a key target for treatment in aggressive B-cell lymphomas. Methods: While immunohistochemical studies have shown widespread expression of CD79b in mature B-cell-derived lymphomas, flow cytometry allows for precise measurement and differentiation between surface and intracellular localization. Results: In our comparative analysis, we discovered that CD79b expression percentages and mean fluorescence intensity (MFI) were lower in a group of 127 cases of aggressive B-cell lymphomas compared to a control group of benign reactive hyperplasia. We also observed significant variability in the surface expression of CD79b among lymphoma cases, with 18% showing predominantly intracellular positivity. There was a strong correlation between the surface expression of CD79b and clonal light chains. Notably, primary mediastinal B-cell lymphomas exhibited significantly lower surface CD79b expression compared to other lymphoma subtypes (median 0.8% IQR 0–48.5 vs. 80% IQR 24–97, p = 0.0005). Furthermore, patients over 60 years old and those with a higher Revised International Prognostic Index (R-IPI) had significantly higher CD79b expression, both of which are associated with a significant benefit from adding an anti-CD79b drug conjugate to first-line chemotherapy in diffuse large B-cell lymphomas. Conclusions: In conclusion, the quantitative flow cytometric analysis of CD79b surface expression in aggressive B-cell lymphomas provides clinically relevant information, highlighting its potential usefulness in guiding therapeutic decisions. Full article

Background: Spontaneous remission of cancer is a rare and poorly understood phenomenon characterized by complete or partial remission of a malignancy in the absence of or with inadequate treatment. The underlying mechanism for such occurrences is poorly understood, however, immune mechanisms seem to play an important role in such cases. In recent years increasingly more data have become available in favor of the clinical benefit of low levels of chimerism in hematologic malignancies. One such instance of naturally occurring low-level chimerism is feto-maternal microchimerism which has been shown to influence cancer progression and, in some instances, to be a protective factor against malignancy. Case report: We report a case of a young female patient with aggressive primary mediastinal large B cell lymphoma refractory to two lines of chemo-immunotherapy achieving sustained complete metabolic remission of tumor while pregnant with twins. Results: A focus on feto-maternal microchimerism during and after pregnancy revealed transient levels of feto-maternal microchimerism in the peripheral blood of the patient as measured by quantifying the Y-chromosome-linked SRY gene. Conclusions: Microchimerism presents significant potential for enhancing our comprehension of disease mechanisms, uncovering novel therapeutic targets, and refining diagnostic and treatment approaches, especially concerning cancer. Full article

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT. Full article

In this study, the health impacts of improving access to treatment with axicabtagene ciloleucel (axi-cel) was assessed in patients with relapsed/refractory diffuse large B-cell lymphoma after ≥2 lines of therapy in Spain. A partitioned survival mixture cure model was used to estimate the lifetime accumulated life years gained (LYG) and quality-adjusted life years (QALYs) per patient treated with axi-cel versus chemotherapy. Efficacy data were extracted from the ZUMA-1 trial for axi-cel and from the SCHOLAR-1 study for chemotherapy. In the base case, the incremental outcomes of axi-cel versus chemotherapy were evaluated in a cohort of 187 patients treated with CAR T-cell therapies, as reported by the “Spanish National Health System Plan for Advanced Therapies”, and in the alternative scenario in the full eligible population based on epidemiological estimates (n = 490). Taking those currently treated with axi-cel, compared with chemotherapy, axi-cel provided an additional 1341 LYGs and 1053 QALYs. However, when all eligible patients (n = 490) were treated, axi-cel provided an additional 3515 LYs and 2759 QALYs. Therefore, if all eligible patients were treated with axi-cel rather than those currently treated as per the registry (n = 187), there would have been an additional 303 patients treated, resulting in an additional 2173 LYGs and 1706 QALYs in total. The lack of access in Spain has led to a loss of a substantial number of LYGs and QALYs, and efforts should be made to improve access for all eligible patients. Full article

The interaction of programmed death-1 (PD-1) on T lymphocytes with its ligands Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) on tumor cells and/or tumor-associated macrophages results in inhibitory signals to the T-cell receptor pathway, consequently causing tumor immune escape. PD-L1/PD-L2 are currently used as predictive tissue biomarkers in clinical practice. Virtually PD-L1 levels expressed by tumor cells are associated with a good response to immune checkpoint blockade therapies targeting the PD-1/PD-L1 axis. These therapies restore T-cell antitumor immune response by releasing T-lymphocytes from the inhibitory effects of tumor cells. Immune checkpoint therapies have completely changed the management of patients with solid cancers. This therapeutic strategy is less used in hematological malignancies, although good results have been achieved in some settings, such as refractory/relapsed classic Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Variable results have been obtained in diffuse large B-cell lymphoma and T-cell lymphomas. Immunohistochemistry represents the main technique for assessing PD-L1 expression on tumor cells. This review aims to describe the current knowledge of PD-L1 expression in various types of lymphomas, focusing on the principal mechanisms underlying PD-L1 overexpression, its prognostic significance and practical issues concerning the evaluation of PD-L1 immunohistochemical results in lymphomas. Full article

Non-Hodgkin lymphoma (NHL) is among the five most common pediatric cancer diagnoses in children and adolescents and consists of a heterogeneous group of lymphoid tissue malignancies –with B-cell-derived NHL accounting for nearly 80% of cases. Novel and high-throughput diagnostic tools have significantly increased our understanding of B-NHL biology and molecular pathogenesis, leading to new NHL classifications and treatment options. This retrospective cohort study investigated 17 cases of both mature B-cell NHL (Burkitt lymphoma or BL; Diffuse large B-cell lymphoma or DLBCL; Primary mediastinal large B-cell lymphoma or PMBCL; Follicular lymphoma or FL) and immature B-cell progenitor NHL (B-lymphoblastic lymphoma or BLL) that were treated in a tertiary Pediatric Hematology-Oncology Department during the last 20 years. Modern NHL protocols for children, adolescents, and young adults, along with the addition of rituximab, are safe and efficient (100% overall survival; one relapse). Elevated ESR was more prevalent than elevated LDH. Analyses have focused on immune reconstitution (grade ≥3 infections, lymphocyte and immunoglobulin levels recovery) and body-mass-index changes post-treatment, late effects (in 53% of patients), and the presence of histology markers BCL2, BCL6, CD30, cMYC, and Ki-67%. One patient was diagnosed with a second malignant neoplasm (papillary thyroid cancer). Full article

We aimed to analyze the management of the ectopic mediastinal thyroid (EMT) with respect to EMT-related cancer and non-malignant findings related to the pathological report, clinical presentation, imaging traits, endocrine profile, connective tissue to the cervical (eutopic) thyroid gland, biopsy or fine needle aspiration (FNA) results, surgical techniques and post-operatory outcome. This was a comprehensive review based on revising any type of freely PubMed-accessible English, full-length original papers including the keywords “ectopic thyroid” and “mediastinum” from inception until March 2024. We included 89 original articles that specified EMTs data. We classified them into four main groups: (I) studies/case series (n = 10; N = 36 EMT patients); (II) malignant EMTs (N = 22 subjects; except for one newborn with immature teratoma in the EMT, only adults were reported; mean age of 62.94 years; ranges: 34 to 90 years; female to male ratio of 0.9). Histological analysis in adults showed the following: papillary (N = 11/21); follicular variant of the papillary type (N = 2/21); Hürthle cell thyroid follicular malignancy (N = 1/21); poorly differentiated (N = 1/21); anaplastic (N = 2/21); medullary (N = 1/21); lymphoma (N = 2/21); and MALT (mucosa-associated lymphoid tissue) (N = 1/21); (III) benign EMTs with no thyroid anomalies (N = 37 subjects; mean age of 56.32 years; ranges: 30 to 80 years; female to male ratio of 1.8); (IV) benign EMTs with thyroid anomalies (N = 23; female to male ratio of 5.6; average age of 52.1 years). This panel involved clinical/subclinical hypothyroidism (iatrogenic, congenital, thyroiditis-induced, and transitory type upon EMT removal); thyrotoxicosis (including autonomous activity in EMTs that suppressed eutopic gland); autoimmune thyroiditis/Graves’s disease; nodules/multinodular goiter and cancer in eutopic thyroid or prior thyroidectomy (before EMT detection). We propose a 10-item algorithm that might help navigate through the EMT domain. To conclude, across this focused-sample analysis (to our knowledge, the largest of its kind) of EMTs, the EMT clinical index of suspicion remains low; a higher rate of cancer is reported than prior data (18.8%), incident imagery-based detection was found in 10–14% of the EMTs; surgery offered an overall good outcome. A wide range of imagery, biopsy/FNA and surgical procedures is part of an otherwise complex personalized management. Full article