Mediastinal Lymphoma Research Articles

Progressive Pulmonary Infiltrates in a Man with Mediastinal Lymphoma.

Progressive Pulmonary Infiltrates in a Man with Mediastinal Lymphoma.

The impact of modern radiotherapy on radiation-induced late sequelae: Focus on early-stage mediastinal classical Hodgkin Lymphoma. A critical review by the Young Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

The historically feared radiation-induced secondary cancers and cardiac toxicities observed among mediastinal classical Hodgkin Lymphoma (cHL) patients may still negatively burden the benefit of radiotherapy among long-term survivors. Modern radiotherapy (RT) delivery techniques, including intensity-modulated RT (IMRT) and deep inspiration breath-hold (DIBH) solutions, are drastically changing this scenario. Results of a literature overview are reported and discussed in this paper. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used. This paper contains a narrative report and a critical discussion of organs-at-risk dose-volume metrics linked with radiation-induced toxicities in cHL patients. The scenario of early-stage cHL presents long-life expectancies, thus the goal of treatment should aim at maintaining high cure rates and limiting the onset of late complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring.

On the Importance of Individualized, Non-Coplanar Beam Configurations in Mediastinal Lymphoma Radiotherapy, Optimized With Automated Planning.

Background and PurposeLiterature is non-conclusive regarding selection of beam configurations in radiotherapy for mediastinal lymphoma (ML) radiotherapy, and published studies are based on manual planning with its inherent limitations. In this study, coplanar and non-coplanar beam configurations were systematically compared, using a large number of automatically generated plans.Material and MethodsAn autoplanning workflow, including beam configuration optimization, was configured for young female ML patients. For each of 25 patients, 24 plans with different beam configurations were generated with autoplanning: 11 coplanar CP_x plans and 11 non-coplanar NCP_x plans with x = 5 to 15 IMRT beams with computer-optimized, patient-specific configurations, and the coplanar VMAT and non-coplanar Butterfly VMAT (B-VMAT) beam angle class solutions (600 plans in total).ResultsAutoplans compared favorably with manually generated, clinically delivered plans, ensuring that beam configuration comparisons were performed with high quality plans. There was no beam configuration approach that was best for all patients and all plan parameters. Overall there was a clear tendency towards higher plan quality with non-coplanar configurations (NCP_x≥12 and B-VMAT). NCP_x≥12 produced highly conformal plans with on average reduced high doses in lungs and patient and also a reduced heart Dmean, while B-VMAT resulted in reduced low-dose spread in lungs and left breast.ConclusionsNon-coplanar beam configurations were favorable for young female mediastinal lymphoma patients, with patient-specific and plan-parameter-dependent dosimetric advantages of NCP_x≥12 and B-VMAT. Individualization of beam configuration approach, considering also the faster delivery of B-VMAT vs. NCP_x≥12, can importantly improve the treatments.

Selection of Mediastinal Lymphoma Patients for Proton Therapy Within the Proton Collaborative Group Registry: Concordance With the ILROG Guidelines.

As patients with mediastinal lymphoma are typically young with curable disease, advanced radiation techniques such as proton therapy are often considered to minimize subacute and late toxicity. However, it is unclear which mediastinal lymphoma patients are treated with proton therapy. Within a prospective, multi-institutional proton registry, we characterized mediastinal lymphoma patients treated with proton therapy and assessed concordance with consensus recommendations published in 2018 by the International Lymphoma Radiation Oncology Group (ILROG). Eligible patients included those with lymphoma of the mediastinum treated exclusively with proton therapy for whom digital imaging and communications in medicine (DICOM) treatment data were available for review. Given the challenge with reliably visualizing the left mainstem coronary artery, the inferior-most aspect of the left pulmonary artery (PA) was used as a surrogate. Extent of disease was characterized as upper mediastinum (above level of left PA), middle mediastinum (below left PA but at or above level of T8), or low mediastinum (below T8). Between November 2012 and April 2019, 56 patients were treated and met inclusion criteria. Patients treated with proton therapy were young (median, 24 y; range: 12 to 88), with over half being female (55%). Patients were most commonly treated at initial diagnosis (86%) and had Hodgkin lymphoma (79%). Most patients (96%) had mediastinal disease that extended down to the level of the heart: 48% had middle and 48% had low mediastinal involvement. Nearly all patients (96%) met the ILROG consensus recommendations: 95% had lower mediastinal disease, 46% were young females, and 9% were heavily pretreated. Heart (mean) and lung dose (mean, V5, V20) were significantly associated with lowest extent of mediastinal disease. Mediastinal lymphoma patients treated with proton therapy are typically young with lower mediastinal involvement. Within a prospective, multi-institutional proton registry, nearly all treated patients fit the ILROG consensus recommendations regarding which mediastinal lymphoma patients may most benefit from proton therapy.

Mutational landscape of gray zone lymphoma

The mutational landscape of gray zone lymphoma (GZL) has not yet been established, and differences from related entities are largely unknown. Here, we studied coding sequence mutations of 50 Epstein-Barr virus (EBV)-negative GZLs and 20 polymorphic EBV+ diffuse large B-cell lymphoma (DLBCL) not otherwise specified (poly-EBV-L) in comparison with classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), and DLBCL. Exomes of 21 GZL and 7 poly-EBV-L cases, along with paired constitutional DNA, were analyzed as a discovery cohort, followed by targeted sequencing of 217 genes in an extension cohort of 29 GZL and 13 poly-EBV-L cases. GZL cases with thymic niche involvement (anterior mediastinal mass) exhibited a mutation profile closely resembling cHL and PMBCL, with SOCS1 (45%), B2M (45%), TNFAIP3 (35%), GNA13 (35%), LRRN3 (32%), and NFKBIA (29%) being the most recurrently mutated genes. In contrast, GZL cases without thymic niche involvement (n = 18) had a significantly distinct pattern that was enriched in mutations related to apoptosis defects (TP53 [39%], BCL2 [28%], BIRC6 [22%]) and depleted in GNA13, XPO1, or NF-κB signaling pathway mutations (TNFAIP3, NFKBIE, IKBKB, NFKBIA). They also exhibited more BCL2/BCL6 rearrangements compared with thymic GZL. Poly-EBV-L cases presented a distinct mutational profile, including STAT3 mutations and a significantly lower coding mutation load in comparison with EBV− GZL. Our study highlights characteristic mutational patterns in GZL associated with presentation in the thymic niche, suggesting a common cell of origin and disease evolution overlapping with related anterior mediastinal lymphomas.

Cytology of Feline Nodal Lymphoma: Low Interobserver Agreement and Variable Accuracy in Immunophenotype Prediction

Nodal lymphomas are less common in cats than in dogs and, consequently, no specific studies have been published. Cytology is the first step in the diagnosis of nodal lymphoma but is highly subjective. Morphological features have been introduced for the cytological classification of canine lymphomas but not for cats. Therefore, the aim of this study was to evaluate interobserver agreement on various cytological features of feline nodal lymphomas and to investigate the accuracy in predicting B or T immunophenotypes. Four veterinary cytologists examined 25 feline nodal and mediastinal lymphoma cytological samples by adapting the criteria used for the evaluation of canine lymphomas and setting histopathology and immunohistochemistry as the gold standard. High interobserver variability was found in the evaluation of most features except for the presence or absence of cytoplasmic vacuoles, which were more common in B-cell lymphomas. Cytology training centre was the major factor influencing the extent of agreement among evaluators. Diagnostic accuracy in predicting lymphoma immunophenotype varied from 35% to 75% and did not appear to be correlated with the experience of the evaluators. We conclude that cytological criteria, commonly used to describe canine lymphomas, are not adaptable to the counterpart feline neoplasms. Cytology-based immunophenotyping of feline lymphomas from different laboratories, and different cytologists within the same laboratory, differ substantially and should not be considered reliable. Specific cytological criteria are needed to describe feline lymphoma.

A heart on fire: Primary mediastinal T-cell lymphoblastic lymphoma involving the whole mediastinum in adult patient

A heart on fire: Primary mediastinal T-cell lymphoblastic lymphoma involving the whole mediastinum in adult patient

Deep inspiration breath hold versus free breathing technique in mediastinal radiotherapy for lymphoma.

Objective:Radiotherapy plays an important role in the management of lymphoma and many patients with lymphoma are cured with treatment. Risk of secondary malignancy and long-term cardiac and pulmonary toxicity from mediastinal radiotherapy exists. Delivery of radiotherapy using a deep inspiration breath-hold (DIBH) technique increases lung volume and has the potential to reduce dose to heart and lungs. We undertook a prospective study to assess the dosimetric differences in DIBH and free breathing (FB) plans in patients requiring mediastinal radiotherapy in clinical practice.Methods:We performed both FB and DIBH planning scans on 35 consecutive patients with mediastinal lymphoma needing radiotherapy. Contours and plans were generated for both data sets and dosimetric data were compared. All patients were planned using volumetric modulated arc therapy (VMAT). Data were compared for FB and DIBH plans with each patient acting as their own control using the related-samples Wilcoxon signed rank test.Results:DIBH significantly reduced lung doses (mean 10.6 vs 11.4Gy, p < 0.0005; V20 16.8 vs 18.3%, p = 0.001) and spinal cord maximum dose (20.6 vs 22.8Gy, p = 0.001). DIBH increased breast V4 (38.5% vs 31.8%, p = 0.006) and mean right breast dose (4.2 vs 3.6Gy, p = 0.010). There was no significant difference in heart doses when the entire study cohort was considered, however, mean heart dose tended to be lower with DIBH for upper mediastinal (UM) tumours (4.3 vs 4.9Gy, p = 0.05).Conclusion:Our study describes the potential benefit of DIBH in a population reflective of clinical practice. DIBH can decrease radiation dose to lungs, heart and spinal cord, however, may increase dose to breasts. DIBH is not always superior to FB, and the clinical significance of differences in dose to organs at risk in addition to the time required to treat patients with DIBH must be considered when deciding the most appropriate radiotherapy technique for each patient.Advances in knowledge:To our knowledge, this is the largest study comparing DIBH and FB planning for patients with lymphoma receiving mediastinal radiotherapy in clinical practice. It demonstrates the impact of an increasingly common radiotherapy technique on dose to organs at risk and the subsequent potential for long-term radiotherapy side-effects.

Retrospective study of retroviruses by immunoenzymatic test on cats in Grande Vitória (ES, Brazil) and associated neoplasms.

Retroviruses are among the leading causes of death in domestic cats. Retroviruses associate with the host cell in a persistent and permanent way, leading to diverse clinical conditions. The feline leukemia virus (FeLV) is the most pathogenic retrovirus with the potential to cause both degenerative diseases and immunosuppression, as well as proliferative diseases, as its association with the cell may lead to a direct oncogenic effect. The feline immunodeficiency virus (FIV), in turn, can lead to the classic immunodeficiency syndrome, usually has a chronic, less aggressive course and has no direct oncogenic effect. The use of vaccines and control measures has resulted in a decrease in the prevalence of FeLV in the United States of America (USA) and Europe, however, in Brazil, statistics show prevalence rates above 50%. This study aimed to assess the prevalence of feline retroviruses, by immunoenzymatic assay testing, in the region of Grande Vitória, in Espírito Santo and also point out the frequency of neoplasms in these cats. A total of 388 cats were retrospectively evaluated (2014-2016). The prevalence of FIV was 2.3% and FeLV was 33.7%. Neoplasms were identified in the three cats seropositive for FIV and FeLV and in three cats infected only with FIV. Neoplasms were also found in 26.6% of cats that were seropositive only for FeLV, especially mediastinal lymphoma. The high prevalence of FeLV demonstrated in this study highlights the need for establishing effective control measures, with emphasis on vaccination.

A Case of Recurrence/Refractory Mediastinal Hodgkin&amp;apos;s Lymphoma Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation: Immunotherapy Brings Hope

Hodgkin lymphoma (HL), is a B-cell lymphoma. HL is a common hematological malignancy, mostly seen in young and middle-aged people. According to NCCN guidelines, common treatment options include ABVD, BEACOPP, StandfordV, etc. Most HL have a good prognosis and even can be cured. However, some Refractory / Recurrent (R/R) HL, continue to progress during treatment or even relapse after the completion of a complete chemotherapy course 3 months. At this time, the best treatment for R/R HL is high-dose chemotherapy / Autologous Hematopoietic Stem Cell Transplantation (HDC/HSCT). This paper reports a case of Recurrence/Refractory (R/R) mediastinal Hodgkin's lymphoma that relapsed after Allogeneic Hematopoietic Stem Cell Transplantation. After receiving a variety of treatments, including chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation and so on, no long-term sustained remission was achieved. Traditional chemotherapy regimen has not brought ideal therapeutic effect to patients, but the rapid development of immunotherapy in recent years has brought new hope to patients. Finally sustained remission was achieved under the treatment of Brentuximab Vedotin combined with PD-1 inhibitor. This paper combined with the literature reports and discussed the clinical characteristics, treatment process and related experience and thinking methods of immunotherapy related to PD-1 inhibitors in this refractory and easy-to-relapse case. To provide more clinical data for the application of immunotherapy in R/R HL.

Intensity-modulated Radiotherapy Planning at Mediastinal Lymphoma Treatment: Sandglass, Rainbow and Butterfly Techniques

Intensity-modulated Radiotherapy Planning at Mediastinal Lymphoma Treatment: Sandglass, Rainbow and Butterfly Techniques

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Fidelity of Diagnosis Using WHO Criteria

PurposeDiagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity between a working diagnosis of PMBCL at our institution and the clinicopathologic criteria established within the 2017 World Health Organization (WHO) classification. Patients and MethodsMedical records and archived tissue of patients treated for stage I-II PMBCL from 1998 to 2018 were retrospectively reviewed for clinical and pathologic conformity with current WHO criteria. Disease was characterized as definitely PMBCL if all of the following were present: anterior mediastinal mass with or without lymph node involvement, no extranodal disease, B-cell antigen expression, Epstein-Barr virus negativity, and at least one supportive feature: female gender under age 40, bulky primary tumor, CD30 weakly positive, compartmentalizing alveolar fibrosis, lack of surface immunoglobulin expression, and MUM1 or CD23 positivity. Disease without supportive features or other pathologic findings more suggestive of other entities was characterized as equivocal for PMBCL. Lack of an anterior mediastinal mass, presence of distant lymph node involvement or extranodal disease, lack of B-cell antigen expression, or Epstein-Barr virus positivity were characterized as definitely not PMBCL. Clinical management and outcomes were also assessed. ResultsOf 63 patients treated for presumed stage I-II PMBCL, 58 (92%) met the criteria for PMBCL. The most common reason for a discordant diagnosis was lack of an anterior mediastinal mass (n = 3). Two additional patients were characterized as having disease equivocal for PMBCL. In retrospect, one patient most likely had a mediastinal gray zone lymphoma due to CD15 positivity and another diffuse large B cell, not otherwise specified, at pathologic review. Five-year progression-free and overall survival were 67% (95% confidence interval, 54-77) and 81% (95% confidence interval, 68-89), respectively, for all patients. ConclusionDespite the complexity of the clinicopathologic criteria of PMBCL, most patients (92%) who were treated for stage I-II PMBCL at our institution appear to have been accurately diagnosed.

Mediastinal Gamma-Delta T-Cell Lymphoblastic Lymphoma Successfully Treated With Chemotherapy Alone

Mediastinal Gamma-Delta T-Cell Lymphoblastic Lymphoma Successfully Treated With Chemotherapy Alone

Young Man With Blunt Chest Trauma

A 19-year-old man with mediastinal lymphoma experienced blunt chest trauma because of a motorcycle crash. On initial presentation to the emergency department (ED), he was conscious but irritable, with a pulse rate of 131 beats/min, blood pressure of 137/59 mm Hg, and ambient air saturation of 70%. Intubation and tube thoracostomy were performed promptly because of respiratory distress and decreased breath sounds on the right side. The focused sonography showed no intra-abdominal free fluid. The chest radiograph revealed faint lung opacities and borderline mediastinal widening, suggesting a bilateral medial lung contusion injury.

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Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study

Nivolumab Combined with Brentuximab Vedotin for Relapsed/Refractory Mediastinal Gray Zone Lymphoma: Primary Efficacy and Safety Analysis of the Phase 2 CheckMate 436 Study

A Multi-Center, Dose-Finding Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of a Novel IRAK4 Inhibitor CA-4948 in Combination with Ibrutinib, in Patients with Relapsed or Refractory Hematologic Malignancies

A Multi-Center, Dose-Finding Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of a Novel IRAK4 Inhibitor CA-4948 in Combination with Ibrutinib, in Patients with Relapsed or Refractory Hematologic Malignancies

The Easix (Endothelial Activation and Stress Index) Score Predicts for CAR T Related Toxicity in Patients Receiving Axicabtagene Ciloleucel (axi-cel) for Non-Hodgkin Lymphoma (NHL)

The Easix (Endothelial Activation and Stress Index) Score Predicts for CAR T Related Toxicity in Patients Receiving Axicabtagene Ciloleucel (axi-cel) for Non-Hodgkin Lymphoma (NHL)

PO-0924: Impact of radiation techniques on lung toxicity in patients with mediastinal Hodgkin lymphoma

PO-0924: Impact of radiation techniques on lung toxicity in patients with mediastinal Hodgkin lymphoma

PO-1429: Risk for radiation-induced cancer following proton vs.photon radiotherapy of mediastinal lymphoma

PO-1429: Risk for radiation-induced cancer following proton vs.photon radiotherapy of mediastinal lymphoma