The Pathobiology and Treatment of Hodgkin Lymphoma. Where do We go from Gianni Bonadonna's Lesson?

2017 ◽  
Vol 103 (2) ◽  
pp. 101-113 ◽  
Author(s):  
Simonetta Viviani ◽  
Valentina Tabanelli ◽  
Stefano A. Pileri
Keyword(s):  
Hodgkin Lymphoma ◽  
Targeted Therapies ◽  
Early Stage ◽  
Treatment Strategies ◽  
Risk Groups ◽  
Diagnosis And Treatment ◽  
Molecular Characteristics ◽  
Seminal Contribution ◽  
Molecular Information ◽  
New Treatment

This article reviews the evolution of the diagnosis and treatment of Hodgkin lymphoma (HL) since its discovery in 1832. The morphological, phenotypic and molecular characteristics of both nodular lymphocyte-predominant HL and classical HL are revised in the light of recent molecular information and possible impact on the identification of risk groups as well as the use of targeted therapies. The seminal contribution of Gianni Bonadonna to developing new treatment strategies for both advanced and early-stage HL is highlighted.

Proteomic analysis of extracellular vesicles from medullospheres reveals a role for iron in the cancer progression of medulloblastoma

2019 ◽  
pp. 1-12
Author(s):  
Maja Larsen ◽  
Matthias Kuhlmann Kuhlmann ◽  
Michael Hvam ◽  
Kenneth Howard
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Early Stage ◽  
Cell Communication ◽  
Treatment Strategies ◽  
Iron Chelators ◽  
High Morbidity ◽  
New Treatment ◽  
Stem Cell Populations

Background: Medulloblastoma (MB) is the most common malignant childhood brain tumor with the propensity todisseminate at an early stage, and is associated with high morbidity. New treatment strategies are needed toimprove cure rates and to reduce life-long cognitive and functional deficits associated with current therapies.Extracellular Vesicles (EVs) are important players in cell-to-cell communication in health and diseases. A clearerunderstanding of cell-to-cell communication in tumors can be achieved by studying EV secretion inmedullospheres. This can reveal subtle modifications induced by the passage from adherent to non-adherentgrowth, as spheres may account for the adaptation of tumor cells to the mutated environment.Methods: Formation of medullospheres from MB cell lines stabilized in adherent conditions was obtained throughculture conditioning based on low attachment flasks and specialized medium. EVs collected by ultracentrifugation,in adherent conditions and as spheres, were subjected to electron microscopy, NanoSight measurements andproteomics.Results: Interestingly, iron carrier proteins were only found in EVs shed by CSC-enriched tumor cell population ofspheres. We used iron chelators when culturing MB cell lines as spheres. Iron chelators induced a decrease innumber/size of spheres and in stem cell populations able to initiate in vitro spheres formation.Conclusions: This work suggests a not yet identified role of iron metabolism in MB progression and invasion andopens the possibility to use chelators as adjuvants in anti-tumoral chemotherapy.

Nodular lymphocyte-predominant and classical Hodgkin lymphoma subtypes: Differences in biology, survival, and impact of radiotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8550-8550
Author(s):  
Shihab Ali ◽  
Adam J. Olszewski
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Treatment Strategies ◽  
Relative Survival ◽  
Parametric Models ◽  
Steady Increase ◽  
Secondary Malignancies ◽  
Early Stage Disease ◽  
Immortal Time Bias ◽  
The Impact

8550 Background: Hodgkin lymphoma (HL) is a heterogeneous disease, but differences between nodular lymphocyte predominant (NLPHL) and classical (CHL) subtypes were previously studied in small cohorts preventing adjustment for confounders. We studied those differences based on the Surveillance, Epidemiology and End Results (SEER) program data. Methods: We analyzed SEER HL cases aged 16 years and over, diagnosed between 1995 and 2009. We studied the following endpoints: crude probability of HL-related death (HLRD), relative survival (using individual data in multivariate flexible parametric models) and risk of secondary malignancies (using competing risk regression). We studied the impact of radiotherapy (RT) in early-stage disease using a propensity score, adjusting for treatment selection and immortal time bias. Results: We identified 25,903 patients, with disparate age, race and stage distributions between subtypes. In a multivariate model, NLPHL demonstrated significantly better crude and net survival outcomes (Table), but in contrast to all CHL subtypes, it showed a steady increase in mortality rate after 2 years. The risk of secondary non-Hodgkin lymphoma was significantly higher in both NLPHL (hazard ratio, HR, 2.28, P=0.002) and lymphocyte-rich (LR) CHL (HR 2.08, P=0.01) than in nodular sclerosis (NS). The risk of other secondary malignancies did not differ between subtypes. After balancing confounding factors in treatment arms, RT in stage I/II was associated with improved survival in NS (HR, 0.78, P=0.001) and LR-CHL (HR 0.36, P<0.001), but not in NLPHL (HR 0.98, P=0.94) or in the remaining CHL subtypes. Conclusions: Studies of NLPHL and CHL subtypes should account for their disparate biology and clinical course. Prospective evaluation of NLPHL treatment strategies without RT is justified. [Table: see text]

scholarly journals Advances in Biomarker-Driven Targeted Therapies in Thyroid Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6194
Author(s):  
Prachi Mishra ◽  
Dipranjan Laha ◽  
Robert Grant ◽  
Naris Nilubol
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapies ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Treatment Strategies ◽  
Disease Recurrence ◽  
Receptor Kinase ◽  
New Treatment ◽  
Tyrosine Receptor Kinase ◽  
Multiple Receptor

Thyroid cancer is the most common type of endocrine malignancy comprising 2–3% of all cancers, with a constant rise in the incidence rate. The standard first-line treatments for thyroid cancer include surgery and radioactive iodine ablation, and a majority of patients show a good response to these therapies. Despite a better response and outcome, approximately twenty percent of patients develop disease recurrence and distant metastasis. With improved knowledge of molecular dysregulation and biological characteristics of thyroid cancer, the development of new treatment strategies comprising novel targets has accelerated. Biomarker-driven targeted therapies have now emerged as a trend for personalized treatments in patients with advanced cancers, and several multiple receptor kinase inhibitors have entered clinical trials (phase I/II/III) to evaluate their safety and efficacy. Most extensively investigated and clinically approved targeted therapies in thyroid cancer include the tyrosine receptor kinase inhibitors that target antiangiogenic markers, BRAF mutation, PI3K/AKT, and MAPK pathway components. In this review, we focus on the current advances in targeted mono- and combination therapies for various types of thyroid cancer.

Favorable Early-Stage Hodgkin Lymphoma

2006 ◽  
Vol 4 (3) ◽  
pp. 233-240 ◽  
Author(s):  
Joachim Yahalom
Keyword(s):  
Radiation Therapy ◽  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Combined Modality Therapy ◽  
Treatment Strategies ◽  
Cooperative Groups ◽  
Early Stage Disease ◽  
Bulky Disease ◽  
Combined Modality ◽  
Radiotherapy Alone

The category of favorable early-stage Hodgkin lymphoma (HL) includes patients with Ann Arbor stages I or II disease with no bulky disease or B symptoms. The precise definition of favorable versus unfavorable early-stage disease may vary among American and European cooperative groups. The overall 10-year survival rate of patients with favorable early-stage HL exceeds 90%. Indeed, effective treatments for this group of patients have been available for more than 4 decades. However, treatment strategies have radically changed over the past 15 years and focus now on maintaining the high cure rate while reducing the risk of treatment-related long-term morbidity. The optimal treatment is still evolving, and more recently, reduction in the total amount of chemotherapy and in radiation field and dose has shown excellent results. Combined modality therapy is the preferred treatment for patients with classical favorable early-stage HL (nodular sclerosis or mixed cellularity histology). Patients with early-stage lymphocyte predominance HL are highly curable using involved-field radiation therapy (IFRT) alone and do not require chemotherapy. Classical favorable HL is also curable with radiotherapy alone or with chemotherapy alone, but larger fields and higher-dose radiation or longer chemotherapy is required compared with combined modality. The freedom from treatment failure rate is significantly better with a combination of short chemotherapy and IFRT than with either chemotherapy or radiotherapy alone. Although combined modality is the standard preferred treatment for favorable disease, radiation therapy alone or chemotherapy alone could be considered under special circumstances or as part of an investigational protocol.

The molecular pathogenesis of primary mediastinal large B-cell lymphoma

Blood ◽  
2011 ◽  
Vol 118 (10) ◽  
pp. 2659-2669 ◽  
Author(s):  
Christian Steidl ◽  
Randy D. Gascoyne
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Immune Escape ◽  
Cell Lymphoma ◽  
Treatment Strategies ◽  
B Cell Lymphoma ◽  
Janus Kinase ◽  
Molecular Characteristics ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Primary mediastinal large B-cell lymphoma (PMBCL) is a recognized non-Hodgkin lymphoma entity with unique pathologic, clinical, and molecular characteristics distinct from those of other diffuse large B-cell lymphomas. Immunohistochemical characterization and molecular studies strongly suggest that PMBCL is of germinal center or postgerminal center origin. Pivotal gene expression profiling work defined major deregulated pathway activities that overlap with Hodgkin lymphoma and prompted a more detailed analysis of candidate genes. In particular, the nuclear factor-κB and the Janus Kinase-Signal Transducer and Activator of Transcription signaling pathways are targeted by multiple genomic hits, and constitutive activity of both pathways can be considered molecular hallmark alterations of PMBCL. Moreover, data are emerging giving unique insight into remodeling of the epigenome that affects transcriptional regulation of a multitude of genes. More recently, the tumor microenvironment of PMBCL has shifted into focus based on a number of gene perturbations altering expression of surface molecules that contribute to immune escape. These findings highlight the importance of immune privilege in the pathogenesis of PMBCL and suggest that disrupting crosstalk between the tumor cells and the microenvironment might be a rational new therapeutic target in conjunction with traditional treatment strategies.

scholarly journals Diagnosis and Treatment of Childhood Non-Hodgkin Lymphoma

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 285-296
Author(s):  
Alfred Reiter
Keyword(s):  
Hodgkin Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Large Cell ◽  
Salvage Regimen ◽  
Treatment Groups ◽  
Non Hodgkin Lymphoma ◽  
Appropriate Treatment ◽  
New Treatment

Major advances have been made in the treatment of childhood non-Hodgkin lymphoma (NHL). The recognition that different NHL subtypes require different treatment strategies was fundamental to developing successful therapy regimens. Currently established therapy groups are lymphoblastic lymphoma (LBL) of precursor B- or T-cell type, mature B-cell neoplasms (B-NHL), and anaplastic large cell lymphoma (ALCL). Accurate diagnostic classification is crucial for allocating patients to appropriate treatment groups. Therapy protocols designed to treat children with acute lymphoblastic leukemia (ALL) have proven highly efficacious for treating children with LBL and are associated with event-free survival (EFS) rates up to 80%. For children with B-NHL, a strategy of rapidly repeated short, dose-intense courses proved more efficacious, with EFS rates up to 90%. In patients with ALCL, comparable results are achieved with either strategy, although this group has the highest relapse rate. The price of these efficacious treatments is considerable toxicity. On the other hand, the chance to survive after relapse is still dismal due to the almost complete lack of established salvage regimen. Thus, refinement of the balance between treatment burden and individual patient risk for failure is a major future task. A variety of new treatment options, some already established for treating adult NHL, await evaluation in childhood NHL.

scholarly journals HER2-Low Breast Cancer: Molecular Characteristics and Prognosis

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2824
Author(s):  
Elisa Agostinetto ◽  
Mattia Rediti ◽  
Danai Fimereli ◽  
Véronique Debien ◽  
Martine Piccart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
The Cancer Genome Atlas ◽  
Survival Outcomes ◽  
Molecular Characteristics ◽  
Prognostic Impact ◽  
Intrinsic Subtypes ◽  
Free Interval ◽  
New Treatment ◽  
The Impact

Background: We aimed to determine the distribution of intrinsic subtypes within HER2-low breast cancer (BC), and to describe the prognostic impact of HER2-low status on survival outcomes. Methods: This is a retrospective, observational study of primary BC extracted from The Cancer Genome Atlas dataset. We described the distribution of PAM50 intrinsic subtypes within HER2-low BC subtype according to hormonal receptor status (positive (HR+) and negative (HR−)). Secondly, we assessed the impact of HER2-low on survival outcomes (progression-free interval (PFI), disease-free interval (DFI), and overall survival (OS)). Results: We analyzed 804 primary BCs, including 410 (51%) HER2-low BCs (336 HR+ and 74 HR−). The proportion of HER2-enriched tumors was higher in the HER2-low/HR− group compared to HER2-low/HR+ (13.7% versus 1.2%, respectively). HER2-enriched tumors were more frequent in HER2-low/HR− and HER2-low/HR+ subtypes, compared to HER2-negative/HR− and HER2-negative/HR+ subtypes, respectively (13.7% versus 1.6% and 1.2% versus 0.5%, respectively). We observed no significant differences in PFI, DFI, and OS between HER2-low subtypes and each non-HER2-low subtype paired by HR status. Conclusions: Our characterization of PAM50 intrinsic subtypes within HER2-low breast cancer may explain the different clinical behaviors and responses to treatment, and ultimately support further investigation of new treatment strategies in the HER2-low category. Moreover, it highlights the importance of considering HR status in the HER2-low category.

scholarly journals Controversies in the management of early-stage Hodgkin lymphoma

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 234-239
Author(s):  
Kristie A. Blum
Keyword(s):  
Hodgkin Lymphoma ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Similar Efficacy ◽  
Interim Pet ◽  
Positron Emission ◽  
Frontline Treatment ◽  
Frontline Therapy

Abstract Positron emission tomography (PET)–adapted chemotherapy and radiotherapy approaches are currently used for the initial treatment of early-stage Hodgkin lymphoma (HL) with progression-free survival and overall survival exceeding 85% and 95%, respectively. However, despite general agreement on the prognostic value of interim PET in HL, frontline treatment approaches vary among institutions with respect to how pretreatment clinical risk factors determine treatment selection, the definition of PET negativity, which chemotherapy regimen to initiate and how many cycles to administer, and when to incorporate radiation. Furthermore, as recent trials have confirmed improved efficacy and manageable toxicity when brentuximab and checkpoint inhibitors are combined with frontline regimens such as doxorubicin, vinblastine, and dacarbazine in advanced-stage HL, these agents are now under evaluation as frontline therapy in early-stage HL. A number of issues will affect the use of these agents in early-stage HL, including the costs, early and late toxicities with these agents, patient population (favorable or unfavorable risk groups), how to incorporate them (concurrently or sequentially), and whether they can ultimately replace cytotoxic therapy with similar efficacy and fewer late effects. Future treatment paradigms for early-stage HL may change significantly once randomized studies are completed incorporating these agents into frontline therapy. Ideally, frontline use of brentuximab and checkpoint inhibitors in early-stage HL will result in improved outcomes compared with current PET-adapted approaches with decreased risks of late toxicities that continue to afflict long-term survivors of HL.

Sign in / Sign up

Export Citation Format

Share Document