scholarly journals Transcriptomic Changes During Stage Progression of Mycosis Fungoides

2021 ◽  
Author(s):  
Maggie Xiao ◽  
Dylan Hennessey ◽  
Aishwarya Iyer ◽  
Sandra O'Keefe ◽  
Frederick Zhang ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Late Stage ◽  
Early Stage ◽  
Skin Lesions ◽  
Advanced Stage ◽  
Stage Progression ◽  
Whole Exome ◽  
Stage Disease ◽  
Skin Biopsies ◽  
Transcriptomic Changes

Background: Mycosis fungoides (MF) is the most common cutaneous T cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ~25% of MF patients develop skin tumors, a hallmark of progression to the advanced stage and associated with high mortality. The mechanisms involved in stage progression are poorly elucidated. Methods: We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n=12), and plaques and tumors from patients in late-stage disease (late-stage plaques, LSP, n=10, and tumors, TMR, n=15). Gene Ontology (GO) and KEGG analysis were used to determine pathway changes specific for different lesions which we linked to the recurrent somatic mutations overrepresented in MF tumors. Results: The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), Th2/Th9 signaling (IL4, STAT3, STAT5, STAT6), meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, and REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via hematogenous self-seeding. Conclusion: Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions are probably caused by hematogenous cell percolation between discrete skin lesions.

Causes of death in nodular lymphocyte predominant Hodgkin's lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20016-e20016
Author(s):  
Anas M Saad ◽  
Ahmed Afifi ◽  
Mohamed Gad ◽  
Muneer J. Al-Husseini ◽  
Firas Baidoun ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Late Stage ◽  
Hodgkin’S Lymphoma ◽  
Causes Of Death ◽  
Early Stage ◽  
Hodgkin's Lymphoma ◽  
Disease Stage ◽  
Advanced Stage ◽  
Stage Disease ◽  
Late Stage Disease

e20016 Background: Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) accounts for 5% of all cases of HL. The outcomes of patients with NLPHL is generally regarded as better than those with classical HL. However, causes of death (COD) of patients with NLPHL have not been previously described. Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program was used to identify all patients with NLPHL diagnosed between 1990 and 2015. Patient characteristics and disease stage, using the Ann-Arbor system, was extracted and tabulated. COD were identified and proportions were calculated for deaths within 5 years and after 5 years of diagnosis for patients with early and late stage NLPHL. Results: We identified 1,937 cases of NLPHL. The majority were younger than 65 years (86%), white (70%), male (67%), and diagnosed between 2001-2015 (85%), when rituximab was introduced. Of all cases, 1336 (69%) were classified as early stage. At a median follow-up of 91 months (IQR 41, 152) for early stage disease, and 73 months (IQR 30-123) for late stage disease, the median cancer-specific or overall survival were not reached. The estimated 5-year survival was 92% and 81% for early stage and late stage disease, respectively. Of all patients with early stage NLPHL, 186 (14%) died by the end of 2015, and 87 (46%) deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 30 (35%). Beyond 5 years from diagnosis, NLPHL was the COD in 27% followed by other cancers (23%), and cardiovascular disease (18%). Of all patients with late stage NLPHL, 107 (21%) died, and 75 (70%) of deaths occurred within 5 years of diagnosis. During the first 5 years after diagnosis, COD was NLPHL in 44 (59%). Beyond 5 years from diagnosis, cardiovascular disease was the COD in 25%, followed by NLPHL (22%). Conclusions: The prognosis of NLPHL is excellent. Of all patients with NLPHL, those with advanced stage disease are more likely to die of their disease within 5 years of diagnosis. Patients with early and advanced stage disease beyond 5 years of diagnosis are more likely to die of causes other than NLPHL.

scholarly journals How I treat mycosis fungoides and Sézary syndrome

Blood ◽  
2016 ◽  
Vol 127 (25) ◽  
pp. 3142-3153 ◽  
Author(s):  
Sean Whittaker ◽  
Richard Hoppe ◽  
H. Miles Prince
Keyword(s):  
Mycosis Fungoides ◽  
Histone Deacetylase Inhibitors ◽  
Early Stage ◽  
Prognostic Index ◽  
Interferon Α ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Advanced Stage ◽  
Early Stage Disease ◽  
Stage Disease

AbstractMycosis fungoides (MF) is the most common primary cutaneous T-cell lymphoma variant and is closely related to a rare leukemic variant, Sézary syndrome (SS). MF patients at risk of disease progression can now be identified and an international consortium has been established to address the prognostic relevance of specific biologic factors and define a prognostic index. There are a lack of randomized clinical trial data in MF/SS and evidence is based on a traditional “stage-based” approach; treatment of early-stage disease (IA-IIA) involves skin directed therapies which include topical corticosteroids, phototherapy (psoralen with UVA or UVB), topical chemotherapy, topical bexarotene, and radiotherapy including total skin electron beam therapy. Systemic approaches are used for refractory early-stage and advanced-stage disease (IIB-IV) and include bexarotene, interferon α, extracorporeal photopheresis, histone deacetylase inhibitors, and antibody therapies such as alemtuzumab, systemic chemotherapy, and allogeneic transplantation. However, despite the number of biologic agents available, the treatment of advanced-stage disease still represents an unmet medical need with short duration of responses. Encouragingly, randomized phase 3 trials are assessing novel agents, including brentuximab vedotin and the anti-CCR4 antibody, mogamulizumab. A broader understanding of the biology of MF/SS will hopefully identify more effective targeted therapies.

Specific TCR gene rearrangements in mycosis fungoides: does advanced clinical stage show a preference?

2018 ◽  
Vol 71 (12) ◽  
pp. 1072-1077
Author(s):  
Etan Marks ◽  
Yanhua Wang ◽  
Yang Shi ◽  
Joseph Susa ◽  
Mark Jacobson ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Late Stage ◽  
Gene Rearrangement ◽  
Early Stage ◽  
Clinical Stage ◽  
Disease Stage ◽  
Gene Rearrangements ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Late Stage Disease

AimsThe relationship between the presence of specific T-cell receptor (TCR) gene rearrangements and clinical stage in mycosis fungoides (MF) has not been studied. We analysed a cohort of patients with a diagnosis of MF to determine the different types of specific TCR gene rearrangements present and their relationship to disease stage.MethodsA retrospective chart review was used to select patients with a diagnosis of MF who had a skin biopsy and a positive TCR gene rearrangement study in either blood or tissue and at least 2 years of clinical follow-up.Results43 patients were identified and divided into two groups. The first group consisted of 23 patients with early stage disease (IA-IIA) that was either stable or went into partial or complete remission with minimal intervention. None of these patients advanced to late stage disease. The second group consisted of 20 patients who had either late stage disease at diagnosis or progressed to late stage disease at some point in time. In the first group, only 4/23 (17%) patients had a single TCR gene rearrangement in the Vɣ1–8 region. In contrast, the second group had 13/20 (65%) patients with a single TCR gene rearrangement in the Vɣ1–8 region (p=0.002).ConclusionThe presence of a single TCR gene rearrangement in the Vɣ1–8 region could possibly be related to a more advanced stage of MF. However, more comprehensive studies, such as next generation sequencing, with a larger cohort is necessary for a more definitive conclusion.

scholarly journals Transcriptomic Changes During Stage Progression of Mycosis Fungoides

2021 ◽  
Author(s):  
M.Z.X. Xiao ◽  
D. Hennessey ◽  
A. Iyer ◽  
S. O’Keefe ◽  
F. Zhang ◽  
...  
Keyword(s):  
Mycosis Fungoides ◽  
Stage Progression ◽  
Transcriptomic Changes

scholarly journals Prognostic and Predictive Value of Circulating and Disseminated Tumor Cells in Breast Cancer: A National Cancer Database (NCDB) Analysis

2020 ◽  
Vol 19 ◽  
pp. 153303382098010
Author(s):  
Nadeem Bilani ◽  
Leah Elson ◽  
Hong Liang ◽  
Elizabeth Blessing Elimimian ◽  
Rafael Arteta-Bulos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Late Stage ◽  
Early Stage ◽  
Disseminated Tumor Cells ◽  
Her2 Status ◽  
National Cancer Database ◽  
Factors Associated ◽  
Stage Disease ◽  
Chemotherapy Efficacy

Importance: Our understanding of the utility of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) as clinical biomarkers continues to evolve. Objective: This study evaluated (1) clinicopathologic factors associated with the presence of CTCs or DTCs, (2) the prognostic value of CTCs or DTCs by disease stage, 3), the value of these biomarkers in predicting the benefit of chemotherapy. Design: This is a retrospective analysis of patients with breast cancer (BC) diagnosed between 2004 and 2016 using the National Cancer Database (NCDB). To evaluate variables associated with the presence of CTCs or DTCs at the univariate level, we used chi-squared and Wilcoxon rank-sum tests. Multivariate logistic regression models were then constructed using significant variables. Consequently, we included CTC or DTC status (i.e. positive or negative) in multivariate, stage-by-stage Cox regression analyses for overall survival (OS). After stratifying by receptor status and staging, we used the Kaplan-Meier method to explore chemotherapy efficacy in CTC- or DTC-positive vs. CTC- or DTC-negative subsets. Results: Factors significantly associated with CTCs were race, progesterone receptor status, HER2 status, histology and AJCC N- and M-staging. Factors associated with DTCs were race, HER2 status, histology and AJCC N-staging. CTCs were associated with poor OS in late-stage (III and IV) but not early-stage (0-II) BC. DTCs were not significantly associated with OS in either context. In hormone receptor (HR)-positive disease, chemotherapy was associated with better OS when CTC status was positive, both in early-stage and late-stage disease. In a subset of patients without CTCs, however, chemotherapy conferred no survival benefit. DTC status was not a significant predictor of chemotherapy efficacy in early or late-stage, HR+ disease. Conclusions: This study suggests that CTC-status is a significant prognostic factor at later stages of BC; yet it can also help guide management of early-stage disease as it appears predictive for chemotherapy benefit.

Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation

Blood ◽  
2008 ◽  
Vol 112 (8) ◽  
pp. 3082-3087 ◽  
Author(s):  
Suzanne O. Arulogun ◽  
H. Miles Prince ◽  
Jonathan Ng ◽  
Stephen Lade ◽  
Gail F. Ryan ◽  
...  
Keyword(s):  
De Novo ◽  
Cell Transformation ◽  
Early Stage ◽  
Large Cell ◽  
Tumor Stage ◽  
Advanced Stage ◽  
Long Term Outcomes ◽  
Stage Disease ◽  
Large Cell Transformation

Abstract Although mycosis fungoides (MF) is typically an indolent disease, patients with advanced-stage disease (stages IIB-IVB), including Sézary syndrome (SS), often have a poor outcome. A 31-year, retrospective analysis of our cutaneous lymphoma database, of 297 patients with MF and SS, was undertaken to study long-term outcomes and identify clinical predictors of outcome in patients with advanced-stage disease (ASD, n = 92) and large cell transformation (LCT, n = 22). Two-thirds of patients with ASD presented with de novo ASD. The median overall survival (OS) for ASD was 5 years with a 10-year predicted OS of 32%. Age at initial diagnosis (P = .01), tumor stage (P = .01), and clinical stage (P = .001) were found to be significant predictors of outcome. Patients who presented with de novo ASD demonstrated better outcomes that were not statistically significant than those with a prior diagnosis of early-stage MF (P = .25). Transformation developed in 22 of the 297 MF/SS patients (7.4%), with a transformation rate of only 1.4% in patients with early-stage disease, compared with stage IIB (27%) and stage IV (56%-67%) disease. The median OS from diagnosis of LCT was 2 years. We confirm that the incidence of LCT is strongly dependent on tumor stage at diagnosis, and we demonstrate a much lower overall risk of LCT than previously reported.

Vaginal sarcoma: the Royal Marsden experience

1994 ◽  
Vol 4 (5) ◽  
pp. 337-341 ◽  
Author(s):  
H. Y.S. Ngan ◽  
J. H. Shepherd ◽  
C. Fisher ◽  
P. Blake
Keyword(s):  
Late Stage ◽  
Poor Prognosis ◽  
Recurrent Disease ◽  
Early Stage ◽  
Tumor Grade ◽  
Intermediate Grade ◽  
Early Stage Disease ◽  
The Poor ◽  
Stage Disease ◽  
Prognostic Importance

Six patients with vaginal sarcoma are reported here. This clinicopathologic review confirms the poor prognosis of this disease. However, there were three 5-year survivors, all of whom had early stage disease and low to intermediate grade tumors. Apart from tumor grade, stage was of prognostic importance. Late recurrences at 5 and 21 years were noted in two of the three 5-year survivors. Neither chemotherapy nor radiotherapy were of use in the treatment of late stage or recurrent disease.

Should Albumin Be Considered a Prognostic Factor For Brazilian Patients Diagnosed With Classical Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5049-5049
Author(s):  
Guilherme Fleury Perini ◽  
Egyla M Cavalcante ◽  
Joao Garibaldi Rezende ◽  
Davimar Miranda Borducchi ◽  
Fernanda Cunha Vieira ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Partial Response ◽  
Early Stage ◽  
Progression Free Survival ◽  
Refractory Disease ◽  
Advanced Stage ◽  
Classical Hodgkin Lymphoma ◽  
Free Survival ◽  
Stage Disease

Abstract Introduction In 1998, Hasenclever et al published the International Prognostic Factor for patients with advanced stage classical Hodgkin lymphoma (cHL). Since then, the IPS has been considered the most important prognostic score for cHL and has been validated in different populations, and also in early stage cHL. From the seven factors analyzed in the IPS, albumin is the only that can be influenced by environmental, economic and nutritional status. We hypothesized if, in developing countries, albumin should still be a prognostic factor, and if so, what is the ideal cutoff value. Objectives To assess if albumin at diagnosis of cHL patients in Brazil was prognostic for overall survival (OS) and progression free survival (PFS) and what would be the best cutoff. Patient and Methods This is a retrospective multicenter study conducted by the Universidade Federal de São Paulo, São Paulo, Brazil. Only confirmed cases of cHL, diagnosed between April 1996 To January 2013, with clinical, epidemiological and laboratorial parameters available after a thorough chart review were included in this study. Response was defined as complete (CR) or less than CR (partial response or refractory disease). Event was defined as treatment related mortality, progression (defined as time for initiation of salvage therapy) or relapse. Advanced stage disease was defined as stage I or II with B symptoms and/or bulky disease and stage III or IV. Patients with conflicted data or loss of follow up were excluded from the analysis. Results A total of 179 patients were selected for this study. Nodular sclerosis subtype was diagnosed in 125 (68.9%) of all patients. Median age at diagnosis was 28 years old (ranging from 13-76). Only 22.9% of patients presented with early stage disease. ABVD chemotherapy protocol was the initial therapy in 91% of patients. Consolidation radiotherapy was done in 48.6%. Median serum albumin was 3.74 (range: 1.34 – 5.52). Median albumin for patients treated in private hospital was 3.6 (range: 2.7 – 4.7) in contrast to patients treated in public hospitals with a median level of 3.0 (range: 1.34 – 5.52), although this difference was not statistically different. Overall responses were: CR in 90%, Partial response/Refractory disease in 10%; one patient died due to treatment-related toxicity. Overall Survival (OS) for the entire group was 93% in 5 years (CI95% 87-96%), with a progression free survival (PFS) of 79% (CI95% 73-86%). When applying the cutoff of 4g/dL, albumin was not related to OS (91% vs 98%, p=ns) or PFS (85 vs 77%, p=ns). However, an albumin value greater than 2g/dL was related to a better OS (94% vs 71%, p=0.01). Conclusions Prognostic factors may differ from different studied populations. This is particularly truth for albumin, which is the only IPS factor influenced by the environment. In our study, however, albumin was not significantly related to OS or PFS, unless when a cutoff of 2g/dL was used. Disclosures: No relevant conflicts of interest to declare.

Neuroendocrine carcinoma of the cervix: A single institution’s experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Megan Preston ◽  
Georgia Anne-Lee McCann ◽  
David M. O'Malley ◽  
Christina Boutsicaris ◽  
Larry J. Copeland ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Survival Data ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Advanced Stage ◽  
Single Institution ◽  
Early Stage Disease ◽  
Stage Disease

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.

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