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Medicine Sep 2022Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and... (Meta-Analysis)
Meta-Analysis
PURPOSE
Double-expressor lymphoma (DEL) is associated with a poor prognosis. The standard treatment for patients with DEL remains controversial. A comparison of the safety and feasibility of R-CHOP and DA-EPOCH-R as the first-line therapy for patients with DEL is urgently needed.
METHODS
The clinical and treatment outcomes of 75 DEL patients were retrospectively analyzed. The role of DA-EPOCH-R was determined and compared to that of R-CHOP in DEL patients. PubMed, Embase, the Cochrane Central Library, and ClinicalTrials.gov were systematically searched up to November 1, 2021 and were evaluated by Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Articles comparing DA-EPOCH-R versus R-CHOP in patients with DEL were included.
RESULTS
Overall, 49 and 26 DEL patients received R-CHOP and DA-EPOCH-R, respectively. Although the difference in response for patients who received R-CHOP and DA-EPOCH-R was not significant (P = .347), DA-EPOCH-R may improve the prognosis compared to R-CHOP (P = .056 for progression-free survival [PFS], P = .009 for overall survival [OS]). A systematic review and meta-analysis including 412 DEL patients in six articles were conducted. The event rate for 3-year PFS was significantly lower in patients receiving DA-EPOCH-R treatment than in those undergoing R-CHOP treatment (OR = 0.63, 95% CI = 0.42-0.94, P = .02), whereas no statistically significant difference was found in the HRs for both PFS and OS or the event rate for 3-year OS.
CONCLUSION
The results of this study indicated that DA-EPOCH-R might improve the prognosis of DEL patients compared with R-CHOP.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Etoposide; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Prognosis; Retrospective Studies; Rituximab; Vincristine
PubMed: 36197215
DOI: 10.1097/MD.0000000000030620 -
Leukemia & Lymphoma Aug 2020Genomic studies have revealed molecular mechanisms involved in the pathogenesis of Burkitt's lymphoma, including the ID3/TCF3-dependent centroblast gene expression... (Review)
Review
Genomic studies have revealed molecular mechanisms involved in the pathogenesis of Burkitt's lymphoma, including the ID3/TCF3-dependent centroblast gene expression program, tonic PI3K-AKT-mTOR signaling, and deregulation of cell cycle and apoptosis through mutations in cyclin D3, , or . Unfortunately, these advances have not been translated into treatment, which relies on dose-intense cytotoxic chemotherapy. While most patients achieve long-term survival, options for relapsed/refractory disease are lacking, as Burkitt lymphoma is often excluded from clinical trials of novel approaches. The lower-intensity, dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) regimen constitutes a major advance allowing for treatment of older and HIV-positive patients but needs augmentation to better address the central nervous system involvement. Furthermore, DA-EPOCH-R provides a platform for the study of targeted or immunotherapeutic approaches while de-escalating cytotoxic agents and their associated adverse effects. In this review we discuss the epidemiology and molecular genetics of BL, first-line treatment considerations, and potential novel treatment strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Humans; Molecular Biology; Phosphatidylinositol 3-Kinases; Rituximab; Signal Transduction
PubMed: 32255708
DOI: 10.1080/10428194.2020.1747068 -
American Journal of Hematology Feb 2023Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ...
Plasmablastic lymphoma (PBL) is a rare entity, commonly associated with immunosuppressed states such as human immunodeficiency virus (HIV) infection or solid organ transplant. The clinical course is characterized by high relapse rates and a poor prognosis, leading some clinicians to recommend aggressive frontline therapy. However, a specific review of limited stage (LS) PBL patients is not available to evaluate outcomes and justify treatment recommendations. We performed a retrospective review of LS PBL cases to provide insight into this rare disease. Our cohort consisted of 80 stage I or II PBL patients from 13 US academic centers. With a median follow up of 34 months (1-196), the 3-year progression-free survival (PFS) and overall survival (OS) of the entire cohort were 72% (95% CI 62, 83) and 79% (95% CI 70, 89), respectively. The 3-year PFS and OS of patients treated with frontline chemotherapy alone was 65% (95% CI 50, 84) and 71% (95% CI 56, 89), respectively, compared to 85% (95% CI 72, 100) and 96% (95% CI 89, 100), respectively, in patients treated with combined frontline chemotherapy with radiation consolidation. Our data demonstrate favorable outcomes in LS PBL with no improvements in outcome from aggressive frontline treatment including Hyper-CVAD or auto-SCT consolidation. Multivariate regression analysis (MRA) demonstrated improved PFS for patients receiving EPOCH based frontline therapy versus CHOP (HR: 0.23; p = 0.029). Frontline chemotherapy followed by radiation consolidation versus chemotherapy alone appeared to be associated with improved relapse and survival outcomes but did not show statistical significance in MRA.
Topics: Humans; Plasmablastic Lymphoma; Retrospective Studies; Neoplasm Recurrence, Local; Antineoplastic Combined Chemotherapy Protocols; Progression-Free Survival; HIV Infections; Prognosis
PubMed: 36588409
DOI: 10.1002/ajh.26784 -
Stroke Jun 2009To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for... (Review)
Review
Treatment time-specific number needed to treat estimates for tissue plasminogen activator therapy in acute stroke based on shifts over the entire range of the modified Rankin Scale.
BACKGROUND AND PURPOSE
To make informed treatment decisions, patients and physicians need to be aware of the benefits and risks of a proposed treatment. The number needed to treat (NNT) for benefit and harm are intuitive and statistically valid measures to describe a treatment effect. The aim of this study is to calculate treatment time-specific NNT estimates based on shifts over the entire spectrum of clinically relevant functional outcomes.
METHODS
The pooled data set of the first 6 major randomized acute stroke trials of intravenous tissue plasminogen activator was used for this study. The data were stratified by 90-minute treatment time windows. NNT for benefit and NNT for harm estimates were determined based on expert generation of joint outcome distribution tables. NNT for benefit estimates were also calculated based on joint outcome distribution tables generated by a computer model.
RESULTS
NNT for benefit estimates based on the expert panel were 3.6 for patients treated between 0 and 90 minutes, 4.3 with treatment between 91 and 180 minutes, 5.9 with treatment between 181 and 270 minutes, and 19.3 with treatment between 271 and 360 minutes. The computer simulation yielded very similar results. The NNT for harm estimates for the corresponding time intervals are 65, 38, 30, and 14.
CONCLUSIONS
Up to 4(1/2) hours after symptom onset, tissue plasminogen activator therapy is associated with more benefit than harm, whereas there is no evidence of a net benefit in the 4(1/2)- to 6-hour time window. The NNT estimates for each 90-minute epoch provide useful and intuitive information based on which patients may be able to make better informed treatment decisions.
Topics: Acute Disease; Age Factors; Algorithms; Computer Simulation; Female; Fibrinolytic Agents; Humans; Male; Models, Statistical; Randomized Controlled Trials as Topic; Sex Factors; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 19372447
DOI: 10.1161/STROKEAHA.108.540708 -
British Journal of Haematology Aug 2016Since grey zone lymphoma (GZL) was originally included in the 2008 World Health Organization classification as a B-cell lymphoma unclassifiable with features... (Review)
Review
Since grey zone lymphoma (GZL) was originally included in the 2008 World Health Organization classification as a B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL), new biological and clinical knowledge have been learned. It is important to highlight that diagnosis of this entity is complex and involvement by haematopathologists with expertise in this disease is recommended. It is recognized now that patients with GZL may present clinically with primary mediastinal localization or systemic disease without mediastinal involvement. Regardless of clinical presentation, patients with GZL have relatively high relapse rates, especially compared with primary mediastinal DLBCL or cHL. Interestingly, relapsed/refractory GZL patients appear to be salvaged fairly successfully, especially with haematopoietic stem cell transplantation (HSCT). Off of a clinical trial, we recommend R-CHOP (rituximab, cyclophosphamide, doxorubicin, oncovin, prednisolone) or dose-adjusted EPOCH-R (etoposide, prednisolone, oncovin, cyclophosphamide, doxorubicin, rituximab) for frontline treatment of GZL. Additionally, we advocate use of consolidative radiotherapy for localized and/or bulky disease. For patients with relapsed/refractory GZL, salvage chemotherapy followed by consolidative autologous HSCT should be considered. Finally, continued biological and pathologic examination of this unique disease entity is warranted as well as exploration towards the integration of targeted therapeutic agents (e.g., brentuximab vedotin, programmed cell death 1inhibitors, B-cell receptor inhibitors, proteasome inhibitors, etc.) into the treatment paradigm of GZL.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease Management; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Mediastinal Neoplasms; Radiotherapy; Recurrence; Salvage Therapy
PubMed: 27301470
DOI: 10.1111/bjh.14174 -
Blood Nov 2013Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective... (Review)
Review
Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.
Topics: Anti-HIV Agents; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antiretroviral Therapy, Highly Active; Clinical Trials as Topic; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Etoposide; HIV; HIV Infections; Humans; Infusions, Intravenous; Lymphoma, AIDS-Related; Lymphoma, Non-Hodgkin; Prednisone; Rituximab; Survival Analysis; Treatment Outcome; Vincristine
PubMed: 24014242
DOI: 10.1182/blood-2013-04-498964 -
World Journal of Gastroenterology May 2015The incidence of gastric cancer (GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancer-related... (Review)
Review
The incidence of gastric cancer (GC) fell dramatically over the last 50 years, but according to IARC-Globocan 2008, it is the third most frequent cause of cancer-related deaths with a case fatality GC ratio higher than other common malignancies. Surgical resection is the primary curative treatment for GC though the overall 5-year survival rate remains poor (approximately 20%-25%). To improve the outcome of resectable gastric cancer, different treatment strategies have been evaluated such as adjuvant or perioperative chemotherapy. In resected gastric cancer, the addition of radiotherapy to chemotherapy does not appear to provide any additional benefit. Moreover, in metastatic patients, chemotherapy is the mainstay of palliative therapy with a median overall survival of 8-10 mo and objective response rates of merely 20%-40%. Therefore, the potential for making key beneficial progress is to investigate the GC molecular biology to realize innovative therapeutic strategies, such as specific immunotherapy. In this review, we provide a panoramic view of the different immune-based strategies used for gastric cancer treatment and the results obtained in the most significant clinical trials. In detail, firstly we describe the therapeutic approaches that utilize the monoclonal antibodies while in the second part we analyze the cell-based immunotherapies.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Chemoradiotherapy; Chemotherapy, Adjuvant; Humans; Immunotherapy; Immunotherapy, Adoptive; Neoadjuvant Therapy; Neoplasm Metastasis; Stomach Neoplasms; Time Factors; Treatment Outcome
PubMed: 26019442
DOI: 10.3748/wjg.v21.i19.5778 -
Leukemia & Lymphoma May 2023Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase...
Treatments for adults with newly-diagnosed acute lymphoblastic leukemia (ALL) may be prohibitively toxic and/or resource-intense. To address this, we performed a phase II study of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH). Imatinib or dasatinib was added for Ph + disease; rituximab was added when CD20+. Fifty-three patients were evaluable: 28 with Ph + disease, and 25 with Ph-. All patients had ≥1 high-risk clinical feature. Measurable residual disease-negativity by multiparameter flow cytometry within 4 cycles was achieved in 71% in patients with Ph + ALL and 64% in Ph - ALL. Median overall survival (OS) was 49 months, with a 2-year OS of 71%. Median relapse-free survival (RFS) in the 47 patients that attained morphologic remission was 24 months, with a 2-year RFS of 57%. Early mortality was 2%. In summary, DA-EPOCH yields deep and durable remissions in adults with ALL comparable to some resource-intense strategies but with a low rate of treatment-related death.
Topics: Adult; Humans; Vincristine; Prednisone; Etoposide; Cyclophosphamide; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Rituximab
PubMed: 36938892
DOI: 10.1080/10428194.2023.2189803 -
Haematologica Aug 2018Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately... (Clinical Trial)
Clinical Trial
Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUV in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUV was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R ().
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Decision-Making; Cyclophosphamide; Diagnosis, Differential; Doxorubicin; Etoposide; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Mediastinal Neoplasms; Middle Aged; Positron-Emission Tomography; Prednisone; Rituximab; Survival Analysis; Treatment Failure; Treatment Outcome; Vincristine; Young Adult
PubMed: 29748435
DOI: 10.3324/haematol.2018.192492 -
Frontiers in Cardiovascular Medicine 2022Contrast and non-contrast echocardiography are crucial for cardiovascular diagnoses and treatments. Correct view classification is a foundational step for the analysis...
BACKGROUND
Contrast and non-contrast echocardiography are crucial for cardiovascular diagnoses and treatments. Correct view classification is a foundational step for the analysis of cardiac structure and function. View classification from all sequences of a patient is laborious and depends heavily on the sonographer's experience. In addition, the intra-view variability and the inter-view similarity increase the difficulty in identifying critical views in contrast and non-contrast echocardiography. This study aims to develop a deep residual convolutional neural network (CNN) to automatically identify multiple views of contrast and non-contrast echocardiography, including parasternal left ventricular short axis, apical two, three, and four-chamber views.
METHODS
The study retrospectively analyzed a cohort of 855 patients who had undergone left ventricular opacification at the Department of Ultrasound Medicine, Wuhan Union Medical College Hospital from 2013 to 2021, including 70.3% men and 29.7% women aged from 41 to 62 (median age, 53). All datasets were preprocessed to remove sensitive information and 10 frames with equivalent intervals were sampled from each of the original videos. The number of frames in the training, validation, and test datasets were, respectively, 19,370, 2,370, and 2,620 from 9 views, corresponding to 688, 84, and 83 patients. We presented the CNN model to classify echocardiographic views with an initial learning rate of 0.001, and a batch size of 4 for 30 epochs. The learning rate was decayed by a factor of 0.9 per epoch.
RESULTS
On the test dataset, the overall classification accuracy is 99.1 and 99.5% for contrast and non-contrast echocardiographic views. The average precision, recall, specificity, and F1 score are 96.9, 96.9, 100, and 96.9% for the 9 echocardiographic views.
CONCLUSIONS
This study highlights the potential of CNN in the view classification of echocardiograms with and without contrast. It shows promise in improving the workflow of clinical analysis of echocardiography.
PubMed: 36186996
DOI: 10.3389/fcvm.2022.989091