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Current Opinion in Oncology Nov 2015Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes... (Review)
Review
PURPOSE OF REVIEW
Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes these trends and implications for elderly patients.
RECENT FINDINGS
The vast majority of diffusely infiltrating gliomas in elderly patients share an unfavorable molecular phenotype, that is, telomerase reverse transcriptase promoter mutation in the absence of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. Histopathologically, these are mostly astrocytic tumors and treatment is guided by the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter. 1p/19q codeletion indicates oligodendroglial histology and benefit from the addition of procarbazine, chlorethyl-cyclohexyl-nitroso-urea/lomustine, and vincristine polychemotherapy to radiotherapy. These tumors are almost exclusively associated with IDH mutations, but their molecular profile is rare in elderly patients. Two large phase III trials, RTOG 0825 and AVAglio, failed to demonstrate an overall survival benefit from antiangiogenic therapy with bevacizumab added to combined chemoradiotherapy (TMZ) in patients with newly diagnosed glioblastoma, but a trend toward improved survival with increasing age can be noted. Ongoing clinical trials in elderly patients with diffusely infiltrating glioma will clarify the role of combined chemoradiotherapy, and of bevacizumab or other antiangiogenic agents as an adjunct to radiotherapy.
SUMMARY
The choice of first-line therapy in elderly patients with diffusely infiltrating glioma is between postoperative hypofractionated radiotherapy and chemotherapy, guided by MGMT methylation in most patients.
Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Central Nervous System Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; DNA Methylation; DNA Modification Methylases; Epigenomics; Gene Expression Regulation, Neoplastic; Glioma; Humans; Isocitrate Dehydrogenase; Molecular Targeted Therapy; Telomerase
PubMed: 26397765
DOI: 10.1097/CCO.0000000000000236 -
Frontiers in Pharmacology 2021Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic... (Review)
Review
Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic regimens. Nevertheless, some treatments were accompanied with toxicities. In the current study, a network meta-analysis (NMA) was conducted to compare the efficacies and toxicities of different chemotherapy regimens for advanced Hodgkin lymphoma (HL). We reviewed PubMed and EMBASE databases from inception to May 2018, and identified randomized controlled trials (RCTs) in which advanced HL patients received chemotherapy. Fourteen eligible RCTs published between 1992 and 2017 were enrolled in this NMA. These studies included a total of 5,964 HL patients, and assessed at least one of seven different chemotherapy regimens. Direct and indirect evidence was combined to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and to establish a surface under the cumulative ranking (SUCRA) curve. A cluster analysis was performed to evaluate efficacies and toxicities of different regimens. The COPP + ABVD (cyclophosphamide + vincristine + procarbazine + prednisone + doxorubicin + bleomycin + vinblastine + dacarbazine) regimen had the highest SUCRA partial response and overall remission rate values, while the ABVD regimen resulted in the lowest incidences of anemia, thrombocytopenia, neutropenia, and leucopenia. Cluster analysis revealed that COPP + ABVD had the best efficacy against advanced HL among the seven regimens, and ABVD had the lowest toxicity.
PubMed: 34867316
DOI: 10.3389/fphar.2021.694545 -
Journal of Clinical Oncology : Official... Jan 2024JCO We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of...
JCO We analyzed long-term results of the response-adapted trial for adult patients with advanced-stage Hodgkin lymphoma. The aim was to confirm noninferiority of treatment de-escalation by omission of bleomycin from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) for interim fluorodeoxyglucose positron emission tomography (iPET)-negative patients and assess efficacy and long-term safety for iPET-positive patients who underwent treatment intensification with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP/BEACOPP14). The median follow-up is 7.3 years. For all patients, the 7-year progression-free survival (PFS) and overall survival (OS) are 78.2% (95% CI, 75.6 to 80.5) and 91.6% (95% CI, 89.7 to 93.2), respectively. The 1.3% difference in 3-year PFS (95% CI, -3.0 to 4.7) between ABVD and doxorubicin, vinblastine, and dacarbazine (AVD) now falls within the predefined noninferiority margin. Among 172 patients with positive iPET, the 7-year PFS was 65.9% (95% CI, 58.1 to 72.6) and the 7-year OS was 83.2% (95% CI, 76.2 to 88.3). The cumulative incidence of second malignancies at 7 years was 5.5% (95% CI, 4.0 to 7.5) for those receiving ABVD/AVD and 2.5% (95% CI, 0.8 to 7.7) for those escalated to BEACOPP. With extended follow-up, these results confirm noninferiority of treatment de-escalation after a negative iPET. Escalation with BEACOPP for iPET-positive patients is effective and safe, with no increase in second malignancies.
Topics: Adult; Humans; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Neoplasms, Second Primary; Prednisone; Vinblastine; Vincristine
PubMed: 37883739
DOI: 10.1200/JCO.23.01177 -
Journal of Neurosurgery Mar 2023Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its...
OBJECTIVE
Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the "wait-and-see" strategy or immediate treatment. Therefore, in this study the authors explored iLGG's clinical and molecular landscape to improve its management.
METHODS
The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed.
RESULTS
There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation-related, cell migration-related, epithelial-to-mesenchymal transition-related, and negative regulation of cell death-related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide.
CONCLUSIONS
The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.
Topics: Humans; Brain Neoplasms; Retrospective Studies; Glioma; Prognosis; Carmustine; Mutation; Isocitrate Dehydrogenase
PubMed: 35986732
DOI: 10.3171/2022.6.JNS22967 -
Frontiers in Oncology 2022Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The...
Oligodendrogliomas are a subtype of adult diffuse glioma characterized by their better responsiveness to systemic chemotherapy than other high-grade glial tumors. The World Health Organization (WHO) 2021 brain tumor classification highlighted defining molecular markers, including 1p19q codeletion and IDH mutations which have become key in diagnosing and treating oligodendrogliomas. The management for patients with oligodendrogliomas includes observation or surgical resection potentially followed by radiation and chemotherapy with PCV (Procarbazine, Lomustine, and Vincristine) or Temozolomide. However, most of the available research about oligodendrogliomas includes a mix of histologically and molecularly diagnosed tumors. Even data driving our current management guidelines are based on subgroup analyses of the 1p19q codeleted population in landmark prospective trials. Therefore, the optimal treatment paradigm for molecularly defined oligodendrogliomas is incompletely understood. Many questions remain open, such as the optimal timing of radiation and chemotherapy, the response to different chemotherapeutic agents, or what genetic factors influence responsiveness to these agents. Ultimately, oligodendrogliomas are still incurable and new therapies, such as targeting IDH mutations, are necessary. In this opinion piece, we present relevant literature in the field, discuss current challenges, and propose some studies that we think are necessary to answer these critical questions.
PubMed: 35957904
DOI: 10.3389/fonc.2022.934426 -
Strahlentherapie Und Onkologie : Organ... Sep 2016
Randomized Controlled Trial
Topics: Antineoplastic Combined Chemotherapy Protocols; Astrocytoma; Brain Neoplasms; Chemoradiotherapy; Disease-Free Survival; Female; Follow-Up Studies; Humans; Lomustine; Male; Neoplasm Grading; Prevalence; Procarbazine; Prognosis; Risk Assessment; Survival Analysis; Treatment Outcome; United States; Vincristine; Young Adult
PubMed: 27402390
DOI: 10.1007/s00066-016-1016-6 -
Comparison of the efficiency of ABVD versus BEACOPP for Hodgkin lymphoma treatment: a meta-analysis.International Journal of Hematology Oct 2016To compare the efficiency of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) against that of bleomycin, etoposide, doxorubicin, cyclophosphamide,... (Comparative Study)
Comparative Study Meta-Analysis Review
To compare the efficiency of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) against that of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) for treating Hodgkin lymphoma (HL). An extensive English-language literature retrieval on clinical outcomes after treatment by ABVD versus BEACOPP was conducted on Medline, PubMed, and Embase through the period ending December 2015. Odds ratio (OR) with corresponding 95 % confidence interval (95 % CI) was pooled based on the heterogeneity across individual studies. In total, seven articles reporting on four trials were included in this meta-analysis. Patients assigned to BEACOPP therapy had a better complete remission (CR) rate (OR = 0.55, 95 % CI 0.35, 0.87), overall survival (OS) greater than 5 years (OR = 0.64, 95 % CI 0.51, 0.81), and progression-free survival (PFS, OR = 0.56, 95 % CI 0.38, 0.81) than patients assigned to ABVD therapy. Subgroup analysis stratified using a different strategy showed no significant difference for OS between short courses of escalated BEACOPP combined with standard BEACOPP and that for ABVD (OR = 0. 72, 95 % CI 0. 45, 1.15). Reduced progression/relapse, better CR, and similar OS were observed with BEACOPP, indicating its superior efficiency of BEACOPP in the treatment of HL. However, more analysis of treatment-related toxicity is needed.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Prednisone; Procarbazine; Survival Analysis; Treatment Outcome; Vinblastine; Vincristine
PubMed: 27531149
DOI: 10.1007/s12185-016-2080-5 -
American Journal of Hematology Jan 2016Hodgkin lymphoma is a rare lymphoid malignancy affecting ∼9,200 new patients in the United States annually. Progress in the management of this disease over the past 50... (Review)
Review
Hodgkin lymphoma is a rare lymphoid malignancy affecting ∼9,200 new patients in the United States annually. Progress in the management of this disease over the past 50 years has been remarkable and the prognosis of this malignancy has changed from a uniformly fatal process to one in which the vast majority of patients are expected to be cured. This remarkable progress has been due to the use of combination approaches incorporating chemotherapy and radiation therapy, and now more recently antibody-drug conjugates and immune checkpoint inhibitors. The goal for the future is to develop treatment combinations that successfully treat all patients and markedly decrease the long-term side effects.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Clinical Trials as Topic; Dacarbazine; Disease-Free Survival; Doxorubicin; Hodgkin Disease; Humans; Mechlorethamine; Molecular Targeted Therapy; Prednisone; Procarbazine; Programmed Cell Death 1 Receptor; Vinblastine; Vincristine
PubMed: 26505486
DOI: 10.1002/ajh.24226 -
Journal of Clinical Oncology : Official... Aug 2022JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization...
JCO Anaplastic oligodendroglial tumors (AOTs) are chemotherapy-sensitive brain tumors. We report the final very long-term survival results from European Organization for the Research and Treatment of Cancer 26951 and Radiation Therapy Oncology Group 9402 phase III trials initiated in 1990s, which both studied radiotherapy with/without neo/adjuvant procarbazine, lomustine, and vincristine (PCV) for newly diagnosed anaplastic oligodendroglial tumors. The median follow-up duration in both was 18-19 years. For European Organization for the Research and Treatment of Cancer 26951, median, 14-year, and probable 20-year overall survival rates without versus with PCV were 2.6 years, 13.4%, and 10.1% versus 3.5 years, 25.1%, and 16.8% (N = 368 overall; hazard ratio [HR] 0.78; 95% CI, 0.63 to 0.98; = .033), with 1p19q codeletion 9.3 years, 26.2%, and 13.6% versus 14.2 years, 51.0%, and 37.1% (n = 80; HR 0.60; 95% CI, 0.35 to 1.03; = .063), respectively. For Radiation Therapy Oncology Group 9402, analogous results were 4.8 years, 16.5%, and 11.2% versus 4.8 years, 29.1%, and 24.6% (N = 289 overall; HR 0.79; 95% CI, 0.61 to 1.03; = .08), with codeletion 7.3 years, 25.0%, and 14.9% versus 13.2 years, 46.1%, and 37% (n = 125; HR 0.61; 95% CI, 0.40 to 0.94; = .02), respectively. With that, the studies show similar long-term survival even without tumor recurrence in a significant proportion of patients after first-line treatment with radiotherapy/PCV.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Clinical Trials, Phase III as Topic; Humans; Lomustine; Neoplasm Recurrence, Local; Oligodendroglioma; Procarbazine; Vincristine
PubMed: 35731991
DOI: 10.1200/JCO.21.02543 -
Immunology and Allergy Clinics of North... Aug 2014Use of cytotoxic agents is associated with potential hypersensitivity reactions which are common with platinum compounds, L-asparaginase, taxanes, procarbazine and... (Review)
Review
Use of cytotoxic agents is associated with potential hypersensitivity reactions which are common with platinum compounds, L-asparaginase, taxanes, procarbazine and epipodophyllotoxins. Mechanisms underlying the reactions may involve IgE, non-allergic or a number of pathogenetically unclear events. Targeted therapies produce less collateral damage but demonstrate their own unique reactions. Cytopenias occur less often and mucocutaneous reactions to EGFR inhibitors, including papulopustular rash, are common. Fifteen currently approved mAbs provoke all four types of hypersensitivities including immune cytopenias, vasculitis, serum sickness and pulmonary events. Some successful desensitization protocols have been developed. Prevention of hypersensitivity reactions is based on skin testing, premedication and/or desensitization.
Topics: Antineoplastic Agents; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Premedication; Risk Factors
PubMed: 25017678
DOI: 10.1016/j.iac.2014.04.003