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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 -
Leukemia & Lymphoma Sep 2022The optimal high-dose methotrexate (HDMTX)-based combination therapy for primary central nervous system lymphoma is unknown. We report our experience with rituximab,...
The optimal high-dose methotrexate (HDMTX)-based combination therapy for primary central nervous system lymphoma is unknown. We report our experience with rituximab, HDMTX, procarbazine and lomustine (R-MPL) given as first-line treatment in our center. Fifty-two patients between 2006 and 2019 were included. Eighteen patients proceeded to autologous transplant or two cycles of intermediate-dose cytarabine. The median age was 62 y (range 28-94) and the Eastern Cooperative Oncology Group performance status (ECOG-PS) was ≥2 in 62% (32/52). The overall/complete response rates were 79% (41/52) and 52% (27/52), respectively. The median progression-free/overall survival was 19 m/84m, respectively. Grade 3-4 adverse events included infections (17%) and kidney injury (13%). Ten patients (19%) discontinued therapy for toxicity. There were no treatment-related deaths. In summary, in a cohort enriched in frail patients, R-MPL achieved good responses and OS and was safe for all ages. The PFS was sub-optimal, possibly explained by a low proportion of consolidation. This regimen should be evaluated prospectively.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cytarabine; Humans; Lomustine; Lymphoma; Methotrexate; Middle Aged; Procarbazine; Receptors, Thrombopoietin; Rituximab
PubMed: 35491706
DOI: 10.1080/10428194.2022.2064996 -
Klinicka Onkologie : Casopis Ceske a... 2021Advanced stages of classical Hodgkin lymphoma can be cured by the first-line treatment in 80% of patients. Conventional treatment options include ABVD chemotherapy... (Review)
Review
BACKGROUND
Advanced stages of classical Hodgkin lymphoma can be cured by the first-line treatment in 80% of patients. Conventional treatment options include ABVD chemotherapy (doxorubicin bleomycin, vinblastine, dacarbazine) or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are commonly used in advanced stages. The result of interim positron emission tomography allows adjustment of the treatment intensity during chemotherapy and this approach can affect the treatment results and toxicity.
PURPOSE
This review summarizes current options of conventional chemotherapy and implementation of brentuximab vedotin and PD-1 inhibitors in combination with chemotherapy into the first-line treatment.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brentuximab Vedotin; Hodgkin Disease; Humans; Immune Checkpoint Inhibitors; Nivolumab; Positron-Emission Tomography
PubMed: 34911330
DOI: 10.48095/ccko2021450 -
Acta Clinica Croatica Feb 2022Treatment of glioblastoma is challenging due to its aggressive and highly invasive nature, and no significant advances in survival have been achieved recently. The aim...
Treatment of glioblastoma is challenging due to its aggressive and highly invasive nature, and no significant advances in survival have been achieved recently. The aim of our retrospective study was identification of predictive factors and consequent survival outcome in patients who underwent surgical and oncologic treatment of glioblastoma. The study was conducted at the Department of Neurosurgery, Osijek University Hospital Centre. The authors designed a retrospective cohort study in 63 patients who underwent surgical and oncologic treatment between January 1, 2012 and December 31, 2017. Data were collected by reviewing medical records of the patients with histologically proven glioblastoma. Statistical analysis of study results revealed a significant impact of postoperative radiotherapy (p=0.002) and chemotherapy (p=0.016) on progression-free survival and overall survival (p=0.001 and p=0.009, respectively). Postoperative Karnofsky performance scale (p=0.027) was found to be significant in progression-free survival, and so was the interval between surgery and commencement of oncologic therapy (p=0.049). In conclusion, overall survival and prognosis in the treatment of glioblastoma remain poor, although prompt approach in postoperative adjuvant treatments improved progression-free survival.
Topics: Brain Neoplasms; Glioblastoma; Humans; Neurosurgical Procedures; Prognosis; Retrospective Studies
PubMed: 35282478
DOI: 10.20471/acc.2021.60.03.06 -
Journal of Feline Medicine and Surgery Apr 2020The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory...
OBJECTIVES
The aims of this study were to evaluate the safety of mustargen, vincristine, procarbazine and prednisone (MOPP) chemotherapy in the treatment of relapsed or refractory feline lymphoma, and to determine the overall response rate and median remission time with this protocol.
METHODS
The medical records of 38 cats with relapsed or refractory lymphoma treated with MOPP chemotherapy at three institutions (University of Pennsylvania, the Animal Medical Center, and VCA Western Veterinary Specialist and Emergency Centre) were examined. Information evaluated included patient signalment, feline immunodeficiency virus/feline leukemia virus status, anatomic location(s) of lymphoma, prior protocols (type and number), MOPP doses, MOPP response, remission duration, hematologic and biochemical parameters, and owner-reported adverse effects.
RESULTS
Overall, 70.3% of cats responded to MOPP chemotherapy. Among the responders, the median remission duration was 166 days. The most common adverse effects were neutropenia and gastrointestinal upset, which were reported in 18.4% of cats. In 55.3% of cats, no adverse effects were reported. In total, 30.8% of responders continued to respond 6 months following the initiation of MOPP, and 15.4% maintained a response 1 year after starting MOPP.
CONCLUSIONS AND RELEVANCE
MOPP is a safe protocol for the treatment of relapsed or refractory feline lymphoma, with a promising overall response rate and median remission time.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cat Diseases; Cats; Lymphoma; Mechlorethamine; Prednisone; Procarbazine; Treatment Outcome; Vincristine
PubMed: 30994392
DOI: 10.1177/1098612X19841916 -
Radiation and chemotherapy for high-risk lower grade gliomas: Choosing between temozolomide and PCV.Cancer Medicine Jan 2020The majority of patients with high-risk lower grade gliomas (LGG) are treated with single-agent temozolomide (TMZ) and radiotherapy despite three randomized trials... (Review)
Review
PURPOSE
The majority of patients with high-risk lower grade gliomas (LGG) are treated with single-agent temozolomide (TMZ) and radiotherapy despite three randomized trials showing a striking overall survival benefit with adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy and radiotherapy. This article aims to evaluate the evidence and rationale for the widespread use of TMZ instead of PCV for high-risk LGG.
METHODS AND MATERIALS
We conducted a literature search utilizing PubMed for articles investigating the combination of radiotherapy and chemotherapy for high-risk LGG and analyzed the results of these studies.
RESULTS
For patients with IDH mutant 1p/19q codeleted LGG tumors, there is limited evidence to support the use of TMZ. In medically fit patients with codeleted disease, existing data demonstrate a large survival benefit for PCV as compared to adjuvant radiation therapy alone. For patients with non-1p/19q codeleted LGG, early data from the CATNON study supports inclusion of adjuvant TMZ for 12 months. Subset analyses of the RTOG 9402 and EORTC 26951 do not demonstrate a survival benefit for adjuvant PCV for non-1p/19q codeleted gliomas, however secondary analyses of RTOG 9802 and RTOG 9402 demonstrated survival benefit in any IDH mutant lower grade gliomas, regardless of 1p/19q codeletion status.
CONCLUSIONS
At present, we conclude that current evidence does not support the widespread use of TMZ over PCV for all patients with high-risk LGG, and we instead recommend tailoring chemotherapy recommendation based on IDH status, favoring adjuvant PCV for patients with any IDH mutant tumors, both those that harbor 1p/19q codeletion and those non-1p/19q codeleted. Given the critical role radiation plays in the treatment of LGG, radiation oncologists should be actively involved in discussions regarding chemotherapy choice in order to optimize treatment for their patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain; Brain Neoplasms; Chemoradiotherapy, Adjuvant; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Glioma; Humans; Isocitrate Dehydrogenase; Lomustine; Mutation; Neoplasm Grading; Procarbazine; Progression-Free Survival; Randomized Controlled Trials as Topic; Temozolomide; Vincristine
PubMed: 31701682
DOI: 10.1002/cam4.2686 -
Archives of Toxicology Mar 2021The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory...
The Organisation for Economic Co-Operation and Development Test Guideline 488 (TG 488) uses transgenic rodent models to generate in vivo mutagenesis data for regulatory submission. The recommended design in TG 488, 28 consecutive daily exposures with tissue sampling three days later (28 + 3d), is optimized for rapidly proliferating tissues such as bone marrow (BM). A sampling time of 28 days (28 + 28d) is considered more appropriate for slowly proliferating tissues (e.g., liver) and male germ cells. We evaluated the impact of the sampling time on mutant frequencies (MF) in the BM of MutaMouse males exposed for 28 days to benzo[a]pyrene (BaP), procarbazine (PRC), isopropyl methanesulfonate (iPMS), or triethylenemelamine (TEM) in dose-response studies. BM samples were collected + 3d, + 28d, + 42d or + 70d post exposure and MF quantified using the lacZ assay. All chemicals significantly increased MF with maximum fold increases at 28 + 3d of 162.9, 6.6, 4.7 and 2.8 for BaP, PRC, iPMS and TEM, respectively. MF were relatively stable over the time period investigated, although they were significantly increased only at 28 + 3d and 28 + 28d for TEM. Benchmark dose (BMD) modelling generated overlapping BMD confidence intervals among the four sampling times for each chemical. These results demonstrate that the sampling time does not affect the detection of mutations for strong mutagens. However, for mutagens that produce small increases in MF, sampling times greater than 28 days may produce false-negative results. Thus, the 28 + 28d protocol represents a unifying protocol for simultaneously assessing mutations in rapidly and slowly proliferating somatic tissues and male germ cells.
Topics: Animals; Dose-Response Relationship, Drug; Germ Cells; Male; Mice; Mice, Transgenic; Mutagenesis; Mutagenicity Tests; Mutagens; Mutation; Time Factors
PubMed: 33506374
DOI: 10.1007/s00204-021-02977-6 -
Medicine Sep 2020Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma.
A comparative study of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma: A protocol for systematic review and meta-analysis.
BACKGROUND
Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma.
METHODS
Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis.
RESULTS
These results obtained in this study will be published in a peer-reviewed journal.
CONCLUSION
Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma.
SYSTEMATIC REVIEW REGISTRATION NUMBER
INPLASY202080078.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Glioma; Humans; Lomustine; Meta-Analysis as Topic; Neoplasm Grading; Neoplasm Recurrence, Local; Procarbazine; Systematic Reviews as Topic; Vincristine; Young Adult
PubMed: 32957367
DOI: 10.1097/MD.0000000000022238