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Cancers May 2024The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the... (Review)
Review
The last 3 decades have witnessed a major evolution in the treatment of advanced-stage Hodgkin lymphoma (HL). The most prominent of these developments include the introduction of the international prognostic scoring (IPS) system; therapeutic decision-making based on both IPS and interim PET/CT data; the finding that a negative interim PET/CT result could be safely used for treatment de-escalation; the introduction of intensive combination chemotherapy like escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, oncovin (vincristine), procarbazine, and prednisone); and further modification of this protocol with the incorporation of a conjugated anti-CD30 antibody brentuximab vedotin (BV) into first-line regimens, like BV-AVD (BV+ adriamycin, vinblastine and dacarbazine) and BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone). The accruing data about the toxicity of the escalated BEACOPP protocol have led to decreasing the number of therapeutic cycles, substitution of toxic agents like procarbazine with dacarbazine (e.g., BEACOPDac), and reduction/omission of radiation therapy. Lately, a significant advancement has been made by the integration of checkpoint inhibitors in the first-line treatment, with preliminary results demonstrating the superiority of anti-PD1 combined with chemotherapy (nivolumab-AVD) compared to the BV-AVD regimen. This review aims to analyze recently published studies whose findings could change the treatment practice in advanced-stage HL.
PubMed: 38893177
DOI: 10.3390/cancers16112059 -
Frontiers in Veterinary Science 2024Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy...
Canine gastrointestinal (GI) and hepatosplenic (HS) high-grade (large cell) lymphomas are uncommon forms of canine lymphomas, with a very poor response to chemotherapy and a very poor prognosis. Currently, there are no established effective chemotherapy protocols for canine GI/HS lymphomas. This case series aimed to retrospectively evaluate the efficacy of lomustine-based protocols L-LOP (L-asparaginase, lomustine, vincristine, and prednisolone) and L-LOPP (with the addition of procarbazine) for treatment of canine GI/HS lymphomas. Medical records of dogs with cytologically or histologically diagnosed lymphoma at CityU Veterinary Medical Centre from 2019 to 2022 were retrospectively reviewed. The L-LOP/LOPP treatment protocol was well tolerated with rare severe adverse events. Median progression-free survival for GI and HS lymphoma was 56 days (range, 10-274 days) and 57 days (range 8-135 days) respectively; while median survival time for GI and HS lymphoma was 93 days (range 10-325 days) and 210 days (range 8-240 days) respectively.
PubMed: 38846784
DOI: 10.3389/fvets.2024.1373180 -
International Journal of Radiation... Apr 2024Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin...
Involved-site Radiation Therapy is Equally Effective and Less Toxic Than Involved-field Radiation Therapy in Patients Receiving Combined Modality Treatment for Early-stage Unfavorable Hodgkin Lymphoma-An Analysis of the Randomized Phase 3 HD17 Trial of the German Hodgkin Study Group.
PURPOSE
Combined modality treatment with chemotherapy followed by consolidation radiation therapy (RT) provides excellent outcomes for patients with early-stage Hodgkin lymphoma. The international standard of care for consolidation RT, involved-site/involved-node radiation therapy (ISRT/INRT), has never been evaluated in a randomized phase 3 trial against the former standard involved-field radiation therapy (IFRT).
METHODS AND MATERIALS
In the multicenter phase 3 GHSG (German Hodgkin Study Group) HD17 trial, patients with early-stage unfavorable Hodgkin lymphoma were randomized between the standard Combined modality treatment group and a positron-emission tomography (PET)-guided group. In the standard group, patients received 2 cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) and 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy IFRT. In the experimental group, patients received no further therapy if postchemotherapy PET was negative and 30 Gy GHSG INRT, comparable to and therefore termed here ISRT, if PET was positive. Here, we analyze the interim PET-positive patients in a post hoc analysis, and therefore the randomized comparison of IFRT versus INRT/ISRT.
RESULTS
A total of 1100 patients were randomized, of which 311 had a positive PET after chemotherapy. Kaplan-Meier estimates of 4-year progression-free survival were 96.8% (95% CI, 91.6%-98.8%) in the IFRT group and 95.4% (95% CI, 89.9%-97.9%; HR, 1.40; 95% CI, 0.44-4.42) in the ISRT group. The pattern of recurrence analyses indicated that none of the cases of disease progression or recurrence in the ISRT group would have been prevented by the use of IFRT. Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients and 2.6% of ISRT patients (P = .03).
CONCLUSIONS
For the first time, consolidation INRT/ISRT was randomly compared with IFRT in a phase 3 trial. Regarding progression-free survival, no advantage of IFRT could be demonstrated. In summary, our data confirm the status of INRT/ISRT as the current standard of care.
PubMed: 38631539
DOI: 10.1016/j.ijrobp.2024.04.015 -
Frontiers in Oncology 2024Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies... (Review)
Review
Gliomas are a group of heterogeneous tumors that account for substantial morbidity, mortality, and costs to patients and healthcare systems globally. Survival varies considerably by grade, histology, biomarkers, and genetic alterations such as IDH mutations and promoter methylation, and treatment, but is poor for some grades and histologies, with many patients with glioblastoma surviving less than a year from diagnosis. The present review provides an introduction to glioma, including its classification, epidemiology, economic and humanistic burden, as well as treatment options. Another focus is on treatment recommendations for IDH-mutant astrocytoma, IDH-mutant oligodendroglioma, and glioblastoma, which were synthesized from recent guidelines. While recommendations are nuanced and reflect the complexity of the disease, maximum safe resection is typically the first step in treatment, followed by radiotherapy and/or chemotherapy using temozolomide or procarbazine, lomustine, and vincristine. Immunotherapies and targeted therapies currently have only a limited role due to disappointing clinical trial results, including in recurrent glioblastoma, for which the nitrosourea lomustine remains the standard of care. The lack of treatment options is compounded by frequently suboptimal clinical practice, in which patients do not receive adequate therapy after resection, including delayed, shortened, or discontinued radiotherapy and chemotherapy courses due to treatment side effects. These unmet needs will require significant efforts to address, including a continued search for novel treatment options, increased awareness of clinical guidelines, improved toxicity management for chemotherapy, and the generation of additional and more robust clinical and health economic evidence.
PubMed: 38571509
DOI: 10.3389/fonc.2024.1368606 -
Journal of Cancer & Allied Specialties 2024High-grade gliomas are malignant, recurring primary central nervous system (CNS) tumors requiring extensive postoperative chemotherapy and radiation treatment....
INTRODUCTION
High-grade gliomas are malignant, recurring primary central nervous system (CNS) tumors requiring extensive postoperative chemotherapy and radiation treatment. Isocitrate dehydrogenase (IDH), 1p19q, and ATRX mutations significantly influence survival and response to chemotherapy, as seen in many extensive studies from the Global North. This study aims to report data from the local region regarding progression-free survival and overall survival in light of molecular characteristics.
MATERIALS AND METHODS
A 10-year retrospective series was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, with 285 patients presenting from 2008 to 2018. Prospective follow-up data was collected, and complete molecular profiles were available for patients presenting from 2010 onwards. Survival analysis was conducted through the Kaplan-Meier method, with log-rank reported.
RESULTS
70.53% (201) of patients were male, with a mean age at diagnosis of 43.33 ± 15.1 years. 265 patients within the cohort completed postoperative radiotherapy, while 141 patients underwent chemotherapy (procarbazine, lomustine, and vincristine, or temozolomide). Mean survival, in months, within the cohort was as follows: glioblastoma (14.1), anaplastic astrocytoma (27.5), and anaplastic oligodendroglioma (39.8). Survival curves showed a lower survival for IDH wild-type ( < 0.0001), ATRX mutated ( = 0.029), and 1p19q non-deleted ( = 0.008) tumors from Pakistan.
DISCUSSION
Our findings quantified long-term survival outcomes for high-grade glioma from Pakistan, analyzing the various treatment patterns. Of particular importance, molecular sub-classification significantly predicted survival outcomes for IDH, ATRX, and 1p19 co-deletion mutations. Expanding brain tumor epidemiology will benefit assessing the efficacy of regional oncological centers and establishing standards of care.
PubMed: 38259678
DOI: 10.37029/jcas.v10i1.565 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Yonsei Medical Journal Jan 2024Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity...
PURPOSE
Surgery, radiotherapy (RT), and chemotherapy have prolonged the survival of patients with anaplastic oligodendroglioma. However, whether RT induces long-term toxicity remains unknown. We analyzed the relationship between the RT dose to the fornix and symptomatic radiation necrosis (SRN).
MATERIALS AND METHODS
A total of 67 patients treated between 2009 and 2019 were analyzed. SRN was defined according to the following three criteria: 1) radiographic findings, 2) symptoms attributable to the lesion, and 3) treatment resulting in symptom improvement. Various contours, including the fornix, were delineated. Univariate and multivariate analyses of the relationship between RT dose and SRN, as well as receiver operating characteristic curve analysis for cut-off values, were performed.
RESULTS
The most common location was the frontal lobe (n=40, 60%). Gross total resection was performed in 38 patients (57%), and 42 patients (63%) received procarbazine, lomustine, and vincristine chemotherapy. With a median follow-up of 42 months, the median overall and progression-free survival was 74 months. Sixteen patients (24%) developed SRN. In multivariate analysis, age and maximum dose to the fornix were associated with the development of SRN. The cut-off values for the maximum dose to the fornix and age were 59 Gy (equivalent dose delivered in 2 Gy fractions) and 46 years, respectively. The rate of SRN was higher in patients whose maximum dose to the fornix was >59 Gy (13% vs. 43%, =0.005).
CONCLUSION
The maximum dose to the fornix was a significant factor for SRN development. While fornix sparing may help maintain neurocognitive function, additional studies are needed.
Topics: Humans; Oligodendroglioma; Brain Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Vincristine; Radiation Dosage; Necrosis
PubMed: 38154474
DOI: 10.3349/ymj.2023.0112 -
Asian Journal of Neurosurgery Sep 2023The 2021 WHO Classification of Central Nervous System Tumors taxonomy laid further stress on molecular classification and prognostication of glial tumors in...
The 2021 WHO Classification of Central Nervous System Tumors taxonomy laid further stress on molecular classification and prognostication of glial tumors in comparison to histopathological grading. Research shows that low-grade gliomas (LGGs) can go through malignant differentiation and lead to severe disability and death. Data from various populations will be necessary to ascertain the exact interplay between genotypic predictors of LGG and outcomes. To assess the molecular pathology for glial tumors in the Pakistani population, the Shaukat Khanum Memorial Cancer Hospital carried out a retrospective chart review of electronic health records from 2008 to 2018, with immunohistochemistry analysis findings from 2010 to 2018. Patients with a pathological diagnosis of a glioma were included. Analysis was performed using IBM SPSS Statistics Version 23 and STATA Version 16. A -value of less than 0.05 was considered statistically significant with 95% confidence intervals reported. In all, 281 operable tumors were recorded. The most common procedure was a subtotal resection, and astrocytomas (64.77%) were the most common tumors. Radiation therapy and PCV (procarbazine, CCNU, and vincristine) was received by 85 patients, while radiation therapy and temozolomide were administered to 15 patients. Isocitrate dehydrogenase (IDH) wild-type LGG had a lower survival time, while improved survival times were seen for alpha-thalassemia X-linked intellectual disability syndrome (ATRX) retained and 1p19q co-deleted LGGs. Further studies are required to gain a better understanding of lower-grade glial tumor treatment and survival in Pakistan.
PubMed: 38152532
DOI: 10.1055/s-0043-1771369 -
Journal of Clinical Medicine Nov 2023The genotoxic methylating agents temozolomide (TMZ) and procarbazine and the chloroethylating nitrosourea lomustine (CCNU) are part of the standard repertoire in the... (Review)
Review
The genotoxic methylating agents temozolomide (TMZ) and procarbazine and the chloroethylating nitrosourea lomustine (CCNU) are part of the standard repertoire in the therapy of malignant gliomas (CNS WHO grade 3 and 4). This review describes the mechanisms of their cytotoxicity and cytostatic activity through apoptosis, necroptosis, drug-induced senescence, and autophagy, interaction of critical damage with radiation-induced lesions, mechanisms of glioblastoma resistance to alkylating agents, including the alkyltransferase MGMT, mismatch repair, DNA double-strand break repair and DNA damage responses, as well as IDH-1 and PARP-1. Cyclin-dependent kinase inhibitors such as regorafenib, synthetic lethality using PARP inhibitors, and alternative therapies including tumor-treating fields (TTF) and CUSP9v3 are discussed in the context of alkylating drug therapy and overcoming glioblastoma chemoresistance. Recent studies have revealed that senescence is the main trait induced by TMZ in glioblastoma cells, exhibiting hereupon the senescence-associated secretory phenotype (SASP). Strategies to eradicate therapy-induced senescence by means of senolytics as well as attenuating SASP by senomorphics are receiving increasing attention, with therapeutic implications to be discussed.
PubMed: 38068493
DOI: 10.3390/jcm12237442