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Medicine Apr 2021Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a...
BACKGROUND
Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach.
METHODS
We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years.
RESULTS
Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas.
CONCLUSIONS
Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Deoxycytidine; Doxorubicin; Female; Humans; Immunotherapy; Leiomyosarcoma; Molecular Targeted Therapy; Treatment Outcome; Uterine Neoplasms; Gemcitabine
PubMed: 33787622
DOI: 10.1097/MD.0000000000025309 -
Gynecologic Oncology Jul 2021Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status.
PATIENTS AND METHODS
We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series.
RESULTS
Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00-3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004-0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant.
CONCLUSIONS
In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
Topics: BRCA1 Protein; BRCA2 Protein; Drug Hypersensitivity; Female; Genes, BRCA1; Genes, BRCA2; Germ-Line Mutation; Humans; Multicenter Studies as Topic; Observational Studies as Topic; Organoplatinum Compounds; Retrospective Studies
PubMed: 33896588
DOI: 10.1016/j.ygyno.2021.04.018 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2020Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold...
A closed vitrification system enables a murine ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting activity of microcystins.
Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth (eIVFG) is a robust in vitro model for ovotoxicity testing. However, the follicle preparation process is complex and highly dependent on technical skills. Here, we aimed to use vitrification method to cryopreserve murine immature follicles for a high-content eIVFG, chemical exposure, and ovotoxicity screening. Results indicated that a closed vitrification system combined with optimized vitrification protocols preserved mouse follicle viability and functionality and vitrified follicles exhibited comparable follicle and oocyte reproductive outcomes to freshly harvested follicles during eIVFG, including follicle survival and development, ovarian steroidogenesis, and oocyte maturation and ovulation. Moreover, vitrified follicles consistently responded to ovotoxic chemical, doxorubicin (DOX). We further used vitrified follicles to test the response of microcystins (MCs), an emerging category of environmental contaminants produced by cyanobacteria associated with harmful algal blooms (HABs), and found that different congeners of MCs exhibited differential ovotoxicities. In summary, our study demonstrates that vitrification enables a long-term-storage and ready-to-use ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting effects of MCs.
Topics: Animals; Antibiotics, Antineoplastic; Cryopreservation; Doxorubicin; Endocrine Disruptors; Female; High-Throughput Screening Assays; Mice; Microcystins; Ovarian Follicle; Vitrification
PubMed: 32017985
DOI: 10.1016/j.reprotox.2020.01.009 -
Journal of the American Heart... Mar 2021Background Anthracyclines are a key chemotherapeutic agent used against hematological and solid organ malignancies. However, their benefits in cancer survival are... (Meta-Analysis)
Meta-Analysis
Cardiotoxic Effect of Modern Anthracycline Dosing on Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Placebo Arms From Randomized Controlled Trials.
Background Anthracyclines are a key chemotherapeutic agent used against hematological and solid organ malignancies. However, their benefits in cancer survival are limited by cumulative, dose-related cardiotoxicity. The impact of anthracyclines on left ventricular ejection fraction (LVEF), in the era of modern chemotherapy regimens, remains unclear. Methods and Results Three databases (CENTRAL, MEDLINE, and SCOPUS) were systematically searched for randomized trials evaluating cardioprotective agents against placebo, in preventing cardiotoxicity. Echocardiography or magnetic resonance measured LVEF pre- and post-anthracycline-based chemotherapy was abstracted from placebo trial arms. The key terms included "anthracycline," "cardiotoxicity" and "randomized." A doxorubicin equivalent anthracycline dose metric was calculated to compare different anthracyclines. A random-effects model was used to pool mean difference in LVEF after anthracycline. Meta-regressions were calculated to identify variation sources. We included 660 patients from 19 trials. The weighted mean baseline LVEF across studies was 62.6%, and follow-up LVEF assessment was performed at 6 months. The pooled mean decline in LVEF among placebo arms was 5.4% (95% CI, 3.5%-7.3%) with a doxorubicin equivalent anthracycline dose of 385 mg/m. Meta-regression analysis showed no significant difference in LVEF against doxorubicin equivalent anthracycline dose as continuous (=0.29) or against published cut-offs for cardiotoxicity (250 mg/m, =0.21; 360 mg/m, =0.40; and 400 mg/m, =0.66). The differences in mean LVEF were not associated with sex, adjunct chemotherapy, or cancer type. Conclusions The magnitude of LVEF impairment post-anthracycline therapy appears less than previously described with modern dosing regimens. This may improve the accuracy of power calculation for future clinical trials assessing the role of cardioprotective therapy.
Topics: Anthracyclines; Cardiotoxicity; Humans; Neoplasms; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 33660514
DOI: 10.1161/JAHA.120.018802 -
Haematologica Jul 2020Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing...
Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review.
Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been performed in the era of anti-CD20 monoclonal antibody therapy. A comprehensive search (01/2002-01/2019) was systematically performed using Ovid MEDLINE, Ovid EMBASE and Cochrane. Studies were selected from a total of 804, screened based on predefined inclusion/exclusion criteria, and were critically appraised. Three post hoc analyses (RICOVER-60, RCHOP-14/21, GOYA), one prospective database and 10 retrospective series were included. 7,357 rituximab/obinutuzumab-exposed patients were analysed. The median percentage receiving intrathecal prophylaxis was 11.9%. Cumulative CNS relapse incidence ranged from 1.9% at 6.5 years to 8.4% at 5 years. Median time (of medians) to CNS relapse was 10 months. 73% developed isolated CNS relapses, 24% concurrent CNS/systemic relapse, and 3% post-systemic relapse. Reported CNS relapse sites were: parenchymal (58%), leptomeningeal (27%), and both (12%). Event rates were low resulting in limited power within each study to provide robust univariable/multivariable analysis. Intrathecal prophylaxis was not a univariable or multivariable factor associated with a reduction in CNS relapse in any study. We found no strong evidence for the benefit, or indeed genuine lack of benefit, of stand-alone intrathecal prophylaxis in preventing CNS relapse in diffuse large B-cell lymphoma-treated patients using anthracycline-based immunochemotherapy. Current published study designs limit the strength of such conclusions.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Retrospective Studies; Rituximab; Vincristine
PubMed: 31488560
DOI: 10.3324/haematol.2019.229948 -
Artificial Organs May 2020An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination...
An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination therapy. Some VAD patients require radiotherapy due to concomitant oncologic morbidities, including thoracic malignancies. This raises the potential of VAD malfunction via radiation-induced damage. So far, only case reports and small case series on radiotherapy have been published, most of them on HeartMate II (HMII, Abbott, North Chicago, IL, USA). Significantly, the effects of irradiation on the HeartMate 3 (HM3, Abbott) remain undefined, despite the presence of controller components engineered within the pump itself. We report the first case of a patient with a HM3 who successfully underwent stereotactic hypofractionated radiotherapy due to an early-stage non-small-cell lung cancer. The patient did not suffer from any complications, including toxicity or VAD malfunction. Based on this case report and on published literature, we think that performing radiotherapy after VAD implantation with the aid of a multidisciplinary team could be performed, but more in vitro studies and cases series are needed to reinforce this statement.
Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Ductal, Breast; Cardiomyopathies; Doxorubicin; Female; Heart-Assist Devices; Humans; Lung Neoplasms; Middle Aged; Radiation Dose Hypofractionation; Radiotherapy, Intensity-Modulated
PubMed: 31769042
DOI: 10.1111/aor.13612 -
Cell Transplantation 2024Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell...
Posttransplant lymphoproliferative disorder (PTLD) is a rare lymphoid and/or plasmocytic proliferation that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the pathologic features and clinical outcomes of T-cell PTLD, an extremely rare subtype of PTLD, after allo-HSCT. In this study, six allo-HSCT recipients with T-cell PTLD from five transplant centers in China were enrolled. All the T-cell PTLD were donor-derived, and three patients were with monomorphic and three with polymorphic types, respectively. All patients received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy. Five patients achieved complete response (CR), and one experienced progressive disease (PD). The median time from HSCT to onset was 4 (range: 0.6-72) months, analyzed in combination with the other 16 patients with T-cell PTLD identified from previous reports. About 56.3% of the T-cell samples (9/16) were positive for in situ hybridization with an Epstein-Barr virus (EBV)-encoded small nuclear early region (EBER ISH). CHOP-based chemotherapy might be the optimal strategy for patients who showed no response to empiric therapy with a CR rate of 87.5%. In conclusion, our study observed that T-cell PTLD has distinct clinical manifestations and morphological features, which characterized by less relation to EBV, later occurrence, and poorer prognosis when compared with B-cell PTLD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Lymphoproliferative Disorders; Male; Female; Adult; T-Lymphocytes; Transplantation, Homologous; Adolescent; Child; Middle Aged; Young Adult; Cyclophosphamide
PubMed: 38856035
DOI: 10.1177/09636897241259722