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Clinical Oncology (Royal College of... Dec 2023Extraskeletal osteosarcoma (ESOS) is a malignant tumour developing in soft tissues, characterised by the production of osteoid or bone matrix by tumour cells. The... (Meta-Analysis)
Meta-Analysis
Survival Differences of Patients with Resected Extraskeletal Osteosarcoma Receiving Two Different (Neo)Adjuvant Chemotherapy Regimens: A Systematic Review and Meta-analysis.
AIMS
Extraskeletal osteosarcoma (ESOS) is a malignant tumour developing in soft tissues, characterised by the production of osteoid or bone matrix by tumour cells. The standard treatment for localised ESOS is wide resection. Radiotherapy and chemotherapy are usually incorporated into the management of patients. Two types of chemotherapy regimen are mostly used: an osteosarcoma-type chemotherapy, based on cisplatin, and a soft-tissue sarcoma (STS)-type chemotherapy, using the combination of doxorubicin and ifosfamide. To investigate the difference in survival between these two chemotherapy regimens, a systematic review of studies reporting the 5-year disease-free survival (DFS) rates among patients with ESOS submitted to surgery and who received (neo)adjuvant chemotherapy with osteosarcoma-type or STS-type chemotherapy was carried out.
MATERIALS AND METHODS
Of the 401 articles identified by systematically searching the PubMed, Embase and Cochrane Central Register of Controlled Trials databases, six retrospective studies were included in the final analysis. In total, 319 patients with localised/resected ESOS were included in the study.
RESULTS
Our meta-analysis showed a benefit in 5-year DFS favouring the use of osteosarcoma-type chemotherapy (relative risk = 1.32, 95% confidence interval 1.03-1.69; P = 0.54); I heterogeneity was 0%. The 5-year DFS rate was 56.3% (95% confidence interval 48.3-64.3) with osteosarcoma-type chemotherapy and 45.2% (95% confidence interval 34.5-55.9) with STS-type chemotherapy, with I heterogeneity of 27% and 0%, respectively.
CONCLUSIONS
Our analysis suggests that there may be a difference regarding the type of (neo)adjuvant chemotherapy regimen used in the treatment of patients with resected ESOS in favour of osteosarcoma-type chemotherapy. Future studies evaluating the role of this treatment modality in this scenario need to consider the type of chemotherapy regimen when comparing with an arm of surgery with/without radiotherapy alone.
Topics: Humans; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Osteosarcoma; Soft Tissue Neoplasms; Doxorubicin; Chemotherapy, Adjuvant; Bone Neoplasms
PubMed: 37777356
DOI: 10.1016/j.clon.2023.09.009 -
Blood Cancer Journal Jan 2022Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We... (Meta-Analysis)
Meta-Analysis
Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1-3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Cyclophosphamide; Doxorubicin; Humans; Immunotherapy; Lymphoma, Follicular; Maintenance Chemotherapy; Prednisone; Progression-Free Survival; Randomized Controlled Trials as Topic; Rituximab; Treatment Outcome; Vincristine
PubMed: 34987165
DOI: 10.1038/s41408-021-00598-x -
Molecules (Basel, Switzerland) Oct 2021Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer...
Zeolites and zeolitic imidazolate frameworks (ZIFs) are widely studied as drug carrying nanoplatforms to enhance the specificity and efficacy of traditional anticancer drugs. At present, there is no other systematic review that assesses the potency of zeolites/ZIFs as anticancer drug carriers. Due to the porous nature and inherent pH-sensitive properties of zeolites/ZIFs, the compounds can entrap and selectively release anticancer drugs into the acidic tumor microenvironment. Therefore, it is valuable to provide a comprehensive overview of available evidence on the topic to identify the benefits of the compound as well as potential gaps in knowledge. The purpose of this study was to evaluate the potential therapeutic applications of zeolites/ZIFs as drug delivery systems delivering doxorubicin (DOX), 5-fluorouracil (5-FU), curcumin, cisplatin, and miR-34a. Following PRISMA guidelines, an exhaustive search of PubMed, Scopus, Embase, and Web of Science was conducted. No language or time limitations were used up to 25th August 2021. Only full text articles were selected that pertained to the usage of zeolites/ZIFs in delivering anticancer drugs. Initially, 1279 studies were identified, of which 572 duplicate records were excluded. After screening for the title, abstract, and full texts, 53 articles remained and were included in the qualitative synthesis. An Inter-Rater Reliability (IRR) test, which included a percent user agreement and reliability percent, was conducted for the 53 articles. The included studies suggest that anticancer drug-incorporated zeolites/ZIFs can be used as alternative treatment options to enhance the efficacy of cancer treatment by mitigating the drawbacks of drugs under conventional treatment.
Topics: Animals; Antineoplastic Agents; Doxorubicin; Drug Carriers; Drug Delivery Systems; Female; Humans; Hydrogen-Ion Concentration; Male; Nanoparticles; Neoplasms; Porosity; Tumor Cells, Cultured; Tumor Microenvironment; Zeolites
PubMed: 34684777
DOI: 10.3390/molecules26206196 -
Scientific Reports Mar 2021Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients... (Meta-Analysis)
Meta-Analysis
Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p < 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.
Topics: Animals; Cardiomyopathies; Cardiotoxicity; Doxorubicin; Echocardiography; Exercise; Female; Heart; Humans; Male; Neoplasms; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley
PubMed: 33737561
DOI: 10.1038/s41598-021-83877-8 -
Diseases of the Colon and Rectum Feb 2020Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment;...
Pressurized Intraperitoneal Aerosol Chemotherapy, a Palliative Treatment Approach for Patients With Peritoneal Carcinomatosis: Description of Method and Systematic Review of Literature.
BACKGROUND
Peritoneal metastases arise in patients with a variety of primary cancers, and are associated with a poor prognosis. Systemic chemotherapy is the mainstay of treatment; however, the morbidity is considerable and the survival benefit is modest. Cytoreductive surgery and heated intraperitoneal chemotherapy is a potentially curative treatment available to a minority of patients; however, most develop recurrent disease. A novel palliative treatment for peritoneal metastases, pressurized intraperitoneal aerosol chemotherapy, has recently been introduced. Pressurized intraperitoneal aerosol chemotherapy utilizes an aerosol of chemotherapy in carbon dioxide gas. It is instilled into the abdomen under pressure via laparoscopic ports. No cytoreduction is performed. Pressurized intraperitoneal aerosol chemotherapy can be repeated at 6-week intervals. Oxaliplatin or cis-platinum and doxorubicin have been used to date.
OBJECTIVE
This study aims to systematically review and evaluate the method, and the preclinical and early clinical results of pressurized intraperitoneal aerosol chemotherapy.
DATA SOURCES
Medline and the Cochrane Library were the data sources for the study.
STUDY SELECTION
Peer-reviewed series of greater than 10 patients, with sufficient patient data, through April 2019, were selected.
INTERVENTION
Patients with peritoneal metastases underwent pressurized intraperitoneal aerosol chemotherapy.
MAIN OUTCOME MEASURES
Patient dropout, histologic tumor response, adverse events, and 30-day mortality were the primary outcomes measured.
RESULTS
A total of 921 patients with peritoneal metastases were brought to the operating room for pressurized intraperitoneal aerosol chemotherapy. The number of pressurized intraperitoneal aerosol chemotherapy treatments administered was as follows: 1 treatment, 862 (94%); 2 treatments, 645 (70%); and 3 treatments, 390 patients (42%). Initial laparoscopic access was not possible in 59 patients (6.4%). Common Terminology Criteria for Adverse Events grade 3 or higher were noted in 13.7% of the patients who, collectively, underwent a total of 2116 treatments. The 30-day mortality was 2.4% (22/921).
LIMITATIONS
This study was limited by the heterogeneity of reported data and primary tumor types and by the lack of long-term survival data.
CONCLUSIONS
Early clinical results are encouraging, but tumor-specific, prospective, randomized trials are needed to compare pressurized intraperitoneal aerosol chemotherapy to systemic chemotherapy. This method has yet to be introduced to the United States. It is another therapeutic option for patients with peritoneal metastases and will broaden the patient base for future clinical trials.
Topics: Aerosols; Aged; Antineoplastic Combined Chemotherapy Protocols; Carbon Dioxide; Cisplatin; Cytoreduction Surgical Procedures; Doxorubicin; Humans; Hyperthermia, Induced; Instillation, Drug; Laparoscopy; Middle Aged; Oxaliplatin; Palliative Care; Peritoneal Neoplasms; Pressure; Treatment Outcome
PubMed: 31914116
DOI: 10.1097/DCR.0000000000001565 -
Asian Cardiovascular & Thoracic Annals Mar 2022Primary intravenous leiomyosarcomas are rare vascular tumors with aggressive disease biology. The diagnosis and management have been challenging as little data exist...
INTRODUCTION
Primary intravenous leiomyosarcomas are rare vascular tumors with aggressive disease biology. The diagnosis and management have been challenging as little data exist from large databases.
METHODS
A literature search was done to identify all cases of primary leiomyosarcomas in the last five years. Clinicopathological features and management strategies were evaluated.
RESULTS
The median age was 53 years, predominantly females (2.5:1), presenting as metastases in up to 12.1% cases. Most tumors were locally advanced with a median size of 10cm. Inferior vena cava involvement from renal veins to infrahepatic veins remains the most frequent site (57.1%cases) while nearly half (52.8%) proceeded for surgery without histological proof. Most patients could undergo upfront resection (88.0%) with few patients receiving neoadjuvant chemotherapy (4.3%) or neoadjuvant radiotherapy (2.2%). Significant multivisceral resections included right nephrectomy (41.3%), liver resection (25.7%) and left nephrectomy (2.2%). Most patients (91.8%) needed an inferior vena cava graft placement with remarkable microscopically negative margins (85.5% cases). Doxorubicin and ifosfamide were the most frequently used combination chemotherapy regimens in both pre and postoperative settings with partial responses. The median overall and disease free survival among operated patients was 60 months and 28 months respectively. In multivariate analysis large tumor, extensive inferior vena cava involvement, and need for adjuvant chemotherapy appeared significant predictors for overall survival.
CONCLUSIONS
Aggressive upfront surgical resection with clear margin remains the key for long-term survival. Doxorubicin-based regimens were preferred as neoadjuvant chemotherapy while adjuvant treatment with chemotherapy, radiotherapy, or both may be considered in high-risk patients.
Topics: Doxorubicin; Female; Humans; Leiomyosarcoma; Male; Margins of Excision; Middle Aged; Treatment Outcome; Vascular Neoplasms; Vena Cava, Inferior
PubMed: 34672808
DOI: 10.1177/02184923211049911 -
Annals of Hematology Dec 2021The addition of molecular targeted agents (MTAs) to R-CHOP has been one of the main focuses of research in patients with DLBCL. Despite encouraging preliminary results,... (Meta-Analysis)
Meta-Analysis
Combination of novel molecular targeted agent plus R-CHOP-based regimen versus R-CHOP alone in previously untreated diffuse large B-cell lymphoma (DLBCL) patients: a systematic review and meta-analysis.
The addition of molecular targeted agents (MTAs) to R-CHOP has been one of the main focuses of research in patients with DLBCL. Despite encouraging preliminary results, recent randomized controlled trials (RCT) have not shown a definitive benefit over standard R-CHOP. Here we conducted a systematic review and meta-analysis to investigate the impact of this strategy. A systematic literature review was conducted to identify RCT that evaluated the addition of MTA to R-CHOP-based regimen versus R-CHOP alone in previously untreated DLBCL patients. Fixed and random effects models were used to estimate pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI). Progression-free survival (PFS), overall survival, and adverse events (AE) were analyzed. A total of seven RCT including 3,255 patients with DLBCL met the eligibility criteria. Three different types of MTAs (bortezomib, ibrutinib, and lenalidomide) were investigated in combination with R-CHOP. Overall, R-CHOP plus MTA showed a slightly better PFS (HR=0.86; 95% CI: 0.76-0.98). No differences were observed according to the cell of origin subtype of DLBCL. Interestingly, patients younger than 60 years had a significantly better PFS with R-CHOP plus MTAs (HR=0.72; 95% CI: 0.56-0.93), while no benefit was observed in patients older than 60 years (HR=0.96). The combination strategy showed higher odds to develop serious AEs (OR= 1.46, 95% CI 1.11-1.91). R-CHOP plus MTA seems only to slightly improve PFS in patients with DLBCL, particularly in younger patients. An increase in toxicity was observed in comparison to R-CHOP.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Drug Discovery; Humans; Lymphoma, Large B-Cell, Diffuse; Molecular Targeted Therapy; Prednisone; Progression-Free Survival; Rituximab; Treatment Outcome; Vincristine
PubMed: 34378095
DOI: 10.1007/s00277-021-04623-8 -
Acta Oncologica (Stockholm, Sweden) Jun 2021Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard of care first line treatment for diffuse large B-cell lymphoma... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is standard of care first line treatment for diffuse large B-cell lymphoma (DLBCL), though outcomes remain suboptimal.
METHODS
We performed a systemic review and meta-analysis of randomized controlled trials comparing the efficacy and safety of R-CHOP vs. R-CHOP + X (addition of another drug to R-CHOP) as first line treatment for DLBCL. We searched Cochrane Library, PubMed and conference proceedings up to September 2020.
RESULTS
Our search yielded ten trials including 4206 patients. The added drug was bortezomib or lenalidomide in three trials each, and gemcitabine, bevacizumab and ibrutinib, each drug in one trial. R-CHOP + X was associated with statistically significant improved disease control (HR 0.88, 95% CI 0.78-0.99). The point estimate was in favor of improved overall survival with R-CHOP + X (hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.75-1.00), although this was not statistically significant. Subgroup analysis revealed improved disease control with the addition of lenalidomide and in patients younger than 60 years. R-CHOP + X was associated with an increase in serious adverse events and grade III/IV hematologic toxicity.
CONCLUSION
The addition of another drug to frontline R-CHOP treatment for DLBCL did not result in a significant improvement in OS, although we did observe improved disease control compared to R-CHOP, perhaps most evident with the addition of lenalidomide. Yet, RCHOP + X was associated with an increased risk for serious and hematological adverse events. Further studies could reveal subgroups that would benefit most from augmentation of standard R-CHOP.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Rituximab; Vincristine
PubMed: 33734921
DOI: 10.1080/0284186X.2021.1898048 -
Japanese Journal of Clinical Oncology Oct 2020The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. The guideline committee for clinical care of extra-abdominal...
OBJECTIVE
The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. The guideline committee for clinical care of extra-abdominal desmoid-type fibromatosis in Japan conducted a systematic review of treatment with doxorubicin-based chemotherapy for desmoid-type fibromatosis.
METHODS
We searched the pertinent literature. Two reviewers evaluated and screened it independently for eligibility and extracted data. They rated each report according to the grading of recommendations development and evaluation methodology. Based on the 'body of evidence', which the reviewers created, the clinical guideline committee decided a recommendation for the clinical question, 'Is doxorubicin-based chemotherapy effective for patients with extra-abdominal desmoid-type fibromatosis?'
RESULTS
Fifty-three articles were extracted by the literature search, and one from hand search. After the first and second screenings, five articles were subjected to the final evaluation. There were no randomized controlled trials. According to response evaluation criteria in solid tumors criteria, the response rates of doxorubicin-based regimens and liposomal doxorubicin were 44% (28.6-54) and 33.3% (0-75) on average, respectively. In two reports, the response rates of doxorubicin-based regimens were higher than those of non-doxorubicin-based ones; 54% vs 12%, 40% vs 11%, respectively. The rates of G3 or G4 complications according to common terminology criteria for adverse events were 28% and 13% with doxorubicin-based and liposomal doxorubicin chemotherapy, respectively, including neutropenia or cardiac dysfunction. None of the reports addressed the issue of QOL.
CONCLUSION
Although the evidence level was low in the evaluated studies, doxorubicin-based and liposomal doxorubicin chemotherapy was observed to be effective. However, doxorubicin-based chemotherapy is associated with non-ignorable adverse events, and is not covered by insurance in Japan. We weakly recommend doxorubicin-based chemotherapy for patients with extra-abdominal desmoid-type fibromatosis in cases resistant to other treatments.
Topics: Abdomen; Antineoplastic Agents; Doxorubicin; Fibromatosis, Aggressive; Humans; Japan; Polyethylene Glycols; Treatment Outcome
PubMed: 32700733
DOI: 10.1093/jjco/hyaa125 -
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