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BMC Medicine Jul 2022Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Umbrella clinical trials in precision oncology are designed to tailor therapies to the specific genetic changes within a tumor. Little is known about the risk/benefit ratio for umbrella clinical trials. The aim of our systematic review with meta-analysis was to evaluate the efficacy and safety profiles in cancer umbrella trials testing targeted drugs or a combination of targeted therapy with chemotherapy.
METHODS
Our study was prospectively registered in PROSPERO (CRD42020171494). We searched Embase and PubMed for cancer umbrella trials testing targeted agents or a combination of targeted therapies with chemotherapy. We included solid tumor studies published between 1 January 2006 and 7 October 2019. We measured the risk using drug-related grade 3 or higher adverse events (AEs), and the benefit by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). When possible, data were meta-analyzed.
RESULTS
Of the 6207 records identified, we included 31 sub-trials or arms of nine umbrella trials (N = 1637). The pooled overall ORR was 17.7% (95% confidence interval [CI] 9.5-25.9). The ORR for targeted therapies in the experimental arms was significantly lower than the ORR for a combination of targeted therapy drugs with chemotherapy: 13.3% vs 39.0%; p = 0.005. The median PFS was 2.4 months (95% CI 1.9-2.9), and the median OS was 7.1 months (95% CI 6.1-8.4). The overall drug-related death rate (drug-related grade 5 AEs rate) was 0.8% (95% CI 0.3-1.4), and the average drug-related grade 3/4 AE rate per person was 0.45 (95% CI 0.40-0.50).
CONCLUSIONS
Our findings suggest that, on average, one in five cancer patients in umbrella trials published between 1 January 2006 and 7 October 2019 responded to a given therapy, while one in 125 died due to drug toxicity. Our findings do not support the expectation of increased patient benefit in cancer umbrella trials. Further studies should investigate whether umbrella trial design and the precision oncology approach improve patient outcomes.
Topics: Antineoplastic Agents; Humans; Medical Oncology; Neoplasms; Precision Medicine
PubMed: 35799149
DOI: 10.1186/s12916-022-02420-2 -
Pediatric Research Mar 2022Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline...
BACKGROUND
Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries.
METHODS
We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted.
RESULTS
In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested.
CONCLUSIONS
Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs.
IMPACT
This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.
Topics: Child; Humans; Leukemia; Neoplasms; Physical Fitness; Physical Functional Performance; Reproducibility of Results
PubMed: 33859367
DOI: 10.1038/s41390-021-01523-5 -
Apoptosis : An International Journal on... Aug 2023Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the...
Pyroptosis is one of the mechanisms of programmed cell death (PCD) activated by inflammasomes and involved by the caspase family and the gasdermin family. During the oncogenesis and progression of tumors, pyroptosis is crucial, and complex withal. Currently, pyroptosis is the focus topic in the research field of oncology, but there is no single bibliometric analysis systematically studying 'pyroptosis and cancer'. Our study aimed to visualize the research status of pyroptosis in oncology and excavate the hotspots and prospects in this field. Furthermore, in consideration of the professional direction of researchers, we particularly emphasized articles on pyroptosis in gynecology and formed a mini systematic review. This bibliometric work integrated and analyzed all articles from ISI Web of Science: Science Citation Index Expanded (SCI-Expanded) (dated April 25th, 2022), based on quantitative and visual mapping approaches. Systematically reviewing articles on pyroptosis in gynecology helped us complement our analysis of research advancements in this field. Including 634 articles, our study found that the number of articles on pyroptosis in cancer increased exponentially in recent years. These publications came from 45 countries and regions headed by China and the US mainly aiming at the mechanism of pyroptosis in cell biology and biochemistry molecular biology, as well as the role of pyroptosis in the development and therapeutic application of various cancers. The top 20 most cited studies on this topic mostly came from the US, followed by China and England, and half of the articles cited more than 100 times in total were published in Nature. Moreover, as for gynecologic cancer, in vitro and bioinformatics analysis were the main methodology conducting to explore roles of pyroptosis-related genes (PRGs) and formation of inflammasomes in cancer progression and prognosis. Pyroptosis has evolved into a burgeoning research field in oncology. The cellular and molecular pathway mechanism of pyroptosis, as well as the effect of pyroptosis in oncogenesis, progression, and treatment have been the hot topic of the current study and provided us the future direction as the potential opportunities and challenges. We advocate more active cooperation to improve therapeutic strategies for cancer.
Topics: Female; Humans; Apoptosis; Bibliometrics; Carcinogenesis; Cell Transformation, Neoplastic; Inflammasomes; Neoplasms; Pyroptosis
PubMed: 37071294
DOI: 10.1007/s10495-023-01821-9 -
Cancer Medicine Sep 2023Survival of children and adolescents diagnosed with cancer improved over the last decades due to better diagnostics, treatment, and supportive care. Quality criteria... (Review)
Review
INTRODUCTION
Survival of children and adolescents diagnosed with cancer improved over the last decades due to better diagnostics, treatment, and supportive care. Quality criteria that measure, compare, and make the quality of care of individual pediatric oncology centers more transparent are heterogeneous and inconsistent.
AIM
With this systematic review, we aimed to summarize existing quality criteria for pediatric oncology centers in countries with highly developed health-care systems.
METHODS
We searched three databases for publications, and websites for guidelines about quality criteria for pediatric oncology centers in February 2022. We considered all types of publications except expert opinions. We excluded publications not focusing on highly developed health-care systems, addressing the certification of professionals, or focusing on subspecialties (e.g., pediatric neuro-oncology). We discarded quality criteria if they were too specific (e.g., for a specific treatment center), too broad (e.g., national 5-year overall survival), or if the aspect was covered by standardized clinical procedures or at the national level. We grouped the identified criteria thematically.
RESULTS
We identified 18 publications and guideline documents with 530 criteria, of which 201 fulfilled the inclusion criteria. The combination of similar criteria resulted in 90 overarching criteria, which we assigned to the following categories: facilities and networks, multidisciplinary team and other experts, supportive care, treatment, long-term care, and volume and numbers.
CONCLUSION
Our results provide a comprehensive overview of existing quality criteria for pediatric oncology in countries with highly developed health-care systems. These criteria can serve as a basis to develop national quality criteria in pediatric oncology.
Topics: Child; Adolescent; Humans; Medical Oncology; Neoplasms; Delivery of Health Care
PubMed: 37584279
DOI: 10.1002/cam4.6452 -
Radiotherapy and Oncology : Journal of... Oct 2022Recurrence remains the main bottleneck hindering outcomes of hepatectomy for hepatocellular carcinoma (HCC). Owing to technological advances, external beam radiotherapy... (Review)
Review
BACKGROUND AND AIM
Recurrence remains the main bottleneck hindering outcomes of hepatectomy for hepatocellular carcinoma (HCC). Owing to technological advances, external beam radiotherapy (EBRT) is being increasingly used in the management of HCC; however, there is no consensus on the role of adjuvant EBRT following hepatectomy.
METHODS
A systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. PubMed, MedLine, Embase, the Cochrane Library, Web of Knowledge were used to screen eligible studies (published as of May 1st, 2022) that evaluated the clinical safety and efficacy of EBRT for HCC receiving hepatectomy. The endpoints were disease-free survival (DFS), overall survival (OS), and adverse events (AEs).
RESULTS
A total of ten studies were eligible (three randomized controlled trials, one phase II trial, and six retrospective comparative studies). The pooled hazard ratio (HR) for median DFS and OS were both in favor of adjuvant EBRT compared with surgery alone (all P < 0.05), and the advantage of adjuvant EBRT was also confirmed in subgroups stratified by different populations (narrow margin, P < 0.05; microvascular invasion, P < 0.05; portal vein tumor thrombus, P < 0.05) and study designs (prospective studies, P < 0.05; retrospective studies, P < 0.05). Adjuvant EBRT was also found to be superior to adjuvant TACE (P < 0.05). Pooled rates of overall AEs and severe AEs were 65.3% and 12.2%, but no fatal AEs were reported.
CONCLUSION
Adjuvant EBRT can be considered for HCC patients, especially those with a high risk of recurrence. Further studies are required for validation of these findings.
Topics: Humans; Carcinoma, Hepatocellular; Hepatectomy; Liver Neoplasms; Retrospective Studies; Prospective Studies; Treatment Outcome; Radiotherapy, Adjuvant; Chemoembolization, Therapeutic; Randomized Controlled Trials as Topic; Clinical Trials, Phase II as Topic
PubMed: 35998838
DOI: 10.1016/j.radonc.2022.08.019 -
Pharmacology Research & Perspectives Dec 2023Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims... (Review)
Review
Pharmacogenomics remains underutilized in clinical practice, despite the existence of internationally recognized, evidence-based guidelines. This systematic review aims to understand enablers and barriers to pharmacogenomics implementation in pediatric oncology by assessing the knowledge, attitudes, and practice of healthcare professionals and consumers. Medline, Embase, Emcare, and PsycINFO database searches identified 146 relevant studies of which only three met the inclusion criteria. These studies reveal that consumers were concerned with pharmacogenomic test costs, insurance discrimination, data sharing, and privacy. Healthcare professionals possessed mostly positive attitudes toward pharmacogenomic testing yet identified lack of experience and training as barriers to implementation. Education emerged as the key enabler, reported in all three studies and both healthcare professionals and consumer groups. However, despite the need for education, no studies utilizing a pediatric oncology consumer or healthcare professional group have reported on the implementation or analysis of a pharmacogenomic education program in pediatric oncology. Increased access to guidelines, expert collaborations and additional guidance interpreting results were further enablers established by healthcare professionals. The themes identified mirror those reported in broader pediatric genetic testing literature. As only a small number of studies met inclusion criteria for this review, further research is warranted to elicit implementation determinants and advance pediatric pharmacogenomics.
Topics: Humans; Child; Pharmacogenetics; Health Knowledge, Attitudes, Practice; Health Personnel; Medical Oncology; Neoplasms
PubMed: 38013228
DOI: 10.1002/prp2.1150 -
Critical Reviews in Oncology/hematology Feb 2024Cancer-related fatigue (CRF) is a distressing side effect of cancer and treatment, affecting both patients during active treatment and survivors, negatively impacting... (Review)
Review
Cancer-related fatigue (CRF) is a distressing side effect of cancer and treatment, affecting both patients during active treatment and survivors, negatively impacting quality of life. While its exact cause remains uncertain, various mechanisms such as immune dysfunction, HPA-axis dysfunction, and treatment toxicity are proposed. Inflammatory biomarkers of CRF have been explored in previous research, but non-inflammatory markers have not been comprehensively studied. This systematic review analysed 33 studies to identify non-inflammatory peripheral blood biomarkers associated with CRF. Promising markers included Hb, blood coagulation factors, BDNF, tryptophan, GAA, mtDNA, platinum, CA125, and cystatin-C. Inconsistent findings were observed for other markers like VEGF, leptin, and stress hormones. Most studies focused on adults. Research in pediatrics is limited. This review showed partial evidence for the inflammaging hypothesis (neurotoxicity due to neuro-inflammation) laying at the basis of CRF. Further research, especially in pediatrics, is needed to confirm this hypothesis and guide future biomarker studies.
Topics: Adult; Humans; Child; Quality of Life; Neoplasms; Biomarkers; Survivors; Fatigue
PubMed: 38141868
DOI: 10.1016/j.critrevonc.2023.104245 -
The American Surgeon Dec 2023Metastatic, malignant phyllodes tumor (PT) of the breast is a rare and aggressive neoplasm. Currently, there is no agreed upon consensus as to best management practices.... (Review)
Review
Metastatic, malignant phyllodes tumor (PT) of the breast is a rare and aggressive neoplasm. Currently, there is no agreed upon consensus as to best management practices. A systematic review of literature was conducted investigating surgical, chemotherapeutic, and radiotherapeutic management for metastatic PT. Databases employed to identify articles included Embase, PubMed, and SAGE Journals. Diagnosis of metastatic PT has been of significant difficulty to radiologists as it is often confused with fibroadenomas. Surgically, metastatectomy has been correlated with increased overall survival (of 25.9 versus 9.9 months; = .01). Radiotherapy has often been associated with palliation and pain control in metastatic, malignant neoplasia. However, one study showed that in malignant PT, radiation was associated with significantly lower rates of local recurrence (OR: 0.048 versus 0.209). Anthracycline containing chemotherapy regimens has been associated with improved overall survival (22.4 months versus 13.2 months; = .040). Further research must be conducted into this rare malignancy to elucidate accurate diagnosis and care for patients with advanced metastatic or malignant phyllodes tumors.
Topics: Humans; Female; Phyllodes Tumor; Breast; Neoplasm Recurrence, Local; Breast Neoplasms; Retrospective Studies
PubMed: 37611540
DOI: 10.1177/00031348231198114 -
Critical Reviews in Oncology/hematology Aug 2023Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian,... (Review)
Review
Lynch syndrome (LS) is a genetic predisposition leading to colorectal and non-colorectal tumors such as endometrial, upper urinary tract, small intestine, ovarian, gastric, biliary duct cancers and glioblastoma. Though not classically associated with LS, growing literature suggests that sarcomas might develop in patients with LS. This systematic review of literature identified 44 studies (N = 95) of LS patients who developed sarcomas. It seems that most sarcomas developed in patients with a germline mutation of MSH2 (57 %) exhibit a dMMR (81 %) or MSI (77 %) phenotype, as in other LS-tumors. Although undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma, and liposarcoma remain the most represented histologic subtype, a higher proportion of rhabdomyosarcoma (10 %, especially pleomorphic rhabdomyosarcoma) is reported. Further studies are required to better characterize this sub-population.
Topics: Humans; Colorectal Neoplasms, Hereditary Nonpolyposis; Colorectal Neoplasms; Genetic Predisposition to Disease; Germ-Line Mutation; Sarcoma; Rhabdomyosarcoma; DNA Mismatch Repair; Microsatellite Instability
PubMed: 37301271
DOI: 10.1016/j.critrevonc.2023.104055 -
Journal of Cancer Research and Clinical... Jun 2023Urothelial adenocarcinoma (UA) is a rare subtype of primary urothelial carcinoma, which is more common in women and has a poor prognosis. Because of their low incidence,...
BACKGROUND
Urothelial adenocarcinoma (UA) is a rare subtype of primary urothelial carcinoma, which is more common in women and has a poor prognosis. Because of their low incidence, most of the existing literature is based on case reports and there is a lack of comprehensive literature on this type of tumor.
PURPOSE
This article provides a comprehensive and systematic review of the epidemiology, pathological types, treatment, and prognosis of UA. Especially in the treatment section, we reviewed the various treatment methods including surgery, radiotherapy, chemotherapy, immunotherapy and molecular targeted therapy. This review aims to provide a theoretical basis for the clinical diagnosis and management of UA.
METHODS
We reviewed the relevant literature of UA from Pubmed.
CONCLUSION
There is no standard treatment for UA. Multidisciplinary therapy, including surgery, radiotherapy and chemotherapy, is the current trend. Immunotherapy and molecular targeted therapy will also become viable options for the treatment of UA in future.
Topics: Female; Humans; Adenocarcinoma; Carcinoma, Transitional Cell; Prognosis; Urethral Neoplasms; Urinary Bladder Neoplasms
PubMed: 36414814
DOI: 10.1007/s00432-022-04481-5