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Arthritis & Rheumatology (Hoboken, N.J.) Oct 2023Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most...
The 2022 EULAR/ACR Points to Consider at the Early Stages of Diagnosis and Management of Suspected Haemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS).
OBJECTIVE
Haemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are life-threatening systemic hyperinflammatory syndromes that can develop in most inflammatory contexts. They can progress rapidly, and early identification and management are critical for preventing organ failure and mortality. This effort aimed to develop evidence-based and consensus-based points to consider to assist clinicians in optimising decision-making in the early stages of diagnosis, treatment and monitoring of HLH/MAS.
METHODS
A multinational, multidisciplinary task force of physician experts, including adult and paediatric rheumatologists, haematologist/oncologists, immunologists, infectious disease specialists, intensivists, allied healthcare professionals and patients/parents, formulated relevant research questions and conducted a systematic literature review (SLR). Delphi methodology, informed by SLR results and questionnaires of experts, was used to generate statements aimed at assisting early decision-making and optimising the initial care of patients with HLH/MAS.
RESULTS
The task force developed 6 overarching statements and 24 specific points to consider relevant to early recognition of HLH/MAS, diagnostic approaches, initial management and monitoring of HLH/MAS. Major themes included the simultaneous need for prompt syndrome recognition, systematic evaluation of underlying contributors, early intervention targeting both hyperinflammation and likely contributors, careful monitoring for progression/complications and expert multidisciplinary assistance.
CONCLUSION
These 2022 EULAR/American College of Rheumatology points to consider provide up-to-date guidance, based on the best available published data and expert opinion. They are meant to help guide the initial evaluation, management and monitoring of patients with HLH/MAS in order to halt disease progression and prevent life-threatening immunopathology.
Topics: Adult; Child; Humans; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation Syndrome; Consensus; Physicians; Advisory Committees
PubMed: 37486733
DOI: 10.1002/art.42636 -
The Oncologist Oct 2023HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR... (Meta-Analysis)
Meta-Analysis
BACKGROUND
HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes.
METHODS
A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses.
RESULTS
Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates.
CONCLUSIONS
While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.
Topics: Humans; Antibodies, Monoclonal; Colorectal Neoplasms; Retrospective Studies; ErbB Receptors; Panitumumab; Colonic Neoplasms; Rectal Neoplasms; Proto-Oncogene Proteins p21(ras); Antineoplastic Combined Chemotherapy Protocols
PubMed: 37463037
DOI: 10.1093/oncolo/oyad200 -
The Oncologist Nov 2023A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically...
PURPOSE
A systematic literature review was conducted to estimate the global prevalence of Kirsten rat sarcoma virus gene (KRAS) mutations, with an emphasis on the clinically significant KRAS G12C mutation, and to estimate the prognostic significance of these mutations in patients with colorectal cancer (CRC).
DESIGN
Relevant English-language publications in the Embase, MEDLINE, and the Cochrane Library databases (from 2009 to 2021) and congress presentations (from 2016 to 2021) were reviewed. Eligible studies were those that reported the prevalence and clinical outcomes of the KRAS G12C mutation in patients with CRC.
RESULTS
A total of 137 studies (interventional [n = 8], post hoc analyses of randomized clinical trials [n = 6], observational [n = 122], and longitudinal [n =1]) were reviewed. Sixty-eight studies reported the prevalence of KRAS mutations (KRASm) in 42 810 patients with CRC. The median global prevalence of KRASm was 38% (range, 13.3%-58.9%) and that of the KRAS G12C mutation (KRAS G12C) 3.1% (range, 0.7%-14%). Available evidence suggests that KRASm are possibly more common in tumors that develop on the right side of the colon. Limited evidence suggests a lower objective response rate and inferior disease-free/relapse-free survival in patients with KRAS G12C compared with patients with KRASwt or other KRASm.
CONCLUSION
Our analysis reveals that KRAS G12C is prevalent in 3% of patients with CRC. Available evidence suggests a poor prognosis for patients with KRAS G12C. Right-sided tumors were more likely to harbor KRASm; however, their role in determining clinical outcomes needs to be investigated further.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Prevalence; Colorectal Neoplasms; Neoplasm Recurrence, Local; Mutation; Lung Neoplasms
PubMed: 37432264
DOI: 10.1093/oncolo/oyad138 -
BMC Anesthesiology Jul 2023Cook Stage extubation is a tool developed by Cook Medical for patients with difficult airways. Multiple clinical studies demonstrated the effectiveness and safety of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cook Stage extubation is a tool developed by Cook Medical for patients with difficult airways. Multiple clinical studies demonstrated the effectiveness and safety of Cook Stage extubation Set (CSES). Currently, no systematic review evidence has been published in this field. Therefore, this study aimed to review the clinical success rate, safety, and tolerability of CSES in patients with difficult airways.
METHOD
The inclusion criteria were based on the population, intervention, comparator, outcomes, and study designs. An electronic search was conducted, and the following databases were used: PubMed, EMBASE, Cochrane Library, and Web of Science. Search keywords included difficult airway and CSES. The primary outcome was the CSES clinical success rate.The Joanna Briggs Institute Critical Appraisal tools for Case Series were used to assess the risk of bias in the included studies. R studio, version 4.2.2. was used to perform the statistical analysis. The Cochrane Q and I statistics were used to test the heterogeneity among all studies. Details of the included case reports were summarized in the systematic review part.
RESULTS
Five studies were eligible for meta-analysis, and 7 case reports were included for systematic review. The pooled overall CSES clinical success rate was 93% (95% CI: 85%, 97%). The CSES intolerable and complication incidence rates were 9% (95% CI: 5%, 18%) and 5% (95% CI: 2%, 12%), respectively. CSES clinical success rate was influenced by the study center and study design. The success rate of CSES was higher in multicenter and prospective design studies. Seven case reports have documented the successful operation of CSES intubation in obese, tall, oncologist, and pediatric patients.
DISCUSSION
This meta-analysis suggested that CSES have achieved a high clinical success rate in adult and pediatric patients with different physical conditions and types of surgery. The results of all original studies and meta-analysis confirmed a remarkably high tolerance rate and low overall complication rate. However, regardless of the tools chosen, a personalized, safe intubation strategy and a highly qualified anesthesiologist should be considered as the fundamental guarantee of a high clinical success rate. Future studies should also focus on the success rate of reintubation using CSES in patients with airway difficulties.
Topics: Adult; Humans; Child; Airway Extubation; Intubation, Intratracheal; Prospective Studies; Obesity; Incidence; Multicenter Studies as Topic
PubMed: 37420175
DOI: 10.1186/s12871-023-02191-0 -
European Urology Oncology Feb 2024Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical... (Review)
Review
Does Research from Clinical Trials in Metastatic Hormone-sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the "Real World"? A Systematic Review.
CONTEXT
Since 2015 there have been major advances in the management of primary metastatic hormone-sensitive prostate cancer (mHSPC) following the publication of key clinical trials that demonstrated significant clinical benefits with docetaxel chemotherapy or novel hormone therapy (NHT) in addition to androgen deprivation therapy (ADT). Despite these advances, there is evidence to show that these treatments are not being utilised for mHSPC in clinical practice.
OBJECTIVE
To determine the utilisation of docetaxel and NHT in mHSPC in routine practice and the determinants of variation in their use.
EVIDENCE ACQUISITION
MEDLINE and Embase were searched systematically for studies on utilisation of treatments for primary mHSPC that were based on regional or national data sets and published after January 2005. Study results were summarised using a narrative synthesis.
EVIDENCE SYNTHESIS
Thirteen papers were included in the analysis, six full-text articles and seven abstracts, on studies that included a total of 166 876 patients. The utilisation rate of treatment intensification with either docetaxel or NHT (enzalutamide, apalutamide, or abiraterone) in addition to ADT ranged from 9.3% to 38.1% across the studies. Younger, White patients with fewer comorbidities and living in more urban settings were more likely to be prescribed treatment intensification. Patients treated in private academic institutions by oncologists were more likely to receive docetaxel or NHT. Socioeconomic status did not impact receipt of systemic therapy. NHT utilisation rates appear to have increased over time.
CONCLUSIONS
These results highlight the need to change the approach to the treatment of primary mHSPC in the real world by harnessing the practice-changing results from recent trials in this setting to optimise upfront systemic therapy for this patient population.
PATIENT SUMMARY
We reviewed the use of treatments for primary metastatic hormone-sensitive prostate cancer that showed a benefit in key clinical trials. We found that these treatments are underused, particularly among certain patient groups.
Topics: Male; Humans; Prostatic Neoplasms; Docetaxel; Androgen Antagonists; Treatment Outcome; Hormones; Health Services Accessibility
PubMed: 37380578
DOI: 10.1016/j.euo.2023.05.002 -
Journal of Cancer Education : the... Oct 2023As cancer continues to be a significant global health challenge, the education of oncology professionals plays a crucial role in providing quality cancer care and...
As cancer continues to be a significant global health challenge, the education of oncology professionals plays a crucial role in providing quality cancer care and achieving optimal patient outcomes. In order to meet the growing need for flexible, accessible, and effective training, this study examines the role of technology-enhanced learning (TEL) in the education of oncology medical professionals. Following the PRISMA guidelines, this systematic review included 34 articles published between 2012 and 2022 in EBSCO and PubMed databases. Findings reveal a diverse range of digital tools being used in oncology training, despite a shortage of advanced educational technologies and limited functional improvement compared to traditional instruction. Since the training primarily targeted at multiple professions in the medical expert role, with radiation oncologists being overrepresented, other oncology domains should be examined more thoroughly in the future, taking into account distinct professional abilities, e.g. communication, collaboration, and leadership skills with reference to the CanMEDS framework. Although the training programmes generally resulted in positive outcomes according to the Kirkpatrick evaluation model, experimental research designs were rather limited. Therefore, the substantial contribution and limitations of TEL in oncology education need to be clarified. Precise reporting of digital tools and instructional processes, as well as challenges encountered, is highly recommended to increase transparency and replicability. Research methodology in digital oncology education remains a major concern and should be addressed accordingly in future research.
Topics: Humans; Health Personnel; Learning; Computer-Assisted Instruction; Technology
PubMed: 37365373
DOI: 10.1007/s13187-023-02329-1 -
The Oncologist Jan 2024Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous meta-analyses have indicated that aspirin could affect breast cancer outcomes, particularly when taken post-diagnostically. However, several recent studies appear to show little to no association between aspirin use and breast cancer mortality, all-cause mortality, or recurrence.
AIMS
This study aims to conduct an updated systematic review and meta-analysis on the associations of pre-diagnostic and post-diagnostic aspirin use with the aforementioned breast cancer outcomes. It also looks, through subgroup analyses and meta-regressions, at a range of variables that could explain the associations between aspirin use and breast cancer outcomes.
RESULTS
In total, 24 papers and 149 860 patients with breast cancer were included. Pre-diagnostic aspirin use was not associated with breast-cancer-specific mortality (HR 0.98, 95% CI, 0.80-1.20, P = .84) or recurrence (HR 0.94, 95% CI, 0.88-1.02, P = .13). Pre-diagnostic aspirin was associated with non-significantly higher all-cause mortality (HR 1.27, 95% CI, 0.95-1.72, P = .11). Post-diagnostic aspirin was not significantly associated with all-cause mortality (HR 0.87, 95% CI, 0.71-1.07, P = .18) or recurrence (HR 0.89, 95% CI, 0.67-1.16, P = .38). Post-diagnostic aspirin use was significantly associated with lower breast-cancer-specific mortality (HR 0.79, 95% CI, 0.64-0.98, P = .032).
CONCLUSIONS
The only significant association of aspirin with breast cancer outcomes is lower breast-cancer-specific mortality in patients who used aspirin post-diagnostically. However, factors such as selection bias and high inter-study heterogeneity mean that this result should not be treated as conclusive, and more substantial evidence such as that provided by RCTs is needed before any decisions on new clinical uses for aspirin should be made.
Topics: Humans; Female; Aspirin; Breast Neoplasms
PubMed: 37358878
DOI: 10.1093/oncolo/oyad186 -
The Cochrane Database of Systematic... Jun 2023Continual improvement in adjuvant therapies has resulted in a better prognosis for women diagnosed with breast cancer. A surrogate marker used to detect the spread of... (Review)
Review
BACKGROUND
Continual improvement in adjuvant therapies has resulted in a better prognosis for women diagnosed with breast cancer. A surrogate marker used to detect the spread of disease after treatment of breast cancer is local and regional recurrence. The risk of local and regional recurrence after mastectomy increases with the number of axillary lymph nodes affected by cancer. There is a consensus to use radiotherapy as an adjuvant treatment after mastectomy (postmastectomy radiotherapy (PMRT)) in women diagnosed with breast cancer and found to have disease in four or more positive axillary lymph nodes. Despite data showing almost double the risk of local and regional recurrence in women treated with mastectomy and found to have one to three positive lymph nodes, there is a lack of international consensus on the use of PMRT in this group.
OBJECTIVES
To assess the effects of PMRT in women diagnosed with early breast cancer and found to have one to three positive axillary lymph nodes.
SEARCH METHODS
We searched the Cochrane Breast Cancer Group's Specialised Register, CENTRAL, MEDLINE, Embase, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov up to 24 September 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs). The inclusion criteria included women diagnosed with breast cancer treated with simple or modified radical mastectomy and axillary surgery (sentinel lymph node biopsy (SLNB) alone or those undergoing axillary lymph node clearance with or without prior SLNB). We included only women receiving PMRT using X-rays (electron and photon radiation), and we defined the radiotherapy dose to reflect what is currently being recommended (i.e. 40 Gray (Gy) to 50 Gy in 15 to 25/28 fractions in 3 to 5 weeks. The included studies did not administer any boost to the tumour bed. In this review, we excluded studies using neoadjuvant chemotherapy as a supportive treatment before surgery.
DATA COLLECTION AND ANALYSIS
We used Covidence to screen records. We collected data on tumour characteristics, adjuvant treatments and the outcomes of local and regional recurrence, overall survival, disease-free survival, time to progression, short- and long-term adverse events and quality of life. We reported on time-to-event outcome measures using the hazard ratio (HR) and subdistribution HR. We used Cochrane's risk of bias tool (RoB 1), and we presented overall certainty of the evidence using the GRADE approach.
MAIN RESULTS
The RCTs included in this review were subgroup analyses of original RCTs conducted in the 1980s to assess the effectiveness of PMRT. Hence, the type and duration of adjuvant systemic treatments used in the studies included in this review were suboptimal compared to the current standard of care. The review involved three RCTs with a total of 829 women diagnosed with breast cancer and low-volume axillary disease. Amongst the included studies, only a single study pertained to the modern-day radiotherapy practice. The results from this one study showed a reduction of local and regional recurrence (HR 0.20, 95% confidence interval (CI) 0.13 to 0.33, 1 study, 522 women; low-certainty evidence) and improvement in overall survival with PMRT (HR 0.76, 95% CI 0.60 to 0.97, 1 study, 522 women; moderate-certainty evidence). One of the other studies using radiotherapy techniques that do not reflect modern-day practice reported on disease-free survival in women with low-volume axillary disease (subdistribution HR 0.63, 95% CI 0.41 to 0.96, 1 study, 173 women). None of the included studies reported on PMRT side effects or quality-of-life outcome measures.
AUTHORS' CONCLUSIONS
Based on one study, the use of PMRT in women diagnosed with breast cancer and low-volume axillary disease indicated a reduction in locoregional recurrence and an improvement in survival. There is a need for more research to be conducted using modern-day radiotherapy equipment and methods to support and supplement the review findings.
Topics: Female; Humans; Neoplasm Recurrence, Local; Breast Neoplasms; Combined Modality Therapy; Mastectomy; Lymph Nodes
PubMed: 37327075
DOI: 10.1002/14651858.CD014463.pub2 -
The Oncologist Dec 2023Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially...
BACKGROUND
Patients diagnosed with cancer are frequent users of the emergency department (ED). While many visits are unavoidable, a significant portion may be potentially preventable ED visits (PPEDs). Cancer treatments have greatly advanced, whereby patients may present with unique toxicities from targeted therapies and are often living longer with advanced disease. Prior work focused on patients undergoing cytotoxic chemotherapy, and often excluded those on supportive care alone. Other contributors to ED visits in oncology, such as patient-level variables, are less well-established. Finally, prior studies focused on ED diagnoses to describe trends and did not evaluate PPEDs. An updated systematic review was completed to focus on PPEDs, novel cancer therapies, and patient-level variables, including those on supportive care alone.
METHODS
Three online databases were used. Included publications were in English, from 2012-2022, with sample sizes of ≥50, and reported predictors of ED presentation or ED diagnoses in oncology.
RESULTS
45 studies were included. Six studies highlighted PPEDs with variable definitions. Common reasons for ED visits included pain (66%) or chemotherapy toxicities (69.1%). PPEDs were most frequent amongst breast cancer patients (13.4%) or patients receiving cytotoxic chemotherapy (20%). Three manuscripts included immunotherapy agents, and only one focused on end-of-life patients.
CONCLUSION
This updated systematic review highlights variability in oncology ED visits during the last decade. There is limited work on the concept of PPEDs, patient-level variables and patients on supportive care alone. Overall, pain and chemotherapy toxicities remain key drivers of ED visits in cancer patients. Further work is needed in this realm.
Topics: Humans; Emergency Service, Hospital; Neoplasms; Patients; Pain; Retrospective Studies
PubMed: 37302801
DOI: 10.1093/oncolo/oyad161 -
The Oncologist Dec 2023Circulating tumor DNA (ctDNA) is increasingly used as a biomarker for metastatic rectal cancer and has recently shown promising results in the early detection of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating tumor DNA (ctDNA) is increasingly used as a biomarker for metastatic rectal cancer and has recently shown promising results in the early detection of recurrence risk.
METHODS
We conducted a systematic review and meta-analysis to explore the prognostic value of ctDNA detection in LARC patients undergoing neoadjuvant chemoradiotherapy (nCRT). We systematically searched electronic databases for observational or interventional studies that included LARC patients undergoing nCRT. Study selection according to the PRISMA guidelines and quality assessment of the REMARK tool for biomarker studies. The primary endpoint was the impact of ctDNA detection at different time points (baseline, post-nCRT, post-surgery) on relapse-free survival (RFS) and overall survival (OS). The secondary endpoint was to study the association between ctDNA detection and pathological complete response(pCR) at different time points.
RESULTS
After further review and analysis of the 625 articles initially retrieved, we finally included 10 eligible studies. We found no significant correlation between ctDNA detection at baseline and long-term survival outcomes or the probability of achieving a pCR. However, the presence of ctDNA at post-nCRT was associated with worse RFS (HR = 9.16, 95% CI, 5.48-15.32), worse OS (HR = 8.49, 95% CI, 2.20-32.72), and worse pCR results (OR = 0.40, 95%CI, 0.18-0.89). The correlation between the presence of ctDNA at post-surgery and worse RFS was more obvious (HR = 14.94; 95% CI, 7.48-9.83).
CONCLUSIONS
Our results suggest that ctDNA detection is a promising biomarker for the evaluation of response and prognosis in LARC patients undergoing nCRT, which merits further evaluation in the following prospective trials.
Topics: Humans; Prognosis; Neoadjuvant Therapy; Prospective Studies; Chemoradiotherapy; Neoplasm Recurrence, Local; Rectal Neoplasms; Biomarkers, Tumor
PubMed: 37294663
DOI: 10.1093/oncolo/oyad151