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International Journal of Molecular... Jul 2023In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options... (Review)
Review
In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1β) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1β inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. Recent advancements in our understanding of the intricate relationship between inflammation and oncogenesis, particularly involving the IL-1β/PD-1/PD-L1 pathway, have shed light on their application in lung cancer development and clinical outcomes of patients. Targeting these pathways in cancers like NSCLC holds immense potential to revolutionize cancer treatment, particularly for patients lacking targetable genetic mutations. However, despite these promising prospects, there remain certain aspects of this pathway that require further investigation, particularly regarding treatment resistance. Therefore, the objective of this review is to delve into the role of IL-1β in NSCLC, its participation in inflammatory pathways, and its intricate crosstalk with the PD-1/PD-L1 pathway. Additionally, we aim to explore the potential of IL-1β as a therapeutic target for NSCLC treatment.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Interleukin-1beta
PubMed: 37511306
DOI: 10.3390/ijms241411547 -
Current Oncology (Toronto, Ont.) Jul 2023Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy... (Review)
Review
Metastatic cervical lymph nodes are a frequent finding in head and neck squamous cell carcinoma (HNSCC). If a non-surgical approach is primarily chosen, a therapy response evaluation of the primary tumor and the affected lymph nodes is necessary in the follow-up. Supplementary contrast-enhanced ultrasound (CEUS) can be used to precisely visualize the microcirculation of the target lesion in the neck, whereby malignant and benign findings differ in their uptake behavior. The same applies to many other solid tumors. For various tumor entities, it has already been shown that therapy monitoring is possible through regular contrast-enhanced sonography of the primary tumor or the affected lymph nodes. Thus, in some cases, maybe in the future, a change in therapy strategy can be achieved at an early stage in the case of non-response or, in the case of therapy success, a de-escalation of subsequent (surgical) measures can be achieved. In this paper, a systematic review of the available studies and a discussion of the potential of therapy monitoring by means of CEUS in HNSCC are presented.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Lymph Nodes; Neck; Head and Neck Neoplasms; Ultrasonography
PubMed: 37504354
DOI: 10.3390/curroncol30070494 -
Journal of Geriatric Oncology Sep 2023Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older... (Review)
Review
INTRODUCTION
Blood biomarkers are potentially useful prognostic markers and may support treatment decisions, but it is unknown if and which biomarkers are most useful in older patients with solid tumors. The aim of this systematic review was to evaluate the evidence on the association of blood biomarkers with treatment response and adverse health outcomes in older patients with solid tumors.
MATERIALS AND METHODS
A literature search was conducted in five databases in December 2022 to identify studies on blood biomarkers measured before treatment initiation, not tumor specific, and outcomes in patients with solid tumors aged ≥60 years. Studies on any type or line of oncologic treatment could be included. Titles and abstracts were screened by three authors. Data extraction and quality assessment, using the Quality in Prognosis Studies (QUIPS) checklist, were performed by two authors.
RESULTS
Sixty-three studies were included, with a median sample size of 138 patients (Interquartile range [IQR] 99-244) aged 76 years (IQR 72-78). Most studies were retrospective cohort studies (63%). The risk of bias was moderate in 52% and high in 43%. Less than one-third reported geriatric parameters. Eighty-six percent examined mortality outcomes, 37% therapeutic response, and 37% adverse events. In total, 77 unique markers were studied in patients with a large variety of tumor types and treatment modalities. Neutrophil-to-lymphocyte ratio (20 studies), albumin (19), C-reactive protein (16), hemoglobin (14) and (modified) Glasgow Prognostic Score ((m)GPS) (12) were studied most often. The vast majority showed no significant association of these biomarkers with outcomes, except for associations between low albumin and adverse events and high (m)GPS with mortality.
DISCUSSION
Most studies did not find a significant association between blood biomarkers and clinical outcomes. The interpretation of current evidence on prognostic blood biomarkers is hampered by small sample sizes and inconsistent results across heterogeneous studies. The choice for blood biomarkers in the majority of included studies seemed driven by availability in clinical practice in retrospective cohort studies. Ageing biomarkers are rarely studied in older patients with solid tumors. Further research is needed in larger and more homogenous cohorts that combine clinical parameters and biomarkers before these can be used in clinical practice.
Topics: Humans; Aged; Retrospective Studies; Neoplasms; Prognosis; Biomarkers; Outcome Assessment, Health Care
PubMed: 37453811
DOI: 10.1016/j.jgo.2023.101567 -
PloS One 2023Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not... (Review)
Review
Electrochemotherapy vs radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies: A systematic review and narrative synthesis.
BACKGROUND
Electrochemotherapy has gained international traction and commendation in national guidelines as an effective tool in the management of cutaneous malignancies not amenable to surgical resection. Despite this, no level 5 evidence exists comparing it to radiotherapy in the treatment of cutaneous malignancies. This systematic review aimed to examine the literature directly and indirectly comparing electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases from primary solid organ malignancies.
MATERIALS & METHODS
The protocol for this review was registered on the PROSPERO International Prospective Register of Systematic Reviews with the protocol ID CRD42021285415. Searches of MEDLINE, Embase, CINAHL, CENTRAL and ClinicalTrials.gov databases were undertaken from database inception to 28 December 2021. Studies in humans comparing treatment with electrochemotherapy to radiotherapy and reporting tumour response with a minimum four week follow-up were eligible. Risk of bias was assessed using the ROBINS-I tool. Results are provided as a narrative synthesis.
RESULTS
Two case series with a total of 92 patients were identified as relevant to this study. Both case series examined patients with cutaneous squamous cell carcinoma. One case series examined elderly patients with predominantly head/neck lesions. The other examined younger patients with predominantly limb lesions who had cutaneous squamous cell carcinoma directly attributable to a rare skin condition.
CONCLUSION
There is little literature presenting comparative data for electrochemotherapy and radiotherapy in the treatment of primary cutaneous malignancies or cutaneous metastases. Included studies were marred by serious risk of bias particularly due to confounding. The inherent bias and heterogeneity of the included studies precluded synthesis of a consolidated comparison of clinical outcomes between the two therapies. Further research is required in this domain in the form of clinical trials and observational studies to inform guidelines for electrochemotherapy treatment.
Topics: Humans; Aged; Skin Neoplasms; Carcinoma, Squamous Cell; Electrochemotherapy
PubMed: 37440502
DOI: 10.1371/journal.pone.0288251 -
ESMO Open Aug 2023Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis.
MATERIALS AND METHODS
A systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777).
RESULTS
Among 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found.
CONCLUSIONS
Compared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Disease-Free Survival; Progression-Free Survival; Proportional Hazards Models
PubMed: 37413762
DOI: 10.1016/j.esmoop.2023.101592 -
JCO Precision Oncology Jun 2023Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Evidence suggests that neurotrophic tyrosine receptor kinase () gene fusions in solid tumors are predictive biomarkers for targeted inhibition across a number of adult and pediatric tumor types. However, despite robust clinical response to tyrosine receptor kinase (TRK) inhibitors, the natural history and prognostic implications of fusions in solid tumors are poorly understood. It is important to evaluate their prognostic significance on survival to provide some context to the clinical effectiveness observed in clinical trials of TRK-targeted therapies.
METHODS
A systematic literature review was conducted in Medline, Embase, Cochrane, and PubMed to identify studies comparing the overall survival (OS) of patients with fusion-positive (+) versus fusion-negative (-) tumors. Five retrospective matched case-control studies published before 11 August 2022 were assessed for inclusion, and three were selected for the meta-analysis (sample size: 69 +, 444 -). Risk of bias was assessed using the Risk of Bias Assessment tool for Non-randomized Studies tool. The pooled hazard ratio (HR) was estimated using a Bayesian random-effects model.
RESULTS
In the meta-analysis, the median follow-up ranged from 2 to 14 years and the median OS was between 10.1 and 12.7 months (where reported). Comparing patients with tumors + and -, the pooled HR estimate for OS was 1.51 (95% credible interval, 1.01 to 2.29). The patients analyzed had no previous or current exposure to TRK inhibitors.
CONCLUSION
In patients not treated with TRK inhibitor therapies, those with + solid tumors have a 50% increased risk of mortality within 10 years from diagnosis or the start of standard therapy compared with those with - status. Although this is the most robust estimate of the comparative survival rate to date, further studies are required to reduce uncertainty.
Topics: Adult; Child; Humans; Prognosis; Bayes Theorem; Retrospective Studies; Neoplasms; Gene Fusion
PubMed: 37384865
DOI: 10.1200/PO.22.00651 -
Frontiers in Immunology 2023This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
METHODS
We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.
RESULTS
59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.
CONCLUSION
Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier 345350.
Topics: Humans; Immune Checkpoint Inhibitors; Pancreatitis; Neoplasms; Amylases; Lipase
PubMed: 37359551
DOI: 10.3389/fimmu.2023.1166299 -
Cancer Medicine Jul 2023To assess the impact of primary-site surgery plus systemic therapy compared to systemic therapy alone on overall survival in common metastatic cancer types. (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the impact of primary-site surgery plus systemic therapy compared to systemic therapy alone on overall survival in common metastatic cancer types.
METHODS
Data sources included Embase, PubMed, and Web of Science (January 1, 1995-March 22, 2023). Randomized controlled trials were included that enrolled patients diagnosed with the 10 most common de novo metastatic cancer types in the Surveillance, Epidemiology, and End Results database and randomized patients to resection of the primary site and systemic therapy versus systemic treatment alone. Random-effects models were used to pool associations by cancer type.
RESULTS
Eight studies with 1774 patients evaluating the efficacy of surgery in breast, renal, stomach, and colorectal cancer were included. There was no statistically significant reduction in risk of all-cause mortality associated with surgical intervention for metastatic breast (HR = 0.94, 95% CI 0.63-1.40) or renal cancer (HR = 0.79, 95% CI 0.53-1.20), although results were heterogeneous (I = 73.7% and 80.6%, respectively). One study evaluating gastrectomy in metastatic stomach cancer found no benefit (HR = 1.09, 95% CI 0.78-1.52), while a small trial suggested that surgery and hyperthermic intraperitoneal chemotherapy might be beneficial for colorectal cancer with peritoneal metastasis (HR = 0.55, 95% CI 0.32-0.95).
CONCLUSIONS
Few randomized trials have evaluated cancer-directed surgery among patients with metastatic solid malignancies.
Topics: Humans; Stomach Neoplasms; Colorectal Neoplasms
PubMed: 37309837
DOI: 10.1002/cam4.6061 -
Frontiers in Immunology 2023Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression.
METHODS
In this article we performed a systematic review and meta-analysis on the association between HLA-G expression and outcome in solid tumors. This study was performed in accordance with PRISMA guidelines and registered in PROSPERO.
RESULTS
A total of 25 studies met the inclusion criteria. These studies comprised data from 4871 patients reporting overall survival (OS), and 961 patients, reporting disease free survival (DFS). HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance.
DISCUSSION
In summary, we describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311973.
Topics: Humans; Disease-Free Survival; HLA-G Antigens; Neoplasms; Prognosis; Progression-Free Survival
PubMed: 37275862
DOI: 10.3389/fimmu.2023.1165813 -
BMC Health Services Research May 2023Shared medical appointments, also known as group visits, are a feasible and well-accepted approach for women receiving antenatal care, yet the feasibility and efficacy...
BACKGROUND
Shared medical appointments, also known as group visits, are a feasible and well-accepted approach for women receiving antenatal care, yet the feasibility and efficacy of this approach for female-specific reproductive conditions is uncertain.
OBJECTIVE
The aim of this systematic review was to (a) determine the feasibility of group visits in adults with any female-specific reproductive condition, and (b) identify whether delivering group care for these conditions impacts clinical outcomes.
METHOD
Six databases and two clinical trials registries were searched from inception through to 26 January 2022 for original research examining group medical visits or group consultation interventions for adults with female reproductive conditions or pathologic conditions specific to the female reproductive system.
RESULTS
The search yielded 2584 studies, of which four met the inclusion criteria. Included studies sampled women with breast cancer, chronic pelvic pain, polycystic ovary syndrome and gynaecological cancers. Studies reported high levels of patient satisfaction, with participants indicating their expectations had been met or exceeded. The impact of group visits on clinical outcomes was inconclusive however.
DISCUSSION/CONCLUSIONS
The studies in this review indicate delivery of female-specific healthcare via a group model maybe feasible and well-accepted. The review provides a solid basis for proposing larger and longer studies on group visits for female reproductive conditions.
TRIAL REGISTRATION
The review protocol was registered with PROSPERO (CRD42020196995).
Topics: Adult; Pregnancy; Female; Humans; Feasibility Studies; Prenatal Care; Women's Health; Patient Satisfaction; Breast Neoplasms
PubMed: 37237255
DOI: 10.1186/s12913-023-09582-6