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BMC Medical Informatics and Decision... Jun 2024Enhancing Local Control (LC) of brain metastases is pivotal for improving overall survival, which makes the prediction of local treatment failure a crucial aspect of...
BACKGROUND
Enhancing Local Control (LC) of brain metastases is pivotal for improving overall survival, which makes the prediction of local treatment failure a crucial aspect of treatment planning. Understanding the factors that influence LC of brain metastases is imperative for optimizing treatment strategies and subsequently extending overall survival. Machine learning algorithms may help to identify factors that predict outcomes.
METHODS
This paper systematically reviews these factors associated with LC to select candidate predictor features for a practical application of predictive modeling. A systematic literature search was conducted to identify studies in which the LC of brain metastases is assessed for adult patients. EMBASE, PubMed, Web-of-Science, and the Cochrane Database were searched up to December 24, 2020. All studies investigating the LC of brain metastases as one of the endpoints were included, regardless of primary tumor type or treatment type. We first grouped studies based on primary tumor types resulting in lung, breast, and melanoma groups. Studies that did not focus on a specific primary cancer type were grouped based on treatment types resulting in surgery, SRT, and whole-brain radiotherapy groups. For each group, significant factors associated with LC were identified and discussed. As a second project, we assessed the practical importance of selected features in predicting LC after Stereotactic Radiotherapy (SRT) with a Random Forest machine learning model. Accuracy and Area Under the Curve (AUC) of the Random Forest model, trained with the list of factors that were found to be associated with LC for the SRT treatment group, were reported.
RESULTS
The systematic literature search identified 6270 unique records. After screening titles and abstracts, 410 full texts were considered, and ultimately 159 studies were included for review. Most of the studies focused on the LC of the brain metastases for a specific primary tumor type or after a specific treatment type. Higher SRT radiation dose was found to be associated with better LC in lung cancer, breast cancer, and melanoma groups. Also, a higher dose was associated with better LC in the SRT group, while higher tumor volume was associated with worse LC in this group. The Random Forest model predicted the LC of brain metastases with an accuracy of 80% and an AUC of 0.84.
CONCLUSION
This paper thoroughly examines factors associated with LC in brain metastases and highlights the translational value of our findings for selecting variables to predict LC in a sample of patients who underwent SRT. The prediction model holds great promise for clinicians, offering a valuable tool to predict personalized treatment outcomes and foresee the impact of changes in treatment characteristics such as radiation dose.
Topics: Humans; Machine Learning; Brain Neoplasms
PubMed: 38907265
DOI: 10.1186/s12911-024-02579-z -
Journal of Clinical Medicine May 2024Atypical Spitz tumor (AST) is an intermediate category among Spitz melanocytic neoplasms. Sentinel node biopsy (SNB) has been proposed in the clinical management of AST... (Review)
Review
BACKGROUND
Atypical Spitz tumor (AST) is an intermediate category among Spitz melanocytic neoplasms. Sentinel node biopsy (SNB) has been proposed in the clinical management of AST patients, but this approach remains the subject of debate. This systematic review aims to summarize the available evidence on SNB procedures in AST patients.
METHODS
A comprehensive search was conducted, including MEDLINE/Pubmed, EMBASE, and SCOPUS, through April 2023. Case series, cohort studies, and case-control studies of AST patients were eligible for inclusion. PRISMA guidelines were followed.
RESULTS
Twenty-two studies with a total of 756 AST patients were included. The pooled SNB prevalence was 54% (95% CI 32 to 75%), with substantial heterogeneity (I2 90%). The pooled SNB+ prevalence was 35% (95% CI 25 to 46%) with moderate heterogeneity (I2 39%). Lymphadenectomy was performed in 0-100% of SNB+ patients. Overall survival rates ranged from 93% to 100%, and disease-free survival ranged from 87% to 100% in AST patients. Overall and disease-free survival rates were 100% in SNB patients. Pooled survival estimates were not calculated due to the heterogeneous timing of the survival assessment and/or the small size of the subgroups. All studies clearly reported inclusion criteria and measured the condition in a standard way for all participants, but only 50% indicated valid methods for the identification of the condition.
CONCLUSIONS
The oncologic behavior of AST is related to an almost always favorable outcome. SNB does not seem to be relevant as a staging or prognostic procedure, and its indication remains debatable and controversial.
PubMed: 38892943
DOI: 10.3390/jcm13113232 -
American Journal of Cancer Research 2024Cutaneous melanoma is a prevalent tumor associated with a poor prognosis. This systematic review and meta-analysis aimed to identify and evaluate prognostic factors for... (Review)
Review
Cutaneous melanoma is a prevalent tumor associated with a poor prognosis. This systematic review and meta-analysis aimed to identify and evaluate prognostic factors for patients with cutaneous melanoma following surgery, thereby providing crucial insights for enhancing patient outcomes. We searched PubMed, Embase, Cochrane Library, CINAHL, and Web of Science for studies on postoperative prognostic factors of cutaneous melanoma up to March 2024. Literature screening, data extraction, and quality assessment were performed, followed by meta-analysis using RevMan 5.3 software. Trial Sequential Analysis (TSA) was conducted with Stata 17 software to verify the robustness of the findings. Eleven studies encompassing 27,352 patients were included. The meta-analysis identified several prognostic factors impacting disease-specific survival post-surgery: age over 50 years (HR=1.05, 95% CI: 1.02-1.08), female gender (HR=0.71, 95% CI: 0.57-0.87), Breslow thickness greater than 2 mm (HR=1.11, 95% CI: 1.06-1.17), presence of ulceration (HR=2.06, 95% CI: 1.63-2.60), and positive sentinel lymph node (HR=3.03, 95% CI: 2.50-3.66). TSA confirmed the adequacy of the sample size. Aggressive treatment strategies are recommended for patients exhibiting these characteristics to improve prognosis and extend 5-year survival rates.
PubMed: 38859868
DOI: 10.62347/SQZT7285 -
Frontiers in Oncology 2024There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma...
BACKGROUND
There is evidence of a modest reduction in skin cancer risk among metformin users. However, no studies have further examined the effects of metformin on melanoma survival and safety outcomes. This study aimed to quantitatively summarize any influence of metformin on the overall survival (OS) and immune-related adverse effects (irAEs) in melanoma patients.
METHODS
Selection criteria: The inclusion criteria were designed based on the PICOS principles. Information sources: PubMed, EMBASE, Cochrane Library, and Web of Science were searched for relevant literature published from the inception of these databases until November 2023 using and as keywords. Survival outcomes were OS, progression-free survival (PFS), recurrence-free survival (RFS), and mortality; the safety outcome was irAEs. Risk of bias and data Synthesis: The Cochrane tool for assessing the risk of bias in randomized trial 2 (RoB2) and methodological index for non-randomized studies (MINORS) were selected to assess the risk of bias. The Cochrane Q and statistics based on Stata 15.1 SE were used to test the heterogeneity among all studies. Funnel plot, Egger regression, and Begg tests were used to evaluate publication bias. The leave-one-out method was selected as the sensitivity analysis tool.
RESULTS
A total of 12 studies were included, involving 111,036 melanoma patients. The pooled HR for OS was 0.64 (95% CI [0.42, 1.00], p = 0.004, I 73.7%), HR for PFS was 0.89 (95% CI [0.70, 1.12], p = 0.163, I 41.4%), HR for RFS was 0.62 (95% CI [0.26, 1.48], p = 0.085, I 66.3%), and HR for mortality was 0.53 (95% CI [0.46, 0.63], p = 0.775, I 0.0%). There was no significant difference in irAEs incidence (OR = 1.01; 95% CI [0.42, 2.41]; p = 0.642) between metformin and no metformin groups.
DISCUSSION
The improvement in overall survival of melanoma patients with metformin may indirectly result from its diverse biological targets and beneficial effects on multiple systemic diseases. While we could not demonstrate a specific improvement in the survival of melanoma patients, the combined benefits and safety of metformin for patients taking the drug are worthy of recognition.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024518182.
PubMed: 38846983
DOI: 10.3389/fonc.2024.1399693 -
Frontiers in Immunology 2024The emergence of immunotherapy has changed the treatment modality for melanoma and prolonged the survival of many patients. However, a handful of patients remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The emergence of immunotherapy has changed the treatment modality for melanoma and prolonged the survival of many patients. However, a handful of patients remain unresponsive to immunotherapy and effective tools for early identification of this patient population are still lacking. Researchers have developed machine learning algorithms for predicting immunotherapy response in melanoma, but their predictive accuracy has been inconsistent. Therefore, the present systematic review and meta-analysis was performed to comprehensively evaluate the predictive accuracy of machine learning in melanoma response to immunotherapy.
METHODS
Relevant studies were searched in PubMed, Web of Sciences, Cochrane Library, and Embase from their inception to July 30, 2022. The risk of bias and applicability of the included studies were assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Meta-analysis was performed on R4.2.0.
RESULTS
A total of 36 studies consisting of 30 cohort studies and 6 case-control studies were included. These studies were mainly published between 2019 and 2022 and encompassed 75 models. The outcome measures of this study were progression-free survival (PFS), overall survival (OS), and treatment response. The pooled c-index was 0.728 (95%CI: 0.629-0.828) for PFS in the training set, 0.760 (95%CI: 0.728-0.792) and 0.819 (95%CI: 0.757-0.880) for treatment response in the training and validation sets, respectively, and 0.746 (95%CI: 0.721-0.771) and 0.700 (95%CI: 0.677-0.724) for OS in the training and validation sets, respectively.
CONCLUSION
Machine learning has considerable predictive accuracy in melanoma immunotherapy response and prognosis, especially in the former. However, due to the lack of external validation and the scarcity of certain types of models, further studies are warranted.
Topics: Melanoma; Humans; Machine Learning; Immunotherapy; Prognosis; Treatment Outcome
PubMed: 38835779
DOI: 10.3389/fimmu.2024.1281940 -
Journal of Cancer 2024Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable... (Review)
Review
Immune-activating anti-CTLA4 and anti-PD1 monoclonal antibodies (alone or in combination) are being used to treat advanced melanoma patients and can lead to durable remissions, and long-term overall survival may be achieved in between 50-60% of patients. Although intracranial metastases are very common in melanoma (about 50-75% of all patients with advanced disease), most of the pivotal prospective clinical trials exclude patients with intra-cranial metastases, certainly if their lesions are symptomatic and steroid-requiring and the degree of sensitivity of intra-cranial melanoma to immunotherapy remains uncertain, and requires further investigation especially in view of the demonstrable activity of RAF-MEK inhibitors in this clinical setting and the emergence of stereotactic radiotherapy. Our study aimed to evaluate the efficacy and toxicity of immunotherapy against advanced melanoma patients with brain metastases. In terms of comparative studies, only retrospective analyses could be identified. Based on 3 retrospective studies, treatment of patients with melanoma brain metastases with immunotherapeutic approaches improves overall survival substantially compared with supportive measures alone (no active anticancer treatment). The efficacy of targeted therapy appeared to be comparable to that of immune therapy in terms of overall survival, based on a small number of patients. The combination of concurrent radiation therapy to the brain and systemic immunotherapy led to improved overall survival compared to radiotherapy alone, suggesting potential synergism between the approaches, and combination treatment could be delivered safely. Our review supports the use of immunotherapeutic strategies for these patients although treatment efficacy appears to be lower for symptomatic lesions. In view of the extremely high efficacy of stereotactic radiotherapy approaches in the brain, understanding the interaction between radiotherapy and immunotherapy is vital and should be an area of active investigation.
PubMed: 38817862
DOI: 10.7150/jca.93306 -
Journal of Personalized Medicine May 2024Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to... (Review)
Review
BACKGROUND
Acral amelanotic melanomas (AAMs), a rare subset of melanomas located on acral sites such as the palms, soles, and subungual areas, are diagnostically challenging due to their lack of typical pigmentation and often benign clinical appearance. Misdiagnosis is common, leading to delays in treatment and potentially worse outcomes. This systematic review aims to synthesise evidence on cases of AAM initially misdiagnosed as other conditions, to better understand their clinical and epidemiological characteristics, diagnostic pitfalls, and management strategies.
METHODS
A comprehensive search of the MEDLINE/PubMed, EMBASE, and SCOPUS databases was conducted up to March 2024. Case reports and small case series of AAMs initially misdiagnosed as other conditions were included. Data on patient demographics, clinical presentation, and diagnostic methods were collected and analyzed.
RESULTS
Of the 152 records identified, 26 cases from 23 articles met the inclusion criteria. A demographic analysis revealed that the gender distribution appears to be perfectly balanced, with an age range of 38 to 91 years. Misdiagnoses included non-healing ulcers or traumatic lesions (37.5%), benign proliferative lesions (29.2%) and infectious lesions (20.8%). The foot was the most affected site (53.8%). Notably, a histological evaluation was performed in 50% of cases involving the upper extremities, in contrast to only 7.1% of cases involving the foot and 0% of cases of the heel. This discrepancy suggests a reluctance to perform biopsies in the lower extremities, which may contribute to a higher misdiagnosis rate in these areas.
CONCLUSIONS
The underutilization of biopsy in the diagnosis of lower extremity lesions contributes significantly to the misdiagnosis and delay in treatment of AAMs. Especially when the clinical assessment and dermoscopy are inconclusive, biopsies of suspicious lesions are essential. Immunohistochemistry and markers such as PRAME are critical in differentiating melanoma from other malignancies such as clear cell sarcoma. This review highlights the need for increased vigilance and a proactive diagnostic approach to increase early detection rates and improve prognostic outcomes.
PubMed: 38793100
DOI: 10.3390/jpm14050518 -
NPJ Digital Medicine May 2024
PubMed: 38789723
DOI: 10.1038/s41746-024-01138-0 -
Journal of Controlled Release :... Jul 2024Ultrasound is widely used in the diagnosis and therapy of cancer. Tumors can be treated by thermal or mechanical tissue ablation. Furthermore, tumors can be manipulated... (Meta-Analysis)
Meta-Analysis
Ultrasound is widely used in the diagnosis and therapy of cancer. Tumors can be treated by thermal or mechanical tissue ablation. Furthermore, tumors can be manipulated by hyperthermia, sonodynamic therapy and sonoporation, e.g., by increasing tumor perfusion or the permeability of biological barriers to enhance drug delivery. These treatments induce various immune responses in tumors. However, conflicting data and high heterogeneity between experimental settings make it difficult to generalize the effects of ultrasound on tumor immunity. Therefore, we performed a systematic review to answer the question: "Does ultrasound alter the immune reaction of peripheral solid tumors in humans and animals compared to control conditions without ultrasound?" A systematic literature search was performed in PubMed, EMBASE, and Web of Science and 24,401 potentially relevant publications were identified. Of these, 96 publications were eligible for inclusion in the systematic review. Experiments were performed in humans, rats, and mice and focused on different tumor types, primarily breast and melanoma. We collected data on thermal and non-thermal ultrasound settings, the use of sono-sensitizers or sono-enhancers, and anti-tumor therapies. Six meta-analyses were performed to quantify the effect of ultrasound on tumor infiltration by T cells (cytotoxic, helper, and regulatory T cells) and on blood cytokines (interleukin-6, interferon-γ, tumor necrosis factor-α). We provide robust scientific evidence that ultrasound alters T cell infiltration into tumors and increases blood cytokine concentrations. Furthermore, we identified significant differences in immune cell infiltration based on tumor type, ultrasound settings, and mouse age. Stronger effects were observed using hyperthermia in combination with sono-sensitizers and in young mice. The latter may impair the translational impact of study results as most cancer patients are older. Thus, our results may help refining ultrasound parameters to enhance anti-tumor immune responses for therapeutic use and to minimize immune effects in diagnostic applications.
Topics: Animals; Neoplasms; Humans; Ultrasonic Therapy
PubMed: 38777126
DOI: 10.1016/j.jconrel.2024.05.030 -
Journal of Bone Oncology Jun 2024Skeletal metastases make up 17% of all metastases from advanced-stage melanoma. Bone metastases are associated with increased morbidity and mortality and decreased... (Review)
Review
BACKGROUND
Skeletal metastases make up 17% of all metastases from advanced-stage melanoma. Bone metastases are associated with increased morbidity and mortality and decreased quality of life due to their association with skeletal-related events (SREs), including pathological fracture, spinal cord compression, hypercalcemia, radiotherapy, and surgery. The study aimed to determine the incidence of bone metastases and SREs in melanoma, identify possible risk factors for the development of bone metastases and SREs, and investigate survival rates in this patient population.
METHODS
A computer-based literature search was conducted using Pubmed, Embase, and Cochrane Central Register of Controlled Trials up to July 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was utilized for quality assessment. Study characteristics, patient information, risk factors for developing bone metastases and SREs, and characteristics for survival were recorded.
RESULTS
We included 29 studies. The average bone metastasis-free interval ranged from four to 72 months. Incidence of bone metastases varied from 2 % to 49 % across 14 studies. 69 % (20/29) of studies described the location of bone metastases, with 24 % (7/29) focusing solely on spinal metastases. In one study, 129 SREs were recorded in 71 % (59/83) of the patient cohort, with various manifestations. The use of bone-directed agents was independently associated with lower risk of SREs. Survival after detection of bone metastasis ranged from three to 13 months. Factors associated with survival included clinical, tumor-related, and treatment features.
CONCLUSION
This review highlights the notable prevalence and risk factors of developing bone metastases and subsequent SREs in patients with melanoma. The surge in bone metastases poses a challenge in complication management, given the high prevalence of SREs. While this study offers a comprehensive overview of the incidence, risk factors, and outcomes associated with bone metastases and SREs in melanoma patients that may guide patient and physician decision-making, a notable gap lies in the limited availability of high-quality data and the heterogeneous design of the existing literature. Future research should address predictive factors for bone metastases and SREs in melanoma to facilitate patient and physician decision-making and ultimately improve outcomes in this patient population.
PubMed: 38765703
DOI: 10.1016/j.jbo.2024.100603