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Pathologica Apr 2022Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and... (Review)
Review
Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and 2.5% of all fibroepithelial breast tumors. PT are classified into benign, borderline and malignant based upon their stromal morphology with a distribution of 60%, 20%, and 20%, respectively. Malignant PT of the breast constitute an uncommon challenging group of fibroepithelial neoplasms. They have a relatively high tendency to recur, although distant metastasis is uncommon, and nearly exclusive to malignant PT. Adequate surgical resection remains the standard approach to achieve maximal local control. Giant malignant PT are rare and a pose a diagnostic dilemma for pathologists, especially when comprised of sarcomatous elements. This review highlights the morphological features of PT detected in cytology and histology specimens and discusses diagnostic pitfalls and differential diagnosis.
Topics: Breast; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Fibroepithelial; Phyllodes Tumor
PubMed: 35414723
DOI: 10.32074/1591-951X-754 -
Lancet (London, England) May 2014Individual participant data meta-analyses of postoperative chemotherapy have shown improved survival for patients with non-small-cell lung cancer (NSCLC). We aimed to do... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Individual participant data meta-analyses of postoperative chemotherapy have shown improved survival for patients with non-small-cell lung cancer (NSCLC). We aimed to do a systematic review and individual participant data meta-analysis to establish the effect of preoperative chemotherapy for patients with resectable NSCLC.
METHODS
We systematically searched for trials that started after January, 1965. Updated individual participant data were centrally collected, checked, and analysed. Results from individual randomised controlled trials (both published and unpublished) were combined using a two-stage fixed-effect model. Our primary outcome, overall survival, was defined as the time from randomisation until death (any cause), with living patients censored on the date of last follow-up. Secondary outcomes were recurrence-free survival, time to locoregional and distant recurrence, cause-specific survival, complete and overall resection rates, and postoperative mortality. Prespecified analyses explored any variation in effect by trial and patient characteristics. All analyses were by intention to treat.
FINDINGS
Analyses of 15 randomised controlled trials (2385 patients) showed a significant benefit of preoperative chemotherapy on survival (hazard ratio [HR] 0·87, 95% CI 0·78-0·96, p=0·007), a 13% reduction in the relative risk of death (no evidence of a difference between trials; p=0·18, I(2)=25%). This finding represents an absolute survival improvement of 5% at 5 years, from 40% to 45%. There was no clear evidence of a difference in the effect on survival by chemotherapy regimen or scheduling, number of drugs, platinum agent used, or whether postoperative radiotherapy was given. There was no clear evidence that particular types of patient defined by age, sex, performance status, histology, or clinical stage benefited more or less from preoperative chemotherapy. Recurrence-free survival (HR 0·85, 95% CI 0·76-0·94, p=0·002) and time to distant recurrence (0·69, 0·58-0·82, p<0·0001) results were both significantly in favour of preoperative chemotherapy although most patients included were stage IB-IIIA. Results for time to locoregional recurrence (0·88, 0·73-1·07, p=0·20), although in favour of preoperative chemotherapy, were not statistically significant.
INTERPRETATION
Findings, which are based on 92% of all patients who were randomised, and mainly stage IB-IIIA, show preoperative chemotherapy significantly improves overall survival, time to distant recurrence, and recurrence-free survival in resectable NSCLC. The findings suggest this is a valid treatment option for most of these patients. Toxic effects could not be assessed.
FUNDING
Medical Research Council UK.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24576776
DOI: 10.1016/S0140-6736(13)62159-5 -
Effect of BRCA germline mutations on breast cancer prognosis: A systematic review and meta-analysis.Medicine Oct 2016The contribution of BRCA germline mutational status to breast cancer patients' prognosis is unclear. We aimed to systematically review and perform meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The contribution of BRCA germline mutational status to breast cancer patients' prognosis is unclear. We aimed to systematically review and perform meta-analysis of the available evidence of effects of BRCA germline mutations on multiple survival outcomes of breast cancer patients as a whole and in specific subgroups of interest, including those with triple negative breast cancer, those with Ashkenazi Jewish ancestry, and patients with stage I-III disease.
METHODS
Sixty studies met all inclusion criteria and were considered for this meta-analysis. These studies involved 105,220 breast cancer patients, whose 3588 (3.4%) were BRCA mutations carriers. The associations between BRCA genes mutational status and overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) were evaluated using random-effect models.
RESULTS
BRCA1 mutation carriers have worse OS than BRCA-negative/sporadic cases (hazard ratio, HR 1.30, 95% CI: 1.11-1.52) and worse BCSS than sporadic/BRCA-negative cases among patients with stage I-III breast cancer (HR 1.45, 95% CI: 1.01-2.07). BRCA2 mutation carriers have worse BCSS than sporadic/BRCA-negative cases (HR 1.29, 95% CI: 1.03-1.62), although they have similar OS. Among triple negative breast cancer, BRCA1/2 mutations carriers had better OS than BRCA-negative counterpart (HR 0.49, 95% CI: 0.26-0.92). Among Ashkenazi Jewish women, BRCA1/2 mutations carriers presented higher risk of death from breast cancer (HR 1.44, 95% CI: 1.05-1.97) and of distant metastases (HR 1.82, 95% CI: 1.05-3.16) than sporadic/BRCA-negative patients.
CONCLUSION
Our results support the evaluation of BRCA mutational status in patients with high risk of harboring BRCA germline mutations to better define the prognosis of breast cancer in these patients.
Topics: Breast Neoplasms; Female; Genes, BRCA1; Genes, BRCA2; Genes, Tumor Suppressor; Germ-Line Mutation; Humans; Jews; Neoplasm Staging; Prognosis; Survival Analysis; Triple Negative Breast Neoplasms
PubMed: 27749552
DOI: 10.1097/MD.0000000000004975 -
The Oncologist Sep 2021Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.
MATERIALS AND METHODS
Head-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.
RESULTS
Eight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).
CONCLUSION
The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.
IMPLICATIONS FOR PRACTICE
Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
Topics: Chemoradiotherapy; Disease-Free Survival; Humans; Neoadjuvant Therapy; Rectal Neoplasms; Rectum; Treatment Outcome
PubMed: 33987952
DOI: 10.1002/onco.13824 -
International Journal of Molecular... Feb 2023Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC).... (Review)
Review
Around 40-50% of all triple-negative breast cancer (TNBC) patients achieve a pathological complete response (pCR) after treatment with neoadjuvant chemotherapy (NAC). The identification of biomarkers predicting the response to NAC could be helpful for personalized treatment. This systematic review provides an overview of putative biomarkers at baseline that are predictive for a pCR following NAC. Embase, Medline and Web of Science were searched for articles published between January 2010 and August 2022. The articles had to meet the following criteria: patients with primary invasive TNBC without distant metastases and patients must have received NAC. In total, 2045 articles were screened by two reviewers resulting in the inclusion of 92 articles. Overall, the most frequently reported biomarkers associated with a pCR were a high expression of Ki-67, an expression of PD-L1 and the abundance of tumor-infiltrating lymphocytes, particularly CD8+ T cells, and corresponding immune gene signatures. In addition, our review reveals proteomic, genomic and transcriptomic markers that relate to cancer cells, the tumor microenvironment and the peripheral blood, which also affect chemo-sensitivity. We conclude that a prediction model based on a combination of tumor and immune markers is likely to better stratify TNBC patients with respect to NAC response.
Topics: Humans; Neoadjuvant Therapy; Triple Negative Breast Neoplasms; Proteomics; Lymphocytes, Tumor-Infiltrating; Biomarkers; Tumor Microenvironment
PubMed: 36769287
DOI: 10.3390/ijms24032969 -
BMJ (Clinical Research Ed.) Sep 2022To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer.
DESIGN
Prospectively registered systematic review and meta-analysis of literature.
DATA SOURCES
Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors.
ELIGIBILITY CRITERIA
Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm).
RESULTS
68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins.
CONCLUSIONS
Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised.
SYSTEMATIC REVIEW REGISTRATION
CRD42021232115.
Topics: Breast; Breast Neoplasms; Female; Humans; Margins of Excision; Mastectomy; Mastectomy, Segmental; Neoplasm Recurrence, Local
PubMed: 36130770
DOI: 10.1136/bmj-2022-070346 -
The Journal of Investigative Dermatology Feb 2013The worldwide incidence and prevalence of psoriasis is poorly understood. To better understand this, we performed a systematic review of published population-based... (Review)
Review
The worldwide incidence and prevalence of psoriasis is poorly understood. To better understand this, we performed a systematic review of published population-based studies on the incidence and prevalence of psoriasis. Three electronic databases were searched from their inception dates to July 2011. A total of 385 papers were critically appraised; 53 studies reported on the prevalence and incidence of psoriasis in the general population. The prevalence in children ranged from 0% (Taiwan) to 2.1% (Italy), and in adults it varied from 0.91% (United States) to 8.5% (Norway). In children, the incidence estimate reported (United States) was 40.8/100,000 person-years. In adults, it varied from 78.9/100,000 person-years (United States) to 230/100,000 person-years (Italy). The data indicated that the occurrence of psoriasis varied according to age and geographic region, being more frequent in countries more distant from the equator. Prevalence estimates also varied in relation to demographic characteristics in that studies confined to adults reported higher estimates of psoriasis compared with those involving all age groups. Studies on the prevalence and incidence of psoriasis have contributed to a better understanding of the burden of the disease. However, further research is required to fill existing gaps in understanding the epidemiology of psoriasis and trends in incidence over time.
Topics: Global Health; Humans; Incidence; Prevalence; Psoriasis
PubMed: 23014338
DOI: 10.1038/jid.2012.339 -
The Cochrane Database of Systematic... Mar 2018Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Metastatic breast cancer is not a curable disease, but women with metastatic disease are living longer. Surgery to remove the primary tumour is associated with an increased survival in other types of metastatic cancer. Breast surgery is not standard treatment for metastatic disease, however several recent retrospective studies have suggested that breast surgery could increase the women's survival. These studies have methodological limitations including selection bias. A systematic review mapping all randomised controlled trials addressing the benefits and potential harms of breast surgery is ideal to answer this question.
OBJECTIVES
To assess the effects of breast surgery in women with metastatic breast cancer.
SEARCH METHODS
We conducted searches using the MeSH terms 'breast neoplasms', 'mastectomy', and 'analysis, survival' in the following databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed) and Embase (by OvidSP) on 22 February 2016. We also searched ClinicalTrials.gov (22 February 2016) and the WHO International Clinical Trials Registry Platform (24 February 2016). We conducted an additional search in the American Society of Clinical Oncology (ASCO) conference proceedings in July 2016 that included reference checking, citation searching, and contacting study authors to identify additional studies.
SELECTION CRITERIA
The inclusion criteria were randomised controlled trials of women with metastatic breast cancer at initial diagnosis comparing breast surgery plus systemic therapy versus systemic therapy alone. The primary outcomes were overall survival and quality of life. Secondary outcomes were progression-free survival (local and distant control), breast cancer-specific survival, and toxicity from local therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently conducted trial selection, data extraction, and 'Risk of bias' assessment (using Cochrane's 'Risk of bias' tool), which a third review author checked. We used the GRADE tool to assess the quality of the body of evidence. We used the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes and the hazard ratio (HR) for time-to-event outcomes. We calculated 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies.
MAIN RESULTS
We included two trials enrolling 624 women in the review. It is uncertain whether breast surgery improves overall survival as the quality of the evidence has been assessed as very low (HR 0.83, 95% CI 0.53 to 1.31; 2 studies; 624 women). The two studies did not report quality of life. Breast surgery may improve local progression-free survival (HR 0.22, 95% CI 0.08 to 0.57; 2 studies; 607 women; low-quality evidence), while it probably worsened distant progression-free survival (HR 1.42, 95% CI 1.08 to 1.86; 1 study; 350 women; moderate-quality evidence). The two included studies did not measure breast cancer-specific survival. Toxicity from local therapy was reported by 30-day mortality and did not appear to differ between the two groups (RR 0.99, 95% CI 0.14 to 6.90; 1 study; 274 women; low-quality evidence).
AUTHORS' CONCLUSIONS
Based on existing evidence from two randomised clinical trials, it is not possible to make definitive conclusions on the benefits and risks of breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. Until the ongoing clinical trials are finalised, the decision to perform breast surgery in these women should be individualised and shared between the physician and the patient considering the potential risks, benefits, and costs of each intervention.
Topics: Breast Neoplasms; Combined Modality Therapy; Female; Humans; Mastectomy; Neoplasm Metastasis; Prognosis; Randomized Controlled Trials as Topic
PubMed: 29542106
DOI: 10.1002/14651858.CD011276.pub2 -
Artificial Intelligence in Medicine May 2023Cervical cancer is one of the most common cancers in women with an incidence of around 6.5 % of all the cancer in women worldwide. Early detection and adequate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical cancer is one of the most common cancers in women with an incidence of around 6.5 % of all the cancer in women worldwide. Early detection and adequate treatment according to staging improve the patient's life expectancy. Outcome prediction models might aid treatment decisions, but a systematic review on prediction models for cervical cancer patients is not available.
DESIGN
We performed a systematic review for prediction models in cervical cancer following PRISMA guidelines. Key features that were used for model training and validation, the endpoints were extracted from the article and data were analyzed. Selected articles were grouped based on prediction endpoints i.e. Group1: Overall survival, Group2: progression-free survival; Group3: recurrence or distant metastasis; Group4: treatment response; Group5: toxicity or quality of life. We developed a scoring system to evaluate the manuscript. As per our criteria, studies were divided into four groups based on scores obtained in our scoring system, the Most significant study (Score > 60 %); Significant study (60 % > Score > 50 %); Moderately Significant study (50 % > Score > 40 %); least significant study (score < 40 %). A meta-analysis was performed for all the groups separately.
RESULTS
The first line of search selected 1358 articles and finally 39 articles were selected as eligible for inclusion in the review. As per our assessment criteria, 16, 13 and 10 studies were found to be the most significant, significant and moderately significant respectively. The intra-group pooled correlation coefficient for Group1, Group2, Group3, Group4, and Group5 were 0.76 [0.72, 0.79], 0.80 [0.73, 0.86], 0.87 [0.83, 0.90], 0.85 [0.77, 0.90], 0.88 [0.85, 0.90] respectively. All the models were found to be good (prediction accuracy [c-index/AUC/R] >0.7) in endpoint prediction.
CONCLUSIONS
Prediction models of cervical cancer toxicity, local or distant recurrence and survival prediction show promising results with reasonable prediction accuracy [c-index/AUC/R > 0.7]. These models should also be validated on external data and evaluated in prospective clinical studies.
Topics: Humans; Female; Uterine Cervical Neoplasms; Prospective Studies; Quality of Life; Prognosis
PubMed: 37100501
DOI: 10.1016/j.artmed.2023.102549 -
BioMed Research International 2022Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing... (Review)
Review
BACKGROUND
Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAF mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAF mutation potential of these lesions and new prevention strategies in PTC patients.
METHODS
A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAF mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021.
RESULTS
The following variables were associated with an increased risk of BRAF mutation in PTC patients: age ≥ 45 years (OR = 1.39, 95%CI = 1.21-1.60, < 0.00001), male gender (OR = 1.13, 95%CI = 0.99-1.28, = 0.06), multifocality (OR = 1.22, 95%CI = 1.07-1.40, = 0.004), lymph node metastasis (OR = 1.33, 95%CI = 0.79-2.23, = 0.28), extrathyroidal extension + (OR = 1.61, 95%CI = 1.06-2.44, = 0.03), vascular invasion + (OR = 2.04, 95%CI = 1.32-3.15, = 0.001), and tumor node metastasis stage (OR = 1.61, 95%CI = 1.38-1.88, < 0.00001). In addition, tumor size (>1 cm) (OR = 0.51, 95%CI = 0.32-0.81, = 0.005) and distant metastasis (OR = 0.69, 95%CI = 0.22-2.21, = 0.54) had no association or risk with BRAF mutation in PTC patients.
CONCLUSION
Our systematic review identified the following significant risk factors of BRAF mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAF mutation in PTC patients.
Topics: Carcinoma, Papillary; Humans; Lymphatic Metastasis; Male; Middle Aged; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 35647194
DOI: 10.1155/2022/9959649