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Frontiers in Oncology 2022Breast cancer with distant metastases is a systemic disease. While systemic therapies are the main treatment strategy, locoregional therapy for metastatic breast cancer... (Review)
Review
Breast cancer with distant metastases is a systemic disease. While systemic therapies are the main treatment strategy, locoregional therapy for metastatic breast cancer (MBC) is generally palliative only. However, recent progress in systemic and local therapies has improved the prognosis of patients with MBC and some may expect long-term survival. More vigorous local therapies for MBC may, therefore, be clinically justified in selected patients. A number of clinical trials and studies have investigated the clinical significance of surgical therapy for primary tumors and distant metastases in patients with MBC. Four prospective randomized trials and multiple retrospective studies have investigated the benefit of surgical resection of primary lesions in patients with MBC, with conflicting results. There have been a number of case-control studies examining the impact of surgical resection of distant metastases, but the benefit of this approach in terms of survival is controversial because selection bias is unavoidable in retrospective studies. The present review discusses the state of the literature relating to local management of the primary breast cancer through surgical resection and surgical management of distant metastatic lesions including pulmonary and liver metastases with future perspectives.
PubMed: 35600412
DOI: 10.3389/fonc.2022.910544 -
Frontiers in Oncology 2023Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs.... (Review)
Review
Metastasis is considered as the major cause of cancer death. Cancer cells can be released from primary tumors into the circulation and then colonize in distant organs. How cancer cells acquire the ability to colonize in distant organs has always been the focus of tumor biology. To enable survival and growth in the new environment, metastases commonly reprogram their metabolic states and therefore display different metabolic properties and preferences compared with the primary lesions. For different microenvironments in various colonization sites, cancer cells must transfer to specific metabolic states to colonize in different distant organs, which provides the possibility of evaluating metastasis tendency by tumor metabolic states. Amino acids provide crucial precursors for many biosynthesis and play an essential role in cancer metastasis. Evidence has proved the hyperactivation of several amino acid biosynthetic pathways in metastatic cancer cells, including glutamine, serine, glycine, branched chain amino acids (BCAAs), proline, and asparagine metabolism. The reprogramming of amino acid metabolism can orchestrate energy supply, redox homeostasis, and other metabolism-associated pathways during cancer metastasis. Here, we review the role and function of amino acid metabolic reprogramming in cancer cells colonizing in common metastatic organs, including lung, liver, brain, peritoneum, and bone. In addition, we summarize the current biomarker identification and drug development of cancer metastasis under the amino acid metabolism reprogramming, and discuss the possibility and prospect of targeting organ-specific metastasis for cancer treatment.
PubMed: 36998464
DOI: 10.3389/fonc.2023.1123192 -
Journal of Gastrointestinal Surgery :... Jul 2023Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the digestive tract, among which patients with distant metastases tend to have a poor prognosis. This... (Review)
Review
A New Online Dynamic Nomogram: Construction and Validation of a Predictive Model for Distant Metastasis Risk and Prognosis in Patients with Gastrointestinal Stromal Tumors.
BACKGROUND
Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the digestive tract, among which patients with distant metastases tend to have a poor prognosis. This study aimed to develop a model for predicting distant metastasis in GIST patients and to develop two models for monitoring overall survival (OS) and cancer-specific survival (CSS) in GIST patients with metastasis. This would allow us to develop an optimal, individualized treatment strategy.
METHODS
We reviewed demographic and clinicopathological characteristics data from 2010 to 2017 of patients diagnosed with GIST in the Surveillance, Epidemiology, and End Results (SEER) database. The data of the external validation group was reviewed from the Forth Hospital of Hebei Medical University. Univariate and multivariate logistic regression analyses were used to confirm the independent risk factors for distant metastasis in the GIST patients, and univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factors for OS and CSS in the GIST patients with distant metastasis. Subsequently, three web-based novel nomograms were developed, which were evaluated by the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).
RESULTS
Of the 3639 patients who met the inclusion criteria, 418 (11.4%) had distant metastases. The risk factors for distant metastasis in GIST patients included sex, primary site, grade, N stage, tumor size, and mitotic count. For OS, the independent prognosis factors for GIST patients with metastasis included age, race, marital, primary site, chemotherapy, mitotic count, and metastasis at the lung, and for CSS, age, race, marital, primary site, and metastasis at the lung were the independent prognosis factors. Three web-based nomograms were constructed based on these independent factors, respectively. The ROC curves, calibration curves, and DCA were performed in the training, testing, and validation sets which confirmed the high accuracy and strong clinical practice power for the nomograms.
CONCLUSION
Population-based nomograms can help clinicians predict the occurrence and prognosis of distant metastases in patients with GIST, which may be helpful for clinicians to formulate clinical management and appropriate treatment strategies.
Topics: Humans; Nomograms; Gastrointestinal Stromal Tumors; Prognosis; Databases, Factual; SEER Program
PubMed: 37231240
DOI: 10.1007/s11605-023-05706-9 -
The Journal of Investigative Dermatology Apr 2024The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched...
The evolution of primary melanoma to lymph node and distant metastasis is incompletely understood. We examined the genomic diversity in melanoma progression in matched primary melanomas and lymph node and distant metastases from 17 patients. FISH analysis revealed cancer cell fractions with monotonic copy number alterations, including PHIP gain and PTEN loss, in the metastatic cascade. By contrast, the cancer cell fraction with copy number alterations for BPTF and MITF was reduced in lymph node metastases but increased in distant metastases. Separately, the cancer cell fraction with NCOA3 copy number alteration was comparable between primary tumors and lymph node metastases yet increased in distant metastases. These results suggest enrichment of the phosphoinositide 3-kinase and MITF pathways in the transition through the metastatic cascade. By contrast, next-generation sequencing analysis did not identify a consistent pattern of changes in variant allele frequency while revealing several intriguing findings, including decreased variant allele frequency in distant metastases and distinct drivers in lymph node versus distant metastases. These results provide evidence that distant melanoma metastasis does not always emanate from lymph node metastasis. These results enhance our understanding of clonal patterns of melanoma metastasis, with possible implications for targeted therapy and metastasis competency.
PubMed: 38582370
DOI: 10.1016/j.jid.2024.03.029 -
Annals of Surgical Oncology Jan 2021Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this...
BACKGROUND
Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy with a propensity for regional and distant spread. Because of the relative infrequency of this disease, the patterns of metastasis in MCC are understudied.
METHODS
Patients with American Joint Committee on Cancer (8th edition) stage I-IV MCC treated at our institution were identified (1/1/2008-2/28/2018). The first site of metastasis was classified as regional [regional lymph node (LN) basin, in-transit] or distant. Distant metastasis-free (DMFS) and MCC-specific (MSS) survival were estimated.
RESULTS
Of 133 patients, 64 (48%) had stage I, 13 (10%) stage II, 48 (36%) stage III, and 8 (6%) stage IV disease at presentation. The median follow-up time in patients who remained alive was 36 (interquartile range 20-66) months. Regional or distant metastases developed in 78 (59%) patients. The first site was regional in 87%, including 73% with isolated LN involvement, and distant in 13%. Thirty-seven (28%) patients eventually developed distant disease, which most commonly involved the abdominal viscera (51%) and distant LNs (46%) first. The lung (0%) and brain (3%) were rarely the first distant sites. Stage III MCC at presentation was significantly associated with worse DMFS (hazard ratio 4.87, Pā=ā0.001) and stage IV disease with worse MSS (hazard ratio 6.30, Pā=ā0.002).
CONCLUSIONS
Regional LN metastasis is the most common first metastatic event in MCC, confirming the importance of nodal evaluation. Distant disease spread appears to have a predilection for certain sites. Understanding these patterns could help to guide surveillance strategies.
Topics: Aged; Aged, 80 and over; Carcinoma, Merkel Cell; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Skin Neoplasms
PubMed: 32405979
DOI: 10.1245/s10434-020-08587-3 -
Cancers Nov 2022Anaplastic thyroid cancer (ATC) is derived from follicular thyroid cells and is associated with high mortality risk. Obtaining information to characterize ATC is...
Anaplastic thyroid cancer (ATC) is derived from follicular thyroid cells and is associated with high mortality risk. Obtaining information to characterize ATC is difficult because ATC with distant metastasis is extremely rare. This study determined the clinical characteristics of ATC with distant metastasis. The medical records of 152 patients with ATC at Gangnam Severance Hospital were reviewed between January 2004 and March 2022. The primary endpoint was the overall survival of the total patient sample, patients with ATC and distant metastasis, and those with ATC and brain metastasis. Of the 152 patients with ATC, 88 had distant metastasis at diagnosis. The 5-year disease-specific survival was 24% for total ATC and 10% for ATC with distant metastasis. Survival for >1 year was 32% for total ATC and 15% for ATC with distant metastasis. The median survival rate differed significantly between the total ATC and ATC with distant metastasis groups (228.5 vs. 171 days). Among the ATC cases, 11% had brain metastasis; thus, brain MRI or CT is worth considering at diagnosis and follow-up, even if there were no statistical difference in overall survival between patients with ATC with and without brain metastasis.
PubMed: 36497268
DOI: 10.3390/cancers14235784 -
Journal of Cancer Research and Clinical... Sep 2023The mechanisms of distant metastasis in pancreatic cancer (PC) have not been elucidated, and this study aimed to explore the risk factors affecting the metastasis and...
BACKGROUND
The mechanisms of distant metastasis in pancreatic cancer (PC) have not been elucidated, and this study aimed to explore the risk factors affecting the metastasis and prognosis of metastatic patients and to develop a predictive model.
METHOD
Clinical data from patients meeting criteria from 1990 to 2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, and two machine learning methods, random forest and support vector machine, combined with logistic regression, were used to explore risk factors influencing distant metastasis and to create nomograms. The performance of the model was validated using calibration curves and ROC curves based on the Shaanxi Provincial People's Hospital cohort. LASSO regression and Cox regression models were used to explore the independent risk factors affecting the prognosis of patients with distant PC metastases.
RESULTS
We found that independent risk factors affecting PC distant metastasis were: age, radiotherapy, chemotherapy, T and N; the independent risk factors for patient prognosis were: age, grade, bone metastasis, brain metastasis, lung metastasis, radiotherapy and chemotherapy.
CONCLUSION
Together, our study provides a method for risk factors and prognostic assessment for patients with distant PC metastases. The nomogram we developed can be used as a convenient individualized tool to facilitate aid in clinical decision making.
Topics: Humans; Prognosis; Nomograms; Pancreatic Neoplasms; Machine Learning; SEER Program
PubMed: 37278826
DOI: 10.1007/s00432-023-04903-y -
Statistical Methods in Medical Research Dec 2022The few existing statistical models of breast cancer recurrence and progression to distant metastasis are predominantly based on multi-state modelling. While useful for...
The few existing statistical models of breast cancer recurrence and progression to distant metastasis are predominantly based on multi-state modelling. While useful for summarising the risk of recurrence, these provide limited insight into the underlying biological mechanisms and have limited use for understanding the implications of population-level interventions. We develop an alternative, novel, and parsimonious approach for modelling latent tumour growth and spread to local and distant metastasis, based on a natural history model with biologically inspired components. We include marginal sub-models for local and distant breast cancer metastasis, jointly modelled using a copula function. Different formulations (and correlation shapes) are allowed, thus we can incorporate and directly model the correlation between local and distant metastasis flexibly and efficiently. Submodels for the latent cancer growth, the detection process, and screening sensitivity, together with random effects to account for between-patients heterogeneity, are included. Although relying on several parametric assumptions, the joint copula model can be useful for understanding - potentially latent - disease dynamics, obtaining patient-specific, model-based predictions, and studying interventions at a population level, for example, using microsimulation. We illustrate this approach using data from a Swedish population-based case-control study of postmenopausal breast cancer, including examples of useful model-based predictions.
Topics: Humans; Female; Breast Neoplasms; Case-Control Studies; Neoplasm Recurrence, Local; Models, Statistical; Mass Screening
PubMed: 36120891
DOI: 10.1177/09622802221122410 -
Cancer Medicine Dec 2023Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and...
BACKGROUND
Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA-miRNA-mRNA ceRNA network in distant metastasis of CRC are still unclear.
METHODS
In this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT-PCR and univariate and multivariate analysis of the metastasis- and prognosis-related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC.
RESULTS
Two key distant metastasis-related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA-associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1- and LINC01871-associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs.
CONCLUSION
The DElncRNA AP002498.1 and the LINC01871/miR-4644 and miR-185-5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.
PubMed: 38083905
DOI: 10.1002/cam4.6823 -
Frontiers in Oncology 2023Distant organ metastasis is a common event in lung cancer (LC). However, the preferential metastatic pattern of different pathological types of LC and its effect on...
BACKGROUND
Distant organ metastasis is a common event in lung cancer (LC). However, the preferential metastatic pattern of different pathological types of LC and its effect on prognosis have not been comprehensively elucidated. This study aimed to explore the distant metastasis pattern and construct nomograms predicting the metastasis and survival of LC patients using the Surveillance, Epidemiology, and End Results (SEER) database.
METHODS
LC data were downloaded from the SEER database to conduct logistic regression and investigate risk factors for developing organ metastasis. A Cox regression analysis was conducted to investigate prognostic factors of LC. A Kaplan-Meier analysis was used to estimate overall survival outcomes. Nomograms were constructed to predict the probability of organ metastasis and the 1-, 3- and 5-year survival probability of LC patients. Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of the nomograms. All statistical analyses were conducted within R software.
RESULTS
The liver is the most common metastatic organ of small cell carcinoma. The brain is the most likely metastasis site of large cell carcinoma, and bone is the most likely metastasis site for squamous cell carcinoma and adenocarcinoma. Patients with triple metastases (brain-bone-liver) have the worst prognosis, and for nonsquamous carcinoma with single organ metastasis, liver metastases conferred the worst prognosis. Our nomograms based on clinical factors could predict the metastasis and prognosis of LC patients.
CONCLUSION
Different pathological types of LC have different preferential metastatic sites. Our nomograms showed good performance in predicting distant metastasis and overall survival. These results will provide a reference for clinicians and contribute to clinical evaluations and individualized therapeutic strategies.
PubMed: 37377915
DOI: 10.3389/fonc.2023.1075385