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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 -
Cancer Diagnosis & Prognosis 2022Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor...
BACKGROUND/AIM
Chondrosarcoma (CS) is a rare primary malignant bone tumor, which is the second most common tumor after osteosarcoma. Since chemotherapy and radiotherapy have poor efficacy for CS, amputation or surgical wide resection is the main strategy for localized high-grade CS, making CS therapy difficult. As studies on high-grade CS are limited owing to its rare nature, there are many unknown prognostic factors for survival.
PATIENTS AND METHODS
This retrospective cohort study included 44 patients with high-grade CS who underwent surgery at a single institution. Overall survival (OS), distant failure-free survival (DFFS), and local failure-free survival (LFFS) were evaluated using the Kaplan-Meier method. Furthermore, we evaluated prognostic factors for survival in patients with high-grade CS using univariate and multivariate analyses.
RESULTS
The 5-year OS, LFFS, and DFFS rates of high-grade CS were 75.9%, 90.8%, and 66.5%, respectively. Univariate analysis revealed that tumor size, tumor grade, and surgical margin were significant prognostic factors for OS and DFFS, and distant metastasis was significantly associated with OS. Furthermore, the multivariate analysis indicated that the presence of local recurrence and distant metastasis was significantly associated with OS.
CONCLUSION
Local recurrence and distant metastasis were significant prognostic factors for high-grade CS.
PubMed: 36340450
DOI: 10.21873/cdp.10159 -
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 -
Cancer Medicine Jul 2021Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have not...
OBJECTIVE
Owing to its rarity and heterogeneity, the biological behavior and optimal therapeutic management of mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) have not been established. Herein, we aimed to evaluate the clinicopathological characteristics and metastatic patterns of MiNEN.
METHODS
Continuous clinicopathological data of MiNEN patients treated at our hospital were retrospectively collected and analyzed.
RESULTS
This study had enrolled 169 patients since January 2010 to January 2020. Pathological components were assessed in 129 patients with MiNEN (76.3%), and a focal (non-)neuroendocrine component was observed in 40 patients (23.7%; <30% of the tumor). Among the enrolled patients, 80 underwent surgical removal of the primary tumor and lymph nodes (LNs), and 34 with distant metastasis underwent biopsy of both primary tumor and metastatic lesions. In patients with LN metastasis, 68.8% (55/80) exhibited a pure component of either neuroendocrine (NE) or adenocarcinoma/squamous carcinoma (AS) in metastatic LNs, while 20% (16/80) showed different components in different LNs, and only 11.2% (9/80) exhibited both NE and AS components in the same LN. In patients with distant metastases, 26.5% (9/34) possessed coexisting NE and AS components in the distant metastases, 70.6% (24/34) were regarded as a pure NE component, and 2.9% (1/34) were comprised of a pure AS component.
CONCLUSION
Lymph node and distant metastases exhibited distinct metastatic patterns in patients with MiNEN. The major pathological component in regional LNs may have influenced the proportion of the two components within the primary tumor, but distant metastases were dominated by the NE component.
Topics: Adenocarcinoma; Biliary Tract Neoplasms; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Duodenal Neoplasms; Esophageal Neoplasms; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasms, Complex and Mixed; Neuroendocrine Tumors; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms
PubMed: 34109756
DOI: 10.1002/cam4.4031 -
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 -
Acta Medica Okayama Apr 2022Cases of breast cancer metastasis after achieving a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) are sometimes encountered in clinical...
Cases of breast cancer metastasis after achieving a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) are sometimes encountered in clinical practice. We investigated the prognostic factors for pCR in patients with breast cancer after NAC. This retrospective cohort study included patients with localized breast cancer who underwent NAC followed by surgery between 2004 and 2020 and achieved a pCR. The associations between clinical factors and distant metastasis-free survival rate were statistically analyzed. We analyzed data for 127 patients. Twelve patients (9.4%) had distant metastases, and seven (5.5%) died. For estrogen receptor (ER)-positive patients, the distant metastasis-free survival rate was 94.6% for both 5 and 8 years. In contrast, ER-negative patients had a distant metastasis-free survival rate of 87.6% and 85.4% for 5 and 8 years (p=0.094), respectively. In cT0-2 patients, the distant metastasis-free survival rate was 92.4% for 5 years and 90.5% for 8 years, whereas in cT3-4 patients, the distant metastasis-free survival rate was 83.5% for 5 years and 83.5% for 8 years (p=0.301). This study suggested that patients with ER-negative, pre-NAC cT3 or T4 breast cancer who had achieved a pCR after NAC tended to have a worse prognosis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy; Prognosis; Retrospective Studies
PubMed: 35503437
DOI: 10.18926/AMO/63403 -
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 -
Frontiers in Oncology 2024Extraocular sebaceous carcinoma (SC), particularly those outside the head and neck region, is rare and not well-described.
INTRODUCTION
Extraocular sebaceous carcinoma (SC), particularly those outside the head and neck region, is rare and not well-described.
PURPOSE
This study aimed to explore the epidemiology and identify the prognostic factors of non-head and neck SC, describe the possible relevant factors of distant metastasis, and provide implications for distant metastasis screening.
METHODS
Data from the 17 registries in the Surveillance, Epidemiology, and End Results database were retrospectively collected for patients with SC outside the head and neck from 2000 through 2020. Overall survival (OS) and disease-specific survival (DSS) were the primary endpoints. Survival analysis was conducted through Kaplan-Meier curves, and multivariate analysis was carried out using Cox proportional hazard models.
RESULTS
A total of 1,237 patients with SC outside the head and neck were identified. The mean age at diagnosis of the entire patient cohort was 67.7 years (30 to 90+ years), and the mean tumor size was 2.2 cm (0.1-16 cm). Patients with distant disease experienced the lowest OS (mean, 29.5 months) than those with localized disease and regional disease ( < 0.0001). Multivariate analysis revealed that age, tumor size, and stage were independent determinants of OS; age, stage, and primary site were independent determinants of DSS. Tumor grade and lymph node status had less prognostic value for survival. Undifferentiated tumors have a trend toward distant metastasis, especially those at the primary site of the trunk.
CONCLUSION
The prognosis of the non-head and neck SC is excellent, while the survival of distant disease is very poor. Distant metastasis screening can be considered for undifferentiated tumors, especially those located in the trunk region with large tumor sizes.
PubMed: 38800410
DOI: 10.3389/fonc.2024.1395273