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Oncoimmunology 2023The evolution of immune profile from primary tumors to distant and local metastases in non-small cell lung cancer (NSCLC), as well as the impact of the immune background...
The evolution of immune profile from primary tumors to distant and local metastases in non-small cell lung cancer (NSCLC), as well as the impact of the immune background of primary tumors on metastatic potential, remains unclear. To address this, we performed whole-exome sequencing and immunohistochemistry for 73 paired primary and metastatic tumor samples from 41 NSCLC patients, and analyzed the change of immune profile from primary tumors to metastases and involved genetic factors. We found that distant metastases tended to have a decreased CD8+ T cell level along with an increased chromosomal instability (CIN) compared with primary tumors, which was partially ascribed to acquired DNA damage repair (DDR) deficiency. Distant metastases were characterized by immunosuppression (low CD8+ T cell level) and immune evasion (high PD-L1 level) whereas local metastases (pleura) were immune-competent with high CD8+ T cell, low CD4+ T cell and low PD-L1 level. Primary tumors with high levels of CD4+ T cells were associated with distant metastases rather than local metastases. Analysis of TCGA data and a single-cell RNA-sequencing dataset revealed a decreasing trend of major immune cells, such as CD8+ T cells, and an increasing trend of CD4 T helper cells (Th2 and Th1) in primary tumors with metastases from local to distant sites. Our study indicates that there are differences in the immune evolution between distant and local metastases, and that acquired DDR deficiency contributes to the immunosuppression in distant metastases of NSCLC. Moreover, the immune background of primary tumors may affect their metastatic potential.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; CD8-Positive T-Lymphocytes; DNA Damage
PubMed: 37261085
DOI: 10.1080/2162402X.2023.2215112 -
Frontiers in Endocrinology 2021Distant metastasis in papillary thyroid microcarcinoma (PTMC) is rare but fatal, and its relationship with patient age remains unclear. The objective of this study was...
OBJECTIVE
Distant metastasis in papillary thyroid microcarcinoma (PTMC) is rare but fatal, and its relationship with patient age remains unclear. The objective of this study was to examine the association between age at diagnosis and metachronous distant metastasis in PTMC.
METHODS
Consecutive patients who underwent thyroidectomy for PTC measuring 10 mm or less at a tertiary hospital from January 2000 to December 2016 were enrolled. Patients who had evidence of distant metastasis at diagnosis or underwent postoperative radioiodine (RAI) ablation were excluded. A Cox proportional hazards model with restricted cubic splines (RCS) was applied to examine the association between age at diagnosis and distant metastasis.
RESULTS
A total of 4,749 patients were evaluated. The median age was 44 years (range, 8-78 years), and 3,700 (78%) were female. After a median follow-up of 65 months, 21 distant metastases (20 lung, 1 liver) were recognized. A univariate Cox proportional model using a 5-knot RCS revealed a significant overall ( = 0.01) and a potential nonlinear association ( = 0.08) between distant metastasis and age at diagnosis. In multivariate analysis, age at diagnosis, extrathyroidal extension (ETE), and lymph node metastasis (pN+) were independent risk factors for distant metastasis. Compared with the middle-aged group (30-45 years old), younger and older patients had a higher risk of distant metastasis [HR, 95% CI, -value, age ≤ 30, 4.54 (0.91-22.60), 0.06, age > 45, 6.36 (1.83-22.13), <0.01].
CONCLUSION
Age at diagnosis is associated with metachronous distant metastasis of PTMC, and patients with younger or older age have a higher risk of distant metastasis than middle-aged patients.
Topics: Adolescent; Adult; Age Factors; Aged; Carcinoma, Papillary; Child; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Thyroid Neoplasms; Young Adult
PubMed: 35002953
DOI: 10.3389/fendo.2021.748238 -
Neurosurgical Focus Aug 2023The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at...
OBJECTIVE
The aim of this study was to investigate associations between genomic alterations in resected brain metastases and rapid local and distant CNS recurrence identified at the time of postoperative adjuvant radiosurgery.
METHODS
This was a retrospective study on patients who underwent resection of intracranial brain metastases. Next-generation sequencing of more than 500 coding genes was performed on brain metastasis specimens. Postoperative and preradiosurgery MR images were compared to identify rapid recurrence. Genomic data were associated with rapid local and distant CNS recurrence of brain metastases using nominal regression analyses.
RESULTS
The cohort contained 92 patients with 92 brain metastases. Thirteen (14.1%) patients had a rapid local recurrence, and 64 (69.6%) patients had rapid distant CNS progression by the time of postoperative adjuvant radiosurgery, which occurred in a median time of 25 days (range 3-85 days) from surgery. RB1 and CTNNB1 mutations were seen in 8.7% and 9.8% of the cohort, respectively, and were associated with a significantly higher risk of rapid local recurrence (RB1: OR 13.6, 95% CI 2.0-92.39, p = 0.008; and CTNNB1: OR 11.97, 95% CI 2.25-63.78, p = 0.004) on multivariate analysis. No genes were found to be associated with rapid distant CNS progression. However, the presence of extracranial disease was significantly associated with a higher risk of rapid distant recurrence on multivariate analysis (OR 4.06, 95% CI 1.08-15.34, p = 0.039).
CONCLUSIONS
Genomic alterations in RB1 or CTNNB1 were associated with a significantly higher risk of rapid recurrence at the resection site. Although no genomic alterations were associated with rapid distant recurrence, having active extracranial disease was a risk factor for new lesions by the time of adjuvant radiotherapy after resection.
Topics: Humans; Retrospective Studies; Neoplasm Recurrence, Local; Brain Neoplasms; Brain; Radiotherapy, Adjuvant; Radiosurgery
PubMed: 37527682
DOI: 10.3171/2023.5.FOCUS23214 -
Hormone and Metabolic Research =... Jan 2022This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid...
This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, which are ill-defined. On multivariable logistic regression analyses, lymph node metastasis consistently emerged as an independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4 and 2.8 for follicular thyroid cancer and the follicular variant of papillary thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer. Another independent risk factor consistently associated with distant metastasis, most strongly in follicular thyroid cancer and the follicular variant of papillary thyroid cancer (OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk patterns of distant metastasis were identified, which were modulated by other cancer type-dependent risk factors: one with lymph node metastasis as leading component (classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer), and another one with age as leading component (follicular thyroid cancer and the follicular variant of papillary thyroid cancer). Distant metastasis was exceptional in node-negative patients with sporadic medullary thyroid cancer (1.7%) and the classical variant of papillary thyroid cancer (1.4%), and infrequent in node-negative patients with the follicular variant of papillary thyroid cancer (4.4%). These findings delineate windows of opportunity for early surgical intervention before distant metastasis has occurred.
Topics: Adenocarcinoma, Follicular; Adult; Carcinoma, Neuroendocrine; Female; Humans; Logistic Models; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Risk Factors; Thyroid Cancer, Papillary; Thyroid Neoplasms; Tumor Burden
PubMed: 34758495
DOI: 10.1055/a-1668-0094 -
Cancer Management and Research 2022This study aimed to summarize the clinical characteristics, treatment, and outcomes of distant metastatic retinoblastoma with event-free survival.
AIM
This study aimed to summarize the clinical characteristics, treatment, and outcomes of distant metastatic retinoblastoma with event-free survival.
DESIGN
Retrospective interventional case series.
METHODS
We screened patients with retinoblastoma who survived without events after the comprehensive treatment of distant metastases from June 2015 to February 2021 and collected information regarding their basic characteristics, diagnosis, and treatment. All patients received systemic intravenous chemotherapy. Other treatments included surgical treatment, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation.
RESULTS
Among 780 hospitalized patients with retinoblastoma in the pediatric ward, a total of 94 patients with retinoblastoma were diagnosed with distant metastases, and 16 patients with distant metastatic retinoblastoma who survived more than 6 months without events were screened, including eight male and eight female patients. The median age of onset was 29 (range, 11-120) months. Among the 16 patients, central nervous system metastasis (8/16), bone metastasis (8/16), bone marrow infiltration (4/16), lymph node metastasis (4/16), and parotid gland metastasis (3/16) were presented. All patients received treatment for more than 6 months, completed their regimen by February 2021, and survived without events. The median survival time after the onset of retinoblastoma was 50.5 (range, 23-102) months, the median survival time after metastasis was 43.5 (range, 16-71) months, and the median event-free survival was 29.0 (range, 6-59) months.
CONCLUSION
Metastatic retinoblastoma may benefit from comprehensive treatments including systemic intravenous chemotherapy and hematopoietic stem cell transplantation. However, recurrence after treatment still needs attention, and patients in complete remission still need long-term follow-up.
PubMed: 35115833
DOI: 10.2147/CMAR.S349035 -
Clinical Otolaryngology : Official... May 2022The aim of this study was to define the suitability of microscopic lymphatic and venous invasion for prediction of lymph node and distant metastases in papillary thyroid...
OBJECTIVES
The aim of this study was to define the suitability of microscopic lymphatic and venous invasion for prediction of lymph node and distant metastases in papillary thyroid cancer.
DESIGN
Stratification by microscopic lymphatic and venous invasion, and multivariable analyses on lymph node and distant metastases including microscopic lymphatic and venous invasion as independent variables.
SETTING
Tertiary referral centre.
PARTICIPANTS
422 patients who had ≥5 lymph nodes removed at initial thyroidectomy.
MAIN OUTCOME MEASURES
Lymph node and distant metastases.
RESULTS
Patients with microscopic lymphatic invasion had larger primary tumours than patients without and more often revealed microscopic venous invasion, multifocal tumour growth and lymph node metastases. Patients with microscopic venous invasion exhibited larger primary tumours than patients without and more commonly had microscopic lymphatic invasion, poor tumour differentiation, lymph node metastases and distant metastases. Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (61.0 vs. 33.3%) and positive predictive value (92.6 vs. 20.9%), comparable regarding specificity (89.6 and 93.4%), and worse regarding negative predictive value (51.9 vs. 95.3%) and accuracy (70.1 vs. 87.7%). On multivariable logistic regression analysis, microscopic lymphatic invasion was associated with lymph node metastasis (odds ratio [OR] 11.1) and multifocal tumour growth (OR 2.4), whereas primary tumour size (OR 5.8 for tumours >40 mm relative to tumours ≤20 mm) and multifocal tumour growth (OR 3.1) were associated with distant metastasis.
CONCLUSION
Stricter histopathological criteria are warranted to enhance the utility of microscopic vascular invasion for prediction of distant metastases in papillary thyroid cancer.
Topics: Humans; Lymph Nodes; Lymphatic Metastasis; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy
PubMed: 35184405
DOI: 10.1111/coa.13919 -
IEEE Transactions on Visualization and... Feb 2022Studying variation among time-evolved translations is a valuable research area for cultural heritage. Understanding how and why translations vary reveals cultural,...
Studying variation among time-evolved translations is a valuable research area for cultural heritage. Understanding how and why translations vary reveals cultural, ideological, and even political influences on literature as well as author relations. In this article, we introduce a novel integrated visual application to support distant and close reading of a collection of Othello translations. We present a new interactive application that provides an alignment overview of all the translations and their correspondences in parallel with smooth zooming and panning capability to integrate distant and close reading within the same view. We provide a range of filtering and selection options to customize the alignment overview as well as focus on specific subsets. Selection and filtering are responsive to expert user preferences and update the analytical text metrics interactively. Also, we introduce a customized view for close reading which preserves the history of selections and the alignment overview state and enables backtracing and re-examining them. Finally, we present a new Term-Level Comparisons view (TLC) to compare and convey relative term weighting in the context of an alignment. Our visual design is guided by, used and evaluated by a domain expert specialist in German translations of Shakespeare.
PubMed: 32746287
DOI: 10.1109/TVCG.2020.3012778 -
The Annals of Thoracic Surgery Feb 2021Despite the superiority of mitral valve repair (MVr) over replacement for degenerative disease, repair rates vary widely across centers. Traveling to a mitral reference...
BACKGROUND
Despite the superiority of mitral valve repair (MVr) over replacement for degenerative disease, repair rates vary widely across centers. Traveling to a mitral reference center (MRC) is 1 way to increase the odds of MVr. This study assessed the economic value (quality/cost) and long-term outcomes of distant referral to an MRC.
METHODS
Among 746 mitral surgery patients between January 2011 and June 2013, low-risk patients with an ejection fraction greater than 40% undergoing isolated degenerative MVr were identified and included 26 out-of-state (DISTANT) and 104 in-state patients (LOCAL). Short- and long-term outcomes and institutional financial data (including travel expenses) were used to compare groups. National average and MRC-specific MVr rates, clinical outcomes, and marginal value of quality-adjusted life-years collected from The Society of Thoracic Surgeons database and Medicare estimates were used to perform a nationally representative cost-benefit analysis for distant referral.
RESULTS
Age, ejection fraction, operative time, blood transfusions, and annuloplasty ring size did not differ between groups. Median charges were $76,022 for LOCAL and $74,171 for DISTANT (P = .35), whereas median payments (including travel expenses) were $57,795 for LOCAL and $58,477 for DISTANT (P = .70). Short- and long-term outcomes were similar between groups and median follow-up was 7.1 years. Estimated 5-year survival was 97% (96% for LOCAL and 100% for DISTANT; P = .24). Cost-benefit analysis showed a net benefit through distant referral to an MRC ranging from $436 to $6078 to the payer and $22,163 to $30,067 to the patient, combining for an estimated $22,599 to $32,528 societal benefit.
CONCLUSIONS
These data suggest that distant referral to an MRC is achievable and reasonable.
Topics: Chronic Disease; Costs and Cost Analysis; Female; Follow-Up Studies; Heart Valve Prosthesis Implantation; Humans; Male; Medicare; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Referral and Consultation; Retrospective Studies; Time Factors; Treatment Outcome; United States
PubMed: 32693045
DOI: 10.1016/j.athoracsur.2020.05.114 -
Journal of Gastrointestinal Oncology Apr 2021High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in...
BACKGROUND
High neutrophil-lymphocyte ratio (NLR) is linked to poor overall survival (OS) in gastrointestinal tract cancers. This study explores the clinical value of NLR, in addition to absolute lymphocyte count (ALC) and other hematologic parameters in association with distant metastases and OS in primary gastric lymphoma (PGL) patients.
METHODS
Clinical data of 139 PGL patients who received treatment at King Hussein Cancer Center (KHCC), Amman-Jordan were retrospectively evaluated. Using data from complete blood count (CBC) tests, the following hematologic parameters: absolute neutrophil count (ANC), ALC, absolute eosinophil count (AEC), absolute monocyte count (AMC), NLR, platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR) were assessed in association with the following clinical outcomes: presence or absence of baseline distant metastases and OS. We conducted univariate and multivariate analyses assessing the various hematologic parameters in association with distant metastases.
RESULTS
Univariate and multivariate analyses indicated that patients with an elevated NLR (>3.14) displayed more baseline distant metastases compared to patients with a low NLR (≤3.14), (P value: 0.02 and 0.018, respectively). High baseline ALC (>1,819/µL) was associated with lower baseline distant metastases (P value: 0.04). In the OS analysis, high baseline ANC (>5,100/µL), NLR (>2.75), and PLR (>0.16) were associated with poor OS, (P value: 0.027, 0.016, and 0.011 respectively).
CONCLUSIONS
High NLR and ALC were associated with baseline distant metastases. High baseline ANC, NLR, and PLR were associated with poor OS. Hematologic parameters might be potentially helpful in assessing and correlating NLR with the response success to treatment in PGL.
PubMed: 34012632
DOI: 10.21037/jgo-20-383 -
Cancer Science Mar 2022Data on treatment and survival of patients with advanced unresectable esophageal squamous cell carcinoma (ESCC) from Western populations are limited. Here we describe...
Data on treatment and survival of patients with advanced unresectable esophageal squamous cell carcinoma (ESCC) from Western populations are limited. Here we describe treatment and survival in patients with advanced unresectable ESCC: patients with cT4b disease without metastases (cT4b), metastases limited to the supraclavicular lymph nodes (SCLNM) or distant metastatic ESCC at the population level. All patients with unresectable (cT4b) or synchronous metastatic ESCC at primary diagnosis (2015-2018) or patients with metachronous metastases after primary non-metastatic diagnosis in 2015-2016 were selected from the Netherlands Cancer Registry. Fifteen percent of patients had cT4b disease (n = 146), 12% SCLNM (n = 118) and 72% distant metastases (n = 681). Median overall survival (OS) time was 6.3, 11.2, and 4.4 months in patients with cT4b, SCLNM, and distant metastases, respectively (P < .001). Multivariable Cox regression showed that patients with cT4b (hazard ratio 1.44, 95% CI 1.04-1.99) and patients with distant metastases (hazard ratio 1.42, 95% CI 1.12-1.80) had a worse survival time compared with patients with SCLNM. Among patients who received chemoradiotherapy and/or underwent resection (primary tumor and/or metastases), median OS was 11.9, 16.1, and 14.0 months in patients with cT4b, SCLNM, and distant metastases, respectively (P = .76). Patients with SCLNM had a better survival time compared with patients with cT4b and patients with distant metastases. Survival of patients with advanced unresectable ESCC in clinical practice was poor, even in patients treated with curative intent.
Topics: Aged; Chemoradiotherapy; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Middle Aged; Netherlands; Pneumonectomy; Registries; Retrospective Studies; Survival Rate
PubMed: 34986523
DOI: 10.1111/cas.15262