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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 -
Cancer Management and Research 2021This study aims to summarize the clinical features and prognoses of the malignant rhabdoid tumor of the kidney (MRTK) in children. It further aims to analyze the...
OBJECTIVE
This study aims to summarize the clinical features and prognoses of the malignant rhabdoid tumor of the kidney (MRTK) in children. It further aims to analyze the high-risk factors affecting MRTK prognosis.
METHODS
Clinical data from 14 children with MRTK treated in Paediatrics of Beijing Tongren Hospital from January 2010 to December 2019, along with the high-risk factors affecting prognosis, were retrospectively analyzed.
RESULTS
There were 14 children with MRTK included in the study, with a median onset age of 13 (3-46) months. Thirteen patients had distant metastases, the most common site for metastases being inside the lung. A comprehensive treatment protocol combined with chemotherapy was mainly applied during the surgery. A surgical resection of primary tumors was performed on 13 (13/14) patients, and all 14 children received chemotherapy with ifosfamide + carboplatin + etoposide, ifosfamide + etoposide, and vincristine + pirarubicin + cyclophosphamide regimens, alternately. Three patients received radiotherapy and two received oral targeted drugs after partial response. The median follow-up was after 16.5 months (3-53 months) and the four-year overall survival (OS) was 41.8%. In children aged ≤24 months and children aged >24 months, the two-year OS was 67.2% and 100% (χ = 108.998, P<0.05), respectively. In children with Ki 67 > 70% and children with Ki 67 < 70%, the two-year OS was 52.6% and 86.9% (χ = 8.544, P = 0.003), respectively. In children with distant metastases and children without distant metastasis, the two-year OS was 70% and 100% (χ = 14.239, P<0.05), respectively.
CONCLUSION
The most common MRTK distant metastasis site is the lung. Risk factors for poor MRTK prognoses include an age of <24 months, Ki 67 > 70%, and distant metastases.
PubMed: 34188539
DOI: 10.2147/CMAR.S309274 -
European Journal of Surgical Oncology :... Sep 2023Patients with locally recurrent rectal cancer (LRRC) generally have poor prognosis, especially those who have (a history of) distant metastases. The aim of this study...
INTRODUCTION
Patients with locally recurrent rectal cancer (LRRC) generally have poor prognosis, especially those who have (a history of) distant metastases. The aim of this study was to investigate the impact of distant metastases on oncological outcomes in LRRC patients undergoing curative treatment.
METHODS
Consecutive patients with surgically treated LRRC between 2005 and 2019 in two tertiary referral hospitals were retrospectively analysed. Oncological survival of patients without distant metastases were compared with outcomes of patients with synchronous distant metastases with the primary tumour, patients with distant metastases in the primary-recurrence interval, and patients with synchronous LRRC distant metastases.
RESULTS
A total of 535 LRRC patients were analysed, of whom 398 (74%) had no (history of) metastases, 22 (4%) had synchronous metastases with the primary tumour, 44 (8%) had metachronous metastases, and 71 (13%) had synchronous LRRC metastases. Patients with synchronous LRRC metastases had worse survival compared to patients without metastases (adjusted hazard ratio: 1.56 [1.15-2.12]), whilst survival of patients with synchronous primary metastases and metachronous metastases of the primary tumour was similar as those patients who had no metastases. In LRRC patients who had metastases in primary-recurrence interval, patients with early metachronous metastases had better disease-free survival as patients with late metachronous metastases (3-year disease-free survival: 48% vs 22%, p = 0.039).
CONCLUSION
LRRC patients with synchronous distant metastases undergoing curative surgery have relatively poor prognosis. However, LRRC patients with a history of distant metastases diagnosed nearby the primary tumour have comparable (oncological) survival as LRRC patients without distant metastases.
Topics: Humans; Retrospective Studies; Neoplasm Recurrence, Local; Rectal Neoplasms; Proportional Hazards Models; Disease-Free Survival
PubMed: 37002176
DOI: 10.1016/j.ejso.2023.03.005 -
The Journal of Thoracic and... Oct 2021The purpose of this study was to recognize clinically meaningful differences in lung transplant outcomes based on local or distant lung procurement. This could identify...
OBJECTIVE
The purpose of this study was to recognize clinically meaningful differences in lung transplant outcomes based on local or distant lung procurement. This could identify if the lung allocation policy change would influence patient outcomes.
METHODS
This single-center retrospective cohort study analyzed adult patients who underwent lung transplant from 2006 to 2017. Donor and recipient data were abstracted from a collaborative, prospective registry shared by our local organ procurement organization, and tertiary medical center. Short-term outcomes, 1-year survival, and hospitalization costs were compared between local and distant lung transplants defined by donor service area.
RESULTS
Of the 722 lung transplants performed, 392 (54%) had local donors and 330 (46%) had distant donors. Donors were similar in age and cause of death. Recipients were significantly different in diagnosis and local recipients had lower median lung allocation scores (local, 37.3 and distant, 44.9; P < .01). Distant lung transplants had longer total ischemic times (local, 231 ± 52 minutes and distant, 313 ± 48 minutes; P < .01). The rate of major complications, length of hospital stay, and 1-year survival were similar between groups. Distant lung transplants were associated with higher median overall cost (local, $183,542 and distant, $229,871; P < .01). Local lung transplants were more likely to be performed during daytime (local, 333 out of 392 [85%] and distant, 291 out of 330 [61%]; P < .01).
CONCLUSIONS
Local lung transplants are associated with shorter ischemic times, lower cost, and greater likelihood of daytime surgery. Short- and intermediate-term outcomes are similar for lung transplants from local and distant donors. The new lung allocation policy, with higher proportion of distant lung transplants, is likely to incur greater costs but provide similar outcomes.
Topics: Adult; Cold Ischemia; Female; Graft Survival; Humans; Lung; Lung Transplantation; Male; Outcome Assessment, Health Care; Policy Making; Postoperative Complications; Registries; Resource Allocation; Retrospective Studies; Tertiary Care Centers; Tissue Donors; Tissue and Organ Procurement; Topography, Medical; Transplants; United States
PubMed: 32977961
DOI: 10.1016/j.jtcvs.2020.07.115 -
Journal of Cancer 2022To evaluate the recurrent patterns and effect of clinicopathological factors on survival after recurrence (R-OS) in early stage endometrial cancer (EC). Patients with...
To evaluate the recurrent patterns and effect of clinicopathological factors on survival after recurrence (R-OS) in early stage endometrial cancer (EC). Patients with FIGO stage I-II EC, who underwent post-surgery radiotherapy (RT) at our institution between 2000 and 2017, were enrolled. First recurrent patterns, overall survival (OS), and R-OS were evaluated. Univariate and multivariate analyses (MVA) were used to evaluate factors associated with R-OS. 756 patients were analyzed including 510 patients who received vaginal brachytherapy (VBT) and 246 patients who received external beam radiotherapy (EBRT) ± VBT, of whom 66 patients experienced recurrence, including 21 locoregional relapses and 45 distant metastases. Outside RT field recurrence predominated intra-RT field recurrence (106 versus 10 lesions). The 5-year OS rates for patients with and without recurrence were 62.2% and 98.2%, respectively (p<0.001). Among patients who underwent previous VBT, the 5-year OS rates were 61.1%, 92.3%, and 99.1% for distant metastasis, locoregional relapse, and non-recurrence, respectively (p<0.001); among patients who received EBRT ± VBT, the 5-year OS rates were 51.4%, 50.0%, and 98.3%, respectively (p<0.001).On Cox MVA of R-OS for locoregional recurrence patients, para-aortic lymph node metastasis was associated with poorer R-OS (hazard ratio [HR] 10.047, p=0.039), and salvage RT was superior to other therapies (HR 0.06, p=0.026). On Cox MVA of R-OS for distant metastasis, patients with brain metastasis (p=0.041) had the worst R-OS and patients benefited most from combined therapy (HR 0.02, p=0.001). Recurrent patterns were dominated by outside RT field and distant metastasis for early-stage ECs after adjuvant RT. The modality of prior RT had an impact on the choice of salvage therapy. RT could still be an effective salvage treatment for patients who develop locoregional recurrence. Patients with distant metastasis may benefit from combined therapies.
PubMed: 34976183
DOI: 10.7150/jca.65246 -
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 -
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 -
BMC Medical Informatics and Decision... Apr 2023This research was designed to compare the ability of different machine learning (ML) models and nomogram to predict distant metastasis in male breast cancer (MBC)...
OBJECTIVES
This research was designed to compare the ability of different machine learning (ML) models and nomogram to predict distant metastasis in male breast cancer (MBC) patients and to interpret the optimal ML model by SHapley Additive exPlanations (SHAP) framework.
METHODS
Four powerful ML models were developed using data from male breast cancer (MBC) patients in the SEER database between 2010 and 2015 and MBC patients from our hospital between 2010 and 2020. The area under curve (AUC) and Brier score were used to assess the capacity of different models. The Delong test was applied to compare the performance of the models. Univariable and multivariable analysis were conducted using logistic regression.
RESULTS
Of 2351 patients were analyzed; 168 (7.1%) had distant metastasis (M1); 117 (5.0%) had bone metastasis, and 71 (3.0%) had lung metastasis. The median age at diagnosis is 68.0 years old. Most patients did not receive radiotherapy (1723, 73.3%) or chemotherapy (1447, 61.5%). The XGB model was the best ML model for predicting M1 in MBC patients. It showed the largest AUC value in the tenfold cross validation (AUC:0.884; SD:0.02), training (AUC:0.907; 95% CI: 0.899-0.917), testing (AUC:0.827; 95% CI: 0.802-0.857) and external validation (AUC:0.754; 95% CI: 0.739-0.771) sets. It also showed powerful ability in the prediction of bone metastasis (AUC: 0.880, 95% CI: 0.856-0.903 in the training set; AUC: 0.823, 95% CI:0.790-0.848 in the test set; AUC: 0.747, 95% CI: 0.727-0.764 in the external validation set) and lung metastasis (AUC: 0.906, 95% CI: 0.877-0.928 in training set; AUC: 0.859, 95% CI: 0.816-0.891 in the test set; AUC: 0.756, 95% CI: 0.732-0.777 in the external validation set). The AUC value of the XGB model was larger than that of nomogram in the training (0.907 vs 0.802) and external validation (0.754 vs 0.706) sets.
CONCLUSIONS
The XGB model is a better predictor of distant metastasis among MBC patients than other ML models and nomogram; furthermore, the XGB model is a powerful model for predicting bone and lung metastasis. Combining with SHAP values, it could help doctors intuitively understand the impact of each variable on outcome.
Topics: Humans; Male; Aged; Breast Neoplasms, Male; Area Under Curve; Databases, Factual; Lung Neoplasms; Machine Learning
PubMed: 37085843
DOI: 10.1186/s12911-023-02166-8