RESUMO
Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012-2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin's link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23-3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05-1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17-2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67-11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.
This pioneering study identified potential independent risk factors and the cycle-to-shock of oxaliplatin-associated shock which is a rare but life-threatening adverse event Why was the study done? Oxaliplatin-induced anaphylactic shock (referred to as shock) is a rare but life-threatening adverse event which is a harmful and undesirable experience associated with medical care in a patient. What did the researchers do? This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock and assess the cycle-to-shock during oxaliplatin treatment. All newly diagnosed stage III CRC patients were identified from the CRC Health Database (20122016). The study utilized a nested case-control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Conditional logistic regression was used to quantify the association between oxaliplatin and shock incidence. What did the researchers find? Among 6,932 oxaliplatin recipients, 331 suffered shock. 3,309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock. Independent risk factors were male sex and heart diseases. The risk of shock was 33% higher for males and 65% higher for people with heart diseases compared to females and those without heart diseases. The case-crossover analysis revealed a more than four-fold risk of shock of oxaliplatin. Twenty-two of 331 shock cases were exposed to oxaliplatin within two days before the shock onset. The median cycle-to-shock time is at the seventh cycle. What do the findings mean? Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and having heart diseases are two independent risk factors.
RESUMO
OBJECTIVE: To investigate the prognostic value of 18F-FDG PET-based intensity, volumetric features, and deep learning (DL) across different generations of PET scanners in patients with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma receiving tyrosine kinase inhibitor (TKI) treatment. METHODS: We retrospectively analyzed the pre-treatment 18F-FDG PET of 217 patients with advanced-stage lung adenocarcinoma and actionable EGFR mutations who received TKI as first-line treatment. Patients were separated into analog (n = 166) and digital (n = 51) PET cohorts. 18F-FDG PET-derived intensity, volumetric features, ResNet-50 DL of the primary tumor, and clinical variables were used to predict progression-free survival (PFS). Independent prognosticators were used to develop prediction model. Model was developed and validated in the analog and digital PET cohorts, respectively. RESULTS: In the analog PET cohort, female sex, stage IVB status, exon 19 deletion, SUVmax, metabolic tumor volume, and positive DL prediction independently predicted PFS. The model devised from these six prognosticators significantly predicted PFS in the analog (HR = 1.319, p < 0.001) and digital PET cohorts (HR = 1.284, p = 0.001). Our model provided incremental prognostic value to staging status (c-indices = 0.738 vs. 0.558 and 0.662 vs. 0.598 in the analog and digital PET cohorts, respectively). Our model also demonstrated a significant prognostic value for overall survival (HR = 1.198, p < 0.001, c-index = 0.708 and HR = 1.256, p = 0.021, c-index = 0.664 in the analog and digital PET cohorts, respectively). CONCLUSIONS: Combining 18F-FDG PET-based intensity, volumetric features, and DL with clinical variables may improve the survival stratification in patients with advanced EGFR-mutated lung adenocarcinoma receiving TKI treatment. Implementing the prediction model across different generations of PET scanners may be feasible and facilitate tailored therapeutic strategies for these patients.
Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Receptores ErbB , Fluordesoxiglucose F18 , Neoplasias Pulmonares , Mutação , Humanos , Receptores ErbB/genética , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/patologia , Idoso , Prognóstico , Estudos Retrospectivos , Terapia de Alvo Molecular , Tomografia por Emissão de Pósitrons , Adulto , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. METHODS: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. RESULTS: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC-1 and P-selectin when exposed to agonist stimulations. PAC-1 expression increased under high adenosine diphosphate (ADP) stimulation, while P-selectin expression increased under both high ADP and thrombin receptor-activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC-1 and P-selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet-derived microparticles showed a significant increase. CONCLUSION: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet-derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice.
Assuntos
Plaquetas , Neoplasias Hematológicas , Transfusão de Plaquetas , Humanos , Transfusão de Plaquetas/métodos , Neoplasias Hematológicas/terapia , Plaquetas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Testes de Função Plaquetária , Contagem de Plaquetas , Selectina-P/sangue , Micropartículas Derivadas de Células/metabolismoRESUMO
Lethal toxin (LT) is the critical virulence factor of Bacillus anthracis, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34-megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.
Assuntos
Antraz , Bacillus anthracis , Leucemia Eritroblástica Aguda , Trombocitopenia , Animais , Humanos , Camundongos , Antígenos de Bactérias/metabolismo , Bacillus anthracis/metabolismo , Fator 1 de Resposta a Butirato/metabolismo , Diferenciação Celular , Trombocitopenia/induzido quimicamente , Trombocitopenia/genéticaRESUMO
Hematopoietic stem cell (HSC) transplantation, using either bone marrow (BM) or peripheral blood stem cells (PBSC), is a well-established therapy for various hematologic and non-hematologic diseases. However, the long-term health outcomes after HSC donation remain a major concern for several potential donors. Thus, we aimed to conduct a matched cohort study of 5003 unrelated donors (1099 BM and 3904 PBSC) and randomly selected 50,030 matched controls based on age, sex, and resident area from the donor registry between 1998 and 2018. The medical insurance claims of all the participants were retrieved from the Taiwan National Health and Welfare Data Science Center after de-identification. Our findings revealed no differences in the incidence of cancer, death, and catastrophic diseases between HSC donors and matched healthy participants during long-term follow-up. Kaplan-Meier curves depicting the cumulative incidence of cancer and overall mortality throughout the follow-up period also demonstrated similar outcomes between donors and non-donors. In conclusion, our results indicate that HSC donation, whether through BM or PBSC, is safe and not associated with an increased risk of cancer, death, or catastrophic diseases. These findings provide valuable information for counseling potential HSC donors and for long-term management of HSC donor health.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias , Humanos , Neoplasias/terapia , Masculino , Feminino , Seguimentos , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Pessoa de Meia-Idade , Estudos de Coortes , Doença Catastrófica , Taiwan/epidemiologia , Doadores de TecidosRESUMO
BACKGROUND: In recent years, advancements in cancer treatment have enabled cancer cell inhibition, leading to improved patient outcomes. However, the side effects of chemotherapy, especially leukopenia, impact patients' ability to tolerate their treatments and affect their quality of life. Traditional Chinese medicine is thought to provide complementary cancer treatment to improve the quality of life and prolong survival time among patients with cancer. OBJECTIVE: This study aims to evaluate the effectiveness of Chinese herbal medicine (CHM) as a complementary treatment for neutropenia prevention and immunity modulation during chemotherapy in patients with breast cancer. METHODS: We will conduct a real-world pragmatic clinical trial to evaluate the effectiveness of CHM as a supplementary therapy to prevent neutropenia in patients with breast cancer undergoing chemotherapy. Patients will be classified into CHM or non-CHM groups based on whether they received CHM during chemotherapy. Using generalized estimating equations or repeated measures ANOVA, we will assess differences in white blood cell counts, absolute neutrophil counts, immune cells, and programmed cell death protein 1 (PD-1) expression levels between the 2 groups. RESULTS: This study was approved by the research ethics committee of Hualien Tzu Chi Hospital (IRB 110-168-A). The enrollment process began in September 2021 and will stop in December 2024. A total of 140 patients will be recruited. Data cleaning and analysis are expected to finish in the middle of 2025. CONCLUSIONS: Traditional Chinese medicine is the most commonly used complementary medicine, and it has been reported to significantly alleviate chemotherapy-related side effects. This study's findings may contribute to developing effective interventions targeting chemotherapy-related neutropenia among patients with breast cancer in clinical practice. TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry ITMCTR2023000054; https://tinyurl.com/yc353hes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55662.
RESUMO
Background: Primary pericardial mesothelioma (PPM) is an exceedingly rare malignant cancer and has a poor prognosis, which has been partly attributed to its frequently delayed diagnosis due to its nonspecific syndromes, its similar presentation to benign pericardial diseases, and its non-definitive etiology. In many PPM cases, the time from presentation to definite diagnosis may last for several months or even over one year. Unlike pleural mesothelioma, the relationship between PPM and asbestos exposure remains unsettled. To date, there is no consensus on the treatment of PPM. Case report: The patient is a 57-year-old male who had nonspecific syndromes and inconclusive image findings. The occupational long-term asbestos exposure history of this patient raised our concerns regarding potential malignancy when confronted with unexplained pericardial effusion accompanied by cardiac tamponade. The heightened suspicion prompted us to perform pericardiocentesis and biopsy on the third day after admission to our department. An early diagnosis of PPM was established by the pathological and immunohistochemical evaluation of the biopsy specimen two weeks after admission. Positron emission tomography-computed tomography revealed that the lesion was localized at the anterior part of the mediastinum without distant metastasis. This patient refused to receive cardiac surgery. He subsequently underwent six cycles of chemotherapy (cisplatin plus pemetrexed) in combination with bevacizumab (a humanized anti-VEGF antibody) as the first-line treatment, resulting in complete relief of symptoms and satisfactory outcomes with no complications. Four months after the first course, the patient initiated a second course of chemotherapy with a similar regimen, but he opted to discontinue the medical treatment after the initiation of the second course. The patient was transferred to the hospice care unit and unfortunately expired one year after the initial presentation. Conclusion: We present a case of an early multidisciplinary clinical approach to diagnose and manage PPM with consideration of occupational asbestos exposure history and clinical symptoms. Bevacizumab-based chemotherapy remains an option for the treatment of PPM.
RESUMO
OBJECTIVE: The performance of 18 F-FDG PET-based radiomics and deep learning in detecting pathological regional nodal metastasis (pN+) in resectable lung adenocarcinoma varies, and their use across different generations of PET machines has not been thoroughly investigated. We compared handcrafted radiomics and deep learning using different PET scanners to predict pN+ in resectable lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18 F-FDG PET from 148 lung adenocarcinoma patients who underwent curative surgery. Patients were separated into analog (nâ =â 131) and digital (nâ =â 17) PET cohorts. Handcrafted radiomics and a ResNet-50 deep-learning model of the primary tumor were used to predict pN+ status. Models were trained in the analog PET cohort, and the digital PET cohort was used for cross-scanner validation. RESULTS: In the analog PET cohort, entropy, a handcrafted radiomics, independently predicted pN+. However, the areas under the receiver-operating-characteristic curves (AUCs) and accuracy for entropy were only 0.676 and 62.6%, respectively. The ResNet-50 model demonstrated a better AUC and accuracy of 0.929 and 94.7%, respectively. In the digital PET validation cohort, the ResNet-50 model also demonstrated better AUC (0.871 versus 0.697) and accuracy (88.2% versus 64.7%) than entropy. The ResNet-50 model achieved comparable specificity to visual interpretation but with superior sensitivity (83.3% versus 66.7%) in the digital PET cohort. CONCLUSION: Applying deep learning across different generations of PET scanners may be feasible and better predict pN+ than handcrafted radiomics. Deep learning may complement visual interpretation and facilitate tailored therapeutic strategies for resectable lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão , Aprendizado Profundo , Neoplasias Pulmonares , Humanos , Fluordesoxiglucose F18 , Metástase Linfática , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgiaRESUMO
Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana-Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient's skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis.
RESUMO
BACKGROUND: The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS: Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS: Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION: Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.
Assuntos
Hepatite B , Leucemia Mielogênica Crônica BCR-ABL Positiva , Masculino , Humanos , Feminino , Vírus da Hepatite B , Incidência , Proteínas de Fusão bcr-abl/uso terapêutico , Taiwan/epidemiologia , Inibidores de Proteínas Quinases/efeitos adversos , Hepatite B/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologiaRESUMO
Incessant ovulation is believed to be a potential cause of epithelial ovarian cancer (EOC). Our previous investigations have shown that insulin-like growth factor (IGF2) and hepatocyte growth factor (HGF) in the ovulatory follicular fluid (FF) contributed to the malignant transformation initiated by p53 mutations. Here we examined the individual and synergistic impacts of IGF2 and HGF on enhancing the malignant properties of high-grade serous carcinoma (HGSC), the most aggressive type of EOC, and its precursor lesion, serous tubal intraepithelial carcinoma (STIC). In a mouse xenograft co-injection model, we observed that FF co-injection induced tumorigenesis of STIC-mimicking cells, FE25. Co-injection with IGF2 or HGF partially recapitulated the tumorigenic effects of FF, but co-injection with both resulted in a higher tumorigenic rate than FF. We analyzed the different transformation phenotypes influenced by these FF growth signals through receptor inhibition. The IGF signal was necessary for clonogenicity, while the HGF signal played a crucial role in the migration and invasion of STIC and HGSC cells. Both signals were necessary for the malignant phenotype of anchoring-independent growth but had little impact on cell proliferation. The downstream signals responsible for these HGF activities were identified as the tyrosine-protein kinase Met (cMET)/mitogen-activated protein kinase and cMET/AKT pathways. Together with the previous finding that the FF-IGF2 could mediate clonogenicity and stemness activities via the IGF-1R/AKT/mammalian target of rapamycin and IGF-1R/AKT/NANOG pathways, respectively, this study demonstrated the cooperation of the FF-sourced IGF and HGF growth signals in the malignant transformation and progression of HGSC through both common and distinct signaling pathways. These findings help develop targeted prevention of HGSC.
Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Feminino , Humanos , Camundongos , Animais , Tubas Uterinas/metabolismo , Tubas Uterinas/patologia , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Líquido Folicular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Ovarianas/patologia , Proteína Supressora de Tumor p53/genética , Células Epiteliais/metabolismo , Carcinogênese/patologia , Carcinoma Epitelial do Ovário/patologia , Cistadenocarcinoma Seroso/metabolismo , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/metabolismo , Neoplasias das Tubas Uterinas/patologia , Transformação Celular Neoplásica/patologia , Mamíferos/metabolismoRESUMO
BACKGROUND/AIM: Infection is a common cause of morbidity and mortality in patients treated for diffuse large B-cell lymphoma (DLBCL). However, there is limited information on the impact and risk factors for infection among patients receiving rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone (R-CHOP). PATIENTS AND METHODS: A retrospective study evaluating patients with DLBCL receiving R-CHOP and R-COP between 2004 and 2021 was conducted at a medical center. Hospital patients' records for the five-item modified frailty index (mFI-5), sarcopenia, blood-based inflammatory markers, and clinical outcomes were statistically analyzed. RESULTS: Patients with frailty, sarcopenia, and high neutrophil-to-lymphocyte ratio (NLR) were associated with a higher risk of infections. The revised International Prognostic Index poor-risk group, high NLR, infections, and treatment modality were risk factors for shorter progression-free and overall survival. CONCLUSION: Pre-treatment high NLR was a predictor of infection and survival outcome in DLBCL patients.
Assuntos
Fragilidade , Linfoma Difuso de Grandes Células B , Sarcopenia , Humanos , Neutrófilos , Estudos Retrospectivos , Linfócitos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina , Rituximab/uso terapêutico , Vincristina/efeitos adversosRESUMO
Radiogenomic heterogeneity features in 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) have become popular in non-small cell lung cancer (NSCLC) research. However, the reliabilities of genomic heterogeneity features and of PET-based glycolytic features in different image matrix sizes have yet to be thoroughly tested. We conducted a prospective study with 46 NSCLC patients to assess the intra-class correlation coefficient (ICC) of different genomic heterogeneity features. We also tested the ICC of PET-based heterogeneity features from different image matrix sizes. The association of radiogenomic features with clinical data was also examined. The entropy-based genomic heterogeneity feature (ICC = 0.736) is more reliable than the median-based feature (ICC = -0.416). The PET-based glycolytic entropy was insensitive to image matrix size change (ICC = 0.958) and remained reliable in tumors with a metabolic volume of <10 mL (ICC = 0.894). The glycolytic entropy is also significantly associated with advanced cancer stages (p = 0.011). We conclude that the entropy-based radiogenomic features are reliable and may serve as ideal biomarkers for research and further clinical use for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/metabolismo , Estudos Prospectivos , Entropia , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons/métodos , Biomarcadores , Genômica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate whether combining primary tumor and metastatic nodal glycolytic heterogeneity on 18 F-fluorodeoxyglucose PET ( 18 F-FDG PET) improves prognostic prediction in nonsmall cell lung cancer (NSCLC) with locoregional disease. METHODS: We retrospectively analyzed 18 F-FDG PET-derived features from 94 patients who had undergone curative treatments for regional nodal metastatic NSCLC. Overall survival (OS) and progression-free survival (PFS) were analyzed using univariate and multivariate Cox regression models. We used the independent prognosticators to construct models to predict survival. RESULTS: Combined entropy (entropy derived from the combination of the primary tumor and metastatic nodes) and age independently predicted OS (both P = 0.008) and PFS ( P = 0.007 and 0.050, respectively). At the same time, the Eastern Cooperative Oncology Group status was another independent risk factor for unfavorable OS ( P = 0.026). Our combined entropy-based models outperformed the traditional staging system (c-index = 0.725 vs. 0.540, P < 0.001 for OS; c-index = 0.638 vs. 0.511, P = 0.003 for PFS) and still showed prognostic value in subgroups according to sex, histopathology, and different initial curative treatment strategies. CONCLUSION: Combined primary tumor-nodal glycolytic heterogeneity independently predicted survival outcomes. In combination with clinical risk factors, our models provide better survival predictions and may enable tailored treatment strategies for NSCLC with locoregional disease.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Fluordesoxiglucose F18 , Estudos Retrospectivos , Entropia , Neoplasias Pulmonares/patologia , Prognóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Myelodysplastic syndromes (MDS) represent a diagnostic challenge. This prospective multicenter study was conducted to evaluate pre-defined flow cytometric markers in the diagnostic work-up of MDS and chronic myelomonocytic leukemia (CMML). METHODS: Thousand six hundred and eighty-two patients with suspected MDS/CMML were analyzed by both cytomorphology according to WHO 2016 criteria and flow cytometry according to ELN recommendations. Flow cytometric readout was categorized 'non-MDS' (i.e. no signs of MDS/CMML and limited signs of MDS/CMML) and 'in agreement with MDS' (i.e., in agreement with MDS/CMML). RESULTS: Flow cytometric readout categorized 60% of patients in agreement with MDS, 28% showed limited signs of MDS and 12% had no signs of MDS. In 81% of cases flow cytometric readouts and cytomorphologic diagnosis correlated. For high-risk MDS, the level of concordance was 92%. A total of 17 immunophenotypic aberrancies were found independently related to MDS/CMML in ≥1 of the subgroups of low-risk MDS, high-risk MDS, CMML. A cut-off of ≥3 of these aberrancies resulted in 80% agreement with cytomorphology (20% cases concordantly negative, 60% positive). Moreover, >3% myeloid progenitor cells were significantly associated with MDS (286/293 such cases, 98%). CONCLUSION: Data from this prospective multicenter study led to recognition of 17 immunophenotypic markers allowing to identify cases 'in agreement with MDS'. Moreover, data emphasizes the clinical utility of immunophenotyping in MDS diagnostics, given the high concordance between cytomorphology and the flow cytometric readout. Results from the current study challenge the application of the cytomorphologically defined cut-off of 5% blasts for flow cytometry and rather suggest a 3% cut-off for the latter.
Assuntos
Leucemia Mielomonocítica Crônica , Síndromes Mielodisplásicas , Humanos , Citometria de Fluxo/métodos , Síndromes Mielodisplásicas/diagnóstico , Leucemia Mielomonocítica Crônica/diagnóstico , Leucócitos , ImunofenotipagemRESUMO
OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Fluordesoxiglucose F18 , Glucose , Estudos Retrospectivos , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos RadiofarmacêuticosRESUMO
OBJECTIVES: Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder with thrombocytopenia. Flow cytometric immunophenotyping of blood cells has been instrumental in diagnosis as co-criteria, but the data regarding platelets remains lacking. This study aims to determine if there is a difference in surface antigen levels on platelets by comparing surface antigen levels in MDS patients and healthy control subjects. Concurrently, as flow cytometric gating can reveal the diameter of cells, this study will investigate differences in giant platelet percentage by comparing these percentages in high- and low-risk MDS patients. STUDY DESIGN: Twenty newly diagnosed MDS patients were enrolled in this study. Platelet surface antigen levels were determined by measuring the binding capacity of antibodies with flow cytometry. RESULTS: Platelets of MDS patients were shown to have a lower level of CD61 and higher levels of CD31 and CD36 than healthy controls. Judged by forward scatter (FSC), MDS patients' platelets appeared to be larger than those of healthy control subjects, whereas the MFI adjusted by diameter (MFI/FSC ratio) of CD31, CD41a, CD42a, CD42b and CD61 on platelets were lower in MDS patients than in healthy control subjects. There was a significant quantity of giant platelets found in MDS patients, and the high-risk MDS patients tended to have a higher percentage of giant platelets than low-risk patients. Conclusions: All the results indicate that MDS patients exhibit a lower antigen presentation (MFI) adjusted by diameter on platelets than healthy controls and the giant platelets detected by flow cytometry might correlate with the condition of MDS.
Assuntos
Antígenos de Plaquetas Humanas , Síndromes Mielodisplásicas , Humanos , Imunofenotipagem , Plaquetas/metabolismo , Projetos Piloto , Síndromes Mielodisplásicas/diagnóstico , Antígenos de Superfície/metabolismoRESUMO
The incidence and mortality of epithelial ovarian cancer (EOC) are increasing in Taiwan and worldwide. The prognosis of this disease has improved little in the last few decades due to insufficient knowledge of the etiology. Previous studies on the role of ovulation in the development of EOC have unveiled IGF2, HGF, and other carcinogens in ovulatory follicular fluid (FF) that exert transformation activities on the exposed fallopian tube fimbria epithelium. However, an orthotopic proof in an animal model is lacking. By using the murine ID8 EOC cells and the syngenic transplantation model, this study explored the effect of FF on the oncogenesis of mouse ovarian cancer. We found FF promoted clonogenicity and anchorage-independent growth of ID8 cells, largely through the IGF-1R and cMET signaling. In contrast, FF modestly promoted cell proliferation independent of the two signals and did not affect cell migration and invasion. Transplantation of ID8 cells into the ovarian bursa of C57BL6/J mice orthotopically grew ovarian tumors and metastasized to the peritoneum with ascites formation. The tumorigenic rate and severity of the disease were positively correlated with the level of IGF-1R and cMET receptors on the cell surface. Our data demonstrated that ovulation, through the signaling of IGF/IGF-1R and HGF/cMET, promotes oncogenic phenotypes in a murine EOC model. The results provide further proof of the carcinogenic effect of ovulation in the development of EOC.
Assuntos
Neoplasias Ovarianas , Animais , Carcinogênese , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos , Neoplasias Ovarianas/patologia , Ovulação , Transdução de SinaisRESUMO
OBJECTIVE: The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). CONCLUSIONS: Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.
Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
The fallopian tube fimbrial epithelium, which is exposed to the follicular fluid (FF) contents of ovulation, is regarded as the main origin of ovarian high-grade serous carcinoma. Previously, we found that growth factors in FF, such as IGF2, are responsible for the malignant transformation of fallopian tube epithelium. However, ovulation is a monthly transient event, whereas carcinogenesis requires continuous, long-term exposure. Here, we found the transformation activity of FF sustained for more than 30 days after drainage into the peritoneal fluid (PF). Hepatocyte growth factor (HGF), activated through the ovulation injury-tissue factor-thrombin-HGF activator (HGFA)-HGF cleavage cascade confers a sustained transformation activity to fallopian tube epithelium, high-grade serous carcinoma. Physiologically, the high reserve of the coagulation-HGF cascade sources a sustained level of HGF in PF, then to the blood circulation. This HGF axis promotes the growth of the corpus luteum and repair of tissue injury after ovulation.