RESUMO
PURPOSE: The survival rate of patients with medullary thyroid carcinoma (MTC) who fail to achieve a biochemical cure after surgery is reduced. This study aimed to investigate the prognostic factors affecting the survival of MTC patients who do not achieve a biochemical cure after surgery. METHODS: Cox univariate and multivariate proportional hazard models were used to determine the influence of different variables on overall survival (OS). Pearson's chi-square test was used for categorical variables, and paired t-test was used for continuous variables. RESULTS: In our study of 277 MTC patients treated between 2012 and 2022, there were 96 with raised postoperative 1-month calcitonin (Ct) levels (0-9.52 pg/ml). The overall survival (OS) rates of patients with high postoperative 1-month Ct values at 1, 3, and 5 years were 97.9%, 94.6%, and 86.8%, respectively. The univariate analysis revealed that patients with a postoperative 1-month Ct > 441.9 pg/ml had a greater risk of mortality than patients with postoperative 1-month Ct values ranging from 9.52 to 73.4 pg/ml (p = 0.043). Subsequent analyses revealed that receiving targeted therapy did not improve the OS of patients with distant metastasis among those with high postoperative 1-month Ct values (p = 0.527). CONCLUSION: This study confirmed that MTC patients who did not achieve biochemical remission after surgery had an increased risk of death when the Ct level was > 441.9 pg/ml 1 month after surgery. Additionally, for MTC patients who have not achieved biochemical remission and have experienced disease progression or distant metastasis after surgery, the use of targeted therapy does not prolong survival.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/terapia , Masculino , Feminino , Calcitonina/sangue , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/terapia , Taxa de Sobrevida , Prognóstico , Seguimentos , Adulto , Estudos Retrospectivos , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Terapia de Alvo Molecular/métodos , Adulto Jovem , Período Pós-Operatório , AdolescenteRESUMO
Pulmonary high-grade neuroendocrine carcinomas (HGNECs) have poor prognoses and require multimodal treatment, and interstitial lung disease (ILD) restricts sufficient treatment of patients with lung cancer. We aimed to clarify ILD's prognostic impact on pulmonary HGNEC, which has previously gone unreported. We retrospectively analyzed 53 patients with HGNEC who underwent resections at our department between 2006 and 2021 and evaluated the clinicopathological prognostic features, including ILD. The patients' mean age was 70 years; 46 (87%) were male, and all were smokers. Large-cell neuroendocrine and small-cell lung carcinomas were diagnosed in 36 (68%) and 17 (32%) patients, respectively. The pathological stages were stage I, II, and III in 31 (58%), 11 (21%), and 11 (21%) patients, respectively. Nine patients (17%) had ILD, which was a significant overall survival prognostic factor in a multivariate Cox proportional hazards regression analysis (p = 0.048), along with lymph node metastasis (p = 0.004) and non-administration of platinum-based adjuvant chemotherapy (p = 0.003). The 5 year survival rate of the ILD patients was 0%, significantly worse than that of patients without ILD (58.7%; p = 0.003). Patients with HGNEC and ILD had a poor prognosis owing to adjuvant therapy's limited availability for recurrence and the development of acute exacerbations associated with ILD.
Assuntos
Carcinoma Neuroendócrino , Doenças Pulmonares Intersticiais , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Doenças Pulmonares Intersticiais/patologia , Doenças Pulmonares Intersticiais/mortalidade , Idoso , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/complicações , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Gradação de Tumores , Estadiamento de Neoplasias , Taxa de SobrevidaRESUMO
Nearly half of lung large cell neuroendocrine carcinoma (LCNEC) patients are diagnosed at an advanced stage and face a high early death risk. Our objective was to develop models for assessing early death risk in stage IV LCNEC patients. We used surveillance, epidemiology, and end results (SEER) databases to gather data on patients with stage IV LCNEC to construct models and conduct internal validation. Additionally, we collected a dataset from the Second Affiliated Hospital of Nanchang University for external validation. We used the Pearson correlation coefficient and variance inflation factor to identify collinearity among variables. Logistic regression analysis and least absolute shrinkage and selection operator analysis were employed to identify important independent prognostic factors. Prediction nomograms and network-based probability calculators were developed. The accuracy of the nomograms was evaluated using receiver operating characteristic curves. The goodness of fit of the nomograms was evaluated using the Hosmer-Lemeshow test and calibration curves. The clinical value of the models was assessed through decision curve analysis. We enrolled 816 patients from the surveillance, epidemiology, and end results database and randomly assigned them to a training group and a validation group at a 7:3 ratio. In the training group, we identified 9 factors closely associated with early death and included them in the prediction nomograms. The overall early death model achieved an area under the curve of 0.850 for the training group and 0.780 for the validation group. Regarding the cancer-specific early death model, the area under the curve was 0.853 for the training group and 0.769 for the validation group. The calibration curve and Hosmer-Lemeshow test both demonstrated a high level of consistency for the constructed nomograms. Additionally, decision curve analysis further confirmed the substantial clinical utility of the nomograms. We developed a reliable nomogram to predict the early mortality risk in stage IV LCNEC patients that can be a helpful tool for health care professionals to identify high-risk patients and create personalized treatment plans.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Pulmonares , Estadiamento de Neoplasias , Nomogramas , Programa de SEER , Humanos , Masculino , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/epidemiologia , Feminino , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Incidência , Curva ROC , Prognóstico , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/epidemiologia , Medição de Risco/métodosRESUMO
OBJECTIVE: Large cell neuroendocrine carcinoma of the lung is a rare type of lung cancer. There is a limited number of studies on clinical and histopathological characteristics that are effective in survival. The aim of this study was to investigate the relationship between histopathological and clinical characteristics, mainly Ki-67 proliferation index, and survival in patients diagnosed with large cell neuroendocrine carcinoma of the lung. METHODS: The data of 38 patients followed up with the diagnosis of large cell neuroendocrine carcinoma of the lung were evaluated. The mean Ki-67 value was determined to be 65.8% (±20.8). The patients' clinical characteristics and survival times were compared according to the cut-off value determined for Ki-67 index. RESULTS: When median overall survival times were compared, it was seen that overall survival was numerically lower in patients aged 65 years and over, in tumors located on the right side, in cases who were in the metastatic stage at diagnosis, whose Ki-67 index was 65% and above, who did not receive chemotherapy, who did not undergo curative surgery, and in patients with chronic diseases (p>0.05). In the Kaplan-Meier analysis, the median overall survival was determined to be 22.2 months (95%CI 21.7-22.7) in the patients with Ki-67<65%, while it was found to be 20.3 months (95%CI 4.5-36.2) in the patients with Ki-67≥65% (p=0.351). CONCLUSION: Our study identified subgroups with decreased survival in large cell neuroendocrine carcinoma of lung patients. Studies including a larger number of patients are needed to identify the prognostic importance of these clinical and histopathological characteristics.
Assuntos
Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Antígeno Ki-67 , Neoplasias Pulmonares , Humanos , Antígeno Ki-67/análise , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Proliferação de Células , Adulto , Estimativa de Kaplan-Meier , Prognóstico , Idoso de 80 Anos ou mais , Estadiamento de NeoplasiasRESUMO
Background: The necessity and therapeutic value of lymph node dissection (LND) in early stage T1 MTC patients remain controversial. Methods: Patients with T1MTC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Poisson regression analysis was utilized to investigate promotive factors for lymph node metastasis in T1MTC patients. Fisher's exact test was employed to calculate baseline differences between non-LND and LND groups. Propensity score match (PSM) was used to control baseline bias. Survival outcomes were calculated by Kaplan-Meier method and log-rank test. Multivariable Cox regression assessed the prognostic impact of LND across subgroups. Results: Of 3298 MTC cases, 50.4% were T1MTC. The lymph node metastasis rate increased along with the T stage (from 22.2% to 90.5%). Among 1231 T1MTC patients included after exclusion criteria, 72.0% underwent LND and 22.0% had lymph node metastasis. Patients aged younger than 44 years (RR=1.700, p<0.001), male (RR=1.832, p<0.001), and with tumor larger than 10mm (RR=2.361, p<0.001) were more likely to have lymph node metastasis, while elderly patients (p<0.001) and those with microcarcinoma (p<0.001) were more likely to undergo non-LND procedures. LND provided no OS or DSS benefit over non-LND before and after propensity score match (matched 10-year OS/DSS: LND 83.8/96.2% vs non-LND 81.9/99.3%, p>0.05). Subgroup analyses revealed no prognostic gain with LND in any subgroup (p>0.05). Conclusion: Nearly half of MTC patients were diagnosed at T1 stage and had low lymph node risk. Different from ATA guidelines, avoiding routine LND conferred similar prognosis to standard procedures while potentially improving quality of life. Large-scale prospective multi-center studies should be conducted to further validate these findings.
Assuntos
Excisão de Linfonodo , Metástase Linfática , Programa de SEER , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Masculino , Feminino , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Pessoa de Meia-Idade , Estudos de Coortes , Prognóstico , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Estadiamento de Neoplasias , Idoso , Adulto JovemRESUMO
BACKGROUND: The post-surgical prognosis for Pulmonary Large Cell Neuroendocrine Carcinoma (PLCNEC) patients remains largely unexplored. Developing a precise prognostic model is vital to assist clinicians in patient counseling and creating effective treatment strategies. RESEARCH DESIGN AND METHODS: This retrospective study utilized the Surveillance, Epidemiology, and End Results database from 2000 to 2018 to identify key prognostic features for Overall Survival (OS) in PLCNEC using Boruta analysis. Predictive models employing XGBoost, Random Forest, Decision Trees, Elastic Net, and Support Vector Machine were constructed and evaluated based on Area Under the Receiver Operating Characteristic Curve (AUC), calibration plots, Brier scores, and Decision Curve Analysis (DCA). RESULTS: Analysis of 604 patients revealed eight significant predictors of OS. The Random Forest model outperformed others, with AUC values of 0.765 and 0.756 for 3 and 5-year survival predictions in the training set, and 0.739 and 0.706 in the validation set, respectively. Its superior validation cohort performance was confirmed by its AUC, calibration, and DCA metrics. CONCLUSIONS: This study introduces a novel machine learning-based prognostic model with a supportive web-based platform, offering valuable tools for healthcare professionals. These advancements facilitate more personalized clinical decision-making for PLCNEC patients following primary tumor resection.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Pulmonares , Aprendizado de Máquina , Programa de SEER , Humanos , Masculino , Feminino , Estudos Retrospectivos , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/mortalidade , Prognóstico , Idoso , Taxa de Sobrevida , Carcinoma de Células Grandes/cirurgia , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/mortalidade , Adulto , Estudos de CoortesRESUMO
PURPOSE: Metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive cancer with generally poor outcomes. Effective methods for predicting survival in patients with metastatic LCNEC are needed. This study aimed to identify independent survival predictors and develop nomograms for predicting survival in patients with metastatic LCNEC. PATIENTS AND METHODS: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, identifying patients with metastatic LCNEC diagnosed between 2010 and 2017. To find independent predictors of cancer-specific survival (CSS), we performed Cox regression analysis. A nomogram was developed to predict the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC. The concordance index (C-index), area under the receiver operating characteristic (ROC) curves (AUC), and calibration curves were adopted with the aim of assessing whether the model can be discriminative and reliable. Decision curve analyses (DCAs) were used to assess the model's utility and benefits from a clinical perspective. RESULTS: This study enrolled a total of 616 patients, of whom 432 were allocated to the training cohort and 184 to the validation cohort. Age, T staging, N staging, metastatic sites, radiotherapy, and chemotherapy were identified as independent prognostic factors for patients with metastatic LCNEC based on multivariable Cox regression analysis results. The nomogram showed strong performance with C-index values of 0.733 and 0.728 for the training and validation cohorts, respectively. ROC curves indicated good predictive performance of the model, with AUC values of 0.796, 0.735, and 0.736 for predicting the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC in the training cohort, and 0.795, 0.801, and 0.780 in the validation cohort, respectively. Calibration curves and DCAs confirmed the nomogram's reliability and clinical utility. CONCLUSION: The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Pulmonares , Nomogramas , Programa de SEER , Humanos , Masculino , Feminino , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Pessoa de Meia-Idade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Estudos Retrospectivos , Prognóstico , Idoso , Carcinoma de Células Grandes/mortalidade , Carcinoma de Células Grandes/patologia , Carcinoma de Células Grandes/secundário , Carcinoma de Células Grandes/terapia , Curva ROC , Estadiamento de Neoplasias , Adulto , Taxa de SobrevidaRESUMO
Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.
Assuntos
Carcinoma Neuroendócrino , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Idoso , Adulto , Estudos Retrospectivos , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Taxa de SobrevidaRESUMO
PURPOSE: Neuroendocrine carcinoma of the cervix (NECC) is rare but results in poor prognosis. The causes of death (CODs) in NECC patients are rarely reported. Our study aimed to explore the distributions of death causes of NECC patients compared with squamous cell carcinoma (SCC) and adenocarcinoma (ADC) and to develop a validated survival prediction model. METHODS: Patients diagnosed with NECC, SCC, or ADC were identified from the Surveillance, Epidemiology, and End Results Program database from 1975 to 2019. We analyzed the standardized mortality ratio (SMR) to determine each cause of death for each survival time category. The Kaplan-Meier method was used for survival analysis. Univariate and multivariate Cox regression analyses were used to establish a nomogram model. RESULTS: A total of 358 NECC patients were included in this study, and 270 (75.4%) died during the follow-up period. Patients with NECC had 5.55 times (95% CI, 4.53-6.79, p < 0.0001) higher risk of death compared with patients with SCC and 10.38 times (95% CI, 8.28-13.01, p < 0.0001) higher compared with ADC. Cervical cancer is the main cause of death in NECC. As the diagnosis time increased, the risk of death from all causes and cervix cancer gradually decreased. While after at least 10 years of follow-up time, the highest and most dramatical SMR values were observed for metastasis (SMR, 138.81; 95% CI, 37.82-355.40; p < 0.05) and other cancers as the reason for death has an over 7-fold higher SMR (SMR: 7.07; 95% CI: 2.60-15.40, p < 0.05) more than 5 years after the cancer diagnosis. Race, FIGO stage, and surgery were independent risk factors for the overall survival (OS) of NECC patients. For the predictive nomogram, the C-index was 0.711 (95% CI: 0.697-0.725) and was corrected to 0.709 (95% CI: 0.680, 0.737) by bootstrap 1000 resampling validation. CONCLUSION: Compared with SCC and ADC, NECC patients have an elevated risk of mortality due to cervical cancer and metastasis. We successfully constructed a prognostic nomogram for patients with NECC. Based on refractoriness and high mortality of NECC, targeted treatment strategies and follow-up plans should be further developed according to the risk of death and distribution characteristics of CODs.
Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Escamosas , Causas de Morte , Nomogramas , Programa de SEER , Neoplasias do Colo do Útero , Humanos , Feminino , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Adulto , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Estimativa de Kaplan-MeierRESUMO
Tumor deposits (TDs) are defined as discontinuous neoplastic masses within the lymphatic drainage pathway of the primary tumor. The poor prognostic implication of these masses have been demonstrated in various cancers. The aim of this study is to investigate the incidence of TDs in our thyroid carcinoma cases, which has not been studied so far to the best of our knowledge, and to determine the prognostic value of their existence. In this retrospective cohort study, 194 thyroid carcinoma cases with cervical lymph node sampling and/or dissection were reevaluated for TDs. The case series consisted of 176 thyroid papillary carcinoma (TPC) and 18 thyroid medullary carcinoma (TMC) patients. TDs were detected in 54 (27.8%) patients. TMC cases (55.6%) had significantly more TDs compared to TPCs (25.0%; Pâ =â .006). TDs were more common in women (Pâ =â .045), and in multifocal tumors (Pâ =â .017). In addition, cases with TDs had larger tumor size (Pâ =â .002), more lymphatic invasion (Pâ =â .009), extrathyroidal extension (Pâ <â .001), and distant metastasis (Pâ <â .001). The mean follow-up period of the patients was 120.1 months (range, 4-341 months). Locoregional recurrence detected in 17 patients (8.8%) was more common in TMC (33.3%) than TPC cases (6.3%; Pâ =â .002). Distant metastasis was identified in 27 patients (13.9%). Ten-year recurrence free survival (RFS) and overall survival (OS) for all patients were 89.0% and 92.4%, respectively. Mean estimated OS time for TD negative and TD positive cases were: 281.9 (±17.2), 325.6 (±6.2) and 217.6 (±27.4) months, respectively (Pâ =â .002). Sex (Pâ =â .001), tumor type (Pâ =â .002), pT classification of the tumor (Pâ <â .001), perineural invasion (Pâ =â .002) and TDs (Pâ =â .002) were significantly associated with OS. In TPC cases individually, extrathyroidal extension (Pâ =â .001) and TDs (Pâ =â .002) were significantly correlated with distant metastasis. In multivariate analysis, only tumor size was detected as an independent prognostic marker in TPC cases (Pâ =â .005). Our results demonstrate the existence of TDs in thyroid carcinoma cases, and indicate a more aggressive behavior pattern of TDs in these tumors.
Assuntos
Metástase Linfática , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Metástase Linfática/patologia , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/epidemiologia , Prognóstico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Carcinoma Papilar/patologia , Adulto JovemRESUMO
BACKGROUND: Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients. METHODS: This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers. RESULTS: The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4-60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7-46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9-51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS. CONCLUSION: The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum. GOV IDENTIFIER: NCT03387592.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Carcinoma Neuroendócrino , Fluoruracila , Leucovorina , Humanos , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Pessoa de Meia-Idade , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Fluoruracila/uso terapêutico , Fluoruracila/efeitos adversos , Idoso , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Adulto , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Camptotecina/efeitos adversos , Etoposídeo/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/administração & dosagem , Temozolomida/uso terapêutico , Temozolomida/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
Few studies have investigated the impact of primary tumor resection (PTR) on patients with distant metastasis medullary thyroid carcinoma (DMMTC). This population-based study aims to assess the application of PTR in DMMTC patients, ascertain its benefits, and identify optimal surgical indications. DMMTC Patients diagnosed between 2010 and 2020 were included through the Surveillance, Epidemiology, and End Results (SEER) program. Logistic regression analysis identified driving factors of surgical decision-making. Propensity score matching (PSM), Kaplan-Meier method, and Cox regression were utilized to compare overall survival (OS) and disease-specific survival (DSS) between surgical and non-surgical groups. Subgroup analyses were performed to determine optimal surgical indications. Of 238 DMMTC patients included, 122 (51.3%) patients underwent PTR. Extrathyroidal extension and N1 stage emerged as independent factors promoting the surgical decision. PSM-adjusted survival analyses revealed significant advantages in both OS and DSS for the surgical group. Moreover, subgroup analyses indicated that except for patients aged ≥ 65 years, tumors ≤ 20 mm, or with multiple metastasized sites (> 1), the others significantly benefit from PTR. PTR significantly improves prognosis in selected DMMTC patients. The decision to undergo PTR in other patients should be based on a comprehensive assessment of the disease, surgeon's experience, and family discussions for potential survival benefits.
Assuntos
Carcinoma Neuroendócrino , Pontuação de Propensão , Programa de SEER , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Idoso , Adulto , Prognóstico , Metástase Neoplásica , Estudos de Coortes , Estimativa de Kaplan-Meier , Tireoidectomia , Estudos RetrospectivosRESUMO
Background: Medullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages. Methods: 3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied. Results: A linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45-50, 50-55, and 55-60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly "5%" increase in MTC-specific death risks and an approximately "3 times" increase in non-MTC-specific death risks. Conclusions: The survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.
Assuntos
Carcinoma Neuroendócrino , Programa de SEER , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Pessoa de Meia-Idade , Masculino , Feminino , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Estudos Retrospectivos , Fatores Etários , Taxa de Sobrevida , Idoso , Prognóstico , Adulto , Estudos de Coortes , SeguimentosRESUMO
BACKGROUND: High-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years. METHODS: A retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre. RESULTS: During the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44-86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1-96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %. CONCLUSION: This case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.
Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Masculino , Idoso , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Feminino , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/mortalidade , Gradação de Tumores , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seguimentos , Prognóstico , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/mortalidade , Terapia CombinadaRESUMO
Neuroendocrine carcinoma (NEC) is a rare yet potentially perilous neoplasm. The objective of this study was to develop prognostic models for the survival of NEC patients in the genitourinary system and subsequently validate these models. A total of 7125 neuroendocrine neoplasm (NEN) patients were extracted. Comparison of survival in patients with different types of NEN before and after propensity score-matching (PSM). A total of 3057 patients with NEC, whose information was complete, were extracted. The NEC influencing factors were chosen through the utilization of the least absolute shrinkage and selection operator regression model (LASSO) and the Fine & Gary model (FGM). Furthermore, nomograms were built. To validate the accuracy of the prediction, the efficiency was verified using bootstrap self-sampling techniques and receiver operating characteristic curves. LASSO and FGM were utilized to construct three models. Confirmation of validation was achieved by conducting analyses of the area under the curve and decision curve. Moreover, the FGS (DSS analysis using FGM) model produced higher net benefits. To maximize the advantages for patients, the FGS model disregarded the influence of additional occurrences. Patients are expected to experience advantages in terms of treatment options and survival assessment through the utilization of these models.
Assuntos
Carcinoma Neuroendócrino , Nomogramas , Humanos , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/diagnóstico , Neoplasias Urogenitais/patologia , Prognóstico , Adulto , Curva ROCRESUMO
BACKGROUND: Pulmonary high-grade neuroendocrine carcinomas(pHGNEC) encompassing small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) are clinically aggressive tumors with poor prognosis. The role of surgery and prognostic factors guiding management remain unclear. We aimed to analyze prognosis following resection and identify predictive variables. METHODS: This retrospective study analyzed 259 patients undergoing pHGNEC resection from 2001-2023. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier curves. Prognostic factors were assessed with Cox regression and visualized using nomogram tools. RESULTS: Minimally invasive surgery was associated with better OS (p = 0.001) and DFS (p = 0.001). Higher T stage predicted worse OS (T2 p = 0.044, T4 p = 0.007) and DFS (T2 p = 0.020, T4 p = 0.004). Advanced TNM stage III (OS p = 0.018; DFS p = 0.015) and IV (OS p < 0.001; DFS p < 0.001) also correlated with poorer prognosis. In the SCLC subgroup, elevated preoperative CEA independently predicted worse OS (p = 0.012) and DFS (p = 0.004). T4 disease (OS p < 0.001; DFS p = 0.002) and advanced TNM staging (stage III OS p = 0.043; DFS p = 0.045; stage IV OS p < 0.001, DFS p < 0.001) were associated with worse outcomes. In LCNEC patients, VATS resection improved OS (p = 0.048) and DFS (p = 0.027) despite conversion. Prior malignancy predicted worse OS (p < 0.001). Advanced TNM disease (stage III OS p = 0.047; stage IV OS p = 0.003, DFS p = 0.005) were also negative prognostic factors. The prognostic nomogram incorporating above variables effectively stratified risk. Calibration plots revealed good correlation between predicted and actual survival. CONCLUSIONS: We identified minimally invasive surgery, early TNM stage, younger age, and normal preoperative CEA as positive prognostic factors following pHGNEC resection. Our study provides an applicable prognostic nomogram to facilitate personalized pHGNEC management.
Assuntos
Carcinoma Neuroendócrino , Neoplasias Pulmonares , Nomogramas , Humanos , Feminino , Masculino , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Adulto , Idoso de 80 Anos ou maisRESUMO
PURPOSE: There is still controversy in different guidelines regarding the necessity of routine preoperative calcitonin (Ctn) testing in medullary thyroid cancer (MTC). The level of preoperative Ctn may influence the extent of surgery. METHODS: This retrospective multicenter cohort study involved 149 MTC patients from 6 centers between 2013 to 2023. Clinical characteristics, surgical procedure and clinical outcomes were compared between Ctn-screened and Non-screened group. Kaplan-Meier method was used to estimate recurrence-free survival (RFS) and overall survival (OS). RESULTS: In total, 127 MTC patients with preoperative Ctn screening and 22 MTC patients without screening were analyzed. MTC patients with preoperative Ctn screening underwent more radical surgical procedures including total thyroidectomy and lymph node dissection, compared to those without screening (84.3% vs. 68.2% and 91.3% vs. 72.7%, respectively). The rate of recurrence and death were lower in the Ctn-screened group (16.1% vs. 36.4%, 0.8% vs. 18.2%, respectively). The survival curve showed a significantly better overall survival in Ctn-screened group than Non-screened group (HR:17.932, 95% CI 1.888-170.294, p-value = 0.001), while no significant difference was observed of RFS between two groups (HR:1.6, 95% CI 0.645-3.966, p-value = 0.307). CONCLUSION: Preoperative Ctn screening can prompt surgeons choosing more radical initial surgical treatment for MTC patients, potentially leading to better long-term outcomes. Further evaluation of the cost-effectiveness of routine Ctn screening in thyroid nodule patients is warranted.
Assuntos
Calcitonina , Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/mortalidade , Estudos Retrospectivos , Feminino , Masculino , Calcitonina/sangue , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/diagnóstico , Adulto , Prognóstico , Idoso , Cuidados Pré-Operatórios/métodosRESUMO
Objective: Correct diagnosis and prognostic evaluation of medullary thyroid cancer (MTC) are crucial to treat patients. The purpose of this study was to evaluate the diagnostic and prognostic value of [18F]F-DOPA PET/CT in patients with MTC. Methods: We reviewed MTC patients who underwent [18F]F-DOPA PET/CT from June 2008 to November 2023. Clinical characteristics, follow-up data, and the following [18F]F-DOPA PET/CT parameters were recorded: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and SUVmean of multiple organs. The diagnostic value of PET/CT for the detection of tumor lesions was calculated. Serum basal calcitonin (bCt) and stimulated calcitonin (sCt) were determined. Receiver operating characteristics, Kaplan-Meier, and Cox regression analyses were performed. Results: In total, 109 patients (50 women, 59 men; average age, 55 ± 14 years) were included in the analysis. The patient-related sensitivity, specificity, and accuracy of [18F]F-DOPA PET/CT were 95%, 93%, and 94%, respectively. The lesion-related sensitivity, specificity, and accuracy were 65%, 99%, and 72%, respectively. The optimal cutoff values of bCt, sCt, and CEA to obtain positive [18F]F-DOPA PET/CT results were 64 pg/mL, 1808 pg/mL, and 4 µg/L, respectively. Patients with negative [18F]F-DOPA PET/CT had longer overall survival than patients with positive [18F]F-DOPA PET/CT results (P = 0.017). Significant positive correlations were found between bCt, sCt, and CEA with SUVmax, SUVmean, and MTV of [18F]F-DOPA PET/CT (P < 0.001). [18F]F-DOPA PET/CT results and MTV may be useful for the evaluation of the prognosis of patients with recurrent MTC, while age and MTV were independent prognostic factors in patients with primary MTC. For all patients, SUVmean of the left kidney, liver, aorta, and pancreas might be used to independently predict OS. Conclusion: [18F]F-DOPA PET/CT had great value for diagnosis and prognostic assessment in patients with MTC. The DOPA PET/CT parameter SUVmean and MTV showed significant association with OS.
Assuntos
Carcinoma Neuroendócrino , Di-Hidroxifenilalanina , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Glândula Tireoide , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/patologia , Di-Hidroxifenilalanina/análogos & derivados , Estudos Retrospectivos , Compostos Radiofarmacêuticos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: This study aims to investigate the clinical and pathological characteristics, treatment approaches, and prognosis of gallbladder neuroendocrine carcinoma (GB-NEC). METHODS: Retrospective analysis was conducted on the clinical data of 37 patients with GB-NEC admitted to Shanxi Cancer Hospital from January 2010 to June 2023. The study included an examination of their general information, treatment regimens, and overall prognosis. RESULTS: Twelve cases, either due to distant metastasis or other reasons, did not undergo surgical treatment and received palliative chemotherapy (Group 1). Two cases underwent simple cholecystectomy (Group 2); four patients underwent palliative tumor resection surgery (Group 3), and nineteen patients underwent radical resection surgery (Group 4). Among the 37 GB-NEC patients, the average pre-surgery CA19-9 level was 113.29 ± 138.45 U/mL, and the median overall survival time was 19 months (range 7.89-30.11 months). Of these, 28 cases (75.7%) received systemic treatment, 25 cases (67.6%) underwent surgical intervention, and 16 cases (64.0%) received postoperative adjuvant treatment, including combined radiochemotherapy or chemotherapy alone. The median overall survival time was 4 months (0.61-7.40 months) for Group 1 (n = 12), 8 months for Group 2 (n = 2), 21 months (14.67-43.33 months) for Group 3 (n = 4), and 19 months (range 7.89-30.11 months) for Group 4 (n = 19). A significant difference in median overall survival time was observed between Group 1 and Group 4 (P = 0.004). CONCLUSION: Surgery remains the primary treatment for GB-NEC, with radical resection potentially offering greater benefits to patient survival compared to other therapeutic options. Postoperative adjuvant therapy has the potential to extend patient survival, although the overall prognosis remains challenging.
Assuntos
Carcinoma Neuroendócrino , Colecistectomia , Neoplasias da Vesícula Biliar , Humanos , Neoplasias da Vesícula Biliar/terapia , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico , Masculino , Feminino , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/cirurgia , Carcinoma Neuroendócrino/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Taxa de Sobrevida , Adulto , Seguimentos , Terapia CombinadaRESUMO
BACKGROUND: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. METHODS: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. RESULTS: Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. CONCLUSIONS: We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.