RESUMEN
OBJECTIVE: To evaluate whether the maximum standardized uptake value (SUVmax) from initial 18F-FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) scans could be a predictor of complete response and recurrence in patients with endometrial cancer who are undergoing fertility sparing management. METHODS: We conducted a retrospective review of patients who were diagnosed with endometrial cancer through biopsy and chose to undergo fertility sparing management using progestin at the Asan Medical Center, from January 2011 to December 2020. Of these, 113 patients who had an 18-FDG-PET/CT scan before starting treatment were included in our study. We measured SUVmax and examined its correlation with complete response and time to progression after achieving complete response to progestin therapy. RESULTS: Of 113 patients, 73 (64.6%) achieved a complete response through fertility sparing management. The receiver operating characteristic curve analysis revealed that the optimal cut-off value of SUVmax for predicting complete response was 6.2 (sensitivity 79.5%, specificity 57.5%, p=0.006). After analyzing recurrence in the 73 patients who achieved complete response, we found that patients with an SUVmax value >6.2 had a significantly shorter time to progression compared with those with a value <6.2. (p=0.04). CONCLUSIONS: SUVmax values of PET-CT, along with other clinicopathological parameters, could be used to predict treatment response and recurrence risk in patients with stage I endometrial cancer undergoing fertility sparing management.
Asunto(s)
Neoplasias Endometriales , Preservación de la Fertilidad , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Radiofármacos , Humanos , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18/administración & dosificación , Neoplasias Endometriales/diagnóstico por imagen , Neoplasias Endometriales/patología , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/terapia , Estudios Retrospectivos , Adulto , Preservación de la Fertilidad/métodos , Radiofármacos/administración & dosificación , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Recurrencia Local de Neoplasia/diagnóstico por imagenRESUMEN
OBJECTIVE: The addition of immune checkpoint inhibitors (ICIs), pembrolizumab or dostarlimab, to paclitaxel and carboplatin (TC) has shown better response rates and survival outcomes for patients with primary advanced mismatch repair-deficient (MMRd) endometrial cancer (EC) in NRG-GY018 and RUBY, respectively. Nonetheless, the high cost of ICIs remains a major concern when implementing this strategy in the real world. This study aimed to determine the cost-effectiveness of pembrolizumab and dostarlimab with chemotherapy compared to TC for primary advanced MMRd EC. METHODS: We developed a Markov model including 6600 patients with primary advanced MMRd EC to simulate treatment outcomes. The initial decision points in the model were treatment with pembrolizumab with TC (PEM-TC), dostarlimab with TC (DOS-TC), and TC. Model probabilities, costs, and health utility values were derived with assumptions from published literature. Effectiveness was determined as average quality-adjusted life years (QALYs) gained. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: TC was the least costly strategy, whereas PEM-TC was the most effective strategy for primary advanced MMRd EC. TC was cost-effective based on a willingness-to-pay (WTP) threshold of $100,000/QALY compared with PEM-TC (ICER, $377,718/QALY), and DOS-TC exhibited absolute dominance (ICER, $401,859/QALY). PEM-TC was cost-effective when the cost of pembrolizumab 200 mg was reduced to $4361 (61% reduction). PEM-TC was selected in 16.5% with a WTP threshold of $300,000/QALY, but in <1% with a WTP threshold range of $100,000-200,000/QALY. CONCLUSION: PEM-TC can become cost-effective for primary advanced MMRd EC when the cost of pembrolizumab substantially decreases.
Asunto(s)
Neoplasias Endometriales , Inhibidores de Puntos de Control Inmunológico , Humanos , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Análisis de Costo-Efectividad , Reparación de la Incompatibilidad de ADN , Análisis Costo-Beneficio , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Años de Vida Ajustados por Calidad de Vida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.
Asunto(s)
Cistadenocarcinoma Seroso , Neoplasias de las Trompas Uterinas , Neoplasias Ováricas , Neoplasias Peritoneales , Femenino , Humanos , Salpingooforectomía , Proteína BRCA1/genética , Ovariectomía , Neoplasias Peritoneales/epidemiología , Estudios Retrospectivos , Proteína BRCA2/genética , Neoplasias de las Trompas Uterinas/patología , Neoplasias Ováricas/patología , Mutación , Pronóstico , Cistadenocarcinoma Seroso/patología , República de CoreaRESUMEN
OBJECTIVE: We aimed to investigate the effectiveness of continuing medical therapy in patients who did not achieve complete response (CR) despite 9 months of progestin treatment. We also sought to determine the prognostic factors associated with achieving CR among these patients. METHODS: We retrospectively analyzed 51 patients with presumed stage IA, grade 1 or 2 endometrioid adenocarcinoma who had persistent disease on biopsy performed at 9-12 months after at least 9 months of progestin-based therapy. Data on clinicopathological factors and oncological and obstetrical outcomes following continuous hormonal treatment were extracted from the patients' medical records and analyzed. Univariate and multivariate analyses for predicting CR were performed. RESULTS: Thirty-seven (72.5%) of 51 patients achieved CR after prolonged fertility-sparing treatment. Median time to CR from starting initial progestin was 17.3 months (range, 12.1-91.7 months). On univariate analysis, history of polycystic ovarian syndrome, histologic grade 2, and not achieving partial response (PR) until 12 months were significantly associated with failure to CR (odds ratio [OR], 6.188, 95% confidence interval [CI], 1.405-27.244, p = 0.018; OR, 9.722, 95% CI, 1.614-58.581, p = 0.013; and OR, 21.750, 95% CI, 4.016-117.783, p < 0.001, respectively). Multivariate analysis revealed that not achieving PR until 12 months was an independent prognostic factor predicting failure to CR after prolonged progestin therapy (OR, 21.803, 95% CI, 3.601-132.025, p = 0.001). CONCLUSIONS: Continued medical treatment is effective for persistent early endometrial carcinoma after at least 9 months of progestin therapy in young women who want to preserve their fertility.
Asunto(s)
Antineoplásicos Hormonales/administración & dosificación , Carcinoma Endometrioide/tratamiento farmacológico , Neoplasias Endometriales/tratamiento farmacológico , Preservación de la Fertilidad/métodos , Recurrencia Local de Neoplasia/epidemiología , Administración Oral , Biopsia , Carcinoma Endometrioide/diagnóstico , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/patología , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Endometrio/diagnóstico por imagen , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Estudios de Seguimiento , Humanos , Dispositivos Intrauterinos , Levonorgestrel/administración & dosificación , Imagen por Resonancia Magnética , Acetato de Medroxiprogesterona/administración & dosificación , Acetato de Megestrol/administración & dosificación , Miometrio/diagnóstico por imagen , Miometrio/efectos de los fármacos , Miometrio/patología , Clasificación del Tumor , Invasividad Neoplásica/diagnóstico por imagen , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasia Residual , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Insuficiencia del Tratamiento , Resultado del Tratamiento , UltrasonografíaRESUMEN
PURPOSE: The primary objective of our study was to investigate the effectiveness and safety of olaparib maintenance therapy in patients with BRCA-mutated recurrent ovarian cancer in daily practice. The secondary objective of this study was to identify prognostic factors associated with prolonged progression-free survival (PFS) in such patients. METHODS: We conducted a retrospective analysis of 40 patients who received olaparib maintenance treatment. Data on clinicopathological factors, oncological outcomes, and adverse events were obtained from medical records and analyzed. RESULTS: All patients had high-grade serous recurrent ovarian cancer with BRCA mutation and achieved complete or partial response to the most recent platinum-based chemotherapy. After a median follow-up of 14.3 months, the median PFS was 23.7 months (95% confidence interval, 14.1-33.4); however, the median overall survival was not reached. In the log-rank test, the PFS was significantly longer for patients with most recent platinum-free interval (PFI) ≥ 12 months, complete response to the last platinum-based chemotherapy, and less than three lines of previous chemotherapy (p = 0.005, p = 0.016, and p = 0.023, respectively). Most hematologic and non-hematologic adverse events were of grade 1 or 2, and the common adverse events were mostly related to myelosuppression. CONCLUSION: Olaparib maintenance treatment in BRCA-mutated recurrent ovarian cancer is effective and safe in clinical practice. Most recent PFI, response to the last platinum-based chemotherapy, and the number of previous chemotherapy lines were associated with PFS in patients with BRCA-mutated recurrent ovarian cancer.
Asunto(s)
Neoplasias Ováricas , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/efectos adversos , Piperazinas , Estudios RetrospectivosRESUMEN
Immunoprofiling has an established impact on the prognosis of several cancers; however, its role and definition in high-grade serous ovarian cancer (HGSOC) are mostly unknown. This study is to investigate immunoprofiling which could be a prognostic factor in HGSOC. We produced tumor microarrays of 187 patients diagnosed with HGSOC. We performed a multiplexed immunofluorescence staining using Opal Multiplex IHC kit and quantitative analysis with Vectra-Inform system. The expression intensities of programmed death-ligand 1 (PD-L1), CD4, CD8, CD20, FoxP3, and CK in whole tumor tissues were evaluated. The enrolled patients showed general characteristics, mostly FIGO stage III/IV and responsive to chemotherapy. Each immune marker showed diverse positive densities, and each tumor sample represented its immune characteristics as an inflamed tumor or noninflamed tumor. No marker was associated with survival as a single one. Interestingly, high ratios of CD8 to FoxP3 and CD8 to PD-L1 were related to the favorable overall survival (77 vs. 39 months, 84 vs. 47 months, respectively), and CD8 to PD-L1 ratio was also a significant prognostic factor (HR 0.621, 95% CI 0.420-0.917, p = 0.017) along with well-known clinical prognostic factors. Additionally, CD8 to PD-L1 ratio was found to be higher in the chemosensitive group (p = 0.034). In conclusion, the relative expression levels of CD8, FoxP3, and PD-L1 were significantly related to the clinical outcome of patients with HGSOC, which could be a kind of significant immunoprofiling of ovarian cancer patients to apply for treatment.
Asunto(s)
Biomarcadores de Tumor/análisis , Cistadenocarcinoma Seroso/metabolismo , Técnica del Anticuerpo Fluorescente/métodos , Neoplasias Ováricas/metabolismo , Coloración y Etiquetado/métodos , Adulto , Anciano , Antígeno B7-H1/análisis , Antígenos CD8/análisis , Cistadenocarcinoma Seroso/diagnóstico , Femenino , Factores de Transcripción Forkhead/análisis , Humanos , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Neoplasias Ováricas/diagnóstico , Pronóstico , Análisis de SupervivenciaRESUMEN
The clinical utility of BRCA1/2 genotyping was recently extended from the selection of subjects at high risk for hereditary breast and ovary cancer to the identification of candidates for poly (ADP-ribose) polymerase (PARP) inhibitor treatment. This underscores the importance of accurate interpretation of BRCA1/2 genetic variants and of reducing the number of variants of uncertain significance (VUSs). Two recent studies by Findlay et al. and Starita et al. introduced high-throughput functional assays, and proactively analyzed variants in specific regions regardless of whether they had been previously observed. We retrospectively reviewed all BRCA1 and BRCA2 germline genetic test reports from patients with breast or ovarian cancer examined at Asan Medical Center (Seoul, Korea) between September 2011 and December 2018. Variants were assigned pathogenic or benign strong evidence codes according to the functional classification and were reclassified according to the ACMG/AMP 2015 guidelines. Among 3684 patients with available BRCA1 and BRCA2 germline genetic test reports, 429 unique variants (181 from BRCA1) were identified. Of 34 BRCA1 variants intersecting with the data reported by Findlay et al., three missense single-nucleotide variants from four patients (0.11%, 4/3684) were reclassified from VUSs to likely pathogenic variants. Four variants scored as functional were reclassified into benign or likely benign variants. Three variants that overlapped with the data reported by Starita et al. could not be reclassified. In conclusion, proactive high-throughput functional study data are useful for the reclassification of clinically observed VUSs. Integrating additional evidence, including functional assay results, may help reduce the number of VUSs.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Neoplasias Ováricas/genética , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Variación Genética/genética , Genotipo , Mutación de Línea Germinal/genética , Humanos , Persona de Mediana Edad , Mutación Missense/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Poli(ADP-Ribosa) Polimerasas/genética , República de Corea/epidemiologíaRESUMEN
STUDY OBJECTIVE: To investigate the prognostic factors and impact of minimally invasive surgery (MIS) in surgically treated early-stage high-grade (HG) neuroendocrine cervical carcinoma (NECC). DESIGN: Retrospective cohort study. SETTING: Asan Medical Center, Seoul, Korea. PATIENTS: Patients with International Federation of Obstetrics and Gynecology (2009) stages IB1 to IIA HG NECC. INTERVENTIONS: All patients underwent radical hysterectomy (RH) with a laparotomy or an MIS approach. MEASUREMENTS AND MAIN RESULTS: Between 1993 and 2017, 47 patients with International Federation of Obstetrics and Gynecology stages IB1 to IIA1 HG NECC were initially treated with RH. Clinicopathologic variables of patients were retrospectively reviewed from electronic medical records. The median follow-up period was 28.2 months (interquartile range, 17.1-42). Stage IB1 disease was the most common (70.2%). Twenty-nine patients (61.7%) underwent RH by MIS. The overall survival (OS) and disease-free survival (DFS) rates were 63.8% and 38.3%, respectively. Lymph node metastasis and resection margin involvement were significant risk factors for DFS (hazard ratio [HR], 2.227; 95% confidence interval [CI], 1.018-4.871; p =.045 and HR, 6.494; 95% CI, 1.415-29.809; p =.016, respectively) and OS (HR, 3.236; 95% CI, 1.188-8.815; p =.022 and HR, 12.710; 95% CI, 1.128-143.152; p =.040, respectively). The Kaplan-Meier survival curves revealed no significant differences in OS and DFS between the laparotomy and MIS groups (50% vs 72.4% log-rank p =.196, 38.9% vs 37.9% p =.975). CONCLUSION: Lymph node metastasis and resection margin involvement were poor prognostic factors of survival outcomes in initially surgically treated early-stage HG NECC. No difference was observed in the survival outcomes between the MIS and laparotomy approaches.
Asunto(s)
Carcinoma Neuroendocrino/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Carcinoma Neuroendocrino/diagnóstico , Carcinoma Neuroendocrino/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía , Metástasis Linfática , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estadificación de Neoplasias , Pronóstico , República de Corea , Estudios Retrospectivos , Procedimientos Quirúrgicos Robotizados , Resultado del Tratamiento , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
BACKGROUND: As next-generation sequencing (NGS) technology matures, various amplicon-based NGS tests for BRCA1/2 genotyping have been introduced. This study was designed to evaluate an NGS test using a newly released amplicon-based panel, AmpliSeq for Illumina BRCA Panel (AmpliSeq panel), for detection of clinically significant BRCA variants, and to compare it to another amplicon-based NGS test confirmed by Sanger sequencing. METHODS: We reviewed BRCA test results done by NGS using the TruSeq Custom Amplicon kit from patients suspected of hereditary breast/ovarian cancer syndrome (HBOC) in 2018. Of those, 96 residual samples with 100 clinically significant variants were included in this study using predefined criteria: 100 variants were distributed throughout the BRCA1 and BRCA2 genes. All target variants were confirmed by Sanger sequencing. Duplicate NGS testing of these samples was performed using the AmpliSeq panel, and the concordance of results from the two amplicon-based NGS tests was assessed. RESULTS: Ninety-nine of 100 variants were detected in duplicate BRCA1/2 genotyping using the AmpliSeq panel (sensitivity, 99%; specificity, 100%). In the discordant case, one variant (BRCA1 c.3627dupA) was found only in repeat 1, but not in repeat 2. Automated nomenclature of all variants, except for two indel variants, was in consensus with Human Genome Variation Society nomenclature. CONCLUSION: Our findings confirm that the analytic performance of the AmpliSeq panel is satisfactory, with high sensitivity and specificity.
Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Análisis de Secuencia de ADN , Femenino , Variación Genética/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/normas , Humanos , Sensibilidad y Especificidad , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ADN/normasRESUMEN
This study was designed to analyze urinary proteins associated with ovarian cancer (OC) and investigate the potential urinary biomarker panel to predict malignancy in women with pelvic masses. We analyzed 23 biomarkers in urine samples obtained from 295 patients with pelvic masses scheduled for surgery. The concentration of urinary biomarkers was quantitatively assessed by the xMAP bead-based multiplexed immunoassay. To identify the performance of each biomarker in predicting cancer over benign tumors, we used a repeated leave-group-out cross-validation strategy. The prediction models using multimarkers were evaluated to develop a urinary ovarian cancer panel. After the exclusion of 12 borderline tumors, the urinary concentration of 17 biomarkers exhibited significant differences between 158 OCs and 125 benign tumors. Human epididymis protein 4 (HE4), vascular cell adhesion molecule (VCAM), and transthyretin (TTR) were the top three biomarkers representing a higher concentration in OC. HE4 demonstrated the highest performance in all samples withOC(mean area under the receiver operating characteristic curve (AUC) 0.822, 95% CI: 0.772-0.869), whereas TTR showed the highest efficacy in early-stage OC (AUC 0.789, 95% CI: 0.714-0.856). Overall, HE4 was the most informative biomarker, followed by creatinine, carcinoembryonic antigen (CEA), neural cell adhesion molecule (NCAM), and TTR using the least absolute shrinkage and selection operator (LASSO) regression models. A multimarker panel consisting of HE4, creatinine, CEA, and TTR presented the best performance with 93.7% sensitivity (SN) at 70.6% specificity (SP) to predict OC over the benign tumor. This panel performed well regardless of disease status and demonstrated an improved performance by including menopausal status. In conclusion, the urinary biomarker panel with HE4, creatinine, CEA, and TTR provided promising efficacy in predicting OC over benign tumors in women with pelvic masses. It was also a non-invasive and easily available diagnostic tool.
Asunto(s)
Biomarcadores de Tumor/orina , Neoplasias Ováricas/orina , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Modelos Estadísticos , Prealbúmina/orina , Molécula 1 de Adhesión Celular Vascular/orina , Proteína 2 de Dominio del Núcleo de Cuatro Disulfuros WAP/análisisRESUMEN
BACKGROUND: Palliative chemotherapy should be used with caution when attempting to alleviate symptoms in patients with end-stage cancer. However, palliative chemotherapy continues to be utilized in cancer patients during their last stages of life. In this study, we analyzed the pattern of chemotherapy administered during the last 6 months of life in patients with end-stage gynecologic cancer who were treated with active palliative chemotherapy for the past 10 years. METHOD: We retrospectively analyzed the data for patients with gynecologic cancer who died after undergoing active palliative chemotherapy without receiving hospice management at Asan Medical Center from 2006 to 2015. Patients were divided into two groups: those who died between 2006 and 2010, and those who died between 2011 and 2015. Based on the electronic medical records, the demographic and baseline characteristics of the patients, hospital admission during the last 6 months, invasive procedures, palliative chemotherapy patterns, and the time of the last chemotherapy session were confirmed. RESULTS: A total of 193 patients with gynecologic cancer were eligible for this study. 92 patients died during 2006 to 2010, and 101 patients died during 2011 to 2015. The mean frequency of admission during the last 6 months was 5.12 for those who died in 2006-2010 and 6.06 for those who died during 2011-2015 (p = 0.003); similarly, the mean frequency of palliative chemotherapy during the last 6 months was 3.84 (2006-2010) vs. 4.93 times (2011-2015; p < 0.001). The proportion of patients undergoing invasive procedures during the last 3 months was 41.3% (2005-2010) vs. 56.4% (2011-2015; p = 0.044). CONCLUSIONS: The frequency of palliative chemotherapy and the rate of invasive procedures have increased in patients with end-stage gynecologic cancer who were treated aggressively without hospice management over 2011-2015 when compared to 2006-2010, along with an increase in the mean frequency of admission during the last 6 months at our institution. Gynecologic oncologists need to evaluate whether active palliative chemotherapy is beneficial to patients at the end-of-life stage, and if not helpful, should communicate with the patients and caregivers about when the palliative chemotherapy should be discontinued.
Asunto(s)
Neoplasias de los Genitales Femeninos/terapia , Cuidado Terminal/tendencias , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia/métodos , Quimioterapia/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida/psicología , República de Corea , Estudios Retrospectivos , Cuidado Terminal/métodosRESUMEN
OBJECTIVE: To identify risk factors for distant recurrence in node-positive cervical cancer patients who underwent radical hysterectomy and pelvic lymph node dissection (PLND) with para-aortic lymph node sampling (PALNS) or para-aortic lymph node dissection (PALND). METHODS: A total of 299 patients in whom lymph node metastasis was confirmed after radical surgery at Asan Medical Center for stage IA2 to IIB cervical cancer from February 2001 to December 2012 were identified. In all, 72 (24.1%) patients underwent PLND only and 227 (75.9%) underwent PLND with PALNS or PALND. Four patients were excluded due to diagnosed with small cell carcinoma. The clinicopathologic data of 223 patients were retrospectively analyzed. Distant recurrence was defined as recurrence at a site over the pelvic radiation field. RESULTS: Among all 223 study patients, the mean number of positive lymph nodes was 4.46. There were 54 (24.2%) patients with distant metastasis. Multivariate analyses using the Cox proportional hazards model showed that histologic types (HR=3.031, P≤0.001 for adenocarcinoma, HR=2.302, P=0.066 for adenosquamous carcinoma), number of positive lymph nodes (HR=1.077, P≤0.001), and surgical stage (HR=1.264, P=0.022) were independent risk factors for distant recurrence of cervical cancer. A scoring system for the prediction of distant recurrence was generated by incorporating these factors and showed good discrimination and calibration (concordance index of 0.753). In an internal validation set, this scoring system showed good discrimination with a C-statistics of 0.777. According to the Hosmer-Lemeshow test, the chi-square was 0.650 and the P-value was 0.723. CONCLUSIONS: We have developed a robust scoring system that can predict the risk of distant recurrence in node-positive cervical cancer patients after radical operation. This scoring system was used to identify a group of patients who required systemic control of distant micrometastasis. This group of patients is an appropriate target for consolidation chemotherapy after concurrent chemoradiation therapy.
Asunto(s)
Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/patología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Aorta , Quimioterapia de Consolidación , Femenino , Humanos , Histerectomía/métodos , Escisión del Ganglio Linfático/métodos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Factores de Riesgo , Neoplasias del Cuello Uterino/diagnósticoRESUMEN
OBJECTIVE: Concurrent chemoradiotherapy is usually administered to patients with locally advanced cervical cancer (LACC). Extended-field chemoradiotherapy is required if para-aortic lymph node (PALN) metastasis is detected. This study aimed to construct a prediction model for PALN metastasis in patients with LACC before definitive treatment. METHODS: Between 2009 and 2016, all consecutive patients with LACC who underwent para-aortic lymphadenectomy at two tertiary centers were retrospectively analyzed. A multivariate logistic model was constructed, from which a prediction model for PALN metastasis was developed and internally validated. Before analysis, risk grouping was predefined based on the likelihood ratio. RESULTS: In total, 245 patients satisfied the eligibility criteria. Thirty-four patients (13.9%) had pathologically proven PALN metastases. Additionally, 16/222 (7.2%) patients with negative PALNs on positron emission tomography/computed tomography (PET/CT) had PALN metastasis. Moreover, 11/105 (10.5%) patients with both negative PALNs and positive pelvic lymph nodes on PET/CT had PALN metastasis. Tumor size on magnetic resonance imaging and PALN status on PET/CT were independent predictors of PALN metastasis. The model incorporating these two predictors displayed good discrimination and calibration (bootstrap-corrected concordance index=0.886; 95% confidence interval=0.825-0.947). The model categorized 169 (69%), 52 (22%), and 23 (9%) patients into low-, intermediate-, and high-risk groups, respectively. The predicted probabilities of PALN metastasis for these groups were 2.9, 20.8, and 76.2%, respectively. CONCLUSION: We constructed a robust model predicting PALN metastasis in patients with LACC that may improve clinical trial design and help clinicians determine whether nodal-staging surgery should be performed.
Asunto(s)
Carcinoma/diagnóstico por imagen , Carcinoma/secundario , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patología , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Aorta , Femenino , Humanos , Funciones de Verosimilitud , Modelos Logísticos , Escisión del Ganglio Linfático , Metástasis Linfática , Imagen por Resonancia Magnética , Persona de Mediana Edad , Pelvis , Tomografía Computarizada por Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo/métodos , Carga TumoralRESUMEN
OBJECTIVE: The study aims to identify preoperative predictors of complete cytoreduction and early recurrence and death in epithelial ovarian, tubal, and peritoneal cancer after neoadjuvant chemotherapy (NACT). METHODS: We performed a retrospective analysis of 85 patients who underwent 3 cycles of NACT. Patients were divided into 2 groups according to residual tumor at interval debulking surgery (IDS), and clinicopathologic, surgical, and follow-up data were compared. RESULTS: Cancer antigen 125 (CA-125) levels before the IDS after completion of NACT were higher in the residual tumor group (42.0 vs 116.6 U/mL, P = 0.006). The drop rate of CA-125 after NACT was higher in the no residual tumor group (96.8% vs 89.9%, P = 0.001). Patients with residual tumor showed lower disease-free and overall survival outcomes than patients with no residual tumor. In univariate analysis, CA-125 of 100 U/mL or less before IDS and a drop rate after NACT greater than 80% were preoperative predictive factors for complete cytoreduction. In multivariate analysis, a drop rate of CA-125 after NACT greater than 80% was an independent preoperative predictive factor for complete cytoreduction (P = 0.002). Progressive disease on follow-up image during NACT was an independent preoperative predictive factor for early recurrence and death (P < 0.001, both). CONCLUSIONS: A significant drop of CA-125 after NACT and progressive disease on follow-up image are independent preoperative predictors for complete cytoreduction and early recurrence and death.
Asunto(s)
Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Antígeno Ca-125/metabolismo , Carcinoma Epitelial de Ovario , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias de las Trompas Uterinas/metabolismo , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Humanos , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/metabolismo , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/metabolismo , Neoplasias Peritoneales/cirugía , Valor Predictivo de las Pruebas , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The purpose of this study was to identify preoperative clinicopathological predictive factors for lymph node (LN) metastasis in women diagnosed with uterine papillary serous carcinoma (UPSC). METHODS: Women diagnosed with UPSC in our institution from 1997 to 2012 were identified. All patients underwent hysterectomy and bilateral salpingo-oophorectomy plus pelvic and/or para-aortic lymphadenectomy. The predictive values of the risk factors for LN metastasis were analyzed using χ and multivariate logistic regression analyses. RESULTS: A total of 94 patients met our study criteria. A CA-125 cutoff of 47.5 IU/mL on the receiver operating characteristic curve provided the best sensitivity and specificity (56.5% vs 90.1%, respectively) for LN metastasis prediction. The sensitivities and specificities of old age (≥60 years), body mass index of 25 kg/m or greater, deep myometrial invasion, tumor size greater than 2 cm, tumor size greater than 4 cm, preoperative CA-125 greater than 47.5 IU/mL, LN metastasis on imaging, and extrauterine spread on imaging for the presence of a positive LN were 39.1%, 34.8%, 30.4%, 34.8%, 21.7%, 56.5%, 43.5%, and 52.2%, and 52.1%, 45.1%, 78.9%, 57.7%, 83.1%, 90.1%, 93.0%, and 90.1%, respectively. Preoperative CA-125 (P < 0.001), LN metastasis on preoperative imaging (P < 0.001), and extrauterine spread on preoperative imaging (P = 0.009) were risk factors for LN metastasis on univariate analysis. Multivariate analysis revealed that preoperative CA-125 (P = 0.001) was the only independent risk factor for LN metastasis. CONCLUSIONS: Preoperative CA-125 is a preoperative predictive factor for LN metastasis in UPSC.
Asunto(s)
Cistadenocarcinoma Papilar/secundario , Cistadenocarcinoma Seroso/secundario , Neoplasias Endometriales/secundario , Neoplasias Uterinas/patología , Adulto , Anciano , Cistadenocarcinoma Papilar/cirugía , Cistadenocarcinoma Seroso/cirugía , Neoplasias Endometriales/cirugía , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Ovariectomía , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Uterinas/cirugíaRESUMEN
STUDY OBJECTIVE: To compare the operative outcomes of patients undergoing either single-port or multiport laparoscopic hysterectomy (LH). METHODS: Two hundred fifty-six women scheduled for LH for symptomatic myoma and/or adenomyosis from 8 tertiary teaching hospitals were randomized to single-port or multiport groups. Primary outcome was conversion and/or complication proportion of the planned procedure to determine whether the success proportion of the single-port approach was not inferior to that of the multiport approach. Secondary outcomes were postoperative pain and operative scar. RESULTS: Demographic parameters including age, body mass index, parity, and history of vaginal and cesarean delivery were comparable between the 2 groups. The primary outcome of a combined conversion and/or complication rate was similar between the single-port and multiport groups at 8% and 10.3%, respectively. Conversions were similar between the groups with 4% of single-port cases and .8% of multiport cases. Transfusions were the most frequent complication required in 4.0% of single-port cases and 7.9% of multiport cases, with no difference between the groups. Concerning secondary outcomes, postoperative pain score and patient and observer scar assessment were not different between the 2 groups. Although not a specific outcome measure, there was no difference between the groups in blood loss, operative time, and postoperative hospital stay. CONCLUSION: Single-port LH is not inferior to multiport LH in terms of conversion and/or complications rates, including transfusion. However, the single-port approach did not have any advantage over multiport LH with regard to pain or cosmetic outcomes. These findings were demonstrated by multi-institutional surgeons in Korea.
Asunto(s)
Adenomiosis/cirugía , Histerectomía , Laparoscopía , Leiomioma/cirugía , Neoplasias Uterinas/cirugía , Adulto , Femenino , Humanos , Histerectomía/métodos , Laparoscopía/métodos , Persona de Mediana Edad , Tempo Operativo , Dolor Postoperatorio/etiología , Periodo Posoperatorio , Estudios Prospectivos , República de Corea , Resultado del TratamientoRESUMEN
AIMS: We investigated the prognosis of patients with small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) in relation to treatment modalities. METHODS: We retrospectively reviewed the medical records and pathological reports of 102 patients who were histologically diagnosed with SCNEC at 5 different institutes. Time to progression (TTP) and overall survival (OS) were analyzed for each treatment modality. RESULTS: Of the patients with early-stage [International Federation of Obstetrics and Gynecology (FIGO) stage IB2 or below] SCNEC, 57.8 and 79.3% underwent radical hysterectomy followed by adjuvant therapy. In advanced-stage SCNEC, concurrent chemoradiation therapy was given to 51.4% of the patients. The overall recurrence rate was 51.6%. In early- and advanced-stage SCNEC, the TTP was not different (22.3 vs. 13.3 months, p = 0.104), but the OS was different (40.7 vs. 21.4 months, p = 0.029). Parametrial involvement and lymph vascular space invasion were found to be associated with an unfavorable prognosis. Interestingly, survival was the most unfavorable in patients with early-stage SCNEC who had never received chemotherapy. FIGO stage and use of chemotherapy were identified as independent prognostic factors in SCNEC patients. CONCLUSIONS: SCNEC requires systemic chemotherapy as part of the initial treatment, along with surgery or radiation, even in patients with early-stage disease.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Neuroendocrino/terapia , Carcinoma de Células Pequeñas/terapia , Cuello del Útero/patología , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/patología , Carcinoma de Células Pequeñas/mortalidad , Carcinoma de Células Pequeñas/patología , Quimioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
The purpose of this study was to evaluate the surgical feasibility of and survival outcome after laparoscopy in obese Korean women with endometrial cancer which has recently been increasing. We reviewed the medical records of the patients treated at our medical institution between 1999 and 2012. The patients were divided into three groups, non-obese (Body Mass Index [BMI]<25.0), overweight (BMI 25-27.99), and obese (BMI≥28.0). These patient groups were compared in terms of their clinical characteristics, treatment methods, as well as surgical and survival outcomes. In total, 55 of the 278 eligible patients were obese women. There were no differences in the three groups in terms of the proportion of patients who underwent lymphadenectomy, their cancer stage, histologic type, type of adjuvant treatment administered, intra-, post-operative, and long-term complications, operative time, number of removed lymph nodes, blood loss, and duration of hospitalization (P=0.067, 0.435, 0.757, 0.739, 0.458, 0.173, 0.076, 0.124, 0.770, 0.739, and 0.831, respectively). The Disease-Free Survival (DFS) times were 139.1 vs. 121.6 vs. 135.5 months (P=0.313), and the Overall Survival (OS) times were 145.2 vs. 124.8 vs. 139.5 months (P=0.436) for each group, respectively. Obese women with endometrial cancer can, therefore, be as safely managed using laparoscopy as women with normal BMIs.
Asunto(s)
Neoplasias Endometriales/diagnóstico , Obesidad/diagnóstico , Adulto , Anciano , Índice de Masa Corporal , Supervivencia sin Enfermedad , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/mortalidad , Femenino , Humanos , Histerectomía , Tiempo de Internación , Escisión del Ganglio Linfático , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Obesidad/complicaciones , República de Corea , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. METHODS: CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. RESULTS: ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. CONCLUSION: The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer.
Asunto(s)
Liposomas , Nanopartículas , Proteínas Oncogénicas Virales , Neoplasias del Cuello Uterino , Femenino , Humanos , Animales , Ratones , ARN Interferente Pequeño/genética , Cisplatino/farmacología , Cisplatino/uso terapéutico , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología , Proteína p53 Supresora de Tumor/genética , Ratones Desnudos , Xenoinjertos , Línea Celular Tumoral , Proteínas Oncogénicas Virales/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , ARN Mensajero/genéticaRESUMEN
PURPOSE: To evaluate the safety and clinical outcome of two-session catheter-directed sclerotherapy (CDS) with 99% ethanol in patients with endometrioma. MATERIALS AND METHODS: This prospective study was approved by the institutional review board with written informed consent obtained from all participants and was registered on clinicaltrial.gov. Consecutive patients with ovarian endometrioma between June 2020 and March 2023 were prospectively evaluated for two sessions of CDS. After successful transvaginal ultrasound-guided puncture of the endometrioma, the biopsy needle was exchanged for a 7- or 8.5-F catheter for aspiration and ethanol injection. The catheter was retained in situ for a second session the next day. Endometrioma volume was measured on ultrasound before and 1, 3, and 6 months after CDS, and volume reduction ratio (VRR) was calculated. Serum anti-Müllerian hormone (AMH) was measured before and 6 months after CDS to assess ovarian reserve. RESULTS: Thirty-one endometriomas in 22 patients (mean age, 31.0 years; range, 19-44 years) were treated; 28 endometriomas were successfully treated with two-session CDS, while one session was incomplete in three endometriomas in three patients due to contrast medium leakage or pain. Minor procedure-related complications developed in four patients and resolved spontaneously before discharge on the same day of the second session. No recurrence was identified during follow-up. At the 6-month follow-up, the mean endometrioma diameter decreased from 5.5 ± 1.7 to 1.4 ± 0.9 cm (P < 0.001), and the serum AMH level was lowered without statistical significance (1.37 ± 0.96 ng/mL vs. 1.18 ± 0.92 ng/mL; P = 0.170). VRRs at 1, 3, and 6 months after CDS were 84.3 ± 13.7%, 94.3 ± 5.8%, and 96.4 ± 4.7%, respectively. CONCLUSION: Two-session CDS with 99% ethanol is safe, feasible, and effective for treating endometrioma with the ovarian function well preserved.