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1.
Medicine (Baltimore) ; 99(20): e20053, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443311

RESUMO

INTRODUCTION: Platinum-resistant ovarian cancer is characterized by its poor prognosis and limited treatment options. Angiogenesis plays a fundamental role in the development of drug-resistance in ovarian cancer. Anlotinib, a novel oral multi-targeted tyrosine kinase inhibitor which targets a board spectrum of angiogenesis-associated growth factor receptors, has shown promising anti-tumor efficacy in clinical trials. Herein, we report a case of ovarian cancer treated with anlotinib plus etoposide after secondary cytoreductive surgery. PATIENT CONCERNS: A 45-year-old female with primary platinum-resistant ovarian cancer who progressed rapidly after the first cytoreductive surgery, the second cytoreductive surgery, and several lines of treatment. The patient refused to receive intravenous chemotherapy any more. DIAGNOSIS: Primary platinum-resistant ovarian cancer. INTERVENTIONS: The oral combination treatment of anlotinib (12 mg, qd) and etoposide (100 mg, qd) were delivered. OUTCOMES: Finally, the patient was responsive to the orally treatment of anlotinib combined with etoposide. The patient has been alive with no evidence of disease progression for 18 weeks. CONCLUSION: Our case suggests that oral treatment of anlotinib combined with etoposide which is acceptable and convenient, may be an additional option for the management of platinum-resistant ovarian cancer.


Assuntos
Antineoplásicos/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Etoposídeo/uso terapêutico , Indóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Quinolinas/uso terapêutico , Administração Oral , Protocolos de Quimioterapia Combinada Antineoplásica , Cistadenocarcinoma Seroso/diagnóstico por imagem , Cistadenocarcinoma Seroso/cirurgia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/cirurgia
2.
Curr Oncol Rep ; 22(1): 8, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31989304

RESUMO

PURPOSE OF REVIEW: This review provides an overview of the current clinical standard in low-grade serous ovarian cancer (LGSOC). The available evidence for surgery and standard treatments is elaborated. In addition, we discuss recent findings and novel treatments for LGSOC. RECENT FINDINGS: Two large multicenter trials studying MEK inhibitors in LGSOC have been presented in the last year. Binimetinib demonstrated an activity in LGSOC, especially in KRAS-mutated disease. Trametinib was associated with an improved progression-free survival in relapsed LGSOC. Based on the current results, MEK inhibitors could be an alternative treatment for LGSOC. Surgery is an important step in the treatment of LGSOC. Hormonal therapy and bevacizumab can be beneficial, next to chemotherapy. Targeted treatments, such as the MEK-inhibitor trametinib, seem to be efficient and should be introduced into clinical practice.


Assuntos
Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Terapia de Alvo Molecular/métodos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Proteínas Proto-Oncogênicas/genética
3.
Gynecol Oncol ; 156(3): 662-668, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918995

RESUMO

OBJECTIVE: To identify novel immunologic targets and biomarkers associated with overall survival (OS) in high-grade serous ovarian cancer (HGSC). METHODS: In this retrospective study, microarray data from 51 HGSC specimens were analyzed (Affymetrix HG-U133A). A panel of 183 immune/inflammatory response related genes linked to 279 probe sets was constructed a priori and screened. Associations between gene expression and OS were assessed using logrank tests. Multiple testing was addressed within the False Discovery Rate (FDR) framework. For external validation, TCGA Ovarian dataset and five GSE publicly available HGSC datasets were evaluated. RESULTS: In Duke data, 110 probe sets linked to 83 immunologic/inflammatory-related genes were differentially expressed in tumors from long versus short-term HGSC survivors (adjusted p < 0.05). In TCGA, concordant with the results from the Duke discovery cohort, high expression of one probe (IL6R) demonstrated a consistent significance and concordant association with higher expression in long-term HGSC survivors (Duke q-value = 0.022) and improved OS in the TCGA dataset (p-value = 0.015, HR = 0.8). Thirteen genes in GSE14764 (N = 4) and GSE26712 (N = 9) datasets had significant p-values and consistent concordant with Duke Data. Despite the significant associations of gene expression and OS in the individual GSE datasets, in the GSE meta-analysis no genes were consistently concordant and significantly associated with survival. CONCLUSIONS: Evaluation of IL6R expression may be warranted based on higher expression in long-term survivors and association with improved survival in advanced HGSC. The other candidate genes may also be of worthy of further exploration to enhance immuno-oncology drug discovery.


Assuntos
Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/imunologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/cirurgia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Bases de Dados Genéticas , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Receptores de Interleucina-6/biossíntese , Receptores de Interleucina-6/genética , Receptores de Interleucina-6/imunologia , Estudos Retrospectivos
4.
Gynecol Oncol ; 156(3): 744-745, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31955860

RESUMO

OBJECTIVE/BACKGROUND: Laparoscopic splenectomy is a potential surgical option for the treatment of isolated gynecologic cancer recurrence to the spleen [1-7]. The purpose of this video is to demonstrate a step-by-step approach for laparoscopic splenectomy in the setting of recurrent, oligometastatic ovarian cancer. METHODS: We present the case of a 47-year-old female with recurrent, platinum-sensitive high-grade serous ovarian cancer. A computer tomographic scan demonstrated an isolated 1.5 × 1.0 cm recurrence in the splenic hilum. A laparoscopic secondary cytoreduction with splenectomy was planned. The surgical procedure was recorded via the video camera tower, and the key steps for a laparoscopic splenectomy were identified and highlighted. RESULTS: The indications for secondary cytoreductive surgery, the appropriate candidates for minimally invasive surgery, patient positioning principles to set the surgeon up for success, and left upper quadrant anatomy are reviewed. In the surgical case and in the setting of hilar disease, the technique and rationale for ligating the major splenic ligaments in a particular order are reviewed. The procedure for isolating and ligating the dominant vascular structures - the splenic artery and vein - are reviewed. Finally, perioperative and oncologic outcomes, including an estimated blood loss of 100 cc, operative time of 3 h, a disease-free interval and "no evidence of disease" status after chemotherapy at 14 months, are emphasized. CONCLUSIONS: In this video, both anatomical references and the surgical technique for a laparoscopic splenectomy in the setting of recurrent ovarian cancer are illustrated. We demonstrate that laparoscopic splenectomy is feasible and safe with proper patient selection and positioning as well as meticulous surgical technique.


Assuntos
Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos em Ginecologia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Esplenectomia/métodos , Feminino , Humanos , Pessoa de Meia-Idade
5.
Int J Gynecol Cancer ; 30(1): 67-73, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31754067

RESUMO

OBJECTIVES: The chemotherapy response score (CRS) has been developed for measuring response to neoadjuvant chemotherapy in tubo-ovarian high-grade serous carcinoma. This study aimed to validate the ability of this three-tier scoring system of pathologic response on omental specimens to determine prognosis in a subgroups of patients who had clinical complete response to neoadjuvant chemotherapy. METHODS: This was a retrospective study, conducted in women receiving interval debulking surgery at the Division of Gynecologic Oncology, between December 2007 and April 2017. Inclusion criteria were: high-grade serous ovarian cancer, FIGO stage IIIC/IV, platinum-based neoadjuvant chemotherapy, and clinical complete response after neoadjuvant chemotherapy (normalization in CA125 levels, disappearance of all target and non-target lesions according to RECIST 1.1). CRS was defined by a single pathology review and classified as previously reported: CRS1, no or minimal tumor response with fibroinflammatory changes limited to a few foci ranging from multifocal or diffuse regression-associated fibroinflammatory changes with viable tumor in sheets, or nodules to extensive regression-associated fibroinflammatory changes with multifocal residual tumor; CRS2, appreciable tumor response with viable tumor readily identifiable; and CRS3, complete absence of tumor or nodules with maximum size of 2 mm. CRS was analyzed according to clinical variables and survival. RESULTS: A total of 108 patients were eligible for analysis. The average age was 65 (range 36-85) years. A total of 91 (84.3%) patients had stage IIIC disease and 17 (15.7%) patients had stage IV disease. No statistically significant differences were observed in terms of age, FIGO stage, CA125 serum levels, type of chemotherapy schedules, and number of cycles between the three groups. Patients in the CRS3 group had a longer median progression-free survival (25.8 months) compared with CRS2 or CRS 1 (20.3 vs 17.4 months, respectively; p=0.001). Median overall survival was 68.9 months for CRS3, 35.0 months for CRS2, and 45.9 months for CRS1 (p=0.034). CONCLUSION: Complete or near-complete pathologic response assessed in the omental specimens of advanced epithelial ovarian carcinoma patients after neoadjuvant chemotherapy (CRS3) is predictive of prolonged progression-free and overall survival. In particular, this is true in women with a clinical complete response.


Assuntos
Cistadenocarcinoma Seroso/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Ca-125/sangue , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/cirurgia , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do Tratamento
6.
Gynecol Oncol ; 156(1): 62-69, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31776037

RESUMO

OBJECTIVES: To compare survival after nodal assessment using a sentinel lymph node (SLN) algorithm versus comprehensive pelvic and paraaortic lymphadenectomy (LND) in serous or clear cell endometrial carcinoma, and to compare survival in node-negative cases. METHODS: Three-year recurrence-free survival (RFS) and overall survival were compared between one institution that used comprehensive LND to the renal veins and a second institution that used an SLN algorithm with ultra-staging with inverse-probability of treatment weighting (IPTW) derived from propensity scores to adjust for covariate imbalance between cohorts. RESULTS: 214 patients were identified (118 SLN cohort, 96 LND cohort). Adjuvant therapy differed between the cohorts; 84% and 40% in the SLN and LND cohorts, respectively, received chemotherapy ± radiation therapy. The IPTW-adjusted 3-year RFS rates were 69% and 80%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 77%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of surgical approach (SLN vs LND) with progression and death was 1.46 (95% CI: 0.70-3.04) and 0.44 (95% CI: 0.19-1.02), respectively. In the 168 node-negative cases, the IPTW-adjusted 3-year RFS rates were 73% and 91%, respectively. The IPTW-adjusted 3-year OS rates were 88% and 86%, respectively. In this subgroup, IPTW-adjusted HR for the association of surgical approach (SLN vs LND) with progression and death was 3.12 (95% CI: 1.02-9.57) and 0.69 (95% CI: 0.24-1.95), respectively. CONCLUSION: OS was not compromised with the SLN algorithm. SLN may be associated with a decreased RFS but similar OS in node-negative cases despite the majority receiving chemotherapy. This may be due to differences in surveillance.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Algoritmos , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Adenocarcinoma de Células Claras/patologia , Idoso , Estudos de Coortes , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Excisão de Linfonodo/métodos , Metástase Linfática , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
7.
Am J Surg Pathol ; 44(2): 206-213, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31651523

RESUMO

The chemotherapy response score (CRS) is used to score histopathologic response to neoadjuvant chemotherapy (NACT) of patients with extrauterine high-grade serous carcinoma. This study was undertaken to determine if the CRS in the omentum, adnexa or when combined correlates with (1) progression-free survival (PFS) or overall survival (OS), (2) laparoscopic score of abdominal disease, (3) Cancer antigen 125 levels, (4) BRCA status, and (5) platinum-resistant disease. A total of 158 cases were retrospectively collected that received NACT between April 2013 and February 2018 at a single institution. The 3-tier Böhm CRS system was applied to the omentum and adnexa. Survival outcomes between scored subgroups were analyzed using Cox proportional hazards regression. Spearman rank correlation analyses were used to assess CRS and clinical data. A total of 119 cases were treated only with carboplatin/paclitaxel. Omental CRS was: 1 (23 cases, 19.3%), 2 (65 cases, 54.6%), and 3 (31 cases, 26.1%), whereas adnexal CRS was: 1 (50 cases, 42%), 2 (48 cases, 40.3%) and 3 (21 cases, 17.6%). The omental CRS was significantly associated with PFS as a 2-tier score (hazard ratio [HR]=0.612, 95% confidence interval [CI]: 0.378-0.989, P=0.045) but not associated with the PFS using the 3-tier score or with OS using either system. Adnexal CRS was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.49, 95% CI: 0.263-0.914, P=0.025) and 2-tier scores (HR=0.535, 95% CI: 0.297-0.963, P=0.037). The combined score was not associated with OS but was significantly associated with PFS using the 3-tier (HR=0.348, 95% CI: 0.137-0.88, P=0.026) and 2-tier scores (HR=0.364, 95% CI: 0.148-0.896, P=0.028). No CRS system used associated with laparoscopic assessment of disease. CRS in the omentum had no significant association with platinum resistance; however, the adnexal CRS 1/2 were 3 times as likely to develop platinum resistance compared with CRS 3 (relative risk=3.94, 95% CI: 1.03-15.09, P=0.046). The CRS, when used on the omentum, adnexa, and as a combined score, was significantly associated with PFS but not with OS. Adnexal CRS 1/2 are more likely to develop platinum-resistant disease. Therefore, the use of this pathology parameter may be useful for clinical management.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Regras de Decisão Clínica , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias das Tubas Uterinas/mortalidade , Neoplasias das Tubas Uterinas/patologia , Neoplasias das Tubas Uterinas/cirurgia , Feminino , Seguimentos , Humanos , Laparoscopia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
8.
Gynecol Oncol ; 156(1): 70-76, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739992

RESUMO

OBJECTIVES: The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND). METHODS: We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test. RESULTS: 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8). CONCLUSIONS: SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting.


Assuntos
Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Linfonodo Sentinela/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Análise de Sobrevida
9.
Gynecol Oncol ; 156(1): 154-161, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31759772

RESUMO

OBJECTIVE: Adjuvant management of women with high-intermediate- and high-risk early-stage endometrial cancer remains controversial. Recently published results of GOG 249 revealed that vaginal brachytherapy plus chemotherapy (VBT + CT) was not superior to whole pelvic radiation therapy (WPRT) and was associated with more toxicities and higher nodal recurrences. This study examined off-study utilization of VBT + CT among women who met criteria for GOG 249 in the period prior to study publication. METHODS: Women diagnosed with FIGO IA-IIB endometrioid, serous, or clear cell uterine cancer between 2004-2015 and treated with hysterectomy and radiotherapy (RT) were identified in the National Cancer Database. Cochrane-Armitrage trend test was used to assess trends over time. Univariate and multivariate Cox analyses were performed to calculate odds ratio (OR) of VBT + CT receipt and hazard ratio (HR) of OS. Propensity-score matched analysis was conducted to account for baseline differences. RESULTS: 9956 women met inclusion criteria. 7548 women (75.8%) received WPRT while 2408 (24.2%) received VBT + CT in the study period. From 2004-2015, there was a significant increase in VBT + CT use (p < 0.001) with the largest overall increase occurring in 2009 to 22%. Factors significantly associated with VBT + CT receipt included higher socioeconomic status (p < 0.001), higher grade endometrioid cancer (p < 0.001), and aggressive histology (p < 0.001). After propensity-score matching, VBT + CT was associated with improved OS (HR 0.74, 95% CI 0.58-0.93); however, when stratified by FIGO stage, VBT + CT was only associated with improved OS for FIGO stage 1B (HR 0.62, 95% CI 0.44-0.87). CONCLUSIONS: There was significant use of experimental arm off-study treatment in the United States prior to report of GOG 249 results. Providers should be cautious when offering off-study treatment utilizing an experimental regimen given uncertainty about efficacy and toxicity.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/radioterapia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Endometrioide/tratamento farmacológico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/radioterapia , Carcinoma Endometrioide/cirurgia , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Adulto Jovem
10.
Eur J Radiol ; 122: 108747, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760275

RESUMO

PURPOSE: To develop a radiomics model in the preoperative differentiation of mucinous cystic neoplasm (MCN) and macrocystic serous cystadenoma (MaSCA) and to compare its diagnostic performance with conventional radiological model. METHODS: 57 Patients (MCN = 31, MaSCA = 26) with preoperative multidetector computed tomography (MDCT) scans were retrospectively included in this study. A radiological model was constructed from radiological features evaluated by radiologists. A radiomics model was constructed with high-dimensional quantitative features extracted from manually segmented volume of interests (VOIs). A combined model was constructed using both radiomics features and radiological features. The diagnostic performance of three models were assessed by the area under the receiver-operating characteristic curve (AUC), sensitivity, specificity, accuracy, and the calibration curves. RESULTS: The radiological model yielded an AUC of 0.775, sensitivity of 74.2 %, specificity of 80.8, and accuracy of 77.2 %. The radiomics model yielded an AUC of 0.989, sensitivity of 93.6 %, specificity of 96.2 %, and accuracy of 94.7 %. The combined model yielded an AUC of 0.994, sensitivity of 96.8 %, specificity of 100 %, and accuracy of 98.2 %. Both combined model and radiomics model showed higher AUC, sensitivity, and accuracy than radiological model (all P <  .05). The combined model showed higher AUC than radiomics model, though no significant difference was found (P =  .41). The combined model showed better calibration than radiomics model (P =  .91 vs. P <  .001). CONCLUSIONS: Combined model which contained both radiomics features and radiological features outperformed radiomics model and radiological model in the preoperative differentiation of MCN and MaSCA.


Assuntos
Adenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Seroso/patologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Neoplasias Pancreáticas/cirurgia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Gynecol Oncol ; 156(1): 77-84, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31796203

RESUMO

OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.


Assuntos
Algoritmos , Cistadenocarcinoma Papilar/tratamento farmacológico , Cistadenocarcinoma Seroso/tratamento farmacológico , Aprendizado de Máquina , Neoplasias Uterinas/tratamento farmacológico , Idoso , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Estadiamento de Neoplasias , Nomogramas , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Neoplasias Uterinas/patologia , Neoplasias Uterinas/cirurgia
12.
In Vivo ; 34(1): 397-400, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882505

RESUMO

BACKGROUND/AIM: Ovarian cancer presents an aggressive tumor biology, a significant number of patients experiencing recurrent disease. The aim of this study was to examine the feasibility and effectiveness of secondary debulking surgery for relapsed ovarian cancer. PATIENTS AND METHODS: Between 2014 and 2018, debulking surgery for relapsed ovarian cancer was performed in 40 cases. RESULTS: Debulking surgery to no residual disease was achieved in 31 cases; among the remaining cases, an R1 resection was feasible in six cases, while in the remaining three cases an R2 resection was performed. The most commonly performed visceral resections were represented by rectosigmoidian resection, right colon resection, total or partial cystectomy and unilateral or bilateral ureteral resection. The early postoperative morbidity rate was 32.5% while the postoperative mortality rate was 2.5%. CONCLUSION: Extended pelvic resections are feasible in patients with relapsed ovarian cancer and might be performed with acceptable rates of postoperative complications.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Pélvicas/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Adulto , Idoso , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pélvicas/patologia , Prognóstico , Estudos Retrospectivos
13.
In Vivo ; 34(1): 407-411, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882507

RESUMO

BACKGROUND/AIM: The role of upper abdominal resection as part of debulking surgery for advanced-stage or relapsed ovarian cancer has been widely debated. The aim of this study was to investigate the safety and efficacy of upper abdominal resection as part of tertiary cytoreduction. PATIENTS AND METHODS: Between 2005 and 2019, 11 cases presenting upper abdominal recurrences after surgically treated ovarian cancer were submitted to surgery with radical intent. RESULTS: Complete debulking surgery was feasible in eight cases, optimal debulking was performed in two cases, while in one case a suboptimal resection was performed. The most commonly performed upper abdominal resections consisted of liver resection in seven cases, splenectomy in four cases, diaphragmatic resection in three cases, pancreatic tail resection in two cases and partial gastrectomy in another two cases. Postoperative complications were encountered in two cases, while postoperative mortality was null. CONCLUSION: Extended upper abdominal resection can be safely performed in order to increase the chances of optimal debulking surgery at the time of tertiary cytoreduction.


Assuntos
Adenocarcinoma de Células Claras/cirurgia , Adenocarcinoma Mucinoso/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias do Endométrio/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/patologia , Idoso , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos
14.
Gynecol Oncol ; 155(3): 400-405, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31606285

RESUMO

OBJECTIVE: The role of secondary cytoreductive surgery (SCS) in platinum-sensitive recurrent ovarian cancer (PSROC) is still controversial. We investigated the role of SCS in PSROC patients with BRCA1/2 mutation (BRCAmut) who received platinum-based chemotherapy followed by olaparib maintenance. METHODS: This is a case-control study. Patients with first PSROC admitted to our Gynecologic Oncology Unit between 2014 and 2018 were identified. Main eligibility criteria: positive BRCA1/2 germline or somatic mutation status and olaparib maintenance at primary recurrence after response to platinum-based chemotherapy. Cases were those who received SCS followed by medical treatment (SCS-CT-OLA, group 1), controls were those who received medical treatment alone (CT-OLA, group 2). RESULTS: Overall, 46 patients were identified; 23 (50%) BRCAmut women undergoing SCS followed by platinum-based chemotherapy and olaparib maintenance were matched with 23 (50%) BRCAmut women who only received medical treatment. Groups were well balanced: no statistical differences were found with regard of age, mutational status, treatment's approach at diagnosis, timing and patterns of disease presentation at recurrence. Median time to first subsequent therapy (TFST) was significantly longer in the SCS-CT-OLA than in the CT-OLA group (42 months vs 16 months; p = 0.05). Also, SCS-CT-OLA patients had the best post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS-CT-OLA group versus 42% in CT-OLA group (p = 0.02). CONCLUSIONS: SCS increases TFST and PRS in PSROC patients with BRCAmut candidate for olaparib maintenance after platinum-based chemotherapy. Prospective studies are needed. In the era of personalized medicine, indication to SCS should be individualized.


Assuntos
Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Ftalazinas/administração & dosagem , Piperazinas/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Estudos de Casos e Controles , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Doxorrubicina/administração & dosagem , Feminino , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Humanos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Paclitaxel/administração & dosagem
15.
Int J Gynecol Cancer ; 29(9): 1377-1380, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31575614

RESUMO

OBJECTIVES: To assess outcomes and patterns of recurrence in patients with high-grade serous ovarian/tubal/primary peritoneal cancers with radiographic supraclavicular lymphadenopathy at diagnosis. METHODS: We evaluated all patients with newly diagnosed high-grade serous ovarian cancers treated at our center between January 1, 2008 and May 1, 2013 who had supraclavicular lymphadenopathy (defined as ≥1 cm in short axis) on radiographic imaging (either computed tomography or positron emission tomography) at the time of diagnosis. RESULTS: Of 586 patients with high-grade serous ovarian cancer receiving primary treatment during the study period, we identified 13 (2.2%) with supraclavicular lymphadenopathy diagnosed on pre-treatment imaging. The median age at diagnosis was 52.0 years (range 38.2-72.3). Five (31%) had clinically palpable nodes on physical examination. Four (31%) had a known BRCA mutation. All 13 patients underwent neoadjuvant chemotherapy, followed by interval debulking surgery. Each patient received a median of four cycles of neoadjuvant intravenous chemotherapy (range 3-7). At interval debulking surgery, complete gross resection was achieved in nine (70%) patients, and optimal resection (0.1-1 cm residual disease) in four (30%). Eleven patients (85%) recurred; however, only one (8%) recurred in the supraclavicular lymph nodes. Median follow-up time was 44.3 months (range 22.4-95.0). Median progression-free survival for the cohort was 11.7 months (95% CI 9.2 to 14.1). Median overall survival was 44.3 months (95% CI 41.5 to 47.1). In patients obtaining complete gross resection at interval debulking surgery, median progression-free survival and overall survival were 13.9 months (95% CI 8.9 to 18.9) and 78.1 months (95% CI 11.1 to 145.1), respectively. CONCLUSIONS: In our study, approximately 2% of patients with high-grade serous ovarian cancer presented with radiographic evidence of supraclavicular lymphadenopathy. Supraclavicular lymphadenopathy at diagnosis did not portend an unfavorable outcome when complete gross resection was achieved at interval debulking surgery.


Assuntos
Cistadenocarcinoma Seroso/patologia , Linfadenopatia/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Quimioterapia Adjuvante , Estudos de Coortes , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida
17.
Gynecol Oncol ; 155(2): 192-200, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521322

RESUMO

PURPOSE: To determine if the primary treatment approach (primary debulking surgery (PDS) versus neoadjuvant chemotherapy and interval debulking surgery (NACT-IDS)) influences the pattern of first recurrence in patients with completely cytoreduced advanced high-grade serous ovarian carcinoma (HGSOC). MATERIALS AND METHODS: This retrospective study included 178 patients with newly diagnosed stage IIIC-IV HGSOC, complete gross resection during PDS (n = 124) or IDS (n = 54) from January 2008-March 2013, and baseline and first recurrence contrast-enhanced computed tomography scans. Clinical characteristics and number of disease sites at baseline were analyzed for associations with time to recurrence. In 135 patients who experienced recurrence, the overlap in disease locations between baseline and recurrence and the number of new disease locations at recurrence were analyzed according to the primary treatment approach. RESULTS: At univariate and multivariate analyses, NACT-IDS was associated with more overlapping locations between baseline and first recurrence (p ≤ 0.003) and fewer recurrences in new anatomic locations (p ≤ 0.043) compared with PDS. The same results were found in a subgroup that received intra-peritoneal adjuvant chemotherapy after either treatment approach. At univariate analysis, patient age, primary treatment approach, adjuvant chemotherapy route, and number of disease locations at baseline were associated with time to recurrence (p ≤ 0.009). At multivariate analysis, older patient age, NACT-IDS, and greater disease locations at baseline remained significant (p ≤ 0.018). CONCLUSION: The distribution of disease at the time of first recurrence varied with the choice of primary treatment. Compared to patients treated with PDS, patients who underwent NACT-IDS experienced recurrence more often in the same locations as the original disease.


Assuntos
Cistadenocarcinoma Seroso/cirurgia , Recidiva Local de Neoplasia/etiologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia Computadorizada por Raios X
18.
J Surg Oncol ; 120(7): 1208-1219, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531879

RESUMO

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Peritônio/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Quimioterapia Adjuvante , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Taxa de Sobrevida
19.
N Engl J Med ; 381(25): 2403-2415, 2019 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-31562800

RESUMO

BACKGROUND: Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. METHODS: In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA-mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA-mutation cohort), and the intention-to-treat population. RESULTS: A total of 1140 patients underwent randomization. In the BRCA-mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. CONCLUSIONS: Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ClinicalTrials.gov number, NCT02470585.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzimidazóis/efeitos adversos , Carboplatina/administração & dosagem , Terapia Combinada , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/cirurgia , Método Duplo-Cego , Feminino , Genes BRCA1 , Genes BRCA2 , Humanos , Análise de Intenção de Tratamento , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida
20.
J Obstet Gynaecol Res ; 45(10): 2074-2081, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373110

RESUMO

AIM: The aim of this study was to analyze the survival outcomes of stage IIIC ovarian high-grade serous carcinoma (HGSC) patients with both peritoneal and lymphatic dissemination (IP+/RP+) who had undergone maximal or optimal cytoreduction followed by intravenous carboplatin/paclitaxel chemotherapy compared to those women with stage IIIC ovarian HGSC with only peritoneal involvement (IP+/RP-) who were treated similarly. METHODS: We performed a retrospective, multicenter study with the participation of five gynecological cancer centers. First, the stage IIIC ovarian HGSC patients were classified into optimally or maximally debulked cohorts. Then, in each cohort, the patients were divided into two groups; the IP+/RP- group included those women with transcoelomic spreading outside the pelvis with no nodal disease, and the IP+/RP+ group included those patients with transcoelomic dissemination outside the pelvis in addition to a positive nodal status. The survival outcomes were compared between the two groups in each cohort. RESULTS: A total of 405 ovarian HGSC patients were analyzed. In the optimally debulked cohort (n = 257), the progression-free survival (PFS) and overall survival (OS) medians for the IP+/RP- group (n = 69) were 24 and 57 months, respectively, compared to 21 and 58 months, respectively, for the IP+/RP+ group (n = 188) (P = 0.78 and P = 0.40, respectively). In the maximally debulked cohort (n = 148), the PFS and OS medians for the IP+/RP- group (n = 55) were 35 and 63 months, respectively, compared to 25 and 51 months, respectively, for the IP+/RP+ group (n = 93) (P = 0.49 and P = 0.31, respectively). CONCLUSION: Our findings indicated no survival differences between the IP+/RP- and the IP+/RP+ groups.


Assuntos
Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Peritônio/patologia , Estudos Retrospectivos , Turquia/epidemiologia
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