RESUMEN
Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.
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Células Mieloides/patología , Neoplasias/genética , Neoplasias/patología , Análisis de la Célula Individual , Transcripción Genética , Línea Celular Tumoral , Linaje de la Célula , Células Dendríticas/metabolismo , Femenino , Humanos , Proteínas de Membrana de los Lisosomas/metabolismo , Macrófagos/metabolismo , Masculino , Mastocitos/patología , Monocitos/metabolismo , Proteínas de Neoplasias/metabolismo , Transcriptoma/genéticaRESUMEN
BACKGROUND: Platinum-resistant or refractory ovarian cancer is a highly lethal gynecologic disease with limited treatment options. Chiauranib is a novel small-molecule selective inhibitor, which could effectively target multiple pathways including Aurora B and CSF-1R to inhibit cell cycle process and improve anti-tumor immune function, as long as VEGF pathway for tumor extinction. METHODS: A phase II study was sequentially conducted after a phase Ib monotherapy study to evaluate the efficacy of chiauranib combined with chemotherapy. Chinese patients with recurrent ovarian cancer were enrolled. Eligible patients received chiauranib combined with a maximum of six cycles of chemotherapy: etoposide (CE group) or weekly-paclitaxel (CP group). Patients, who exhibited a complete or partial response, or stable disease following combo treatment, progressed to maintenance phase to receive chiauranib monotherapy. Primary endpoint was progression-free survival (PFS) according to RECIST v1.1. RESULTS: From November 2017 to March 2019, 25 patients were enrolled in a phase 1b study and a median PFS of 3.7 months (95% CI 1.8-NE) was achieved by chiauranib monotherapy. From July 2019 to December 2020, a total of 47 patients were enrolled in the phase II study. One CP patient did not receive the study drugs, and three patients withdrew before the first tumor assessment. Thus, 43 patients (CE group: 22 patients; CP group: 21 patients) were included in the evaluation. The median PFS was 5·4 months (95% CI 2·8-5·6) and 5·6 months (95% CI 3·4-7·0), respectively. CONCLUSIONS: This was the first study to evaluate chiauranib, a novel multi-targeted kinase inhibitor in patients with ovarian cancer. The administration of chiauranib along with etoposide or weekly-paclitaxel significantly enhanced the efficacy with manageable adverse events. This warrants further clinical studies on this novel treatment. A phase III study is promising and ongoing. TRIAL REGISTRATION: ClinicaTrials.gov identifier: NCT03901118 (phase II) and NCT03166891 (phase Ib).
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Protocolos de Quimioterapia Combinada Antineoplásica , Resistencia a Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resistencia a Antineoplásicos/efectos de los fármacos , Anciano , Adulto , Resultado del Tratamiento , Paclitaxel/uso terapéutico , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversosRESUMEN
Objective: The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors. Methods: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1). Results: Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs. Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
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BACKGROUND: Immune checkpoint inhibitors targeting PD-1 or CTLA-4 individually have shown substantial clinical benefits in the treatment of malignancies. We aimed to assess the safety and antitumour activity of cadonilimab monotherapy, a bispecific PD-1/CTLA-4 antibody, in patients with advanced solid tumours. METHODS: This multicentre, open-label, phase 1b/2 trial was conducted across 30 hospitals in China. Patients aged 18 years or older with histologically or cytologically confirmed, unresectable advanced solid tumours, unsuccessful completion of at least one previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible for inclusion. Patients who had previously received anti-PD-1, anti-PD-L1, or anti-CTLA-4 treatment were not eligible for inclusion. In the dose escalation phase of phase 1b, patients received intravenous cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks. In the dose expansion phase of phase 1b, cadonilimab at 6 mg/kg and a fixed dose of 450âmg were given intravenously every 2 weeks. In phase 2, cadonilimab at 6 mg/kg was administered intravenously every 2 weeks in three cohorts: patients with cervical cancer, oesophageal squamous cell carcinoma, and hepatocellular carcinoma. The primary endpoints were the safety of cadonilimab in phase 1b and objective response rate in phase 2, based on the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The safety analysis was done in all patients who received at least one dose of cadonilimab. Antitumour activity was assessed in the full analysis set for the cervical cancer cohort, and in all patients with measurable disease at baseline and who received at least one dose of cadonilimab in the oesophageal squamous cell carcinoma and hepatocellular carcinoma cohorts. The study is registered on ClinicalTrial.gov, NCT03852251, and closed to new participants; follow-up has been completed. FINDINGS: Between Jan 18, 2019, and Jan 8, 2021, 240 patients (83 [43 male and 40 female] in phase 1b and 157 in phase 2) were enrolled. Phase 2 enrolled 111 female patients with cervical cancer, 22 patients with oesophageal squamous cell carcinoma (15 male and seven female), and 24 patients with hepatocellular carcinoma (17 male and seven female). During dose escalation, no dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events occurred in 67 (28%) of 240 patients; the most frequent grade 3 or worse treatment-related adverse events were anaemia (seven [3%]), increased lipase (four [2%]), decreased bodyweight (three [1%]), decreased appetite (four [2%]), decreased neutrophil count (three [1%]), and infusion-related reaction (two [1%]). 17 (7%) patients discontinued treatment due to treatment-related adverse events. 54 (23%) of 240 patients reported serious treatment-related adverse events, including five patients who died (one due to myocardial infarction; cause unknown for four). In phase 2, in the cervical cancer cohort, with a median follow-up of 14·6 months (IQR 13·1-17·5), the objective response rate was 32·3% (32 of 99; 95% CI 23·3-42·5). In the oesophageal squamous cell carcinoma cohort, with a median follow-up of 17·9 months (IQR 4·0-15·1), the objective response rate was 18·2% (four of 22; 95% CI 5·2-40·3). In the hepatocellular carcinoma cohort, with a median follow-up of 19·6 months (IQR 8·7-19·8), the objective response rate was 16·7% (four of 24; 95% CI 4·7-37·4). INTERPRETATION: Cadonilimab showed an encouraging tumour response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumours. FUNDING: Akeso Biopharma. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Antineoplásicos Inmunológicos , Carcinoma Hepatocelular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias Hepáticas , Neoplasias del Cuello Uterino , Humanos , Masculino , Femenino , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Antígeno CTLA-4 , Receptor de Muerte Celular Programada 1 , Empatía , Anticuerpos Monoclonales Humanizados , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/inducido químicamente , Neoplasias Hepáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: The effect of the combination of an anti-angiogenic agent with a poly (ADP-ribose) polymerase (PARP) inhibitor in cancer treatment is unclear. We assessed the oral combination of fuzuloparib, a PARP inhibitor, and apatinib, a VEGFR2 inhibitor for treating advanced ovarian cancer (OC) or triple-negative breast cancer (TNBC). METHODS: This dose-escalation and pharmacokinetics-expansion phase 1 trial was conducted in China. We used a standard 3 + 3 dose-escalation design, with 7 dose levels tested. Patients received fuzuloparib orally twice daily, and apatinib orally once daily. The study objectives were to determine the safety profile, recommended phase 2 dose (RP2D), pharmacokinetics, preliminary efficacy, and efficacy in relation to germline BRCA mutation (gBRCAmut). RESULTS: Fifty-two pre-treated patients were enrolled (30 OC/22 TNBC). 5 (9.6%) patients had complete response, 14 (26.9%) had partial response, and 15 (28.8%) had stable disease. Objective response rate (ORR) and disease control rate were 36.5% (95% CI 23.6-51.0) and 65.4% (95% CI 50.9-78.0), respectively. At the highest dose level of fuzuloparib 100 mg plus apatinib 500 mg, the ORR was 50.0% (4/8; 95% CI 15.7-84.3); this dose was determined to be the RP2D. Patients with gBRCAmut had higher ORR and longer median progression-free survival (PFS) than those with gBRCAwt, both in OC (ORR, 62.5% [5/8] vs 40.9% [9/22]; PFS, 9.4 vs 6.7 months) and TNBC (ORR, 66.7% [2/3] vs 15.8% [3/19]; PFS, 5.6 vs 2.8 months). Two dose-limiting toxicities occurred: grade 4 febrile neutropenia (fuzuloparib 100 mg plus apatinib 250 mg) and thrombocytopenia (fuzuloparib 100 mg plus apatinib 375 mg). Maximum tolerated dose was not reached. The most common treatment-related grade ≥ 3 toxicities in all patients were hypertension (19.2%), anaemia (13.5%), and decreased platelet count (5.8%). Exposure of apatinib increased proportionally with increasing dose ranging from 250 to 500 mg, when combined with fuzuloparib 100 mg. CONCLUSIONS: Fuzuloparib plus apatinib had acceptable safety in patients with advanced OC or TNBC. Fuzuloparib 100 mg bid plus apatinib 500 mg qd was established as the RP2D. With the promising clinical activity observed, this combination is warranted to be further explored as a potential alternative to chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03075462 (Mar. 9, 2017).
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Neoplasias de la Mama Triple Negativas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , China , Mutación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
BACKGROUND: The molecular subtypes of endometrial carcinoma are significantly correlated with survival outcomes and can guide surgical methods and postoperative adjuvant therapy. Among them, the TP53mut subtype has the worst prognosis and can only be determined by detection after surgery. Therefore, identifying preoperative noninvasive clinical parameters for early prediction of the TP53mut subtype would provide important guidance in choosing the appropriate surgical method and early warning for clinicians. Our study aimed to establish a model for the early prediction of the TP53mut subtype by using preoperative noninvasive parameters of endometrial cancer and screen out potential TP53mut patients. METHODS: Information and pathological specimens of 376 patients who underwent surgery for FIGO stage I-IV endometrial cancer in the Department of Gynecology, Peking University Cancer Hospital, from June 2011 to July 2020 were collected, and 178 cases were finally included in the study as the training dataset (part A). Thirty-six cases from January 2022 to March 2023 were collected as the validation dataset (part B). Molecular subtyping was performed using a one-stop next-generation sequencing (NGS) approach. Compared with the TP53mut subtype, the POLE EDM, MSI-H and TP53 wild-type subtypes were defined as non-TP53mut subtypes. Univariate Cox regression analysis and multivariate logistic analysis were performed to determine the preoperative clinical parameters associated with the TP53mut subtype. A nomogram prediction model was established using preoperative noninvasive parameters, and its efficacy in predicting TP53mut subtype and survival outcomes was verified. RESULTS: The TP53mut subtype was identified in 12.4% of the part A and 13.9% of the part B. Multivariate logistic regression analysis showed that HDL-C/LDL-C level, CA125 level, and cervical or lower uterine involvement were independent influencing factors associated with the TP53mut subtype (p = 0.016, 0.047, <0.001). A TP53mut prognostic model (TPMM) was constructed based on the factors identified in the multivariate analysis, namely, TPMM = -1.385 × HDL-C/LDL-C + 1.068 × CA125 + 1.89 × CI or LUI, with an AUC = 0.768 (95% CI, 0.642 to 0.893) in the part A. The AUC of TPMM for predicting TP53mut subtype in the part B was 0.781(95% CI, 0.581 to 0.980). The progression-free survival (PFS) and overall survival (OS) of patients with the TP53mut subtype were significantly worse than those of patients with the non-TP53mut subtype, as predicted by the model in the part A. CONCLUSIONS: TP53mut prediction model (TPMM) had good diagnostic accuracy, and survival analysis showed the model can identify patients with different prognostic risk.
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Neoplasias Endometriales , Nomogramas , Femenino , Humanos , LDL-Colesterol , Pronóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/cirugía , Supervivencia sin ProgresiónRESUMEN
OBJECTIVE: T-cell receptor (TCR) repertoire diversity is getting increasing attention as a predictive biomarker in cancer patients. However, the characteristics of the TCR together with its predictive significance for high grade serous ovarian cancer (HGSOC) patients receiving poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy remain unknown. METHODS: Twenty-seven patients with HGSOC were analyzed including 22 patients receiving PARPi maintenance therapy and 5 untreated patients as control. Peripheral blood samples were collected for TCR sequencing at baseline as well as one month and three months after the exposure to PARPi. To determine whether TCR diversity was related to PARPi efficacy, we compared the TCR repertoire between patients who had received PARPi and those who had not. RESULTS: For patients receiving PARPi treatment or not, we evaluated changes in clone abundance during PARPi maintenance and the similarity of the TCR repertoire before and after the treatment. The results revealed that patients receiving PARPi had TCR repertoires that were more stable than those of untreated cases. We next correlated TCR diversity with the efficacy of PARPi in the treatment group. The rising trend of TCR diversity after three months with PARPi treatment was associated with a longer PFS (21.7 vs 7.4 months, hazard ratio = 0.19, p < 0.001) and a better response to PARPi (91.7% vs 25.0%, p = 0.004). Furthermore, we discovered that the primary characteristic with predictive value for the effectiveness of PARPi is the considerable reduction of the high-frequency T cell clones. CONCLUSION: We suggested that the circulating TCR diversity could be a potential predictive biomarker for PARPi maintenance therapy in HGSOC.
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Antineoplásicos , Neoplasias Ováricas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Biomarcadores , Receptores de Antígenos de Linfocitos TRESUMEN
OBJECTIVE: The purpose of this study was to retrospectively assess the pattern, compliance, efficacy and safety of bevacizumab in Chinese ovarian cancer patients. METHODS: We reviewed the clinicopathological data of patients with histologically confirmed epithelial ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma, who were diagnosed and treated at the Department of Gynecologic Oncology of Peking University Cancer Hospital between May 2012 and January 2022. RESULTS: A total of 155 patients were eventually enrolled in this study, with 77 as first-line chemotherapy (FL) and 78 as recurrence therapy (RT) among which 37 patients were platinum sensitive and 41 were platinum resistant. Among the 77 patients in the FL group, 35 received bevacizumab during neoadjuvant chemotherapy (NACT) alone (NT), 23 received bevacizumab during both neoadjuvant and first-line chemotherapy (NT + FL) and 19 received bevacizumab during first-line chemotherapy alone (FLA). Among the 43 patients of NT and NT + FL groups undergoing interval debulking surgery (IDS), 38(88.4%) patients achieved optimally debulking and 24 (55.8%) patients had no residual disease after IDS. The patients in the FL group had a median progression free survival (PFS) of 15(95%CI: 9.951-20.049) months, and the 12-month PFS was 61.7%. In the RT group, the overall response rate (ORR) was 53.8%. According to multivariate analysis, the patients' platinum sensitivity had a significant impact on the PFS in the RT group. 13(8.4%) patients discontinued bevacizumab due to toxicity. Seven patients were in the FL group while 4 patients were in the RT group. The most common adverse event associated with bevacizumab therapy was hypertension. CONCLUSION: Bevacizumab is effective and well-tolerated in the real world setting of ovarian cancer treatment. Adding bevacizumab to NACT is feasible and tolerable. Receiving the regimen containing bevacizumab in the last preoperative chemotherapy did not result in increased intraoperative bleeding of IDS. Platinum sensitivity is the most important factor affecting the effectiveness of bevacizumab in recurrent patients.
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Pueblos del Este de Asia , Neoplasias Ováricas , Humanos , Femenino , Bevacizumab/uso terapéutico , Bevacizumab/efectos adversos , Estudios Retrospectivos , Neoplasias Ováricas/patología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
AIM: To gain a better understanding of the use of sentinel lymph node mapping by Chinese oncologists for endometrial cancer staging and analyze factors influencing its application. METHODS: Questionnaires were collected online before and by phone after the symposium to evaluate the general characteristics of oncologists who participated in the endometrial cancer seminar and factors associated with the application of sentinel lymph node mapping in endometrial cancer patients. RESULTS: Gynecologic oncologists from 142 medical centers participated in the survey. 35.4% of doctors employed sentinel lymph node mapping for endometrial cancer staging, 57.3% chose indocyanine green as the tracer. Multivariate analysis revealed that cancer research center (odds ratio = 4.229, 95% CI 1.747-10.237), physician familiarity with sentinel lymph node mapping (odds ratio = 126.188, 95% confidence interval 43.220-368.425) and the use of ultrastaging (odds ratio = 2.657, 95% confidence interval 1.085-6.506) were related to the doctors' selection of sentinel lymph node mapping. There was a significant difference in the surgical procedure for early endometrial cancer, the number of removed sentinel lymph node, and the reason for not adopting sentinel lymph node mapping before and after the symposium. CONCLUSIONS: The theoretical knowledge of sentinel lymph node mapping, the use of ultrastaging, and cancer research center are related to a higher acceptance of sentinel lymph node mapping. Distance learning is conducive to the promotion of this technology.
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Neoplasias Endometriales , Oncólogos , Ganglio Linfático Centinela , Femenino , Humanos , Ganglio Linfático Centinela/patología , Ganglio Linfático Centinela/cirugía , Biopsia del Ganglio Linfático Centinela , Escisión del Ganglio Linfático/métodos , Pueblos del Este de Asia , Neoplasias Endometriales/patología , Encuestas y Cuestionarios , Ganglios Linfáticos/patología , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: To produce high-quality, real-world evidence for oncologists by collating scattered gynaecologic oncology (GO) medical records in China. DESIGN: Retrospective study. SETTING: The National Union of Real-world Gynaecological Oncology Research and Patient Management Platform (NUWA platform). SAMPLE: Patient-centred data pool. METHODS: The NUWA platform integrated inpatient/outpatient clinical, gene and follow-up data. Data of 11 456 patients with ovarian cancer (OC) were collected and processed using 91 345 electronic medical records. Structured and unstructured data were de-identified and re-collated into a patient-centred data pool using a predefined GO data model by technology-aided abstraction. MAIN OUTCOME MEASURES: Recent treatment pattern shifts towards precision medicine for OC in China. RESULTS: Thirteen first-tier hospitals across China participated in the NUWA platform up to 7 December 2021. In total, 3504 (30.59%) patients were followed up by a stand-alone patient management centre. The percentage of patients undergoing breast cancer gene (BRCA) mutation tests increased by approximately six-fold between 2017 and 2018. A similar trend was observed in the administration rate of poly(ADP-ribose) polymerase inhibitors as first-line treatment and second-line treatment after September 2018, when olaparib was approved for clinical use in China. CONCLUSION: The NUWA platform has great potential to facilitate clinical studies and support drug development, regulatory reviews and healthcare decision-making.
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Pueblos del Este de Asia , Neoplasias Ováricas , Femenino , Humanos , Estudios Retrospectivos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , ChinaRESUMEN
INTRODUCTION: To evaluate the pelvic floor muscle function (PFMF) of cervical cancer patients after type QM-C hysterectomy and to explore the relationship between decreased PFMF and related factors. METHODS: This was a multi-centered retrospective cohort study. 181 cervical cancer patients who underwent type QM-C hysterectomy were enrolled from 9 tertiary hospitals. Strength of PFMF were measured using neuromuscular apparatus (Phenix U8, French). Risk factors contributing to decreased PFMF were analyzed by univariate and multivariate ordinal polytomous logistic regression. RESULTS: Totally 181 patients were investigated in this study. 0-3 level of type I muscle fibre strength (MFSI) was 52.6% (95/181), 0-3 level of type IIA muscle fibre strength (MFSIIA) was 50% (91/181). Subjective stress urinary incontinence was 46% (84/181), urinary retention was 27.3% (50/181), dyschezia was 41.5% (75/181), fecal incontinence was 9% (18/181). â MFSI: Multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05), chemotherapy and radiotherapy (p = 0.038) are independent risk factors of MFSI's reduction after type QM-C hysterectomy. â¡ MFSIIA: multivariate ordinal polytomous logistic regression shows that the follow-up time (p < 0.05) are independent risk factors of MFSIIA's reduction after type QM-C hysterectomy. The pelvic floor muscle strength (PFMS) increased after 9 months than in 9 months after operation, which showed that the PFMS could be recovered after operation. CONCLUSIONS: We advocate for more attention and emphasis on the PFMF of Chinese female patients with cervical cancer postoperation. PEKING UNIVERSITY PEOPLE'S HOSPITAL: PFMF after QM-C hysterectomy has not been analyzed by current study. The contribution is that patients with radical hysterectomy should do pelvic floor rehabilitation exercises in 3 months after operation. Clinical Trails NCT number of this study is 02492542.
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Incontinencia Urinaria de Esfuerzo , Neoplasias del Cuello Uterino , Femenino , Humanos , Histerectomía/efectos adversos , Diafragma Pélvico , Estudios Retrospectivos , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/cirugía , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
PURPOSE: Maintenance therapy with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib provided a substantial progression-free survival (PFS) benefit compared with placebo in patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (BRCAm) who were in clinical complete or partial response following platinum-based chemotherapy in the Phase III SOLO1 global study. This led to the approval of maintenance olaparib in China, USA, EU, Japan and other countries, in the newly diagnosed setting. This separate China cohort of the SOLO1 study investigated the efficacy and safety of maintenance olaparib within the Chinese population. PATIENTS AND METHODS: In this double-blind, multicentre study, patients were randomized 2:1 to receive oral olaparib tablets (300 mg twice daily) or placebo. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). RESULTS: Of the 64 randomized patients, 44 received olaparib and 20 placebo. Olaparib reduced the risk of disease progression or death by 54% compared with placebo (HR 0.46, 95% Cl 0.23-0.97; median PFS was not reached in the olaparib arm vs 9.3 months in the placebo arm). The most common AEs in the olaparib arm were nausea (63.6 vs 25.0% with placebo), anaemia (59.1 vs 15.0%) and leukopenia (54.5 vs 20.0%). Grade ≥3 AEs were experienced by 56.8% of olaparib patients and 30.0% of placebo patients. CONCLUSIONS: Results in the SOLO1 China cohort support the use of olaparib as maintenance treatment for Chinese patients with newly diagnosed advanced ovarian cancer who have a BRCAm and are in complete or partial response after platinum-based chemotherapy.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/administración & dosificación , Piperazinas/administración & dosificación , Pueblo Asiatico/genética , China , Estudios de Cohortes , Método Doble Ciego , Femenino , Mutación de Línea Germinal , Humanos , Quimioterapia de Mantención , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Ftalazinas/efectos adversos , Piperazinas/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversosRESUMEN
AIMS: To assess the pelvic floor function in cervical cancer patients after radical hysterectomy and its relationship with urinary incontinence (UI). METHODS: Cervical cancer patients who underwent radical hysterectomy were recruited from 18 hospitals in China from January 2012 to March 2015. Pelvic floor examinations were conducted by measuring the pelvic floor muscle strength, fatigue of pelvic floor muscle fatigue, dynamic pressure of vaginal, nerve injury, A3 feedback, muscle potential, static tension, and dynamic tension. Postoperative urinary incontinence (UI) was identified using the International Consultation on Incontinence Questionnaire. Multivariable logistic regression analysis was used to assess the association of pelvic floor function examination results with postoperative UI. RESULTS: Totally 169 patients were included in this study. The prevalence of UI was 39.6% (67/169). The proportion of abnormal fatigue of Type I muscle (64% vs. 36%, p = .04) and abnormal A3 feedback (53.9% vs. 46.1%, p = .03) were higher among patients with postoperative UI compared to those without UI. In the multivariable analysis, abnormal fatigue of Type I muscle (odds ratio [OR] = 3.73, 95% confidence interval [CI]: 1.42-9.84), abnormal A3 feedback (OR = 2.40, 95% CI: 1.04-5.51), and length of resected vagina > 3 cm (OR = 3.44, 95% CI: 1.27-9.31) were associated with postoperative UI. Compared to laparoscopy, laparotomy was less likely to cause postoperative UI (OR = 0.12, 95% CI:0.04-0.33). CONCLUSIONS: The abnormal function of the pelvic floor muscle is related to postoperative UI. Early assessment among these patients is needed to prevent the development of pelvic floor disorder postoperatively.
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Histerectomía/efectos adversos , Diafragma Pélvico/fisiopatología , Incontinencia Urinaria/fisiopatología , Neoplasias del Cuello Uterino/complicaciones , Adulto , Femenino , Humanos , Histerectomía/métodos , Masculino , Persona de Mediana Edad , Trastornos del Suelo Pélvico/fisiopatología , Periodo Posoperatorio , Neoplasias del Cuello Uterino/cirugíaRESUMEN
OBJECTIVES: Our study aimed to evaluate the quality of life (QoL) and pelvic floor function of cervical cancer (CC) patients after treatment. DESIGN: This was a cross-sectional observational cohort study. PARTICIPANTS: The participants included in this study were CC patients who underwent radical hysterectomy (RH) from 2012 to 2018 at 18 medical centers across China. METHODS: The validated versions of the Pelvic floor Distress Inventory-Short Form 20, Overactive Bladder Symptom Score, and Euro Qol Five-Dimension questionnaires were used to evaluate postoperative pelvic floor dysfunction (PFD) and QoL. RESULTS: A total of 689 CC patients were enrolled. The incidence of stress urinary incontinence (SUI), incomplete urinary emptying, and constipation were 32.7, 27.7, and 28.6%, respectively. Multivariate analysis confirmed that laparoscopic RH (LRH) and vaginal wall resection greater than 3 cm were risk factors for lower urinary tract symptoms (LUTS). LRH and chemotherapy were risk factors for SUI. Chemoradiotherapy and LRH were risk factors for overactive bladder (OAB). A high body mass index and LRH were risk factors for more severe defecation symptoms. ARH and large amount of operative blood loss were risk factors for poor QoL. CONCLUSION: PFD is common in CC patients after treatment. LRH seems to increase the postoperative distress, including LUTS and defecation symptoms. Postoperative urinary incontinence and OAB are more bothersome for patients undergoing chemotherapy and radiotherapy. We recommend evaluating pelvic floor function as a standard assessment during follow-up.
Asunto(s)
Diafragma Pélvico , Neoplasias del Cuello Uterino , Estudios Transversales , Femenino , Humanos , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/cirugíaRESUMEN
AIM: To investigate the value of pretreatment neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in predicting lymph node metastasis in patients with endometrial cancer. METHODS: A retrospective analysis of 145 patients with endometrial cancer who were treated at the Peking University Cancer Hospital and Institute between October 2010 and November 2013 was performed. Preoperative NLR, PLR, serum CA125 and HE4 were assessed. Clinicopathological parameters were evaluated for LN metastasis using logistic regression. Receiver operating characteristic (ROC) curves were plotted and the optimal cut-off values of NLR, PLR, CA125 and HE4 were calculated for predicting lymph node metastasis. RESULTS: The levels of NLR, PLR, serum CA125 and HE4 were significantly higher in patients with lymph node metastasis than those without lymph node metastasis. Multivariate analysis showed that only the higher NLR and HE4 were independent predictors for lymph node metastasis (odds ratio, OR = 3.509, P = 0.016; OR = 1.446, P = 0.016). The optimal cut-off values of NLR and HE4 for predicting lymph node metastasis were 2.50 (area under the curve, AUC = 0.809) and 80.4 pmol/L (AUC = 0.713). The sensitivity and specificity were 75.0% and 84.9% for NLR, 86.7% and 73.8% for HE4, respectively. When HE4 was combined with NLR to predict lymph node metastasis, the sensitivity and specificity were significantly improved. CONCLUSION: Preoperative higher NLR and serum HE4 are predictors of lymph node metastasis in endometrial cancer, and the predictive value was superior to that of serum CA125.
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Neoplasias Endometriales , Neutrófilos , Neoplasias Endometriales/cirugía , Femenino , Humanos , Metástasis Linfática , Linfocitos , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
OBJECTIVE: The purpose of this study was to explore the factors influencing the sexual quality of life of patients with cervical cancer who underwent radical hysterectomy. METHODS: This multicenter retrospective cohort study was conducted from June 2013 to June 2018 at nine hospitals in China. In total, 204 women diagnosed with stage IA to stage IIB cervical cancer who underwent radical hysterectomy completed the questionnaire. Sexual function was measured with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ). All analyses were performed with R version 3.4.3 statistical software packages. A two-sided significance level of 0.05 was used to evaluate the statistical significance. RESULTS: The mean sexual quality of life score was 37.21 ± 17.28, where a higher PISQ score indicates a better sexual quality of life, and we identified the factors associated with sexual dysfunction. The average follow-up time was 29.0 ± 16.0 months. In addition to radical hysterectomy, 182 (89.2%) patients underwent ovarian suspension, 93 (45.6%) underwent chemotherapy, and 74 (36.3%) underwent concurrent radiotherapy. The univariate analysis confirmed that age represents a protective factor for sexual function (odds ratio (OR) 6.0, 95% confidence interval (CI) 1.1-10.8, p = 0.017). The patients who underwent ovarian suspension were more likely to experience a good sexual quality of life (OR - 7.2, 95% CI [- 14.8, - 0.4], p = 0.035) compared to those who did not undergo ovarian suspension. A significant negative association was observed between radiotherapy and the behavioral-emotive, physical and partner-related domains of the PISQ (behavioral-emotive, OR - 1.5, 95% CI [- 2.6, - 0.4], p = 0.011; physical, OR - 0.9, 95% CI [- 1.5, - 0.3], p = 0.006; partner-related, OR - 0.7, 95% CI [- 1.3, 0.0], p = 0.043). Chemotherapy and radiotherapy were common risk factors for sexual dysfunction, and radiotherapy exerted a stronger effect than chemotherapy. CONCLUSIONS: This study shows that the sexual function of cervical cancer patients tends to be related to age, radiotherapy, and chemotherapy. However, across these factors, patients with preserved ovaries tend to return to a satisfactory sexual quality of life after recovering from surgery.
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Supervivientes de Cáncer , Prolapso de Órgano Pélvico , Neoplasias del Cuello Uterino , Femenino , Humanos , Calidad de Vida , Estudios Retrospectivos , Conducta Sexual , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/terapiaRESUMEN
LESSONS LEARNED: Pharmacokinetics characteristics of niraparib in Chinese patients were similar to those in white patients. Niraparib could be well tolerated by Chinese patients, and adverse events were manageable in this study. Population pharmacokinetics analysis indicated that baseline body weight had a modest impact on pharmacokinetics parameters of niraparib; however, it was not considered clinically important. BACKGROUND: This randomized, open-label, single-arm, phase I study was designed to investigate the pharmacokinetics (PK) and safety of niraparib in Chinese patients with epithelial ovarian cancer. METHODS: Eligible patients were randomized in a 1:1:1 ratio to receive 100, 200, or 300 mg of niraparib once daily. PK parameters were analyzed after single and multiple dose administrations. RESULTS: Thirty-six Chinese patients were enrolled in total. Niraparib was rapidly absorbed after administration, and median time-to-peak (Tmax ) was 3 hours. The long terminal elimination half-life (T1/2 â¼ 35 hours) supports once-daily dosing regimen. The exposure to niraparib showed linear and dose-proportional pharmacokinetics, whereas other PK parameters such as Tmax , T1/2 , and accumulation ratio were dose independent. Population PK analysis indicated that there was no effect of race on niraparib PK parameters, whereas baseline body weight had a modest impact on niraparib exposure. Grade 3/4 treatment-emergent adverse events (TEAEs; reported in ≥10% of patients) included platelet count decreased (a total of five patients who were all from the 300-mg group) and neutrophil count decreased. The TEAEs were manageable after dose modification. CONCLUSION: The PK profile of niraparib in Chinese patients is consistent with that in white patients. Niraparib is safe and well tolerated in Chinese patients with ovarian cancer.
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Indazoles/farmacocinética , Indazoles/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Piperidinas/farmacocinética , Piperidinas/uso terapéutico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Femenino , Humanos , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacologíaRESUMEN
AIM: The use of prophylactic antibiotics has greatly reduced the incidence of surgical site infections after hysterectomy. It is worth discussing which antibiotic is better. The purpose of this study was to investigate the role of the combined utilization of cefazolin and metronidazole for the prevention of surgical site infection in laparoscopic staging surgery of endometrial cancer. METHODS: A retrospective analysis was performed on the incidence of surgical site infection in patients with endometrial cancer who underwent laparoscopic surgical staging from January 2000 to June 2019 within 1 month after surgery. Logistic regression model was used for univariate and multivariate analysis. RESULTS: A total of 1783 patients were included in this study, of which 641 were treated with cefazoline plus metronidazole (group 1) as a prophylactic antibiotic, while the other 1142 were treated with cefoxitin (group 2). There was no difference in clinical characteristics between the two groups. The rates of surgical site infection in groups 1 and 2 were 3.6% (n = 23) and 5.7% (n = 65), respectively. The most common site of infections was vaginal, with the incidence of 1.7% (n = 11) and 3.3% (n = 38) in groups 1 and 2, respectively. The multivariate analysis disclosed that cefazoline plus metronidazole significantly reduced the incidence of surgical site infections compared with cefoxitin (logistic, odds ratio = 2.213, 95% confidence interval 1.193 to 4.107). CONCLUSION: Cefazolin plus metronidazole as prophylactic antibiotics for surgical staging of endometrial cancer can more effectively reduce the incidence of surgical site infections than cefoxitin.
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Cefazolina , Neoplasias Endometriales , Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Cefoxitina , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/cirugía , Femenino , Humanos , Metronidazol , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
OBJECTIVE: The role of selective lymphadenectomy at the time of interval debulking surgery in patients with advanced ovarian cancer remains a topic of debate. This study aimed to evaluate the value of selective lymphadenectomy during interval debulking surgery in patients with radiologic evidence of lymph node metastasis at initial diagnosis that ultimately become negative on imaging after neoadjuvant chemotherapy. METHODS: A retrospective analysis including patients with stage IIIC-IV epithelial ovarian cancer and suspicious pelvic or para-aortic lymph node metastasis by imaging at diagnosis that resolved after neoadjuvant chemotherapy. The study was conducted from January 1996 to June 2016 with R0 interval debulking surgery. The patients with disease progression after neoadjuvant chemotherapy were excluded. Suspicious metastatic lymph nodes at initial diagnosis by computed tomography/magnetic resonance imaging were excised by selective lymphadenectomy. Survival curves were constructed by the Kaplan-Meier method, and a multivariate analysis was performed using Cox regression. RESULTS: There were a total of 330 patients included in the analysis. Selective lymphadenectomy of suspicious nodes (Group 1) was performed in 145 patients. Systematic lymphadenectomy (Group 2) was performed in 118 patients. Sixty-seven patients did not undergo lymphadenectomy (Group 3). There were no significant differences in clinicopathologic features among the groups. Median progression-free survival was 28, 30.5, and 22 months in Groups 1, 2, and 3, respectively (log-rank, p=0.049). No-lymphadenectomy was an independent factor affecting progression-free survival (Cox analysis, HR=1.729, 95% CI 1.213 to 2.464, p=0.002), with no difference between Groups 1 and 2 (Cox analysis, HR=1.097, 95% CI 0.815 to 1.478, p=0.541). Median overall survival was 50, 59, and 57 months in Groups 1, 2, and 3, respectively (Cox analysis, p=0.566). Patients who underwent selective lymphadenectomy had lower 1-year frequencies of lower extremity lymphedema and lymphocysts than those with systematic lymphadenectomy (6.2% vs 33.1%, p<0.001, and 6.2 % vs 27.1%, p<0.001, respectively). CONCLUSIONS: Extent of lymphadenectomy (systematic or selective) had no significant impact on progression-free survival or overall survival. In addition, the risks of lower extremity lymphedema and lymphocysts were lower in patients who underwent selective lymphadenectomy.
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Carcinoma Epitelial de Ovario/cirugía , Ganglios Linfáticos/cirugía , Neoplasias Ováricas/cirugía , Anciano , Carcinoma Epitelial de Ovario/diagnóstico por imagen , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/patología , Quimioterapia Adyuvante , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/patología , Metástasis Linfática , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/dietoterapia , Neoplasias Ováricas/patología , Estudios RetrospectivosRESUMEN
OBJECTIVE: The aim of this study was to explore the role of chemotherapy as adjuvant treatment for early-stage endometrial cancer (EC) with high-intermediate-risk (HIR) factors. METHODS: A prospective study of patients with early-stage EC with HIR factors for recurrence was performed between 2006 and 2014. A total of 96 patients were enrolled, and 50 patients received 3 cycles of platinum-based chemotherapy after surgery. Five-year disease-free survival and overall survival were evaluated. RESULTS: A total of 11 (11.5%) of the 96 patients had recurrence, with a median recurrent time of 15.4 months. Of these 11 patients with recurrence, 2 received adjuvant chemotherapy after surgery, whereas 9 did not receive any treatment. Patients without adjuvant chemotherapy exhibited a significantly higher recurrence rate than those with adjuvant chemotherapy (19.6% vs 4%; P = 0.024). Meanwhile, patients with adjuvant chemotherapy had significantly higher 5-year disease-free survival compared with the control group (92.1% vs 70.0%, P = 0.024). CONCLUSIONS: Chemotherapy is feasible and safe as adjuvant treatment for early-stage EC with HIR factors. Three cycles of platinum-based chemotherapy are sufficient for reducing the risk of recurrence. Further, large sample randomized studies are needed to confirm these results.