Analysis of prognosis and associated factors in multiple recurrent epithelial ovarian cancer with three times or more cytoreductive surgeries / 中华妇产科杂志

Objective:To explore the prognosis of epithelial ovarian cancer patients with multiple recurrences (≥2 times) who underwent three times or more cytoreductive surgeries, and to analyze the factors associated with prognosis.Methods:The clinicopathological data and follow-up data of 23 patients with ovarian cancer admitted to the Obstetrics and Gynecology Hospital of Fudan University from January 1, 2015 to January 30, 2022 with three times or more cytoreductive surgeries were collected. The degree of surgical resection, site of recurrence and metastasis, postoperative complications, and prognosis were retrospectively analyzed. The univariate Cox proportional hazards model was performed to identify the variables associated with survival.Results:(1) The median age of 23 patients with multiple recurrent ovarian cancer was 48 years old (44-55 years). Among them, 18 cases underwent tertiary cytoreductive surgery (TCS), 2 cases underwent quaternary cytoreductive surgery, 2 cases underwent quinary cytoreductive surgery, and 1 case underwent senary cytoreductive surgery. Among the 23 patients with multiple recurrent ovarian cancer, 21 cases (91%, 21/23) had serous carcinoma, 16 cases (70%, 16/23) had advanced stage (stage Ⅲ-Ⅳ), and 19 cases (83%, 19/23) had high differentiation. (2) Based on the premise that satisfactory cytoreduction was achieved by primary debulking surgery (PDS) and no visible residual disease (R0) was achieved by secondary cytoreductive surgery (SCS), the maximum diameter of the recurrent tumors was up to 10.0 cm and 62% (20/32) of patients with multiple metastatic sites. The R0 rate for three times or more cytoreductive surgeries (32 times in total) reached 88% (28/32), with a postoperative complication rate of 47% (15/32), and only 3% (1/32) for grade Ⅲ or above. During a median follow-up time of 31.1 months (20.6-43.9 months) after TCS, 20 patients (87%, 20/23) recurred after TCS, and 8 patients (35%, 8/23) eventually died of ovarian cancer. Among them, the three-year postoperative survival rate of 22 patients with R0 was 57.6%, and the patient with residual lesions ≥1 cm died at 9.2 months after TCS. (3) In univariate analysis, ages, the time interval between PDS and SCS >32 months, the interval between SCS and TCS >16 months, and no metastatic peritoneal carcinoma were associated with longer progression free survival after TCS (all P<0.05); while treatment-free interval (TFI) >10 months after SCS, the interval between SCS and TCS >16 months, no ascites and platinum-sensitive status were associated with disease-specific survival after TCS (all P<0.05). Conclusions:It is feasible to perform three times or more cytoreductive surgeries in patients with multiple recurrent ovarian cancer who are expected to achieve R0 and have manageable complications. However, the pros and cons of surgery need to be carefully evaluated for the patients whose ascites are massive and whose previous cytoreduction does not achieve R0. A prolonged TFI and previously longer surgical interval might get potential survival benefits.

Real-world clinical data analysis of PARPi as first-line maintenance therapy in newly diagnosed epithelial ovarian cancer patients / 中华妇产科杂志

Objective:The real-world clinical data of patients with newly diagnosed ovarian cancer (including fallopian tube cancer and primary peritoneal cancer) who received first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi) were retrospectively analyzed, and the prognostic factors were preliminarily explored.Methods:(1) The clinicopathological data and follow-up data of ovarian cancer patients treated with PARPi first-line maintenance therapy from August 2018 (PARPi was launched in China) to December 31, 2021 in Sichuan Cancer Hospital were collected (real-world clinical data). (2) According to the different types of PARPi, real-world clinical data were divided into olaparib group and niraparib group, which were respectively compared with the inclusion and exclusion criteria of representative domestic and foreign phase Ⅲ randomized controlled trials (RCT), including olaparib as first-line maintenance therapy for advanced ovarian cancer patients with BRCA1/2 gene mutation (SOLO-1 study), niraparib as first-line maintenance therapy (PRIMA study), and niraparib as first-line maintenance therapy for Chinese advanced ovarian cancer patients (PRIME study). (3) The prognosis of the two groups and the prognostic factors were analyzed.Results:(1) A total of 83 patients were included in this study, with a median age of 51 years (47-57 years), including 75 cases of ovarian cancer, 5 cases of fallopian tube cancer, and 3 cases of primary peritoneal cancer; 5 cases of stage Ⅰ, 9 cases of stage Ⅱ, 55 cases of stage Ⅲ, 12 cases of stage Ⅳ, and 2 cases of unknown stage; neoadjuvant chemotherapy (NACT) was performed in 40 cases and non-NACT in 43 cases; 62 cases had no visible residual lesion after surgery (R0), 9 cases had residual disease lesions <1 cm (R1), 8 cases had residual disease lesions ≥1 cm (R2), and 4 cases with unknown postoperative residual disease. Thirty-two cases had PARPi treatment interruption, 40 cases had PARPi reduction, and 1 case terminated treatment due to acute leukemia. Of the 83 patients, 35 were in the olaparib group and 48 were in the niraparib group. The proportion of patients with high-grade serous carcinoma (100% and 75%, respectively) and the proportion of BRCA mutant patients (91% and 10%, respectively) in the olaparib group were higher than those in the niraparib group (all P<0.01). (2) Compared with the inclusion and exclusion criteria of the SOLO-1 study, the olaparib group had only 60% (21/35) coincidence rate; compared with the inclusion and exclusion criteria of PRIMA and PRIME studies, the coincidence rates of niraparib group were only 31% (15/48) and 69% (33/48). The most common reasons for non-compliance were number of chemotherapy courses, histopathological type, and surgical pathological stage. (3) Of the 83 cases received first-line maintenance therapy with PARPi, the median follow-up was 15.9 months (11.3-22.9 months), the median progression-free survival (PFS) was 29.7 months (95% CI: 25.9-33.6 months), and the median overall survival was 49.8 months (95% CI: 47.4-52.2 months). Univariate analysis showed that unilateral or bilateral ovarian cancer, efficacy after platinum-containing chemotherapy, presence or absence of measurable lesions at the end of chemotherapy, and total number of chemotherapy courses were significantly associated with PFS (all P<0.05). Multivariate analysis showed that unilateral or bilateral ovarian cancer, total number of chemotherapy courses, and efficacy after platinum-containing chemotherapy were independent factors affecting PFS in stage Ⅱ-Ⅳ patients with PARPi first-line maintenance therapy (all P<0.05). Conclusions:Unilateral ovarian cancer, the total number of chemotherapy courses no more than 9, and achieving complete response after platinum-containing chemotherapy before maintenance therapy are independent influencing factors of PFS benefit in patients with PARPi first-line maintenance therapy. Due to the large differences between the patients in real clinical practice and the research subjects of phase Ⅲ RCT, the results of representative retrospective studies still have important clinical reference significance.

Impact of proper surgical treatment on the survival of patients with epithelial ovary cancer / Impacto do tratamento cirúrgico adequado na sobrevida de mulheres com carcinoma epitelial ovariano

ABSTRACT Objective: to evaluate the quality of surgical treatment of ovarian cancer patients and assess the impact of adequate surgical oncological treatment on disease-free survival and overall survival of patients with advanced epithelial ovarian cancer. Methods: this is an observational, retrospective study with quantitative analysis, with the collection of data in medical records of a temporal convenience sample of patients diagnosed with ovarian cancer admitted to a High Complexity Oncology Unit, in Belo Horizonte, from the period of 2014 to 2020. Results: a total of 91 patients diagnosed with ovarian cancer were evaluated, with the epithelial histopathological type being the most frequent (85%). Of this total, 68 patients (74.7%) had advanced-stage ovarian cancer. Appropriate surgical treatment was performed in 30.9% of patients with advanced epithelial ovarian cancer and the type of performed surgery was statistically significant for overall survival. This low proportion of appropriate surgical oncological treatment was not related to surgical specially or surgeon competence, but mainly to advanced disease related to patient flow at UNACON. It was not possible to confirm if the advanced-stage disease was related to tumor biology or losing time from diagnosis to oncological surgery. Conclusion: overall survival of advanced-stage epithelial ovarian cancer patients is directly influenced by appropriate surgical treatment, however, in this study, the percentage of advanced ovarian cancer receiving adequate surgical treatment was much lower than the rates reported in the literature. To improve these outcomes, we believe that surgeons should keep following patients during neoadjuvant chemotherapy to point to a better time for surgery, and clinical oncologists should better consider adequate oncological surgery as one of the pillars of ovarian cancer treatment and get more involved in facilitating surgeries.

RESUMO Objetivo: avaliar a qualidade do tratamento cirúrgico de pacientes com câncer de ovário e o impacto do tratamento oncológico cirúrgico adequado na sobrevida livre de doença e sobrevida global de pacientes com câncer de ovário epitelial avançado. Métodos: Trata-se de um estudo observacional, retrospectivo, de análise quantitativo, com coleta de dados em prontuários de uma amostra de conveniência temporal de pacientes com diagnóstico de câncer de ovário internadas em uma Unidade de Oncologia de Alta Complexidade (UNACON), em Belo Horizonte, no período de 2014 a 2020. Resultados: foram avaliadas 91 pacientes diagnosticadas com câncer de ovário, sendo o tipo histopatológico epitelial o mais frequente (85%). Desse total, 68 pacientes (74,7%) apresentavam câncer de ovário em estágio avançado. O tratamento cirúrgico adequado foi realizado em 30,9% das pacientes com câncer de ovário epitelial avançado e o tipo de cirurgia realizada foi estatisticamente significativo para a sobrevida global. Essa baixa proporção de tratamento cirúrgico oncológico adequado não esteve relacionada à especialidade cirúrgica ou competência do cirurgião, mas principalmente à doença avançada relacionada ao fluxo de pacientes na UNACON. Não foi possível confirmar se a doença em estágio avançado estava relacionada à biologia tumoral ou à perda de tempo do diagnóstico para a cirurgia oncológica. Conclusão: A sobrevida global de pacientes com câncer de ovário epitelial em estágio avançado é diretamente influenciada pelo tratamento cirúrgico adequado. Porém, o percentual de câncer de ovário avançado recebendo tratamento cirúrgico adequado foi muito inferior aos índices relatados na literatura. Para melhorar esses resultados, acreditamos que os cirurgiões devem continuar acompanhando as pacientes durante a quimioterapia neoadjuvante para apontar um melhor momento para a cirurgia, e os oncologistas clínicos devem considerar melhor a cirurgia oncológica adequada como um dos pilares do tratamento do câncer de ovário e se envolver mais na facilitação das cirurgias.

Preliminary study on the diagnostic value of serum-derived exosomal lncRNA in epithelial ovarian cancer / 中华妇产科杂志

Objective:To investigate the diagnostic value of long noncoding RNA (lncRNA) extracted from serum exosomes in epithelial ovarian cancer (EOC).Methods:(1) Patients with ovarian tumors who were hospitalized in the Affiliated Tumor Hospital of Guangxi Medical University from August 2018 to December 2019, including 35 cases of EOC patients (malignant group) and 20 cases of benign ovarian tumor patients (benign group) were collected; during the same period, 15 healthy women (normal group) who underwent physical examination in the Affiliated Tumor Hospital of Guangxi Medical University were used as controls. Fasting venous blood serum was collected from the above three groups of women, and serum exosomes were isolated and purified using commercial kits. The morphology of exosomal particles was observed with transmission electron microscope, and the particle size distribution of the exosomes was detected by NanoSight technology. The expression of specific proteins cluster of differentiation (CD) 63, CD 81, and tumor susceptibility gene 101 (TSG101) of exosomes were analyzed by western blot. (2) Four cases of EOC patients and three cases of healthy women were randomly selected. High-throughput sequencing technology was used to analyze the differentially expressed lncRNA in serum exosomes of these four EOC patients and three healthy women, and screen out the significantly differentially expressed lncRNA. The screened lncRNA with different expression levels was verified by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) in these seven original clinical samples, furtherly confirmed and tested with QRT-PCR in larger clinical samples (a total of 70 serum samples). (3) The receiver operating characteristic (ROC) curve of the target lncRNA was drawn and its diagnostic indicators such as sensitivity and specificity were evaluated. By using logistic binary regression model, multi-factor joint diagnostic models were constructed and evaluated. Results:(1) Under transmission electron microscope, clear lipid bilayer structure was observed in serum exosomes, and one side presented a concave hemispheric or cup like structure; the peak diameter of the exosomal particles detected with NanoSight technology was 127.6 nm, and the particles between 30 and 150 nm accounted for 58.9%; western blot confirmed that the obtained (exosomal) particles could detect the expression of the marker proteins CD 63, CD 81, and TSG101. (2) Analysis of high-throughput sequencing technology showed that compared with the women in the normal sequencing group (3 cases), 425 differentially expressed lncRNAs (including 23 up-regulated and 402 down-regulated) were screened in the serum exosomes of the malignant sequencing group (4 cases). Six types of lncRNA with significantly abnormal expression levels (including FER1L6-AS2, LINC00470, LINC01811, CXXC4-AS1, LINC02343, and LINC02428) were randomly selected for original sample verification, and the results were consistent with the sequencing results. Subsequently, these six lncRNAs were used for larger samples QRT-PCR verification. Compared with the benign and normal groups, the expression of FER1L6-AS2, LINC00470 and LINC01811 in malignant group increased by 1.66 and 1.84-fold, 2.05 and 2.46-fold, 2.94 and 2.35-fold, respectively; the expressions of CXXC4-AS1, LINC02343 and LINC02428 were down-regulated to 29% and 34%, 40% and 46%, 42% and 42%, respectively. For the same lncRNA, there were statistical differences between the malignant group and the benign group, between the malignant group and the normal group (all P<0.05), and there were no statistical differences between the benign group and the normal group (all P>0.05). (3) The results showed that the area under curve (AUC) of these six lncRNAs ranged from 0.722 to 0.805, which had moderate diagnostic efficiency. To use logistic binary regression model to establish multi-indicator joint diagnostic models and establish different joint factor ROC curves. The results showed that the AUC of the joint factor prediction model 1 (composed of FER1L6-AS2 and LINC01811), the joint factor prediction model 2 (composed of CXXC4-AS1, LINC02343, and LINC02428), and the joint factor prediction model 3 (composed of FER1L6-AS2, CXXC4-AS1, LINC02343, and LINC02428) were 0.865, 0.934, and 0.962, respectively. The diagnostic efficacy of the combined factor prediction models was higher than that of the single lncRNA (all P<0.05). Conclusions:High-throughput sequencing technology is an effective method for screening out the different expression levels of lncRNA extracted from serum exosomes. The combined detection of multiple serum exosomal lncRNA indicators has a certain diagnostic efficacy for patients with EOC. Detection of serum exosomal lncRNA indicators will provide new ideas for the diagnosis of EOC.

Establishment and application of a nomogram model for prognostic risk prediction in patients with epithelial ovarian cancer / 中华妇产科杂志

Objective:To explore the prognostic factors of epithelial ovarian carcinoma (EOC), construct a nomogram model, and evaluate the prognosis of EOC patients.Methods:A retrospective analysis was performed on clinicopathological data of 208 cases of EOC patients who received initial treatment in the First Affiliated Hospital of Army Medical University from August 11, 2016 to July 11, 2018, including age, preoperative ascites, preoperative neoadjuvant chemotherapy, surgical method, pathological type, pathological differentiation degree, surgical pathology stage, preoperative and post-chemotherapy serum cancer antigen 125 (CA 125) level, human epididymal protein 4 (HE4) level, platelet count and platelet/lymphocyte number ratio (PLR). The univariate and multivariate Cox risk ratio models were used to analyze the related factors affecting progression free survival (PFS) in EOC patients, and the prediction nomogram of PFS in EOC patients was established to evaluate its efficacy in predicting PFS. Results:Univariate analysis showed that preoperative neoadjuvant chemotherapy, pathological type, pathological differentiation degree, surgical pathology stage, serum CA 125 and HE4 level before operation and after chemotherapy, platelet count and PLR before operation and after chemotherapy were significantly correlated with PFS in EOC patients (all P<0.05). Multivariate analysis showed that surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy were independent prognostic factors affecting PFS of EOC patients (all P<0.01). The index coefficient of the prediction model for the prognosis of EOC patients established by this method was 0.749 (95% CI: 0.699-0.798), which had good prediction ability, and could help clinicians to more accurately evaluate the prognosis of EOC patients. Conclusion:The nomogram model constructed based on surgical pathology stage, preoperative PLR, serum CA 125 and HE4 level after chemotherapy could effectively predict the PFS of EOC patients after initial treatment, could help clinicians to screen high-risk patients, provide individualized treatment, and improve the prognosis of EOC patients.

Expression of lnc-MyD88 and its relationship with the prognosis of patients with epithelial ovarian cancer / 中华妇产科杂志

Objective:To explore the expression of long non-coding RNA-myeloid differentiation factor 88 (lnc-MyD88) and its relationship with the prognosis of patients with epithelial ovarian cancer (EOC).Methods:A total of 70 EOC patients who underwent initial cytoreductive surgery and platinum-based drugs combined with paclitaxel for 6 to 8 courses were selected at Sichuan Cancer Hospital from January 2016 to January 2019. The fresh cancer tissue specimens were collected. In addition, 28 fresh normal ovarian tissues from patients who underwent surgery for benign gynecological diseases during the same period were collected as control group. Reverse transcription (RT) and real-time quantitative polymerase chain reaction (qPCR) were used to detect the expression of lnc-MyD88 and myeloid differentiation factor 88 (MyD88) mRNA in EOC tissues and normal ovarian tissues. The correlation between the expression of lnc-MyD88 and MyD88 mRNA in EOC was analyzed by Pearson′s correlation coefficient. The relationship between lnc-MyD88 expression and clinicopathological characteristics of patients with EOC was analyzed. Kaplan-Meier method was used to calculate the survival rate of patients. The log-rank test was used for univariate survival analysis, and Cox proportional hazard model was used for multivariate survival analysis.Results:(1) RT-qPCR showed that the relative expression level of lnc-MyD88 and MyD88 mRNA in EOC were 0.009 (0.000-0.049) and 0.001 (0.000-0.006), respectively, which were significantly higher than those of normal ovarian tissues (all P<0.01); Pearson′s correlation coefficient showed that the expression of lnc-MyD88 and MyD88 mRNA in EOC was positively correlated ( r2=0.610, P<0.01). (2) The high expression rate of lnc-MyD88 in EOC patients with lymph node metastasis, distant metastasis and chemotherapy resistance (71%, 64% and 70%, respectively) were significantly higher than the patients in control group (41%, 40% and 35%, respectively; all P<0.05). There were no statistically significant in the high expression rate of lnc-MyD88 in EOC patients with different ages, pathological types, pathological grades, surgical pathological stages, postoperative residual lesion size, and ascites cancer cells (all P>0.05). (3) Univariate analysis showed that surgical pathological staging, lymph node metastasis, distant metastasis, postoperative residual tumor size, and high expression of lnc-MyD88 and MyD88 mRNA significantly affected the progression-free survival (PFS) and overall survival (OS) of EOC patients (all P<0.05), ascites cancer cells were the risk factors that significantly affected PFS in EOC patients ( P=0.040); multivariate analysis showed that surgical pathological staging and high expression of lnc-MyD88 and MyD88 mRNA were independent factors affecting PFS and OS in EOC patients (all P<0.05), the size of residual lesions after surgery was an independent factor affecting PFS in EOC patients ( P=0.001). Conclusions:The level of lnc-MyD88 expression in ovarian cancer tissues was significantly increased. Lnc-MyD88, as a molecular marker for the poor prognosis of EOC, is related to the expression of MyD88 in EOC, and may be involved in its expression regulation, thereby affecting the survival and prognosis of EOC patients.

Progress of exosomes involved in multiple origins of ovarian epithelial carcinoma / 肿瘤研究与临床

The periovarian peritoneal cavity lacks a local barrier, and exosomes derived from body fluids such as follicular fluid and ascites are important non-cellular components in the tumor microenvironment of ovarian cancer. The contents carried by exosomes are highly similar to their source cells and become a new direction for studying the unique biological origin possessed by a variety of histological types of ovarian cancer. The article reviews the research progress of exosomes in the multiple origins of ovarian epithelial carcinoma.

Overexpression of long noncoding RNA PTPRG-AS1 is associated with poor prognosis in epithelial ovarian cancer

SUMMARY OBJECTIVE Long noncoding RNAs (lncRNAs) have been shown to play a critical role in tumor progression. Abnormal expression of LncRNA PTPRG antisense RNA 1 (PTPRG-AS1) has been reported in several tumors. Hence, we aimed to determine the expression and clinical significance of PTPRG-AS1 in epithelial ovarian cancer (EOC) patients. METHODS The expressions of PTPRG-AS1 were assessed in 184 pairs of EOC tumor specimens and adjacent normal tissues. The levels of target lncRNAs and GAPDH were examined using standard SYBR-Green methods. The relationships between the expressions of PTPRG-AS1 and the clinicopathological features were analyzed using the chi-square test. Multivariate analysis using the Cox proportional hazards model was performed to assess the prognostic value of PTPRG-AS1 in EOC patients. RESULTS We confirmed that the expressions of PTPRG-AS1 were distinctly higher in the EOC tissue compared with the adjacent non-tumor specimens (p < 0.01). Higher levels of PTPRG-AS1 in EOC patients were associated with advanced FIGO stage (p = 0.005), grade (p = 0.006), and distant metastasis (p = 0.005). Survival analyses revealed that patients with high expressions of PTPRG-AS1 had a distinctly decreased overall survival (p = 0.0029) and disease-free survival (p = 0.0009) compared with those with low expressions of PTPRG-AS1. Multivariate assays indicated that PTPRG-AS1 expression was an independent prognostic factor for both overall survival and disease-free survival in EOC (Both p < 0.05). CONCLUSIONS Our study suggests that PTPRG-AS1 may serve as a novel prognostic biomarker for EOC patients.

RESUMO OBJETIVO Sabe-se que RNAs longos não codificantes (lncRNAs) desempenham um papel crítico na progressão tumoral. A expressão anormal do RNA 1 anti-senso LncRNA PTPRG (PTPRG-AS1) já foi relatada em diversos tumores. Assim, buscamos determinar a expressão e significância clínica do PTPRG-AS1 em pacientes com câncer de ovário epitelial (COE). METODOLOGIA As expressões do PTPRG-AS1 foram avaliadas em 184 pares de amostras tumorais de COE e tecidos normais adjacentes. Os níveis de lncRNAs e GAPDH alvo foram examinados usando o método padrão de SYBR Green. As relações entre as expressões do PTPRG-AS1 e as características clínico-patológicas foram analisadas através do teste qui-quadrado. Uma análise multivariada utilizando o modelo de riscos proporcionais de Cox foi realizada para avaliar o valor prognóstico do PTPRG-AS1 em pacientes com COE. RESULTADOS Constatou-se que as expressões do PTPRG-AS1 foram nitidamente maiores nos tecidos de COE em relação aos espécimes adjacentes não tumorosos (p<0,01). Níveis mais elevados do PTPRG-AS1 em pacientes com COE foram associados a um estágio avançado de FIGO (p = 0,005), grau (p = 0,006) e metástases à distância (p = 0,005). As análises de sobrevida revelaram que pacientes com expressões elevadas do PTPRG-AS1 tiveram uma diminuição significativa da sobrevida global (p = 0,0029) e da sobrevida livre de doença (p = 0,0009) em relação àqueles com baixas expressões do PTPRG-AS1. As análises multivariadas indicaram que a expressão do PTPRG-AS1 foi um fator de prognóstico independente tanto para a sobrevida global quanto para a sobrevida livre de doença em pacientes com EOC (p < 0,05). CONCLUSÃO Nosso estudo sugere que o PTPRG-AS1 pode ser um novo biomarcador prognóstico para pacientes com COE.

Supervivencia de pacientes con cáncer epitelial de ovario en el Instituto Nacional de Cancerología, resultados a partir del registro hospitalario de cáncer (2005-2014) / Survival of patients with epithelial ovarian cancer, results of the hospital-based cancer registry of the National Cancer Institute (2005-2014)

Resumen Objetivo: Proporcionar características demográficas y clínicas, así como estimaciones de supervivencia global a tres años de pacientes con cáncer epitelial de ovario (CEO) tratadas entre 2005 y 2014 en el Instituto Nacional de Cancerología de Colombia (INC). Métodos: Se incluyeron 783 pacientes diagnosticadas y tratadas por primera vez en el INC por CEO en los periodos 2005-2008, 2009-2011 y 2012-2014 sin un diagnóstico previo de otro cáncer. Se cruzaron datos del registro hospitalario de cáncer con bases de datos gubernamentales para obtener información de seguimiento. Utilizando el método Kaplan-Meier se estimó la probabilidad de sobrevivir a 36 meses a partir de la fecha de ingreso, evaluando diferencias en supervivencia entre grupos con la prueba de rango logarítmico. Se utilizaron modelos multivariados de riesgos proporcionales de Cox para evaluar: el efecto relativo de edad, el estadio clínico, el subtipo histológico y el tipo de tratamiento inicial en la supervivencia. Resultados: La probabilidad de supervivencia global a 36 meses fue de 56,5% (IC 95%: 53,0; 60,0), que se mantuvo estable en los tres periodos. La edad avanzada, el estadio clínico y el subtipo histológico afectaron significativamente la supervivencia global a tres años: 49,5% (IC 95%: 43; 55,6) para mujeres >59 años; 21,9% (IC 95%: 14,7; 29,2) para la enfermedad en estadio IV y 56,3% (IC 95%: 37,5; 54,3) para los tumores serosos. Las estimaciones de hazard fueron significativamente más altas en pacientes de 59 años o más (HR 1,54 (IC del 95%: 1,04 a 2,27)) y en cánceres con estadio avanzado (HR 13,47 (IC 95%: 7,92-22,92)); la cirugía más quimioterapia tuvo una reducción en el riesgo en comparación con otros tratamientos (HR 0,84 (IC 95% 0,52-1,36). Conclusiones: La supervivencia del cáncer epitelial de ovario se mantuvo estable con el tiempo. La variación se presentó en factores como: la edad, el estadio clínico y el primer tratamiento.

Abstract Aims: To provide demographical and clinical characteristics and estimations of 3-year overall survival of epithelial ovarian cancer (EOC) patients treated at the Colombian National Cancer Institute (INC) between 2005 and 2014. Methods: All 783 patients first treated at INC for EOC in the three periods: (2005-2008, 2009-2011, 2012-2014), without a prior cancer diagnosis, were included in this study. Follow-up was realized by cross-linkage with governmental databases using person identification numbers. Probability of surviving 36 months since the date of entry at INC was estimated using Kaplan-Meier methods, using the log-rank test to evaluate differences between groups. We used multivariate Cox proportional hazard models to evaluate the relative effect of age, clinical stage, histological subtype and treatment first on survival. Results: The overall survival probability at 36 months was 56.5% (95% CI: 53.0, 60.0), which was stable over time. Advanced age and clinical stage significantly affected 3-year overall survival, being 49.5°% (95°% CI: 43.4, 55.6) for age > 59, 21.9°% (95°% CI: 14.7, 29.2) for stage IV disease and 56.3% (95% CI: 37.5, 54.3) for serous tumors. Hazard ratios were significantly higher for patients aged 59 and over (HR 1.54 (95%CI 1.04-2.27)) and advanced stage cancers (HR 13.47 (95%CI 7.92-22.92)), whereas patients with surgery plus chemotherapy had a strongly reduced risks compared to other treatments (HR 0.84 (95%CI 0.52-1.36)). Conclusions: Survival of epithelial ovarian cancer was stable over time, with a variation according to age, clinical stage and first treatment.

Prognostic value of neutrophil-to-lymphocyte ratio in early-stage ovarian clear-cell carcinoma / 부인종양

OBJECTIVES: There is increasing evidence that systemic inflammatory response (SIR) markers are prognostic factors for various types of cancers. This is the first study to evaluate the usefulness of SIR markers for the prognosis of early-stage ovarian clear-cell carcinoma (OCCC). METHODS: We retrospectively investigated 83 patients diagnosed with stage I–II OCCC who underwent surgery between 2005 and 2017. Initially, receiver operating characteristic curve analysis for overall survival (OS) was used to determine optimal cut-off values for neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). Patients were stratified into 2 groups by the cut-off values (NLR=3.26, PLR=160). Univariate and multivariate analyses were performed to elucidate the significance of SIR markers as prognostic factors. RESULTS: In the median follow-up period of 64.1 months, 16 patients experienced recurrence, and nine patients died. The Kaplan-Meier curve showed that OS of the NLR-low group was significantly longer than the NLR-high group (p=0.021). There was no significant difference in progression-free survival between the 2 groups (p=0.668), but the post-recurrence survival of the NLR-low group was significantly longer than the NLR-high group (p=0.019). Furthermore, multivariate analysis showed that increase in NLR is a significant independent prognostic factor for poor prognosis (hazard ratio=7.437, p=0.017). There was no significant difference between PLR-low and PLR-high group. CONCLUSION: Results suggest that NLR can be a significant independent prognostic factor for early-stage OCCC.

Relationship between the precursors of high grade serous ovarian cancer and patient characteristics: decreased incidence of the p53 signature in pregnant women / 부인종양

OBJECTIVE: To investigate the relationship between the precursors of high grade serous ovarian cancer (HGSOC) and the characteristics of patients with a low HGSOC risk in terms of the effects of pregnancy. METHODS: We prospectively examined consecutive cases in which the bilateral fallopian tubes were removed during benign gynecological or obstetric surgery and assessed the relationship between the patient characteristics, including parity and pregnancy, and the incidence of HGSOC precursors. All the fallopian tubes were examined by applying the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) Protocol. RESULTS: Of the 113 patients enrolled, 67 were gynecological and 46 were obstetric. The p53 signature was identified in 21 patients. No other precursors were identified. In a comparison of the p53 signature-positive and negative groups, parous women and pregnant women were significantly fewer in the p53 signature-positive group (53% vs. 86%, p=0.002, 10% vs. 47%, p=0.001, respectively). Current pregnancy was also associated with a significantly lower incidence of the p53 signature after multivariate adjustment (odds ratio [OR]=0.112; 95% confidence interval [95% CI]=0.017–0.731; p=0.022). Among gynecological patients, parous women were fewer in the p53 signature-positive group on univariate (47% vs. 73%, p=0.047) and multivariate analysis (OR=0.252; 95% CI=0.069–0.911; p=0.036). No other characteristics were associated with p53 signature positivity. CONCLUSIONS: The incidence of the p53 signature was significantly lower in parous women and pregnant women. This decreased incidence of early phase serous carcinogenesis may be one of the possible mechanisms underlying HGSOC risk reduction among parous women.

The efficacy of secondary cytoreductive surgery for recurrent ovarian, tubal, or peritoneal cancer in Tian-model low-risk patients / 부인종양

OBJECTIVE: In patients with recurrent ovarian cancer (ROC) in whom surgery is likely to render them disease-free, it is unclear whether secondary cytoreductive surgery (SCS) combined with chemotherapy is superior to chemotherapy alone. The aim of this study was to evaluate the 2 treatment options in Tian-model low-risk patients. METHODS: We retrospectively reviewed 118 ROC cases treated in our hospital between 2004 and 2016. Of these, 52 platinum-sensitive cases were classified as low-risk (complete resection anticipated) using the Tian model. Prognostic factors were assessed with univariate and multivariate analysis using Cox's regression model. Progression-free survival (PFS) and overall survival (OS) were compared in patients treated with SCS plus chemotherapy (SCS group) and those treated with chemotherapy alone (chemotherapy group), using a propensity-score-based matching method. RESULTS: By multivariate analysis, the only factor associated with better OS was SCS. PFS and OS were significantly longer in the SCS group compared to the chemotherapy group in the matched cohort (median PFS: 21.7 vs. 15.1 months, p=0.027 and median OS: 91.4 vs. 33.4 months, p=0.008, respectively). In cases with multiple-site recurrence, the SCS group also showed significantly longer OS than the chemotherapy group (median 91.4 vs. 34.8 months, p=0.022). In almost all SCS cases, cooperation was required from other departments, and operation time was lengthy (median 323 minutes); however, no serious complications occurred. CONCLUSION: SCS combined with chemotherapy results in better PFS and OS than chemotherapy alone in first platinum-sensitive ROC patients categorized as low-risk by Tian's model.