BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Objective:To investigate the incidence of port-site metastasis (PSM) after laparoscopic surgery in patients with epithelial ovarian cancer and prognostic factors influencing outcomes in those with abdominal wall PSM.Methods:Clinicopathological and follow-up data of 22 ovarian epithelial cancer patients diagnosed with abdominal wall PSM after laparoscopic surgery, who were treated in the Sichuan Cancer Hospital between May 2014 and July 2023, were retrospectively collected. A retrospective analysis of PSM characteristics and prognostic factors influencing outcomes, was conducted in these patients.Results:(1) Between May 2014 and July 2023, a total of 369 ovarian cancer patients with a history of laparoscopic surgery performed at other hospitals were admitted. Among them, 24 cases (6.5%, 24/369) were diagnosed with tumor lesions at the abdominal wall port sites via postoperative pathological examination, with a median interval time of 25.5 days (interquartile range: 19.5, 32.0 days) after laparoscopic surgery. Of these, 22 cases with complete clinicopathological and follow-up data were included in this study. (2) The age of the 22 PSM patients was (53.0±8.6) years, and the median follow-up time was 37.6 months (24.7, 63.4 months). Surgical-pathological staging revealed stage Ⅰ-Ⅱ disease in 4 cases and stage Ⅲ-Ⅳ disease in 18 cases. Histopathological differentiation included 5 cases of well-to-moderately differentiated tumors and 17 cases of poorly differentiated tumors. Pathological subtypes comprised 11 cases of high-grade serous adenocarcinoma, 5 cases of low-grade serous adenocarcinoma, and 6 cases of clear cell carcinoma or cystadenocarcinoma. Lymph node status was as follows: negative for lymph node metastasis ( n=16), positive ( n=5), and no lymphadenectomy performed ( n=1). Postoperative residual disease was categorized as no macroscopic residual disease ( n=13), residual disease ≤1 cm ( n=7), and residual disease >1 cm ( n=2). (3) Following secondary cytoreductive surgery combined with postoperative adjuvant therapy, the median progression-free survival and overall survival (OS) time of the patients were 8.8 months (4.6, 14.3 months) and 27.7 months (15.5, 38.4 months), respectively. Univariate Cox regression analysis demonstrated that surgical-pathological stage, histopathological differentiation grade, and lymph node metastasis status were significantly associated with OS time in patients with abdominal wall PSM (all P<0.05). In contrast, age, Eastern Cooperative Oncology Group performance status score, histopathological subtype, preoperative serum cancer antigen 125 level, presence of residual lesions after surgery and poly adenosine diphosphate ribose polymerase inhibitor usage showed no significant correlation with OS time (all P>0.05). Multivariate Cox regression analysis identified surgical-pathological stage ( HR=4.579，95% CI：1.111-18.866； P=0.035) and histopathological differentiation grade ( HR=5.307，95% CI：1.042-27.031； P=0.045) as independent risk factors for OS time in PSM patients. Conclusion:Abdominal wall PSM following laparoscopic surgery for epithelial ovarian cancer maybe adversely affect patient prognosis, particularly in cases with advanced stage and poorly differentiated tumors, which warrants significant clinical attention.

Objective:To investigate the incidence of port-site metastasis (PSM) after laparoscopic surgery in patients with epithelial ovarian cancer and prognostic factors influencing outcomes in those with abdominal wall PSM.Methods:Clinicopathological and follow-up data of 22 ovarian epithelial cancer patients diagnosed with abdominal wall PSM after laparoscopic surgery, who were treated in the Sichuan Cancer Hospital between May 2014 and July 2023, were retrospectively collected. A retrospective analysis of PSM characteristics and prognostic factors influencing outcomes, was conducted in these patients.Results:(1) Between May 2014 and July 2023, a total of 369 ovarian cancer patients with a history of laparoscopic surgery performed at other hospitals were admitted. Among them, 24 cases (6.5%, 24/369) were diagnosed with tumor lesions at the abdominal wall port sites via postoperative pathological examination, with a median interval time of 25.5 days (interquartile range: 19.5, 32.0 days) after laparoscopic surgery. Of these, 22 cases with complete clinicopathological and follow-up data were included in this study. (2) The age of the 22 PSM patients was (53.0±8.6) years, and the median follow-up time was 37.6 months (24.7, 63.4 months). Surgical-pathological staging revealed stage Ⅰ-Ⅱ disease in 4 cases and stage Ⅲ-Ⅳ disease in 18 cases. Histopathological differentiation included 5 cases of well-to-moderately differentiated tumors and 17 cases of poorly differentiated tumors. Pathological subtypes comprised 11 cases of high-grade serous adenocarcinoma, 5 cases of low-grade serous adenocarcinoma, and 6 cases of clear cell carcinoma or cystadenocarcinoma. Lymph node status was as follows: negative for lymph node metastasis ( n=16), positive ( n=5), and no lymphadenectomy performed ( n=1). Postoperative residual disease was categorized as no macroscopic residual disease ( n=13), residual disease ≤1 cm ( n=7), and residual disease >1 cm ( n=2). (3) Following secondary cytoreductive surgery combined with postoperative adjuvant therapy, the median progression-free survival and overall survival (OS) time of the patients were 8.8 months (4.6, 14.3 months) and 27.7 months (15.5, 38.4 months), respectively. Univariate Cox regression analysis demonstrated that surgical-pathological stage, histopathological differentiation grade, and lymph node metastasis status were significantly associated with OS time in patients with abdominal wall PSM (all P<0.05). In contrast, age, Eastern Cooperative Oncology Group performance status score, histopathological subtype, preoperative serum cancer antigen 125 level, presence of residual lesions after surgery and poly adenosine diphosphate ribose polymerase inhibitor usage showed no significant correlation with OS time (all P>0.05). Multivariate Cox regression analysis identified surgical-pathological stage ( HR=4.579，95% CI：1.111-18.866； P=0.035) and histopathological differentiation grade ( HR=5.307，95% CI：1.042-27.031； P=0.045) as independent risk factors for OS time in PSM patients. Conclusion:Abdominal wall PSM following laparoscopic surgery for epithelial ovarian cancer maybe adversely affect patient prognosis, particularly in cases with advanced stage and poorly differentiated tumors, which warrants significant clinical attention.

Background: The impact of para-aortic lymphadenectomy (PALD) on prognosis and quality of life (QoL) for IB2-IIA2 cervical cancer patients remain controversial. And whether intraoperative frozen pathology exam on common iliac lymph nodes could help predict para-aortic lymph node (PALN) metastasis was unanswered with high-level evidence. Methods A multi-center, randomized controlled study is intended to investigate the effect of PALD on the prognosis and QoL in cervical cancer patients and to assess the value of intraoperative frozen pathological evaluation of common iliac nodes metastasis for the prediction of PALN metastasis. After choosing whether to receive intraoperative frozen pathological examination of bilateral common iliac lymph nodes, eligible patients will be randomly assigned (1:1) to receive PALD or not. The primary end point is 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events (AEs) caused by PALD, AEs caused by radiotherapy and QoL. A total of 728 patients will be enrolled from 8 hospitals in China within 3-year period and followed up for 5 years.

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.

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.

Objective:To explore the prognostic factors of patients with advanced epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS).Methods:The clinical and pathological data of patients with stage Ⅲc-Ⅳ EOC underwent surgical treatment in Sichuan Cancer Center from January 1st, 2014 to December 31th, 2018 were retrospectively analyzed, and the prognosis was followed up.Results:(1) A total of 216 EOC patients were included in the study, whose age was (52.1±8.7) years old, the median follow-up time was 44.6 months (17.2-80.1 months), the median progression free survival (PFS) was 11.1 months (8.5-13.8 months), and the median overall survival (OS) was 40.0 months (32.7-47.3 months). (2) Among 216 patients with advanced EOC, there were 75 cases in the primary debulking surgery (PDS) group and 141 cases in the NACT+IDS group. Compared with the PDS group, the serum CA 125 level before treatment (median: 859.4 vs 1 371.0 kU/L), proportion of stage Ⅳ patients [5.3% (4/75) vs 23.4% (33/144)] and no visible residual disease (R0) cytoreduction rate in the NACT+IDS group were significantly higher [(41.3% (31/75) vs 61.7% (87/144); all P<0.05]. The median PFS in the NACT+IDS group was significantly shorter than that of the PDS group (9.1 vs 15.2 months; χ2=7.014, P=0.008), but there was no significant difference in the median OS between the two groups (42.6 vs 38.0 months; χ2=1.325, P=0.250). (3) Univariate analysis showed that body mass index (BMI), preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, time to initiation of postoperative chemotherapy and chemotherapy regimen were significantly correlated with PFS in the NACT+IDS group (all P<0.05); preoperative serum CA 125 level, surgical-pathological stage, NACT effect, postoperative residual tumor size, postoperative chemotherapy regimen were significantly related with OS in the NACT+IDS group (all P<0.05). Multivariate analysis showed that BMI, postoperative residual tumor size, time to initiation of postoperative chemotherapy were independent factors of PFS in the NACT+IDS group (all P<0.05); preoperative serum CA 125 level, surgical-pathological stage, postoperative residual tumor size were independent factors of OS in the NACT+IDS group (all P<0.05). The results showed that the PFS of patients with normal preoperative serum CA 125 level and (or) chemotherapy ≤7 days after IDS was longer, while no significant difference comparable with those in the PDS group ( P>0.05), and OS was also showing an prolonged trend, but the difference was also not statistically significant ( P>0.05). Conclusions:Normal CA 125 before IDS and time received chemotherapy no longer than 7 days after IDS are two related factors of prognosis benefit in advance EOC patients treated with NACT+IDS. Therefore, timely adjustment of the dose and regimen of NACT to reduce CA 125 level to normal range in about three cycles before IDS, and strengthen IDS perioperative management to promote postoperative recovery and perform chemotherapy as soon as possible might help to improve the prognosis of patients.

Objective:To explore the management strategies for patients with gynecological malignant tumors during the outbreak and transmission of COVID-19.Methods:We retrospectively analyzed the clinical characteristics, treatment, and disease outcomes of three patients with gynecological malignancies associated with COVID-19 in Renmin Hospital of Wuhan University, and proposed management strategies for patients with gynecological tumors underriskof COVID-19.Results:Based on the national diagnosis and treatment protocol as well as research progress for COVID-19, three patients with COVID-19 were treated. Meanwhile, they were also appropriately adjusted the treatment plan in accordance with the clinical guidelines for gynecological tumors. Pneumonia was cured in 2 patients, and one patient died of COVID-19.Conclusions:Patients with gynecological malignant tumors are high-risk groups prone to COVID-19, and gynecological oncologists need to carry out education, prevention, control and treatment according to specific conditions. While, actively preventing and controlling COVID-19, the diagnosis and treatment of gynecological malignant tumors should be carried out in an orderly and safe manner.

Objective:To introduce the technical essentials of cytoreduction surgery (CRS) with extensive peritonectomy （“rolling carpet” surgery） in stage Ⅲc epithelial ovarian cancer (EOC) and evaluate the feasibility and safety of the operation by analyzing the incidence of surgical complications and perioperative mortality.Methods:From December 2017 to December 2019, 30 patients with stage IIIc EOC who underwent “rolled carpet” CRS and 30 patients who underwent traditional CRS at the same period in Sichuan Cancer Hospital were collected. To summarize the key points of “rolled carpet” CRS operation technology, i.e. the extraperitoneal space was the cut path of ovarian cancer operation, and the tumor in the pelvic cavity was dissociated from the extraperitoneal space of the pelvic cavity. The tumor in the pelvic cavity and all the implants or potential metastases on the parietal peritoneum were removed completely. The clinical and pathological characteristics between the two groups were analyzed retrospectively, and the feasibility and safety of “rolling carpet” CRS were evaluated by comparing the operation related indexes and the occurrence of surgical complications between the two groups.Results:(1) Clinicopathological features: the age of patients in “rolling carpet” CRS group and traditional CRS group were respectively (55.4±9.6) and (54.6±9.5) years, and the median peritoneal cancer index (PCI) was 12 (range, 4-24) and 10 (range, 5-18), respectively. There were no statistical significance between the two groups (all P>0.05). (2) Operation related indexes: in the “rolled carpet” CRS group, all patients （100%, 30/30） were performed optimal CRS, reaching completeness of cytoreduction score （CC score）, named CC-0 score, and there was no visible residual lesion after operation. While, in the traditional CRS group, 23 patients （77%, 23/30） reached CC-0 score, 5 cases （17%, 6/30） reached CC-1 score, 2 cases （7%, 2/30） reached CC-2 score, and there were statistical significance between the two groups ( P=0.011). The median surgical time was 315 minutes (range, 252-446 minutes) vs 268 minutes (range, 215-372 minutes), the median intraoperative blood loss was 589 ml (range, 300-900 ml) vs 450 ml (range, 250-800 ml), the median ICU hospital stay time was 2 days (range, 1-7 days) vs 1 day (range, 0-5 days), the median total hospital stay time was 14 days (range, 9-17 days) vs 12 days (range, 7-15 days). There were no statistical significance between the two groups (all P>0.05). (3) Surgical complications: there were respectively 5 cases (17%, 5/30) and 3 cases (10%, 3/30) complications with Clavien-Dindo grading Ⅰ-Ⅱ, which was significant no difference between the “rolled carpet” CRS group and the traditional CRS groups ( P>0.05). No re-operations were needed and the operative mortality was 0. Conclusion:It is safe and feasible to perform “rolled carpet” CRS in patients with advanced stage Ⅲc EOC with peritoneum implantation and metastasis, which could achieve optimal CRS, and has an acceptable incidence of perioperative complications, no perioperative death.