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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.
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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.
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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.
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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.
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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.
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Objective To evaluate the incidence and significance of perineural invasion (PNI) in cervical cancer. Methods Retrospective chart review of patients with cervical cancer (stages Ⅰa2-Ⅱb) who underwent radical hysterectomy and pelvic lymphadenectomy from 2007 to 2012. To evaluate the incidence and significance of PNI in cervical and uterine tissues by microscopic examination. Results A total of 238 patients were included, 9.2% (22/238) patients with PNI in the cervical stroma. Patients with PNI were more likely to have adverse histopathologic features, including lymphoma vascular space invasion, parametrical invasion, depth of invasion, tomor size and lymph nodes metastases (all P0.05). Patients with PNI had shorter disease-free and overall survival (P=0.002 and P=0.008, respectively). On multivariate analysis, risk factors for recurrence and death included parametrical invasion and depth of invasion (P0.05). Conclusions PNI exists in early cervical cancer. PNI is associated with tumor size, depth of invasion, parametrical invasion, lymphoma vascular space invasion and lymph nodes metastases. PNI represente a decreasing disease-free and overall survival in patients with early-stage cervical cancer, and is independently associated with multiple high-risk factors, which be informed management decisions regarding adjuvant therapy.
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Objective To evaluate the clinical significance of changes in peripheral lymphocyte count after surgery in early cervical cancer.Methods The 123 patients with stage Ⅰ bl and Ⅱ al treated by abdominal type Ⅲ radical hysterectomy from May 2008 to December 2012 were reviewed.The median age of patients was 43 years old (range:30 to 66 years).The median follow-up was 25 months with a range of 5-61 months.Peripheral blood samples were obtained on pre-operative,post-operation day 3 and 7.The log-rank test was used to compare the homogeneity of progression-free survival functions across strata defined by categories of prognostic variables.The Cox proportional hazard model was used to assess the significance of potential prognostic factors for progression-free survival.Results Univariate analyses preoperative lymphocyte count (P =0.012) and lymph nodes metastases status (P =0.001) and parametrial invasion (P =0.013) were significant risk factors for progression-free survival rate.On multivariate analyses,preoperative lymphocyte count [hazard ratio (HR) =6.087,95％ CI:1.743-21.251,P =0.005] and lymph nodes metastases status (HR =5.984,95％ CI:1.803-19.802,P =0.003) were independent risk factor of progression-free survival rate.Conclusion Peripheral lymphocyte counts after cervical cancer surgery may be a important prognostic factor.
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Objective To investigate the efficacy of uterine artery chemoembolization in the treatment of locally advanced cervical cancer.Methods A total of 268 patients with locally advanced cervical cancer were treated with uterine artery chemoembolization in our department.The stage distribution among the patients included 132 stage Ⅰ B2,85 stage Ⅱ A1 and 51 stage Ⅱ A2.There were 223 patients of squamous cell carcinoma,24 patients of adenocarcinoma,9 patients of adenosquamous carcinoma,small cell carcinoma of the 7 patients,5 patients of neuroendocrine carcinoma.Transcatheter uterine artery infusion of paclitaxel and nedaplatin,gelatin sponge particles was applied for uterine artery embolization.The clinicopathological parameters were analyzed,and their impacts on tumor response were investigated.RECIST criteria were used to evaluate the response in solid tumors.Student t test was used to compare cervical tumor diameter before and after treatment,and Chi-square test was used for comparison of categorical data.Follow up examinations included pelvic ultrasound,gynecology,vaginal stump cell smears.Results Of the 268 patients,74 (27.6％) patients showed a complete response,160 (59.7％) patients had a partial response to uterine artery chemoembolization,and the overall response rate was 87.3％.A total of 258 (96.3 ％) patients underwent surgery,and pathological complete response were identified in 46 (17.2％).Forty (14.9％) patients were found to have lymph node metastasis after surgery.Response rates of stage Ⅰ B2 and Ⅱ A cases were 94.7％ and 80.1％,respectively,P ＜ 0.05.Patients with squamous cell carcinoma showed a better response rate than patents with other pathological types (94.2％ vs.53.3％),P ＜ 0.05.Initial tumor volume and cycles of preoperative uterine artery chemoembolization had no effect onthe response rate.Conclusions Uterine artery chemoembolization can increase the rate of surgical resectionof patients with locally advanced cervical cancer and can improve the reaction rate with tolerable side effect.It is an applicable option of treatment for patients with locally advanced cervical cancer in the neoadjuvanttreatment.
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Objective To evaluate the effectiveness and safety of combination chemotherapy with bleomycin,etoposide and cisplatin (BEP) regimen on the patients with high-risk gestational trophoblastic neoplasia (GTN).Methods Forty-two patients with high-risk GTN admitted in Sichuan Cancer Hospital between Jan.1997 and Oct.2011 were analyzed retrospectively.The International Federation of Gynecology and Obstetrics (FIGO) prognostic score of all patients was more than 7.The mean age of patients was 30.2years (range 20 -49 years).All patients were treated with more than two cycles BEP regimen and followed up to the patients' death or at the end of Feb.2012.The clinical response,toxicity and the occurrence of secondary tumors were investigated.Results Forty-two high-risk GTN patients received the total of 251courses of the BEP regimen,the average number of courses for each patient was 6.0 courses.Thirty-seven patients achieved complete remission and 5 patients showed drug-resistant.The total complete remission rate of BEP regimen was 88％ ( 37/42 ).Among the complete remission patients,the total courses of BEP regimen of cases getting normal serum β-hCG level was 129 courses ( average 3.5 courses),and the total courses of cases achieving complete remission was 227 courses (average 6.1 courses ).Among the 37 complete remission patients,31 cases were treated with BEP regimen chemotherapy alone,4 patients with BEP regimen chemotherapy combined with surgical treatment (1 case had no cancer after surgery) and 2 cases with BEP regimen chemotherapy combined with radiation therapy.Therefore,the complete remission rate of BEP regimen chemotherapy alone was 74％ (31/42 ).There were 5 patients who showed drug-resistance after 24 courses of BEP regimen chemotherapy (average 4.8 courses),then received etoposide,methotrexate and dactinomycin( EMA )/cyclophosphamide and vincristine sulfate ( CO ) regimen chemotherapy after drugresistance,2 cases combined with radiation therapy,1 case combined with surgical treatment.Ultimately,4cases achieved complete remission,1 case died of cancer.The major toxicities of BEP regimen were included bone marrow suppression,digestive tract side effect and alopecic,followed by mild peripheral neuritis and abnormal liver function,rare cases of mild pulmonary toxicity.There were no severe anaphylaxis and obvious impairment of cardiac,liver,pulmonary and kidney function,except 1 patient (49 years old) had grade Ⅳbone marrow suppression and pulmonary fibrosis worsened after chemotherapy.The bone marrow suppression was mainly Ⅰ - Ⅲ degree neutropenia,and Incidence rate was 66.5％ ( 167/251 ).All the survival patients without secondary tumor.Conclusion For young high-risk GTN patients,BEP regimen chemotherapy may be safe and effective.
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Objective To study the influence of survivin mutant-T34A ( survivinT34A) and survivin deletant-N-terminal 8 amino acids residues ( survivinN-8AA ) on the cell cycle distribution and chemosensitivity in human ovarian cancer HO-8910 cells for explorating the roles of modified survivin-mediated apoptosis induced by chemotherapeutic agents and possible signaling pathways involved. Methods pcDNA3.1 plasmid contained wild-type, survivinT34A and survivinN-8AA genes were transfected into HO-8910 cells,respectively, the control groups were HO-8910 cells transfected with pcDNA3. 1 plasmids. The expression of mRNA was examined by reverse transcription(RT) PCR and identified by DNA sequencing; the cell cycles were determined by flow cytometer analysis ( FCM ); the growth inhibitions rate of cisplatin ( DDP),paclitaxel (PTX) and LY294002 on the transfected cells were determined using methyl thiazolyl tetrazolium (MTT) assay. Results (1) The RT-PCR procedures and genome sequences showed that the survivin mRNA were expressed stable in the transfected HO-8910 cells. (2) There was lower percent of G0/G1 phase cells in SN-HO-8910 cells than that in PC-HO-8910 cells (44. 72% vs. 49.64%, P ＜0. 05) ;while higher percentage of G2/M phase and S phase cells( 1.06% and 54. 22% vs. 0. 56% and 49. 80%, P ＜ 0. 05 ).There was lower the G2/M phase and S phase cells in M-HO-8910 cells 0. 16% and 36. 33%, than that in PC-HO-8910 cells( P ＜ 0. 05 ); while higher percentage of G0/G1 phase cells(63. 51% ,P ＜ 0. 05 ). G0/G1 ,G2/M and S phase cells in Sur-HO-8910 cells were 54. 46%, 0. 62% and 44. 92%, and there were not significantly difference ( P ＞ 0. 05 ), compared to those in PC-HO-8910 cells. ( 3 ) The inhibitory concentration ( IC50 ) of DDP and PTX were higher in Sur-HO-8910 cells than those in control cells [(20. 4 ±6. 1)vs. (14.4 ±3.9)μmol/L,(36.7 ±4.0) vs. (28.6 ±3.6) μmol/L;all P＜0.05]. The IC50 of DDP and LY294002 in SN-HO-8910 cells were lower than those in control cells[(7. 6 ± 1.0) vs. ( 14. 4 ± 3.9)μmol/L, ( 13.2 ± 4. 0) vs. (41.0 ± 7. 9 ) μmol/L; all P ＜ 0. 01]. The IC50 of PTX [( 37. 9 ± 4. 8 ) μmol/L]in SN-HO-8910 cells were higher than that in control cells(P ＜0. 05). The IC50 of DDP in M-HO-8910 cells [(9.9 ± 1.2) μmol/L] were lower than that in control cells(P ＜0. 05) ,and the IC50 of LY294002 in M-HO-8910 cells [(66. 9 ± 4. 8) μ mol/L] higher than that in control cells ( P ＜ 0. 01 ). Conclusions The changes of cells cycle distribution caused by survivinT34A or survivinN-8AA enhanced the G2/M cell cycle-dependent chemosensitivity of PTX. Compared to survivinT34A, survivinN-8AA preferentially to mediate the cytotoxicity of DDP and LY294002, suggesting that it may be related to the cell cycle-dependence of survivin function and to blockage of the formation of its active dimer.