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.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

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.