| Clinical characteristics and prognostic outcomes of gynecological multiple primary malignant neoplasmsObjectives: To investigate the clinical characteristics and the prognostic outcomes of patients with gynecological multiple primary malignant neoplasms(MPMN).Methods: The patients with gynecological MPMN were retrospectively and continuously enrolled from January 2008 to December 2018.The clinical data including the onset age,the clinical diagnosis,FIGO stage,the involved organ or tissue,as well as the interval time and the treatment of multiple neoplasms,were collected for analyzing the characteristics of gynecological MPMN.Survival curve analysis and multivariate COX regression analysis were performed for detecting the possible risk factors or protective factors of gynecological MPMN.Results: A total of 126 patients with gynecological MPMN were enrolled,including 15 synchronous MPMN and 111 metachronous MPMN,59(46.8%)patients were endometrial cancer associated MPMN,29(23%)patients were ovarian cancer associated MPMN,46(36.5%)patients were cervical cancer associated MPMN,and 62(49.2%)patients’ first neoplasm was gynecological cancer.The average age of the patients with gynecological MPMN was 57.6 ± 10.8 years,and the overall survival(OS)of 1,2,3,and 5 years were 88.6%,82.6%,76.9% and 68.7%,respectively.The OS of m MPMN was seemingly better than s MPMN,but this difference was not statistically significant(HR: 0.509,95%CI: 0.192-1.348,P=0.17).The OS of patients with gynecological cancer as first neoplasm was worse than those with nongynecological cancer as first neoplasm(HR: 2.2,95%CI: 1.002-4.829,P=0.049),while there was no statistically significant difference of OS in the subgroups of endometrial cancer,ovarian cancer or cervical cancer(P=0.39),although the endometrial cancer subgroup seemed to be better than the other two subgroups from the survival curve;the OS of patients accompanied with breast cancer was better than those accompanied with other cancers(HR: 0.346,95%CI: 0.131-0.915,P=0.033).Univariate regression analysis showed that “age”,“FIGO stage” and “first neoplasm as gynecological cancer” were the factors for poor survival;“accompanied with breast cancer” and “operation for first or second neoplasm” were the factors for favorable survival.Multivariate COX regression analysis showed that “FIGO stage” was the independent risk factor(HR: 2.339,95%CI: 1.449-3.776,P=0.001),and “operation for second neoplasm” was the independent protective factor(HR: 0.212,95%CI: 0.073-0.622,P=0.005).Conclusion: The overall survival(OS)of gynecological MPMN at 1,2,3,and 5 years were 88.6%,82.6%,76.9% and 68.7%,respectively.“First neoplasm as gynecological cancer” was a factor for poor survival of patients with gynecological MPMN,and “FIGO stage” was the independent risk factor.“Accompanied with breast cancer” and “operation for neoplasm” were the factors for favorable survival of them.Especially,“operation for second neoplasm” was the independent protective factor for gynecological MPMN.The value and application of homologous recombination repair related gene testing in gynecological multiple primary malignant neoplasm and related familiesObjective: In the first part of this research,the clinical characteristics and survival prognosis of gynecological multiple primary malignant neoplasm(MPMN)had been explored and analyzed.In the second part,we introduced "homologous recombination repair(HRR)" gene testing into the gynecological MPMN,aiming to investigating the mutation characteristics of HRR gens in MPMN individuals and related families,and the value of HRR gene testing in clinical guidance and genetic counselin.Methods: The gynecological patients with HRR gene testing results(over 20 HRR genes or more extensive exon sequencing,not only for BRCA1/2 gene)were retrospectively and continuously enrolled from January 2017 to June 2020.The clinical data including onset age,clinical diagnosis,FIGO stage,accompanied tumor,family history of multiple tumors,therapeutic schedule,as well as the results of embryo detection and system detection for HRR gene,were collected and analyzed.The incidence of MPMN between HRR positive group and negative group was compared.According to the classification of "MPMN" and "family history of multiple tumors",the proportion and type differences of HRR 3-5 gene mutations among groups were compared and analyzed;the types and characteristics of HRR gene mutations related to MPMN individuals or families and the relationship between HRR gene mutations and different tumors were further explored.Survival curve and multivariate COX regression analysis were performed for detecting the possible risk factors or protective factors of these gynecological patients with HRR gene testing.Results: Totally,63 gynecological patients with HRR gene testing results met the criteria and had been included.There were 30 cases in HRR gene mutation positive group(type 4-5)and 22 cases in HRR negative group(type 1-2).The incidence of MPMN was significantly higher in HRR positive group than in HRR negative group(OR: 5.54,P=0.02).There were 18 cases in MPMN group and 45 cases in non MPMN group.MPMN group trended to have a higher incidence of HRR gene type 3-5 mutation than non MPMN group(OR: 2.97,P=0.06).The incidence of HRR gene type 4-5 mutation in MPMN group was higher than that in non MPMN group(OR: 6.34,P=0.004).A total of 53 patients underwent embryo detection,including 31 patients with a family history of and 22 patients without a family history of multiple tumors.The multiple tumors family history group trend to have a higher incidence of HRR gene type 4-5 mutation than non multiple tumors family history group(OR: 2.97,P=0.06).The incidence of HRR gene type 5 mutation in the multiple tumors family history group was higher than that in non multiple tumors family history group(OR: 3.71,P=0.045).All the 63 patients completed the followe-up,the time window of which ranging from 2 months to 204 months.In the end,14 patients reached endpoint events(death),and the median survival time was 66 months.The overall survival of 1,2,3,and 5 years were 92.5%,80.8%,77% and 54.4%,respectively.Survival analysis showed that the prognosis of HRR gene mutation positive group was slightly better than that of negative group,but the difference did not reach statistical significance(HR: 0.58,P=0.3).The survival prognosis of MPMN group was not inferior to that of non MPMN group(HR: 0.63,P=0.4).The patients with family history of multiple tumors trended to have a better survival prognosis than the patients without family history of multiple tumors(HR: 0.32,P=0.07).Multivariate COX regression analysis indicated that “high FIGO stage” was the independent risk factor(HR:3.868,P=0.025)and “operation” was the independent protective factor of these gynecological patients with HRR gene testing(HR:0.135,P=0.016).Conclusions: HRR gene mutations(4-5),inducing homologous recombination deficiency(HRD),may increase the incidence of MPMN in patients with gynecological malignant tumors.In turn,patients with gynecological MPMN or family history of multiple tumors are more likely to have HRR gene mutations(4-5).The survival prognosis of patients with HRR gene mutation and family history of multiple tumors seems to be slightly better."High FIGO stage" is an independent risk factor for poor prognosis,while "operation" is an independent protective factor for survival prognosis. |
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