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1.The Association Between Vital Gene Mutations And Clinicopathological Factors In Ovarian Malignancies 2.The Characteristics Of PARP Inhibitors Induced Anemia In Ovarian Cancer

Posted on:2022-04-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:J ZengFull Text:PDF
GTID:1484306353458084Subject:Oncology
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Part 1 The association between vital gene mutations and clinicopathological factors in ovarian malignanciesObjective:To identify the key gene mutations in ovarian malignancies and investigate the association between gene mutations and clinicopathological factorsMethods:Patients diagnosed with ovarian cancer and treated with surgery at Cancer Hospital Chinese Academy of Medical Sciences(CAMS)between June 2019 and December 2020 were accrued.The data included the gene mutation in tumor tissue,which was tested by using the panel of 825 gene through NGS(Next Generation Sequencing).Using Mann-Whitney Test to analyze the association between the clinicopathological factors and tumoral gene mutation.Result:A total of 32 ovarian tumor tissue samples were tested through the panel of 825 genes,while 87 mutations were reported.The mutation frequencies of TP53,PIK3CA,STEN,SMC3,TEK and POT1 were 62.5%(20/32),21.9%(7/32),18.8%(6/32),18.8%(6/32),9.4%(3/32)and 9.4%(3/32).PTEN and KRAS mutations were associated with clinical stage(p=0.007 and p=0.011);p53 mutation was associated with pathological types(p=0.004);PIK3CA,PTEN and KRAS mutations were associated with differentiation(p=0.002,p=0.001 and p<0.001);TEK and POT 1 mutations were associated with lymphadenopathy.Conclusion:In ovarian malignancies,the common tumoral gene mutations were p53,PIK3CA,STEN,SMC3,TEK,and POT1,while TEK and POT1 mutations were associated with lymphadenopathy which had potential value for clinical guidance.Part 2 The Characteristics of PARP Inhibitors Induced Anemia in Ovarian CancerObjective:To explore the clinical features of PARP(Poly ADP-ribose polymerase)inhibitor-related anemia in ovarian cancerMethods:Patients diagnosed with ovarian cancer and treated with PARP inhibitor at Cancer Hospital Chinese Academy of Medical Sciences(CAMS)between January 2015 and October 2020 were accrued.The data included PARP inhibitors,treatment details,and Lab tests before treatment and during treatment.Results:A total of 107 patients with a median age was 58 years old(range 30?82 years old)were enrolled in this study,treated by PARP inhibitor(70 cases of Olaparib,21 cases of Niraparib,and 16 cases of Fluzoparib).The median treatment duration was 33 weeks(range 4?119 weeks).The anemia rate was 38.3%(41/107),including 4.7%of grade 1(5/107),13.1%of grade 2(14/107),12.1%of grade 3(13/107),and 8.4%of grade 4(9/107).The median anemia occurrence time was 6.5 weeks(range 1?52 weeks),including 41.5%(17/41)of anemia cases occurred in 4 weeks,24.4%(10/41)occurred in 5-8 weeks,14.6%(6/41)occurred in 9-12 weeks,2.4%(1/41)occurred in 12-16 weeks,and 17.1%(7/41)occurred after 16 weeks.The median anemia duration was 11.5 weeks(rage 1?72 weeks).The median value of MCV(mean corpuscular volume)was 106fl(rage 76?118fl)(normal range 80-100fl),75.6%of anemia patients had an elevated MCV level(31/41);The median value of MCH(mean corpuscular hemoglobin)was 36pg(rage 28?42pg)(Normal range 27-34pg),56.1%of anemia patients had an elevated MCH level(23/41);The median value of MCHC(mean corpuscular hemoglobin concentration)was 320g/l(range 289?352 g/l)(Normal range 320-360g/L),70.7%of anemia patients had a normal MCHC level(29/41);92.8%of anemia patients had a normal level of plasma iron(38/41);80.5%of anemia patients had a normal level of transferrin(33/41).The anemia rate between the patients without pre-treatment anemia and patients with pre-treatment anemia was 33.7%vs.88.9%(p<0.001).Conclusion:Anemia was a common adverse effect of PARP inhibitors.The PARP inhibitors-related anemia in ovarian cancer patients was macrocytic anemia,which was not caused by iron deficiency.Most anemia events occurred in the first three months of treatment.The median persistence time of anemia was 11.5 weeks.Patients with pre-treatment anemia are more likely to suffer an exacerbated anemia during treatment.
Keywords/Search Tags:ovarian cancer, tumoral gene mutation, TEK, POT1, lymphadenopathy, Ovarian cancer, PARP inhibitor, Complications, Anemia
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