Retrospective Analysis Of The Efficacy And Safety Of Neoadjuvant Chemotherapy In Patients With Locally Advanced Cervical Cancer

Purposes To evaluate the efficacy and safety of Neoadjuvant Chemotherapy(NACT)in patients with Locally Advanced Cervical Cancer(LACC).Method1.Study design: retrospective analysis of NACT chemotherapy response and toxic side effects in FIGO stage IB2-IIA2 cervical cancer patients,compared with Radical Surgery(RS)and Primary Radical Surgery(PRS)Clinical pathology,postoperative cumulative radiotherapy and progression free survival(PFS)and overall survival(OS)were observed between the two groups.2.Study subjects: Between January 2008 and December 2017,2-3 courses of TP(Paclitaxel +Carboplatin)3-week regimen of IB2-IIA2 phase of NACT or PRS were performed at the Union Hospital of Tongji Medical College,Huazhong University of Science and Technology.Patients with cervical cancer.3.Treatment: Patients who met the inclusion criteria according to NACT were divided into two groups,NACT group and PRS group.NACT regimen is 2-3 intravenous infusions of TP for 21days/course,tumor size is assessed before and after NACT,next cycle of chemotherapy is given every 3 weeks,surgery is performed within 3 weeks after NACT,and NACT+ radiotherapy is not available for patients who cannot undergo surgery;PRS The group underwent surgery immediately after diagnosis.The operation was C2 radical hysterectomy + pelvic lymphadenectomy.Patients with pathological risk factors were treated with chemotherapy and/or radiotherapy.4.NACT safety assessment: According to the WHO toxicity grading standard,NACT toxic side effects are classified into grade 0,grade I,grade II,grade III,and grade IV,and the severe toxicity is grade III-IV.5.NACT effectiveness evaluation:(1)Chemotherapy reactivity: According to the Response Evaluation Criteria in Solid Tumors(RECIST)(version 1.1),chemotherapy reactivity is divided into complete remission(CR)and local remission(PR).),Stable Disease(SD)and Progressive Disease(PD),NACT response group included CR and PR patients,non-response group including SD and PD patients,response rate(CR + PR)/ all NACT patients.(2)Pathological risk factors:including positive margin,parametrial infiltration,lymph node metastasis,deep interstitial infiltration(interstitial infiltration depth > 1/3),vascular invasion and tumor size.Chi-square testwas used to compare the difference of surgical pathological risk factors between chemotherapy response group and non-response group and NACT+RS group and PRS group.Logistic regression analysis was used to compare the effects of different pathological factors on chemotherapy response.(3)Postoperative cumulative radiotherapy: Kaplan-Meier risk function describes the cumulative radiotherapy from the diagnosis to the first radiotherapy or the last follow-up time in the NACT+RS group and the PRS group,and the difference between the log-rank test groups.(4)Survival time:PFS is defined as the time from tumor resection to the first progression of the disease or the last follow-up;OS is defined as the time from the diagnosis of cervical cancer to death or the time of the last follow-up.Kaplan-Meier depicts survival curves and log-rank tests for differences between groups.Result1.Basic characteristics of clinical pathology: 466 patients with FIGO stage IB2-IIA2 meeting the inclusion criteria,225 patients with NACT+RS,241 patients with PRS,and those with NACT+RS group were later than those with PRS(P<0.001).The tumor diameter was larger(P<0.001).There was no significant difference in age,pathological type and differentiation between the two groups(P≥0.05).2.NACT toxicity: common side effects of neoadjuvant chemotherapy are mainly manifested in bone marrow suppression,liver function damage,nausea and vomiting and hair loss.Severe toxicity(grade III-IV)was mainly manifested in myelosuppression,and the incidence of leukopenia was 10.22%(23/225).One patient discontinued NACT due to chemotherapy drug allergy,and no patient died of NACT.3.NACT response rate and influencing factors: 143 cases(57.4%)of NACT responders,including CR cases(15.7%),including pathological complete remission in 34 cases(13.7%).Tumor size >5cm chemotherapy response rate was lower(44.5% vs.70.9%,P=0.032),chemotherapy 2 cycle was lower than chemotherapy 3 late chemotherapy(70.9% vs.44.5%,P=0.032),deep interstitial The response rate of infiltrates was lower(42.1% vs.65.8%,P=0.007),and the rate of chemotherapy response was lower in patients with positive vascular invasion(42.3%vs.64.2%,P=0.005).Chemotherapy response in patients with positive paravalval infiltration The rate was lower(38.5% vs.61.8%,P=0.023),and lymph node metastasis-positive patients had lower chemotherapy response(40.3% vs.68.0%,P<0.001),age,stage,pathological type,degree of differentiation,and NACT response.There was no significant correlation between the rates(P ≥0.05).Multivariate regression analysis showed that tumor ≥ 5 cm was an independent influencing factor for chemotherapy response(OR: 0.207,95% CI: 0.092-0.466,P < 0.001).4.The pathological risk factors of NACT+RS group and PRS group were compared.The pathological size of NACT+RS group was significantly smaller than that of PRS group(P<0.001).The deep interstitial infiltration rate of NACT+RS group was significantly lower than that of PRS group(P< 0.001);there was no significant difference between the two groups(P≥0.05)in vascular tumor thrombus,positive margin,parametrial positive and lymph node metastasis.5.Postoperative cumulative radiotherapy rate: 95 cases(48.72%)of postoperative radiotherapy in NACT+RS group,126 cases(59.43%)in postoperative radiotherapy in PRS group,and the cumulative radiotherapy rate in NACT+RS group was lower than PRS group(P<0.001).The stratified analysis showed that the cumulative radiotherapy rate of the NACT+RS reaction group was significantly lower than that of the NACT+RS non-responder group(P=0.003).There was no significant difference between the NACT+RS non-response group and the PRS group(P≥0.05).Survival analysis: The 5-year PFS was 62.70% in the NACT+RS group and 67.80% in the PRS group.The difference was not statistically significant(P>0.05).The stratified curve showed that the5-year PFS of NACT+RS responders,NACT+RS non-responders and PRS group were 73.3%,48.1%,and 63.9%,respectively.The PACT of NACT+RS responders was higher than that of NACT+RS(P There was no significant difference in PFS between the NACT+RS and the PRS group(P>0.05).The 5-year OS of the NACT+RS group was 80.50%,and the 5-year OS of the PRS group was 82.20%.The difference was not statistically significant(P>0.05).The stratified curve showed that the NACT+RS responders,NACT+RS non-responders,and PRS group had 73.3%,48.1%,and 63.9% of the 5-year OS,and the NACT+RS response group had higher OS than the non-responder group(P=0.017).There was no significant difference in OS between NACT+RS reaction group and non-response group and PRS group(P>0.05).ConclusionThe response rate of NACT in patients with LACC is about 60%.The tumors with less than 5cm are more responsive to chemotherapy,and the toxicity of chemotherapy is acceptable.NACT can reduce tumor size,reduce interstitial infiltration,and reduce postoperative radiotherapy.There was no significant difference in survival between the NACT group and the PRS group,but the PRS and OS in the chemotherapy-free group were significantly lower than those in the chemotherapy-reactive group.Compared with the PRS group,the risk of relapse inchemotherapy-free patients increased.This study supports NACT as an alternative treatment option for patients with LACC(especially chemotherapy-sensitive patients).