| کلیدواژههای انگلیسی مقاله |
Uterine cervical neoplasms, Hysterectomy, Recurrence, Survival, What&,rsquo s Known As an alternative treatment for locally advanced cervical cancer, neoadjuvant chemotherapy (NACT) has been administered before radical hysterectomy to shrink large tumors. NACT before surgery reduces the need for postoperative radiotherapy in patients with locally advanced cervical cancer. What&,rsquo s New Lower rate of postoperative adjuvant radiotherapy is required after preoperative NACT, particularly in young patients. NACT reduces the recurrence rate and increases the overall survival of patients. Favorable clinical and pathological response to NACT before radical hysterectomy according to disease stage was observed. IntroductionCervical cancer is the most frequent gynecologic malignancy and the fourth most common cancer in women worldwide. Over five million new cases of cervical cancer are diagnosed annually, and more than 2.5 million women die from the disease. 1, In 2012, cervical cancer among Iranian women was ranked the twelfth leading cause of death with just under 1,000 new cases and 370 deaths. 2, Primary radical hysterectomy with bilateral pelvic lymphadenectomy or primary chemoradiotherapy is the gold standard treatment for the IA2, IIA, and IIB stages of cervical cancer. Adjuvant radiotherapy is administered if the surgical pathology report indicates lymph node (LN) or parametrial involvement, positive surgical margin, or deep cervical stromal invasion. On the other hand, large cervical tumors (lesion diameter &,gt 4cm) and stage IIB cervical cancer are mainly treated with chemoradiation. 3, The side effects of radiotherapy are premature ovarian dysfunction, sexual dysfunction, vaginal fibrosis, and obstructive endarteritis. These may lead patients to perceive the therapy as ineffective, and that the radiation may even be the cause of a new type of cancer. 3, In recent years, as an alternative treatment for locally advanced cervical cancer, neoadjuvant chemotherapy (NACT) has been administered before radical hysterectomy to shrink large tumors. 1, - 9, It has been reported that this treatment significantly reduces the need for radiation therapy after surgery. 10, However, it is also reported that NACT has no effect on the overall survival rate, even though it limits tumor size, lymph node involvement, and far metastasis. 11, NACT has become the main alternative treatment at Iranian oncology centers due to the limited accessibility of patients to radiotherapy and subsequent treatment delays. The present study aimed to assess the outcome of NACT therapy, followed by radical hysterectomy and primary surgery, in locally advanced cervical cancer according to disease stage. In addition, we evaluated the recurrence rate, five-year survival rate, and the need for adjuvant radiotherapy.Materials and MethodsIn a retrospective cohort study, the records of 258 patients with cervical cancer (stages IB2, IIA, or IIB), who referred to Imam Khomeini Hospital (Tehran, Iran) from 2007 to 2017 were evaluated. The study was approved by the Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (registration code, IR.TUMS.IKHC.REC.1396.4552). Written informed consent was obtained from all participants. Based on a Magnetic resonance imaging (MRI) scan and clinical examination, all patients had been classified according to the International Federation of Gynecology and Obstetrics (FIGO) staging system. 3, The exclusion criteria were concurrent malignancies or other comorbidities that had an adverse effect on cancer survival as well as incomplete records. The inclusion criteria were patients aged &,lt 80 years with performance status &,lt 2 normal liver, cardiovascular, renal, and bone marrow function, normal complete blood count (CBC) test, no other malignancies, coagulation disorders, or previous chemotherapy and willingness to undergo NACT. The patients were assigned into two groups. Group A (n=58) included patients with cancer stages IB2 and IIA, who underwent radical hysterectomy with negative margins. Group B (n=44) included patients, who underwent a radical hysterectomy after NACT. Demographic information from the records included parity, age at marriage, disease stage, LN involvement, lymph-vascular space invasion (LVSI), type of tumor, radiotherapy requirement, adjuvant hysterectomy, vaginal involvement, response to chemotherapy, survival time, and recurrence rate.The NACT procedure included three cycles of 80 mg/m2 cisplatin (Milan&,reg , France) and 60 mg/m2 paclitaxel (Stragen-Sobhan&,reg , Iran) at 10 days intervals followed by radical hysterectomy, if the patient achieved a complete or partial response. Two weeks after the final chemotherapy cycle, patients with no clinical parametrial involvement underwent surgery. Patients underwent three cycles of chemotherapy with paclitaxel and cisplatin postoperatively.Based on a pelvic MRI scan, the clinical response of a tumor was evaluated and categorized as,&,#9679 Complete response, Total disappearance of the tumor and elimination of all pathologic lymph nodes.&,#9679 Partial response, At least 30% decrease in tumor size.&,#9679 Permanent disease, Less than 30% decrease in tumor size.&,#9679 Progressive disease, At least 5 mm or 20% increase in tumor size or emergence of a new tumor.&,#9679 Suitable response, Combination of complete and partial responses.The pathological response of a tumor was categorized as,&,#9679 Complete response, Disappearance of the tumor with negative lymph nodes&,#9679 Optimal partial response, Disease with less than 3 mm stromal invasion&,#9679 Sub-optimal partial response, Tumoral invasion into stroma more than 3 mm&,#9679 Suitable pathologic response, Combination of complete and optimal responses Statistical AnalysisData analysis was performed using SPSS software version 21.0. The data were analyzed for normality using the Kolmogorov-Smirnov test. The hypothesis test was carried out on two variable groups using t test for numerical data or Mann-Whitney test for non-parametric data. Chi-square test or Fisher&,rsquo s exact test was used for data on nominal group depending on appropriateness. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and log-rank test. Independent prognostic factors were determined using Cox regression modeling. P&,#8202 &,lt &,#8202 0.05 was considered statistically significant. The confidence interval was considered 0.95 to obtain a study power of 80% beside 0.05 as significance with type one error (&,alpha ) of 0.05.ResultsOut of the 258 records of patients with cervical cancer, 140 patients underwent chemoradiation (not the main topic of our study), 52 received NACT followed by a hysterectomy, and 66 underwent primary radical hysterectomy. Sixteen records were excluded due to incomplete information or comorbidities that affected survival. Eventually, 58 records of patients with primary radical hysterectomy were assigned into group A and 44 records with NACT followed by radical hysterectomy were assigned into group B. Table 1, presents demographic and basic information about the patients. There was no statistically significant difference in age, age at marriage, and parity between the groups. However, the groups differed significantly in terms of cancer stage, type of tumor, vaginal invasion, lymph node involvement, and LVSI. VariableNACT+RS(n=44) Surgery (n=58)P valueAge (mean&,plusmn SD)46.09&,plusmn 12.0748.04&,plusmn 10.140.38&,dagger ,Age at marriage (mean&,plusmn SD)18.25&,plusmn 4.516.77&,plusmn 4.10.09&,dagger ,Parity median (IQR)3 (2-6)5 (2.75-6.25)0.28&,Dagger ,Stage (n, %)Ib213 (29.5)41 (70.7)0.001&,sect ,*,IIa11 (25)16 (27.6)IIb20 (45.5)1 (1.7)Vaginal invasion (n,%)None16 (36.4)40 (69)0.002&,sect ,*,Fornix11 (25)9 (15.5)1/3 upper11 (25)9 (15.5)2/3 upper6 (13.60)0 (0)LN (n,%)Yes23 (52.27)16 (27.59)0.01&,sect ,*, No 21 (47.72)42 (72.41)LVSI (n, %)Yes15 (34.09)41 (70.69)&,lt 0.001&,sect ,*,No29 (65.91)17 (29.31)Tumor type (n, %)SCC41 (93.20)41 (70.70)0.02&,sect ,*,Adenocarcinoma3 (6.80)16 (27.60)Others0 (0)1 (1.70)NACT, Neoadjuvant chemotherapy RS, Radical surgery LN, Lymph node LVSI, Lymph-vascular space invasion SCC, Squamous cell carcinoma IQR, Interquartile range=Q3-Q1 &,dagger t test &,Dagger Mann-Whitney U test &,sect Chi-square or Fisher&,rsquo s exact test *P&,#8202 &,lt &,#8202 0.05 was considered statistically significant |