Neoadjuvant Chemotherapy In Cervical Cancer Research Articles

PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer

Neoadjuvant chemotherapy (NACT) is a therapeutic option for locally advanced cervical cancer (LACC) patients. This study was aimed to identify potential liquid biopsy biomarkers to monitor the NACT response. Through targeted next-generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) and tumor tissue DNA (ttDNA) taken from LACC patients undergoing platinum-based NACT, 64 genes with mutations emerge during NACT in the non-responders but none in the responders. Among them, the PBRM1, SETD2, and ROS1 mutations were frequently detected in the ctDNA and ttDNA of the non-responders, and mutant PBRM1 was associated with poorer survival of patients. Invitro, PBRM1 knockdown promoted resistance to cisplatin through boosting STAT3 signaling in cervical cancer cells, while it sensitized tumor cells to poly-ADP-ribose-polymerase inhibitor olaparib. These findings suggest that mutant PBRM1 is a potential ctDNA marker of emerging resistance to NACT and of increased sensitivity to olaparib, which warrants further clinical validation.

Successful neoadjuvant chemotherapy plus sintilimab for locally advanced cervical cancer: case series and review of the literature

BackgroundThe locally advanced cervical cancer (LACC) of FIGO stage IB3-IIA2 is characterized by large local mass, poor prognosis and survival rate. Tumor response to neoadjuvant chemotherapy for LACC, utilized as a surrogate endpoint, is urgently needed to improve. Given that the antitumor immune response can be suppressed by programed death-1 axis, the treatment paradigm of neoadjuvant chemotherapy combined with immunotherapy has been explored as one of the prognostic treatments in a variety of solid carcinoma. So far, the application of sintilimab, a domestic immune checkpoint inhibitor, combined with neoadjuvant chemotherapy is still limited in LACC, especially in large lesions.Case descriptionWe present three postmenopausal women diagnosed with FIGO stage IB3-IIA2 cervical squamous cell carcinoma with lesions larger than 5 cm. Demographic, clinical, histopathological, laboratory and imaging data were record. At the completion of the neoadjuvant therapy with paclitaxel plus carboplatin combined with sintilimab, all patients underwent hysterectomy. After neoadjuvant treatment, a pathologic complete response in case 1 and partial responses in case 2 and case 3 were achieved, and neither patient showed any relapse during the follow-up period of 16 to 22 months.ConclusionsThis report provide evidence to support the combination of sintilimab with neoadjuvant chemotherapy in cervical cancer, which has yet to be validated in prospective studies. More clinical data are needed to verify the effectiveness of the combined regimens. This literature review also collected studies involving potential predictors of response to NACT and immunotherapy, which would be helpful in stratifying patients for future trials.

Reversal of the immunosuppressive tumor microenvironment via platinum-based neoadjuvant chemotherapy in cervical cancer

BackgroundImmunotherapy favors patients with tumors; however, only 3–26.3% of patients with cervical cancer benefit from single-agent immune checkpoint inhibitors. Combined immunotherapy and chemotherapy has been explored against tumor; however, the combination remains controversial. This study aimed to investigate the tumor immune microenvironment (TIME) and the effects of platinum-based neoadjuvant chemotherapy (NACT) in cervical cancer to identify the clinical value of combining chemotherapy with immunotherapy. MethodsMultiplex immunohistochemistry (IHC) with 11 markers (cluster of differentiation [CD]3, CD8, CD4, CD11c, CD68, forkhead box P3 [Foxp3], programmed cell death 1 [PD-1], programmed cell death 1 ligand 1 [PD-L1], indoleamine 2,3-dioxygenase [IDO], cyclin-dependent kinase inhibitor 2A [p16], and cytokeratin [CK]) was performed to evaluate TIME from 108 matched pre- and post-NACT cervical cancer samples. The mechanism of antitumor immunity triggered by NACT was explored using RNA sequencing (RNA-seq) from four paired samples and subsequently verified in 41 samples using IHC. ResultsThe infiltration rate of the CD8+ T cells in treatment-naive cervical cancer was 0.73%, and those of Foxp3+ regulatory T cells (Tregs) and IDO+ cells were 0.87% and 17.15%, respectively. Moreover, immunoreactive T cells, dendritic cells, and macrophages were more in the stromal than the intratumor region. NACT increased dendritic, CD3+ T, CD8+ T, and CD4+ T cells and decreased Tregs. The aforementioned alterations occurred predominantly in the stromal region and were primarily in responders. Non-responders primarily showed decreased Tregs and no increase in CD8+ T or dendritic cell infiltration. Furthermore, dendritic cells interacted more closely with CD3+ T cells after NACT, an effect primarily observed in responders. RNA-seq data revealed activation of the antigen receptor-mediated signaling pathway and upregulation of major histocompatibility complex (MHC) I and MHC II after chemotherapy, validated using IHC. ConclusionsNACT can reduce Tregs, and when tumor cells are effectively killed, antigen presentation is enhanced, subsequently activating antitumor immunity finitely. Our study provides the molecular characteristics and theoretical basis for the simultaneous or sequential combination of platinum-based NACT and immunotherapy for cervical cancer.

Laparoscopic Radical Hysterectomy Combined with Neoadjuvant Chemotherapy for Cervical Cancer Patients Effectively Improves Immune Function.

Objective To evaluate the clinical efficacy of neoadjuvant chemotherapy plus laparoscopic radical hysterectomy for cervical cancer and the effect on the immune function of patients. Methods Between January 2021 and December 2021, 42 patients with cervical cancer diagnosed and treated at our hospital were recruited and randomly assigned at a 1 : 1 ratio to receive neoadjuvant chemotherapy plus open radical hysterectomy (control group) or neoadjuvant chemotherapy plus laparoscopic radical hysterectomy (treatment group) (study group). Outcome measures included surgical indices, clinical outcomes, and immunological function. Results There were no significant differences in the operative time between the two groups (P > 0.05). Patients receiving laparoscopic surgery had significantly less intraoperative bleeding and shorter time lapse before postoperative anal exhaustion, time lapse before out-of-bed activities, and hospital stay versus patients receiving open surgery (P < 0.05). Laparoscopic surgery resulted in a significantly higher efficacy (90.48%) versus open surgery (57.14%) (P < 0.05). After treatment, patients in the study group showed lower levels of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and cancer antigen (CA125) than those in the control group (P < 0.05). After treatment, patients given laparoscopic surgery showed significantly lower CD3+, CD4+, and CD8+ levels and higher CD4+/CD8+ levels versus those with open surgery (P < 0.05). The postoperative conditions of the two groups, including recatheterization, postoperative blood transfusion, and secondary anti-inflammation were not significantly different (P > 0.05). The study group showed a significantly lower incidence of complications (19.05%) than the control group (71.43%) (P < 0.05). Patients in the study group had a lower reoperation rate and a higher survival rate (0.00%, 95.24%) than those in the control group (19.05%, 66.67%) (P < 0.05). Conclusion Neoadjuvant chemotherapy plus laparoscopic radical hysterectomy effectively improves clinical efficacy, lowers cancer marker levels, improves patients' immune function, reduces the risk of adverse events, and improves patients' prognosis with less intraoperative bleeding, less trauma, faster postoperative recovery, and shorter hospital stay for cervical cancer patients.

Neoadjuvant Chemotherapy in Stadium IB3, IIA2 and IIB Cervical Cancer a Narrative Review

This study aimed to describe Paclitaxel-Carboplatin chemotherapy as neoadjuvant chemotherapy in stage IB3, IIA2 and IIB cervical cancer. The review was conducted by collecting journals from previous studies discussing neoadjuvant chemotherapy in cervical cancer stages IB3, IIA2, and IIB and in this case specifically discussing Paclitaxel-Carboplatin chemotherapy. Neoadjuvant chemotherapy refers to systemic therapy intended to reduce the size of the tumour before the definitive operation. Several studies have shown that neoadjuvant chemotherapy has greater advantages than surgery alone for early stage cancers (IB3, IIA2, and IIB). Paclitaxel and Carboplatin are known chemotherapeutic agents that can be used as neoadjuvant chemotherapy. Neoadjuvant Chemotherapy regimen Paclitaxel Carboplatin is one of the options in performing therapy for early stage cervical cancer which can be very helpful in healing and cancer-free patient condition. Neoadjuvant chemotherapy followed by radical surgery has significant benefits that have been described in several previous studies. Neoadjuvant Chemotherapy regimen Paclitaxel Carboplatin may be used as therapy regimen for early stage cervical cancer with all advantage compared to only surgery. Thus, this type of regimen can be used to decrease mortality and morbidity in patient with stadium IB3, IIA2 and IIB cervical cancer.

Pretreatment Systemic Immune-Inflammation Index Can Predict Response to Neoadjuvant Chemotherapy in Cervical Cancer at Stages IB2-IIB.

Background: The systemic immune-inflammation index (SII) has been identified as a predictor of chemotherapy efficacy for a variety of cancers, and we aimed to determine its ability to predict the response to chemotherapy and its long-term prognosis for patients with cervical squamous cell carcinoma (CSCC) who have underwent platinum-based neoadjuvant chemotherapy (NACT). Methods: The date from 210 patients (133 in the training cohort and 77 in the validation cohort) with CSCC who received NACT were analyzed retrospectively. The association between SII and the pathological complete response (pCR) was determined using Pearson’s chi-square test, receiver operating characteristic (ROC) curve, and Logistic regression analysis. The Kaplan-Meier method and Cox proportional regression model were used to assess the relationship between SII and progression-free survival (PFS) or overall survival (OS). Results: The calculated optimal SII cutoff values for pCR and survival were 568.7051 and 600.5683, respectively, and patients were divided into two groups: a low SII group (≤568.7051 or ≤600.5683) and a high SII group (>568.7051 or >600.5683). A high SII was associated significantly with a lower pCR. Further analysis determined that SII was a more efficient predictor of pCR than the prognostic nutritional index, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Upon multivariate logistic analysis, SII proved to be an independent risk factor to predict the pCR of patients with CSCC. Kaplan-Meier analysis demonstrated that PFS and OS rates were significantly higher in the low-SII group compared with those in the high-SII group. Additional multivariate analysis indicated that the SII is an independent prognostic factor for patients with CSCC treated with NACT. Conclusion: The results confirmed that the pre-treatment SII is not only an independent predictor of pCR but also an independent prognostic factor of CSCC patients treated with platinum based NACT.

Simple trachelectomy following neoadjuvant chemotherapy in cervical cancer over 2 cm in size: A case report and review of literature

In the past few decades fertility preservation has emerged as a treatment modality for cervical cancer patients. Different surgical methods have been described, such as open or minimally invasive trachelectomy and gross cervical conisation combined with laparoscopic lymphadenectomy. A thirty-year-old nulliparous woman with uterine cervical cancer FIGO stage IB2 (classification from 2009) underwent neoadjuvant chemotherapy. After three cycles of chemotherapy with cisplatin and iphosphamide there was no colposcopic findings of cervical invasion, therefore a conservative surgery was performed. The patient underwent laparoscopic pelvic lymphadenectomy, cervical amputation and the endocervical curettage. The histopathology confirmed a complete response to chemotherapy.

Rs2686344 and serum squamous cell carcinoma antigen could predict clinical efficacy of neoadjuvant chemotherapy for cervical cancer

ObjectiveTo evaluate the predictive value of a single nucleotide polymorphism (SNP) rs2686344 and squamous cell carcinoma antigen (SCCAg) levels in the clinical efficacy of neoadjuvant chemotherapy (NACT) for cervical cancer. MethodsA total of 92 patients with stage IB2-IIIB carcinoma of the uterine cervix who received NACT treatment were enrolled. The relationship between the genotypes of SNP rs2686344 which is located on CAMKK2 on chromosome 12, SCCAg levels and the response to NACT was analyzed. The relationship between the SNP rs2686344 genotypes, SCCAg levels, the response to NACT and the five-year survival rate was evaluated. ResultsThe effective group accounted for 84.85% in patients with low level (≤3.5 ng/mL) of post-treatment SCCAg (post-SCCAg), while the ineffective group accounted for 15.15%. The post-SCCAg levels and the genotypes of rs2686344 were significantly correlated with NACT response (P = 0.003, and P = 0.006). In patients with CC or CT genotype of SNP rs2686344, effective group accounted for 81.18%, while ineffective group accounted for 18.82%; For patients with TT genotype, effective response group accounted for 28.57%, ineffective group accounted for 71.43%. Post-SCCAg level >3.5 ng/mL and TT genotype of SNP rs2686344 showed as independent risk factors for NACT response in the multivariate analysis (P = 0.002, and P = 0.048). There was no significant difference in 5-year overall survival and 5-year disease-free survival between patients with different levels of post-SCCAg, or among different rs2686344 genotypes. ConclusionThe high level of post-SCCAg (>3.5 ng/mL) and TT genotype of rs2686344 may suggest a higher risk of poor response to NACT.

CD34 and Bcl-2 as predictors for the efficacy of neoadjuvant chemotherapy in cervical cancer

BackgroundSuccessful neoadjuvant chemotherapy (NACT) could improve the surgical resection rate and radical curability of patients with cervical cancer, but only a subset of patients benefits. Therefore, identifying predictive biomarkers are urgently needed. The aim of this study was to evaluate the predictive value of CD34 and Bcl-2 in the NACT effectiveness of cervical cancer.MethodsSixty-seven patients with locally advanced cervical cancer (FIGO stages IB3, IIA2 or IIB) were classified into two groups based on effective (n = 48) and ineffective (n = 19) response to NACT. Immunohistochemistry was employed to identify CD34 and Bcl-2 expression before and after NACT. We analyzed the associations between the pre-NACT expression of these two biomarkers and the response of NACT. The expression of these two biomarkers before and after NACT was also assessed and compared.ResultsMore patients were CD34 positive expression before NACT in effective group compared to ineffective group (p = 0.005). However, no statistically significant difference in Bcl-2 expression before NACT were found between two groups (p = 0.084). In NACT effective group, the expression of both CD34 and Bcl-2 after NACT are down-regulated (p < 0.001 and p < 0.001, respectively), while there are no statistical differences between the pre- and post-NACT expression of CD34 and Bcl-2 in NACT ineffective group (p = 0.453 and p = 0.317, respectively).ConclusionThe positive CD34 expression before NACT may serve as a predictive biomarker for NACT of cervical cancer, but the pre-NACT expression of Bcl-2 is not an independent predictor. The down-regulated expression of these two indicators after NACT may indicate effective NACT.

Combined dynamic DCE-MRI and diffusion-weighted imaging to evaluate the effect of neoadjuvant chemotherapy in cervical cancer.

To prospectively investigate changes in quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the apparent diffusion coefficient (ADC) of diffusion-weighted imaging (DWI) in patients with cervical cancer before and after neoadjuvant chemotherapy (NACT). Thirty-eight patients with cervical cancer underwent DCE-MRI and DWI 1 week before and 4 weeks after NACT. The patients were classified into 2 groups: significant reaction (sCR) group and the non-sCR group. DCE-MRI parameters and ADC values were measured and compared between the 2 groups. Before NACT, the mean Ktrans value was higher, but the mean Ve was lower, in the sCR group compared with the non-sCR group; these differences were statistically significant (p<0.05). After NACT, the mean Ktrans value and the delta (i.e., changed) value of Ktrans were significantly lower in the sCR group compared with the non-sCR group (p<0.05). However, the mean ADC and the delta value of the mean ADC between the 2 groups were slightly higher in the sCR group compared with the non-sCR group (p<0.05). The area under the curve of pre-mean Ktrans, DKtrans, and pre-mean Ktrans combined with post-mean ADC values were 0.801, 0.955, and 0.878, respectively (p<0.05). The optimal cutoff values for distinguishing sCR from non-sCR were pretreatment Ktrans (0.7020 min-1) and DKtrans (0.0437 min-1). Quantitative parameters (pre-mean Ktrans, DKtrans, and pre-mean Ktrans) combined with post-mean ADC could predict treatment efficacy more precisely. However, quantitative DCE-MRI combined with DWI could not significantly improve prognostic efficacy.

Values of SCCAg, TAP and CEA in evaluating the efficacy of neoadjuvant chemotherapy for cervical cancer

Objective To investigate the values of squamous cell carcinoma antigen (SCCAg), tumor abnormal protein (TAP), carcinoembryonic antigen (CEA) in evaluating the efficacy of neoadjuvant chemotherapy for cervical cancer. Methods A total of 100 patients with cervical cancer treated by neoadjuvant chemotherapy were selected from September 2015 to September 2017 in our hospital, and 100 healthy persons were selected as the control group at the same time. The serum levels of SCCAg, TAP and CEA were detected and the relationships between the levels of SCCAg, TAP, CEA and the efficacy of neoadjuvant chemotherapy were analyzed. Results The serum levels of SCCAg [(4.95±0.65) μg/L vs. (0.22±0.04) μg/L], TAP [(175.21±25.42) μm2vs. (75.45±9.98) μm2], CEA [(35.65±4.23) ng/ml vs. (1.26±0.34 )ng/ml] in patients with cervical cancer were significantly higher than those of control group, and the differences were statistically significant (t=75.382, P<0.001; t=62.215, P<0.001; t=55.452, P<0.001). Three months after neoadjuvant chemotherapy for 100 cervical cancer patients, complete remission (CR) was achieved in 6 cases (6.00%), partial remission (PR) in 50 cases (50.00%), stable disease (SD) in 26 cases (26.00%), and progression disease (PD) in 18 cases (18.00%). The SCCAg, TAP and CEA levels of patients with CR [(2.12±0.32) μg/L vs. (4.90±0.52) μg/L, (133.12±14.22) μm2vs. (175.12±24.32) μm2, (10.34±2.42) ng/ml vs. (38.21±7.82) ng/ml] and PR after chemotherapy were significantly lower than those before chemotherapy [(3.22±0.47) μg/L vs. (4.94±0.53) μg/L, (145.22±17.77) μm2vs. (179.52±25.53) μm2, (16.75±3.02) ng/ml vs. (39.12±7.92) ng/ml], and the differences were statistically significant (t=11.153, P<0.001; t=3.562, P=0.004; t=8.340, P<0.001; t=17.169, P<0.001; t=7.797, P<0.001; t=18.662, P<0.001). The above indicators of patients with PD after chemotherapy were significantly higher than those before chemotherapy [(7.21±0.84) μg/L vs. (5.06±0.57) μg/L, (213.21±29.64) μm2vs. (171.56±26.87) μm2, (46.64±5.12) ng/ml vs. (35.75±7.88) ng/ml], and the differences were statistically significant (t=8.986, P<0.001; t=4.417, P<0.001; t=4.917, P<0.001). The differences of the above indicators before and after chemotherapy in patients with SD were not statistically significant [(5.03±0.57) μg/L vs. (4.97±0.55) μg/L; (175.51±23.37) μm2vs. (176.27±26.55) μm2; (35.26±7.34) ng/ml vs. (37.04±7.73) ng/ml; t=0.386, P=0.701; t=0.110, P=0.913; t=0.851, P=0.399]. The results of receiver operating characteristic (ROC) curve analysis showed that the sensitivity, specificity and accuracy of SCCAg in evaluating the neoadjuvant chemotherapy for cervical cancer were 85.71%, 81.82%, 84.00%, those of TAP were 82.14%, 77.27%, 80.00%, those of CEA were 78.57%, 77.27%, 78.00%, and those of the combined detection were 96.43%, 95.45%, 96.00%. The sensitivity, specificity and accuracy of the combined detection were significantly higher than those of the three alone, and the differences were statistically significant (χ2=14.434, P<0.001, χ2=15.421, P<0.001, χ2=21.741, P<0.001). Conclusion The serum levels of SCCAg, TAP and CEA in patients with cervical cancer are decreased after neoadjuvant chemotherapy. Their level changes can be used as important indicators to evaluate the efficacy of chemotherapy, and the combination of the three has better evaluation efficiency, which is worth for further clinical promotion. Key words: Uterine cervical neoplasms; Carcinoembryonic antigen; Chemotherapy, adjuvant; Squamous cell carcinoma antigen; Tumor abnormal protein

Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer

BackgroundNeoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.MethodsWe recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.ResultsFoxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z = − 8.635, p < 0.001) and peritumoral (median 113.53 vs. 82.48; Z = − 3.741, p < 0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z = − 0.817,p = 0.414) and peritumoral (median 402.56 vs. 390.84; Z = − 1.138,p = 0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z = − 2.009, p = 0.045) and peritumoral areas(median 63.31 vs. 98.48; Z = − 2.469, p = 0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR = 0.297; 95% CI, 0.109–0.810, p = 0.018) and overall survival (HR = 0.078; 95% CI, 0.010–0.598, p = 0.014).ConclusionsNACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.

Neoadjuvant Chemotherapy in Cervical Cancer: A Review Article

Neoadjuvant Chemotherapy in Cervical Cancer: A Review Article

PD-L1 Expression Correlates With Tumor Infiltrating Lymphocytes And Response To Neoadjuvant Chemotherapy In Cervical Cancer.

Programmed death-ligand 1 (PD-L1) has been reported to be expressed in many types of tumor cells, and bind to PD-1 on T lymphocytes to inhibit immune response. Immunologic checkpoint blockade with antibodies that target the PD1/PD-L1 pathway has demonstrated to have impressive antitumor effects on many malignancies. However, the significance of PD1/PD-L1 pathway in cervical cancer remains unclear. Here we studied PD-L1, PD-1, CD8 and HPV expression in cervical cancer and normal cervix by immunohistochemical staining. Our results showed that there was more frequently positive for PD-L1, PD-1 and CD8 in cervical cancer tissues compared to normal tissues, especially those strongly stained HPV. Additionally, PD-L1, PD-1 and CD8 were more frequently stained in tissues from advanced tumor and tumor with lymphoid nodes or vascular invasion respectively. Tissues from patients with chemotherapy history had over expression of PD-L1 in tumor cells and more PD-1 and CD8 in stromal mononuclear cells, which were identified as tumor infiltrated lymphocytes (TILs). These findings point to a key role of PD-L1 in immune escape of cervical cancer, and provide a rationale for therapeutic targeting of the PD-1/PD-L1 pathway.

Clinical Efficacy of Intra-Arterial Neoadjuvant Chemotherapy for Cervical Cancer

Standard treatment for early-stage cervical cancer (Ib2-IIa and IIb with parametrial invasion) is concurrent chemoradiotherapy and/or radical hysterectomy. The efficacy of intra-arterial delivery of neoadjuvant chemotherapy (IANAC) for this cancer remains unclear. We present three cases treated by IANAC for Ib-II stage cervical cancer, with results suggesting that IANAC is an effective treatment. J Clin Gynecol Obstet. 2017;6(2):37-40 doi: https://doi.org/10.14740/jcgo435w

Genome-wide association study identifies four SNPs associated with response to platinum-based neoadjuvant chemotherapy for cervical cancer

To identify genomic markers associated with the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. A total of 596 patients with stage IA2-IIIB cervical cancer were enrolled in this study. One single nucleotide polymorphism (SNP) (rs6812281, per allele OR = 2.37, P = 9.0 × 10−9) located at 4q34.3 reached GWAS significance (P < 5.0 × 10−8). Another three SNPs, rs4590782 (10q26.2, P = 1.59 × 10−5, per allele OR = 0.48), rs1742101 (14q32.11, P = 7.11 × 10−6, per allele OR = 0.52), and rs1364121 (16q23.3, P = 3.15 × 10−6, per allele OR = 1.98), exhibited strong evidence of associations with response to neoadjuvant chemotherapy. Patients with a C allele (CT + CC) of rs4590782 had better 5-year overall survival rates (82.9% vs. 75.8%, P = 0.083) and 5-year disease-free survival rate (80.8% vs. 72.7%, P = 0.021) than those without a C allele. Our findings help to characterize the genetic etiology of the response to neoadjuvant chemotherapy in patients with cervical cancer.

Clinical Efficacy of Intra-Arterial Neoadjuvant Chemotherapy for Cervical Cancer

Clinical Efficacy of Intra-Arterial Neoadjuvant Chemotherapy for Cervical Cancer

The efficacy and safety of irinotecan and cisplatin as neoadjuvant chemotherapy for cervical cancer

Objective To explore the efficacy and safety of irinotecan as neoadjuvant chemotherapy (INAC) plus radical surgery (RS) for cervical cancer. Methods According to International Federation of Gynecology and Obstetrics (FIGO), 81 cases were divided into ⅡB, ⅡA, and ⅠB2 groups. According to the tests of UGT1A1 gene polymorphisms, we adjusted the injection dose of irinotecan. The parameters were analyzed, including the efficacy, operation time and bleeding volume, postoperative pathology, survival time, and adverse reactions. The articles on irinotecan or paclitaxel combined with cisplatin for neoadjuvant chemotherapy between 2005 and 2015 were collected, and compared. Results The effective rate of chemotherapy was 81.5% (ⅠB2 group: 85.7%; ⅡA group: 83.3%; and ⅡB group: 72.2%), operation time was (5.3±1.1)h, and blood loss was (781±361.7)ml. After chemotherapy, 37 cases were delayed diarrhea, 70 cases were nausea, 48 cases were vomiting, and 40 cases were bone marrow suppression. The infiltration rate, operation time, and blood loss on ⅡB group was significantly higher than that on ⅡA andⅠB2 groups(P 0.05). Compared to three articles, the total effective rate in this study was higher than that in previous studies, also in ⅡA and ⅡB group. Conclusions Irinotecan chemotherapy regimens combined with cisplatin is effective and well tolerated. It is worthy of popularization and application. Detection of UGT1A1 gene polymorphism has guiding significance for chemotherapy regimen on irinotecan combined with cisplatin. Key words: Camptothecin/AA/AD; Cisplatin/AD; Chemotherapy, adjuvant; Uterine cervical neoplasms/DT

Assessing the Early Response of Advanced Cervical Cancer to Neoadjuvant Chemotherapy Using Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging: A Pilot Study.

Background:Diffusion-weighted imaging (DWI) with the intravoxel incoherent motion (IVIM) model has shown promising results for providing both diffusion and perfusion information in cervical cancer; however, its use to predict and monitor the efficacy of neoadjuvant chemotherapy (NACT) in cervical cancer is relatively rare. The study aimed to evaluate the use of DWI with IVIM and monoexponential models to predict and monitor the efficacy of NACT in cervical cancer.Methods:Forty-two patients with primary cervical cancer underwent magnetic resonance exams at 3 time points (pre-NACT, 3 weeks after the first NACT cycle, and 3 weeks after the second NACT cycle). The response to treatment was determined according to the response evaluation criteria in solid tumors 3 weeks after the second NACT treatment, and the subjects were classified as two groups: responders and nonresponders groups. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion-related pseudo-diffusion coefficient (D*), and perfusion fraction (f) values were determined. The differences in IVIM-derived variables and ADC between the different groups at the different time points were calculated using an independent samples t-test.Results:The D and ADC values were all significantly higher for the responders than for the nonresponders at all 3 time points, but no significant differences were observed in the D* and f values. An analysis of the receiver operating characteristic (ROC) curves indicated that a D value threshold <0.93 × 10−3 mm2/s and an ADC threshold <1.11 × 10−3 mm2/s could differentiate responders from nonresponders at pre-NACT time point, yielding area under the curve (AUC) of which were 0.771 and 0.806, respectively. The ROC indicated that the AUCs of D and ADC at the 3 weeks after the first NACT cycle and 3 weeks after the second NACT cycle were 0.823, 0.763, and 0.787, 0.794, respectively. The AUC values of D and ADC at these 3 time points were not significantly different (P = 0.641, 0.512, and 0.547, respectively).Conclusions:D and ADC values may be useful for predicting and monitoring the efficacy of NACT in cervical cancer. An IVIM model may be equal to monoexponential model in predicting and monitoring the efficacy of NACT in cervical cancer.

DNA Damage and Repair Biomarkers in Cervical Cancer Patients Treated with Neoadjuvant Chemotherapy: An Exploratory Analysis.

Cervical cancer cells commonly harbour a defective G1/S checkpoint owing to the interaction of viral oncoproteins with p53 and retinoblastoma protein. The activation of the G2/M checkpoint may thus become essential for protecting cancer cells from genotoxic insults, such as chemotherapy. In 52 cervical cancer patients treated with neoadjuvant chemotherapy, we investigated whether the levels of phosphorylated Wee1 (pWee1), a key G2/M checkpoint kinase, and γ-H2AX, a marker of DNA double-strand breaks, discriminated between patients with a pathological complete response (pCR) and those with residual disease. We also tested the association between pWee1 and phosphorylated Chk1 (pChk1), a kinase acting upstream Wee1 in the G2/M checkpoint pathway. pWee1, γ-H2AX and pChk1 were retrospectively assessed in diagnostic biopsies by immunohistochemistry. The degrees of pWee1 and pChk1 expression were defined using three different classification methods, i.e., staining intensity, Allred score, and a multiplicative score. γ-H2AX was analyzed both as continuous and categorical variable. Irrespective of the classification used, elevated levels of pWee1 and γ-H2AX were significantly associated with a lower rate of pCR. In univariate and multivariate analyses, pWee1 and γ-H2AX were both associated with reduced pCR. Internal validation conducted through a re-sampling without replacement procedure confirmed the robustness of the multivariate model. Finally, we found a significant association between pWee1 and pChk1. The message conveyed by the present analysis is that biomarkers of DNA damage and repair may predict the efficacy of neoadjuvant chemotherapy in cervical cancer. Further studies are warranted to prospectively validate these encouraging findings.