Stage IB-IIB Cervical Cancer Research Articles

Assessing the Adequacy of Traditional Vertebral Landmarks as Upper Border of Whole Pelvic Radiotherapy Field for Stage IB2-IIB Cervical Cancer.

This study investigates the impact of insufficient common iliac lymph node (CIN) irradiation on treatment outcomes in patients with stage IB2-IIB cervical cancer receiving concurrent chemoradiotherapy (CCRT). We retrospectively analyzed 68 patients with Federation of Gynecology and Obstetrics stage IB2-IIB, treated with weekly cisplatin-based CCRT from 2008 to 2018. Patients received external-beam whole pelvic radiotherapy (WPRT) and concurrent cisplatin chemotherapy, followed by high-dose-rate brachytherapy. The WPRT upper border was at L4-5 in 61 patients and L3-4 in 7 patients. Thirty-seven patients had the CIN area fully included (full-CIN group), while 31 had partial inclusion (partial-CIN group). Recurrence rates and survival outcomes were analyzed over a median follow-up of 111 months. Patient characteristics and the irradiated dose were comparable. Treatment failure occurred in three patients (8.1%) in the full-CIN group and in six patients (19.4%) in the partial-CIN group, with CIN and para-aortic lymph node recurrence in two and one patients, respectively. The 5-year cumulative recurrence rate was 0% for the full-CIN group and 11.4% for the partial-CIN group (p = 0.04). Cause-specific survival was 100% vs. 87.1% (p = 0.025), and the overall survival was 94.3% vs. 87.1% (p = 0.44). Fully including the CIN area in WPRT is crucial for stage IB2-IIB cervical cancer. Vascular anatomical margins should be considered over vertebral landmarks.

Predicting recurrence in intermediate‑ and high‑risk stage IB‑IIB cervical cancer treated with adjuvant cisplatin and paclitaxel chemotherapy post‑radical hysterectomy: The role of TBX2 expression.

Cervical cancer remains a significant global health concern despite advances in prevention and treatment. Current management for intermediate- to high-risk stage IB-IIB cervical cancer post-radical hysterectomy involves irradiation or concurrent chemoradiation, although patients can exhibit several adverse events. Adjuvant chemotherapy has emerged as a promising alternative; however, its efficacy remains unclear. T-box (TBX)2 is a transcription factor that is involved in the regulation of cell cycle progression during cancer and embryonic development. Additionally, elevated expression of TBX2 is associated with resistance to DNA-damaging chemotherapeutic agents, such as cisplatin, carboplatin and doxorubicin. The aim of the present study was to investigate the relationship between TBX2 expression and recurrence in patients receiving adjuvant cisplatin and paclitaxel (TP) chemotherapy post-radical hysterectomy. Additionally, the impact of TBX2 knockdown on cisplatin sensitivity was assessed in vitro. A retrospective analysis was performed on 100 patients. Patients were categorized into two groups based on recurrence within 2 years of treatment initiation: The non-recurrent group (n=85) and the recurrent group (n=15). TBX2 expression was assessed immunohistochemically, and multiple logistic regression analysis was performed to identify predictors of recurrence. Additionally, the impact of small interfering RNA-mediated TBX2 knockdown on cervical cancer cell sensitivity to cisplatin was evaluated. TBX2 expression was significantly higher in the recurrent group compared with that in the non-recurrent group (P<0.01). Patients were stratified into low TBX2 expression (weighted score ≤8; n=80) and high TBX2 expression (weighted score ≥9; n=20) groups. The high TBX2 expression group exhibited a higher recurrence rate compared with the low expression group (P<0.01). Multivariate analysis identified TBX2 expression as an independent predictor of recurrence (P<0.01). Moreover, TBX2 knockdown significantly enhanced cervical cancer cell sensitivity to cisplatin in vitro (P<0.05). These findings highlight TBX2 expression as a potential predictive biomarker for recurrence amongst patients with intermediate- to high-risk stage IB-IIB cervical cancer receiving adjuvant TP chemotherapy post-radical hysterectomy.

Prediction of outcomes after chemoradiotherapy for cervical cancer by neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio

Background Cervical cancer ranks as the second most fatal tumour globally among females. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been widely applied to the diagnosis of cancers. Methods The clinicopathologic data of 180 patients with stage IB2-IIB cervical cancer who underwent radical concurrent chemoradiotherapy from January 2018 to December 2019 were retrospectively analysed. Receiver operating characteristic (ROC) curves were plotted to analyse the optimal cut-off values of NLR and PLR for predicting the therapeutic effects of concurrent chemoradiotherapy. The associations of PLR and other clinicopathological factors with 1-year survival rates were explored through univariate analysis and multivariate Cox regression analysis, respectively. Results NLR was significantly associated with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 2.89, area under the ROC curve (AUC) of 0.848 (95% confidence interval [CI]: 0.712–0.896), sensitivity of 0.892 (95% CI: 0.856–0.923) and specificity of 0.564 (95% CI: 0.512–0.592). PLR had a significant association with the therapeutic effects of neoadjuvant therapy, with the optimal cut-off value of 134.27, AUC of 0.766 (95% CI: 0.724–0.861), sensitivity of 0.874 (95% CI: 0.843–0.905) and specificity of 0.534 (95% CI: 0.512–0.556). Lymphatic metastasis ([95% CI: 1.435–5.461], [95% CI: 1.336–4.281], depth of invasion ([95% CI: 1.281–3.546], [95% CI: 1.183–3.359]) and tumour size ([95% CI: 1.129–3.451], [95% CI: 1.129–3.451]) were independent factors influencing the overall survival and disease-free survival (DFS) of patients with cervical cancer. NLR (95%CI: 1.256-4.039) and PLR (95%CI:1.281-3.546) were also independent factors affecting DFS. Conclusion NLR and PLR in the peripheral blood before treatment may predict DFS of patients with stage IB2-IIB cervical cancer.

Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.

This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma. Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL). After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80). This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

Heterogeneous treatment effects of adjuvant therapy for patients with cervical cancer in the intermediate-risk group.

The efficacy of adjuvant therapy for patients with cervical cancer with intermediate risk (CC-IR) remains controversial. We examined the impact of adjuvant therapy on survival outcomes in patients with CC-IR and evaluated the heterogeneous treatment effects (HTEs) of adjuvant therapies based on clinicopathologic characteristics. We retrospectively analyzed a previous Japanese nationwide cohort of 6192 patients with stage IB-IIB cervical cancer who underwent radical hysterectomy. We created two pairs of propensity score-matched treatment/control groups to investigate the treatment effects of adjuvant therapies: (1) adjuvant therapy versus non-adjuvant therapy; (2) chemotherapy versus radiotherapy conditional on adjuvant therapy. Multivariate analyses with treatment interactions were performed to evaluate the HTEs. Among the 1613 patients with CC-IR, 619 and 994 were in the non-treatment and treatment groups, respectively. Survival outcomes did not differ between the two groups: 3-year progression-free survival (PFS) rates were 88.1% and 90.3% in the non-treatment and treatment groups, respectively (p = 0.199). Of the patients in the treatment group, 654 and 340 received radiotherapy and chemotherapy, respectively. Patients who received chemotherapy had better PFS than those who received radiotherapy (3-year PFS, 90.9% vs. 82.9%, p = 0.010). Tumor size was a significant factor that affected the treatment effects of chemotherapy; patients with large tumors gained better therapeutic effects from chemotherapy than those with small tumors. Adjuvant therapy is optional for some patients with CC-IR; however, chemotherapy can be recommended as adjuvant therapy, particularly for patients with large tumors.

CLPTM1L expression predicts recurrence of patients with intermediate‑ and high‑risk stage IB‑IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

According to the National Comprehensive Cancer Network clinical practice guidelines of cervical cancer, concurrent chemoradiotherapy or radiotherapy is suggested for patients who receive radical hysterectomy and have intermediate- and high-risk cervical cancer. However, adjuvant chemotherapy has been increasingly chosen given the adverse events associated with chemoradiotherapy or radiotherapy and the increase in evidence regarding the efficacy of adjuvant chemotherapy. Given that adjuvant chemotherapy is not a standard treatment at present, if recurrence after adjuvant chemotherapy could be predicted, it would assist the decision of gynecological oncologists selecting which adjuvant therapy (chemotherapy or radiation therapy) to use. Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L; also known as cisplatin resistance-related protein 9) is associated with apoptotic mechanisms and is related to the proliferation of the tumor cells and resistance against chemotherapy. In the present study, the association between CLPTM1L expression and recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by treatment with cisplatin and paclitaxel (TP) as adjuvant chemotherapy was determined. Patients were divided into two groups: Recurrence group and no-recurrence group. CLPTM1L expression was examined using immunohistochemistry in paraffin-embedded sections using weighted scores. Regarding the characteristics of the patients, a histology of non-squamous cell carcinoma, lymph node metastasis and parametrium invasion were more common in the recurrence group compared with the non-recurrence group. In the recurrence group, CLPTM1L expression was significantly higher than that in the no-recurrence group. Next, patients were divided into low and high-expression groups based on the weighted score with a cut-off value of 6. In the high expression group, patients exhibited a higher rate of recurrence (37.5 vs. 5.1%) and had worse overall survival. Multivariate analysis revealed that high CLPTM1L expression was independently related to recurrence. In in vitro analysis, small interfering RNA-mediated knockdown of CLPTM1L enhanced the sensitivity of cervical cancer cells to cisplatin. In conclusion, the present study revealed that CLPTM1L expression may be a predictive biomarker of recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

Evaluation of parametrial infiltration in patients with IB-IIB cervical cancer by a radiomics model integrating features from tumoral and peritumoral regions on 18 F-FDG PET/MRI images.

Parametrial infiltration (PMI) is an essential factor in staging and planning treatment of cervical cancer. The purpose of this study was to develop a radiomics model for accessing PMI in patients with IB-IIB cervical cancer using the features from 18 F-FDG PET/MRI images. In this retrospective study, 66 patients with FIGO stage IB-IIB cervical cancer (22 with PMI and 44 without PMI) underwent 18 F-FDG PET/MRI were divided into a training (n = 46) and a testing dataset (n = 20). Features were extracted from both tumoral and peritumoral regions on 18 F-FDG PET/MRI. Single-modality and multi-modality radiomics models were developed with random forest to predict PMI. The performance of models was evaluated with F1 score, accuracy and AUC. Kappa test was used to observe the differences between pathological results and PMI evaluated by radiomics-based models. Intraclass correlation coefficient for features extracted from each ROI was measured. Three-fold cross-validation was conducted to confirm the diagnostic ability of the features. The radiomics models developed by features from primary tumor on T2 weighted (F1 Score = 0.400, accuracy = 0.700, AUC = 0.708, Kappa = 0.211, P = 0.329) and peritumoral region on PET (F1 Score = 0.533, accuracy = 0.650, AUC = 0.714, Kappa = 0.271, P = 0.202) achieved better performances in the testing dataset among four single-ROI radiomics models. The combined model using the features from primary tumor on T2 weighted and peritumoral region on PET achieved the best performance (F1 Score = 0.727, accuracy = 0.850, AUC = 0.774, Kappa = 0.625, P < 0.05). The results suggest that 18 F-FDG PET/MRI could provide complementary information of cervical cancer. The radiomics-based method integrating the features from tumoral and peritumoral regions on 18 F-FDG PET/MRI had a superior performance on PMI evaluation.

The prognostic value of the presence of pelvic and/or para-aortic lymph node metastases in cervical cancer patients; the influence of the new FIGO classification (stage IIIC)

IntroductionOne of the major changes in the revised (2018) FIGO-staging system is the addition of stage IIIC to the previously used 2009 system. We evaluated the prognostic value of positive pelvic and/or para-aortic lymph nodes in patients with cervical cancer. MethodsA nationwide retrospective cohort study was performed by analyzing data from the Netherlands Cancer Registry. All patients newly diagnosed with stage IB-IVA between 2005 and 2018 were identified. Three-year, 5-year and 15-year overall survival (OS) rates were estimated with the Kaplan-Meier method. ResultsOf the included 6082 patients, 1740 patients (29%) had pelvic and/or para-aortic lymph node metastases. For patients with FIGO 2009 stage IB-IB1-IIA-IIA1 and stage IB2-IIA2-IIB with pelvic and/or para-aortic lymph node metastases the OS was significantly different (p < 0.001 and p = 0.009), with a 5-year OS of 77% and 67%, compared with 92% and 74% for women without lymph node metastases. For FIGO 2009 stage IIIA-IIIB-IVA with and without lymph node metastases, survival rates are not significantly different (p = 0.064). For FIGO 2018 stage IIIC the 3y-OS, 5y-OS and 15-year OS are 72%, 65% and 59% respectively. Survival rates of IIIC diagnosed based on imaging (IIICr) are significantly impaired compared to stage IIIC diagnosed based on pathology (IIICp) (p < 0.001). ConclusionPatients with FIGO 2009 stage IB–IIB cervical cancer with pelvic and/or para-aortic lymph node metastases have significantly impaired survival compared to patients without metastases. Survival rates of patients with FIGO 2009 stage IIIA–IVA are not affected by lymph node metastases.

Neoadjuvant chemotherapy followed by surgery for stage IB2-IIB cervical cancer is not superior to chemoradiation

Neoadjuvant chemotherapy followed by surgery for stage IB2-IIB cervical cancer is not superior to chemoradiation

Multiparametric Magnetic Resonance Imaging in Determining Prognostic Factors for Cervical Cancer IB2-IIB Stages after Neoadjuvant Chemotherapy

Background : Comprehensive treatment of locally advanced cervical cancer (CC) requires the use of informative diagnostic methods to assess tumor size, extent of the tumor and other factors that determine prognosis of the disease. Purpose : Determination of diagnostic opportunities of multiparametric magnetic resonance imaging (mpMRI) in the visualization of residual tumor and assessment of the main prognostic factors in patients with stage IB2-IIB cervical cancer (FIGO) after neoadjuvant chemotherapy (NACT). Material and methods : Patients with stage IB2-IIB cervical cancer (n = 120) were prospectively enrolled in the study; they received NACT followed by surgical treatment or chemoradiotherapy (CRT). Patients underwent mpMRI before NACT and not later than 14 days after the 3rd course of NACT. To determine the diagnostic opportunities of mpMRI, MRI-data were compared with pathomorphological results. In the comparative analysis were included the following factors: residual tumor size (maximum diameter), depth of stromal invasion (mm), presence of parametrial invasion. Potential MRI-signs suggestive for lymphovascular invasion (LVI) of the parametrium were also assessed. Results : Obtained MRI-data about the size of the residual tumor and the depth of stromal invasion showed statistically significant correlation with the results of pathomorphological study (p &lt; 0.0001) — R 2 = 0.77 and 0.69, respectively. Difference value in measuring the maximum diameter of the residual tumor was on the average 2.52±6.76 mm. MRI sensitivity in the assessment of parametrial invasion was 71.4 %, specificity — 95.1 %, accuracy — 88.9 %, PVPR — 71.4 %, PVNR — 95.1 %. Potential predictors significantly associated with parametrial LVI were identified: parametrial edema (p = 0.001) and dilatation of parametrial vessels (&gt; 3 mm) (p = 0.015). According to these factors was developed a mathematical model, which predicts the risk of having parametrial LVI before surgery in patients after NACT. Conclusion : Multiparametric MRI is an effective technique in assessing the size of the residual tumor, depth of stromal invasion and parametrial invasion in patients with stage IB2-IIB cervical cancer after NACT. MpMRI makes it possible to assess potential signs, associated with parametrial LVI in patients with locally advanced cervical cancer.

Multiparametric MRI radiomics nomogram for predicting lymph-vascular space invasion in early-stage cervical cancer.

To develop a radiomics nomogram based on multiparametric MRI (mpMRI) to pre-operatively predict lymph-vascular space invasion (LVSI) in patients with early-stage cervical cancer. This retrospective study included 233 consecutive patients with Stage IB-IIB cervical cancer. According to the ratio of 2:1, 154 patients and 79 patients were randomly assigned to the primary and validation cohorts, respectively. Features with intraclass and interclass correlation coefficient (ICCs) greater than 0.75 were selected for radiomics features. The significant features for predicting LVSI were selected using the least absolute shrinkage and selection operator (LASSO) algorithm based on the primary cohort. The rad-score for each patient was constructed via a linear combination of selected features that were weighted by their respective coefficients. The radiomics nomogram was developed using multivariable logistic regression analysis by incorporating the rad-score and clinical risk factors. A total of 19 radiomics features and 3 clinical risk factors were selected. The rad-score exhibited a good performance in discriminating LVSI with a C-index of 0.76 and 0.81 in the primary and validation cohorts, respectively. The radiomics nomogram also exhibited a good discriminating performance in two cohorts (C-index of 0.78 and 0.82). The calibration curve of the radiomics nomogram demonstrated no significant differences was found between prediction and observation outcomes for the probability of LVSI in two cohorts (p = 0.86 and 0.98, respectively). The decision curve analysis indicated that clinician and patients could benefit from the use of radiomics nomogram and rad-score. The nomogram and rad-score could be used conveniently and individually to predict LVSI in patients with early-stage cervical cancer and facilitate the treatment decision for clinician and patients. The nomogram could pre-operatively predict LVSI in early-stage cervical cancer.

Deep learning nomogram for predicting lymph node metastasis using computed tomography image in cervical cancer.

Deep learning (DL) has been used on medical images to grade, differentiate, and predict prognosis in many tumors. To explore the effect of computed tomography (CT)-based deep learning nomogram (DLN) for predicting cervical cancer lymph node metastasis (LNM) before surgery. In total, 418 patients with stage IB-IIB cervical cancer were retrospectively enrolled for model exploration (n = 296) and internal validation (n = 122); 62 patients from another independent institution were enrolled for external validation. A convolutional neural network (CNN) was used for DL features extracting from all lesions. The least absolute shrinkage and selection operator (Lasso) logistic regression was used to develop a deep learning signature (DLS). A DLN incorporating the DLS and clinical risk factors was proposed to predict LNM individually. The performance of the DLN was evaluated on internal and external validation cohorts. Stage, CT-reported pelvic lymph node status, and DLS were found to be independent predictors and could be used to construct the DLN. The combination showed a better performance than the clinical model and DLS. The proposed DLN had an area under the curve (AUC) of 0.925 in the training cohort, 0.771 in the internal validation cohort, and 0.790 in the external validation cohort. Decision curve analysis and stratification analysis suggested that the DLN has potential ability to generate a personalized probability of LNM in cervical cancer. The proposed CT-based DLN could be used as a personalized non-invasive tool for preoperative prediction of LNM in cervical cancer, which could facilitate the choice of clinical treatment methods.

The Okabayashi Radical Hysterectomy: Basic Principle and Step-by-Step Procedure.

Abdominal radical hysterectomy is the standard operation for stage IB–IIB cervical cancer in the world, which was established by Professor Hidekazu Okabayashi in 1921. In this article, the basic principle and step-by-step procedure of Okabayashi radical hysterectomy are presented, especially for young doctors to understand clearly the important points of this surgery and to realize its radicality and safety for better survival and quality of life of patients with cervical cancer.

Laterally extended parametrectomy

ObjectiveTo describe the laterally extended parametrectomy (LEP) surgical technique, emphasizing the main challenges of the procedure.MethodsLEP was designed as a more radical surgical procedure aiming to remove the entire parametrial tissue from the pelvic sidewall. Its initial indications were for lymph node positive Stage Ib (current International Federation of Gynecology and Obstetrics 2018 Stage IIIc) and Stage IIb cervical cancer. Currently, with most guidelines recommending definitive radiochemotherapy for these cases, initial LEP indications have become debatable. LEP is now mainly indicated for removing tumors involving the soft structures of the pelvic sidewall during a pelvic exenteration, aiming to obtain lateral free margins. This expands the lateral borders of the dissection to not only the medial surface of internal iliac vessels, but also to the true limits of the pelvic sidewall.ResultsDuring LEP, the parietal and visceral branches of the hypogastric vessels are divided at the entry and exit level of the pelvis. Consequently, the entire internal iliac system is excised, and no connective or lymphatic tissue remain on the pelvic sidewall. The main technical challenges of LEP are caused by the difficulty in ligating large caliber vessels (internal iliac artery and vein) and the variable anatomic distribution of pelvic sidewall veins.ConclusionLEP is a feasible technique for removing pelvic sidewall recurrences, aiming to obtain surgical free margins.

Combination of weekly paclitaxel-carboplatin plus standard bevacizumab as neoadjuvant treatment in stage IB–IIB cervical cancer

ObjectiveIn this study we investigated response rates of bevacizumab in addition to weekly paclitaxel and carboplatin in neoadjuvant setting in cervical cancer stage IB–IIB.MethodsIn this retrospective study we included patients...

Prognostic Factors Associated with 5-Year Overall Survival in Cervical Cancer Patients Treated with Radical Hysterectomy Followed by Adjuvant Concurrent Chemoradiation Therapy at a Tertiary Care Center in Eastern Europe.

Background: This retrospective observational study aims to assess the 5-year overall survival and the prognostic significance of risk factors of patients who underwent radical hysterectomy followed by adjuvant concurrent chemoradiation therapy (CCRT) for FIGO stage IB1-IIB cervical cancer in a tertiary care center in Eastern Europe. Methods: From January 2010 to February 2019, 222 patients with stage IB1-IIB cervical cancer were treated with radical hysterectomy followed by adjuvant CCRT in our institution. The baseline information consisting of demographic and clinicopathologic data, treatment choices, recurrences, and outcome information was collected and examined. The survival rates were illustrated using Kaplan–Meier curves and prognosis analyses were accomplished using Cox multivariate analyses. Results: The 222 participants had a mean age of 51.2 years (28–76). The median follow-up time was 65.5 months (3–128). Tumor characteristics revealed FIGO stage (IB1 2.3%, IB2 35.1%, IB3 16.7%, IIA1 9%, IIA2 8.6%, IIB 28.4%) and the most encountered histologic cell type was squamous cell carcinoma (80.06%) followed by adenocarcinoma (11.3%). At the time of examination, 157 patients (70.07%) were alive, of which 135 (61%) were alive free of disease and 22 (9%) were alive with disease. The multivariate Cox regression analysis acknowledged stage IIB, parametrial involvement, and the presence of lymph node metastases as independent prognostic risk factors, significantly worsening the oncologic outcomes influencing the survival with a P-value of 0.076, 0.0001, and 0.008, respectively. The 5-year overall survival was 69.9%. Conclusions: Altogether, the study enhances the significance of prognostic risk factors on the 5-year overall survival of patients who underwent radical hysterectomy followed by adjuvant CCRT for FIGO stages IB1-IIB cervical cancer, allowing comparisons with other regions.

A Fifteen-Gene Classifier to Predict Neoadjuvant Chemotherapy Responses in Patients with Stage IB to IIB Squamous Cervical Cancer.

Neoadjuvant chemotherapy (NACT) remains an attractive alternative for controlling locally advanced cervical cancer. However, approximately 15–34% of women do not respond to induction therapy. To develop a risk stratification tool, 56 patients with stage IB‐IIB cervical cancer are included in 2 research centers from the discovery cohort. Patient‐specific somatic mutations led to NACT non‐responsiveness are identified by whole‐exome sequencing. Next, CRISPR/Cas9‐based library screenings are performed based on these genes to confirm their biological contribution to drug resistance. A 15‐gene classifier is developed by generalized linear regression analysis combined with the logistic regression model. In an independent validation cohort of 102 patients, the classifier showed good predictive ability with an area under the curve of 0.80 (95% confidence interval (CI), 0.69–0.91). Furthermore, the 15‐gene classifier is significantly associated with patient responsiveness to NACT in both univariate (odds ratio, 10.8; 95% CI, 3.55–32.86; p = 2.8 × 10−5) and multivariate analysis (odds ratio, 17.34; 95% CI, 4.04–74.40; p = 1.23 × 10−4) in the validation set. In conclusion, the 15‐gene classifier can accurately predict the clinical response to NACT before treatment, representing a promising approach for guiding the selection of appropriate treatment strategies for locally advanced cervical cancer.

A randomized phase III trial of adjuvant chemotherapy versus concurrent chemoradiotherapy for postoperative cervical cancer: Japanese Gynecologic Oncology Group study (JGOG1082)

BackgroundThe standard treatment for stage IB–IIB cervical cancer is radiotherapy or radical hysterectomy; after radical hysterectomy, adjuvant concurrent chemoradiotherapy is recommended for patients with high risk factors. However, adjuvant concurrent...

Dose-dense Neoadjuvant Chemotherapy With Paclitaxel and Carboplatin in Cervical Cancer: Efficacy on Pathological Response.

The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

Postoperative Adjuvant Chemotherapy Improved the Prognosis in Locally Advanced Cervical Cancer Patients With Optimal Response to Neoadjuvant Chemotherapy.

BackgroundFew studies investigated the effectiveness of adjuvant chemotherapy (ACT) in patients with optimal response to neoadjuvant chemotherapy (NACT), and an optimal number of treatment cycles for these patients remains unknown.MethodsA total of 261 Chinese patients with FIGO stage IB2-IIB cervical cancer who obtained an optimal response to NACT were included after radical surgery, and the disease-free survival (DFS) and overall survival (OS) of these patients treated with different cycles of postoperative ACT were compared using the Log-rank test and multivariate analysis.ResultsWe found that the prognosis of optimal responders treated with postoperative ACT was significantly better than those without further adjuvant therapy. The multivariate analysis showed that postoperative ACT was an independent prognostic factor for DFS. However, there was no significant difference in the DFS and OS between patients who had three cycles of ACT and those with six cycles. Further analysis revealed a significant association of six cycles of ACT with the risk of leukopenia, nausea/vomiting, and rash.ConclusionOur data suggest that additional three cycles of ACT after surgery may improve the clinical outcome of optimal responders in terms of DFS, OS, and drug toxicity.