Prediction of Postoperative Pathologic Risk Factors in Cervical Cancer Patients Treated with Radical Hysterectomy by Machine Learning.

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

Nomogram model for predicting postoperative survival of patients with stage IB-IIA cervical cancer.

To establish a prediction model based on clinical and pathological information for the long-term survival of patients with cervical cancer, we retrospectively analyzed the clinical data of patients pathologically diagnosed with stage IB-IIA cervical cancer between July 2007 and September 2017 in the Chinese Academy of Medical Sciences Cancer Hospital. Factors affecting the overall survival of the patients were analyzed using a Cox model, and a cervical cancer patient prediction nomogram model was established. A total of 2,319 patients were included in the study. According to the multivariate Cox regression analysis, number of complications, surgical methods, neoadjuvant treatment, lymph node metastasis, postoperative treatment, lymphovascular space invasion (LVSI), and other independent factors affecting prognosis were included to establish a nomogram. The nomogram consistency index in the training and validation cohorts was 0.691 and 0.615, respectively. The study established a highly accurate predictive model for the postoperative survival of cervical cancer patients.

A Preoperative Nomogram for Predicting Chemoresistance to Neoadjuvant Chemotherapy in Patients with Locally Advanced Cervical Squamous Carcinoma Treated with Radical Hysterectomy.

PURPOSE: This study aimed to investigate the factors associated with chemoresistance to neoadjuvant chemotherapy (NACT) followed by radical hysterectomy (RH) and construct a nomogram to predict the chemoresistance in patients with locally advanced cervical squamous carcinoma (LACSC). MATERIALS AND METHODS: This retrospective study included 516 patients with International Federation of Gynecology and Obstetrics (2003) stage IB2 and IIA2 cervical cancer treated with NACT and RH between 2007 and 2017. Clinicopathologic data were collected, and patients were assigned to training (n=381) and validation (n=135) sets. Univariate and multivariate analyses were performed to analyze factors associated with chemoresistance to NACT. A nomogram was built using the multivariate logistic regression analysis results. We evaluated the discriminative ability and accuracy of the model using a concordance index and a calibration curve. The predictive probability of chemoresistance to NACT was defined as > 34%. RESULTS: Multivariate analysis confirmed menopausal status, clinical tumor diameter, serum squamous cell carcinoma antigen level, and parametrial invasion on magnetic resonance imaging before treatment as independent prognostic factors associated with chemoresistance to NACT. The concordance indices of the nomogram for training and validation sets were 0.861 (95% confidence interval [CI], 0.822 to 0.900) and 0.807 (95% CI, 0.807 to 0.888), respectively. Calibration plots revealed a good fit between the modelpredicted probabilities and actual probabilities (Hosmer-Lemeshow test, p=0.597). Furthermore, grouping based on the nomogram was associated with progression-free survival. CONCLUSION: We developed a nomogram for predicting chemoresistance in LACSC patients treated with RH. This nomogram can help physicians make clinical decisions regarding primary management and postoperative follow-up of the patients.

Paclitaxel Plus Platinum Neoadjuvant Chemotherapy Followed by Surgery Versus Primary Surgery in Locally Advanced Cervical Cancer-A Propensity Score Matching Analysis.

OBJECTIVE: To compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery (NACTS) and primary surgery (PS) in locally advanced cervical cancer (LACC). METHODS: LACC (stage IB2/IIA2, FIGO 2009) patients who accepted NACTS or PS in the Cancer Hospital of the Chinese Academy of Medical Sciences from 2007 to 2017 were enrolled, and a database was established. A 1:1 ratio propensity score matching (PSM) was performed for the NACTS group and PS group according to pretreatment characteristics. After PSM, the clinicopathological features and prognosis between the matched groups were compared. RESULTS: Of 802 cases in the database, 639 met the inclusion criteria, with 428 received paclitaxel plus platinum NACTS, and 211 received PS. After PSM, the two groups had comparable pretreatment characteristics, with 190 cases in each group. In the NACTS group, the operation parameters were similar to the PS group except for the longer operation time (median 255 min vs. 239 min, P = 0.007); pathological intermediate-risk factors including tumor diameter (P < 0.001) and LVSI(+) (P < 0.001) were significantly decreased; fewer patients were with ≥2 intermediate-risk factors (10.5 vs. 53.2%, P < 0.001) so that the rate of adjuvant radiotherapy was reduced (54.2 vs. 70.0%, P = 0.002). DFS and OS were similar between the NACTS group and PS group (P > 0.05). However, for patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml, DFS of the NACTS group was significantly prolonged (P = 0.016, P = 0.007). CONCLUSION: Paclitaxel plus platinum neoadjuvant chemotherapy can reduce adjuvant radiotherapy by decreasing pathological risk factors. Patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml may obtain survival benefits.

Analysis of Clinicopathological Features of Cervical Mucinous Adenocarcinoma with a Solitary Ovarian Metastatic Mass as the First Manifestation.

PURPOSE: To avoid misdiagnosis, clinicopathological features were analyzed in cases of cervical mucinous adenocarcinoma with solitary ovarian metastatic masses. PATIENTS AND METHODS: Three cases misdiagnosed as primary ovarian adenocarcinoma before surgery were filtered from the database of the Cancer Hospital/Chinese Academy of Medical Sciences from January 1998 to December 2016. The clinical data were thoroughly collected and compared, and both frozen and paraffin-embedded pathological sections were reviewed by two expert pathologists. RESULTS: None of the patients experienced cervical contact bleeding, and no typical cervical neoplasms were found. The cervical canals were slightly thickened in two patients, as detected by either palpation or imaging. The high-risk human papillomavirus (HPV) test results were all negative, and the thin-prep cytologic test (TCT) screened only one case of atypical glandular epithelial cells. All cases were indicative of higher serum CA19-9 levels (79.49-6124 U/mL). The ovarian masses showed no regular laterality, while they were all cystic or solid-cystic. Their pathological sections indicated a benign appearance of the capsule tissue with well-differentiated mucinous glands infiltrating the ovarian cortex with focal necrosis. CONCLUSION: Attention should be paid to cervical examinations before and during surgery for cervical mucinous adenocarcinoma with a metastatic ovarian mass as the first manifestation. Such patients may gain a better prognosis after active treatment.

Detection of sentinel lymph node in laparoscopic surgery for uterine cervical cancer using carbon nanoparticles.

BACKGROUND AND OBJECTIVES: Carbon nanoparticles (CNPs) has been widely confirmed the efficiency in sentinel lymph node (SLN) mapping for various solid tumors. This study aims to explore the feasibility and effectiveness of CNPs during laparoscopic surgery for cervical cancer. METHODS: We analyzed 45 women with stage IB1-IIA1 cervical cancer who underwent SLN mapping using CNPs during laparoscopic surgery. The effectiveness of CNPs was evaluated by the detection rate and accuracy parameters. Factors associated with SLN laterality and SLNs localizations were analyzed. RESULTS: The overall and bilateral detection rate was 93.3% (42/45) and 60.0% (27/45), respectively. Elevated body mass index was associated with decreased bilateral detection rate (P = .015). A total of 225 SLNs were harvested, with a mean number of 5.0 ± 3.6. A total of 81.3% of SLNs were in expected localizations including external iliac (39.1%), internal iliac (25.8%), and obturator (16.4%) regions, while 18.7% in unusual localizations including common iliac (10.7%), parametrial (7.6%), and presarcal (0.4%) regions. None positive lymph node was found in non-SLNs with a false-negative rate of 0%. CONCLUSION: Laparoscopic SLN mapping with CNPs appears to be simple and efficient for patients with early-stage cervical cancer.

Separate lateral parametrial lymph node dissection improves detection rate of parametrial lymph node metastasis in early-stage cervical cancer: 10-year clinical evaluation in a single center in China.

OBJECTIVE: To investigate the clinical significance of separate lateral parametrial lymph node dissection (LPLND) in improving parametrial lymph node (PLN) and its metastasis detection rate during radical hysterectomy for early-stage cervical cancer. METHODS: From July 2007 to August 2017, 2,695 patients with cervical cancer in stage IB1-IIA2 underwent radical hysterectomy were included. Of these patients, 368 underwent separate dissection of PLNs using the LPLND method, and 2,327 patients underwent conventional radical hysterectomy (CRH). We compared the surgical parameters, PLN detection rate and PLN metastasis rate between the two groups. RESULTS: Compared with CRH group, the rate of laparoscopic surgery was higher (60.3% vs. 15.9%, P<0.001), and the blood transfusion rate was lower (19.0%vs. 29.0%, P<0.001) in the LPLND group. PLNs were detected in 356 cases (96.7%) in the LPLND group, and 270 cases (11.6%) in the CRH group (P<0.001), respectively. The number of PLNs detected in the LPLND group was higher than that in the CRH group (median 3vs. 1, P<0.001). The PLN metastases were detected in 25 cases (6.8%) in the LPLND group, and 18 cases (0.8%) in the CRH group (P<0.001), respectively. In multivariable analysis, LPLND is an independent factor not only for PLN detection [odds ratio (OR)=228.999, 95% confidence interval (95% CI): 124.661-420.664; P<0.001], but also for PLN metastasis identification (OR=10.867, 95% CI: 5.381-21.946; P<0.001). CONCLUSIONS: LPLND is feasible and safe. The surgical method significantly improves the detection rate of PLN and avoids omission of PLN metastasis during radical hysterectomy for early-stage cervical cancer.

Clinical Outcomes in Early Cervical Cancer Patients Treated with Nerve Plane-sparing Laparoscopic Radical Hysterectomy.

STUDY OBJECTIVE: To explore the feasibility of nerve plane-sparing laparoscopic radical hysterectomy (NPS-LRH) as a simplified C1-type surgery for cervical cancer patients and to compare this technique with laparoscopic radical hysterectomy (LRH). DESIGN: A retrospective comparative study. SETTING: An academic tertiary hospital affiliated with the Chinese National Cancer Center. PATIENTS: Six hundred fifteen patients with Fédération Internationale de Gynécologie et d'Obstétrique stage Ib and IIa cervical cancer who underwent laparoscopic radical hysterectomy between January 2010 and December 2017 were enrolled. Among them, 263 patients underwent the NPS-LRH surgery, and 352 patients underwent the LRH surgery. Intraoperative data and postoperative outcomes were compared between the 2 groups. INTERVENTIONS: NPS-LRH is a simplified type C1 procedure that preserves the ureteral mesentery and its nerve plane, whereas LRH is a type C2 procedure in the Querleu-Morrow surgical classification system. MEASUREMENTS AND MAIN RESULTS: There were no statistically significant differences in age, body mass index, Fédération Internationale de Gynécologie et d'Obstétrique stage, tumor differentiation, pathological type, depth of invasion, lymphovascular space invasion, parametrial tissue invasion, lymphatic metastasis, neoadjuvant chemotherapy, or postoperative adjuvant radiotherapy and chemotherapy between the 2 groups. Compared with the LRH group, the NPS-LRH group had a shorter length of operation (238.7 ± 53.9 minutes vs 259.8 ± 56.6 minutes, p < .01), less intraoperative bleeding (p < .01), more resected lymph nodes (p = .028), shorter duration of urinary catheterization (p < .01), lower incidences of postoperative hydronephrosis (p = .044), less long-term frequent urination (p < .01), less acute urinary incontinence (p < .01), poor bladder sensation (p = .028), and constipation (p = .029). There were no statistically significant differences in the disease-free survival and overall survival between the 2 groups (p = .769 and .973, respectively). CONCLUSION: NPS-LRH is a simplified, safe, and feasible type C1 operation that had a shorter length of operation, less intraoperative bleeding, more resected lymph nodes, and better postoperative bladder function compared with the LRH group. Further studies are required to assess its benefits on rectal function and long-term prognosis.

Limited energy parametrial resection/dissection during modified laparoscopic nerve-sparing radical hysterectomy.

OBJECTIVE: The aim of this study was to investigate the feasibility of using ultrasonic scalpel combined with vascular clip in parametrial management, called limited energy parametrial resection/dissection (LEPRD), in laparoscopic nerve plane-sparing radical hysterectomy (NPSRH), a modified nerve-sparing radical hysterectomy (NSRH); and to evaluate its effectiveness in pelvic autonomic nerve preservation. METHODS: From July 2012 to January 2016, 257 consecutive patients with stage IB1 to IIA2 cervical cancer who underwent NPSRH were included in this study. Patients were divided into three cohorts according to the different parametrial resection modality. The clinical, pathological and surgery-related parameters were compared between the three groups. Short- and long-term postoperative bladder functions were evaluated. RESULTS: LEPRD was attempted in 94 patients, and was successful in 65 (69.1%) patients (LEPRD group). The remaining 29 (30.9%) patients required bipolar coagulation after failure of vascular clipping (combined modality group). Routine bipolar cautery was used in the other 163 patients during the parametrial resection (bipolar group). The blood loss in the LEPRD group was significantly lower than those in the other two groups (P<0.001). The rate of successful Foley removal on postoperative day 7 was significantly higher in the LEPRD group than in the bipolar group (P=0.022). The incidence of chronic voiding dysfunction was significantly lower in the LEPRD group than in the bipolar group (P=0.019). CONCLUSIONS: It is feasible to perform LEPRD in NPSRH for cervical cancers. This kind of limited energy surgical technique is associated with less blood loss, and leads to improved postoperative bladder function.

Prognostic evaluation of postoperative adjuvant therapy for operable cervical cancer: 10 years' experience of National Cancer Center in China.

OBJECTIVE: The aim of this study was to investigate the prognostic factors and to evaluate the impact of adjuvant therapy on clinical outcome for early-stage cervical cancer. METHODS: The clinical-pathological data of all 1,335 patients with the International Federation of Gynecology and Obstetrics (FIGO) Ib-IIa cervical cancer treated with primary radical surgery at the Chinese National Cancer Center between May 2007 and Dec 2013 were retrospectively reviewed. The median follow-up was 70 months. RESULTS: Of all the patients, 61.6% of the cases received adjuvant therapy, with 5-year disease-free survival (DFS) of 92.1% and 5-year overall survival (OS) of 95.0%. In multivariate analysis, differentiation of G3 (P<0.05), lymph node metastasis (LNM, P<0.05) and lymphovascular space invasion (LVSI, P<0.05) were independent predictors for OS, while LNM (P<0.05), deep stroma invasion (DSI, P<0.05) and LVSI (P<0.05) were independent factors for DFS. The samples were stratified by histologic type, and cervical squamous cell carcinoma (SCC) was found to share the same independent factors except for differentiation of OS. As to patients with cervical adenocarcinoma/adenosquamous carcinoma (AC/ASC), differentiation was the independent predictor of OS (P<0.05); and LVSI of DFS (P<0.05). Of 236 patients with high-risk factors, there was no significant difference in survival between concurrent chemoradiotherapy (CCRT, n=195), radiotherapy (RT, n=24), and chemotherapy (CT, n=17). Among the 190 patients with LNM who underwent CCRT, 124 cases showed improved DFS after sequential CT (P=0.118), with a recurrence rate decrease of 14%, though the difference was not statistically significant. Patients with single intermediate-risk factors like DSI or LVSI were found to partially benefit from adjuvant therapy, but the difference was not statistically significant. CONCLUSIONS: LNM, LVSI, DSI and differentiation were found to be independent prognostic factors for operable cervical cancer. Aggressive postoperative adjuvant therapy based on single risk factors in Chinese National Cancer Center could benefit survival. CCRT+CT outperformed CCRT in high-risk patients. For patients with single non-high-risk factor, the role of adjuvant therapy needs to be further discussed.