Lymph-vascular Space Invasion Research Articles

Semiquantitative evaluation of lymph-vascular space invasion in patients affected by endometrial cancer: Prognostic and clinical implications.

The interpretation of lymph-vascular space invasion (LVSI) is usually qualitative, as presence or absence. The aim of this study is to investigate the prognostic role of LVSI in patients affected by endometrial cancer, when evaluated with a semiquantitative analysis. This retrospective multicentre study enrolled patients who received a histologically confirmed diagnosis of endometrial cancer. The assessment of LVSI was semiquantitative in accordance with the three-tiered scoring system (absent, focaland diffuse). Among 1258 patients with surgical-stage endometrial cancer, LVSI has been found in 32.8% of cases (n=412), whose 12.7% (n=160) were focal, and 20% (n=252) diffuse. The rate of lymph node metastasis increased from the 5% in patients with no LVSI to 15% in patients with focal LVSI and 33% in those with diffuse LVSI (p<0.001). Distant recurrences were more frequent in patients with diffuse LVSI than in focal or no LVSI (24.9% versus 14.7% and 6.6%, respectively, p<0.001). Diffuse LVSI was found to significantly increase the risk of distant metastasis (adjusted odds ratio (A OR) 2.57, p<0.001). Adjuvant radiation were associated with improved overall survival (OS) and disease-free survival (DFS) in patients with diffuse LVSI. The presence of diffuse LVSI is an independent risk factor for both lymph node metastasis and distant recurrence in endometrial cancer patients, and it is associated with a significantly decreased OS and DFS. Adjuvant radiation improved survival regardless of grading, histotypeand lymph nodal metastasis in women with diffuse LVSI.

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

Background: Pathologic risk factors (PRF) are correlated with treatment and prognosis in cervical cancer patients treated with radical hysterectomy (RH). Machine learning methods can be used in medical research and practice as a decision-making tool. However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in cervical cancer. Methods: The data set was collected from 1260 stage IB-IIA cervical cancer patients treated with RH. Tumor-related factors, and 75 blood parameters were included. The simulations involved 6 machine learning methods: Gradient Boosting Machine, RF (Random Forest), Cforest (Conditional Random Forest), etc. The prediction ability of the models was determined based on the area under receiver operating characteristic curve (AUC). Findings: The best results were obtained by the RF model in deep stromal infiltration prediction with an accuracy of 72.7% and the AUC of 0.792, and the Cforest model acquired an accuracy of 65.6% and the AUC of 0.675 in lymph vascular space invasion prediction. The accuracy of the model for lymph node metastasis prediction was less than 65%. Blood markers including D-dimer and uric acid were associated with PRF. Interpretation: Machine learning methods based on blood parameters can provide critical diagnostic prediction of postoperative PRF for cervical cancer, which may promote personalized treatment strategy. Fund: This work was supported by National Natural Science Foundation of China (81802619), CAMS Initiative for Innovative Medicine (No.2017-I2M-2-003), Special fund for China Cancer Foundation Beijing Hope Marathon (LC2018A13), and Graduate Education Reform Project of PUMC (10023201800302). Declaration of Interests: The authors have nothing to disclose. Ethics Approval Statement: The study was conducted in accordance with the ethical principles of the Declaration of CICAMS. This study was approved by the institutional review board of the center.

A Case of Robotic Radical Parametrectomy for the Treatment Uterine Cervical Cancer Discovered after Simple Hysterectomy.

Study Objective Radical parametrectomy (RP) is one of effective treatment option for patients with invasive cervical cancer incidentally diagnosed after simple hysterectomy. To demonstrate the technique of robotic RP as a minimally invasive approach. Design A case report Setting Gynecology and Obstetrics department of a general hospital. Patients or Participants N/A Interventions A 50-year-old woman, G1P1with previous cesarean section, underwent robotic simple hysterectomy and bilateral salpingo-oophorectomy for the treatment of adenomyosis. Cervical cytology before surgery was negative (NILM). The final pathological examination showed stage 1B1 cervical cancer, 19mm-basaloid carcinoma with LVSI (lymph vascular space invasion) and positive surgical margin. Basaloid carcinoma of the uterine cervix is a more aggressive tumor than SCC. Robotic RP with an upper vaginectomy and pelvic lymphadenectomy was performed as an adjuvant treatment. The operative time was 343min, the estimated blood loss was 400ml, and the number of pelvic lymph nodes removed was 65. Right ureteral adventitia injury was suspected during surgery because of severe pelvic adhesion related with previous surgery, so we successfully repaired it with ureteroneocystostomy and there were no postoperative complications. 1mm-pathological residual disease of basaloid carcinoma in the resected tissue was found (pTb1N0M0). She received adjuvant chemotherapy and no recurrence has been observed. Measurements and Main Results Results to be presented Conclusion The indications for RP have been unclear as the surgical procedure is difficult and may possibly increase the complication rate. Robotic surgery may make RP a more feasible optiondepending on the individual case.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer

BackgroundVaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact...

Prolonged waiting times for surgery in patients with endometrial cancer is associated with lymph-vascular space invasion but has limited effect on clinical outcome

Prolonged waiting times for surgery in patients with endometrial cancer is associated with lymph-vascular space invasion but has limited effect on clinical outcome

Comparative analysis of the prognosis of patients with locally advanced cervical cancer undergoing laparoscopic or abdominal surgery

Objective: To compare the prognosis of patients with cervical cancer in stage Ⅰb2-Ⅱa2 undergoing laparoscopic radical hysterectomy or abdominal radical hysterectomy. Methods: From January 1, 2009 to December 31, 2018, patients with stage Ⅰb2-Ⅱa2 who underwent laparoscopic or abdominal radical hysterectomy (laparoscopic group and abdominal group) in Peking University People's Hospital were collected. The clinicopathological data were retrospectively analyzed. There were 237 cases in this study, including 115 cases in laparoscopic group and 122 cases in abdominal group. The clinicopathological characteristics, surgery-related complications, recurrence and death were analyzed between the two groups. The related factors of recurrence and death were also analyzed.During laparoscopic surgery, the pressure of the carbon dioxide pneumoperitoneum were controlled, to try avoid the tumor tissue in the vagina from being exposed to the abdominal cavity when taking out the uterine specimen through the vagina, and fully flushed the abdominal cavity with sterile water after the specimen was taken out. Results: (1) Clinicopathological characteristics: there was no significant differences between the two groups among age, pathological type, pathological grade, clinical stage, depth of interstitial infiltration, lymph node metastasis,parametrial infiltration, vaginal stump infiltration, lymph-vascular space invasion (LVSI), neoadjuvant chemotherapy, and postoperative adjuvant treatments (all P>0.05). (2) Surgery-related complications: the incidence of surgery-related complications in the laparoscopic group and the abdominal group were 32.2% (37/115) and 25.4% (31/122), respectively. There was no statistically significant difference between the two groups (P>0.05). (3) Recurrence and death: during the follow-up period, the recurrence rates of the laparoscopic group and the abdominal group were respectively 15.7% (18/115) and 12.3% (15/122). There was no statistically significant difference between the two groups (P=0.456). The 5-year overall survival rates of the laparoscopic group and the open group were 86.8% and 87.8%, and the 5-year tumor-free survival rates were 81.7% and 84.6%, respectively. There were no statistically significant differences between the two groups (P=0.405, P=0.429). (4) Analysis of related factors of recurrence and death: univariate analysis showed that neoadjuvant chemotherapy, lymph node metastasis, vaginal stump infiltration, LVSI and interstitial infiltration depth were risk factors for postoperative recurrence of cervical cancer patients (all P<0.05); neoadjuvant chemotherapy, lymph node metastasis, parametrial infiltration, vaginal stump infiltration, LVSI and interstitial infiltration depth were risk factors for postoperative death in patients with cervical cancer (all P<0.05). Multivariate analysis showed that neoadjuvant chemotherapy and lymph node metastasis were independent risk factors for postoperative recurrence and death of cervical cancer patients (P<0.05). Conclusion: There is no significant difference in the prognosis of patients with cervical cancer in stage Ⅰb2-Ⅱa2 undergoing laparoscopic radical hysterectomy with non-touch operative technique and abdominal radical hysterectomy.

Efficacy and safety of laparoscopic radical hysterectomy for early cervical adenocarcinoma

Objective: To investigate the efficacy and safety of laparoscopic radical hysterectomy for early cervical adenocarcinoma. Methods: A retrospective observational study was performed by reviewing medical records of patients with staging Ⅰb1-Ⅱa2 International Federation of Gynecology and Obstetrics (FIGO, 2009) cervical adenocarcinoma who underwent laparoscopic or abdominal radical hysterectomy from 2007 to 2017 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. The difference among clinicopathologic characteristics, surgery-related parameters and complications, and prognosis were analyzed between the laparoscopic group and abdominal group. Results: Two hundreds and ninety-three patients were included with 88 cases in laparoscopic group and 205 cases in abdominal group. （1） There was no significant difference in clinicopathologic characteristics between the two groups （all P>0.05）, including age, body mass index, menopause status, history of abdominal surgery, clinical stage, tumor diameter, neoadjuvant chemotherapy, differentiation, lymph-vascular space invasion, positive of surgical margin, parametrial invasion, and lymph node metastasis. But the abdominal group showed a higher proportion of deep stromal invasion (38.5% vs 25.0%, P<0.05). No significant difference was observed between two groups with number of lymph nodes resected, urinary catheter retention, short-term surgical complications (including ureteral injury, ileus, infection, hydronephrosis and poor wound healing), and long-term complications (including voiding dysfunction, defecation dysfunction and lower limb edema； all P>0.05）. （2） The laparoscopic group was significantly associated with a longer operation time [(260±51) minutes vs (244±53) minutes, P<0.05], but less bleeding (100 ml vs 300 ml, P<0.01), shorter hospital stay [(13±5) days vs (16±8) days, P<0.01] and lower incidence of lymphedema (12.5% vs 27.8%, P<0.01). （3） The 5-year progression-free survival (PFS; 85.7% vs 86.4%, P=0.971) and 5-year overall survival (OS; 91.4% vs 93.0%, P=0.657) of laparoscopic group were comparable to that of abdominal group. （4） Multivariate analysis demonstrated that lymph node metastasis (HR=2.44, 95%CI: 1.16-5.15, P=0.019) was independent poor prognostic factors related to PFS, while adenosquamous carcinoma (HR=2.54, 95%CI: 1.02-6.35, P=0.046), lymph-vascular space invasion (HR=3.86, 95%CI: 1.60-9.33, P=0.003) and lymph node metastasis (HR=5.92, 95%CI: 2.45-14.34, P<0.01) were independent poor prognostic factors related to OS. The laparoscopy surgery was not an independent poor prognostic factor (P=0.396). Conclusion: The laparoscopic radical hysterectomy for early cervical adenocarcinoma has comparable prognosis to abdominal radical hysterectomy with a higher surgery quality.

A 70-Gene Signature for Predicting Treatment Outcome in Advanced-Stage Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide. The current approaches still have limitations in predicting the therapy outcome of each individual because of cancer heterogeneity. The goal of this study was to establish a gene expression signature that could help when choosing the right therapeutic method for the treatment of advanced-stage cervical cancer. The 666 patients were collected from four independent datasets. The 70-gene expression signature was established using univariate Cox proportional hazard regression analysis. The 70-gene signature was significantly different between low- and high-risk groups in the training dataset (p = 4.24e−6) and in the combined three validation datasets (p = 4.37e−3). Treatment of advanced-stage cancer patients in the high-risk group with molecular-targeted therapy combined with chemoradiotherapy yielded a better survival rate than with only chemoradiotherapy (p = 0.0746). However, treatment of the patients in the low-risk group with the combined therapy resulted in significantly lower survival (p = 0.00283). Functional classification of 70 genes revealed involvement of the angiogenesis pathway, specifically phosphatidylinositol 3-kinase signaling (p = 0.040), extracellular matrix organization (p = 0.0452), and cell adhesion (p = 0.011). The 70-gene signature could predict the prognosis and indicate an optimal therapeutic modality in molecular-targeted therapy or chemotherapy for advanced-stage cervical cancer.

Circulating Tie2-Expressing Monocytes: A Potential Biomarker for Cervical Cancer.

BackgroundTyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2)-expressing monocytes (TEMs) are a highly proangiogenic subset of myeloid cells, which are characterized by expressing the angiopoietin receptor Tie2 with pro-tumor activity.PurposeThe present study aimed to determine the clinical value of circulating TEMs (cTEMs) for cervical cancer.Patients and MethodsPeripheral blood mononuclear cells (PBMCs) were obtained from 7 healthy volunteers, 17 uterine fibroid patients, 24 cervical intraepithelial neoplasia (CIN) II patients, 31 CIN III patients and 99 patients with cervical cancer. The cTEMs were evaluated by the ratio of Tie2+ CD14+ cells to all CD14+ monocytes in the PBMCs through flow cytometry. The diagnostic value of cTEM was assessed by receiver operating characteristic (ROC) curves and the correlation between cTEM and clinicopathological characters in cervical cancer patients was analyzed.ResultsThe proportion of cTEMs was gradually increasing from healthy volunteers to patients with non-invasive lesions, then to cervical cancer patients. The area under the ROC curve was 0.913 when the level of cTEMs was used to distinguish cervical cancer from all the other women ranging from healthy volunteers to CIN III patients. In cervical cancer, an increased cTEM fraction was significantly correlated with advanced tumor stage, larger tumor size, lymph node metastasis (LNM), deep stromal infiltration, parametrial involvement and lymph-vascular space invasion and was an independent risk factor for LNM.ConclusionThe cTEM proportion might be a promising biomarker for the malignant transformation of cervical lesions and the progression of cervical cancer.

An Australian, single-centre study of surgical management outcomes for early-stage cervical cancer.

The Laparoscopic Approach to Cervical Cancer (LACC) trial is the first phase III randomised, multicentred trial to compare oncologic outcomes associated with open radical hysterectomy vs minimally invasive surgery (MIS) for treatment of early cervical cancer. To evaluate our surgical experience in patients with early cervical cancer. The Lifehouse Gynaecologic Oncology database was queried based upon the eligibility criteria of the LACC study and included all FIGO 2009 stage (1A1 with lymph vascular space invasion, 1A2, 1B1) cervical cancer women from 2008-2018. Patients were also included in our study if they had abdominal radical trachelectomy (ART), laparoscopic radical hysterectomy (TLRH) and robotic radical trachelectomy (RRT). Forty-six women were identified with four exclusions. Thirty-seven women had stage 1B1 disease, 24 had a squamous cell carcinoma, 15 had an adenocarcinoma and three had an adenosquamous carcinoma of the cervix. Of the 42 eligible patients, 32 underwent an open abdominal approach (26 total abdominal radical hysterectomy (TARH), six ART) and ten a MIS approach (nine TLRH and one RRT) with a mean follow-up of 4.8years. All 42 women had a pelvic lymph node dissection, eight women had nodal metastases and 16 patients received adjuvant chemoradiation. Two of the nine women in the laparoscopic radical hysterectomy group had a recurrence. Both had adenocarcinoma, stage 1B1 disease. There were no recurrences in the TARH group or radical trachelectomy groups. Our data, albeit limited in number, have reflected the results of the LACC trial that MIS was associated with a lower disease-free survival than open radical hysterectomy.

Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort study

BackgroundHuman epidermal growth factor receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in advanced stage and recurrent uterine serous carcinoma (USC). The significance of tumoral HER2 expression in early-stage disease has not been established. MethodsThis multi-center cohort study included women with stage I USC treated from 2000 to 2019. Demographic, treatment, recurrence, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0–3+. Equivocal IHC results (2+) were further tested with fluorescence in-situ hybridization (FISH). HER2 positivity was defined as 3+ IHC or FISH positive. ResultsOne hundred sixty-nine patients with stage I USC were tested for HER2; 26% were HER2-positive. There were no significant differences in age, race, stage, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. Presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p = .003).After a median follow-up of 50 months, there were 43 (25.4%) recurrences. There were significantly more recurrences in the HER2-positive cohort (50.0% vs 16.8%, p < .001). HER2 positive tumors were associated with worse progression-free (PFS) and overall survival (OS) (p < .001 and p = .024). On multivariate analysis, HER2 positive tumors were associated with inferior PFS (aHR 3.50, 95%CI 1.84–6.67; p < .001) and OS (aHR 2.00, 95%CI 1.04–3.88; p = .039) compared to HER2-negative tumors. ConclusionsGiven its significant association with worse recurrence and survival outcomes, HER2 positivity appears to be a prognostic biomarker in women with stage I uterine serous carcinoma. These data provide support for clinical trials with anti-HER2-directed therapy in early-stage disease.

Angiopoietin-1 is associated with a decreased risk of lymph node metastasis in early stage cervical cancer.

Lymph node metastasis (LNM) is an important determinant of prognosis in patients with cervical cancer. Members of the angiopoietin family have been demonstrated to regulate tumor-associated angiogenesis and lymphangiogenesis. This study aimed to investigate the expression levels of angiopoietin-1 (ANG1) and angiopoietin-2 (ANG2) in clinically early stage of cervical cancer along with their correlations with LNM. In total, 124 human cervical cancer cases classified into stage IA-IIB in accordance with the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging criteria were included. ANG1 and ANG2 expression levels in the tumor sections were assessed by immunohistochemistry (IHC). Univariate and multivariate logistic regression models, including age at diagnosis, FIGO stage, tumor size, pathological type, histological grading, depth of stromal invasion, lymph-vascular space invasion (LVSI) and the expression status of ANG1 and ANG2, were used to evaluate the odds ratios (ORs) for LNM. ANG1 and ANG2 were positively expressed in 75 (60.5%) and 89 (71.8%) cervical cancers respectively, with predominant staining in the cytoplasm. ANG1 expression was significantly decreased in tumors with LNM, while no correlation was observed between ANG2 expression and LNM. More importantly, the multivariate logistic regression analysis demonstrated that high ANG1 expression was an independent protective factor of LNM (OR 0.107, 95% confidential interval [CI] 0.020~0.567), while LVSI was an independent risk factor of LNM (OR 34.313, 95% CI 5.914~199.092). ANG1 is associated with a significantly decreased risk of LNM in early stage cervical cancer. The predictive value and role of ANG1 in LNM needs to be further investigated in future studies.

Nomograms based on the novel platelet index score predict postoperative prognosis in endometrial cancer

ObjectiveTo identify preoperative platelet indexes with prognostic value and to develop and validate nomograms for predicting the survival of endometrial cancer (EC) patients. MethodsA total of 1198 women who received primary surgical treatment between January 2008 and January 2017 were included in the study. Data were randomly divided into a training set (70%, N = 840) and an external validation set (30%, n = 358). Cox regression analysis was performed in the training cohort to identify independent prognostic factors and develop nomograms for survival rate prediction. ResultsHigh platelet count (PLT ≥350), high mean platelet volume (MPV ≥8.8) and low platelet distribution width (PDW <12.1) were independently associated with poor RFS and OS. PLT, MPV and PDW were thus incorporated in an innovative score called the platelet index score (PIS). The PIS was also an independent indicator, which was related to histology, lymph-vascular space invasion, lymph node involvement and FIGO stage (P = 0.007, P = 0.042, P < 0.001 and P < 0.001, respectively). Furthermore, we developed and validated two nomograms based on Cox regression models. The discriminative ability and calibration of the nomograms revealed good predictive ability, as indicated by the C-indexes and calibration plots. Moreover, both the IDI and NRI were improved. ConclusionsNomograms based on the PIS and clinicopathological features accurately predict recurrence-free survival and overall survival for EC patients.

The Role of Lymph-vascular Space Invasion towards Disease of Free Survival and Overall Survival Cancer in High-Risk Endometrial Cancer Endometrioid Type Patients

Major prognostic factors of endometrial cancer include stage, age, histopathological type, grading, depth of invasion of myometrium, and presence of Lymph-vascular Space Invasion (LVSI). This study evaluated the LVSI in disease free survival (DFS) and overall survival (OS) in high-risk endometrial cancer endometrioid type. This was a retrospective study. Survival analysis using Kaplan-Maier curve, log rank test, cox-regression and logistic regression were used to determine effects among variables. Among fifty-six patients, 43% of patients were <60 years, 73% with BMI <30, 17% were multiparous, and 79% were menopausal patients. There were 32% of patients with positive LVSI. Most clinical stages were found in stage III with 31 cases (55%). Patients with positive LVSI had OS lower than patients with negative LVSI (50% vs 55.3%). There were no significant results of LVSI as prognostic factor for OS. Patients with LVSI positive had survival time of 26.5 months (20.5 – 32.5). There were no significant results of LVSI as prognostic factor for DFS. Patients with positive LVSI had lower DFS than patients with negative LVSI (81.8% vs 85.7%). There were significant results of LVSI as prognostic factor for high-risk endometrioid type endometrial cancer with stage endometrial cancer with p = 0.01. LVSI acts as prognostic factor for high-risk endometrioid type endometrial cancer associated with stage endometrial cancer. However, there was no effect in DFS and OS.

Is Perineural Invasion a Novel Prognostic Factor Useful to Tailor Adjuvant Treatment in Patients Treated With Primary Surgery for Cervical and Vulvar Carcinoma?

Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment.

Beyond Sedlis: A novel, histology-based nomogram for predicting recurrence risk and need for adjuvant radiation in cervical cancer—A NRG/GOG ancillary analysis.

6019 Background: In GOG 49, factors associated with a 3-year, 30% recurrence risk in squamous cell carcinoma of the cervix (SCC) after surgery alone were defined. These "intermediate" risk factors [tumor size (TS), depth of tumor invasion (DOI), and lymphvascular space invasion (LVSI)] were then studied in GOG 92, which demonstrated the utility of treating patients (pts) with ≥2 intermediate risk factors with adjuvant radiation (RT), Sedlis Criteria. However, pts with &lt; 30% recurrence risk were not eligible and few pts with adenocarcinoma (AC) were included. Our study purpose was 1) to evaluate recurrence risk factors for AC vs SCC, and 2) to define contemporary nomograms for adjuvant treatment in pts with both histologies. Methods: We performed an ancillary analysis of GOG 49, 92, and 141, and included Stage I pts who received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were created separately for AC and SCC to evaluate independent risk factors for recurrence. Model accuracy was tested with ROC curves. Prognostic nomograms were generated for 2-year recurrence risk for AC and SCC. Results: We identified 715 with SCC and 105 pts with AC; 142 with SCC (19.9%) and 18 with AC 17.1%) recurred. For SCC, factors associated independently with recurrence were: LVSI [HR 1.58 (CI 1.12-2.22)], DOI [middle 1/3, HR 4.31 (CI 1.81-10.26); deep 1/3, HR 7.05 (CI 2.99-16.64)] and TS [≥4cm HR 2.67 (CI 1.67-4.29)]. In contrast, for AC, only TS ≥4cm was independently associated with recurrence [HR 4.69 (CI 1.25-17.63)]. At 3 years, ROC curves for these models predicted recurrence with 76% and 75% accuracy for SCC and AC, respectively. Utilizing a nomogram generated from these models, for SCC, DOI had the greatest impact on recurrence, with mid 1/3 conferring an 18% risk and deep 1/3 a 32% risk, while LVSI and TS increased risk by 4-10%, respectively. In contrast, for AC, TS alone had the greatest impact on recurrence risk with TS 2-4cm conferring a 20% risk over 3 years and TS ≥4cm, a 28% risk. Conclusions: Our nomogram differs from the Sedlis Criteria in demonstrating that single, as well as a combination of risk factors predict substantial 3-year recurrence rates in Stage I cervical cancer. Furthermore, these factors differ by AC and SCC subtypes, suggesting that distinct, histology-specific nomograms may have greater utility in identifying pts who will most benefit from adjuvant therapy.

Human epidermal growth factor 2 (HER2) in early stage uterine serous carcinoma: A multi-institutional cohort.

6084 Background: Uterine serous carcinoma (USC) is a rare and aggressive malignancy, accounting for 40% of all endometrial cancer deaths. Human Epidermal Growth Factor Receptor 2 (HER2) has emerged as an important prognostic and therapeutic target in USC. Given recent randomized trial results, HER2-directed therapy is now recommended in advanced-stage or recurrent, HER2-positive disease. The significance of tumoral HER2 expression in early-stage disease has not yet been established. Methods: In this IRB-approved, retrospective, multi-institutional cohort, women diagnosed with stage I USC from 2000-2018 were identified. Patient demographic, treatment, and survival data were collected. Immunohistochemistry (IHC) was performed for HER2 and scored 0-3+. Equivocal IHC results (2+) were further tested with in-situ hybridization (ISH) per the 2007 ASCO-CAP HER2 breast cancer guidelines. HER2 overexpression (“positive”) was defined as 3+ IHC or ISH positive. Kaplan-Meier analyses and Cox-proportional hazards were used to compare survival between the cohorts. Results: In total, 173 patients with stage I USC were tested for HER2; 25% were HER2-positive, 77.4% had stage IA and 22.6% had stage IB disease. Adequate clinical follow up was available for 168 patients. There were no significant differences in age, race/ethnicity, body mass index, surgical management, sub-stage, tumor size, adjuvant therapy, or follow-up duration between the HER2-positive and negative cohorts. On univarite analysis, presence of lymph-vascular space invasion was correlated with HER2-positive tumors (p=0.003). After a median follow-up of 50 months, there were 41 (24.4%) recurrences. Significantly more recurrences were observed in the HER2-positive cohort (47.6% vs. 16.7%, p&lt;0.001). HER2 overexpression was also associated with poorer progression-free (PFS) and overall survival (OS) (p&lt;0.001 and p=0.012). After adjusting for prognostic factors including sub-stage and adjuvant treatment, those with HER2-positive tumors experienced inferior PFS (aHR 3.67, 95%CI 1.92-6.98; p&lt;0.001) and OS (aHR 2.03, 95%CI 1.03-4.01; p=0.042) compared to HER2-negative tumors. Conclusions: Uterine serous carcinoma is a poor prognostic tumor, even in patients with early-stage disease. Given its significant association with worse survival outcomes, tumoral HER2 overexpression appears to be a prognostic biomarker in women with stage I disease. These data provide rationale for clinical trials with HER2-directed therapy in early-stage uterine serous carcinoma.

Neoadjuvant Chemotherapy Followed by Vaginal Radical Trachelectomy as Fertility-Preserving Treatment for Patients with FIGO 2018 Stage 1B2 Cervical Cancer.

BackgroundStandard treatment for International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1B2 cervical cancer (i.e., tumor size between 2 and 4 cm) is a radical hysterectomy (RH) with pelvic lymph node dissection (PLND). We evaluated the oncological and fertility outcomes treatment in patients receiving a fertility‐sparing alternative consisting of neoadjuvant chemotherapy (NACT) followed by vaginal radical trachelectomy (VRT).MethodsPatients with stage 1B2 cervical cancer who wished to preserve fertility were included from September 2009 to September 2018. NACT consisted of 6‐week cycles of cisplatin or carboplatin with paclitaxel. If tumor size decreased to 2 cm or smaller, NACT was followed by a robot‐assisted PLND and VRT.ResultsEighteen patients were included. Median follow‐up time was 49.7 months (range 11.4–110.8). Median tumor size was 32 mm (range 22–40 mm). Complete remission after NACT occurred in seven women. Four women had a poor response on NACT. Three underwent RH with PLND; one received chemoradiation after PLND instead of VRT because of positive lymph nodes. The remaining 14 patients received VRT 3–4 weeks after NACT. Four recurrences occurred: three after NACT and VRT and one after NACT and RH. Median time to recurrence was 20.8 months (range 17.0–105.7). Three recurrences occurred in women with adenocarcinoma with lymph vascular space invasion (LVSI). In four women fertility could not be preserved. To date, four women had six pregnancies, including three live births born at term, two first trimester miscarriages, and one currently ongoing pregnancy. ConclusionNACT and VRT in women with stage 1B2 cervical cancer showed promising results. In 78% fertility was preserved. However, patients with poor response on NACT and with adenocarcinoma and/or LVSI were possibly at risk for recurrence. Long‐term results in relation to fertility and oncological outcome are needed to corroborate these findings.Implications for PracticeStandard treatment for women with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1B2 cervical cancer (tumor size 2–4 cm) is a radical hysterectomy and pelvic lymph node dissection (PLND). However, many of these women are young and wish to preserve fertility. Data on fertility‐sparing treatment options are sparse, but neoadjuvant chemotherapy followed by a vaginal radical trachelectomy and PLND could be an alternative. Since 2009 we performed an observational cohort study in which 18 women opted for this treatment in our center. In 14 women fertility could be preserved. In four patients the tumor recurred. In four women six pregnancies occurred. After careful selection this treatment could be a good fertility‐sparing treatment option.

Metabolomics in endometrial cancer diagnosis: A systematic review.

Endometrial cancer (EC) is the most common gynecological malignancy in the developed world. The prognosis of EC strongly depends on tumor stage, hence the importance of improving diagnosis. Metabolomics has recently appeared as a promising test for a non-invasive diagnosis of several diseases. Nevertheless, no metabolic marker has been approved for use in the routine practice. We aimed to provide an overview of metabolomics findings in the diagnosis of EC. A systematic review was performed by searching eight electronic databases from their inception to October 2019 for studies assessing metabolomics in EC diagnosis. Extracted data included characteristics of patients and EC, serum concentration of metabolites in women with and without EC and its association with EC diagnosis, tumor behavior and pathological characteristics. Six studies with 732 women (356 cases and 376 controls) were included. Several metabolites were found able to predict the presence of EC, tumor behavior (progression and recurrence) and pathological characteristics (histotype, myometrial invasion and lymph vascular space invasion). Metabolomics might be suitable for a non-invasive diagnosis and screening of EC, offering the possibility to predict tumor behavior and pathological characteristics. Further studies are necessary to validate these results.

Analysis of factors related to perineural invasion in cervical cancer and its relationship with prognosis

Objective To investigate the relationship between perineural invasion (PNI) and the clinicopathological features of cervical cancer, and to explore its influence on the prognosis of cervical cancer patients. Methods Retrospective analysis the clinical data of 76 patients with early cervical cancer who received radical hysterectomy+ pelvic lymphadenectomy±paraaortic lymphadenectomy from November 2015 to December 2019 in Xuanwu Hospital. The clinicopathological characteristics of the postoperative pathological results of cervical cancer patients were analyzed to explore the related factors of PNI and its influence on prognosis. Results Single factor analysis suggested that the incidence of PNI was related to tumor diameter, depth of stroma invasion, lymph-vascular space invasion, lymph node metastasis and clinical stage (P 0.05). Conclusions PNI is related to the depth of interstitial infiltration. PNI has no significant effect on the short-term recurrence rate and short-term survival rate of cervical cancer patients. Key words: Uterine cervical neoplasms; Perineural invasion; Prognosis; Factor analysis, statistical