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Radical hysterectomy and complete pelvic lymphadenectomies are the most commonly performed procedures for women with early-stage cervical cancer. Sentinel lymph node (SLN) mapping could be an alternative to routine pelvic lymphadenectomy, aiming to diagnose accurately nodal extension and decrease lymphatic morbidity. To compare 3-year disease-free survival and health-related quality of life after SLN biopsy or SLN biopsy + pelvic lymphadenectomy in early cervical cancer. We hypothesize that disease-free survival is non-inferior and health-related quality of life superior after SLN biopsy compared with SLN biopsy + pelvic lymphadenectomy. International, randomized, multicenter, single-blind trial. The study will be run by teams trained to carry out SLN biopsy, belonging to clinical research cooperative groups or recognized as experts in this field. Patients with an optimal mapping (Memorial Sloan Kettering Cancer Center [MSKCC] criteria) and a negative frozen section will be randomized 1:1 to SLN biopsy only or SLN biopsy + pelvic lymphadenectomy. Patients with early stages (Ia1 with lymphovascular invasion to IIa1) of disease. Histological types are limited to squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma. Main endpoint will be co-primary endpoint, associating 3-year disease-free survival and quality of life (QLQ-C30 and QLQ-CX24). 950 patients need to be randomized. Estimated dates for completing accrual and presenting results: study started on Q2 2018, last accrual is scheduled for Q2 2021, and last follow-up in Q2 2026. ClinicalTrials.gov identifier: NCT03386734.

Postoperative residual tumor is the major prognostic factor in ovarian cancer. The feasibility of complete cytoreductive surgery is assessed by laparoscopy. Our goal was to develop a predictive score prior to laparoscopy to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer. We developed a score to predict incomplete cytoreductive surgery by performing multiple logistic regressions after bootstrap procedures on data from a retrospective cohort of 247 patients with advanced ovarian cancer. This score was validated on a different population of 45 patients with ovarian cancer. Four criteria were independently associated with incomplete cytoreduction, confirmed by surgery: BMI ≥ 30 kg/m2 (adjusted odds ratio [aOR], 3.07; 95% confidence interval [95% CI], 1.0-9.6), CA125 > 100 IU/L (aOR, 3.99; 95% CI, 1.6-10.1), diaphragmatic and/or omental carcinomatosis by CT-Scan (aOR, 5.82; 95% CI, 2.6-13.1), and positive parenchymal metastases by PET/CT (aOR, 3.59; 95% CI, 1.0-12.8). The 100-point score was based on these criteria. The area-under-the-curve of the score was 0.79 (95% CI, 0.73-0.86). In the validation group, no patient ranked in the high-risk group of incomplete cytoreductive surgery had a complete upfront cytoreductive surgery (95% CI 0-16). Three of 29 patients for whom primary complete cytoreduction was not possible were classified in the group at low risk of incomplete cytoreductive surgery (12%; 95% CI 4-27). This pre-operative score may be useful for distinguishing which patients may have complete cytoreductive surgery from those who will receive neoadjuvant chemotherapy, while avoiding unnecessary laparoscopy.

BackgroundSentinel lymph node biopsy represents an alternative to pelvic lymphadenectomy for lymph node staging of early-stage cervical carcinoma, but prospective evidence on long-term oncological safety of sentinel lymph node biopsy alone versus pelvic lymphadenectomy is missing.ObjectiveTo investigate, with this meta-analysis, the impact of sentinel lymph node biopsy alone versus pelvic lymphadenectomy on survival for patients with early-stage cervical cancer.MethodsA systematic literature review was performed. We excluded studies in which pelvic lymphadenectomy was systematically performed after every sentinel lymph node biopsy, including only articles where pelvic lymphadenectomy was performed because sentinel lymph node biopsy was not conclusive. A meta-analysis was carried out combining 5-year disease-free survival and overall survival rates with a random and fixed effect model. Heterogeneity was tested using the Cochran Χ2 test and quantified with Higgins information I2.ResultsThe search of databases and registers found 927 items and six articles (two retrospective and four prospective). The median time of follow-up was 34.8 months (range 13–53). Overall common effect disease-free survival was 98% while random effect disease-free survival was 94%. Overall heterogeneity was 77%. A subgroup analysis was applied, dividing studies into one group including sentinel lymph node biopsy negative data only (common effect disease-free survival 91%; random effect disease-free survival 90%), and one group with a negative and positive sentinel lymph node biopsy (common effect disease-free survival 98%; random effect disease-free survival 96%). In the analysis of overall survival, positive and negative sentinel lymph node biopsy cases were examined together (common and random effect overall survival 99%). Ultrastaging did not affect disease-free survival (common and random effect disease-free survival 92% in the ultrastaging group vs common effect disease-free survival 99% and random effect disease-free survival 96% in the non-ultrastaging group).ConclusionsBoth 5-year disease-free survival and overall survival rate after sentinel lymph node biopsy alone are higher than 90% and do not differ from pelvic lymphadenectomy survival data. Ultrastaging did not impact survival.

IntroductionSentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance.MethodsA Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability.ResultsSeventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88).ConclusionSpecific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP + CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8 + T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1 + CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8 + T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8 + T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC. An important contribution of cancer associated fibroblasts (CAFs) in regulating chemoresistance has been reported. Here the authors investigate the impact of chemotherapy on CAF subsets in patients with high-grade serous ovarian cancer, suggesting that residual ANTXR1+ myofibroblasts are associated with inhibition of anti-tumor immunity.

BackgroundThe sentinel lymph node (SLN) biopsy may be an alternative to systematic lymphadenectomy in early cervical cancer. The SLN biopsy is less morbid and has been shown to have high sensitivity for metastasis detection. However, the sensitivity of the SLN technique might be overevaluated because SLNs are examined with ultra-staging, and non-sentinel nodes usually are examined only with routine techniques. This study aimed to validate the negative predictive value (NPV) of the SLN technique by the ultra-staging of SLNs and non-sentinel nodes (NSLNs). MethodsThe SENTICOL 1 study data published in 2011 were used. All nodes (i.e., SLNs and NSLNs) were secondarily subjected to ultra-staging. The ultra-staging consisted of sectioning every 200 µm, in addition to immunohistochemistry. Moreover, the positive slides and 10% of the negative slides were reviewed.ResultsThe study enrolled 139 patients, and SLNs were detected in 136 (97.8%) of these patiets. Bilateral SLNs were detected in 104 (76.5%) of the 136 patients. A total of 2056 NSLNs were identified (median, 13 NSLNs per patient; range 1–54). Of the 136 patients with SLNs, 23 were shown to have positive SLNs after serial sectioning and immunohistochemical staining. The NSLNs were metastatic in six patients. In the case of bilateral SLN detection, the NPV was 100%, with no false-negatives (FNs).ConclusionsThe pelvic SLN technique is safe and trustworthy for determining the nodal status of patients with early-stage cervical cancer. In the case of optimal mapping with bilateral detection, the NPV was found to be 100%.

Therapeutic management of early-stage cervical cancer is mainly based on surgery.

Introduction In patients affected by epithelial ovarian cancer (EOC) complete cytoreduction (CC) has been associated with higher survival outcomes. Artificial intelligence (AI) systems have proved clinical benefice in different areas of healthcare. Objective To systematically assemble and analyze the available literature on the use of AI in patients affected by EOC to evaluate its applicability to predict CC compared to traditional statistics. Material and Methods Data search was carried out through PubMed, Scopus, Ovid MEDLINE, Cochrane Library, EMBASE, international congresses and clinical trials. The main search terms were: Artificial Intelligence AND surgery/cytoreduction AND ovarian cancer. Two authors independently performed the search by October 2022 and evaluated the eligibility criteria. Studies were included when data about Artificial Intelligence and methodological data were detailed. Results A total of 1899 cases were analyzed. Survival data were reported in 2 articles: 92% of 5-years overall survival (OS) and 73% of 2-years OS. The median area under the curve (AUC) resulted 0,62. The model accuracy for surgical resection reported in two articles reported was 77,7% and 65,8% respectively while the median AUC was 0,81. On average 8 variables were inserted in the algorithms. The most used parameters were age and Ca125. Discussion AI revealed greater accuracy compared against the logistic regression models data. Survival predictive accuracy and AUC were lower for advanced ovarian cancers. One study analyzed the importance of factors predicting CC in recurrent epithelial ovarian cancer and disease free interval, retroperitoneal recurrence, residual disease at primary surgery and stage represented the main influencing factors. Surgical Complexity Scores resulted to be more useful in the algorithms than pre-operating imaging. Conclusion AI showed better prognostic accuracy if compared to conventional algorithms. However further studies are needed to compare the impact of different AI methods and variables and to provide survival informations.

Combining immunotherapy with chemoradiation is effective in locally advanced cervical cancer. However, the impact of induction combination immunotherapy on immune modulation and treatment response is poorly understood. In this phase II trial (NCT04256213), 40 females with locally advanced cervical carcinoma received one cycle of nivolumab-plus-ipilimumab immunotherapy before standard chemoradiation, followed by maintenance nivolumab. We show, using multiplex-immunofluorescence tissue imaging, a significantly increased CD8 + /FOXP3 + cell ratio (primary endpoint; increase of 0.87 cells/mm², P  = 0.0164) and proliferative CD8 + T-cell density after one cycle of combination immunotherapy. HOT score (27-gene-based signature identifying immunologically active tumors) also increased significantly (exploratory analysis; 0.17, P  < 0.0001). Objective response rates (secondary endpoint) were 13% immediately after combination immunotherapy, 98% (65% complete response) after chemoradiation, and 90% at treatment completion. High HOT score at baseline and immune changes induced by combination immunotherapy were associated with complete response at treatment completion. Induction immunotherapy may prime tumors for improved response to standard therapy. Pre-treatment dual immune checkpoint blockade in cervical cancer remains understudied. In this trial, the authors show that neoadjuvant immune checkpoint blockade enhances immune activation and correlates with improved response to subsequent chemoradiation in patients with cervical carcinoma.

Background Sentinel lymph node (SLN) biopsy may improve nodal staging in cervical cancer. The aims of this study are to determine the rate of unusual patterns of cervical lymphatic drainage, to determine the rates of micrometastases and isolated tumor cells (ITCs) in SLNs, and to assess the clinical impact of SLN biopsy. Methods Multicenter prospective study conducted between January 2005 and June 2007 in women undergoing laparoscopic surgery for early cervical cancer. Combined technetium/Patent Blue labeling was used. Lymphoscintigraphy was performed before surgery. SLN location was recorded, and factors associated with location were explored. SLNs underwent step sectioning ± immunohistochemistry. Results 145 patients were enrolled and 139 included in a modified intention-to-diagnose analysis. Although 80.6 % of SLNs were in external iliac and interiliac areas, 38.2 % of patients had at least one SLN in an unexpected area and 5.1 % had SLNs only in unexpected areas. In unexpected areas, the number of SLNs per patient was not significantly different between lymphoscintigraphy and intraoperative detection (0.79 [0.62–1.02] versus 0.50 [0.37–0.68]; P  = 0.096). In expected locations, there were significantly more blue and hot SLNs per patient than blue or hot SLNs (1.70 [1.45–1.99], 0.42 [0.30–0.57], 0.52 [0.39–0.69]). Of 28 metastatic SLNs, 17 contained micrometastases or ITCs. SLN involvement was found only by immunohistochemistry in 39.1 % of patients with positive nodes, and involved SLNs were located in unexpected areas in 17 % of those patients. Conclusions Sentinel lymph node biopsy detects unusual drainage pathways and micrometastases in a substantial proportion of patients, thus improving nodal staging.