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Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy Maria Luisa Gasparri1, Ilary Ruscito2, Filippo Bellati2, Fabio Corsi3, Rosa Di Micco4, Oreste D. Gentilini4, Thorsten Kuehn5, Andrea Papadia1, Donatella Caserta2, Lorenzo Rossi6, Arianna Calcinotto7 1 Department of Gynecology and Obstetrics, Ente Ospedaliero Cantonale, Ospedale Regionale di Lugano, Lugano, Switzerland 2 Department of Medical and Surgical Science and Translational Medicine, Sapienza University of Rome, Azienda Ospedaliera Sant’Andrea, Rome, Italy 3 Breast Unit, Department of Surgery, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy; Department of Biomedical and Clinical Sciences "Luigi Sacco", Università di Milano, Milan, Italy 4 Breast Surgery Unit, San Raffaele University Hospital, Milan, Italy 5 Interdisciplinary Breast Center, Department of Gynecology and Obstetrics, Klinikum Esslingen, Esslingen, Germany 6 Oncology Institute of Southern Switzerland, Bellinzona, Switzerland 7 Cancer Immunotherapy lab, IOR Institute of Oncology Research, Bellinzona, Switzerland Background: Almost 20% of breast cancer patients present at diagnosis with clinically positive nodes. Most of these patients undergo neoadjuvant therapy in order to de-escalate the axillary surgery in case of response (sentinel lymph node biopsy, targeted axillary dissection or targeted axillary dissection, instead of an axillary lymphadenectomy). The conversion from positive to negative nodes after neoadjuvant therpy is expected in approximately the 60% of the cases, depending by tumor subtypes. Several models have been proposed with the goal of identifying predictors of nodal response prior to neoadjuvant treatment. The immune system plays a pivotal role in cancer invasion and progression. Its role in treatment response is currently under investigation in several settings. Primary endpoint: to identify a preoperative immune profiling of breast cancer patients with nodal involvement at diagnosis and to correlate the immune changes after neoadjuvant therapy with the nodal response (macrometastases, micrometastasis, isolated tumor cells, complete response). Trial design: It is an international prospective cohort study including breast cancer patients undergoing standard neoadjuvant therapy, who present initially with biopsy-proven axillary lymph node metastasis. Ten immune markers will be analyzed using immunohistochemistry and tissue microarray in primary tumor and nodal tissue samples (tumor associated neutrophils, CD4 lymphocytes, CD8 lymphocytes, T regulatory cells, Macrophages, Follicular dendritic cells(DC), plasmocytoid DC, interdigitant DC, mature DC, Lysosomal associated membrane protein 3). The tissue analysis will be performed on the biopsy collected at diagnosis (prior to neoadjuvant therapy) and during the axillary surgery (after neoadjuvant therapy). Target accrual/sample size: 210 patients Statistical analysis: To compare the distribution of immune cells according to the state of lymph node metastasis, Student’s t test will be performed. Pearson’s chi-square test will be used to evaluate the correlation between immune profile and nodal response, based on clinic-pathological features. Odds ratios (ORs) and 95% confidence intervals (CIs) will be calculated using logistic regression analysis. Multivariable analysis will be performed using the multivariable logistic regression model. Logistic regression models will be used to identify the clinical, pathologic and immunological variables associated with the nodal response. P-values less than 0.05 will be considered significant. Analyses will be performed using Microsoft IBM SPSS® version 20.0 for Mac. Current status: Recruitment has not started yet. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Ilary Ruscito, Filippo Bellati, Fabio Corsi, Rosa Di Micco, Oreste Davide Gentilini, Thorsten Kuehn, Andrea Papadia, Donatella Caserta, Lorenzo Rossi, Arianna Calcinotto. Immunological predictors of nodal response in breast cancer patients undergoing neoadjuvant therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-12-01.

OBJECTIVE To compare outcomes after hysterectomy and hysterectomy plus sentinel node mapping (SNM) in endometrial cancer (EC) patients. MATERIALS AND METHODS This is a retrospective study, collecting data of EC patients treated between 2006 and 2016 in nine referral centers. RESULTS The study population included 398 (69.5%) and 174 (30.5%) patients having hysterectomy and hysterectomy plus SNM. As the results of the adoption of a propensity-score matched analysis, we selected two homogeneous cohort of patients (150 having hysterectomy only vs. 150 having hysterectomy plus SNM). The SNM group had a longer operative time, but did not correlate with length of hospital stay and estimated blood loss. Overall severe complication rates were similar between groups (0.7% in the hysterectomy group vs. 1.3% in the hysterectomy plus SNM group; p = 0.561). No lymphatic-specific complication occurred. Overall, 12.6% of patients having SNM were diagnosed with disease harboring in their lymph nodes. Adjuvant therapy administration rate was similar between groups. Considering patients having SNM, 4% of patients received adjuvant therapy on the basis of nodal status alone; all the other patients received adjuvant therapy also on the basis of uterine risk factors. Five-year disease-free (p = 0.720) and overall (p = 0.632) survival was not influenced by surgical approach. CONCLUSIONS Hysterectomy (with or without SNM) is a safe and effective method for managing EC patients. Potentially, these data support the omission of side specific lymphadenectomy in case of unsuccessful mapping. Further evidence is warranted in to confirm the role SNM in the era of molecular/genomic profiling.

PURPOSE We aimed to assess the impact of low-volume metastasis (micrometastasis and isolated tumor cells) on disease-free survival (DFS) of women with early-stage cervical cancer. METHODS Women with clinically suspected stage 1A-IB2 (FIGO 2018 classification) disease who underwent retroperitoneal nodal staging between October 2010 and April 2018, were retrospectively analyzed. The group of women who had undergone lymphadenectomy and standard node pathologic analysis (H&E group), were compared to the group undergoing sentinel node mapping (SLN) and ultrastaging with or without lymphadenectomy (ultrastaging group). At a median follow-up of 45 months, the DFS curves were analyzed. RESULTS Overall, 573 patients were revised (272 in the H&E group and 302 in the ultrastaging group). Eighty-five patients presented lymph node metastasis (32 in H&E, 53 in ultrastaging). Ultrastaging protocol increased the rate of low-volume metastasis by 5.6%. Twenty patients showed exclusive micrometastasis or ITC's. Seventy-three recurrences occurred (35 in H&E, 38 in ultrastaging). Only 1 out of 53 patients in the ultrastaging group (1.9%) presented with micrometastasis recurred. The 3-year disease-free survival was 89% for the H&E group, and 88% for the ultrastaging group, respectively (p = 0.175). CONCLUSION Ultrastaging analysis allowed increasing the detection of low volume metastasis in women with early-stage cervical cancer. However, the type of nodal staging did not have an impact on patients' 3-year disease-free survival.

Surgical staging in endometrial cancer has evolved and sentinel lymph node (SLN) mapping has replaced a full pelvic and paraaortic lymphadenectomy in several cases. An intraoperative evaluation of SLN might identify patients who could benefit the most from a full lymphadenectomy. The aim of this study is to evaluate the clinical relevance of frozen section of SLN. A retrospective analysis in patients with endometrial cancer who underwent SLN mapping with intraoperative evaluation at frozen section between February 2016 and September 2019 was performed. In case of metastatic involvement, a full lymphadenectomy was performed. Fifty-eight patients met the inclusion criteria. Clinical–pathologic characteristics of the patients and surgical data were analyzed. Overall, bilateral and unilateral detection rates were 100% (58/58), 89.7% (52/58), and 10.3% (6/58), respectively. Eight patients had a stage IIIC disease at permanent section. Frozen section detected SLN metastases in four of eight patients. Of these, two were micrometastases and two were macrometastases. At frozen section of the SLNs, no macrometastases were misdiagnosed. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of frozen section in detecting metastases was 50%, 100%, 93%, 100% and 92.6%, respectively. The intraoperative evaluation of SLN in endometrial cancer accurately identifies patients with macrometastases. This is the cohort that might benefit the most of a full lymphadenectomy for a higher risk of additional lymph node metastases.

To evaluate the difference in oncologic outcome between vulvar cancer patients with uni- and bilateral inguino-femoral lymph nodal involvement and to identify factors affecting their oncologic outcome Patients who underwent inguino-femoral lymphadenectomy for vulvar cancer were classified into three groups according to their lymph nodal status at the histology analysis (negative, positive one side, positive bilaterally). PFS and OS survival were calculated using the Kaplan–Meier method. Univariate and multivariate analyses were performed to analyze factors predicting overall survival and progression-free survival. Multivariable models were used for variables reporting a p value ≤ 0.1 at the univariate analysis. p values ≤ 0.05 were considered statistically significant. One hundred and forty-six patients were considered for the analysis. Patients with bilaterally negative lymph nodes had significantly longer PFS and OS as compared to patients with unilateral and bilateral involvement. Patients with unilateral lymph nodal involvement had better PFS than patients with bilateral lymph nodal involvement. Among these patients, the difference in the OS approached but did not reach statistical significance. At the multivariate analysis, the tumor size affected PFS and lymph nodal involvement affected OS. Vulvar cancer patients with bilateral positive lymph nodes have worse oncologic outcome as compared to patients with unilateral lymph nodal involvement; similarly, patients with unilateral lymph nodal involvement have worse oncological outcome as compared to patients with bilateral negative lymph nodes. Furthermore, tumor size and lymph nodal status are independent factors predicting recurrence rate and overall survival, respectively.

OBJECTIVE Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. METHODS This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. RESULTS Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. CONCLUSION Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

Background: The primary objective of this study was to assess the associations of computed tomography (CT)-based whole-body composition values with overall survival (OS) and progression-free survival (PFS) in epithelial ovarian cancer (EOC) patients. The secondary objective was the association of body composition with chemotherapy-related toxicity. Methods: Thirty-four patients (median age 64.9 years; interquartile range 55.4–75.4) with EOC and thorax and abdomen CT scans were included. Clinical data recorded: age; weight; height; stage; chemotherapy-related toxicity; and date of last contact, progression and death. Automatic extraction of body composition values was performed by dedicated software. Sarcopenia was defined according to predefined cutoffs. Statistical analysis included univariate tests to investigate associations of sarcopenia and body composition with chemotoxicity. Association of body composition parameters and OS/PFS was evaluated by log-rank test and Cox proportional hazard model. Multivariate models were adjusted for FIGO stage and/or age at diagnosis. Results: We found significant associations of skeletal muscle volume with OS (p = 0.04) and PFS (p = 0.04); intramuscular fat volume with PFS (p = 0.03); and visceral adipose tissue, epicardial and paracardial fat with PFS (p = 0.04, 0.01 and 0.02, respectively). We found no significant associations between body composition parameters and chemotherapy-related toxicity. Conclusions: In this exploratory study, we found significant associations of whole-body composition parameters with OS and PFS. These results open a window to the possibility to perform body composition profiling without approximate estimations.

Contains fulltext : 283074.pdf (Publisher’s version ) (Open Access) OBJECTIVE: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). METHODS: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. RESULTS: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%-97.9%) and 76.5% (95% CI=68.1%-84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%-15.2%) in patients with grade 1-2 endometrial cancer and 11.8% (95% CI=8.1%-16.1%) in patients with grade 1-3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%-100%) in studies that included grade 1-2 endometrial cancer and 99.2% (95% CI=97.9%-99.9%) in studies that also included grade 3. CONCLUSION: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediate-risk endometrial cancer.

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV.

Introduction Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). Material and methods Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. Results Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. Conclusion Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve., Graphical abstract Image 1, Highlights • BRCAm carriers have similar AMH levels to wild-type women. • In women under 42 years old, AMH level is statistically lower in BRCA1m. • Fertility preservation counselling should be offered once BRCA pathogenic variant is diagnosed.

Simple Summary Ovarian cancer represents the most lethal gynecological malignancy. Since many new drugs have been recently introduced as adjunctive treatments for this pathology, an early prediction of outcome might be helpful to further improve outcomes. Radiomics represents a recent advancement, relying on extraction of quantitative features from imaging examinations. Indeed, clinical images, such as computed tomography images, may contain quantitative information, reflecting the underlying pathophysiology of a tumoral tissue. Radiomic analyses can be performed in tumor regions and metastatic lesions, as well as in normal tissues. The radiomic process relies on quantitative features, usually extracted by dedicated software, and then culminates in analysis and model building, according to a defined clinical question. This systematic review aims to evaluate association between radiomics based on computed tomography images and survival (in terms of overall survival and progression free survival) in ovarian cancer patients. Abstract The objective of this systematic review was to assess the results of radiomics for prediction of overall survival (OS) and progression free survival (PFS) in ovarian cancer (OC) patients. A secondary objective was to evaluate the findings of papers that based their analyses on inter-site heterogeneity. This systematic review was conducted according to the PRISMA statement. After the initial retrieval of 145 articles, the final systematic review comprised six articles. Association between radiomic features and OS was evaluated in 3/6 studies (50%); all articles showed a significant association between radiomic features and OS. Association with PFS was evaluated in 5/6 (83%) articles; the period of follow-up ranged between six and 36 months. All the articles showed significant association between radiomic models and PFS. Inter-site textural features were used for analysis in 2/6 (33%) articles. They demonstrated that high levels of inter-site textural heterogeneity were significantly associated with incomplete surgical resection in breast cancer gene-negative patients, and that lower heterogeneity was associated with complete resectability. There were some differences among papers in methodology; for example, only 3/6 (50%) articles included validation cohorts. In conclusion, radiomic models have demonstrated promising results as predictors of survival in OC patients, although larger studies are needed to allow clinical applicability.

Endometrial cancer care has undergone major changes in the past 30 years. In 1988, staging transitioned from clinical to surgical. Moreover, the surgical approach of choice is no longer open surgery, but minimally invasive surgery. An improvement in terms of nodal evaluation followed. Full systematic lymphadenectomy has been continuously replaced by sentinel lymph node mapping. Although sentinel lymph node mapping with a cervical injection of indocyanine green dye is rapidly gaining clinical acceptance, we lack consistent recommendations on a well-defined procedure that accurately and indolently assesses the lymph node status. Such recommendations are indispensable, as nodal status is the most important predictive factor of survival and is essential for tailoring adjuvant treatment to the risk of recurrence. This paper focuses on transitions in endometrial cancer care and highlights current data on sentinel lymph node mapping in endometrial cancer. We demonstrate that sentinel lymph node mapping is a safe and accurate strategy for nodal status evaluation with appropriate sensitivity, false-negative rate and negative predictive value in high- as well as low-risk settings. Furthermore, we elaborate on type and dose of tracer, site of injection, number of sentinel lymph nodes to be removed, sentinel lymph node mapping learning curve, operation mode and sentinel lymph node ultrastaging. In the future, guidelines with consistent recommendations on the above outlined features of sentinel lymph node mapping should be established to allow for a uniform and wide-spread application of the sentinel lymph node mapping procedure.

BackgroundThis study aimed to evaluate the clinical value of indocyanine green sentinel lymph node (SLN) mapping in patients with vulvar cancer. The conventional procedure of SLN mapping in vulvar cancer includes peritumoral injection of technetium-99m nanocolloid before surgery and intraoperative injection of a blue dye. However, these techniques harbor some limitations. Near-infrared fluorescence imaging with indocyanine green has gained popularity in SLN mapping in different types of cancer.MethodsWe analyzed retrospectively vulvar cancer patients at our institution between 2013 and 2020 undergoing indocyanine green SLN mapping by applying video telescope operating microscope system technology.Results64 groins of 34 patients were analyzed. In 53 groins we used technetium-99m nanocolloid, in four patent blue, and in five both techniques, additionally to indocyanine green for SLN detection. In total, 120 SLNs were identified and removed. The SLN detection rate of indocyanine green was comparable to technetium-99m nanocolloid (p=.143) and higher than patent blue (p=.003). The best results were achieved using a combination of ICG and technetium-99m nanocolloid (detection rate of 96.9%). SLN detection rates of indocyanine green were significantly higher in patients with positive lymph nodes (p=.035) and lymphatic space invasion (p=.004) compared to technetium-99m nanocolloid.ConclusionIndocyanine green SLN mapping in vulvar cancer is feasible and safe, with reasonable detection rates. Due to its easy application and few side effects, it offers a sound alternative to the conventional SLN mapping techniques in vulvar cancer. In patients with lymph node metastasis, indocyanine green even outperformed technetium-99m nanocolloid in terms of detection rate.

OBJECTIVE Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p��=��0.416, log-rank test) and overall survival (p��=��0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

IntroductionLong-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more personalized therapeutic approach. The objective of this study is to determine further characteristics of long-term survivors with high-grade serous ovarian cancer.MethodsLong-term survivors were defined as patients living longer than 8 years after first diagnosis and were recruited within seven high volume centers across Europe from November 1988 to November 2008. The control group included patients with high-grade serous ovarian cancer with less than 5 years' survival identified from the systematic ‘Tumorbank ovarian cancer’ database. A subanalysis of Charité patients only was performed separately for in-depth analysis of tumor dissemination. Propensity score matching with nearest-neighbor caliper width was used to match long-term survivors and the control group regarding age, FIGO stage, and residual tumor.ResultsA total of 276 patients with high-grade serous ovarian cancer were included, divided into 131 long-term survivors and 145 control group patients. After propensity score matching and multivariable adjustment, platinum sensitivity (p=0.002) was an independent favorable prognostic factor whereas recurrence (pConclusionPlatinum sensitivity constitutes a favorable factor for long-term survival whereas tumor involvement of the upper abdomen, ascites, and recurrence have a negative impact. Based on clinical estimation, long-term survival is associated with combinations of clinical, surgical, and molecular factors.

Ovarian cancer is a leading cause of death among gynecologic malignancies. This disappointing prognosis is closely related to intrinsic or acquired resistance to conventional platinum-based chemotherapy, which can affect a third of patients. As such, investigating relevant molecular targets is crucial in the fight against this disease. So far, many mutations involved in ovarian cancer pathogenesis have been identified. Among them, a few pathways were implicated. One such pathway is the P13K/AKT/mTOR with abnormalities found in many cases. This pathway is considered to have an instrumental role in proliferation, migration, invasion and, more recently, in chemotherapy resistance. Many miRNAs have been found to influence P13K/AKT/mTOR pathway with different potential role in tumor genesis and ovarian cancer behaviour. In particular, their biological function was recently investigated as regards chemoresistance, therefore, leading to the identification of potential specific indirect biomarker of platinum sensitivity in ovarian cancer.

Sentinel lymph node (SLN) mapping in endometrial cancer (EMCA) is rapidly gaining acceptance in the clinical community. As compared to a full lymphadenectomy in every patient, to a selective lymphadenectomy after frozen section of uterus in selected patients with intrauterine risk factors or to a strategy in which a lymphadenectomy is always omitted, SLN mapping seems to be a reasonable and oncologically safe middle ground. Various protocols can be used when applying an SLN mapping. In this manuscript we review the characteristics, toxicity and clinical impact of technetium-99m radiocolloid (Tc-99m), of the blue dyes (methylene blue, isosulfan blue and patent blue) and of indocyanine green (ICG). ICG has an excellent toxicity profile, has higher overall and bilateral detection rates as compared to blue dyes and higher bilateral detection rates as compared to a combination of Tc-99m and blue dye. The detrimental effect of BMI on the detection rates is attenuated when ICG is used as a tracer. The ease of use of the ICG SLN mapping is perceived by the patients as a better quality of care delivered. Whenever possible, ICG should be favored over the other tracers for SLN mapping in EMCA patients.

BackgroundAlthough pivotal in the oncological management of most tumors, radical lymphadenectomy is associated with a significant number of lymphatic complications. The aim of this meta-analysis is to evaluate the efficacy of fibrinogen sealant patches in reducing lymphadenectomy-related postoperative complications.Methods/MaterialsThe electronic databases PubMed, Medline, and Scopus were searched using the terms “lymphadenectomy” or “lymph node dissection” and “TachoSil,” “TachoComb,” or “fibrin sealant patch.” Series evaluating the efficacy of fibrin-thrombin collagen sealant patches were included in the meta-analysis.ResultsOverall, 26 studies were retrieved through the literature search. Ten studies including 720 patients met selection criteria. The use of fibrin-thrombin sealant patches to the sole scope of reducing lymphadenectomy-related complications significantly reduced the incidence of lymphocele, symptomatic lymphocele, the need of percutaneous drainage procedures, the volume of lymph drained, and the duration of the drainage. No effect on wound and/or lymphocele infection was noted.ConclusionsThis meta-analysis demonstrates that the use of fibrin-thrombin sealant patches significantly reduces the total volume of lymph drained, the duration of the drainage, the incidence of lymphocele and symptomatic lymphocele, and the need for postoperative percutaneous drainage procedures. Its use does not affect the incidence of wound or lymphocele infections.

Appropriate and accurate pre-operative imaging in epithelial ovarian cancer patients may allow selection of patients that may mostly benefit either from primary cytoreductive surgery or from neoadjuvant chemotherapy. If the patient is considered suitable for upfront surgery, pre-operative imaging may help in planning the surgical approach, to forecast the operating time, and to estimate the need for other consulting specialists. Currently, computed tomography (CT) imaging is the standard of care for pre-operative evaluation of ovarian cancer patients; however, advanced magnetic resonance imaging (MRI) is emerging as a technique that may overcome the limitations of CT imaging, especially for small peritoneal deposits in difficult-to-resect sites. Positron emission tomography (PET)-CT imaging in the pre-operative setting is currently limited, whereas the use of the new hybrid technique PET-MRI is still under evaluation. Since criteria that may preclude optimal cytoreductive surgery may vary, depending on the aggressiveness of the surgical procedure and surgeon skill, multidisciplinary consensus conferences are the ideal platform to evaluate extent of the disease and surgical strategy.

Objective To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). Methods This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. Results 428 patients were included in the analysis. With a median follow-up of 56 months (1–162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01–1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34–20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11–0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01–1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58–24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12–0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13–0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39–17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. Conclusions In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Women carrying a BRCA mutation have an increased risk of developing breast and ovarian cancer. The most effective strategy to reduce this risk is the bilateral salpingo-oophorectomy, with or without additional risk-reducing mastectomy. Risk-reducing bilateral salpingo-oophorectomy (RRBSO) is recommended between age 35 and 40 and between age 40 and 45 years for women carriers of BRCA1 and BRCA2 mutations, respectively. Consequently, most BRCA mutation carriers undergo this procedure prior to a natural menopause and develop an anticipated lack of hormones. This condition has a detrimental impact on various systems, affecting both the quality of life and longevity; in particular, women carrying BRCA1 mutation, who are likely to have surgery earlier as compared to BRCA2. Hormonal replacement therapy (HRT) is the only effective strategy able to significantly compensate the hormonal deprivation and counteract menopausal symptoms, both in spontaneous and surgical menopause. Although recent evidence suggests that HRT does not diminish the protective effect of RRBSO in BRCA mutation carriers, concerns regarding the safety of estrogen and progesterone intake reduce the use in this setting. Furthermore, there is strong data demonstrating that the use of estrogen alone after RRBSO does not increase the risk of breast cancer among women with a BRCA1 mutation. The additional progesterone intake, mandatory for the protection of the endometrium during HRT, warrants further studies. However, when hysterectomy is performed at the time of RRBSO, the indication of progesterone addition decays and consequently its potential effect on breast cancer risk. Similarly, in patients conserving the uterus but undergoing risk-reducing mastectomy, the addition of progesterone should not raise significant concerns for breast cancer risk anymore. Therefore, BRCA mutation carriers require careful counselling about the scenarios following their RRBSO, menopausal symptoms or the fear associated with HRT use.

Simple Summary Axillary dissection is a highly mobile procedure with severe lymphatic consequences. The off-label application of fibrin sealants in the axilla, with the sole aim to eliminate dead space and to provoke sealing of the disrupted lymphatic vessels at the end of axillary dissection, is an experimental procedure to reduce lymphatic morbidity. The aim of our systematic review and meta-analysis is to investigate the effects of fibrin sealants on lymphatic morbidity after axillary dissection. Our results show that this experimental procedure is able to decrease the total axillary drainage output, the number of days before the axillary drainage is removed, and the length of hospital stay. However, no effects on the occurrence rate of axillary lymphocele or on the surgical site complications rate were demonstrated Abstract Background: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. Methods: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. Results: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin’s disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). Conclusion: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.

PURPOSE The aim of this study was to compare technetium radiocolloid (Tc99(m)) + blue dye (BD) versus Indocyanine green (ICG) fluorescent dye in terms of the overall detection rate and bilateral sentinel lymph node (SLN) mapping in patients with endometrial carcinoma. METHODS Patients from five European centers with apparently confined clinical stage I endometrial cancer were reviewed. A comparison was made between women who received SLN mapping with pelvic and/or aortic lymphadenectomy (LND), and women who underwent SLN algorithm (SA), was also performed between the two groups. RESULTS Three hundred and forty-two (342) women were involved (147 in the Tc99(m) + BD group and 195 in the ICG group). The overall detection rate of SLN biopsy was 97.3% (143/147) for women in the Tc99(m) + BD group and 96.9% (189/195) for women in the ICG group (p = 0.547). The bilateral mapping rate for ICG was 84.1%-significantly higher with respect to the 73.5% obtained with Tc99(m) + BD (p = 0.007). No differences in overall sensitivity (OS) and overall false negative rate (FNR) were seen between LND and SA (p value = 0.311), whereas the negative predictive value (NPV) was in favor of SA group (p value = 0.030). CONCLUSIONS In this study, fluorescent mapping using ICG resulted equivalent to the standard combined radiocolloid and BD, but real-time SLN mapping achieves a higher bilateral detection rate. The added value that this fast emerging technology promises to give certainly warrants future studies to further consolidate the advantages there are over the standard technique.

PURPOSE The adoption of a sentinel lymph node (SLN) algorithm and the presence of high bilateral detection rates have been associated with increased accuracy of SLN mapping in cervical and endometrial cancer patients. In this context, the significance of the number of SLNs removed has not yet been investigated. The aim of this study was to evaluate (a) whether or not a higher SLN removal count is associated with a reduced false-negative rate and (b) which clinical factors correlate with the number of SLNs removed. METHODS Patients with cervical or endometrial cancer who underwent SLN mapping with bilateral SLN detection followed by lymphadenectomy were evaluated retrospectively. On the basis of the mean number of the SLNs removed, the patients were divided in two groups: Group 1 included patients with up to 3 SLNs removed and Group 2 included patients with more than 3 SLNs removed. Factors predicting a higher SLN count were evaluated using univariate and multivariate analysis. RESULTS Eighty-four patients met the inclusion criteria. The two groups consisted of 42 patients each and differed only by the median SLN count. Two endometrial cancer patients in Group 1 had false-negative pelvic SLNs and isolated para-aortic metastases; no false-negative SLNs were recorded in Group 2 (p = n.s.). The results of multivariate analysis indicted that the number of SLNs removed was influenced only in cases where the operating surgeon had performed more than 20 laparoscopic ICG SLN mappings. CONCLUSIONS A higher SLN count does not seem to increase the accuracy of SLN mapping in cervical and endometrial cancer patients.

Simple Summary The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of breast cancer gene 1 (BRCA1) gene hypermethylated breast cancer in women, and to pool the results in order to provide a unique clinical profile of this cancer setting population. Identifying the clinical profile of breast cancer in women harboring BRCA1 gene hypermethylation may help oncologists select a subgroup of patients who may be candidates for BRCA1 methylation assessment, thus, possibly enlarging the cancer population who may benefit from new target-therapy agents. Results showed that BRCA1 gene hypermethylation should be suspected in all breast cancer patients with advanced disease stages, positive lymph nodes, and premenopausal age at diagnosis. Multidisciplinary groups treating women with breast cancer should take into account the possibility of addressing patients with these characteristics with a BRCA1 gene methylation status analysis. Abstract Background: DNA aberrant hypermethylation is the major cause of transcriptional silencing of the breast cancer gene 1 (BRCA1) gene in sporadic breast cancer patients. The aim of the present meta-analysis was to analyze all available studies reporting clinical characteristics of BRCA1 gene hypermethylated breast cancer in women, and to pool the results to provide a unique clinical profile of this cancer population. Methods: On September 2020, a systematic literature search was performed. Data were retrieved from PubMed, MEDLINE, and Scopus by searching the terms: “BRCA*” AND “methyl*” AND “breast”. All studies evaluating the association between BRCA1 methylation status and breast cancer patients’ clinicopathological features were considered for inclusion. Results: 465 studies were retrieved. Thirty (6.4%) studies including 3985 patients met all selection criteria. The pooled analysis data revealed a significant correlation between BRCA1 gene hypermethylation and advanced breast cancer disease stage (OR = 0.75: 95% CI: 0.58–0.97; p = 0.03, fixed effects model), lymph nodes involvement (OR = 1.22: 95% CI: 1.01–1.48; p = 0.04, fixed effects model), and pre-menopausal status (OR = 1.34: 95% CI: 1.08–1.66; p = 0.008, fixed effects model). No association could be found between BRCA1 hypermethylation and tumor histology (OR = 0.78: 95% CI: 0.59–1.03; p = 0.08, fixed effects model), tumor grading (OR = 0.78: 95% CI :0.46–1.32; p = 0.36, fixed effects model), and breast cancer molecular classification (OR = 1.59: 95% CI: 0.68–3.72; p = 0.29, random effects model). Conclusions: hypermethylation of the BRCA1 gene significantly correlates with advanced breast cancer disease, lymph nodes involvement, and pre-menopausal cancer onset.

Background: Proper patient selection is crucial to maximize aestethic outcome in breast reconstructive surgery. No specific patients selection criteria have been developed to choose between prepectoral versus subpectoral implant-based reconstruction. A quantitative tool able to determine the pectoralis muscle individual characteristics might be helpful to discriminate a priori the patients who will experience better aesthetic outcome and less complications following a pre-pectoral versus a sub-pectoral approach. Preoperative pectoralis muscle assessment may optimize patients’ selection for the breast reconstructive technique. Trial design: This is a multicentric trial in which, patients candidated to risk reducing mastectomy fulfilling inclusion criteria, will undergo a preoperative MRI prior to randomization to pre-pectoral versus sub-pectoral implant placement in immediate breast reconstruction. Volumetric analysis of the pectoralis major muscle (cm2) and measurement of the subcutaneous adipose tissue in the breast region, will be performed to assess anatomic characteristics of the pectoralis muscle using a sagittal T1 fat suppressed sequence. The volume of the pectoralis muscle will be calculated by measuring differences in density with the MRI. In all patients, the pectoralis muscle area on the left and right side will be determined separately and the two values will be averaged. The volumetric assessment will be performed by two expert radiologists. BREAST-Q© questionnaire will be completed by each patient prior to surgery and at the follow up evaluations. Breast reconstruction will be performed immediately after nipple-sparing mastectomy (Arm 1: breast implant placed above the pectoralis major muscle (pre-pectoral); Arm 2: breast implant placed below the pectoralis major muscle (sub-pectoral)). Number of revisional surgeries, explantations, infections, seromas, flap necrosis, will be compared between two groups and correlated with MRI pectoralis muscle volume. Post-operative follow-up evaluations at 6 and 12-months to assess capsular contracture and BREAST-Q changes will be performed. Eligibility criteria: Inclusion criteria: •Female patient•Ages 18-60•Patients undergoing risk reducing mastectomy with immediate implant-based reconstruction •Signed informed consent Exclusion Criteria: •Prior chest wall irradiation •Patients with a contraindication to immediate breast reconstruction.•Patients with history of smoking, •BMI> 40, •D cup breast size•grade III ptosis Aims: To identify variables measured at preoperative MRI pectoralis muscle’s volumetric analysis that correlate with aesthetic outcome and complication rate in pre-pectoral versus sub-pectoral implant based reconstruction. Statistical methods: The assumption of distributional normality will be tested using the Shapiro-Wilk test. Comparisons of two variables will be carried out using the Wilcoxon test for paired groups and the Mann-Whitney test for unpaired groups. Present accrual and target accrual: The trial has been submitted for IRB approval at the ethical commission of Italian Switzerland. Recruitment has not started yet. With an enrollment ratio of 1:1, fifty patients (25 per arm) need to be recruited to ensure a power of 80% with a two sides alpha error of 0.05. Contact information: marialuisa.gasparri@eoc.ch Citation Format: Maria Luisa Gasparri, Thorsten Kuehn, Isabel Rubio, Philip Poortmans, Diana Lueftner, Orit Kaidar-Pearson, Beat Thuerlimann, Yves Harder, Daniel Schmauss, Francesco Meani, Claudia Rauh, Michael David Mueller, Malgorzata Banys-Paluchowski, Andrea Papadia, Valerio Vitale, Stefania Rizzo, Oreste Davide Gentilini. Volumetric analysis of the pectoralis major muscle as preoperative tool to select patients undergoing pre-pectoral versus sub-pectoral implant based breast reconstruction after risk reducing mastectomy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-23-02.

Background and Purpose: In endometrial cancer, staging is performed surgically. Controversy about the required extent of lymph node removal is ongoing. In low-risk endometrial cancer (FIGO Stage 1, endometrioid histology, Grades 1 and 2), the risk of lymph-node involvement is 4–17%. Since the introduction of near-infrared optics and the use of indocyanine green, the role of sentinel lymph node removal is increasing and could offer an appropriate balance between the morbidity of a complete lymph-node dissection and the risk of missing lymph-node involvement. Methods In this retrospective comparative study on low-risk endometrial cancer, the extent of surgical lymph-node assessment (no lymphadenectomy vs removal vs lymphadenectomy) in two European institutions was compared and analyzed on the basis of perioperative data and oncological outcome. Results The study included 279 patients from: 103 (36.9%) had no lymphadenectomy, 118 (42.3%) underwent SLN removal and 58 (20.8%) underwent pelvic and/or para-aortic lymphadenectomy. There were significant differences among the groups in blood loss (p = 0.000), operation time (p = 0.000), and severity of postoperative complications (p = 0.063). In comparing only sentinel lymph-node removal vs no lymphadenectomy, there were no significant differences. No significant difference was seen between the extent of lymphadenectomy removal and the risk of recurrence. Age and Lymphovascular space invasion positivity were significant risk factors for recurrence (p = 0.004 and p = 0.019). Conclusions In early-stage, endometrial cancer, Grade 1 and 2, sentinel lymph node removal offers a convincing balance between oncological safety and perioperative morbidity. Especially in LVSI-positive cases, lymph-node evaluation in any form is crucial.

Background To evaluate sensitivity, false negative rate and negative predictive value of the combination of sentinel lymph node (SLN) mapping and frozen section (FS) in triaging cervical cancer patients to a definitive chemo-radiotherapy. Methods A retrospective analysis of patients with histologically proven cervical cancer undergoing laparoscopic SLN mapping and frozen section of the SLNs followed by a completion radical hysterectomy, pelvic and/or paraarotic lymphadenectomy. Sensitivity, false negative rate and negative predictive value of the SLN mapping, of the frozen section and of the combination of the two in identifying micro- and macrometastases were calculated. Results One-hundred and four patients with cervical cancer underwent surgery. Of these, 87 (83.7%) had bilateral detection rates at the SLN mapping and underwent FS evaluation and were selected for statistical analysis. Twenty-five patients had lymph nodal metastases at H&E staining. Of these, 24 displayed metastatic disease to the SLNs and one to a NSLN accounting for a FN rate of 4.0%. Metastases were identified in 21 patients at the FS analysis. Four patients had metastases in the SLNs that were missed at the FS analysis. The FN rate of the FS is 12.5% if we excluded isolated tumour cells in the analysis. The FN rate of the combined methodology (SLN mapping and FS of the SLN) is 16%. Twenty-one out of 25 patients (84.0%) could correctly be triaged to a definitive chemo-radiotherapy. Conclusions The combination of SLN mapping and FS of the SLNs is efficient in triaging patients to a definitive chemo-radiotherapy.

In several malignancies, it has been demonstrated that the lymph nodal status is the most important pathologic factor affecting prognosis and giving the indication to further adjuvant treatment. The surgical assessment of the lymph nodal status in endometrial cancer is debated since 30 years. Recently, the sentinel lymph node mapping is rapidly gaining clinical acceptance in endometrial cancer. The adoption of Indocyanine Green as a safe and user friendly tracer for sentinel lymph node mapping increased the speed to which this procedure is getting applied in clinical practice. As a consequence of this rapid growth, several fundamental questions have been raised and are still debatable. In this manuscript, we discuss the importance of a known pathological lymph nodal status, the technique of the sentinel lymph node mapping with the reported false negative rates and detection rates according to the different tracers adopted, and the clinical scenarios in which a sentinel lymph node mapping could be employed.

INTRODUCTION Aim of the study is to evaluate the impact of different doses of indocyanine green (ICG) on the sentinel lymph-node (SLN) mapping in endometrial cancer (EC). MATERIALS AND METHODS A retrospective analysis of EC patients undergoing a laparoscopic SLN mapping at two institutions was performed. Two different injection protocols were used (protocol # 1: 5 mg/ml and a volume of 8 ml; protocol # 2: 1.25 mg/ml and a volume of 4 ml). In every case, the injection was intracervical. The laparoscopic equipment adopted was the same among both institutions. Overall and bilateral detection rates (DR) and median number of retrieved SLNs were calculated. At uni- and multivariate analysis factors (including ICG dose) associated with DR and number of detected SLNs were investigated. RESULTS Overall, 168 patients were included. The overall and bilateral DR were 96.3 and 84.5%. Median number of removed SLNs was 3 (0-18). In 56% of the patients, a median number of 6 (1-93) non-SLNs (NSLNs) were removed. Seventeen (10.1%) patients had metastatic SLNs. At multivariate analysis, no factors were associated with bilateral DR. ICG dose was the only factor associated with number of removed SLNs at multivariate analysis. CONCLUSION A larger dose of ICG is associated with a higher number of retrieved SLNs but not with an increased bilateral DR.

Objective The aim of this study was to determine the impact of the sentinel lymph node mapping algorithm (SLN-A) on the staging in high-risk endometrial cancer (EC) compared to SLN plus selective lymphadenectomy (S-LND). Methods We retrospectively analyzed the database from a multicenter collaboration that included women with high risk features who underwent primary surgical staging. Results One-hundred and seventy-one women were identified (171), 66 in the SLN-A and 105 in the S-LND group, respectively. Pelvic LD was performed on 115 patients (67.2%) and aortic dissection was performed in 54/105 of the women in the S-LND group (51%). The 5-year comparison did not show a significant difference in the strategy adopted for nodal staging, regarding disease-free survival (DFS) [HR: 0.82; 95% CI 0.53–1.28; p = 0.390]. Conclusions In this study focusing on women with EC in the HR groups, we did not find a difference in the 5-year DFS when comparing the SLN-A strategy with S-LND. The SLN strategy did not seem to compromise the prognosis of patients with a higher risk of recurrence.

Breast cancer (BC) is the most common malignancy in women worldwide. Breast cancer related mortality has dropped significantly since the widespread adoption of mammographic screening. Approximately, 5% of the patients with BC carry germline mutations that are responsible for their condition. Women carrying a BRCA 1 or 2 mutation have a 57% and 49% lifetime risk of developing breast cancer, respectively. For BRCA1/2 patients reluctant to a prophylactic surgery, the only risk reducing strategy remains an increased imaging and clinical surveillance. Whereas a closer screening mammogram program is helpful in detecting BC at an earlier stage, no laboratory markers exist. New markers would be helpful in identifying BC, once the mutations are identified, and in monitoring the cancer behavior and response to treatment, once the cancer is diagnosed. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional level by regulating gene expression. Aberrant miRNA expression was documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. MiRNAs can be detected in human fluids and could be used as biomarkers. A different pattern expression of miRNA in biological fluids of BC patients as compared to healthy control is currently under consideration in many clinical trials. The biologic mechanism of miRNAs, a rationale of its use as biomarker in cancer, and a literature review of the most significant results achieved about miRNAS in BC will be reported and discussed in this chapter.

PURPOSE To evaluate the sensitivity, negative predictive value (NPV) and false-negative (FN) rate of the near infrared (NIR) indocyanine green (ICG) sentinel lymph node (SLN) mapping in patients with poorly differentiated endometrial cancer who have undergone a full pelvic and para-aortic lymphadenectomy after SLN mapping. METHODS We performed a retrospective analysis of patients with endometrial cancer undergoing a laparoscopic NIR-ICG SLN mapping followed by a systematic pelvic and para-aortic lymphadenectomy. Inclusion criteria were a grade 3 endometrial cancer or a high-risk histology (papillary serous, clear cell carcinoma, carcinosarcoma, and neuroendocrine carcinoma) and a completion pelvic and para-aortic lymphadenectomy to the renal vessels after SLN mapping. Overall and bilateral detection rates, sensitivity, NPV, and FN rates were calculated. RESULTS From December 2012 until January 2017, 42 patients fulfilled inclusion criteria. Overall and bilateral detection rates were 100 and 90.5%, respectively. Overall, 23.8% of the patients had lymph node metastases. In one patient, despite negative bilateral pelvic SLNs, a metastatic non-SLN-isolated para-aortic metastasis was detected. This NSLN was clinically suspicious and sent to frozen section analysis during the surgery. FN rate, sensitivity, and NPV were 10, 90, and 97.1%, respectively. For the SLN mapping algorithm, FN rate, sensitivity, and NPV were 0, 100, and 100%, respectively. CONCLUSIONS Laparoscopic NIR-ICG SLN mapping in high-risk endometrial cancer patients has acceptable sensitivity, FN rate, and NPV.

ObjectiveThe aim of this study was to investigate the frozen section (FS) accuracy in tailoring the surgical staging of patients affected by endometrial cancer, using 2 different risk classifications.Methods/MaterialsA retrospective analysis of 331 women affected by type I endometrial cancer and submitted to FS assessment at the time of surgery. Pathologic features were examined on the frozen and permanent sections according to both the GOG33 and the Mayo Clinic algorithms. We compared the 2 models through the determination of Landis and Koch kappa statistics, concordance rate, sensitivity, specificity, positive predictive value, and negative predictive value for each risk algorithm, to assess whether there are differences in FS accuracy depending on the model used.ResultsThe observed agreement between the frozen and permanent sections was respectively good (k = 0.790) for the GOG33 and optimal (k = 0.810) for the Mayo classification. Applying the GOG33 algorithm, 20 patients (6.7%) were moved to an upper risk status, and 20 (6.7%) were moved to a lower risk status on the permanent section; the concordance rate was 86.5%. With the Mayo Clinic algorithm, discordant cases between frozen and permanent sections were 19 (7.6%), and the risk of lymphatic spread was underestimated only in 1 case (0.4%); the concordance rate was 92.4%. The sensitivity, specificity, positive predictive value, and negative predictive value for the GOG33 were 92%, 94%, 92%, and 93%, whereas with the Mayo algorithm, these were 98%, 91%, 77%, and 99%, respectively.ConclusionsAccording to higher correlation rate and observed agreement (92.4% vs 86.5% and k = 0.810 vs 0.790, respectively), the Mayo Clinic algorithm minimizes the number of patients undertreated at the time of surgery than the GOG33 classification and can be adopted as an FS algorithm to tailor the surgical treatment of early-stage endometrial cancer even in different centers.

Introduction Extramammary Paget disease (EMPD) is a rare neoplasm of the skin that presents with erythematous or leukoplacic plaques causing pruritus and pain. Standard treatment is surgical but local failures and recurrences are frequent, leading to multiple mutilating surgeries. Aim of the study is to evaluate the effectiveness of photodynamic therapy (PDT) to obtain a clinical response and symptom control with a non surgical approach in these patients. Materials and methods After disease extension evaluation and symptoms assessment women with EMPD were prospectively treated with aminolevulinic-acid methyl-esther (M-ALA) PDT. Clinical and symptoms response were evaluated after 3cycles and after any further PDT. Results Thirty-two patients with vulvar EMPD underwent M-ALA PDT. In sixteen (50%) patients the lesion extended to the perineal and/or perianal area. After three courses of treatment, three patients (9.4%) had a complete resolution of the symptoms; 25 patients (78.1%) a partial resolution and a stable disease was recorded in four patients (12.5%). None of the patients had progression of disease. Both size of the lesion and EMPD associated symptoms decreased significantly after three courses of treatment. Eighteen patients (56.2%) recurred and 16 (88.9%) were treated with further PDT. Among the 26 patients who underwent a further PDT, 16 patients (61.5%) achieved at least a partial response. Conclusion M-ALA PDT even if not curative is a reliable strategy to control EMPD and its associated symptoms even in an outpatient setting. M-ALA PDT is able to control large and multiple lesions regardless of the area involved, preserving cosmetic and/or functional anatomy.

Breast cancer is the most common malignancy in women worldwide, and ovarian cancer is the most lethal gynecological malignancy. Women carrying a BRCA1/2 mutation have a very high lifetime risk of developing breast and ovarian cancer. The only effective risk-reducing strategy in BRCA-mutated women is a prophylactic surgery with bilateral mastectomy and bilateral salpingo-oophorectomy. However, many women are reluctant to undergo these prophylactic surgeries due to a consequent mutilated body perception, unfulfilled family planning, and precocious menopause. In these patients, an effective screening strategy is available only for breast cancer, but it only consists in close radiological exams with a significant burden for the health system and a significant distress to the patients. No biomarkers have been shown to effectively detect breast and ovarian cancer at an early stage. MicroRNAs (miRNAs) are key regulatory molecules operating in a post-transcriptional regulation of gene expression. Aberrant expression of miRNAs has been documented in several pathological conditions, including solid tumors, suggesting their involvement in tumorigenesis. miRNAs can be detected in blood and urine and could be used as biomarkers in solid tumors. Encouraging results are emerging in gynecological malignancy as well, and suggest a different pattern of expression of miRNAs in biological fluids of breast and ovarian cancer patients as compared to healthy control. Aim of this study is to highlight the role of the urinary miRNAs which are specifically associated with cancer and to investigate their role in early diagnosis and in determining the prognosis in breast and ovarian cancer.

INTRODUCTION The aim of the study was to evaluate the use of PET/CT and/or SLN mapping alone or in combination in cervical cancer patients. MATERIALS AND METHODS Data on stage IA1-IIA cervical cancer patients undergoing PET/CT and SLN mapping were retrospectively collected. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PET/CT and SLN mapping, alone or in combination, in identifying cervical cancer patients with lymph node metastases were calculated. RESULTS Sixty patients met the inclusion criteria. PET/CT showed a sensitivity of 68%, a specificity of 84%, a PPV of 61% and a NPV of 88% in detecting lymph nodal metastases. SLN mapping showed a sensitivity of 93%, a specificity of 100%, a PPV of 100% and a NPV of 97%. The combination of PET/CT and SLN mapping showed a sensitivity of 100%, a specificity of 86%, a PPV of 72% and a NPV of 100%. For patients with tumors of >2 cm in diameter, the PET/CT showed a sensitivity of 68%, a specificity of 72%, a PPV of 61% and a NPV of 86%. SLN mapping showed a sensitivity of 93%, a specificity of 100%, a PPV of 100% and a NPV of 95%. The combination of PET/CT and SLN mapping showed a sensitivity of 100%, a specificity of 76%, a PPV of 72% and a NPV of 100%. CONCLUSION PET/CT represents a "safety net" that helps the surgeon in identifying metastatic lymph nodes, especially in patients with larger tumors.

ObjectiveThe objective of this study was to determine the patterns of recurrence of stage IB–IIA endometrioid endometrial adenocarcinoma (EMCA) with lymphovascular invasion (LVSI).MethodsA multicenter retrospective study of 1988 International Federation of Gynecology and Obstetrics stage IB–IIA EMCA patients with LVSI treated with surgery with or without radiation was conducted. Those with papillary serous or clear cell histologies and women treated with chemotherapy were excluded. Data regarding surgical-pathologic factors, treatment, and outcome were collected. Data were analyzed using χ2test, Kaplan-Meier estimates, and Cox multivariate proportional hazards models.ResultsFrom 1997 to 2008, we identified 131 patients with LVSI who met entry criteria among 5 institutions. Median age was 67 years (25%–75%: 60–75 years), and median follow-up was 4.25 years (25%–75%: 3–10 years). Following surgery, 45 patients were observed (Obs), and 86 patients received adjuvant radiation. We observed 30 total relapses 30/131 (23%): 11/45 (24%) in the Obs group and 19/86 (22%) in the adjuvant radiation group. Recurrence rates were similar between staged and unstaged patients: 24% (20/84) and 21% (10/47), respectively. Among Obs patients, 82% of relapses were local, whereas in patients treated with adjuvant radiation, 84% were distant. Relapses were significantly associated with invasion of the lower uterine segment (LUS) (P= 0.035). Both cancer-related survival and overall survival (OS) were not significantly impacted by adjuvant radiation, because of distant failure rates. Adjuvant radiation significantly improved pelvic control (P= 0.007). In a multivariate analysis, OS correlated with LUS invasion (P= 0.008) and was borderline-associated with stage (P= 0.06), whereas age (P= 0.12), grade (P= 0.31), myometrial invasion (P= 0.99), and radiation treatment (P= 0.23) were not.ConclusionsOverall recurrence rates for stage IB–IIA EMCA patients with LVSI are high (23%). Although adjuvant radiation therapy improved pelvic control, it did not impact recurrence rates, cancer-related survival, and OS, likely secondary to distant failures. The role of systemic therapy with or without radiotherapy for early-stage EMCA with LVSI should be evaluated, particularly in patients with high-grade tumors or involvement of the LUS.

PURPOSE To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC). METHODS Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping. RESULTS Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ = 0.244) when based on frozen section of the uterus and excellent (κ = 1) when based on SLN mapping. CONCLUSIONS ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

BACKGROUND In patients with a diagnosis of occult cervical cancer made on a hysterectomy specimen after surgery for a benign indication, lymph node assessment is crucial to determine treatment. We aimed to compare sentinel lymph node (SLN) mapping between patients with postoperative diagnosis of occult cervical carcinoma and patients with cervical cancer and uterus in situ. METHODS A retrospective analysis of cervical cancer patients International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIA disease undergoing laparoscopic SLN mapping was performed. Patients were divided into two groups: those with a diagnosis of occult cervical cancer made on a hysterectomy specimen (group 1) and those with a diagnosis of cervical cancer and uterus in situ (group 2). Tracers used for SLN mapping included technetium-99m ((99m)Tc), blue dye, and indocyanine green. After detection and excision, the SLN was sent for frozen section analysis, and the planned surgical procedure was aborted in case of metastatic disease in favor of a chemoradiotherapeutic treatment. RESULTS Groups 1 and 2 included 9 and 62 patients, respectively. Clinicopathologic characteristics were similar among the two groups. Overall and bilateral detection rates were 66.6 and 33.3 and 95.1 and 87 % in groups 1 and 2, respectively (p

Unfortunately, the P value at multivariate analysis for ICG concentration in Table 3 was incorrectly published.