Identification of patients with ductal carcinoma in situ at high risk of postoperative upstaging: A comprehensive review and an external (un)validation of predictive models developed.

BACKGROUND: Between 8% and 56% of pure ductal carcinoma in situ are upstaged to microinvasive or invasive carcinoma on definitive pathological examination. The first objective of this study was to perform a comprehensive review of the literature on factors associated with increased risk of pre-operative underestimation. The second objective was to perform an external validation of the predictive models developed to enable their use in daily practice if relevant. MATERIALS AND METHODS: A literature search using Medline was undertaken. For each model selected, external validation within the study cohort was undertaken. The study cohort consisted of patients with histologically proven ductal carcinoma in situ who underwent surgical treatment at a French referral centre for cancer treatment between January 2007 and November 2018. RESULTS: Two hundred and thirteen articles were identified; of these, 34 articles focused on factors associated with pre-operative underestimation of invasive carcinoma, 11 studies were identified as predictive models, and three studies were selected for external validation within the study cohort. Four hundred and eighty-eight eligible patients were identified in the study cohort, with an underestimation rate of 9.2%. The Jakub nomogram concordance index was 0.45 [95% confidence interval (CI) 0.39-0.51], the Park nomogram concordance index was 0.57 (95% CI 0.48-0.55), and the Coufal nomogram concordance index was 0.52 (95% CI 0.48-0.55). CONCLUSION: While the literature is rich on this topic, this review clearly highlights the lack of consensus regarding parameters associated with underestimation. It was not possible to validate previously published models for use in daily practice.

Recurrence Pattern of Cervical Cancer Based on the Platinum Sensitivity Concept: A Multi-Institutional Study from the FRANCOGYN Group.

The standard of care for patients with advanced cervical cancer (ACC) includes platinum-based chemotherapy. The concept of platinum sensitivity is a major prognostic factor for patients with ovarian cancer. The aim of this study was to validate the applicability of the platinum sensitivity concept to ACC patients, and to estimate its prognostic interest in terms of overall survival (OS) and pattern of recurrence (location, timing). Data of women with histologically proven FIGO 2019 stages IB3-IV ACC, treated between May 2000 and November 2017 with platinum-based regimens, were retrospectively abstracted from 12 institutions from the FRANCOGYN Group. Respective 3-year OSs were 52% (95% CI: 40.8%-66.8%), 21.6% (95% CI: 12.6%-37.2%), and 14.6% (95% CI: 4.2%-50.2%), in case of recurrence <6 months, between 6 and 17 months, and ≥18 months (p < 0.001). Risk of metastatic or multisite recurrence was significantly higher in case of recurrence <6 months, and risk of local or isolated infradiaphragmatic nodal recurrence was significantly higher in case of recurrence >18 months (p < 0.001). In multivariate analysis, platinum sensitivity status was a strong prognostic factor for OS after recurrence, independent of histological grade, lympho-vascular space involvement, final lymph node status, and treatment. Platinum sensitivity status may help to classify patients in three prognostic subgroups for OS after recurrence, and appears to be a strong prognostic factor correlated to the pattern of recurrence.

Benign polypoid adenomyomatous endometrium associated with hpt-JT syndrome: a case report.

Hyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder responsible for benign and/or malignant tumors. Affected women often present life-threatening menorrhagia that leads to the identification of uterine tumors, and experience miscarriages and infertility. Overall though, fewer data concerning gynecological pathologies related to HPT-JT syndrome are available. We report the case of a 32-year-old woman with HPT-JT syndrome, referred for recurrent vaginal bleeding, with a history of repeated endometrial polyps and infertility. We also review the literature that explores medical options for these women.

Cervical cancer recurrence: Proposal for a classification based on anatomical dissemination pathways and prognosis.

INTRODUCTION: Precise definitions of recurrences and optimal treatment strategy are yet to be clearly defined among patients with cervical cancer (CC). The purpose of this study was to develop a reproducible classification of CC recurrence. MATERIEL AND METHODS: Data of women with FIGO stages I-IV CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. We proposed a rTNM classification for recurrence: locoregional (rT), nodal (rN), or distant organ (rM). According to rTNM prognosis, we then defined a rSTAGE classification (I, II, IIIA, IIIB, IVA, IVB). RESULTS: Among the 1028 women treated for FIGO stages I-IV CC during the study period, 216 recurrences were observed (21%). The 3-year survival after recurrence was 38.8%, with a median time to recurrence of 9 months (95% CI, 30.9-48.7). A trend for a lower 3-year survival after recurrence was observed in women with multiple-site vs single-site recurrence (p = 0.1). Among the women in the rT group, a difference in 3-year survival after recurrence was found between rT1 single site, rT2 single site and rT3 single site (p = 0.02). The 3-year survival after recurrence was 69.1%, 49.2%, 37.5%, 34.2%, 23.1% and 24.4% for rStage I, II, IIIA, IIIB, IVA and IVB, respectively (p = 0.007). CONCLUSION: rTNM classifications and rSTAGE are discriminatory and allow all recurrence modalities to be classified.

The Use of microRNAs in the Management of Endometrial Cancer: A Meta-Analysis.

Introduction: Endometrial cancer (EC) is the most important gynecological cancer in terms of incidence. microRNAs (miRs), which are post-transcriptional regulators implicated in a variety of cellular functions including carcinogenesis, are particularly attractive candidates as biomarkers. Indeed, several studies have shown that the miR expression pattern appears to be associated with prognostic factors in EC. Our objective is to review the current knowledge of the role of miRs in carcinogenesis and tumor progression and their association with the prognosis of endometrial cancer. Materials and Method: We performed a literature search for miR expression in EC using MEDLINE, PubMed (the Internet portal of the National Library of Medicine) and The Cochrane Library, Cochrane databases "Cochrane Reviews" and "Clinical Trials" using the following keywords: microRNA, endometrial cancer, prognosis, diagnosis, lymph node, survival, plasma, FFPE (formalin-fixed, paraffin-embedded). The miRs were classified and presented according to their expression levels in cancer tissue in relation to different prognostic factors. Results: Data were collected from 74 original articles and 8 literature reviews which described the expression levels of 261 miRs in ECs, including 133 onco-miRs, 110 miR onco-suppressors, and 18 miRs with discordant functions. The review identified 30 articles studying the expression pattern of miR in neoplastic endometrial tissue compared to benign and/or hyperplastic tissues, 12 articles detailing the expression profile of miRs as a function of lymph node status, and 14 articles that detailed the expression pattern of miRs in endometrial tumor tissue according to overall survival or in the absence of recurrence. Conclusions: The findings presented here suggest that miR analysis merits a role as a prognostic factor in the management of patients with endometrial cancer.

Patterns of recurrence and prognosis in locally advanced FIGO stage IB2 to IIB cervical cancer: Retrospective multicentre study from the FRANCOGYN group.

INTRODUCTION: Evidence-based data describing patterns of recurrence and prognosis in women with FIGO stage IB2 to IIB locally advanced cervical cancer (LACC) are scarce. The purpose of this study was to analyse patterns of recurrence in LACC and their correlation with prognosis, depending on FIGO stage, lymph node (LN) status and treatment modalities. The endpoints of this study were the type of recurrence (locoregional or distant, and time to recurrence), the recurrence free survival, the overall survival and the cumulative incidence for both locoregional and distant recurrence. MATERIALS AND METHODS: Data of women with FIGO stage IB2 to IIB CC treated between April 1996 and May 2016 were retrospectively abstracted from nine French institutions. RESULTS: The median follow-up for the 501 women included was 35.6 months. Recurrences were observed in 158 (31.5%), with a mean time to recurrence of 20.7 months. Women with IIB CC had poorer prognosis, lower 3-year RFS and higher 3-year cumulative incidence of both locoregional and distant recurrences. Women with positive or unknown LN status had poorer prognosis with higher 3-year cumulative incidence of distant recurrence. Women who underwent concomitant chemo-radiotherapy ±â€¯vaginal brachytherapy had poorer prognosis, with lower 3-year RFS and higher 3-year cumulative incidence of distant recurrence. CONCLUSIONS: Recurrence location and time to recurrence differ widely depending on the FIGO stage, LN status and treatment modalities, with potential impact on follow-up modalities and therapeutic approaches.

Comparison of pelvic and para-aortic lymphadenectomy versus para-aortic lymphadenectomy alone for locally advanced FIGO stage IB2 to IIB cervical cancer using a propensity score matching analysis: Results from the FRANCOGYN study group.

INTRODUCTION: Pre-treatment evaluation of nodal status is crucial in women presenting with locally advanced cervical cancer (LACC). However, the prognostic impact of surgical staging remains to be proved, as published results comparing surgical versus radiological staging are contradictory. The aim of this study was to compare the prognosis of women with FIGO stage IB2-IIB CC who underwent surgical nodal staging including either exclusive para-aortic lymphadenectomy (PAL) or comprehensive pelvic + para-aortic lymphadenectomy (P-PAL). MATERIALS AND METHODS: Data of 314 women with FIGO stage IB2 to IIB CC treated between January 2000 and January 2015 were retrospectively abstracted from nine French institutions. The prognosis and outcomes were compared by Propensity score (PS) matching (PSM) analysis. RESULTS: The median follow-up was 33 months (2-114). When comparing women who underwent PAL vs P-PAL, the recurrence rates were 26% (37/144) and 28% (41/144), respectively (p = 0.595). The respective 3-year recurrence free survival (RFS) for P-PAL and PAL were 72.9% (95% CI, 65.7-81.0) and 70.7% (95% CI, 62.4-80.2), (p = 0.394). The respective 3-year overall survival (OS) rates for P-PAL and PAL were 86.8% (95% CI, 81.1-92.9) and 78.6% (95% CI, 70.4-87.7) (p = 0.592). In the sub-group of women with lymph node metastases, RFS was improved for women who underwent P-PAL compared to those with exclusive PAL (p = 0.027), with no difference in OS (p = 0.187). CONCLUSIONS: Comprehensive P-PAL does not seem to be of significant therapeutic benefit compared to exclusive PAL.

Identification of micro-RNA expression profile related to recurrence in women with ESMO low-risk endometrial cancer.

BACKGROUND: Actual European pathological classification of early-stage endometrial cancer (EC) may show insufficient accuracy to precisely stratify recurrence risk, leading to potential over or under treatment. Micro-RNAs are post-transcriptional regulators involved in carcinogenic mechanisms, with some micro-RNA patterns of expression associated with EC characteristics and prognosis. We previously demonstrated that downregulation of micro-RNA-184 was associated with lymph node involvement in low-risk EC (LREC). The aim of this study was to evaluate whether micro-RNA signature in tumor tissues from LREC women can be correlated with the occurrence of recurrences. METHODS: MicroRNA expression was assessed by chip analysis and qRT-PCR in 7 formalin-fixed paraffin-embedded (FFPE) LREC primary tumors from women whose follow up showed recurrences (R+) and in 14 FFPE LREC primary tumors from women whose follow up did not show any recurrence (R-), matched for grade and age. Various statistical analyses, including enrichment analysis and a minimum p-value approach, were performed. RESULTS: The expression levels of micro-RNAs-184, -497-5p, and -196b-3p were significantly lower in R+ compared to R- women. Women with a micro-RNA-184 fold change < 0.083 were more likely to show recurrence (n = 6; 66%) compared to those with a micro-RNA-184 fold change > 0.083 (n = 1; 8%), p = 0.016. Women with a micro-RNA-196 fold change < 0.56 were more likely to show recurrence (n = 5; 100%) compared to those with a micro-RNA-196 fold change > 0.56 (n = 2; 13%), p = 0.001. CONCLUSIONS: These findings confirm the great interest of micro-RNA-184 as a prognostic tool to improve the management of LREC women.

Atypical Distant Metastasis of Breast Malignant Phyllodes Tumors: A Case Report and Literature Review.

Malignant phyllodes tumors (MPT) are rare breast neoplasms. Preoperative diagnosis is often challenging due to the unspecific clinical, radiological, and histological characteristics of the tumor. Dissemination pathways are local with chest wall invasion, regional with lymph nodes metastasis, and distant, hematogenous, mostly to the lungs, bones, and brain. Distant metastasis (DM) can be synchronous or appear months to years after the diagnosis and initial management. The current report describes the case of a 57-year-old woman presenting with a giant/neglected MPT of the breast, with no DM at initial staging, treated by radical modified mastectomy. Motor disorders due to medullar compression by a paravertebral mass appeared at short follow-up, also treated surgically. The patient died from several DM of rapid evolution. To our knowledge, this is the only case described of MPT with metastases to soft tissue causing medullar compression. We present a literature review on unusual metastatic localizations of MPT.