Surgery after upfront chemoradiation in locally advanced squamous cell vulvar cancer: Analysis of postoperative outcomes and survival.

OBJECTIVE: The aim of the study was to assess the survival rates and surgery-related toxicity in patients with locally advanced squamous cell vulvar cancer (LAVC) managed by upfront chemoradiation (CRT) with/without following by surgery. CRT is the primary treatment for patients with unresectable locally advanced squamous cell vulvar carcinoma (LAVC), followed by surgery in case of residual tumor. METHODS: Patients with AJCC stage II-IV squamous cell vulvar carcinoma referred to Gynecologic Oncology Unit at Fondazione Policlinico Universitario Agostino Gemelli I.R.C.C.S. from January 2016 to February 2023, managed by upfront CRT, were included. RESULTS: 63 patients were included, 21 (33 %) had complete response (cCR) to CRT, 26 (41 %) had partial response (cPR), 1 (2 %) stable disease (cSD), 15 (24 %) had disease progression (cPD). In the whole population, cPR/SD and cPD were associated with reduced PFS (p < 0.001) and overall survival (OS) (p < 0.001), p16 expression was associated with improved PFS (p < 0.001) and OS (p = 0.001). Among patients with clinical residual disease after CRT, 23 patients undergoing surgery experienced improved PFS (p = 0.003) and OS (p = 0.003) compared to those receiving other treatments. Eight (35 %) patients experienced severe (grade ≥ III) postoperative complications; vulvar and groin wound dehiscence/infection were the most common complications; one (4 %) patient died in the postoperative. Patients with pathological residual disease experienced worse PFS (p = 0.013) and OS (p = 0.034). CONCLUSIONS: Clinical response to CRT and p16 expression strongly predict survival in LAVC. Surgery for residual disease might be associated with improved survival but is burdened by high rates of complications. Pathologic residual disease correlates with high recurrence rates and poor survival.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

The standard surgical treatment of endometrial carcinoma, consisting of total hysterectomy with bilateral salpingo-oophorectomy, drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) provide comprehensive information on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment.A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment (patient selection, tumor clinicopathological characteristics, treatment, special issues) in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts from across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified by a systematic search, was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives.

Human papillomavirus independent status on pathologic response and outcomes in locally advanced cervical cancer managed with chemoradiotherapy followed by surgery.

OBJECTIVE: While human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent). METHODS: In this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival. RESULTS: Of 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (p<0.001). In the HPV associated cervical cancer group, 5 year disease free survival was found to be 80.8% versus 59.9% in the HPV independent group (p=0.014). Overall survival was also higher in the HPV associated group (87.9%) compared with the HPV independent patients (69.4%) (p=0.023). In the multivariate analysis, the International Federation of Gynecology and Obstetrics (FIGO) stage and HPV genotypes maintained their relevant impact on pathologic complete response to chemoradiotherapy: FIGO stages IIIC1 and IIIC2 were associated with a 13-fold increased risk for the presence of metastatic lymph nodes compared with group 1 (p<0.001). HPV independent cervical cancers showed the highest risk for the development of macroscopic/stable disease (p=0.007), and persistence of metastatic lymph nodes (p=0.004) versus group 1, respectively. CONCLUSIONS: This study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Endometrial carcinosarcoma.

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma.

Deep-Learning to Predict BRCA Mutation and Survival from Digital H&E Slides of Epithelial Ovarian Cancer.

BRCA 1/2 genes mutation status can already determine the therapeutic algorithm of high grade serous ovarian cancer patients. Nevertheless, its assessment is not sufficient to identify all patients with genomic instability, since BRCA 1/2 mutations are only the most well-known mechanisms of homologous recombination deficiency (HR-d) pathway, and patients displaying HR-d behave similarly to BRCA mutated patients. HRd assessment can be challenging and is progressively overcoming BRCA testing not only for prognostic information but more importantly for drugs prescriptions. However, HR testing is not already integrated in clinical practice, it is quite expensive and it is not refundable in many countries. Selecting patients who are more likely to benefit from this assessment (BRCA 1/2 WT patients) at an early stage of the diagnostic process, would allow an optimization of genomic profiling resources. In this study, we sought to explore whether somatic BRCA1/2 genes status can be predicted using computational pathology from standard hematoxylin and eosin histology. In detail, we adopted a publicly available, deep-learning-based weakly supervised method that uses attention-based learning to automatically identify sub regions of high diagnostic value to accurately classify the whole slide (CLAM). The same model was also tested for progression free survival (PFS) prediction. The model was tested on a cohort of 664 (training set: n = 464, testing set: n = 132) ovarian cancer patients, of whom 233 (35.1%) had a somatic BRCA 1/2 mutation. An area under the curve of 0.7 and 0.55 was achieved in the training and testing set respectively. The model was then further refined by manually identifying areas of interest in half of the cases. 198 images were used for training (126/72) and 87 images for validation (55/32). The model reached a zero classification error on the training set, but the performance was 0.59 in terms of validation ROC AUC, with a 0.57 validation accuracy. Finally, when applied to predict PFS, the model achieved an AUC of 0.71, with a negative predictive value of 0.69, and a positive predictive value of 0.75. Based on these analyses, we have planned further steps of development such as proving a reference classification performance, exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting this specific task. These actions may allow the model to improve performances for all the considered outcomes.

The role of 18F-FDG-PET/CT in predicting the histopathological response in locally advanced cervical carcinoma treated by chemo-radiotherapy followed by radical surgery: a prospective study.

PURPOSE: This prospective study aimed to evaluate whether 18F-FDG-PET/CT performed before, during and after neoadjuvant chemo-radiotherapy (CRT) could predict histopathological response in patients with locally advanced cervical cancer (LACC) treated with CRT followed by radical surgery. METHODS: Between October 2010 and June 2014, 88 patients with LACC were enrolled. For each patient, three 18F-FDG-PET/CT scans (baseline, early and final) were acquired and evaluated by qualitative and quantitative analysis. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured as absolute values and their percentage variation (delta) (early vs. baseline and final vs. baseline). The role of 18F-FDG-PET/CT in predicting lymph node (LN) residual disease was evaluated by qualitative analysis only. Histopathology was the reference standard. RESULTS: At histopathology, 40 patients had complete response (CR, pR0), 48 had partial response (PR: 21 microscopic [pR1] and 27 macroscopic [pR2]). At baseline, SUVmax and SUVmean were significantly higher in pR0 than in pR1-pR2 patients. At early evaluation, MTV and TLG were significantly higher in pR1-pR2 than in pR0 patients. At final evaluation, SUVmax, SUVmean and TLG were significantly higher in pR1-pR2 than in pR0 patients. Delta SUV parameters and delta TLG were significantly lower in PR group both during and after CRT. Delta MTV was significantly lower in patients with PR in the early phase only. In receiver operating characteristic (ROC) curve analysis, baseline SUVmean, early delta TLG, and final delta SUVmax better discriminated PR, providing 83.3%, 67.6% and 85% positive predictive value (PPV) and 60.3%, 90% and 70.8% negative predictive value (NPV), respectively. For LN assessment, high NPV was observed at early and final 18F-FDG-PET/CT (93.5% and 92.3%, respectively). CONCLUSION: In LACC patients treated with CRT followed by surgery, early variations in metabolic parameters effectively discriminate histopathological PR of the primary tumor, suggesting the potential role of 18F-FDG-PET/CT in early personalized treatment. The high NPV of early and final PET/CT could enable "tailored surgery" by avoiding lymphadenectomy in selected patients.

Endometriosis-associated clear cell carcinoma arising in caesarean section scar: a case report and review of the literature.

BACKGROUND: Malignant transformation has been reported in approximately 1% of the endometriosis cases; herein, we report a case of clear cell endometrial carcinoma arising from endometriosis foci located within a caesarean section scar. CASE PRESENTATION: In November 2014, a Caucasian, 44-year-old woman was transferred to our institution because of severe respiratory failure due to massive lung embolism and rapid enlargement of a subcutaneous suprapubic mass. Abdomino-pelvic magnetic resonance showed a 10.5 × 5.0 × 5.0 cm subcutaneous solid mass involving the rectus abdominis muscle. Pelvic organs appeared normal, while right external iliac lymph nodes appeared enlarged (maximum diameter = 16 mm). A whole-body positron emission tomography/computed tomography scan showed irregular uptake of the radiotracer in the 22 cm mass of the abdominal wall, and in enlarged external iliac and inguinal lymph nodes. In December 2014, the patient underwent exploratory laparoscopy showing normal adnexae and pelvic organs; peritoneal as well as cervical, endometrial and vesical biopsies were negative. The patient was administered neo-adjuvant chemotherapy with carboplatin and paclitaxel, weekly, without benefit and then underwent wide resection of the abdominal mass, partial removal of rectus abdominis muscle and fascia, radical hysterectomy, bilateral salpingo-oophorectomy, and inguinal and pelvic lymphadenectomy. The muscular gap was repaired employing a gore-tex mesh while the external covering was made by a pedicled perforator fasciocutaneous anterolateral thigh flap. Final diagnosis was clear cell endometrial adenocarcinoma arising from endometriosis foci within the caesarean section scar. Pelvic and inguinal lymph nodes were metastatic. Tumor cells were positive for CK7 EMA, CKAE1/AE3, CD15, CA-125, while immunoreaction for Calretinin, WT1, estrogen, and progesterone receptors, cytokeratin 20, CD10, alpha fetoprotein, CDX2, TTF1, and thyroglobulin were all negative. Liver relapse occurred after 2 months; despite 3 cycles of pegylated liposomal doxorubicin (20 mg/m2, biweekly administration), the death of the patient disease occurred 1 month later. CONCLUSIONS: Attention should be focused on careful evaluation of patient history in terms of pelvic surgery, and symptoms suggestive of endometriosis such as repeated occurrence of endometriosis nodules at CS scar, or cyclic pain, or volume changes of the nodules.

Neuroendocrine neoplasms of the breast: a review of literature.

Primary neuroendocrine neoplasms (NENs) of the breast are characterized by neuroendocrine architectural and cytological features, which must be supported by immunohistochemical positivity for neuroendocrine markers (such as Chromogranin and Synaptophysin). According to the literature, making a diagnosis of primary neuroendocrine breast cancer always needs to rule out a possible primary neuroendocrine neoplasm from another site. Currently, the latest 2022 version of the WHO of endocrine and neuroendocrine neoplasms has classified breast NENs as well-differentiated neuroendocrine tumours (NETs) and aggressive neuroendocrine carcinomas (NECs), differentiating them from invasive breast cancers of no special type (IBCs-NST). with neuroendocrine features. The current review article describes six cases from our series and a comprehensive review of the literature in the field of NENs of the breast.

ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma.

STUDY QUESTION: How should fertility-sparing treatment of patients with endometrial carcinoma be performed? SUMMARY ANSWER: Forty-eight recommendations were formulated on fertility-sparing treatment of patients with endometrial carcinoma. WHAT IS KNOWN ALREADY: The standard surgical treatment of endometrial carcinoma consisting of total hysterectomy with bilateral salpingo-oophorectomy drastically affects the quality of life of patients and creates a challenge for clinicians. Recent evidence-based guidelines of the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) provide comprehensive guidelines on all relevant issues of diagnosis and treatment in endometrial carcinoma in a multidisciplinary setting. While addressing also work-up for fertility preservation treatments and the management and follow-up for fertility preservation, it was considered relevant to further extend the guidance on fertility-sparing treatment. STUDY DESIGN SIZE DURATION: A collaboration was set up between the ESGO, the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynaecological Endoscopy (ESGE), aiming to develop clinically relevant and evidence-based guidelines focusing on key aspects of fertility-sparing treatment in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. PARTICIPANTS/MATERIALS SETTING METHODS: ESGO/ESHRE/ESGE nominated an international multidisciplinary development group consisting of practising clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (11 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2016, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgement was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 95 independent international practitioners in cancer care delivery and patient representatives. MAIN RESULTS AND THE ROLE OF CHANCE: The multidisciplinary development group formulated 48 recommendations in four sections; patient selection, tumour clinicopathological characteristics, treatment and special issues. LIMITATIONS REASONS FOR CAUTION: Of the 48 recommendations, none could be based on level I evidence and only 16 could be based on level II evidence, implicating that 66% of the recommendations are supported only by observational data, professional experience and consensus of the development group. WIDER IMPLICATIONS OF THE FINDINGS: These recommendations provide guidance to professionals caring for women with endometrial carcinoma, including but not limited to professionals in the field of gynaecological oncology, onco-fertility, reproductive surgery, endoscopy, conservative surgery and histopathology, and will help towards a holistic and multidisciplinary approach for this challenging clinical scenario. STUDY FUNDING/COMPETING INTERESTS: All costs relating to the development process were covered from ESGO, ESHRE and ESGE funds. There was no external funding of the development process or manuscript production. G.S. has reported grants from MSD Italia S.r.l., advisory boards for Storz, Bayer, Astrazeneca, Metronic, TESARO Bio Italy S.r.l and Johnson & Johnson, and honoraria for lectures from Clovis Oncology Italy S.r.l. M.G. has reported advisory boards for Gedeon Richter and Merck. The other authors have reported no conflicts of interest. DISCLAIMER: This document represents the views of ESHRE, ESGO and ESGE which are the result of consensus between the relevant stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type.

Isolated humeral metastasis in cervical cancer: A case report and review of the literature.

There are a few reported cases of isolated localized metastasis to bone arising from cancer of uterine cervix in the literature. This is a case of uterine cervix cancer with isolated metastasis to the humerus. A 57-year-old female with a diagnosis of FIGO Stage IIB invasive squamous cell carcinoma of uterine cervix underwent neoadjuvant chemoradiation therapy (CRT) and radical surgery with complete pathological response. Nine months after the surgery, a total body positron emission tomography/computed tomography (PET/CT) scan documented a lesion localized in the proximal part of the right humerus, whereas no evidence of skeletal metastasis found elsewhere. The biopsy from the bone lesion showed a metastatic squamous cell carcinoma of the uterine cervix. A surgical excision of the humeral lesion plus chemotherapy and zoledronic acid was performed. After 9 months, the patient experienced liver metastases and died 2 months later. Bone metastasis is not so infrequent in patients with locally advanced cervical cancer. Total body PET/CT scan should be included in staging work up, and an appropriate treatment should have the primary objective of quality of life preservation.

Infiltrating T lymphocytes and programmed cell death protein-1/programmed death-ligand 1 expression in endometriosis-associated ovarian cancer.

OBJECTIVE: To characterize T lymphocyte infiltration and programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) expression in early-stage endometriosis-associated ovarian cancer (EAOC), ovarian endometriosis (OE), atypical endometriosis (AE), and deep endometriosis (DE). DESIGN: Case-control, retrospective study. SETTING: Research University Hospital. PATIENT(S): A total of 362 patients with a histologic diagnosis of EAOC, OE, AE, or DE were identified between 2000 and 2019 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Gemelli Molise SpA tissue data banks. A 1:1 propensity score-matched method yielded matched pairs of 55 subjects with EAOC, 55 patients with OE, 12 patients with AE, and 42 patients with DE, resulting in no differences in family history of cancer, parity, and use of oral contraceptives. INTERVENTION(S): Immunohistochemistry assays using the following primary antibodies: CD3+; CD4+; CD8+; PD-1; and PD-L1. MAIN OUTCOME MEASURE(S): To characterize T lymphocyte infiltration and PD-1/PD-L1 expression in 4 different endometriosis-related diseases. RESULT(S): Endometriosis-associated ovarian cancer cases displayed significantly higher levels of PD-1/PD-L1 expression compared with all other endometriosis-related diseases (vs. OE vs. AE vs. DE). Moreover, a significantly lower count of infiltrating T lymphocytes was observed in EAOC cases compared with OE ones. Finally, one-third of OE cases showed a cancer-like PD-1/PD-L1 expression profile. CONCLUSION(S): Endometriosis-associated ovarian cancer is characterized by higher levels of PD-1/PD-L1 expression compared with benign endometriosis-related diseases. This profile was found in one-third of clinically benign cases, suggesting that it develops early in the carcinogenesis process.

Uterine tumor resembling ovarian sex-cord tumor: Conservative surgery with successful delivery and case series.

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare distinct cancer included in the current World Health Organization classification of endometrial stromal tumors. A battery of immunohistochemical markers are necessary for accurate diagnosis. Although few case reports and case series have been documented and therefore providing robust prognostic information several authors agree to consider UTROSCT as a low malignant potential tumour. In literature only five cases of conservative management were reported. We reported our experience and a review of conservative cases of literature. In this article we describe a series of 10 cases of UTROSCT and their clinical and pathologic feature. We report two cases of conservative surgical approach obtaining a successfully pregnancies. All of the patients are still alive. In conclusion, fertility sparing surgery should be offered to patients who wish preserve their fertility however radical surgery must be considerate after childbirth. Close follow-up is required for all patients due to the lack of prognostic biomarkers and long follow up is needed to evaluate safety of conservative surgery.

Multicentre Evaluation of Hepika Test Clinical Accuracy in Diagnosing HPV-Induced Cancer and Precancerous Lesions of the Uterine Cervix.

OBJECTIVE: To evaluate the clinical accuracy of Hepika test to identify cancer/precancerous lesions of the uterine cervix. MATERIALS AND METHODS: A multicentre retrospective study was carried out in 2018 and included 330 liquid-based cytology samples from three Italian centres of women aged 25-64 who had been tested for the human papillomavirus (HPV) and whose histology or follow-up outcome was known. Hepika is an enzyme-linked immunosorbent assay (ELISA) targeting the protein complexes E6#p53 and E7#pRb. After excluding samples without sufficient residual material, the clinical accuracy of Hepika test was evaluated in 274 samples: adenocarcinoma (ADC) (4), squamous cell carcinoma (SCC) (7), adenocarcinoma in situ (AIS) (1), cervical intraepithelial neoplasia (CIN) grade 3 (60), CIN2 (51), CIN1 (34), and negative histology (117). Association, sensitivity, and specificity for carcinoma, CIN3+ and CIN2+ are reported. RESULTS: Positive Hepika test was associated with a high probability of carcinoma (odds ratio (DOR) = 33.68, 95% confidence interval (CI) 7.0-163.1); sensitivity was 81.8%, specificity, 88.2%. A positive Hepika test showed a weaker association with CIN3+ lesions (DOR = 3.5; 95% CI 1.75-6.99) and lower sensitivity (27.8%). CONCLUSION: The Hepika test was found to be an accurate biomarker for HPV-induced cervical carcinoma. Population-based prospective studies are needed to confirm the clinical usefulness of the Hepika test in the differential diagnosis of HPV-induced invasive lesions.

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

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

Femur metastasis in carcinoma of the uterine cervix: a rare entity.

PURPOSE: We report the first case of isolated femur metastasis in a locally advanced cervical cancer (LACC) patients. CASE: A 40-year-old woman presenting with carcinoma of the uterine cervix, FIGO stage IIb was administered concomitant chemo-radiation and achieved clinical partial response. Before the planned surgery, she developed an isolated metastatic lytic lesion of the left femur. After surgical excision of metastasis, she refused palliative chemotherapy, and radiotherapy, and died 3 months later because of progression of the disease. CONCLUSION: Bone metastasis is not so infrequent in patients with LACC. Because the prognosis of these patients is poor and most of them die within 1 year after the diagnosis of metastatic disease, the policy of treatment should be directed to maintain their quality of life.

Impact of COVID-19 in gynecologic oncology: a Nationwide Italian Survey of the SIGO and MITO groups.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. METHODS: The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. RESULTS: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. CONCLUSIONS: National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.