Exploring the interplay between Kaposi's sarcoma and SARS-CoV-2 infection: A case series and systematic review.

Kaposi's sarcoma (KS) is an angio-proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS-CoV-2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non-latent viral infections. We report a case series of KS characterized by tumor progression after SARS-CoV-2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS-CoV-2," "HHV-8," "Kaposi's sarcoma," "IL-6," and "COVID-19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID-19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS-CoV-2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS-CoV-2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.

COVID-19 in patients with thymic epithelial tumors with or without Good's syndrome: a single-center retrospective study.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. METHODS: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. RESULTS: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. CONCLUSIONS: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols.

Intermediate clinical endpoints in early-stage breast cancer: an analysis of individual patient data from the Gruppo Italiano Mammella and Mammella Intergruppo trials.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials. Methods: Individual patient level data from adjuvant phase III RCTs conducted by the Gruppo Italiano Mammella (GIM) and Mammella Intergruppo (MIG) study groups were used. ICEs were computed according to STEEP criteria. Using a two-stage meta-analytic model, we assessed the surrogacy of each ICE at both the outcome (i.e., OS and ICE are correlated irrespective of treatment) and trial (i.e., treatment effects on ICE and treatment effect on OS are correlated) levels. The following ICEs were considered as potential surrogate endpoints of OS: disease-free survival (DFS), distant disease-free survival (DDFS), distant relapse-free survival (DRFS), recurrence-free survival (RFS), recurrence-free interval (RFI), distant recurrence-free interval (DRFI), breast cancer-free interval (BCFI), and invasive breast cancer-free survival (IBCFS). The estimates of the degree of correlation were obtained by copula models and weighted linear regression. Kendall's τ and R2 ≥ 0.70 were considered as indicators of a clinically relevant surrogacy. Findings: Among the 12,397 patients enrolled from November 1992 to July 2012 in six RCTs, median age at enrolment was 57 years (interquartile range (IQR) 49-65). After a median follow-up of 10.3 years (IQR 6.4-14.5), 2131 (17.2%) OS events were observed, with 1390 (65.2%) attributed to breast cancer. At the outcome-level, Kendall's τ ranged from 0.69 for BCFI to 0.84 for DRFS. For DFS, DDFS, DRFS, RFS, RFI, DRFI, BCFI, and IBCFS endpoints, over 95% of the 8-year OS variability was attributable to the variation of the 5-year ICE. At the trial-level, treatment effects for the different ICEs and OS were strongly correlated, with the highest correlation for RFS and DRFS and the lowest for BCFI. Interpretation: Our results provide evidence supporting the use of DFS, DDFS, DRFS, RFS, RFI, DRFI, and IBCFS as primary endpoint in breast cancer adjuvant trials. Funding: This analysis was supported by the Italian Association for Cancer Research ("Associazione Italiana per la Ricerca sul Cancro", AIRC; IG 2017/20760) and by Italian Ministry of Health-5 × 1000 funds (years 2021-2022).

Machine Learning and Texture Analysis of [18F]FDG PET/CT Images for the Prediction of Distant Metastases in Non-Small-Cell Lung Cancer Patients.

The aim of our study was to predict the occurrence of distant metastases in non-small-cell lung cancer (NSCLC) patients using machine learning methods and texture analysis of 18F-labeled 2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography {[18F]FDG PET/CT} images. In this retrospective and single-center study, we evaluated 79 patients with advanced NSCLC who had undergone [18F]FDG PET/CT scan at diagnosis before any therapy. Patients were divided into two independent training (n = 44) and final testing (n = 35) cohorts. Texture features of primary tumors and lymph node metastases were extracted from [18F]FDG PET/CT images using the LIFEx program. Six machine learning methods were applied to the training dataset using the entire panel of features. Dedicated selection methods were used to generate different combinations of five features. The performance of selected machine learning methods applied to the different combinations of features was determined using accuracy, the confusion matrix, receiver operating characteristic (ROC) curves, and area under the curve (AUC). A total of 104 and 78 lesions were analyzed in the training and final testing cohorts, respectively. The support vector machine (SVM) and decision tree methods showed the highest accuracy in the training cohort. Seven combinations of five features were obtained and introduced in the models and subsequently applied to the training and final testing cohorts using the SVM and decision tree. The accuracy and the AUC of the decision tree method were higher than those obtained with the SVM in the final testing cohort. The best combination of features included shape sphericity, gray level run length matrix_run length non-uniformity (GLRLM_RLNU), Total Lesion Glycolysis (TLG), Metabolic Tumor Volume (MTV), and shape compacity. The combination of these features with the decision tree method could predict the occurrence of distant metastases with an accuracy of 74.4% and an AUC of 0.63 in NSCLC patients.

Corrigendum: Aromatase inhibitors: the journey from the state of the art to clinical open questions.

[This corrects the article DOI: 10.3389/fonc.2023.1249160.].

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial.

No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

Coefficient of Variation in Metastatic Lymph Nodes Determined by 18F-FDG PET/CT in Patients with Advanced NSCLC: Combination with Coefficient of Variation in Primary Tumors.

Purpose The aim of the present study was to test whether the coefficient of variation (CoV) of 18F-FDG PET/CT images of metastatic lymph nodes and primary tumors may predict clinical outcome in patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods Fifty-eight NSCLC patients who had undergone 18F-FDG PET/CT at diagnosis were evaluated. SUVmax, SUVmean, CoV, MTV and TLG were determined in targeted lymph nodes and corresponding primary tumors along with Total MTV (MTVTOT) and Whole-Body TLG (TLGWB) of all malignant lesions. Univariate analysis was performed using Cox proportional hazards regression whereas the Kaplan-Meier method and log-rank tests were used for survival analysis. Results Fifty-eight metastatic lymph nodes were analyzed and average values of SUVmax, SUVmean, CoV, MTV and TLG were 11.89 ± 8.54, 4.85 ± 1.90, 0.37 ± 0.16, 46.16 ± 99.59 mL and 256.84 ± 548.27 g, respectively, whereas in primary tumors they were 11.92 ± 6.21, 5.47 ± 2.34, 0.36 ± 0.14, 48.03 ± 64.45 mL and 285.21 ± 397.95 g, respectively. At univariate analysis, overall survival (OS) was predicted by SUVmax (p = 0.0363), SUVmean (p = 0.0200) and CoV (p = 0.0139) of targeted lymph nodes as well as by CoV of primary tumors (p = 0.0173), MTVTOT (p = 0.0007), TLGWB (p = 0.0129) and stage (p = 0.0122). Using Kaplan-Meier analysis, OS was significantly better in patients with CoV of targeted lymph nodes ≤ 0.29 than those with CoV > 0.29 (p = 0.0147), meanwhile patients with CoV of primary tumors > 0.38 had a better prognosis compared to those with CoV ≤ 0.38 (p = 0.0137). Finally, we combined the CoV values of targeted lymph nodes and primary tumors in all possible arrangements and a statistically significant difference was found among the four survival curves (p = 0.0133). In particular, patients with CoV of targeted lymph nodes ≤ 0.29 and CoV of primary tumors > 0.38 had the best prognosis. Conclusions The CoV of targeted lymph nodes combined with the CoV of primary tumors can predict prognosis of NSCLC patients.

SNP of Aromatase Predict Long-term Survival and Aromatase Inhibitor Toxicity in Patients with Early Breast Cancer: A Biomarker Analysis of the GIM4 and GIM5 Trials.

PURPOSE: In estrogen receptor-positive (ER+) breast cancer, single-nucleotide polymorphisms (SNP) in the aromatase gene might affect aromatase inhibitors (AI) metabolism and efficacy. Here, we assessed the impact of SNP on prognosis and toxicity of patients receiving adjuvant letrozole. EXPERIMENTAL DESIGN: We enrolled 886 postmenopausal patients in the study. They were treated with letrozole for 2 to 5 years after taking tamoxifen for 2 to 6 years, continuing until they completed 5 to 10 years of therapy. Germline DNA was genotyped for SNP rs4646, rs10046, rs749292, and rs727479. Log-rank test and Cox model were used for disease-free survival (DFS) and overall survival (OS). Cumulative incidence (CI) of breast cancer metastasis was assessed through competing risk analysis, with contralateral breast cancer, second malignancies and non-breast cancer death as competing events. CI of skeletal and cardiovascular events were assessed using DFS events as competing events. Subdistribution HR (sHR) with 95% confidence intervals were calculated through Fine-Gray method. RESULTS: No SNP was associated with DFS. Variants rs10046 [sHR 2.03, (1.04-2.94)], rs749292 [sHR 2.11, (1.12-3.94)], and rs727479 [sHR 2.62, (1.17-5.83)] were associated with breast cancer metastasis. Three groups were identified on the basis of the number of these variants (0, 1, >1). Variant-based groups were associated with breast cancer metastasis (10-year CI 2.5%, 7.6%, 10.7%, P = 0.035) and OS (10-year estimates 96.5%, 93.0%, 89.6%, P = 0.030). Co-occurrence of rs10046 and rs749292 was negatively associated with 10-year CI of skeletal events (3.2% vs. 10%, P = 0.033). A similar association emerged between rs727479 and cardiovascular events (0.3% vs. 2.1%, P = 0.026). CONCLUSIONS: SNP of aromatase gene predict risk of metastasis and AI-related toxicity in ER+ early breast cancer, opening an opportunity for better treatment individualization.

Tucatinib's journey from clinical development to clinical practice: New horizons for HER2-positive metastatic disease and promising prospects for brain metastatic spread.

Approximately 20% of breast cancers (BCs) overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein with tyrosine kinase activity, encoded by ERBB2 gene. Historically, HER2 overexpression has been linked with increased disease recurrence and a worse prognosis. However, the increasing availability of different anti-HER2 compounds and combinations is progressively improving HER2-positive BC outcome, thus requiring expertise to prioritize both overall survival (OS) prolongation and quality of life, without neglecting the accessibility to further treatment lines with a low attrition rate. In this context, tucatinib, an oral tyrosine kinase inhibitor, has recently been granted approval by regulatory agencies based on evidence from the HER2CLIMB, a clinical trial which randomized patients with metastatic BC to receive trastuzumab and capecitabine with either tucatinib or placebo. A distinctive feature of this study was the inclusion of patients with new or active brain metastases (BMs) at study entry, a population traditionally excluded from clinical trials. Thus, HER2CLIMB provides the first solid evidence of an OS benefit in patients with BC and BMs, addressing a long standing unmet medical need, especially given the high incidence of central nervous system metastatic spread in patients with HER2-positive disease. This review provides an overview of the molecular and clinical landscape of tucatinib for the treatment of advanced BC. It focuses on the technological journey that drove the development of this therapeutic innovation, from preclinical data to clinical practice.

Heterogeneity of Glycolytic Phenotype Determined by 18F-FDG PET/CT Using Coefficient of Variation in Patients with Advanced Non-Small Cell Lung Cancer.

We investigated the role of Coefficient of Variation (CoV), a first-order texture parameter derived from 18F-FDG PET/CT, in the prognosis of Non-Small Cell Lung Cancer (NSCLC) patients. Eighty-four patients with advanced NSCLC who underwent 18F-FDG PET/CT before therapy were retrospectively studied. SUVmax, SUVmean, CoV, total Metabolic Tumor Volume (MTVTOT) and whole-body Total Lesion Glycolysis (TLGWB) were determined by an automated contouring program (SUV threshold at 2.5). We analyzed 194 lesions: primary tumors (n = 84), regional (n = 48) and non-regional (n = 17) lymph nodes and metastases in liver (n = 9), bone (n = 23) and other sites (n = 13); average CoVs were 0.36 ± 0.13, 0.36 ± 0.14, 0.42 ± 0.18, 0.30 ± 0.14, 0.37 ± 0.17, 0.34 ± 0.13, respectively. No significant differences were found between the CoV values among the different lesion categories. Survival analysis included age, gender, histology, stage, MTVTOT, TLGWB and imaging parameters derived from primary tumors. At univariate analysis, CoV (p = 0.0184), MTVTOT (p = 0.0050), TLGWB (p = 0.0108) and stage (p = 0.0041) predicted Overall Survival (OS). At multivariate analysis, age, CoV, MTVTOT and stage were retained in the model (p = 0.0001). Patients with CoV > 0.38 had significantly better OS than those with CoV ≤ 0.38 (p = 0.0143). Patients with MTVTOT ≤ 89.5 mL had higher OS than those with MTVTOT > 89.5 mL (p = 0.0063). Combining CoV and MTVTOT, patients with CoV ≤ 0.38 and MTVTOT > 89.5 mL had the worst prognosis. CoV, by reflecting the heterogeneity of glycolytic phenotype, can predict clinical outcomes in NSCLC patients.

Impaired Seroconversion After Severe Acute Respiratory Syndrome Coronavirus 2 mRNA Vaccine in Patients With Thymic Epithelial Tumors.

INTRODUCTION: Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system and humoral- and cell-mediated immunity abnormalities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine is effective in preventing coronavirus disease 2019 morbidity and mortality. The aim of this study was to evaluate the seroconversion in patients with TET after two doses of mRNA vaccine. METHODS: This is a prospective study in which consecutive patients with TET were enrolled before receiving the first dose of SARS-CoV-2 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding immunoglobulin (Ig)G antibody serologic levels were analyzed at different time points, including before first vaccine dose (T0), 1 month after the second dose (T2), and 3 months after the second dose (T3). RESULTS: Overall, 39 patients were included in the analysis. All patients had negative antibody titer results at T0. There were 19 patients (48.7%) in the follow-up with no residual tumor lesion/s (referred as no evidence of disease), and 20 (51.3%) had evidence of disease (ED) and were receiving systemic treatment. Dysregulations of the immune system were diagnosed in 29 patients (74.4%) with Good syndrome (GS) being the most frequent immune disorder (48.7%). At univariate analysis, lack of seroconversion at T2 was significantly associated with ED (p < 0.001) and with GS (p = 0.043). A significant association with impaired seroconversion was confirmed at multivariate analysis for ED (p = 0.00101) but not for GS (p = 0.625). CONCLUSIONS: Our data revealed that patients with TET with ED had substantially higher probability of impaired seroconversion after SARS-CoV-2 mRNA vaccine as compared with patients with no evidence of disease.

Prognostic and clinical impact of the endocrine resistance/sensitivity classification according to international consensus guidelines for advanced breast cancer: an individual patient-level analysis from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) studies.

Background: Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary (1ER)/secondary (2ER) resistant. However, this classification is largely based on expert opinion and no proper evidence exists to date to support its possible prognostic and clinical impact. Methods: This analysis included individual patient-level data from 4 adjuvant phase III randomized trials by the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. The impact of endocrine resistance/sensitivity classification on overall survival (mOS, defined as time between date of distant relapse and death) was assessed in both univariate and multivariate Cox proportional hazards models. Findings: Between November 1992 and July 2012, 9058 patients were randomized in 4 trials, of whom 6612 had HR+/HER2- BC. Median follow-up was 9.1 years (interquartile range [IQR] 5.6-15.0). In the whole cohort, disease-free survival and OS were 90.4% and 96.6% at 5 years, and 79.1% and 89.4% at 10 years, respectively. The estimated hazard of recurrence raised constantly during the first 15 years from diagnosis, being more pronounced during the first 2 years and less pronounced after year 7. Among the 493 patients with a distant relapse as first disease-free survival event and available date on ET completion, 72 (14.6%), 207 (42.0%) and 214 (43.4%) were classified as having 1ER, 2ER and ES, respectively. Median follow-up from diagnosis of a distant relapse was 3.8 years (IQR 1.6-7.5). Patients with 1ER were significantly more likely to be younger, to have N2/N3 nodal status, grade 3 tumours and to develop visceral metastases. Site of first distant relapse was significantly different between the 3 groups (p = 0.005). In patients with 1ER, 2ER and ES breast cancer, median mOS was 27.2, 38.4 and 43.2 months, respectively (p = 0.03). As compared to patients with ES disease, a higher risk of death was observed in those with 1 ER (adjusted Hazard Ratio [aHR] 1.54; 95% CI 1.03-2.30) and 2ER (aHR 1.17; 95% CI 0.87-1.56) (p = 0.11). Interpretation: This large analysis with long-term follow-up provides evidence on the prognostic and clinical impact of the currently adopted endocrine resistance/sensitivity classification in patients with HR+/HER2- advanced BC. This classification may be considered a valid tool to guide clinical decision-making and to design future ET trials in the metastatic setting. Funding: AIRC.

Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.

Sarcomas of the thoracic cavity are rare entities that predominantly affect children and young adults. They can be very heterogeneous encompassing several different histological entities. Ewing Sarcoma (ES) can potentially arise from every bone, soft tissue, or visceral site in the body. However, it represents an extremely rare finding when it affects the thoracic cavity. It represents the second most frequent type of thoracic sarcoma, after chondrosarcoma. ES arises more frequently in sites that differ from the thoracic cavity, but it displays the same biological features and behavior of extra-thoracic ones. Current management of ES often requires a multidisciplinary treatment approach including surgery, radiotherapy, and systemic therapy, as it can guarantee local and distant disease control, at least transiently, although the long-term outcome remains poor. Unfortunately, due to the paucity of clinical trials purposely designed for this rare malignancy, there are no optimal strategies that can be used for disease recurrence. As a result of its complex biological features, ES might be suitable for emerging biology-based therapeutic strategies. However, a deeper understanding of the molecular mechanisms driving tumor growth and treatment resistance, including those related to oncogenic pathways, epigenetic landscape, and immune microenvironment, is necessary in order to develop new valid therapeutic opportunities. Here, we provide an overview of the most recent therapeutic advances for ES in both the preclinical and clinical settings. We performed a review of the current available literature and of the ongoing clinical trials focusing on new treatment strategies, after failure of conventional multimodal treatments.

Prognostic Value of Body Mass Index in Stage II/III Colon Cancer: Posthoc Analysis From the TOSCA Trial.

BACKGROUND: High body mass index (BMI) plays a key role in the development of colon cancer (CC). Our post-hoc analysis from the TOSCA trial analyzed the association between BMI and survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS) in stage II/III CC patients. PATIENTS AND METHODS: Patients enrolled in the TOSCA trial between 2007-2013 with BMI data entered the study. The prognostic impact of BMI on survival outcomes was investigated through uni- and multivariable Cox regression analyses. RESULTS: Overall, 1455 patients with stage II/III CC patients were included. The median follow-up was of 61.5 months; 16.1% of patients relapsed, 11.2% died and 19.5% patients relapsed or died. No impact of BMI on RFS was detected at univariate or multivariable analyses. By univariate analysis for OS, a significantly impact of a BMI > 30 kg/m2 was reported (HR [>30 vs <25] 1.57, 95% CI 1.00-2.47, p = 0.049; HR [>30 vs <30] 1.55, 95% CI 1.01-2.37, p = 0.045). Multivariable analyses did not confirm this data. In the subgroup of stage III patients, a negative survival impact of BMI was found in univariate and multivariable models both for RFS and for OS. CONCLUSIONS: In our study, obesity with BMI > 30 kg/m2 was an independent prognostic factor for RFS and OS in CC patients treated with adjuvant chemotherapy, regardless of its duration (3 or 6 months). However, the prognostic impact of adiposity and body composition measurement should be considered to better classify patients with high visceral fat and refine their risk assessment.

How SARS-CoV-2 Infection Impacts the Management of Patients with Vulvar Cancer: Experience in a Third-Level Hospital of Southern Italy.

Background: Since February 2020, the spread of Coronavirus Disease 2019 (COVID-19) in Italy has induced the government to call for lockdown of any activity apart from primary needs, and changing the lives of each of us. All that has dramatically impacted the management of patients affected by cancer. Patients with vulvar cancer (VC) represent a particularly frail population because they are elderly and affected by multiple comorbidities. The aim of this study is to evaluate the clinical impact of the SARS-CoV-2 infection on VC patients in terms of delay or impossibility of carrying out the scheduled treatment. Methods: The medical records of patients affected by vulvar tumors, referred to "DAI Materno-Infantile" of AOU Federico II of Naples between February 2020 and January 2022 were retrospectively analyzed. The presence of a positive reverse transcription-polymerase chain reaction (RT-PCR) in nasopharyngeal swab defined the positivity to SARS-CoV-2. Results: Twenty-four patients with VC were analyzed and scheduled for treatment. The median age was 70.7 years (range: 59-80). Seven (29.2%) patients were diagnosed with SARS-CoV-2 infection: In three (42.8%) patients, the treatment was delayed with no apparent consequences, in four (57.2%), the treatment was delayed or changed due to cancer progression and, of these four, one died due to respiratory complications of COVID-19, and one died due to oncologic disease progression. Conclusion: COVID-19 caused, in most cases, significant delays in oncologic treatments and high mortality in our series of patients affected by VC.

Extraskeletal Ewing's sarcoma of the mediastinum: Case report.

Background: Ewing sarcoma (ES) represents the second most common malignant bone tumor in children and young adults. ES is not a frequent finding in sites different from the skeletal. Common sites of appearance of ES are lower extremities, the pelvis, paravertebral spaces and head and neck. Primary extraskeletal ES located in the anterior mediastinum are very rare. These neoplasms should be discussed in specialized contests with a high volume of patients treated. Here, we present an uncommon mediastinal mass challenging in its characterization and management. Case description: A thirty-year-old woman performed a thoracic CT scan for dyspnea and persistent cough. Imaging showed a solid mass of 14 x 11 cm involving the left thorax with mediastinal deviation to the right side. Patient underwent an en bloc resection of the mass. Initial histological examination was suggestive for B3 thymoma/thymic carcinoma. Patient was then referred to our rare tumor reference center where a histological review excluded the diagnosis of thymic/thymoma neoplasms meanwhile a third revision assessed a diagnosis of ES. Patient refused adjuvant chemotherapy due to her desire of maternity and radiation therapy was not indicated because surgery was performed too many months earlier. A close follow-up was considered. After a few months the patient relapsed and first line chemotherapy was proposed. She reached a complete response at the first evaluation maintained also at the end of the protocol. In order to consolidate the obtained response, high dose chemotherapy followed by autologous stem cell transplantation (HDCT/ASCT) was suggested and the patient agreed. Conclusions: This case underlined that, potentially, ES can arise from any soft tissue site in the body, even in rare sites such as mediastinum. The evaluation of expert centers was critical to establish a correct diagnosis and therapeutic approach in this complex case. Taking into account the time lasting from the diagnosis and the aggressiveness of this kind of neoplasm, frequently relapsing, the patient after a multidisciplinary discussion was a candidate for a multimodal treatment.