P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results:HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.

Preliminary data of immunogenicity of SARS-COV-2 mRNA vaccine in thymic epithelial tumors

Background Thymic epithelial tumors (TETs) are rare malignancies associated with dysregulation of the immune system with humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients. The aim of our study is evaluating immunization in TET patients, who received both doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods Starting from 14 April 2021, we enrolled 50 TET patients (pts), who received COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody serological levels were analysed by chemiluminescent immunoassay (CLIA) at different time-points: T0 (before the first vaccine dose), T1 (1 week after second dose), T2 (4 weeks after second dose), and late monitoring T3, T4, T5, T6 (at 3, 6, 9, 12 months after second dose, respectively). Preliminary data relative to12 pts, collected at T0, T1 and T2, were available for this report. Local ethical committee approved this study and all enrolled patients signed informed consent. Results Among the 12 patients, 8 were female and 4 males;9 pts had thymoma and 3 thymic carcinomas;myasthenia gravis (autoimmunity) was diagnosed in one patient, and 4 patients suffered from Good Syndrome (immunodeficiency). None had COVID-19 infection prior to immunization. All 12 pts had received both vaccine doses by the time of this analysis. At baseline, all pts were negative for the serological antibody titers (method range, 3.80–400 AU/mL, positivity for titer >25);at T1, 11 pts (92%) were negative;at T2, 10 pts (84%) remained negative. Interestingly, the only 2 pts with positive titers at T2 were both in remission of disease. Conclusions Our preliminary data showed that the majority of TET patients enrolled in this study had no seroconversion after 4 weeks from the second dose of COVID 19 vaccine. Despite preliminary, our data might have important implications for the immunization of TET patients.

Synchronous thymic and breast malignancies: a single institutional experience

Breast cancer is the most frequent neoplasm in female population. Conversely, thymic epithelial tumors (TETs) are rare diseases, often discovered in late stages. TET patients have a high risk of developing secondary malignancies compared with general population, with an incidence rate from 8 to 31%. We recently observed the synchronous appearance of both these neoplasms in two patients. The first patient, a 60-year-old female, was diagnosed with breast cancer. She underwent quadrantectomy and sentinel axillary lymph node dissection. Pathological diagnosis was invasive breast cancer non special type (NST), G2 pT1 N0, estrogen receptor (ER) 95%, progesterone receptor (PR) 90%, human epidermal growth factor receptor 2 (Her2) negative, Ki67: 30%. Staging work-up (chest X-ray followed by CT scan) discovered a solid mass of 70 mm in the anterior mediastinum, suspect for thymic tumor lesion, that also showed a tracer uptake at FDG scan (SUVmax 10). Patient underwent thymectomy with pathologic diagnosis of thymoma, subtype B2/B3, stage pT1a pN0 (AJCC TNM 8th edition). The second patient, a 62-year-old woman experiencing post-COVID persistent dyspnea, underwent a CT scan and an FDG PET scan. Imaging showed a thoracic lesion suspicious for thymic neoplasm infiltrating the chest wall (tracer uptake SUVmax 6.7) and simultaneously two contrast-enhanced nodules, one in each breast (left breast: 15 mm, SUVmax 2;right breast: 20 mm, SUVmax 2.6). Surgical biopsies were performed in all the 3 lesions. The pathological diagnoses were: (I) non keratinizing squamous cell carcinoma of the thymus;(II) invasive left breast cancer (NST) ER 90 %, PR 30%, Her2 negative, Ki67: 10%;(III) invasive right breast cancer (NST) ER 90%, PR 30%, Her2 positive (3+), Ki67 10%. The presence of synchronous thymic and breast malignancies appears to be very singular and requires personalized treatment strategies. Furthermore, additional studies are needed to understand if TETs and their related immune system dysregulation could increase the risk of secondary tumors, or whether genetic disorders might be responsible for an increased predisposition to develop synchronous malignancies. In both scenarios, future studies should explore the utility of tailoring screening procedures for TET patients.

Incidental discovery of thymic masses during syndrome coronavirus type 2 (SARS-CoV-2) infection

Recently, syndrome coronavirus type 2 (SARS-CoV-2) infection outbreak has determined the use of thoracic CT scan for diagnostic purposes, leading to incidental detection of mediastinal masses. However, the differential diagnosis between benign and malignant mediastinal neoplasms could be challenging. Furthermore, in a recent study, thymus hyperplasia was observed significantly more frequently in COVID 19 patients compared to controls. Here, we describe a case series of patients with incidental detection of mediastinal masses after COVID 19 infection. (I) The first patient was a 43-year-old male, who performed a CT scan in December 2020 after COVID infection, showing a hypodense lesion of 48×31 mm in the superior anterior mediastinum. Subsequently, the patient developed dysphagia, difficulty in swallowing and right eye ptosis, thus he underwent FDG-PET scan that revealed an uptake of the tracer with a standardized uptake value (SUVmax) of 6. Therefore, thymectomy by robotic assisted surgery was performed. The histological diagnosis was: “thymoma AB, Stage: pT1 a”. (II) The second patient was a 33-year-old female, who performed in January 2021 high resolution chest CT scan, after COVID infection, due to persistence of breath shortness and fatigue. Imaging detected a mass of about 30 mm in the anterior mediastinal space, although a subsequent FDG-PET scan showed no significant tracer uptake. The patient, who is still symptomatic, is currently in follow up. (III) The third patient, a 36-year-old female, performed in April 2021 a chest CT scan due to persistent respiratory distress syndrome, related to SARS-Cov-2 infection that was contracted during pregnancy. The imaging was performed after delivering and showed a solid wedge-shaped lesion of 26 mm in the thymic loggia. The FDG PET scan carried out in June 2021 showed tracer uptake (SUVmax 2.7) in anterior mediastinal space. The patient was initially candidate to thymectomy, but due to the size reduction of the thymic mass observed on a follow-up CT scan, she was deemed eligible for follow up. In conclusion, our experience suggests that differential diagnosis in young symptomatic patients experiencing mediastinal masses after COVID infection is challenging and requires multidisciplinary expertise.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region. METHODS: This survey (25 questions), promoted by the young section of SCITO (Società Campana di ImmunoTerapia Oncologica) Group, was circulated among Italian young oncologists practicing in regions variously affected by the pandemic: high (group 1), medium (group 2) and low (group 3) prevalence of SARS-CoV-2-positive patients. For Campania region, the physician responders were split into those working in cancer centers (CC), university hospitals (UH) and general hospitals (GH). Percentages of agreement, among High (H) versus Medium (M) and versus Low (L) group for Italy and among CC, UH and GH for Campania region, were compared by using Fisher's exact tests for dichotomous answers and χ2 test for trends relative to the questions with 3 or more options. RESULTS: This is the first Italian study to investigate the COVID-19 impact on cancer immunotherapy, unique in its type and very clear in the results. The COVID-19 pandemic seemed not to affect the standard practice in the prescription and delivery of ICIs in Italy. Telemedicine was widely used. There was high consensus to interrupt immunotherapy in SARS-CoV-2-positive patients and to adopt ICIs with longer schedule interval. The majority of the responders tended not to delay the start of ICIs; there were no changes in supportive treatments, but some of the physicians opted for delaying surgeries (if part of patients' planned treatment approach). The results from responders in Campania did not differ significantly from the national ones. CONCLUSION: Our study highlights the efforts of Italian oncologists to maintain high standards of care for CPs treated with ICIs, regardless the regional prevalence of COVID-19, suggesting the adoption of similar solutions. Research on patients treated with ICIs and experiencing COVID-19 will clarify the safety profile to continue the treatments, thus informing on the most appropriate clinical conducts.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.