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.

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.

Optimising triage procedures for patients with cancer needing active anticancer treatment in the COVID-19 era.

BACKGROUND: Immunosuppression induced by anticancer therapy in a COVID-19-positive asymptomatic patient with cancer may have a devastating effect and, eventually, be lethal. To identify asymptomatic cases among patients receiving active cancer treatment, the Federico II University Hospital in Naples performs rapid serological tests in addition to hospital standard clinical triage for COVID-19 infection. METHODS: From 6 to 17 April 2020, all candidates for chemotherapy, radiotherapy or target/immunotherapy, if negative at the standard clinical triage on the day scheduled for anticancer treatment, received a rapid serological test on peripheral blood for COVID-19 IgM and IgG detection. In case of COVID-19 IgM and/or IgG positivity, patients underwent a real-time PCR (RT-PCR) SARS-CoV-2 test to confirm infection, and active cancer treatment was delayed. RESULTS: Overall 466 patients, negative for COVID-19 symptoms, underwent serological testing in addition to standard clinical triage. The average age was 61 years (range 25-88 years). Most patients (190, 40.8%) had breast cancer, and chemotherapy with or without immunotherapy was administered in 323 (69.3%) patients. Overall 433 (92.9%) patients were IgG-negative and IgM-negative, and 33 (7.1%) were IgM-positive and/or IgG-positive. Among the latter patients, 18 (3.9%), 11 (2.4%) and 4 (0.9%) were IgM-negative/IgG-positive, IgM-positive/IgG-negative and IgM-positive/IgG-positive, respectively. All 33 patients with a positive serological test, tested negative for RT-PCR SARS-CoV-2 test. No patient in our cohort developed symptoms suggestive of active COVID-19 infection. CONCLUSION: Rapid serological testing at hospital admission failed to detect active asymptomatic COVID-19 infection. Moreover, it entailed additional economic and human resources, delayed therapy administrationand increased hospital accesses.

Oncological care organisation during COVID-19 outbreak.

BACKGROUND: COVID-19 appeared in late 2019, causing a pandemic spread. This led to a reorganisation of oncology care in order to reduce the risk of spreading infection between patients and healthcare staff. Here we analysed measures taken in major oncological units in Europe and the USA. METHODS: A 46-item survey was sent by email to representatives of 30 oncological centres in 12 of the most affected countries. The survey inquired about preventive measures established to reduce virus spread, patient education and processes employed for risk reduction in each oncological unit. RESULTS: Investigators from 21 centres in 10 countries answered the survey between 10 April and 6 May 2020. A triage for patients with cancer before hospital or clinic visits was conducted by 90.5% of centres before consultations, 95.2% before day care admissions and in 100% of the cases before overnight hospitalisation by means of phone calls, interactive online platforms, swab test and/or chest CT scan. Permission for caregivers to attend clinic visits was limited in many centres, with some exceptions (ie, for non-autonomous patients, in the case of a new diagnosis, when bad news was expected and for terminally ill patients). With a variable delay period, the use of personal protective equipment was unanimously mandatory, and in many centres, only targeted clinical and instrumental examinations were performed. Telemedicine was implemented in 76.2% of the centres. Separated pathways for COVID-19-positive and COVID-19-negative patients were organised, with separate inpatient units and day care areas. Self-isolation was required for COVID-19-positive or symptomatic staff, while return to work policies required a negative swab test in 76.2% of the centres. CONCLUSION: Many pragmatic measures have been quickly implemented to deal with the health emergency linked to COVID-19, although the relative efficacy of each intervention should be further analysed in large observational studies.

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.

Clinical Characteristics of Metastatic Prostate Cancer Patients Infected with COVID-19 in South Italy.

BACKGROUND: To date, the clinical characteristics of coronavirus disease 19 (COVID-19)-infected urologic cancer patients are unknown. METHODS: We have analyzed all patients with prostate cancer undergoing hormonal or chemotherapy treatment and receiving telephone and in person pre-triage between March 1 and 27, 2020, at the Tortora Hospital, Pagani, Italy. RESULTS: Among 72 patients, 48 and 24 were hormone-sensitive (HS) and castration-resistant prostate cancer (CRPC), respectively; 0 HS and 2 (8.3%) CRPC (p < 0.05) were positive for COVID-19. Both patients were receiving LHRH agonist therapy, and 1 patient was receiving enzalutamide. Urgent intensive care unit admission was required due to clinical worsening. Blood tests showed severe lymphopenia, anemia, and an increase in platelets. Retroviral therapy, antibiotics, heparin, and chloroquine were prescribed at the beginning. One patient also received tocilizumab as a salvage treatment. After 3 weeks of hospitalization, the patients were discharged from the hospital. Both patients suffered from an aggressive COVID-19 course due to concomitant comorbidities. CONCLUSIONS: Investigating whether hormonal therapy, especially in advanced disease, acts as a protective factor or a risk factor during COVID-19 could be useful.