High-sensitivity analysis of clonal hematopoiesis reveals increased clonal complexity of potential-driver mutations in severe COVID-19 patients.

Whether Clonal Hematopoiesis (CH) represents a risk factor for severity of the COVID-19 disease remains a controversial issue. We report the first high- sensitivity analysis of CH in COVID-19 patients (threshold of detection at 0.5% vs 1 or 2% in previous studies). We analyzed 24 patients admitted to ICU for COVID-19 (COV-ICU) and 19 controls, including healthy subjects and asymptomatic SARS-CoV2-positive individuals. Despite the significantly higher numbers of CH mutations identified (80% mutations with <2% variant allele frequency, VAF), we did not find significant differences between COV-ICU patients and controls in the prevalence of CH or in the numbers, VAF or functional categories of the mutated genes, suggesting that CH is not overrepresented in patients with COVID-19. However, when considering potential drivers CH mutations (CH-PD), COV-ICU patients showed higher clonal complexity, in terms of both mutation numbers and VAF, and enrichment of variants reported in myeloid neoplasms. However, we did not score an impact of increased CH-PD on patient survival or clinical parameters associated with inflammation. These data suggest that COVID-19 influence the clonal composition of the peripheral blood and call for further investigations addressing the potential long-term clinical impact of CH on people experiencing severe COVID-19. We acknowledge that it will indispensable to perform further studies on larger patient cohorts in order to validate and generalize our conclusions. Moreover, we performed CH analysis at a single time point. It will be necessary to consider longitudinal approaches with long periods of follow-up in order to assess if the COVID-19 disease could have an impact on the evolution of CH and long-term consequences in patients that experienced severe COVID-19.

Lower probability and shorter duration of infections after COVID-19 vaccine correlate with anti-SARS-CoV-2 circulating IgGs.

The correlation between immune responses and protection from SARS-CoV-2 infections and its duration remains unclear. We performed a sanitary surveillance at the European Institute of Oncology (IEO) in Milan over a 17 months period. Pre-vaccination, in 1,493 participants, we scored 266 infections (17.8%) and 8 possible reinfections (3%). Post-vaccination, we identified 30 infections in 2,029 vaccinated individuals (1.5%). We report that the probability of infection post-vaccination is i) significantly lower compared to natural infection, ii) associated with a significantly shorter median duration of infection than that of first infection and reinfection, iii) anticorrelated with circulating antibody levels.

COVID-19 and radiotherapy: impact on work and personal life of Lombardy residents during first lockdown, survey endorsed by AIRO Young.

AIM: Since 20 February 2020, Lombardy has been one of the most affected areas worldwide by the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate work and psychological impact of COVID-19 on Lombardy radiation therapy (RT) residents in the first 3 months of the outbreak (first lockdown). METHODS: An online questionnaire (22 multiple choice questions) via Microsoft Forms was administered on 30 May 2020 to RT residents. RESULTS: Nineteen Lombardy RT residents responded to the survey. Nineteen percent of residents underwent a nasal swab and 11% were quarantined. Seventeen residents (89%) reported an increase in workload. Twelve residents (63%) did not find any difference in terms of work distress; worsening was highlighted in 5 cases (26%). The majority has never considered the possibility of stopping work due to excessive stress (89%). Almost all the residents experienced self- or relative-referred apprehension (95%). Ninety-five percent reported having missed extra-work social relationships. Most of the sample noted worsening sleep quality and difficulty concentrating (69%). No residents requested psychological support, even if provided by the hospital. CONCLUSION: Overall, the residents adapted to the new workplace scenario, although some health risks and well-being challenges have been reported. An extension of the survey to all Italian RT residents endorsed by Italian Association of Radiotherapy and Clinical Oncology "Young AIRO" will allow an evaluation of COVID-19 impact on a national level. A second survey is planned to underline differences between the first lockdown and the current situation of the pandemic.

Outcomes of head and neck cancer management from two cancer centres in Southern and Northern Europe during the first wave of COVID-19.

OBJECTIVE: To describe the approach and outcomes from two cancer centres in Southern and Northern Europe during the first wave of coronavirus disease 2019 (COVID-19) of patients with head and neck cancer (HNC). METHODS: Data collection was performed on a retrospective cohort of patients surgically treated for primary HNC between March and May 2020, using data from two tertiary hospitals: the European Institute of Oncology (Milan) and Guy's & St Thomas' NHS Foundation Trust (London). RESULTS: We included 77 patients with HNC. More patients with COVID-19 were taking angiotensin-converting enzyme (ACE) inhibitors and had Clavien-Dindo Classification grade I compared to negative patients, respectively (60% vs 22% [p = 0.058] and 40% vs 8% [p = 0.025]). Multivariate logistic regression analyses confirmed our data (p = 0.05 and 0.03, respectively). Sex and age were statistically significantly different (p = 0.05 and <0.001 respectively), showing more male patients (75% vs 53.66%, respectively) and more elderly patients in Italy than in the United Kingdom (patients aged >63 years: 69.44% vs 29.27%). CONCLUSIONS: This study presents a large cohort of patients with HNC with nasopharyngeal swab during the first peak of the COVID-19 pandemic in Europe. Patients with HNC with COVID-19 appeared more likely to develop postsurgical complications and to be taking ACE inhibitors. The preventive measures adopted guaranteed the continuation of therapeutic surgical intervention.

Next generation diagnostic algorithm in non-small cell lung cancer predictive molecular pathology: The KWAY Italian multicenter cost evaluation study.

AIMS: The KWAY project aims to investigate the economic sustainability of the up-front NGS technologies adoption in the analysis of clinically relevant molecular alterations in NSCLC patients. METHODS: The diagnostic workflow and the related sustained costs of five Italian referral centers were assessed in four different evolving scenarios were analyzed. For each scenario, two alternative testing strategies were evaluated: the Maximized Standard strategy and the Maximized NGS strategy. RESULTS: For each center, the robustness of obtained results was verified through a deterministic sensitivity analysis, observing the variation of total costs based on a variation of ±20 % of the input parameters and ensuring that results would present a consistent behavior compared to the original ones. CONCLUSIONS: our project, highlighted that the adoption of NGS allows to save personnel time dedicated to testing activities and to reduce the overall cost of testing per patient.

Coping With Oral Tongue Cancer and COVID-19 Infection.

To date, April 19, 2021, the coronavirus disease 2019 (COVID-19) caused about 140,886,773 confirmed cases and more than 3,000,000 deaths worldwide since the beginning of the pandemic. Oncology patients are usually frail due to the fear of prognosis, recurrence, and outcomes of treatments. Thus, coping with cancer is a complicated process that is necessary to overcome oncological challenge, even more in case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) disease. This is a brief case report on a middle-aged man affected by advanced oral tongue cancer and COVID-19, describing his experience of cancer diagnosis, surgical treatment, and rehabilitation during the hospital quarantine for COVID-19. Besides the traumatic experience due to the functional alteration in breathing, eating, and speaking caused by major surgery and the concurrent facial disfigurement, our patient had to face a COVID-19 diagnosis, which implied hospital and social isolation. The aim of this perspective work is to focus on the role of the psychological support in the management of hospital distress related to COVID-19 psychophysical loneliness or alienation. In our experience, such support should anticipate patients' oncological surgery or treatment and should be implemented through telemedicine in case of isolation or after hospital discharge.

Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

COVID-19 impact in radiotherapy practice in an oncology hub: a screenshot from Lombardy, Italy.

OBJECTIVE: During 2020, medical clinical activities were dramatically modified by the coronavirus disease 2019 (COVID-19) emergency. We aim to evaluate the impact of COVID-19 on radiotherapy (RT) practice in a hub cancer center. METHODS: Retrospective data collection of patients with suspected COVID-19 infection, identified by pathognomonic symptoms feedback at triage realized at the entrance to RT division. Inclusion criteria were diagnosis of oncologic disease, COVID-19-related symptoms, and signed written informed consent. RESULTS: Between 1 March and 30 June 2020, 1,006 patients accessed our RT division for RT simulation or treatment. Forty-four patients matched inclusion criteria (4.4% of all patients): 29 women and 15 men. Seventeen patients had metastatic disease. Twenty-one patients reported fever, 6 presented dyspnea, 4 complained of ageusia and anosmia, and 3 developed conjunctivitis. Thirty-six patients underwent nasal swab, with 7 positive results. From our cohort, 4 cases of pneumonia were diagnosed with computed tomography scan imaging: 3 were related to COVID-19 infection, while the fourth was evaluated as an RT adverse event. From the entire series, 4 patients died: 3 during hospitalization in intensive care unit of complications of COVID-19 and 1 of other causes neither COVID-19 nor cancer-related. CONCLUSIONS: Cancer hub allows for safe RT practice continuation while minimizing the spread of contagion in this frail patient population. A challenge for the future will be to understand pandemic consequences in cancer natural history and manage its clinical impact.

Head and neck cancer radiotherapy amid COVID-19 pandemic: Report from Milan, Italy.

BACKGROUND: Management of head and neck cancers (HNC) in radiation oncology in the coronavirus disease 2019 (COVID-19) era is challenging. Aim of our work is to report organization strategies at a radiation therapy (RT) department in the first European area experiencing the COVID-19 pandemic. METHODS: We focused on (a) dedicated procedures for HNC, (b) RT scheduling, and (c) health care professionals' protection applied during the COVID-19 breakdown (from March 1, 2020 to April 30, 2020). RESULTS: Applied procedures are reported and discussed. Forty-three patients were treated. Image-guided, intensity modulated RT was performed in all cases. Median overall treatment time was 50 (interquartile range: 47-54.25) days. RT was interrupted/delayed in seven patients (16%) for suspected COVID-19 infection. Two health professionals managing HNC patients were proven as COVID-19 positive. CONCLUSION: Adequate and well-timed organization allowed for the optimization of HNC patients balancing at the best of our possibilities patients' care and personnel's safety.

A Guide for Oncologic Patient Management during Covid-19 Pandemic: The Initial Experience of an Italian Oncologic Hub with Exemplificative Focus on Uro-Oncologic Patients.

The recent exponential increase in the number of COVID-19 patients in Italy led to the adoption of specific extraordinary measures, such as the need to convey treatment of all non-deferrable cancer patients to specialized centres (hubs). We reported a comprehensive summary of guidelines to create and run an oncologic hub during the COVID-19 pandemic. Oncologic hubs must fulfil some specific requirements such as a high experience in oncologic patient treatment, strict strategies applied to remain a "COVID-19-free" centre, and the creation of a dedicated multidisciplinary "hub team". Cancer treatment of patients who belong to external centres, namely spoke centres, could be organized in different pathways according to the grade of involvement and/or availability of the medical team of the spoke centre. Moreover, dedicated areas should be created for the management and treatment of patients who developed COVID-19 symptoms after hospitalization (i.e., dedicated wards, operation rooms and intensive care beds). Lastly, hospital staff must be highly trained for both preventing COVID-19 contagion and treating patients who develop the infection. We provided a simplified, but complete and easily applicable guide. We believe that this guide could help those clinicians who have to treat oncologic patients during the COVID-19 pandemic.

Results of Multilevel Containment Measures to Better Protect Lung Cancer Patients From COVID-19: The IEO Model.

A novel coronavirus causing severe acute respiratory syndrome (SARS), named SARS-CoV-2, was identified at the end of 2019. The spread of coronavirus disease 2019 (COVID-19) has progressively expanded from China, involving several countries throughout the world, leading to the classification of the disease as a pandemic by the World Health Organization (WHO). According to published reports, COVID-19 severity and mortality are higher in elderly patients and those with active comorbidities. In particular, lung cancer patients were reported to be at high risk of pulmonary complications related to SARS-CoV2 infection. Therefore, the management of cancer care during the COVID-19 pandemic is a crucial issue, to which national and international oncology organizations have replied with recommendations concerning patients receiving anticancer treatments, delaying follow-up visits and limiting caregiver admission to the hospitals. In this historical moment, medical oncologists are required to consider the possibility to delay active treatment administration based on a case-by-case risk/benefit evaluation. Potential risks associated with COVID-19 infection should be considered, considering tumor histology and natural course, disease setting, clinical conditions, and disease burden, together with the expected benefit, toxicities (e.g., myelosuppression or interstitial lung disease), and response obtained from the planned or ongoing treatment. In this study, we report the results of proactive measures including social media, telemedicine, and telephone triage for screening patients with lung cancer during the COVID-19 outbreak in the European Institute of Oncology (Milan, Italy). Proactive management and containment measures, applied in a structured and daily way, has significantly aided the identification of advance patients with suspected symptoms related to COVID-19, limiting their admission to our cancer center; we have thus been more able to protect other patients from possible contamination and at the same time guarantee to the suspected patients the immediate treatment and evaluation in referral hospitals for COVID-19.

Breast Adjuvant Radiotherapy Amid the COVID-19 Crisis in a Hub Cancer Center, Lombardy, Italy.

INTRODUCTION: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here. METHODS: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables. RESULTS: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant (p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions. CONCLUSION: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals.

OECI accreditation of the European Institute of Oncology of Milan: strengths and weaknesses.

The European Institute of Oncology began the process to reach the accreditation promoted by the Organisation of European Cancer Institutes (OECI) in 2012. This accreditation integrates the quality and safety path started in 2001 with accreditation by the Joint Commission International. Despite the presence of diversified accreditations and certifications and the clear need of time, effort, and commitment, the models are complementary. Each model is not to be considered as an end but as a tool for improvement: e.g., mixing accreditation standards led to an improvement in the quality and safety of processes. The present article details the OECI accreditation experience of the European Institute of Oncology, in particular the following strengths of OECI standards: collaboration among several involved parties (patient, volunteer, patient's general practitioner) in the clinical and quality/safety processes; a larger involvement of support personnel (psycho-oncologists, dieticians, physical therapists); and the development of clinical/translational research and innovation in prevention, diagnosis, and treatment to guarantee the best available practice in diagnosis and treatment. The OECI accreditation is specific to oncology and therefore its standards are tailored to a cancer center, both in terms of language used in the standards manual and in terms of patient needs. The OECI accreditation system puts an auditor team with a standards manual in charge of verifying quality and confirms the definition of IEO as a Comprehensive Cancer Center.

Planning availability in stroke rehabilitation units.

The sequelae of cerebrovascular diseases constitute, and in the coming years will increasingly constitute, a major health problem. Stroke is already the leading cause of permanent invalidity, the second leading cause of dementia, and the third (on course to become the second) leading cause of death, after cardiovascular diseases and cancer. In view of the aging of the population and of the fact that stroke is strictly age-related, the incidence of stroke, in Italy, looks set to rise progressively over the coming years. In recent years, units have been set up for the specialist inpatient treatment of stroke victims, both in the acute phase (known as stroke units) and in the subsequent rehabilitative phase (stroke rehabilitation units), the aim being to improve both the management of these patients and, as a result, their functional outcome. Health policies and programming will have to take into account the need for more beds in both types of stroke unit.