Primum non Nocere: How to ensure continuity of care and prevent cancer patients from being overlooked during the COVID- 19 pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread to all countries since December 2019, triggering a pandemic within weeks of the initial outbreak. Doctors were presented with the challenge of having to reimagine the traditional hospital organisation in order to effectively manage patients. PATIENTS AND METHODS: During the months of the COVID-19 pandemic our Institution was assisted by a call-center (CC) that triaged cancer patients planned for follow-up in our outpatient clinics: C1 (for female cancers), C2 (for gastrointestinal, urogenital, and thoracic tumours), and D1 (for melanoma and for patients with tumours in over 5 years follow up). Data refers to the period between 15 April and 3 July 2020. RESULTS: A total of 1054 patients have been included in our study and 1005 (95%) of the contacts were successful. The analysis showed a majority of female patients (74%) and patients affected by breast cancer (56%). Among the options provided 646 patients (92.4%) opted for online consultancy. CONCLUSION: This study has shown that cancer patients valued technology-mediated follow-up visits mainly during the beginning of the pandemic because patients themselves were afraid to come to the hospital. Although telemedicine has intrinsic limitations, it is important for providing assistance and preventing cancer patients from feeling isolated during an emergency.

Pandemic Phase-Adjusted Analysis of COVID-19 Outcomes Reveals Reduced Intrinsic Vulnerability and Substantial Vaccine Protection From Severe Acute Respiratory Syndrome Coronavirus 2 in Patients With Breast Cancer.

PURPOSE: Although representing the majority of newly diagnosed cancers, patients with breast cancer appear less vulnerable to COVID-19 mortality compared with other malignancies. In the absence of patients on active cancer therapy included in vaccination trials, a contemporary real-world evaluation of outcomes during the various pandemic phases, as well as of the impact of vaccination, is needed to better inform clinical practice. METHODS: We compared COVID-19 morbidity and mortality among patients with breast cancer across prevaccination (February 27, 2020-November 30, 2020), Alpha-Delta (December 1, 2020-December 14, 2021), and Omicron (December 15, 2021-January 31, 2022) phases using OnCovid registry participants (ClinicalTrials.gov identifier: NCT04393974). Twenty-eight-day case fatality rate (CFR28) and COVID-19 severity were compared in unvaccinated versus double-dosed/boosted patients (vaccinated) with inverse probability of treatment weighting models adjusted for country of origin, age, number of comorbidities, tumor stage, and receipt of systemic anticancer therapy within 1 month of COVID-19 diagnosis. RESULTS: By the data lock of February 4, 2022, the registry counted 613 eligible patients with breast cancer: 60.1% (n = 312) hormone receptor-positive, 25.2% (n = 131) human epidermal growth factor receptor 2-positive, and 14.6% (n = 76) triple-negative. The majority (61%; n = 374) had localized/locally advanced disease. Median age was 62 years (interquartile range, 51-74 years). A total of 193 patients (31.5%) presented ≥ 2 comorbidities and 69% (n = 330) were never smokers. In total, 392 (63.9%), 164 (26.8%), and 57 (9.3%) were diagnosed during the prevaccination, Alpha-Delta, and Omicron phases, respectively. Analysis of CFR28 demonstrates comparable estimates of mortality across the three pandemic phases (13.9%, 12.2%, 5.3%, respectively; P = .182). Nevertheless, a significant improvement in outcome measures of COVID-19 severity across the three pandemic time periods was observed. Importantly, when reported separately, unvaccinated patients from the Alpha-Delta and Omicron phases achieved comparable outcomes to those from the prevaccination phase. Of 566 patients eligible for the vaccination analysis, 72 (12.7%) were fully vaccinated and 494 (87.3%) were unvaccinated. We confirmed with inverse probability of treatment weighting multivariable analysis and following a clustered robust correction for participating center that vaccinated patients achieved improved CFR28 (odds ratio [OR], 0.19; 95% CI, 0.09 to 0.40), hospitalization (OR, 0.28; 95% CI, 0.11 to 0.69), COVID-19 complications (OR, 0.16; 95% CI, 0.06 to 0.45), and reduced requirement of COVID-19-specific therapy (OR, 0.24; 95% CI, 0.09 to 0.63) and oxygen therapy (OR, 0.24; 95% CI, 0.09 to 0.67) compared with unvaccinated controls. CONCLUSION: Our findings highlight a consistent reduction of COVID-19 severity in patients with breast cancer during the Omicron outbreak in Europe. We also demonstrate that even in this population, a complete severe acute respiratory syndrome coronavirus 2 vaccination course is a strong determinant of improved morbidity and mortality from COVID-19.

Vaccination against SARS-CoV-2 protects from morbidity, mortality and sequelae from COVID19 in patients with cancer.

BACKGROUND: Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined. METHODS: Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients. RESULTS: 2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p < 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320). CONCLUSIONS: This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries.

BACKGROUND: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer. METHODS: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. FINDINGS: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098). CONCLUSION: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

Rising incidence of late stage breast cancer after COVID-19 outbreak. Real-world data from the Italian COVID-DELAY study.

PURPOSE: Breast cancer (BC) patients' (pts) management was affected by a global reorganization after Coronavirus disease 2019 (COVID-19). Our multicenter study aimed to assess the impact of COVID-19 on access to diagnosis, staging and treatment for BC pts compared to pre-pandemic. METHODS: Medical records of all consecutive newly diagnosed BC pts referred to 6 Italian Institutions between March and December 2020 were assessed. Monthly access rate and temporal intervals between date of symptoms onset, radiological, cytohistological diagnosis and treatment start were analyzed and compared with 2019. RESULTS: A reduction (25%) in newly diagnosed BC was observed compared to 2019 (666 vs 890). New BC pts in 2020 were less likely to be diagnosed with early stage BC (77% vs 83%, p < 0.01), had a worse performance status according to the Eastern Cooperative Oncology Group (ECOG PS) (19.8% had PS > 0 in 2020 vs 16.5% in 2019, p < 0.01) and fewer pts were asymptomatic at diagnosis in 2020 (54% vs 71%,p < 0.01). COVID-19 did not negatively impact in terms of access to diagnosis, staging and treatment. Time intervals between symptom onset and radiological diagnosis, symptom onset and cytohistological diagnosis, cytohistological diagnosis and treatment start were maintained or improved. However, less cases were discussed in multidisciplinary tumor meetings during 2020 (60% vs 73%, p < 0.01). CONCLUSIONS: Our data proved an alarming reduction of early stage BC associated with the COVID-19 crisis in 2020. Despite the upheaval generated by the pandemic, our study shed light on the effective performance delivered by Italian Oncology Departments to guarantee diagnostic-therapeutic pathways.

Management of lung cancer patients during COVID-19 pandemic: dos, don'ts and don't knows.

Aim: During the coronavirus disease 2019 (COVID-19) pandemic two needs have overlapped: on one hand continuing to provide the best care for patients with lung cancer and preventing the spread of the virus between patients and healthcare professionals on the other hand. Due to the pandemic's unpredictable duration, physicians had to evaluate the risk/benefit ratio of anti-cancer therapeutic strategy to do the best for their patients and to protect patients themselves, as well as healthcare workers. Methods: Systematic literature research was performed with the aim to assess the available guidelines for the management of lung cancer patients during the COVID-19 pandemic. Thirteen potentially relevant articles were selected and recommendations have been divided into three main categories: dos, don'ts and don't knows. Results: All guidelines and recommendations highlighted the relevance of being able to delay, if possible and based on risk stratification, and curative interventions. The selected recommendations should be considered adaptable and flexible because they might be contextualized on the basis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection prevalence and the availability of diagnostic-therapeutic resources. Conclusions: It remains of fundamental importance to discuss each diagnostic and therapeutic decision with the patient taking into account risks and benefits that might vary from case to case.

Alarming Drop in Early Stage Colorectal Cancer Diagnoses After COVID-19 Outbreak: A Real-World Analysis from the Italian COVID-DELAY Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter Italian study aimed to evaluate whether COVID-19 has impacted access to diagnosis, staging, and treatment for patients newly diagnosed with colorectal cancer (CRC), compared with pre-pandemic time. METHODS: All consecutive new CRC patients referred to 8 Italian oncology institutions between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset, radiological and cytohistological diagnosis, treatment start and first radiological evaluation were analyzed and compared with the same months of 2019. RESULTS: A reduction (29%) in newly diagnosed CRC cases was seen when compared with 2019 (360 vs 506). New CRC patients in 2020 were less likely to be diagnosed with early stage (stages I-II-III) CRC (63% vs 78%, P < .01). Gender and sidedness were similar regardless of the year. The percentage of tumors with any mutation among BRAF, NRAS, and KRAS genes were significantly different between the 2 years (61% in 2020 vs 50% in 2019, P = .04). Timing of access to cancer diagnosis, staging, and treatment for patients with CRC has not been negatively affected by the pandemic. Significantly shorter temporal intervals were observed between symptom onset and first oncological appointment (69 vs 79 days, P = .01) and between histological diagnosis and first oncological appointment (34 vs 42 days, P < .01) during 2020 compared with 2019. Fewer CRC cases were discussed in multidisciplinary meetings during 2020 (38% vs 50%, P = .01). CONCLUSIONS: Our data highlight a significant drop in CRC diagnosis after COVID-19, especially for early stage disease. The study also reveals a remarkable setback in the multidisciplinary management of patients with CRC. Despite this, Italian oncologists were able to ensure diagnostic-therapeutic pathways proper operation after March 2020.

SARS-CoV-2 vaccine in patients with thymic epithelial tumours with and without active or pre-existing autoimmune disorders: Brief report of a TYME network safety analysis.

BACKGROUND: International guidelines recommend severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for patients with cancer. A substantial risk of developing vaccine-related autoimmune toxicities could be hypothesised for patients with thymic epithelial tumours (TETs) due to their high risk of autoimmune disorders (ADs). Moreover, a cross-reaction between SARS-CoV-2 spike protein antibodies and various tissue proteins has been shown, and antibodies against nucleoproteins showed overlaps in the autoimmune cross-reaction with antibodies to spike protein. Due to the rarity of TETs, no data addressing this hypothesis are available. METHODS: Patients with TETs who received SARS-CoV-2 vaccine, treated in 4 referral centres of the Italian Collaborative Group for ThYmic MalignanciEs (TYME) network between February 2021 and September 2021, were interviewed through a standardised 15-items questionnaire in order to describe the safety of SARS-CoV-2 vaccine in patients affected by TETs. RESULTS: Data from 245 doses of vaccine administered to 126 patients (41 = thymic carcinoma, 85 = thymoma; 38 with AD, of which 26 with active AD) were collected. Nine patients had a previous COVID-19-positive swab. No cases of AD reactivation or worsening of a pre-existing AD were seen in the study population. A new diagnosis of myasthenia gravis likely unrelated to the vaccine was made in two patients after the vaccination. Sixty-four patients (51%) experienced a total of 103 adverse events, all G1/G2, most commonly fatigue, new or worsening muscle pain and chills. None AE required patients' hospitalisation. CONCLUSIONS: SARS-CoV-2 mRNA vaccines appear to be safe in patients with TET, even in case of active or pre-existing AD.

COVID-19 in breast cancer patients: a subanalysis of the OnCovid registry.

BACKGROUND: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. METHODS: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. RESULTS: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like (n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common (n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. CONCLUSION: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible.

Cancer patient perspective in the arena of COVID-19 pandemic.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has been declared a global pandemic of unprecedented proportions. Italy is a country which has been heavily affected. Cancer patients are at a higher risk owing to their intrinsic fragility related to their underlying disease and oncologic treatment. Against this backdrop, we conducted a survey to investigate how patients perceived their condition, clinical management and availability of information during the pandemic. METHODS: Between 15 April and 1 May 2020 a survey was submitted to cancer patients at oncology departments in the Marche region. Questions regarding the perception of personal safety, continuity of cancer care, information quality and psychological distress. RESULTS: Seven hundred patients participated in the survey; 59% were female and 40% were aged between 46 and 65. The majority of the participants perceived compliance with appropriate safety standards by cancer care providers and 80% were reassured about their concerns during the medical interview. 40% were worried of being at a higher risk of infection and 71% felt they were at a greater risk because of chemotherapy. 55% felt that postponing cancer treatment could reduce its efficacy, however 76% declared they did not feel abandoned at the time of treatment postponement. Patients between 46 and 65 years declared a significant reduction in sleep (p < 0.01) and in concentration (p = 0.03). CONCLUSIONS: The emergency care offered to cancer patients has been deemed satisfactory in terms of both safety standards and care management. However, the majority of participants perceived the mutual negative influence between their oncologic disease and the risk of infection highlighting the need for special measures to ensure safe continuity of care.

Scientia Potentia Est: How the Italian World of Oncology Changes in the COVID-19 Pandemic.

PURPOSE: After coronavirus disease 2019 (COVID-19) was declared a pandemic by the WHO, a response from the Italian Health System to react to an unprecedented condition became necessary and sudden. The COVID-19 pandemic has required oncologists to redefine clinical organization and patient management. The purpose of our study was to document the difficulties emerging during the SARS-CoV-2 pandemic in Italian oncology. METHODS: We broadcasted an electronic survey to oncologic health care professionals. It consisted of 45 questions ranging from individual perception of pandemic management by hospital centers to physicians' and nurses' psychological distress and patient care. RESULTS: A total of 383 oncology health workers participated in the survey. The majority were female (71.8%) and from central Italy (46.2%). Impressively, a total of 357 (93%) participants declared the oncologic department reorganized routine clinical activity, but only 40.5% were adequately trained about the required procedures; 20% of the survey respondents think they have not received adequate and timely protective devices. CONCLUSION: Our survey demonstrated the flexibility of oncologic teams. However, the emergency response quality has been heterogeneous, and several drawbacks have emerged from the first analyses investigating how the world of oncology changes in the COVID-19 pandemic. Information, protection, testing, and training of health care professionals are key words that should be kept in mind to encourage recovery after this tragedy and to be ready to face a similar emergency in the future.

COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study.

BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.