key: cord-0994012-7wmyq3h5 authors: Lauricella, Eleonora; Cives, Mauro; Bracigliano, Alessandra; Clemente, Ottavia; Felici, Valentina; Lippolis, Rossella; Amoruso, Brunella; Pelle', Eleonora; Mandriani, Barbara; Esposto, Chiara; Forte, Cira; Perri, Francesco; Porta, Camillo; Tafuto, Salvatore title: The psychological impact of COVID‐19 pandemic on patients with neuroendocrine tumors: Between resilience and vulnerability date: 2021-10-01 journal: J Neuroendocrinol DOI: 10.1111/jne.13041 sha: 01c8364a0bd888e2948302b95e9871ed38669726 doc_id: 994012 cord_uid: 7wmyq3h5 The COVID‐19 pandemic has added another layer of complexity to the fears of patients with neuroendocrine tumors (NETs). Little is known regarding the psychological impact of the COVID‐19 outbreak on patients with gastroenteropancreatic or bronchopulmonary (BP) NETs. We longitudinally surveyed the mental symptoms and concerns of NET patients during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy. Seven specific constructs (depression, anxiety, stress, health‐related quality of life, NET‐related quality of life, patient–physician relationship, psychological distress) were investigated using validated screening instruments, including DASS‐21, EORTC QLQ‐C30, EORTC QLQ GI.NET21, PDRQ9 and IES‐R. We enrolled 197 patients (98 males) with a median age of 62 years. The majority of the patients had G1/G2 neoplasms. Some 38% of the patients were on active treatment. At W1, the prevalence of depression, anxiety and stress was 32%, 36% and 26% respectively. The frequency of depression and anxiety increased to 38% and 41% at W2, whereas no modifications were recorded in the frequency of stress. Poor educational status was associated with higher levels of anxiety at both W1 (odds ratio [OR] = 1.33 ± 0.22; p = .07) and W2 (OR = 1.45 ± 0.26; p = .03). Notably, post‐traumatic stress symptoms were observed in the 58% of the patients, and both single marital status (OR = 0.16, 95% confidence interval [CI] = 0.06–0.48; p = .0009) and low levels of formal education (OR = 0.47, 95% CI = 0.23–0.99; p = .05) predicted their occurrence. No significant deteriorations of health‐related quality of life domains were observed from W1 to W2. High patient care satisfaction was documented despite the changes in health systems resource allocation. NET patients have an increased risk of developing post‐traumatic stress symptoms as result of the COVID‐19 pandemic. Specific screening measures and psychological interventions should be implemented in NET clinics to prevent, recognize and treat mental distress in this vulnerable population. In early December 2019, the first cluster of pneumonia cases of unknown origin was identified in Wuhan, the capital city of the Hubei province in China. 1 The causative agent was subsequently identified as a novel enveloped RNA betacoronavirus that was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2 Some 3 months after its first description, the SARS-CoV-2-associated disease (COVID-19) spread globally, and the World Health Organization (WHO) declared pandemic status on March 11, 2020. 3 The COVID-19 pandemic poses unprecedented medical, economic and social challenges. The need for social distancing, the isolation induced by lockdowns and quarantine orders enforced by national governments, the fear of infection and death from the virus, and the financial problems caused by the epidemic (i.e., job loss, income cuts, etc.) have been described as major threats for mental health. 4 In this context, multiple studies have already shown rising levels of psychological distress and mental illness in the general population as result of the pandemic surge. [5] [6] [7] Patients with cancer are at higher risk of morbidity and mortality from COVID-19 compared to the general population, probably as consequence of advanced age, coexisting chronic comorbidities, and cancer-related and drug-related immunosuppression. 8 The present study was carried out in two tertiary hospitals in Italy (Policlinico di Bari, Bari; National Cancer Institute Foundation "G. Pascale", Naples). Both centers have a specific expertise in managing patients with NETs, and represent the two main institutions specialized in treatment of NETs in South Italy. As of the last day of data collection (November 14, 2020), 1,144,552 confirmed COVID-19 infections and 44,683 deaths were recorded in Italy. To manage the pandemic, the Italian government instituted a full lockdown from March 11, 2020 to May 4, 2020, as well as a partial lockdown from October 13, 2020. During this period, we longitudinally surveyed the demographics, mental symptoms and concerns of NET patients twice, namely during the plateau phase of the first (W1) and second epidemic waves (W2) in Italy ( Figure 1 ). In both occurrences, information was collected over 2 weeks via phone interviews by medical oncology fellows or research assistants. The study was approved by the Ethics Committee of both participating institutions. Enrolled patients provided their written informed consent to participate in the study. We searched a prospective database of patients with GEP or BP NETs managed at our institutions. Within this group, we identified adult patients (age ≥ 18 years) with advanced, inoperable disease or who underwent R0/R1 surgical resection up to 5 years prior to enrollment. Patients with stage IV disease could receive any type of treatments. Patients with an Eastern Cooperative Oncology Group performance status ≥ 2, subjects on active therapy with psychotropic agents and subjects with a history of infection by SARS-CoV-2 before enrollment were excluded from the study. Patients with mixed adenoneuroendocrine tumors were also excluded. The following information was collected by review of patient Seven specific constructs (depression, anxiety, stress, quality of life, NET-related quality of life, patient-physician relationship, psychological distress) were investigated using validated screening instru- To mitigate this bias, we carried out separate analyses for patients with and without personal or family history of confirmed SARS-CoV-2 infection. Demographic variables and clinicopathological characteristics of the 197 patients included in the study are provided in Table 1 . The number of male and female patients was similar, and the median age at were also recorded before W2. At W1, the prevalence of depression, anxiety and stress by DASS-21 questionnaire was 32%, 36% and 26%, respectively ( Figure 2 ). The frequency of depression and anxiety increased to 38% and 41% at W2, in the absence of modifications in the frequency of stress. Although the levels of depression and anxiety (mild, moderate, severe and extremely severe 15 ) appeared to be similarly distributed at W1, moderate depression and anxiety tended to prevail at W2. No substantial modifications in the rate of depression, anxiety and stress at W2 were observed after removing patients who were diagnosed with COVID-19 (see Supporting information, Figure S1 ). At W1, patients with hormonal syndromes showed a significantly higher frequency of depression (p = .001) and anxiety (p = .04). Moreover, subjects with education lower than secondary level displayed higher rates of depression (p = .02), whereas the prevalence of stress was significantly higher among females (p = .01). At W2, depression was documented more frequently in patients older than 65 years (p = .01), with poor education (p = .01) and in those who were previously treated with psychotropic agents (p = .007). Low-level education (p = .009) and advanced age (p = .03) were also significantly associated with the occurrence of anxiety (Table 2) . When patients with a personal or family history of COVID-19 were removed from analysis, low tumor grade showed a significant association with depression at W2 (p = .04). After adjusting for variables that showed a p ≤ . 2 Mean and median HRQoL scores are detailed in Table 3 . Overall, the global health status of study participants did not change between W1 and W2. Intriguingly, a significant improvement of the physical (p = .03) and emotional functioning domains (p = .001) was observed over time. Moreover, both nausea/vomiting (p = .0002) and appetite (p = .02) improved significantly between W1 and W2. Treatment-related symptoms (p = .005) and disease-related worries (p = .0006) were reported less commonly at W2 compared to W1, and an improvement of sexual function was also noted between W1 and W2 (p = .02). We then analyzed separately HRQoL (Table 4) . By multivariable analysis, advanced age remained significantly associated with a worsening in the physical functioning, cognitive functioning, fatigue, constipation and financial difficulties domains. A drastic reduction in the number of outpatient visits for NET patients has been recorded in our country during the COVID-19 pandemic. 22 We therefore investigated possible changes in the patient-physician relationship between W1 and W2. The mean (± SD) score of the PDRQ9 questionnaire was 4.36/5 (±0.76) at W1 and 4.35/5 (±0.56) at W2. In the evaluable population (n = 195; two patients died before all NET patients and the bio-psychological basis of such an elevated PTSD frequency should be investigated further. HRQoL is increasingly recognized as a crucial endpoint in clinical trials for cancer patients, and contrasting data have been reported so far regarding the effects of the COVID-19 pandemic on the QoL of patients with cancer. [39] [40] [41] [42] In the present study, we longitudinally assessed intraindividual changes between W1 and W2 in patients with NETs. By contrast to our expectations, only a minority of patients underwent a clinically significant HRQoL deterioration throughout the pandemic, thus suggesting that NET patients were able to cope with The relationship between patients and doctors is an essential component of patient care. Evidence demonstrates that HRQoL is positively associated with all aspects of care among cancer patients in general, 44 and also that care satisfaction is strictly related to better HRQoL and psychosocial function of NET patients in particular. [45] [46] [47] In the present study, the confidence in NET specialists was very high, and no longitudinal changes were noted despite the TA B L E 3 Health-related quality of life (HRQoL) scores in the first and second epidemic waves satisfaction might contribute to explain the absence of significant HRQoL deterioration and the relatively small increase in depressive symptoms and anxiety from W1 to W2. We advise a systematic screening of post-traumatic stress symptoms for all NET patients until the end of the pandemic. Specific psychological interventions should be developed to treat this vulnerable population. This work was supported by the Associazione Italiana per la Ricerca sul Cancro (MFAG #23583) and Associazione per la Ricerca Biomolecolare Onlus, Acquaviva, Italy (2020). The authors declare that they have no conflicts of interest. Writing -review & editing. The peer review history for this article is available at https://publo ns.com/publo n/10.1111/jne.13041. 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A longitudinal report Additional supporting information may be found in the online ver-