key: cord-0839226-7vn284zy
authors: Kabalak, Pınar Akın; Kızılgöz, Derya; Kavurgacı, Suna; Yılmaz, Ülkü
title: Clinical management of lung cancer patients with respiratory symptoms during the COVID‐19 pandemic
date: 2021-11-05
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14993
sha: 58e705f4fea781acebd5a85282194574d615f298
doc_id: 839226
cord_uid: 7vn284zy

OBJECTIVE: There are many clinical conditions, such as lung cancer, that need to be followed up and treated during a pandemic. Providing health care for patients who are immune‐suppressive requires extra care. METHOD: Among 108 lung cancer patients who had been hospitalized during the COVID‐19 pandemic, 18 with respiratory symptoms were evaluated retrospectively. RESULTS: The patients’ median age was 64 ± 9.4 with a male predominance (male n = 16, female n = 2). Thirteen had non‐small cell lung cancer (NSCLC), and 5 had small cell lung cancer (SCLC). Nine (50%) patients were receiving chemotherapy. The most common symptom was shortness of breath (n = 14, 77.8%), followed by fever (n = 10, 55.6%). The findings confirmed on computed thorax tomography (CTT) were as follows: consolidation (n = 8, 44.4%), ground glass opacities (n = 8, 44.4%) and thoracic tumour/mediastinal‐hilar lymphadenopathy (n = 3, 16.7%). Hypoxia was seen in 11 patients (61.1%), twelve patients had an elevated LDH (median = 302 ± 197) and lymphopenia (median = 1055 ± 648) and 5 (27.7%) were highly suspected of having contracted COVID‐19. None of their nasopharyngeal swaps was positive. Two of these 5 patients received COVID‐19 specific treatment even though they thrice had negative reverse transcription polymerase chain reaction (RT‐PCR) results. The two patients responded well to both clinical and radiological treatments. For one case with SCLC receiving immunotherapy, methylprednisolone was initiated for radiation pneumonitis after excluding COVID‐19. CONCLUSION: In line with a country's health policies and the adequacy of its health system, the necessity of a multidisciplinary approach in the management and treatment of complications in patients with lung cancer has become even more important during the COVID‐19 pandemic.

given. Epidemiological data from China have revealed that, while total COVID-19 mortality is 2.3%, it is 5.6% among patients with malignant tumours. 3 Among patients with cancer, lung cancer (5/18, 28%) is the most common type, but patients with lung cancer have no higher incidence of malignant events during the pandemic (20% and 62%, respectively, P = .294). 4 When compared with normal populations, patients with cancer tend to be older and have more polypnea. They have also already had severe baseline tomographic findings. Overall, according to Cox regression analyses, patients with cancer are at risk of severe events (intensive care unit requiring invasive ventilation or death) and of deteriorating rapidly (Fisher's exact P = .0003). 4 Therefore, additional concern is needed, depending on the capabilities of a country's health system.

Underlying comorbidities are related to increased case fatality rates (CFR = %). Cancer is one such comorbidity, but among all types of malignancies there are many risk factors specific to complications in lung cancer patients. 5 These patients have structural lung injuries due to smoking, decreased functional capacity, treatment-related immune suppression and defects secondary to pulmonary mass and treatments (surgery and radiotherapy). 5 More common complications in hospitalised lung cancer patients are pneumonia, pneumonitis and acute respiratory distress syndrome. 6 Moreover, systemic steroids used to treat lung cancer patients for many reasons (cranial metastasis, vena cava superior syndrome or emesis) can suppress the symptoms of COVID-19. Many clinical conditions, especially pulmonary infections, present with cough, fever and dyspnoea similar to COVID-19 in patients without cancer. 6 Additionally, tomographic findings secondary to lung tumours can overlap with COVID-19 radiology. 9 As a result, the early detection of COVID-19, management of differential diagnosis and scheduling treatment should be processed carefully by a multidisciplinary team for this group of patients. 5, 7 Another difficulty is the differential diagnosis of infection-related complications in lung cancer patients, especially during the pandemic.

If a suspected or confirmed case of COVID-19 pneumonia is diagnosed in a lung cancer patient, transfer to a specially prepared hospital department for isolation must be provided. 7 The possibility of false-negative detection of nasopharyngeal swabs for new coronavirus nucleic acids should be a concern, and in case of persistent clinical suspicion, secondary sampling should be done. 10 While awaiting COVID-19 test results, other causes related to infection or non-infection (radiation pneumonia, immune-checkpoint inhibitor-associated pneumonia, cancer progression, pulmonary embolism, cardiac insufficiency, etc) must be examined so as not to lose time if treatment is required. 9 After thoracic surgery for lung cancer, in the case of indications for adjuvant therapy, decisions should be made case by case. If a patient in pathological stage ⅠB-ⅡA is elderly and in poor physical condition, the follow-up treatment plan should be considered using a network platform with the relevant physician(s). 7, 8 For patients in pathological stage ⅡB-ⅢA, the time frame for adjuvant chemotherapy can be extended. In the presence of pathological N2 or epidermal growth factor receptor (EGFR), gene mutations may be evaluated as one possible adjuvant treatment option. 11 In advanced stage patients without a targetable mutation, the initiating or continuing of chemotherapy must be comprehensively evaluated. Being engaged in the process of consolidation chemotherapy or two and above line protocols and/or becoming fragile from prior chemotherapies are clinical factors involved in extending the intervals of chemotherapy, which should be considered in close communication with the patient's physician(s). 7, 8 Therefore, this study aimed to reveal how lung cancer patients with respiratory symptoms were managed during the COVID-19 pandemic in a thoracic oncology unit. laboratory parameters (LDH with a range of 0-247 IU/L, hemogram analyses and C reactive protein), and radiological findings on chest X-ray and high resolution thorax tomography (HRTT) were recorded.

In our clinic, all patients with signs of respiratory tract infection are examined for acid-resistant bacillus (ARB) and given a bacterial and fungal culture examination. When required, considering the patient's epidemiological history and clinical symptoms, nasopharyngeal swabs for new coronavirus nucleic acids were obtained according to the local guidance for COVID-19. 1 In Turkey, a patient suspected of being infected with COVID-19 completes the diagnosis and treatment process in the hospital. Patients with a suspected contact or high risk for COVID-19 are transferred to a specially prepared department for centralised isolation and treatment in the hospital. In case of continuing clinical suspicion, a second test swab was taken.

In the meantime, the necessary tests for differential diagnosis were continued, and empirical antibacterial treatment was started in all cases.

This study was approved by our hospital ethical committee (number 673-14.05.2020), and the necessary permission was obtained from the Turkish Ministry of Health (application number 2020-05-08T00_20_42).

Eighteen patients with a median age of 64 ± 9.4 were included.

There was male predominance (male n = 16, female n = 2). Among the cases, 13 of them were non-small cell lung cancer (NSCLC) (including 8 squamous cell and 5 adenocarcinoma), and 5 of them were small cell lung cancer (SCLC). The distribution of TNM stages was as follows: 10 patients with stage IV, 6 patients with stage III and 2 patients with early stage cancer. The number of patients receiving chemotherapy was 9 (50%), only 1 of whom was undergoing adjuvant therapies. Other treatments were palliative cranial radiotherapy (RT) for 1 patient, best supportive care for 3 patients, chemoradiotherapy for 2 patients, immunotherapy for 1 patient and follow-up after the completion of planned treatment for 2 patients ( Table 1) .

The most common symptom was shortness of breath (n = 14, 77.8%), followed by fever (n = 10, 55.6%). Five patients had a cough along with other symptoms. But in 16 patients (88.9%), at least two but sometimes more, respiratory symptoms were present together.

All patients had fatigue, whereas 3 patients had severe myalgia (Table 1) .

According to the results of the radiological evaluations, 14 (77.8%) patients presented a pathology on their chest X-rays (eg con- No pleural effusion was detected by CTT in patients having ground glass opacities (Table 1) . Hypoxia was seen in 11 patients (61.1+%), whereas in 12 patients, an elevated LDH (median = 302 ± 197) and lymphopenia (median = 1055 ± 648) were observed (Table 1) .

There were 5 (27.7%) patients highly suspected of having contracted COVID-19 and thus requiring a nasopharyngeal swab test.

None of them was positive for COVID-19. Two of these 5 patients received COVID-19 specific treatment while a differential diagnosis was ongoing (Table 2, case numbers 1 and 3). Regarding the radiological features of these patients, 4 presented ground glass opacities on CTT. One patient presented with consolidation and tumour progression on CTT, but due to having a fever that did not respond to broad-spectrum antibiotics, he was required to take a COVID-19 Among the patients suspected of having COVID-19, (n = 5), 3 responded to broad-spectrum antibiotic therapy. In 1 case (Table 2, case number 2) with SCLC receiving immunotherapy following chemo-radiotherapy within the scope of an international, multicentre clinical trial, the patient was diagnosed with radiation pneumonitis after excluding COVID-19 with a negative nasopharyngeal swab test. He responded well to methylprednisolone treatment ( Figure 1 ). For 2 patients (Table 2 , case numbers 1 and 3), although 3 RT-PCRresults were negative, they were hospitalised in the isolated service, and significant clinical and radiological results were obtained with COVID-19 specific treatment (Figures 2 and 3 ).

During the pandemic, our unit tended to avoid unnecessary minimal invasive procedures such as bronchoscopies or endobronchial ultrasound (EBUS). Only 1 patient required a bronchoscopy to obtain intrabronchial secretion clearance, and his bronchial lavage culture was positive for Escherichia coli. According to some suggestions on the diagnosis of and treatment strategies for lung cancer patients from China, where the outbreak began and was dealt with first, highly suspected or confirmed patients must be transferred to a specially prepared isolated department of the hospital. 7 Five patients in the current study suspected of contracting COVID-19 were admitted to the outpatient clinic of our chemotherapy unit, and the differential diagnosis process took place in an isolated area until COVID-19 was ruled out.

Each case should be handled separately, especially in terms of the treatments (chemotherapy, targeted therapies, immune-checkpoint inhibitor, radiotherapy, etc) they receive at the time of admission.

Their history of suspected contact(s) and visits to another country are important issues. 10 In total, 11 (61.1%) patients were receiving chemotherapy (including concurrent chemoradiotherapy).

Even though ground glass opacities are a widely accepted radiological presentation of COVID-19 pneumonia, they can be presented in different manifestations in lung cancer patients. 13 There are a small number of cases in the literature. One is a case of diagnosed lung adenocarcinoma with a simultaneous diagnosis of COVID-19 by the RT-PCR technique. Even though the patient had no COVID-19 specific symptoms, she had been in contact with an infected physician. There were no typical patient's CTT findings (showed diffuse, irregular, small, ground-glass opacities with partial consolidation in bilateral lungs), even at the beginning (when she had no symptoms) and after symptoms appeared. Finally, her complaints and radiological findings were determined to be obstructive pneumonia caused by the tumour. 14 Another reported case is a 73-year-old male who had been operated on for NSCLC in 2016. Even though he had no suspected COVID-19 symptoms, the patient was diagnosed with COVID-19 with PET-CT taken during re-staging. Bilateral diffuse, peripheral predominant ground-glass opacities suggesting active inflammatory processes on 18F-FDG PET/CT were the condition leading to the suspicion of COVID-19. 15 The most common radiological findings in our cases were consolidation (44%) and GGOs (44%), even in 5 cases considered highly suspicious for COVID-19 ( was diagnosed with radiation pneumonia and responded well to methylprednisolone therapy (Figure 1 ).

With this study, we aimed to emphasise that the diagnosis, treatment and management of complications in lung cancer patients require more care than in the normal population during the current pandemic. In the face of a multifactorial clinical condition, including the type of treatment, dose, duration of cytotoxic therapy and stage of the disease, as clinicians we should carry out the differential diagnosis process quickly to minimise the risk of transmission. We need to accumulate more knowledge concerning patients whose immunity has already been suppressed and whose cytokine responses have differentiated.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. 

COVID-19 (SARS-CoV-2 ENFEKSİYONU) REHBERİ. 14 NİSAN 2020. https:// covid 19bil gi.saglik.gov.tr/depo/rehbe rler/COVID -19_Rehbe ri.pdf 2. Infection prevention and control during health care when COVID-19 is suspected

Epidemiological Group of Emergency Response Mechanism of New Coronavirus Pneumonia of Chinese Centre for Disease Control and Prevention. Analysis of epidemiological characteristics of new coronavirus pneumonia

Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China

Testing for COVID-19 in lung cancer patients

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

ESMO Management and treatment adapted recommendations in the COVID-19 era: Lung cancer

Panel members. Managing cancer patients during the COVID-19 pandemic: an ESMO multidisciplinary expert consensus

Treatment guidance for patients with lung cancer during the coronavirus 2019 pandemic

Clinical Management of Lung Cancer Patients during the Outbreak of 2019 Novel Coronavirus Disease (COVID-19)

OA 16.04 Efficacy and safety of erlotinib vs vinorelbine/cisplatin as adjuvant therapy for stage ⅢA EGFR mutant NSCLC patients

Clinical features of 85 fatal cases of COVID-19 from Wuhan. A retrospective observational study

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China

Atypical lung feature on chest CT in a lung adenocarcinoma cancer patient infected with COVID-19

18F-fluorodeoxyglucose uptake in patient with asymptomatic severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019) referred to positron emission tomography/computed tomography for NSCLC restaging

CT imaging features of 4121 patients with COVID-19: A meta-analysis

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

A rapid fatal evolution of Coronavirus Disease-19 in a patient with advanced lung cancer with a long-time response to nivolumab