key: cord-1003446-fyf1j7n1
authors: Youssef, Irini; Donahue, Bernadine; Flyer, Mark; Thompson, Sharon; Huang, Alice; Gallant, Fleure
title: Covert Covid-19: CBCT Lung Changes in An Asymptomatic Patient Receiving Radiotherapy
date: 2020-05-19
journal: Adv Radiat Oncol
DOI: 10.1016/j.adro.2020.04.029
sha: 257f1d40341b7b4084ff94ff36594e2bfd6eb7d8
doc_id: 1003446
cord_uid: fyf1j7n1

INTRODUCTION: COVID-19 profoundly impacted the United States, with New York City (NYC) rapidly becoming the epicenter of the disease. Cancer patients represent a vulnerable population in this pandemic, with data suggesting a higher risk for severe events and unfavorable outcomes. Timely identification of COVID-19 in cancer patients has been thwarted by the lack of outpatient testing for SARS-CoV-2. Chest computed tomography (CT) plays a major role in the identification of COVID-19 pneumonia, with radiologic hallmarks including bilateral, peripheral ground-glass opacities (GGOs) and consolidation. Cancer patients undergoing radiotherapy (RT) commonly have daily cone beam computed tomography (CBCT) obtained for image-guided radiotherapy (IGRT), and such imaging frequently includes the chest. METHODS: We retrospectively reviewed the CBCTs of an initially asymptomatic patient undergoing IGRT for breast cancer, who developed COVID-19 symptoms during the second week of RT. Lung windows of daily CBCTs were reviewed with Diagnostic Radiology to survey for changes consistent with COVID-19. Diagnostic CTs obtained at the time of recovery were obtained and compared with the CBCTs. RESULTS: Five consecutive CBCTs were retrospectively reviewed. Bilateral, peripheral GGOs were noted on the 4(th) and 5(th) CBCTs in the two days prior to symptom onset. CBCT on the day of RT resumption demonstrated substantial worsening of the GGO compared with those obtained during the asymptomatic phase. Diagnostic CTs demonstrated bilateral, peripheral GGOs and mediastinal lymphadenopathy, findings suggesting COVID-19 pneumonitis. Repeat diagnostic CT three days later showed improved pulmonary findings and the patient resumed RT without incident. CONCLUSION: Familiarity with typical CT changes of COVID-19 pneumonitis may allow for early detection in cancer patients undergoing CBCT for RT treatment. Prompt review of the lung windows is recommended in order to identify such changes, with the hope that pre-symptomatic diagnosis leads to expedited patient management, improved outcomes, and a reduction of inadvertent COVID-19 dissemination.

Running Title: Covid-19 Consistent Changes Detected on CBCT Introduction: COVID-19 profoundly impacted the United States, with New York City (NYC) rapidly becoming the epicenter of the disease. Cancer patients represent a vulnerable population in this pandemic, with data suggesting a higher risk for severe events and unfavorable outcomes.

Timely identification of COVID-19 in cancer patients has been thwarted by the lack of outpatient testing for SARS-CoV-2. Chest computed tomography (CT) plays a major role in the identification of COVID-19 pneumonia, with radiologic hallmarks including bilateral, peripheral ground-glass opacities (GGOs) and consolidation. Cancer patients undergoing radiotherapy (RT) commonly have daily cone beam computed tomography (CBCT) obtained for image-guided radiotherapy (IGRT), and such imaging frequently includes the chest.

We retrospectively reviewed the CBCTs of an initially asymptomatic patient undergoing IGRT for breast cancer, who developed COVID-19 symptoms during the second week of RT. Lung windows of daily CBCTs were reviewed with Diagnostic Radiology to survey for changes consistent with COVID-19. Diagnostic CTs obtained at the time of recovery were obtained and compared with the CBCTs. Since the initial cases of COVID-19 were reported in December 2019 in Wuhan, China

[1], the SARS-CoV-2 virus disseminated internationally, rapidly reaching pandemic proportions.

The United States has reported the largest number of cases worldwide and New York City has become the epicenter of the crisis [2] . In the face of COVID-19, cancer patients represent a particularly vulnerable population with data suggesting a higher risk for severe events such as ICU admission, ventilator requirement, or death compared to the general population [3, 4] . There is a wide variation in clinical presentation with up to 80% of patients estimated to be asymptomatic [5] , and the remainder experiencing symptoms ranging from transient fever, dry cough, and dyspnea, to respiratory failure, multi-organ failure, and death [6] . Rare symptoms including anosmia and ageusia, as well as gastrointestinal symptoms have also been described [7, 8] . Adverse outcomes and death are more common in the elderly and those with comorbidities, with a fatality rate ranging from 4-11% [9] .

There have been several reports documenting the pulmonary imaging abnormalities associated with COVID-19, including in the setting of subclinical disease [10] [11] [12] [13] . A study from

China reported on temporal patterns of SARS-CoV-2 pneumonia on computed tomography (CT); the most common CT patterns in such patients were ground-glass opacities (GGO), air bronchograms, crazy-paving patterns, and thickening of the adjacent pleura [10] . Cone Beam Computed Tomography (CBCT) is a medical imaging technique capturing cone-shaped X-ray beam images that are reconstructed to form a 3D axial representation of the patient [14] . CBCT is one of many image-guided radiotherapy (IGRT) tools used for the verification of patient set-up to ensure accurate radiotherapy (RT) delivery [15] . In patients undergoing breast or thoracic RT, the lungs are encompassed in the daily CBCT, allowing the unique opportunity to monitor lung findings over several weeks. Typically, bone and soft tissue windows are utilized to allow for anatomic matching on specified structures for RT targeting. However, timely review of lung windows on CBCT may afford the opportunity to assess for lung changes indicative of asymptomatic SARS-CoV-2 infection.

Patients undergoing RT must present to a health care facility for treatment as delay, interruption, and/or premature termination of RT is associated with suboptimal oncologic outcomes [16] [17] [18] [19] . Unfortunately, daily travel to a health care facility increases the risk of exposure to SARS-CoV-2 and, in the case of asymptomatic patients, inadvertent dissemination of the virus to other patients, healthcare professionals, and administrative staff. Rapid recognition of COVID-associated lung abnormalities on routine daily CBCTs may allow for early clinical assessment and the prompt initiation of appropriate precautions and/or treatment for these patients. The purpose of this case-report is to describe an initially asymptomatic patient in our radiation oncology clinic who was noted to have imaging changes consistent with SARS-CoV-2 pulmonary changes on CBCT prior to the onset of symptoms.

The patient is a 63-year-old female diagnosed as having pathologic T2N0M0, moderately differentiated invasive ductal carcinoma of the right breast, ER+/PR+/HER2-. The patient was treated with lumpectomy and sentinel-lymph node biopsy, to be followed by adjuvant after symptom onset, she reported a transient mild dry cough, dysgeusia ("everything tastes salty") and dysosmia ("smelling coffee all day"). The patient defervesced on the 8 th day after symptom onset and she was no longer symptomatic. On the 11 th day after symptom onset, the patient met our departmental criteria for resuming RT with the appropriate precautions for COVID-recovered patients. CBCT that day showed substantial worsening of the GGO, bilaterally ( Figure 2 ). The case was reviewed with Diagnostic Radiology and Infectious Disease;

given the severity of the radiologic findings and the unknown consequence of RT in a patient recovering from probable SARS-CoV-2 pneumonia, it was decided to hold RT again and obtain serial diagnostic imaging in order to monitor the progression of lung disease.

The patient underwent diagnostic CT chest on the 13 th day after symptom onset, demonstrating bilateral peripheral GGO most prominent on the right side, as well as lymph nodes in the pre-tracheal space and AP window measuring up to 1.2cm (Figure 3 , Column A).

Diagnostic impression was consistent with a viral pneumonitis, including COVID-19 pneumonia.

Comparison made with CBCT from two days prior showed stable to improved pulmonary findings. Repeat diagnostic CT chest was performed on the 16 th day after symptom onset, demonstrating improvement in bilateral, peripheral GGOs with decreased lymphadenopathy, suggesting an amelioration (Figure 3 , Column B). The patient resumed RT and remained asymptomatic with continued improvement in her pulmonary GGO on subsequent CBCTs.

COVID-19 infection disproportionately impacts patients with underlying comorbidities, including cancer [21] . Given that cancer patients require frequent medical visits to treatment facilities, the risk of inadvertent dissemination of COVID-19 poses a serious threat to this vulnerable patient population. Adding to this challenge is the covert nature of the SARS-CoV-2 virus, with rates of asymptomatic infection being reported as high as 80%. Up to 50% of asymptomatic patients can have radiographic abnormalities prior to the onset of symptoms [22] .

Radiographic imaging findings are important in the diagnosis and treatment of this disease. In cancer patients receiving CBCT as part of their RT, review of lung windows to screen for COVID-19 changes could lead to early detection of the infection in asymptomatic patients.

Studies have described the radiographic characteristics of distinct groups of patients and temporal changes associated with disease progression [10] . The imaging features of this viral pneumonia are diverse, typically ranging from normal appearance to diffuse changes in the lungs; patients with multiple comorbidities are more likely to have bilateral and diffuse disease [10] . Overall, there is a slight predilection for the right lower lobe. The extent of disease on CT increases gradually from the subclinical period throughout the first 3 weeks, then decreases thereafter [10] , but radiographic changes may continue to evolve beyond 26 days of symptoms [10, 12] . Asymptomatic patients are more likely to have unilateral, multifocal GGOs. After symptom onset, bilateral and diffuse GGOs are predominant. In the progressive stage, GGOs are relatively decreased in frequency, with a transition to consolidation and mixed-pattern development. As the disease peaks, GGOs decrease further, and peak lung involvement is characterized by increasing crazy-paving patterns, reticulation, along with bronchiolectasis and thickening of the adjacent pleura. The resolving stage demonstrates decreasing consolidation and absence of crazy-paving patterns following the first 2-3 weeks of disease [11] [12] [13] [23] [24] [25] . Our patient's radiographic changes were generally consistent with the above findings; during the subclinical period, GGO's were predominantly located in the peripheral right lower lobe and progressed in the symptomatic stage to become more diffuse and bilateral. Based on our patient's available imaging, her CT lung abnormalities appeared to peak in severity approximately 11 days after symptom onset, followed by gradual resolution of GGO's as demonstrated in her diagnostic CTs ( Figure 3 ).

Radiographic evolution of the disease typically mirrors the clinical course, with time to medical ventilation and intensive-care unit admission paralleling the severity of CT findings [26] . Timely detection has been shown to be associated with improved clinical outcomes and prognosis [27] . One retrospective series demonstrated as many as 75% of patients with negative RT-PCR COVID-19 testing had positive CT findings; some patients continued to test negative on repeat RT-PCR before eventually testing positive, indicating CT findings may have greater sensitivity than RT-PCR. Interestingly, 40% of patients had improvement in CT findings prior to serial RT-PCR results converting from positive to negative [13] , suggesting RT-PCR results lag behind radiographic findings.

Patients undergoing therapeutic radiation typically undergo radiographic confirmation of set-up prior to treatment delivery. Modalities include KV port-films using 2D x-ray and/or conebeam CT scans [15, 28] . 

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