Once a remedy, later a disease

KC Shikha; Sudin Koshy; Padmanabhan Arjun

doi:10.4103/jalh.jalh_33_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 68-71

Once a remedy, later a disease

KC Shikha, Sudin Koshy, Padmanabhan Arjun
Department of Respiratory Medicine, KIMS Health, Thiruvananthapuram, Kerala, India

Date of Submission	23-Oct-2022
Date of Acceptance	13-Nov-2022
Date of Web Publication	02-May-2023

Correspondence Address:
Dr. Sudin Koshy
Department of Respiratory Medicine, KIMS Health, Anayara P.O., Thiruvananthapuram - 695 029, Kerala
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jalh.jalh_33_22

Abstract

Radiation-induced lung injury (RILI) encompasses any lung toxicity induced by radiation therapy (RT). It manifests acutely as radiation pneumonitis (RP) and chronically as radiation pulmonary fibrosis. It is usually seen in patients who have undergone thoracic irradiation for the treatment of lung, breast, or hematologic malignancies. The volume of lung irradiated and the mean lung dose are important risk factors. The diagnosis is usually based on a combination of typical symptoms (e.g., cough, dyspnea, and occasionally fever), timing, dose, and location of radiation therapy, compatible imaging findings, and exclusion of other causes. We report a case of a patient with breast cancer, who had received locoregional radiotherapy (RT) and then palliative RT for metastasis in the rib, following which she developed symptoms and radiological manifestations consistent with RILI. The patient recovered clinically and radiologically with conservative management. It was important to accurately diagnose the entity early since RP with moderate-to-severe symptoms and impaired respiratory function needs to be treated early to prevent irreversible lung damage.

Keywords: Once a remedy, later a disease

How to cite this article:
Shikha K C, Koshy S, Arjun P. Once a remedy, later a disease. J Adv Lung Health 2023;3:68-71

How to cite this URL:
Shikha K C, Koshy S, Arjun P. Once a remedy, later a disease. J Adv Lung Health [serial online] 2023 [cited 2023 Jun 10];3:68-71. Available from: https://www.jalh.org//text.asp?2023/3/2/68/375536

Introduction

Radiation-induced lung injury (RILI) which could present acutely as radiation pneumonitis (RP) or chronically as radiation pulmonary fibrosis is to be suspected in patients with symptoms such as cough, dyspnea, and fever postirradiation. The timing of radiation, dose, site of radiation therapy, and compatible imaging findings provide the clue for diagnosis. This entity requires a high index of suspicion, as those patients who develop severe symptoms with pulmonary function impairment if left untreated are at risk of developing irreversible lung damage.

Here, we report a case of RILI in a patient with breast cancer, who had received locoregional radiation therapy (RT) in 2019, followed by palliative RT for a lytic lesion in her rib in 2021, following which her lung injury manifested 4 weeks postirradiation.

Case Report

A 70-year-old woman, who is known to have Type 2 diabetes mellitus, systemic hypertension, and asthma, incidentally detected a lump in her left breast. On evaluation, trucut biopsy revealed a signet-ring cell variant of invasive lobular carcinoma and she underwent left modified radical mastectomy with axillary lymph node dissection in 2018. Histopathology examination showed Grade 3 pleomorphic lobular carcinoma with metastasis to lymph node. Triple negative on immunohistochemistry. She received adjuvant chemotherapy with five cycles of doxorubicin + cyclophosphamide and four cycles of paclitaxel, followed by adjuvant radiotherapy by image-guided intensity-modulated radiotherapy and gating – 23 cycles with 46 Gy in 2019.

During her follow-up visit in September 2021, she was found to have swelling in the supraclavicular region. Fluorodeoxyglucose-positron emission tomography scan revealed an intense lytic lesion with a soft-tissue component of the right first rib. Biopsy of the same was consistent with metastasis from pleomorphic lobular carcinoma breast. For this, she received palliative RT-five cycles, 20 Gy.

Four weeks postradiation, she presented with complaints of shortness of breath, fatigue, and cough with mucoid expectoration for 10 days. It was not associated with fever or wheezing. She was not hypoxic. Physical findings were unremarkable except for fine inspiratory crackles in the right infraclavicular area. Initially, a diagnosis of a lower respiratory infection was considered.

On evaluation, the C-reactive protein level was elevated, with a white blood cell count of 9000 cells/mm³. Chest X-ray showed right upper zone haziness [Figure 1]. Computed tomography of the thorax revealed a ground glassing and interlobular septal thickening. High-resolution computed tomography (HRCT) showed air-space opacity in the right upper lobe in paramediastinal distribution with traction bronchiectasis corresponding to the area of irradiation [Figure 2]. HRCT coronal view showed volume loss of the right upper lobe and traction bronchiectasis [Figure 3].

Figure 1: Chest X-ray showing right upper zone haziness – 4 weeks postradiation

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Figure 2: HRCT of the thorax axial view showing ground glassing with interlobular septal thickening involving the right upper lobe. Air-space opacity in the right upper lobe in paramediastinal distribution with traction bronchiectasis corresponding to the area of irradiation. HRCT: High-resolution computed tomography

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Figure 3: HRCT coronal view showing volume loss of the right upper lobe and traction bronchiectasis. HRCT: High-resolution computed tomography

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At this point, the differentials considered were infective causes including pulmonary tuberculosis considering her immunocompromised state and upper lobe lung lesion or metastatic spread of the primary tumor. Our third differential was RP considering the temporal relationship between the timing and location of radiotherapy, although her previous thoracic radiation did not result in the same.

Her HRCT of the thorax was compared with the previous HRCT has taken on July 2021, which showed normal lung parenchyma. Sputum smear for acid-fast bacilli, Mycobacterium tuberculosis, and cartridge-based nucleic acid amplification test and sputum cytology were negative. Sputum and blood cultures were sterile. A provisional diagnosis of subacute RP was made and she was given supportive care and antitussives. A bronchoscopy was planned in the event if she did not show improvement or showed persistent symptoms. However, she improved on supportive care, and a repeat chest radiograph after 3 months showed near-total resolution of the right upper zone opacity [Figure 4], thus supporting our diagnosis of subacute RP.

Figure 4: Repeat chest radiograph after 3 months showed near-total resolution of the right upper zone opacity

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Discussion

RILI is usually encountered in patients who receive thoracic irradiation for breast, lung, or hematological malignancies. The pathogenesis is uncertain but appears to involve both direct lung tissue toxicity and inflammatory response.^[1] Two distinct forms, namely, RP and radiation fibrosis are described depending on the time of onset of symptoms and radiographic infiltrates, after exposure to radiation.

Symptoms associated with subacute RP usually develop 4–12 weeks following irradiation but symptoms of late or fibrotic RP usually develop after 6–12 months. Typical symptoms include dyspnea, cough, chest pain, fever, and malaise.

Acute RP typically develops following exposure to doses ≥8 Gy of low linear energy transfer radiation, with a latent period (up to 4 weeks): an exudative phase (3–8 weeks) and an acute pneumonitic phase (2–6 months).^[2] The risk factors for the development of RILI include the volume of lung irradiated, dose of radiation, time-dose factor, and method of irradiation.

In breast cancer, pneumonitis is rare when treatment is restricted to the chest wall after mastectomy or to the intact breast after conservative surgery, although a small, insignificant, restrictive ventilatory impairment may occur. When the supraclavicular fossa and axilla are also treated and the volume includes the lung apex, the incidence of sporadic pneumonitis increases from 0.9% to 4.1%.^[3] It has also been studied that there is an increased incidence of RP among patients treated with local-regional radiotherapy versus those receiving local RT only.^[4] This is demonstrated in our case, where initial locoregional RT did not result in pneumonitis, whereas the same developed after she received palliative RT for a lytic rib lesion.

The diagnosis of RILI is usually based on the presence of typical symptoms, temporal relation to radiotherapy, information regarding dose and location of irradiation, compatible imaging findings, and most importantly exclusion of other causes. These include infection, heart failure, pulmonary embolism, drug-induced pneumonitis, bleeding, and progression of the primary tumor. Among laboratory parameters, a low-grade peripheral blood polymorphonuclear leukocytosis maybe present, and the sedimentation rate, serum lactic dehydrogenase, and C-reactive protein may be modestly elevated. Procalcitonin is typically low, but all these findings are nonspecific.

The key step in diagnosis is the comparison of pretreatment radiographic images with diagnostic images obtained at the time of symptom presentation. Lung involvement in RP typically aligns closely with the irradiated area.

Patients who are asymptomatic or have minimal symptoms may experience a spontaneous resolution. It is advisable to monitor these patients at regular intervals with the assessment of symptoms, chest radiography, and pulmonary function as indicated. Patients may benefit from supportive care, such as antitussive therapy.^[3] Oral glucocorticoids are suggested for patients with a sub-acute onset of RP with moderate to severe symptoms and evidence of impaired respiratory function. A number of experimental agents such as pentoxifylline,^[5] colchicine, and angiotensin-converting enzyme inhibitors^[6] are being assessed.

Preventive strategies include those that limit the radiation dose and volume of normal lung tissue irradiated. It is suggested that the mean lung dose should be kept below 20 Gy, when possible, and the volume of lung receiving more than 20 Gy (V20) should be kept below 35%–40% to keep the risk of pneumonitis ≤20%.^[7]

This case is reported to emphasize the need to have a high index of suspicion for RILI in patients who present with dyspnea, cough, chest pain, fever, and malaise in the postradiation phase. This case also demonstrates that although chest wall radiation in breast cancer patients does not usually lead to lung injury, the same can occur if the radiation field involves the supraclavicular fossa and hence should still be one of the differentials in such patients.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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