AJTCCM VOL. 30 NO. 2 2024 69
CORRESPONDENCE: CASES
To the editor: Stereotactic body radiotherapy (SBRT) oers small
fractions of focused high-dose radiation to a targeted lesion with
high accuracy.[1] Excellent local tumour control with minimal normal
tissue toxicity can be achieved with SBRT. However, despite accurate
targeting, normal tissues near the tumour can receive higher doses
of radiation than with standard treatment, which can cause harm
if the structures are exceptionally radiosensitive. In central airway-
located lesions, particularly in the ‘no-y zone’, dened asa 2 cm
radius around the proximal bronchial tree, the chances of SBRT
toxicity to adjacent structures are therefore relatively high, especially
with higher radiation doses.[2,3] One of the significant airway
complications of SBRT is airway necrosis with or without stenosis,
strictures or stulas.[4] We present a case of stage IV squamous cell
lung cancer in which tracheal necrosis developed aer SBRT.
A 70-year-old man, an ex-smoker, was diagnosed in late 2020 with
squamous cell carcinoma of the lung, stage IVA (cT2a N1 M1b). A
positron emission tomography-computed tomography (PET-CT) scan
showed intense uorodeoxyglucose uptake in a large right upper lobe
lesion and focal intense uptakes in a few nodules in the superior and
apical segments of the right lower and le upper lobes, respectively. A
percutaneous core biopsy specimen from the right upper lobe lesion
showed poorly dierentiated carcinoma with squamous morphology,
and immunohistochemistry conrmed squamous cell carcinoma of
the lung. e patient had no driver mutations on the comprehensive
genomic molecular prole, and the programmed cell death ligand 1
(PD-L1) tumour proportion score was 90%. He therefore received
four cycles of palliative chemoimmunotherapy with carboplatin (area
under the curve 5) every 3 weeks, nab-paclitaxel 100 mg/m2 on days
1, 8 and 15, plus pembrolizumab 200 mg every 3 weeks for four cycles
with an excellent partial response. He was subsequently continued on
maintenance pembrolizumab every 6 weeks. However, regional nodal
oligometastatic lesions were detected in the right lower paratracheal
lymph nodes aer 12 months at follow-up PET-CT. e patient was
oered SBRT, a total dose of 60 Gy in eight fractions, in late 2021.
Subsequent imaging showed a complete response, so pembrolizumab
was continued.
Fourteen months later, in February 2023, the patient presented
with a cough and mild haemoptysis of 1 month’s duration. e
cough was dry and did not respond to symptomatic measures. He
did not have other symptoms and was feeling well otherwise. On
examination, he was stable and was not in respiratory distress. His
vital signs were within normal limits. Oxygen saturation was 96%
on room air. e sputum looked yellowish and was stained with
blood. Chest examination was unremarkable, with normal breath
sounds bilaterally. Routine laboratory values were within normal
limits. A CT scan of the chest showed a subtle disruption in the
wall of the medial aspect of the lower part of the trachea with
loss of the C-shaped tracheal cartilage (Fig.1A).Bronchoscopy
showed a focal area of inamed mucosa lined by a thick layer of
yellowish secretions/crust on the right anterolateral wall of the
lower trachea just above the carina (Fig.1B). Multiple biopsies were
taken. Histopathological examination revealed granulation tissue
with necrosis and destruction of the cartilage and a few bacterial
colonies in the background (Fig.1C). There was no growth in
Tracheal necrosis aer sandwich immunotherapy and stereotactic
body radiotherapy for lung cancer
A
B
C
Fig.1. (A) Computed tomography scan of the chest, so-tissue view,
showing disruption of the medial aspect of the lower part of the
trachea with loss of the C-shaped tracheal cartilage (arrow). (B) Focal
area of creamy-coloured mucosa in the right anterolateral wall of the
lower trachea just above the carina. (C) Histopathology specimen
demonstrating necrotic cartilage (red arrow), inammatory granulation
tissue (yellow arrow) and bronchial epithelium (H&E × 200).
70 AJTCCM VOL. 30 NO. 2 2024
CORRESPONDENCE: CASES
fungal and tuberculosis cultures of the biopsy sample, while the
bacterial culture grew Corynebacterium amycolatum, which is
commonly found in the normal microbiome of the human skin and
mucosal membranes. However, it has been regarded as a potential
opportunistic pathogen in immunocompromised patients.[5]
Multidisciplinary team discussion favoured a diagnosis of tracheal
necrosis with superimposed infection based on the clinical and
pathological features, and the patient was therefore treated with
broad-spectrum antibiotics for 4 weeks. He had an excellent clinical
response and reported no more cough or haemoptysis on follow-up
at 8 weeks. Bronchoscopy was not repeated, as he was asymptomatic
and had returned to normal activities. He also completed 35 cycles
of pembrolizumab and has since been in remission.
Tracheal necrosis is a rare condition that can occur in
immunocompromised patients, usually due to an infective aetiology,
including fungal infections such as Aspergillus and infections with
bacterial organisms such as Actinomyces. Other causes include
tracheostomy, neck surgery and radiation.[6-8] Airway damage due
to SBRT is a late complication, usually occurring after months
of treatment.[9] The pathogenesis of airway necrosis is not well
understood, but it seems that the radiation causes direct damage to
the wall of the airways, leading to necrosis and subsequent brosis.
A protracted fractionation scheme is therefore advised for treating
centrally located tumours to avoid these complications. Patients who
received concurrent antivascular growth factor therapy were found to
have an increased risk of post-SBRT toxicity.[10] Possible associations
between SBRT-induced pneumonitis and immune checkpoint
inhibitors have been reported.[11,12] Whether immune checkpoint
inhibitors contributed to the SBRT-induced tracheal injury in our
patient needs to be discussed, especially as the dose was delivered
during a longer time frame, eight fractions, to reduce the chances of
late toxicity in this no-y zone.
The radiological findings in tracheal necrosis can be subtle,
and bronchoscopy is often required to confirm the diagnosis.
The bronchoscopic finding of a focal yellowish thick crusty
lining is nonspecic for necrotising tracheitis and can be seen in
endobronchial tuberculosis, invasive fungal infections, primarily
Aspergillus or Candida, and infections due to other bacteria,
including Staphylococcus aureus and Haemophilus inuenzae. It
occurs less commonly in viral infections such as herpes simplex,
cytomegalovirus and inuenza B, and sometimes in inammatory
lesions secondary to systemic illness such as ulcerative colitis.
Cultures from our patient’s bronchoscopy specimens were not
definitive, the biopsy specimen showing only destruction and
granulation without any evidence of malignant spread. e diagnosis
is usually made at an advanced stage with signicant tissue damage
and anatomical distortion.
In conclusion, despite advances in interventional pulmonology,
treating complications such as anatomical deformations, strictures
and stulas can be challenging. Hyperbaric oxygen therapy, local
debridement and antibiotics in combination have been used
successfully to treat complicated tracheal radionecrosis.[13] The
mainstay of treatment is still a conservative approach. However,
surgery for tracheal necrosis can be oered on a case-by-case basis.
In airway stenosis and strictures, balloon dilatation with or without
airway stenting can also be considered.
S M Bennji, MB ChB, MMed (Int), FCP (SA), Cert Pulmonology
(SA), MPhil (Pulm), Dip (ERS)
oracic Oncology, Sultan Qaboos Comprehensive Cancer Care and
Research Centre, Muscat, Oman
saminj12@gmail.com
B Jayakrishnan, BSc, MBBS, MD, DTCD, DNB, MRCP, FRCP,
FCCP, FICS
oracic Oncology, Sultan Qaboos Comprehensive Cancer Care and
Research Centre, Muscat, Oman
Z Al-Hashami, MD, FRCP
oracic Oncology, Sultan Qaboos Comprehensive Cancer Care and
Research Centre, Muscat, Oman
L Mula-Hussain, MB ChB, MSc, EF, FRCP (Edin)
Radiation Oncology, Sultan Qaboos Comprehensive Cancer Care and
Research Centre, Muscat, Oman
R B Telugu, MBBS, MD, DipRCPath
Onco-Pathology, Sultan Qaboos Comprehensive Cancer Care and
Research Centre, Muscat, Oman
1. Lo SS, Fakiris AJ, Chang EL, etal. Stereotactic body radiation therapy: A novel
treatment modality. Nat Rev Clin Oncol 2010;7(1):44-54. https://doi.org/10.1038/
nrclinonc.2009.188
2. Timmerman R, McGarry R, Yiannoutsos C, etal. Excessive toxicity when treating
central tumors in a phase II study of stereotactic body radiation therapy for medically
inoperable early-stage lung cancer. J Clin Oncol 2006;24(30):4833-4839. https://doi.
org/10.1200/JCO.2006.07.5937
3. Lindberg K, Onjukka E. Medical consequences of radiation exposure of the bronchi
– what can we learn from high-dose precision radiation therapy? J Radiol Prot
2021;41(4). https://doi.org/10.1088/1361-6498/ac28ef
4. Song SY, Choi W, Shin SS, etal. Fractionated stereotactic body radiation therapy for
medically inoperable stage I lung cancer adjacent to central large bronchus. Lung
Cancer 2009;66(1):88-93. https://doi.org/10.1016/j.lungcan.2008.12.016
5. Jesus HNR, Rocha DJPG, Ramos RTJ, etal. Pan-genomic analysis of Corynebacterium
amycolatum gives insights into molecular mechanisms underpinning the transition
to apathogenic phenotype. Front Microbiol 2022;13:1011578. https://doi.org/10.3389/
fmicb.2022.1011578
6. Aerni MR, Parambil JG, Allen MS, Utz JP. Nontraumatic disruption of the
brocartilaginous trachea: Causes and clinical outcomes. Chest 2006;130(4):1143-
1149. https://doi.org/10.1378/chest.130.4.1143
7. Louie BH, Stramiello J, Senyei G, etal. Necrotizing tracheitis complicated by tracheal
wall perforation. Ear Nose Throat J 2022;101(10_Suppl):26S-29S. https://doi.
org/10.1177/01455613221123664
8. Warrior K, Pandya S, Tran B. Tracheal necrosis: A pathologic mediastinal window. Am
J Respir Crit Care Med 2017;195:A6043. https://www.atsjournals.org/doi/abs/10.1164/
ajrccm-conference.2017.195.1_MeetingAbstracts.A6043 (accessed 8 May 2024).
9. Corradetti MN, Haas AR, Rengan R. Central-airway necrosis aer stereotactic body-
radiation therapy. N Engl J Med 2012;366(24):2327-2329. https://doi.org/10.1056/
nejmc1203770
10. Haseltine JM, Rimner A, Gelblum DY, etal. Fatal complications aer stereotactic body
radiation therapy for central lung tumors abutting the proximal bronchial tree. Pract
Radiat Oncol 2016;6(2):e27-e33. https://doi.org/10.1016/j.prro.2015.09.012
11. Louvel G, Bahleda R, Ammari S, etal. Immunotherapy and pulmonary toxicities:
Can concomitant immune-checkpoint inhibitors with radiotherapy increase
the risk of radiation pneumonitis? Eur Respir J 2018;51(1):1701737. https://doi.
org/10.1183/13993003.01737-2017
12. Tian S, Switchenko JM, Buchwald ZS, etal. Lung stereotactic body radiation therapy
and concurrent immunotherapy: A multicenter safety and toxicity analysis. Int J Radiat
Oncol Biol Phys 2020;108(1):304-313. https://doi.org/10.1016/j.ijrobp.2019.12.030
13. Ariza-Prota M, Morales A, Grajeda J, etal. Successful healing of tracheal radionecrosis:
Role of hyperbaric oxygen therapy. Chest 2016;150(6):e147-e150. https://doi.
org/10.1016/j.chest.2016.03.027
Received 18 October 2023. Accepted 25 March 2024. Published 4 July 2024.
Afr J Thoracic Crit Care Med 2024;30(2):e1620. https://doi.
org/10.7196/AJTCCM.2024.v30i2.1620
