Hypofractionated radiotherapy for a feline tracheal epithelial tumour

Abstract

Case summary

An 8-year-old spayed female Ragdoll cat presented with a several-month history of coughing and exertional dyspnoea. Initial treatment for presumed feline asthma was unsuccessful. Thoracic CT revealed an intraluminal mass at the carina and complete atelectasis of the right middle lung lobe. Endoscopy initially identified an intraluminal mass. As biopsy was considered unsafe owing to the risk of acute airway obstruction, brush cytology was performed instead; however, it was non-diagnostic. As a result of progressive obstructive respiratory failure, urgent palliative radiation therapy was initiated (6 Gy × 6 fractions weekly; total dose 36 Gy). By the fourth fraction, the cat showed marked clinical improvement, and imaging confirmed tumour shrinkage. Before the fifth fraction, endoscopic biopsies were repeated and histopathology established a diagnosis of an epithelial malignant tumour, most consistent with adenocarcinoma. Toceranib phosphate was introduced on an alternate-day schedule as adjuvant therapy. The short-term outcome was favourable, with resolution of clinical signs. The cat remained clinically well more than 150 days after the start of radiation therapy.

Relevance and novel information

Primary tracheal tumours are rare in cats, and treatment protocols are not well defined. Surgical excision of masses involving the carina is technically challenging, and radiation therapy for this location has not previously been reported. In this case, a short course of hypofractionated radiation therapy rapidly alleviated airway obstruction, allowing stabilisation of ventilation and subsequent histopathological confirmation. This staged diagnostic–therapeutic approach highlights the utility of hypofractionated radiation therapy as an emergency airway-sparing treatment for cats with obstructive tracheal tumours.

Plain language summary

Radiation therapy helped a cat breathe again after a tracheal tumour blocked her airway

An 8-year-old Ragdoll cat developed a persistent cough and shortness of breath that worsened over several months. Initial treatment for suspected feline asthma did not help. Radiographs and CT scans revealed a mass growing inside the windpipe (trachea), at the point where it divides into the main bronchi. This tumour was blocking airflow and causing collapse of one lung lobe. Because surgery at this location is difficult and risky, the veterinary team decided to use radiation therapy to shrink the mass and restore breathing. The cat received a total of six radiation treatments (6 Gy each, once a week). After just a few sessions, the cat’s breathing improved, coughing stopped, and appetite and activity returned to normal. Follow-up imaging showed that the tumour had become much smaller and that the collapsed lung had reinflated. A biopsy performed later confirmed that the tumour was a type of epithelial cancer, most likely an adenocarcinoma. After radiation therapy, the cat received an oral targeted anticancer drug (toceranib phosphate) to help prevent recurrence. More than 5 months after treatment, the cat continues to do well, with no breathing difficulty or visible tumour regrowth. This case is important because tracheal tumours are very rare in cats, and treatment guidelines are limited. Radiation therapy provided fast relief from life-threatening airway obstruction and allowed for later diagnostic confirmation. The results suggest that carefully planned, short-course (hypofractionated) radiation therapy can be an effective and safe emergency treatment for cats with airway-blocking tumours when surgery is not possible.

Introduction

Primary tracheal tumours in cats are extremely rare. Among the histological types described are adenocarcinoma, squamous cell carcinoma and lymphoma.^{1 –4} Recent retrospective and systematic studies have shown that lymphoma is the most common histological subtype in cats, consistently outnumbering epithelial tumours.^{5 –7} Owing to their anatomical location, these tumours can cause upper airway obstruction, often requiring invasive diagnostic or therapeutic procedures carrying substantial anaesthetic and respiratory risks, potentially leading to fatal outcomes.^2,8 Although lymphoma may respond favourably to chemotherapy,^3,5,6 epithelial tumours (adenocarcinoma and squamous cell carcinoma) are generally considered less responsive to systemic treatments. For intratracheal masses that are not amenable to surgical excision, radiation therapy (RT) can offer a possible alternative treatment option. In feline tracheal adenocarcinoma, there are isolated reports of long-term survival after definitive fractionated RT, as well as cases achieving disease control with re-irradiation and adjunctive use of targeted therapies at recurrence. ¹

Case description

An 8-year-old spayed female Ragdoll cat was presented with decreased activity, chronic coughing and dyspnoea. The coughing episodes, once initiated, lasted several minutes. Before referral, the cat had exhibited coughing and dyspnoea for approximately 5 months and had been treated for presumed feline asthma with prednisolone (0.5 mg/kg SC q12h) and terbutaline hydrochloride (0.1 mg/kg PO q12h), but clinical signs did not improve. On initial examination, the cat weighed 3.4 kg, with a rectal temperature of 38.3°C, heart rate of 180 beats/min and respiratory rate of 72 breaths/min. Thoracic radiographs revealed a soft tissue opacity at the carina (Figure 1) and demonstrated evidence of rib fractures consistent with trauma from persistent coughing. CT identified an intraluminal mass at the carina with complete atelectasis of the right middle lung lobe (Figure 2a). Tracheobronchoscopy revealed a broad-based mass occupying the carinal region and copious mucopurulent secretions (Figure 3a). Given the high risk of haemorrhage and resulting acute airway compromise, debulking or biopsy by snare was considered unsafe; therefore, only brush cytology was performed. Cytology revealed inflammatory changes dominated by bacteria and clusters of epithelial cells but was insufficient for definitive diagnosis of malignancy.

Figure 1

(a) Thoracic radiograph in ventral recumbency showing increased opacity of the right middle lung lobe, consistent with atelectasis. (b) Thoracic radiograph in right lateral recumbency demonstrating an intraluminal radiopaque mass at the carina, with concurrent chronic rib fractures likely secondary to prolonged coughing

Figure 2

Axial thoracic CT images (window level 50 Hounsfield units [HU], window width 300 HU). (a) Pre-radiotherapy axial CT image showing a soft tissue-attenuating mass at the carina arising ventrally (yellow arrow). The oesophagus is dilated secondary to aerophagia (red arrow). (b) After four fractions of radiotherapy, the trachea is markedly expanded, with only a small residual mass remaining (yellow arrow). Oesophageal dilatation is no longer evident

Figure 3

Bronchoscopic images. (a) Pre-radiotherapy bronchoscopic image showing a mass nearly occluding the tracheal lumen, associated with profuse mucus. (b) After four fractions of radiotherapy, the carina is clearly visualised and the mass has markedly regressed

Based on the clinical progression and high suspicion of malignancy, three-dimensional conformal radiation therapy (CRT) was initiated with the mass treated with a single 6 Gy fraction. Radiation therapy was delivered under CT-based simulation (Aquilion LB; Canon Medical Systems) with treatment planning performed using Monaco v6.1.3.0 (Elekta). Irradiation was delivered using a linear accelerator (Infinity; Elekta) with a 6 MV flattened photon beam. The gross tumour volume was contoured as equal to the clinical target volume (CTV), and a uniform 5 mm margin was applied to generate the planning target volume (PTV). The cat was immobilised in a vacuum cushion (VACUFORM 2.0 half body; BuW Schmidt) in sternal recumbency. Image-guided set-up verification was performed before each fraction using kilovoltage cone beam computed tomography to confirm isocentre alignment with reference landmarks. A multi-field three-dimensional CRT plan was generated with multileaf collimator shaping and margin expansion to encompass the PTV. For safety management, supplementary oxygen and emergency airway access equipment were prepared, and respiratory status was evaluated before each treatment fraction. Concurrently, amoxicillin (10 mg/kg PO q12h) was prescribed as a therapeutic measure to control secondary bacterial infection associated with the mucopurulent secretions.

Within several days of the first irradiation, the cat’s cough rapidly decreased, dyspnoea resolved and activity increased. By day 7 after irradiation, appetite had improved and body weight began to increase. At the owner’s request, a course of hypofractionated RT (6 Gy × 6 fractions, once weekly; total dose 36 Gy) was continued. By the fourth fraction, the cat showed marked clinical improvement, and imaging confirmed tumour shrinkage. Before the fifth fraction (day 29), repeat tracheobronchoscopy was performed with additional sampling. Grossly, the mass was notably reduced in size (Figure 3b) and both mainstem bronchi were clearly visible (Figure 2b). Endoscopic biopsies were obtained using biopsy forceps without complication.

Histopathological examination of the tracheal biopsy revealed neoplastic cells proliferating in trabecular and reticular patterns with mild atypia and frequent mitoses, lacking goblet cells (Figure 4). Owing to the small and fragmented biopsy specimen, reliable assessment of invasiveness and mitotic index could not be performed. Immunohistochemistry was not performed. These findings strongly suggest an epithelial tumour, most consistent with adenocarcinoma. By day 34 after the first fraction, coughing was minimal and body weight had increased to 3.86 kg. Follow-up CT after completion of six fractions demonstrated further reduction of the tracheal mass, re-expansion of the bronchial lumen and resolution (reinflation) of the right middle lobe atelectasis. Toceranib phosphate (2.6 mg/kg PO q48h) was initiated as adjuvant therapy. Mild myelosuppression (Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events grade 1–2) was observed, but no associated clinical signs developed. As of 120 days after the initial RT, the cat remains clinically well with good quality of life.

Figure 4

Tracheal biopsy specimen showing neoplastic epithelial cells arranged in trabecular and reticular patterns, with mild atypia and frequent mitoses (arrowheads). Goblet cells are absent. Haematoxylin and eosin stain. Bar = 100 μm

Discussion

The present case, involving a cat with advanced disease due to diagnostic delay, provides valuable information to the very limited literature by describing the application of urgent hypofractionated RT, the subsequent diagnostic process and short-term outcome assessment. Primary tracheal tumours in cats are exceptionally rare, with the literature consisting mainly of isolated case reports and very small series spanning several decades.^{1 –3,8,9} In the largest available series (n = 8), the authors emphasised that this represented a disproportionately high number compared with the entire published record, and that overall prognosis was guarded to grave, with most cats surviving less than 1 month after treatment; severe respiratory distress frequently precipitated euthanasia. ⁴ A retrospective series of 27 cats with laryngeal, laryngotracheal or tracheal masses reported a median survival time of only 5 days, regardless of whether the lesions were inflammatory or neoplastic, emphasising the clinical fragility of such cases. ¹⁰

When surgery is feasible, isolated successes have been reported (eg, tracheal squamous cell carcinoma resection and anastomosis) but are highly case selected, and margins or periprocedural risk remain problematic in broad-based, carinal lesions. ² In unstable cats, invasive airway procedures (endoscopic debulking or biopsy) carry non-trivial anaesthetic and respiratory risks – including desaturation and bronchospasm – so rapid decompensation is common; careful case selection is essential.^4,10,11 Thus, for anatomically unfavourable, obstructive lesions – particularly at the bifurcation – early airway-sparing therapy may be safer than aggressive upfront surgery.

Definitive multi-fraction radiation therapy has yielded the longest survival time reported to date: Azevedo et al ¹ described a cat that survived 755 days using 3 Gy × 18 definitive RT with multimodal therapy (carboplatin/piroxicam initially; toceranib and palliative re-irradiation at recurrence). This case suggests that RT and multimodal therapy can deliver durable control when patients can tolerate a longer course.

In the present case, we prioritised urgent hypofractionated RT (6 Gy × 6; total 36 Gy) to relieve central airway obstruction, followed by staged histological confirmation once ventilation was stabilised. This sequence addresses a key vulnerability highlighted in the literature – diagnostic or surgical delays with periprocedural decompensation – by first rescuing the airway and then completing diagnostics under safer conditions.^4,10,11

Radiobiological analysis using the linear–quadratic model shows that the hypofractionated protocol of 6 Gy delivered in six fractions provides a tumour biologically effective dose (BED) of approximately 57.6 Gy₁₀ (equivalent dose in 2 Gy fractions [EQD2] ≈ 48 Gy), whereas a conventional definitive schedule of 3 Gy delivered in 18 fractions yields a higher tumour BED of 70.2 Gy₁₀ (EQD2 ≈ 58.5 Gy). This indicates that hypofractionation sacrifices some degree of tumoricidal potential in exchange for more rapid palliation of obstruction and fewer anaesthetic episodes, which is particularly important in dyspnoeic cats. By contrast, when late-responding normal tissues are considered (alpha:beta [α:β] = 3), both regimens result in essentially identical values (BED₃ ≈ 108 Gy₃, EQD2_{late} ≈ 64.8 Gy). Thus, although tumour control probability may be modestly reduced, the expected risk of late airway toxicity is comparable between schedules, provided that dose hotspots are limited and conformal planning is applied.^{12 –14}

For lung injury, human Quantitative Analysis of Normal Tissue Effects in the Clinic-derived constraints remain the strongest empirical anchors (eg, V20 [ie, percentage of lung volume receiving ⩽~20 Gy] ⩽30–35%, mean lung dose [MLD] ⩽~20 Gy); exceeding these correlates with higher pneumonitis risk across multiple data sets.^14,15 In centrally located, small-volume targets, these metrics can usually be respected during short courses, mitigating pneumonitis risk.

Regarding the proximal bronchial tree/trachea, prospective central-tumour stereotactic body radiation therapy data (Radiation Therapy Oncology Group 0813) demonstrate toxicity risk at high doses per fraction, ¹⁶ and further analyses emphasise that small-volume high-dose constraints better predict events. ¹⁷ Our regimen (36 Gy in six fractions; EQD2_{α:β = 3} ≈ 64.8 Gy) sits well below exploratory airway tolerance thresholds (≈ EQD2₃ ~100 Gy), supporting a low probability of central airway necrosis/stenosis when hotspots are limited and fraction size remains moderate.^{16 –18} In canine models, the trachea is characterised as a late-responding tissue with a low α:β ratio, making it relatively sensitive to large fraction sizes that can predispose to ulceration and fibrosis. ¹⁸ Although this raises a theoretical concern for hypofractionation, the total dose in our protocol (36 Gy in six fractions) delivered a biologically effective dose comparable to, but not exceeding, the ranges associated with late injury in dogs. No acute adverse effects were observed clinically, and the short overall treatment time was considered appropriate for urgent airway decompression while keeping the predicted late-tissue burden within an acceptable range.

Finally, our case supports the potential role of a stepwise, multimodal approach for managing feline tracheal tumours. In this strategy, early hypofractionated RT can provide rapid airway relief, while subsequent targeted therapy (eg, toceranib) may contribute to sustained disease control. Although the therapeutic benefits of both RT and toceranib in tracheal carcinomas remain largely unestablished, limited evidence suggests possible efficacy. For instance, Park and Song ¹⁹ reported a feline tracheal carcinoma that achieved 4 months of disease stabilisation after surgery and adjuvant toceranib therapy. In our case, no re-irradiation or endoscopic debulking was performed, but previous reports – including a 755-day survivor treated with definitive RT and multimodal therapy – illustrate the feasibility of such sequential interventions.^1,20 The present findings, together with emerging data on tyrosine kinase inhibitors in feline oncology, ²¹ support further investigation of such combination strategies to prolong disease control while maintaining quality of life.

Conclusions

This case demonstrates a staged strategy – urgent 6 Gy × 6 hypofractionated RT to stabilise ventilation followed by safe histological confirmation – for a broad-based carinal mass in a cat, and situates this approach within the available evidence. On BED modelling, the chosen schedule provides rapid decompression with a similar predicted late-tissue burden to conventional 3 Gy × 18, while lung V20, MLD and central airway EQD2 {3} remain comfortably within evidence-based tolerance ranges. Given the poor short-term survival reported in series and the hazards of invasive procedures in dyspnoeic cats, early airway-sparing RT emerges as a rational, evidence-informed option when surgery is anatomically high risk. Further cases will be important to refine dose – volume constraints for feline lungs and proximal airways, and to clarify the role of re-irradiation and targeted therapies in long-term control.