Introduction
Oropharyngeal carcinoma (OPC) is among the most common head and neck malignancies, treated with surgery, radiotherapy (RT), chemotherapy (CT) or immunotherapy (IT). Reference Anderson, Ebadi and Vo1 While effective, these modalities often cause toxicities, including opportunistic infections such as fungal infections. Thus, healthcare providers balance cure with preserving patients’ quality of life. Reference Alolayan, Rieger and Yoon2
Candida colonises up to 70% of patients; normally controlled by mucosal barriers and T-cell immunity, it becomes pathogenic after chemoradiation (CTRT)-induced mucosal damage and immunosuppression. Reference Saito, Shodo and Yamazaki3 These infections range from mild superficial to invasive, influenced by fungal virulence, host immunity, infection site and comorbidities. Reference Pathakumari, Liang and Liu4 Such infections are often persistent and challenging to treat. We report a 77-year-old male with OPC who developed refractory oral candidiasis resolving with immune recovery.
Case Presentation
A 77-year-old male with Type II diabetes mellitus (DM), dyslipidaemia and hypertension was newly diagnosed with OPC (right tonsil). He received definitive CTRT at an outside hospital, consisting of 60 Gy in 30 fractions with a 10 Gy boost in five fractions (5th July–7th September 2024) along with six cycles of concurrent weekly carboplatin and three cycles of biweekly nivolumab. One-week post-treatment, he presented to our department with complaints of difficulty and pain while swallowing (Numerical Rating Scale [NRS] score: 6), with a resting pain score of 3, cough on swallowing and a white patch over the tongue. Examination revealed grade II mucositis, grade II xerostomia, grade I dermatitis, graded according to the Common Terminology Criteria for Adverse Events, version 5.0, along with a fungal patch over the tongue (Supplementary Figure 1) and reduced tongue mobility with impaired protrusion.
He was started on intravenous (IV) fluconazole 200 mg daily and supportive care. Baseline blood counts were normal [total leukocyte count (TLC) 6,000 cells/µL and an absolute neutrophil count (ANC) 4700 cells/µL]. Oral candidiasis was confirmed by potassium hydroxide (KOH), and laryngoscopy showed grade 2 mucositis and whitish tongue lesions. After 5 days of fluconazole, he was then started on itraconazole (200 mg loading, then 100 mg daily for 7 days), followed by oral posaconazole (100 mg thrice daily for 10 days). During this period, counts dropped (TLC 3520 cells/µL, ANC 2680 cells/µL, platelets 73,000/µL).
Despite antifungal therapy, infection persisted. Fungal culture identified Candida pararugosa (Supplementary Figure 2, Supplementary Figure 3), sensitive to fluconazole, voriconazole and amphotericin B. An opinion from the Department of Otorhinolaryngology (ENT) was sought, and surgical debridement was recommended, but the patient declined. The treatment plan was revised after consultation with the Department of Microbiology and General Medicine, and the patient was started on liposomal amphotericin B with an initial dose of 50mg followed by an escalated dose of 3 mg/kg (150 mg) daily for 7 days. Regular monitoring of renal function, liver function, electrolytes and complete blood counts was done. Counts remained stable (TLC 5,370 cells/µL, ANC 3840 cells/µL), but by day 4 the patient developed hypokalaemia (3.32 mEq/L) and hypomagnesemia (1.4 mEq/L), managed conservatively. Consequently, the dose was reduced to 100 mg on days 5–7. Following completion, electrolytes normalised (potassium 4.34 mEq/L, magnesium 1.6 mEq/L) with stable counts (TLC 5140 cells/µL, ANC 4,140 cells/µL).
Although the fungal patch showed mild reduction (Supplementary Figure 4–6), the infection persisted. Ultimately, further antifungal therapy was withheld, allowing natural immune recovery. At 3-month (Supplementary Figure 7) and 6-month follow-ups, the infection had completely resolved (as shown in Figure 1), highlighting the body’s remarkable ability to combat the infection through its immune response.
Comparing initial presentation of fungal infection and post-6-month-follow-up.
Discussion
OPC incidence is rising globally, with 100,000 new cases and 23,000 in India (GLOBOCAN 2022). Early disease is managed with RT or surgery, while advanced cases require combined modalities. Reference Machiels, René Leemans and Golusinski5 RT toxicities include mucositis, odynophagia, xerostomia, dermatitis, malnutrition and opportunistic infections such as oral candidiasis, influenced by age, DM, CTRT, xerostomia and poor nutrition. While many resolve, some persist and significantly affect quality of life. Reference Brook6
Fungal infections following chemoradiation
CT and RT cause immunosuppression, increasing the risk of oral candidiasis, including pseudomembranous, erythematous, hyperplastic forms and angular cheilitis, with the first two being most common. Reference Lalla, Latortue and Hong7 Candida overgrowth causes discomfort, altered taste, dysphagia, poor nutrition, delayed recovery and prolonged hospitalisation. Reference Lokesh, Naveen and Sathish Kumara8 Xerostomia after RT resulting from glandular tissue damage makes patients more prone to infections. Reference Singh, Capoor and Nair9 While Candida albicans is most common, non-albicans species are increasing and often azole-resistant, requiring early diagnosis and tailored therapy. Reference Singh, Capoor and Nair9 Similar findings have been reported in the literature, where patients receiving immunotherapy developed persistent oral mucosal lesions that showed limited response to antifungal therapy.
Challenges in antifungal treatment
Antifungals include systemic agents (fluconazole, amphotericin B, itraconazole and voriconazole) and topical agents (azoles, polyenes and gentian violet). Reference Lokesh, Naveen and Sathish Kumara8 Choice depends on infection type, severity, efficacy and toxicity. Candida biofilms increase drug tolerance and antifungal resistance through extracellular matrix and persister cells. Reference Kaur and Nobile10 Refractory infections may require liposomal amphotericin B, though risks include nephrotoxicity, hypokalaemia and hypomagnesemia, necessitating close monitoring for effective and safe treatment. Despite persistent fungal infection, the patient’s infection gradually resolved without further antifungal treatment, underscoring the vital role of immune recovery in overcoming CTRT-induced mucosal damage. From the patient’s perspective, the persistent fungal patch over the tongue was a major source of psychological distress despite ongoing treatment. Following complete resolution of the lesion, the patient expressed significant relief and reassurance. Similar findings have been reported in the literature, where patients receiving immunotherapy developed persistent oral mucosal lesions that showed limited response to antifungal therapy. Clinical improvement was observed only after discontinuation of immunotherapy, suggesting that immune-mediated mechanisms may contribute to the persistence of these lesions. Reference Elad, Yarom and Zadik11
Practical challenges during radiotherapy
Persistent oral fungal infection during radiotherapy can pose practical challenges beyond its direct clinical manifestations. Pain and discomfort associated with oral mucosal lesions may affect patient tolerance of immobilisation devices, including thermoplastic masks, and may influence compliance during daily treatment. In addition, distinguishing radiation-induced mucositis from a superimposed fungal infection during routine treatment assessment can be challenging, particularly when symptoms persist despite standard supportive measures. This distinction is important for timely initiation of appropriate antifungal therapy and continuation of radiotherapy. Persistent symptoms may also increase the risk of treatment interruptions, which can potentially affect the overall treatment time and treatment outcomes. Therefore, recognition of persistent or atypical oral lesions during daily radiotherapy assessment and close communication between the radiation oncology team and the treating physicians are important for maintaining treatment continuity and ensuring appropriate supportive management.
Clinical decision-making in the management of persistent oral fungal infection
The clinical management of this patient required a stepwise approach to distinguish persistent post-radiation mucosal toxicity from a superimposed fungal infection and to assess the response to antifungal therapy. The initial presentation was managed with standard antifungal treatment and supportive measures. However, the persistence of the oral fungal lesion despite treatment prompted repeated clinical assessment and escalation of antifungal therapy. Throughout the treatment course, the patient was monitored clinically and with relevant laboratory investigations, including complete blood count, renal function tests, liver function tests and serum electrolytes. The persistent nature of the lesion despite antifungal therapy, followed by its eventual resolution after discontinuation of immunotherapy, raised the possibility of an immune-mediated contribution to the clinical course. The stepwise clinical reasoning and management pathway are summarised in Figure 2.
Clinical decision-making pathway in a patient with persistent oral fungal infection during concurrent chemoradiotherapy and immunotherapy.
Implications for therapeutic radiographers and the multidisciplinary team
Persistent oral fungal infection during radiotherapy requires early recognition and timely escalation when symptoms fail to respond to standard supportive measures. Therapeutic radiographers, through their frequent patient contact during treatment, can play an important role in identifying atypical or persistent oral lesions and facilitating prompt review. Close communication among the radiotherapy team and relevant multidisciplinary services, including microbiology/infectious disease, nursing and dietetics, can support appropriate management, nutritional care and continuity of radiotherapy.
Beyond documenting a rare clinical occurrence, this case highlights the diagnostic and therapeutic challenges of persistent oral fungal infection in the setting of concurrent chemoradiotherapy and immunotherapy. It underscores the need to recognise treatment-refractory oral lesions early, differentiate them from routine radiation-induced mucosal toxicity and adopt an individualised multidisciplinary approach when conventional antifungal therapy fails.
Conclusion
This case shows that refractory candidiasis after CTRT and IT may require more than antifungals, with immune recovery playing a key role. It highlights the need for close monitoring, judicious antifungal use and consideration of natural immune restoration in infection management.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S1460396926100636.
Acknowledgements
The authors thank all the staff of the Department of Radiation Oncology and Microbiology at St. John’s Medical College and Hospital.
Author contribution
Sakshi Garg: Writing—original draft, investigation, data curation, conceptualisation; Hadrian Noel Alexander F: Writing—original draft, investigation, data curation, conceptualisation; Avinash H. Udayashankara: Writing—review and editing, supervision, conceptualisation; Sandeep Muzumder: Writing—review and editing, supervision, conceptualisation; Nirmala Srikantia: Writing—review and editing, supervision; Priyadarshini A. Padaki: Writing—review and editing, investigation; Jayanthi Savio: Writing—review and editing, conceptualisation; Jayalekshmi R: Writing—review and editing, investigation.
Financial support
None.
Competing interests
None.
Ethics approval and consent to participate
Written informed consent was obtained from the patient for publication of this case report and accompanying images; hence, ethical approval was not required.
Consent for publication
Obtained.
Open access
