Exploration of Medicine

Table 1. Clinical timeline of the case.

Date	Event	Details/Visit summary
Sep 2020	Initial presentation & diagnosis	59-year-old Asian male; bilateral epistaxis; right neck mass. CT/PET-CT: NPC left posterolateral wall, bilateral cervical adenopathy. EBER-ISH positive. Stage IVA (cT2N3M0, AJCC 8th ed.)
Oct–Dec 2020	Induction chemotherapy	Cisplatin 80 mg/m² + gemcitabine 1,000 mg/m² Q21d × 3 cycles. Major partial response.
Jan–Mar 2021	Definitive chemoradiotherapy (CCRT)	IMRT 69.96 Gy/33 fr to primary + PET+ nodes; 59.40 Gy to high-risk nodes. Concurrent cisplatin 100 mg/m² → carboplatin AUC4 (grade 2 AKI).
Mar 2021	Complete response confirmed	MRI + PET-CT: complete clinico-radiologic and metabolic response.
Apr 2021–Apr 2023	Surveillance (26 months)	Serial endoscopy, cross-sectional imaging, and plasma EBV DNA monitoring: all unremarkable.
May 2023	First relapse	Multifocal cutaneous tumour deposits (right lateral neck/supraclavicular region); cervical, axillary, and mediastinal lymphadenopathy. Biopsy: recurrent non-keratinising NPC, CPS 70. Plasma EBV DNA 76.4 copies/mL.
Jun–Dec 2023	1st-line salvage: cisplatin + gemcitabine	Cisplatin 70 mg/m² + gemcitabine 1,000 mg/m² (75% dose) Q21d × 6 cycles → partial radiologic response; EBV DNA → undetectable. Gemcitabine maintenance × 6 cycles.
Feb 2024	Biochemical relapse (EBV lead time)	Rising plasma EBV DNA from undetectable to low–positive levels; new nodular skin lesions. Imaging: stable disease by RECIST 1.1. EBV DNA preceded radiologic progression by ~6–8 weeks.
Mar–May 2024	2nd-line: Pembrolizumab	Compassionate use. Pembrolizumab 200 mg Q3W. Transient EBV DNA clearance; cutaneous inflammatory reaction (possible pseudoprogression). CT cycle 4: confirmed PD; new occipital scalp deposits.
Jun–Oct 2024	3rd-line: paclitaxel + cetuximab	Biweekly paclitaxel + cetuximab. Complicated by grade 2 acneiform rash and grade 3 inguinal skin toxicity → dose reductions. EBV DNA: 485 → 1,009 → 4,092 → 13,000 copies/mL. CT Oct 2024: unequivocal PD.
Dec 2024–Mar 2025	4th-line: MDNA11 + pembrolizumab (ABILITY-1 trial)	Phase I/II ABILITY-1 (NCT05086692). MDNA11 IV Q2W + pembrolizumab 400 mg Q6W. iUPD at 8 wks (unconfirmed). EBV DNA rose to 4,062 copies/mL. Clinical PD (worsening cervical ulceration, dysphagia). Trial discontinued after 3 cycles.
Apr 2025	Palliative radiotherapy	30 Gy/10 fr (HexaSkin technique) to cervical cutaneous deposits. Partial haemostatic and analgesic response.
May–Jul 2025	5th-line: carboplatin + paclitaxel	Weekly carboplatin AUC2 + paclitaxel 70 mg/m². EBV DNA: > 4,000 → 252 copies/mL. Partial skin regression. Grade 2 anaemia; 1 episode of febrile neutropenia (G-CSF). Disease re-progression after ~2 months.
Aug–Nov 2025	6th-line: methotrexate	Methotrexate 40 mg/m² weekly. No meaningful disease control. PEG tube placement (oropharyngeal tumour encroachment).
Nov 2025	Death	Transition to comprehensive palliative care after shared decision-making. Patient died in November 2025. Total survival: ~62 months from initial diagnosis.

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CCRT: concurrent chemoradiotherapy; EBV: Epstein–Barr virus; G-CSF: granulocyte colony-stimulating factor; IMRT: intensity-modulated radiotherapy; iUPD: unconfirmed progressive disease (iRECIST); PD: progressive disease; PEG: percutaneous endoscopic gastrostomy; Q21d: every 21 days; RECIST: Response Evaluation Criteria in Solid Tumours; AJCC: American Joint Committee on Cancer; AKI: acute kidney injury; AUC: area under the curve; CPS: combined positive score; CT: computed tomography; EBER-ISH: Epstein–Barr encoding region in situ hybridisation; fr: fractions; IV: intravenous; MRI: magnetic resonance imaging; NPC: nasopharyngeal carcinoma; PET-CT: positron emission tomography-computed tomography; Q2W: every 2 weeks; Q3W: every 3 weeks; Q6W: every 6 weeks.

Declarations

Acknowledgments

We sincerely acknowledge all the patients and their families, whose trust and participation have been the driving force behind this research.

Author contributions

CGR: Conceptualization, Data curation, Methodology, Investigation, Writing—original draft, Writing—review & editing. SCC: Data curation, Validation, Methodology, Investigation, Writing—review & editing. MPK: Data curation, Validation, Methodology, Software. ARR: Methodology, Validation, Writing—review & editing. OJGCM: Validation, Writing—review & editing. SJCS: Validation, Writing—review & editing. BCO: Data curation, Visualization, Investigation, Methodology, Supervision, Writing—original draft, Writing—review & editing. LCG: Conceptualization, Data curation, Validation, Methodology, Investigation, Supervision, Writing—original draft, Writing—review & editing. All authors read and approved the final version of the manuscript.

Conflicts of interest

Luis Cabezón-Gutiérrez declares the following conflicts of interest: Advisory roles: AstraZeneca, Roche, Eisai, and Bristol-Myers Squibb. Speaker’s bureau/honoraria: Roche, AstraZeneca, Bristol-Myers Squibb, Merck Serono, Grünenthal, Pfizer and Eisai. Travel, accommodation, and expenses (Conferences): Merck, Servier. Magda Palka-Kotlowska declares: Advisory roles: GlaxoSmithKline and Esteve. Speaker’s bureau/honoraria: Pfizer, Gilead, Daiichi Sankyo, GlaxoSmithKline, AstraZeneca, and Novartis. Sara Custodio-Cabello declares: Speaker’s bureau / Honoraria: Fresenius, Abbott, Astellas. Claudia García-Ruíz, Otto José Guillermo Chacón-Medina, Samuel Jesús Castañeda-Sánchez, Beatriz Chacón-Ovejero and Adriana Rosero-Rodriguez declare no conflicts of interest.

Ethical approval

Ethical approval for this case report was not required, as it has been exempted in accordance with institutional regulations governing retrospective single-patient reports. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki.

Consent to participate

Written informed consent for participation in this case report was obtained from the patient’s next of kin (family members), given that the patient is deceased.

Consent to publication

Written informed consent for publication of this case report, including accompanying clinical images, was obtained from the patient’s next of kin (family members), given that the patient is deceased.

Availability of data and materials

The data that support the findings of this case report are not publicly available due to patient privacy and confidentiality restrictions, but are available from the corresponding author upon reasonable request and subject to institutional approval.

Funding

Not applicable.

Copyright

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