Teaching pack: Nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) in endemic regions is EBV-associated non-keratinising carcinoma with distinct biology (NF-κB pathway alterations, immune-rich stroma, low TMB), while sporadic Western cases include keratinising HPV- or smoking-related tumours. Plasma EBV DNA is a diagnostic, prognostic and surveillance marker, and population screening with EBV DNA detected early-stage cancers in Hong Kong (Chan, NEJM 2017).

IMRT is the backbone: radiotherapy alone for stage I, concurrent cisplatin-radiotherapy for stage II-IVA (Intergroup 0099), with induction gemcitabine-cisplatin improving survival in locoregionally advanced disease (Zhang, NEJM 2019) and adjuvant metronomic capecitabine adding benefit in high-risk patients (Chen, Lancet 2021). Recurrent or metastatic disease is treated with gemcitabine-cisplatin plus a PD-1 inhibitor: toripalimab (JUPITER-02; FDA approval 2023, the first US approval for NPC), camrelizumab (CAPTAIN-1st), tislelizumab (RATIONALE-309) and penpulimab (FDA 2025). Nasopharyngectomy (endoscopic) and re-irradiation are options for local recurrence. Late toxicities of radiotherapy (xerostomia, hearing loss, temporal-lobe necrosis, carotid stenosis) drive de-escalation trials guided by EBV DNA.

• Plasma EBV DNA is the most mature liquid biopsy in oncology: it screens, stages, guides adjuvant therapy and detects relapse.
• PD-1 inhibitors with GP chemotherapy roughly doubled PFS in metastatic disease; toripalimab was the first FDA approval for NPC and among the first for a Chinese-developed PD-1 antibody.
• Induction GP and adjuvant capecitabine are the standard for locoregionally advanced disease.
• De-escalation (omitting concurrent cisplatin in low-risk stage II, reducing neck irradiation) is being validated in trials led from Guangzhou.

1. 1921Regaud and Schmincke describe lymphoepithelioma
2. 1966EBV antibodies linked to NPC (Old et al.)
3. 1998Intergroup 0099: concurrent cisplatin-RT improves survival (Al-Sarraf)
4. 1999Plasma EBV DNA quantified as a tumour marker (Lo, Cancer Res)
5. 2017EBV DNA screening detects early NPC in 20,000 men (Chan, NEJM)
6. 2019Induction gemcitabine-cisplatin improves survival (Zhang, NEJM)
7. 2021JUPITER-02, CAPTAIN-1st, RATIONALE-309: PD-1 + GP first line
8. 2023Toripalimab: first FDA approval for NPC
9. 2025Penpulimab approved (FDA)

• Toripalimab (product)
• Penpulimab (product)
• Camrelizumab (product)
• Tislelizumab (product)
• Proton therapy (technology)

• Radiation late effects in a disease cured young.
• Western access to PD-1 inhibitors studied in Asia; regulatory lag.
• EBV-targeted therapy (vaccines, EBV-specific T cells) still investigational.
• Distant metastasis remains the main cause of death after chemoradiation.

1. What is the standard treatment for stage II-III triple-negative breast cancer today?
   Answer

   Neoadjuvant pembrolizumab with carboplatin/paclitaxel then anthracycline chemotherapy, surgery, and adjuvant pembrolizumab (KEYNOTE-522); adjuvant olaparib for germline BRCA carriers with residual disease (OlympiA); capecitabine for residual disease without BRCA.
2. What fraction of advanced melanoma patients on nivolumab plus ipilimumab are alive at ten years?
   Answer

   About 43% overall survival (CheckMate 067), with melanoma-specific survival around 52%.
3. Which cooperative group ran the trial that put nivolumab into first-line Hodgkin lymphoma?
   Answer

   SWOG (S1826, nivolumab-AVD vs BV-AVD), leading to FDA approval in March 2026 for ages 12 and over.

• CSCO/ASCO NPC guideline (JCO 2021): https://doi.org/10.1200/JCO.20.03237
• EBV DNA screening (NEJM 2017): https://doi.org/10.1056/NEJMoa1701717
• NCI PDQ: nasopharyngeal cancer: https://www.cancer.gov/types/head-and-neck/patient/adult/nasopharyngeal-treatment-pdq
• Wikipedia: https://en.wikipedia.org/wiki/Nasopharyngeal_carcinoma
• Guideline: https://doi.org/10.1200/JCO.20.03237