Background Reliable biomarkers for predicting clinical outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) treated with immunotherapy remain limited. This study evaluated the association between longitudinal EBV DNA trajectories and clinical outcomes in patients with R/M NPC receiving immune checkpoint inhibitors.Methods This post hoc analysis used data from a multicenter, single-arm, Phase II trial evaluating the programmed cell death-ligand 1 (PD-L1) inhibitor KL-A167 in patients with previously treated R/M NPC. Plasma EBV DNA was measured at baseline and at each scheduled efficacy assessment, which was conducted every six weeks until disease progression. EBV DNA trajectories were distinguished through a logistic trajectory model. Multivariable Cox models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for survival outcomes.Results We identified three distinct trajectories: persistently undetectable (n = 17, 13.8%), fluctuating (n = 40, 32.5%), and persistently detectable (n = 66, 53.7%). Compared with the persistently undetectable group, HRs of death were 4.96 (95% CI, 1.60-15.40) and 12.59 (95% CI, 4.01-39.51) for the fluctuating and persistently detectable groups, respectively. HRs of disease progression were 1.96 (95% CI, 0.97-3.96) and 3.22 (95% CI, 1.56-6.67), respectively.Conclusion This study suggests that plasma EBV DNA trajectories could be a promising biomarker for monitoring treatment response and longitudinal risk stratification.
Background TTMV-HPV DNA testing is prognostic during post-treatment surveillance of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but the significance of testing before conventional 3-month response assessment remains unclear.Methods We retrospectively analyzed 332 patients across 8 US sites with biopsy-proven HPV-associated OPSCC who underwent initial definitive treatment and had >= 1 TTMV-HPV DNA test performed 1 to 89 days after treatment completion. Event-free survival (EFS) was evaluated using a 90-day landmark approach.Results The first TTMV-HPV DNA test obtained 1-89 days after treatment was negative in 310 patients (93%), indeterminate in 3 (1%), and positive in 19 (6%). Among 59 patients with repeat testing after an initially negative result, 57 (97%) remained negative and 2 (3%) converted to positive; both patients who converted subsequently developed recurrence. Of 13 patients with an initially positive result and sufficient follow-up for trajectory analysis, 6 (46%) subsequently resolved to negative and none developed recurrence, whereas 7 (54%) remained persistently positive and 6 (86%) developed recurrence. In a 90-day landmark analysis, the last early post-treatment TTMV-HV DNA result was associated with subsequent event-free survival.Conclusions TTMV-HPV DNA testing during the 1-89-day post-treatment interval was associated with subsequent clinical outcomes in HPV-associated OPSCC. Persistent positivity identified patients at increased risk, whereas positive results that resolved were not followed by recurrence in this cohort.
ABSTRACT Background and Importance Chordoma is a rare, malignant neoplasm arising from notochordal remnants. Addressing recurrent disease is challenging due to scar tissue formation, proximity to neurovascular structures, and altered clinical anatomy from prior surgery and/or radiation therapy. Herein, this work describes technical considerations and operative principles utilized in endoscopic transcervical resection for recurrent craniocervical chordoma extending into the right prevertebral/parapharyngeal space. Clinical Presentation A 16‐year‐old male with a history of clival chordoma was found to have an expansile mass spanning the C1‐C2 levels in the right prevertebral/parapharyngeal space on surveillance MRI. He had previously undergone definitive chemoradiation therapy as this tumor was initially misdiagnosed as rhabdomyosarcoma in another country at 13 years of age. He subsequently underwent multiple surgical procedures and treatments, including far lateral craniotomy with occiput‐to‐C2 posterior spinal fusion, combined endoscopic endonasal and transoral resection, and definitive proton therapy at our institution. An endoscopic transcervical approach was selected for salvage surgery as this provided an unoperated corridor with direct access to the neoplastic focus. The patient underwent uncomplicated gross total resection of recurrent chordoma. Conclusion This case demonstrates the safety and efficacy of far medial endoscopic neck dissection for recurrent craniocervical chordoma extending into parapharyngeal/retropharyngeal space in a pediatric patient. Key advantages of this approach include early identification and control of proximal great vessels and lower cranial nerves, dynamic visualization, bimanual surgical technique, and low risk of suboptimal wound healing by avoiding previously operated and/or irradiated tissue.
ABSTRACT Background Dysphagia is a common complication of head and neck cancer (HNC) and its treatment. This study examined swallowing‐related quality of life from diagnosis to 12 months after treatment, compared swallowing outcomes across tumor sites and treatment modalities, and identified predictors of moderate‐to‐severe dysphagia. Methods The M. D. Anderson Dysphagia Inventory (MDADI) was completed by 445 patients receiving curatively intended HNC treatment pre‐treatment and at 3‐, 6‐, and 12‐months post‐treatment. Results Swallowing‐related quality of life worsened during treatment, the poorest scores at 3 months post‐treatment; 21.6% reported moderate‐to‐severe dysphagia, decreasing to 12.5% at 12 months. Risk factors for dysphagia at 12 months included stage IV disease, surgery combined with (chemo)radiotherapy, smoking cessation within 12 months, and pre‐treatment sick leave. Patients with cervical carcinoma of unknown primary (CCUP) had the poorest outcomes. Conclusions Swallowing function declined during treatment. Patients receiving surgery combined with (chemo)radiotherapy and patients with CCUP are at increased risk of long‐term dysphagia and require closer follow‐up.
ABSTRACT Background Skull base reconstruction has continued to evolve in parallel with advances in endoscopic skull base ablation in order to accomplish the goal of restoring larger and more complicated defects between the cranial and nasal cavities while balancing morbidity, cost, and recovery. Methods We reviewed recent literature on advances in skull base reconstruction including graded endoscopic reconstruction, appropriate use of perioperative adjuncts, endoscopic free tissue inset, patient‐specific planning, dural substitutes, regenerative scaffolds, and autologous biologics. Results Graded reconstruction supports free grafts or local flaps for selected low‐flow defects and multilayer vascularized closure for high‐flow defects. Lumbar drainage benefits selected high‐risk patients, whereas routine packing and prolonged antibiotic prophylaxis are not consistently supported. Endoscopic free flap inset, virtual surgical planning, and patient‐specific implants expand options for complex composite and salvage defects. Synthetic dural substitutes can reduce donor‐site morbidity in appropriate cases. Leukocyte‐ and platelet‐rich fibrin (L‐PRF) has emerging clinical support, while most regenerative scaffolds, platelet‐rich plasma (PRP), and cell‐based strategies remain preclinical. Conclusions With advancements in skull base reconstruction, the paradigm has shifted toward using the least morbid construct that reliably restores the intracranial‐sinonasal barrier while preserving function and quality of life. Standardized, prospective studies with attention to patient‐ and value‐centric outcomes are crucial for improving care. Material science advances will continue to expand reconstructive options.
