BACKGROUND:Distant metastasis remains a major cause of treatment failure in nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiotherapy (IMRT), particularly among patients with advanced nodal disease. Although lymph node necrosis (LNN) is an adverse imaging feature, its prognostic significance may vary according to accompanying nodal characteristics. METHODS:This retrospective cohort study included 800 patients with newly diagnosed node-positive non-metastatic NPC treated with definitive IMRT between 2016 and 2023. Pretreatment MRI was reviewed for LNN-related features, including radiologic extranodal extension (rENE), necrotic nodal burden, and anatomic distribution. Associations with distant metastasis-free survival (DMFS) were assessed using Cox regression and overlap weighting. RESULTS:Among 800 patients, 450 (56.3%) had LNN. After overlap weighting, LNN remained independently associated with inferior DMFS (5-year DMFS, 87.0% vs. 94.2%; weighted HR, 2.26; 95% CI, 1.24-4.12; P = 0.008). Among patients with LNN, severe rENE, higher necrotic nodal burden, and multi-area necrosis were associated with increased metastatic risk. The predefined adverse necrotic nodal phenotype did not further stratify N2 disease but identified significant heterogeneity within N3 disease, with inferior DMFS in N3b compared with N3a patients (HR, 2.52; 95% CI, 1.18-5.39; P = 0.017). CONCLUSIONS:Pretreatment MRI-defined necrotic nodal phenotypes provide additional risk stratification beyond LNN alone and may identify a subgroup of N3 NPC patients with increased risk of distant metastasis. These findings require external validation before clinical implementation.
Salivary duct carcinomas present challenges to diagnosis and treatment due to diversity in histopathology and clinical behavior (Laurie & Licitra, 2006; Seethala, 2009). A 76-year-old male presented with gradual left-sided facial weakness that was discovered to be left parotid malignant salivary gland carcinoma. Treatment with fam-trastuzumab deruxtecan-nxki, a HER2-directed antibody-drug conjugate, produced a favorable response. Results support an emerging "HER2-low" treatment protocol across diverse salivary gland malignancies.
Postoperative treatment selection for head and neck squamous cell carcinoma remains largely anchored to static pathological risk factors, particularly extranodal extension and positive surgical margins. Although these features identify patients at increased risk of recurrence, they do not directly determine whether residual disease persists after surgery. Circulating tumor DNA-based minimal residual disease (MRD) assessment may help bridge this gap by providing a dynamic molecular measure of residual disease burden. Emerging evidence supports the prognostic value of postoperative MRD detection and longitudinal monitoring in head and neck cancer, creating opportunities to refine surveillance and explore risk-adapted treatment strategies. However, residual disease burden alone may not identify which therapy is most likely to be effective, particularly as immune checkpoint blockade becomes integrated into perioperative and postoperative treatment. In this Perspective, we propose a framework that combines longitudinal MRD assessment with clinicopathological risk factors and complementary tumor and immune profiling. Such an approach could shift postoperative decision-making from static recurrence-risk classification toward dynamic, biology-informed treatment selection. Prospective interventional trials will be essential to determine whether MRD-guided strategies can improve outcomes while limiting unnecessary treatment.
PURPOSE:Preoperative differentiation between benign and malignant parotid tumors (PTs) remains challenging despite clinical examination, cross-sectional imaging, and biopsy. Accurate malignancy assessment is crucial to optimize surgical planning and minimize morbidity. METHODS:We retrospectively analyzed 66 patients who underwent parotidectomy between 2008 and 2024, including 33 with malignant and 33 with benign PTs matched for demographics. All patients had contrast-enhanced computed tomography (CE-CT), and segmented tumor volumes were evaluated using a three-dimensional convolutional neural network. Diagnostic performance was compared with standard clinical and radiologic workup. RESULTS:Standard clinical and radiologic workup achieved a sensitivity of 60.6 %, increasing to 69.7 % with fine needle aspiration cytology (FNAC) or core needle biopsy (CNB). The deep learning model achieved an area under the ROC curve of 0.94, with both sensitivity and specificity exceeding 90 % at optimized thresholds, outperforming conventional diagnostics. CONCLUSION:Deep learning applied to CE-CT demonstrated strong diagnostic performance for the preoperative classification of PTs in this cohort and may serve as a powerful non-invasive adjunct to standard diagnostic modalities without adding procedural burden to the diagnostic workup.
Background Human papilloma virus (HPV)-related head and neck squamous cell carcinoma (HNSCC) incidence is rising. Despite the prognostic and therapeutic implication of HPV status, standardised detection methods are lacking. This study compared multiple HPV detection methods and evaluated the prognostic value of viral transcriptional activity in archival HNSCC tissues. Methods HPV-DNA status and subtyping was determined by GP5+/GP6 + PCR. Multiplex immunohistochemistry (p16INK4) and chromogenic in-situ hybridization (CISH for E6/E7 mRNA) was performed on tissue microarrays (TMAs) from a retrospective cohort of HNSCC (n = 207). Viral load was quantified using QuPath and an independent deep-learning HPV prediction algorithm was validated on H&E-stained tissue cores. Results The multiplex approach accurately detected active HPV in HNSCC primary tumours and metastases, including archival tissue > 20 years old. HPV-DNA was detected exclusively in oropharyngeal SCC and was absent in all other head and neck subsites. Receiver operating curve analysis confirmed all three tested methods match the diagnostic performance of the gold standard HPV-DNA PCR. Furthermore, viral load was identified as an independent predictor of overall survival, maintaining prognostic significance even after adjusting for age, stage and lifestyle factors. Conclusions This study underscores the importance of detecting transcriptionally active HPV to better clinical decision-making of HNSCC patients and supports broader adoption of CISH alongside emerging AI-based analysis in clinical practice.
BACKGROUND:Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS:FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS:Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6 m; 95 % CI, 4.1-53.1; P = 0.023). EP also improved lower-limb functionality (P < 0.001) and was associated with better preservation in the QLQ-C30 summary score (P = 0.008), social functioning (P = 0.038) and body image (P = 0.011). CONCLUSION:EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.
PURPOSE:Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS:We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS:A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23 months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS:HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.
Radiation-associated dysphagia (RAD) is a major short and long-term complication of treatment in head and neck cancer (HNC) patients associated with malnutrition, aspiration pneumonia, and markedly reduced quality of life. This review focuses exclusively on the management of RAD for the surgeon, emphasizing surgical techniques, functional rehabilitation, and emerging technologies. Post-operative dysphagia following surgical disease management (tumor resection, reconstruction, nerve injury) is an important but separate entity and is beyond the scope of this review. We discuss the pathophysiology of RAD, common clinical presentations, evidence-based surgical interventions, and future directions for study in optimizing post-radiotherapy swallowing function.
BACKGROUND:Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M SCCHN) is aggressive, with limited therapeutic options. Guidelines recommend immunotherapy (IO) or cetuximab ± chemotherapy 1st-line, depending on patient/tumour characteristics. Data on subsequent treatment sequencing are limited. We investigated treatment sequences for R/M SCCHN in France. METHODS:Patients with R/M SCCHN who received 1st-line pembrolizumab or cetuximab (November 2020-December 2022) were identified retrospectively from a hospital discharge database, which covers 85% of the French population. Treatment sequences, overall survival (OS) and time to next treatment or death (TTNT-D) were analysed. Outcomes were compared between sequences of interest (pembrolizumab-based 1st-line followed by cetuximab ± chemotherapy, or vice versa). RESULTS:Of 4757 patients who received 1st-line IO or cetuximab, 2529 (53%) received 2nd-line. Fewer patients who received IO-based vs. cetuximab-based 1st-line treatment received 2nd-line (45.4% vs. 61.5%): more on 1st-line IO reached end of follow-up without 2nd-line (26.6% vs. 8.2%). 2nd-line/subsequent treatments were heterogeneous. For patients receiving ≥1 treatment line, median OS was 13.2 months overall (15.4 months for patients receiving ≥2 lines). For 1,742 patients who received sequences of interest, there were no significant differences between 1st-line IO vs. cetuximab for OS (hazard ratio [HR] 0.98, [95%CI 0.90, 1.11], p=0.84) or TTNT-D (HR 0.92 [0.83, 1.03]. p=0.15). CONCLUSIONS:In this nationwide cohort study, OS did not differ significantly between patients who received IO followed by cetuximab vs. cetuximab followed by IO. These findings support flexibility in treatment sequencing and highlight the need for further research to optimize treatment strategies.
BACKGROUND:Transoral endoscopic surgery, using either conventional laser techniques or supported by robotic assistance, represents an established treatment modality for selected patients with T2-T3 laryngeal carcinoma. The goal is complete tumor removal, as positive resection margins have been associated with worse oncological outcomes. This systematic review and meta-analysis aimed to determine the positive margin rate following transoral endoscopic surgery for T2-T3 laryngeal carcinoma and to evaluate its impact on oncologic outcomes. METHODS:A systematic search of Medline, Embase, Web of Science, Cochrane CENTRAL, and Google Scholar was performed from inception through March 2025, identifying studies reporting on surgical margin status after transoral resection of T2 and/or T3 laryngeal carcinoma. A random-effects meta-analysis of proportions was used to estimate a pooled positive margin rate. The oncologic impact of margin status is presented descriptively owing to data heterogeneity. RESULTS:Thirty-nine studies comprising 3,281 patients with T2-T3 laryngeal carcinoma met the inclusion criteria. The positive margin rate was 22.0% (95% CI 17.6 - 27.3, I2 = 83.8%) for the total T2-T3 cohort, with stratified rates of 22.4% for T2 and 30.8% for T3 tumors. Among the eight studies assessing the impact of positive margins in T2-T3 stages, three found a significant association with worse oncological outcomes. Conclusion A 22% positive margin rate was identified in T2-T3 laryngeal cancer treated with transoral endoscopic resection. However, the impact of margin status on oncological outcomes remains uncertain, largely due to challenges in sampling and histopathological assessment.
INTRODUCTION:Recent encouraging outcomes with neoadjuvant immune checkpoint inhibitors (ICIs) in mucosal head and neck squamous cell carcinoma (HNSCC) have generated interest in surgical de-escalation. However, the oncologic safety of response-adapted surgery (RAS) and its ability to achieve survival outcomes comparable to baseline-planned surgery (BPS) remain uncertain. METHODS:A systematic search of the PubMed, EMBASE, Cochrane Library, and the Clinical Trials Registry for studies of neoadjuvant ICIs, with or without chemotherapy, in resectable mucosal HNSCC, that explicitly report surgical extent, between 2020-2025 was performed. Two independent reviewers extracted data following PRISMA guidelines. Main outcomes included major pathologic response (MPR), pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS). Study-level proportions were pooled by random effects models. Heterogeneity was assessed by the I2 statistic. RESULTS:The comparative analysis consisted of 4 RAS studies (involving 202 patients) and 11 BPS studies (403 patients). The pooled overall EFS was 83.3% (76.9-88.2) for the former and 82% (75.2-87.2) for the latter (P=.751), and the respective pooled OS was 92.3% (87.5-95.3) and 91.4% (80.3-96.5) (P=.839). The pooled pCR rate was 41.7% (95% CI 5.4-48.4; I2=.0) for RAS and 19.8% (95%CI 13.3-29.6; I2=.62) for BPS (P=.001), while the MPR was not significantly different (59.6%, versus 48.5%, P=.245). RAS was associated with greater organ preservation and reduced need for mandibulectomy and free-flap reconstruction. CONCLUSIONS:RAS following neoadjuvant ICIs in mucosal HNSCC may enable surgical de-escalation with preserved oncologic outcomes and improved function in selected patients. Larger prospective studies are warranted.
BACKGROUND:Despite carrying significant complication risk, titanium plates remain the standard-of-care in the reconstruction of segmental mandibulectomy defects. Radiation therapy (RT) is known to impair wound healing and cause dose perturbation at the metal-tissue interface. In this study, we sought to investigate the relationship between RT dosimetry and hardware-related complications. METHODS:A retrospective review of 99 patients who underwent segmental mandibulectomy with osseous free flap and titanium plate reconstruction between 2013 and 2022 was performed. Multivariable logistic and linear regression were performed to evaluate hardware-related complications, including plate exposure, fracture, screw loosening, and fistula/infection, adjusting for age, tumor stage, diabetes, and tobacco history. RESULTS:Overall, 60 patients (60.6 %) experienced at least one plate-related complication at a median of 11.2 months (range 0.33-93.1 months) and mean of 22.1 ± 15.8 months from surgery. Plate removal was required in 28.3 % of the cohort. Each 1 Gy of radiation conferred a 6.8 % increase in the odds of any plate complication (OR 1.07, 95 % CI 1.00-1.14, P = 0.037), with > 60 Gy predicting any plate complication (OR 3.07, 95 % CI 1.12-8.41, P = 0.03), plate removal (OR 3.13, 95 % CI 1.15-8.53, P = 0.026) and fistula or soft tissue infection (OR 2.99, 95 % CI 1.13-7.87, P = 0.027) after controlling for age, tumor stage, diabetes, and tobacco use. CONCLUSIONS:Titanium reconstruction plates carry a high complication rate, with a threshold of > 60 Gy associated with a three-fold increase in complication risk. These findings suggest a need for alternative plating strategies or materials to reduce patient morbidity.
BACKGROUND:Post-radiation nasopharyngeal necrosis (PRNN) is a rare but life-threatening late complication in patients with nasopharyngeal carcinoma (NPC). Diabetes mellitus (DM) has been reported as a risk factor for PRNN; however, the impact of long-term glycaemic control on PRNN risk and severity remains unclear. PATIENTS AND METHODS:We conducted a retrospective cohort study of diabetic patients with newly diagnosed NPC treated with intensity-modulated radiotherapy (IMRT) between 2019 and 2022. Long-term glycaemic control was assessed using hemoglobin A1c (HbA1c) levels obtained within 3 months prior to the initiation of radiotherapy and categorized as optimal (<7 %) or suboptimal (≥7 %). Propensity score matching (PSM) was applied to minimize confounding. RESULTS:Among 315 eligible patients, PRNN occurred in 43 (13.7 %) over a median follow-up of 39.7 months. After PSM, 232 patients were included. PRNN developed in 19.0 % of patients with suboptimal glycaemic control compared with 7.8 % of those with optimal control. Suboptimal glycaemic control was significantly associated with an increased risk of PRNN (odds ratio: 2.86, 95 % confidence interval: 1.21-6.76). Higher HbA1c levels were associated with progressively increased PRNN risk (P for trend < 0.0001) and greater necrosis severity. In addition, suboptimal glycaemic control was associated with inferior local recurrence-free, distant metastasis-free, progression-free, and overall survival (all P < 0.05). CONCLUSIONS:Poor glycaemic control is independently associated with increased risk and severity of PRNN and adverse survival outcomes in diabetic patients with NPC. These findings suggest that optimized glycaemic management may represent a clinically actionable strategy to reduce PRNN risk in this vulnerable population.
OBJECTIVE:Oral cancer treatment frequently results in postoperative oral dysfunction, which may contribute to dysphagia, malnutrition, and impaired quality of life. Although objective and patient-reported oral/swallowing function measures are used in clinical practice, the minimal clinically important differences (MCIDs) corresponding to patient-perceived deterioration remain unclear. This study aimed to determine the MCIDs of objective and patient-reported oral/swallowing function measures associated with the oral health-related quality of life in patients with oral cancer. METHODS:This study included patients treated by an oral and maxillofacial surgery team at a tertiary university hospital from September 30, 2019, to December 31, 2025, and followed up at the end of the primary treatment. A total of 146 patients were evaluated before treatment and at discharge after primary therapy. Six oral function measures and the Geriatric Oral Health Assessment Index (GOHAI) were assessed, and anchor- and distribution-based methods were used to estimate the MCIDs. RESULTS:The total GOHAI scores decreased significantly. Multivariate analyses demonstrated that postoperative tongue pressure and EAT-10 scores were independently associated with GOHAI scores. Using a 3-point change in GOHAI as the primary anchor, estimated MCIDs were 0.5 for microorganisms, -3.05 for oral dryness, -321.6 N for occlusal force, -6.05 kPa for tongue pressure, -26.5 mg/dL for masticatory function, and 7.5 points for EAT-10. Distribution-based approaches yielded higher threshold values. CONCLUSION:These findings provide exploratory reference thresholds for interpreting clinically meaningful changes in oral and swallowing functions after oral cancer treatment and underscore the importance of MCID-based evaluation beyond statistical significance alone.
