Background: Head and neck squamous cell carcinoma (HNSCC) presents significant treatment challenges, particularly in cases unrelated to human papillomavirus (HPV). The chemokine receptor CXCR4, interacting with its ligand CXCL12, plays a crucial role in tumor proliferation, metastasis, and treatment resistance. This study explores the therapeutic potential of engineered monomeric and dimerized CXCL12 variants (CXCL121 and CXCL122, respectively) in HNSCC and evaluates potential additive effects when combined with radiation therapy.
Methods: Clinical HNSCC biopsies were evaluated for CXCR4 expression in both previously untreated and radiorecurrent disease. HNSCC cell lines were then treated with combinations of CXCL12 variants and radiotherapy and interrogated for proliferation, gene expression change, and underlying molecular mechanisms. In vivo studies evaluated the biodistribution of engineered CXCL12 and tested these treatments in humanized cell line-derived xenograft (CDX) models.
Results: CXCL122 significantly reduced HNSCC cell proliferation and enhanced the effects of radiotherapy, likely through biased agonism at the CXCR4 receptor and upregulation of the KISS1R pathway. In vivo, CXCL122 localized to tumor sites and augmented the effects of radiation to inhibit tumor growth.
Conclusions: CXCL122, in combination with radiation, demonstrates potent anti-tumor effects in HNSCC. These findings support further clinical investigation of CXCL122 to enhance the effects of radiotherapy.
Background: To evaluate the effectiveness of trilobed forearm flaps in repairing postoperative defects in T2 stage oral cancer patients, while minimizing the impact on the donor site.
Methods: 16 male patients with oral cancer were treated at two tertiary medical centers. Patients' demographic characteristics, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and University of Washington Quality of Life Questionnaire (UW-QoL) were recorded.
Results: Postoperatively, all flaps survived with primary closure of donor site. One patient experienced neck wound edema, which healed after re-drainage. The quality-of-life evaluation shows a UW-QoL score indicating an excellent quality of life, with the mean score of 78.86 ± 4.26 and a mean DASH score of 23.29 ± 9.89, indicating good function preservation of the donor site.
Conclusion: The trilobed forearm flap technique significantly improves the repair range for oral cancer defects while maintaining donor site integrity and is recommended for wider application.
Objective: The objective of this study is to provide a retrospective review of the 40-year experience of three oncology referral centers in the field of reconstructive laryngeal surgery.
Materials and methods: A multi-institutional retrospective analysis included adult patients who underwent reconstructive laryngeal surgery for cT2-T4a laryngeal cancer (LC) between 1 June 1987 and 1 July 2019. Patients were stratified according to the European Laryngological Society classification for open partial horizontal laryngectomy (OPHL).
Results: The final study group included 805 patients (668 men and 137 women). 561 tumors were glottic, while 244 showed supraglottic origin; 644 were considered anterior and 161 posterior. Arytenoid motility was normal in 712 patients, while the motility of the vocal folds appeared to be impaired in 501 patients. All patients underwent OPHL, of which 20 patients underwent OPHL I, 636 patients underwent OPHL II, and 149 patients underwent type III OPHL. 257 patients underwent adjuvant RT based on multiple risk factors/pathological findings. The 5-year overall survival rate was 89.7% (95% CI 87.2-94). The 5-year disease-free survival rate was 78.4% (95% CI 76.8-84.9), and the 5-year disease-specific survival was 64.3% (95% CI 62.2-69.6). Complications were observed in 7.5% of patients, while long-term sequelae were observed in 21% of patients.
Conclusion: The findings of this work reveal four decades of surgical evolution in the school of Enrico de Campora. Despite the retrospective analysis and the extremely long follow-up, our analysis shows how OPHLs play a crucial role in LC (even cT4a), with excellent results in terms of functional outcome and organ preservation.
Background: The submental artery island flap (SIF) is a valid option for palatal reconstruction. However, the main limitation for its application for palatal defects is the arc of rotation. A novel modification for tunneling of the antegrade design of SIF that allows a compliant easy reach to the defect is described.
Methods: Eighteen patients with Brown class II maxillectomy defects were included. Reconstruction started using reversed flow SIF in five patients then shifted to the modified antegrade technique in the remaining patients. Speech, swallowing, chewing, other parameters, and oncological outcomes were assessed.
Results: The reversed flow group has high complications. In the antegrade SIF group, all flaps survived. One developed marginal flap necrosis that healed spontaneously. The follow-up period ranged from 1 to 4.2 years with favorable functional outcome and with no evidence of recurrence.
Conclusion: The modified SIF antegrade design is a reliable option for palate reconstruction that allows favorable functional and oncological outcome.
Background: The p16/CDKN2A protein is being explored as an independent prognostic marker in laryngeal cancer, with studies suggesting that p16-positive patients may have a better prognosis. While its role is well-established in oropharyngeal squamous cell carcinoma (OPSCC) related to HPV, ongoing research indicates its potential prognostic value in laryngeal cancer, even in HPV-negative cases.
Methods: In this study, we investigated the association between survival outcomes and p16 expression in a cohort of 310 laryngeal cancer patients from the Cancer Genome Atlas (TCGA) Program and the University of Maryland Medical Center (UMMC).
Results: In the TCGA cohort, patients with high p16 protein expression had a significantly higher probability of disease-free survival (DFS) at 89%, compared to 51% in the low p16 protein group (p = 0.0266). Additionally, the mean relative p16 protein expression decreased significantly with advancing TNM stage, measured at 1.116 for stage II, 1.075 for stage III, and 0.6204 for stage IV (p = 0.7871 for stage II vs. stage III, p = 0.0065 for stage III vs. stage IV, p = 0.0031 for stage I vs. stage IV). Protein expression for p16 also correlated with CDKN2A retention/deletion status (p = 0.0077), where the DFS was higher in patients with retained CDKN2A than those with deleted CDKN2A (p = 0.0187). Multivariate analysis of the UMMC and TCGA cohorts revealed that both an increase in the patient's age and higher T stage significantly increased the risk of mortality (p = 0.05, p = 0.01, respectively).
Conclusion: While this study observes trends suggesting that low p16 protein expression is associated with longer DFS and advanced TNM stage in laryngeal cancer, the multivariate analysis did not establish p16 as an independent prognostic factor. These findings suggest that while p16 may have a biological role in tumor progression, its utility as a standalone prognostic marker in clinical outcomes requires further validation.
Background: Dysphagia (difficulty swallowing) is a common morbidity resulting from the treatment of head-and-neck squamous-cell carcinoma (HNSCC) due to surgery and chemoradiation. Transoral robotic surgery (TORS) is a minimally invasive surgical technique for the management of HNSCC, which ideally avoids many of the known complications of open surgery. Research describing physiologic swallowing impairment after surgery using videofluoroscopy is lacking.
Methods: We evaluated videofluoroscopic swallowing studies of 37 patients who received TORS for head and neck cancer using a validated scoring tool, the Modified Barium Swallow Impairment Profile (MBSImP), at three time points including baseline.
Results: Patients had worsened physiologic impairments in the immediate post-operative and late post-operative periods, particularly in components related to airway protection. Many patients also had baseline swallowing impairment.
Conclusions: Further research is required to elucidate dysphagia at discrete time points before and after treatment as well as with different and evolving adjuvant therapy protocols.
This study aimed to evaluate the safety, efficacy, and oncologic outcomes of thermal ablation techniques, including radiofrequency, laser, and microwave ablation, in treating primary thyroid cancer compared with surgical resection.
We conducted a systematic review and network meta-analysis, which included 21 comparative studies and 40 noncomparative studies.
The three thermal ablation techniques showed significant superiority over surgical resection in terms of operative time, pain, cost, quality of life, and complications. Three years after the procedure, the tumor volume reduction and complete disappearance rates for the three thermal ablation techniques were similar, at approximately 99% and 93%–95%, respectively. The recurrence rate remained comparable (approximately 2%–3%) among the three thermal ablation techniques and surgical resection during a follow-up period exceeding 3 years.
The safety, efficacy, and oncologic outcomes of thermal ablation techniques may be acceptable and comparable to surgical resection for selected cases of primary thyroid cancer.
Background: Head and neck reconstruction after resection of cutaneous malignancies spans the entire reconstructive ladder. Local flaps, such as the bilobed flap, offer excellent versatility, negligible morbidity, and minimal hospitalization. However, there is sparse data regarding the bilobed flap for large defects of the head and neck.
Methods: A retrospective case series identified patients undergoing head and neck reconstruction with a large bilobed flap for defect sizes ≥ 5 x 5 cm. Data collected included demographics, risk factors for impaired healing, operative variables, and complications.
Results: Nineteen patients were included; 15 (79%) were male, and median age was 80 years (47-88). Twelve patients had pertinent comorbidities and risk factors, including diabetes mellitus, current smoker, prior radiation to the operative area, and immunosuppressive state. Ten (53%) patients experienced complications, including infection, necrosis, or hematoma. Eleven (58%) patients received adjuvant radiation. Eleven (58%) patients were discharged within 1 day.
Conclusion: The large bilobed flap is an effective reconstructive technique for large head and neck cutaneous defects in properly selected patients. This flap can be a useful alternative to free tissue transfer in elderly patients.
Objective: To characterize the perioperative complications after ablative and reconstructive surgery in patients with head and neck cancer (HNC) based on race.
Methods: We conducted a retrospective study of the 2015-2020 National Surgical Quality Improvement Program Database. We compared the perioperative outcomes between White, Asian, Black, Native Hawaiian or Pacific Islander, and American Indian or Alaskan Native patients with bivariate analysis. Multivariate logistic regression assessed the independent association of race with perioperative complications.
Results: Black patients experienced longer surgeries (aβ, 43; 95% CI, 33, 53), longer hospital stays (aβ, 1.6 [95% CI, 1.1-2.1]), and were less likely to be discharged home (aOR, 0.64; [95% CI, 0.54, 0.76]). Black patients also had higher major complications risk (aOR, 1.38; [95% CI, 1.13-1.67]) with the most common being reintubation/ventilation (Black, 4.4% vs. White 2.7%; p = 0.003) and sepsis/septic shock (Black, 3.4% vs. White 1.8%; p = < 0.001). Black patients had higher reoperation rates (aOR, 1.33; [95% CI, 1.12-1.56]) with incision and drainage of abscess and hematoma, exploration of postoperative hemorrhage, thrombosis or infection, or surgical debridement being the top reasons for reoperation. Concordantly, they were at higher risk of postoperative transfusion (Black, 18%; White, 7.2%; p = < 0.001) and wound dehiscence (Black, 4.1%; White, 2.1%; p = < 0.001).
Conclusion: There is evidence of racial disparities in HNC surgery perioperatively. Black patients face an increased risk of major complications, reoperation, extended hospital stay, and non-home discharge. Developing a comprehensive surgical database with more social determinants of health variables and using a socioecological framework of health can help us identify contributors to these disparities and design high-leverage solutions.
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