The tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is comprised of cancer-associated fibroblasts (CAFs), immune cells, and other supporting cells. Genetic changes in ...the carcinoma cells, such as alterations to TP53, NOTCH1, and specific gene expression profiles, contribute to derangements in cancer and microenvironment cells such as increased ROS, overproduction of cytokines, and epithelial to mesenchymal transition (EMT). CAFs are among the most critical elements of the TME contributing to proliferation, invasion, and metastasis. The adaptive immune response is suppressed in HNSCC through overexpression of cytokines, triggered apoptosis of T cells, and alterations in antigen processing machinery. Overexpression of critical cytokines, such as transforming growth factor-β (TGF-β), contributes to EMT, immune suppression, and evolution of CAFs. Inflammation and hypoxia are driving forces in angiogenesis and altered metabolism. HNSCC utilizes glycolytic and oxidative metabolism to fuel tumorigenesis via coupled mechanisms between cancer cell regions and cells of the TME. Increased understanding of the TME in HNSCC illustrates that the long-held notion of “condemned mucosa” reflects a process that extends beyond the epithelial cells to the entire tissue comprised of each of these elements.
Objectives/Hypothesis
We present our experience with telemedicine visits in an otolaryngology outpatient setting within our institution's Center for Head and Neck Surgery.
Study Design
Retrospective ...chart review.
Methods
A review of telemedicine outpatient encounters examining patient demographics, visit type, and wait times was conducted. Internet‐based navigation applications were used to calculate travel distance and estimate commute time to our clinic. Patient survey responses were reviewed.
Results
Two hundred fifty telemedicine encounters were reviewed between December 2015 and June 2017. The average age of patients was 50 years (range, 4–87 years). Patients waited an average of 10 minutes for their telemedicine appointments and avoided an average estimated commute time of 78 minutes (64 miles). The majority of visits were postoperative encounters (70%). Clinical follow‐up of recent results or nonpostoperative complaints accounted for the remaining 30% of visits. All patients were offered a post‐telemedicine survey, and 78 (31%) completed the survey. Of the respondents, 95% of patients reported that they were satisfied with their visit. Among patients who were dissatisfied, wait time and technical issues were cited as reasons.
Conclusions
With appropriate patient selection, telemedicine is an effective way to safely conduct outpatient clinic visits while maintaining high patient satisfaction. It can be particularly useful for institutions with large catchment areas to minimize travel times and increase ease of communication.
Level of Evidence
4. Laryngoscope, 128:2072–2075, 2018
The progression and clinical course of head and neck squamous cell carcinoma (HNSCC) relies on complex interactions between cancer and stromal cells in the tumor microenvironment (TME). Among the ...most abundant of these stromal cells are cancer-associated fibroblasts (CAFs). While their contribution to tumor progression is widely acknowledged, and various CAF-targeted treatments are under development, the relationship between CAF density and the clinicopathologic course of HNSCC has not been clearly defined. Here we examine the published evidence investigating the relationship of cancer-associated fibroblasts to local recurrence and indicators of prognostic significance in HNSCC.
We conducted a meta-analysis of existing publications that compare the relationship between CAF density, local recurrence, and clinically significant pathologic criteria of disease development (T stage, nodal positivity, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation). Thirteen studies met the selection criteria, providing a total study population of 926 patients. Forest plots and risk ratios were generated to illustrate overall relationships.
Higher CAF density within the tumor microenvironment is associated with advanced T stage, nodal infiltration, clinical stage, vascular invasion, perineural invasion, Ki67 expression, and differentiation (p <0.05). High CAF density is also associated with increased rates of local recurrence (p <0.001).
Across multiple studies, increased CAF density is correlated with histopathological criteria of poor prognosis in HNSCC. These findings highlight that CAFs may play a pivotal role in HNSCC development and progression. Staining for CAFs may represent a valuable addition to current pathologic analysis and help to guide prognosis and treatment. Understanding the mechanisms by which CAFs reciprocally interact with cancer cells will be crucial for optimization of TME-focused treatment of HNSCC.
Objective
To assess if there is increased risk of free flap failure in renal failure patients undergoing head and neck reconstruction. We seek to primarily assess free flap outcomes based on stages ...of chronic kidney disease (CKD) and secondarily determine increased risk for postoperative complications.
Methods
Retrospective chart review was performed at five tertiary care centers. Patients were identified that had undergone microvascular free flap reconstruction of the head and neck with diagnosis of renal failure, classified as Stage 3 CKD or higher. Demographic data was collected. Outcomes in the postoperative period were examined.
Results
Seventy‐three patients met inclusion criteria. The average patient age was 69 years with a male predominance (n = 48). The majority of patients had CKD Stage 3 (n = 52). Overall flap failure rate was 12.33% (n = 9, CKD stage 3 = 7.69%, CKD stage 4 = 30%, CKD stage 5 = 18%). There was an increased risk of flap failure on multivariate analysis for CKD stage 4/5 patients when compared to CKD 3 patients (p = 0.0095). When compared to matched controls, there was an increased risk of flap failure in CKD patients (p = 0.01) as well as an increased risk of overall complications (p < 0.0001).
Conclusions
Patients with CKD undergoing head and neck reconstruction are at a higher risk of flap failure and overall complications. When comparing CKD stages there may be increased risk of flap failure in later stages of CKD compared to CKD 3. Appropriate patient counseling is recommended pre‐operatively in this patient population with consideration for regional flaps in the appropriate patient.
Level of Evidence
3 Laryngoscope, 134:688–694, 2024
Background
Recurrent head and neck squamous cell carcinoma (rHNSCC) represents a significant global health burden with an unmet medical need. In this study we determined the safety and efficacy of ...RM‐1929 photoimmunotherapy in patients with heavily pretreated rHNSCC.
Methods
RM‐1929 (anti‐EGFR–IR700 dye conjugate) was infused, followed by tumor illumination. We evaluated safety, tumor response, and pharmacokinetics.
Results
Nine patients were enrolled in Part 1 (dose‐finding) and 30 patients in Part 2 (safety and efficacy). No dose‐limiting toxicities were experienced in Part 1; 640 mg/m2 with fixed light dose (50 J/cm2 or 100 J/cm) was recommended for Part 2. Adverse events (AEs) in Part 2 were mostly mild to moderate but 19 (63.3%) patients had AE ≥Grade 3, including 3 (10.0%) with serious AEs leading to death (not treatment related). Efficacy in Part 2: unconfirmed objective response rate (ORR) 43.3% (95% CI 25.46%–62.57%); confirmed ORR 26.7% (95% CI 12.28%–45.89%); median overall survival 9.30 months (95% CI 5.16–16.92 months).
Conclusions
Treatment was well tolerated. Responses and survival following RM‐1929 photoimmunotherapy in heavily pretreated patients with rHNSCC were clinically meaningful and warrant further investigation.
Clinical Trial Information
NCT02422979.
Objectives/Hypothesis
The transoral robotic approach to parapharyngeal space (PPS) tumors is a new technique with limited data available on its feasibility, safety, and efficacy. We analyzed our ...experience with transoral robotic excisions of PPS tumors to evaluate the safety and efficacy of this technique.
Study Design
Retrospective chart analysis at tertiary academic medical center. From July 2010 to June 2014, 17 patients who had transoral robotic excision of PPS tumors were included in the study. Our cohort had an average age of 61.6 years and was 52.9% male.
Results
All patients had successful removal of their PPS tumors, and the average size of the tumors was 27.3 cm3 (range 2–80 cm3). Two cases (11.7%) required a cervical incision to assist with tumor removal. The average total operative time was 140.5 minutes. Two PPS PAs had focal areas of capsule rupture and one was fragmented. The average length of stay was 1.8 days (range 1–7 days), and all patients were discharged on an oral diet. Three patients experienced complications. There was no clinical or radiographic evidence of recurrence.
Conclusion
This is the largest single‐institution case series of transoral robotic approaches to PPS tumors. We demonstrate that this approach is feasible and safe but also note limitations of the robotic approaches for tumors on the far lateral and superior areas of the PPS, which required transcervical assistance. There were no patients who demonstrated recurrent tumor either radiographically or clinically.
Level of Evidence
4. Laryngoscope, 126:1776–1782, 2016
Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing ...primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear.
To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT.
This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform.
Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy.
Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT.
Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79).
This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.
Secondary revision of osseous flap reconstructions of the maxilla can enhance facial symmetry, but can be challenging due to the absence of normal anatomy and landmarks. We report four cases of ...maxillectomy reconstruction with scapula tip flap employing a novel combined approach with preoperative virtual surgical planning (VSP) and intraoperative navigation (ION) for secondary revision. VSP was employed to superimpose mirrored normal anatomy upon the reconstructed anatomy, and ION used for real‐time intraoperative anatomical mapping. VSP and ION can be used to optimize maxillary bony revisions and recontouring, thereby improving anatomic symmetry and funtionality. Laryngoscope, 131:E2655–E2659, 2021
Background
Perioperative management of advanced osteoradionecrosis of the head and neck requiring free flap (FF) reconstruction varies. Our objectives included assessment of practice patterns and ...outcomes.
Methods
Multi‐institutional, retrospective review of FF reconstruction for head and neck osteoradionecrosis (n = 260).
Results
Administration of preoperative antibiotics did not correlate with reduction in postoperative complications. Preoperative alcohol use correlated with higher rates of hardware exposure (p = 0.03) and 30‐day readmission (p = 0.04). Patients with FF compromise had higher TSH (p = 0.04) and lower albumin levels (p = 0.005). Prealbumin levels were lower in patients who required neck washouts (p = 0.02) or a second FF (p = 0.03). TSH levels were higher in patients undergoing postoperative debridement (p = 0.03) or local flap procedures (p = 0.04).
Conclusion
Malnutrition, hypothyroidism, and substance abuse correlated with a higher incidence of postoperative wound complications in patients undergoing FF reconstruction for advanced osteoradionecrosis. Preoperative antibiotics use did not correlate with a reduction in postoperative wound complications.
Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be ...prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p<0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p<0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.
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