Effect of Rurality in Head and Neck Cancer: A Scoping Review.

OBJECTIVES: This scoping review sought to evaluate the current literature regarding the following outcomes in relation to rurality: stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes of head and neck cancer (HNC). DATA SOURCES: A literature search was performed using PubMed (MEDLINE), Science Direct, EMBASE, SCOPUS, and Web of Science databases. REVIEW METHODS: A 20-year study cutoff from the initial search was used to increase the comparability of the studies regarding population and standards of clinical care. These searches were designed to capture all primary studies reporting HNC incidence, presenting characteristics, treatments, and treatment outcomes. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the Joanna Briggs Institute Quality Assessment Tool for Cohort Studies. FINDINGS: Twenty eligible original articles were included. Stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes were measured. Our review indicates that although this relationship is unclear, there may be variations in treatment choice for laryngeal cancer based on geographic location and rural residency status. The studies assessing HNC outcomes related to stage at diagnosis, clinical characteristics, treatment characteristics, and overall survival demonstrated conflicting findings, indicating a need for further research examining HNC outcomes with a focus on rurality as the main exposure. CONCLUSIONS: The relationship between HNC and rural-urban status remains unclear. More studies are needed, along with a consistent metric for measuring rurality and recruitment of comparable populations from both rural and urban areas. Laryngoscope, 2024.

Salivary Duct Carcinoma with Rhabdoid Features of the Parotid Gland with No E-Cadherin Expression: A Report with Anti-HER2 Therapy and Review of the Literature.

Salivary duct carcinoma with rhabdoid features (SDC-RF) is a rare form of salivary gland neoplasm that was recently described. We report a case of SDC-RF of the parotid gland with loss of E-cadherin and decreased ß-catenin expression in a 73-year-old male who presented with right facial/neck swelling and intermittent pain. Morphologically, the tumor presented with a discohesive infiltrate of isolated and cords of pleomorphic round cells containing moderate amount of eosinophilic to fine-vacuolated cytoplasm and hyperchromatic nuclei infiltrating through fibroadipose tissue and salivary parenchyma. Immunophenotypically, the tumor was positive for Cytokeratins Oscar and 7, GATA3, GCDFP, HER2, and an androgen receptor but negative for CK20, S100, p40, Melan A, CDX2, TTF1, ER, SATB2, DOG1, synaptophysin, and chromogranin. Due to its diffuse infiltrating pattern, involvement of the parapharyngeal space, supraclavicular fat pad, dermis, and skin without a defined surgical target, the tumor was deemed unresectable. Anti-HER2 therapy (Herceptin and Pertuzumab) was utilized. At the last follow-up, the patient is alive, with complete locoregional control and brain metastases. An electronic search was performed in the following registries for papers published up to June 2023: PubMed, Embase, and Web of Science. For the database searches, the keywords searched were "salivary gland", "salivary duct carcinoma", and "salivary duct carcinoma with rhabdoid features". Our review of the literature identified 30 cases of SDC-RF that reveal there is a predilection for males (83%), parotid gland (72%), and patients older than the 6th decade of life (83%). Immunophenotypically, all SDC-RF cases except one were positive for AR and GCDFP (97%), 81% were positive for HER2, and loss or decreased expression of E-cadherin in 93% of cases. In conclusion, we described a rare case of SDF-RF of the parotid gland with no E-cadherin expression, decreased ß-catenin expression, and its immunophenotypic profile.

Botox for the prevention of radiation-induced Sialadenitis and xerostomia in head and neck cancer patients: A pilot study.

BACKGROUND: To determine the safety of Botox and its potential effect on alleviating radiation therapy (RT)-induced sialadenitis in head and neck cancer patients. METHODS: Twenty patients with stage III/IV head and neck cancer were randomized to receive Botox or saline injections into both submandibular glands (SMG). There were three visits: one before RT (V1); 1 week after RT (V2); and 6 weeks after RT (V3), each of which included saliva collection, a 24-h dietary recall, and a quality-of-life survey. RESULTS: No adverse events were observed. While the control group was much older, the Botox group more commonly underwent induction chemotherapy compared with controls. From V1 to V2, salivary flow decreased in both groups, but only in the control group from V1 to V3. CXCL-1 (GRO), a neutrophil chemoattractant, was lower in the Botox group compared with the control group at V3. CONCLUSION: Botox can be safely administered to the salivary glands prior to external beam radiation without observed complications or side-effects. After an initial reduction in salivary flow following RT, the Botox group showed lack of further flow reduction compared with controls. The inflammatory marker CXCL 1, which was reduced in the in Botox group at V3, may be a candidate for further studies of radiation-induced sialadenitis.

The Role of Dental Practitioners in the Management of Oncology Patients: The Head and Neck Radiation Oncology Patient and the Medical Oncology Patient.

This narrative review addresses the role of a dentist in the management of oncology patients, highlighting the oral complications that arise in head and neck radiation oncology patients and medical oncology patients. The prevention and management of these complications are discussed.

Porcine small intestine graft for reconstruction of oral defects.

OBJECTIVE: To evaluate the feasibility and outcomes of porcine submucosal allograft (Biodesign Sinonasal Repair Graft [Cook Medical, Bloomington, IN]) in oral cavity and oropharynx reconstruction after ablative surgery. METHODS: We conducted a prospective and retrospective review of patients who underwent Biodesign Sinonasal Repair Graft reconstruction for oral and oropharyngeal surgical defects at a single institution between 2018 and 2020. A total of 11 patients were included in the study. Data points included their perioperative medical and demographic data, immediate postoperative course, and follow-up visits at 10 days and at 2 months. The clinicopathologic characteristics of their disease, postoperative esthetic, and functional outcomes were recorded and analyzed. RESULTS: Eleven procedures have been performed, and all patients received Biodesign reconstruction either immediately after ablation or after they failed a previous reconstruction. None of the patients had bone exposure. The subsites included oral tongue (n = 6), floor of the mouth (n = 3), buccal mucosa (n = 1), and soft palate (n = 1). In all cases, the operations and the postoperative course were uneventful. The mean defect size was 22 cm2. The median start of oral intake was at 2 days postoperatively. The Biodesign graft healed well in all patients with no total graft loss. There was one complication that required revision surgery due to obstruction of Wharton's duct by the Biodesign material. CONCLUSIONS: Biodesign can be a viable option for small and medium-sized oral and oropharyngeal defects in patients who are medically unfit or do not want to undergo a free flap surgery. LEVEL OF EVIDENCE: 4.

Outcomes of primary radiotherapy with or without chemotherapy for advanced oral cavity squamous cell carcinoma: Systematic review.

BACKGROUND: Surgery with adjuvant radiotherapy is the accepted standard for treatment of advanced oral cavity squamous cell carcinoma (OCSCC); however, alternative evidence suggests that definitive (chemo)radiotherapy may have similar outcomes. METHODS: Systematic review was performed to assess the therapeutic value of radiotherapy or chemoradiotherapy as a primary modality for treating OCSCC. Meta-analysis of outcomes was performed between articles comparing radiotherapy and primary surgical treatment. RESULTS: Meta-analysis showed less favorable results of radiotherapy compared to surgery: overall survival at 3-years (odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.34-0.77) and 5-years (OR = 0.42; 95% CI = 0.29-0.60); disease-specific survival at 3-years (OR = 0.55; 95% CI = 0.32-0.96) and 5-years (OR = 0.55; 95% CI = 0.32-0.96). Odds of feeding tube dependency were higher in primary radiotherapy group (OR = 2.67; 95% CI = 1.27-5.64). CONCLUSIONS: Results of this study support the current perspective favoring primary surgical treatment for OCSCC in the absence of surgical contraindications.

Robotic-Assisted Tubular Transoral Parapharyngeal Approach to the Ventral Craniovertebral Junction.

BACKGROUND: Transoral robotic surgery (TORS) has become a routine technique for treating benign and malignant lesions of the oropharynx with the advantage of reducing morbidity compared to open surgical techniques. However, TORS has not been used routinely for accessing lesions of the spine. OBJECTIVE: To describe how TORS can be used to access spinal lesions. METHODS: We describe our technique of accessing the parapharyngeal space using the robotic technique, and then dissecting the prevertebral muscles to expose the ventral craniovertebral junction. Tubular retraction with endoscopic visualization is then employed for surgical resection. We then report a case of a 14-yr-old competitive athlete who presented with an osseous lesion of C1, which underwent resection using this novel TORS approach. RESULTS: Our patient underwent successful resection of a lateral C1 osteoid osteoma utilizing a combined TORS/endoscopic approach. She tolerated soft diet immediately and was discharged on postoperative day 2. Postoperative imaging revealed complete resection of the lesion, and she returned to competitive athletics within 6 wk. CONCLUSION: Utilizing this novel, robotic-assisted approach can definitively treat osseous cervical spine lesions while reducing morbidity, allowing for early return to normal diet and minimizing overall length of hospital stay.

Osteosarcoma of the jaw: report of 3 cases (including the rare epithelioid variant) with review of literature.

Osteosarcoma of the jaw (OSJ) is a rare malignancy, accounting for less than 1% of head and neck malignancies. OSJ can arise as a primary malignancy or secondary to locoregional radiation treatment. Radiologically, these tumors show large, destructive growth with periosteal reaction, which can suggest the diagnosis of osteosarcoma (OS). However, histology with demonstration of neoplastic, "lacelike" osteoid is the key to determining the diagnosis. Small tissue samples can complicate the diagnosis, especially in cases of high-grade OS with sheetlike growth and scant areas of immature osteoid formation. We report 3 cases of OSJ, including 1 rare case of epithelioid OS of the mandible, diagnosed at our hospital over a 6-month period: case 1: a 48-year-old male with history of Hodgkin lymphoma, who was treated with radiation and developed osteoblastic OS of the mandible 14 years later; case 2: a 79-year-old female with a history of fibrous dysplasia, who presented with a large destructive maxillary mass, which was diagnosed as histologically fibroblastic OSJ of the maxilla; and case 3: a 70-year-old male with radiation-induced high-grade epithelioid OS, which had been incorrectly diagnosed as poorly differentiated squamous cell carcinoma on a small biopsy specimen; this patient experienced recurrence with multiple neck nodules after treatment, underwent repeat resection, and was finally diagnosed with high-grade OS (epithelioid type).

Surgical outcomes in the elderly patient after osteocutaneous free flap transfer.

OBJECTIVES/HYPOTHESIS: Morbidity of free tissue transfer in the elderly patient is controversial. Recent studies have shown no significant difference in elderly fasciocutaneous free-flap donor site morbidity. The purpose of this study is to assess surgical outcomes in elderly patients receiving osteocutaneous free-tissue transfer. STUDY DESIGN: Retrospective chart review of patients 70 years and older undergoing osteocutaneous free flaps from 2000 to 2013. METHODS: Fibular, radial forearm, and scapular flaps were reviewed. Younger patients randomly selected from the same time period served as controls. Data collected included donor site morbidity, flap complications, feeding tube and tracheostomy dependence, and hospital stay. RESULTS: Forty-four osteocutaneous free flaps were performed in elderly patients. Overall, there was no significant difference in donor site morbidity between older and younger patients (P = 0.50) (tendon exposure, P = 1.00; split-thickness skin graft loss, P = 0.36; infections, P = 0.52; dehiscence, P = 1.00; and seroma, P = 1.00). There was no significant difference between older and younger patients being decannulated (P = 0.61) or the time to decannulation (P = 0.24). There was no difference in those who returned to baseline diet (P = 0.67). All patients returned to baseline ambulatory and shoulder status. Length of postoperative hospitalization (P = 0.78) and intensive care unit stay (P = 0.94) were also equal. The only significant difference was that more elderly patients were discharged to skilled nursing facilities (SNF) (40.9% vs. 15.9%, P < 0.01). CONCLUSION: Elderly patients undergoing free tissue transfer have similar flap and donor site outcomes, feeding tube and tracheostomy outcomes, ambulatory status, and hospital stays compared to younger patients. They are, however, more likely to require SNF care posthospitalization. LEVEL OF EVIDENCE: 4.

Assessment of donor site morbidity for free radial forearm osteocutaneous flaps.

PURPOSE: Assessment of donor site morbidity and recipient site complications following free radial forearm osteocutaneous flap (FRFOCF) harvest and evaluation of patient perceived upper limb disability for free radial forearm osteocutaneous versus fasciocutaneous flaps (FRFF). METHODS: First a case series was undertaken of 218 patients who underwent an FRFOCF at two tertiary referral centers between February 1998 and November 2010. Outcomes included forearm donor site morbidity and recipient site complications. Second, the disability of the arm, shoulder, and hand (DASH) questionnaire assessing patient perceived arm disability was administered by phone to 60 consecutive patients who underwent an FRFOCF or FRFF. RESULTS: Mean patient age was 63 years with male predominance (62.8%). Median bone length harvested was 8 cm (range, 3-12 cm) with prophylactic plating of the radius following harvest. Donor site morbidity included fracture (1 patient, 0.5%) and sensory neuropathy (5 patients, 2.3%). Mean DASH scores were comparative between groups and to established normative values. Mandibular malunion rate was 3.2% and hardware extrusion at the recipient site occurred in 15.6%. CONCLUSION: Reluctance to perform FRFOCF by surgeons usually centers on concerns regarding potential donor site morbidity and adequacy of available bone stock; however, we identified minimal objective or patient perceived donor site morbidity or recipient site complications following harvest of FRFOCFs. Mild wrist weakness and stiffness are common but do not impede ability to perform activities of daily living. Data from this and other reports suggest this flap is particularly useful for midfacial and short segment mandibular reconstruction.

Stereomicroscopic fluorescence imaging of head and neck cancer xenografts targeting CD147.

PURPOSE: To demonstrate that systemically administered fluorescently labeled anti-CD147 antibody can detect head and neck squamous cell carcinoma xenografts in vivo. EXPERIMENTAL DESIGN: In vivo immunodeficient murine model. RESULTS: Peak tumor fluorescence was visualized by near infrared stereomicroscopy in SCC-1 tumors at 24 hours after systemic injection of anti-CD147:Cy5.5 bioconjugate. SCC-1 xenografts demonstrated significantly higher fluorescent intensity after administration of CD147:Cy5.5 (48 au, p < 0.0001) compared to IgG1k:Cy5.5 isotype control antibody (9 au). FaDu tumors overexpressing CD147 (FaDu/E) demonstrated higher fluorescence (53 au) compared to control vector transfected cells (FaDu, 33 au, p < 0.0001) which was higher than CD147 knockdown cells (FaDu/siE, 5 au, p < 0.0001). METHODS: To determine if fluorescently labeled anti-CD147 antibody was specific for tumors in vivo, anti-CD147 and non-specific IgG1k antibody were labeled with a near infrared fluorophore (Cy5.5) and administered systemically to immunodeficient mice bearing SCC-1 xenografts. Imaging was performed over a 72 hour period using brightfield and fluorescent (685-735 nm) stereomicroscopy. To determine if fluorescence varied with receptor expression, SCID mice were xenografted with cell lines expressing variable amounts of CD147: FaDu (control vector transfected), FaDu/siE (siRNA CD147 knockdown) or FaDu/E (CD147 overexpressing) cells. CONCLUSIONS: This data suggests fluorescently labeled anti-CD147 may have clinical utility in detection of HNSCC.

Fluorescent labeled anti-EGFR antibody for identification of regional and distant metastasis in a preclinical xenograft model.

BACKGROUND: Detection of regional and distant metastatic disease has significant implications for patient management. Fluorescent imaging may be a useful technique for metastasis detection and removal. METHODS: Anti-epidermal growth factor receptor antibody (cetuximab) and isotype-matched control antibody (immunoglobulin G [IgG]) were labeled with a near-infrared fluorophore (Cy5.5), then systemically administered to mice with tumors resulting from either intraoral or intravenous injections of head and neck squamous cell carcinoma. Mice were sacrificed before undergoing fluorescent stereomicroscopy to assess pulmonary or cervical lymph node metastasis. Fluorescent areas were serially excised until wound bed demonstrated negative fluorescence. RESULTS: Mice bearing pulmonary metastases displayed diffuse background after IgG-Cy5.5 injection, but demonstrated a speckled fluorescent pattern across lung surface following cetuximab-Cy5.5 injection. Mice bearing cervical metastases demonstrated clear fluorescence of primary tongue tumor and bilateral cervical nodes. Fluorescence correlated with histopathology. CONCLUSION: These data suggest that cetuximab-Cy5.5 may have clinical utility in the detection and guided the removal of regional and distant micrometastasis.

Assessment of indocyanine green-labeled cetuximab to detect xenografted head and neck cancer cell lines.

OBJECTIVE: The aim of this study is to determine the efficacy of indocyanine green (ICG) conjugated to antiepidermal growth factor receptor antibody (cetuximab) to image head and neck cancer. STUDY DESIGN: Mice (n = 3) were injected with unconjugated ICG and imaged at 100-second intervals for a total of 1000 seconds to assess imaging characteristics. Mice (n = 10) xenografted with SCC-1 cells were then systemically injected with cetuximab conjugated to indocyanine green and imaged over a 72-hour period. To assess the sensitivity and specificity, xenografted tumors underwent subtotal resections and then were assessed for residual disease by fluorescence stereomicroscopy and confirmed by histology. RESULTS: Tumors demonstrated excellent fluorescence 24 hours after injection of cetuximab-ICG. There was a direct relationship between fluorescence and the given dose of cetuximab-ICG. Following subtotal resection, we found fluorescence correlated with a sensitivity of 78.4% and specificity of 96%. CONCLUSIONS: This study provides evidence that supports further preclinical investigation of cetuximab in the evaluation of surgical margins, but linkage to ICG lacks the sensitivity for use in a clinical setting.

Fluorescently labeled cetuximab to evaluate head and neck cancer response to treatment.

OBJECTIVE: Combining the therapeutic and diagnostic properties of targeted antibodies may improve clinical assessment of disease with limited added toxicity during treatment. METHODS: Mice (n = 10) were xenografted with SCC-1 tumor cells and then treated with radiation, cisplatin and cetuximab. Brightfield and fluorescent imaging was performed after systemically injecting fluorescently labeled cetuximab prior to treatment and at six or ten weeks after initiation of treatment. The relative fluorescence intensity was determined for each image. RESULTS: The tumor luminosity measured before (week 0), during (week 6) and after treatment (week 10) did not significantly change. Actual tumor measurement corresponded to fluorescent measurements of tumors both before treatment and after treatment. Complete response to therapy occurred in one animal, where resolution of the tumor correlated with loss of fluorescent activity. CONCLUSIONS: This preclinical data suggests combining the diagnostic and therapeutic properties of cetuximab may be clinically useful.