Functional Outcomes After Transoral Plus Lateral Pharyngotomy Approach for Advanced Oral and Oropharyngeal Tumors.

Objective: The aim of this study was to evaluate our institutional experience with the combined transoral plus lateral pharyngotomy (TO+LP) approach in a subset of patients with advanced or recurrent oral and oropharyngeal malignancy. Study Design: A retrospective study of procedures utilizing TO+LP for cancer resection between January 2007 and July 2019. Setting: Tertiary academic medical center. Methods: Thirty-one patients underwent a TO+LP approach for the resection of oral and oropharyngeal tumors. Functional and oncologic outcomes were analyzed. Results: Eighteen (58.1%) patients were treated with TO+LP for recurrent disease. Twenty-nine required free tissue transfer and 2 (6.5%) had positive margins. The median time to decannulation was 22 days (range 6-100 days). Thirteen (41.9%) patients still required enteral feeding at their most recent follow-up. Patients without a history of prior radiation were decannulated sooner (p = .009) and were less likely to require enteral feeding at the first postoperative follow-up (p = .034) than those who had prior head and neck radiotherapy. Conclusion: A TO+LP approach can be used to achieve good functional and oncologic results for selected patients with advanced or recurrent oral and oropharyngeal cancer when minimally invasive options such as transoral robotic surgery, transoral laser microsurgery, or radiotherapy are not possible.

Interstitial Brachytherapy for Lip Cancer: Technical Aspects to Individualize Treatment Approach and Optimize Outcomes.

Primary radiation therapy using interstitial brachytherapy (IBT) provides excellent local tumor control for early-stage squamous cell carcinoma of the lip. Technical aspects of treatment are important to optimize outcomes. In this report, we discuss patient selection criteria, procedural details, and dosimetric considerations for performing IBT for cancers of the lip. Catheters are inserted across the length of tumor entering and exiting approximately 5 mm beyond the palpable tumor extent. A custom mouthpiece is fabricated to facilitate normal tissue sparing. Patients undergo computed tomography imaging, the gross tumor volume is contoured based on physical examination and computed tomography findings, and an individualized brachytherapy plan is generated with the goals of achieving gross tumor volume D90% ≥ 90% and minimizing V150%. Ten patients with primary (n = 8) or recurrent (n = 2) cancers of the lip who received high-dose-rate lip IBT using 2.0- to 2.5-week treatment regimens are described (median prescription: 47.6 Gy in 14 fractions of 3.4 Gy). Local tumor control was 100%. There were no cases of acute grade ≥4 or late grade ≥2 toxicity, and cosmesis scores were graded as good to excellent in all patients. IBT represents an excellent treatment option for patients with lip squamous cell carcinoma. With careful attention to technical considerations furthered described in the present report, high rates of tumor control, low rates of toxicity, and favorable esthetic and functional outcomes can be achieved with IBT for lip cancer.

Patterns of failure for hypopharynx cancer patients treated with limited high-dose radiotherapy treatment volumes.

PURPOSE: Optimal radiotherapy treatment volumes for patients with locally advanced hypopharynx squamous cell carcinoma should ensure maximal tumor coverage with minimal inclusion of normal surrounding structures. Here we evaluated the effectiveness of a direct 3-mm high-dose gross tumor volume to planning target volume expansion on clinical outcomes for hypopharynx cancers. MATERIALS AND METHODS: We performed a retrospective analysis of patients with hypopharynx carcinoma treated between 2004 and 2018 with primary radiotherapy using a direct high-dose gross tumor volume to planning target volume expansion and with or without concurrent systemic therapy. Diagnostic imaging of recurrences was co-registered with the planning CT. Spatial and volumetric analyses of contoured recurrences were compared with planned isodose lines. Failures were initially defined as in field, marginal, elective nodal, and out of field. Each failure was further classified as central high-dose, peripheral high-dose, central intermediate/low-dose, peripheral intermediate/low-dose, and extraneous. Clinical outcomes were analyzed by Kaplan-Meier estimation. RESULTS: Thirty-six patients were identified. At a median follow-up at 52.4 months, estimated 5-year overall survival was 59.3% (95% confidence interval [CI], 36.3%-74.1%), 5-year local and nodal control was 71.7% (95% CI, 47.1%-86.3%) and 69.9% (95% CI, 57.0%-82.6%), respectively. The most common failure was in the high-dose primary target volume. The gastrostomy tube retention rate at 1 year among patients without recurrence was 13.0% (95% CI, 3.2%-29.7%). CONCLUSION: Minimal high-dose target volume expansions for hypopharynx cancers were associated with favorable locoregional control. This approach may enable therapy intensification to improve clinical outcomes.

Prospective Study of PET/MRI Tumor Response During Chemoradiotherapy for Patients With Low-risk and Intermediate-risk p16-positive Oropharynx Cancer.

OBJECTIVE: The objective of this study was to examine tumor response with positron emission tomography (PET)/magnetic resonance imaging (MRI) during chemoradiotherapy as a predictor of outcome in patients with p16-positive oropharynx cancer. MATERIALS AND METHODS: Patients with p16-positive oropharynx cancer were treated with chemoradiotherapy. Low-risk (LR) disease was defined as T1-T3 and N0-2b and ≤10 pack-years and intermediate-risk (IR) disease as T4 or N2c-3 or >10 pack-years. Patients underwent a PET/MRI scan pretreatment and at fraction 10. Change in value of imaging means were analyzed by analysis of variance. K-means clustering with Euclidean distance functions were used for patient clustering. Silhouette width was used to determine the optimal number of clusters. Linear regression was performed on all radiographic metrics using patient and disease characteristics. RESULTS: Twenty-four patients were enrolled with 7 LR and 11 IR patients available for analysis. Pretreatment imaging characteristics between LR and IR patients were similar. Patients with LR disease exhibited a larger reduction in maximum standardized uptake value (SUV) compared with IR patients (P<0.05). Cluster analysis defined 2 cohorts that exhibited a similar intratreatment response. Cluster 1 contained 7 of 7 LR patients and 8 of 11 IR patients. Cluster 2 contained 3 of 11 IR patients. Cluster 2 exhibited significant differences compared with cluster 1 in the change in primary tumor peak SUV and largest lymph node median SUV. CONCLUSIONS: We identified that IR p16-positive oropharynx cancers exhibit heterogeneity in their PET/MRI response to chemoradiotherapy. These data support further study of intratreatment imaging response as a potential mechanism to identify patients with IR oropharynx cancer suitable for treatment deintensification.

The radial forearm snake flap: An underutilized technique for fasciocutaneous and osteocutaneous forearm flaps with primary closure.

BACKGROUND: The radial forearm free flap (RFFF) is associated with troublesome donor site morbidity related to split thickness skin grafting (STSG). The radial forearm snake flap with primary closure of the donor site may reduce donor site complications. METHODS: Single institution, retrospective cohort study comparing rates of delayed donor site wound healing and tendon exposure in 52 patients undergoing radial forearm snake flap and 95 patients undergoing conventional RFFF with STSG closure of the donor site. RESULTS: Tendon exposure occurred in zero (0%) patients undergoing snake flap and four (4.2%) patients undergoing conventional RFFF (0/52 vs. 4/95; p = 0.297). Delayed wound healing occurred in zero (0%) patients undergoing snake flap and 19 (20.0%) patients undergoing conventional RFFF (0/52 vs. 19/95; p < 0.001). CONCLUSIONS: The radial forearm snake flap provides an alternative to conventional RFFF harvest, which enables primary donor site closure with reduced rates of delayed donor site healing.

Prognostic Significance of Pain in Parotid Gland Malignancy.

OBJECTIVES/HYPOTHESIS: To better understand the significance of pain as a predictor of disease severity in parotid gland malignancy. STUDY DESIGN: A retrospective chart review of patients treated for primary parotid gland malignancy at our institution between 1991 and 2020 was performed. METHODS: Patient records were retrospectively reviewed and relevant clinical parameters were collected. Patients were stratified into low stage (I and II) disease and high stage (III and IV) disease groups to analyze the independent effect of pain at initial presentation on disease recurrence rate and disease-free survival using Kaplan-Meier survival curves and an independent two-sample t-test. RESULTS: Of 154 patients evaluated, there were 69 patients in the low stage group and 80 patients in the high stage group. Thirty-seven high stage patients presented with pain. High stage patients with pain were significantly more likely to develop disease recurrence than high stage patients without pain (58.5% [22/37] versus 33.3% [13/39], P = .022). High stage patients with pain also had significantly decreased disease-free survival time compared to high stage patients without pain (P = .027). CONCLUSION: Pain on presentation appears to be a poor prognostic factor for patients with parotid gland malignancy. For patients with demonstrated high stage disease, pain is independently associated with increased risk of recurrence and decreased disease-free survival time. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1503-1508, 2021.

Clinical outcomes for larynx patients with cancer treated with refinement of high-dose radiation treatment volumes.

BACKGROUND: To evaluate disease control, toxicities, and dose to dysphagia/aspiration risk structures (DARS) using a direct gross tumor volume (GTV70Gy ) to planning target volume expansion (dPTV70Gy ) for patients with squamous cell carcinoma of the larynx (LSCC). METHODS: A retrospective review was performed on patients with LSCC treated between 2003 and 2018. Clinical outcomes, toxicities, and dosimetric data were analyzed. RESULTS: Seventy-three patients were identified. Overall survival at 5-years was 57.8%. Five-year local and regional control was 79.8% and 88.2%, respectively. Distant metastatic-only failure was 2.7%. Eighty percent of failures were 95% contained within the dPTV70Gy . Mean dose and the volume of DARS receiving 70 Gy was significantly lower for dPTV70Gy compared to a consensus-defined PTV70Gy . DISCUSSION: Judicious reduction in high-dose target volumes can preserve high tumor control rates while reducing dose to normal surrounding structures underscoring the potential benefit of this approach in enabling local therapy intensification to improve locoregional control.

Opioid use in patients undergoing treatment for oral cavity cancer.

OBJECTIVE: In the context of the opioid epidemic, there is value in examining the use of opioids in specific cancer patient cohorts. We analyzed opioid use in patients undergoing adjuvant therapy for oral cavity cancer to define the incidence of new persistent use beyond 3 months. STUDY DESIGN: Retrospective. SETTING: Comprehensive academic cancer center. SUBJECTS AND METHODS: We performed a retrospective IRB-approved analysis of opioid use in patients who received adjuvant radiotherapy with or with concurrent systemic therapy for surgically resected oral cavity cancer between 2003 and 2016. Factors associated with opioid use were evaluated by Chi-square test and one-way ANOVA. The Kaplan-Meier method was used to estimate overall survival. RESULTS: Of 77 identified patients, 10 (13%) patients received opioid prescriptions at 3 months or greater following completion of radiotherapy. Patients who were opioid naive prior to surgery required significantly fewer opioid prescriptions than intermittent or chronic opioid users. No specific factors were associated with new persistent opioid use. CONCLUSIONS: Patients undergoing surgery and adjuvant radiotherapy for oral cavity cancer who required opioids for cancer treatment related pain are at minimal risk for new dependency. Judicious pain management should be applied for patients with a history of prior opioid use. Larger patient cohorts will be needed to identify patient, disease, and treatment characteristics associated with new persistent use given its limited incidence.

A Comparison of E6H4 and G175-405 p16-specific Monoclonal Antibodies in Oropharyngeal Squamous Cell Carcinoma.

The purpose of this investigation is to directly compare G175-405 and E6H4 p16-specific antibodies as immunomarkers of HPV-driven oropharyngeal carcinoma. The investigators designed a retrospective analysis using specimens from an archived tissue bank with known in situ hybridization and polymerase chain reaction status for HPV DNA. Fifty randomly selected oropharyngeal specimens were evaluated with both the G175-405 and E6H4 p16-specific monoclonal antibodies. Two pathologists, blinded to the HPV-specific testing status, evaluated p16 positivity for both antibody clones. Interrater agreement was determined using a Cohen κ coefficient. Sensitivity and specificity values were calculated using a standard 2×2 contingency table, then compared using McNemar test. Interrater agreement for interpretation of p16 expression was 92% (κ=0.84) for the G175-405 clone and 100% for the E6H4 clone (κ=1.0). The G175-405 stain had a sensitivity of 0.917 and specificity of 0.846. The E6H4 stain had a sensitivity of 1.000 and specificity of 0.769. Using McNemar test, there were no significant differences found for sensitivity (P=0.480) or specificity (P=0.480) values. The results of this study suggest that though both G175-405 and E6H4 antibody stains are statistically comparable immunomarkers for HPV-driven oropharyngeal carcinoma, the E6H4 clone offers improved interobserver reliability.

Auriculotemporal Nerve Involvement in Parotid Bed Malignancy.

OBJECTIVE: To identify and evaluate patients with parotid bed malignancy demonstrating radiographic findings of auriculotemporal (AT) nerve involvement. METHODS: A retrospective review of patients with parotid bed malignancy was performed to identify patients with imaging findings of AT nerve involvement and record associated clinical findings, symptoms, and pathology information. Independent, blinded review of radiographic images by a senior neuroradiologist was performed to identify imaging characteristics and categorize patients into highly likely or possible involvement groups. RESULTS: Of 547 patients identified with parotid bed malignancy, 23 patients exhibited radiographic findings suggestive of AT nerve involvement. Thirteen patients met criteria for highly likely involvement, and 10 patients met criteria for possible involvement. Cutaneous malignancy with metastasis to the parotid bed accounted for 11 of 23 patients, and the most common histology was squamous cell carcinoma (9 patients). Primary parotid malignancy accounted for 12 of 23 patients, and the most common histology was salivary ductal carcinoma (3 patients). All 13 highly likely patients reported periauricular pain, and 11 of 13 demonstrated facial weakness. Features suggesting advanced disease included radiographic findings of intracranial involvement (10/23 patients), nonsurgical primary treatment (13/23 patients), and positive margins on pathology report (7/10 patients). CONCLUSION: AT nerve involvement is an uncommon but important phenomenon that often occurs in the setting of advanced disease and is commonly associated with periauricular pain and coexisting facial weakness. Awareness of the associated clinical features and imaging patterns can allow for appropriate identification of this pattern of spread and help to optimize treatment planning.

Is HPV-Associated Oropharyngeal Cancer Becoming More Common in Older Patients?

OBJECTIVE: To evaluate changing age demographics over a 15-year period for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective review of patients identified with p16-positive OPSCC at our institution over a 15-year timeframe. Materials/Methods: p16-positive immunohistochemistry was used as a surrogate for HPV-associated OPSCC. Patients were categorized according to year of diagnosis (2002-2010 versus 2011-2016). Mean age and proportion of patients over age 65 were statistically evaluated and compared. RESULTS: From 2002 to 2010, 100 patients were identified with p16-positive OPSCC, mean age at diagnosis was 55.2, and the proportion of patients over 65 was 10.0%. From 2011 to 2016, 188 patients were identified with p16-positive OPSCC, mean age was 58.5, and the proportion of patients over 65 was 19.6%. Both the mean age difference and the difference in proportion of patients over 65 were statistically significant (P = .001 and P = .034, respectively). CONCLUSION: The mean age at diagnosis and proportion of patients over 65 has increased over the past 15 years at our institution. This data suggests that HPV-associated OPSCC is being diagnosed more frequently in older persons and that the age demographic may be shifting. Confirmation of this trend with larger patient numbers on a national level will be valuable. This study highlights the importance of maintaining a high clinical suspicion for HPV-associated OPSCC regardless of patient age. LEVEL OF EVIDENCE: 4.

Incidental Findings on FDG PET/CT in Head and Neck Cancer.

Objective 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG PET/CT) imaging is common in head and neck cancer and often identifies incidental findings that necessitate additional patient evaluations. Our goal was to assess the frequency and nature of these incidental imaging findings on FDG-PET/CT. Study Design Retrospective cohort study. Setting Tertiary medical center. Subjects and Methods All patients with head and neck cancer who had undergone FDG-PET/CT imaging between January 2014 and June 2015 at our institution were evaluated for incidental findings. Results A total of 293 patients met criteria; more than one-third (n = 103) had at least 1 finding unrelated to their head and neck cancer, for a total of 134 incidental findings. Incidental findings within the head and neck (33.5% of all) excluding the thyroid were most common: 35% incidental findings were concerning for malignancy; of these, 25.5% were malignant with further workup. Recommendations were given by the head and neck radiologist on 72 (53.7%) findings: 74.5% of potentially malignant findings and 42.5% of benign findings had recommendations for follow-up. Significantly more patients with findings described as malignant were given recommendations for follow-up ( P = .0004). Conclusion Incidental findings on FDG-PET/CT are present in more than one-third of patients with head and neck cancer. More than one-third of incidental findings were concerning for malignancy. This study illustrates how the incidental findings discovered on FDG PET/CT frequently necessitate additional evaluations unrelated to the index head and neck cancer. The impact of these additional assessments on the cost and quality of health care warrants future evaluation.

Lymph Node Yield in Therapeutic Neck Dissection: Impact of Dissection Levels and Prior Radiotherapy.

OBJECTIVE: Lymph node yield in therapeutic neck dissection is clinically significant and incompletely studied. We quantified node yield based on extent of neck dissection and presence of preoperative radiation. We also evaluated factors affecting incidence of extracapsular spread (ECS). METHODS: Retrospective review of 499 patients undergoing therapeutic neck dissection; 414 patients met inclusion criteria and were divided into 2 groups: neck dissection alone or before radiation (surgery first: 280 patients; 385 dissections) and primary radiation before surgery (radiation first: 134 patients; 157 dissections). Node yield relative to levels dissected and incidence of ECS were examined. RESULTS: Dissection-specific node yield was greater in the surgery first group for dissection of levels I-V (31.1 ± 16.7 vs 24.0 ± 14.7, P < .001) and levels II-V (26.7 ± 14.4 vs 21.1 ± 10.7). Extracapsular spread incidence was 32.1% (98/305) in the surgery first group and 15.4% (23/149) in the radiation first group ( P < .001). CONCLUSION: This study clarifies anticipated node yield based on number of levels dissected and presence of preoperative radiation. Node yield and incidence of ECS are lower in patients undergoing preoperative radiation.

Use of sialendoscopy as an aid to identify a large retained foreign body.

We describe the novel use of sialendoscopy in a 51-year-old man to identify a large and long-standing foreign body (wood) within the facial soft tissues that had eluded detection on previous imaging and surgical exploration. The identification of this foreign body was elusive on both computed tomography and magnetic resonance imaging, illustrating the limitations of imaging in identifying vegetable matter within soft tissues.

Clinical outcomes for patients presenting with N3 head and neck squamous cell carcinoma: Analysis of the National Cancer Database.

BACKGROUND: There is a paucity of data regarding head and neck squamous cell carcinomas (HNSCCs) and N3 nodal disease. METHODS: Retrospective analysis of patients with N3 HNSCC identified in the National Cancer Database (NCDB) was performed. RESULTS: We identified 4867 patients with N3 HNSCC treated with primary surgery or chemoradiotherapy (CRT). Propensity-adjusted median survival was 54.2 and 44.8 months for surgery and CRT, respectively (P = .06). Oropharyngeal primary subsite demonstrated a survival advantage with surgery versus CRT with propensity-adjusted median survivals of 86.0 and 61.9 months, respectively (P < .05). CONCLUSION: Management of N3 HNSCC relies largely on CRT. Patients with N3 nodal disease with nonoropharyngeal primary tumors exhibit 5-year overall survival approaching 30% independent of initial treatment modality. Patients with oropharyngeal primaries exhibit improved outcomes with surgery largely influenced by the human papillomavirus (HPV)-negative subset. These data represent the most comprehensive analysis of N3 HNSCC outcomes and serves as a foundation for future research and clinical management.