Association of HPV status with survival after surgical salvage of oropharyngeal cancers.

OBJECTIVES: This study used the National Cancer Database to determine the effect of human papillomavirus (HPV) on survival outcomes for recurrent oropharyngeal cancer treated with salvage surgery after initial treatment with radiation therapy or chemoradiation therapy. METHODS: Patients with recurrent oropharyngeal cancer receiving salvage surgery after initial treatment with adjuvant therapy were identified through the National Cancer Database. Demographics, tumor characteristics, and survival data were collected. The data were analyzed to identify factors that may be associated with survival. RESULTS: A total of 169 patients were included, 59% of which were HPV-positive cases and 41% were HPV-negative. On univariate analysis, HPV-positive cases had higher overall survival compared to HPV-negative cases. However, on multivariate analysis, the association with HPV status was no longer statistically significant while positive surgical margins, higher T-stage at initial diagnosis, and a greater comorbidity burden were significantly associated with poorer survival. CONCLUSION: In the salvage setting for treatment of recurrent oropharyngeal squamous cell carcinoma, HPV status may not be associated with improved survival.

Effect of histopathological grade on treatment and survival in base of tongue adenocarcinoma.

OBJECTIVES: The purpose of this study was to investigate survival differences between low-grade and high-grade base of tongue (BOT) adenocarcinoma by examining demographics, tumor characteristics, and treatment modalities. METHODS: The National Cancer Database was queried for patients with BOT adenocarcinoma between 2004 and 2017. Univariate and multivariate analyses were performed for all cases of BOT adenocarcinoma. Subsequent analysis focused on low-grade (grade 1 and grade 2) and high-grade (grade 3 and grade 4) BOT adenocarcinoma. RESULTS: A total of 286 patients with BOT adenocarcinoma were included in the main cohort and divided into low grade (n = 137) and high grade (n = 66). The 5-year overall survival for all patients, low-grade, and high-grade was 67%, 85%, and 58%, respectively. Prognostic factors associated with decreased survival for the main cohort include advanced age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02-1.06), non-white race (HR: 1.79; 95% CI: 1.04-3.25), public insurance (HR: 1.79; 95% CI: 1.02-3.14) and high-grade 3,4 (HR: 2.63; 95% CI: 1.51-4.56). The prognostic factor associated with increased survival for the main cohort was surgery (HR: 0.59; 95% CI: 0.36-0.96). Radiotherapy was associated with improved overall survival for high-grade BOT adenocarcinoma (HR: 0.09; 95% CI: 0.02-0.49) but not for low-grade BOT adenocarcinoma (HR: 0.93; 95% CI: 0.38-2.32). CONCLUSIONS: This investigation is the largest to date analyzing the association of treatment modalities with overall survival in BOT adenocarcinoma. Surgery remains standard of treatment, particularly in low-grade cases, with radiotherapy offering additional survival benefit for high-grade BOT adenocarcinoma.

Cytopathologic assessment of gloves and instruments after major head and neck surgery.

PURPOSE: To investigate the potential for cancer cells to be transferred between anatomic sites via instruments and other materials. MATERIALS AND METHODS: Pilot prospective study from April 2018-January 2019 at Rush University Medical Center. Glove and instrument washings were collected from 18 high-risk head and neck cancer resection cases (36 samples total). Each case maintained at least one of the following features in addition to a diagnosis of squamous cell carcinoma or sarcoma: palliative/salvage surgery, positive margins, extensive tumor burden, and/or extra capsular extension (ECE). Surgical gloves and four main instruments were placed through washings for blind cytological assessment (2 samples/case). RESULTS: 18 patients undergoing surgical tumor resection for biopsy-proven squamous cell carcinoma with at least one of the aforementioned characteristics were included. 26.7% of cases had ECE, 40.0% had positive final margins and 46.7% had close final margins. Tumor locations included: oral cavity (10), neck (4), parotid gland (2), and skin (2). Malignant cells were isolated on glove washings in 1 case (5.5%). No malignant cells were isolated from instrument washings. The single case of malignant cells on glove washings occurred in a recurrent, invasive squamous cell carcinoma of the scalp with intracranial extension. Anucleated squamous cells likely from surgeon skin were isolated from 94.4% of washings. Squamous cells were differentiated from mature cells by the absence of nuclei. CONCLUSIONS: Malignant squamous cells can be isolated from surgical glove washings, supporting the practice of changing of gloves after gross tumor resection during major head and neck cancer resections.

Functional outcomes after extracapsular dissection with partial facial nerve dissection for small and large parotid neoplasms.

PURPOSE: Multiple surgical options exist for benign parotid tumors without agreement upon a single, best approach. We evaluated the short-term outcomes and rate of complications using the ECD-FND technique for small and large parotid neoplasms involving the superficial and deep lobes of the parotid gland using a categorical approach. MATERIAL AND METHODS: A single surgeon retrospective cohort study with analysis of patient demographics, outcomes, and complication rates was conducted of patients undergoing the ECD-FND for benign parotid neoplasm. Cases from May 2014 to May 2020 with at least 6 months follow up were considered. Complications were assessed by chart review and tumors were categorized by size and by European Salivary Gland Society (ESGS) classification assigned by a neuroradiologist. RESULTS: Fifty-one patients who underwent ECD-FND of suspected benign parotid mass met inclusion criteria. The most common histology was pleomorphic adenoma (56.9%) followed by Warthin's tumor (19.6%). Overall rate of complications was 31.4% with no major complications. Most patients (88.2%) had normal facial nerve function immediately after surgery and all recovered completely in the post operative period. Sialocele occurred in 15.7% of patients with 87.5% resolved within one month and seromas occurred in four patients (7.8%). There was no significant difference in complication rates between the size of tumor (p = 0.889), depth (p = 0.770), or ESGS classification (p = 0.846). CONCLUSIONS: The ECD-FND technique achieved excellent facial nerve outcomes among our cohort, which included a - proportion of large (>3 cm) and deep lobe tumors. Complications rates and outcomes were similar for larger and deep lobe tumors that underwent a ECD-FND approach. LEVEL OF EVIDENCE: 3.

Enhanced recovery protocol for transoral robotic surgery demonstrates improved analgesia and narcotic use reduction.

BACKGROUND: No study has evaluated the impact of the Enhanced Recovery After Surgery (ERAS) protocol on opioid usage among patients undergoing transoral robotic surgery (TORS). METHODS: In this retrospective study, patients undergoing TORS were enrolled in an ERAS protocol and compared to control patients. Primary outcome measures included postoperative mean morphine equivalent dose (MED), Defense and Veterans Pain Rating Scale (DVPRS) pain scores, and opioid prescriptions on discharge. RESULTS: The mean MED administered postoperatively was lower in the ERAS group (17.6 mg) than in the control group (65.0 mg) (p < .001). Average postoperative DVPRS scores were 2.9 in the ERAS group vs. 4.2 in the control group (p = .042). Fewer patients in the ERAS group received opioid prescriptions on discharge (31.6%) than controls (96.2%) (p < .001). CONCLUSION: The TORS ERAS protocol is associated with reduced postoperative opioid usage, lower pain scores, and reduced opioid requirements on discharge.

Clinical features and outcomes in young adults with oral tongue cancer.

OBJECTIVE: To evaluate outcomes and survival in young patients with oral tongue cancer (OTC). METHODS: Retrospective chart review of patients aged 18-40 with OTC treated between 2000 and 2016. Tumor characteristics of p16 expression, perineural invasion (PNI), and lymph-vascular invasion (LVI) were evaluated. Recurrence-free (RFS) and overall survival (OS) data were analyzed according to Kaplan-Meier method with univariate analysis. RESULTS: A total of 23 patients were identified: 12 with early stage disease (ESD, stage I), and 11 with advanced stage disease (ASD, stage III or IV), (17 men and 6 women). Mean age at presentation was 34.5 years (±5 months) and mean follow-up was 46.6 months. For all patients, 5-year RFS was 62% and OS 66%. RFS for ESD was 73% and ASD 25% (log rank p = 0.011). OS for ESD was 100% and ASD 55% (log rank p = 0.012). 22% indicated tobacco use >5 pack-years and 9% heavy alcohol use. Factors associated with worse OS were neck disease (log rank p = 0.073), positive margins (log rank p = 0.001), and LVI (log rank p = 0.002). Factors associated with worse RFS were chemotherapy or radiation therapy prior to surgery (log rank p = 0.002), neck disease (log rank p = 0.047), positive margins (log rank p = 0.039), and PNI (log rank p = 0.001). Expression of p16 was observed in five cases and was not significantly associated with OS or RFS. CONCLUSION: In young patients with OTC, factors associated with worse outcomes are similar to known predictors in older patients. Expression of p16 was not statistically associated with improved OS. OS in patients with ESD was excellent (100%), and significantly worse for ASD.

Heterogeneity in the clinical presentation, diagnosis, and treatment initiation of p16-positive oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has a patient demographic, presentation, and clinical treatment response distinct from HPV-unassociated OPSCC. The heterogeneity in presentation and diagnosis within a patient population with HPV-positive OPSCC and its impact on times to presentation, diagnosis, and treatment have yet to be characterized. PARTICIPANTS: Patients with biopsy-proven p16-positive OPSCC seen and/or treated at our institution between 2008 and 2018. Of 136 patients with OPSCC seen and/or treated at our institution, 101 met criteria for inclusion. METHODS: Patients were grouped by several parameters including presenting symptom category (asymptomatic neck mass, neck mass with primary-site symptoms, or primary-site symptoms without a neck mass), p16 status on fine-needle aspiration (FNA), and date of presentation. Median time intervals between presentation to imaging, biopsy, and treatment were compared within each parameter using the Kruskal-Wallis test with a significance level of 0.05. RESULTS: Sixty-five of the 101 study patients presented with a neck mass. Patients without a neck mass had a longer interval from presentation to imaging than patients with a neck mass (median 4 vs 0 days, p = 0.025). Initial FNA obtained on 61 patients was positive for p16 in 19 patients. Unknown or negative p16 status on FNA was associated with shorter intervals from initial imaging to treatment initiation (39 vs 46.5 days, p = 0.045). Patients presenting in the final three years had a longer interval from presentation to treatment initiation (55 vs 41 days, p = 0.024). CONCLUSION: A neck mass is absent from the clinical picture of a substantial proportion of HPV-associated OPSCC patients. Primary-site symptom category and regional metastasis were not associated with differences in times to diagnosis or treatment initiation at this major referral center. The increased awareness and complexity of treatment decisions related to OPSCC may contribute to the delays in treatment initiation observed in patients with p16-positive FNAs and those who presented in more recent years.

A Nationwide Analysis of Head and Neck Fibromatoses.

BACKGROUND: Head and neck fibromatoses (HNFs) are a rare, diverse group of soft tissue tumors characterized by an abnormal proliferation of fibroblasts. Available literature on these tumors is limited to case reports and small single-institutional studies. OBJECTIVE: We aim to provide demographic, socioeconomic, tumor-related, and treatment characteristics of HNFs. DESIGN: Retrospective cohort analysis using the National Cancer Database (NCDB). METHODS: The NCDB was queried for fibromatosis-related histologic codes located within the head and neck region. Various factors were analyzed. Univariate and multivariate survival analyses were performed. RESULTS: Between 2004 and 2016, 130 patients were included in the analyses. Average age was 57.4 years old with a predominance of White (83.6%) males (61.5%). Non-desmoid HNFs accounted for 60%-70% of the tumors. The salivary gland was the most common location (38.5%) and more than half of the tumors were high grade. The majority were treated surgically (90.8%) and 25% had positive margins. Mean and median overall survival (OS) were 98.9 and 135.4 months, respectively. Surgery is associated with better OS than nonsurgical alternatives. Addition of adjuvant treatments was not associated with differences in survival. CONCLUSION: In the largest study to date, we describe demographic, socioeconomic, tumor-related, and treatment patterns of patients with this rare disease. These tumors are most frequently present in middle-aged males with high-grade histology. Most are treated surgically and positive surgical margins are common. Surgery has better OS than nonsurgical alternatives. While adjuvant radiation has become more common, we found no difference in survival compared to surgery alone. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2228-2235, 2024.

Air pollution is associated with increased incidence-rate of head and neck cancers: A nationally representative ecological study.

INTRODUCTION: Early studies show conflicting findings regarding particulate matter ≤ 2.5 µm in diameter (PM2.5) exposure and development of head and neck cancers (HNC). We analyzed the relationship between PM2.5 exposure and various types of HNC in a nationally representative ecological sample. METHODS: We determined HNC incidence in 608 US counties from 2011 to 2019 using the Surveillance, Epidemiology and End Results (SEER) Program from the National Cancer Institute. We also collected information on sociodemographic factors from SEER and data on smoking and alcohol intake from CDC data frames (county level). PM2.5 exposure levels were estimated using satellite and meteorological data via previously validated general additive models. Flexible semi-nonparametric regression models were used to test the relationship between PM2.5 exposure levels and HNC incidence, adjusting for demographics, socioeconomic factors, and comorbidity. RESULTS: Increased PM2.5 exposure levels were associated with higher incidence-rates of oral cavity and pharyngeal cancers controlling for confounders in our primary analyses (IRR = 1.04, 95 % CI 1.01, 1.07, p = 0.02 per 1 µg/m3 increase in PM2.5). This relationship was maintained after adjusting for multiple testing (Holm s method, p = 0.04) and in ordinary least squares (OLS) regression (ß = 0.17, 95 % CI 0.01, 0.57, p = 0.01). Increased exposure was also associated with other HNC: esophagus (IRR = 1.06, 95 % CI 1.01, 1.11, p = 0.02), lip (IRR = 1.16, 95 % CI 1.03, 1.31, p = 0.01), tonsil (IRR = 1.10, 95 % CI 1.03, 1.16, p < 0.01). However, these relationships were not maintained in secondary analyses. CONCLUSIONS: This nationally representative ecological study shows that increased levels of air pollution are associated with increased incidence of overall oral cavity and pharyngeal cancers in the US.

A nationwide analysis of salvage surgery for laryngeal cancer in the elderly.

BACKGROUND: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. METHODS: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. RESULTS: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30-day and 90-day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). CONCLUSION: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30-day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population.

The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer.

Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020-April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment. Safety was the primary endpoint; secondary endpoints were non-LRR, survival, cancer cell death, and the preservation of surrounding healthy tissue. CHCP did not impact intraoperative physiological data (p > 0.05) or cause any related adverse events. Overall response rates at 26 months for R0 and R0 with microscopic positive margin (R0-MPM) patients were 69% (95% CI, 19-40%) and 100% (95% CI, 100-100.0%), respectively. Survival rates for R0 (n = 7), R0-MPM (n = 5), R1 (n = 6), and R2 (n = 2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative overall survival rate was 24% at 31 months (n = 20, 95% CI, 5.3-100.0). CHCP treatment combined with surgery is safe, selective towards cancer, and demonstrates exceptional LRR control in R0 and R0-MPM patients. (Clinical Trials identifier: NCT04267575).

Laparoscopic Transhiatal Esophagectomy With En Bloc Posterior Tracheal Wall Resection.

Esophageal adenoid cystic carcinoma is a rare cancer that is a challenge to treat because the tumor often invades local structures. Complete resection with grossly negative margins is key to disease-free survival. We describe a case in which the esophageal tumor invaded a significant portion of the posterior trachea, making a tracheal resection with primary anastomosis impossible. Therefore, to resect the tumor completely, we performed a laparoscopic esophagectomy and posterior tracheal resection with tracheoplasty using a rotational flap while the patient was on venovenous extracorporeal membrane oxygenation.

Presence of CrkI-containing microvesicles in squamous cell carcinomas could have ramifications on tumor biology and cancer therapeutics.

Recently, we described a phenomenon whereby apoptotic cells generate and release CrkI-containing microvesicles, which stimulate proliferation in surrounding cells upon contact to compensate for their own demise. We termed these microvesicles "ACPSVs" for Apoptotic Compensatory Proliferation Signaling microvesicles. As immune cells and a majority of current cancer therapeutics destroy tumor cells primarily by apoptosis, we conducted a small pilot study to assess the possibility that ACPSVs may also be generated in squamous cell carcinomas. We first evaluated a primary and a metastatic squamous cell carcinoma cancer cell lines for their ability to produce ACPSVs under normal and apoptotic conditions. We next conducted a pilot study to assess the occurrence of ACPSVs in solid tumors extracted from 20 cancer patients with squamous cell carcinomas. Both cancer cell lines produced copious amounts of ACPSVs under apoptotic conditions. Interestingly, the metastatic squamous cell carcinoma cancer cell line also produced high levels of ACPSVs under healthy condition, suggesting that the ability to generate ACPSVs may be hijacked by these cells. Importantly, ACPSVs were also abundant in the solid tumors of all squamous cell carcinoma cancer patients. Detection of ACPSVs in cancer has potentially important ramifications in tumor biology and cancer therapeutics which warrants further investigation.

Laryngeal Chondrosarcoma Characteristics and Survival Analysis in the National Cancer Database.

OBJECTIVE: To highlight various patient, tumor, diagnostic, and treatment characteristics of laryngeal chondrosarcoma (LC) as well as elucidate factors that may independently affect overall survival (OS) for LCs. STUDY DESIGN: Retrospective cohort study. SETTING: National Cancer Database (NCDB). METHODS: All LC cases from 2004 to 2016 were extracted from the NCDB. Several demographic, diagnostic, and treatment variables were compared between LC subgroups using χ2 and analysis of variance tests. Univariate and multivariate survival analyses were performed for LCs using univariate Kaplan-Meier analysis and Cox proportional hazards regression models. RESULTS: There were 348 LCs included in the main cohort. LCs were predominantly non-Hispanic white males with similar rates of private and government insurance (49.4% vs 45.4%). Most LCs (81.6%) underwent primary surgery, particularly partial and total laryngectomy. The 1-, 5-, and 10-year survivals for LC were 95.7%, 88.2%, and 66.3%, respectively. On multivariate analysis, lack of insurance (P = .019; hazard ratio [HR], 8.21; 95% CI, 1.40-48.03), high grade (P = .001; HR, 13.51; 95% CI, 3.08-59.26), and myxoid/dedifferentiated histological subtypes (P = .0111; HR, 10.74; 95% CI, 1.71-67.33) correlated with worse OS. No difference in OS was found between partial and total laryngectomy. CONCLUSION: This is the first multivariate survival analysis and largest single cohort study of LCs in the literature. Overall, LCs enjoy an excellent prognosis, with insurance status, grade, and histology as the main predictors of survival.

Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation.

BACKGROUND: It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT. METHODS: The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor-prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5-fluorouracil, hydroxyurea, and a third agent. RESULTS: One hundred sixty-six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow-up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2-year rates for OS, disease-free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty-three patients (19.9%) died of treatment-related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2-year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full-dose ReRT, and radiotherapy interval. CONCLUSIONS: CReRT achieved a long-term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients.

Prognostic Indicators in Base of Tongue Adenocarcinoma: A Population-Based Analysis.

INTRODUCTION: The objectives of this investigation are to characterize the epidemiology of base of tongue adenocarcinoma utilizing a population-based database and to identify prognostic factors that may affect survival. METHODS: A retrospective cohort study was conducted using the Surveillance, Epidemiology, and End Results database. Univariate Kaplan-Meier analysis and multivariate Cox-regression analysis were performed to evaluate the association of suspected prognostic factors with survival. Overall survival (OS) and disease-specific survival (DSS) were the primary outcome measures. RESULTS: A total of 176 cases were eligible based on inclusion criteria. The 5-year OS and DSS were 49% and 66%, respectively. On multivariate analysis, surgical management was associated with improved OS and DSS (OS hazard ratio [HR]: 0.34, 95% confidence interval [CI]: 0.20-0.58, P < .001; DSS HR: 0.20, 95% CI: 0.09-0.48, P < .001), while higher tumor grade was associated with worse OS and DSS (OS HR: 1.58, 95% CI: 1.14-2.19, P = .006; DSS HR: 1.68, 95% CI: 1.01-2.79, P = .045). Administration of chemotherapy or radiation did not have a significant association with OS or DSS. CONCLUSION: This investigation is the largest to date to analyze the base of tongue adenocarcinoma as its own entity. Surgery remains the mainstay of treatment, and lower tumor grade is associated with improved survival in these patients. Administration of radiation or chemotherapy was not associated with improved survival.

Occult Lymph Node Metastasis in Early-Stage Glottic Cancer in the National Cancer Database.

OBJECTIVES: Early-stage glottic cancer (cT1-T2 cN0) may be treated by primary surgery or radiation. Elective treatment of the neck in clinically N0 disease is usually not performed due to low rates of regional lymph node metastasis. This study examines the role of elective neck dissection (END) and rate of occult nodal metastasis in cT1-T2 cN0 glottic cancer treated with primary surgery. STUDY DESIGN: Retrospective cohort study. METHODS: The National Cancer Database was used to identify patients treated for early-stage glottic cancer. Demographic variables, disease characteristics, and overall survival were compared between the subgroups of patients who did and did not receive END. Factors predictive of occult lymph node metastasis were also identified using a multivariate logistic regression model. RESULTS: Thirty-eight percent of the 991 patients in this cohort underwent END. Younger age, treatment at an academic facility, advanced T-stage, and higher tumor grade were associated with receiving END. Sixteen percent of the 372 patients undergoing END had occult nodal metastasis. Higher tumor histopathologic grade was associated with occult metastasis (P = .004). While undergoing END did not affect significantly survival, those with occult metastasis had poorer survival (P < .001). CONCLUSIONS: END should be considered in cT1-T2 N0 glottic cancers with poorly differentiated or undifferentiated tumor histopathology. While END itself may not improve overall survival, identification of occult nodal metastasis is an important finding for prognostication. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 131:E1139-E1146, 2021.

Phase 1/2a, open-label, multicenter study of RM-1929 photoimmunotherapy in patients with locoregional, recurrent head and neck squamous cell carcinoma.

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.

Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations.

OBJECTIVE: Opioid use disorder (OUD), which includes the morbidity of dependence and mortality of overdose, has reached epidemic proportions in the United States. Overprescription of opioids can lead to chronic use and misuse, and unused narcotics after surgery can lead to their diversion. Research supports that most patients do not take all the prescribed opioids after surgery and that surgeons are the second largest prescribers of opioids in the United States. The introduction of opioids in those with OUD often begins with prescription opioids. Reducing the number of extra opioids available after surgery through smaller prescriptions, safe storage, and disposal should reduce the risk of opioid use disorder in otolaryngology patients and their families. PURPOSE: The purpose of this specialty-specific guideline is to identify quality improvement opportunities in postoperative pain management of common otolaryngologic surgical procedures. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. Employing these action statements should reduce the variation in care across the specialty and improve postoperative pain control while reducing risk of OUD. The target patients for the guideline are any patients treated for anticipated or reported pain within the first 30 days after undergoing common otolaryngologic procedures. The target audience of the guideline is otolaryngologists who perform surgery and clinicians who manage pain after surgical procedures. Outcomes to be considered include whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.The guideline addresses assessment of the patient for OUD risk factors, counseling on pain expectations, and identifying factors that can affect pain duration and/or severity. It also discusses the use of multimodal analgesia as first-line treatment and the responsible use of opioids. Last, safe disposal of unused opioids is discussed.This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not a comprehensive guide on pain management in otolaryngologic procedures. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experiences and assessments of individual patients. ACTION STATEMENTS: The guideline development group made strong recommendations for the following key action statements: (3A) prior to surgery, clinicians should identify risk factors for opioid use disorder when analgesia using opioids is anticipated; (6) clinicians should advocate for nonopioid medications as first-line management of pain after otolaryngologic surgery; (9) clinicians should recommend that patients (or their caregivers) store prescribed opioids securely and dispose of unused opioids through take-back programs or another accepted method.The guideline development group made recommendations for the following key action statements: (1) prior to surgery, clinicians should advise patients and others involved in the postoperative care about the expected duration and severity of pain; (2) prior to surgery, clinicians should gather information specific to the patient that modifies severity and/or duration of pain; (3B) in patients at risk for OUD, clinicians should evaluate the need to modify the analgesia plan; (4) clinicians should promote shared decision making by informing patients of the benefits and risks of postoperative pain treatments that include nonopioid analgesics, opioid analgesics, and nonpharmacologic interventions; (5) clinicians should develop a multimodal treatment plan for managing postoperative pain; (7) when treating postoperative pain with opioids, clinicians should limit therapy to the lowest effective dose and the shortest duration; (8A) clinicians should instruct patients and caregivers how to communicate if pain is not controlled or if medication side effects occur; (8B) clinicians should educate patients to stop opioids when pain is controlled with nonopioids and stop all analgesics when pain has resolved; (10) clinicians should inquire, within 30 days of surgery, whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.

Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations Executive Summary.

OBJECTIVE: Opioid use disorder (OUD), which includes the morbidity of dependence and mortality of overdose, has reached epidemic proportions in the United States. Overprescription of opioids can lead to chronic use and misuse, and unused narcotics after surgery can lead to their diversion. Research supports that most patients do not take all the prescribed opioids after surgery and that surgeons are the second largest prescribers of opioids in the United States. The introduction of opioids in those with OUD often begins with prescription opioids. Reducing the number of extra opioids available after surgery through smaller prescriptions, safe storage, and disposal should reduce the risk of opioid use disorder in otolaryngology patients and their families. PURPOSE: The purpose of this specialty-specific guideline is to identify quality improvement opportunities in postoperative pain management of common otolaryngologic surgical procedures. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. Employing these action statements should reduce the variation in care across the specialty and improve postoperative pain control while reducing risk of OUD. The target patients for the guideline are any patients treated for anticipated or reported pain within the first 30 days after undergoing common otolaryngologic procedures. The target audience of the guideline is otolaryngologists who perform surgery and clinicians who manage pain after surgical procedures. Outcomes to be considered include whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.The guideline addresses assessment of the patient for OUD risk factors, counseling on pain expectations, and identifying factors that can affect pain duration and/or severity. It also discusses the use of multimodal analgesia as first-line treatment and the responsible use of opioids. Last, safe disposal of unused opioids is discussed.This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not a comprehensive guide on pain management in otolaryngologic procedures. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experiences and assessments of individual patients. ACTION STATEMENTS: The guideline development group made strong recommendations for the following key action statements: (3A) prior to surgery, clinicians should identify risk factors for opioid use disorder when analgesia using opioids is anticipated; (6) clinicians should advocate for nonopioid medications as first-line management of pain after otolaryngologic surgery; (9) clinicians should recommend that patients (or their caregivers) store prescribed opioids securely and dispose of unused opioids through take-back programs or another accepted method.The guideline development group made recommendations for the following key action statements: (1) prior to surgery, clinicians should advise patients and others involved in the postoperative care about the expected duration and severity of pain; (2) prior to surgery, clinicians should gather information specific to the patient that modifies severity and/or duration of pain; (3B) in patients at risk for OUD, clinicians should evaluate the need to modify the analgesia plan; (4) clinicians should promote shared decision making by informing patients of the benefits and risks of postoperative pain treatments that include nonopioid analgesics, opioid analgesics, and nonpharmacologic interventions; (5) clinicians should develop a multimodal treatment plan for managing postoperative pain; (7) when treating postoperative pain with opioids, clinicians should limit therapy to the lowest effective dose and the shortest duration; (8A) clinicians should instruct patients and caregivers how to communicate if pain is not controlled or if medication side effects occur; (8B) clinicians should educate patients to stop opioids when pain is controlled with nonopioids and stop all analgesics when pain has resolved; (10) clinicians should inquire, within 30 days of surgery, whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.