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.

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).

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.

Management of the Clinical and Academic Mission in an Urban Otolaryngology Department During the COVID-19 Global Crisis.

OBJECTIVE: The objective of this study was to assess the strategic changes implemented in the departmental mission to continue safe delivery of otolaryngology care and to support the broader institutional mission during the COVID-19 pandemic response. STUDY DESIGN: Retrospective assessment was performed to the response and management strategy developed to transform the clinical and academic enterprise. SETTING: Large urban tertiary care referral center. RESULTS: The departmental structure was reorganized along new clinical teams to effectively meet the system directives for provision of otolaryngology care and support for inpatient cases of COVID-19. A surge deployment schedule was developed to assist frontline colleagues with clinical support as needed. Outpatient otolaryngology was consolidated across the system with conversion of the majority of visits to telehealth. Operative procedures were prioritized to ensure throughput for emergent and time-critical urgent procedures. A tracheostomy protocol was developed to guide management of emergent and elective airways. Educational and research efforts were redirected to focus on otolaryngology care in the clinical context of the COVID-19 crisis. CONCLUSION: Emergence of the COVID-19 global health crisis has challenged delivery of otolaryngology care in an unparalleled manner. The concerns for preserving health of the workforce while ethically addressing patient career needs in a timely manner has created significant dilemmas. A proactive, thoughtful approach that reorganizes the overall departmental effort through provider and staff engagement can facilitate the ability to meet the needs of otolaryngology patients and to support the greater institutional mission to combat the pandemic.

Enhanced recovery after surgery in head and neck surgery: Reduced opioid use and length of stay.

OBJECTIVES: Enhanced recovery after surgery (ERAS) protocols were first developed in colorectal surgery and sought to standardize patient care. There have been several studies in the head and neck surgical literature looking at outcomes after ERAS protocol, but no studies focusing on narcotic use and length of stay. This study aimed to evaluate narcotic usage and length of stay, in addition to several other outcomes, following the implementation of an ERAS protocol. METHODS: A head and neck-specific ERAS protocol was implemented at this tertiary care center beginning July 2017. A retrospective cohort study was performed comparing this cohort to that of a retrospective control group. Outcomes included mean morphine equivalent dose, mean pain score, and percentage of patients prescribed narcotics on discharge. Secondary outcomes included ICU and total length of stay. RESULTS: The mean morphine equivalent dose (MED) administered within 72 hours postoperatively was significantly lower in the ERAS group (17.5 ± 46.0 mg vs. 82.7 ± 116.1 mg, P < .001). Average postoperative pain scores in the first 72 hours were lower in the ERAS group (2.6 ± 1.8 vs. 3.6 ± 1.9; P < .001). The average length of stay was shorter for ERAS patients (7.8 ± 4.8 vs. 9.7 ± 4.7 days, P = .008); however, there was no significant difference in ICU length of stay. CONCLUSION: Following implementation of an ERAS protocol, patients undergoing head and neck surgery had decreased narcotic use in the immediate postoperative period and at discharge, while also demonstrating improved postoperative analgesia. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 130:1227-1232, 2020.

Association of Perioperative Opioid-Sparing Multimodal Analgesia With Narcotic Use and Pain Control After Head and Neck Free Flap Reconstruction.

IMPORTANCE: An increase in narcotic prescription patterns has contributed to the current opioid epidemic in the United States. Opioid-sparing perioperative analgesia represents a means of mitigating the risk of opioid dependence while providing superior perioperative analgesia. OBJECTIVE: To assess whether multimodal analgesia (MMA) is associated with reduced narcotic use and improved pain control compared with traditional narcotic-based analgesics at discharge and in the immediate postoperative period after free flap reconstructive surgery. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed a consecutive sample of 65 patients (28 MMA, 37 controls) undergoing free flap reconstruction of a through-and-through mucosal defect within the head and neck region at a tertiary academic referral center from June 1, 2017, to November 30, 2018. Patients and physicians were not blinded to the patients' analgesic regimen. Patients' clinical courses were followed up for 30 days postoperatively. INTERVENTIONS: Patients were administered a preoperative, intraoperative, and postoperative analgesia regimen consisting of scheduled and as-needed neuromodulating and anti-inflammatory medications, with narcotic medications reserved for refractory cases. Control patients were administered traditional narcotic-based analgesics as needed. MAIN OUTCOMES AND MEASURES: Narcotic doses administered during the perioperative period and at discharge were converted to morphine-equivalent doses (MEDs) for comparison. Postoperative Defense and Veterans Pain Rating Scale pain scores (ranging from 0 [no pain] to 10 [worst pain imaginable]) were collected for the first 72 hours postoperatively as a patient-reported means of analyzing effectiveness of analgesia. RESULTS: A total of 28 patients (mean [SD] age, 64.1 [12.3] years; 17 [61%] male) were included in the MMA group and 37 (mean [SD] age, 65.0 [11.0] years; 22 [59%] male) in the control group. The number of MEDs administered postoperatively was 10.0 (interquartile range [IQR], 2.7-23.1) in the MMA cohort and 89.6 (IQR, 60.0-104.5) in the control cohort (P < .001). Mean (SD) Defense and Veterans Pain Rating Scale pain scores postoperatively were 2.05 (1.41) in the MMA cohort and 3.66 (1.99) in the control cohort (P = .001). Median number of MEDs prescribed at discharge were 0 (IQR, 0-18.8) in the MMA cohort and 300.0 (IQR, 262.5-412.5) in the control cohort (P < .001). CONCLUSIONS AND RELEVANCE: The findings suggest that after free flap reconstruction, MMA is associated with reduced narcotic use at discharge and in the immediate postoperative period and with superior analgesia as measured by patient-reported pain scores. Patients receiving MMA achieved improved pain control, and the number of narcotic prescriptions in circulation were reduced. LEVEL OF EVIDENCE: 3.

Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

OBJECTIVES: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. MATERIALS AND METHODS: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. RESULTS: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades. CONCLUSION: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. RESULTS: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.

Performance and quality of life outcomes for T4 laryngeal cancer patients treated with induction chemotherapy followed by chemoradiotherapy.

Organ-sparing approaches with chemoradiotherapy are often used in the treatment of patients with laryngeal cancer, and the oncologic outcomes of these patients are similar to patients who undergo laryngectomy. However, chemoradiotherapy for laryngeal cancer patients with large or locally-invasive (T4) tumors has been more slowly incorporated due to concern for poor post-treatment function of the preserved larynx. Here, we characterize acute and long-term performance and quality-of-life (QOL) outcomes of T4 laryngeal cancer patients treated with induction chemotherapy followed by combined chemoradiotherapy. Using several validated metrics, we find patients experience a decline in most measures of performance and QOL during and immediately following treatment. However, the majority of patients improve to baseline over varying lengths of time following completion of treatment, and many go on to exceed pre-treatment levels of function. Gender, race, alcohol, and tobacco usage were found to be associated with differences in performance and QOL scores across time points. This study suggests that patients with advanced laryngeal tumors who historically had been considered poor candidates for organ-sparing treatment are able to return to, and in many cases exceed pre-treatment performance and QOL following induction chemotherapy and combined chemoradiotherapy.

A phase II study of lapatinib in recurrent/metastatic squamous cell carcinoma of the head and neck.

PURPOSE: This study sought to determine the efficacy and safety profile of lapatinib in patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). EXPERIMENTAL DESIGN: This phase II multiinstitutional study enrolled patients with recurrent/metastatic SCCHN into two cohorts: those without (arm A) and those with (arm B) before exposure to an epidermal growth factor receptor (EGFR) inhibitor. All subjects were treated with lapatinib 1,500 mg daily. Primary endpoints were response rate (arm A) and progression-free survival (PFS; arm B). The biologic effects of lapatinib on tumor growth and survival pathways were assessed in paired tumor biopsies obtained before and after therapy. RESULTS: Forty-five patients were enrolled, 27 in arm A and 18 in arm B. Diarrhea was the most frequent toxicity occurring in 49% of patients. Seven patients experienced related grade 3 toxicity (3 fatigue, 2 hyponatremia, 1 vomiting, and 1 diarrhea). In an intent-to-treat analysis, no complete or partial responses were observed, and stable disease was the best response observed in 41% of arm A (median duration, 50 days, range, 34-159) and 17% of arm B subjects (median, 163 days, range, 135-195). Median PFS was 52 days in both arms. Median OS was 288 (95% CI, 62-374) and 155 (95% CI, 75-242) days for arms A and B, respectively. Correlative analyses revealed an absence of EGFR inhibition in tumor tissue. CONCLUSION: Lapatinib as a single agent in recurrent/metastatic SCCHN, although well tolerated, appears to be inactive in either EGFR inhibitor naive or refractory subjects.

Airway management before chemoradiation for advanced head and neck cancer.

BACKGROUND: Patients with upper aerodigestive tract tumors can have development of airway compromise both before and during chemoradiotherapy (CRT). Tracheotomy is the classic method for securing a safe airway, but tumor debulking may also be used. METHODS: This was a retrospective review of locoregionally advanced tumors of the base of tongue, larynx, or hypopharynx undergoing CRT between 1995 and 2007. RESULTS: Forty-two of the 109 patients presented with signs or symptoms of airway obstruction. Of these, 28 underwent tracheotomy before CRT, and 11 had tumor debulking. Two of the 11 patients who underwent debulking required tracheotomy within 1 year after CRT for persistent edema and fibrosis. Larynx tumors were more likely to require tracheotomy or debulking than other tumors (p = .01). CONCLUSIONS: Debulking is a safe and effective alternative to tracheotomy in select patients with tumor-related airway obstruction before CRT. Patients who undergo debulking should be monitored closely for recurrence of airway compromise during and after CRT.

Chemoradiation for patients with large-volume laryngeal cancers.

BACKGROUND: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ-preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies. METHODS: Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction. RESULTS: Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of ≤5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%. CONCLUSIONS: Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function-preservation rates.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies.

BACKGROUND: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1). CONCLUSIONS: Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

Concurrent chemotherapy and intensity-modulated radiotherapy for organ preservation of locoregionally advanced oral cavity cancer.

OBJECTIVES: To report outcomes of oral cavity cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy (chemoIMRT). METHODS: Between 2001 and 2004, 21 patients with oral cavity squamous cell carcinoma underwent definitive chemoIMRT. Sites included were oral tongue (n = 9), floor of mouth (n = 6), buccal mucosa (n = 3), retromolar trigone (n = 2), and hard palate (n = 1). Most had stage III-IV disease (n = 20). The most common regimen was 5 days infusional 5-fluorouracil (600 mg/m(2)/d × 5 days), hydroxyurea (500 mg, PO BID), and 1.5 Gy twice-daily irradiation to 72 to 75 Gy. RESULTS: The median follow-up for surviving patients was 60 months. Treatment failure occurred as follows: local-1, regional-1, and distant metastases-2. The 2- and 5-year estimates of locoregional progression-free survival, disease-free survival, and overall survival were 90% and 90%, 71% and 71%, and 76% and 76%, respectively. Late complications included osteoradionecrosis (3 patients, 14%). CONCLUSIONS: Concurrent chemoIMRT results in promising locoregional control for oral cavity squamous cell carcinomas with acceptable toxicity.

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.

Factors associated with long-term speech and swallowing outcomes after chemoradiotherapy for locoregionally advanced head and neck cancer.

OBJECTIVE: to identify factors that influence patient-centered measures of speech and swallowing function after successful use of chemoradiotherapy to treat cancers of the head and neck. DESIGN: patients previously enrolled in a phase 2 trial using induction chemotherapy consisting of carboplatin and paclitaxel followed by chemoradiotherapy with paclitaxel, fluorouracil, hydroxyurea, and 1 of 3 radiation dose levels were assigned speaking and swallowing scores at follow-up ranging from 1 to 4, with 1 representing normal speech or swallowing and 4 representing significant sustained deficits. PATIENTS: one hundred eighty-four patients with locoregionally advanced head and neck cancer. MAIN OUTCOME MEASURES: speech and swallowing function after chemoradiotherapy. RESULTS: of the 222 patients originally enrolled in the trial, 184 were alive and free of locoregional recurrence at the outset of this study. Of these eligible patients, 163 (88.6%) were assigned a speaking score of 1 through 4 at an average of 34.8 (range, 1.5-76.4) months after completion of treatment, whereas 166 patients (90.2%) were assigned a swallowing score of 1 through 4 at an average of 34.5 (range, 1.0-76.4) months after completion of treatment. Most patients (84.7% with speaking scores and 63.3% with swallowing scores) had no residual deficit and were assigned scores of 1. Factors that were associated with worse speaking outcomes included female sex, smoking history, hypopharyngeal or laryngeal primary sites, and poor response to induction chemotherapy; factors associated with worse swallowing outcomes included advanced patient age, poor performance status, primary site, and neck dissection. CONCLUSIONS: among patients successfully treated for locoregionally advanced cancers of the head and neck, several factors correlate with speaking and swallowing outcomes. Because advances in therapy have led to improved survival in these patients, understanding and controlling adverse effects of treatment should continue to be an active area of investigation.

Adjuvant chemotherapy prior to postoperative concurrent chemoradiotherapy for locoregionally advanced head and neck cancer.

BACKGROUND AND PURPOSE: Induction chemotherapy prior to definitive concurrent chemoradiotherapy (CCRT) is a promising treatment option for unresectable head and neck cancer (HNC). In the postoperative setting, the efficacy of such an approach with adjuvant chemotherapy (AdjCT) followed by postoperative CCRT is unclear. MATERIALS AND METHODS: Forty-one postoperative patients with stage III-IV (M0) HNC enrolled on 3 consecutive phase II clinical trials were retrospectively analyzed. Twenty-five of the patients were treated on a protocol which included AdjCT with carboplatin and paclitaxel prior to postoperative CCRT (AdjCT group). Sixteen were treated on protocols with similar postoperative CCRT but without AdjCT (control group). CCRT consisted of paclitaxel, 5-fluorouracil, hydroxyurea, and twice-daily radiotherapy. RESULTS: After a median follow-up of 72 months, there were no locoregional failures (LRF) or distant metastases (DM) in the AdjCT group. In the control group, there were 2 LRF and 2 DM. The 5-year risk of disease recurrence was 0% in the AdjCT group, compared to 28.9% in the control group (p=0.0074). No patients had disease progression during AdjCT, and all proceeded to postoperative CCRT without delay. CONCLUSIONS: Adjuvant chemotherapy after surgery followed by CCRT may be a treatment strategy associated with favorable disease outcomes in locoregionally advanced HNC. These results pose a hypothesis which warrants further investigation.

Retrograde endoscopic-assisted esophageal dilation.

BACKGROUND: Esophageal stricture is a well-known complication of chemoradiotherapy for head and neck malignancies. These strictures almost exclusively occur in the cervical esophagus within the field of radiation. For some patients, identification of the esophageal lumen for antegrade dilation of these strictures can be a challenge, and creation of a false lumen can occur during attempts at dilation. METHODS: We report a method of identifying the esophageal lumen using retrograde esophagoscopy through an existing gastrostomy, thereby allowing confident dilation of an esophageal stricture. RESULTS AND DISCUSSION: The esophagoscope is used to pass a guide wire from below the stricture, and this guide wire is used for bougie dilation of the stricture. Following retrograde dilation, we often place a modified feeding tube to preserve the lumen for future dilation attempts. CONCLUSION: This method can be used to safely place a guide wire for dilation in patients who have a difficult cervical esophageal stricture and an established gastrostomy.