Establishing a Multidisciplinary Head and Neck Clinical Pathway: An Implementation Evaluation and Audit of Dysphagia-Related Services and Outcomes.

Head and neck cancer (HNC) guidelines recommend regular multidisciplinary team (MDT) monitoring and early intervention to optimize dysphagia outcomes; however, many factors affect the ability to achieve these goals. The aims of this study were to explore the barriers/facilitators to establishing and sustaining a MDT HNC care pathway and to examine the dysphagia-related speech-language pathology (SLP) and dietetic components of the pathway. Using the Consolidated Framework for Implementation Research (CFIR), a mixed methods study design was used to evaluate an established MDT HNC pathway. Ten MDT members provided perceptions of facilitators/barriers to implementing and sustaining the pathway. Patients attending the SLP and dietetic components of the pathway who commenced treatment between 2013 and 2014 (n = 63) were audited for attendance, outcome data collected per visit, and swallowing outcomes to 24-month post-treatment. Dysphagia outcomes were compared to a published cohort who had received intensive prophylactic dysphagia management. Multiple CFIR constructs were identified as critical to implementing and sustaining the pathway. Complexity was a barrier. Patient attendance was excellent during treatment, with low rates of non-compliance (< 15%) to 24 months. Collection of clinician/patient outcome tools was good during treatment, but lower post-treatment. Dysphagia outcomes were good and comparable to prior published data. The pathway provided patients with access to regular supportive care and provided staff opportunities to provide early and ongoing dysphagia monitoring and management. However, implementing and sustaining a HNC pathway is complex, requiring significant staff resources, financial investment, and perseverance. Regular audits are necessary to monitor the quality of the pathway.

Prophylactic Swallow Therapy for Patients with Head and Neck Cancer Undergoing Chemoradiotherapy: A Randomized Trial.

Evidence supporting prophylactic swallow exercises for patients with head and neck cancer (HNC) has not been universally demonstrated. This RCT examined diet level, feeding tube use, swallow function, and quality of life (QOL) of patients undergoing chemoradiotherapy who performed prophylactic swallowing exercises. Sixty HNC patients were randomized into exercise versus control groups. Swallowing, oromotor, toxicity, and QOL data were recorded (baseline, 3, 6, 12, 24 months). Physiological swallow function was examined at baseline and 3 months. Swallow exercises were completed twice daily. Oral intake at 3 months was 10% better in the exercise group, which was not statistically significant (p = 0.49). Significant (p < 0.05) differences in secondary outcomes including oromotor function, pharyngeal impairment, oral pharyngeal swallow efficiency, and incisal opening were noted at early time points (3-6 months) in the exercise group. Possible positive early improvements in swallow function are associated with swallowing exercises, although these improvements are not significant longer term.

Neutrophil-to-lymphocyte ratio: Prognostic indicator for head and neck squamous cell carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has prognostic significance for many cancers, with higher values correlating with poor outcomes. The purpose of this study was to determine the prognostic significance of this inflammatory marker for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Univariate logistic regression and multivariate Cox regression analyses were performed on a retrospective cohort of 123 patients treated with primary chemoradiotherapy. RESULTS: The NLR is an indicator of both recurrence-free and overall survival, but the NLR does not have independent prognostic significance when the favorable prognostic influence of human papillomavirus (HPV) status is incorporated into multivariate models. CONCLUSION: The interaction between NLR and HPV status suggests that HPV status may be a determining factor in the favorable prognosis associated with a decreased NLR in HNSCC; these findings also suggest that HPV status may interact with the prognostic associations of indicators of systemic inflammation in HNSCC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 662-667, 2017.

Tadalafil augments tumor specific immunity in patients with head and neck squamous cell carcinoma.

PURPOSE: To determine if phosphodiesterase 5 (PDE5) inhibitors can augment immune function in patients with head and neck cancer through inhibition of myeloid-derived suppressor cells (MDSC). EXPERIMENTAL DESIGN: We performed a randomized, prospective, double blinded, placebo controlled, phase II clinical trial to determine the in vivo effects of systemic PDE5 inhibition on immune function in patients with head and neck squamous cell carcinoma (HNSCC). RESULTS: Tadalafil augmented immune response, increasing ex vivo T-cell expansion to a mean 2.4-fold increase compared with 1.1-fold in control patients (P = 0.01), reducing peripheral MDSC numbers to mean 0.81-fold change compared with a 1.26-fold change in control patients (P = 0.001), and increasing general immunity as measured by delayed type hypersensitivity response (P = 0.002). Tumor-specific immunity in response to HNSCC tumor lysate was augmented in tadalafil-treated patients (P = 0.04). CONCLUSIONS: These findings demonstrate that tadalafil augments general and tumor-specific immunity in patients with HNSCC and has therapeutic potential in HNSCC. Evasion of immune surveillance and suppression of systemic and tumor-specific immunity is a significant feature of head and neck cancer development. This study demonstrates that a PDE5 inhibitor, tadalafil, can reverse tumor-specific immune suppression in patients with head and neck cancer, with potential for therapeutic application.

Pharyngocutaneous fistula after total laryngectomy: a single-institution experience, 2001-2012.

PURPOSE: The purpose of this study was to determine the incidence of and risk factors for pharyngocutaneous fistula in patients undergoing total laryngectomy at a single institution. MATERIALS AND METHODS: The records of 59 patients undergoing primary or salvage total laryngectomy at our institution from 2001 to 2012 were retrospectively reviewed. Data collected included patient, tumor and treatment characteristics, and surgical technique. Risk factors were analyzed for association with pharyngocutaneous fistula formation. RESULTS: Twenty patients (34%) developed fistulas. Preoperative tracheostomy (OR 4.1; 95% CI 1.3-13 [p=0.02]) and low postoperative hemoglobin (OR 9.1; 95% CI 1.1-78 [p=0.04]) were associated with fistula development. Regarding surgical technique, primary sutured closure of the total laryngectomy defect had the lowest fistula rate (11%). In comparison, primary stapled closure and pectoralis onlay flap over primary closure had nonsignificantly increased fistula rates (43%, OR 6.0; 95% CI 1.0-37.3 [p=0.06] and 25%, OR 2.7; 95% CI 0.4-23.9 [p=0.38], respectively). Pectoralis flap incorporated into the suture line had a significantly increased fistula rate (50%, OR 7.1; 95% CI 1.4-46 [p=0.02]). After stratification for salvage status, patient comorbidities were associated with fistula in non-salvage cases whereas disease-related characteristics were associated with fistula in salvage cases. Fistula development was associated with increased length of hospital stay (p<0.001) and increased time before oral diet initiation (p<0.001). CONCLUSIONS: Pharyngocutaneous fistula is a common complication of total laryngectomy. Preoperative tracheostomy, postoperative hemoglobin, and surgical technique are important in determining the risk of fistula.

Transcervical ultrasonography is feasible to visualize and evaluate base of tongue cancers.

BACKGROUND: Base of tongue (BOT) is a difficult subsite to examine clinically and radiographically. Yet, anatomic delineation of the primary tumor site, its extension to adjacent sites or across midline, and endophytic vs. exophytic extent are important characteristics for staging and treatment planning. We hypothesized that ultrasound could be used to visualize and describe BOT tumors. METHODS: Transcervical ultrasound was performed using a standardized protocol in cases and controls. Cases had suspected or confirmed BOT malignancy. Controls were healthy individuals without known malignancy. RESULTS: 100% of BOT tumors were visualized. On ultrasound BOT tumors were hypoechoic (90.9%) with irregular margins (95.5%). Ultrasound could be used to characterize adjacent site involvement, midline extent, and endophytic extent, and visualize the lingual artery. No tumors were suspected for controls. CONCLUSIONS: Ultrasonography can be used to transcervically visualize BOT tumors and provides clinically relevant characteristics that may not otherwise be appreciable.

Audio-visual biofeedback does not improve the reliability of target delineation using maximum intensity projection in 4-dimensional computed tomography radiation therapy planning.

PURPOSE: To investigate whether coaching patients' breathing would improve the match between ITVMIP (internal target volume generated by contouring in the maximum intensity projection scan) and ITV10 (generated by combining the gross tumor volumes contoured in 10 phases of a 4-dimensional CT [4DCT] scan). METHODS AND MATERIALS: Eight patients with a thoracic tumor and 5 patients with an abdominal tumor were included in an institutional review board-approved prospective study. Patients underwent 3 4DCT scans with: (1) free breathing (FB); (2) coaching using audio-visual (AV) biofeedback via the Real-Time Position Management system; and (3) coaching via a spirometer system (Active Breathing Coordinator or ABC). One physician contoured all scans to generate the ITV10 and ITVMIP. The match between ITVMIP and ITV10 was quantitatively assessed with volume ratio, centroid distance, root mean squared distance, and overlap/Dice coefficient. We investigated whether coaching (AV or ABC) or uniform expansions (1, 2, 3, or 5 mm) of ITVMIP improved the match. RESULTS: Although both AV and ABC coaching techniques improved frequency reproducibility and ABC improved displacement regularity, neither improved the match between ITVMIP and ITV10 over FB. On average, ITVMIP underestimated ITV10 by 19%, 19%, and 21%, with centroid distance of 1.9, 2.3, and 1.7 mm and Dice coefficient of 0.87, 0.86, and 0.88 for FB, AV, and ABC, respectively. Separate analyses indicated a better match for lung cancers or tumors not adjacent to high-intensity tissues. Uniform expansions of ITVMIP did not correct for the mismatch between ITVMIP and ITV10. CONCLUSIONS: In this pilot study, audio-visual biofeedback did not improve the match between ITVMIP and ITV10. In general, ITVMIP should be limited to lung cancers, and modification of ITVMIP in each phase of the 4DCT data set is recommended.

Complete resolution of laryngeal amyloidosis with radiation treatment.

BACKGROUND: Localized amyloidosis of the larynx is a rare entity of unclear etiology. Surgical debulking is the primary treatment modality but often is not curative. METHODS AND RESULTS: A 41-year-old woman presenting with increasing hoarseness, dysphagia, dyspnea, and weight loss was found to have a submucosal mass in the left false vocal fold. Biopsy of the specimen revealed amyloid. After negative work-up for systemic disease, the patient underwent surgical debulking. Specimens revealed a population of clonal plasma cells demonstrating lambda restriction. The patient was treated with adjuvant external beam radiation to a dose of 45 Gy. At 11 months, the patient's voice, breathing, and swallowing have all improved substantially. CONCLUSIONS: Recent pathologic studies suggest that localized amyloidosis of the larynx is caused by a localized, nonmalignant plasma cell disorder. Because full resection is difficult, we recommend a combination of surgery and radiation therapy to cure this disease.

Similar survival with breast conservation therapy or mastectomy in the management of young women with early-stage breast cancer.

PURPOSE: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. RESULTS: A total of 14,764 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and 15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). CONCLUSIONS: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.

High-dose spatially fractionated GRID radiation therapy (SFGRT): a comparison of treatment outcomes with Cerrobend vs. MLC SFGRT.

PURPOSE: Spatially fractionated GRID radiotherapy (SFGRT) using a customized Cerrobend block has been used to improve response rates in patients with bulky tumors. The clinical efficacy of our own multileaf collimator (MLC) technique is unknown. We undertook a retrospective analysis to compare clinical response rates attained using these two techniques. METHODS AND MATERIALS: Seventy-nine patients with bulky tumors (median diameter, 7.6 cm; range, 4-30 cm) treated with SFGRT were reviewed. Between 2003 and late 2005, the Cerrobend block technique (n = 39) was used. Between late 2005 and 2008, SFGRT was delivered using MLC-shaped fields (n = 40). Dose was prescribed to dmax (depth of maximum dose) and was typically 15 Gy. Eighty percent of patients in both groups received external beam radiotherapy in addition to SFGRT. The two-sided Fisher-Freeman-Halton test was used to compare pain and mass effect response rates between the two groups. RESULTS: Sixty-one patients (77%) were treated for palliative intent and 18 (23%) for curative intent. The majority of patients had either lung or head-and-neck primaries in both groups; the most frequent site of SFGRT application was the neck. The majority of patients complained of either pain (65%) or mass effect (58%) at intake. Overall response rates for pain and mass response were no different between the Cerrobend and MLC groups: pain, 75% and 74%, respectively (p = 0.50), and mass effect, 67% and 73%, respectively (p = 0.85). The majority of toxicities were Grade 1 or 2, and only 3 patients had late Grade 3-4 toxicities. CONCLUSIONS: MLC-based and Cerrobend-based SFGRT have comparable and encouraging response rates when used either in the palliative or curative setting. MLC-based SGFRT should allow clinics to more easily adopt this novel treatment approach for the treatment of bulky tumors.

Accelerated partial breast irradiation via brachytherapy: a patterns-of-care analysis with ASTRO consensus statement groupings.

PURPOSE: The 2002 Food and Drug Administration approval of the MammoSite catheter (Hologic, Inc., Beford, MA) led to a surge of interest in accelerated partial breast irradiation (APBI). Until recently, guidelines as to the optimal candidates for this treatment were unavailable. We performed a patterns-of-care analysis for patients undergoing breast brachytherapy and compared these results with the American Society for Radiation Oncology (ASTRO) consensus statement. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was used to examine female breast cancer patients treated with brachytherapy between 2002 and 2007. The patients were then categorized into suitable, cautionary, and unsuitable groups based on the ASTRO guidelines. RESULTS: We identified 4172 female breast cancer patients treated within the stated years. The number of brachytherapy cases increased nearly 10-fold over the time period studied from 163 in 2002 to 1427 in 2007 (p<0.0001). Patients with data missing were excluded, leaving a total of 3593 patients available for analysis. The mean patient age was 64 years. Most patients had small (<2cm in 80.9%) estrogen receptor-positive (86.7%) invasive (88.6%) tumors. The percentage of patients treated for ductal carcinoma in situ increased with time (p<0.001), whereas the percentage of patients treated with positive lymph nodes decreased with time (p<0.001). Using the data available, 1369 (38.1%), 1563 (43.5%), and 661 (18.3%) patients were characterized as suitable, cautionary, and unsuitable, respectively. CONCLUSIONS: More than 60% of patients who received APBI via brachytherapy would fall into the ASTRO cautionary or unsuitable groupings. This is the largest patterns-of-care analysis for APBI patients and serves as a baseline for future comparison.

Chemoradiotherapy for esophageal cancer.

Radiotherapy and surgery have both played prominent roles in the treatment of esophageal cancer since the beginning of the 20th century. Although the use of radiotherapy alone to treat esophageal cancer has a long history, it has not demonstrated improved outcomes compared with surgery alone. The disappointing rates of survival and local control associated with single-modality therapy and the need for effective nonsurgical management led to the development of definitive chemoradiotherapy paradigms for esophageal cancer. Adding cytotoxic chemotherapy to radiotherapy for additive or synergistic effect was described as early as 1968, and over time, treatment has shifted from single-modality therapy toward combined-modality therapy using chemotherapy and radiotherapy. This approach eventually demonstrated superior outcomes in patients with esophageal cancer when compared to radiotherapy alone. Maximum benefit of this therapy depends on the appropriate addition of surgery and the optimization of radiosensitizing chemotherapy. A burgeoning area of research has focused on improving definitive chemoradiotherapy strategies through the incorporation of newer chemotherapeutic agents and targeted biologic agents. An overview of the history of chemoradiotherapy in the treatment of esophageal cancer is presented, as well as a discussion of ongoing studies and future areas of promising research.

The impact of self-control indices on peer smoking and adolescent smoking progression.

OBJECTIVE: To determine the direct impact of self-control variables on baseline smoking and smoking progression and determine whether self-control had indirect effects on smoking practices through effects on peer smoking. METHODS: Study participants were 918 adolescents who were followed from 9th through the 12th grade and completed self-report measures of peer smoking, self-control, and cigarette smoking. An exploratory factor analysis (EFA) was conducted to assess the factor structure of a 41-item self-control measure. The EFA indicated a six-factor structure comprising of impulsive control, planning, hostile blaming, attentional disregulation, conscientiousness, and physical aggression. RESULTS: The results of a latent growth model indicated that conscientiousness (OR = 0.81, CI = 0.73-0.90), hostile blaming (OR = 0.89, CI = 0.81-0.99), and physical aggression (OR = 1.16, CI = 1.06-1.27) had direct effects on baseline smoking, whereas planning (OR = 0.90, CI = 0.82-0.99) and impulse control (OR = 1.15, CI = 1.02-1.28) had indirect effects on adolescent smoking at baseline through baseline peer smoking. There were no significant direct or indirect effects of the self-control indices on smoking progression. There was a direct effect of peer smoking progression (number of peers who smoked) on adolescent smoking progression, such that increases in the number of peers who smoked across time increased the odds that an adolescent would progress to a higher level of smoking. CONCLUSIONS: Youth smoking prevention and intervention program outcomes may potentially improve by addressing self-control behaviors as they appear to have direct effects on smoking and indirect effects through peers who smoke.

Cigarette smoking practices among American college students: review and future directions.

Cigarette smoking among college students is a critical public health problem. In this article, the authors review available research on cigarette smoking practices among college students and suggest directions for future research. Studies show that smoking by college students is associated with being White, living in housing where smoking is permitted, using alcohol and other substances, and having a lower psychological sense of well-being. Depression, life satisfaction, and coping style are also related to college smoking, but the causal relationship remains unclear. Although a large proportion of college students have made an attempt to quit smoking, only a minority actually succeed. Most study designs examining college smoking have been cross-sectional, descriptive, or both. Thus, conclusions regarding predictors of smoking onset, maintenance, and cessation cannot be made. Future studies should use longitudinal designs that can identify psychological and socioenvironmental determinants of smoking among college students. Such information could inform the development of smoking prevention and cessation interventions targeted to the college student population.