Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston Texas.

Transcription

1 ORIGINAL ARTICLE Gastrostomy tube placement in patients with hypopharyngeal cancer treated with radiotherapy or chemoradiotherapy: Factors affecting placement and dependence Mihir K. Bhayani, MD, Katherine A. Hutcheson, PhD, Denise A. Barringer, MS, Dianna B. Roberts, PhD, Jan S. Lewin, PhD,* Stephen Y. Lai, MD, PhD* Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston Texas. Accepted 17 September 2012 Published online 16 January 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. Placement of gastrostomy tubes (g-tubes) in patients with hypopharyngeal cancers undergoing radiation and chemotherapy is generally empirically determined. We examined our experience to identify predictive factors for g-tube placement and length of dependence. Methods. We performed a retrospective review of all patients with primary hypopharyngeal cancer treated with nonsurgical modalities at a tertiary care center between 2002 and Rates of g-tube placement and length of dependence on enteral feedings were analyzed in relationship to multiple risk factors. Results. Forty-three patients with hypopharyngeal primary tumors (77%) who had a complete response at the primary site after treatment were included. Thirteen patients (30%) never required g-tube placement. At 1-year follow-up, 11 patients (28%) maintained a g-tube. No clinical variables were significantly associated with g-tube placement. Duration of g-tube dependence was significantly longer in patients with a posterior hypopharyngeal wall primary tumors (p ¼.026), current smokers (p ¼.001), and patients with >40 pack-years (p ¼.010). The duration of g-tube dependence was significantly shorter in those who maintained oral intake at the end of treatment (p ¼.05), and those who reported adherence to dysphagia exercise regimens (p ¼.048). Conclusion. Approximately one third of patients with hypopharyngeal tumors treated on organ preservation regimens may be able to avoid g-tube placement, but further research is needed to identify clinical factors that predict g-tube placement in this population. A posterior hypopharyngeal wall primary and smoking history correlated with longer gastrostomy tube dependence. Adherence to aggressive targeted swallowing exercise regimens may help to prevent long-term dependence on feeding tubes. VC 2013 Wiley Periodicals, Inc. Head Neck 35: , 2013 KEY WORDS: hypopharynx, gastrostomy tube, dysphagia, speech pathology, radiation therapy INTRODUCTION Tumors arising in the hypopharynx are rare, accounting for approximately 5% of all head and neck malignancies. 1,2 These tumors have unique characteristics that create significant challenges in the treatment of these patients. Surgery typically requires partial or total laryngopharyngectomy; therefore, many patients are referred for organ preserving protocols that combine radiation therapy (RT) and chemotherapy. RT with or without chemotherapy has been shown to provide locoregional control and organ preservation without adversely affecting survival in patients with locally advanced head and neck cancer, but it is also associated with considerable side effects. 3,4 *Corresponding author: S. Y. Lai, Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard Unit 1445, Houston, TX sylai@mdanderson.org or J. Lewin, Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. Unit 1445, Houston TX jlewin@mdanderson.org Ehab Y. Hanna, MD, was recused from consideration of this manuscript. This work was presented at the Dysphagia Research Society Meeting, San Antonio, Texas, February Jan S. Lewin and Stephen Y. Lai contributed equally to this work. Treatment-related side effects such as mucositis and xerostomia contribute to decreased oral intake and may intensify baseline tumor-related dysphagia and odynophagia. 5 7 Among all sites of head and neck cancer, patients with hypopharyngeal cancer also are most likely to develop pharyngeal dysphagia and pharyngoesophageal stricture because of radiation-induced fibrosis of the pharyngeal constrictors, larynx, and esophageal inlet that predisposes patients to long-term swallowing dysfunction. 8 Dysphagia can ultimately lead to severe weight loss, malnutrition, and aspiration in this high-risk population. For these reasons, a feeding tube is often required for supplemental nutrition. There is no consensus in clinical practice, however, regarding the use of enteral nutrition during RT or chemoradiotherapy. Some centers place feeding tubes prophylactically in all patients before treatment, and others elect to wait until feeding tube placement is clinically indicated. Thus, identification of clinical factors that predict the need for nutritional support and prolonged gastrostomy tube (gtube) dependence has been identified as a priority area for research to help guide clinical decisions. 9 Published literature has historically grouped multiple subsites of head and neck cancer in studies of nutritional support, but head and neck subsites each have unique characteristics that may affect g-tube placement and swallowing-related outcomes. 9 In an accompanying report, we HEAD & NECK DOI /HED NOVEMBER

2 BHAYANI ET AL. describe the risk factors associated with g-tube placement and dependence in patients with oropharyngeal carcinoma (Bhayani et al, accompanying article in this issue). This report serves to identify potential variables unique to patients with hypopharyngeal carcinomas that are predictive of feeding tube placement and prolonged dependence. PATIENTS AND METHODS We retrospectively reviewed the records of consecutive patients who had a primary hypopharyngeal cancer of any histology referred for RT alone or chemoradiotherapy (CRT) at The University of Texas MD Anderson Cancer Center after approval by the institutional review board. New patient referrals occurred between January 2002 and December Patients who had a complete response at the primary site after radiation treatment were included in this analysis. At MD Anderson Cancer Center, it is standard practice to refer all patients with tumors of the aerodigestive tract for consultation with a speech pathologist and dietitian before the initiation of RT or CRT. Feeding tubes are not placed prophylactically in all patients before RT or CRT. Rather, feeding tubes are placed when clinically indicated based on patients nutritional status and ability to safely maintain an oral diet. Patient, disease, and treatment characteristics were collected from the patients medical records. Baseline variables included self-reported dysphagia and odynophagia, weight loss over 6 months before treatment, and diet level. Type of radiation, fractionation schedule, total dose, duration of treatment, and number of treatment breaks, if any, were recorded. Chemotherapy type, number of cycles, and schedule were also noted. Smoking history was collected from the patients medical records. Patients were listed as non-smoker (<100 lifetime cigarettes), current smoker (smoking within 1 year of diagnosis), or former smoker (quit >1 year before diagnosis). Pack-years of smoking were calculated by multiplying the packs smoked by the number of years smoked. G-tube data included type, timing of placement (before, during, or after primary radiation), duration of placement, and maximum number of cans of nutritional formula used per day. We defined feeding tube dependence as the length of time from placement of the feeding tube until removal. If the feeding tube was not removed, date of removal was censored at last follow-up. Data regarding amount of oral versus enteral intake and weight were collected at 1, 6 to 12, and 18 to 24 months after completion of primary treatment. All patients were referred to a speech pathologist before treatment initiation. Results of clinical swallow evaluations or modified barium swallow studies were collected at 1, 6 to 12, and 18 to 24 months after treatment. Swallowing exercises targeting tongue base retraction, suprahyoid movement, and laryngeal closure were provided by the speech pathologist. 10 We recorded patients self-reported adherence to these exercises during followup visits. Adherence was divided into full adherence, which was defined by performing exercises >4/day; partial adherence was 4/day; and no adherence. Patients continued exercises until self-directed goals were met. TABLE 1. Two primary outcome variables were considered: (1) g- tube placement (yes/no), and (2) length of g-tube dependence. For statistical analyses, length of dependence was considered a continuous variable for any use of the g- tube. Covariates included T classification, subsite of disease (pharyngeal wall vs pyriform sinus), RT parameters, chemotherapy parameters, smoking history, and swallowing therapy variables. Associations between g-tube outcomes and study variables were compared for statistical significance using SPSS software (SPSS for Windows, SPSS, Chicago, IL). Statistical differences in proportions of patients in the various groups with the outcomes listed above were tested using Pearson chi-square and t test. A p value of <.05 was considered statistically significant. RESULTS Patient characteristics and disease variables. Characteristic No. of patients % Age (median 61.7 y) Sex Male Female Subsite Pyriform sinus Pharyngeal wall T classification Smoking Never Former Current >40 pack-years <40 pack-years Self-reported baseline dysphagia Yes No Patient and treatment characteristics We identified 56 patients with a hypopharyngeal primary tumor referred for nonsurgical therapy during the time period studied. Forty-three of these patients (77%) had a complete response at the primary site after initial treatment and were included for analysis. The median age of patients at diagnosis was 61.7 years (range, years), and 37 patients (86%) were men. Most patients presented with T3/4 disease (29 patients; 67%). Median follow-up was 24.7 months (range, months). Additional patient and tumor information are shown in Table 1. Twenty-nine of 42 patients (69%) received intensity-modulated RT (IMRT) and 13 patients (31%) had 3D conformal RT. Chemotherapy was administered to 41 patients. Table 2 provides further information regarding treatment variables HEAD & NECK DOI /HED NOVEMBER 2013

3 GASTROSTOMY TUBE PLACEMENT IN HYPOPHARYNGEAL CANCER TABLE 2. Distribution of radiation and chemotherapy types and treatment regimens delivered. Treatment type No. of patients % Radiation IMRT D conformal Concomitant boost Chemotherapy Induction Concurrent Induction and concurrent None Chemotherapy agent Adriamycin 1 Pemetrexed 1 Docetaxel 3 Paclitaxel 13 Cetuximab 3 Cisplatin 26 Carboplatin 14 Ifosfamide 4 5-FU 4 Abbreviations: IMRT, intensity-modulated radiation therapy; 3D, 3-dimensional; 5-FU, 5- fluorouracil. Gastrostomy tube placement G-tubes were placed in 30 patients (70%). Six patients (20%) had the g-tube placed before initiation of radiation treatment, 20 (67%) during radiation, and 4 (13%) after the completion of radiation (Table 3). None of the patients who had the feeding tube placed during radiation required a treatment break. Patients receiving sequential induction chemotherapy followed by concurrent chemoradiotherapy were more likely to have a g-tube placed compared to those patients being treated with concurrent regimens alone (78% vs 68%), but none of the study variables analyzed were significantly associated with placement of a g-tube. Table 4 summarizes these results. Gastrostomy tube dependence and follow-up At the end of treatment, 26 patients (60%) had feeding tubes in place. Nine patients (21%) were non-oral and TABLE 3. Descriptive data of patients receiving gastrostomy tubes. Parameter No. of patients % G-tube placed Yes No Treatment break for placement Yes No Timing of placement Before RT During RT After RT G-tube dependence 1 y 11/ y 1/ Abbreviations: G-tube, gastrostomy tube; RT, radiation. TABLE 4. Gastrostomy tube placement and factors affecting placement. Parameter G-tube placed, no. (%) No g-tube placed, no. (%) p value Smoking Never 3 (75) 1 (25) Former 12 (80) 3 (20).443 Current 14 (62.5) 9 (37.5) >40 pack-years 16 (72.7) 6 (27.3).762 <40 pack-years 13 (68.4) 6 (31.6) T classification 1 6 (85.7) 1 (14.3) 2 5 (71.4) 2 (28.6) (62.5) 6 (37.5) 4 9 (69.2) 4 (30.8) Subsite Pyriform sinus 26 (72.2) 10 (27.8).427 Pharyngeal wall 4 (57.1) 3 (42.9) RT IMRT 20 (69.0) 9 (31.0).994 3D conformal 9 (69.2) 4 (30.8) Concomitant boost Yes 10 (76.9) 3 (23.1).712 No 20 (66.7) 10 (33.3) Chemotherapy Induction 2 (100) Concurrent 17 (68) 8 (32) Both 11 (78.6) 3 (21.4) Baseline dysphagia Yes 14 (70) 6 (30).975 No 16 (69.6) 7 (30.4) Abbreviations: g-tube, gastrostomy tube; RT, radiation therapy; IMRT, intensity-modulated radiation therapy; 3D, 3-dimensional. fully dependent on tube feedings for nutrition, whereas 17 patients (39%) supplemented their tube feedings with some oral intake. At 12-month follow-up, 11 patients (26%) maintained feeding tubes; 3 (6.9%) of whom were exclusively using the g-tube for nutrition and 8 (19%) were supplementing their oral intake with tube feedings. At 2 years, only 1 of 29 patients (2.4%) who continued follow-up had a feeding tube, and this specific patient had g-tube placement for malnutrition from metastatic disease 15 months after completion of initial treatment. At this point, 6 patients were deceased and 8 patients were lost to follow-up. Patients who maintained some oral intake at the conclusion of RT had significantly shorter durations of g-tube dependence compared with those who had no oral intake (nil per os, NPO) at completion of RT (p ¼.05), on average approximately 14 weeks less. Smoking status was significantly associated with length of g-tube dependence. Those patients who had a smoking history of >40 pack-years and reported to be current smokers had significantly longer durations of g-tube dependence (Table 5, Figure 1A). Patients with a posterior pharyngeal wall primary site also had significantly longer g-tube dependence compared to a pyriform sinus primary. Although all patients were referred to a speech pathologist, only 34 patients (79%) were evaluated and given targeted swallowing exercises. The proportion of patients who had their feeding tube removed was higher among those who were taught swallowing exercises before or HEAD & NECK DOI /HED NOVEMBER

4 BHAYANI ET AL. TABLE 5. Variables associated with increased duration of gastrostomy tube placement. Parameter Average duration of g-tube dependence, wk p value Median length of g-tube duration 23.8 Oral intake at completion of RT Yes No 40.8 Adherence to swallowing exercises Yes No 38.6 Smoking Current Former/never 25.5 >40 pack-years <40 pack-years 24.8 Subsite Pyriform sinus Posterior pharyngeal wall 29.9 Post-RT stricture Yes No 25.9 Weight loss after RT from baseline >10% <10% 25.8 Abbreviations: g-tube, gastrostomy tube; RT, radiation therapy. during radiotherapy but the difference was not statistically significant (p ¼.070). However, the rate of g-tube tube removal was significantly higher and the duration of g-tube dependence was significantly shorter in patients who reported adherence to dysphagia exercise regimens (p ¼.048) as shown in Figure 1B, on average approximately 12 weeks less. DISCUSSION Radiation-based regimens commonly are used for primary curative treatment of hypopharyngeal carcinomas because they offer potential for functional organ preservation without significantly affecting survival. 11,12 However, acute treatment toxicities necessitate g-tube placement for nutritional support in a majority of patients treated with RT or CRT. The parameters that define the timing of g-tube placement remain poorly defined, and typically are determined by the practitioner and the patient s medical status and preference. Prophylactic feeding tube placement has been shown to prevent weight loss during treatment and reduce hospitalizations for severe malnutrition and dehydration. 13 However, prophylactic placement may encourage prolonged NPO intervals and negatively affect long-term functional outcomes. In addition, studies suggest that in many cases, the g-tube remains unused, but to date, these analyses have combined multiple sites of head and neck cancer making it difficult to generalize their conclusions to specific high-risk subsites of disease such as the hypopharynx. Furthermore, the hypopharynx is in close proximity to the larynx and cervical esophagus, leading to inclusion of these structures in the radiation treatment fields that would otherwise be spared in other head and neck subsites. 17 Thus, a major strength of our analysis is the inclusion of only patients with hypopharyngeal cancer treated with nonsurgical modalities. Many practitioners recommend prophylactic feeding tube placement before RT or CRT in all patients with hypopharyngeal tumors because of their high risk for dysphagia. However, 30% of patients with hypopharyngeal carcinoma in this cohort did not require a feeding tube during or after their primary treatment. It is our practice to refer patients for feeding tube placement based on a closely monitored "watch-and-wait" policy. Swallow evaluations are routinely scheduled with speech pathologists before, during, and after definitive treatment to ensure that swallowing function is sufficient to safely continue oral (per os, PO) intake. Under the guidance of these evaluations and weekly nutritional assessments, a feeding tube is placed if and when a patient is unable to sustain nutrition and hydration by mouth. This practice is similar to other investigators who have also found that g- tube placement can be avoided in some patients with hypopharyngeal cancer treated with RT, despite their high-risk for dysphagia. Mekhail et al, 18 reviewed multiple subsites, but in their series, they showed 26% of patients with hypopharyngeal cancer did not require a feeding tube. Our outcomes are also comparable to those found by Nguyen et al, 19 which showed 37% of patients in their series did not require a feeding tube, but they FIGURE 1. Kaplan Meier curves showing gastrostomy tube (g-tube) removal with (A) current smokers having longer duration of g-tube placement (p ¼.014) and (B) patients who exhibited full adherence to swallowing exercises had shorter interval to g-tube removal (p ¼.048) HEAD & NECK DOI /HED NOVEMBER 2013

5 GASTROSTOMY TUBE PLACEMENT IN HYPOPHARYNGEAL CANCER also combined the patients with hypopharyngeal cancer with patients with laryngeal cancer. Beaver et al 20 showed 65% of patients with hypopharyngeal cancer did not require a g-tube during RT. However, this data set also included postsurgical patients that may have had a different set of treatment-related side effects that were not covered in the report. A particularly important finding from our study showed that no patients required a treatment break or hospitalization for g-tube placement, suggesting that it is reasonable to reserve g-tube placement in patients with hypopharyngeal cancer until the patient proves unable to maintain adequate oral intake. This practice may avoid the burden of unnecessary feeding tube placement in as much as 30% of patients. Although g-tube placement may be avoided in select patients, a majority of patients (70%) in our study still required a feeding tube during the course of therapy for nutritional support. Placement of a feeding tube is typically required because of acute toxicities of treatment. Surprisingly, no study variables that we analyzed were statistically associated with rates of g-tube placement. This result may be a function of our small sample size and requires further investigation. Despite a lack of significance, we found elevated rates of g-tube placement in patients treated with induction chemotherapy followed by concomitant chemoradiation compared with those who did not receive induction chemotherapy. Higher rates of g-tube placement in these patients are likely a marker of acute toxicities associated with these intensified treatment regimens. We identified multiple factors that correlated with duration of g-tube dependence. These factors may contribute to potentiating both acute and late effects of radiotherapy. In our study group, patients who had a history of smoking 40þ pack-years or were current smokers had a longer duration of g-tube dependence posttreatment. Continued smoking during treatment likely enhances treatmentinduced mucositis, which delays the healing process, and consequently lengthens the interval of g-tube dependence. Nicotine also acts as an appetite suppressant; thus, diminishing a patient s potential desire to increase oral nutrition. 21 Zevallos et al 22 found that mucositis and g-tube placement in patients with head and neck cancer with multiple subsites was more common in smokers; however, these associations were not found to be significant. We also found that posterior wall subsite within the hypopharynx is associated with longer g-tube dependence compared with the pyriform sinus. This is the first report, to our knowledge, differentiating the subsites within the hypopharynx and their outcomes. The reason for this difference could be related to the circumferential mucosal treatment fields of posterior hypopharyngeal tumors. The mucosal treatment field of the pyriform sinus is typically unilateral and spares the contralateral pyriform sinus mucosa. Therefore, wider fields used for posterior pharyngeal wall tumors relative to pyriform sinus fields may be associated with increased risk for dysphagia and stricture formation, and lead to prolonged feeding tube dependence in this subgroup. 21 Prevention of prolonged g-tube dependence is an important goal of functional rehabilitation in patients with head and neck cancer. Temporary placement of a nasogastric tube in lieu of g-tube placement has been suggested as a strategy to facilitate this goal. Although some data suggest decreased stricture rate and mucositis in patients who received nasogastric tubes versus g-tubes, 18 others report that the nasogastric tube is much less tolerated and leads to increased aspiration rates. 23 An alternative to reduce the long-term pharyngoesophageal toxicity is to maintain oral intake during treatment. Investigators demonstrated long intervals without oral intake may encourage pharyngoesophageal fibrosis and dysphagia. 24 In our subset of patients, we found that patients who maintained some oral intake along with their tube feedings throughout treatment had shorter duration of g-tube dependence compared with those patients who were NPO at the end of treatment. Many patients experience significant alteration in their swallowing mechanism because of RT and can tolerate little oral intake by the conclusion of RT despite their best efforts. In our study, patients were referred to the speech pathologist to learn targeted swallowing exercises designed to maintain strength and flexibility of the swallowing musculature to avoid long-term swallowing deterioration. We found those who remained adherent to the preventative exercise regimens had significantly decreased length of g-tube duration. This result is consistent with our accompanying report in patients with oropharyngeal carcinoma. At our institution, all patients who have or are at risk for dysphagia are referred to and evaluated by speech pathologists, as we have found that early and targeted swallowing intervention is the best prevention against long-term swallowing deterioration after RT. This study is strengthened by a focused analysis of a specific subsite of patients with head and neck cancer at high-risk for adverse swallowing outcomes; however, the relatively small number of hypopharyngeal cancer patients available for inclusion limits our ability to draw definitive conclusions. Despite our small sample size, we present outcomes for the largest group of patients with hypopharyngeal cancer treated with primary RT and CRT over the period analyzed compared with other published studies. We believe this to be notable because of the rare incidence of cancer of the hypopharynx. In addition to our report of g-tube placement in patients with hypopharyngeal cancer, an accompanying report from our group details a similar analysis of g-tube placements in patients with cancers of the oropharynx. Conclusions from that data set found multiple significant variables contributing to placement and long-term dependence of g-tubes. This contrast in identified variables may reflect the larger sample size (474 patients), decreased comorbidities seen in patients with oropharyngeal carcinoma (secondary to changing demographics related to human papillomavirus), and differences in treatment protocols in oropharyngeal carcinoma compared to hypopharyngeal carcinoma. In addition, analysis of these variables found adherence to a swallowing exercise regimen contributed to maintenance of PO intake and reduced rates of g-tube placement and long-term dependence. This finding coincides with our univariate analysis from the patients with hypopharyngeal cancer stressing the importance of patient participation in treatment provided by a speech HEAD & NECK DOI /HED NOVEMBER

6 BHAYANI ET AL. pathologist. From these 2 reports, we can infer that patients with cancer of the hypopharynx may avoid placement of a g-tube in up to 30% of cases with swallowing therapy despite risk factors that predict for placement of a feeding tube. CONCLUSION This study demonstrates that g-tube placement may be avoided in approximately one-third of patients who are treated with RT or CRT for high-risk hypopharyngeal primary tumors. Based on the findings from this study and our experience, patients with hypopharyngeal carcinoma undergoing RT should be referred to a speech pathologist, as adherence to a proactive swallowing exercise regimen is critical to reduce the risk of long-term use and dependence on feeding tubes. Further investigation will be useful to help identify the specific risk factors that predispose to g-tube placement. REFERENCES 1. Hall SF, Groome PA, Irish J, O Sullivan B. The natural history of patients with squamous cell carcinoma of the hypopharynx. Laryngoscope 2008; 118: Takes RP, Strojan P, Silver CE, et al. Current trends in initial management of hypopharyngeal cancer: the declining use of open surgery. Head Neck 2012;34: Newlin HE, Amdur RJ, Riggs CE, Morris CG, Kirwan JM, Mendenhall WM. Concomitant weekly cisplatin and altered fractionation radiotherapy in locally advanced head and neck cancer. Cancer 2010;116: Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 2008;26: Caudell JJ, Schaner PE, Meredith RF, et al. Factors associated with longterm dysphagia after definitive radiotherapy for locally advanced headand-neck cancer. Int J Radiat Oncol Biol Phys 2009;73: Salama JK, Stenson KM, List MA, et al. Characteristics associated with swallowing changes after concurrent chemotherapy and radiotherapy in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 2008;134: Garden AS, Harris J, Trotti A, et al. Long-term results of concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: a phase II trial of the radiation therapy oncology group (RTOG 99-14). Int J Radiat Oncol Biol Phys 2008;71: Chen AM, Li BQ, Jennelle RL, et al. Late esophageal toxicity after radiation therapy for head and neck cancer. Head Neck 2010;32: Paleri V, Patterson J. Use of gastrostomy in head and neck cancer: a systematic review to identify areas for future research. Clin Otolaryngol 2010;35: Rosenthal DI, Lewin JS, Eisbruch A. Prevention and treatment of dysphagia and aspiration after chemoradiation for head and neck cancer. J Clin Oncol 2006;24: Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88: Lefebvre JL, Rolland F, Tesselaar M, et al. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst 2009;101: Wiggenraad RG, Flierman L, Goossens A, et al. Prophylactic gastrostomy placement and early tube feeding may limit loss of weight during chemoradiotherapy for advanced head and neck cancer, a preliminary study. Clin Otolaryngol 2007;32: Locher JL, Bonner JA, Carroll WR, et al. Gastrostomy tube placement and use in patients with head and neck cancer. Head Neck 2012;34: Locher JL, Bonner JA, Carroll WR, et al. Prophylactic percutaneous endoscopic gastrostomy tube placement in treatment of head and neck cancer: a comprehensive review and call for evidence-based medicine. JPEN J Parenter Enteral Nutr 2011;35: Madhoun MF, Blankenship MM, Blankenship DM, Krempl GA, Tierney WM. Prophylactic PEG placement in head and neck cancer: how many feeding tubes are unused (and unnecessary)? World J Gastroenterol 2011; 17: Eisbruch A, Schwartz M, Rasch C, et al. Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys 2004;60: Mekhail TM, Adelstein DJ, Rybicki LA, Larto MA, Saxton JP, Lavertu P. Enteral nutrition during the treatment of head and neck carcinoma: is a percutaneous endoscopic gastrostomy tube preferable to a nasogastric tube? Cancer 2001;91: Nguyen NP, Frank C, Moltz CC, et al. Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys 2005;61: Beaver ME, Matheny KE, Roberts DB, Myers JN. Predictors of weight loss during radiation therapy. Otolaryngol Head Neck Surg 2001;125: Li B, Li D, Lau DH, et al. Clinical-dosimetric analysis of measures of dysphagia including gastrostomy-tube dependence among head and neck cancer patients treated definitively by intensity-modulated radiotherapy with concurrent chemotherapy. Radiat Oncol 2009;4: Zevallos JP, Mallen MJ, Lam CY, et al. Complications of radiotherapy in laryngopharyngeal cancer: effects of a prospective smoking cessation program. Cancer 2009;115: Dwolatzky T, Berezovski S, Friedmann R, et al. A prospective comparison of the use of nasogastric and percutaneous endoscopic gastrostomy tubes for long-term enteral feeding in older people. Clin Nutr 2001;20: Ames JA, Karnell LH, Gupta AK, et al. Outcomes after the use of gastrostomy tubes in patients whose head and neck cancer was managed with radiation therapy. Head Neck 2011;33: HEAD & NECK DOI /HED NOVEMBER 2013