Accepted 12 August 2010 Published online 15 December 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: /hed.21624

Transcription

1 ORIGINAL ARTICLE IMPACT OF EARLY PERCUTANEOUS ENDOSCOPIC GASTROSTOMY TUBE PLACEMENT ON NUTRITIONAL STATUS AND HOSPITALIZATION IN PATIENTS WITH HEAD AND NECK CANCER RECEIVING DEFINITIVE CHEMORADIATION THERAPY Charles E. Rutter, BS, 1 Susannah Yovino, MD, 2 Rodney Taylor, MD, 3 Jeffrey Wolf, MD, 3 Kevin J. Cullen, MD, 4 Robert Ord, MD, 5 Mindy Athas, RD, 4 Ann Zimrin, MD, 4 Scott Strome, MD, 3 Mohan Suntharalingam, MD 2 1 University of Maryland School of Medicine, Baltimore, Maryland 2 Department of Radiation Oncology, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland. msuntha@umm.edu 3 Department of Otorhinolaryngology, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland 4 Department of Medical Oncology, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland 5 Department of Oral-Maxillofacial Surgery, University of Maryland Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland Accepted 12 August 2010 Published online 15 December 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI: /hed Abstract: Background. This study analyzed the impact of timing of percutaneous endoscopic gastrostomy (PEG) tube placement on clinical endpoints in patients undergoing concurrent chemoradiation therapy (CRT). Methods. In all, 111 patients who underwent CRT for locally advanced squamous cell carcinoma of the head and neck (SCCHN) were retrospectively analyzed to determine the effect of timing of PEG placement on weight loss, hospitalizations, and rates of PEG complications/dependence. Results. Early PEG tube placement was correlated to reductions in weight loss during CRT (p <.001, R ¼ 0.495), hospitalization for nutritional deficits (p ¼.011, R ¼ 0.262), and magnitude of persistent weight loss at 6 weeks post-crt (p ¼.003, R ¼ 0.347). Disease control was the only predictor of PEG dependence. No differences were seen in PEG complication or dependence rates with earlier placement. Conclusions. The results of our series show that patients with locally advanced SCCHN undergoing definitive CRT may derive significant clinical benefit from the early placement of PEG tubes for nutritional supplementation. VC 2010 Wiley Periodicals, Inc. Head Neck 33: , 2011 Keywords: gastrostomy tube; nutrition; radiation; chemoradiation Patients with squamous cell carcinoma of the head and neck (SCCHN) often present with advanced disease, requiring aggressive therapy to achieve adequate locoregional control. Concurrent chemotherapy and radiation (CRT) and altered-fractionation Correspondence to: M. Suntharalingam VC 2010 Wiley Periodicals, Inc. radiation therapy schedules are 2 examples of treatment regimens that have been developed in an attempt to improve disease control. However, these treatment regimens may cause significant acute toxicity including mucositis, dysphagia/odynophagia, xerostomia, and weight loss. These treatment-related effects can exacerbate pre-existing nutritional issues, leading to significant compromise of patients nutrition. Malnutrition can lead to unplanned breaks during therapy, which are associated with worse disease control, as well as compromised wound healing, which imparts a slower recovery from toxicities of therapy. Furthermore, malnutrition has long been known to decrease survival and increase surgical complication rates in patients with head and neck cancer. Maintaining adequate nutrition is therefore an essential part of the management of head and neck cancer. Percutaneous endoscopic gastrostomy (PEG) tubes have become a primary means for securing the nutrition of patients with head and neck cancer, attributed to a minimally invasive placement technique as well as improved patient comfort and cosmesis. However, controversy exists regarding the appropriate use and timing of PEG placement, with some physicians advocating PEG tube placement immediately upon commencement of therapy (prophylactic placement) and others using feeding tubes only upon manifestation of significant nutritional deficit (therapeutic placement). This study analyzes the relationship between timing of PEG placement and weight loss, rates of hospitalization for nutritional support, treatment time, rates of PEG complications and dependence, and Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October

2 persistent weight loss following treatment completion in patients with SCCHN receiving definitive CRT. MATERIALS AND METHODS Patient and Tumor Characteristics. A retrospective chart review was performed on 111 consecutive patients with locally advanced SCCHN receiving definitive CRT at the University of Maryland Greenebaum Cancer Center between August 12, 2004 and June 9, All patients provided informed consent for treatment as well as research based on review of their electronic and paper medical records. This retrospective review was approved by the University of Maryland Institutional Review Board. Patient and tumor characteristics are shown in Table 1. Four patients with a single focus of metastatic disease (3 to the lung, 1 to the bone) received chemoradiation to achieve local tumor control in the head and neck. A majority of the patients (83%, n ¼ 92) were men, and the median age was 58 (range, 35 82) years. The most common primary site was the oropharynx (32%, n ¼ 36). Median follow-up time was 9.2 months following the completion of CRT. Radiation Treatment and Chemotherapy. All patients received definitive platinum-based CRT. In all, 62 of 111 patients (56%) were treated with 3-dimensional (3D) conformal radiation therapy, with the remaining 49 patients (44%) receiving intensity-modulated radiation therapy (IMRT). For 3D-conformal plans, opposed lateral fields were treated to a dose of 45 Gray (Gy). A supraclavicular field was matched to the inferior border of the opposed lateral neck fields and received a dose of 50 Gy in 2-Gy fractions. Off-cord photon and posterior neck electron fields were combined to ensure adequate nodal coverage in the offcord phase of treatment. For both IMRT and 3D-conformal plans, involved nodal chains received 59.4 Gy, and uninvolved nodal chains thought to be at high risk for microscopic disease involvement received 50.4 Gy. A small field boost was added to ensure that all gross disease (at primary and nodal sites) was treated to a total dose of at least 70 Gy. The most typical fractionation scheme was 70.2 Gy, administered in 39 fractions of 1.8 Gy. All patients in this series received concurrent platinum-based chemotherapy. The most common regimen was cisplatin alone (45% of patients, n ¼ 50). An additional 30 patients (27%) were treated on an institutional protocol with carboplatin, paclitaxel, and cetuximab. Table 1. Patient and tumor characteristics. Characteristic No. of patients (%) Age, y (median 58 y) 111 Sex Male 92 (82.9) Female 19 (17.1) Primary site Oropharynx 36 (32.4) Oral cavity 26 (23.4) Larynx 25 (22.5) Hypopharynx 13 (11.7) Nasopharynx 7 (6.3) Nasal cavity 2 (1.8) Unknown primary 2 (1.8) AJCC Stage II 1 (0.9) III 20 (18.0) IV 90 (81.1) T classification T1 13 (11.7) T2 28 (25.2) T3 42 (37.8) T4 25 (22.5) Tx 3 (2.7) N classification N0 16 (14.4) N1 15 (13.5) N2a 13 (11.7) N2b 30 (27.0) N2c 34 (30.6) N3 3 (2.7) M classification M0 107 (96.4) M1 4 (3.6) Abbreviation: AJCC, American Joint Committee on Cancer. Nutritional Support. Prior to therapy, patients were counseled by the treating radiation oncologist regarding the possibility of mucositis and dysphagia causing significant nutritional compromise. All patients were offered a PEG prior to the beginning of CRT. Any patient not explicitly refusing a PEG tube was evaluated by a gastroenterologist and a nutritionist regarding PEG tube placement. During therapy, patients were evaluated weekly by their treating physician and were weighed at least once a week. A multidisciplinary team consisting of the treating radiation oncologist, medical oncologist, nursing staff, and a nutritionist all engaged in intensive nutritional counseling with patients throughout the course of CRT. A nutritionist titrated the type and volume of tube feeds to prevent further weight loss. If patients refused pretreatment placement, PEG tubes remained available throughout the course of therapy and placement was again recommended upon clinically significant weight loss. Once CRT was completed, patients were seen on a monthly basis (or more frequently as needed) for the first year. Weight was recorded at each follow-up visit, and nutritional counseling continued. PEG tubes were removed once the patient demonstrated the ability to maintain weight on oral intake alone without the need for any supplemental PEG tube feedings. Patients who experienced delayed recovery of swallowing function were referred to a speech pathologist as soon as persistent post-therapy swallowing dysfunction was noted Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October 2011

3 Data Collection. Patient records were reviewed to collect data on weekly weights during treatment, monthly weights post-therapy, treatment time, hospitalizations for nutritional deficits or PEG tube-related complications, and PEG tube dependence. Hospitalization for dehydration, malnutrition, and difficulty with tube feeds was defined as nutrition-related. Hospitalization for PEG repositioning/replacement or infection at the PEG site was defined as PEG complication-related. PEG tube dependence was defined as the inability to maintain weight without the use of any supplemental nutrition via the PEG tube. Statistical Analyses. The goals of this analysis were 3-fold: (1) to assess the effects of timing of PEG placement on clinical and nutrition-related endpoints (survival, weight loss, etc.) in those patients receiving a PEG at any point during therapy; (2) to compare the same set of endpoints between patients receiving a PEG tube at any time during CRT to patients who never had a PEG tube placed; and (3) to observe the impact of timing of PEG placement on long-term PEG dependence. For the first analysis, correlation analysis was used to correlate the time to PEG tube placement to the percentage weight lost during treatment among patients receiving a PEG tube. Additionally, independent-samples t tests were used to compare endpoints described earlier between those patients who had a PEG tube placed before a given week of treatment began and those who had a PEG tube placed after that week of treatment began. This process was repeated in a serial fashion, using each week of treatment to dichotomize the patients who received a PEG, to identify any time points that served as a cutoff between improved and worsened outcomes. For the second analysis, independent-samples t tests were used to ascertain whether patients receiving a PEG at any time versus those who did not receive a PEG tube had any difference in mean weight loss, mean treatment time, or mean number of hospital days. For the third analysis, Kaplan Meier analysis was conducted to determine if there was any statistically significant difference in time to PEG tube removal between those patients who had a PEG tube placed before CRT began versus those who received a PEG tube after the commencement of therapy. Patient and tumor characteristics were compared between patients who relied on a PEG tube for some portion of their nutritional intake at 6 months post- CRT and those who did not, to identify potential predictors of long-term PEG dependence. RESULTS Rates and Timing of PEG Tube Placement. Ninety patients (81%) had a PEG placed at some point before, during, or immediately after treatment. The Table 2. Timing of PEG tube placement by week of treatment. Week of PEG placement No. of patients (%) Before start of treatment 53 (58.9) Week 1 3 (3.3) Week 2 4 (4.4) Week 3 12 (13.3) Week 4 8 (8.9) Week 5 5 (5.6) Week 6 0 (0.0) Week 7 2 (1.8) After completion of treatment 3 (2.7) Total 90 Abbreviation: PEG, percutaneous endoscopic gastrostomy. remaining 21 patients (19%) did not receive a PEG tube. The majority of patients (59%) receiving a PEG had it placed before the start of treatment. Table 2 shows the time of PEG placement, separated by week of treatment. Effects on Weight Loss During Treatment and Following Treatment. Among the 90 patients who received a PEG, correlation of PEG tube placement timing with percentage weight loss revealed that patients who received a tube earlier in the course of therapy had a significantly lower percentage weight loss (R ¼ and R 2 ¼ 0.245, p <.001). Results of the regression analysis are shown in Figure 1. Moreover, earlier PEG tube placement was significantly associated with less weight loss following the completion of CRT. Placement prior to the beginning of therapy was associated with less persistent weight loss compared with placement during therapy at both 6 weeks post-crt (14.8 vs 26.2 pounds, p ¼.003) and 6 months post- FIGURE 1. The relationship between percutaneous endoscopic gastrostomy (PEG) tube placement timing (by week of treatment) and percentage weight loss during treatment. Note: In the x-axis of the figure above, S indicates those patients with a PEG placed before the start of treatment, and C indicates those who had a PEG placed after the completion of treatment. Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October

4 CRT (12.2 vs 26.7 pounds, p ¼.011). Correlation of PEG placement timing and lasting weight loss at 6 weeks follow-up revealed an R value of and R 2 of (p ¼.003). Patients who had a PEG tube placed at any time during treatment had a mean weight loss of 9.2% of their pretreatment baseline weight, compared with a mean weight loss of 11.8% in patients without a PEG tube (p ¼.064). PEG tubes reduced the magnitude of persistent weight loss following the completion of CRT. At 6 weeks following CRT, patients who never had a PEG tube placed had a mean persistent weight loss of 30.1 pounds compared with 19.5 pounds among patients who did have a PEG tube (p ¼.02). This difference was maintained over time; at 3 months following CRT, patients without a PEG tube had a mean weight loss of 34.6 pounds compared with 19.8 pounds for patients who had a tube (p ¼.008). By 6 months after therapy, there was no statistically significant difference in weight loss between the 2 groups, although a large absolute difference in weight loss was still seen at 6 months (28.6 vs 19.0 pounds) and 1 year (27.2 vs pounds) following therapy (p >.05). Effects on Hospital Admissions and Overall Treatment Time. Among the patients receiving a PEG tube, earlier placement was correlated to a decrease in total inpatient days (R ¼ 0.21, p ¼.012) as well as a lower risk of admission for nutritional deficits (R ¼ 0.26, p ¼.01). The greatest benefit was seen when the PEG tube was placed before the beginning of week 3 of therapy versus after the beginning of week 3 of therapy (mean ¼ 0.41 vs 1.97 days admitted, p ¼.036). Earlier PEG tube placement was not associated with a difference in the number of days admitted for PEG tube-related complications. Overall, 7 of 90 patients (7.8%) receiving a PEG had a complication requiring admission; 3 had an isolated PEG site cellulitis, 2 had a cellulitis with PEG dislodgement, and 2 had isolated PEG dislodgement. There were no mortalities from PEG complications in this cohort. The timing of PEG tube placement did not have a statistically significant impact on overall treatment time. Analysis comparing patients who received a PEG tube and those who did not showed no difference in the number of hospitalization days for nutritional issues and no difference in overall treatment time between the 2 patient groups. OS of 81% (p ¼.3). Two-year PFS was 50% in the before-therapy group compared with 47% in the during-therapy group (p ¼.5). Analysis between patients who received a PEG tube and those who did not showed no statistically significant difference in OS or PFS. Long-term PEG Tube Dependence. Fifty-nine of 90 patients (66%) eventually had their PEG tube removed following completion of therapy, with a median time to removal of 4 months (range, 14 days to 35 months). Among the remaining 31 patients, 27 had a PEG in place at the time of their death (median, 9.8 months; range, 4 days to 41 months, post- CRT), and 4 remain PEG dependent, with a median follow-up of 24.9 months. As shown in Figure 2, mean time to removal of PEG tubes following CRT was not affected by the timing of PEG tube placement; ie, patients who had their tubes placed before or early in the course of CRT were not at higher risk for PEG tube dependence following therapy. Disease control was the only predictor of PEG dependence following the completion of CRT. At 6 months post-crt, 82.8% of patients who had disease recurrence (n ¼ 35) continued to use their PEG tube for some portion of their nutritional intake, compared with 40% in patients with disease control (n ¼ 55, p ¼.004). Kaplan Meier analysis (see Figure 3) also showed that patients with recurrent disease had a significantly longer time to PEG tube removal (p <.001). Figure 4 is a schematic of PEG tube removal rates in patients separated by tumor control. As seen in Figure 4, 83.6% of disease-free patients have had their PEG tube removed since completing therapy. Survival. The 2-year overall survival (OS) for the entire cohort of patients was 71%. Two-year progression-free survival (PFS) was 52%. The timing of PEG tube placement did not have a statistically significant effect on OS or PFS; patients who had a PEG tube placed before the beginning of therapy had a 2-year OS of 71%. Patients whose PEG tube was placed at any point after the first week of therapy had a 2-year FIGURE 2. PEG placement prior to versus during therapy is not associated with a prolonged time to PEG tube removal Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October 2011

5 FIGURE 3. Comparison of time to PEG removal between patients who suffered a disease recurrence/progression and those who did not. Among these patients, median time to PEG tube removal was approximately 4.7 months (range, 1 35 months). DISCUSSION Advances in therapy for head and neck cancer represent a double-edged sword for patients and clinicians. Although concurrent chemoradiation and hyperfractionated radiotherapy have significantly improved locoregional control and overall cure rates, the increased intensity of treatment is associated with higher rates of hospitalization and prolonged treatment times. 1 5 Longer treatment times have been associated with worse local control rates. 6,7 PEG tubes have been used as a strategy to reduce the severity of nutritional compromise experienced by patients with head and neck cancer during therapy, in the hopes of thereby shortening treatment times and avoiding hospitalization during the course of aggressive cancer therapy. Most data currently available on outcomes among patients receiving PEG tubes during radiotherapy for head and neck cancer are retrospective. Additionally, many of the published reports include a heterogeneous mix of patients who received either concurrent CRT, intensified radiation schedules (hyperfractionated, accelerated, or concomitant boost radiotherapy), postoperative radiotherapy, or conventionally fractionated RT alone. Most of these series have demonstrated that PEG tubes can ameliorate malnutrition in patients with head and neck cancer undergoing radiation therapy. Beaver et al 8 conducted a retrospective review of 249 patients treated at MD Anderson Cancer Center. The vast majority of patients in this series (240/249) were treated with radiation alone, with only 9 patients receiving concurrent CRT. The overall rate of PEG tube placement was low (32%). Patients who had PEG tubes placed before the beginning of RT experienced significantly less weight loss than either patients who never had a PEG tube placed or patients who had a PEG tube placed during RT. Additionally, having a PEG tube placed during RT was associated with a significantly increased rate of emergency room visits and admissions for dehydration (compared with patients who had a PEG tube placed prior to RT). 8 Scolapio et al 9 reported a series of 54 patients (only 6 treated with CRT), 41 of whom received PEG tubes before RT and 13 of whom received a PEG tube during RT. Patients receiving a prophylactic PEG tube had a lower mean weight loss FIGURE 4. Comparison of overall rates of PEG tube removal and PEG tube dependence following chemoradiation therapy (CRT), based on disease progression/recurrence. Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October

6 (2.7 vs 5.4 kg) and lower rates of hospitalization for dehydration (0% vs 31%) compared with patients who received their PEG tubes during therapy. 9 Lee et al 10 published on 88 patients with head and neck cancer treated with either twice-daily radiation or chemoradiation, and showed a significant improvement in weight loss among patients who had PEG tubes placed before therapy (mean, 3.1 vs 7.0 kg). Although the overall rate of hospital admissions did not differ significantly between patients who had PEG tubes placed before beginning treatment, patients with a prophylactic PEG tube were less likely to be admitted for poor nutritional status or dehydration. Furthermore, among patients with good performance status, there was a trend to shorter treatment times in the group of patients undergoing PEG placement before RT. 10 In this series, complications were rare, with only 2 patients experiencing PEG-tube related complications requiring further invasive intervention. One alternative to the placement of PEG tubes for enteral nutrition in this patient population is nasogastric (NG) tube placement. NG tubes may be associated with shorter indwelling enteral therapy time and earlier recovery of swallowing function when compared with PEG tubes. However, the disadvantages of NG tube placement are not insignificant and include greater patient discomfort and emotional distress, enhancement of mucosal irritation in the pharynx and upper esophagus, and higher rates of gastroesophageal reflux. Furthermore, feedings can be given at a faster rate via PEG tube than via NG tubes, which may enhance patient mobility and improve quality of life during therapy. 11 Data to support the superiority of 1 method of enteral nutrition over the other in this setting are sparse. A recently published prospective study conducted by Corry et al 12 reported on 105 patients with SCCHN treated with either CRT (81%) or concomitant boost RT (19%). The initial intent of this study was to randomize patients to NG tube versus PEG tube placement. Because of poor accrual, this was revised to be a prospective trial in which patients chose their preferred route of enteral nutrition. In all, 70% of the patients had an NG tube placed. NG tube patients had greater median weight loss during treatment (3.7 vs 0.8 kg, p <.001), which persisted up to 6 months following the completion of therapy. 12 However, patients with an NG tube placed did use their tubes for a shorter period of time, with a median indwelling time of 57 days, compared with 146 days in patients with a PEG tube (p <.001). Lower rates of dysphagia at 6 months were also reported in the NG tube group. However, because of the methodological difficulties described earlier, it is difficult to use these data to draw any definitive conclusions regarding whether PEG or NG tube is the most appropriate form of enteral supplementation in patients with head and neck cancer. Our analysis focused primarily on the impact of the timing of PEG tube placement on clinical outcomes and is not able to provide a direct comparison of patients who had PEG tubes versus NG tubes. Treatment planning factors also have an impact on swallowing outcomes. Eisbruch and colleagues have published prospective data demonstrating that radiation doses to the pharyngeal constrictor muscles and upper cervical esophagus are correlated with the development of chronic aspiration and esophageal strictures. 13 When generating IMRT plans, the pharyngeal constrictors and upper cervical esophagus should be considered as a critical normal structure and dose to these structures limited to the extent possible, although this may be difficult to achieve for patients with laryx/hypopharynx primaries or lowlying retropharyngeal adenopathy. Alternatively, for oropharyngeal tumors, matching a conventional field (with a midline block for laryngeal shielding) to treat lymphatics in the low neck may be considered. 14 To our knowledge, our experience is the largest published report of PEG tube outcomes among a group of patients receiving exclusively chemoradiation therapy. The current literature also contains no studies assessing the effect of PEG placement timing as a continuous variable. We noted a positive correlation between a longer delay in the placement of a PEG tube and worsened severity of weight loss, which persisted throughout the course of treatment. Patients receiving a PEG tube early in treatment also had less persistent weight loss compared with that of patients who received PEG tube support at a later point. Similarly, the number of nutrition-related hospital admission days was reduced in those receiving a PEG tube earlier in therapy. Because of the retrospective nature of our data, the impact of reduction in weight loss and hospitalization for nutritional deficiency on quality of life could not be assessed. This is an area that deserves further study. Despite the efficacy of PEG tube placement in reducing weight loss among patients receiving radiation treatment for SCCHN, concerns are frequently raised about rates of complications, primarily infection and difficulty recovering normal swallowing function, among patients receiving PEG tubes early in the course of therapy. A recent meta-analysis of the rates of major complications among patients with head and neck cancer undergoing PEG tube placement reported a 7.4% rate of significant procedure-related morbidity (including both severe infection and hemorrhage) in a large multi-institutional group of 1281 patients. 15 In a Dutch report of 50 patients treated with CRT for locally advanced SCCHN, all of whom received PEG tubes before the start of treatment, 81% of diseasefree patients were PEG tube free at 6 months following the completion of treatment. 16 In the series published by Scolapio et al, 9 median duration of tube use in this report was 165 days and did not differ between patients whose tube was placed before versus during therapy Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October 2011

7 In our series, long-term PEG dependence rates were unaffected by the timing of tube placement. We did not observe higher rates of PEG tube dependence nor PEG complications among patients who received their PEG tube either before beginning CRT or early in the course of therapy. At 6 months after completing CRT, the only group of patients with a significantly higher risk of PEG tube dependence were those with recurrent disease. Overall, this group had a significantly longer period of PEG dependence, likely secondary to persistent tumor-related nutritional compromise, as well as the need for a secured route of nutrition during treatment of the recurrent disease. The vast majority of patients (83.6%) without disease recurrence or progression have had their PEG tube removed since completing CRT. One important limitation of our data is that formal prospective evaluation of swallowing function was not performed. In the retrospective analysis, it was also difficult to quantify the exact percentage of an individual patient s oral versus enteral intake. Instead, the inability to maintain a steady weight without the use of enteral nutrition was used as a surrogate for the presence of severe swallowing dysfunction. Although this is a relatively crude endpoint, the ability to maintain weight without enteral supplementation is clinically important. Further analysis using these more exact indicators is warranted to clearly address the effect of early placement on longterm PEG dependence and rehabilitation of swallowing function following the completion of CRT. Although the vast majority of patients in our experience of CRT, as in previous studies, required a PEG (81%), the remaining 19% of patients not requiring a PEG deserve further comment. These patients clearly represent a select group in their ability to sustain oral nutrition through the rigors of CRT. Our analyses found that this select group experiences no negative nutritional impact beyond lasting weight loss following CRT when compared with patients with a PEG in place. However, patient and tumor characteristics, which can be reliably used to identify this type of patient, remain undefined. CONCLUSIONS The results of our series show that early placement of PEG tubes in patients undergoing CRT for SCCHN was associated with decreased weight loss during CRT and less persistent weight loss after the completion of therapy, compared with patients who deferred placement of a PEG tube until nutritional deficits developed. Furthermore, neither increases in the rate of acute complications nor the risks of long-term PEG tube dependence were observed in patients whose PEG tubes were placed earlier in the course of treatment. The published literature detailed earlier indicates the clinical and nutritional advantages of prophylactic PEG placement over both therapeutic placement and the nonuse of PEG tubes in patients with locally advanced SCCHN. Therefore, based on the combined findings of the published literature and this series, our recommendation is to consider prophylactic PEG placement for all patients receiving definitive CRT for locally advanced head and neck cancer, following a thorough discussion of risks such as long-term PEG dependence. In patients who initially refuse a PEG tube, earlier PEG tube placement is associated with improved nutritional status and decreased hospitalization rates, and early therapeutic PEG placement should be strongly considered as soon as patients begin to develop nutritional deficits. REFERENCES 1. Fu KK, Pajak TF, Trotti A, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG Int J Radiat Oncol Biol Phys 2000;48: Brizel DM, Albers ME, Fisher SR, et al. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998;338: Al-Sarraf M, LeBlanc M, Giri PGS, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized intergroup study J Clin Oncol 1998;16: Eisbruch A, Lyden T, Bradford CR, et al. Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 2002; 53: Donaldson SS, Lenon RA. Alterations of nutritional status, impact of chemotherapy and radiation therapy. Cancer 1979;43: Rosenthal DI. Consequences of mucositis-induced treatment breaks and dose reductions on head and neck cancer treatment outcomes. J Support Oncol 2007;9: Suntharalingam M, Haas ML, Van Echo DA, et al. Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck. Cancer 2001;91: Beaver ME, Matheny KE, Roberts DB. Predictors of weight loss during radiation therapy. Otolaryngol Head Neck Surg 2001;125: Scolapio JS, Spangler PR, Romano MM. Prophylactic placement of gastrostomy feeding tubes before radiotherapy in patients with head and neck cancer: is it worthwhile? J Clin Gastroenterol 2001;33: Lee JH, Machtay M, Unger LD. Prophylactic gastrostomy tubes in patients undergoing intensive irradiation for cancer of the head and neck. Arch Otolaryngol Head Neck Surg 1998;124: Nugent B, Lewis S, O Sullivan J. Enteral feeding methods for nutritional management in patients with head and neck cancer: a systematic review. Cochrane Database Syst Rev 2010, Issue Corry J, Poon W, McPhee N, et al. Prospective study of percutaneous endoscopic gastrostomy tubes versus nasogastric tubes for enteral feeding in patients with head and neck cancer undergoing (chemo)radiation. Head Neck 2009;31: Feng FY, Kim HM, Lyden TH, et al. Intensity-modulated radiotherapy of head and neck cancer intending to reduce dysphagia: early dose effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 2007;32: Amdur R, Liu C, Li J, et al. Matching intensity-modulated radiation therapy to an anterior low neck field. Int J Radiat Oncol Biol Phys 2007;69;S46 S Grant DG, Bradley PT, Pothier DD, et al. Complications following gastrostomy tube insertion in patients with head and neck cancer: a prospective multi-institution study, systematic review and meta-analysis. Clin Otolaryngol 2009;34: 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: Impact of PEG Placement Timing on Nutritional Outcomes HEAD & NECK DOI /hed October