Reactive versus prophylactic percutaneous gastrostomy: outcomes in a cohort of advanced oropharyngeal carcinoma patients

INTRODUCTION

Head and neck cancer (HNC) patients are at risk of malnourishment, both from disease burden, and as a result of combined treatment modalities.¹ Malnutrition effects on wound healing may prolong recovery following treatment and increase the risk of morbidity for those undergoing subsequent salvage treatments.^2,3

Percutaneous gastrostomy (PEG) is one of the most commonly used enteral feeding methods in HNC patients.⁴ This is a safe procedure with a low complication rate5. It might be used as the sole way of feeding, or it might be used in conjunction with oral intake, to optimize it.

Optimal timing for PEG placement is still up to much debate, leading to inconsistencies in practice between centers. Prophylactic placement (pPEG) might prevent further weight loss in HNC patients that is expected with the beginning of chemoradiotherapy with/without surgery. On the other hand, prophylactic enteral feeding might hinder swallowing outcomes, prolonging the dependency on PEG. Reactive PEG placement (rPEG) is defined as placement after treatment initiation. Although there is compelling evidence showing increased difficulty on regaining weight during on-going cancer therapy, most studies could not prove a difference in disease outcomes with both strategies.

The primary goal of our study was to analyze differences in nutritional and survival outcomes between patients who used pPEG and rPEG in our institution.

METHODS

This retrospective cohort study included oropharyngeal cancer patients treated in Centro Hospitalar Vila Nova de Gaia / Espinho center, between January 2013 and December 2020. Adult patients with advanced oropharyngeal cancer were included. These patients received chemoradiotherapy ±surgery. Patients were excluded if they presented other synchronous tumors and/or early stage tumors.

Before the beginning of treatment, all patients were referred to a multidisciplinary consultation, where decision between reactive or prophylactic PEG was made, according to clinical and patient preferences. Similarly to other studies, we classified pPEG if performed before the beginning of radiotherapy and rPEG if performed after.

Demographics characteristics (sex, age) and clinical characteristics (staging, treatment, percentage of weight loss pre-treatment) were collected at baseline from medical records. Clinical stage was categorized into four groups: stage III, IVa, IVb and IVc.

Both nutritional and survival outcomes were measured. Nutritional outcomes included days until PEG removal, and weight variation at 3 and 6 months. Considering survival outcomes, we measured overall survival as the primary outcome. Survival time was defined as the time between the first day of the radiotherapy treatment until the date of death or censored to last day of data updating on death.

Comparisons between groups were conducted using Chisquare test and exact Fisher test for categorical variables, and student t-test and Mann–Whitney test for continuous variables. We used Kaplan–Meier procedure to estimate the distribution of time to death and log-rank tests for the difference in survival time. Control for confounders was performed by using a hierarchical multiple regression analysis. Significance level was set at p<0.05. Data was analyzed using Statistical package for social sciences (SPSS) version 26.0.

RESULTS

This cohort consisted of 49 advanced oropharyngeal cancer patients, subdivided in two groups: rPEG (n=17) and pPEG (n=32).

* p<0.05. BMI – body mass index; QT – chemotherapy; RT – Radiotherapy.

Mean of age was not statistically different between rPEG (59.9±9.2 y.o.) and pPEG (56.5±7.4 y.o.), p=0.23. Other demographic and clinical variables are summarized in Table 1. There was a statistically significant difference between both groups regarding overall staging, with rPEG being comprised of patients with lower advanced stages. Other variables were not statistically different between groups.

*p<0.05

Prophylactic PEG patients had a median of 205.5 days of PEG placement, compared with 159.5 days for rPEG. On multivariate analysis, after controlling for confounders (age, stage, initial weight), PEG dependence was significantly associated with PEG strategy (r=0.41; p=0.03).

After controlling for confounders, this variable was the only one related to timing of PEG. No difference on percentage of weight loss was apparent at 3 months between both groups (p=0.824). Despite a trend for less weight loss at 6 months is apparent, this value did not achieve statistical significance (p=0.08).

Analyzing overall survival, there was no difference between both strategies (Log-rank test p=0.49) (Figure 1). After controlling for confounders, PEG placement was not significantly related to overall survival (p=0.17).

DISCUSSION

In this study, we retrospectively analyze the influence of PEG timing on nutritional and survival outcomes in a cohort of advanced-stage oropharyngeal tumors. PEG timing had an impact on PEG dependence in our cohort, with a trend of influence in weight loss at 6 months, and no impact on overall survival.

Advanced stage oropharynx tumors have variable consequences on a patient’s swallowing function that are somewhat predictable, depending on the structures or treatment modality involved.⁶ Combined treatment modalities like chemoradiotherapy regimens may lead to additional dysphagia and aspiration due to weakness of the base of the tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, reduced laryngeal closure, and epiglottic inversion.⁷ PEG can provide effective long-term enteral nutrition in dysphagia patients.⁸ These patients might be completely dependent on enteral nutrition, or on other hand, using it to complement oral feeding.

PEG timing is still a controversial topic in literature, with protocols differing between major centers. Prophylactic strategies are used to decrease the risk of malnourishment during treatment, as this can be associated with treatment delays as well as decreased overall survival.⁹ Therefore, theoretically, this approach would favor better survival outcomes. However, most studies found no differences between groups in overall survival and/or treatment delay.¹⁰ Some other endpoints, such as acute kidney insufficiency or increased hospital admissions were, however, correlated with a rPEG approach in some studies.^11,12

There is, on the other hand, a high rate of unnecessary PEG placement using a pPEG approach, with approximately 50% of patients not using it during the course of treatment and in the posterior follow-up.¹³ PEG placement tube carries risks such as infection, diarrhea, constipation, electrolyte abnormalities, bleeding, and/or metastatic seeding at the gastrostomy site.¹⁴ It is also possible that decreased oral intake by prophylactic placement might further worsen pharyngeal muscle weakness, theoretically contributing to increased PEG dependence.^15,16 Published studies regarding this subject have, a high risk of bias, and this impact remains unclear.¹⁷

Reactive strategies are favored by some clinicians and/or patients. The downfall of this approach is a possible increased difficulty in weight recuperation during the course of the treatment.¹⁸ It is estimated that between 11%-79% of patients will subsequently need PEG placement if a reactive approach is undertaken.¹⁹ Some studies tried to understand which risk factors could make PEG needs more probable in the course of the treatment. Strom et al found an association with BMI <25, accelerated irradiation fractionation, T stage of 3 or higher, and a cumulative cisplatin dose of 200 mg/m2.²⁰ One favored approach in most centers is to identify patients who have a higher risk of malnourishment pretreatment, and to propose pPEG to them. This should be, however, a conjoint decision between clinician and patient.

Previous studies have addressed possible outcome differences between these two subgroups of patients. Kramer et al, described similar results to ours in a cohort of head and neck cancer patients, noting mainly a difference in PEG dependence in the prophylactic subgroup, with no statistical difference in weight loss at 2, 6, or 12 months, or overall survival.²¹ McClelland et al report in a systematic review (n=7) similar findings, with an apparent benefit at weight loss at 6 months, but no difference in tumor control or increased survival.²² Quality of life (QoL) investigations performed in these two subsets of patients have found that, although QoL seems to be worse during treatment for pPEG patients, there seems to exist a difference at 6-months favoring pPEG approach.²³

Our study is limited by its retrospective protocol and small sample. It reports the experience of a single institution. However, as most published studies take all HNC subsites as a whole in their analysis, this study is one of the few only analyzing a specific subsite for HNC. In our sample, comparability could have been hindered by the fact that HNC staging was statistically different between the two subgroups. However, after multivariate analysis, it is apparent that this difference did not have an impact in the measured outcomes.

CONCLUSION

Nutritional and survival outcomes were not statistically different between the two analyzed subgroups. However, PEG dependence seems to be influenced by PEG timing strategy. Better protocols are needed to reduce unnecessary prophylactic PEG placement while maintaining adequate nutrition during the treatment of these patients, to maximize outcomes.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: The study was approved by the Institutional Ethics Committee

REFERENCES

1. 1. Hunter M, Kellett J, Toohey K, D’cunha NM, Isbel S, Naumovski N. Toxicities caused by head and neck cancer treatments and their influence on the development of malnutrition: Review of the literature. Eur J Investig Heal Psychol Educ. 2020;10:935-49.
2. 2. Stechmiller JK. Understanding the role of nutrition and wound healing. Nutr Clin Pr. 2010;25(1):61-8.
3. 3. Mueller SA, Mayer C, Bojaxhiu B. Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer. J Otolaryngol Head Neck Surg. 2019;48(1):25.
4. 4. Rahnemai-Azar AA, Rahnemaiazar AA, Naghshizadian R, Kurtz A, Farkas DT. Percutaneous endoscopic gastrostomy: Indications, technique, complications and management. World J Gastroenterol. 2014;20(24):7739-51.
5. 5. Kohli DR, Kennedy KF, Desai M, Sharma P. Safety of endoscopic gastrostomy tube placement compared with radiologic or surgical gastrostomy: nationwide inpatient assessment. Gastrointest Endosc. 2021;93(5):1067-85.
6. 6. Gaziano JE. Evaluation and management of oropharyngeal dysphagia in head and neck cancer. Cancer Control. 2002;9(5):400-9.
7. 7. 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(5):1425-39.
8. 8. NICE. Nutrition support for adults: oral nutrition support, enteral tube feeding and parenteral nutrition | Guidance and guidelines. NICE. Available at: Https://Www.Nice.Org.Uk/Guidance/Cg32. 2017. Accessed on 20 Janauary 2022.
9. 9. Bese NS, Hendry J, Jeremic B. Effects of Prolongation of Overall Treatment Time Due To Unplanned Interruptions During Radiotherapy of Different Tumor Sites and Practical Methods for Compensation. Int J Radiat Oncol Biol Phys. 2007;68(3):654-61.
10. 10. Chen AM, Li BQ, Lau DH. Evaluating the role of prophylactic gastrostomy tube placement prior to definitive chemoradiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2010;78(4):1026-32.
11. 11. Dave AA, Mozer MA, Zhang Y. Impact of reactive gastrostomy tube placement on clinical course of oropharynx cancer patients treated with chemoradiation. J Clin Oncol. 2019;37(15).
12. 12. Brown TE, Banks MD, Hughes BGM, Lin CY, Kenny LM, Bauer JD. Comparison of Nutritional and Clinical Outcomes in Patients with Head and Neck Cancer Undergoing Chemoradiotherapy Utilizing Prophylactic versus Reactive Nutrition Support Approaches. J Acad Nutr Diet. 2018;118(4):627-36.
13. 13. 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(8):1004-08.
14. 14. Lawson JD, Gaultney J, Saba N, Grist W, Davis L, Johnstone PAS. Percutaneous feeding tubes in patients with head and neck cancer: rethinking prophylactic placement for patients undergoing chemoradiation. Am J Otolaryngol. 2009;30(4):244-9.
15. 15. Langmore S, Krisciunas GP, Miloro KV, Evans SR, Cheng DM. Does PEG use cause dysphagia in head and neck cancer patients? Dysphagia. 2012;27(2):251-9.
16. 16. Hutcheson KA, Bhayani MK, Beadle BM. Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: Use it or lose it. JAMA Otolaryngol Head Neck Surg. 2013;139(11):1127-34.
17. 17. Shaw SM, Flowers H, O’Sullivan B, Hope A, Liu LWC, Martino R. The Effect of Prophylactic Percutaneous Endoscopic Gastrostomy (PEG) Tube Placement on Swallowing and Swallow-Related Outcomes in Patients Undergoing Radiotherapy for Head and Neck Cancer: A Systematic Review. Dysphagia. 2015;30:152-75.
18. 18. Wiggenraad RGJ, Flierman L, Goossens A. 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(5):384-90.
19. 19. Lang K, Elshafie RA, Akbaba S. Percutaneous endoscopic gastrostomy tube placement in patients with head and neck cancer treated with radiotherapy. Cancer Manag Res. 2020;12:127-136.
20. 20. Strom T, Trotti AM, Kish J. Risk factors for percutaneous endoscopic gastrostomy tube placement during chemoradiotherapy for oropharyngeal cancer. JAMA Otolaryngol - Head Neck Surg. 2013.
21. 21. Kramer S, Newcomb M, Hessler J, Siddiqui F. Prophylactic versus reactive PEG tube placement in head and neck cancer. Otolaryngol Head Neck Surg. 2014;150(3):407-12.
22. 22. McClelland S, Andrews JZ, Chaudhry H, Teckie S, Goenka A. Prophylactic versus reactive gastrostomy tube placement in advanced head and neck cancer treated with definitive chemoradiotherapy: A systematic review. Oral Oncol. 2018;87:77-81.
23. 23. Salas S, Baumstarck-Barrau K, Alfonsi M. Impact of the prophylactic gastrostomy for unresectable squamous cell head and neck carcinomas treated with radio-chemotherapy on quality of life: Prospective randomized trial. Radiother Oncol. 2009;93(3):503-9.