Edited by: Youssef Zeidan, American University of Beirut, Lebanon
Reviewed by: Stephan Bodis, Kantonsspital Aarau, Switzerland; John M. Watkins, University of Iowa, United States
Specialty section: This article was submitted to Radiation Oncology, a section of the journal Frontiers in Oncology
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Though better studied in head/neck cancers, there are currently no studies on timing of feeding tube (FT) placement in patients with gastroesophageal cancer. This study sought to discern characteristics of patients who used versus did not use a prophylactic FT (pFT), and also analyzed factors associated with placement of FTs during chemoradiotherapy (CRT).
From 1998 to 2013, 1,329 patients underwent neoadjuvant CRT, of which 323 received an FT. Patients for whom FTs were placed prior to treatment due to tumor occlusion or substantial weight loss (
No significant differences were found in any parameter between cohorts that used (
Of our cohort who received pFTs, there were no clinical factors that predicted for their use. Patients must be closely monitored for weight loss and esophagitis when receiving CRT in order to intervene prior to further worsening of toxicities.
Feeding tubes (FTs) can be used for nutritional support in cancer patients and are either placed prophylactically or as a response to toxicities during or after oncologic therapy. Though most commonly used in head and neck cancers, timing of use—especially prophylactically—is controversial and without consensus at present (
No evidence has been published to date examining factors associated with FT insertion at various time points, as well as evaluating prophylactic placement of FTs in GE cancers. As such, the National Comprehensive Cancer Network insinuates that FT placement be considered on a case-by-case basis, especially in conditions of low caloric intake and/or esophageal obstruction (
In this study, we sought to examine the population of GE cancers that received FTs, treated at a high-volume, tertiary care academic medical center. Specifically, our study had two principal goals. First, because prophylactic FTs (pFTs) may or may not be utilized, we aimed to ascertain factors associated with needing to use a pFT. Second, a comparison of factors was made between patients who used a pFT and those who required an FT during radiotherapy (RT), in efforts to delineate a high-risk population that could benefit from aggressive supportive care and possibly a lower threshold for FT placement during RT.
This single-institutional analysis examined 1,329 patients with cancer of the esophagus or GE junction treated with concurrent chemoradiotherapy (CRT) as part of neoadjuvant therapy (1998–2013). Of these patients, the analyzed population consisted of those who underwent FT placement, which numbered 323 patients. Each patient provided informed consent to place an FT if recommended. Figure
Schematic representation of patient subgroups in this study. CRT, chemoradiotherapy; FT, feeding tube; RT, radiotherapy; PWL, profound weight loss; pFT, prophylactic feeding tube.
These criteria left 150 patients for further investigation. Of these patients, 50 had placement during RT, and 100 were placed prophylactically. Reasons for FT placement during RT included odynophagia, dysphagia, decreased appetite, and nausea/vomiting. pFT placement was performed at the clinician’s discretion, based on clinical concern but not due to any of the aforementioned rationale for FT placement. Whether FTs were utilized for nutrition (defined as at least one administration of enteral feeding) was then recorded; 66 patients used the FT and 34 did not.
Two comparisons between patient subgroups were made in this study: (1) factors associated with use of a pFT (
Radiotherapy was administered in three possible modalities: three-dimensional conformal RT, intensity-modulated RT, or proton beam RT. Briefly, for each modality, patients were immobilized using custom molds and simulated in the supine position with four-dimensional computed tomography simulation. Positron emission tomography fusion aided in target volume definition. In general, doses consisted of 41.4–50.4 Gy and were delivered with concurrent chemotherapy, which consisted of various regimens over time and at the medical oncologist’s discretion. Patients were seen weekly by the medical and radiation oncologists on treatment, with reassessment of toxicities and potential intervention at each visit. Surgery was performed several weeks after cessation of CRT and most commonly was transthoracic esophagectomy.
Data analysis was performed using Stata/MP14 statistical software (College Station, TX, USA). The Wilcoxon rank-sum and Fisher’s exact tests were used to compare the factors associated with use and lack of use of a pFT, as well as to compare the characteristics of patients who used a pFT against those whom required an FT placed during treatment. Univariate and multivariate logistic regression were performed in order to examine variables associated with placement of FTs in various circumstances.
Table
Clinical characteristics of patients who used versus did not use a pFT.
Parameter | All patients with pFT ( |
Did not use pFT ( |
Used pFT ( |
|
---|---|---|---|---|
Median age at diagnosis (years) (range) | 64 (21–84) | 65 (29–84) | 63.5 (21–84) | 0.951 |
Gender | ||||
Male | 80 (80%) | 29 (85%) | 51 (77%) | 0.434 |
Female | 20 (20%) | 5 (15%) | 15 (23%) | |
Median body mass index (kg/m2) (range) | 26.8 (16.5–43.0) | 27.3 (19.9–35.5) | 25.5 (16.5–43.0) | 0.334 |
Karnofsky performance status | ||||
60 | 2 (2%) | 1 (3%) | 1 (2%) | 0.569 |
70 | 6 (6%) | 1 (3%) | 5 (8%) | |
80 | 44 (44%) | 16 (47%) | 28 (42%) | |
90 | 40 (40%) | 15 (44%) | 25 (38%) | |
100 | 8 (8%) | 1 (3%) | 7 (11%) | |
Location | ||||
Upper | 17 (17%) | 8 (24%) | 9 (14%) | 0.171 |
Middle | 7 (7%) | 4 (12%) | 3 (5%) | |
Lower | 76 (76%) | 22 (65%) | 54 (82%) | |
Median tumor length (cm) (range) | 6 (1–15) | 7 (2–13) | 5 (1–15) | 0.065 |
AJCC clinical T stage | ||||
T1 | 1 (1%) | 0 (0%) | 1 (2%) | 0.651 |
T2 | 9 (9%) | 4 (12%) | 5 (8%) | |
T3 | 83 (83%) | 29 (85%) | 54 (82%) | |
T4 | 7 (7%) | 1 (3%) | 6 (9%) | |
AJCC clinical N stage | ||||
N0 | 32 (32%) | 10 (29%) | 22 (33%) | 0.822 |
N1 | 68 (68%) | 24 (71%) | 44 (67%) | |
Receipt of induction chemotherapy | ||||
No | 47 (47%) | 17 (50%) | 30 (45%) | 0.679 |
Yes | 53 (53%) | 17 (50%) | 36 (54%) | |
Dysphagia symptoms at diagnosis | ||||
No | 28 (28%) | 7 (21%) | 21 (32%) | 0.347 |
Yes | 72 (72%) | 27 (79%) | 45 (68%) | |
Odynophagia symptoms at diagnosis | ||||
No | 81 (81%) | 28 (82%) | 53 (80%) | 0.999 |
Yes | 19 (19%) | 6 (18%) | 13 (20%) | |
Median weight loss at diagnosis (kg) (range) | 3.0 (0–27) | 1.5 (0–20) | 3 (0–27) | 0.238 |
Median total RT dose (Gy) (range) | 50.4 (16.2–66) | 50.4 (16.2–66) | 50.4 (32.4–62.8) | 0.098 |
Median PTV volume (cm3) (range) | 800 (45–3,080) | 798 (210–2,168) | 801 (45–3,080) | 0.743 |
RT modality | ||||
3DCRT | 47 (47%) | 16 (47%) | 31 (47%) | 0.835 |
IMRT | 47 (47%) | 17 (50%) | 30 (45%) | |
PBT | 6 (6%) | 1 (3%) | 5 (8%) | |
Median weight loss during RT (kg) (range) | 3.9 (0–16.5) | 3.0 (0–15.0) | 4.5 (0–16.5) | 0.143 |
Univariate analysis of factors associated with use of a prophylactic feeding tube.
Parameter | Odds ratio | 95% CI | |
---|---|---|---|
Median age at diagnosis | |||
Continuous variable | 1 | 0.97–1.04 | 0.876 |
Gender | |||
Male versus female | 0.59 | 0.19–1.78 | 0.346 |
Body mass index | |||
Continuous variable | 0.98 | 0.89–1.07 | 0.602 |
Karnofsky performance status | |||
Continuous variable | 1.01 | 0.96–1.06 | 0.668 |
Location | |||
Middle versus upper | 0.67 | 0.11–3.93 | 0.654 |
Lower versus upper | 2.18 | 0.75–6.38 | 0.154 |
Tumor length | |||
Continuous variable | 0.86 | 0.72–1.01 | 0.072 |
AJCC clinical T stage | |||
T3/4 versus T1/2 | 1.33 | 0.35–5.09 | 0.674 |
AJCC clinical N stage | |||
N1 versus N0 | 0.83 | 0.34–2.05 | 0.691 |
Receipt of induction chemotherapy | |||
Yes versus no | 1.2 | 0.52–2.75 | 0.666 |
Dysphagia symptoms at diagnosis | |||
Yes versus no | 0.56 | 0.21–1.48 | 0.24 |
Odynophagia symptoms at diagnosis | |||
Yes versus no | 1.14 | 0.39–3.34 | 0.805 |
Weight loss at diagnosis | |||
Continuous variable | 1.05 | 0.98–1.14 | 0.178 |
Total RT dose | |||
Continuous variable | 0.96 | 0.90–1.02 | 0.199 |
PTV volume | |||
Continuous variable | 1 | 0.99–1.01 | 0.613 |
RT modality | |||
IMRT versus 3DCRT | 0.91 | 0.39–2.13 | 0.829 |
PBT versus 3DCRT | 2.58 | 0.28–24.00 | 0.405 |
Weight loss during RT | |||
Continuous variable | 1.1 | 0.98–1.23 | 0.117 |
Next, attention was shifted to compare patients who used a pFT (
Clinical characteristics of patients who used a pFT versus those who received one during RT.
Parameter | Used pFT ( |
FT during RT ( |
|
---|---|---|---|
Median age at diagnosis (years) (range) | 63.5 (21–84) | 63.5 (22–91) | 0.863 |
Gender | 0.999 | ||
Male | 51 (77%) | 39 (78%) | |
Female | 15 (23%) | 11 (22%) | |
Median body mass index (kg/m2) (range) | 25.5 (16.5–43.0) | 23.9 (17.4–39.6) | |
Karnofsky performance status | |||
60 | 1 (2%) | 0 (0%) | 0.104 |
70 | 5 (8%) | 6 (12%) | |
80 | 28 (42%) | 23 (46%) | |
90 | 25 (38%) | 21 (42%) | |
100 | 7 (11%) | 0 (0%) | |
Location | |||
Upper | 9 (14%) | 5 (10%) | 0.43 |
Middle | 3 (5%) | 5 (10%) | |
Lower | 54 (82%) | 40 (80%) | |
Median tumor length (cm) (range) | 5 (1–15) | 5 (1–10) | 0.351 |
AJCC clinical T stage | |||
T1 | 1 (2%) | 1 (2%) | 0.861 |
T2 | 5 (8%) | 6 (12%) | |
T3 | 54 (82%) | 38 (76%) | |
T4 | 6 (9%) | 4 (8%) | |
TX | 0 (0%) | 1 (2%) | |
AJCC clinical N stage | |||
N0 | 22 (33%) | 13 (26%) | 0.54 |
N1 | 44 (67%) | 36 (72%) | |
NX | 0 (0%) | 1 (2%) | |
Receipt of induction chemotherapy | |||
No | 30 (45%) | 32 (64%) | 0.061 |
Yes | 36 (54%) | 18 (36%) | |
Dysphagia symptoms at diagnosis | |||
No | 21 (32%) | 11 (22%) | 0.296 |
Yes | 45 (68%) | 39 (78%) | |
Odynophagia symptoms at diagnosis | |||
No | 53 (80%) | 43 (86%) | 0.467 |
Yes | 13 (20%) | 7 (14%) | |
Median weight loss at diagnosis (kg) (range) | 3.0 (0–27) | 6.8 (0–27) | 0.074 |
Median total RT dose (Gy) (range) | 50.4 (32.4–62.8) | 50.4 (16.2–66) | |
Median PTV volume (cm3) (range) | 801 (45–3,080) | 683 (118–1,525) | 0.106 |
RT modality | |||
3DCRT | 31 (47%) | 19 (38%) | 0.535 |
IMRT | 30 (45%) | 25 (50%) | |
PBT | 5 (8%) | 6 (12%) | |
Median weight loss during RT (kg) (range) | 4.5 (0–16.5) | 7.4 (0–18.1) | |
Grade of weight loss | |||
0 | 33 (50%) | 9 (18%) | |
1 | 25 (37%) | 27 (54%) | |
2 | 7 (11%) | 12 (24%) | |
3 | 0 (0%) | 2 (4%) | |
Unknown | 1 (2%) | 0 (0%) | |
Grade of dysphagia | |||
0 | 18 (27%) | 7 (14%) | |
1 | 14 (21%) | 3 (6%) | |
2 | 21 (32%) | 11 (22%) | |
3 | 13 (20%) | 29 (58%) | |
Grade of esophagitis | |||
0 | 14 (21%) | 2 (4%) | |
1 | 7 (11%) | 3 (6%) | |
2 | 33 (50%) | 9 (18%) | |
3 | 12 (18%) | 36 (72%) |
Univariate analysis of factors associated with placement of a feeding tube during RT treatments.
Parameter | Odds ratio | 95% CI | |
---|---|---|---|
Median age at diagnosis | |||
Continuous variable | 0.99 | 0.96–1.02 | 0.631 |
Gender | |||
Male versus female | 0.96 | 0.40–2.32 | 0.926 |
Body mass index | |||
Continuous variable | 1.08 | 1.00–1.18 | 0.064 |
Karnofsky performance status | |||
Continuous variable | 1.03 | 0.98–1.08 | 0.207 |
Location | |||
Middle versus upper | 0.33 | 0.06–2.02 | 0.232 |
Lower versus upper | 0.75 | 0.23–2.41 | 0.629 |
Tumor length | |||
Continuous variable | 1.13 | 0.96–1.34 | 0.152 |
AJCC clinical T stage | |||
T3/4 versus T1/2 | 1.67 | 0.52–5.31 | 0.388 |
AJCC clinical N stage | |||
N1 versus N0 | 0.72 | 0.32–1.63 | 0.434 |
Receipt of induction chemotherapy | |||
Yes versus no | 2.13 | 1.00–4.53 | |
Dysphagia symptoms at diagnosis | |||
Yes versus no | 0.6 | 0.26–1.41 | 0.243 |
Odynophagia symptoms at diagnosis | |||
Yes versus no | 1.51 | 0.55–4.11 | 0.423 |
Weight loss at diagnosis | |||
Continuous variable | 0.95 | 0.90–1.00 | |
Total RT dose | |||
Continuous variable | 0.93 | 0.86–1.00 | |
PTV volume | |||
Continuous variable | 1 | 1.00–1.00 | |
RT modality | |||
IMRT versus 3DCRT | 0.74 | 0.34–1.60 | 0.44 |
PBT versus 3DCRT | 0.51 | 0.14–1.91 | 0.317 |
Weight loss during RT | |||
Continuous variable | 0.87 | 0.80–0.95 | |
Grade of weight loss | |||
2–3 versus 0–1 | 0.31 | 0.11–0.84 | |
Grade of dysphagia | |||
2–3 versus 0–1 | 0.27 | 0.11–0.62 | |
Grade of esophagitis | |||
2–3 versus 0–1 | 0.24 | 0.08–0.69 |
Optimal timing of FT placement in GE cancers is controversial from limited evidence. In our cohort of patients, there were no pretreatment predictors that associated with utilization of a pFT. Hence, because none of the analyzed pretreatment patient, oncologic, or treatment characteristics predicted for utilization of a pFT, these data do not argue in favor of pFT placement. Moreover, receipt of more aggressive therapy (e.g., induction chemotherapy) along with greater symptoms (e.g., weight loss, esophagitis) associated with insertion of FT during RT; hence, select patients must be aggressively monitored for symptoms in order to perform early interventions. Not doing so may risk greater symptomatic suffering and potentially even compromised outcomes from missing RT sessions.
In high-risk patients, both patient-reported and physician-appraised symptoms should be continually re-assessed weekly (at minimum) during treatment, although this may not necessarily mean a lower threshold for FT insertion (other measures such as oral supplements may be considered first). This is important because early intensive nutritional intervention in patients with upper GI cancers results in significantly improved quality of life and body weight (
Our data are consistent with those of head and neck cancers; for instance, investigators determined in a report that nearly half of pFTs were not “used” (defined as <2 weeks of feeding) (
Limitations to these data are as follows. Though retrospective, there are few prospective data that even detail FT insertion rates; secondary analyses of the many trials examining trimodality therapy are therefore important. The low sample sizes are also noteworthy, but the volume of applicable patients in this study is nearly twice as large as any prospective trial. Our results were not aimed to address factors that are associated with FT or pFT insertion, which would necessitate comparison with the 1,006 patients who did not have FT insertion. Because insertion of (p)FTs is often clinician- and institution-dependent, such results may not be applicable to other institutional policies. Moreover, it is acknowledged that specific reasons for (p)FT placement are also largely institution- and clinician-dependent, limiting applicability to all centers. However, this is a noted limitation facing any study (whether GE cancers or head and neck cancers) examining FTs, and hence may still pertain to practices with somewhat similar reasons for FT placement. Lastly, we excluded 43 patients with post-CRT FT insertion, largely because a proportion undergo placement in anticipation of surgery and not necessarily as a result of toxicities. However, it is still acknowledged that esophagitis peaks 1–2 weeks after CRT, and excluding these patients may miss a proportion of patients with toxicity-related FT placement. This necessitates further research as to which patients are at greatest need for enteral feeding from postoperative complications (
In GE cancers, with exception of patients having tumor obstruction and/or PWL, these data do not support insertion of FTs prophylactically prior to CRT. In patients receiving induction chemotherapy, higher-dose RT, and/or having lower pretreatment BMI, early and active symptomatic surveillance is indicated in order to intervene before toxicities worsen.
This study was carried out in accordance with the recommendations of the University of Texas MD Anderson Institutional Review Board and Ethics Committee with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. Permission was obtained to conduct and publish the study.
VV wrote the manuscript, PA analyzed data, SL supervised the study and conceived of its design. All authors read, edited, and approved the final manuscript.
This has been presented in part at the 2016 annual meeting of the American Society of Radiation Oncology, September 2016.
SL has research funding from Elekta, STCube Pharmaceuticals, Peregrine, Bayer, and Roche/Genentech, has served as consultant for AstraZeneca, and received honorarium from US Oncology and ProCure. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We would like to acknowledge Sameer Rajendra Gajjar, M.D., for his help with data collection for this study.