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To evaluate a nutrition pathway that promoted early and aggressive dietetic intervention in patients receiving definitive chemoradiation for esophageal cancer.

• Synchronous chemoradiation
• Most subjects were entered on the Trans Radiation Oncology Group (TROG) trials 89-04, 96-02 or 98-06 during 1990-2001
• Previously untreated patients

None listed

Recruitment

Not described

 

Design

Retrospective chart review

• Control group consisted of historical controls: any patient planned to receive definitive treatment for esophageal cancer from 1990-1996 prior to implementation of the nutrition pathway
• Nutrition pathway (NP) group consisted of any patient presenting to the esophagel clinic from 1997-2001 who was planned to receive definitive treatment

Intervention

Nutrition Pathway group: Interviewed by RD at initial presentation to the esophageal clinic then weekly throughout chemoradiation courses

• Initial consultation nutrition assessment
  • Nutrition risk (low, moderate or severe) determined by RD per NP criteria
  • Low risk subjects received information and support to help maintain nutritional status
  • Moderate risk subjects
    
    • Presence of anorexia/dysphagia and/or unintentional weight loss 5-9%
    • received consistency modified, high protein/high energy diet education
  • Severe risk subjects received PEG or nasogastric (NG) tube placement depending on the treatment week in which risk was identified
    • Severe dysphagia (puree/fluids only) and/or unintentional wt loss > 10% and/or BMI < 18 kg/m²
  • PEGs were placed for severe risk subjects before starting treatment in all cases and instruction for home use was provided.
  • Enteral feeding for both PEG or NG consisted of a 1.5 kcal/ml formula, nutritionally complete in 1690 calories.
  • Regular follow up occurred to assess nutritional status and nutrient prescriptions were adjusted as necessary.
• Inpatients - Day 1 Chemoradiation Nutrition Assessment
  • Low risk: nutrition education addressing strategies for managing nausea/vomiting and fluid intake
  • Moderate risk: presence of anorexia/dysphagia and/or weight loss 5-9%
    • nutrition education including textured modified, high protein/energy diet and/or managing nausea/vomiting and fluid intake
  • Severe risk: severe dysphagia (puree only) and/or weight loss > 10%
    • PEG placement in the first 3 weeks of chemoradiation
• Outpatients - Day 8 after chemotherapy
  • Low risk: weight loss < 4 kg in past week, adequate hydration
    • nutrition education reinforcing prior dietary advice
  • Moderate risk: weight loss > 4 kg in past week, dehydration
    • nutrition education addressing adequate fluid intake, strategies for managing nausea/anorexia, high protein/high energy diet (+/- texture modification)
• Outpatients: weekly nutrition assessment
  • Low and moderate risk: weight stabilized
  • Severe risk: failure to stabilize weight, weight loss > 10%
    • NG tube placement if > 50% of chemoradiation therapy had been provideded

 

 

Control Group

• Received nutrition support in a reactive manner
• Referred to RD only as problems arose
  
• Nutrition risk (low, moderate or severe) classified retrospectively per nutrition pathway criteria

Planned medical therapy

• Chemoradiation treatment
  • Cisplatin 80 mg/m2 by IV infusion on day 1 and day 21 (or day 28) plus 5-fluorouracil 800 mg/m2 by continuous infusion on days 22-25 (or days 29-32)
  • Radiation dose of 60 Gy to the tumor-bearing volume and 30 Gy to the regional lymphatics using daily incremental fractions of 2 Gy over 6 weeks.

 

Statistics

• Categorical variables were analyzed by chi-squared or Fisher's Exact test
• Differences in continuous variables between groups were compared using Students t-test or Mann-Whitney test, depending on distribution
• All statistical analyses were two-tailed and a value of P<0.05 was considered statistically significant
• Statistics package SPSS 10.0 for Windows

Timing of Measurements

 

Dependent Variables

• Weight status
• Percentage of planned treatment delivered
• Number of unplanned hospital admissions
• Length of hosital stay during unplanned hospital admissions
  

Independent Variables

• Nutrition pathway management

 

Control Variables

 

Initial N:

Control: n=24

Nutrition pathway: n=24

Attrition (final N):

Control: n=24

Nutrition pathway: n=24

Age: See table below

Ethnicity: Not described

Other relevant demdographics: See table below

Anthropometrics See table below

Location:

Newcastle Mater Misericordiae Hospital, New South Wales, Australia

Comparison of demograpic, oncological and nutritional characteristics

		Nutrition Pathway	P value
	(n=24)	(n=24)
% male	67	71	0.77
age (yrs)*	71.9±9.8	66.4±10.9	0.07
Tumor type %
Squamous	71	71
Adenocarcinoma	29	29	1.00
Tumor length (cm)*	6.1±2.2	6.3±3.2	0.34
Tumor position %
Top	17	8	0.79
Middle	17	26
Lower	58	58
Esophago-gastric junction	8	8
% patients w/ dysphagia	92	83	0.38
Usual BMI*	25.5±5.1	27.4±6.1	0.27
% usual wt loss at presentation*	7.3±5.6	7.4±6.3	0.92
Nutrition risk %
At low risk	21 (n=5)	16 (n=4)	0.47
At moderate risk	25 (n=6)	42 (n=10)
At severe risk	54 (n=13)	42 (n=10)

*mean±standard deviation for normal variables

 

Timing and Reasons for Initial Dietetic Intervention

	Control	Nutrition Pathway	P value
	(n=24)	(n=24)
% patients w/ first intervention at:
First presentation to the unit	38 (9)	96 23)	<0.05
Start of treatment	29 (7)	4 (1)
During treatment*	33 (8)	0 (0)
Reason for intervention %
Dysphagia	100 (24)	83 (20)	0.04
Wt loss	83 (20)	79 (19)	>0.05
Anorexia	46 (11)	46 (11)	>0.05
Automatic referral per NP	0 (0)	96 (23)	<0.05
Referred for other reasons§	21 (5)	17 (4)	>0.05

*Interventions occurred week 2 (n=6), week 3 (n=1), week 7 (n=1).

§Other reasons for referral in control group: enteral nutrition required pre-treatment (n=2), low albumin/diabetes/nausea (n=1 subject each). Other reasons for referral in NP group: enteral nutriiton review as enteral nutrition had been commenced elsewhere (n=1), reflux/social situation/diabetes (n=1 patient each).

1. Automatic referral as a reason for intervention occurred in 23/24 subjects, highlighting excellent compliance (96%) with the nutrition pathway protocol.
2. In the control group, 33% of the subjects not seen by a RD until at least the second week of treatment.

Comparison of Enteral Nutrition (EN) Delivered

	Control	Nutrition Pathway	Pvalue
	(n=8)	(n=13)
% Receiving EN	33 (8/24)	54 (13/24	>0.05
Week EN started	3.6±3.0	-0.31±2.8	0.001
Administration method %
PEG	25 (2)	77 (10)	0.06
NG	63 (5)	15 (2)
NG then PEG	12 (1)	8 (1)
BMI at start of EN*	19.0±3.6	22.3±4.1	0.08
% usual wt loss at start of EN*	17.9±5.5	12.3±4.7	0.02
Problems during EN (%)
Nausea	38 (3)	46 (6)	>0.05
Diarrhea	13 (1)	0 (0)	>0.05
Bloating	38 (3)	46 (6)	>0.05
Tube blockage	13 (1)	23 (3)	>0.05
Vomiting	25 (2)	15 (2)	>0.05
Tube dislodgement	13 (1)	0 (0)	>0.05
Reflux	13 (1)	15 (2)	>0.05
PEG site infection	0 (0)	8 (1)	>0.05
Subjects receiving EN by nutrition risk assessment (%)
Severe	38 (5/13)	100 (10/10)	0.003
Moderate	33 (2/6)	30 (3/10)	>0.05
Low	20 (1/5)	0 (0/10)	>0.05

*mean±standard deviation for normal variables

1. In the control group, 13 subjects were assessed retrospectively as "severe nutrition risk", but only 2 received a PEG pre-treatment. In contrast, all 10 subjects in the nutrition pathway group assessed as "severe nutrition risk received a PEG pre-treatment.
2. There was a significant difference in the timing of EN between the groups; however, the total number of subjects receiving EN was not different.

Comparison of Weight Outcomes

	Control	Nutrition Pathway	P value
	(n=16) completed	(n=22) completed
% usual wt lost at end of treatment*	16.2±6.8	11.0±4.9	0.04
% wt change during treatment*	-8.9±5.9	-4.2±6.4	0.03
% wt change over treatment course/nutrition risk*
Severe	-6.33±6.0	0.38±6.1	0.06
Moderate	-11.8±7.6	-8.0±6.3	0.48
Low	-9.5±4.4	-6.3±4.9	0.21

*mean±standard deviation for normal variables

1. Subjects in the nutrition pathway group lost less weight over the treatment period.

Comparison of Chemotherapy Outcomes

	Control	Nutrition Pathway	P  value
	(n=24)	(n=24)
Treatment received
2 cycles of cisplatin & 5-FU	92 (22)	83 (20)*	0.33
1 cycle of cisplatin & 5-FU	8 (2)	4 (1)
1 cycle of cisplatin & 2 cycles of 5-Fu	0 (0)	8 (2)
Half cycle of cisplatin & 5-FU	0 (0)	4 (1)
% subjects experiencing chemotherapy delay	71 (17)	67 (16)
Number of weeks delay§	median 1 (0-3)	median 1 (0-3)	0.40
% subjects who had a dose reduction	42 (10)	29 (7)	0.34
% planned cisplatin dose received§	median 100 (50-100)	median 100 (5-100)	0.40
% planned 5-FU dose received§	median 100 (50-100)	median 100 (50-100)	0.29

* Three subjects had 4 cycles of cisplatin/5-FU, but only the first 2 cycles were included in the analysis
§ Median (range) for non-normal variables

1. The nutrition pathway had no effect on chemotherapy delivery compared with controls.
2. There was a trend towards fewer dose reductions in subjects in the nutrition pathway group.

Comparison of Radiotherapy Outcomes

	Control	Nutrition Pathway	P value
	(n=24)	(n=24)
% subjects completing radiotherapy	50 (12)	92 (22)	0.001
% subjects who had radiotherapy break (those completing treatment)	33 (4/12)	27 (6/22)	0.71
Number of days break (for those completing treatment)*	0 (0-18)	0 (0-13)	0.48
% planned radiotherapy dose delivered*	median 95 (37-100)	median 100 (60-100)	0.004
% radiotherapy dose delivered/nutrition risk*
Severe	83 (37-100)	100 (60-100)	0.06
Moderate	100 (58-100)	100 (93-100)	0.20
Low	100 (50-100)	100 (100-100)	0.18

* Median (range) for non-normal variables.

1. There was a significant difference in the percentage of subjects who completed the planned  radiotherapy course: 92% of the nutrition pathway group compared with 50% of the control group, p=0.003.
2. the percentage of radiotherapy dose delivered to the nutrition pathway group was also more than the percentage delivered to the control group.
3. In the control group, 9/12 subjects discontinued treatment because of side effects while only 2 subjects in the nutrition pathway group did not complete treatment (both because of coincidental myocardial infarctions).

Comparison of Hospital Admissions Outcomes

	Control	Nutrition Pathway	P value
	(n=24)	(n=24)
% patients w/ UHA	75/(18)	46 (11)	0.04
Number of UHA/patient*	median 1 (0-2)	median 0 (0-4)	0.05
Total number UHA/group	24	16
Total LOS for all UHA (days)§	13.5±14.1	3.2±5.4	0.002
LOS admission 1 (days)*	median 6.5 (0-52)	median 0 (0-11)	0.002
LOS admission 2 (days)*	median 0 (0-31)	median 0 (0-17)	>0.05
Reason for admission 1: for EN (%)	33 (6/18)	9 (1/11)	>0.05
Reason for admission 2: for EN (%)	17 (1/6)	0 (0/3)	>0.05
Total LOS/nutrition risk (days)§
Severe	16 (0-52)	2 (0-8)	0.006
Moderate	2.5 (0-11)	0 (0-20)	>0.05
Low	16 (0-34)	2 (0-16)	>0.05

* Median (range) for non-normal variables.
§ Mean±standard deviation for normal variables
UHA: unplanned hospital admission; LOS: length of stay; EN: enteral nutrition

1. Subjects in the control group were more likely to have an unplanned hospital admission (UHA) during the treatment period with 75% of control subjects having a UHA compared with 46% of subjects in the nutrition pathway group (P=0.04).
2. Although the total number of UHA was not not different betwen the groups (P=0.05), the total length of stay for all UHA was greatly reduced in the nutrition pathway group: 13.5 days (±14.1) for the control group compared with 3.2 days (±5.4) for the nutrition pathway group (P=0.002).
3. Only one patient in the nutrition pathway group was admitted for enteral nutrition (1/11, a 1-day admisison for PEG placement for a patient crossing over from moderte to severe risk), whereas 6 of the 18 admissions in the control group were primarily for nutritional support.

 

Other Findings

 

1. Implementation of this nutrition pathway has been associated with improved clinical outcomes, including decreased weight loss, number of unplanned hospital admissions and length of stay during the treatment course, and a higher tolerance of planned treatment.
2. Recommend that all patients with esophageal cancer who will receive definitive chemoradiation receive a proactive nutritional assessment by a RD specializing in oncology on initial presentation, and appropriate nutritional support and follow-up within the multidisciplinary team.

Not-for-profit

0 Foundation associated with industry:

• Primary weakness of the study was the use of historical controls; however, it would have been unethical to deny control subjects nutrition management via the nutrition pathway.
• No data provided re: the amount of nutrition received vs goal
• No survival data reported