We included nine RCTs and one prospective uncontrolled study in the meta-analysis.
Four studies, three of which were RCTs (Brown 1980; Capirci 2000; McGough 2008), and one prospective uncontrolled study (Craighead 1998), investigated the effect of elemental diet on GI symptoms; one RCT investigated the effect of elemental diet and dietary modification; and five RCTs investigated dietary modification with a lactose restricted diet (Stryker 1986), a low or modified fat diet (Wedlake 2012), a low fat and low lactose diet (Bye 1992), fibre modification (Murphy 2000), and lactose and fibre modification (Pettersson 2012).
Methods of measuring nutritional status in each study are summarised in Table 2. Methods of measuring GI symptoms and QoL in each study are summarised in Table 3. The nutritional intervention used in each study is summarised in Table 4. The comparison of the timing of assessments in each study is shown in Table 5.
Table 3. Method of assessing gastrointestinal symptoms and quality of life used in each included study
| Study ID|| GI symptom/Quality of Life Measurement Tool|
| EORTC-QLQ-PR25|| EORTC-QLQ-C30|| GISEQ|| RTOG|| Diarrhoea Scale*|| MDS*|| Stool frequency|| Duration of diarrhoea|| IBDQ*|| IBDQ-B*|| Vaizey|
| Brown 1980|| -|| -|| -|| -||- || -||X|| -|| -|| -|| -|
| Bye 1992|| -||X|| -|| -||X|| -|| -|| -|| -|| -|| -|
| Capirci 1993||-||-||-||X||-||-||-||-||-||-||-|
| Capirci 2000|| -|| -|| -||X|| -|| -|| -|| -|| -|| -|| -|
| Craighead 1998|| -|| -|| -||X|| -|| -|| -||X|| -|| -|| -|
| McGough 2008|| -|| -|| -||X|| -|| -|| -|| -|| -||X||X|
| Murphy 2000|| -|| -||- || -|| -||X|| -|| -|| -|| -|| -|
| Pettersson 2012||X||X||X|| -|| -|| -|| -|| -|| -|| -|| -|
| Stryker 1986|| -|| -|| -|| -|| -|| -||X|| -|| -|| -|| -|
| Wedlake 2012|| -|| -|| -|| -|| -|| -|| -|| -||X||X||X|
Table 5. Timing of assessment point for each study
| Study ID|| Pre-EBRT|| During EBRT|| Post-EBRT|| Unclear|
| Baseline|| Week 1|| Week 2|| Week 3|| Week 4|| Week 5|| Week 6|| Weekly during treatment|| Pre and post EBRT|| Summary of symptoms during RT|| Week 8|| Week 10|| Week 12|| 2 months after end of RT†|| 12 Months|
| Brown 1980|| - || -|| -|| -|| -|| -|| -||X|| -|| -|| -|| -|| -|| -|| -|| -|
| Bye 1992||X|| -|| -|| -|| -|| -||X|| -|| -|| -|| -|| -||X|| -|| -|| -|
| Capirci 1993|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -|| -||X|
| Capirci 2000|| -|| -|| -|| -|| - || -|| -|| -||X||X|| -|| -|| -|| -|| -|| -|
| Craighead 1998|| -|| -|| -|| -|| -|| -|| -|| -|| -||X|| -|| -|| -|| -|| -|| -|
| McGough 2008||X|| -|| -||X|| -||X|| -|| -|| -|| -||X|| -|| -|| -|| -|| -|
| Murphy 2000|| -|| -|| -|| -|| -|| -|| -|| -|| -||X|| -|| -|| -|| -|| -|| -|
| Pettersson 2012||X|| -|| -|| -||X|| -|| -|| -|| -|| -||X|| -|| -||X|| -|| -|
| Stryker 1986|| -||X||X||X||X||X|| -||X|| -|| -|| -|| -|| -|| -|| -|| -|
| Wedlake 2012||X|| -|| -|| -||X|| -|| -|| -|| -|| -|| -|| -|| -|| -||X|| -|
One single-centre parallel group unblinded RCT of 50 patients (29 women and 21 men) with histologically confirmed gynaecological, urological or lower GI malignancy was performed to determine the feasibility and efficacy of replacing one-third of the normal diet with elemental diet during the first three weeks of radiotherapy. The radiotherapy technique used was predominantly a three-field technique with a fraction size of 1.8 to 2.0 Gy per fraction. The primary outcome was GI symptoms at week five using the Inflammatory Bowel Disease Questionnaire Bowel subset (IBDQB) as a measure. Other outcomes were GI symptoms using the Vaizey Incontinence Questionnaire (VIQ), Radiation Therapy Oncology Group (RTOG) toxicity grade and nutritional status (weight and BMI). Assessments were made at baseline (immediately before the start of radiotherapy), week three, week five and week 10. Faecal calprotectin was also measured, but this was not a relevant outcome for this review.
Patients were randomised to either intervention (25 people) or no intervention (25 people). The no intervention group continued to take their normal diet throughout radiotherapy and the intervention group were asked to replace one meal per day (33% of daily calories) with elemental diet in the form of E028 Extra ready to drink cartons and E028 Extra flavoured powder sachet (SHS International, Liverpool, UK). Compliance was monitored with a diary, pharmacy dispensing records and counts of patients returned unused sachets. Patients in the intervention group were encouraged not to snack for one to two hours either side of the elemental meal.
The intervention group contained a slightly larger proportion of gynaecological cancer patients (44%) and the control arm had a higher proportion of urological cancer patients (36%). The median intake of elemental diet was 571 mL (range 71 to 1000) in week one, 500 mL (range 0 to 1000) in week two and 500 mL (range 0 to 1000) in week three. There was no significant decrease over time (P value > 0.1) but, unfortunately, this was lower than the prescribed volume required to provide 33% of caloric requirement. Six patients were non-compliant.
There were no differences in GI symptoms found at baseline using IBDQ, IBDQB, VIQ and RTOG between the two groups. GI symptoms increased between baseline and both weeks three and five (P value < 0.001) in both groups but there was no difference between groups at week three (P value = 0.214).
For the week 10 follow-up assessment, three patients were missing with no reason given. GI symptoms for both groups had improved compared with week five using IBDQ, IBDQB and RTOG (P value < 0.001). VIQ scores improved for patients in the intervention group comparing week 10 versus week five (P value < 0.001) but not in the control group (P value = 0.06). There was no difference between GI toxicity data comparing compliant and non-compliant patients on post-hoc analysis.
The authors reported that nutritional status was comparable between both groups at baseline and did not change between baseline and other time points, although actual data for this were not published.
Overall there was poor compliance with the intervention (6/25, 24%) and no improvement was seen in terms of GI symptoms or nutritional status. Total IBDQ score was used as a QoL measure. Furthermore, this was a clinically heterogeneous group of patients with different baseline characteristics in terms of primary tumour and, therefore, treatment regimen. This may have confounded the results. Elemental diet was poorly tolerated.
One single-centre parallel group unblinded RCT was performed to compare reduced fibre diet (control) versus three sachets of Vivonex HN (Eaton Laboratories Ltd, Woking, UK) daily along with a reduced fibre diet (intervention). The Vivonex HN supplementation, if complied with, provided 900 kcal and 40g of mixed amino acids daily. Dietary changes were implemented from day one of radiotherapy. There was no description of who gave the reduced fibre diet instruction or what the level of fibre intake was or how this was standardised. Data for 68 patients were reported, although it was unclear if this is the total number entered into the study. Seventeen patients were in the control group, with 30 patients who adhered to the Vivonex HN diet and 21 who did not adhere to the full period of supplementation. The radiotherapy technique used was not clearly described, but patients received 4000 to 6000 rads in 20 to 24 fractions.
Biochemical and metabolic data from this study were reported in a separate publication (Foster 1980), but this was not an outcome for our review. This paper reported weight and stool frequency. Weight was measured weekly and patients recorded stool pattern during treatment. The endpoint of this study was not clear. Twenty-one patients did not adhere to the Vivonex HN diet reporting that it was time-consuming to ingest (six people), gave an unacceptable degree of bloating (six people), potentiated nausea (14 people), was unpalatable (12 people) and induced vomiting (six people). The mean stool frequency was four per day for all three groups (i.e. controls versus Vivonex HN adherents versus Vivonex HN non-adherents). It was not clear how this was determined (i.e. whether this represents the mean stool frequency over the whole of treatment or at a particular time point). No measure of variance was given as either SD or standard error. Mean weight loss was 1.6 kg, 0.5 kg and 1.7 kg for the control, Vivonex HN adherent and Vivonex HN non-adherent groups, respectively. Again no measure of variance was given. The authors reported that this difference was not significant, but the exact statistical test used and the P values were not reported.
Participants had mainly urological tumours, but this study also contained patients with many other types of primary tumours, thus creating a clinically heterogeneous group. The study was underpowered and only means were reported for stool frequency with no measurement of variance given. There was no benefit of elemental diet in terms of stool frequency or change in weight. Elemental diet was poorly tolerated with 41% (21/51) of the reported patients being non-adherent with the intervention. QoL was not assessed.
One conference abstract of a multicentre randomised study evaluating the efficacy of "natural diet" plus elemental diet compared with standard diet on acute enteric toxicity during pelvic radiotherapy was published. Although this abstract was published in 2000, there is no full report in the public domain and there was no response from the authors when contacted. Therefore, available data were limited.
The abstract reported that 677 patients were recruited into this trial with 332 patients randomised into the intervention group (natural diet plus elemental diet) and 345 patients randomised into the control group. Most patients had a primary rectal cancer (439 people), with 228 patients having primary uterine cancer and 10 patients with prostate cancer. The cases were intracentre stratified for amount of irradiated small bowel and concomitant chemotherapy as both these variables correlate with incidence of radiation-related diarrhoea. The outcomes were RTOG score and change in weight comparing pre- and post-radiotherapy weight. It was not clear which elemental diet was used and in what quantities, what the "natural diet" comprised and when the elemental diet was taken. Radiotherapy technique was not reported, neither were the number of patients treated with chemotherapy.
The authors reported that in the intervention group, 17% of patients had grade 1 toxicity, 12% had grade 2 toxicity and 1% had grade 3-4 toxicity, whereas in the control group, 25%, 27% and 4% had grade 1, grade 2 and grades 3-4 toxicity, respectively. The authors also reported that in the intervention group patients with grade 1 toxicity put on 1 kg of weight, those with grade 2 toxicity had no change in weight and those with grade 3-4 toxicity lost 5.5 kg of weight. For the control group, patients with grade 1 toxicity had no weight change, those with grade 2 toxicity lost 1.3 kg of weight and those with grade 3-4 toxicity lost 4 kg of weight. Twelve versus 44 patients required a break in radiotherapy due to GI toxicity in the intervention and control group, respectively. The authors reported that the toxicity reduction remained when data were stratified for concomitant chemotherapy or toxicity grade.
The total numbers with each grade of diarrhoea were not reported. It was not clear whether change in weight reported was mean change in weight and no measure of variance was reported. The authors reported that the differences between the intervention and control group were significant, but the statistical methods used were not described and the P values have not been published.
This was a clinically heterogeneous group. Given the large numbers of patients, it is surprising that subgroup analysis was not performed for rectal cancer and uterine cancer patients. RTOG grade is not validated and is a coarse tool that is known to underestimate toxicity. While the reported results suggest that natural diet with elemental diet reduces radiation enteritis and weight loss during treatment, the lack of reported data makes further analysis difficult.
One single-centre uncontrolled phase II prospective cohort study was performed to assess the feasibility of using elemental supplements to reduce acute enteritis in patients receiving radical pelvic radiotherapy and to assess compliance in primary cervical and endometrial cancer patients. Seventeen patients were selected to have elemental supplements (Vital HNR, Ross Products Division, Abbott Laboratories, Illinois) and a cohort of 45 patients was used to determine the baseline data for radiation enteritis. Both cohorts had a restricted diet which comprised restricted lactose, low fibre (12g daily), moderate fat intake (< 30% calories from fat) with adequate protein and carbohydrate. Intake of fruits, caffeine and other bowel stimulants was restricted. The authors did not document who delivered the information regarding the restricted diet. Patients in the intervention cohort had two or three servings of Vital HNR, each of which comprised 39g of Vital HNR powder mixed with 250 mL of liquid, which provided between 1050 and 1260 J. The treatment period was from three days before the start of radiotherapy to the last day of radiotherapy. Radiotherapy was delivered using a standard four-field arrangement using 10 mV or 15 mV photons to the whole pelvis to a dose of 4500 cGy.
Compliance was assessed using patient diaries and a sachet count at the end of radiotherapy. Bowel function and weight were recorded at baseline, weekly during radiotherapy and at 12 months. Bowel function was assessed using the RTOG grade for acute lower GI enteritis during treatment as assessed by a clinical oncologist. The presence of diarrhoea was assessed at 12 months. Duration of diarrhoea during treatment was also calculated in days. The study was powered to assess compliance not bowel function.
Most patients in the intervention cohort were having adjuvant radiotherapy following surgery for endometrial cancer (nine people). Two patients had adjuvant radiotherapy following surgery for cervical cancer. Six patients were treated with radical radiotherapy for cervical cancer and two of these had intracavity treatment. Fourteen patients reported normal stool consistency at baseline. Baseline data were not published for the control cohort. Thirteen patients complied with the enteral diet as defined by taking two or three sachets of Vital HNR daily at least 80% of the time. Four patients did not comply due to nausea.
The authors combined the non-compliant intervention group patients with the non-intervention cohort and found a greater proportion of patients in this new group had RTOG grade 2/3 diarrhoea as compared the compliant intervention cohort (55% versus 15%, Chi2 = 0.01, P value < 0.001). Mean (SD) duration of diarrhoea during treatment was 5.85 days (4.44) for the intervention compliant cohort, 18.75 days (3.48) in the intervention non-compliant cohort and 12.2 days (6.95) in the comparison cohort. At 12 months, no patients in the intervention compliant cohort had diarrhoea, all patients in the intervention non-compliant group had diarrhoea and 19/45 patients in the control group had diarrhoea. It is not reported how this was assessed and "diarrhoea" was not defined. Weight data for the control cohort were not reported, but intervention compliant group (13 people) gained a mean 1.19 kg and the intervention non-compliant group (four people) lost a mean 1.80 kg of weight. SDs or standard errors were not reported.
The authors concluded that there was acceptable compliance with the elemental diet with dietician support and that this was associated with weight gain and no diarrhoea at 12 months. The study was small and not powered for GI symptoms or weight. In addition, the study was neither randomised nor controlled. Diarrhoea was not clearly defined. QoL was not assessed. RTOG is a non-validated and coarse tool for detecting GI symptoms and has been noted to under-report these symptoms. It was not clear whether there were any differences between baseline characteristics of the cohorts.
Elemental diet with dietary modification
One conference abstract was published of a five-centre parallel group RCT of 275 patients undergoing pelvic radiotherapy to determine the effect of a computerised diet on acute enteric toxicity. Despite the fact that this abstract was published in 1993, there is no full report in the public domain and there was no response from the authors when contacted. Therefore, the data available were limited.
Patients were randomised into one of two groups. The intervention group comprised a diet, selected by a computer, which was "ipolipidic (predominantly medium chain triglycerides), ipercaloric and without lactose" with a supplement of 500 kcal of elemental diet as an adjunct. Patients started this diet four days before radiotherapy and finished four days after radiotherapy was completed. The exact nature of the diet and whether all patients in the intervention group had the same diet were not reported, neither was compliance with the diet. Patients were stratified for concomitant chemotherapy and amount of small bowel within the planned treatment volume (high dose volume). Radiotherapy technique and number of patients receiving chemotherapy were not reported. Outcomes were weight and acute enteric toxicity using European Organisation for Research and Treatment of Cancer (EORTC), although the authors reported grades that appear to be more like the RTOG grading system rather than the EORTC.
Data were analysed from 268 patients although the reasons for the drop-out or withdrawal of seven patients were not given. The authors reported that there was no difference in weight for the control group comparing before and after treatment weight but there was an increase of mean 1.1 kg for intervention group. No measure of variance was reported. Weight loss during radiotherapy was reported to be statistically significantly associated with toxicity. In terms of GI symptoms, in the intervention group, 69% had grade 0, 16% had grade 1, 14% had grade 2 and 2% had grades 3-4 toxicity. In the control group, 47% had grade 0, 25% had grade 1, 20% had grade 2 and 2% had grades 3 to 4 toxicity. The authors reported that this represents a significant difference between the two groups, although no P values were published.
The authors reported that they used EORTC to measure toxicity, but the scores that they used seem to be more in keeping with the RTOG grade. EORTC has several questionnaires that measure QoL and not toxicity and this is not reported as grades. RTOG grade is not validated and is a coarse tool that is known to underestimate toxicity. EORTC is not validated to measure toxicity. While the reported results suggest that computerised diet with elemental diet reduces acute enteric toxicity and weight loss during treatment, the lack of reported data makes further analysis difficult.
One single centre (two sites) parallel group unblinded randomised controlled pilot study of 84 patients (72 men and 12 women) with prostate or gynaecological cancer was performed to determine the effect of fibre modification with Metamucil on the severity and incidence of diarrhoea. Patients were randomised to take or not take Metamucil. All patients received a booklet called "Nutritional guidelines to help control diarrhoea", which advised on a low-fibre diet with limited fat, caffeine and alcohol intake. Researchers gave the dietary information. Subjects in the intervention group were instructed to take 5 mL of Metamucil powder mixed into 250 mL of water once a day in the morning and could take a second dose in the afternoon if diarrhoea persisted. Radiotherapy technique was not reported. Compliance was measured through patient diaries. Outcomes were based on patient diaries completed from the first day of radiotherapy to 28 days after completion of treatment. Patients recorded stool frequency, stool consistency, antidiarrhoeal use and daily dose of Metamucil. Data from diaries were converted into the Murphy Diarrhoea Scale (MDS), which gives a summary score for diarrhoea over the whole treatment period (Table 6), which takes account of stool frequency and texture, and use of antidiarrhoeals to determine "days-with-diarrhoea" as a numerical score. This is not a validated tool.
Table 6. Murphy Diarrhoea Scale
| Description|| Score|
|Mild diarrhoea (< 11% days-with-diarrhoea*)||1|
|Moderate diarrhoea (11-20% days-with-diarrhoea*)||2|
|Mild diarrhoea (> 20% days-with-diarrhoea*)||3|
Data from 24 subjects were excluded from analysis due withdrawal (one person), incomplete diaries (two people), inaccurate diary entries (six people), failure to return diaries (13 people) and using Metamucil while in the non-Metamucil group (two people). There were no differences between these two groups for mean age or weight at baseline. Participants in the Metamucil group (intervention) had lower mean MDS scores compared with the control group (1.8 versus 2.33, P value = 0.03) and lower incidence of diarrhoea compared with the control group (605 versus 83%, P value = 0.049). There was no difference with respect to the mean percentage days that patients took antidiarrhoeal medication (P value = 0.062). The mean time to onset of diarrhoea was not different between the two groups (P value = 0.895), neither was the mean duration of diarrhoea (P value = 0.905).
The use of Metamucil did appear to reduce the incidence and severity of diarrhoea during radiotherapy. There are no long-term follow-up data and no QoL data. This was the only study in which the intervention was applied when GI symptom occurred, rather than being used prophylactically in all patients regardless of symptoms.
Lactose and fibre modification
One parallel group single-centre unblinded RCT of 130 patients with prostate cancer was performed to determine the effect of a lactose- and insoluble fibre-restricted diet (64 people) compared with no dietary change (66 people) on acute GI side effects and other aspects of health-related QoL. Patients were treated with external beam radiotherapy and either high-dose rate brachytherapy or proton therapy and patients were stratified according to radiation technique (brachytherapy versus proton therapy). The intervention was standardised dietary advice from a research dietician in face-to-face sessions at baseline (prior to radiotherapy), after four weeks of radiotherapy and via a telephone consultation at eight weeks following the start of radiotherapy (one week after radiotherapy completion) as well as a study-specific brochure at all time points. The advice was to avoid foods high in insoluble fibre and lactose and instead consume foods with a higher proportion of soluble fibres and low in lactose for the whole of the study period (from baseline up to 24 months after the end of radiotherapy). The control group comprised patients who received no dietary intervention and continued on their normal diet. The exact radiotherapy technique used was not described, but daily fractions of 2 Gy were delivered to 50 Gy with a treatment volume comprising the prostate only and seminal vesicles for T3 tumours.
Assessments were made at baseline, four weeks after onset of radiotherapy, eight weeks after onset of radiotherapy and two months after radiotherapy completion. Nutritional status was only assessed pre-treatment with the patient-generated subjective global assessment (PGSGA) and weight/BMI. Outcomes were GI symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate-specific module (EORTC-QLQ-PR25) along with the study-specific Gastrointestinal Side Effects Questionnaire (GISEQ), which assessed how much patients were "bothered" by GI symptoms. Global health status, functioning and symptoms were assessed using EORTC-QLQ-C30 and EORTC-QLQ-PR25. The study was powered for EORTC-QLQ-PR25 mean value for bowel symptoms. Adherence to dietary instructions was monitored by the study-specific Food Frequency Questionnaire (FFQ), in which patients reported how often they consumed certain foods (with unspecified portion sizes) over the preceding month. Foods were categorised on the basis of insoluble fibre and lactose content. The scale ranged from 0 (never) to 7 (three or more times per day).
There was no difference between the two groups at baseline in terms of clinical characteristics, FFQ scores, GI side effects and other aspects of QoL. There was no difference between the two groups in terms of bowel symptoms using EORTC-QLQ-C30, EORTC-QLQ-PR25 or GISEQ at eight weeks (one week after the completion of radiotherapy) except in the GISEQ item intestinal cramps (P value = 0.039). There was also no difference between the two groups in terms of QoL using EORTC-QLQ-C30 and EORTC-QLQ-PR25 although P values were not reported. There was no relationship between adherence to diet and bowel symptoms using FFQ scores. FFQ data showed that the control group did not change their diet but the intervention group had lower scores in the FFQ at all time points compared with baseline.
Overall, there was no benefit found for dietary modification of insoluble fibre and lactose in men undergoing pelvic radiotherapy for prostate cancer in terms of GI symptoms as determined by the EORTC-QLQ-C30, EORTC-QLQ-PR25 or GISEQ. However, these tools are not validated for detecting GI toxicity and, in particular, an exact definition of diarrhoea does not appear to have been given including both a change in stool frequency and consistency. This may have influenced the findings.
One single-centre parallel group unblinded RCT of 64 patients (57 women and 7 men) undergoing pelvic radiotherapy for either gynaecological, prostate or sigmoid cancers was performed to determine whether modification of lactose in the diet affects the severity of GI symptoms experienced during pelvic radiotherapy. Patients were treated using parallel opposing anterior-posterior (AP) portals except in larger patients who were treated with four portals (box technique). Patients were randomised into three groups: normal diet containing at least 480 mL of milk daily (control); lactose-restricted diet with calcium replacement of 625 mg three times a day or lactose-hydrolysed diet containing 480 mL of milk daily where 90% of the lactose was hydrolysed to glucose and galactose. The details of the diets have not been specified and the professional modifying the diet was not specified. Outcomes were mean stool frequency and antidiarrhoeal use, although the latter was not an outcome for the purpose of this review.
There was discrepancy in the numbers reported. Sixty-four patients were randomised into one of the three groups. The author reported that 21 patients were randomised to the control group, 20 to the lactose-restricted group and 22 in the lactose-hydrolysed group. Several patients were excluded or dropped out: three patients were withdrawn from analysis for the control group; one patient was withdrawn from analysis for the lactose-restricted group and six patients were withdrawn from analysis for the lactose-hydrolysed group. All withdrawals were because patients did not complete four weeks of treatment on the protocol. There was no reported power calculation.
Baseline mean (SD) stool frequency was not significantly different between the groups (P value = 0.7071) with a frequency of 1.3 (0.8) for the control group, 1.0 (0.6) for the lactose-restricted group and 1.1 (1.0) for the lactose-hydrolysed group daily. The mean weekly stool frequency at week five was 22.5, 19 and 26 for the control, lactose-restricted and lactose-hydrolysed groups, respectively. A measure of variance was not reported. There was no significant difference between the three dietary regimens for mean weekly stool frequency (P value = 0.2153). Mean numbers of diphenoxylate tablets at week five were 8.5, 7 and 18 for the control, lactose-restricted and lactose-hydrolysed groups, respectively. A measure of variance was not reported. There was no significant difference between the three dietary regimens for mean number of diphenoxylate tablets used weekly (P value = 0.7526).
This study showed no benefit of lactose-restricted diet during radiotherapy, although the radiotherapy techniques used are no longer standard practice and the details regarding the lactose-restricted diet were lacking so it is difficult to comment on whether this would be comparable with a lactose-restricted diet used in the 2010s. In addition, 10 recruited patients were excluded from the analysis potentially leading to attrition bias. QoL was not measured.
Lactose and fat modification
One single-centre parallel group unblinded RCT of 143 patients with either endometrial (49 women), cervical (93 women) or ovarian (one women) cancer undergoing pelvic radiotherapy was performed to determine the effect of a fat- and lactose-restricted diet on radiation-induced diarrhoea. Radiotherapy was delivered using AP fields followed by intracavity treatment for 90 of those with cervix cancer. Patients were randomised into two groups: regular hospital diet (control) or lactose- and fat-restricted diet comprising a maximum of 40g of fat and 5g of lactose daily prescribed by a dietician and individualised to patient tastes (intervention). The dietary modification was started before the start of radiotherapy and continued for six weeks after radiotherapy. Outcomes measured were weight, stool frequency/consistency, use of antidiarrhoeals, QoL using EORTC-QLQ-C36, arm muscle circumference and serum transferrin at baseline, six and 12 weeks.
There were no baseline imbalances in stool frequency, use of antidiarrhoeals, total energy intake or total fat intake. Fourteen patients were excluded from analysis: seven patients did not comply with the dietary modification, one control patient changed over to lactose- and fat-restricted diet, six patients left for personal reasons (three from each group).
At week six, there was a difference in stool frequency between control and intervention group (P value < 0.01) with patients passing a mean of 1.1 loose and watery stools per day in the control group and 1.7 loose and watery stools per day in the intervention group. When converted to the diarrhoea scale reported in the paper (Table 7), 14 of 61 patients versus 32 of 67 patients had diarrhoea in the intervention and control group, respectively (P value < 0.01). Patients in the intervention group took fewer antidiarrhoeals compared with the control group (P value < 0.01). Patients in the intervention group had a greater reduction in body weight during treatment (mean 2.6 kg) compared with controls (mean 1.7 kg) (P value = 0.006).
Table 7. Diarrhoea scale used in Bye 1992
| Score|| Description|
| 0||No change in stool frequency|
| 1||Increase of 1-3 stools a day, normal or soft|
| 2||Increase in 4-6 stools a day, all watery|
| 3||Increase in > 6 stools a day|
At week 12, there were no differences between the groups with respect to stool frequency and antidiarrhoeal use. Patients in the intervention group had gained a mean of 0.6 kg of weight whereas the control had gained a mean of 1.1 kg of weight.
There was no difference in QoL. No patients had an arm muscle circumference (AMC) less than 19 cm at baseline. No patients in the control group and one (2%) in the intervention group had an AMC less than 19 cm at week six. Two patients (2%) and one patient (1%) in the control and intervention group, respectively, had a serum transferrin less than 1.4 g/L at baseline. Four patients (6%) and eight patients (13%) in the control and intervention group, respectively, had a serum transferrin less than 1.4 g/L at week six. The significance of these differences between groups was not reported.
This study did demonstrate that a low-fat, low-lactose diet reduced the incidence of diarrhoea during radiotherapy, with the control group taking twice as many antidiarrhoeals as the intervention group. Efforts were made to define diarrhoea clearly in terms of changes in stool frequency and consistency, although the scoring system used was not a validated tool.
One two-centre three-arm parallel group unblinded RCT of 117 patients (79 men and 38 women) was performed to determine the efficacy of low- or modified-fat diets on reducing GI toxicity. Patients were randomised into one of three groups: low-fat (40 people), modified-fat (38 people) and control (39 people) group. The low-fat group was prescribed a low-fat diet with long-chain triglyceride dietary fats calculated to comprise 20% of total energy intake. Patients in this group were advised to have a stable diet and maintain total energy intake from carbohydrate- and protein-based sources. The modified-fat group were prescribed a diet with fats calculated to comprise 40% of total energy intake with 50% of this derived from long-chain triglycerides and 50% from a medium-chain triglyceride-based emulsion (Liquigen). The control group were prescribed a normal fat diet with long-chain triglyceride dietary fats calculated to comprise 40% of total energy intake. Prescriptions were given in terms of "fat points" where one fat point was equal to 5 g of fat. The intervention period was the first four weeks of radiotherapy. The radiotherapy technique was not described.
At baseline, the groups were well matched for age, gender, radiotherapy, weight and long-chain triglyceride fat intake but a higher proportion of patients in the modified-fat group were treated with chemotherapy. The low-fat group contained a higher proportion of patients with urological cancer and a lower proportion of patients with lower GI cancer. Median radiotherapy dose was 54 Gy (range 36 to 74) with a dose per fraction of 1.8 to 2.0 Gy.
Outcomes were daily fat point consumption recorded in patient diaries; GI toxicity, measured by IBDQB, VIQ and RTOG; nutritional parameters, that is, weight, BMI and handgrip strength; and QoL, measured using total IBDQ score. Outcomes were assessed at baseline, after two weeks of radiotherapy, after four weeks of radiotherapy and at one year post-treatment. Percentage compliance with Liquigen was also recorded at two and four weeks. The study was powered for change in mean IBDQ score from baseline to week four (35 patients per arm were required).
Ten patients withdrew during the first four weeks of the study due to intolerance to Liquigen (six people), voluntary withdrawal (three people) and entering a mutually exclusive study (one person). These patients were not included in the analysis. A further 32 patients were lost to follow-up by one year (12 deceased, six were too ill, there was no reply from 10 patients and four patients had moved residence).
Mean IBDQB score fell in all patients between baseline and week four, indicating an increase in GI toxicity (66.2 versus 58.9, 106 people). There were no differences in the change in paired scores comparing baseline and week four between low-fat and modified-fat groups (P value = 0.914), low-fat and normal-fat groups (P value = 0.793) and modified-fat and normal-fat groups (P value = 0.890). There was no report of whether there was a difference in VIQ scores between baseline and week four or baseline and one year; IBDQB score between baseline and one year and RTOG grades.
There was a reduction in mean weight in all groups between baseline and week four and in the modified- and normal-fat groups between baseline and one year, although the level of statistical significance is not reported. By study group, mean grip strength fell by 0.2 kg in the low-fat group, rose by 2.2 kg in the modified-fat group and rose by 1.2 kg in the normal-fat group. No measure of variance of this change was reported. QoL, as determined by change in total IBDQ score during treatment, improved for all groups, as reflected in a fall in total IBDQ score. The magnitude of this fall in score was -13 for the low-fat and modified-fat groups and by -14.7 for the normal-fat groups, where an increase represents a deterioration in QoL. Change in QoL comparing baseline versus one year was a change in total IBDQ score of 2.5 for the low-fat, -9.6 for the modified-fat and -4.0 for the normal-fat groups, respectively. Compliance was variable in the different groups, ranging from 93% in the low-fat group to 76% in the modified-fat group to 9% in the normal-fat group. Compliance was poor in the normal-fat group as they reduced their fat intake too much. Compliance with Liquigen was poor with only 58% achieving 76% or greater compliance.
This study did not demonstrate that low- or modified-fat diet reduced GI symptoms. This may reflect the fact that the mean peri-radiotherapy self reported fat points (1 fat point = 5 g of fat) was 6.7 (SD 1.98) in the low-fat group, 8.2 (SD 1.40) in the modified-fat group and 12.6 (SD 3.28) in the normal-fat group, where the mean prescription was 19 points. These are quite similar and perhaps the similarity of fat intake between groups meant that differences could not be observed. In addition, the control group of "normal fat diet" is not necessarily reflective of the normal diet of most patients, rather a reflection of recommended fat intake.