Curation of myeloma observational study MALIMAR using XNAT: solving the challenges posed by real-world data.

OBJECTIVES: MAchine Learning In MyelomA Response (MALIMAR) is an observational clinical study combining "real-world" and clinical trial data, both retrospective and prospective. Images were acquired on three MRI scanners over a 10-year window at two institutions, leading to a need for extensive curation. METHODS: Curation involved image aggregation, pseudonymisation, allocation between project phases, data cleaning, upload to an XNAT repository visible from multiple sites, annotation, incorporation of machine learning research outputs and quality assurance using programmatic methods. RESULTS: A total of 796 whole-body MR imaging sessions from 462 subjects were curated. A major change in scan protocol part way through the retrospective window meant that approximately 30% of available imaging sessions had properties that differed significantly from the remainder of the data. Issues were found with a vendor-supplied clinical algorithm for "composing" whole-body images from multiple imaging stations. Historic weaknesses in a digital video disk (DVD) research archive (already addressed by the mid-2010s) were highlighted by incomplete datasets, some of which could not be completely recovered. The final dataset contained 736 imaging sessions for 432 subjects. Software was written to clean and harmonise data. Implications for the subsequent machine learning activity are considered. CONCLUSIONS: MALIMAR exemplifies the vital role that curation plays in machine learning studies that use real-world data. A research repository such as XNAT facilitates day-to-day management, ensures robustness and consistency and enhances the value of the final dataset. The types of process described here will be vital for future large-scale multi-institutional and multi-national imaging projects. CRITICAL RELEVANCE STATEMENT: This article showcases innovative data curation methods using a state-of-the-art image repository platform; such tools will be vital for managing the large multi-institutional datasets required to train and validate generalisable ML algorithms and future foundation models in medical imaging. KEY POINTS: • Heterogeneous data in the MALIMAR study required the development of novel curation strategies. • Correction of multiple problems affecting the real-world data was successful, but implications for machine learning are still being evaluated. • Modern image repositories have rich application programming interfaces enabling data enrichment and programmatic QA, making them much more than simple "image marts".

What do readers want? Results of an online survey to involve readers in updating the seventh edition of the Manual of dietetic practice.

BACKGROUND: The Manual of dietetic practice ('Manual') is the core textbook for qualified and student dietitians. A survey was conducted to explore views on the scope, content and presentation of the Manual to inform the forthcoming edition. METHODS: The survey comprised of questions on demographics, structure, content, access (print/digital), missing topics, strengths and weaknesses. It was distributed to members of the British Dietetic Association (BDA) and other relevant groups in August 2022. Responses are presented as frequencies and free text as themes. RESULTS: Of 1179 responses, 91% were from professionals, of whom 72% were registered dietitians with a mean of 12.7 years (range: 1-44) in practice: 60% worked in the United Kingdom with 52% based in a clinical setting. The printed version was preferred: 59% professionals, 60% students, 94% professionals and 88% students were satisfied with the structure; however, 26% professionals and 22% students identified content that was lacking or outdated, including mental health and sustainability. The strengths were its comprehensive coverage and respected contributing authors. Weaknesses included the cost, size, lack of visual aids and currency. Professionals indicated the seventh edition should focus on more practical information required for clinical practice, whereas students wanted more emphasis on summarised information and visual formats. CONCLUSIONS: The survey proved a valuable method to engage with the readership to ensure the next edition reflected their requirements. Although nearly all respondents were satisfied with the scope and content, the results highlighted those topics lacking and/or outdated. Results also showed that the next edition should focus on practical information required for clinical practice, with more summarised and visual formats.

Assessing the collection and reporting of patient-reported outcome data in interventional cancer trials: a single institution, retrospective systematic evaluation.

BACKGROUND: To understand our performance with respect to the collection and reporting of patient-reported outcome (PRO) measure (PROM) data, we examined the protocol content, data completeness and publication of PROs from interventional trials conducted at the Royal Marsden NHS Foundation Trust (RM) and explored factors associated with data missingness and PRO publication. DESIGN: From local records, we identified closed, intervention trials sponsored by RM that opened after 1995 and collected PROMs as primary, secondary or exploratory outcomes. Protocol data were extracted by two researchers and scored against the SPIRIT-PRO (PRO protocol content checklist; score 0-100, higher scores indicate better completeness). For studies with locally held datasets, the information team summarized for each study, PRO completion defined as the number of expected (as per protocol) PRO measurements versus the number of actual (i.e. completed) PRO measurements captured in the study data set. Relevant publications were identified by searching three online databases and chief investigator request. Data were extracted and each publication scored against the CONSORT-PRO (PRO manuscript content checklist; scored as SPIRIT-PRO above). Descriptive statistics are presented with exploratory comparisons of point estimates and 95% confidence intervals. RESULTS: Twenty-six of 65 studies were included in the review. Nineteen studies had accessible datasets and 18 studies published at least one article. Fourteen studies published PRO results. Most studies had a clinical (rather than PRO) primary outcome (16/26). Across all studies, responses in respect of 35 of 69 PROMs were published. Trial protocols scored on average 46.7 (range 7.1-92.9) on the SPIRIT-PRO. Among studies with accessible data, half (10/19) had less than 25% missing measurements. Publications scored on average 80.9 (range 36-100%) on the CONSORT-PRO. Studies that published PRO results had somewhat fewer missing measurements (19% [7-32%] vs 60% [- 26 to 146%]). For individual PROMs within studies, missing measurements were lower for those that were published (17% [10-24%] vs 41% [18-63%]). Studies with higher SPIRIT-PRO scores and PROs as primary endpoints (13% [4-22%] vs 39% [10-58%]) had fewer missing measurements. CONCLUSIONS: Missing data may affect publication of PROs. Extent of inclusion of SPIRIT-PRO protocol items and PROs as primary endpoints may improve data completeness. Preliminary evidence from the study suggests a future larger study examining the relationship between PRO completion and publication is warranted.

Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study.

INTRODUCTION: Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS: This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION: MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER: NCT03574454.

The FOCCUS study: a prospective evaluation of the frequency, severity and treatable causes of gastrointestinal symptoms during and after chemotherapy.

BACKGROUND: The underlying mechanisms of chemotherapy-induced gastrointestinal (GI) symptoms are poorly researched. This study characterised the nature, frequency, severity and treatable causes for GI symptoms prospectively in patients undergoing chemotherapy for GI malignancy. METHODS: Patients receiving chemotherapy for a GI malignancy were assessed pre-chemotherapy, then monthly for 1 year using the Gastrointestinal Symptom Rating Scale, a validated patient-reported outcome measure. Patients with new, troublesome GI symptoms were offered investigations to diagnose the cause(s). Their oncologist was alerted when investigations were abnormal. RESULTS: A total of 241 patients, 60% male, median age 63 years (range 30-88), were enrolled; 122 patients were withdrawn, 93%, because of progressive disease or death. During the study, > 20% patients reported chronic faecal incontinence and > 10% reported moderate or severe problems with taste, dysphagia, belching, heartburn, early satiety, appetite, nausea, abdominal cramps, peri-rectal pain, rectal flatulence, borborygmi, urgency of defecation or tenesmus. Thirty percent reported continuing passage of hard stools and 30% on-going diarrhoea. Moderate or severe fatigue affected 40% participants at its peak and persisted in 15% at 1 year. Toxicity dictated change in chemotherapy for 13-29% patients/month. Common Terminology Criteria for Adverse Events underestimated gastrointestinal morbidity. Pre-chemotherapy screening identified previously undiagnosed pathology: exocrine pancreatic insufficiency (9%), vitamin B12 deficiency (12%) and thyroid dysfunction (20%). Patients often refused investigations to diagnose their chemotherapy-induced symptoms; however, for every three investigations performed, one treatable cause was diagnosed: particularly small intestinal bacterial overgrowth (54%), bile acid malabsorption (43%), previously not described after chemotherapy, and unsuspected urinary tract infection (17%). CONCLUSIONS: Patients undergoing chemotherapy for GI malignancy commonly have difficult GI symptoms requiring active management which does not occur routinely. The underlying causes for these symptoms are often treatable or curable. Randomised trials are urgently needed to show whether timely investigation and treatment of symptoms improve quality of life and survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02121626.

Nutritional strategies to prevent gastrointestinal toxicity during pelvic radiotherapy.

Radiotherapy-induced damage to non-cancerous gastrointestinal mucosa has effects on secretory and absorptive functions and can interfere with normal gastrointestinal physiology. Nutrient absorption and digestion may be compromised. Dietary manipulation is an attractive option with sound rationale for intervention. The aim of this review was to synthesise published evidence for the use of elemental formulae, low or modified fat diets, fibre, lactose restriction and probiotics, prebiotics and synbiotics to protect the bowel from gastrointestinal side effects during long-course, radical pelvic radiotherapy. Thirty original studies (recruiting n 3197 patients) were identified comprising twenty-four randomised controlled trials, four cohort studies and two comparator trials. Endpoints varied and included symptom scales (Inflammatory Bowel Disease Questionnaire, Common Technology Criteria for Adverse Events, Radiation Therapy Oncology Group) and Bristol Stool Scale. Dietary and supplement interventions were employed with many studies using a combination of interventions. Evidence from RCT was weak for elemental, low or modified fat and low-lactose interventions and modestly positive for the manipulation of fibre during radiotherapy. Evidence for probiotics as prophylactic interventional agents was more promising with a number of trials reporting positive results but strength and strains of interventions vary, as do methodologies and endpoints making it difficult to arrive at firm conclusions with several studies lacking statistical power. This consolidated review concludes that there is insufficient high-grade evidence to recommend nutritional intervention during pelvic radiotherapy. Total replacement of diet with elemental formula could be effective in severe toxicity but this is unproven. Probiotics offer promise but cannot be introduced into clinical practice without rigorous safety analysis, not least in immunocompromised patients.

Interventions to reduce acute and late adverse gastrointestinal effects of pelvic radiotherapy for primary pelvic cancers.

BACKGROUND: An increasing number of people survive cancer but a significant proportion have gastrointestinal side effects as a result of radiotherapy (RT), which impairs their quality of life (QoL). OBJECTIVES: To determine which prophylactic interventions reduce the incidence, severity or both of adverse gastrointestinal effects among adults receiving radiotherapy to treat primary pelvic cancers. SEARCH METHODS: We conducted searches of CENTRAL, MEDLINE, and Embase in September 2016 and updated them on 2 November 2017. We also searched clinical trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions to prevent adverse gastrointestinal effects of pelvic radiotherapy among adults receiving radiotherapy to treat primary pelvic cancers, including radiotherapy techniques, other aspects of radiotherapy delivery, pharmacological interventions and non-pharmacological interventions. Studies needed a sample size of 20 or more participants and needed to evaluate gastrointestinal toxicity outcomes. We excluded studies that evaluated dosimetric parameters only. We also excluded trials of interventions to treat acute gastrointestinal symptoms, trials of altered fractionation and dose escalation schedules, and trials of pre- versus postoperative radiotherapy regimens, to restrict the vast scope of the review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. We used the random-effects statistical model for all meta-analyses, and the GRADE system to rate the certainty of the evidence. MAIN RESULTS: We included 92 RCTs involving more than 10,000 men and women undergoing pelvic radiotherapy. Trials involved 44 different interventions, including radiotherapy techniques (11 trials, 4 interventions/comparisons), other aspects of radiotherapy delivery (14 trials, 10 interventions), pharmacological interventions (38 trials, 16 interventions), and non-pharmacological interventions (29 trials, 13 interventions). Most studies (79/92) had design limitations. Thirteen studies had a low risk of bias, 50 studies had an unclear risk of bias and 29 studies had a high risk of bias. Main findings include the following:Radiotherapy techniques: Intensity-modulated radiotherapy (IMRT) versus 3D conformal RT (3DCRT) may reduce acute (risk ratio (RR) 0.48, 95% confidence interval (CI) 0.26 to 0.88; participants = 444; studies = 4; I2 = 77%; low-certainty evidence) and late gastrointestinal (GI) toxicity grade 2+ (RR 0.37, 95% CI 0.21 to 0.65; participants = 332; studies = 2; I2 = 0%; low-certainty evidence). Conformal RT (3DCRT or IMRT) versus conventional RT reduces acute GI toxicity grade 2+ (RR 0.57, 95% CI 0.40 to 0.82; participants = 307; studies = 2; I2 = 0%; high-certainty evidence) and probably leads to less late GI toxicity grade 2+ (RR 0.49, 95% CI 0.22 to 1.09; participants = 517; studies = 3; I2 = 44%; moderate-certainty evidence). When brachytherapy (BT) is used instead of external beam radiotherapy (EBRT) in early endometrial cancer, evidence indicates that it reduces acute GI toxicity (grade 2+) (RR 0.02, 95% CI 0.00 to 0.18; participants = 423; studies = 1; high-certainty evidence).Other aspects of radiotherapy delivery: There is probably little or no difference in acute GI toxicity grade 2+ with reduced radiation dose volume (RR 1.21, 95% CI 0.81 to 1.81; participants = 211; studies = 1; moderate-certainty evidence) and maybe no difference in late GI toxicity grade 2+ (RR 1.02, 95% CI 0.15 to 6.97; participants = 107; studies = 1; low-certainty evidence). Evening delivery of RT may reduce acute GI toxicity (diarrhoea) grade 2+ during RT compared with morning delivery of RT (RR 0.51, 95% CI 0.34 to 0.76; participants = 294; studies = 2; I2 = 0%; low-certainty evidence). There may be no difference in acute (RR 2.22, 95% CI 0.62 to 7.93, participants = 110; studies = 1) and late GI toxicity grade 2+ (RR 0.44, 95% CI 0.12 to 1.65; participants = 81; studies = 1) between a bladder volume preparation of 1080 mls and that of 540 mls (low-certainty evidence). Low-certainty evidence on balloon and hydrogel spacers suggests that these interventions for prostate cancer RT may make little or no difference to GI outcomes.Pharmacological interventions: Evidence for any beneficial effects of aminosalicylates, sucralfate, amifostine, corticosteroid enemas, bile acid sequestrants, famotidine and selenium is of a low or very low certainty. However, evidence on certain aminosalicylates (mesalazine, olsalazine), misoprostol suppositories, oral magnesium oxide and octreotide injections suggests that these agents may worsen GI symptoms, such as diarrhoea or rectal bleeding.Non-pharmacological interventions: Low-certainty evidence suggests that protein supplements (RR 0.23, 95% CI 0.07 to 0.74; participants = 74; studies = 1), dietary counselling (RR 0.04, 95% CI 0.00 to 0.60; participants = 74; studies = 1) and probiotics (RR 0.43, 95% CI 0.22 to 0.82; participants = 923; studies = 5; I2 = 91%) may reduce acute RT-related diarrhoea (grade 2+). Dietary counselling may also reduce diarrhoeal symptoms in the long term (at five years, RR 0.05, 95% CI 0.00 to 0.78; participants = 61; studies = 1). Low-certainty evidence from one study (108 participants) suggests that a high-fibre diet may have a beneficial effect on GI symptoms (mean difference (MD) 6.10, 95% CI 1.71 to 10.49) and quality of life (MD 20.50, 95% CI 9.97 to 31.03) at one year. High-certainty evidence indicates that glutamine supplements do not prevent RT-induced diarrhoea. Evidence on various other non-pharmacological interventions, such as green tea tablets, is lacking.Quality of life was rarely and inconsistently reported across included studies, and the available data were seldom adequate for meta-analysis. AUTHORS' CONCLUSIONS: Conformal radiotherapy techniques are an improvement on older radiotherapy techniques. IMRT may be better than 3DCRT in terms of GI toxicity, but the evidence to support this is uncertain. There is no high-quality evidence to support the use of any other prophylactic intervention evaluated. However, evidence on some potential interventions shows that they probably have no role to play in reducing RT-related GI toxicity. More RCTs are needed for interventions with limited evidence suggesting potential benefits.

Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy.

Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P < 0.001). The difference between groups in the change in IBDQ-B scores between the start and nadir was not significant (P = 0.093). However, the change in score between the start and end of radiotherapy was smaller in the high-fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT 01170299.

Comparison of a novel, simple nutrition screening tool for adult oncology inpatients and the Malnutrition Screening Tool (MST) against the Patient-Generated Subjective Global Assessment (PG-SGA).

BACKGROUND: Oncology inpatients are at high risk of malnutrition. Identification of at risk patients by nutrition screening requires a practical and easy to use tool. In this study, we have compared a simple, novel nutrition screening tool designed for an oncology inpatient setting and the Malnutrition Screening Tool (MST) against the Patient-Generated Subjective Global Assessment (PG-SGA). METHODS: This was an observational study to compare assessment of nutritional status by PG-SGA with nutrition screening using the Royal Marsden Nutrition Screening Tool (RMNST) and the MST. Patients were recruited from a single tertiary cancer centre. RESULTS: One hundred and twenty-six oncology inpatients underwent a full nutritional assessment and nutrition screening. The PG-SGA tool identified 90 (71%) patients as malnourished or at risk and 36 (29%) patients as well-nourished. The RMNST had a sensitivity of 93% and a specificity of 53%, and the MST had a sensitivity of 66% and a specificity of 83 %. Predictive value (ROC AUC) of both screening tools was excellent at 0.84 and 0.83 for RMNST and MST, respectively. CONCLUSIONS: This study identified a high prevalence of malnutrition in the population with 71% of patients being identified as malnourished or at risk of malnutrition. The RMNST had an excellent sensitivity for identifying patients who were malnourished or at risk of malnutrition in the inpatient setting although it had a poor specificity. The MST had a poorer sensitivity of 66 %. We would recommend that the RMNST is trialled in other oncology inpatient settings and also in the outpatient setting.

A systematic review: effectiveness of rectal emptying preparation in prostate cancer patients.

While the importance of a consistent rectal volume during radiation therapy planning and treatment for patients receiving radiation therapy to the prostate is recognized, there is no clear guidance as to the most effective method. This review examines the evidence for the efficacy of rectal preparations. Eighteen papers were found where the primary aim was to investigate a rectal emptying intervention and included 5 different strategies. These included evacuation techniques, dietary interventions, laxatives, and enemas and were either investigated alone or in combination. There is no robust evidence to recommend one rectal emptying strategy over another. Further investigation in adequately powered clinical trials is advised.

Guidance on the management of diarrhoea during cancer chemotherapy.

Diarrhoea induced by chemotherapy in cancer patients is common, causes notable morbidity and mortality, and is managed inconsistently. Previous management guidelines were based on poor evidence and neglect physiological causes of chemotherapy-induced diarrhoea. In the absence of level 1 evidence from randomised controlled trials, we developed practical guidance for clinicians based on a literature review by a multidisciplinary team of clinical oncologists, dietitians, gastroenterologists, medical oncologists, nurses, pharmacist, and a surgeon. Education of patients and their carers about the risks associated with, and management of, chemotherapy-induced diarrhoea is the foundation for optimum treatment of toxic effects. Adequate--and, if necessary, repeated--assessment, appropriate use of loperamide, and knowledge of fluid resuscitation requirements of affected patients is the second crucial step. Use of octreotide and seeking specialist advice early for patients who do not respond to treatment will reduce morbidity and mortality. In view of the burden of chemotherapy-induced diarrhoea, appropriate multidisciplinary research to assess meaningful endpoints is urgently required.

Fiber in the treatment and maintenance of inflammatory bowel disease: a systematic review of randomized controlled trials.

BACKGROUND: Dietary fiber may favorably influence fermentation, gastrointestinal inflammation, and disease progression in Crohn's disease, ulcerative colitis (UC), and pouchitis and offer an attractive therapeutic addition to pharmacological treatment. This systematic review appraised data from randomized controlled trials of fiber in the management of inflammatory bowel disease. METHODS: The review followed Cochrane and PRISMA recommendations. Seven electronic databases were searched along with hand searching and contacting experts. Inclusion criteria were randomized controlled trials of the effects of fiber on clinical endpoints (primarily disease activity for treatment or maintenance) or physiological outcomes in patients with inflammatory bowel disease. RESULTS: In total, 23 randomized controlled trials fulfilled the inclusion criteria (UC, 10; Crohn's disease, 12; and pouchitis, 1) recruiting 1296 patients. In UC, 3/10 studies reported fiber supplementation to benefit disease outcomes. In Crohn's disease, 0/12 studies and in pouchitis 1/1 study reported a benefit on disease activity. Despite this, a number of studies reported favorable intragroup effects on physiological outcomes including fecal butyrate, fecal calprotectin, inflammatory cytokines, microbiota, and gastrointestinal symptom indices. Meta-analysis was not possible. CONCLUSIONS: There is limited weak evidence for the efficacy of fiber in improving disease outcomes in UC and pouchitis. The potential antiinflammatory role of fiber is intriguing and merits further investigation in adequately powered clinical trials. Excluding overt gastrointestinal obstruction, there was no evidence that fiber intake should be restricted in patients with inflammatory bowel disease.

The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS: a pilot study.

It is well known that the electronic nose can be used to identify differences between human health and disease for a range of disorders. We present a pilot study to investigate if the electronic nose and a newer technology, FAIMS (Field Asymmetric Ion Mobility Spectrometry), can be used to identify and help inform the treatment pathway for patients receiving pelvic radiotherapy, which frequently causes gastrointestinal side-effects, severe in some. From a larger group, 23 radiotherapy patients were selected where half had the highest levels of toxicity and the others the lowest. Stool samples were obtained before and four weeks after radiotherapy and the volatiles and gases emitted analysed by both methods; these chemicals are products of fermentation caused by gut microflora. Principal component analysis of the electronic nose data and wavelet transform followed by Fisher discriminant analysis of FAIMS data indicated that it was possible to separate patients after treatment by their toxicity levels. More interestingly, differences were also identified in their pre-treatment samples. We believe these patterns arise from differences in gut microflora where some combinations of bacteria result to give this olfactory signature. In the future our approach may result in a technique that will help identify patients at "high risk" even before radiation treatment is started.

Evaluating the efficacy of statins and ACE-inhibitors in reducing gastrointestinal toxicity in patients receiving radiotherapy for pelvic malignancies.

INTRODUCTION: 3-Hydroxy-methylglutaryl coenzyme-a reductase inhibitors (statins) improve survival following pelvic irradiation for cancer. Large studies suggest that patients with hypertension may have reduced gastrointestinal (GI) toxicity. Animal data suggest that statins and ACE inhibitors (ACEi) may protect against normal tissue injury. Their efficacy in humans has not been reported. AIMS/METHODS: To evaluate the impact of statins and ACEi on normal tissue toxicity during radical pelvic radiotherapy. GI symptomatology was recorded prospectively before radiotherapy, weekly during treatment and 1 year later using the inflammatory bowel disease questionnaire-bowel (IBDQ-B) subset. Cumulative acute toxicity (IBDQ-B AUC) and worst score were determined. Dose, brand and duration of statin and/or ACEi usage were obtained from General Practitioners. RESULTS: Of 308 patients recruited, 237 had evaluable acute drug and toxicity data and 164 had data at 1year. Acutely, 38 patients (16%) were taking statins, 39 patients (16.5%) were taking ACEi and 18 patients (7.6%) were taking statin+ACEi. Mean changes in acute scores were 7.3 points (non-statin users), 7.3 (non-ACEi users) and 7.0 (non-statin+ACEi users) compared to 4.8 points (statin users), 5.0 points (ACEi users) and 4.9 points (statin+ACEi users). Statin use (p=0.04) and combined statin+ACEi use (p=0.008) were associated with reduced acute IBDQ-B AUC after controlling for baseline scores (ANOVA). At 1 year, users maintained higher IBDQ-B scores than non-users in all user subgroups. CONCLUSION: Use of statin or statin+ACEi medication during radical pelvic radiotherapy significantly reduces acute gastrointestinal symptoms scores and also appears to provide longer-term sustained protection.

Can diet combined with treatment scheduling achieve consistency of rectal filling in patients receiving radiotherapy to the prostate?

BACKGROUND AND PURPOSE: This pilot study investigates whether an individualized fluid and fibre prescription combined with a constant treatment can improve rectal filling consistency during radiotherapy. METHODS AND MATERIALS: Fibre, fluid intake and bowel function were assessed in 22 patients at a standard planning scan (SCT) and individualized dietary advice was prescribed to regularize bowel habit. Patients were requested to record frequency and type of bowel movements, fibre and fluid intake daily. Two subsequent CT scans were acquired at 7 (CCT1) and 10 days (CCT2) after SCT at a similar time. Rectal volume and gas were measured planning CT's and 'on treatment' cone beam CT scans. We hypothesised that the difference in volume between CCT1 and CCT2 would be less than the difference between SCT and CCT1. RESULTS: The mean (SD) change in volume between SCT to CCT1 and CCT1 to CCT2 was 5.68 cm(3) (26.2) and -8.6 cm(3) (40.1), respectively (p=0.292). Of the 22 patients scanned 20 provided a complete record of dietary intake and bowel motion. The majority of patients either achieved or exceeded prescription. Change in rectal gas was the only correlation with change in rectal volume. CONCLUSION: Patient self reporting of bowel motion, fibre, fluid intake was achievable but consistency of rectal filling was not improved. Improved understanding of the aetiology and management of rectal gas is indicated.

Predicting late effects of pelvic radiotherapy: is there a better approach?

PURPOSE: Significant chronic symptoms following pelvic radiotherapy occur more frequently than commonly realized. Predictive factors for the development of late symptoms are poorly defined. Moderate sustained acute (cumulative) toxicity might predict severe late effects better than peak reaction. METHODS AND MATERIALS: To determine prospectively whether peak or cumulative gastrointestinal (GI) acute symptoms better predict late symptoms in patients receiving pelvic radiotherapy. Symptom scores were measured weekly from the start of radiotherapy, and at 1 year using the Modified Inflammatory Bowel Disease Questionnaire-Bowel subset. The possible prognostic impact of patient-related factors was explored. RESULTS: Three hundred and eight patients were recruited. 100 were excluded due to lack of follow-up data at one year resulting from death, too ill, stoma, relapsed, non-response or withdrawal. A further 15 were excluded for incomplete data, leaving 193 patients with evaluable data. Of these, 28 had GI, 101 urological, and 64 gynecological cancers. Patients' median age was 65 years (range, 23-82), and they were treated with median 60 Gy dose for a median of 6 weeks. Univariate analysis revealed a significant association between cumulative acute symptom scores and scores at 1 year (p < 0.001), which was dose-independent (p < 0.001). Acute peak and 1-year scores were not associated (p = 0.431). The correlation coefficient between cumulative acute symptoms and symptoms at 1 year was 0.367 and for peak acute symptoms was weaker at 0.057. Patients with an abnormal body mass index and current smokers were more likely to experience worse symptoms at 1 year. CONCLUSION: Cumulative acute symptoms are more predictive of late symptoms than peak acute changes in score. This association is independent of the radiotherapy dose delivered and is suggestive of a consequential late effect.