H.J.N. Andreyev

Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies

The aim of this study was to examine whether weight loss at presentation, in patients who were to receive chemotherapy for gastrointestinal carcinomas, influences outcome and whether nutritional intervention would be worthwhile. This study was a retrospective review of prospectively gathered data. The outcomes of patients with or without weight loss and treated for locally advanced or metastatic tumours of the oesophagus, stomach, pancreas, colon or rectum were compared. In 1555 such consecutive patients treated over a 6-year period, weight loss at presentation was reported more commonly by men than women (51 versus 44%, P = 0.01). Although patients with weight loss received lower chemotherapy doses initially, they developed more frequent and more severe dose limiting toxicity--specifically plantar-palmar syndrome (P < 0.0001) and stomatitis (P < 0.0001)--than patients without weight loss. Consequently, patients with weight loss on average received 1 month (18%) less treatment (P < 0.0001). Weight loss correlated with shorter failure-free (P < 0.0001, hazard ratio = 1.25) and overall survival (P < 0.0001, hazard ratio = 1.63), decreased response (P = 0.006), quality of life (P < 0.0001) and performance status (P < 0.0001). Patients who stopped losing weight had better overall survival (P = 0.0004). Weight loss at presentation was an independent prognostic variable (hazard ratio = 1.43). The poorer outcome from treatment in patients with weight loss appears to occur because they receive significantly less chemotherapy and develop more toxicity rather than any specifically reduced tumour responsiveness to treatment. These findings provide a rationale for attempting randomised nutritional intervention studies in these patients.

Symptoms and weight loss in patients with gastrointestinal and lung cancer at presentation

IntroductionWeight loss is an independent prognostic factor for decreased survival in cancer patients. The effectiveness of treatment is impaired in patients with weight loss. The aetiology of this weight loss is complex and poorly characterised. Decreased calorie intake may be important. The reasons for decreased intake are unknown.Aims and methodsTo determine in adult patients with cancer, who had not started chemotherapy or radiotherapy, the prevalence of symptoms which carry a risk to nutritional status and how these relate to weight loss, tumour burden and primary tumour site. New patients referred for treatment of any form of gastrointestinal (GI) cancer, non-small cell lung cancer or lung mesothelioma completed a validated questionnaire recording symptoms contributing to weight loss (Patient-generated Subjective Global Assessment—PG-SGA). In a subset of patients without metastatic disease, computed tomography scans were assessed to determine tumour burden.ResultsBetween August and October 2004, 122 patients with GI and 29 with lung cancers were recruited. There were 48% of GI and 28% of lung cancer patients who had lost weight. Sixty-two percent of the patients had one or more symptoms at presentation. The frequency of symptoms varied according to the site of disease. The most common symptom at all tumour sites was loss of appetite (38%). There was a weak but significant correlation between the number of symptoms and amount of weight loss (r=0.347). Patients reporting a reduced food intake had more symptoms than patients who had not lost weight. Tumour burden did not correlate with weight loss.ConclusionThe symptoms in cancer patients occur across different types of primary tumours, may affect food intake and have a part in causing weight loss. More information on the role of symptom management in improving nutritional status is needed.

Small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy : An observational study

INTRODUCTION Loose stool affects up to 80% of all patients during pelvic radiotherapy and faecal incontinence may occur. Several causes for diarrhoea have been defined, though few oncologists target these causes in affected patients and most treat symptomatically only. It is not known whether small bowel bacterial overgrowth, a frequent cause of gastrointestinal symptoms in other contexts, occurs during radiotherapy. The frequency of new-onset lactose intolerance during pelvic radiotherapy is also not clear. AIMS AND METHODS To perform an observational pilot study to estimate the incidence of small bowel bacterial overgrowth and lactose intolerance during radical pelvic radiotherapy. Before treatment started and at weeks 4-5 of pelvic radiotherapy, a glucose hydrogen breath test and lactose tolerance test were performed. Gastrointestinal symptoms were assessed using the Vaizey incontinence questionnaire and the Radiation Therapy Oncology Group scoring system. RESULTS Twenty two men and 17 women (median age 61, range 42-81) were recruited, four were treated for gastrointestinal, 17 were treated for gynaecological and 18 for urological cancers. Thirty-eight patients underwent glucose hydrogen breath tests and 26 patients underwent lactose breath tests at both time points. Ten patients (26%) were positive for the glucose hydrogen breath test: 60% of these developed new or worsening faecal incontinence during treatment and 60% had worsening bowel frequency. Four patients (15%) developed lactose intolerance. Of these 1 developed worsening faecal incontinence during treatment, 2 (50%) developed new-onset increase in bowel frequency or a change in the quality of bowel habit. CONCLUSION Small bowel bacterial overgrowth and lactose intolerance may occur during radical pelvic radiotherapy and are likely to contribute to gastrointestinal symptoms in some patients.

The NUT study: the effect of dietetic and oral nutritional interventions on survival and quality of life in patients with weight loss undergoing palliative chemotherapy for gastrointestinal (GI) or lung malignancy, a randomised controlled trial

Weight loss in patients with GI and lung cancers is common and is associated with shorter survival and poorer quality of life. Oral nutritional interventions to manage weight loss in a range of clinical conditions improve outcomes but data in cancer patients on the clinical benefits of nutritional intervention are inadequate. The aim of this study was to assess the effect of dietary advice and/or oral nutritional interventions on survival and quality of life of patients with weight loss and advanced GI and lung cancers. Patients with weight loss, in whom radical therapy was not possible and who were instead to receive palliative chemotherapy for histologically proven GI or non-small-cell lung cancer or mesothelioma were randomly assigned to receive (1) no intervention (ad libitum food intake), (2) a nutritional supplement (240 ml, 2510 kJ/d) and a vitamin supplement, (3) dietary advice (an additional 2510 kJ/d) and (4) dietary advice plus a nutritional and vitamin supplement (additional 2510 kJ/d from food plus 2510 kJ from a supplement) for 6 weeks beginning before the start of chemotherapy. EORTC-C30 was used to assess quality of life at 6 weeks and 26 weeks. Patients were followed for 1 year. Five centres recruited 358 patients between 2002 and 2006, 256 men and 102 women (age median 66 (range 24–88) years). A total of 254 had GI cancer (oesophago-gastric, n 71; pancreas, n 72; lower GI, n 111) eighty-one non-small-cell lung cancer or mesothelioma (fourteen other). Ninety-six patients were randomised to group 1, eighty-six to group 2, ninety to group 3 and eighty-six to group 4. The groups were balanced for baseline characteristics. Median follow up for all patients was 6.8 (range 0–50) months. The 1-year survival for all patients combined was 37.8% (95% CI 32.2,43.4). There was no significant difference in survival between the intervention groups.

The impact of radical pelvic radiotherapy on nutrient intake

Malignancy in the gynaecological, urological or lower gastrointestinal tract is responsible for 27% of all newly diagnosed cancer cases in the UK. Pelvic radiotherapy (PRT) is a cornerstone of current treatment, but in more than 90% of patients induces acute bowel symptoms, such as diarrhoea, faecal incontinence, abdominal discomfort and bloating due to underlying changes in intestinal physiology. This prospective, observational study aimed to characterise quantitative changes in nutrient intake and nutritional status at baseline and following the conclusion of 4–5 weeks of adjuvant or radical PRT in outpatients with pelvic malignancies. At baseline (week 0) and at 4–5 weeks patients completed a non-weighed, 3-d food diary. Gastrointestinal symptoms were assessed using validated scoring tools and anthropometry was measured. Food diaries were analysed using Dietplan 6 software (see Table). In total, twenty-three males and twenty-one females (mean age 61.3 (range 42–81) years) completed food diaries at both time points. Although at no nutritional risk at baseline (based on BMI), twenty-six patients (59.1%) lost weight during treatment, with a mean weight loss of 0.61 (SD 1.83) kg (P=0.03).