Impact of a ketogenic diet intervention during radiotherapy on body composition: I. Initial clinical experience with six prospectively studied patients.

BACKGROUND: Based on promising preclinical data, ketogenic diets (KDs) have been proposed as supplementary measures for cancer patients undergoing standard-of-care therapy. However, data is still scarce on the tolerability and effects of KDs on cancer patients undergoing radiotherapy (RT). Here we present six cases of patients who underwent RT and concurrently consumed a self-administered KD in our clinic within a busy community hospital setting. METHODS: All patients were followed prospectively with measurements of blood parameters, quality of life and body weight and composition using bioelectrical impedance analysis. RESULTS: No adverse diet-related side effects occurred. Two patients had no elevated ketone body levels in serum despite self-reporting compliance to the diet. There was consensus that the KD was satiating and weight loss occurred in all patients, although this was only significant in two patients. Our data indicate that weight loss was mainly due to fat mass loss with concurrent preservation of muscle mass. Overall quality of life remained fairly stable, and all subjects reported feeling good on the diet. Tumor regression occurred as expected in five patients with early stage disease; however one subject with metastatic small cell lung cancer experienced slight progression during three cycles of combined chemotherapy + KD and progressed rapidly after ending the KD. CONCLUSIONS: Our data lend support to the hypothesis that KDs administered as supportive measures during standard therapy are safe and might be helpful in preservation of muscle mass. Further studies with control groups are needed to confirm these findings and address questions regarding any putative anti-tumor effects. Based on the experience with these six cases we implemented further steps to improve issues with KD compliance and initiated a clinical study that is described in a companion paper.

[A case of stage IV rectal cancer with whom EPA oral nutritional supplements could resolve cachectic condition and promote patient compliance with cancer chemotherapy].

We report a case of a Stage IV rectal cancer patient for whom EPA oral nutritional supplements promoted treatment compliance with cancer chemotherapy by resolving a refractory cachectic condition. A 76-year-old male who developed a local re-growth of residual disease and multiple lung metastases after abdomino-perineal resection for lower rectal cancer was referred to our clinic for chemotherapy. On admission, he suffered from a loss of appetite as well as a 30% loss of usual body weight, caused by a cachectic condition with systemic inflammatory response. On starting chemotherapy, his daily diet was supplemented with EPA containing oral nutritional supplements (EPA ONS). Within 2 weeks after initiating EPA ONS treatment, the systemic inflammatory response resolved, and at the same time, body weight and the serum level of albumin increased, which allowed treatment compliance with aggressive multidrug chemotherapy. The patient gained 10 kg in body weight even after 12 months of aggressive chemotherapy, and has attained a longstanding partial remission from the disease. Although cancer cachexia is generally regarded as an end-stage irreversible pathological condition, EPA ONS may promote patient compliance with cancer chemotherapy by resolving cachectic condition, and thus may improve survival.

Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.

PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.

Effect of cereal fibre source and processing on rectal epithelial cell proliferation.

BACKGROUND: Low fat and wheat bran interventions significantly reduced the growth of small to large adenomas and modestly suppressed rectal epithelial cell proliferation in the Australian Polyp Prevention Project. AIM: To study the effect of unprocessed wheat bran, unprocessed oat bran and processed wheat bran (Kellogg's All Bran) on rectal epithelial cell proliferation. PATIENTS: Twenty subjects with recent adenomas and a high fat background diet were recruited. METHODS: Rectal biopsy specimens were taken at entry and at the end of three six-week periods of oat bran (64 g/day), wheat bran (25 g/day) and All Bran (38 g/day), all in association with a diet < 25% energy as fat, in a randomised cross-over trial. Each of the bran supplements had a total of 11 g dietary fibre. The biopsy specimens were fixed in methacarn and stained immunohistochemically for presence of the proliferating cell nuclear antigen (PCNA). The kinetics used to measure proliferation were labelling index, whole distribution of labelled cells, and labelled cells in the top two-fifths of crypts using analysis of variance. RESULTS: There were no significant differences in mean labelling indexes between the four diets or in the percentage of labelled cells in the top two-fifths (p = 0.59), but activity in the top two-fifths of crypts was lowest with wheat bran. The mean (SD) labelling indexes were 2.23 (0.11)% for control, 2.13 (0.08)% for wheat bran, 2.19 (0.09)% for oat bran, and 2.12 (0.08)% for All Bran. The proportion in the top two-fifths of the crypts was 2.6 (0.6)% for control, 2.15 (0.5)% for wheat bran, 3.3 (0.9)% for oat bran, and 3.1 (0.9)% for All Bran. On analysis of whole distribution, there was no significant overall effect of diets but there was a difference between subjects. Analysis including total fibre intake also did not identify effects on proliferation. CONCLUSION: In this study of high risk subjects with initial high fat diets, dietary fibre in association with a low fat diet had no effect on rectal epithelial cell proliferation, although wheat bran had the greatest effect on percentage of labelled cells in the top two-fifths of crypts.

Effects of dietary wheat bran fiber on rectal epithelial cell proliferation in patients with resection for colorectal cancers.

A preponderance of carcinogenesis studies in rodents and epidemiologic studies in humans suggests a potential role of dietary fiber in the prevention of colorectal cancer. Recently, wheat bran fiber used as a dietary supplement has been shown to decrease the growth of rectal adenomatous polyps in patients with familial polyposis; however, few studies of high-risk human populations have been attempted to determine the effects of dietary fiber supplementation on markers of carcinogenesis in the colon or rectum. We have designed a one-arm study to evaluate the effects of dietary supplementation with wheat bran fiber [i.e., 13.5 g/day for 8 wk; after 1 mo, 2 g/day (compliance evaluation period)] on [3H]thymidine rectal mucosa cell labeling (i.e., percent of epithelial cells incorporating [3H]thymidine into DNA in intact rectal crypt cells over a 90-min exposure as well as in minced rectal biopsy tissue over a 24-hr exposure) in rectal biopsy specimens. The biopsy specimens were obtained at sigmoidoscopy in 17 compliant patients with a history of resected colon or rectal cancer. We categorized patients as having initially low or initially high [3H]thymidine-labeling indices (i.e., percent of mucosa cells that incorporate [3H]thymidine into DNA during 1.5- or 24-hour in vitro incubations) by using the median baseline labeling index as a cutoff between high and low values. On the basis of a chi-square test used to identify patients with a statistically significant (P less than .001) change, six of the eight patients who initially had high 24-hour outgrowth labeling indices showed a significant decrease in the rectal mucosa biopsy specimens obtained after treatment. An overall 22% decrease was observed in rectal mucosa cell biopsy specimens obtained at study termination (P less than .001). Of the eight patients with initially high total [3H]thymidine-labeling indices in crypt organ culture, four had a significant (P less than .001) decrease from baseline values, one had a significant increase, and three showed no change following the fiber intervention. The wheat bran fiber dietary supplement of 13.5 g/day was well tolerated by this group of older (54-70 yr) patients. Although the [3H]-thymidine labeling index data suggest that the wheat bran fiber supplement can inhibit DNA synthesis and rectal mucosa cell proliferation in high-risk patients, the results of this small pilot study should not be overinterpreted vis à vis the potential role of wheat bran fiber as a chemopreventive agent for colorectal cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.

One hundred ninety-two patients with previously untreated metastatic cancer (102 non-small-cell lung cancer [NSCLC]; 90 colorectal cancer) were randomized to receive either ad lib nutritional intake (control group) or specific nutritional intervention during a 12-week study period when chemotherapy was administered. Those patients randomized to nutritional interventions were counselled to take oral nutrients with caloric intake equal to 1.7 to 1.95 times their basal energy expenditure, depending on their pretreatment nutritional status ("standard" group). An augmented group was counselled to have a caloric intake equivalent to that of the standard group but with 25% of calories provided as protein and additional supplements of zinc and magnesium. Counselling increased caloric intake in both tumor types but reduced weight loss in the short term only for lung cancer patients. Ninety-three NSCLC patients were evaluable for tumor response to vindesine and cisplatin. Overall, only 20.4% of the patients responded, and there were no significant differences in response rates, median time to progression, or overall duration of survival between the nutrition intervention groups and the control group. The tumor response rate to time-sequenced 5-fluorouracil (5-FU) and methotrexate in the 81 evaluable patients with colorectal cancer was only 14.8%, and no significant differences in tumor response rates were noted between the three groups. Furthermore, the median time to progression and overall duration of survival were not different for the control, standard, and augmented groups. Nutritional interventions using dietary counselling had no impact on the percent of planned chemotherapy dose administered, the degree of toxicity experienced by patients, or the frequency of treatment delays. A multivariate prognostic factor analysis demonstrated that for lung cancer, the percent of weight loss, serum albumin concentration, and presence of liver metastases were significant (P less than .05) and independent prognostic variables for survival duration. For colorectal cancer, serum albumin, alkaline phosphatase, lactic dehydrogenase (LDH) levels, and percent targeted caloric intake (TCI) were significant independent predictors of survival duration.

[Modification of immunoglobulins during combined peroral and parenteral nutrition in colitis, ileitis and rectal carcinoma]. / Beeinflussung der Immunglobuline durch kombinierte perorale und parenterale Ernährung bei Kolitis, Ileitis und Rektumkarzinom

Reaction of immunoglobulins (IgA, IgG, IgM) during a four week period under condition with a special parenteral and peroral alimentation was observed in three groups of patients (rectum neoplasm, ulcerative colitis, Crohn's disease) during a period of two weeks all patients received 150 g aminoacids and 510 g carbohydrates by central venous catheter. In the following 14 days parenteral nutrition was limited and oral alimentation began. All patients showed a remarkable approvment of recreation. Globulins rose in between normal spectrum. The most marked changes with a significant uprising of IgG showed patients with rectum carcinoma treated cryosurgically.