Clinical trial NCT03100409: Effect of a Low Residue Diet in Comparison to the Dietetic Recommendations From the INCan in Cervical Cancer Patients
Official title: Effect of a Low Residue Diet in Comparison to the Dietary Recommendations From the INCan: A Randomized Clinical Trial to Assess Malnutrition, Gastrointestinal Toxicity and Quality of Life of Advanced Cervical Cancer Patients (IB2-IVA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Uterine Cervical Neoplasm
Dietary Modification
Radiation Toxicity
Gastrointestinal Complication
Keywords: Cervical cancer
Lead sponsor: National Institute of Cancerología
Sponsor class: OTHER_GOV
Collaborators: name: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
First posted: 2017-04-04
Enrollment: 137
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: SUPPORTIVE_CARE

Brief summary: In Mexico, cervical cancer (CC) ranks second in incidence and mortality among women. The National Institute of Cancer in Mexico (lNCan) receives annually about 500 patients with CC, 80% of which are diagnosed with locally advanced disease. The standard treatment for locally advanced disease consists in concomitant chemo-radiotherapy based on cisplatin (QT-RT), followed by brachytherapy, with an absolute benefit of 10%. Adverse effects include gastrointestinal toxicity, which is the most important factor limiting the dosage of pelvic radiation. Cancer treatment, in any modality, induces malnutrition, more so when combined treatments are administered. Radiation induced gastrointestinal toxicity is caused by different factors, among which are malabsorption of bile, fat and carbohydrates, decrease in brush border enzymes, diverticular disease, proctitis, and psychological factors. International guidelines for cancer patients recommend nutritional assessment in these patients before they start treatment, so nutritional risk can be detected and the patient may get started on dietary intervention to prevent malnutrition. Several authors have studied the dietary management that may help reduce the gastrointestinal effects in cancer patients receiving pelvic radiotherapy. To reduce diarrhea and prevent malnutrition the recommended dietary approach is a low residue diet consisting on 20-25% kcal from fat, 5g of lactose and 20g of fiber. Currently the INCan does not follow the nutrition care process for cervical cancer patients; written recommendations are given to the patients with a list of foods allowed or not allowed, with no further nutritional assessment or intervention. From previous studies, the investigators have demonstrated that the current recommendations do not help the patients maintain their nutritional status, during their treatment most patients become malnourished (81%, p\<0.01). Therefore, the aim of this clinical trial is to evaluate a diet low in residue in CC patients, considering the necessary modifications for each patient if morbidities are present, in comparison with the current dietary recommendations used in the INCan.

Detailed description: In Mexico, cervical cancer (CC) is the second most frequent cause of death among women, with a mortality rate of 4000 women/year. Among the patients attended by the INCan, 80% are diagnosed with locally advanced CC and 30% of these present comorbidities. Hypertension may be present in 20% of patients, obesity in 18% and diabetes in 6.8%. These comorbidities affect the efficacy of treatment, increase the risk of malnutrition, of adverse events, hospitalization, increase hospital stay and worsen the quality of life, and even increase the risk of death. Furthermore, 10 to 20% of patients present kidney deterioration. The main reason for kidney disease is ureteral obstruction. The glomerular filtration rate deteriorates with age and many patients have comorbid medical illnesses that further compromise the kidneys. The standard treatment for CC is concomitant chemo-radiotherapy using cisplatin as a radiosensitizer, and brachytherapy at the end of treatment. Studies developed in the INCan described the acute toxicity symptoms in CC patients using this treatment: nausea, vomiting, diarrhea, cystitis, radioepithelitis, leucopenia, neutropenia, thrombocytopenia. Pelvic radiotherapy causes gastrointestinal toxicity, which is the most important limiting factor for the patients to complete their treatment. Cancer treatment, along with the tumor itself and other factors, causes malnutrition, and this confers a bad prognosis for the patient's response to treatment and survival. There is a nutritional risk in these patients at the moment of diagnosis, because of the metabolic alterations caused by the tumor, and the treatment-induced side effects. International guidelines for cancer patients recommend nutritional assessment in these patients before they start treatment, so nutritional risk can be detected and the patient may get started on dietary intervention to prevent malnutrition. Several authors have studied the dietary management that may help reduce the gastrointestinal effects in cancer patients receiving pelvic radiotherapy. To reduce diarrhea and prevent malnutrition the recommended dietary approach is a low residue diet consisting on 20-25% fat, 5g of lactose and 20g of fiber. Currently the INCan does not follow the nutrition care process for cervical cancer patients; written recommendations are given to the patients with a list of foods allowed or not allowed, with no further nutritional assessment or intervention. The investigators described the nutritional status of CC patients undergoing concomitant chemo-radiotherapy. It was observed that by the end of cancer treatment, a period of 9 weeks, 81.8% of patients became malnourished; 96% of patients lost weight, 78% of which had severe weight loss.

The aim of this clinical trial is to evaluate a diet low in residue in CC patients, considering the necessary modifications for each patient if morbidities are present, in comparison with the current dietary recommendations used in the INCan. A thorough nutritional evaluation including anthropometric data, dietary data, gastrointestinal toxicity and quality of life evaluations, will be performed.

Particular objectives are the following:

1. Identify the nutritional status of CC patients before, during and after treatment with chemo-radiotherapy, in intervention and control groups.
2. Determine the association of malnutrition and gastrointestinal toxicity during and after treatment, in intervention and control groups.
3. Evaluate the quality of life of patients before, during and after treatment, in both groups.
4. Establish the association of nutritional status and response to treatment, in both groups.

The aim is based on the following hypothesis: Patients receiving the personalized nutritional intervention with the low residue diet will maintain a better nutritional status during treatment, reflected in fewer malnourished patients, compared to the control group.

Methods.

Study design. Randomized clinical trial, open, factorial 3X2. To evaluate the efficacy of a low residue diet on the nutritional status, gastrointestinal toxicity and quality of life of CC patients referring to the National Institute of Cancer in Mexico (INCan). 320 patients will be included, with cervical malignant tumors of epithelial origin in the neck of the uterus, candidates for chemo-radiotherapy.

Dietary intervention will consist on a low residue diet: 20% kcal from fat, 5g lactose/day, 20g fiber/day (5g from insoluble fiber).

Dietary intervention will be adapted to the patient's individual requirements, according to the presence of comorbidities or renal deterioration.

1. No comorbidities. Energy: 20-30 kcal/kg of body weight/day. Protein: 1.3 g/kg of body weight/day.
2. Comorbidities (diabetes, hypertension), or geriatric patient. Energy: 25-30 kcal/kg of body weight/day. Protein: 1.5 g/kg of body weight/day.
3. Renal deterioration.

Energy: 30-35 kcal/kg of body weight/day.

Protein: 1 g/kg of body weight/day.

Sodium: 2000-2300 mg/day

Potassium: 1900-2730 mg/day

Phosphorus: 800-1000 mg/day

Control group will receive the standard written recommendations from the INCan, which enlist allowed foods and not allowed foods.

Sample size.

A sample space of 320 patients will be included if prior consent is acquired and if they meet the inclusion criteria. This clinical trial contemplates 3 strata with 2 levels.

Statistical analysis.

A univariate analysis will be performed to describe the study population. Descriptive statistics will be used to obtain measures of central tendency and dispersion, as well as frequency of distribution for qualitative variables. Percentage change of nutritional status will be calculated using the Friedman test. Chi square test will be used to compare basal vs final assessment, and chi square test will be used to compare among study groups. All confidence intervals will be constructed with a confidence of 95% (α=0.05). The interpretation of the study results will be responsibility of researchers. Data processing and analysis will be performed with the SPSS package (version 19.0®) for Microsoft.

Efficacy analysis.

Efficacy will be evaluated in patients that qualify to be included in the protocol analysis. To evaluate efficacy, nutritional diagnosis through the clinical course will be analyzed in both, intervention and control, groups. Also, toxicity and quality of life responses will be obtained.

Procedures.

Treatment. Anticancer treatment will consist of Cisplatin as a radiosensitizer, at a dosage of 40 mg/m2/week for 6 weeks. For patients with renal deterioration Gemcitabine will be used instead of Cisplatin, at a dosage of 300 mg/m2/week for 6 weeks. Concomitantly, external pelvic radiotherapy will be applied at a total dosage of 50.4 Gy divided by 28 fractions, 1.8 Gy/day/5 days a week, for 6 weeks. After completing concomitant chemo-radiotherapy, intracavitary brachytherapy will be administered at low dosage (30 Gy of Cesium 137) or high dosage (Iridium). Before initiating chemo-radiotherapy, a complete evaluation will be applied as mentioned.

Once eligibility criteria are verified, patients will be randomly assigned to intervention group or control group.

Visits during the study. After signing the informed consent, the patient will be informed when she will begin participating in the study (screening visit). If the patient complies with the inclusion criteria, a total of 5 visits will be scheduled: (1) at week -2, 2 weeks before treatment; (2) at week 0, on initiation of treatment; (3) at week 3, on the 3rd cycle of chemotherapy; (4) at week 9, by the end of brachytherapy; and (5) at week 21, 3 months after treatment completion.

Monitoring.

A thorough evaluation on each visit will be performed using the following tools:

* Patient generated subjective global assessment.
* Anthropometric data: weight, height, waist circumference, hip circumference, arm circumference.
* Body mass index.
* Waist to hip ratio.
* Body composition (bioelectrical impedance).
* % weight loss.
* Hand dynamometry.
* Dietary data: 24 hour recall and frequency of food intake questionnaires.
* % recommended energy intake.
* Biochemical markers: serum albumin, number of lymphocytes.
* Gastrointestinal toxicity using the CTCAE v4.03.
* Quality of life using the QLQ-C30 and CxC24.

Sample collection. No tissue or additional blood samples will be obtained, other than the blood samples used as part of the routine clinical laboratory tests.

Informed consent acquisition. On the screening visit, the written consent will be read and explained to the patient, clarifying the risks and benefits involved in the study. Two witnesses, independent from the study, will be present. The patient will have the choice to not participate or withdraw from the study at any time, her decision will not affect the quality of care and treatment that the attending physician will provide. The researcher will be governed by the ethical principles established in the Helsinki Accord. The physician will adequately respond all the matters of interest to the patient.

Ethical considerations.

The Research Committee and the Ethics Committee of the National Institute of Cancer in Mexico has approved the protocol and the informed consent document.

Patients participating in this study will be informed, through the informed consent, of all the details concerning this trial. The patients who agree to participate in the trial will express their willingness by signing the informed consent document, being clarified that they can leave the trial at any time, if they wish to do so.

Regulatory considerations.

This study abides by the ethical principles established by the international community, in accordance to the Good Clinical Practices, the Nüremberg Code, the Helsinki Accord, the Statement of Compliance with International Conference on Harmonization Guidelines for Good Clinical Practice, and the Regulations of the General Law of Health in the matter of research for health.

Eligibility criteria: Inclusion Criteria:

* Women 18 years of age and older.
* Ability to understand the study and be able to sign the informed consent.
* Functional stage ECOG 0 - 2.
* Negative pregnancy test, null reproductive potential, or currently using an contraceptive method.
* Willing and able to attend the programmed visits.
* Diagnosed with cervical malignant tumors of epithelial origin in the neck of the uterus, clinical stages IB2-IVA.
* Candidates to receive concomitant Chemo-Radiotherapy, followed by Brachytherapy.
* In case of presence of diabetes mellitus and/or hypertension, without retinopathy or albuminuria \<300 mg/dl.
* In case of renal deterioration, a creatinine clearance \>20 ml/min.
* Hemoglobin \>10 g/l.
* Leucocytes \> 4000/mm3.
* Platelets \>100000/mm3.

Exclusion Criteria:

* Under a different nutritional treatment using a nutritional supplement.
* Carrying other uncontrolled diseases, including cardiovascular insufficiency, arrhythmia, psychiatric illnesses.
* Concomitant treatment with another experimental drug.
* Active TB.
* Infected with HIV.
* History of LES and other rheumatologic diseases that involve renal deterioration.
* Presence of vesicular-vaginal fistulae at moment of diagnosis.
* Previous malignancy.

Study Discontinuation Criteria:

* Loss of follow up for 21 days.
* Evidence of disease progression.
* At the request of patient.
* By unacceptable toxicity.
* Pregnancy.

Criteria must be followed punctually. If a patient were inappropriately included, she must be discontinued from the study.

Primary outcomes:
measure: Change in Gastrointestinal toxicity symptoms grading scale using the Common Toxicity Criteria for Adverse Events (CTCAE v4)
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Changes in nutritional status
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Changes in food intake
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
Secondary outcomes:
measure: Changes in body weight
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Changes in body composition (phase angle)
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Changes in handgrip strength measures
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Change in quality of life summary score using the the quality of life questionnaire specifically developed for cancer patients (European Organization for Research and Treatment of Cancer Core 30 (EORTC QLQ-C30 v3))
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
measure: Change in quality of life for cervical cancer patients: (European Organization for Research and Treatment of Cancer Cervical cancer module- EORTC QLQ-CX 24)
timeFrame: Baseline, 3 weeks after treatment initiation, 12 weeks after treatment initiation and 6 months after treatment initiation .
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: National Cancer Institute of Mexico
state: Tlalpan
Study officials:
affiliation: National Institute of Cancerología
name: Lucely C Cetina, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Argiles JM. Cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9 Suppl 2:S39-50. doi: 10.1016/j.ejon.2005.09.006.
citation: Arrieta O, Michel Ortega RM, Villanueva-Rodriguez G, Serna-Thome MG, Flores-Estrada D, Diaz-Romero C, Rodriguez CM, Martinez L, Sanchez-Lara K. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study. BMC Cancer. 2010 Feb 21;10:50. doi: 10.1186/1471-2407-10-50.
citation: Bantle JP, Wylie-Rosett J, Albright AL, Apovian CM, Clark NG, Franz MJ, Hoogwerf BJ, Lichtenstein AH, Mayer-Davis E, Mooradian AD, Wheeler ML. Nutrition recommendations and interventions for diabetes--2006: a position statement of the American Diabetes Association. Diabetes Care. 2006 Sep;29(9):2140-57. doi: 10.2337/dc06-9914. No abstract available.
citation: Beale RJ, Bryg DJ, Bihari DJ. Immunonutrition in the critically ill: a systematic review of clinical outcome. Crit Care Med. 1999 Dec;27(12):2799-805. doi: 10.1097/00003246-199912000-00032.
citation: Bye A, Kaasa S, Ose T, Sundfor K, Trope C. The influence of low fat, low lactose diet on diarrhoea during pelvic radiotherapy. Clin Nutr. 1992 Jun;11(3):147-53. doi: 10.1016/0261-5614(92)90075-2.
citation: Calder PC, Kew S. The immune system: a target for functional foods? Br J Nutr. 2002 Nov;88 Suppl 2:S165-77. doi: 10.1079/BJN2002682.
citation: Capra S, Ferguson M, Ried K. Cancer: impact of nutrition intervention outcome--nutrition issues for patients. Nutrition. 2001 Sep;17(9):769-72. doi: 10.1016/s0899-9007(01)00632-3.
citation: Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr. 1997 Aug;66(2):460S-463S. doi: 10.1093/ajcn/66.2.460S.
citation: Rock CL, Moskowitz A, Huizar B, Saenz CC, Clark JT, Daly TL, Chin H, Behling C, Ruffin MT 4th. High vegetable and fruit diet intervention in premenopausal women with cervical intraepithelial neoplasia. J Am Diet Assoc. 2001 Oct;101(10):1167-74. doi: 10.1016/S0002-8223(01)00286-3.
citation: Coia LR, Myerson RJ, Tepper JE. Late effects of radiation therapy on the gastrointestinal tract. Int J Radiat Oncol Biol Phys. 1995 Mar 30;31(5):1213-36. doi: 10.1016/0360-3016(94)00419-L.
citation: Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, Martin FC, Michel JP, Rolland Y, Schneider SM, Topinkova E, Vandewoude M, Zamboni M; European Working Group on Sarcopenia in Older People. Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010 Jul;39(4):412-23. doi: 10.1093/ageing/afq034. Epub 2010 Apr 13.
citation: Pia de la Maza M, Agudelo GM, Yudin T, Gattas V, Barrera G, Bunout D, Hirsch S. Long-term nutritional and digestive consequences of pelvic radiation. J Am Coll Nutr. 2004 Apr;23(2):102-7. doi: 10.1080/07315724.2004.10719349.
citation: Pia de la Maza M, Gotteland M, Ramirez C, Araya M, Yudin T, Bunout D, Hirsch S. Acute nutritional and intestinal changes after pelvic radiation. J Am Coll Nutr. 2001 Dec;20(6):637-42. doi: 10.1080/07315724.2001.10719161.
citation: Shin DW, Nam JH, Kwon YC, Park SY, Bae DS, Park CT, Cho CH, Lee JM, Park SM, Yun YH. Comorbidity in disease-free survivors of cervical cancer compared with the general female population. Oncology. 2008;74(3-4):207-15. doi: 10.1159/000151368. Epub 2008 Aug 20.
citation: Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez-Enciso A, Cetina L, Rivera L, Mariscal I, Montalvo G, Gomez E, de la Garza J, Chanona G, Mohar A. A phase II study of multimodality treatment for locally advanced cervical cancer: neoadjuvant carboplatin and paclitaxel followed by radical hysterectomy and adjuvant cisplatin chemoradiation. Ann Oncol. 2003 Aug;14(8):1278-84. doi: 10.1093/annonc/mdg333.
citation: Duenas-Gonzalez A, Cetina L, Sanchez B, Gomez E, Rivera L, Hinojosa J, Lopez-Graniel C, Gonzalez-Enciso A, de la Garza J. A phase I study of carboplatin concurrent with radiation in FIGO stage IIIB cervix uteri carcinoma. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1361-5. doi: 10.1016/s0360-3016(03)00347-x.
citation: Arends J, Bodoky G, Bozzetti F, Fearon K, Muscaritoli M, Selga G, van Bokhorst-de van der Schueren MA, von Meyenfeldt M; DGEM (German Society for Nutritional Medicine); Zurcher G, Fietkau R, Aulbert E, Frick B, Holm M, Kneba M, Mestrom HJ, Zander A; ESPEN (European Society for Parenteral and Enteral Nutrition). ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Clin Nutr. 2006 Apr;25(2):245-59. doi: 10.1016/j.clnu.2006.01.020. Epub 2006 May 12.
citation: Fearon KC, Moses AG. Cancer cachexia. Int J Cardiol. 2002 Sep;85(1):73-81. doi: 10.1016/s0167-5273(02)00235-8.
citation: Gomez-Candela C, Luengo LM, Cos AI, Martinez-Roque V, Iglesias C, Zamora P, Gonzalez-Baron R. [Subjective global assessment in neoplastic patients]. Nutr Hosp. 2003 Nov-Dec;18(6):353-7. Spanish.
citation: Garcia-Luna PP, Parejo Campos J, Pereira Cunill JL. [Causes and impact of hyponutrition and cachexia in the oncologic patient]. Nutr Hosp. 2006 May;21 Suppl 3:10-6. Spanish.
citation: Gonzalez-Pinto I, Gonzalez EM. Optimising the treatment of upper gastrointestinal fistulae. Gut. 2001 Dec;49 Suppl 4(Suppl 4):iv22-31. doi: 10.1136/gut.49.suppl_4.iv21.
citation: Henson CC, Burden S, Davidson SE, Lal S. Nutritional interventions for reducing gastrointestinal toxicity in adults undergoing radical pelvic radiotherapy. Cochrane Database Syst Rev. 2013 Nov 26;2013(11):CD009896. doi: 10.1002/14651858.CD009896.pub2.
citation: Hernandez-Avila M, Romieu I, Parra S, Hernandez-Avila J, Madrigal H, Willett W. Validity and reproducibility of a food frequency questionnaire to assess dietary intake of women living in Mexico City. Salud Publica Mex. 1998 Mar-Apr;40(2):133-40. doi: 10.1590/s0036-36341998000200005.
citation: Inagaki J, Rodriguez V, Bodey GP. Proceedings: Causes of death in cancer patients. Cancer. 1974 Feb;33(2):568-73. doi: 10.1002/1097-0142(197402)33:23.0.co;2-2. No abstract available.
citation: Isenring EA, Capra S, Bauer JD. Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area. Br J Cancer. 2004 Aug 2;91(3):447-52. doi: 10.1038/sj.bjc.6601962.
citation: National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.
citation: Kizer NT, Thaker PH, Gao F, Zighelboim I, Powell MA, Rader JS, Mutch DG, Grigsby PW. The effects of body mass index on complications and survival outcomes in patients with cervical carcinoma undergoing curative chemoradiation therapy. Cancer. 2011 Mar 1;117(5):948-56. doi: 10.1002/cncr.25544. Epub 2010 Oct 13.
citation: Krauss RM, Eckel RH, Howard B, Appel LJ, Daniels SR, Deckelbaum RJ, Erdman JW Jr, Kris-Etherton P, Goldberg IJ, Kotchen TA, Lichtenstein AH, Mitch WE, Mullis R, Robinson K, Wylie-Rosett J, St Jeor S, Suttie J, Tribble DL, Bazzarre TL. AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000 Oct 31;102(18):2284-99. doi: 10.1161/01.cir.102.18.2284. No abstract available.
citation: Kuenstner S, Langelotz C, Budach V, Possinger K, Krause B, Sezer O. The comparability of quality of life scores. a multitrait multimethod analysis of the EORTC QLQ-C30, SF-36 and FLIC questionnaires. Eur J Cancer. 2002 Feb;38(3):339-48. doi: 10.1016/s0959-8049(01)00369-0.
citation: Le T, Hopkins L, Kee Fung MF. Quality of life assessment during adjuvant and salvage chemotherapy for advance stage epithelial ovarian cancer. Gynecol Oncol. 2005 Jul;98(1):39-44. doi: 10.1016/j.ygyno.2005.03.040.
citation: Levine MN, Ganz PA. Beyond the development of quality-of-life instruments: where do we go from here? J Clin Oncol. 2002 May 1;20(9):2215-6. doi: 10.1200/JCO.2002.20.9.2215. No abstract available.
citation: Mohar A, Frias-Mendivil M. Epidemiology of cervical cancer. Cancer Invest. 2000;18(6):584-90. doi: 10.3109/07357900009012198. No abstract available.
citation: Movsas B. Quality of life in oncology trials: a clinical guide. Semin Radiat Oncol. 2003 Jul;13(3):235-47. doi: 10.1016/S1053-4296(03)00029-8.
citation: Murphy J, Stacey D, Crook J, Thompson B, Panetta D. Testing control of radiation-induced diarrhea with a psyllium bulking agent: a pilot study. Can Oncol Nurs J. 2000 Summer;10(3):96-100. doi: 10.5737/1181912x10396100.
citation: Obarzanek E, Sacks FM, Vollmer WM, Bray GA, Miller ER 3rd, Lin PH, Karanja NM, Most-Windhauser MM, Moore TJ, Swain JF, Bales CW, Proschan MA; DASH Research Group. Effects on blood lipids of a blood pressure-lowering diet: the Dietary Approaches to Stop Hypertension (DASH) Trial. Am J Clin Nutr. 2001 Jul;74(1):80-9. doi: 10.1093/ajcn/74.1.80.
citation: Obermair A, Hagenauer S, Tamandl D, Clayton RD, Nicklin JL, Perrin LC, Ward BG, Crandon AJ. Safety and efficacy of low anterior en bloc resection as part of cytoreductive surgery for patients with ovarian cancer. Gynecol Oncol. 2001 Oct;83(1):115-20. doi: 10.1006/gyno.2001.6353.
citation: Paddon-Jones D, Short KR, Campbell WW, Volpi E, Wolfe RR. Role of dietary protein in the sarcopenia of aging. Am J Clin Nutr. 2008 May;87(5):1562S-1566S. doi: 10.1093/ajcn/87.5.1562S.
citation: Pearcey R, Brundage M, Drouin P, Jeffrey J, Johnston D, Lukka H, MacLean G, Souhami L, Stuart G, Tu D. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002 Feb 15;20(4):966-72. doi: 10.1200/JCO.2002.20.4.966.
citation: Pettersson A, Nygren P, Persson C, Berglund A, Turesson I, Johansson B. Effects of a dietary intervention on gastrointestinal symptoms after prostate cancer radiotherapy: long-term results from a randomized controlled trial. Radiother Oncol. 2014 Nov;113(2):240-7. doi: 10.1016/j.radonc.2014.11.025. Epub 2014 Nov 29.
citation: Ravasco P, Monteiro-Grillo I, Vidal PM, Camilo ME. Cancer: disease and nutrition are key determinants of patients' quality of life. Support Care Cancer. 2004 Apr;12(4):246-52. doi: 10.1007/s00520-003-0568-z. Epub 2004 Mar 3.
citation: Roberts KB, Urdaneta N, Vera R, Vera A, Gutierrez E, Aguilar Y, Ott S, Medina I, Sempere P, Rockwell S, Sartorelli AC, Fischer DB, Fischer JJ. Interim results of a randomized trial of mitomycin C as an adjunct to radical radiotherapy in the treatment of locally advanced squamous-cell carcinoma of the cervix. Int J Cancer. 2000 Aug 20;90(4):206-23. doi: 10.1002/1097-0215(20000820)90:43.0.co;2-o.
citation: Roila F, Cortesi E. Quality of life as a primary end point in oncology. Ann Oncol. 2001;12 Suppl 3:S3-6. doi: 10.1093/annonc/12.suppl_3.s3.
citation: Rose PG, Ali S, Watkins E, Thigpen JT, Deppe G, Clarke-Pearson DL, Insalaco S; Gynecologic Oncology Group. Long-term follow-up of a randomized trial comparing concurrent single agent cisplatin, cisplatin-based combination chemotherapy, or hydroxyurea during pelvic irradiation for locally advanced cervical cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007 Jul 1;25(19):2804-10. doi: 10.1200/JCO.2006.09.4532. Epub 2007 May 14.
citation: Santoso JT, Canada T, Latson B, Aaaadi K, Lucci JA 3rd, Coleman RL. Prognostic nutritional index in relation to hospital stay in women with gynecologic cancer. Obstet Gynecol. 2000 Jun;95(6 Pt 1):844-6. doi: 10.1016/s0029-7844(99)00658-4.
citation: Santoso JT, Cannada T, O'Farrel B, Alladi K, Coleman RL. Subjective versus objective nutritional assessment study in women with gynecological cancer: a prospective cohort trial. Int J Gynecol Cancer. 2004 Mar-Apr;14(2):220-3. doi: 10.1111/j.1048-891X.2004.014203.x.
citation: Sayer AA, Syddall H, Martin H, Patel H, Baylis D, Cooper C. The developmental origins of sarcopenia. J Nutr Health Aging. 2008 Aug-Sep;12(7):427-32. doi: 10.1007/BF02982703. No abstract available.
citation: Segura A, Pardo J, Jara C, Zugazabeitia L, Carulla J, de Las Penas R, Garcia-Cabrera E, Luz Azuara M, Casado J, Gomez-Candela C. An epidemiological evaluation of the prevalence of malnutrition in Spanish patients with locally advanced or metastatic cancer. Clin Nutr. 2005 Oct;24(5):801-14. doi: 10.1016/j.clnu.2005.05.001.
citation: Spirtos NM, Ballon SC. Needle catheter jejunostomy: a controlled, prospective, randomized trial in patients with gynecologic malignancy. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 1):1285-90. doi: 10.1016/0002-9378(88)90358-4.
citation: Thompson DD. Aging and sarcopenia. J Musculoskelet Neuronal Interact. 2007 Oct-Dec;7(4):344-5. No abstract available.
citation: Tian J, Chen JS. Nutritional status and quality of life of the gastric cancer patients in Changle County of China. World J Gastroenterol. 2005 Mar 21;11(11):1582-6. doi: 10.3748/wjg.v11.i11.1582.
citation: Van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9 Suppl 2:S51-63. doi: 10.1016/j.ejon.2005.09.007.
citation: Wedlake LJ, McGough C, Shaw C, Klopper T, Thomas K, Lalji A, Dearnaley DP, Blake P, Tait D, Khoo VS, Andreyev HJ. Clinical trial: Efficacy of a low or modified fat diet for the prevention of gastrointestinal toxicity in patients receiving radiotherapy treatment for pelvic malignancies. J Hum Nutr Diet. 2012 Jun;25(3):247-59. doi: 10.1111/j.1365-277X.2012.01248.x. Epub 2012 Apr 20.
citation: Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 1999 May;17(5):1339-48. doi: 10.1200/JCO.1999.17.5.1339.
citation: Wong LC, Ngan HY, Cheung AN, Cheng DK, Ng TY, Choy DT. Chemoradiation and adjuvant chemotherapy in cervical cancer. J Clin Oncol. 1999 Jul;17(7):2055-60. doi: 10.1200/JCO.1999.17.7.2055.
citation: Xue H, Sawyer MB, Wischmeyer PE, Baracos VE. Nutrition modulation of gastrointestinal toxicity related to cancer chemotherapy: from preclinical findings to clinical strategy. JPEN J Parenter Enteral Nutr. 2011 Jan;35(1):74-90. doi: 10.1177/0148607110377338.
citation: Nagle CM, Purdie DM, Webb PM, Green A, Harvey PW, Bain CJ. Dietary influences on survival after ovarian cancer. Int J Cancer. 2003 Aug 20;106(2):264-9. doi: 10.1002/ijc.11204.