Feasibility Outcomes of a Pilot Randomized Clinical Trial to Increase Cruciferous and Green Leafy Vegetable Intake in Posttreatment Head and Neck Cancer Survivors

Published:January 17, 2019DOI:



      Higher intakes of cruciferous vegetables (CVs) and green leafy vegetables (GLVs) in observational studies are associated with improvements in survival and cancer-related biomarkers in patients diagnosed with head and neck cancer (HNC). These results have yet to be corroborated in a randomized clinical trial (RCT).


      Determine the feasibility of implementing a 12-week RCT to increase CV and GLV intake in posttreatment HNC survivors.

      Design and participants

      This was a two-arm RCT conducted among 24 posttreatment HNC survivors. Survivors were recruited from a southeastern, National Cancer Institute–designated Comprehensive Cancer Center between January 2015 and September 2016.


      There were two groups: (1) an experimental group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist stressing 2.5 cups per week CVs and 3.5 cups per week GLVs, and (2) an attention control group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist focusing on general healthy eating for cancer survivors. Participants completed a baseline survey, three 24-hour dietary recalls, phlebotomy, and anthropometric measures prior to randomization and at the end of the 12-week study period. The experimental group also completed weekly vegetable record recalls.

      Main outcome measures

      Primary outcomes included feasibility, recruitment, retention, adherence, and safety. Secondary outcomes included inflammatory markers and carotenoids.

      Statistical analyses performed

      Descriptive statistics were generated for demographic, epidemiological, and clinical variables as well as the primary feasibility outcomes. Between- and within-group comparisons of mean serum cytokine and carotenoid levels were performed using appropriate statistical tests depending on their respective distributions for the purpose of generating preliminary effect sizes.


      Overall, 350 incident HNC cases were screened for eligibility, and 98 were eligible for study participation. Reasons for ineligibility and exclusion included deceased (n=93); wrong or inactive telephone numbers, or unable to be reached, or lost to follow-up (n=93); not meeting inclusion criteria (n=39); and too ill to participate (n=27). Of the 98 eligible HNC cases, 24 agreed to participate, for an enrollment rate of 25%. The most common reason for nonparticipation was distance (n=48), as participants were asked to report for two on-site assignments. The retention rate was 96%. Mean intervention adherence rates for weekly goals were 67% CV, 74% GLV, and 71% overall. Completion rate of weekly counseling calls was 90%. The experimental group reported an overall mean increase of 5.5 cups GLV and 3.5 cups CV per week from baseline intake, respectively. No significant between- or within-arm differences were observed for inflammatory markers or carotenoids.


      A posttreatment intervention aimed at increasing CV and GLV intake in HNC survivors is feasible. A larger RCT is needed to assess the efficacy of this intervention on disease outcomes.


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        • Ravasco P.
        • Monteiro-Grillo I.
        • Camilo M.E.
        Does nutrition influence quality of life in cancer patients undergoing radiotherapy?.
        Radiother Oncol. 2003; 67: 213-220
        • Ravasco P.
        • Monteiro-Grillo I.
        • Vidal P.M.
        • Camilo M.E.
        Nutritional deterioration in cancer: The role of disease and diet.
        Clin Oncol (R Coll Radiol). 2003; 15: 443-450
        • Langius J.A.
        • Zandbergen M.C.
        • Eerenstein S.E.
        • et al.
        Effect of nutritional interventions on nutritional status, quality of life and mortality in patients with head and neck cancer receiving (chemo)radiotherapy: A systematic review.
        Clin Nutr. 2013; 32: 671-678
        • Isenring E.A.
        • Capra S.
        • Bauer J.D.
        Nutrition intervention is beneficial in oncology outpatients receiving radiotherapy to the gastrointestinal or head and neck area.
        Br J Cancer. 2004; 91: 447-452
        • Demark-Wahnefried W.
        • Rogers L.Q.
        • Alfano C.M.
        • et al.
        Practical clinical interventions for diet, physical activity, and weight control in cancer survivors.
        CA Cancer J Clin. 2015; 65: 167-189
        • Stull V.B.
        • Snyder D.C.
        • Demark-Wahnefried W.
        Lifestyle interventions in cancer survivors: Designing programs that meet the needs of this vulnerable and growing population.
        J Nutr. 2007; 137: 243S-248S
        • Couch M.
        • Lai V.
        • Cannon T.
        • et al.
        Cancer cachexia syndrome in head and neck cancer patients: Part I. Diagnosis, impact on quality of life and survival, and treatment.
        Head Neck. 2007; 29: 401-411
        • Murphy B.A.
        • Gilbert J.
        Dysphagia in head and neck cancer patients treated with radiation: Assessment, sequelae, and rehabilitation.
        Semin Radiat Oncol. 2009; 19: 35-42
        • Ogama N.
        • Suzuki S.
        • Umeshita K.
        • et al.
        Appetite and adverse effects associated with radiation therapy in patients with head and neck cancer.
        Eur J Oncol Nurs. 2010; 14: 3-10
        • Barringer D.A.
        • Hutcheson K.A.
        • Sturgis E.M.
        • Kies M.S.
        • Lewin J.S.
        Effect of induction chemotherapy on speech and swallowing function in patients with oral tongue cancer.
        Head Neck. 2009; 31: 611-617
        • Kubrak C.
        • Olson K.
        • Jha N.
        • et al.
        Nutrition impact symptoms: key determinants of reduced dietary intake, weight loss, and reduced functional capacity of patients with head and neck cancer before treatment.
        Head Neck. 2010; 32: 290-300
        • Schache A.G.
        • Lieger O.
        • Rogers P.
        • Kelly A.
        • Newman L.
        • Kalavrezos N.
        Predictors of swallowing outcome in patients treated with surgery and radiotherapy for advanced oral and oropharyngeal cancer.
        Oral Oncol. 2009; 45: 803-808
        • Kostrzewa J.P.
        • Lancaster W.P.
        • Iseli T.A.
        • Desmond R.A.
        • Carroll W.R.
        • Rosenthal E.L.
        Outcomes of salvage surgery with free flap reconstruction for recurrent oral and oropharyngeal cancer.
        Laryngoscope. 2010; 120: 267-272
        • Cartmel B.
        • Bowen D.
        • Ross D.
        • Johnson E.
        • Mayne S.T.
        A randomized trial of an intervention to increase fruit and vegetable intake in curatively treated patients with early-stage head and neck cancer.
        Cancer Epidemiol Biomarkers Prev. 2005; 14: 2848-2854
        • Falciglia G.A.
        • Whittle K.M.
        • Levin L.S.
        • Steward D.L.
        A clinical-based intervention improves diet in patients with head and neck cancer at risk for second primary cancer.
        J Am Diet Assoc. 2005; 105: 1609-1612
        • Colacino J.A.
        • Arthur A.E.
        • Dolinoy D.C.
        • et al.
        Pretreatment dietary intake is associated with tumor suppressor DNA methylation in head and neck squamous cell carcinomas.
        Epigenetics. 2012; 7: 883-891
        • Arthur A.E.
        • Peterson K.E.
        • Shen J.
        • et al.
        Diet and proinflammatory cytokine levels in head and neck squamous cell carcinoma.
        Cancer. 2014; 120: 2704-2712
        • Crowder S.L.
        • Douglas K.G.
        • Yanina Pepino M.
        • Sarma K.P.
        • Arthur A.E.
        Nutrition impact symptoms and associated outcomes in post-chemoradiotherapy head and neck cancer survivors: A systematic review.
        J Cancer Surviv. 2018; 12: 479-494
        • Arthur A.E.
        • Peterson K.E.
        • Rozek L.S.
        • et al.
        Pretreatment dietary patterns, weight status, and head and neck squamous cell carcinoma prognosis.
        Am J Clin Nutr. 2013; 97: 360-368
        • McDonough E.M.
        • Boyd J.H.
        • Varvares M.A.
        • Maves M.D.
        Relationship between psychological status and compliance in a sample of patients treated for cancer of the head and neck.
        Head Neck. 1996; 18: 269-276
        • Capuano G.
        • Grosso A.
        • Gentile P.C.
        • et al.
        Influence of weight loss on outcomes in patients with head and neck cancer undergoing concomitant chemoradiotherapy.
        Head Neck. 2008; 30: 503-508
        • Wilson J.A.
        • Carding P.N.
        • Patterson J.M.
        Dysphagia after nonsurgical head and neck cancer treatment: patients’ perspectives.
        Otolaryngol Head Neck Surg. 2011; 145: 767-771
        • Terrell J.E.
        • Ronis D.L.
        • Fowler K.E.
        • et al.
        Clinical predictors of quality of life in patients with head and neck cancer.
        Arch Otolaryngol Head Neck Surg. 2004; 130: 401-408
        • American Institute for Cancer Research
        HEAL WELL: A Cancer Nutrition Guide.
        • Bandura A.
        Social Foundations of Thought and Action: A Social Cognitive Theory.
        Prentice-Hall, Upper Saddle River, NJ1986
        • Conway J.M.
        • Ingwersen L.A.
        • Moshfegh A.J.
        Accuracy of dietary recall using the USDA five-step multiple-pass method in men: An observational validation study.
        J Am Diet Assoc. 2004; 104: 595-603
        • Conway J.M.
        • Ingwersen L.A.
        • Vinyard B.T.
        • Moshfegh A.J.
        Effectiveness of the US Department of Agriculture 5-step multiple-pass method in assessing food intake in obese and nonobese women.
        Am J Clin Nutr. 2003; 77: 1171-1178
        • Block G.
        A review of validations of dietary assessment methods.
        Am J Epidemiol. 1982; 115: 492-505
        • Willett W.
        Nutritional Epidemiology.
        3rd ed. Oxford University Press, New York, NY2013
      1. NDS-R. Version 2014. Nutrition Coordinating Center, Minneapolis, MN2015
        • Neupane S.P.
        • Skulberg A.
        • Skulberg K.R.
        • Aass H.C.
        • Bramness J.G.
        Cytokine changes following acute ethanol intoxication in healthy men: A crossover study.
        Mediators Inflamm. 2016; 2016: 3758590
        • Smith J.K.
        • Dykes R.
        • Douglas J.E.
        • Krishnaswamy G.
        • Berk S.
        Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease.
        JAMA. 1999; 281: 1722-1727
        • La Fratta I.
        • Tatangelo R.
        • Campagna G.
        • et al.
        The plasmatic and salivary levels of IL-1beta, IL-18 and IL-6 are associated to emotional difference during stress in young male.
        Sci Rep. 2018; 8: 3031
        • Rodrigues F.M.
        • Ramos D.
        • Xavier R.F.
        • et al.
        Nasal and systemic inflammatory profile after short term smoking cessation.
        Respir Med. 2014; 108: 999-1006
        • Tuck M.K.
        • Chan D.W.
        • Chia D.
        • et al.
        Standard operating procedures for serum and plasma collection: early detection research network consensus statement standard operating procedure integration working group.
        J Proteome Res. 2009; 8: 113-117
      2. Qiagen. Gentra Puregene Handbook. Revised December 2014. Accessed November 2, 2018.

        • Duewer D.L.
        • Thomas J.B.
        • Kline M.C.
        • et al.
        NIST/NCI Micronutrients Measurement Quality Assurance Program: measurement repeatabilities and reproducibilities for fat-soluble vitamin-related compounds in human sera.
        Anal Chem. 1997; 69: 1406-1413
        • Duewer D.L.
        • Kline M.C.
        • Sharpless K.E.
        • Thomas J.B.
        NIST micronutrients measurement quality assurance program: Characterizing the measurement community's performance over time.
        Anal Chem. 2000; 72: 4163-4170
        • Duewer D.L.
        • Kline M.C.
        • Sharpless K.E.
        • Thomas J.B.
        • Stacewicz-Sapuntzakis M.
        • Sowell A.L.
        NIST micronutrients measurement quality assurance program: Characterizing individual participant measurement performance over time.
        Anal Chem. 2000; 72: 3611-3619
        • Yeum K.J.
        • Booth S.L.
        • Sadowski J.A.
        • et al.
        Human plasma carotenoid response to the ingestion of controlled diets high in fruits and vegetables.
        Am J Clin Nutr. 1996; 64: 594-602
        • Du P.
        • Zhang X.
        • Huang C.C.
        • et al.
        Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis.
        BMC Bioinformatics. 2010; 11: 587
        • Lohman T.G.
        • Martorell R.
        • Roche A.F.
        Anthropometric standardization reference manual.
        Human Kinetics Books, Champaign, IL1988
        • Arthur A.E.
        • Bellile E.L.
        • Rozek L.S.
        • et al.
        Pretreatment serum xanthophyll concentrations as predictors of head and neck cancer recurrence and survival.
        Head Neck. 2016; 38: E1591-E1597
        • Rogers L.Q.
        • Malone J.
        • Rao K.
        • et al.
        Exercise preferences among patients with head and neck cancer: Prevalence and associations with quality of life, symptom severity, depression, and rural residence.
        Head Neck. 2009; 31: 994-1005
        • Groll D.L.
        • To T.
        • Bombardier C.
        • Wright J.G.
        The development of a comorbidity index with physical function as the outcome.
        J Clin Epidemiol. 2005; 58: 595-602
        • Rogers L.Q.
        • Anton P.M.
        • Fogleman A.
        • et al.
        Pilot, randomized trial of resistance exercise during radiation therapy for head and neck cancer.
        Head Neck. 2013; 35: 1178-1188
      3. SAS [computer program]. Version 9.4. Cary, NC. 2013.

        • Julious S.A.
        • Owen R.J.
        Sample size calculations for clinical studies allowing for uncertainty about the variance.
        Pharm Stat. 2006; 5: 29-37
        • van Kappel A.L.
        • Steghens J.P.
        • Zeleniuch-Jacquotte A.
        • Chajes V.
        • Toniolo P.
        • Riboli E.
        Serum carotenoids as biomarkers of fruit and vegetable consumption in the New York Women’s Health Study.
        Public Health Nutr. 2001; 4: 829-835
        • Nettleton J.A.
        • Steffen L.M.
        • Mayer-Davis E.J.
        • et al.
        Dietary patterns are associated with biochemical markers of inflammation and endothelial activation in the Multi-Ethnic Study of Atherosclerosis (MESA).
        Am J Clin Nutr. 2006; 83: 1369-1379
        • Silveira B.K.S.
        • Oliveira T.M.S.
        • Andrade P.A.
        • Hermsdorff H.H.M.
        • Rosa C.O.B.
        • Franceschini S.
        Dietary pattern and macronutrients profile on the variation of inflammatory biomarkers: Scientific update.
        Cardiol Res Pract. 2018; 2018: 4762575
        • Smidowicz A.
        • Regula J.
        Effect of nutritional status and dietary patterns on human serum C-reactive protein and interleukin-6 concentrations.
        Adv Nutr. 2015; 6: 738-747
        • Kawakita D.
        • Matsuo K.
        • Sato F.
        • et al.
        Association between dietary folate intake and clinical outcome in head and neck squamous cell carcinoma.
        Ann Oncol. 2012; 23: 186-192
        • Cuozzo C.
        • Porcellini A.
        • Angrisano T.
        • et al.
        DNA damage, homology-directed repair, and DNA methylation.
        PLoS Genet. 2007; 3: e110
        • Hoile S.P.
        • Clarke-Harris R.
        • Huang R.C.
        • et al.
        Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells.
        PloS One. 2014; 9: e109896
        • do Amaral C.L.
        • Milagro F.I.
        • Curi R.
        • Martinez J.A.
        DNA methylation pattern in overweight women under an energy-restricted diet supplemented with fish oil.
        Biomed Res Int. 2014; 2014: 675021
        • Crider K.S.
        • Quinlivan E.P.
        • Berry R.J.
        • et al.
        Genomic DNA methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age [published online December 7, 2011].
        Plos One. 2011; 6 ( e28144
        • Jung A.Y.
        • Smulders Y.
        • Verhoef P.
        • et al.
        No effect of folic acid supplementation on global DNA methylation in men and women with moderately elevated homocysteine [published online September 23, 2011].
        PloS One. 2011; 6 ( e24976
        • Kok D.E.
        • Dhonukshe-Rutten R.A.
        • Lute C.
        • et al.
        The effects of long-term daily folic acid and vitamin B12 supplementation on genome-wide DNA methylation in elderly subjects.
        Clin Epigenetics. 2015; 7: 121
        • McCambridge J.
        • Witton J.
        • Elbourne D.R.
        Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects.
        J Clin Epidemiol. 2014; 67: 267-277
        • Kreuter M.W.
        • Chheda S.G.
        • Bull F.C.
        How does physician advice influence patient behavior? Evidence for a priming effect.
        Arch Fam Med. 2000; 9: 426-433
        • Shalev I.
        • Bargh J.A.
        Use of priming-based interventions to facilitate psychological health: commentary on Kazdin and Blase (2011).
        Perspect Psychol Sci. 2011; 6: 488-492
        • Milat A.J.
        • King L.
        • Bauman A.E.
        • Redman S.
        The concept of scalability: Increasing the scale and potential adoption of health promotion interventions into policy and practice.
        Health Promot Int. 2013; 28: 285-298
        • Gitlin L.N.
        Introducing a new intervention: An overview of research phases and common challenges.
        Am J Occup Ther. 2013; 67: 177-184


      S. L. Crowder is a doctoral candidate, University of Illinois, Urbana


      K. G. Douglas is a research assistant, University of Illinois, Urbana


      Y. T. Chen is a research assistant, University of Illinois, Urbana


      L. Moody is a doctoral candidate, University of Illinois, Urbana


      J. W. Erdman, Jr, is a professor emeritus, Department of Food Science and Human Nutrition and the Division of Nutritional Sciences, University of Illinois at Urbana-Champaign


      M. Black is a laboratory technician, University of Illinois, Urbana


      A. D. Frugé is an assistant professor and director, Didactic Program in Dietetics, Auburn University, Auburn, AL


      A. Delk-Licata is a doctoral candidate, University of Alabama-Birmingham, Birmingham


      W. R. Carroll is department chair and professor, Otolaryngology - Head and Neck, University of Alabama-Birmingham, Birmingham


      S. A. Spencer is a radiation oncologist, University of Alabama-Birmingham, Birmingham


      L. Q. Rogers is a professor, Department of Nutrition Sciences, University of Alabama-Birmingham, Birmingham


      W. Demark-Wahnefried is a professor and Webb endowed chair of nutrition sciences, University of Alabama-Birmingham, Birmingham


      J. L. Locher is a professor, Department of Medicine, University of Alabama-Birmingham, Birmingham.


      A. E. Arthur is an assistant professor and Sylvia D. Stroup Scholar in Nutrition and Cancer, Department of Food Science and Human Nutrition and the Division of Nutritional Sciences, University of Illinois at Urbana-Champaign; and an oncology registered dietitian nutritionist, Carle Cancer Center, Carle Foundation Hospital, Urbana, IL