Background Curative radiotherapy or chemoradiation for head and neck cancer (HNC) may result in severe acute and late side effects, including tube feeding dependence. The purpose of this prospective cohort study was to develop a prediction model for tube feeding dependence 6 months (TUBEM6) after curative (chemo-) radiotherapy in HNC patients. Patients and Methods Tube feeding dependence was scored prospectively. To develop the multivariable model, a group LASSO analysis was carried out, with TUBEM6 as the primary endpoint (n = 427). The model was then validated in a test cohort (n = 183). The training cohort was divided into three groups based on the risk of TUBEM6 to test whether the model could be extrapolated to later time points (12, 18 and 24 months). Results Most important predictors for TUBEM6 were weight loss prior to treatment, advanced T-stage, positive N-stage, bilateral neck irradiation, accelerated radiotherapy and chemoradiation. Model performance was good, with an Area under the Curve of 0.86 in the training cohort and 0.82 in the test cohort. The TUBEM6-based risk groups were significantly associated with tube feeding dependence at later time points (p<0.001). Conclusion We established an externally validated predictive model for tube feeding dependence after curative radiotherapy or chemoradiation, which can be used to predict TUBEM6.
References
[1]
Langendijk JA, Doornaert P, Rietveld DH, Verdonck-de Leeuw IM, Leemans CR, et al. (2009) A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol 90: 189–195. doi: 10.1016/j.radonc.2008.12.017
[2]
Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, Leemans CR, Aaronson NK, et al. (2008) Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol 26: 3770–3776. doi: 10.1200/jco.2007.14.6647
[3]
Verdonck-de Leeuw IM, Eerenstein SE, Van der Linden MH, Kuik DJ, de Bree R, et al. (2007) Distress in spouses and patients after treatment for head and neck cancer. Laryngoscope 117: 238–241. doi: 10.1097/01.mlg.0000250169.10241.58
[4]
Ang KK, Harris J, Garden AS, Trotti A, Jones CU, et al. (2005) Concomitant boost radiation plus concurrent cisplatin for advanced head and neck carcinomas: Radiation therapy oncology group phase II trial 99-14. J Clin Oncol 23: 3008–3015. doi: 10.1200/jco.2005.12.060
[5]
Staar S, Rudat V, Stuetzer H, Dietz A, Volling P, et al. (2001) Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy—results of a multicentric randomized german trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50: 1161–1171. doi: 10.1016/s0360-3016(01)01544-9
[6]
Caglar HB, Tishler RB, Othus M, Burke E, Li Y, et al. (2008) Dose to larynx predicts for swallowing complications after intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys 72: 1110–1118. doi: 10.1016/j.ijrobp.2008.02.048
[7]
Eisbruch A, Schwartz M, Rasch C, Vineberg K, Damen E, et al. (2004) Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: Which anatomic structures are affected and can they be spared by IMRT? Int J Radiat Oncol Biol Phys 60: 1425–1439. doi: 10.1016/j.ijrobp.2004.05.050
[8]
Levendag PC, Teguh DN, Voet P, van der Est H, Noever I, et al. (2007) Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: A dose-effect relationship. Radiother Oncol 85: 64–73. doi: 10.1016/j.radonc.2007.07.009
[9]
Feng FY, Kim HM, Lyden TH, Haxer MJ, Worden FP, et al. (2010) Intensity-modulated chemoradiotherapy aiming to reduce dysphagia in patients with oropharyngeal cancer: Clinical and functional results. J Clin Oncol 28: 2732–2738. doi: 10.1200/jco.2009.24.6199
[10]
Kotz T, Federman AD, Kao J, Milman L, Packer S, et al. (2012) Prophylactic swallowing exercises in patients with head and neck cancer undergoing chemoradiation: A randomized trial. Arch Otolaryngol Head Neck Surg 138: 376–382. doi: 10.1001/archoto.2012.187
[11]
Carroll WR, Locher JL, Canon CL, Bohannon IA, McColloch NL, et al. (2008) Pretreatment swallowing exercises improve swallow function after chemoradiation. Laryngoscope 118: 39–43. doi: 10.1097/mlg.0b013e31815659b0
[12]
Tibshirani R (1996) Regression shrinkage and selection via the lasso. J R Statist Soc B 58: 267–288.
[13]
Xu CJ, van der Schaaf A, Schilstra C, Langendijk JA, Van't Veld AA (2012) Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models. Int J Radiat Oncol Biol Phys 82: e677–84. doi: 10.1016/j.ijrobp.2011.09.036
[14]
Vergouwe Y, Moons KG, Steyerberg EW (2010) External validity of risk models: Use of benchmark values to disentangle a case-mix effect from incorrect coefficients. Am J Epidemiol 172: 971–980. doi: 10.1093/aje/kwq223
[15]
Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, et al. (2010) Assessing the performance of prediction models: A framework for traditional and novel measures. Epidemiology 21: 128–138. doi: 10.1097/ede.0b013e3181c30fb2
[16]
Miller ME, Langefeld CD, Tierney WM, Hui SL, McDonald CJ (1993) Validation of probabilistic predictions. Med Decis Making 13: 49–58. doi: 10.1177/0272989x9301300107
[17]
Pignon JP, le Maitre A, Maillard E, Bourhis J (2009) MACH-NC Collaborative Group (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 92: 4–14. doi: 10.1016/j.radonc.2009.04.014
[18]
Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, et al. (2006) Hyperfractionated or accelerated radiotherapy in head and neck cancer: A meta-analysis. Lancet 368: 843–854. doi: 10.1016/s0140-6736(06)69121-6
[19]
Langendijk JA, Leemans CR, Buter J, Berkhof J, Slotman BJ (2004) The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: A meta-analysis of the published literature. J Clin Oncol 22: 4604–4612. doi: 10.1200/jco.2004.10.074
[20]
Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, et al. (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: A systematic literature review. Radiother Oncol 66: 253–262. doi: 10.1016/s0167-8140(02)00404-8
[21]
Eisbruch A, Lyden T, Bradford CR, Dawson LA, Haxer MJ, et al. (2002) Objective assessment of swallowing dysfunction and aspiration after radiation concurrent with chemotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 53: 23–28. doi: 10.1016/s0360-3016(02)02712-8
[22]
Morton RP, Crowder VL, Mawdsley R, Ong E, Izzard M (2009) Elective gastrostomy, nutritional status and quality of life in advanced head and neck cancer patients receiving chemoradiotherapy. ANZ J Surg 79: 713–718. doi: 10.1111/j.1445-2197.2009.05056.x
[23]
Salas S, Deville JL, Giorgi R, Pignon T, Bagarry D, et al. (2008) Nutritional factors as predictors of response to radio-chemotherapy and survival in unresectable squamous head and neck carcinoma. Radiother Oncol 87: 195–200. doi: 10.1016/j.radonc.2008.02.011
[24]
Mekhail TM, Adelstein DJ, Rybicki LA, Larto MA, Saxton JP, et al. (2001) Enteral nutrition during the treatment of head and neck carcinoma: Is a percutaneous endoscopic gastrostomy tube preferable to a nasogastric tube? Cancer 91: 1785–1790. doi: 10.1002/1097-0142(20010501)91:9<1785::aid-cncr1197>3.0.co;2-1
[25]
Nguyen NP, Frank C, Moltz CC, Vos P, Smith HJ, et al. (2005) Impact of dysphagia on quality of life after treatment of head-and-neck cancer. Int J Radiat Oncol Biol Phys 61: 772–778. doi: 10.1016/j.ijrobp.2004.06.017
[26]
Terrell JE, Ronis DL, Fowler KE, Bradford CR, Chepeha DB, et al. (2004) Clinical predictors of quality of life in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg 130: 401–408. doi: 10.1001/archotol.130.4.401
[27]
Bhide SA, Gulliford S, Kazi R, El-Hariry I, Newbold K, et al. (2009) Correlation between dose to the pharyngeal constrictors and patient quality of life and late dysphagia following chemo-IMRT for head and neck cancer. Radiother Oncol 93: 539–544. doi: 10.1016/j.radonc.2009.09.017
[28]
Christianen ME, Schilstra C, Beetz I, Muijs CT, Chouvalova O, et al. (2011) Predictive modelling for swallowing dysfunction after primary (chemo)radiation: Results of a prospective observational study. Radiother Oncol.
[29]
Dirix P, Abbeel S, Vanstraelen B, Hermans R, Nuyts S (2009) Dysphagia after chemoradiotherapy for head-and-neck squamous cell carcinoma: Dose-effect relationships for the swallowing structures. Int J Radiat Oncol Biol Phys 75: 385–392. doi: 10.1016/j.ijrobp.2008.11.041
[30]
Overgaard J, Hansen HS, Specht L, Overgaard M, Grau C, et al. (2003) Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362: 933–940. doi: 10.1016/s0140-6736(03)14361-9
[31]
Mortensen HR, Overgaard J, Specht L, Overgaard M, Johansen J, et al. (2012) Prevalence and peak incidence of acute and late normal tissue morbidity in the DAHANCA 6&7 randomised trial with accelerated radiotherapy for head and neck cancer. Radiother Oncol 103: 69–75. doi: 10.1016/j.radonc.2012.01.002
