Conditions Affected By Both Chemotherapy and Head/Neck Radiation
Salivary Gland Hypofunction and Xerostomia
Radiation therapy can damage salivary glands, causing salivary hypofunction and xerostomia. (Refer to the Oral Complications of Head and Neck Radiation section of this summary for more information.) In addition, selected chemotherapeutic agents (singly or in combination) have been implicated in causing salivary dysfunction and xerostomia. However, it has not been possible to draw consistent conclusions about the effects of cancer chemotherapy on salivary gland function.
Dysphagia and odynophagia are common in cancer patients and can exist before, during, and after treatment:
- Dysphagia predisposes to aspiration and potentially life-threatening pulmonary complications.
- Swallowing disorders may lead to unfavorable dietary changes and decreased oral intake, which may result in dehydration, malnutrition, delayed wound healing, and decreased resistance to infection.
- Tube feeding may become necessary, which may further compromise swallowing.
- Opioids administered for the management of odynophagia may cause xerostomia and constipation.
- Difficulties with speaking, eating and drinking, or drooling may affect mental health and put patients and family members in social isolation.
Dysphagia is most prominent in patients with head and neck cancers but may also develop in patients with other malignancies as a symptom of oropharyngeal or esophageal mucositis or infection. In addition, dysphagia can be associated with graft-versus-host disease.
The prevalence and severity of pretreatment dysphagia associated with head and neck tumors depend on tumor stage and localization. Pretreatment dysphagia is most prevalent in patients with pharyngeal and laryngeal cancers. Surgical interventions for head and neck tumors result in anatomic or neurologic insults with site-specific patterns of dysphagia. In general, the larger the resection, the more swallowing function will be impaired.
The severity of radiation-induced dysphagia depends on the following:
- Total radiation dose.
- Fraction size and schedule.
- Target volumes.
- Treatment delivery techniques.
- Concurrent chemotherapy.
- Genetic factors.
- Feeding status (via percutaneous endoscopic gastrostomy [PEG] tube or nil per os [NPO, nothing by mouth]).
- Smoking status.
- Psychological coping factors.
Intensified schedules and the use of chemoradiation therapy have been shown to improve locoregional control and survival but come at the cost of more severe acute and chronic side effects. Intensity-modulated radiation therapy (IMRT) has emerged as an effective technique to deliver the full radiation dose to the tumor and regions at risk while reducing exposure of surrounding healthy tissues. However, the preservation of anatomy does not necessarily translate into the preservation of swallowing function.
Mucositis induced by chemoradiation therapy or chemotherapy alone, edema, pain, thickened mucous saliva and hyposalivation, radiation dermatitis, and infection may all contribute to acute dysphagia. The use of epidermal growth factor inhibitors seems not to be associated with increased mucositis and acute dysphagia.
By 3 months posttreatment, acute clinical effects have largely resolved, and normal swallowing function starts to return in most patients. Unfortunately, in head and neck cancer patients treated with chemoradiation, a continuing cascade of inflammatory cytokines triggered by oxidative stress and hypoxia may damage exposed tissues, and dysphagia may develop even years after the completion of treatment. Late sequelae that may contribute to chronic dysphagia include the following:
- Reduced capillary flow.
- Atrophy and necrosis.
- Neuromuscular fibrosis leading to trismus and stricture formation.
Successful management of dysphagia requires the following:
- Interdisciplinary collaboration.
- Accurate and early diagnostic workup.
- Effective preventative and therapeutic strategies.
- An individual approach geared to unique patient characteristics.
Dysphagia- and aspiration-related structures have been identified, and minimizing radiation to these bystander tissues results in better swallowing outcomes. Because hyposalivation affects swallowing function, strategies aimed at sparing salivary glands such as IMRT and the use of amifostine may improve swallowing outcomes.[12,13]
A predictive model for persistent swallowing dysfunction following chemoradiation therapy for head and neck cancer has been developed. Early involvement of a speech and language therapist is critical to assess swallow function and aspiration risk and to generate a treatment plan that includes patient education and swallow therapy. Cooperation with a dietician is important to ensure adequate and safe nutrition. Prosthodontic interventions may improve swallowing performance, and patients may benefit from psychological support.
Dysgeusia can be a prominent symptom in patients who are receiving chemotherapy or head/neck radiation.[16,17] Etiology is likely associated with several factors, including direct neurotoxicity to taste buds, xerostomia, infection, and psychologic conditioning. In addition, taste dysfunction can be associated with damage caused by graft-versus-host disease to the taste perception units. (Refer to the Graft-versus-Host Disease section of this summary for more information.)
Patients receiving chemotherapy may experience unpleasant taste secondary to diffusion of drug into the oral cavity. In addition, chemotherapy patients often describe dysgeusia in the early weeks after cessation of cytotoxic therapy. This symptom in general is reversible, and taste sensation returns to normal in the ensuing months.
By comparison, however, a total fractionated radiation dose higher than 3,000 Gy reduces acuity of sweet, sour, bitter, and salt tastes. Damage to the microvilli and outer surface of the taste cells has been proposed as the principal mechanism for loss of the sense of taste. In many cases, taste acuity returns in 2 to 3 months after cessation of radiation. However, many other patients develop permanent hypogeusia. Zinc supplementation (zinc sulfate 220 mg 2 times a day) has been reported to be useful in some patients; the overall benefit of this treatment remains unclear.;[Level of evidence: I]
Patients with head and neck cancer are at high risk for nutritional problems. Contributing to malnutrition are the following:
- The malignancy itself.
- Poor nutrition before diagnosis.
- Complications of surgery, radiation therapy, and chemotherapy.
In cancer patients, loss of appetite can also occur secondary to mucositis, xerostomia, taste loss, dysphagia, nausea, and vomiting. Quality of life is compromised as eating becomes more problematic. Oral pain with eating may lead to selection of foods that do not aggravate the oral tissues, often at the expense of adequate nutrition. Nutritional deficiencies can be minimized by modifying the texture and consistency of the diet and by adding more frequent meals and snacks to increase calories and protein. Ongoing nutrition assessment and counseling with a registered dietitian should be part of the patient’s treatment plan.
Many patients who receive radiation therapy alone are able to tolerate soft foods; however, as treatment progresses, most patients must transition to liquid diets using high-calorie, high-protein liquid nutritional supplements, and some may require enteral feeding tubes to meet their nutritional needs. Almost all patients receiving concurrent chemotherapy and radiation therapy will become fully dependent on enteral nutritional support within 3 to 4 weeks of therapy. Numerous studies have demonstrated the benefit of enteral feedings initiated at the onset of treatment, before significant weight loss has occurred.[22,23]
Oral nutrition is reinstituted after treatment has concluded and the radiated site has adequately healed. Oral nutrition often requires a team approach. The assistance of a speech and swallowing therapist to assess for any swallowing dysfunction resulting from surgery or treatment is often necessary and beneficial in easing the transition back to solid foods. The number of tube feedings can be decreased as a patient's oral intake increases, with tube feeding being discontinued when 75% of a patient's nutrition needs are being met orally. Although most patients will resume adequate oral intake, many will continue to experience chronic complications such as taste changes, xerostomia, and varying degrees of dysphagia that can affect their nutritional status and quality of life.[20,21]
Cancer patients undergoing high-dose chemotherapy and/or radiation therapy can experience fatigue related to either the disease or its treatment. These processes can produce sleep deprivation or metabolic disorders that collectively contribute to compromised oral status. For example, the fatigued patient will likely have impaired compliance with mouth care protocols designed to otherwise minimize risk of mucosal ulceration, infection, and pain. In addition, biochemical abnormalities are likely involved in many patients. The psychosocial component can also play a major role, with depression contributing to overall fatigue. (Refer to the PDQ summary on Fatigue for more information.)
- Jensen SB, Mouridsen HT, Reibel J, et al.: Adjuvant chemotherapy in breast cancer patients induces temporary salivary gland hypofunction. Oral Oncol 44 (2): 162-73, 2008. [PUBMED Abstract]
- Jensen SB, Pedersen AM, Vissink A, et al.: A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer 18 (8): 1039-60, 2010. [PUBMED Abstract]
- Nguyen NP, Moltz CC, Frank C, et al.: Dysphagia following chemoradiation for locally advanced head and neck cancer. Ann Oncol 15 (3): 383-8, 2004. [PUBMED Abstract]
- Langendijk JA, Doornaert P, Verdonck-de Leeuw IM, et al.: Impact of late treatment-related toxicity on quality of life among patients with head and neck cancer treated with radiotherapy. J Clin Oncol 26 (22): 3770-6, 2008. [PUBMED Abstract]
- Logemann JA, Rademaker AW, Pauloski BR, et al.: Site of disease and treatment protocol as correlates of swallowing function in patients with head and neck cancer treated with chemoradiation. Head Neck 28 (1): 64-73, 2006. [PUBMED Abstract]
- Pauloski BR, Rademaker AW, Logemann JA, et al.: Pretreatment swallowing function in patients with head and neck cancer. Head Neck 22 (5): 474-82, 2000. [PUBMED Abstract]
- Kronenberger MB, Meyers AD: Dysphagia following head and neck cancer surgery. Dysphagia 9 (4): 236-44, 1994. [PUBMED Abstract]
- Platteaux N, Dirix P, Dejaeger E, et al.: Dysphagia in head and neck cancer patients treated with chemoradiotherapy. Dysphagia 25 (2): 139-52, 2010. [PUBMED Abstract]
- Mittal BB, Pauloski BR, Haraf DJ, et al.: Swallowing dysfunction--preventative and rehabilitation strategies in patients with head-and-neck cancers treated with surgery, radiotherapy, and chemotherapy: a critical review. Int J Radiat Oncol Biol Phys 57 (5): 1219-30, 2003. [PUBMED Abstract]
- Curran D, Giralt J, Harari PM, et al.: Quality of life in head and neck cancer patients after treatment with high-dose radiotherapy alone or in combination with cetuximab. J Clin Oncol 25 (16): 2191-7, 2007. [PUBMED Abstract]
- Eisbruch A, Schwartz M, Rasch C, et al.: 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 (5): 1425-39, 2004. [PUBMED Abstract]
- Sasse AD, Clark LG, Sasse EC, et al.: Amifostine reduces side effects and improves complete response rate during radiotherapy: results of a meta-analysis. Int J Radiat Oncol Biol Phys 64 (3): 784-91, 2006. [PUBMED Abstract]
- Büntzel J, Glatzel M, Mücke R, et al.: Influence of amifostine on late radiation-toxicity in head and neck cancer--a follow-up study. Anticancer Res 27 (4A): 1953-6, 2007 Jul-Aug. [PUBMED Abstract]
- Langendijk JA, Doornaert P, Rietveld DH, et al.: A predictive model for swallowing dysfunction after curative radiotherapy in head and neck cancer. Radiother Oncol 90 (2): 189-95, 2009. [PUBMED Abstract]
- Murphy BA, Gilbert J: Dysphagia in head and neck cancer patients treated with radiation: assessment, sequelae, and rehabilitation. Semin Radiat Oncol 19 (1): 35-42, 2009. [PUBMED Abstract]
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- Ripamonti C, Zecca E, Brunelli C, et al.: A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 82 (10): 1938-45, 1998. [PUBMED Abstract]
- Robinson CA: Enteral nutrition in adult oncology. In: Elliott L, Molseed LL, McCallum PD, eds.: The Clinical Guide to Oncology Nutrition. 2nd ed. Chicago, Ill: American Dietetic Association, 2006, pp 138-55.
- Kagan SH, Sweeney-Cordes E: Head and neck cancers. In: Kogut VJ, Luthringer SL, eds.: Nutritional Issues in Cancer Care. Pittsburgh, Pa: Oncology Nursing Society, 2005, pp 103-16.
- Beer KT, Krause KB, Zuercher T, et al.: Early percutaneous endoscopic gastrostomy insertion maintains nutritional state in patients with aerodigestive tract cancer. Nutr Cancer 52 (1): 29-34, 2005. [PUBMED Abstract]
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