Radiation Therapy Adverse Effect Management Requires Long-term Monitoring

Effective treatment strategies established for patients with head and neck cancers often include definitive radiation therapy for primary tumors. However, short- and long-term adverse effects (AEs) associated with these treatments necessitate a comprehensive understanding of the evidence-based management strategies for managing these events, according to Ashley Marenyi, RN, BSN, OCN.¹

In a presentation at the 48th Oncology Nursing Society Annual Congress, Marenyi, a registered nurse in radiation oncology at Rush University Medical Center in Chicago, Illinois, discussed the common radiation-associated AEs to be aware of when caring for patients with head and neck cancers and the importance on long-term survivorship care.¹

“There’s been an increase [in the] rate of head and neck cancer survivors in the past decade, thanks in large part to the improvements of standard therapies,” Marenyi said. “[And] it’s called attention to the need for more structured approaches to survivorship care planning.” As a 5-year papillary thyroid cancer survivor, Marenyi added, “I want to emphasize how important survivorship discussions are with patients, even after they’re done with treatment because a lot of times patients aren’t in the right mind space to talk to you about those AEs when they’re going in for surgery or about to start radiation treatment.”

The cancers grouped in this classification most often include those originating from the squamous cells lining mucosal surfaces of the head and neck. “These can include the oral cavity, the nasal pharynx, hypopharynx, larynx, the paranasal sinuses, or nasal cavity, salivary glands and the thyroid,” Marenyi said. “Head and neck cancers account for nearly 4% of all cancers in the United States.”²

Marenyi noted that a lot goes into the treatment decision-making considering guidelines recommendations and patient preferences. “When talking about radiation, it’s important to define the intent of radiation therapy,” she said. “Radiation can sometimes be used as a curative treatment, but it’s not always used in this way. Definitive radiation is when radiation is used, either alone or with systemic therapies, and the intent is to cure the patient of their cancer. Adjuvant radiation therapy is defined as postoperative radiation, so patients already gone through surgery, and it can be radiation with or without systemic therapy. But again, the goal is cure. Neoadjuvant radiation is when radiation occurs prior to surgery [with] the goal of shrinking the tumor or downstaging the patient's cancer prior to surgery. And then lastly, palliative radiation in this radiation with a goal to improve a patient'’ quality of life or to decrease any functional deficits that the patient may have from their tumor.”

Management of Short-term AEs

Starting at approximately 3 weeks into treatment, short-term effects, including in-filed alopecia, dysgeusia and xerostomia, and radiation dermatitis may begin to develop.^1,3

Patients should be told that hair loss and thinning around the radiation site will occur and that hair growth resumes after radiation therapy concludes. However, Marenyi noted that the hair may be thin, and patients may notice a texture difference. “For patients with head and neck cancer typically, our female patients are not too concerned about…facial hair. But our male patients who have nice beards, this is something that really can affect their self-esteem. It’s something to make sure you talk about with patients, it's good to let them know that this hair loss will typically grow back. And it’s important to let them know that it may be a little bit thinner, or their hair could even become grow back with a different texture.”

Providing symptom relief related to changes in taste and saliva gland function caused by dysgeusia and xerostomia is the primary goal of AE management. For patients with dysgeusia who experience metallic or bitter tastes due to under stimulated saliva glands, sugar-free gum and may help induce saliva production. Having water on-hand for small, frequent sips is also best practice for patients. Marenyi said that saliva substitutes are also an option but are temporary and expensive, whereas FDA-approved agents pilocarpine and cevimeline have their own toxicity profiles.^1,3 “It’s hard to encourage patients to maintain their caloric intake because nothing tastes good or things actively taste bad,” Marenyi said.

Radiation dermatitis has prognostic factors including age, body-mass index, and any additional systemic therapies the patient may be receiving. The toxicity is also dose-dependent and is most likely to occur in the anterior neck region. Grading using the Common Terminology Criteria for Adverse Events (CTCAE) radiation dermatitis is defined as follows: dry desquamation, faint erythema (grade 1); patchy moist desquamation found primarily along skinfolds, moderate to brisk erythema, moderate edema (grade 2); moist desquamation, bleeding induced by minor traumas or abrasions (grade 3); and life-threatening ulceration of full thickness dermis with spontaneous bleeding and skin necrosis, skin grafting indicated (grade 4).⁴

Should patients experience a grade 1 to 3 event of moist desquamation, white vinegar soaks can reduce reactive oxygen species responsible for inflammation as vinegar possesses antimicrobial and antioxidant properties. However, Marenyi said there is a lack of clinical evidence supporting the use of vinegar soaks for treatment of acute radiation dermatitis, but that in practice the soaks work using gauze soaked in 3 to 4 drops of vinegar mixed with 4 cups water applied to the skin for 5 to 10 minutes 3 times per day and air dried.¹

“There are no compelling, statistically significant evidence for recommending any one agent for prevention and management of radiation dermatitis, which means recommendation from radiation oncologists and oncology nurses often are inconsistent, even among providers among institutions,” Marenyi said. As such, oncology nurses should follow practices which include washing skin with warm gentle, fragrance-free soap and water, patting skin in treatment area dry, and applying topical moisturizing lotion. Should a topical product be required, the product should not contain petroleum jelly, alcohol, perfume, or chemical agents. These should be applied to maintain a layer of moisture throughout the day and patients should be advised to avoid direct sunlight and use SPF of at least 30.^1,3 Finally, shaving the treatment field should be done with electric razors, not razor blades.¹

Oral Mucositis Considerations

Patients who are receiving concurrent chemotherapy, high total radiation doses, have comorbidities, and baseline oral hygiene practices are all predictive factors for developing oral mucositis for patients undergoing radiation therapy.

“Oral mucositis is an inflammatory and ulcerative response caused by the disruption of integrity of the oral mucosa as lining it initially can start out as some redness in the mouth, maybe a burning sensation but it can progress to observes and sloughing of the epithelial lining in the mouth, which is obviously very painful and can affect patients’ ability to eat,” Marenyi explained.

The CTCAE grading scale for oral mucositis ranges from asymptomatic/mild symptoms to life-threatening events requiring urgent attention.⁵ “Grade 1 will be asymptomatic or very mild symptoms, moderate pain or alterations that are not quite interfering with oral intake, but it may cause the patient to switch to softer foods,” Marenyi explained. “Grade 3 oral mucositis is going to involve more severe pain that does interfere with patient’s oral intake. Grade 4 is considered life threatening and will require urgent intervention at that point, that may be when we would really want to get [a patient] a feeding tube as soon as possible.”

Management relies on educating patients on basic oral care, including avoiding mouthwashes with alcohol-based substances and the use of coating agents and oral anesthetics to manage symptoms.¹ “Additionally, something that we often recommend is a simple salt water and baking soda [mixture],” she said. “It’s very inexpensive for the patients, and it works very well. We tell patients is to mix a teaspoon of salt, a teaspoon of baking soda, and a quart of water…make it every other morning and then throughout the day, go over to your sink, rinse, gargle with it if you can, and then spit it out…. It’s a great way to clean and sanitize any oral source that they may have.”

Avoiding acidic, spicy, and sugary foods as well as tobacco is also something Marenyi suggested to counsel patients.

Management of Long-term AEs

“Acute AEs can be top of mind for patients as they prepare for treatment, [however] it’s really important that they’re also educated on some of these longer-term late onset AEs,” Marenyi said.

These AEs include parotitis, dental caries, osteoradionecrosis, trismus, pharyngoesophageal stenosis, hypothyroidism, lymphedema, cognitive problems, brachial plexopathy, ototoxicity, radiation retinopathy, secondary cancers, anxiety, and depression.¹

Parotid glands, the largest salivary glands, account for 65% of total saliva in oral cavity and although short-term AEs such as cotton mouth may be managed early in the course of treatment, increased glucose uptake in parotid glands secondary to acute inflammation from radiation therapy can lead to cell damage and fibrosis of tissue.^1,6

“When educating patients, you can tell them that short term their salivary function may be diminished, but long term, depending on where the radiation field [was] and [the dose] those glands were getting, it’s something that can last much longer than treatment completion,” Marenyi said.

In tandem with dry mouth, the risk of dental cavities also rises as mechanical cleansing that occurs with saliva is diminished, Marenyi explained. Should patients require a dental extraction, Marenyi noted that communication with the patient’s dental team becomes important. “Ideally, if there are dental extractions needed, this should happen at least 2 weeks prior to the start of radiation therapy,” she said. “However, especially for patients with more advanced disease, we never want to delay the start of radiation for a dental extraction. There’s a 4-week window typically after the completion of radiation therapy where the vascular changes to the mandible haven’t quite taken full effect…. Work with the patient’s dentist or oral surgeon to come up with a game plan to have a date set for when that patient is going to get their tooth pulled within those few weeks after radiation.”

Trismus may be induced by radiation therapy. “Trismus is something that significantly impacts the head neck patient community. It’s defined as restricted and mouth opening that can be caused by painful contraction of facial muscles. When severe, it can be difficult for patients to open their mouth more than a few inches which, as you can imagine, going to the dentist office for dental cleanings or brushing your teeth regularly can become really difficult when a patient has severe trismus. It can affect their ability to eat and maintain oral hygiene and it’s estimated to affect nearly 40% of patients treated with radiation for an oral cavity or oral pharyngeal,” Marenyi said.

Nonoperative interventions can include facial exercises, laser therapy, or Boxtox injections.

The development of hypothyroidism may not present until approximately 1.5 years following treatment, Marenyi said. “It’s not something that you need to monitor for as soon as treatment is completed. But it’s something that long term you want to discuss with your patients and be monitoring for. It’s estimated that more than 50% of all patients with a head and neck cancer will develop hypothyroidism by 10 years out from treatment completion.”

Monitoring for lymphedema is important because although some cases may resolve without treatment, others can lead to lasting effects. “[Some cases may] form deposits of ibrofatty scar tissue in the interstitial spaces, which for some patients may just mean they have a little bit more limited mobility of their neck, but for others, it can be extremely severe and cosmetically significant,” Marenyi said. “It’s something that you want to talk to patients about early on because there are ways to manage lymphedema. The current standard of care is manual lymph drainage, by a lymphedema specialist. There is a right and a wrong way to do manual lymph drainage, so it’s something that I typically refer [out] to a specialist,” she explained. Acupuncture is also an option for the management of this AE; however, more evidence is needed for before it becomes standard practice.

Hearing and vision impairments may also be observed, and patients should be monitored for changes.

One of the most prevalent long-term AEs are psychological. “[the diagnosis and treatment of head and neck cancers] can cause significant implications on a patient’s quality of life,” Marenyi said. “The levels of psychological distress in patients with head neck cancer are higher than in any other oncology patient population. It’s estimated 15% to 50% of patients undergoing treatment will be affected by major depressive disorder. Suicide rates are 4 times higher in this patient population than in the general patient population. And posttraumatic stress disorder has been found in 13% of patients treated for head and neck cancer within 6 years [of treatment].”⁷

References

1. Marenyi A. More than just tracheostomies: making heads or tails of late and long term side effects of head and neck radiation. Presented at: 48th Annual Oncology Nursing Society Annual Congress; April 25-30, 2023; San Antonio, TX. Accessed April 25, 2023. https://ons.confex.com/ons/2023/meetingapp.cgi/Session/5088
2. Head and neck cancer: statistics. Cancer.net. Updated March 2023. Accessed April 27, 2023. https://www.cancer.net/cancer-types/head-and-neck-cancer/statistics
3. Radiation therapy side effects. American Cancer Society. Updated December 10, 2020. Accessed April 27, 2023. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/radiation/effects-on-different-parts-of-body.html
4. Kawamura M, Yoshimura M, Asada H, Nakamura M, Matsuo Y, Mizowaki T. A scoring system predicting acute radiation dermatitis in patients with head and neck cancer treated with intensity-modulated radiotherapy. Radiat Oncol. 2019;14(1):14. doi:10.1186/s13014-019-1215-2
5. Lee CT, Galloway TJ. Pathogenesis and amelioration of radiation-induced oral mucositis. Curr Treat Options Oncol. 2022;23(3):311-324. doi:10.1007/s11864-022-00959-z
6. Mouminah A, Borja AJ, Hancin EC, et al. 18F-FDG-PET/CT in radiation therapy-induced parotid gland inflammation. Eur J Hybrid Imaging. 2020;4(1):22. doi:10.1186/s41824-020-00091-x
7. Senchak JJ, Fang CY, Bauman JR. Interventions to improve quality of life (QOL) and/or mood in patients with head and neck cancer (HNC): a review of the evidence. Cancers Head Neck. 2019;4:2. doi:10.1186/s41199-019-0041-4