Radiation therapy induced nausea and vomiting

The purpose of this document is to provide guidance to minimise and where possible, prevent radiation therapy induced nausea and vomiting (RINV).

This document has been developed for the Australian clinical context using the most recent international guidelines including MASCC/ESMO antiemetic guidelines 2019^r, ASCO antiemetic guidelines update 2020 ^r and NCCN Clinical Practice Guidelines in Oncology - Antiemesis guidelines v1.2021.^r

Pathophysiology

Nausea and vomiting occur when neurotransmitters are stimulated and an impulse is sent to the autonomic nervous system causing nausea, and to the somatic and visceral system to produce vomiting.^r

Incidence/prevalence

The incidence and severity of RINV are influenced by the specific radiation therapy regimen and by patient-specific factors. Frequency has been reported in 28-39% of patients.^rr Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiation therapy.^r

Onset/duration

Nausea can be one of the earliest side effect of radiation therapy to develop and can appear 1 to 3 days after the commencement of treatment, lasting for several hours after treatment is completed. The first few days after the onset of RINV can be the most severe.

Risk factors

There are multiple risk factors that predispose the patient to the development and severity of RINV. These risk factors can include (but are not limited to) treatment and patient related factors.

Treatment related factors that affect the emetic risk include:

• the area of the body being treated/in the treatment field
  • total body irradiation
  • brain
  • abdomen
  • epigastric region
  • para-aortic area
  • pelvis fields extending into the abdomen
  • chemoreceptor trigger zone (CTZ) in the cerebral cortex of the brain (in rare cases)
• the size of the treatment areas/field
• the per fraction and total dose of radiation delivered.

Patient related factors that may increase the risk of RINV include:

• concurrent or recent chemotherapy
• female
• younger age (<50 years)
• previous history of RINV
• little or no previous alcohol use (chronic high consumption of alcohol appears to protect against RINV).
• history of motion sickness
• pregnancy related nausea/emesis
• anxiety/high pre-treatment expectation of nausea
• poor performance status.

Levels of emetic risk with radiation therapy

The likelihood of experiencing RINV can be divided into the following 4 groups:^r

RINV is generally milder than anti-cancer therapy induced nausea and vomiting (AINV). Patients having concurrent chemoradiation therapy should receive antiemetic prophylaxis according to the emetogenicity of anti-cancer therapy, unless the emetic risk with the planned radiation therapy is higher. Link to prevention of anti-cancer therapy induced nausea and vomiting.

It is important to assess the patient’s risk of RINV prior to the start of radiation therapy to ascertain whether antiemetic therapy should be given routinely as a preventative measure (prior to treatment each day) or rescue once symptoms have presented.

Signs and symptoms

RINV can include the following signs and symptoms:

• nausea
• vomiting
• pallor
• diaphoresis (increased perspiration)
• salivation
• anorexia (in advanced nausea and vomiting)
• signs/symptoms of dehydration:
  • postural hypotension (dizziness)
  • tachycardia (rapid heart rate)
  • low urine output
  • headaches.

Exclude

It is often assumed that nausea and vomiting in a patient who has recently received radiation therapy is the result of their treatment. However, there are several other causes of nausea and vomiting, many of which will commonly present in cancer patients and should therefore be excluded. These include: 

• constipation
• bowel obstruction
• gastroparesis
• malignant ascites
• anxiety
• fluid and electrolyte imbalances (e.g. hypercalcaemia, acute and chronic kidney injury)
• uraemia
• metastases or tumour site involving the gastrointestinal tract, liver or central nervous system
• raised intracranial pressure
• peptic ulcer disease
• recent or concurrent chemotherapy
• vestibular dysfunction
• cannabinoid hyperemesis syndrome^r
• rapid opioid withdrawal^r
• pancreatitis.^r

Investigations and diagnosis

The following should be included in an assessment of nausea and vomiting, as part of a complete patient assessment:

• history and compliance with antiemetics
• the frequency (number of episodes in 24 hours), intensity, onset and duration of vomiting
• concomitant medications (e.g. opioids)
• hydration status
• nutritional intake +/- weight loss
• heartburn/dyspepsia
• haematemesis
• blood test
  • full blood count (to assess for neutropenia and/or anaemia)
  • EUC + calcium, magnesium and phosphate (CMP) to assess for electrolyte imbalance.

Grading 

Common Terminology Criteria for Adverse Events (CTCAE) v5.0, 27 November, 2017

The aims of RINV management are to:

• prevent an initial emetic episode from occurring, or
• manage symptoms once they present as a result of radiation therapy.

The suggested management of RINV varies between risk groups and is outlined below:

Monitor patients for symptoms experienced on days when therapy and prophylaxis not given e.g.  weekends, so as to balance benefits and toxicities of prolonged 5HT₃ receptor antagonist (RA) therapy.
* Either 5HT₃ RA is appropriate; insufficient data on use of palonosetron.
** Dexamethasone is the preferred first agent for the brain. Any antiemetic class is appropriate for head and neck, thorax, and pelvis.
 ^{^} The role of rescue medication for patients at low and minimal risk of RINV needs to be defined in further studies.^r
+ Alternative explanations for symptoms should be investigated to avoid the need for prophylactic therapy for the remainder of radiation therapy.

Anticipatory nausea and vomiting

Anticipatory RINV can occur any time after the first course of radiation therapy and is a conditioned response, typically occurring after a previous negative experience with radiation therapy. Prevention of RINV will also prevent anticipatory phase RINV. Therefore, the best management of anticipatory emesis is to ensure good control of emesis. For patients who do develop anticipatory emesis, non-pharmacologic methods such as behavioural/psychological techniques may be useful and/or benzodiazepines e.g. lorazepam 0.5 mg to 2 mg orally on the night before and then repeated the next day 1-2 hours before treatment.^r

Breakthrough or rescue treatment for nausea and vomiting

The general principle of treatment for breakthrough emesis is to add an additional antiemetic with a different mechanism of action than that of the current prophylactic regimen in addition to continuing the standard antiemetic regimen. Read more about brealthrough nausea and vomiting.

Educate your patient:

• to take antiemetics as prescribed (e.g. prior to radiation therapy)
• to maintain fluid intake and report signs of dehydration such as:
  • reduced urine output
  • rapid heart rate
  • headaches
  • flushed, dry skin
  • coated tongue
  • irritability
  • confusion
  • dizziness.
• to take antiemetics regularly, rather than treating nausea after it has started
• on self care measures:
  • avoid eating or preparing food when they feel sick, and if possible have someone else do the cooking
  • avoid fried foods and foods with a strong smell
  • eat cold or warm food if the smell of hot food makes them feel sick
  • eat several small snacks and meals each day (rather than three large meals), and to chew the food well
  • peppermints or peppermint tea may help with nausea
  • try small amounts of foods containing ginger e.g. ginger tea, ginger biscuits or ginger beer, or taking over the counter ginger supplements. Experts don't all agree on whether this works, but some people find it helpful.
  • sip drinks slowly
  • avoid drinking too much before a meal
  • avoid alcohol
  • avoid high volumes of coffee.

Read more about nausea and vomiting during cancer treatment in the patient information. This patient information sheet is available in several languages.

Read more about food and cancer on the Cancer Council website.

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