Abdomen and pelvis: Symptoms and toxicities

Overview

The severity of radiation-related toxicity is related to the total dose received, fraction size, and overall treatment time, in addition to other patient-related factors such as concurrent receipt of systemic therapy, prior treatments, and predisposition to radiation side effects.

Palliative radiotherapy is typically delivered in a shorter time frame with a larger dose per fraction (though notable exceptions such as palliative spleen radiation exist) in order to minimize treatment burden. These hypofractionated schemes are typically associated with increased risk of late effects, rather than acute morbidity, and can be beneficial in rapid relief of cancer-related symptoms such as bleeding, pain or obstruction. However, with improving systemic therapies and increased survival, consideration of delayed side effects in the setting of palliative radiation must be incorporated with greater frequency.

Acute side effects, occurring within 3 months of receipt of radiotherapy, are typically self-limited and, furthermore, are limited to the site of treatment (unlike systemic therapy). The balance of radiotherapy-related side effects and symptom relief must be weighed, and there will be several clinical scenarios in which radiotherapy should be omitted and instead supportive care should be pursued, especially when the risks of any of these side effects outweigh the benefits of treatment. ^, However, in select patients, the “side effects” of supportive care itself (such as opioid requirements) can be mitigated with short courses of radiotherapy to improve quality of life in advanced cancer patients. When used, radiation-related toxicities should be minimized if not avoided as much as possible, with adherence to normal tissue dose constraints ^, whenever applicable. Pre-treatment prophylactic medication should be considered to help mitigate anticipated nausea, anxiety, and pain (even when unrelated to the site being treated).

Below, we summarize abdominal symptoms related to palliative radiotherapy, including common presentation/diagnosis and grading as per the frequently used Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 definitions, as well as prevalence and management.

Presentation/diagnosis

Unlike many other radiation-related symptoms, nausea and vomiting can occur with the first fraction of radiation or in an anticipatory fashion. Breakthrough radiation-induced nausea and vomiting occurs despite the use of prophylactic antiemetics. CTCAE v5.0 Criteria grading of nausea and vomiting is outlined in Table 32.1 .

Prevalence

Up to 30% to 90% of patients report nausea and vomiting. Patients receiving total body irradiation are at the highest risk (>90%), with upper abdominal radiation and craniospinal radiation at moderate risk (30% to 90%), and other sites at low or minimal risk. ^, Use of prophylactic antiemetics can be prescribed based on risk.

Management

Pharmacologic management of nausea and vomiting includes both prophylaxis and rescue therapy.

Prophylactic pharmacologic therapy includes combined therapy with a serotonin 5-hydroxytriypamine-3 (5-HT3) receptor antagonist and a corticosteroid, once to twice daily, with the first dose given prior to radiotherapy or once daily on day after radiotherapy. For moderate-risk patients, administer dexamethasone for the first 5 days only. Serotonin 5-HT3 receptor antagonists include ondansetron, granisetron, or tropisetron (if moderate-risk) given before each fraction and 24 hours following radiotherapy. Corticosteroids include dexamethasone. Anxiolytics include lorazepam (if anticipatory) before each fraction as an adjunct to combined therapy.

Rescue pharmacologic therapy can be prescribed as needed. Rescue therapies include serotonin 5-HT3 receptor antagonists (preferred) such as ondansetron and granisetron. Dopamine receptor antagonists for rescue therapy include metoclopramide and prochlorperazine. Corticosteroids, including dexamethasone, can also be prescribed.

Nonpharmacologic management of nausea and vomiting includes smaller, more frequent meals and consideration of a decreased dose per fraction for prophylaxis or mild symptoms. Fluid supplementation and electrolyte repletion for moderate to severe symptoms can also be considered. See Table 32.9 .

Comments

Most patients receiving radiotherapy to the upper abdomen are at a risk of developing nausea and/or vomiting. Prophylactic therapy should be used 45 to 60 minutes prior to radiotherapy. For patients at particularly high risk of nausea/vomiting, a combination of a serotonin 5-HT3 receptor antagonist and a corticosteroid should be used daily and on the day after each fraction, even if no radiation is received that day. For moderate-risk patients, a serotonin 5-HT3 receptor antagonist should be used daily, with dexamethasone for the first 5 days of radiotherapy. Those at low risk should receive rescue therapy only. If rescue is needed for breakthrough or unanticipated radiation-induced nausea and vomiting, a serotonin 5-HT3 receptor antagonist should be used, followed by prochlorperazine or metoclopramide, if ineffective. If a low-risk patient is still on therapy and experiences radiation-induced nausea and vomiting, offer prophylactic therapy prior to radiotherapy for the remaining fractions; a decreased dose per fraction can also be considered. If patients are also receiving prophylactic antiemetic therapy for antineoplastic systemic agents and are between cycles, prophylactic therapy (rather than rescue) prior to radiotherapy should be administered.

Presentation/diagnosis

Patients often present with weight loss or malnutrition after radiotherapy. This symptom may be difficult to differentiate from cachexia-anorexia due to malignancy. ^, Control of other radiotherapy-related symptoms (such as gastritis, nausea/vomiting) may assist with management of anorexia during radiotherapy. CTCAE v5.0 Criteria grading of anorexia is outlined in Table 32.2 .

Prevalence

Up to three-quarters of patients will experience anorexia, especially when receiving palliative radiotherapy for gastric cancer ^, or other disease requiring treatment to a large proportion of the stomach.

Management

Symptom rate, severity, and timing of loss and associated symptoms should be assessed. Pharmacologic management of anorexia includes antiemetics (see section on management of Nausea/Vomiting), acid reflux medications (see section on Gastritis) and administration of IV fluids. For appetite stimulation, pharmacologic approaches include low dose steroids, megestrol acetate, marinol, and olanzapine. If anorexia symptoms are related to depression, mirtazapine is a suitable option.

Nonpharmacologic management of anorexia includes education on the condition and risks/benefits of any treatment options, nutrition counseling, intake of small, frequent meals, high-calorie intake. If needed and aligned with a patient’s goals of care, a percutaneous endoscopic gastrostomy (PEG) tube can be considered. See Table 32.9 .

Comments

Assessment for nonradiation-related factors such as malignancy, anorexia/cachexia, dysgeusia, mucositis, gastroparesis, pain, enzymatic insufficiency, or psychiatric considerations should be considered and managed appropriately.

Presentation/diagnosis

In patients with obstructive symptoms, dehydration, oliguria, and/or shock may indicate intestinal perforation. All suspected bowel perforations should be emergently evaluated for medical or surgical intervention. Generally, perforation is a late side effect, but it can occur early due to gastric ulceration. Small bowel ulceration or perforation may present with abdominal cramping and pain. Any perforation can cause fistula formation. CTCAE v5.0 Criteria grading of perforation is outlined in Table 32.3 .

Prevalence

Perforation is very uncommon in gastric cancer or in the palliative setting.

Management

Evaluation for surgical management should be undertaken if consistent with the patient’s goals of care.

Presentation/diagnosis

Bleeding in the abdomen due to radiotherapy alone is uncommon. Most bleeding occurs as a result of malignancy or its sequelae (such as thrombocytopenia or medications such as anticoagulants, nonsteroidal antiinflammatory drugs [NSAIDs], or bevacizumab) rather than as a result of radiotherapy. Common presentations can include anemia, hematemesis, melena, or hematochezia. CTCAE v5.0 Criteria grading of hemorrhage is outlined in Table 32.4 .

Prevalence

In general, approximately 10% to 30% of patients with advanced cancer have at least one episode of bleeding or hemorrhage, although it is unlikely that palliative radiotherapy would be the primary cause.

Management

Goals of care, life expectancy, and quality of life considerations can help guide management. Therapies should be accompanied by a thorough medication history and assessment of volume status, and complete blood count (CBC), and a comprehensive metabolic panel (including liver function evaluation) to understand any predisposing factors. Assessment by gastroenterology via scoping, if appropriate, should be employed to determine the feasibility of local therapy.

Pharmacologic management first includes discontinuation of agents that exacerbate bleeding; use of NSAIDS, warfarin, enoxaparin, or chemotherapies that cause thrombocytopenia should be re-evaluated. Careful consideration of the risks of thromboembolic events and bleeding should be weighed against the benefit of anticoagulation. ^, Blood and blood products can be used for patients who are actively bleeding or unstable according to practice guidelines in coordination with gastroenterology and palliative teams.

Nonpharmacologic ^, management includes endoscopic approaches if the bleeding lesion is visible and amenable to intervention, such as argon plasma coagulation, cautery, sclerosing interventions, and laser. Endovascular approaches may be considered when appropriate if arterial access can be identified and the bleeding vessel can be selectively embolized; transcutaneous embolization may also be appropriate. Surgical interventions can be considered in patients with better functional status and without a significant disease burden.