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Best Practices in Patient Navigation – Second Issue: Supportive Care Edition

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Supportive Care in the Oncology Setting

Margaret Rummel, BSN, RN, MHA, OCN 

There are numerous complications that may develop in patients with cancer; some are related to the disease itself, whereas others are associated with agents or combination regimens used during the course of treatment. As members of the multidisciplinary cancer care team, oncology nurse navigators (ONNs) must understand these complications and be armed with effective interventions to support patients throughout the continuum of care. This article addresses issues related to 2 complications that commonly occur in patients with cancer: myelosuppression and pain.

Myelosuppression

Myelosuppression can be a major complication associated with cancer and its treatment.1 The National Cancer Institute defines myelosuppression as “a condition in which bone marrow activity is decreased, resulting in fewer red blood cells (RBCs), white blood cells (WBCs), and platelets.”2 Decreased RBC production may result in anemia and fatigue, whereas decreased WBC production places patients at risk for infection and sepsis. Patients with decreased platelet production are at greater risk for bleeding and hemorrhage.1

Overview of Anemia

It is estimated that 30% to 90% of patients with cancer develop anemia.3 The majority of anticancer therapies destroy rapidly dividing cells, and since RBCs have relatively rapid growth rates, they are often affected. The protein in the RBC that carries oxygen throughout the body is called hemoglobin. When hemoglobin levels are low, oxygen levels are decreased, and the body must work harder to function, which results in fatigue. Normal hemoglobin and hematocrit values vary between men and women, as shown in Table 1.4

Table

Some chemotherapeutic agents have more powerful myelosuppressive effects than others. For example, in a 2006 study, Barrett-Lee and colleagues discovered that patients treated with platinum-based chemotherapy had double the risk for anemia compared with patients who received other types of chemotherapy.5 In addition to the type of chemotherapy used, low baseline hemoglobin and tumor type were also risk factors for cancer-induced anemia. Specifically, these investigators reported that patients with lower baseline hemoglobin levels (≤12.9 g/dL in women and ≤13.4 g/dL in men) had an almost 4 times greater risk for anemia after chemotherapy. Furthermore, patients with lung cancer or gynecologic cancer had a 3 times greater chance of becoming anemic, compared with patients who had gastrointestinal (GI)/colorectal cancer.5

Patients who have received concurrent chemotherapy and radiation are also at higher risk for developing anemia. According to results from a 2004 European Cancer Anaemia Survey, 50% of patients with lung cancer who received concurrent chemotherapy and radiation had anemia, compared with 39% of patients who received only chemotherapy and 32% of those who received only radiation.6

Managing Patients with Anemia

An important management strategy is to identify patients who are at high risk for developing anemia and evaluate their symptoms. General principles of management include identifying and treating the underlying cause of the anemia and weighing the risks and benefits of transfusion and the administration of erythropoiesis-stimulating agents (ESAs).7

Transfusion can provide a rapid improvement in symptoms, but patients and clinicians must be aware of possible adverse effects related to this procedure, including the risk for viral transmissions (eg, HIV and hepatitis C), circulatory overload, fatal hemolysis, and febrile nonhemolytic reactions. Typically, asymptomatic patients are transfused to maintain a hemoglobin level between 7 g/dL and 9 g/dL, symptomatic patients with hemorrhage are transfused to maintain hemodynamic stability, and symptomatic patients with a hemoglobin level <10 g/dL are transfused to maintain a level between 8 g/dL and 10 g/dL.7

The US Food and Drug Administration (FDA) has approved 3 ESAs for the treatment of patients with anemia.8 These agents work by stimulating the bone marrow to produce RBCs.8 Although ESAs may lessen the need for transfusion, their use is associated with some serious risks.9 These include lower survival rates, decreased time to progression (most notably in patients with a target hemoglobin level >12 g/dL), and increased risk for thrombosis in patients with a history of coagulopathy disorders or coronary artery disease, patients who are obese, and those on certain medications (eg, hormone therapy).9 Prior to administration of ESAs, patients must sign an informed consent form stating that they understand the risks and benefits of treatment.9 In addition, providers must complete a Risk Evaluation and Mitigation Strategy training program before they can prescribe these agents.9

The goals of ESA therapy are to use the lowest dose possible to avoid RBC transfusions and to keep the patient’s hemoglobin level below 10 g/dL. Dose reductions are required if a patient’s hemoglobin level rises more than 1 g/dL in a 2-week period.7

Patients with anemia may benefit from a referral to physical or occupational therapy, where they can participate in cancer fatigue programs and learn energy conservation and self-care techniques. They should also be educated on the following signs and symptoms of anemia, which should be immediately reported to the healthcare team10:

  • Weakness or fatigue
  • Dizziness
  • Headache
  • Shortness of breath or difficulty breathing
  • Palpitations or rapid heartbeat
  • Pale skin
  • Feeling cold, particularly in the hands and feet.

Overview of Neutropenia

Neutrophils are the most prevalent types of WBCs, which help the body’s immune system protect against infection. A normal absolute neutrophil count (ANC) is between 2500 mm3 and 6000 mm3.11 The ANC can be calculated with the following formula12: ANC = WBC × total neutrophils × 10.

Neutropenia is defined as an ANC <500 cells/mm3 or an ANC that is expected to decrease to <500 cells/mm3 during the next 48 hours.13 The lower the neutrophil count, the higher the risk for infection.11 Neutropenia is the most common dose-limiting toxicity associated with chemotherapy.11 WBC counts are most likely to be at their lowest point (also called nadir) 7 to 10 days after treatment.11

Several factors may increase a patient’s risk for neutropenia. These include older age, poor performance status, advanced disease, certain comorbidities, low baseline blood cell counts, low body surface area/body mass index, treatment with myelosuppressive chemotherapies, and specific genetic polymorphisms.14 The risk for severe chemotherapy-induced neutropenia is greatest in the first cycle of chemotherapy.7

Managing Patients with Neutropenia

Patients with neutropenia must be educated on strategies for preventing and minimizing infection. These include frequent handwashing; avoiding large crowds, persons who are sick, and those who have recently been vaccinated; avoiding the handling of animal waste; keeping central catheter sites clean and dry; good oral hygiene; avoiding excess sun exposure; being careful not to cut oneself; and checking with the healthcare team before undergoing dental work.11

Febrile neutropenia is defined as an ANC <1000 cells/mm3 with either a single oral temperature of 101°F or a sustained temperature of 100.4°F for longer than 1 hour. During chemotherapy, febrile neutropenia may be the only indication of a severe underlying infection, because signs and symptoms of inflammation are typically reduced. Therefore, the standard of care for high-risk patients with febrile neutropenia is hospitalization for empiric administration of antibiotics. High-risk patients are those who are expected to have prolonged febrile neutropenia (>7 days) and/or those who have significant comorbidities, including hypotension, pneumonia, new-onset abdominal pain, or neurologic changes.13

Prophylactic use of colony-stimulating factors is recommended if the planned chemotherapy regimen has been associated with a ≥20% risk for febrile neutropenia.7 A list of these regimens is available in the National Comprehensive Cancer Network (NCCN) guidelines for use of myeloid growth factors.15 Three colony-stimulating factors have been approved by the FDA, and their recommended dosages are incorporated in the NCCN guidelines.15 Common side effects associated with these agents are bone pain, myalgias, and arthralgias.15 Bone pain is usually treated with a nonsteroidal anti-inflammatory agent and an antihistamine for 48 to 72 hours.7 Prophylactic use of antibiotics is considered only in patients at very high risk for developing neutropenia or in those with hematologic malignancies.7

If febrile neutropenia does occur, it is considered a medical emergency, and prompt assessment and intervention is essential. In particular, it is necessary to assess the patient’s oncologic history, including chemotherapy and radiation treatments, current medications, and recent exposures to illness. In addition, a physical examination is essential, which should include assessing vital signs (especially temperature) and evaluating for changes in other body systems that may indicate an infection. Management involves implementing an organization-specific febrile neutropenia protocol, which should include obtaining blood/urine/indwelling catheter cultures, chest x-ray, and viral/vancomycin-resistant enterococcus swabs if indicated. Prompt administration of antibiotics is essential to prevent further deterioration of the patient’s condition.7

Overview of Thrombocytopenia

The role of platelets is to prevent bleeding and blood loss by adhering to small breaks in the blood vessels and initiating the clotting cascade.16 A normal platelet count is between 150,000/μL and 400,000/μL.17 Platelets are manufactured by the megakaryocytes in the bone marrow and form the myeloid stem cells in the bone marrow.7 Their normal life span is 10 to 12 days but may be as short as 24 hours in stressful times.7

Thrombocytopenia is defined as a decrease in the number of circulating platelets to <100,000/μL.17 It is important to identify patients at risk for this condition using the standardized grading scale for bleeding developed by the World Health Organization (WHO; Table 2).18

Table

Managing Patients with Thrombocytopenia

The American Society of Clinical Oncology (ASCO) recommends that patients with thrombocytopenia receive prophylactic platelet transfusion to reduce the risk for hemorrhage.19 According to ASCO guidelines, patients with leukemia or solid tumors who have chemotherapy-induced thrombocytopenia should receive prophylactic transfusion when their platelet count falls below 10,000/μL.19 Patients undergoing surgery or certain other invasive procedures, such as placement of a central catheter, should receive prophylactic transfusion if the platelet count is <40,000/μL to 50,000/μL prior to the procedure.19 Therapeutic transfusions should be given when there is active bleeding of grade ≥2 according to the WHO scale.20

Four types of platelet transfusions may be used to treat thrombocytopenia7,19,21:

  • Single-donor platelets come from a single donor who undergoes apheresis. This process yields about 200 mL and is time-consuming for the donor, as the process can take up to 2.5 hours. This process is also more costly than other platelet transfusions
  • Random-donor platelets come from multiple donors and are centrifuged from whole blood. The benefit of this process is that it yields a larger volume and exposes the patient to a variety of donors
  • Leukocyte-depleted platelets are used to reduce the risk of leukocyte-mediated adverse reactions. In this process, leukocytes can be separated/filtered from the blood to prevent an adverse reaction, since leukocytes are recognized as foreign cells by the recipient’s immune system
  • For patients who have failed to respond to 2 ABO-compatible platelet transfusions, ASCO recommends transfusion of platelets from donors who have been matched for human leukocyte antigen (HLA)-A and HLA-B.

There is only 1 thrombopoietic growth factor approved by the FDA specifically for patients with chemotherapy-
induced thrombocytopenia.22 This drug is a recombinant interleukin-11 that stimulates the bone marrow to produce platelets.22 It has been shown to decrease the need for platelet transfusions in patients who underwent platelet transfusion in a prior cycle, then received additional chemotherapy.23 However, this agent has substantial side effects that make it unacceptable for most patients.23

In patients with thrombocytopenia, it is important to obtain an oncologic history, including chemotherapy, radiation treatments, and current medications. Physical examination should include assessment for bleeding. In addition to assessing for petechiae and bruising, it is important to assess for bleeding from body orifices (eg, bleeding gums, epistaxis, vomiting, hematuria, or bloody stools).7

Patients should be advised on the signs of a low platelet count (Table 3) and when to report these symptoms to their healthcare providers.16

Self-care interventions related to thrombocytopenia can be taught to patients and their caregivers to help them become more aware of measures that may decrease the risk for this condition.16

Table

  • Brush teeth gently with a soft bristle toothbrush or a soft toothette to clean teeth and gums
  • Rinse mouth after each meal with a baking soda solution (2 tsp baking soda to 8 oz of water)
  • Do not use dental floss
  • Avoid commercial mouthwashes that contain alcohol, which can dry out the mouth and lead to bleeding
  • Use petroleum jelly or other lip balms to keep lips moist and to prevent cracking
  • Take sips of water or juice frequently for a dry mouth
  • Modify feminine hygiene practices: use sanitary napkins rather than tampons during menstruation, and avoid vaginal douching
  • Do not blow the nose too hard
  • Avoid straining too much with bowel movements (use a stool softener or laxative if constipation occurs)
  • No rectal thermometers, suppositories, or enemas
  • Use an electric razor for shaving (do not use a straight-edge razor)
  • Notify the healthcare team before scheduling any dental work
  • Do not take medications that affect blood clotting (eg, aspirin or aspirin-containing products)
  • Do not take any nonsteroidal anti-inflammatory medications
  • Avoid lifting heavy objects or strenuous activity, including sports and activities that could result in falling and/or injury (eg, bicycling, roller-blading, skating, skiing)
  • Drink 8 to 10 glasses (8 oz each) of nonalcoholic fluid a day to keep the mouth moist, avoid constipation, and keep the intestinal lining in good condition
  • Wear shoes or slippers at all times to protect the feet
  • Avoid tight-fitting clothing
  • Speak with your healthcare team about the safety of sexual activity as it relates to a low platelet count. Vaginal or anal penetration (including toys/props) or oral sex may pose a risk for bleeding. Use a water-based lubricant and avoid vigorous thrusting during sexual intercourse
  • Assess the environment for obstacles that could cause injury.

Cancer-Related Pain

Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage. It may be described as causing a vague discomfort or significant distress, or may be stabbing, aching, pinching, throbbing, or shooting in nature. There are many types of pain that a patient may experience24,25:

  • Acute pain is temporary and lasts for a relatively short time, usually ≤6 months. It is usually confined to 1 area, is easy to describe, and has an identifiable cause, such as surgery
  • Chronic pain is persistent or recurrent pain beyond the usual course of an acute illness or injury. It is not always confined to 1 area and can be difficult to describe. Frequently, patients with chronic pain “do not look like they are in pain”
  • Breakthrough pain is defined as transient pain that may be severe or at least above the patient’s baseline pain level
  • Somatic pain refers to pain that comes from a bone, a joint, or connective tissue. It is often described as sharp and throbbing, and its location is easily identified by the patient
  • Visceral pain comes from stimulation of the pain fibers secondary to distention, compression, or infiltration into the abdominal or thoracic tissue. Patients frequently describe this pain as diffuse, aching, or cramping, and it is not easily localized. It often occurs due to tissue obstruction of the GI tract, liver metastases, or impaired blood flow to the organ involved
  • Neuropathic pain results from compression, inflammation, ischemia, or injury to the peripheral, sympathetic, or central nervous system. Patients will describe this pain as numbing and tingling if it is related to the peripheral nervous system. If the pain is centrally mediated, then the patient will describe shooting and radiating sensations with burning and aching. This type of pain may occur if the patient develops a spinal cord compression, plexopathy, or peripheral neuropathy.

Cancer-related pain is a combination of acute and chronic pain that is associated with direct tumor involvement or treatment. Disease-related cancer pain occurs most often in patients with head and neck cancer, gynecologic malignancies, or GI cancer. Bone metastases are also a source of cancer-related pain. The most common malignancies that cause bone metastases are multiple myeloma and lung, breast, and prostate cancers. Bone pain is a recult of compression of the bone on surrounding nerves or direct destruction of the bone itself.24

The use of certain agents places patients at a greater risk for developing treatment-related pain from mucositis. These agents include platinum-based chemotherapy, antimetabolites, alkylating agents, and taxanes.26 Other chemotherapeutic agents may pose a risk for peripheral neuropathy. These agents include vinca alkaloids, platinum-based therapies, taxanes, and some target therapies.27

Radiation therapy may also cause treatment-related pain. Patients receiving radiation to the head and neck area are at risk for mucositis that may affect the entire GI tract.26 This side effect usually occurs 2 to 3 weeks after the start of treatment and may cause severe pain and affect the patient’s ability to eat and drink.26 Radiation therapy may also cause severe skin changes that are very painful, such as radiation dermatitis and radiation recall.24

Many surgical procedures used to treat cancer may result in chronic pain. One chronic pain syndrome is postmastectomy pain, where the patient experiences tightness and difficulty moving the operative side. Patients who have undergone head and neck surgery or a thoracotomy also experience this type of pain.24

Pharmacologic pain management needs to be individualized based on the 3-step analgesic ladder. This ladder was originated by WHO to describe its guidelines for the use of drugs in the management of patients with pain (Figure).28 It was originally applied to the management of cancer-related pain, but it is now widely used for the management of all types of pain. The general principle is to start with ≥1 drugs on the “first rung,” then “climb the ladder” if pain is still present. Medications range from over-the-counter drugs with minimal side effects at the lowest rung to powerful opioids at the highest rung. Prescribers should start with the least invasive route, which is oral agents, and alter routes and dosages as needed. Sometimes just changing the opioid (opioid rotation) may benefit the patient. Long-acting opioids should be used when the patient experiences constant pain. Breakthrough pain needs to be managed when intermittent episodes of pain occur along with the patient’s constant pain. If the patient is experiencing incident pain, which may occur with a specific event, premedicating before the event will be helpful in decreasing the pain. Any patient who is taking an opioid for pain also needs to be on a bowel regimen to avoid constipation. Other side effects of opioids, such as nausea, also must be managed.28

Table

Other interventions for pain management include bisphosphonates, for relief of osteolytic lesions, and radionuclides, for relief of metastatic bone lesions. Intraspinal analgesia may also provide pain relief and can be given in lower doses with fewer side effects than other analgesics. Radiation therapy is used to alleviate pain associated with bone metastases and to decrease the size of a large tumor that may be causing pain. Nerve blocks may be used for localized pain syndromes.25

Cancer rehabilitation may help in decreasing pain and increasing functional status. Ideally, prehabilitation should be implemented prior to treatment to help minimize the pain associated with therapy and help maintain functional status during therapy.29

There are also many complementary and alternative nonpharmacologic methods used in pain management. Acupuncture may be helpful in relieving the pain associated with cancer treatments. This ancient Chinese medical technique is used to promote or restore health by inserting fine-gauge needles in specific points in the body to increase energy flow. Reiki, yoga, and massage therapy may also be used to help relieve pain. These therapies may assist in decreasing the emotional and physical tension caused by the disease. Guided imagery, meditation, and biofeedback, among other therapies, may help with stress reduction, resulting in better pain management. Counseling and support groups may also be instrumental in the management of stress, depression, and pain.25

There are many more nonpharmacologic therapies that patients may use to help manage the emotional, spiritual, and psychological aspects of pain. It is important for ONNs to know which therapies patients are participating in and to provide education related to the various types of therapies used to relieve pain.

Nursing management includes providing education to patients and caregivers on ways to manage and prevent pain. Assessments should include an oncologic history, including chemotherapy, radiation treatments, and current medications. To get patients on the right pain-relieving regimen, it is essential to complete a thorough pain assessment that focuses on all domains of care, including physical, social, spiritual, and psychosocial. Pain is assessed using a scale of 0 to 10, with 0 being no pain and 10 being the worst pain. Assessments should be done prior to the dose of medication as well as 30 minutes posttherapy to ascertain the effectiveness of the intervention.25

Educating patients on important safety issues surrounding the proper use and disposal of pain medications is critical. Some of the issues to cover include30:

  • Refrain from taking any medications, even over-the-counter medications, without first checking with your doctor or nurse
  • Take the medication as prescribed. Most pain medications start to work in 30 to 60 minutes and can last up to 46 hours. Other medications, such as the anticonvulsants and antidepressants used to treat some types of pain, take a few days to begin working
  • Take the medication when the pain begins. Waiting until the pain is severe before taking the medication will make it more difficult for the medication to work, and it may not be as effective and may take longer to work
  • Keep a record of how often you take your pain medication and how much relief you feel. This should be shared with the healthcare team so that they can evaluate the effectiveness of the pain management regimen
  • Use a daily laxative while taking opioids (unless contraindicated due to a previous medical condition).

Patients should also be advised to report any of the following to the healthcare team30:

  • New pain, especially if it is persistent or severe
  • An increase in the amount or frequency of pain
  • Pain that does not improve after taking pain medication or returns before the next scheduled dose
  • Difficulty with side effects from pain medications (eg, sleepiness, nausea, constipation)
  • Ineffective laxative (no bowel movement for <2 days OR hard/painful bowel movements)
  • Pain that is accompanied by numbness, tingling, or weakness of the arm or leg; difficulty walking, urinating, or having a bowel movement.

Conclusion

Nurses and ONNs play an important role in managing and supporting patients throughout cancer treatment. Nurses are often the first point of contact for patients and possess strong assessment skills and knowledge of cancer treatments and their side effects. ONNs are key members of the healthcare team, as they help patients understand their plan of care and transition through the cancer continuum by providing support, advocacy, and education to reduce barriers to care.


References

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2. National Cancer Institute. NCI Dictionary of Cancer Terms. www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=44173. Accessed June 23, 2015.

3. Knight K, Wade S, Balducci L. Prevalence and outcomes of anemia in cancer: a systematic review of the literature. Am J Med. 2004;116(suppl 7A):11S-26S.

4. Billett HH. Hemoglobin and hematocrit. In: Walker HK, Hall WD, Hurst JW, eds. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd ed. Boston, MA: Butterworths; 1990.

5. Barrett-Lee PJ, Ludwig H, Birgegard G, et al. Independent risk factors for anemia in cancer patients receiving chemotherapy: results from the European Cancer Anaemia Survey. Oncology. 2006;70:34-48.
6. Kosmidis P, Krzakowski M. Anemia profiles in patients with lung cancer: what have we learned from the European Cancer Anaemia Survey (ECAS)? Lung Cancer. 2005;50:401-412.

7. Kurtin S. Myeloid toxicity of cancer treatment. J Adv Pract Oncol. 2012;3:209-224.

8. US Food and Drug Administration. Information on erythropoiesis-stimulating agents (ESA) epoetin alfa (marketed as Procrit, Epogen), darbepoetin alfa (marketed as Aranesp). www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm109375.htm. Accessed June 29, 2015.
9. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Cancer- and Chemotherapy-induced Anemia. Version 2.2015. www.nccn.org. Accessed June 29, 2015.
10. OncoLink. Low red blood cell count (anemia). www.oncolink.org/treatment/article.cfm?id=60. Accessed June 29, 2015.
11. OncoLink. Neutropenia tip sheet. www.oncolink.org/coping/article.cfm?c=358&id=970. Accessed June 29, 2015.
12. Dana-Farber/Harvard Cancer Center. Guidance on determining the absolute neutrophil count. www.dfhcc.harvard.edu/fileadmin/DFHCC_Admin/Clinical_Trials/CTEO/downloads/Guidance_on_Determining_the_ANC.pdf. Accessed June 29, 2015.
13. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52:e56-e93.
14. Lyman GH, Abella E, Pettengell R. Risk factors for febrile neutropenia among patients with cancer receiving chemotherapy: a systematic review. Crit Rev Oncol Hematol. 2014;90:190-199.
15. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Myeloid Growth Factors. Version 2.2014. www.nccn.org. Accessed June 29, 2015.
16. Platelet Research Laboratory. Platelet function. www.platelet-research.org/1/function_hemo.htm. Accessed June 30, 2015.
17. OncoLink. Low platelet count (thrombocytopenia). www.oncolink.org/treatment/article.cfm?c=145&id=69. Accessed June 29, 2015.
18. Webert K, Cook RJ, Sigouin CS, et al. The risk of bleeding in thrombocytopenic patients with acute myeloid leukemia. Haematologica. 2006;91:1530-1537.
19. Schiffer CA, Anderson KC, Bennett CL, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001;19:1519-1538.
20. Slichter SJ. Evidence-based platelet transfusion guidelines. Hematology Am Soc Hematol Educ Program. 2007:172-178.
21. Singh S, Kumar A. Leukocyte depletion for safe blood transfusion. Biotechnol J. 2009;4:1140-1151.
22. Neumega (oprelvekin) [prescribing information]. Philadelphia, PA: Pfizer, Inc; 2011.
23. Kuter DJ. Managing thrombocytopenia associated with cancer chemotherapy. Oncology (Williston Park). 2015;29:282-294.
24. Brant JM, Walton A, Dyk L. Comfort. In: Itano JK, Brant J, Conde F, Saria M, eds. Core Curriculum for Oncology Nursing. 5th ed. Pittsburgh, PA: Oncology Nursing Press; 2014.
25. National Cancer Institute. Pain–for health professionals (PDQ). www.cancer.gov/about-cancer/treatment/side-effects/pain/pain-hp-pdq#section/all. Accessed June 30, 2015.
26. Epstein JB, Thariat J, Bensadoun RJ, et al. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship. CA Cancer J Clin. 2012;62:400-422.
27. Beijers AJ, Jongen JL, Vreugdenhil G. Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. Neth J Med. 2012;70:18-25.
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29. Johnson I, Bourgan R. Complementary and integrative modalities. In: Itano JK, Brant J, Conde F, Saria M, eds. Core Curriculum for Oncology Nursing. 5th ed. Pittsburgh, PA: Oncology Nursing Press; 2014.
30. OncoLink. Understanding and managing pain. www.oncolink.org/coping/article.cfm?c=379&id=570. Accessed June 30, 2015.

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