Supportive care in cancer
Many high-efficacy cancer treatments have been developed over the past decade, bringing with them new benefits as well as challenges for modern cancer therapy. Despite the advances, many patients still experience high rates of morbidity and adverse effects resulting from treatment1. The burden of adverse effects caused by cancer treatments plays a critical part in determining a patient’s clinical outcomes.
There is a growing body of evidence showing that providing supportive care to address the adverse effects of cancer treatment can lead to improvements in quality of life and survival2,3. However, worldwide variations in the definition of supportive care, a lack of clarity on who should provide these services, and lack of a universal clinical model have created barriers to implementation4, creating a significant need for ‘supportive oncology care’ to become a specialty in its own right. With the rising incidence of cancer worldwide5, and many patients living longer with improved treatments6, this need is becoming critical1.
What is supportive care in cancer?
What barriers are preventing implementation of supportive care models?
The Multinational Association of Supportive Care in Cancer (MASCC) defines supportive care as:
The prevention and management of the adverse effects of cancer and its treatment. This includes management of physical and psychological symptoms and side effects across the continuum of the cancer experience from diagnosis through treatment to post-treatment care7
Supportive care manages the toxicities and side effects of cancer treatment, is evidence based and uses a patient-centred approach. With optimal supportive care models implemented into practice, there are numerous benefits for patients, families and healthcare providers (HCPs), including7-9:
- Reduced symptoms and complications of cancer
- Prevention and/or reduction of treatment toxicities and side effects
- Increased adherence to treatment due to better management of side effects
- Increased tolerance, and thus benefits, of cancer treatment
- Improved communication between patients, caregivers and HCPs
- Easing of the emotional burden for patients and caregivers
- Psychosocial support for cancer survivors
Role of the multidisciplinary team in supportive care
Supportive care covers the physical, emotional, social, spiritual and informational needs of the patient, and cannot be provided by a single clinical specialty alone10. As with other multidisciplinary teams (MDTs), a ‘core team’ is required to address everyday problems and concerns of the patient, while an ‘extended team’ will be involved as the need arises1,8. The core team usually consists of oncologists, surgeons, pathologists, radiotherapists, nurses and other specialists according to the type of cancer11. The core team requires regular specific and ongoing training in the principles of supportive care, to ensure the model is being implemented correctly, as well as appropriately engaging members of the extended team in a timely manner1,11. The supportive care team is illustrated in Figure 1.
Is supportive care synonymous with palliative care? What is the difference?
Supportive care emerged to specifically address the toxicities and side effects of cancer treatment throughout the entire cancer continuum12. Palliative care has historical roots in end-of-life and hospice care and, although it encompasses the same principles of supportive care, confusion among HCPs and patients between the use of the terms has created barriers to implementation13. Studies have shown that patients and HCPs are more responsive to the term ‘supportive care’ than ‘palliative care’, with many patients and HCPs hesitant to engage palliative care services because of the association with end-of-life and discontinuing treatment13.
It is a common misconception that supportive care and palliative care are separate, with the latter focused more on end-of-life care. It is important for HCPs to understand that, while these terms originated to address different concerns, they have evolved to encompass the same principles of supportive care and patient-centred care14 The European Society for Medical Oncology (ESMO) has suggested that the term ‘patient-centred care’ be used to cover both supportive and palliative care approaches during the continuum of cancer illness, while the World Health Organization (WHO) and the American Society of Clinical Oncology (ASCO) include the principles of supportive care in their definition of palliative care15. ASCO asserts that the two terms and types of care, though having different origins, are one and the same16. HCPs should therefore take time to dispel the negative connotations surrounding palliative care, while remaining conscious of its potential effect on patients and their families13. Supportive care could therefore be considered an overarching principle, with palliative care an integral part of that care.
The critical role of supportive care in cancer management
Numerous studies have demonstrated that implementing a supportive care model as part of cancer management improves the outcome in many different aspects of a patient’s life2,3,17-19
Systemic treatments have rapidly evolved from being predominantly cytotoxic chemotherapy and radiotherapy, to immunotherapies and targeted therapies9. Despite the advances in cancer therapy, tolerance to treatment remains a key issue. The emergence of novel treatments has seen an increase in new toxicities and side effects, necessitating alternative management approaches9. MASCC has created guidelines for supportive care strategies addressing many of these toxicities, to ensure optimal outcomes for patients that HCPs can familiarise themselves with.
Patients undergoing cancer treatments often experience a high burden from the side effects of treatment (Figure 2). Unmanaged side effects can lead to patient discomfort, treatment non-adherence and suboptimal cancer management. This can subsequently increase the cancer burden through dose delays, dose reductions and treatment withdrawal. Management of side effects is therefore a critical component of providing supportive care that has a direct impact on treatment outcomes20.
Figure 2. Impact of cancer treatment and side effects on the patient *Treatment side effect rates based on a multicentre study of patients in Australia (N=441) with breast, colorectal or lung cancer receiving chemotherapy22
There is evidence to show that a lack of supportive care is associated with profoundly detrimental outcomes. Evidence gathered from populations with limited access to supportive care for reasons of socioeconomic, geographical and racial barriers have shown that survival, secondary complications arising from treatment, and health-related quality of life are all negatively impacted26-29.
In the UK, a national initiative to implement supportive care into existing cancer management plans has been trialled with great success3. Studies have returned positive results including3:
- Improved symptom control and quality of life
- Reduced 30-day mortality
- Improved overall survival
- Reduced healthcare costs
Similarly, initiatives to implement early supportive care in US clinics showed improved overall survival and quality of life30.
Advance care planning
Advance care planning (ACP) is a process that ‘supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences regarding future medical care’31. ACP informs treatment decisions that can be documented in an advance directive (AD). Palliative care specialists are skilled in providing ACP support for patients but are a limited resource. To address this limitation, the CONNECT study was undertaken to investigate the impact of a nurse-led intervention on ACP uptake among patients with advanced cancer. Given that oncology nurses often have special relationships with their patients, they may be well suited to providing ACP support31.
The CONNECT study involved a secondary analysis of a cluster randomised controlled trial examining the impact of nurse-based primary palliative care32. Patients with advanced cancer were randomly assigned to receive either monthly primary palliative care visits with trained nurses within their cancer centre or standard care. Nurses in the intervention arm received special training in ACP32.
ACP uptake was assessed at enrolment and 3 months later, evaluating whether an end-of-life conversation (EOLC) occurred with the oncologist, and whether an AD was completed32. Multivariable logistic regression tested differences in ACP uptake by treatment arm adjusted for various factors.
Of the 672 patients enrolled, 54% (182/336) patients in the intervention arm and 58% (196/336) in the standard care arm lacked an EOLC at baseline and completed the 3-month assessment32. In the intervention arm, 45.1% (82/182) of patients had an EOLC after 3 months, compared with 14.8% (29/196) in the standard care arm. Regarding ADs, 33% (111/336) of patients in the intervention arm and 31% (105/336) in the standard care arm did not have ADs initially but completed the 3-month assessment. Among these, 43.2% (48/111) in the intervention arm and 18.1% (19/105) in the standard care arm completed an AD during the study32.
The study concluded that nurse-led primary palliative care increased ACP uptake among patients with advanced cancer32. Training oncology nurses within community cancer centres to provide primary palliative care may help improve ACP access. These findings highlight the potential of specialist HCPs, including oncology nurses, to provide primary palliative care and contribute to improving the quality of care for patients with advanced cancer32.
Side effects associated with cancer treatments
Side effects of cancer treatment may be short-term, long-term or even life-long and present a significant barrier to receiving adequate treatment as the dose may need to be reduced, delayed or discontinued because of toxicities7. This is a phenomenon labelled ‘dose-limiting toxicity’ and is a major issue faced when administering anti-cancer therapy7.
Adherence to various treatments is influenced by numerous factors including access and cost; however, the biggest influence is the tolerability of side effects33. Tolerability and adherence vary across treatment modalities34,35. Being aware of the side effects and educating patients on what to expect is a critical component of improving adherence, tolerance and treatment outcomes.34,35
General side effects
Fatigue
Cancer-related fatigue (CRF) is one of the most common and distressing symptoms experienced by patients during their treatment36,37 and is reported to be more distressing than pain, nausea or vomiting38. CRF can be dose-limiting and have a negative impact on treatment adherence, efficacy and survival37,39. Despite its frequency, CRF remains under-reported, underdiagnosed and undertreated36. Prevalence rates vary from 50% to 100% depending on the type of treatment, dose, and type and stage of cancer40-42. Patients with brain tumours have the highest prevalence of severe fatigue (approximately 40% of patients)43. Fatigue in cancer is strongly associated with depression, anxiety and physical disability, with severe fatigue being a predictor of shorter survival44,45. Many common adverse effects of cancer treatment contribute to and worsen CRF, including37,38,40:
- Anaemia
- Pain
- Muscle deconditioning
- Sleep–wake disturbance
- Vomiting
- Diarrhoea
- Malnutrition
Haematological side effects
Thrombosis
Chemotherapy and tumour surgery resulting in patient immobilisation frequently cause cancer-associated thrombosis, with the most common complication being venous thromboembolism (VTE)46. Severe complications of VTE constitute a major cause of mortality among people with cancer47. Treating VTE in people with cancer can become complex, as typical management with anticoagulants is associated with an increased risk of bleeding and unfavourable drug interactions, which therefore limits the therapeutic options available for cancer treatment47,48.
Thrombocytopenia
Systemic chemotherapy is the most frequent cause of thrombocytopenia; however, any myelosuppressive cancer treatment can induce this condition49,50. Thrombocytopenia significantly increases the risk of internal haemorrhage and is associated with worse clinical outcomes51.
Thrombocytopenia frequently occurs with thrombosis, making treatment difficult because of the competing risks of recurrent thrombosis and increased bleeding52,53
Healthcare professionals should exercise caution and vigilance when using myelosuppressive cancer treatments by regularly monitoring platelet levels.
Anaemia
Up to 39% of people with cancer present with anaemia at the time of diagnosis, and up to 40% have iron deficiency54. If not identified early, this can be further exacerbated by cancer treatment55. Anaemia causes fatigue, dyspnoea, functional deterioration, and a reduction in quality of life; it has also been associated with a poorer response to cancer treatment and lower survival54. Anaemia can result from myelosuppression due to chemotherapy and radiotherapy and has been linked to immunotherapy, specifically checkpoint inhibitors55,56.
Neutropenia
Neutropenia (including febrile neutropenia and neutropenic colitis) is a life-threatening complication associated with increased morbidity and mortality, and is a leading cause of dose reduction and delay57.
Neutropenia most often results from chemotherapy and radiotherapy, but with the emergence of new targeted and immunotherapies, its prevalence in patients with cancer is rising57,58
Other causes of neutropenia include tumour malignancies and lymphoproliferative malignancies, such as natural killer cell lymphomas, hairy cell leukaemia and chronic lymphocytic leukaemia59.
Lymphoedema
Lymphoedema is the accumulation of lymph fluid that obstructs the flow of the lymphatic system, causing persistent swelling in an affected body part60. Lymphoedema is most commonly seen after radiation therapy or lymph node dissection. It occurs in 10–40% of patients with breast cancer and 80% of patients with lymph node dissection in the groin60. Secondary lymphoedema is caused through fibrotic tissue changes that occur post-treatment, causing structural and functional changes that block the flow of circulating lymph61.
More on management strategies for haematological side effects
Gastrointestinal side effects
Nausea and vomiting
Chemotherapy-induced nausea and vomiting (CINV) is common and distressing for patients, and is the number one cause of dose delays and discontinuation62. CINV occurs in up to 80% of patients and can have a significant impact on quality of life. Prolonged CINV can also result in63:
- Serious electrolyte and metabolic imbalances
- Malnutrition and anorexia
- Cognitive impairments
- Oesophageal tears
- Delayed wound healing and dehiscence
- Withdrawal from potentially useful and curative antineoplastic treatment
- Loss of independence and functional ability
Mucositis (oral and gastrointestinal)
Mucositis refers to inflammatory, erosive and ulcerative lesions in any part of the gastrointestinal (GI) tract, including the mouth and oesophagus, that occur secondary to cancer therapy64. Mucositis can be classified according to the type of cancer therapy involved as chemotherapy-induced mucositis, radiation-induced mucositis, or a combination of the two65. More recently, mucositis following targeted anticancer therapies has been described66-68. Oral mucositis occurs in approximately 20–40% of patients receiving conventional chemotherapy for solid tumours, over 80% of patients receiving head and neck radiotherapy, and about 80% of patients undergoing high-dose chemotherapy prior to haematopoietic stem cell transplantation69. GI mucositis is also prevalent, with an incidence of 50–89% in patients receiving various chemotherapy regimens70.
Diarrhoea and constipation
Diarrhoea and constipation present constant challenges in the treatment of cancer and are primary contributors to dose reductions, delays and cessation of treatment71. Constipation is believed to occur in 16% of patients with cancer72, while incidence of diarrhoea can be as high as 80%73.
Diarrhoea and constipation can persist for many years after the discontinuation of treatment, presenting a significant clinical problem74
Diarrhoea and constipation are usually attributed to conventional cytotoxic drugs, such as chemotherapy, but many molecularly-targeted agents, including tyrosine kinase inhibitors and monoclonal antibodies, are also associated with the conditions71,75.
Cachexia and anorexia
Cachexia is a major cause of morbidity and mortality in late-stage cancer and can occur following prolonged chemotherapy76,77.
Cachexia is a devastating condition characterised by muscle wasting, malnutrition and weakness, with a significant impact on quality of life and treatment success76,78
Two major symptoms of cancer cachexia are anorexia and weight loss that is not improved with increased food intake79,80. Wasting mostly occurs in skeletal muscle and adipose tissue, but other organs, such as the brain, liver, pancreas, heart and gut, are also involved in cachexia, making it a multiorgan syndrome81.
More on management strategies for gastrointestinal side effects
Cardiovascular side effects
Targeted therapies, such as monoclonal antibodies and small molecule inhibitors of protein kinases, are associated with cardiovascular and metabolic sequelae82. These include heart failure or a decline in ejection fraction, peripheral and cardiac ischaemic events, pulmonary hypertension, arrhythmias and QT-prolongation82,83.
Development of cardiac dysfunction secondary to treatment is associated with significantly lower chances of survival84
The effect of antineoplastic drugs on cardiomyocytes can be categorised as either type 1 or type 2 cardiotoxicity84. Type 1 cardiotoxicity is dose-dependent and irreversible, and is characterised by structural changes to cardiomyocytes, leading to apoptosis84. Conversely, in type 2 cardiotoxicity, cardiomyocytes lose contractility, leading to cardiac dysfunction and reduced cardiac output, but this is not associated with any significant changes to cardiac structure84.
Respiratory side effects
Pulmonary toxicity is a well-documented complication of several anti-cancer treatments, with breathlessness and dyspnoea among the most common pulmonary side effects85. A study of 923 people with different types of cancer found that breathlessness was reported by over 50% of patients with primary cancers of the breast, lung, genitourinary organs, head and neck, and those with lymphoma86.
All modalities of cancer treatment, including chemotherapy, radiation therapy, targeted therapy and immunotherapy, can cause significant and potentially fatal pulmonary complications87-90
The presentation of pulmonary toxicity ranges from dry cough and shortness of breath to sudden respiratory failure and may mimic other conditions, such as infection or pulmonary oedema85. Clinicians should therefore maintain heightened awareness and focus on early detection.
Endocrine and metabolic side effects
Hypercalcaemia
Hypercalcaemia, though not directly resulting from any specific treatment, is a common symptom of cancer with huge potential to negatively impact on cancer treatment regimens. Approximately 20–30% of people with cancer develop hypercalcaemia during their illness91. Hypercalcaemia is most common among patients with lung cancer, renal cancer and multiple myeloma92. Hypercalcaemia produces distressing symptoms for the patient and is strongly associated with poor prognosis and higher rates of mortality91,93. Symptoms of hypercalcaemia can be mistaken for normal side effects of cancer treatment and include94,95:
- Anorexia
- Nausea
- Vomiting
- Abdominal pain
- Polyuria
- Muscle weakness
- Fatigue
- Apathy
- Mood changes
- Bone pain
Severe complications of hypercalcaemia include dehydration, nephrolithiasis, acute pancreatitis, acute renal failure, ventricular arrhythmias, and altered mental status including coma94. Because hypercalcaemia can significantly complicate cancer management, this condition should not be overlooked96.
Hyponatraemia
Hyponatraemia is a common electrolyte abnormality associated with substantial morbidity and mortality, and can result from haemorrhage, diarrhoea, vomiting, ascites, oedema or salt-wasting nephropathy97,98. Platinum-based therapies are now among the most widely used anti-cancer therapies, but are associated with hyponatraemia, which can be due to renal salt-wasting syndrome or syndrome of inappropriate antidiuretic hormone (SIADH)99. In an analysis of 29 trials, around 12% of patients treated with platinum-based chemotherapy had grade 3/4 hyponatraemia, compared with 4% of those treated with nonplatinum-based regimens99,100.
Hyponatraemia often follows chemotherapy with platinum-based compounds, which can cause damage to the renal tubules, resulting in renal salt-wasting syndrome99
Malignancy itself can also cause electrolyte imbalances, including hyponatraemia97,98. Nearly 50% of patients with cancer have hyponatraemia and it has been reported to be a negative prognostic factor for many solid and blood tumours, reducing survival at all cancer stages101.
Neurological and muscular side effects
Headache and memory impairment
Chemotherapy agents, such as all-trans retinoic acid, procarbazine and 5-fluorouracil, as well as many others, have been implicated in causing headaches102. Patients receiving radiotherapy may develop acute radiation toxicity, which typically manifests as severe headache, fever, nausea, vomiting, decreased level of consciousness and worsening neurological deficits103.
Treatment with chemotherapy, hormonal therapy, immunotherapy and targeted therapies are associated with cognitive impairment and can be detrimental to learning, attention, executive functions, memory, multitasking and processing speed104. The prevalence of clinically significant cognitive impairment varies and estimates range from 17% to 78% of people receiving treatment for cancer104.
Peripheral neuropathy
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, with a prevalence of 19–85%105. CIPN is a sensory neuropathy accompanied by motor and autonomic changes varying in intensity and duration105,106. Treatment options for CIPN are limited and it is therefore a significant cause of dose reduction and discontinuation105,106.
Dermatological side effects
Dermatological toxicities are well documented for chemotherapy and radiation therapy, but have become more prominent with the evolution of newer targeted therapies and immunotherapies107. Dermatological complications occur in up to 78% of patients receiving chemotherapy108, 90% receiving radiation therapy109, up to 50% receiving immunotherapy110 and 30–50% receiving targeted therapies111. Known side effects include107,110,112,113:
- Alopecia
- Acneiform (papulopustular) rash
- Xerosis
- Extravasation
- Maculopapular rash (morbilliform eruption)
- Hand–foot skin reaction
- Stevens–Johnson Syndrome (SJS)/ toxic epidermal necrolysis (TEN)
- Nail toxicity
- Pruritus
- Psoriasis
- Lichen planus-like rash
- Eczematous dermatitis
While some forms of toxicities do not pose an imminent risk to the patient, other side effects, such as TEN, can prove fatal107.
Acute radiation dermatitis (ARD) is a well-known and frequently observed side effect of external beam radiotherapy (RT), affecting as many as 95% of individuals114. The development of ARD involves a multifaceted process, characterised by radiation-induced harm to both the epidermis and dermis. This damage leads to changes in the growth and differentiation of basal and epidermal keratinocytes, disruptions in the skin's protective barrier, and activation of proinflammatory markers that contribute to the symptoms associated with ARD114,115.
ARD typically appears as redness, darkening, swelling and ulceration in the area that received radiation, and can also cause itching, pain, skin hotness, and skin peeling116. ARD can have a negative impact on a person's quality of life, as it can cause physical discomfort and interfere with daily activities114. It can also affect a person's emotional wellbeing, causing decreased self-esteem and embarrassment114. In severe cases, ARD can lead to delayed or interrupted radiation therapy, which can have a negative impact on the effectiveness of the treatment117.
Common side effects of cancer treatment are summarised in Figure 3.
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