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 survival^2,3. 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?

Dr Aapro discusses the origins and definitions of supportive care in oncology. View transcript

What barriers are preventing implementation of supportive care models?

Dr Aapro discusses barriers preventing implementation of supportive care models. View transcript

The Multinational Association of Supportive Care in Cancer (MASCC) defines supportive care as:

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), including^7-9:

• 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

Dr Aapro details the structure and function of a proposed multidisciplinary team that could support people through their cancer treatment journey. View transcript

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 arises^1,8. 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 manner^1,11. The supportive care team is illustrated in Figure 1.

Figure 1. Members of the supportive care team^8,11.

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

Dr Aapro highlights the impact of cancer treatment and the related toxicities on patient quality of life and treatment outcome. View transcript

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 life^2,3,17-19

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 impacted^26-29.

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.

General side effects

Fatigue

Cancer-related fatigue (CRF) is one of the most common and distressing symptoms experienced by patients during their treatment^36,37 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 survival^37,39. 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 cancer^40-42. 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 survival^44,45. Many common adverse effects of cancer treatment contribute to and worsen CRF, including^37,38,40:

• Anaemia
• Pain
• Muscle deconditioning
• Sleep–wake disturbance
• Vomiting
• Diarrhoea
• Malnutrition

Haematological side effects

Dr Gary Lyman (Fred Hutchinson Cancer Center, Seattle, Washington, USA) discusses common haematological side effects of cancer treatment and their guideline-recommended management approaches. View transcript

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 treatment^47,48.

Thrombocytopenia

Systemic chemotherapy is the most frequent cause of thrombocytopenia; however, any myelosuppressive cancer treatment can induce this condition^49,50. 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 bleeding^52,53 

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 inhibitors^55,56.

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 rising^57,58

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

Dr Lyman highlights the most common and distressing gastrointestinal side effects of cancer treatment experienced by people with cancer. View transcript

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 described^66-68. 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 conditions^71,75.

Cachexia and anorexia

Cachexia is a major cause of morbidity and mortality in late-stage cancer and can occur following prolonged chemotherapy^76,77.

Cachexia is a devastating condition characterised by muscle wasting, malnutrition and weakness, with a significant impact on quality of life and treatment success^76,78

Two major symptoms of cancer cachexia are anorexia and weight loss that is not improved with increased food intake^79,80. 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

Dr Lyman discusses common cardiovascular and respiratory side effects of cancer treatment. View transcript

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-prolongation^82,83.

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 complications^87-90

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 mortality^91,93. Symptoms of hypercalcaemia can be mistaken for normal side effects of cancer treatment and include^94,95:

• 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 nephropathy^97,98. 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 regimens^99,100.

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 hyponatraemia^97,98. 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

Dr Lyman discusses the most common neurological side effects resulting from cancer treatments. View transcript

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 duration^105,106. Treatment options for CIPN are limited and it is therefore a significant cause of dose reduction and discontinuation^105,106.

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 include^{107,110,112,113}:

• 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 ARD^114,115.

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.

Figure 3. Summary of the side effects of cancer treatment on body systems¹¹⁸.