Find out more about our Academic Medical Centre and efforts in Academic Medicine
Academic Medicine Executive Committee (AM EXCO)
Find out more about what JOAM do to support AM initiatives
Find out more about the Office of Duke-NUS Affairs and Study Trip to Duke Durham
Guidelines, forms, and templates for Academic Medicine.
Systemic cancer treatments have increased tremendously in the last decade and with high survival rates general practitioners are more than likely to have cancer survivors as patients, as such knowledge of the common side late effects and management measures will help GPs optimise their care for these patients.
Cancer has ranked consistently as the principal cause of death in Singapore, with 26,891 deaths reported in 2022, attributing up to a 25% of total deaths. The number of cancer cases have been increasing annually and is expected to continue to increase.
Between 2017-2021, 84,002 cancer cases were reported in Singapore. Between 2018 – 2021, the National Cancer Centre Singapore (NCCS) has seen more than 6,000 young adults with cancer. Out of this, 80-85% of cancer patients, especially in the younger adults, is expected to have long-term survival. There is a difference in the types of cancers seen across the age groups, and across genders.
Cancer treatment can be broadly divided into systemic treatment, surgical treatment and radiotherapy. We will focus on systemic treatment in this article. The types of systemic cancer treatment have increased tremendously in the last decade. Beyond the usual chemotherapy that is usually cancer-agnostic, there is now a whole host of different kinds of anti-cancer treatment available.
This includes immunotherapy, targeted therapy, hormone therapy, stem cell transplants, CAR-T (Chimeric Antigen Receptor T-Cell) Therapy, monoclonal antibodies, checkpoint inhibitors, cytokines, angiogenesis inhibitors and PARP (Poly ADP-ribose polymerase) therapies. There are also increasingly more clinical trial drugs that are available to our patients.
Impact on patients
With each treatment, there exists certain specific side effects and also some general toxicities. For some patients, these toxicities are slight and do not affect their overall quality of life. They will likely be able to return to regular life. However, for others, the toxicities can be debilitating and can even be permanent.
These toxicities can be divided into early, mediumterm and late effects. This article will specifically focus on late effects.
In general, late effects (also known as long-term or delayed effects) can occur months or years after cancer treatment has completed.
The extent of toxicities is dependent on:
Exact type of treatment received
Duration and dose of the treatment and
The patient’s co-morbidities
This can occur in almost any organ or system and can include:
Neurological and cognitive impairments
Endocrine derangements
Cardiovascular complications
Subfertility
Osteopenia and osteoporosis
Nephropathies
Gastro-intestinal and hepatotoxicities
Respiratory complications
Psychosocial
Sexuality
Psychosocial distresses
The reversibility of these toxicities is dependent on:
The extent
Timely detection and
The patient’s willingness to try methods to reverse or mitigate them
The methods to treat these symptoms may not be straightforward and may involve not medication, but also a more holistic approach that includes lifestyle changes.
Cancer survivors are defined as any cancer patient from the point of diagnosis. Broadly, this can refer to any cancer patient who is cured, in remission or has stable chronic cancer expected over a period of time.
Caring of the cancer survivors should include:
Screening and prevention of long-term side effects from a holistic standpoint
Surveillance for the original cancer to detect recurrence
Screening for secondary cancers
Care co-ordination between primary care providers and other specialists
General health management including management of risk factors and adoption of a healthy lifestyle such as regular exercise and practicing sun safety.
Concerns with reintegration into work/school/community
Psychosocial and mental health concerns
Below is a general table on some of the common late effects and the advised management.
Can be in the form of numbness, paresthesias, allodynia or shooting electrical pains
Consider X-rays or MRI scans
Consider nerve conduction studies/electromyography
Non-pharmacologic treatments such as physiotherapy, heat/ice therapy, acupuncture/transcutaneous electrical nerve stimulation unit
Pharmacologic treatment with nonopioids/adjuvant analgesics, topicals, vit Bs
Pharmacologic treatments with opioids
Neurology
Orthopaedics
Pain services
Interventional radiologist if there is radiculopathy
Rehabilitation medicine
Palliative care
Consider physiotherapy
2. MYALGIAS/ARTHRALGIAS
Muscle aches
Joint aches
X-rays of affected joints/limbs to rule out fractures/avascular necrosis
DEXA scan to check bone density
Bone scans if bone metastases suspected
Screen for hormonal/endocrine/vitamin deficiencies
Screen through medication/treatment history
Non-pharmacologic treatments such as physiotherapy, heat/ice therapy, acupuncture/ultrasonic stimulation
Braces or orthoses
Pharmacologic treatment from simple analgesics such as paracetamol/anarex, non-opioids/adjuvant analgesics to opioids
Joint replacements may be necessary
Pain Team
Physiotherapy
Refer back to oncologist should there be suspicion of recurrence
3. POOR BONE HEALTH/UNEXPECTED FRACTURES
Unexpected/multiple fractures, especially at an unexpected age
Osteopenia
Osteoporosis
X-rays of affected joints/limbs to rule out fractures
DEXA scan to check bone density annually
Check for calcium, vitamin D, PTH levels
Check renal function
Go through medication list and treatment history
Calcium supplements
Replete vitamin D levels
Bisphosphonates/RANK-ligand inhibitors
Endocrinologist
Referral to dentists before initiating bisphosphonates
Should hormonal replacement therapy be considered, please refer back to primary oncologist to ensure this is acceptable
4. EARLY MENOPAUSE
Symptoms may occur regardless of ovarian function
Menopause is defined as no menses for 1 year, in the absence of prior chemotherapy or tamoxifen use OR no menses after surgical removal of all ovarian tissue
Screen for reversible causes (e.g., anaemia, severe weight loss)
Screen for menopausal symptoms
Assess for contributing factors (e.g., medications, emotional distress, alcohol)
Assess for endocrine/vitamin deficiencies/hormonal imbalances (e.g., FSH, LH, prolactin, estradiol levels, AMH levels for females; morning total testosterone, free testosterone in males)
Review oncologic history and treatment history
Management of menopausal symptoms
Consider non-hormonal pharmacologic treatment of hot flushes such as anti-depressants, anti-convulsants, neuropathic pain relievers, some anti-hypertensives
Non-pharmacologic treatments include acupuncture, exercise, lifestyle modifications, weight management and cognitive behavioural therapy
Limit triggers, such as alcohol
Hormonal replacement therapies or pharmacologic therapies
Consider referral to gynaecologist
Should hormonal replacement therapy be considered, please refer back to primary oncologist to ensure this is acceptable.
Consider referral to counsellor, social worker, psychiatrist
5. SUBFERTILITY
Evaluation should be undertaken for couples who have not conceived 6-12 months of unprotected intercourse
Can be earlier should prior history be expected to affect fertility
Screen for reversible causes such as anaemia, endocrine, vitamin deficiencies, hormonal imbalances
Assess for contributing factors such as medications, emotional distress, alcohol
Assess for structural causes
Review oncologic history and treatment history to assess what is realistically available to patient (e.g., female with hysterectomy will not be able to physically carry a child)
General recommendations is to be disease-free for 2 years before attempting to conceive, be it either naturally or via assisted reproductive technologies
Consider referral to gynaecologist or urologist
Consider referral to assisted reproduction centres with fertility specialists such as CARE
6. SEXUAL HEALTH
Important aspect of Quality of Life. Needs to be sensitively asked/broached.
This would be applicable regardless of sexual orientation
Screen for reversible causes such as anaemia, endocrine, vitamin deficiencies/hormonal imbalances
Review oncologic history and treatment history
Can screen with Sexual Health Inventory for Men/Brief Sexual Symptom Checklist for Women
Assess issues concerning sexual health and see if etiology can be managed (e.g., vaginal dryness may benefit from lubricants)
Sexual health specialist
Endocrinologist
Gynaecologist or urologist
Social worker
Counsellor
Marriage counsellor if appropriate
7. CHRONIC FATIGUE
Distressing, persistent and subjective sense of physical/emotional/cognitive tiredness or exhaustion that is out of proportion to activity. It affects usual functioning.
This is related to cancer or cancer treatment
Screen for reversible causes such as anaemia, insomnia, obstructive sleep apnoea
Assess for endocrine/vitamin deficiencies/hormonal imbalances
Consider 2D Echo
Consider sleep study
Screen for fatigue regularly
Treat any reversible causes or medical causes
Sleep hygiene as appropriate
Physiotherapist as appropriate
Respiratory physician as appropriate
Endocrinologist as appropriate
8. CHEMO BRAIN/BRAIN FOG
Cognitive dysfunction related to cancer and/or
Cancer treatments
Screen for reversible causes (e.g., insomnia/endocrine/vitamin deficiencies/hormonal imbalances)
Consider brain imaging if brain metastases suspected
Offer validation of symptom experience
Practical advice on coping such as taking notes, forming routines
Cognitive training such as brain games
Referral to neurologist
Referral to geriatrician or early dementia clinic or equivalent as appropriate
Speech therapist or occupational therapist as appropriate
9. METABOLIC SYNDROME/HYPERTENSION/HYPERLIPIDAEMIA
Co-occurrence of metabolic risk factors for T2 DM and cardiovascular disease (CVD)
CVD = Hypertension, hyperglycaemia, dyslipidaemia
Review medical history medication/treatment history
Check blood pressure, pulse rates, height and weight
Screen for cardiovascular disease risk assessment and counselling
Consider ECG and 2D Echo assessment
Screen for diabetes and high cholesterol
Advocate for healthy range BMI 18.5 – 24.9 kg/m2
Advocate for healthy lifestyle habits (e.g., physical activity, balanced diet)
2-3 sessions/week of resistance training
at least 150-300 minutes of moderate-intensity activity or 75 minutes of vigorous-intensity activity; or equivalent
Advocate for quitting smoking
Refer dietitian/nutritionist
Refer physiotherapist
Consider referral to endocrinologist/cardiologist as indicated
10. ANXIETY/PANIC/DYSTHMYIA/DEPRESSION
Anxiety
Difficult to control excessive anxiety & worry and ≥3 of following:
Restlessness/on edge, easily fatigued, difficulty concentrating, mind going blank, irritability, muscle tension, sleep disturbance
Panic
Sudden intense fear/discomfort with accompanying symptoms of palpitations, sweating, trembling, breathlessness, nausea, diarrhoea, vasovagal symptoms, chills or heat sensations, paresthesia, loosing sense of reality, fear of losing control/dying
Depression
Having ≥5 of the following for at least 2 weeks:
Depressed, sad, empty, hopeless mood or appearance
Loss of interest or pleasure in activities
Weight loss or gain
Sleep disturbances
Psychomotor agitation or retardation
Lack of energy
Feeling worthless or excessive guilt
Diminished concentration or indecisiveness
Thoughts of death or suicidal ideation
Assess for suicide risk and manage accordingly
Screen for depression/PTSD/mania/psychosis
Screen with GAD-7/Brief Patient Health Questionnaire
Assess for endocrine/hormonal imbalances
Review diet, and consider reducing stimulants such as caffeine
Non-pharmacologic stress-relieving techniques (e.g., yoga and meditation)
Address root cause (e.g., pain)
Encourage exercise and physical activity
Cognitive behavioral therapy
Pharmacologic techniques if the above cannot help
Suicide precautions/managements as appropriate
Psychologist
Psychiatrist
If there is active suicidal ideation, there is a need to actively intervene
11. INSOMNIA
Difficulty falling asleep OR staying asleep OR waking up too early
Usually for ≥3 months
Occurs at least 3 times per week
Assess for sleep practices and advise sleep hygiene
Sleep journal
Assess for medications that may affect sleep
Non-pharmacologic interventions by addressing root cause (such as pain)
Sleep hygiene advice
Pharmacology interventions as per guidelines
antihistamines
benzodiazepines
Consider referral to sleep specialist
12. NUTRITION (EITHER OVER OR UNDER) & WEIGHT MANAGEMENT
Can use BMI as a target
Healthy lifestyle
Maintenance of adequate physical activity
Healthy balanced diet
Gastrointestinologist if there is concern of dysmotility/absorption
Psychiatrist/psychologist should there be a concern of body dysmorphia/eating disorder
Refer back to oncologist should there be a concern with anatomy, possibly relating to cancer history
13. CARDIAC TOXICITY
Cardiac dysfunction that occurs as a result of cancer treatment (including chemotherapy, targeted therapy, radiotherapy etc)
Screen through oncological history and treatment
Screen for cardiovascular risk factors and treat accordingly
ECG, 2D Echo, CK/CKMB/Troponins/BNP
Chest X-ray
Blood tests screening for hormonal/endocrine abnormalities
Advocate for healthy lifestyle including physical activity and balanced diet
Stop smoking
Maintain healthy BMI
Cardiologist
Dietitian/nutritionist
Consider respiratory physician referral if no evidence of structural heart disease found, but patient is symptomatic
Refer back to oncologist if symptoms persist
14. LYMPHOEDEMA
Occurs when fluid accumulates in the interstitial tissue, resulting in limb swelling or swelling in other areas such as neck/trunk, or genitals
Reports of feeling heavy/limb fatigue
Screen for BMI
Screen for haemodynamic circulation
Regular screening via limb volume measurements
Weight control
Elevation of affected limb
Regular exercises that help with motion/mobility and flexibility
Survivor lymphoedema education
Self-care management, skin care, self-bandage
Compression garments
Medical procedures such as venepuncture/blood pressure measurement to avoid on affected limb if possible
Referral to physiotherapist
Referral to occupational therapist
Consider referral back to lymphoedema therapists at tertiary hospitals
Consider referral to lymphoedema surgeon
Refer back to oncologists if new lymphadenopathy
15. CHRONIC PAIN
Pain can be related or unrelated to underlying cancer (e.g., Pain can be due to previous zoster infection as a result of poor immunity while on chemotherapy)
Comprehensive pain assessments to evaluate if this is new or old
Consider specific pain syndromes
Consider multi-modality approach to pain management
If pain is acute, rule out oncologic emergency or other acute non-cancer emergencies such as appendicitis
Treat etiology of pain
Non-opioid adjuvant analgesics
Non-pharmacologic interventions such as heat/cold massage, acupuncture, physical/occupational therapies
Opioid treatment if necessary
Consider chronic pain team
Consider rehabilitation medicine
Consider interventional radiologist if necessary (such as for nerve blocks)
Consider palliative care referral
Consider other referrals as appropriate, depending on site and etiology of pain
16. SECONDARY CANCERS
A development of a new cancer
Consider a repeat of CT scans and basic end-organ blood tests if suspicion is low
However, if suspicion is high it would be better to get these investigations done with the oncologist
Review through cancer history and also treatment history
Should there be a suspicion of cancer relapse or a development of a new cancer, it is always best to refer back to the primary oncologist for an evaluation within 2 weeks
*Definitions as adapted/taken from NCCN Guidelines Version 1.2023: Survivorship*
Ideally, when a patient is discharged from a cancer centre, this should be accompanied with an individualised care plan. This care plan should include details of the cancer and treatment, including what needs to be monitored at what intervals. There should also be clear guidelines on when to refer back, with clear points of contact to reduce the difficulties in referring back to the oncologist.
Should there be no such care plans given, it would be a good idea to get in touch with the primary oncologist for a full report. This will definitely help in the long-term holistic management of the patient, and aid to keep the patient in primary care. It would also be helpful to consider referring young adults cancer survivors to cancer survivorship clinic dedicated for young adult cancer survivors.
A patient’s cancer journey does not start and stop with a cancer diagnosis and treatment. Once a person has been diagnosed with cancer, it will likely result in a lifelong change. It will inevitably lead to a lifetime heightened risk of anxiety and fear, with the need to be more prudent/cautious with health. Inevitably, survivors are also at heightened risks of long-term toxicities and secondary malignancies.
We would want to be able to return our survivors back into community well and be able to function. This need to be able to right-site them is imperative, helping the country to move towards its goal of HealthierSG.
NCCN Guidelines Version1.2023 Survivorship
NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology
Cancer Statistics article from NCCS website (https://www.nccs.com.sg/patient-care/cancer-types/cancer-statistics)
UpToDate – Metabolic Syndrome (insulin resistance syndrome or syndrome X)
Asst Prof Eileen Poon is a consultant with Medical Oncology at NCCS. She sees lymphoma, sarcoma and melanoma patients. Her passion is in working with Adolescents and Young Adults (AYAs) with cancer. This is a field in its infancy, especially in Asia and combines both the science and art of Oncology and Medicine. Dr Eileen is looking to revolutionise the care that AYAs receive to empower them to live well through a cancer diagnosis.
GPs can call the SingHealth Duke-NUS Blood Cancer Centre for appointments at the following hotlines, or click here to visit the website:
Singapore General Hospital: 6326 6060
Sengkang General Hospital: 6930 6000
KK Women's and Children's Hospital: 6692 2984
National Cancer Centre Singapore: 6436 8288
Tags: WHOLE BODY
Tags: