Cancer Pain Syndromes Flashcards
Acute pain with diagnostic procedures: Lumbar Puncture
Lumbar puncture headache
- Best characterised acute pain syndrome associated with a diagnostic intervention
- Believed to be due to reducing in CSF volume (ongoing leaking through the defect in the dural sheath) and compensatory expansion of the pain-sensitive intracerebral veins
Presentation
- Delayed development of a positional headache (worse when upright)
- Typically hours to days after the procedure
- Pain correlates to the calibre of the LP needle
- Dull, occipital dicomfort
- May radiate to the frontal region or the shoulders
- Associated with nausea and dizziness
- Duration is 1-7 days
Prevention
- Longitudinal insertion of the needle bevel to induce less trauma to the longitudinal elastic fibres in the dura (if patient is lateral recumbant, bevel up, if patient is sitting, bevel pointed laterally)
- Use of non-traumatic, conical tipped needles with a lateral opening
- Recumbency after LP (controversial)
Management
- Rest, hydration, analgesics
- Epidural blood patch if persistent
- IV or oral caffeine
Acute pain with diagnostic procedures: Transthoracic needle biopsy
Severe pain may occur if the underlying diagnosis is a neurogenic tumour
Otherwise, not typically a harmful/painful procedure
Acute pain with diagnostic procedures: Transrectal prostatic biopsy
Transrectal ultrasound guided prostate biopsy has a low rate of severe pain, but may occur in slightly less than 20% of patients
- If present, pain may persist up to 4 weeks after biopsy
Prevention:
- Periprostatic lidocaine infiltration
- Intrarectal introduction of 2% lidocaine cream
- Unilateral pudendal nerve block
Acute pain with diagnostic procedures: Mammography
- Pain related to breast compression, may be moderate or rarely severe
- Typically of short duration
- Requires that it be addressed appropriately or patients may refuse future mammograms
Prevention:
- Reduce compression or allow patient-controlled compression
Acute pain with therapeutic interventions: Postoperative pain
- Essentially universal without adequate treatment
- Post op pain that exceed normal duration or severity should prompt evaluation for possibility of infection or other complications
Acute pain with therapeutic interventions: Radiofrequency tumour ablation
- Most commonly used for liver mets, but also adrenal, renal, lung, bone, and breast.
- Percutaneous ablation of liver tumours may be associated with severe RUQ pain, may radiate to the right shoulder
Acute pain with therapeutic interventions: Cryosurgery
- Most commonly for skin, cervical, and prostatic tumours
- Local painful reaction that decreases in severity over 2-7 days
Cervical
- Acute, cramping pain syndrome
- Severity related to duration of the freeze period
- Not diminished by prophylactic NSAIDs
Prostate
- Uncommonly, may result in persistent pain (?consider abscess formation
Acute pain with analgesic techniques: Local anesthetic
- Intradermal and subcutaneous infiltration of lidocaine produces transient burning before onset of analgesia
Prevention:
- Buffered solutions
- Warming the solution
- Note that slower injection does not diminish injection pain
Acute pain with analgesic techniques: Opioid inection pain
- IM and subcut injections can be painful
- IM injection is not recommended if repetitive dosing is required
- SC injection pain is influenced by volume injected and chemical characteristics
Acute pain with analgesic techniques: Opioid headache
- Rarely - reproducible generalised headache after opioid administration
- May be due to opioid-induced histamine release
Acute pain with analgesic techniques: Spinal opioid hyperalgesia syndrome
- Intrathecal/epidural injection of high opioid doses may be complicated by pain (typically perineal, buttock, or leg), hyperalgesia, segmental myoclonus, piloerection, and priapism
- Resolves with discontinuation of the infusion
Acute pain with analgesic techniques: Spinal Injection pain
- Back, pelvic, or leg pain that may occur due to epidural injection or infusion
- Incidence as much as 20%
- May be due to compression of an adjacent nerve root by the injected fluid or pericatheter fibrosis in the case of intrathecal injections
Acute pain with chemotherapy infusion: Intravenous infusion pain
Common issue. Pain syndromes related to IV infusion of chemotherapy:
- Venous spasm (pain not associated with inflammation, may be modified by a warm compress or rate of infusion)
- Chemical phlebitis (especially with potassium, vinorelbine - manifests as linear erythema)
- Vesicant extravasation (intense pain, followed by desquamation and ulceration)
- Anthracycline-associated flare (e.g. with doxorubicin - local urticaria and occasional pain or stinging)
Acute pain with chemotherapy infusion: Hepatic artery infusion pain
- Cytotoxic drugs can be infused directly into the hepatic artery for patients with liver mets
- Often associated with the development of diffuse abdo pain, may lead to persistent pain if there is a continuous infusion
- Normally, resolves with discontinuation of the infusion but complications can occur
- May be possible to reduce the dose/rate of the infusion
Complications:
- Gastric ulceration or erosions
- Cholangitis
Acute pain with chemotherapy infusion: Intraperitoneal chemotherapy pain
Presentation
- Transient mild abdo pain, associated with sensations of fullness or bloating after intraperitoneal chemo (25% incidence)
- Moderate or severe pain requiring opioids or cessation of tx (25% incidence), usually due to chemical serositis or infection, but may be due to abdo distention or intercostal nerve irritation
Always consider infectious peritonitis if there is pain associated with fever and leukocytosis
Acute pain with chemotherapy infusion: Intravesical chemo or immunotherapy
Intravesicular BCG therapy for transitional cell ca of the bladder typically leads to transient bladder irritability syndrome
Symptoms:
- Frequency
- Micturition pain
More rarely, can lead to polyarthritis or full blown Reiter’s syndrome, or localised regional or systemic infections with abscess formation
Intravesicular doxorubicin may lead to chemical cystitis
Acute pain with chemotherapy toxicity: Mucositis
- Common with myeloablative chemo and radiation for BMT
- Less common with standard intensity therapy
Most common agents:
- Cytarabine
- Doxorubicin
- Etoposide
- 5-FU
- Methotrexate
Increased risk with:
- Pretreatment oral pathology
- Poor dental hygenie
- Youth (?higher epithelial mitotic rate)
May be complicated by infection, especially candida albicans and herpes simplex in neutropenic patients
Acute pain with chemotherapy toxicity: Steroid-induced perineal discomfort
- Transient burning sensation in the perineum is described by some patients following rapid infusion of large doses of dex (e.g. 20-100mg)
- Severity is variable
- Prevent with slower infusion
Acute pain with chemotherapy toxicity: Steroid withdrawal pseudorheumatism
- Diffuse myalgias, arthralgias, and tender muscles and joints
- Occurs with either rapid or slow tapers and may occur i patients taking drugs for long or short periods of time
Treatment
- Restart steroids at previous dose and taper more slowly
Acute pain with chemotherapy toxicity: Painful peripheral neuropathy
Associated agents:
- Vinca alkaloids (vincristine, vinorelbine)
- Cisplatin
- Oxaliplatin
- Paclitaxel
Presentation
- May be acute
- Distribution depends on agent
Vincristine: Orofacial pain in distribution of trigeminal and glossopharyngeal nerve (typically self limiting, lasting for 1-3 days only)
Vinorelbine: Mild paraesthesias in 20% (severe neuropathy is rare)
Paclitaxel: Dose related, subacute in onset, resolution after completion of therapy in most (not all) cases
Oxaliplatin: Acute neurotoxicity (paraesthesias and dysesthesias of the hands, feet, perioral region, as well as muscle cramps)
Vinorelbine neuropathy
Vinorelbine: Mild paraesthesias in 20% (severe neuropathy is rare)
Paclitaxel neuropathy
Paclitaxel: Dose related, subacute in onset, resolution after completion of therapy in most (not all) cases
Oxaliplatin neuropathy
Oxaliplatin: Acute neurotoxicity (paraesthesias and dysesthesias of the hands, feet, perioral region, as well as muscle cramps)
May be transient, but can persist as a cumulative toxicity
Vincristine neuropathy
Vincristine: Orofacial pain in distribution of trigeminal and glossopharyngeal nerve (typically self limiting, lasting for 1-3 days only)
Acute pain with chemotherapy toxicity: Intrathecal methotrexate
- Intrathecal methotrexate used for leukemia or leptomeningeal mets
- Produces acute meningitic syndrome in 5-50% (HA is a prominent symptom), associated with nausea, vomiting, nuchal rigidity, fever, irritability, and lethargy
- Symptoms begin hours after treatment and persist for several days
Increased risk:
- Multiple intrathecal injections
- Treatment for leptomeningeal mets
Tends not to recur with subsequent injections
Acute pain with chemotherapy toxicity: L-asparaginase
- Systemic administration of L-asparaginase for acute lymphoblastic leukemia may cause a thrombosis of cerebral veins or dural sinuses (1-2% of patients)
- HA is most common initial symptom, also seizures, hemiparesis, delirium, vomiting, or cranial nerve palsies
- Diagnosis is with MRI (likely MRA?)
Acute pain with chemotherapy toxicity: Transretinoic acid therapy
- Trans-retinoic acid therapy is used in the treatment of acute promyelocytic leukemia (APML)
- May cause severe headache (pseudotumour cerebri induced by hypervitaminosis A)
- May also produce a syndrome of diffuse bone pain (may be due to marrow expansion). Pain is generalised, of variable intensity, and associated with transient neutrophilia
Acute pain with chemotherapy toxicity: Taxol-induced myalgia/arthralgia
Paclitaxel
- Diffuse arthralgias and myalgias in 10-20% of patients
- Related to individual doses, while cumulative dose/infusion duration has a less clear relationship
Presentation:
- Diffuse pain in joints and muscle 1-2 days after the infusion, lasting for median of 4-5 days
- Pain commonly located in back, hips, shoulders, thighs, legs, feet
- Exacerbated by weight bearing, walking, or tactile contact
May be prevented by steroids
Acute pain with chemotherapy toxicity: 5-FU anginal chest pain
- Patients receiving 5-FU may develop ischemic chest pain
- Risk is felt to range between 2-20%, risk higher with continuous infusion than with bolus therapy, and risk is higher in those with pre existing CAD
- Likely due to coronary vasospasm
- Similar reports with capecitabine (5-FU prodrug)
Acute pain with chemotherapy toxicity: Hand food syndrome
Hand food syndrome (aka palmar planter erythrodysesthesia)
Associated with:
- 5-FU continuous infusion
- Capecitabine
- Liposomal doxorubicin
- Paclitaxel
- Sorafenib and sunitinib
- Everolimus
Presentation:
- Tingling or burning sensation in the palms and soles, followed by development of an erythematous rash
Management
- Discontinue therapy or dose reduce
- Treatment with pyridoxine for resolution of the lesions
Acute pain with chemotherapy or hormonal toxicity: Gynecomastia
- Painful gynecomastia can occur as a delayed complication of chemotherapy
- Testicular cancer is the most common underlying cancer, but others may be associated as well
- May also be seen with anti-androgen therapies for prostate cancer (most commonly associated with bicalutamide)
Presentation
- Post-chemo, typically develops after latency of 2-9 months
- Resolves spontaneously within a few months (but may occasional persist)
Acute pain with chemotherapy toxicity: Chemotherapy induced acute digital ischemia
Raynaud’s or transient ischemia of the toes, some case reports of gangrene
Associated agents: - Bleomycin - Vinblastine - Cisplatin (combo of three used for testicular cancer)
Acute pain with chemotherapy toxicity: Chemotherapy induced tumour pain
- Associated with vinorelbine (7%)
- Pain begins within a few minutes of infusion, moderate to severe, and requires analgesia
Prevention: Ketorolac may be helpful
Acute pain with hormonal therapy: LHRH tumour flare in prostate cancer
- Initiation of LHRH agonist therapy for prostate cancer produces transient symptoms in 5-20% of patients
- Short term, creates a transient increase in LH/testosterone, then suppresses levels
Presentation:
- Exacerbation of bone pain or urinary retention
- Case reports of cord compression and sudden death
- Occurs within first week of therapy, lasts 1-3 weeks in absence of an androgen antagonist
Prevention:
- Co-administration of an androgen antagonist
Acute pain with hormonal therapy: Hormone induced pain flare in breast cancer
- Initiation of any hormonal therapy for metastatic breast cancer can be complicated by a sudden onset of diffuse MSK pain
Presentation
- Onset within hours to weeks of initiation of therapy
- Erythema around cutaneous mets
- Changes to LFTs
- Hypercalcemia
- Increased PET avidity
Mechanism not understood, but may be predictive of later tumour response to hormonal therapy
Acute pain with hormonal therapy: Aromatase inhibitor induced arthralgias
- AIs may cause multifocal arthralgias in 10-20% of patients
Presentation:
- Early morning stiffness and hand/wrist pain
- Variable intensity, may interfere with activity
Management
- Occasionally severe enough to justify discontinuation
- NSAIDs often poorly effective
- May be associated with osteoporosis - vit D and targeted therapies being investigated
Acute pain with Immunotherapy: Interferon-induced acute pain
- Essentially all patients treated with interferon experience acute syndrome
Presentation
- Fever
- Chills
- Myalgias
- Arthralgias
- Headache
Onset is shortly after initial dosing, typically improves with continued administration
Prevention:
- Premedicate with acetaminophen
Acute pain with bisphosphonates: Bone Pain
Infusion with IV bisphosphonates may be associated with multifocal bone pain and/or myalgia
Occurs within 24 hours of infusion, may last up to 3 days
Variable, may be severe and require analgesia
Self-limiting
Acute pain associated with growth factors
Typically from GCSF or Granulocyte-macrophage colony stimulating factor (GMCSF)
Presentation
- Mild to mod bone pain
- Constitutional symptoms (fever, headache, myalgias) during administration
- Pain intensity variable, may be severe
Management
- Co-administration with dex
Acute pain associated with radiotherapy
- Incident pain during transport and positioning
- Acute radiation toxicity (inflammation and ulceration of skin or mucous membranes)
- Window specific
Acute pain associated with radiotherapy: Oropharyngeal mucositis
- Invariable at doses above 1000cGy
- Severity of oral pain is variable, but may impact PO intake
- May last several weeks post treatment
Acute pain associated with radiotherapy: Acute radiation enteritis and procotocolitis
- Incidence as high as 50% in patients receiving abdominal/pelvic rads
Presentation:
- Small intestine - cramping, nausea, diarrhea
- Proctocolitis - tenesmal pain, diarrhea, mucous discharge, bleeding
Self-limited, typically resolves after completion but may slowly resolve over 2-6 months
Acute enteritis increases risk of late-onset radiation enteritis
Acute pain associated with radiotherapy: Early- onset brachial plexopathy
- Seen in breast CA patients after rads to the chest wall and adjacent nodal areas, as well as Hodgkin’s lymphoma
- Transient, self-limiting
Presentations:
- Paresthesias in brachial distribution
- Pain and weakness (less common)
Not predictive of delayed onset, progressive plexopathy
Acute pain associated with radiotherapy: Subacute radiation myelopathy
- Uncommon, may occur following rads to extra spinal tumours
- Seen in Head and Neck cancers and with Hodgkin’s Lymphoma
Presentation:
- Lhermitte’s sign (shock like pains in the neck precipitated by neck flexion)
- Pain may radiate down spine, into extremities
- Onset weeks to months post rads, then resolves over 3-6 months
Acute pain associated with radiotherapy: Radiotherapy induced pain flare
- Palliative rads to bony mets can lead to a pain flare in 30-40% immediately post rads
- Occurs 1-2 days post rads, then typically resolves after 3-5 days
- May be predictive of good analgesic response to rads
Prevention:
- Single 8mg dose of dex prior to rads (reduces severity and incidence)
Acute pain associated with herpetic neuralgia
- Higher incidence in cancer patients, especially in heme malignancies and those on immunosuppressive therapies
Presentation
- Continuous or lancinating pain
- Typically resolves within 2 months, otherwise considered post-herpetic neuralgia (more likely in disseminated infection)
- Dermatomal location of correlates with the site of malignancy
Acute pain associated with vascular events: Acute thrombosis
- Thrombosis is a frequent complication and cause of death in malignancy
- Due to prothrombotic factors in cancer (tumour cells, products interacting with platelets/coagulation)
- Highest association with bone, ovary, brain, and pancreas
Acute pain associated with vascular events: Lower extremity DVT
Presentation
- Pain (Variable, often a dull cramp or diffuse heaviness, worse with standing or walking)
- Swelling
- Palpable cord
- Erythema
- Warmth
Rarely, may see ischemic DVT - tissue ischemia or frank gangrene (severe pain, extensive edema, cyanosis). IV thrombolytic may be most appropriate - consult heme, mortality rate is high.
Acute pain associated with vascular events: Upper extremity DVT
Presentation
- Edema
- Dilated collateral circulation
- Pain (typically in arm)
Etiology
- Central venous catheterisation
- Extrinsic compression by tumour
Acute pain associated with vascular events: SVC Obstruction
- Typically due to external compression of the SVC by enlarged mediastinal LN
- Associated with lung cancer and lymphoma most common
Presentation:
- Facial swelling
- Dilated neck and chest collaterals
- Chest pain
- Headache
- Mastalgia
Acute pain associated with vascular events: Acute mesenteric vein thrombosis
- Associated with hypercoagulable states or extrenisic compression by adenopathy
Presentation:
- Acute abdominal pain
- May be incidental finding
Management:
- Bowel rest
- IVF
- IV anticoagulation
- May require lytic
Acute pain associated with vascular events: Superficial thrombophlebitis
- Common in cancer
Presentation
- Development of a palpable tender cord with erythema
- US can rule out DVT
- Trousseau’s syndrome is migratory thrombophlebeitis (recurrent, migratory pattern and involvement of superficial veins, often in usual sites such as arm or chest) - sign of malignancy, especially gastric, pancreatic, and lung CA
Chronic pain: Bone pain
Differential diagnosis:
- Bony mets (often from lung, breast, prostate) - causes pain in 75% of patients
- Osteoporotic fractures
- Focal osteonecrosis (idiopathic or secondary to chemo)
- Osteomalacia
- Paraneoplastic osteomalacia (rare)
Multifocal bone pain
- Bony mets
- Generalised pain due to replacement of the bone marrow (especially in heme malignancies - dx with MRI or PET, not seen on XR or bone scans)
Vertebral syndromes
- Bony mets or multilevel involvement
Chronic bone pain: Atlantoaxial destruction and odontoid fracture
Atlantoaxial destruction and odontoid fracture
Presentation:
- Nuchal or occipital pain
- Radiates over posterior aspect of the skull to the vertex
- Exacerbated by movement of the neck (especially flexion)
- May progress to secondary subluxation and cervical cord compression (early involvement of upper extremities, deficits slowly progress to involve sensory, motor, autonomic function)
Chronic bone pain: C7-T1 Syndrome
C7-T1 Syndrome
- Invasion of the C7 or T1 vertebrae can result in pain referred to interscapular region
- Caution to not miss lesion if only getting XR of area caudal to C7/T1
- May be difficult to see on radiographs due to mediastinal shadows/overlying bone - get XR of cervical and thoracic spine if interscapular pain is present
Chronic bone pain: T12-L1 (Thoracolumbar junction syndrome)
T12-L1 (Thoracolumbar junction syndrome)
- Referred pain to ipsilateral iliac crest or sacroiliac bone
- Ensure spine is included in imaging as pelvic XRs can miss the source of the pain
Chronic bone pain: Sacral syndrome
Sacral syndrome
Presentation:
- Severe focal pain radiation to buttocks, perineum, or posterior thighs
- Excerbated by sitting or laying, relieved by standing/walking
- Destruction of the sacrum, and tumour may extend laterally to involve muscles rotating the hip
- Can produce severe incident pain induced by hip motion or malignant pyriformis syndrome (buttock or posterior leg pain exacerbated by internal hip rotation)
Chronic bone pain: Back pain and epidural compression
Back pain and epidural compression
- Pain typically first symptom, slowly progressive, and may preceded neuro symptoms for some time
- Effective treatment is important to ensure complications and further deficits are prevented
- Most important determinate of efficacy of treatment is degree of neuro impairment when therapy is initiated
- MRI to diagnose, preferred modaility. CT is next best.
Upper Motor neuron symptoms (spinal cord compression)
- Pain excerbated by recumbency, cough, sneeze, strain
- Lhermitte’s sign
- Spasticity
- Hyperreflexia below lesion
- Weakness (symmetric - typically develops to paralysis within 7 days!)
- Numbness/parasthesias (symmetric, ascending, upper level of sensory loss may correspond to location of tumour)
- Sphincter dysfunction (later)
- Spinal tenderness to percussion
Lower Motor neuron symptoms (Cauda equina)
- Hypotonia
- Areflexia or hyporeflexia
- Weakness (symmetric)
- Numbness/parasthesias (especially saddle anesthesia)
- Sphincter dysfunction (later)
- Fasciculations
Consider cerebral mets if there are asymmetric UMN findings!
Sclerotic bone lesions (description, common causes)
Sclerotic lesions/osteoblastic lesions
- Typically more slow growing with sclerosis (bone forming)
- Often seen in breast cancer, prostate CA, SCLC, Hodgkin Lymphoma
- Elevated ALP is a marker of osteoblast activity
Lytic bone lesions (description, common causes)
Lytic lesions/osteoclastic lesions
- Typically more rapid with lysis (bone destructive)
- Most common feature of multiple myeloma, breast cancer, renal cell, melanoma, NSCLC, thyroid cancer
Chronic bone pain: Hip joint syndrome
Hip joint syndrome
- Tumour involvement of the acetabulum or head of the femur
- Produces localized hip pain aggravated by weight bearing and movement of the hip, may radiate to knee or medial thigh
- Evaluate with CT or MRI
Ddx:
- Avascular necrosis
- Radicular pain (L1)
- Occult infections
Chronic bone pain: Acrometastases
Acrometastases
- Mets in hands and feet (rare)
- More often the larger bones in the feet (os calcis or talus)
- Vague symptoms, may vague others (RA, osteomyelitis, etc.)
Chronic arthritic pain: Hypertrophic Pulmonary osteoarthropathy
Hypertrophic Pulmonary osteoarthropathy (HPOA)
- Paraneoplastic syndrome
- Clubbing of the fingers
- Periostitis of the long bones
- Rheumatoid like polyarthritis
- Most commonly associated with NSCLC, but may be associated with pulmonary mets from other sites
Presentation:
- pain, tenderness, and swelling in the knees, wrists and ankles
- Onset typically subacute and may precede cancer dx by several months
- Radiographical appearance
Management:
- May regress with anti tumour therapy
- Bisphosphonates
Chronic muscle pain: Muscle cramps
Muscle cramps
- Typically caused by an identifiable abnormality (neural, muscular, biochem)
- E.g. peripheral neuropathy, nerve root/plexus pathology, polymyositis, hypomagnesemia
Chronic muscle pain: Skeletal muscle tumours
- Pain may arise from soft tissue sarcomas arising from fat, fibrous tissue, or skeletal muscle
- Skeletal muscle mets are unusual, but may occur at sites of prior muscle trauma
- Typically painful but may present with persistent ache
Chronic headache: Intracerebral tumour
- HA is often the first presenting symptom of brain tumour or mets
- Often associated with dizziness
- Pain presumably preduced by traction to pain sensitive vascular/dural tissues
- More pain with multiple mets and posterior fossa mets
Chronic headache: Leptomeningeal Mets
Leptomeningeal mets:
- Diffuse or multifocal involvement of the subarachnoid space by tumour
- Incidence of 1-8% in systemic cancer
- Acute lymphocytic leukemia and Non-Hodgkin’s are often culprits
- Breast adenoca and SCLC ca also common
Presentation:
- HA (Variable, may be associated with changes in mental status, N/V, tinnitus, or nuchal rigidity)
- Cranial nerve palsies (diplopia, hearing loss, numbness, visual impairment)
- Radicular pain in low back and buttocks
- Less commonly - seizures, papilloedema, hemiparesis, ataxia, confusion
Investigation:
- Gad enhanced MRI
- 90% sensitive (10% false negatives!)
- CSF analysis - elevated protein, low gluc, lymphocytes, positive cytology (but may require repeated testing to confirm)
Prognosis:
- If untreated, progressive neurologic dysfunction and death in 4-6 weeks
Treatment:
- Rads
- Steroids
- Intrathecal chemo
Chronic pain due to base of skull mets: Orbital syndrome
Orbital mets
- Progressive pain in the retro-orbital and supra orbital area of the affected eye
- Blurred vision and diplopia
Presentation
- Proptosis
- Chemosis
- External opthalmoparesis
- Ipsilateral papilloedema
- Decreased sensation in the opthalmic division of the trigeminal nerve
Chronic pain due to base of skull mets: Parasellar syndrome
Parasellar syndrome:
- Unilateral supraorbital and frontal HA
- May be associated with diplopia
- May have opthalmoparesis or papilloedema
- Visual field testing may show hemianopsia or quadrantinopsia
Chronic pain due to base of skull mets: Middle cranial fossa syndrome
Middle cranial fossa syndrome:
- Facial numbness
- Paresthesias
- Pain (usually referred to cheek or jaw, trigeminal branch distribution)
- Pain is dull, continual ache, may be paroxysmal or lancinating
- Hypoesthesia in trigeminal nerve, weakness in ipsilateral muscles of mastication
Chronic pain due to base of skull mets: Jugular foramen syndrome
Jugular foramen syndrome
- Hoarseness or dysphagia
- Pain referred to the ipsilateral ear or mastoid region, may be referred to ipsilateral neck or shoulder
- Ipsilateral Horner’s syndrome (mioisis, ptosis, anhydrosis)
- Paresis of the palate, vocal cord, SCM, or trapezius
Chronic pain due to base of skull mets: Occipital condyle syndrome
Occipital condyle syndrome
- Unilateral occipital pain worsened with neck flexion
- Neck stiffness
- Variable pain intensity, can be severe
On exam:
- Head tilt
- Limited ROM in neck
- Tenderness over occiputo-nuchal junction
- Ipsilateral hypoglossal nerve paralysis and SCM weakness
Chronic pain due to base of skull mets: Clivus syndrome
Clivus syndrome
- Vertex headache, often exacerbated by neck flexion
- May also have CN VI-XII dysfunction and extend bilaterally
Chronic pain due to base of skull mets: Sphenoid sinus syndrome
Sphenoid sinus mets
- Bi frontal or retroorbital pain
- May radiate to temporal regions
- Nasal congestion and dipolopia
- PE often normal, but unilateral or bilateral sixth nerve paresis can occur (impaired eye abduction)
Painful cranial neuralgias: Glossopharyngeal neuralgia
Glossopharyngeal neuralgia
- Reported in patients with leptomeningeal mets, jugular foramen syndrome, or head and neck cancer
Presentation
- Severe pain in the throat or neck, may radiate to the ear or mastoid region
- May be worsened by swallowing
- Pain may be associated with sudden orthostasis and syncope
Painful cranial neuralgias: Trigeminal neuralgia
Trigeminal neuralgia
- Pain may be continual, paroxysmal, or lancinating
- May be triggered by chewing, brushing teeth, speaking
- May be induced by tumours in middle or posterior fossa or leptomeningeal mets
- Any cancer patient developing trigeminal neuralgia should be investigated for mets
Painful Otalgia
- Sensation of pain in the ear - may be primary or referred from cranial nerves
- Causes: acoustic neuroma, mets to the temporal bone, infratemporal fossa
- May also be referred from oropharyngeal/hypopharyngeal tumours
Eye pain
- May occur due to choroidal mets if accompanied by blurring vision
- More commonly, mets to the bony orbit, rectus muscles, optic nerve, or caverbus sinus
PRES
- Migraine like headache, conscious disturbance, seizure, cortical vision loss with edema in the posterior regions of the brain on imaging
- Posterior reversible encephalopathy syndrome - most commonly seen in Hodgkin’s disease
Neuropathic pain - Peripheral Nervous System: Painful radiculopathy
Painful radiculopathy
- May occur from any process that compresses, distorts, or inflames nerve roots
- Important presentation of epidural tumours and leptomeningeal mets
Neuropathic pain - Peripheral Nervous System: Post-herpetic neuralgia
- Neuralgia that persists four beyond four months in the same distribution of the original herpes zoster
- Thoracic, cervical, trigeminal nerves most commonly affected
- High prevalence in the cancer population
- Pain may be burning, sharp, or stabbing and constant or intermittent, may also be accompanied by sensory deficits
Neuropathic pain - Peripheral Nervous System: Cervical plexopathy
Cervical plexopathy
- Cervical plexus injury is most commonly due to tumour infiltration or treatment to neoplasms in the area
- May also be due to direct invasion or tumour compression of the cervical plexus from mets of the cervical LN or primary head and neck cancer
- Pain typically experienced in preauricular or postauricular regions, or anterior neck
- May be referred to lateral aspect of the face, head, or ipsilateral shoulder
- Can be associated with ipsilateral Horner’s syndrome (miosis, ptosis, anhydrosis) or hemidiphragmatic paralysis
CT or MRI of neck and C spine to diagnosis
Neuropathic pain - Peripheral Nervous System: Malignant brachial plexuopathy
Malignant brachial plexopathy
- Most prevalent cause of brachial plexopathy
- Most commonly seen in lymphoma, lung ca, or breast ca
- Invading tumour arises from adjacent lymph nodes or lung
Presentation
- Pain typically occurs first, prior to neurologic signs or symptoms
- More commonly involves C7, C8, T1 (reflected in pain distribution affecting elbow, medial forearm, fourth and fifth fingers)
- Lower plexus (C7 - T1) = pain and paresthesias in shoulder, elbow, hand, 4th and 5th finger
- Upper plexus (C5-C6) = pain in shoulder, biceps, elbow, hand, paresthesias
- Pain typically aching, may also be constant or lancinating
Diagnosis
- MRI likely superior to CT
- May require EMG
- PET may help to differentiate tumour progression from radiation-related fibrosis, also note that patients with radiation-induced plexopathy typically have LESS pain
Prognosis
- High risk of epidural extension as the neoplasm grows medially and invades vertebrae or tracks along nerve roots
- Watch for Horner’s syndrome, panplexopathy, or vertebral damage on imaging
Neuropathic pain - Peripheral Nervous System: Radiation induced brachial plexopathy
Radiation-induced brachial plexopathy
- May be early-onset and transient or delayed onset and progressive
Delayed onset progressive brachial plexopathy
- May occur 6 months to 20 years post-rads, if the brachial plexus was included in the window
- Pain is relatively uncommon and not severe if it occurs
- Weakness and sensory changes, especially in the upper plexus
- Associated lymphedema
Diagnosis:
- CT
- EMG (Demyelination on motor nerve conduction studies with widespread myokymia)
Neuropathic pain - Peripheral Nervous System: Malignant Lumbosacral Plexopathy
Malignant Lumbosacral Plexopathy
- Most commonly associated with colorectal, cervical, breast, sarcoma, and lymphoma
- Typically direct invasion from intrapelvic neoplasm, 25% are from mets
Presentation:
- Pain is the first symptom
- Aching, pressure like, or stabbing
- Numbness, paresthesias, weakness weeks to months later
- Common sights include leg weakness involving multiple myotomes, sensory loss crossing dermatomes, reflex asymmetry, focal tenderness, and leg edema
Diagnosis:
- CT or MRI from the L1 vertebral body through the sciatic notch
- MRI likely more sensitive
- If there is any concern for cord compression, ensuring the cord is adequately imaged (e.g. bilat symptoms, incontinence, paraspinal mass)
Neuropathic pain - Peripheral Nervous System: Radiation-induced Lumbosacral Plexopathy
Radiation-induced Lumbosacral Plexopathy
- Uncommon, may occur from 1-30 years after rads
- Presents with progressive weakness and leg swelling, pain not typically a common feature
- Weakness begins in L5-S1 segments, slowly progressive, may be bilateral
- EMG may show myokymic discharge
Painful mononeuropathy: Tumour-related
Tumour related mononeuropathy
- May occur from compression or infiltration of a nerve from tumour arising in an adjacent bony structure
- Most common would be intercostal nerve injury from rib mets
- Sciatica (tumour invasion of sciatic notch)
Painful peripheral neuropathy: Paraneoplastic painful peripheral neuropathy
Paraneoplastic painful peripheral neuropathy
- May be related to injury to the dorsal root ganglion or injury to peripheral nerves
- May present as pain, paresthesias, sensory loss in the extremities, and severe sensory ataxia (associated with SCLC especially)
- Typically develops before tumour is evidence
- May also find coexisting autonomic, cerebellar, or cerebral abnormalities
Diagnosis:
- Anti-Hu antibodies
Hepatic distention syndrome
- Liver capsular pain secondary to tumour growth
- Numerous sensitive structures in the region include the liver capsule, blood vessels, and biliary tract
Presentation
- Right subcostal pain
- Referred pain to right neck or shoulder or in the right scapula
- May result in overlying peritonitis which can result in a palpable or audible rub
Midline retroperitoneal syndrome
Midline retroperitoneal syndrome
- Occurs due to cancers involving the upper abdominal peritoneal structures
- May result in injury to deep somatic structures of the posterior abdominal wall, distortion of pain sensitive connective tissue, vascular and ductal structures, local inflammation, and direct infiltration of the celiac plexus
- Most commonly due to pancreatic cancer or retroperitoneal adenopathy
Presentation:
- Pain in the epigastrum or low thoracic region ot he back
- Diffuse and poorly localised
- Dull, boring in character
- Worse with laying and improved by sitting
Intestinal obstruction pain
- Pain occurs due to smooth muscle contraction, mesenteric tension, and mural ischemia
Presentation:
- Continuous and colicky pain
- Vomiting, anorexia, constipation
Peritoneal carcinomatosis pain
- Pain occurs due to peritoneal inflammation, mesenteric tethering, malignant adhesions, and ascites
- Pain and abdominal distention
Malignant perineal pain
Causes of perineal pain:
- Tumours of the colon or rectum, female reproductive tract, and distal genitourinary system
- May be caused my microscopic perineural invasion by recurrent disease
Presentation:
- Constant and aching pain
- Aggravated by sitting or standing
- May be associated with tenesmus or bladder spasms
Ureteric obstruction pain
- Typically caused by tumour compression or infiltration within the pelvis, but less commonly can be associated with retroperitoneal adenopathy
Presentation
- Dull, chronic flank pain
- Radiation into inguinal region or genitalia
- May be complicated by pyelonephritis
Diagnosis:
- US, CT
Ovarian cancer pain
Ovarian cancer pain
- Moderate to severe chronic abdominopelvic pain (most common symptom of ovarian CA)
- Low back or abdo pain
Lung cancer pain
Lung cancer pain
- May produce visceral pain syndrome (unilateral in most cases)
- May be referred to the shoulder and lower chest
- Early lung CA can generate ipsilateral facial pain (vagal afferent neurons affected)
Tumour-related gynecomastia pain
- Tumours that secrete HCG (Testicular CA) may be associated with chronic breast tenderness
- Approximately 10% of patients with testicular CA have gynecomastia or breast tenderness, higher levels of HCG correlate with gynecomastia
Paraneoplastic pemphigus
Paraneoplastic pemphigus
- Rare mucocutaneous disorder associated with non-Hodgkin’s lymphoma and chronic lymphocytic leukemia
Presentation
- Widespread shallow ulcers
- Hemorrhagic crusting of the lips
- Conjunctival bullae
- Pulmonary lesions (less common)
Paraneoplastic Raynaud’s syndrome
- Reported with lung, ovarian, testicular, and melanoma
Post-chemotherapy pain syndromes: Toxic peripheral neuropathy
Toxic peripheral neuropathy
- Common issue
Presentation
- Painful paresthesias
- Stocking-glove sensory loss (axonopathy)
- Weakness
- Hyporeflexia
- Autonomic dysfunction
- Burning or lancinating pain, may be worsened with contact
Agents
- Vinca alkaloids (vincristine, vinblastine)
- Cisplatin
- Oxaliplatin
- Paclitaxel
Postchemotherapy nerve pain: Avascular necrosis of the femoral or humeral head
AVN
- May occur spontaneously, or as a complication of continuous steroid tx
- Also seen with high dose chemo with BMT
- May be bilateral or unilateral
Presentation
- Most common in the femoral hip, causes pain in the hip, thigh or knee
- In the humeral head, presents as pain in the shoulder, upper arm, or elbow
- Local tenderness may be present over the joint
- Pain worse with movement and relieved by rest
Diagnosis
- Pain precedes radiological changes by weeks to months
- MRI is most sensitive
Treatment
- Analgesia
- DC of steroids
- Sometimes surgery or joint replacement
Postchemotherapy nerve pain: Plexopathy
Chemo Plexopathy
- Lumbosacral or brachial plexopathy may follow cis-platin infusion in tho the iliac artery
- Occurs within 48 hours of infusion
- Neurologic recovery/prognosis unclear
Postchemo pain: Raynaud’s phenomenon
- Raynaud’s observed in 20-30% of individuals with germ cell tumours treated with cisplatin/vinblastine/bleomycin
Chronic pain associated with aromatase inhibitors
- MSK pain and stiffness
- Hand osteoarthritis, tendonitis, trigger finger, carpal tunnel
Chronic pain associated with bisphosphonates: Osteonecrosis of the jaw
Osteonecrosis of the jaw
- May occur after administration of bisphosphonages
- Uncommon
Presentation:
- Unexpected development of necrotic bone in the oral cavity
- Local pain, soft tissue swelling, or loss teeth
- May be mistaken for more routine dental issues
Prevention:
- Dental examination and panoramic jaw radiograph before beginning bisphosphonate therapy
- Ensure patients are informed of risks
- Ensure regular good oral hygiene/regular dental assessment
Chronic pain associated with bisphosphonates: Chronic diffuse pain
- Warning regarding the risk of severe, sometimes incapacitating MSK pain in patients taking bisphosphonates
- Onset is within days, months, or years
- Some patients have relief after discontinuation, others do not
- Risk factors unknown
Chronic post-surgical pain: Breast surgery pain syndromes
Breast surgery pain syndromes
Chronic neuropathic pain
- Common complication, ,especially following axillary dissection
- Risk and severity correlates to number of LN removed
- Constricting and burning discomfort localised to the medial arm, axilla, and anterior chest wall
- Onset may be immediate or months post-surgery
- Variable natural history
- More intense pain immediately post-op predicts worsened chronicity and complications
Ddx:
- Post mastectomy phantom breast pain
- Neuroma pain
- Post mastectomy frozen shoulder
- Breast cellulitis
- Axillary web syndrome
Chronic post-surgical pain: Post-radical neck dissection pain
Post-radical neck dissection pain
- Chronic neck and shoulder pain is common
- Most often due to damage to the spinal accessory nerve (CN XI)
- May also result from muscular imbalance following surgical excision of neck muscles
Ensure imaging is performed to rule out recurrence or soft tissue infection
Chronic post-surgical pain: Post thoracotomy pain
Prolonged post-thoracotomy pain
- Most common pain pattern
- Pain most profound around the surgical site
- Pain is aching, tender, with numbness and burning
- Due to trauma and compression to nerves, injury to chest muscles, fractured and compressed ribs
- Typically resolves within 2 months, may persist up to 10 years
Recurrent or Increasing post-thoracotomy pain
- May be due to infection or disease recurrence
- Requires evaluation with CT or MRI to rule out
Chronic post-surgical pain: Postop frozen shoulder
- Risk for patients with post-thoracotomy pain or post-mastectomy pain
- May result in independent, separate foci of pain
- Ensure mobilization post-op to prevent
Phantom pain syndromes
Phantom limb pain
- Arises from am amputated limb
- 60-80% of patients following limb amputation, but severe or persistent in only 5-10% of cases
- More prevalent after tumour related than traumatic amputations, and post op chemo is an additional risk factor
- Pre-op or post-op neural blockade may reduce incidence during the first year after amputation
May also occur as phantom breast pain after mastectomy or phantom rectal pain after abdominoperineal resection
Stump pain
- Pain occurring at the site of a surgical scar several months to years following amputation
- Most commonly due to development of neuroma at the site of a nerve transection
Presentation:
- Burning or lancinating dysesthesias
- Worse with movement or pressure
- Blocked by local anesthetic
- Look for local inflammation (could indicate abscess formation)
Chronic radiation myelopathy
- Uncommon, late complication of spinal cord irradiation
- Onset typically 12-14 months post rads
Presentation:
- Partial, transverse myelopathy at the cervicothoracic level
- Sensory symptoms, including pain, may precede motor and autonomic dysfunction
- Pain is burning dysesthesia localised to the level of spinal cord damage or below
Diagnosis:
- MRI to rule out recurrence
- MRI will show myelitis (high intensity T2 signals with gad enhancement)
Prognosis:
- Steady progression over months, followed by slow progression or stabilization
Chronic radiation enteritis and proctitis
Chronic radiation enteritis and proctitis
- Delayed complication in patients who under go abdominal or pelvic rads
- Rectum and rectosigmoid most common
Protocitis Presentation:
- Proctitis (bloody diarrhea, tenesus, cramping pain)
- Obstruction due to stricture formation
- Fistulization to vagina or bladder
Small bowel enteritis:
- Colicky abdominal pain
- Chronic nausea or malabsorption
- On barium swallow, narrow tubular segment similar to Crohn’s or ischemic colitis
Diagnosis:
- Endoscopy/biopsy
Radiation cystitis
- Pelvic radiation may result in radiation cystitis
- May result in temporary irritative voiding symptoms and asymptomatic hematuria
- May be more severe - gross hematuria, non-functional bladder, persistent incontinence, FUND sx
Lymphedema pain
- Common following breast cancer and axillary LN dissection
Presentation:
- Pain and tightness in the arm
- May be complicated by secondary rotator cuff tendonitis due to internal derangement of tendon fibres
If a patient has severe or increasing pain in a lymphedematous arm, consider tumour invasion of the brachial plexus
Burning perineum syndrome
- Uncommon, delayed complication of pelvic radiotherapy
- Onset 6-18 months post rads
- Burning pain in the perianal area, may extend anteriorly to involve vagina or scrotum
Osteoradionecrosis
- Late complication of radiotherapy
- Bone necrosis, producing focal pain
Differentiating radiation brachial plexopathy from tumour causing brachial plexopathy
- PET may help to differentiate tumour progression from radiation-related fibrosis
- Patients with radiation-induced plexopathy typically have LESS pain
Tumour infiltration:
- Pain progresses, more severe, and has a dysaesthetic quality
- C7-T1 distribution (neck, shoulder, hand, 5th finger)
- Mass on CT with tissue infiltration
- High T2 signal intensity on MRI
- Denervation on EMG, but no myokymia (ongoing depolarization)
- Horner’s may be present
Radiation fibrosis:
- Pain stabilises with onset of weakness
- C5-C6 distribution (thumb, forearm)
- Diffuse infiltration of tissue on CT
- Low T2 signal intensity on MRI
- Myokymia on EMG (ongoing depolarization)
- No Horner’s syndrome
