Radiation for Symptom Management Flashcards
Radiation: Mechanism of Action
- Ionizing radiation causing damage to DNA
- XRs produced by an XR machine or linear accelerator
- Alternatively, gamma rays produced from a radioactive source
- Cancer cells are more susceptible to radiation damage, as they are less able to repair and dividing more rapidly
DNA damage
- Direct (base deletions, breaks in the DNA chain
- Indirect (free radicals produced from interaction between radiation and water molecules) - most important cause of cell death
- Damage to endothelial cells and interrupted blood flow (when high single doses of >10Gy are given)
Radical radiotherapy
- Aim is complete tumour eradication, while minimizing long term normal tissue damage
- Radiation dose built up in fractionation to allow for higher doses can be given
- Treatment may be ‘accelerated’ (multiple doses in a day over a shorter period of time) to reduce opportunity for tumour cells to repopulate
- Treatment may be ‘hyperfractionated’ (smaller doses over a longer period of time to deliver a higher total dose with greater sparing of normal tissues)
- Typically 6-8 weeks in duration
Palliative radiotherapy
- Aim is symptom control
- Majority of tumour cells (60-80%) killed in first one or two radiation doses, so initial radiation effect may be adequate for symptom control and long radiation course may not be necessary
- Short, relatively low dose schedules results in less acute reaction and minimal risk of late damage to normal tissue
Components of radiation treatment planning
Immobilization
- Small movements could result in irradiation to critical structures
- May involve sandbags, or a plastic shell with individualised facemask
Treatment volume localisation
- Typically with CT, but in some cases plain XR is adequate (e.g. bone mets or primary lung tumour)
Dosimetric planning
- Once volume is defined, dose and field arrangements are planned
- May involve stereotatic rads, 1-4 beams, etc.
- Most machines provide 1 Gy/minute, so the treatment itself is brief
Verification
- Defined beam arrangement is checked by imaging on the treatment machine
Acute effects of radiation
- Due to loss of epithelial cells
- Results in erythema or desquamation
- Depending on the site, can result in mucositis, esophagitis, sterile cystitis, GI irritation, pneumonitis, transient demyelination (Lhermitte’s sign)
- Repair of the denuded surface occurs once treatment is completed over a period of days or weeks
- Poor healing may occur if there is secondary infection/trauma, both risk factors for radionecrosis
Late effects of radiation
- Some patients are genetically predisposed to lower tolerance for radiation, which is typically due to vascular damage
- ‘Progressive endarteritis obliterans’ - closure of small blood vessels and potential tissue ischemia
Skin
- Atrophy, fibrosis
- Telangiectasias, necrosis
GI tract
- Stricture
- Telangiectasias, bleeding
- Perforation
- Malabsorption
- Chronic enteritis/colitis/proctitis
Bladder
- Reduced volume
- Telangiectasies, bleeding
- Urethral/ureteric stricture
- Fistual
Oral cavity
- Mucosal atrophy
- Telangiectasias, bleeding
- Dental caries
- Mandibular necrosis
Lung
- Fibrosis
CNS
- Myelitis
- Necrosis
- Local edema
Eye
- Cataract
- Entropion or ectropion
- Dry eye
Management of radiation side effects: Skin
- Desquamation rare after palliative doses - little in the way of acute effects
- Mild skin reactions typically require no treatment, but if needed, starch powder is recommended over talcum, gentian violet, etc.
Management of radiation side effects: GI
- Nausea typically responds to antiemetics, such as metoclopramide or ondansetron
- If antiemetics are ineffective, dex may be helpful
- Consider prophylactic dosing if the GI tract will be captured in the field
Diarrhea
- low residue diet (avoid fibre, fruit etc.)
- Loperamide or Codeine if an antimotility is needed
Management of radiation side effects: Cystitis
- Tamsulosin (alpha blocker) may be helpful for severe bladder spasm
- Cranberry juice or potassium citrate are anecdotally effective, but have no evidence
- If there is significant dysuria, consider systemic analgesics
- Rule out secondary infection
Management of radiation side effects: Oropharyngeal mucositis
- Maintain regular oral hygiene with chlorhexidine mouthwash and prophylactic anti-candidals (e.g. nystatin)
- Local relief of pain with soluble aspirin mouth wash
- In severe cases, feeds via NG may be required
- In radical radiotherapy, pre-treatment assessment by a dentist and meticulous oral hygiene is important (but not required for simple, low dose palliative rads)
- Avoid alcohol and smoking as it worsens effects
Management of radiation side effects: Pneumonitis
- May occur up to four months after treatment
- Dry cough, dyspnea
Imaging:
- Radiograph showing patchy shadowing confirming to radiation field
Treatment:
- 2-3 week course of steroids and antibiotics for secondary infection
Late radiation fibrosis may occur
Radiation for bone pain
Indications
- Bone pain (highly effective and long lasting effect)
- Pathologic fracture
- Pressure on nerves
Outcomes
- 40% of patients can expect at least 50% pain relief
- Slightly less than 30% can expect complete pain relief at one month
- Pain relief typically within 10 days, some experience it as rapidly as 24 hrs. Others may not experience relief until a month after!
Single dose vs multi-dose
- No difference in pain outcomes between single and multiple fractions
- Single-fraction may result in higher rate of re-treatment, more pain flares, and potentially greater risk of fracture
- Multiple-fraction is preferred for previously irradiated areas, to treat or prevent pathologic fractures, and for spinal cord or cauda equina involvement
Wide field treatment for bony mets
- Useful in cases where there are multiple sites of disease
- Delivers treatment to an area that may include up to half the body
- Dose of 6 Gy to upper half body (dose limited by lungs)
- Dose of 8 Gy to lower body
- Associated with greater toxicity (typically GI or a period of bone marrow suppression)
Radiopharmaceuticals and application to bony mets
- Radioactive agents administered IV, which localize to metastatic bone sites and deliver radiation in a highly focal manner
- Strontium-89 and Smarium-153
- Systematic review shows improved pain control and decreased analgesic consumption
- Main adverse effects are thrombocytopenia and neutropenia
- Onset of analgesia may not occur for MONTHS
Indications:
- Multiple painful bone mets where conventional analgesics are ineffective and local field rads is not possible
- Must consider performance status, marrow function, use of other marrow suppression agents (e.g chemo/rads), alternative treatments, and prognosis
Pain flare following rads for bone pain
- Occurs within first few days of rads
- Generally lasts 1-2 days and is managed with increased doses of opioids
- Prophylactic dosing of dex has been explored but is not generally recommended
Rads for pathologic fracture
- An option when surgery is not possible or indicated
- May also be used post-op internal fixation to prevent further progression of the remaining metastatic tumour (not appropriate if there is widespread mets, limited survival, and adequate pain control)
- Typically single dose of 8 Gy for pain relief (higher doses for healing)
- Goal is pain relief and to enable bone healing
Rads vs surgery for cord compression/cauda equina
- Both rads and decompressive surgery are effective
- One study showed a significant advantage with a surgical approach in terms of functional status and survival
Consider referral to surgery followed by rads if:
- Good performance status
- No mets elsewhere
- Single level of cord compression
Also consider surgery in patients with extensive vertebral collapse with intrusion into the spinal canal, as these patients need surgical stabilization and radiation is unlikely to be of benefit
Rads for cord compression/cauda equina
- Typically simple treatment with a single posterior field
- Most often 20-30 Gy in 5-10 fractions
Prognostication in patients with cord compression
- Typically correlates with severity of deficits
- Most patients who have lost ambulation for >24hrs will not regain it
- 3/4 of patients retain the ability to walk if they begin treatment while ambulatory
- > 3/4 have pain relief
Myeloma and lymphoma respond the best to rads
Rads for brain mets
- 10% of cancers spread to brain
- Isolated brain mets are unusual, typically patient has widespread metastatic disease
- If there is a solitary met, consider referral to surgery with post op rads
- In cases where performance status is very poor, rads is likely inappropriate
Options include:
- Radiosurgery (e.g. gamma knife/stereotactic rads)
- Whole brain rads (better for multiple cerebral mets)
Median survival after brain rads is less than 6 months, as typically it means there is widespread, advanced metastatic disease
Prognostication of survival after irradiation of brain mets
Increased survival
- Brain first site of relapse
- Brain sole site of relapse
- Long disease-free interval prior to brain relapse
- Primary site in brain
- Good PS (0-1)
- Age < 60
Decreased survival
- Multiple lobes involved
- > 3 mets
- Meningeal disease
Acute toxicity from whole brain rads
- Typically little impact
- Scalp alopecia for 2-3 months
- Mild scalp erythema
Long term toxicity from whole brain rads
- Neurocognitive impairment
Primary brain tumours - treatment
- Surgery, radiotherapy, or both with curative intent
- Palliative radiotherapy for Grade III or IV astrocytomas as prognosis is poor, may include adjuvant and concomitant temozolamide if PS is good
Overview/diagnosis/prognosis of diffuse meningeal carcinomatosis
- Median survival of a few weeks if untreated
- May present with symptoms and signs of headache or backache, raised ICP, multifocal radiculopathy or cranial neuropathy
- Diagnosis typically suspected by MR, confirmed by CSF
Associated cancers:
- Leukemia (CNS relapse)
- Breast CA
- Lung CA
Treatment of diffuse meningeal carcinomatosis
Leukemia/lymphoma
- Sustained remission may be achieved by use of intrathecal chemo, +/- CNS rads
- Significant morbidity and mortality, especially in children (impaired spinal growth, intellectual development)
Other solid tumours
- Prognosis a few weeks without treatment, perhaps a few months with intrathecal chemo and CNS rads
- Typically, judicious radiation to specific sites causing symptoms (e.g. skull base when cranial nerves are involved) is a more pragmatic approach
Cranial nerve palsies - pathophys, treatment, prognosis
Arise from
- Brainstem mets
- Leptomeningeal disease
- Compression from extra dural deposits
- Bone involvement in the skull base
Whole brain rads may be worthwhile for brainstem mets or leptomeningeal disease
Skull base rads may also be helpful, and patients with CN palsies secondary to bony mets rather than CNS typically have a median survival of 10-20 months
Peripheral nerve symptoms - radiation therapy
- Consider when there is tumour compression of nerve roots, nerve plexus, or peripheral nerves causing motor or sensory loss, or pain
Choroidal and orbital mets - radiation therapy
- Mets to eye are uncommon, but if untreated result in progressive deterioration and ultimately loss of vision
Choroidal mets
- Breast
- Lung
Other intra orbital sites
- Less common, may be either hematogenous spread or direct tumour extension
Radiation treatment
- May be useful to preserve vision (even if asymptomatic)
- Requires avoidance of direct irradiation the cornea (causes keratitis) and lens should be shielded (to avoid cataracts)
- Note that cataracts take years to evolve and would not be a reason to avoid palliative radiation
CNS lymphoma - treatment
- Seen in advanced HIV infection
- Typically treated with a short course of steroid for some palliation and tumour regression but mainstay is high dose methotrexate
- Previously, whole brain rads with chemo has been given, but now benefit is questionable given impact on cognitive function
- Whole brain rads is an alternative to chemo in patients who cannot tolerate it
SVC syndrome - etiology and presentation
SVC syndrome
- Occlusion by external compression, intraluminal thrombosis, or direct invasion of the vessel wall
- Typically due to tumour (lung ca is most common, or lymphoma)
- Rule out aneurysm, chronic mediastinitis, trauma, or thrombosis from central line
Presentation
- Headaches
- Somnolence
- Dizziness
- Seizures (from cerebral hypertension - rare)
- Edema
- Dysphagia
- Dyspnea
- Cough
- Hoarseness
- Engorgement and dilatation of the superficial skin veines
- Facial edema
SVC syndrome - management
- Steroids (dex), but no great evidence
- SVC stent
- Chemo (e.g. lymphoma, small cell, germ cell tumours)
- Radiotherapy (typically relief within 2 weeks)
Prognosis
- Typically dictated by other spread/underlying disease, with the exception of airway obstruction or cerebral edema
Bronchial obstruction - Etiology and presentation
Central air way obstruction
- Due to intrinsic carcinoma of the bronchus
- Less commonly, mediastinal LN invasion by carcinoma or lymphoma
Presentation
- Dyspnea and cough, especially if obstruction occurs rapidly
Bronchial obstruction - treatment
Intrinsic tumours
- Bronchoscopy with laser therapy or cryo
- Can also provide endobronchial irradiation (laser is likely to be better)
Extrinsic tumours
- Chemo or rads
- Can also provide endobronchial irradiation
Dysphagia - radiation
- Common in patients with advanced cancer within the mediastinum
- Compression from the esophageal tumour, hypopharynx, stomach, mediastinal LN, thymus tumour, thyroid tumour, or adjacent bronchus
Radiation
- May be useful for many patients, especially given risks of procedural intervention
- Swallowing re-established in 80% of patients and maintained for mean duration of 6 months
- Requires 2 weeks or more for effect and may cause esophagitis
Urinary tract obstruction: Radiation
- Typically, nephrostomy, ureteric stents, or transurethral resection is the most appropriate intervention to bypass an obstruction
- In patients where a procedure is inappropriate or not technically possible, radiation is an alternative
- Intraluminal or interstitial radiotherapy may also have a role
Limb edema: Radiation
- Due to venous obstruction, lymphatic obstruction, or both, may also be due to post-radiation changes
- Local radiotherapy may be helpful in cases where there is limb edema secondary to enlarged axillary, inguinal, or pelvic nodes
- Best results are with early treatment (circulatory obstruction may still be reversed)
- Relatively low doses with a preserved ‘channel’ of unirradiated soft tissue for lymph drainage to be maintained despite post-rads changes
Hydrocephalus - radiation
- Obstructive hydrocephalus can occur from primary or secondary tumours obstructing CSF in the ventricular system
- Typically posterior fossa or midbrain tumours obstructing the aqueduct or fourth ventricle
- Also seen with leptomeningeal disease
Treatment
- Typically intraventricular shunt, but if surgery is not feasible or there are multiple intracerebral lesion, palliative rads as per for brain mets
Hemoptysis - radiation
Hemoptysis
- Control rates of up to 80% with palliative rads
- No survival advantage, though tumours >10cm carry significant hemorrhage risk and may be considered for prophylactic treatment*
- When due to pulmonary mets, local rads is only of value if a specific site of hemorrhage can be found or if there is a single site of metastases
- In the case of multiple mets, may need bronchoscopy to determine the origin of the bleeding
Hematuria - radiation
Hematuria
- Must localise bleeding through cysto or CT for treatment planning
- Typically due to a lesion in the bladder due to a primary tumour or secondary infiltration
- Infective or chemical cystitis (cyclophosphamide) may also be causes
- Late change following high dose rads to the pelvis
Role of radiation
- Achieve hemostasis in patients with inoperable tumours
- Use conservative measures first (TXA, cysto dithermy)
- Modest doses of rads may be successful
Side effects of bladder rads
- Diarrhea as bowel may be included in the treatment volume
- Nausea/vomiting if the kidney is treated, resulting in gastritis
Uterine and vaginal bleeding - radiation
Uterine and vaginal bleeding
- Commonly caused by uterine tumours (eg. endometrial, cervical ca, uterine sarcomas) or local infiltration from advanced bladder or rectal CA
- Typically small amounts, but rarely major hemorrhage
Treatment
- Radiation (either external bean or intracavitary brachytherapy) can help provide control
GI bleeding - radiation
GI hemorrhage
- May result from upper or lower GI tract neoplasm, either primary or direct invasion from adjacent structures (e.g. prostate, bladder, uterus)
- Malignant melanoma and Kaposi’s sarcoma are both known to cause hemorrhagic deposits in the small bowel wall
Radiation
- Large bowel lesions can be radiated and will offer reasonable control of bleeding
- Stomach and small bowel are more difficult - more mobile and surrounded by more radiosensitive structures (e.g. liver, small bowel, kidneys)
Chest wall and other skin lesions - radiation
Chest wall and other skin lesions
- Locoregional recurrence common in advanced breast cancer
- Some patients may develop issues with chest wall tumour that will fungate and bleed, which may or may not be operable
- Skin nodules from other tumours typically reflect blood borne mets
- Primary skin cancers can cause similar problems
Treatment
- For breast cancer related chest wall tumours, radiation may be helpful to control growth bleeding, and fungation
- For skin nodules from other tumours or primary skin cancers, symptomatic treatment with rads is appropriate
Fungating lesions - radiation
Fungation
- Occurs with superficial tumours
- Most common in chest wall recurrence after breast CA and with met LN in the neck or groin
Management
- Local radiation, treatment most effective when done while skin is intact
- Once fungation has occurred, typical treatment requires analgesics, antibiotics ,and local rads to reduce tumour bulk and stop surface hemorrhage
Kaposi’s sarcoma - radiation
- Very radiosensitive
- Typical manifestation of multiple skin lesions (purplish raised plaques), but may also have extracutaneous disease in the oral cavity and GI tract
- Small doses of radiation can result in complete regression of lesions
Liver mets - radiation
- In inoperable cases, stereotactic rads may provide ablative radiation
- Local rads may be useful in cases of multiple mets where the patient has good PS, normal bili, and primary site is not stomach or pancreas
Splenomegaly - radiation
Splenomegaly
- Typically associated with hematologic malignancies (especially leukemia and certain NHL, as well as MDS)
- Splenectomy is preferred management, but in advanced disease or patients with poor PS, rads is appropriate
- Consider if patient is symptomatic from bulk (causing pain or discomfort) or hypersplenism (thrombocytopenia and anemia)
- Caution re: TLS (give allopurinol or rasburicase)
Paraneoplastic Syndromes - radiation
Paraneoplastic syndromes
- Most commonly associated with primary carcinoma of the bronchus
- Includes myopathies, neuropathies, myasthenia, cutaneous manifestations, hypercalcemia due to PTHrp
- If a primary identifiable local tumour can be found, worthwhile to radiate in hopes of improving paraneoplastic syndrome
Acute radiodermatitis - presentation and treatment
- Erythema, edema appear within 1-2 weeks and peak around week 3-4
- Followed by dry desquamation and moist desquamation
- May even be accompanied by erosions or ulcers in severe cases
Risk factors
- comorbidities
- Older age
- Previous sun damage
- Dose, fractionation, etc.
Treatment
- No effective prophylaxis
- Wash with mild soaps, avoid deodorants and electric rasis
- Basic care with moisturizers
- No clear benefit to topical steroids
- Consider oil in water emulsions
Chronic radiodermatitis - presentation and treatment
- Occurs due to radiation effect on the vasculature
- Initially, dermal atrophy within 4-6 months, followed by dermal thinning after a year
- May be accompanied by telangiectasias
- Skin necrosis and chronic ulcers may occur
Treatment
- For intact skin, oil in water emollients and prevention of trauma
- Radiation ulcers are treatment resistant and realistic goals are really preventing secondary infection, pain, and fetid smell
- Hydrocolloids may be useful for ulcers (but unlikely to provoke healing)
Radiation recall
- Inflammatory reaction triggered by cytotoxic chemo in previously irradiated areas (mainly skin)
- Radiation could have been administered days or years prior
Presentation
- Well circumscribed area of erythema that fits the radiation field of past treatment
- Chemo most commonly implicated is Gem, anthracyclines, and taxanes
Treatment
- Stop offending agent
- Steroids or NSAIDs may help