Benign Flashcards
Describe the epidemiology and risk factors for heterotopic ossification
- Uncommon issue
- Predominantly impacts young adults (20s and 30s)
- Men>women
- Hip is the most common location; less common jaw, elbow, spine
Risk Factors
1) Prior history of HBO (ipsi or contra) >80% risk 2) Skeletal injury (trauma or surgical) a. Increased risk in traumatic brain injury or spinal cord injury b. Increased risk in multi-trauma or high-energy injuries 3) Rare genetic forms a. Fibrodysplasia ossificans progressiva (FOP) b. Associated with ankylosing spondylitis 4) Men > women 5) >60% risk if: ○ Hypertrophic osteoarthritis ○ Ossifying diathesis (e.g. ankylosing spondylitis) ○ Paget's disease ○ Post-traumatic arthritis ○ Diffuse idiopathic skeletal hyperostosis
Timing
* Commences at 2 weeks, mature by 6-9 months
Incidence
* Up to 30-60%, but symptomatic only in 10%
* At any age but commonly 50-80yo.
Sites:
* Hip - around the femoral neck and adjacent to the greater trochanter
* Less frequently - jaw, elbow, spine
Protective factors
* NSAIDs
* ‘Gentle handling’ of tissues
Clinical presentation
* Commonly asymptomatic
* Hip stiffness, inflammation, joint swelling, limited ROM
* Typically not associated with pain
Diagnosis: Plain x-ray
Describe the pathophysiology and grading of heterotopic ossification
Pathophysiology
Poorly understood
Likely an immune-mediated excess healing response (similar to keloid)
- Upregulation of mesenchymal precursors in surrounding soft tissue
- Differentiate into osteoblasts stem cells/osteocytes in the presence of growth factors (from healing bone)
○ Osteoblasts deposit lamellar bone
Commences at 2 weeks, mature by 6-9 months
HO is defined as the abnormal deposition of extra-skeletal bony material within soft tissues
Commonly asymptomatic , hip stiffness, inflammation (pain)
Impaired function / restricted movement
Grading
Brooker grading based on AP XR
- Simple summary
○ Grades I + II are clinically occult
○ Grades III + IV are clinically significant (i.e. functional impairment)
Based on AP X-ray
- I: Islands of bone within the soft tissue (clinically silent)
- II: Bone spurs from the pelvis or proximal femur; ≥1cm gap between opposing surfaces
- III: Bone spurs from the pelvis or proximal femur; <1cm gap between opposing surfaces
- IV: Ankylosis
*Grade 3/4 are severe HBO which often leads to disability
Describe the management of heterotopic ossification
Surgical Resection
- Can consider upfront resection of heterotopic ossification ○ Only intervene if symptomatic (i.e. restricting movement) - Any surgical resection should typically occur 12-18 months after initial injury ○ Await maturation of the deposited bone - Re-resection without prophylaxis may be associated with high-risk of recurrence ○ Up to 90% risk
Mechanisms for prophylaxis
- NSAIDs ○ Typically indomethacin for a period in the perioperative period § Common use is 25mg TDS for 4-6 weeks post-operatively ○ Note concerns about toxicity from prolonged use (renal and gastric) ○ MA showed overall reduction of HBO from 61 to 27%. Another study showed that despite decr in bone spur, clinical response and pain were similar with higher risk of GI bleed. - Radiotherapy ○ Inactivates mesenchymal pluripotent stem cells, suppresses metaplasia/proliferation ○ Indicated in Brooker Grade III/IV ○ 6Gy equivalent to NSAIDS, therefore 7+Gy is superior to 6Gy or less § At doses of 7+Gy, RT is slightly more effective than NSAIDs ○ Given peri-operatively at a dose of 7-8Gy/1F § Aim to deliver between 12 hours pre-op --> up to 72 hours post-op § Sooner the better ○ RT may reduce risk of recurrence to <20%
Considerations
- In young patients, consideration should be given to NSAIDs rather than RT ○ Less risk of toxicity with NSAIDs ○ Increased concern for late RT toxicity (second malignancy) ○ Small absolute difference in efficacy ○ If recurrent, can consider RT at the next recurrence
Evidence: Efficacy vs NSAIDs
Meta-analysis (Pakos, 2004) Greece
- 1143 patients across 7 studies
- Overall, RT was better than NSAIDs at preventing recurrent Brooker 3 & 4 disease
○ Small absolute benefit
- Subgroup analyses
○ RT given too early was less effective (16-20 hours pre-op)
○ Whilst 7+Gy was better than NSAIDs, 6Gy was equally effective as NSAIDs
Systematic Review (Blokhuis, 2009)
- 384 patients in 5 studies
- RT was superior to NSAIDs with respect to rate of recurrent HO
○ Small overall difference
Describe the radiotherapy technique for heterotopic ossification.
Heterotopic Ossification
Pre-simulation
Fertility considerations
Discussion with orthopaedic surgeon
- Risk of recurrence (i.e. need for RT)
- NSAIDs as alternative
Simulation
Tape external genitalia
Testicular shielding
CT of region with 2mm slices
- NO contrast
Fusion
N/A
Dose Prescription
7-8Gy/1F (prescribed to the prescription point as per ICRU 50)
3D-CRT or AP/PA technique
12 hours pre-op to 72 hours post-op
Target Volumes
Field-based
- Include entire involved region
- Include entire prosthesis (if appropriate)
Caveat: RT field should encompass the region most likely to form HBO- particularly NOF, tip of the greater trochanter, between the greater trochanter and ilium, and btw lesser trochanter and the ischial ramus.
10x10cm centred on femoral neck
Otherwise, ALARA with field placement
- Exclude pelvic organs
- Exclude testes
Target Verification
Daily orthogonal kV XR
OARs
ALARA to relevant organs
Testes <0.1Gy
Toxicities
Few significant SEs
2% cancer risk at 20 years
Describe the epidemiology, risk factors and pathophysiology of keloid scars
- More common in younger patients
- Most commonly occur in the upper body
○ Typically in areas of tension (e.g. sternum, joints) - commonly in Afro-Caribbean and Asian population
- Recurrence common after treatment
- Can be secondary or spontaneous
- Can be painful, pruritic, tender
- Disfiguring
- Sites: ear lobes, shoulder, upper back, mid chest
- Most commonly occur in the upper body
Risk Factors
1) Ethnicity a. African American b. Asian c. Hispanic Familial tendency (no clear genetic cause)
Definition
Benign fibrous growths in scar tissue due to altered wound healing with overproduction of cellular matrix and dermal fibroblasts
Excessive tissue growth in the region of a cutaneous scar
- May be induced by surgery, burns or inflammation
Differentiated from hypertrophic scar
- More infiltrative growth (clinically and histologically)
- Keloids may be extensive and grow outside of confines of the scar region
Pathophysiology
Poorly understood pathophysiology
Alterations in the sequential wound healing process
- Increase in fibroblast proliferation –> collagen deposition
- Growth factors such as TGFb and VEGF are associated with this process
Familial/genetic association has been seen
- No clear genes are proven
Describe the management of keloid scars
Management should only be offered if symptomatic:
- Pain
- Itch
- Cosmesis
- Hyperhidrosis
Key conservative options
1) Intra-lesional corticosteroids
a. Flattens scarring by diminishing collagen synthesis and fibroblast proliferation
b. Repeated every month until effect achieved. Painful
c. Response rate = 50-100%
2) Intra-lesional 5-FU
a. Used if lesions refractory to corticosteroids
b. Induces fibroblast apoptosis (without surrounding necrosis)
c. Response rate = 50-75%
3) Silicone gel sheet (or cream?)
a. The idea is to create an impermeable layer over the skin
i. Mechanism unknown (postulated due to hydration of the stratum corneum)
b. May reduce thickness of keloid, but data are uncertain
4) Others: IFα-2b
Invasive options
1) Surgical resection
a. Indicated if conservative measures have failed
b. Response rates of up to 100%
i. Best when combined with an adjuvant option peri-operatively (e.g. RT)
2) Cryosurgery
a. Excision - RR >50% so use adjunct Tx
2) Peri-operative Radiotherapy
a. 20Gy/5F given immediately post-operatively (within 24 hours)
b. Reduces risk of recurrence compared with surgery alone
i. 10-20% vs 30+%
Considerations
- In young patients, consideration should be given to conservative measures rather than RT
○ Increased concern for late RT toxicity (second malignancy)
○ If recurrent, can consider RT at the next recurrence
EVIDENCE:
Efficacy
- 1 x small RCT comparing RTx vs. steroids à suggestion of reduction of RR with RT (15% vs 30% (not SS, underpowered/small study) but compliance was better with RT
Meta-analysis (Mankowski, 2017)
- 9048 patients from 72 studies
- Outcomes
○ Adjuvant RT after surgery is better than RT alone
○ Brachytherapy is better than EBRT (XR or electron)
○ Chest keloids have highest risk of recurrence
Dose of RT
Retrospective study (Renz, 2018)
- 124 patients with 250 keloids
○ 20Gy/5F compared with 12-16Gy/3-4F
- Reduction in rate of recurrence with higher dose (OR 0.16)
2xMA (Dutch and U.Pitsburg)
- showing higher doses (BED > 30Gy gives RR <10%) i.e. 16Gy/2Fr, 18Gy/3Fror for larger lesions (non-ear-lobes) 24Gy/3Fr, within 24 hrs of surgery (alt 10Gy in 1#)
- 125KvP
Describe the radiotherapy technique for keloid scars.
Pre-simulation
Fertility considerations (if appropriate)
Avoid in young
Discussion with dermatologist/surgeon
- Risk of recurrence (i.e. need for RT)
- Alternative options
Simulation
Sim occurs pre-operatively
Bolus (likely 1cm)
Clinical mark-up (2cm margin)
Selection of appropriately-sized cut-out
- SSD = 100cm
- Applicator stand-off = 5-10cm
CT of region with 2mm slices
- NO contrast
Fusion
N/A
Dose Prescription
20Gy/5F (prescribed to the 90% isodose) ????
18Gy/3Fx
6MeV electrons
Less than 24 hours post-operatively
Target Volumes
Mark-up 2cm margin on pre-op keloid region
Otherwise, ALARA with field placement
Target Verification
D1 = ensure field remains appropriate (assess new scar)
Use of sim acetate to match
OARs
ALARA to relevant organs
Toxicities
Local paraesthesia
<5% mild infield hypopigmentation
Radiation Induced Malignancies (large literature review of 6741 pts with keloids)
Crude risk 1/1348: breast, BCC, mesothelioma, thyroid
Describe the epidemiology and pathophysiology for graves eye disease.
- 25% of all Graves’ patients will develop ophthalmopathy
○ Approximately 1 per 1000 people- Women are more commonly affected (like all autoimmune diseases)
- > 40 yo
- 80% bilateral, 20% unilateral
Aetiology (for Graves’ disease generally)
1) Family history
a. Strong concordance among siblings
2) Gender (female)
3) Smoking
a. Risk factor for ophthalmopathy among Graves’ patients
Definition/Presentation
Inflammatory condition of orbital tissues and extraocular muscles occurring in Graves disease, can be seen in hashimotos (Thyroid eye disease)
(triad of clinical findings: hyperthyroidism, infiltrative opthalmopathy with exopthalmos and localised, infiltrative dermopathy (pretibial myxoedema)
Exophthalmos
Opthalmoplegia/diplopia
Periorbital oedema
Lid retraction corneal ulcer
Pain
Tearing
Optic neuropathy
Pathophysiology
Type 2 hypersensitivity (antibody-mediated autoimmune condition)
- The target for autoimmunity is the TSH receptor
- Antibodies and T-cells bind and activate the receptor (hence hyperthyroidism)
This receptor is not isolated to the thyroid
- Also seen on adipocytes and fibroblasts (ie. Cross reactivity with ocular antigen)
- Periorbital Fibroblasts produce glycoaminoglycan (GAG)
There is also some cross-reactivity with IGF-1 receptors
- Also found on fibroblasts
Presence of TSH receptors in the retro-orbital fat and muscle –> proliferation when TSH receptors activated
- Increase in bulk of extraocular muscles
- Increase in retro-orbital fat
Stages:
1. Initial acute phase - progressive symptoms
2. Partial regression
3. Static phase
4. Long term fibrosis; can get restricted eye movements and compression of optic nerve, proptosis/exopthalmos
Gradual regression may occur, but complete resolution rare
Unrelated to degree/timing of hyperthyroidism
May improve with anti-thyroid treatment alone
Spontaneous exacerbations/remissions possible
Describe the work up and grading for graves eye disease.
Work-Up
1) Bloods
a. TSH
b. T3 and T4
c. Anti-TSH receptor antibodies (Thyroid stimulating Ig - TSI Ab)
d. Thyroid peroxidase Ab (TPO Ab) - (90% hashimotos, 70% graves)
e.
2) Imaging
a. Non-contrast CT
i. Iodinated contrast interferes with systemic Graves’ treatment (often I-131 ablation is considered)
b. MRI
Severity
Disease severity should dictate symptoms specifically directed at ophthalmopathy
- Of course, Graves’ disease in general should be managed
Based on 7-point CAS score system
Severity categories
- Mild = proptosis <3mm, no diplopia
- Moderate = proptosis>3mm, intermittent diplopia
- Severe = proptosis >3mm, constant diplopia
- Sight Threatening = corneal exposure is severe, optic nerve is compressed
Consider directed therapy when moderate to severe
Describe the management of graves eye disease.
Medical Therapy
Control thyroid function
1) Glucocorticoids
a. IV pulsed methylprednisolone (weekly dosing of 250mg)
i. Pulsed steroid better than oral daily
b. 50% response rate (may take 2-3 months)
2) IGF-1 inhibitor (teprotumumab)
a. 60-70% response rate
3) Mycophenylate
a. Under investigation
b. May provide more efficacy compared with dexamethasone (response rate 90% vs 60%)
4) Tocilizumab
a. IL-6 immunomodulator
b. Limited evidence
5) Rituximab
a. Retrospective evidence only
Radiotherapy
- Consider use when refractory to steroids or other modalities
- 20Gy/10F to bilateral posterior orbits
○ Spare the anterior chamber and lens
○ Typically lateral fields
- Rationale is to target radiosensitive lymphocytes and fibroblasts involved in disease proliferation
- Questionable evidence for efficacy
- Symptoms start to resolve after 2 weeks, average resolution time ~5months
Surgery
- Largely out of favour - major surgery, defer for 3-6 months, 30-50% reoperation rate
- Indications:
○ In sight-threatening disease, decompression surgery may be necessary
§ Via emergent resection of an orbital wall
○ Severe corneal ulceration
○ Threatened optic nerve
Describe the radiotherapy technique for graves eye disease.
Graves’ Ophthalmopathy
Pre-simulation
Discussion with ophthalmologist
- Alternate agents trialled
Discussion with endocrinologist
- Maximal disease/thyroid directed therapy
Patient should cease smoking prior
Simulation
Thermoplastic immobilisation mask
2mm CT from vertex to mid neck
- NO contrast
Fusion
N/A
Dose Prescription
20Gy/10F prescribed to the prescription point as per ICRU 50
9 fractions per week
Parallel opposed laterals (4x4cm)
- Half beam block anteriorly to spare the anterior chamber and lens
Target Volumes
CTV = entire retro-orbital space (including muscles)
- Ensure coverage posteriorly to the orbital apex
- Posterior 0.5cm of globe and retrobulbar tissue
- Always treat bilateral eyes
PTV = GTV + 5mm
Target Verification
Daily CBCT
OARs
Minimise lens dose (ideally well less than 5Gy)
ALARA to relevant organs
- Avoid hot-spots in optic nerves
Toxicities
Acute exacerbations - mitigate with concurrent steroids
cataracts 10-30%
XRT retinopathy 1% over 10y
Relative contraindication in HTN/DM due to retinopathy, ~15% if DM
Dry eyes
Describe the epidemiology and pathophysiology for pterygium
- Typically occurs in desert or tropical areas
- Can impact people of any age (20-30s upwards)
- More common in black people
Aetiology
1) UV exposure
a. Geography (hot, dry, dusty environments)
b. Occupation (i.e. outdoors)
Sun protection (sunglasses) reduces risk accordingly
Wedge shaped overgrowth of benign fibrovascular tissue
- Initially involves the conjunctiva, but may extent to obscure the visual axis
- Usually on nasal aspect
Affects visual acuity
Redness
Irritation
Pathophysiology
Poorly understood
Postulated reasons
- UV radiation may result in
○ p53 mutation
○ DNA damage which alters extracellular matrix composition
Abnormal angiogenesis factors
Describe the management of Pterygium
Conservative
The mainstay of therapy for non-obstructive lesions
- Visual axis is preserved
1) Lubricating eye drops 2) Topical NSAIDs 3) Topical glucocorticoids
Surgery
Surgery is the mainstay of treatment, especially if vision is impaired
RF for recurrence: young age, fleshier lesions
1) Bare sclera technique
a. Removal of the connective tissue, leaving bare sclera to heal by second intention
b. Easy and quick (suitable if poorly trained surgeons)
c. Associated with high-rates of recurrence (70-90%)
2) Conjunctival autograft
a. Sampling of the conjunctiva and transposing it to the surgical defect
b. Results in markedly lower recurrence risk (15%)
c. Complex and time-consuming technique
Adjuvant Therapy
Multiple approaches have been proven to reduce the likelihood of recurrence following BST surgery
- Uncertain role of adjuvants after conjunctival autograft (low recurrence rate)
1) Beta-radiation (Sr90 eye plaque) within 24 hours of surgery
a. Options
i. 25Gy/1F via an eye applicator (timed HDR application - depending on source activity)
ii. 24Gy/3F weekly via an eye applicated (improved late toxicity)
b. Local recurrence reduced to 10%
c. Can be associated with scleromalacia and corneal ulceration
2) Mitomycin C (MMC)
a. Injected into pterygium at time of surgery
i. Can also be applied post-operatively
b. Can result in necrosis, ulceration and delayed epithelialisation of the surgical wound
3) Bevacizumab
○ Injected into pterygium at time of surgery
○ Heterogenous dosing
Describe the radiotherapy technique for pterygium
Pterygium
Pre-simulation
Discussion with ophthalmologist
- Likelihood of recurrence
- Alternate adjuvant options (conjunctival autograft, MMC)
Simulation
Uniform ophthalmic applicator is used
Ensure source activity known
- Calculate application time accordingly
Fusion
N/A
Dose Prescription
25Gy/1F prescribed to the surface (within 24 hours of surgery)
- Alternative is 24Gy/3F
Sr90 eye applicator (pure beta –> mean energy = 0.55MeV)
- May be a flat or curved applicator
- 10mm diameter
Procedure
Ensure generous coverage of the surgical field
- 8-12mm applicator is standard
Applicator is constantly moved in a circular motion to cover entire area
- Prescribed dose is “maximum dose”
- Likely that individual areas receive less
Otherwise, ALARA with placement (avoid lens region)
Target Verification
N/A
OARs
ALARA to relevant organs
Toxicities
Scleral thining, infection, corneal ulceration, neovascu
Describe radiotherapy for gynaecomastia
Gynaecomastia: enlargement of male breast tissue dt benign proliferation of glandular component of the breast due to deranged Estrogen: Androgen ratio- usually men with prostate can on ADT or antiandrogen
Management:
* Treatment can be prophylactic or therapeutic
* Main options: Tamoxifen, RT, or surgery (usually if resistant to other Rx)
○ RCT showed TAM and RT are both effective for prophylaxis of gynaecomastia and mastalgia, but TAM (8%) > RT.(34%)
○ Another non -RCT showed that RT can reduce risk of gynaecomastia cf to obs (28 vs 71%)
○ RCT showed that TAM can significantly reduce gynaecomastia and mastalgia at 3 months cf Anastrozole and placebo (11& vs 64 vs 69% respectively)
○ In term of therapeutic, RT can improve/resolve gynaecomastia/ mastalgia in 30-40%., meanwhile TAM is efficacy is 65-70%
○ RT dose: 10-12Gy/1F to breast buds, with either electrons, SXT or Ortho
§ [Yuvnik]- 12Gy/2F Electron, clinical mark up breast tissue, add 1.5cm margin to field edge, treat to post 90% isodose with electron
○ Latent Tox: 2nd malignancy
○ TAM dose: 20mg/d (weekly dosing is inferior to daily)
○ If Gynaecomastia from Oestrogen use: do not use TAM, but use RT instead
