Week 1 - Benign Conditions Treated with Radiation Therapy

ONCOL 309 - Clinical Oncology I. University of Alberta

What is the typical epidemiology of Dupuytren's contracture?

50 years, more common in men, 50% bilateral, frequent in Northern European ancestry, often underreported due to asymptomatic early stages

What are the main risk factors for Dupuytren's contracture?

Genetic predisposition (family history), diabetes, smoking, alcohol

What are the stages of clinical signs in Dupuytren's contracture?

Early: painless palmar nodule; Active: dimpling, rope-like cords; Advanced: cords pull fingers into flexion causing functional limitation

What is the pathology and spread pattern of Dupuytren's contracture?

Benign fibroproliferative disorder with myofibroblast proliferation and collagen deposition; spreads locally along palmar aponeurosis, no metastatic potential

What classification system is used to stage Dupuytren's contracture and what are the stages?

Tubiana classification: I (0–45°), II (45–90°), III (90–135°), IV (>135°)

What is the role of observation in the treatment of Dupuytren's contracture?

Observation is used for early nodules without symptoms

When is radiation therapy used in Dupuytren's contracture and what is its purpose?

Radiation therapy is used for early or active nodules to halt disease progression

What are the main procedural and supportive treatments for Dupuytren's contracture, and what are their key points?

Needle fasciotomy: quick outpatient procedure, high recurrence; Collagenase injections: enzymatic cord disruption, variable recurrence; Surgery: limited fasciectomy or dermofasciectomy + graft, lower recurrence, longer rehab; Splinting/therapy: supportive, not disease-modifying

What is the role of radiation therapy in Dupuytren's contracture?

Stops fibroblast proliferation and prevents progression in early/active disease

What is the rationale for surgery (fasciectomy/dermofasciectomy) in Dupuytren's contracture?

Definitive treatment for fixed contractures; more durable than percutaneous needle fasciotomy (PNF)

What are the key points of needle fasciotomy and collagenase injections in Dupuytren's contracture?

Needle fasciotomy: minimally invasive, rapid recovery, high recurrence; Collagenase: less invasive option if available

Do chemotherapy or hormone therapies have a role in treating Dupuytren's contracture?

No role

How common is combined modality treatment in Dupuytren's contracture?

Rarely used

Why is radiation therapy employed in early Dupuytren's contracture?

Targets actively proliferating fibroblasts, reduces risk of progression, delays or avoids surgery, best used before contracture develops

What are the target volumes and organs at risk for radiation therapy in Dupuytren's contracture?

Target: palmar nodules and cords with margin along involved fascia; Depth: skin → ~5–10 mm to include fascia; OARs: skin, subcutaneous tissue, flexor tendons, digital nerves/vessels, nail beds, MCP/PIP joints

What radiation therapy techniques are commonly used for Dupuytren's contracture?

Orthovoltage (~120 kVp, custom lead shielding, direct apposition); Electrons (6–12 MeV, custom cutout, bolus for surface coverage)

What are validated radiation dose and fractionation regimens for Dupuytren's contracture?

30 Gy in 10 × 3 Gy (split-course: 15 Gy/5 fx, 10–12 week break, repeat); 21 Gy in 7 × 3 Gy over ~2 weeks

What are common acute and chronic side effects of radiation therapy in Dupuytren's contracture?

Acute: redness, tenderness, mild pain, peeling; Chronic: dryness, tightness, skin thickening, decreased sensation, swelling, very low risk of radiation-induced malignancy

What are the expected treatment outcomes for Dupuytren's contracture?

RT (early): stabilizes disease, many avoid/delay surgery; Needle fasciotomy: quick relief, ~85% recurrence at 5 yrs; Surgery: lower recurrence (20–30% at 5 yrs), requires rehab; Collagenase: mixed durability; Without treatment: slow progression, often significant contracture and functional impairment

What is the typical epidemiology of Grave’s disease?

Most common cause of hyperthyroidism in developed countries; strong female predominance; usually diagnosed <40 years; often with a family history

What are the main risk factors and etiology of Grave’s disease?

Autoimmune disorder with TSH receptor autoantibodies; risks include family history, other autoimmune diseases (type 1 diabetes, RA), stress, pregnancy, smoking (↑ risk of ophthalmopathy)

What are the systemic and ocular clinical presentations of Grave’s disease?

Systemic: weight loss, heat intolerance, sweating, tremor; Goiter: diffuse, smooth thyroid enlargement; Ophthalmopathy (~30%): proptosis, lid retraction, gritty sensation, pain, light sensitivity, diplopia, vision loss in severe cases

What is the route of “spread” in Grave’s disease?

Not malignant; orbital disease is autoimmune inflammation of extraocular muscles and orbital fat, not metastatic

What is the pathology of Grave’s disease?

Autoimmune stimulation of thyroid and orbital fibroblasts → ↑ thyroid hormone + cytokine-mediated orbital inflammation

How is ophthalmopathy staged in Grave’s disease?

EUGOGO or NOSPECS classification, ranging from no signs to sight-threatening disease

What are the thyroid-directed treatment options for Grave’s disease?

Antithyroid drugs (methimazole, PTU); Radioactive iodine ablation (I-131); Thyroidectomy if refractory

What are the ophthalmopathy-directed treatment options for Grave’s disease?

Systemic steroids for moderate-severe active disease; Orbital decompression for sight-threatening compression; Radiation therapy for moderate active disease when steroids insufficient or poorly tolerated; Supportive: lubricating drops, prisms, smoking cessation

What is the rationale for radiation therapy in Grave’s ophthalmopathy?

Targets activated orbital fibroblasts and lymphocytes, suppressing cytokine-driven inflammation; reduces orbital swelling, muscle inflammation, compressive effects; preserves vision; allows reduction or discontinuation of steroids

What is the rationale for surgery in Grave’s disease?

Orbital decompression for severe vision-threatening ophthalmopathy; Thyroidectomy if unstable hormone control

Do chemotherapy, biologics, or hormone therapy have a role in Grave’s disease?

Chemo/biologics: not standard (teprotumumab emerging in some centers); Hormones: antithyroid drugs control systemic thyrotoxicosis

How is combined modality therapy used in Grave’s disease?

Radiation therapy often given with steroids to enhance control and allow steroid taper

What are the target volumes and organs at risk for radiation therapy in Grave’s ophthalmopathy?

Target: extraocular muscles and retro-orbital tissue; OARs: lens, retina & optic nerve, lacrimal gland, parotid gland if lateral fields extend

What radiation therapy techniques are commonly used for Grave’s ophthalmopathy?

VMAT/IMRT: best conformality and lens sparing; 3DCRT/LOF: historically common; Small unilateral fields with half-beam block; Gantry ~5° posterior tilt to push dose behind lens

What is the standard radiation dose and fractionation for Grave’s ophthalmopathy?

20 Gy in 10 fractions (2 Gy/fx) over 2 weeks using 6 MV photons; internationally guideline-based; higher doses unnecessary, lower doses less effective

What are common acute and chronic side effects of radiation therapy in Grave’s disease?

Acute: mild eyelid erythema, conjunctival irritation, temporary dry eye, transient symptom flare; Chronic: cataracts, dry eye, rare radiation retinopathy or optic neuropathy; secondary malignancy risk negligible

What are the expected treatment outcomes for Grave’s ophthalmopathy?

RT (20 Gy/10 fx): stabilizes or improves ophthalmopathy in 60–90%; reduces steroid reliance; best in active disease; Surgery: for sight-threatening or persistent proptosis; Systemic treatment: controls systemic thyrotoxicosis but does not reverse ophthalmopathy; Without treatment: may progress to fibrosis, diplopia, vision loss

What is the typical epidemiology of arteriovenous malformations (AVMs)?

Congenital vascular defects; most present between 20–40 years

What is the etiology of AVMs?

Exact cause unknown; may have genetic links to hereditary vascular syndromes (e.g., HHT), but AVMs themselves are not inherited

What are common clinical presentations of AVMs?

Highly variable depending on site: headaches, nausea/vomiting, seizures, neurological deficits (weakness, paralysis, sensory changes, ataxia, speech/vision impairment), cognitive/behavioral issues in children/teens

What is the route of “spread” in AVMs?

Non-neoplastic; confined to vascular structures

What is the pathology of AVMs?

Mass of tangled arteries and veins lacking a normal capillary bed → high-pressure shunting

How are AVMs staged?

Spetzler-Martin grading system based on size, eloquence of location, and venous drainage pattern

What is the role of observation and surgery in AVM management?

Observation is chosen for small, asymptomatic AVMs; Microsurgical resection is first-line for accessible/low-grade AVMs, providing immediate cure and reducing hemorrhage risk

What is the role of endovascular embolization and combined modality therapy in AVMs?

Embolization reduces AVM size or flow, often used as adjunct to surgery or SRS; Combined approaches (embolization + surgery or embolization + SRS) improve safety and effectiveness in selected patients

What is the role and rationale of stereotactic radiosurgery (SRS) in AVMs?

SRS is used for inoperable, deep, or small AVMs; high-dose precise RT causes endothelial damage → gradual vascular sclerosis and occlusion over 1–3 years; reduces hemorrhage risk during latency period; best for lesions <3 cm

Do chemotherapy or hormone therapies have a role in AVMs?

No role

What are the target volumes and organs at risk for radiation therapy in AVMs?

Target: entire AVM nidus (defined on angiography/MRI); OARs: critical brain structures depending on location (optic nerves/chiasm, brainstem, hippocampus, motor/speech areas); dose constraints must be respected

What radiation therapy techniques are commonly used for AVMs?

Stereotactic radiosurgery (SRS): Gamma Knife (Cobalt-60 based, highly conformal) or LINAC-based SRS (frameless or frame-based); sub-mm accuracy with steep dose fall-off

What are validated radiation doses and fractionation for AVMs?

Lesion

What are common acute and chronic side effects of radiation therapy in AVMs?

Acute: headache, nausea, mild local edema; Chronic: radiation necrosis, cognitive deficits if near eloquent areas, visual/motor/sensory deficits if OARs affected; rare secondary malignancy risk

What are expected treatment outcomes for AVMs?

Surgery: immediate cure if complete resection, risk depends on location/grade; SRS: obliteration ~70–90% for <3 cm, lower success for larger AVMs, latency 1–3 yrs; Without treatment: hemorrhage risk ~2–4%/year, cumulative lifetime risk significant, severe hemorrhage may be fatal or disabling

What is the etiology of keloids?

Abnormal wound healing → excessive collagen deposition following dermal injuries (burns, piercings, acne, chickenpox, lacerations, biopsy)

What is the pathology of keloids?

Benign fibroproliferative disorder; collagenous tissue extends beyond wound margins

What is the epidemiology of keloids?

Most common age 10–30 years; more frequent in individuals with darker pigmentation (Black, Hispanic, Asian); genetic predisposition increases risk

What are the clinical features of keloids?

Firm, raised, itchy or painful scar; fibrotic, shiny surface; may be cosmetically disfiguring

What is the route of spread and staging for keloids?

Non-neoplastic; confined to dermis/subcutaneous tissue; no formal staging system

What are the main non-radiation treatment options for keloids?

Surgery: removes keloid but high recurrence if used alone; Injections: steroids, bleomycin, interferon, botox reduce scar tissue; Cryotherapy: freezing damages fibroblasts, best for smaller lesions; Laser therapy: improves cosmesis, reduces vascularity

How is combined modality therapy used in keloid management?

Surgery + adjuvant RT ± injections = best long-term control; multimodal approach needed for difficult locations or large lesions

What is the rationale for radiation therapy in keloids?

Causes fibroblast apoptosis and reduces collagen production; when delivered within 24–72 hours post-surgery, significantly decreases recurrence risk; acts as adjuvant after re-excision

What are the target volumes and organs at risk for keloid radiation therapy?

Target: surgical bed + scar area with small margin; OARs: adjacent normal skin and subcutaneous tissue; careful field shaping and shielding to spare surrounding tissue

What radiation therapy techniques are commonly used for keloids?

Superficial kV or electron beam therapy (MeV) depending on depth; single field technique often with customized shielding; superficial setup to cover dermal tissue only

What are validated radiation dose and fractionation regimens for keloids?

10–15 Gy in 2–3 fractions (preferred); 37.5 Gy in 25 fractions (less common, older regimen); dose based on lesion size, location, and protocol

What are common acute and chronic side effects of keloid radiation therapy?

Acute: epilation, erythema; Chronic: pigmentation changes, telangiectasia (risk rises with cumulative dose), skin atrophy

What are expected treatment outcomes for keloids?

Surgery alone: high recurrence (45–100%); Surgery + post-op radiation therapy: recurrence reduced (~10–20%); best results with multimodal approach (surgery + RT ± injections/cryotherapy); cosmetic and functional outcomes improved when RT timed within 72 hrs

What is the etiology of craniopharyngioma?

Unknown; arises from embryologic remnants of Rathke’s pouch

What is the epidemiology of craniopharyngioma?

Rare: ~1% of adult brain tumors, ~6% of childhood brain tumors; bimodal distribution—children (5–14 yrs) & adults (50–60 yrs)

What is the pathology of craniopharyngioma?

Benign but locally invasive; solid + cystic components, often with calcifications visible on X-ray

What are the common clinical features of craniopharyngioma?

Endocrine dysfunction (delayed puberty, growth failure, amenorrhea, impotence), diabetes insipidus, headaches, fatigue, increased intracranial pressure, vision loss from optic chiasm compression

What is the route of spread and staging for craniopharyngioma?

No metastatic potential; invades locally into pituitary, hypothalamus, optic chiasm, and adjacent brain; staging based on resectability and involvement of adjacent structures

What are the main non-radiation treatment options for craniopharyngioma?

Surgery: craniotomy or transsphenoidal excision; complete resection improves control, subtotal safer to avoid hypothalamic/optic damage; Intracystic agents: bleomycin, interferon-alpha, P-32; Targeted therapy emerging for BRAF-mutated papillary subtype

How is combined modality therapy used in craniopharyngioma?

Subtotal resection + post-op RT balances local control and reduced surgical morbidity; intracystic therapy may be added for cystic recurrences

What is the rationale for radiation therapy in craniopharyngioma?

Provides durable local control when surgery is incomplete or not possible; can shrink cystic and solid components; helps preserve vision and neurological function; SRS and proton therapy allow precise delivery, minimizing dose to optic nerves, hypothalamus, and pituitary

What are the target volumes and organs at risk for radiation therapy in craniopharyngioma?

Target: tumor bed (solid + cystic mass) + margin; OARs: optic nerves/chiasm, hypothalamus, pituitary, temporal lobes, brainstem, hippocampus

What radiation therapy techniques are commonly used for craniopharyngioma?

IMRT/VMAT for conformal coverage; SRS (Gamma Knife or LINAC-based) for small, well-circumscribed lesions; Proton therapy to reduce integral brain dose; Interstitial brachytherapy (intracavitary P-32, bleomycin, interferon-alpha) for recurrent cystic tumors

What are validated radiation dose and fractionation regimens for craniopharyngioma?

EBRT: 50.4–54 Gy in 1.8 Gy/fraction; SRS (Gamma Knife): 9–20 Gy single fraction to tumor margin, up to 20–50 Gy max dose inside lesion; Intracystic therapy: varies by agent

What are common acute and chronic side effects of radiation therapy in craniopharyngioma?

Acute: fatigue, headaches, transient edema; Chronic: hypopituitarism, delayed optic neuropathy, cognitive dysfunction, secondary tumors, vascular effects (stroke, aneurysm, malformations)

What are the expected treatment outcomes for craniopharyngioma?

Generally benign but recurrence common, especially after subtotal resection; 10-year survival 80–90%; prognosis depends on completeness of resection, effectiveness of RT, and preservation of pituitary/optic function; long-term issues include endocrine replacement, neurocognitive decline, vision loss, vascular/metabolic complications

What is the etiology of acoustic neuroma?

Linked to chromosome 22 abnormality (NF2 gene → bilateral cases in Neurofibromatosis type 2)

What is the epidemiology of acoustic neuroma?

Rare, benign, slow-growing; most often diagnosed at 50–55 years

What is the pathology of acoustic neuroma?

Schwann cell tumor of the vestibulocochlear nerve (cranial nerve VIII); benign, encapsulated, localized growth

What are the clinical features of acoustic neuroma?

Auditory: progressive unilateral sensorineural hearing loss (most common), tinnitus; Vestibular: vertigo, imbalance; Neurological: headaches, facial numbness/weakness, hydrocephalus from mass effect

What is the route of spread and staging for acoustic neuroma?

None; purely local growth, compresses adjacent structures (brainstem, cerebellum, cranial nerves); staged by size and neurological impact

What are the main non-radiation treatment options for acoustic neuroma?

Watchful waiting for small, asymptomatic tumors; Surgery for large/symptomatic tumors via translabyrinthine, retrosigmoid, or middle fossa approaches; Supportive therapy: balance rehab, hearing aids, symptom management

What is the role of radiation therapy in acoustic neuroma?

Controls tumor growth in nonsurgical candidates, elderly, or patients wishing to avoid surgery; minimizes cranial nerve risk; preserves facial nerve and sometimes hearing; outpatient, less invasive

How is combined modality therapy used in acoustic neuroma?

Surgery + postoperative RT for residual disease; SRS or FSRT may be used for small-to-medium tumors in nonsurgical candidates

What are the target volumes and organs at risk for radiation therapy in acoustic neuroma?

Target: tumor (internal auditory canal ± cerebellopontine angle extension); OARs: brainstem, cochlea, optic apparatus, trigeminal and facial nerves

What radiation therapy techniques are commonly used for acoustic neuroma?

SRS (Gamma Knife, LINAC, CyberKnife) → 1 fraction, highly conformal; FSRT → fractionated stereotactic RT, useful for larger tumors; Proton therapy → conformal, limits dose to brainstem/temporal lobe

What are validated radiation dose and fractionation regimens for acoustic neuroma?

SRS: 11–14 Gy in 1 fraction to tumor margin; FSRT: 45–54 Gy in 1.8–2 Gy/fraction (~5–6 weeks); Proton therapy: similar fractionation to FSRT, reduced integral dose

What are common acute and chronic side effects of radiation therapy in acoustic neuroma?

Acute: mild fatigue, headaches, transient vestibular irritation; Chronic: hearing loss (progressive), tinnitus, facial/trigeminal neuropathy, balance issues; rare → radiation necrosis, secondary malignancy

What are expected treatment outcomes for acoustic neuroma?

Excellent local control (>90% at 10 yrs with SRS/FSRT); facial nerve preservation >95%; hearing preservation less reliable; surgery effective for large tumors but higher cranial nerve risk; overall prognosis very good, functional outcomes depend on size, location, and treatment

What is the etiology of pterygium?

Strongly linked to UV radiation exposure, dust, chronic eye irritation, and tear film abnormalities

What is the epidemiology of pterygium?

Worldwide; more common in warm, dry climates (within 37° N–S of equator); highest incidence ages 20–49; rare under 15

What is the pathology of pterygium?

Benign, fleshy vascular overgrowth of conjunctival epithelium onto cornea in a wing-shaped formation

What are the clinical features of pterygium?

Burning, irritation, tearing, “foreign body” sensation; astigmatism and vision impairment if cornea invaded; advanced cases may have symblepharon formation → ocular motility restriction, diplopia

What is the route of spread and staging for pterygium?

Local invasion onto cornea only; no metastasis; staged by corneal invasion extent and impact on vision

What are the main non-radiation treatment options for pterygium?

Observation and lubrication for mild/asymptomatic cases; sunglasses/UV protection; Surgical excision (mainstay) for symptomatic/progressive lesions

What adjuvant therapies are used for aggressive/recurrent pterygium?

Steroids: reduce inflammation; Topical Mitomycin C: inhibits DNA synthesis/mitosis to reduce recurrence; Bevacizumab (anti-VEGF): inhibits neovascularization, stabilizes vision

What is the rationale for radiation therapy in pterygium?

Adjunct to surgery; prevents fibroblast proliferation that drives regrowth; most useful for recurrent or aggressive cases; localized with minimal systemic toxicity

What are the target volumes and organs at risk for pterygium radiation therapy?

Target: surgical bed of excised pterygium; OARs: lens (most important), retina, sclera, cornea

What radiation therapy techniques are commonly used for pterygium?

Strontium-90 applicator (β-emitter): localized superficial dose, rapid fall-off, minimal lens exposure; direct contact brachytherapy within 48 hrs post-surgery