general oncology from devita presentation

1. ROLE OF RADIOTHERAPY
IN BENIGN DISEASES
PRESENTER – DR SAJAL GOEL

2. IMPORTANT ASPECTS
✓Nonmalignant diseases can be successfully treated with ionizing radiation
✓These diseases can be classified but topography and morphology are more
relevant
✓Differences in clinical practice exist because of clinical traditions and
differences in organization and training
✓Criteria of evidence-based medicine are relevant for the use of
radiotherapy for non malignant diseases

3. Classification of Non
Malignant Diseases
✓Inflammatory
✓Degenerative
✓Hyperproliferative
✓Functional
✓Other disorders

4. JUSTIFICATION AND INDICATIONS
FOR RADIOTHERAPY
✓Invasive and aggressive growth (desmoids)
✓Cosmetic disfiguration and functional loss (keloids or endocrine orbitopathy
[EO])
✓Life-threatening complications (hepatic hemangioma [Kasabach-Merritt
Syndrome]) or juvenile angiofibroma of face
✓Nonmalignant diseases causing pain or other serious symptoms other
methods have failed, or may induce more side effects

5. LONG TERM RISK OF TUMOR INDUCTION
(UNSCEAR, BIER DATA)
✓Average lifetime risk men (9.5%) < women (11.5%)
✓The individual risk depends on:
individual sensitivity
eg) genetically predisposed diseases
anatomic site and
technical parameters
viz. single and total doses radiation protection

6. TYPES ABSOLUTE LIFETIME RISK
Skin (Basal cell
carcinoma)
0.1% for 100 cm2 field
Osteosarcoma <0.0001% for 1 Gy and 100 cm2 field
Leukemia 1% for 1 Gy TBI
Brain
tumor
0.2% after 20 Gy for endocrine orbitopathy
Thyroid carcinoma 1% per Gray for children < 10 years
Breast
carcinoma
5% for one breast, 1 Gy, age < 35 years
(<3% for age 25-35 years)
Lung
carcinoma
1% within 25 years after a mean lung dose of 1 Gy

7. ✓As RT in most cases is an elective measure, a thorough risk-benefit analysis
is required
✓Organ-specific acute and chronic late effects including potential effects on
reproduction and possible induction of tumors and leukemia are potential
risks that have to be explained to patients within the INFORMED CONSENT

8. PRINCIPLES
✓ Estimate the natural course of disease without therapy
✓ Consider potential consequences of nontreatment
✓ Review data about alternativetherapies and their therapeutic results
✓ Conduct a risk-benefit analysis compared with other possible measures
✓ Proof that the indication is justified:
• if conventional therapies have failed,
• if risks and consequences of other therapies are greater, and if
nontreatment has more dramatic consequences
than irradiation

9. ✓ Consider the individual potential long-term radiogenic risks
✓ Inform patient about all details of radiotherapy:
target volume, single/total dose, duration of session and series,
relevant radiogenic risks, and side effects
✓ Written consent of patient following thorough education
✓ Assurance of long-term aftercare in order to document result
✓ Request a competent second opinion in case of doubts and if the provided
patient data or treatment decision are uncertain

10. ✓ Outside Europe, the use of RT to treat benign disease is not well
established and often regarded with skepticism
✓ The last written recommendations for the treatment of nonmalignant
disease in the United States were made by the Bureau of Radiologic
Health in 1977

14. RADIOBIOLOGICAL ASPECTS
✓increase in capillary permeability and tissue perfusion (perfusion theory)
✓destruction of inflammatory cells and release of mediators,
cytokines, and proteolytic enzymes (fermentative theory)
✓impact on the autonomous nervous system (neuro regulatory theory)
✓impact on the composition of the tissue milieu (electrochemical theory)
✓preventing mitotic cells from proliferating (antiproliferative effect )

15. RADIATION THERAPY MECHANISMS OF ACTION
AND DOSE CONCEPTS
MECHANISMS OF ACTION SINGLE DOSE (Gy) TOTAL DOSE (Gy)
Cellular gene and protein
expression
(Eczemas)
< 2 < 2
Inhibition of inflammation in
lymphocytes (Pseudotumor
orbitae)
0.3 - 1 2 - 6
Inhibition of fibroblast
proliferation
(Keloids)
1.5 - 3 8 - 12
Inhibition of proliferation in
benign tumors
(Desmoids)
1.8 - 3 45 - 60

16. DISORDERS OF CONNECTIVE
TISSUES AND SKIN
DESMOID (AGGRESSIVE FIBROMATOSIS )
INDURATIO PENIS PLASTICA (MORBUS PEYRONIE)
MORBUS DUPUYTREN AND MORBUS LEDDERHOSE
KELOIDS AND HYPERTROPHIC SCARS

17. DESMOID (AGGRESSIVE FIBROMATOSIS)
✓Benign connective tissue tumors of deep muscular-aponeurotic structures in
the region of muscle fascias, aponeuroses, tendons, and scar tissue
✓Incidence 2-4 per 1 million per year
✓Female > Male (1:1.5 to 2.5)
✓Age group - Third and fourth decades of life, but children also
can be affected
✓May suspend spontaneously or grow fast

18. NON RADIOTHERAPEUTIC TREATMENT
✓ Surgical removal with a safety margin of 2 to 5 cm is
the gold standard
R0 resection - no therapy is required
R1 resection - wait and treat the upcoming relapse
✓ Tamoxifen and progesterone - growth inhibitory effects
✓ NSAID’S, vitamin C and alkylating substances
✓ Tested but not yet established

19. RADIOTHERAPEUTIC OPTIONS
✓Indications:
Inoperable cases
R2 resection
R1 resection if repeated surgery already applied
✓Dose:
Postoperatively 50 to 55 Gy ( 1.8 to 2.0 Gy / #)
Inoperable or recurrent desmoids 60 to 65 Gy
Rest tumor or recurrence 50 to 55 Gy
✓ RT is often used as adjuvant or primary treatment

20. Cancer 2000;88:1517–23. 2000 American Cancer Society.

29. Micke et al, IJROBP, 2005

31. ✓ Dose: 50 to 55 Gy in 1.8 to 2 Gy fractions/ one fraction per day
✓ Recommendation: Generous margins
✓ Cover entire operative area and/or area of gross disease to avoid
geographic miss

32. ✓No standard cm of coverage that is recommended
✓Extent of coverage depends on
• tumor size
• number of prior recurrences
• extent of operative hematoma
• proximity of tumor to paths of little resistance
(e.g., along the neurovascular bundle)
✓Fields for aggressive fibromatosis may need to be even more extensive
than those for soft tissue sarcomas

33. PTV = CTV + 0.5 CM
GTV = PREOP GTV
CTV = GTV + 5 CM
MEDIOLATERALLY AND
CRANIOCAUDALLY

37. DOSE PRESCRIPTION:
GTV 60 Gy/ 30 # @ 2 Gy/ #
CTV 50 Gy/ 30 # @1.66 Gy/ #
PTV 50 Gy/ 30 # @ 1.66 Gy/ #
DOSE EVALUATION:
GTV 59.18 Gy/ 30# @ 1.97 Gy/ #
CTV 51 Gy/ 30 # @ 1.7 Gy/ #
PTV 49.9 Gy / 30 # @ 1.66 Gy/ #

38. KELOIDS AND HYPERTROPHIC SCARS
✓Excessive tissue proliferation about scars after skin injury from surgery,
heat, chemical burns, inflammation (e.g., acne), or even spontaneous
proliferation
✓Infiltrative growth pattern
✓Causes local pain, inflammatory reactions and long-term progression
✓Differential Diagnosis - Hypertrophic scars

39. ✓Location - Upper body
Sternum
Earlobes
✓Cause - unknown
✓Genetic and Race-specific
predisposition noted during
adolescence
✓Disturbed cosmesis may be
accompanied by pain, itching, and
dysfunction

40. NONRADIOTHERAPEUTIC TREATMENT
✓Surgical Excision
✓Conservative Measures
Pressure and Silicon bandages
Steroid injections
Plant extracts for small lesions
✓In >50% of patients, local relapse occurs that is not
dependent on the type of resection

41. Indications for RT :
✓Repeated recurrences postoperatively
✓High-risk situations
• marginal resection
• wider spread
• unfavorable location
RADIOTHERAPEUTIC TREATMENT

42. ✓Primary RT:
• Functional inoperability
• Actively proliferating disorders within about 6
months after the triggering trauma
✓Prophylactic RT:
(immediately after excision of the recurrence)
• Fully matured keloids

43. ✓RT is initiated 24 hours after surgery
✓Radiation quality has to be adapted to the local conditions
• Conventional x-rays (70 to 150 kV)
• Electrons (<6 MeV)
• Iridium-192 brachytherapy with implants
• Strontium-90 dermal plates

44. ✓Target volume
Scar plus a 1-cm deep safety
margin on both sides of the scar
✓ Lead absorbers need to be prepared if required
✓ Recommended total dose:
12 to 20 Gy
5 X 3 or 4 X 4 Gy within 1 week
✓ Single-dose RT with 7.5 to 10 Gy is also effective

46. IJROBP VOL 52, P 496-513, 2002

47. CLINICAL RESULTS AND LONG TERM OUTCOMES AFTER
RADIOTHERAPY

48. INDURATIO PENIS PLASTICA
( MORBUS PEYRONIE)
✓Chronic, mostly progressive, inflammation and tissue
proliferation of the penile tunica albuginea
✓Affects men at 40 to 60 years
✓Cause is unknown
✓Diabetes mellitus
✓Arterial and venous vascular disease risk factors
✓Genetic predisposition

49. Inflammatory changes at tunica albuginea
Connective tissue reactions and formation of hard plaques lumps, and
cords (100%)
Penile bending Pain at erection Impair cohabitation (80%)
(80%) (30% to 50%)
Slow progression over several months is typical,
Spontaneous remission may develop rarely

50. NONRADIOTHERAPEUTIC TREATMENT
SO FAR THERE IS NO SUCCESSFUL STANDARD TREATMENT
EARLY PHASE:
Vitamin E, para-aminobenzoate, and steroids
Local treatments but their evidence is small
Ultrasound
Shock waves
Corticoid, procaine, and hyaluronic acid injections
RT may delay induration
softens lumps and strands
reduces pain, bending, and functional problems
ADVANCED STAGES:

51. RADIOTHERAPEUTIC TREATMENT
✓Protect gonads and glans penis with lead apron or capsule
✓Orthovoltage machine - non erected penis/ dorsal field
✓LINAC - electrons upto 6 MeV with 5 to 10 mm bolus
✓Usual dose - 20Gy / 2Gy per fraction
Hypofractionation - 12 to 15 Gy // 2 to 4 Gy / #
2- 4 #per week
✓No response, repeat this regimen after 6 to 12 weeks up to a total
dose of 30 Gy
✓For extensive indurations, high dose rate brachytherapy is suitable

52. ✓Within 1 to 2 years, RT improves symptoms in 2/3rd early-stage patients
✓Local pain and associated clinical symptoms decrease in up to 75%
✓Angulation (25% to 30%) and dysfunction of the penis (30% to 50%)
show less response because these symptoms often indicate that
the disease is already in a more advanced stage

53. IJROBP VOL 52, P 496-513, 2002

54. MORBUS DUPUYTREN AND MORBUS
LEDDERHOSE
✓Connective tissue disorders that
affect the palmar or plantar
aponeurosis
✓Often bilateral
✓Hands (MD) > feet (ML)
✓Mostly, the fourth/fifth
phalanges of the hand (MD) or
the first/second toes of the foot
(ML) are affected
✓Age group 40 and 70 years

55. RISK FACTORS AND PATHOGENESIS
✓Familial disposition
✓Alcohol abuse
✓Diabetes mellitus
✓Epilepsy, and other conditions
✓Causes and pathogenesis are still not adequately determined

57. NONRADIOTHERAPEUTIC TREATMENT
✓Early stage
• Steroids
• Allopurinol
• Nonsteroidal
antiphlogistics
• Enzymes
• Vitamin E and
• Softeners
✓Surgery –
• Functionally impairing
flexion contractions of
fingers
(>30 degrees)
• Strong pain while walking
Preventive strategies are more important

58. RADIOTHERAPEUTIC TREATMENT
✓Prophylactic EBRT during early stages is a good rationale
✓RT makes sense during the early stage (lumps, strands) with
moderate extension deficit ( < =10 degrees)
✓Target cells: proliferating and radiosensitive fibroblasts and
inflammatory cells
✓The goal of treatment is to avoid further progression or later
surgery

59. ✓Orthovolt (100 to 150 kV photons) or linear accelerator with
electrons (up to 6 MeV) via stationary field used
✓Protection of unaffected areas (individually adapted lead shields)
✓Safety margin -1 cm laterally and 2 cm proximally and distally
✓Total dose - 20 to 30 Gy// 2 to 3 Gy/#
Repeat after 6 to 12 weeks up to a total dose of 30 Gy.
4 to 5 Gy / # every 1 to 2 months

60. RESULTS OF THERAPY
✓Many studies have shown good response to RT
• Stabilization of the disease (70% to 80%)
• Regression of nodules and strands (20% to 30%)
• Disease progression in spite of previous irradiation occurs in
20% to 25%
✓Existing extension deficits are normally not improved
✓Patients with extension deficits (stage I/II) have a significantly
increased rate of recurrence or progression

61. IJROBP VOL 52, P 496-513, 2002

62. DISORDERS OF JOINTS AND
TENDONS
GENERAL ASPECTS
DEGENERATIVE ARTHRITIS
ROTATOR CUFF SYNDROME
TENNIS / GOLFER’S ELBOW
CALCANEODYNIA / ACHILLODYNIA

63. GENERAL ASPECTS
✓RT is a last-resort approach, but before surgery is indicated
✓Recommended RT concepts use:
Daily fraction of 0.5 - 3 Gy for acute inflammation
and
0.5 to 1.0 Gy are applied 2-3 times per week up to 6 Gy for chronic
inflammatory reactions
In case of minor response, a second series is delivered after 6 weeks

64. DEGENERATIVE ARTHRITIS
✓A painful joint process associated with cartilage destruction, bone
modification, and structural changes of capsule and synovia
✓Subjective symptoms and radiographic findings are often incongruent
✓Functional loss has an impact on professional and leisure activities and
reduces quality of life

67. NONRADIOTHERAPEUTIC TREATMENT
✓Prevention and early recognition are crucial
✓Pre arthrotic changes - corrective osteotomy
✓Noninvasive measures
✓Invasive measures:
Arthroscopic lavage
Debridement of inflammatory synovial changes
✓Autologous cartilage replacement - small joint areas
✓Partial or total joint replacement with an artificial implant is lat option

68. RADIOTHERAPEUTIC TREATMENT
✓Low-dose RT is indicated if noninvasive measures have failed
- Reduces pain and pain-related dysfunction
- Does not remove pathomorphologic changes
✓The affected joints of the upper (shoulder, elbow, thumb, fingers) and lower
(hip, knee, ankle) extremity are irradiated
✓Lateromedial or ventrodorsal opposing fields using the orthovolt (150 to 200
kV/20 mA, 4-mm Al filter) or linear accelerator low-energy photons (<6 MV)

69. ✓Dose reference point:
Always located in the center of joint (for opposing field setup)
✓A pain record of >2 years and objective findings like joint grinding,
deformity, radiologic OA stage IV, are indicators of unfavorable prognosis
✓Joint replacement surgery might be delayed or completely avoided in
individual cases

70. IJROBP VOL 52, P 496-513, 2002

71. TENDINITIS AND BURSITIS
✓ Causes:
• Acute and chronic strain with macro- or microtrauma
✓ Particularly affected joints:
• Shoulder (peritendinopathia humeroscapularis)
• Elbow (epicondylopathia humeri or tennis/golfer's elbow)
• Ankle joint (plantar fasciitis)
• Achilles tendon (achillodynia)
• Heel region (calcaneodynia)

72. GENERAL MANAGEMENT
✓Immobilization and protection of joint function
✓Local cold or heat
✓Analgesics and antiphlogistics
✓Local injections of anesthetics and corticosteroids
✓Physiotherapy (stretching/deep friction technique)
✓Shock wave therapy
✓Electrotherapy
✓Acupuncture
✓Surgical measures - chronic-recurrent cases

73. RADIOTHERAPEUTIC MANAGEMENT
✓Indication:
when conservative measures have failed and before surgery
✓Energy used:
Orthovlotage (100 to 300 kV)
LINAC (6 to 10 MV)
✓Local and systemic medication can be continued during RT
✓Local response to irradiation is often preceded by short-term
intensification of pain about the irradiated tendon or bursa

74. IJROBP VOL 52, P 496-513, 2002

75. ROTATOR CUFF SYNDROME
✓ Periarthropathia humeroscapularis / subacromial syndrome describes a condition of pain
and functional loss of the shoulder joint
✓ All muscular structures, tendons, and bursae of the shoulder region can be affected
✓ Numerous conditions may trigger this problem:
• Arthritis
• Capsulitis
• Bursitis
• Tendonitis
✓ Local calcifications or ossifications are signs of a chronic reactive disease process

76. NONRADIOTHERAPEUTIC TREATMENT
✓Local injections (corticoids, anesthetics)
✓Oral antiphlogistics and analgesics
✓Physical therapy
✓Surgical measures indicated in the case of tendon rupture
✓Radiation therapy if conservative management fails

77. RADIOTHERAPEUTIC MANAGEMENT
✓Orthovolt machine (200 to 250 kV, 15 mA, 1-mm Cu filter) or linear
accelerator
✓Opposing fields - shoulder joint-related pain
Direct single fields - localized tendinopathies
✓Dose reference point :
• center of the affected joint (5 to 8 cm) or
• at the depth of the tendon attachment site (1 to 2 cm)
✓Field sizes range between 10 x 10 to 10 x 15 cm2

78. ✓Pain relief and improved mobility - in up to 80% of patients
✓Pain record (>2 years) and the extent of joint modifications
(accompanying arthrosis) are determinants for prognosis
✓Short-term intensification of pain during the RT series is frequently a
favorable sign for clinical response
✓Residual pain and functional deficit after one RT series of 6 X 1Gy, a
second series of RT is indicated
✓ The clinical improvement is often long-lasting

79. RADIOTHERAPY FOR REFRACTORY ROTATOR CUFF
SYNDROME:
SELECTED STUDIES

80. TENNIS / GOLFER’S ELBOW
✓A painful inflammation of the tendon attachment site of the finger
and hand muscles of the radial (lateral) or ulnar (medial) epicondylus
of the upper arm
✓Causes
• intensive fine and gross motor activity
• extreme strain of the arm or awkward movements during exercise
• traumatic
• mechanical irritation of the bursae
✓Genders are equally affected
✓Average age for either condition is 45 years

81. ✓First symptoms appear during stress, later also during night and day as
constant pain, resting pain, and start up pain (in the morning)
✓Affected people are impaired in professional work and leisure activities
✓ Radiographs rarely demonstrate clear findings
✓MRI may uncover typical soft tissue modifications (edema of muscles and
insertion zone)
✓Cervical spine syndrome has to be excluded

82. ✓If noninvasive treatments have failed, RT is indicated
✓Orthovoltage photons (100 to 150 kV, 20 mA, 4-mm Al filter) or linear
accelerator low-energy photons (<6 MeV)
✓A stationary field is targeted directly to the affected lateral or medial
epicondylus
✓The dose reference point is calculated at a depth of 5 mm

83. ✓ Even for chronic pain, RT achieves good pain reduction in up to 80% of
cases
✓ >12 months pain record, the response is worse than for early RT
✓ Relapses after therapeutic success are rare (5%)
✓ Disease record (>1 year), number of previous treatments, and long
immobilization are unfavorable prognostic results
✓ If pain reappears after surgery, RT as salvage therapy

84. CALCANEODYNIA / ACHILLODYNIA
✓Pain syndromes of the heel region
✓Entire osseous and tendinous system of the foot and legs is impaired
- flatfoot, splayfoot, and skew foot deformities
- genu varum or valgum malposition
✓Chronic stress leads to plantar and dorsal osseous spurs of up to 20
mm in length

85. ✓Short-term vigorous forces or malpositions and mini
trauma are triggering factors
✓Both genders equally affected
✓Incidence increases with age
✓Running and sports with sudden or impulsive movements
may lead to an earlier onset of disease

87. NONRADIOTHERAPEUTIC TREATMENT
✓Potential anatomic malpositions are corrected to avoid further stress.
✓For Painful heel - special cushion inlays.
✓Local injections (with corticoids, anesthetics) and oral antiphlogistics or
analgesics are used for immediate pain relief
✓Physical therapy and physical measures (cold, ultrasound, microwaves,
shock waves)
✓Surgical incision of the plantar fascia is only done if conservative
therapy fails

88. RADIOTHERAPEUTIC TREATMENT
✓RT is indicated if noninvasive treatment fails.
✓Orthovolt photons (100 to 150 kV, 20 mA, 4-mm Al filter) or linear
accelerator with low-energy photons (<6 MeV)
✓A stationary 6 X 6 to 8 X 8 cm2 field (plantar) or opposing fields (dorsal) are
used
✓Dose of 3 to 6 X 0.5 to 1 Gy to the dose reference point located at a depth
of 5 mm (stationary field) or at the center of the joint (opposing
fields)

90. DISORDERS OF BONY TISSUES
ANEURYSMAL BONE CYST
PIGMENTED VILLONODULAR SYNOVITIS
VERTEBRAL HEMANGIOMAS
HETEROTOPIC OSSIFICATION

91. ANEURYSMAL BONE CYST
✓Benign, vascular cystic lesions
✓ Metaphysis of bones
✓Cause functional impairment,
pathologic fractures,
damage of neighboring structures and
Infiltration into surrounding soft tissue
✓Leads to bone destruction and evoke serious problems, which is why
treatment is recommended once a cyst has been diagnosed, eg)
vertebral column.

92. X RAY APPEARANCE: An eccentric well defined radiolucent area with
expansion of overlying cortex and trabeculation within the substance
of tumor involving upper end of tibia likely Aneurysmal Bone Cyst.

93. NONRADIOTHERAPEUTIC TREATMENT
✓Surgery (resection or curettage) is the gold standard
✓Following curettage, recurrence occurs in up to 60% of patients
✓After complete resection, there is normally no recurrence

94. RADOTHERAPEUTIC TREATMENT
✓Indications:
• If cysts cannot be treated by surgery
• If curettage is difficult because of size or site of the lesion
• Cyst progression or repeated recurrences
• Inaccessible cysts of the vertebral column and the pelvis
✓RT doses should be kept as low as possible.
✓10 – 20 Gy for 1 to 2 weeks - an adequate dose.

95. PIGMENTED VILLONODULAR SYNOVITIS
✓Rare proliferative disease affecting the synovia of joints and the tendon
sheaths.
✓Two types of disease:
the strictly localized and
the diffuse affection of synovial membranes
✓In the majority of cases, the lesion is restricted to one joint and can
spread to muscles, tendons, and skin membranes.

96. NONRADIOTHERAPEUTIC TREATMENT
✓Surgical excision normally consists of synovectomy,
✓Rarely complete, particularly in the large joints like the knee.
✓Therefore, recurrences occur with a frequency of up to 45%.

97. RADIOTHERAPEUTIC TREATMENT
✓ RT applied with radionuclides for localized PVNS or with external-beam
RT for diffuse PVNS.
✓ TORONTO STUDY - Most patients showed excellent functional results
with 30 to 50 Gy in 15 to 20 fractions of 1.8 to 2.5 Gy as standard
regimen for PVNS.
✓ GERMAN MONOCENTRIC STUDY - concluded that combined
treatment should be considered for all patients with
suspected or proven residual D-PVNS.

98. Heyd et al , IJROBP, 2010
Radiation achieves a higher local rate in postoperative setting after
nonradical resection and a salvage treatment option for recurrent and refractory
disease.

99. VERTEBRAL HEMANGIOMAS
✓Benign proliferations of vessels lesions that can affect any tisuue and are
asymptomatic
✓Usually only one vertebral body is affected
✓Most lesions are small and rare and require no therapy
✓Spread of tumor into extradural space, hemorrhage, or compression
fracture can lead to bone marrow compression and severe
consequences

100. Rarefied vertical, dense trabecles – HONEYCOMB PATTERN•

101. NONRADIOTHERAPEUTIC TREATMENT
✓Treatment options:
• Surgical resection
• Vertebroplasty
• Intralesional injections

102. RADIOTHERAPEUTIC TREATMENT
✓IN MOST CASES POSTOPERATIVE IRRADIATION SHOULD BE GIVEN
although radiation alone has been tried
✓Recommended Radiation Dose: 36 to 40 Gy delivered in 2 Gy per fraction
✓Radiation provides pain relief

103. HETEROTOPIC OSSIFICATION
✓Develops after trauma or surgery of the hip
✓They consist of real bone located in the periarticular soft
tissue
✓HO jeopardizes functional outcome and impairs rehabilitation

104. PREDISPOSING FACTORS FOR HO
✓Skeletal diseases : Forestier disease, Bechterew disease
✓Severe trauma of the brain and spinal cord
✓Patients with I/L or C/L HO after a previous total hip arthroplasty
✓Patients with femoral or pelvic bone osteophytes >1 cm in length
✓After acetabular or pelvic fractures
✓Several interventions at the hip joint
✓Men > women
✓Ankylosing spondylitis
✓Disseminated idiopathic hyperostosis of skeleton

105. ETIOLOGY
✓The etiology of HO is not fully understood
✓Pluripotent mesenchymal stem cells present in periarticular soft tissue,
under certain conditions develop into osteoblastic stem cells that finally
form HO’s
✓In vivo experiments showed that differentiation of osteoblastic stem cells
reaches its maximum after 32 hours

106. HETEROTOPIC OSSIFICATION FOLLOWING
TOTAL HIP ARTHROPLASTY

107. HETEROTOPIC OSSIFICATION AROUND ELBOW

108. HETEROTOPIC OSSIFICATION AROUND KNEE

109. BONE SCAN FINDINGS: HETEROTOPIC
OSSIFICATION OF LEFT HIP

110. BROOKER’S CLASSIFICATION
Babloni, IJROBP, 2006

111. NONRADIOTHERAPEUTIC TREATMENT
✓Target groups for prophylactic treatment
• Patients with symptomatic HO
• Those likely to develop clinically relevant postoperative HO
✓Ethylhydroxydiphosphonates (EHDP) has been used for prevention of HO,
but outcome was contradictory
✓Indomethacin is effective in patients at high risk. Administered in different
dosages immediately after surgery for about 3 to 6 weeks.

112. RADIOTHERAPEUTIC TREATMENT
✓Prophylactic RT employed since late 1970s.
Initial dose concepts use 20 Gy/10#
Now 6-8 Gy/#
✓RT should be started no later than day 4 after surgery
✓Keep the postoperative interval as short as possible
24 to 48 hours
✓ Preoperative RT with single fraction of 7 to 8 Gy
has been successfully applied

113. ✓Target volume should encompass typical localizations of periarticular HO
✓Cranial field border: App. 3 cm above the acetabulum and includes about
two thirds of the implant shaft
✓Usual field size is 14 x 14 cm
✓Dose reference point - central beam at the center of the target volume (at
about 8 to 12 cm deep)
✓HO prophylaxis can also be done in paraplegic patients:
• Knee
• Elbow
• Shoulder
• Jaw joints

114. SIMULATION FILM FOR HETEROTOPIC
OSSIFICATION RADIOTHERAPY PROPHYLAXIS

115. Radiation appears more effective
for prevention of HO

116. IJROBP VOL 52, P 496-513, 2002

117. www.themegallery.com

118. MENINGIOMAS
✓Most common benign tumors of the CNS
✓Incidence peaks in seventh decade of life
✓Female-to-male: 2:1
✓Classification:
• WHO Grade I: >90%) are benign
• WHO grade II: Atypical, Clear cell, or Chordoid - Local
recurrence high
• WHO grade III: Malignant - Anaplastic, Rhabdoid,
Papillary- Rare

119. MENINGIOMAS: DIAGNOSIS
✓Most common presenting symptom: headache
✓Other localizing symptoms: depend on tumor location
✓Radiographic diagnosis: CT or MRI
Homogeneously and intensely enhancing extra- axial
mass with or without the presence of a dural tail

120. MENINGIOMAS: MANAGEMENT
✓SURGICAL RESECTION: treatment of choice
✓Primary goal: Maximal Safe Resection
✓Tumors in convexity and olfactory groove: Gross Total
Resection (Relapse rate 10%)
✓Relapse rate depends on Simpson classification

121. SIMPSON GRADE DESCRIPTION RECURRENCE RATE
I
Complete macroscopic tumor removal
with adherent dura as well as the
possibly affected part of cranial calotte 8.9%
II
Complete macroscopic tumor removal
with adherent dura via diathermy 15.8%
III
Complete macroscopic tumor removal
without adherent dura or possibly
additional extradural parts
29.2%
IV
Partial macroscopic tumor removal
while removing intradural tumor parts 39.2%
V
Simple decompressive and bioptic
removal of tumor 88.9%

122. MENINGIOMAS: MANAGEMENT
✓Meningiomas (highly vascularized tumors): In select patients,
preoperative embolization
• decreases blood loss and improve extent of resection
✓Asymptomatic meningiomas: Observe clinically
✓Tumor grows or symptoms develop: Surgery or radiation
therapy

123. SYSTEMIC THERAPY
✓Antihormonal therapy: upto 67% express progesterone or
androgen receptor and 10% express estrogen receptor
(response rates are lower)
✓Hydroxyurea: under investigation in recurrent disease (shown
little efficacy)

124. RADIOTHERAPY
✓Indications:
• Primary radiotherapy (RT):
tumors in locations in which complete resection is not
feasible (i.e., optic nerve, cavernous sinus, major venous sinus)
or for patients who are poor surgical candidates.
• Adjuvant RT: patients with subtotal resection (STR),
recurrent disease, or for WHO grade II or III
tumors.

125. RADIATION TECHNIQUES
✓Conventionally fractionated three-dimensional conformal
radiotherapy (3D-CRT)
✓Conventionally fractionated intensity-modulated radiation
therapy (IMRT)
✓Frame-based or LINAC–based fractionated stereotactic
radiotherapy (FSRT), stereotactic radiosurgery (SRS)
✓Protons and heavy ions

127. RADIATION DOSE
✓Benign meningiomas: the typical dose prescription to the PTV
is 50 to 54 Gy given in 1.8- to 2-Gy daily fractions
✓For patients with more aggressive histology (WHO grade II or
III tumors): the GTV is expanded by at least 2 cm, with a
higher dose prescription in the range of 59.4 to 63 Gy

129. (C) Postoperative axial scan showing complete resection of tumor. (D)
Gamma Knife treatment MRI shows recurrence of convexity tumor.

130. (E, F) Three months after treatment, the tumor is unchanged in size
but there is an increase in surrounding edema as seen on
FLAIR images.

131. (
G) One year later, the tumor has regressed.

132. RADIATION DOSE: SRS
✓Frame-based SRS: 12 to 16 Gy prescribed to the 50% isodose
line (IDL) and
✓Frameless SRS: 14 to 18 Gy prescribed to the 80% IDL.
✓Selected Perioptic tumors, including meningiomas: 24 to 30 Gy
in 3 to 5 fractions

133. (B) Treatment plan with shaped beans, 14 Gy, 90% isodose line, volume 1.07
cm3.

134. Treatment plan with shaped beans, 18 Gy, 90% isodose line, volume 0.65
cm3.

135. INTRACRANIAL MENINGIOMA: FRACTIONATED
RADIATION THERAPY PERSPECTIVE

136. Patients in the above reports typically, but not exclusively, had either known or presumed
low-grade meningiomas. The follow-up and dose columns list the mean or median figures.

151. DURAL TAIL TO BE INCLUDED OR NOT ?

153. Conformal, image-based EBRT. MR image and isodoses for IMRT of a
Cerebellopontine angle meningioma treated to 54 Gy in 40 fractions,
Prescribed to the 90% isodose. The yellow line represents the 70% isodose,
green 50%, and sky-blue 30%. The “dural tail” is not
included within the PTV.

154. AVASCULAR MALFORMATIONS
✓Intracranial AVMs are congenital vessel abnormalities
consisting of widened arteries connected to the normal
capillary bed
✓Nidus of AVM = tangled arteries and veins that are connected
by one or more fistulas
✓Overall prevalence: 18 in 100,000 individuals
✓Age at presentation: typically between 20 and 40 years old

155. CLINICAL PRESENTATION
✓Clinical concern: bleeding risk, 2% to 4% per year.
✓Approximately 50% of patients present with hemorrhage and
50% present with nonfocal (headache, nausea) symptoms or
incidentally found focal neurologic deficits.
✓The risk of death per bleed is up to 10%
✓Approximately 30% have serious morbidity associated with
each bleed

156. INVESTIGATIONS
✓Diagnostic imaging includes angiography, which is invasive
but allows for full grading of the AVM according to the
Spetzler-Martin scale.
✓MRI, MR angiography, and CT angiography are noninvasive
and complementary studies that may be used to visualize the
AVM.

157. SPETZLER MARTIN GRADING SYSTEM
✓Predicts patient outcomes after surgical resection of AVMs.
✓Composed of three components (AVM size, location, and
pattern of venous drainage), this system has been validated.
✓Unfortunately, this grading scale does not appear to correlate
with successful AVM radiosurgery.
Spetzler RF, Martin NA. J Neurosurg 1986; 65:476–483.

158. Predicts patient outcomes after AVM radiosurgery
POLLOCK-FLICKINGER SCORE
Pollock BE, Flickinger JC, Lunsford LD, et al. Neurosurgery 1998

159. TREATMENT ALGORITHM FOR AVM

160. SURGERY
✓Goal of any therapy: Complete obliteration
Provides immediate cure but carries a risk of
intraoperative bleeding, ischemic cerebrovascular
accident, infection, and death
✓Surgery is particularly indicated for AVMs in superficial,
noneloquent regions of the brain

161. EMBOLIZATION
✓Endovascular therapy (embolization) is not curative but may
be used to decrease the risk of intraoperative bleeding or to
decrease the size of the nidus before planned radiotherapy

162. RADIOTHERAPY
✓SRS is the radiation modality of choice for the treatment of
AVMs.
✓SRS is indicated mostly for lesions in deep or eloquent
regions of brain and particularly <3 cm size.
✓The time to obliteration ranges from 1 to 4 years after SRS, so
the patient remains at a continued bleeding risk.

163. ✓Based on the Flickinger et al, typical prescriptions for
treatment of AVM are 21 to 22 Gy prescribed to the 50% IDL
for frame-based radiosurgery.
✓The prescription should be lowered for AVMs near the
brainstem or larger lesions (>3 cm).
✓For linac-based SRS, prescriptions generally range from 16 to
24 Gy in a single fraction to 20 to 22 Gy in 2 fractions for
spinal AVMs.

164. Neuroimaging studies of a 26-year-old woman with an incidentally discovered left basal ganglia
AVM. (A) Lateral and (B) anterior-posterior (B) left internal carotid angiograms showing AVM on
the day of radiosurgery. The AVM volume was 6.5 cm3; the AVM margin dose was 15 Gy.

165. (C) CT performed 6 months after radiosurgery showing both intraparenchymal
and intraventricular hemorrhage.

166. (Left) Post-gadolinium and (right) long-TR MRIs performed 3 years after
radiosurgery of a left sylvian fissure AVM demonstrates persistent enhancement
and edema consistent with radiation necrosis.

167. TRIGEMINAL NEURALGIA
✓A common problem affecting approximately 15,000 patients
each year in the United States
✓Female to male: 1.5 to 1

168. TRIGEMINAL NEURALGIA
✓Type I TN: predominantly (>50%) sharp, lancinating, and
shock-like with pain-free intervals
✓Type II: TN predominantly experience burning, aching, or
throbbing pain
✓Prognostic significance: type I TN patients more likely to be
pain free and have longer disease control than patients with
type II TN after decompression.

169. TRIGEMINAL NEURALGIA
✓The classic clinical feature is recurrent episodes of sudden,
brief, severe, stabbing, or lancinating pain in the area of the
trigeminal nerve sensory distribution
✓It is most commonly unilateral, but some cases are bilateral.
✓Common triggers for attacks include talking, “chewing,
brushing teeth, and cold air.

170. TRIGEMINAL NEURALGIA
✓Clinical symptoms and MRI Brain should be performed to rule
out structural abnormalities that may be causing secondary
TN.

172. MEDICAL THERAPY
✓Carbamazepine
✓Oxcarbazepine
✓Lamotrigine
✓Gabapentin
✓Pimozide
✓Tizanidine
✓Topiramate

173. SURGERY
✓Medically refractory disease:
Microvascular decompression is the treatment of
choice
✓Other options include:
Rhizotomy with either radiofrequency ablation,
Glycerol injection, or
Balloon compression

174. STEREOTACTIC RADIOSURGERY
✓Treatment planning
• CT-MRI fusion
• Target: Root entry zone of the trigeminal nerve as it enters
the pons to the semilunar ganglion
• Typical doses using a frame-based radiosurgery platform
are 70 to 90 Gy, prescribed to the 50% IDL
• Higher rates of pain relief in the high-dose arm (72% vs. 9%
for patients treated with ≥70 Gy vs. <70 Gy)
• Median time to pain relief: 1 month
• Main concern is delayed onset of facial numbness.

175. Gamma Knife treatment plan for a patient with right
trigeminal neuralgia. Isodose coverage of the nerve is seen in the right
upper panel. The 20% line touches the brain stem, and the 10% line
cuts into it.

176. Beam shaping is accomplished by plugging 32 beams as
shown in the left upper panel. The result, seen in the right upper panel,
is a flattened 10% and 20% isodose line such that the brain stem
receives 10% only along the edge.

177. STEREOTACTIC RADIOSURGERY
✓Flickinger et al. who randomized patients to 75 Gy targeted to
a shorter (1 isocenter) or longer (2 isocenters) segment of the
trigeminal nerve.
✓The rates of pain relief were surprisingly identical between
the two groups.
✓There was a trend toward a higher incidence of numbness or
paresthesias in the 2-isocenter patients.

178. STEREOTACTIC RADIOSURGERY
✓Adler et al: frameless robotic radiosurgery platform to a 6-
mm segment of the trigeminal nerve with a mean marginal
prescription dose of 58.3 Gy and mean maximal dose of 73.5
Gy.
✓85% experienced a complete response and
✓96% reported excellent or good outcomes at a mean follow-
up of 15 months
✓Only 15% of patients experienced ipsilateral facial numbness

181. VESTIBULAR SCHWANOMMA
✓Acusticus neurinomas are benign neuroectodermal tumors
originating from Schwann cells of the neurilemma at the
vestibulocochlear nerve (CN IV)
✓Make upto 5% of primary brain tumors.
✓With an incidence of 1 in 100,000, 5% of cases are affected by
patients with neurofibromatosis type II (M. Recklinghausen).

182. VESTIBULAR SCHWANOMMAS
✓Growth in the cerebellopontine angle exerts pressure on the
vestibularis and cochlear nerves, causing hearing impairment,
tinnitus, and vertigo.
✓Later facialis paresis (CN VII), trigeminus neuropathy (CN V),
and brainstem symptoms occur.
✓Diagnosis is made via high-resolution CT and MRI which show
intra- or extrameatal location and size.

183. TREATMENT ALGORITHM

184. NON RADIOTHERAPEUTIC TREATMENT
✓Complete tumor resection is the standard therapy,
particularly for large tumors (>25 mm).
✓Nerve injury can be avoided intraoperatively by
electrophysiological monitoring

185. RADIOTHERAPEUTIC TREATMENT
✓Indication: Progressive and symptomatic primary or recurrent
acusticus neurinoma up to a size of 25 mm (Tos grade 0 to 2).
✓Stereotactic single-dose RT with gamma knife or modified
linear accelerator is the preferred RT technique.
✓Besides direct damage of proliferating tumor cells, tumor
vessels may slowly be occluded
✓40% to 70% of cases will develop a tumor remission.

186. RADIOTHERAPEUTIC TREATMENT
✓Aims of RT:
• disappearance of tumor and symptoms,
• prevention of tumor progression, and
• maintenance of the remaining hearing ability.

187. RADIATION DOSE
✓With single doses of 12 to 14 Gy at tumor edge (depending on
reference isodose 15 to 25 Gy centrally), local control reaches
up to 95%.
✓In order to decrease side effects, FSRT at linear accelerators
has been preferred recently: RT concepts are 5 × 5 Gy, 10 × 3
Gy, 25 × 2 Gy, and 30 × 1.8 Gy.

190. CRANIOPHARYNGIOMA
✓6% to 10% of pediatric CNS tumors
✓Median age of diagnosis: 5 to 10 years, second peak >40
years old
✓They arise from remnants of Rathke’s pouch (hypophyseal-
pharyngeal duct)
✓Most commonly suprasellar, may be found in sella proper

191. CRANIOPHARYNGIOMA
✓Generally abuts hypothalamus and third ventricle.
✓Histologically, divided into the adamantinomatous and
squamous subtypes.
✓The adamantinomatous subtype is characterized by a solid
and cystic pattern with the well-known description of
“machine oil-like” cystic fluid.”

192. CRANIOPHARYNGIOMA
✓Presenting signs and symptoms include
• Headache
• nausea and vomiting
• bitemporal hemianopsia
• endocrine dysfunction (diabetes insipidus, dwarfism, fat tissue
disturbance, adrenal cortical insufficiency)
✓The most common hormone deficiency is lack of GH.

193. INVESTIGATIVE WORKUP
✓Similar to that of pituitary adenoma
✓Includes H&P,
pituitary hormone levels, and
brain MRI with thin slices through the sella

194. SURGERY
✓Primary goal: Complete resection.
✓GTR associated with high rates of neurologic sequelae,
including visual impairment and panhypopituitarism.
✓Most patients are treated with maximal safe resection
followed by adjuvant RT.
✓Intralesional bleomycin directly into cyst decreases cyst
recurrence.

195. RADIOTHERAPY
✓Often used in adjuvant setting.
✓In select patients (<3 years old), RT at the time of relapse
(“salvage” RT)

196. RADIOTHERAPY TECHNIQUE
✓RT techniques include
3D-CRT, IMRT, FSRT, proton therapy, and intralesional
RT with β-emitting isotopes (yttrium-90,
phosphorous-32).
✓Postoperative MRI fused with treatment planning CT scan.

197. IMRT: VOLUMES AND DOSE
✓GTV: postoperative residual tumor volume, including the cyst
wall, if present.
✓PTV: A margin of 1 to 1.5 cm is added to the PTV
✓Dose prescriptions for 3D-CRT and IMRT are typically 54 Gy
given in 1.8-Gy daily fractions.

198. IMAGE GUIDED RADIOTHERAPY
✓Allows for convenient monitoring of cyst regrowth with cone-
beam CT scans while patients are on the treatment table.

199. FRACTIONATED RADIOTHERAPY:
LOMA LINDA SERIES
✓Fractionated proton radiotherapy has demonstrated excellent
results.
✓Loma Linda series: 15 patients treated to a total dose of 50.4
to 59.4 GyE given in 1.8-GyE daily fractions.
✓Local control was achieved in 14 of 15 patients, with few
long-term complications.

200. ✓No failures were seen in 24 patients who received
fractionated proton radiotherapy to a total dose of 52.2 to 54
GyE in 1.8 GyE per fraction.
MASSACHUSETTS GENERAL HOSPITAL

201. STANFORD SERIES
✓Stanford Study: frameless robotic platform, postoperative
doses of 18 to 38 Gy given over 3 to 10 fractions prescribed to
mean IDL of 75%.
✓Local control was 91% with no visual or neuroendocrine
complications.

203. INTRALESIONAL INJECTIONS
✓Cystic craniopharyngiomas: Intralesional radioactive isotope
injection using a β-emitter.
✓Typical prescriptions: 200 to 250 Gy prescribed to the cyst
wall.
✓Optimal results are seen in patients whose tumors have one
cyst and lack a large solid component.

204. EPILEPSY
✓Alternative to surgery in medically refractory epilepsy for
patients who are not surgical candidates.
✓Intractable mesial temporal lobe epilepsy: 24 to 25 Gy in a
single fraction with Gamma Knife.

205. ✓At a follow-up of 2 years, 65% of the patients were seizure
free.
✓However, there was a 1-year lag between treatment and
maximal effect
✓There was a transient increase in seizures before the seizures
started to diminish.

206. THANK YOU