oncology

1. STEREOTACTIC
RADIOTHERAPY AND
RADIOSURGERY
DR SAJAL GOEL

2. INTRODUCTION
Stereotactic radiosurgery and radiotherapy are
techniques to administer precisely directed,
high-dose irradiation that tightly conforms to
an intracranial target to create a desired
radiobiologic response while minimizing radiation
dose to surrounding normal tissue.

3. “Stereotactic refers to using a precise three-
dimensional mapping technique to guide a
procedure.”
The term radiosurgery or stereotactic
radiosurgery (SRS) is used for stereotactically
guided conformal irradiation of a defined target
volume in a single session.

4. The term “Stereotactic radiation therapy
(SRT)” refers to stereotactically guided delivery
of highly conformal radiation to a defined target
volume in multiple fractions, typically using
noninvasive positioning techniques.
The term “Fractionated stereotactic
radiosurgery (FSR)” is limited to stereotactically
guided high-dose conformal radiation
administered to a precisely defined target volume
in two to five sessions. ”

5. KEY REQUIREMENTS FOR OPTIMAL
STEREOTACTIC IRRADIATION
REQUIREMENT RATIONALE
Small
target/treatment
volume
Reducing the volume of normal and target tissues
irradiated to high doses improves tolerance
Sharply defined
target
Can be treated with little or no extra margin of
sorrounding normal tissue and/or without unintentional
underdosage of the target (marginal miss)
Accurate radiation
delivery
No margin of normal tissue needed for setup error and/
or reduced chance of underdosing target
High conformality Reduces the treatment volume to match the target
volume
Sensitive structures
excluded from target
Dose limiting structures (optic chiasma/spinal cord)
should be able to be defined and excluded from the
target volume to limit the risk of radiation injury

6. RADIOBIOLOGIC CONSIDERATIONS
Prior to radiosurgery,
• Essentially all clinical irradiation was
administered with radiation dose fractions
between 1.2 and 3 Gy for intracranial targets.
• Extracranial targets were usually treated with
1.2- to 4- Gy fractions, with 6- to 8-Gy fractions
used occasionally for treatment of bone
metastases or malignant melanoma.

7. RADIOBIOLOGIC CONSIDERATIONS
In the late 1980s,
• Fractionating radiation treatment lessens the relative
risk of injury to normal tissue compared with tumor in
essentially all circumstances.
• Radiobiology validates it for conventionally
fractionated radiotherapy of fast-growing
malignant tumors .

8. RADIOBIOLOGIC CONSIDERATIONS
Increasing the fractionation of radiotherapy for
slow-growing benign tumors may not
necessarily improve the balance between
tumor control and radiation complication.
Stereotactic radiosurgery allowed clinicians to
administer high single doses of radiation to
intracranial targets with relative safety.

9. RADIOBIOLOGIC CONSIDERATIONS
Typical radiosurgery treatment plans use
inhomogeneous dose distributions with the
prescription isodose covering anywhere from
90% to 100% of the target volume.
The absolute minimum dose to the target
typically is 5% to 30% lower than the
prescription dose.

10. RADIOBIOLOGIC CONSIDERATIONS
LQ formula does not explain high stereotactic
doses.
Using single-fraction radiosurgery dose–response
curves for AVM obliteration, α/β ratios yields
values of −30 to −60 rather than 2 to 3 as
expected from conventional fractionated
radiotherapy data.

11. RADIOBIOLOGIC CONSIDERATIONS
Laboratory studies suggest that the radiation
response for the high-dose single fractions used
in radiosurgery is predominantly related to the
supporting endothelial cells.
Pathology studies of benign and malignant
tumors treated by radiosurgery also support a
vascular response.

13. HISTORY
Lars Leksell and his
physicist colleague,
Borje Larsson,
preparing a patient for
SRS with a particle
beam accelerator in
1958.

14. Particle Beam Accelerator (1947): Lawrence
Berkely National Laboratory

15. Raymond Kjellberg
with a frame for proton
beam therapy of a
patient with an AVM.
(Harvard University)

16. LEKSELL GAMMA KNIFE

17. CYBERKNIFE (ACURAY)

18. NOVALIS TX

19. PROTON BEAM RADIOSURGERY

20. TOMOTHERAPY

21. RADIOSURGERY FACE MASK

22. RADOSURGERY INVASIVE HEAD
FRAME

23. RADIOSURGERY NON INVASIVE
HEAD FRAME

24. BRAINLAB

25. NORMAL TISSUE CONSTRAINTS

26. CLINICAL USES OF SRS AND SRT
Functional Radiosurgery
Vascular
Brain Tumors
Brain metastases
Primary malignant brain tumors
Spinal metastases

27. FUNCTIONAL RADIOSURGERY
Typical trigeminal neuralgia refractory to medical
therapy.
Atypical or constant pain does not respond.
TRIGEMINAL NEURALGIA

28. Ronald A. Alberico et al. AJNR Am J Neuroradiol
2001;22:1944-1948
©2001 by American Society of Neuroradiology

29. TRIGEMINAL NEURALGIA
Typically, 4-mm
collimators are
used for
radiosurgery to a
maximum dose of
80 Gy.

30. Response rates reach approximately 85%,
typically 1 week to 4 months after the procedure,
but can develop as late as 6 months later.
Approximately 50% of typical trigeminal neuralgia
patients remain pain-free and off medication 5
years following radiosurgery.
TRIGEMINAL NEURALGIA

31. FUNCTIONAL RADIOSURGERY
Medically refractory unilateral tremor in patients
with essential tremor and/or Parkinson’s
disease
More generalized parkinsonian symptoms:
Radiosurgery of globus pallidus (pallidotomy) to
alleviate symptoms
Severe, refractory OCD: favorable experience
with bilateral radiosurgical capsulotomy
Hypothalamic hamartomas: may help control
refractory gelastic seizures.
An alternative to extensive surgery in medically
refractory mesial temporal lobe epilepsy.

32. VASCULAR MALFORMATIONS
Untreated intracranial AVMs:
bleeding risk of approximately >= 3% per year
if prior bleeds occurred.
Radiosurgery dramatically reduces the risk of
hemorrhage.
Radiosurgery obliterates AVM nidus in
approximately 75% cases within 3 years post-
procedure.
Individual obliteration rates: 50% to 88%
depending on marginal dose.

33. Optimal doses of approximately 23 Gy
required to obliterate AVM’s
Risk of neurologic sequelae averages
approximately 3%
The risk of hemorrhage while waiting for
complete obliteration to develop seems
unaltered.
VASCULAR MALFORMATIONS

34. Re-irradiation: When an AVM nidus fails to
completely obliterate by 3 years after
radiosurgery.
Doses similar to initial surgery to achieve similar
rates of complete obliteration.
VASCULAR MALFORMATIONS

35. VASCULAR MALFORMATIONS
Large AVMs difficult to manage
Staged radiosurgery, can be done in two or
three sections separated by 4- to 6-month
intervals to reduce acute toxicity.
Whether there is any benefit to fractionating
stereotactic irradiation of AVMs is presently
unclear.

36. Cavernous malformations: Annual hemorrhage
risks of
0.5% per year with no prior bleed
4.5% with one prior hemorrhage
app. 32% per year after a history of >=2
hemorrhages
Repeated bleeds cause considerable neurologic
morbidity.
Radiosurgery reduces the risk of subsequent bleeds
to app. 1% per year with acceptable morbidity.
VASCULAR MALFORMATIONS

37. DSA images are registered to CT/MR through Stereoactic Localization.

39. BENIGN TUMORS
Most small benign intracranial tumors are
well managed with radiosurgery, FSR, or
SRT.
Radiosurgery control rates are high with
prescription doses on the order of 12 to
14 Gy.

40. Kondziolka et al.
n=285 (Vestibular schwannomas, Non acoustic
schwannomas, Meningiomas, Pituitary adenomas,
and Craniopharyngiomas).
 Median follow-up =10 years.
 44% patients had prior surgery and 5% had prior
fractionated RT.
 95% patients had imaging-defined local tumor
control.
 Crude tumor control was 95%
 15-year actuarial tumor control rate was 93.7%.
Neurosurgery 2003;53:815–822

41. VESTIBULAR SCHWANOMMAS
Small, minimally symptomatic vestibular
schwannomas: Observation
Large vestibular schwannomas causing
symptomatic brainstem compression with
obstructive hydrocephalus: Surgery
Small to medium vestibular schwannomas: tumor
control rates with Radiosurgery or SRT are
comparable to those of surgical resection.

42. VESTIBULAR SCHWANOMMAS
University of Pittsburgh Study
Gamma knife radiosurgery doses of 12 to 13 Gy
between February 1991 and February 2001
n= 313
The actuarial clinical tumor control rate, free of
surgical intervention, was 98.6% at 7 years.
Flickinger JC, Int J Radiat Oncol Biol Phys 2004;60:225–230.

43. VESTIBULAR SCHWANOMMAS
Various fractionation schemes have similar results
:
18 Gy /3
20 Gy /4 to 5
25 Gy /5
45 to 50 Gy /25,
and 54 Gy /30
Treatment results similar to radiosurgery with 12 to 13
Gy, but an advantage for fractionation cannot be
excluded entirely.Flickinger et al, Neurochirurgie 2004;50:421–426

44. Meijer et al
SRS (10 OR 12.5
Gy)
SRT ( 20 Gy/4-5
#)
p value
n 49 80 0.048
Trigeminal
neuropathy
8% 2% >0.05
Hearing loss 25% 39% >0.05
Facial
neuropathy
7% 3%
5 year actuarial
tumor control
100% 94%
Int J Radiat Oncol Biol Phys 2003;56:1390–1396

45. NON ACOUSTIC SCHWANOMMAS
Schwannomas may occasionally involve other
cranial nerves, particularly V, VII, and XI through
XII in the jugular foramen.
Tumor control rates are similar.
Postradiosurgery neuropathies less common
 somatic sensory and motor nerves seem less
sensitive to radiation injury than special sensory
nerves like VIII.

46. MENINGIOMAS
Radiosurgery and SRS are both excellent management
options for most Small benign meningiomas, with in-
field tumor control rates well above 90%.
Marginal recurrence rates as high as 25% because of
 tight margins used for radiosurgery
 SRT treatment volumes limited to small recurrences
 residual tumor after resection of large parasagittal
meningiomas.

47. MENINGIOMAS
University of Pittsburgh study
n = 219 imaging-diagnosed meningiomas (unbiopsied)
Gamma knife radiosurgery
Dose of 8.9 to 20 Gy (median, 14 Gy)
Treatment volumes of 0.47 to 56.5 mL (median, 5.0 mL)
Follow-up: 2 to 164 months (median, 29 months).
Actuarial tumor control rate was 93.2% at both 5 and 10
years
Flickinger JC Int J Radiat Oncol Biol Phys 2003;56:801–806

48. MENINGIOMAS
Atypical and malignant (anaplastic)
meningiomas have higher rates of local and
marginal recurrence after therapeutic
intervention.
 Complete surgical resection followed by a full
course of conventional radiotherapy with at least
1-cm margins around the tumor volume is
advocated.
 Radiosurgery improves local control of

49. MENINGIOMAS
5-year actuarial control rates
87% for typical meningiomas
49% for atypical meningiomas
0% for malignant meningiomas
in the Sheffield gamma knife experience.
Malik et al, Br J Neurosurg 2005;19:13–20

50. Harris et al
Pittsburg Gamma
Knife Experience
Malignant
Meningioma (n=12)
Atypical Meningioma
(n=18)
5 year LC 72% 83%
10 year Actuarial
survival
59% 0%
Surg Neurol 2003;60:298–305.

51. PITUTARY ADENOMA
Management requires multidisciplinary approach.
Most patients with visual compromise will do better
with initial surgical decompression.
Most other small pituitary adenomas, where the
target volume can be separated from the optic
nerves, are reasonable candidates for
radiosurgery.

52. PITUTARY ADENOMA
Review of 35 peer-reviewed reports
n = 1,621 patients
Most studies reported >90% control (range,
68% to 100%).
Weighted average tumor control rate for all
published series was 96%.
Tumor growth control rates varied from 83% to
100%.
Sheehan et al, J Neurosurg 2005;102:678–691

53. PITUTARY ADENOMA
Twenty-two series have published radiosurgery
results for 314 Cushing’s disease patients.
The mean radiosurgical prescription (margin)
doses for these series varied from 15 to 32 Gy.
In those series with at least 10 patients and a
median follow-up of 2 years, endocrinologic
remission rates range from 17% to 83%.
Wazer, David E. “Perez & Brady's Principles and Practice of Radiation Oncology

54. BRAIN METASTASES
Brain metastases that progressed after prior
whole-brain radiotherapy (WBXRT).

55. BRAIN METASTASES
RTOG 95-08
Phase III randomized trial
Established that Radiosurgery immediately
following standard WBXRT (37.5 Gy in 15
fractions) improves LC and QOL for patients with
one to three brain metastases
while
improving OS for patients with solitary metastasis, all
compared with patients initially managed with
WBXRT only.

56. BRAIN METASTASES
Questions remained about managing brain
metastases with radiosurgery alone,
preserving full-dose WBXRT for later
managing cases with subsequent
progression.

57. BRAIN METASTASES
Prospective RCT
Initial WBXRT + SRS compared to SRS alone.
n =132
Patients with 1-4 brain mets <3 cm in diameter to
SRS either with or without initial WBXRT.
Median survival time and the 1-year actuarial
survival rates were not significantly different.
1-year brain tumor “recurrence rate” was higher in
the SRS-alone group.
JAMA 2006;295:2483–2491

58. BRAIN METASTASES
Administering initial WBXRT and waiting a
month before radiosurgery for subsequent
tumor shrinkage is a reasonable strategy for
limiting “radiation injury reactions and/or
improving tumor control for brain metastases >3
cm in diameter and for brainstem metastases >2
cm in diameter.”

59. BRAIN METASTASES
There is no clear limit as to how many
metastases and what total volume of
metastases can or should be treated by
radiosurgery.
RTOG 95-08 was limited to one to three
metastases, while the trial of Aoyama et al. and a
smaller University of Pittsburgh trial included
patients with up to four brain metastases.

60. BRAIN METASTASES
Bhatnagar et al.
n = 205 patients
Radiosurgery for four to 18 brain metastases
(median, five).
Median survival of 8 months after radiosurgery
Survival correlated with the total volume of
metastases, age, and RTOG-RPA class, but not the
total number of brain metastases.
Int J Radiat Oncol Biol Phys 2006;64(3):898–903

61. BRAIN METASTASES
Presently, many centers use WBXRT alone to
initially manage patients with five or more
metastases and subsequently consider
radiosurgery for patients who are unable to be
withdrawn from steroid medication and for
patients whose brain metastases progress after
WBXRT.

63. GLIOBLASTOMAS
Radiosurgery appears to be a reasonable option
for small, well-circumscribed, high-grade gliomas
that recur after prior conventional large-field
radiotherapy and chemotherapy.

64. RESULTS OF FSRT FOR PRIMARY AND RECURRENT HGG

65. SRS IN THE PRIMARY MANAGEMENT OF HGG

66. SPINAL METASTASES
Radiosurgery has been used to treat spinal
tumors, mostly metastases, either as initial
treatment or for recurrence after prior
fractionated radiotherapy.
Indications for radiosurgery:
Pain: most common indication
Radiographic tumor progression
Postsurgical boost
Progressive neurologic deficit
J Neurosurg Spine 2005;3:288–295

67. SPINAL METASTASES
Dose: 15 - 22.5 Gy (Mean 19 Gy)
Target volumes varied from 0.8 to 197 mL (mean,
27.7 mL).
No radiation-induced toxicity occurred during the
follow-up period (6 to 48 months).
J Neurosurg Spine 2005;3:288–295

68. SPINAL METASTASES
CyberKnife radiosurgery achieved long-term
pain improvement in (96%) who were treated
primarily for pain.
Long-term radiographic tumor control was
seen in all patients who underwent primary
radiosurgery as well as those treated for
radiographic tumor progression after
radiotherapy or as a postsurgical treatment.

69. LUNG CANCER
WHAT IS EARLY STAGE LUNG CANCER?
Early-stage NSCLC: Stage I-II 1
Stage I: TIN0M0
Stage 2: T2N0M0
American Joint Committee on Cancer stages T1-
T2 (<=5 cm) or T3 (<=5 cm peripheral tumors
only) N0M0 cancer based on both mandatory
computed tomography (CT) and positron
emission tomography (PET) screening.2
1) L.W. Brady et al. Decision making in radiation oncology; Volume
1, Page 270

70. INDICATIONS IN EARLY STAGE
LUNG CANCER
Definitive therapy for medically inoperable Stage
I NSCLC using hypofractionated SBRT 1
Definitive therapy for NSCLC patients who are
unable to tolerate chemotherapy
Patient refusal for surgery
1) L.W. Brady et al. Decision making in radiation oncology; Volume 1, P

71. STANDARD INDICATORS FOR MEDICAL
INOPERABLITY
Baseline FEV1 < 40% predicted
Predicted postoperative FEV1 < 30% predicted
Severely reduced diffusion capacity < 40%
predicted,
Baseline hypoxemia (<70 mmHg) and/or
hypercapnia (>50 mmHg) and exercise oxygen
consumption < 50% predicted
Severe pulmonary hypertension
Diabetes mellitus with end-organ damage
Severe cerebral, cardiovascular, or peripheral
vascular disease
Severe chronic heart disease
Robert Timmerman et al; JAMA. 2010; 303(11): 1070-1076
Hiraoka et al; Jpn J Clin Oncol 2010;40 (9) 846–854

72. COMMONLY USED DOSES FOR
SABR
Total Dose Fractions # Example indications
25-34 1 Peripheral, small (<2 cm) tumors, esp >1 cm from
the chest wall
45-60 3 Peripheral tumors and >1 cm from the chest wall
48-50 4 Central or Peripheral tumors (<4-5 cm), esp <1 cm
from chest wall
55-55 5 Central or Peripheral tumors, esp <1 cm from chest
wall
60-70 8-10 Central tumors
Onishi H et al. J Thorac Oncol 2007;2 (Suppl 3):S94–100.
NCCN 2013 Guidelines

73. The basic necessity is to deliver Biologically
Effective dose (BED) > 100 Gy to a peripherally
located tumor.

74. Results of retrospective studies of SBRT for
mainly inoperable patients with T1-3N0M0
NSCLC
Author Patient no
Age Min-Max
(Median)
Dose
Gy/Fraction
s (fx)
Median
follow-up
(months)
Overall
survival
rate
Local
control Toxicity
Uematsu 50 54–86 (71) 50–60 Gy/5–
10 fx
36 66% (at 3
year)
94% Rib fracture: 2%
Wulf 20 58–82 (68) 26–37.5
Gy/1–3 fx
11 32% (at 2
year)
92%
No
complications.
RTOG grade 2
Onishi 35 65–92 (71) 60 Gy/10 fx 13 64% (at 2
year)
88%
NCI-CTC (V2)
grade 3
pneumonia: 9%
Onimaru 28 52–85 (76) 48 Gy/4 fx 27 IA 82%
IB 32%
64%
NCI-CTC (V3.0)
grade 3
pneumonia: 4%
Takeda 63 56–91 (78) 50 Gy/5 fx 31 IA 90%
IB 63%
95%
NCI-CTC (V3.0)
grade 3
pneumonia: 3%

75. PHASE II TRIALS FOR MEDICALLY
INOPERABLE PATIENTS
Author Patient no Age Min-Max
(Median)
Dose
Gy/Fractions
(fx)
Median follow-
up (months)
Three-year
overall
survival rate
Three-year
local
control rate
Toxicity
Nagata 42 51–87 (77) 48/4 (tumor
center)
30 IA 83%,
IB 72%
98% NCI-CTC (V2) grade 2
Timmerman 70 51–86 (70) 60–66 Gy/3fr 17 55% (at 2
year)
95% (at 2
year)
NCI-CTC (V2) grade
3–5: 8.5%
Zimmermann 68 59–92 (76) 37.5 Gy/3–5 fx
(60% isodose)
18 53% 94% RTOG grade 3
pneumonia: 6% Rib
fracture 3%
Fakiris 70 not shown T1: 60 Gy/3 fx
T2: 66 Gy/3 fr
(80% isodose)
50 43% 94% peripheral; NCI-CTC
(V2) grade
3–5: 10% central;
NCI-CTC (V2)
grade 3–5: 27%
Baumann 57 59–87 (75) 45 Gy/3 fx (67%
isodose)
35 60% 92% NCI-CTC (V2) grade 3:
28%
Timmerman 55 48–89 (72) 60 Gy/3 fx (D95) 34 56% 98% Grade 3 NCI-CTC
(V3.0): 12.7%
Grade 4 NCI-CTC
(V3.0): 3.6%
Ricardi 62 53–83 (74) 45 Gy/3 fx (80%
isodose)
28 57% 92% Pneumonia . RTOG
grade 3: 3%
Rib fracture : 2%

76. RESULTS OF SBRT
Local control rate – 95% at 3 years
TABLE 3: Overall survival data
Results: Comparable to surgery
2 years OS = 58 % in inoperable patients
83% in operable patients
5 years OS = 83% (Stage Ia- T1N0M0)
72% (Stage Ib- T2N0M0)
Overall Survival Rate Stage I Stage II
1year 100 73
2 year 91 64
3 year 91 64
Int J Radiat Oncol Biol Phys 66:117-125, 2006; Cancer 2004; 101:
1623–31

77. TOXICITIES OF SBRT
Local progression – 6% of patients
14% Distant or regional lymph node metastasis
Toxicity: 2 – 4 % Grade II Oesophagitis
2 – 3 % Grade III Pneumonitis
9% Grade II Dermatitis

78. MISCELLANEOUS USES
Radiosurgery and hypofractionated SRT have
been used as a substitute for brachytherapy in
the management of recurrent head and neck
tumors.
Liver metastases can also be irradiated with
these techniques.
Hypofractionated prostate SRT is also being
explored.

79. THANKYOU