SBRT for lung,liver and spine metastases

1. STEREOTACTIC BODY RADIOTHERAPY
DOSE-VOLUME CONSTRAINTS
Dr Nanditha
Kishore

2.  Stereotactic body radiation therapy (SBRT) is the
term applied in the United States by the ASTRO
for the management and delivery of image-guided
high-dose radiation therapy with tumor-ablative
intent within a course of treatment that does not
exceed 5 fractions.

3. BIOLOGICAL AND ONCOLOGICAL
RATIONALE OF SBRT
 The appeal of SBRT is based on the nonlinear
relation between radiation dose and cytotoxic
effect.
 one or a few large individual doses of radiation
therapy have substantially more cell-killing effect
than the same dose of radiation given in smaller
individual dose

4.  Traditionally LQ of radiation dose response, often
relied on for the purpose of comparing the biological
potency of different schedules of conventionally
fractionated radiation therapy.
 In the range of dose per fraction used in SBRT LQ
model overestimates the potency of fraction sizes on
the order of 8 to 10 Gy or higher.
 A variety of alternative mathematical models have
been proposed to account for the observed
inaccuracy of the LQ model
 Curtis's lethal-potentially lethal model

5. Methods Of Cell Kill in SBRT
 DNA damage
 Anti Angiogenesis
 Endothelial cell Apoptoses

6.  conceptual theories of cancer growth and numerous lines
of evidence behind use of SBRT for metastatic lesions
are
(a) The Empiric Or Phenomenological,
(B) The Patterns-of-failure Concept,
(C) The Theory Of Oligo metastases,
(D) A Lethal Burden Variation Of The Norton-simon
Hypothesis, Or
(E) Immunological Enhancement.

7. SITES COVERED
 Spine
 Lung
 Pancreas
 Prostrate

8. SBRT SPINE

9. RATIONALE
SBRT is an emerging technology used for the
treatment of spinal tumors.
 Effective dose escalation
 For patients who are not candidates for
conventional radiotherapy
 To improve the quality of life for patients who
may be spared a prolonged treatment course.
 Acute Radiation toxicity is reduced.

10. Indications for Spinal SBRT
 Pain control in vertebral metastases
 Malignant Epidural Spinal Cord compression
 Benign Spinal Cord Tumors

11. VERTEBRAL METASTASES
 Pain control was higher than 90% with single doses over
16 Gy at 1 year(1).
 Strong trend toward increased pain control with higher
radiation dose .
 Higher Radiosurgery dose requirements (>20 Gy) for
local control with higher incidences of vertebral
compression fracture in up to 40% of the patients(2)
1.Gerszten PC et al (2005) Single-fraction Radiosurgery for the treatment of spinal breast
metastases. Cancer 104(10):2244–2254
2.Yamada Y et al (2008) High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions.
Int J Radiat Oncol Biol Phys 71(2):484–490

12. Solitary
Two adjacent
Multiple lesions
separated by
normal vertibrae

13. VOLUMES
Ryu S et al (2007) Partial volume tolerance of the spinal cord and
complications of single-dose Radiosurgery. Cancer109(3):628–636

14. Most critical challenge is to minimize the risk of
spinal cord injury.
Possible exacerbating factors
 Previous Neurotoxic chemotherapy
 Post surgery (Sub clinical vascular injury)
 Prior spinal trauma

15. DOSE CONSTRAINTS
 The Partial volume spinal cord tolerance dose is
10 Gy to the 10% spinal cord volume.
 It is defined from 6mm superior to the target
volume to 6 mm inferior to the target volume
 10 Gy to the volume of 0.35 cc of the spinal
cord.

16. MALIGNANT EPIDURAL SPINAL CORD
COMPRESSION (MESCC)
 It is a common complication of cancer and has a
substantial negative effect on quality of life and
survival.
 It is often associated with early or overt signs of
neurological deficit.
 It requires immediate diagnosis and treatment
 Prime goal of treatment for spinal cord
compression is to decompress the spinal cord and
neuron elements

17.  The Target volume includes the involved spine and
epidural or Paraspinal soft tumor component.
 The dose was 16–20 Gy in a single fraction.
 The mean epidural tumor volume reduction was 65 ±
14% at 2 months after Radiosurgery.
 Thecal sac patency improved from 55 ± 4% to 76 ± 3%
(p < 0.001).
 Overall, neurological function remained stable or
improved in 81%.
Ryu S, Rock J, Jain R, Lu M, Anderson A, Jin JY, Rosenblum M, Movsas M, Kim JH
(2010) Radiosurgical decompression of epidural spine metastasis. Cancer
116(9):2250–2257

18.  Surgical decompression is effective because it
removes the tumor immediately,
 The effect of Radiosurgery is not as immediate
 Decompression was not shown until the 2 month
post-treatment imaging study.

20. BENIGN SPINAL TUMORS
 Gross total resection is the standard of care for benign
spinal tumors and complete removal rates are in excess
of 95% in most neurosurgical experiences.
 Surgical cure, however, may require sacrifice of one or
more nerve roots.
 Surgical intervention, moreover, may exacerbate
underlying neurological symptoms or produce new,
permanent deficits.
 Subtotal tumor removal in an attempt to avoid
neurological morbidity may result in tumor regrowth.

21. Indications for spinal Radiosurgery
 Unresectable tumors
 Refuse surgery,
 Surgery is contraindicated due to co-morbid
conditions.

22.  Target GTV and objects at risk (OARs) are
contoured.
 For benign tumors, no additional margin for CTV
is added.
 An additional margin for the PTV of 1–3 mm is
added to account for errors in imaging,patient
positioning, and intrafractional motion.

25. DOSE VOLUME CONSTRAINTS
 The threshold tolerance of the spinal cord for
myelopathy following radiosurgery was studied
extensively.
 Assuming the tolerance of the human spinal cord is 50
Gy delivered in standard 1.8–2 Gy fractions, the LQ
model (a/b value for cord =2 Gy)
 This predict an isoeffective single-dose tolerance of 13
Gy.

26.  In a Randomized trail of 260 patients investigators have
not observed a single case of Myelopathy at 1 year with
dose of 8Gy *1fr.
 Partial volume tolerance of the human spinal cord to
Radiosurgery was analyzed in 177 patients with 230
metastatic lesions.
 The authors concluded that an acceptable estimate of
partial cord tolerance is 10 Gy to the 10% volume.
1.Rades D, Stalpers LJ, Veninga T et al. J Clin Oncol 23:3366–3375
2.Ryu S, Jin JY, Jin R et al 2007Cancer 109:628–636

27.  The Topographic distribution of radiosurgery dose may also
be important in determining partial volume tolerance of the
spinal cord.
 The ED50 for the lateral cord varied from 29 to 33 Gy
compared to 72 Gy for the central cord.
 The results imply that the lateral corticospinal tract in
humans may be less tolerant of spinal radiosurgery than the
anterior tract or other ventral cord structures.
Bijl HP, van Luijk P, Coppes RP et al 2005.Int J Radiat Oncol Biol Phys
61:543–551

29.  In conclusion, image-guided spinal
radiosurgery using a dedicated linear
accelerator is an emerging technology that has
been safely and effectively applied to spinal
tumors.

30. SBRT LUNG

31.  Stereotactic body radiotherapy (SBRT) is a newly
emerging radiotherapy treatment method to
deliver a high dose of radiation to the target,
utilizing either a single dose or a small number of
fractions with a high degree of precision within
the body.

32. INDICATIONS
 Stage I NSCLC
 Pulmonary metastases

33. STAGE I NSCLC
 The local recurrence rates were 8.4% in patients
who received a biological effective dose (BED) of
100 Gy or more at the isocenter, and 42.9% in
patients receiving less than 100 Gy in BED.
 The local control rate was 95% median follow-up
of 17.5 months AND severe toxicity occurring at a
median of 10.5 months in 17% of those patients
with peripheral lesions versus 46% with central
lesion.
 1.Onishi H, Shirato H, Nagata Y, Hiraoka M, Fujino M,
Gomi K et al (2007 )J Thorac Oncol 2(7 Suppl 3):S94
2.Timmerman R, McGarry R, Yiannoutsos C, et al..J Clin
Oncol 2006;24(30):4833–4839

34.  There was a significant advantage in survival for the
group receiving a dose above 55.6 Gy in equivalent dose
in 2 Gy fractions (EQD2).
 According to Baumann, 55.6 Gy in EQD2 at the PTV
periphery corresponds to BED 100 Gy at the isocenter as
in Onishi’s study.

36.  STEPS
 1.Simulation using SBRT Body frame with build in
reference points for immobilization.
 2.floroscopy to see the tumor motion in all directions.
 3.if tumour movement is more than 8mm then
dampeneng with abdominal compression.
 4. Acquisition of slow CT in free breathing time.

37. Target delineation
 1.Tumor is contoured as GTV on mediastinal window
 2.Internal Target Volume(ITV) is contoured based on
tumor movement seen on fluoroscopy and tuomr on lung
window.
 3.PTV of 5mm given around ITV.
 4.OAR’S are contured and a PRV of 5mm given around
OAR except for cord and lung.

39. DOSE PRESCRIPTIONS
 Prescription should be such that BED > 100Gy
1. 12Gy in 4 fractions
2. 20 Gy in 3 fractions
3. 10Gy in 5 fractions

41. Factors associated with increased risk of Radiation
Pneumonitis
 1.Mean lung Dose (MLD<20Gy)
 2.Location of tumor
Bradley JD, et al. A nomogram to predict radiation
pneumonitis, derived from a combined analysis of
RTOG 9311 and institutional data. Int J Radiat Oncol
Biol Phys 2007;69(4):985–992.

46. Dose Distribution
 It is estimatd after inhomogeniety corrections by
various algorithms
1.Monte carlo algorithm
2.Path correction method

48. PULMONARY METASTASES
 There are several reports on SBRT for metastatic
lung cancer .
 Up to two lesions were simultaneously treated in
most of these reports, except for that by Okunieff
(up to five lesions).
 The local control rate was more than 60% and the
overall survival rate was more than 30% at 2
years.
 These outcomes were thought to be comparable
to surgical metastatectomy.

50.  SBRT results in promising local control and survival in
appropriate patients with lung tumors.
 Multi institutional prospective trials are expected to
confirm the results.
RTOG O236
JCOG 0403
 Further studies are needed to safely apply SBRT to
centrally located tumors or large tumors.

51. SBRT PROSTRATE

52. RATIONALE
 Normal tissues and tumors show different sensitivities to
changes in fractionation due to their varying ability to
repair sub lethal radiation damage (SLD).
 This sensitivity can be quantified through the a/b ratio in
the linear-quadratic model.
Thames HD Jr, Withers HR, Peters LI et al 1982 Int JRadiat Oncol Biol Phys 8:219–226

53.  The a/b ratio of Prostrate Cancer is lower than for most
other tumors. Values between 1.2 and 3 Gy are
suggested.
 It is lower than surrounding normal tissues like rectum
(a/b of 4 Gy for late rectal sequelae).
 It is hypothesized that hypofractionation if accurately
delivered increases the tumor control by sparing
surrounding late responding normal tissues.

54. Indications
 Primary treatment for organ confined low risk
prostrate cancer
 Dose escalation for intermediate and high risk
prostrate cancer

55. Procedure
1.Gold Fiducial placement under trans rectal USG
guidance ( 2 at base and 1 at apex. Each fiducial
1.1mm thickness and 3mm length)
2.Simulation with full bladder
3.Planning CT scan with IR marker guidance

56. 4.CTV Delineation
 Automatic marker localization and delineation of CTV,
bladder and rectum.
 For patients with a low risk (<10%) of SV involvement, the
CTV consists of the prostate only.
 Else it is limited to the proximal half of the SV (Kestin et al.
2002).
 CTV to PTV margins in anteroposterior (AP), craniocaudal
(CC) and left-right (LR) directions are 10–10–6 mm for
patients without implanted markers and 5–5–3 mm for those
with markers.

57. 6.Dose To Prostrate
 Dose of 35- 38Gy in 5 daily fractions as primary
treatment for low risk Prostrate cancer.(1)
 Dose of 50Gy in 5 fractions as dose escalation (2)
1.Katz A, Santoro M, Ashley R, et al.. BMC Urol 2010;10:1.
2.Boike TP, Lotan Y, Chinsoo Cho L, et al. J Clin Oncol 2011;29:2020–
2026.

58. 7. Dose volume constraints
 Rectum were such that the V50% <50%, V80%
<20%, V90% <10%,and V100% <5%.
 The bladder DVH goals were V50% <40% and
 V100% <10%.
 The femoral head DVH goal was V40% <5%.

62.  Most Important Challenge In SBRT Prostrate is
accurate positioning and correction for
inteafraction Prostrate moment and to minimize
set up error.
 This is performed by ExacTrac® X-Ray
Positioning.

63. ExacTrac® X-Ray Positioning
 The setup accuracy of Exac Trac X-ray was first
assessed by phantom measurements (Verellen et
al. 2003).
 Various combinations of known translational and
rotational deviations were introduced and
compared to the translational and rotational
deviations that were actually detected by the
system.

64.  The overall 3-D displacement vector for the co-
registration of X-rays with DRR was 0.6 ± 0.9
mm.
 For marker fusion, an even smaller value of 0.3 ±
0.4 mm was obtained.
 The residual errors (95% confidence interval)
were 2–4 mm for DRR co-registration and 1–2
mm for markers

65. The following positioning procedures were compared:
1. Conventional positioning with skin drawings and lasers
2. ExacTrac positioning using IR markers
3. ExacTrac X-ray co-registration of X-rays with DRRs
without correction for rotations
4. ExacTrac X-ray co-registration of X-rays with DRRs
with correction for rotations (Robotics Tilt Module).
5. ExacTrac X-ray marker fusion without correction for
rotations

66.  The stepwise implementation of the different positioning
procedures gradually reduced setup uncertainty.
 Ultimately in step 4, the setup errors are comparable to the
accuracy of the measurement itself.
 The setup accuracy in case of implanted marker is
comparable to step 4 but obviously offers the additional
advantage of direct prostate targeting and overcomes the
problem of inter fraction prostate motion.

68. Tools to deal with Intra fraction prostrate motion
 Tumor tracking,
 Provide motion feedback to the multileaf collimator
or linac
 Target tracking by dynamic MLC or dynamic
movement of the linac itself.
 The only system combining these features that has
reached clinical implementation so far is the Cyber
KnifeT

69. Treatment techniques
1.Conformal Arc Radiotherapy (CART)
2.Intensity Modulated Radiotherapy

70.  The shape of the PTV was shown to be of crucial
importance for the choice of treatment
delivery.(1)
 For a concave PTV (Prostate +SV), IMRT is
clearly superior to conformal arc therapy in
achieving Rectal sparing.
(Verellen et al. 2002).

72.  For a convex PTV (prostate without SV), IMRT
does not perform better than conformal arc
therapy.
 For CART, the rectum is blocked from the lateral
angles (90 ± 10° and 270 ± 10°) .
 Above results in a posterior blurred dose
distribution in order to meet rectal dose-volume
constraints and at the same time provide adequate
dose coverage of the PTV.

74. CLINICAL DATA

77. SBRT PANCREAS

78.  Pancreatic cancer is the fourth leading cause of cancer-
related deaths, and is the second leading cause of
digestive cancer-related deaths.
 Even with the most aggressive combined modality
therapy, the overall 5 year survival currently remains less
than 5%.

79.  Surgery with R0 resection (> 1 mm surgical margins) is
the only treatment currently available with curative
potential for patients with locally advanced pancreatic
cancer (Verbeke 2008).
 Only 15–20% of pancreatic cancer patients are
candidates for resection (Varadha chary et al. 2006).
 Approximately 52% of patients present with metastatic
disease,
 Another 26% present with locally advanced unresectable
tumors (Jemal et al. 2009).

81. Indications
 Boderline Resectable Pancreatic Ca
 Unresectable Pancreatic Ca

82. Stereotactic body radiation therapy (SBRT) In Pancreas is
indicated for
1.Boderline resectable tumors to improve resectability in
Neo Adjuvuvant setting.
2.In Unresectable due to their lower life expectancy to
reduce 5 -6 weeks treatment to less than 5 days
3.In resectecd Ca Pancreas with positive margins.

83. Challenges of SBRT in Pancreas
 The head of the pancreas, where majority of tumors reside, is
in close proximity to the C-loop of the duodenum
 Delivery of conventionally fractionated radiation (1.8–2
Gy/day) to more than 50 Gy results in damage to the small
bowel such as ulcerations, stenosis, bleeding, and
perforation.
 The pancreas move with respiration, as well as with
peristalsis that is not easily predictable.

84. Defining features include:
(1) Rigorous immobilization due to the longer treatment
times;
(2) Image guidance for accurate set-up of patient from
simulation to treatment;
(3) Use of multiple fields, or large-angle arcs of small
aperture fields to reduce dose to surrounding normal
tissue;

85. (4) Use of internal surrogates such as gold fiducial markers
rather than relying on external tattoos for patient
positioning;
(5) Strategy to account for organ and tumor motion; and
(6) Use of highly ablative doses of radiation therapy in few
sessions (typically 1–5) in order to achieve higher rates of
local control (Potters et al. 2004; Papiez et al. 2003).

88. U C L A TECHNIQUE
 1.Logistically, 2–3 gold fiducials are placed directly into
the tumor under CT guidance for targeting purposes.
 2.A custom immobilization device is created for each
patient,
 3. Four-dimensional CT (4D-CT) images are used for
treatment planning. FDG-PET images are also used for
treatment planning.

89.  4.An internal target volume (ITV) is contoured
based on the 4D-CT.
 5. The ITV is expanded by 0 –3 mm (except for
expansion into the duodenum or stomach) to form
the PTV.

90.  Dose of 36 Gy in three fractions is prescribed to the
isodose surface which covers the 95% of the PTV.
 No more than 5% of the contoured duodenum risk
object (1 cm above and below the GTV) receives more
than 30 Gy,
 No more than 50% of the contoured duodenum risk
object receives more than 21 Gy. For pancreatic head
lesions,
 The dose to the contralateral duodenal wall closest to the
GTV is limited to a total dose of 18 Gy

92. Thank you