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Stereotactic body radiotherapy

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SBRT for lung,liver and spine metastases

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Stereotactic body radiotherapy

  1. 1. STEREOTACTIC BODY RADIOTHERAPY DOSE-VOLUME CONSTRAINTS Dr Nanditha Kishore
  2. 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. 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. 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. 5. Methods Of Cell Kill in SBRT  DNA damage  Anti Angiogenesis  Endothelial cell Apoptoses
  6. 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. 7. SITES COVERED  Spine  Lung  Pancreas  Prostrate
  8. 8. SBRT SPINE
  9. 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. 10. Indications for Spinal SBRT  Pain control in vertebral metastases  Malignant Epidural Spinal Cord compression  Benign Spinal Cord Tumors
  11. 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. 12. Solitary Two adjacent Multiple lesions separated by normal vertibrae
  13. 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. 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. 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. 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. 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. 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.
  19. 19. 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.
  20. 20. Indications for spinal Radiosurgery  Unresectable tumors  Refuse surgery,  Surgery is contraindicated due to co-morbid conditions.
  21. 21.  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.
  22. 22. 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.
  23. 23.  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
  24. 24.  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
  25. 25.  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.
  26. 26. SBRT LUNG
  27. 27.  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.
  28. 28. INDICATIONS  Stage I NSCLC  Pulmonary metastases
  29. 29. 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
  30. 30.  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.
  31. 31.  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.
  32. 32. 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.
  33. 33. 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
  34. 34. 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.
  35. 35. Dose Distribution  It is estimatd after inhomogeniety corrections by various algorithms 1.Monte carlo algorithm 2.Path correction method
  36. 36. 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.
  37. 37.  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.
  38. 38. SBRT PROSTRATE
  39. 39. 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
  40. 40.  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.
  41. 41. Indications  Primary treatment for organ confined low risk prostrate cancer  Dose escalation for intermediate and high risk prostrate cancer
  42. 42. 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
  43. 43. 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.
  44. 44. 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.
  45. 45. 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%.
  46. 46.  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.
  47. 47. 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.
  48. 48.  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
  49. 49. 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
  50. 50.  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.
  51. 51. 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
  52. 52. Treatment techniques 1.Conformal Arc Radiotherapy (CART) 2.Intensity Modulated Radiotherapy
  53. 53.  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).
  54. 54.  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.
  55. 55. CLINICAL DATA
  56. 56. SBRT PANCREAS
  57. 57.  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%.
  58. 58.  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).
  59. 59. Indications  Boderline Resectable Pancreatic Ca  Unresectable Pancreatic Ca
  60. 60. 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.
  61. 61. 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.
  62. 62. 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;
  63. 63. (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).
  64. 64. 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.
  65. 65.  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.
  66. 66.  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
  67. 67. Thank you
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