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Role of SBRT in lung cancer

A topic with precide information regarding role of SBRT in Lung Cancer

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Role of SBRT in lung cancer

  1. 1. ROLE OF SBRT IN LUNG CANCER By Dr. Ayush Garg Senior Resident
  2. 2. Learning Objectives for JRs  What is SBRT?  Why need of SBRT?  Difference between Conventional RT and SBRT  Steps of SBRT  Indications of SBRT  Advantages & Disadvantages of SBRT Learning Objectives for SRs  Various dose regimes  OAR dose tolerances  Evidences of SBRT
  3. 3. Introduction • SBRT is a noninvasive treatment involving the precise delivery of ablative dose radiation • Compared with fractionated radiation, SBRT achieves superior local control and survival • SBRT (also known as SABR) uses short courses of very high (ablative), highly conformal, and dose-intensive RT precisely delivered to limited-size targets. • Current standard-of-care for early-stage, nonoperative NSCLC is stereotactic body radiation therapy (SBRT)
  4. 4. Types of lesions Peripheral lesions • They are located > 2 cm from the primary bronchi or trachea Central lesions • Located within 2 cm of the proximal bronchial tree and/or abutting mediastinal pleura Ultra-Central lesions • Lesions abutting the proximal bronchial tree
  5. 5. The black dashed line defines the location of tumors that are central relative to the proximal bronchial tree. The term central has been widened to include the region within 2 cm in all directions of any mediastinal critical structure, including the bronchial tree/trachea, esophagus, heart, brachial plexus, major vessels, spinal cord, phrenic nerve, and recurrent laryngeal nerve. The region shaded red shows the trachea and main bronchi, and lesions with a PTV which overlaps this region are considered as ultracentral. b Example of an ultracentral tumor (planning target volume in red, and main bronchi/trachea in yellow). c Example of a central tumor
  6. 6. Difference between SBRT & Normal fractionation
  7. 7. Conventional Radiotherapy SBRT
  8. 8. The work flow Pre-SBRT work up Simulation (+/- 4DCT) Tumor & OAR contouring Plan analysis & acceptance Trial setup & off line CBCT Treatment delivery & review Follow up & data collection
  9. 9. Pre requisites for SBRT • Equipment • Staff teaching and training • Patient selection for SBRT • Patient counselling • Treatment planning • Dose and fractionation • Radiotherapy planning steps • Inter- and intra-fraction image guidance • Quality assurance • Follow-up
  10. 10. Equipment Mandatory • C-arm linear accelerator with volumetric in-room image guidance • Respiration correlated 4D-CT Recommended • Dedicated C-arm stereotactic linear accelerator (more advanced IGRT, more precise accuracy) • High-resolution MLC <10 mm
  11. 11. Staff teaching and training • Written departmental protocols • Multi-disciplinary project team for SBRT implementation and application • Structured follow-up for clinical outcome assessment
  12. 12. Patient selection for SBRT SBRT is recommended in the NSCLC for patients with  Stage I and II (T1–3,N0,M0)  NSCLC who are medically inoperable  High risk- elderly  Refuse surgery after appropriate consultation SBRT has no established role in small cell lung cancer  PFT (FEV1 or DLCO < 40%)  DM/CAD  Cerebral disease  Pul. HTN  PS 0-2  Able to lie flat for at least one hour
  13. 13. Early-Stage NSCLC (Stage I, selected node-negative Stage IIA) • SBRT is recommended for patients who are medically inoperable or who refuse to have surgery after thoracic surgery evaluation. • SABR is also an appropriate option for patients with high surgical risk (able to tolerate sublobar resection but not lobectomy [eg, age ≥75 years], poor lung function). • SABR has achieved good primary tumor control rates and overall survival, and higher than conventionally fractionated radiotherapy, although not proven equivalent to lobectomy NCCN Guidelines Version 7.2019 Non-Small Cell Lung Cancer
  14. 14. Patient Counseling Comparison of SBRT with other local treatment options
  15. 15. Patient Positioning and Immobilization • Stable and reproducible patient positioning is essential. If possible, patients should be positioned with both arms above the head as this position permits a greater choice of beam positions. • Reproducible setup can be achieved using a stable arm support, in combination with knee support to improve patient comfort.
  16. 16. Patient Positioning and Immobilization
  17. 17. Fusion Images CT scan • Planning CT scans should be acquired in treatment position, and incorporate techniques for evaluating motion compensation • A planning CT scan should include the entire lung volume, and typically extends from the level of the cricoid cartilage to the second lumbar vertebra • Slice thickness of 2–3 mm is recommended • IV contrast should be used • 4D-CT is recommended
  18. 18. Fusion Images PET scanning The equipment used for patient immobilisation during PET scans should be identical to that used for CT scanning and treatment
  19. 19. Target Volume Definitions GTV • CT with the settings: W= 1600 and L = 600 for parenchyma, and W= 400 and L = 20 for mediastinum should be used • Elective nodal irradiation is not indicated in any patient CTV • In SBRT treatments, CTV margins are generally not used ITV • Target representing the range of GTV motion through the breathing cycle PTV • ITV + 3 to 10 mm margin; Respiratory motion is a patient-specific factor which should be determined before treatment, typically using a pre-treatment 4D-CT or 4D PET/CT scan
  20. 20. Target Volume Definitions Passive motion compensation strategies • Abdominal compression • Internal target volume (ITV) concept • Mid-ventilation concept • Jet-ventilation Active motion compensation strategies • Gating • Breath hold • Tracking Application of one (either active or passive) 4D motion compensation strategy is highly recommended
  21. 21. • Deep inspiration breath hold (DIBH) reduces tumour motion while increasing the lung volume, resulting in decreased doses to lung, and often also to the heart
  22. 22. Target volumes definition PRV For serial organs, including the spinal cord, the main bronchi, the brachial plexus, the oesophagus and large blood vessels, the use of a PRV might be helpful, since it reduces the probability of over dosage
  23. 23. A 57-year-old man with medically inoperable NSCLC of the right upper lobe, treated on an SBRT protocol: 30 Gy/1 fx. (a) From the CT simulation, this image depicts the GTV during free breathing (red), at maximum inhalation (green), and maximum exhalation (blue). (b) ITV (lime) was generated by combining GTVs. PTV (light blue) = ITV + 5 mm. (c) Isodose distribution using a 6-arc plan, 6 MV photons, prescribed to the 80% isodose line
  24. 24. Stephans et al. l SBRT for Central Lung Tumors l 10/ 4/11 l 16 Beam Placement
  25. 25. Beam Placement
  26. 26. Dose and fractionation
  27. 27. Commonly Used Doses for SABR Total Dose # Fractions Example Indications 25–34 Gy 1 Peripheral, small (<2 cm) tumors, esp. >1 cm from chest wall 45–60 Gy 3 Peripheral tumors and >1 cm from chest wall 48–50 Gy 4 Central or peripheral tumors <4–5 cm, especially <1 cm from chest wall 50–55 Gy 5 Central or peripheral tumors, especially <1 cm from chest wall 60–70 Gy 8–10 Central tumors NCCN Guidelines Version 7.2019 Non-Small Cell Lung Cancer PRINCIPLES OF RADIATION THERAPY
  28. 28. Treatment Planning Mandatory • 3D conformal treatment planning • Type B algorithms • Respiration correlated 4D-CT imaging • ITV based motion management strategy Recommended • Dynamic IMRT planning (VMAT) • Use of a fixed dose inhomogeneity in PTV
  29. 29. Treatment Planning Dose calculations Dose calculation algorithms currently used for lung radiotherapy generally take into account changes in electron transport due to density variations, and are referred to as so-called type B or Monte Carlo based algorithms
  30. 30. Radiotherapy Planning • Tumour and nodal changes • Inter-fractional tumour shifts • Intra-fractional tumour shifts • Intra-fractional respiratory and cardiac motion • Anatomical changes during fractionated radiotherapy
  31. 31. Inter- and intrafraction image guidance Mandatory • Daily pre-treatment volumetric image-guidance • Recommended • Daily pre-treatment 4D volumetric image-guidance (in-room 4D- CT, 4D-CBCT)
  32. 32. Tumour and nodal changes Inter-fractional tumour shifts • Inter-fractional shifts between primary tumour and vertebra positions range from 5 to 7 mm on average (3D vector), but may be as high as 3 cm • Image guidance and patient setup corrections are essential
  33. 33. Tumour and nodal changes Intra-fractional tumour shifts • The intra-fractional target shifts are usually of small magnitude, ranging from 0.15 to 0.21 cm • Intra-fractional drifts increase when treatment times exceed 34 min
  34. 34. Tumour and nodal changes Intra-fractional respiratory and cardiac motion • Increased motion has been observed in lower-lobe tumours, for smaller primary tumours and for infra-carinal lymph nodes • For tumours close to heart or aorta, cardiac-induced motion can exceed respiratory motion due to large inter-patient variability, patient-specific motion assessment should be performed
  35. 35. Dose distribution
  36. 36. Red Shell • The Red Shell representing high-risk tissue is shown in red surrounding the clinical target volume (CTV) shown in gray. • The serial critical organs are shown in yellow on the right. • The Red Shell is composed of two sub-shells, the Inner Red Shell (the smaller red ring surrounding the CTV) and the Outer Red Shell (the bigger red ring surrounding the Inner Red Shell). • The internal boundary of the Inner Red Shell is the CTV surface. • The external boundary of the Inner Red Shell is the planning target volume (PTV) surface.
  37. 37. Red Shell • The external boundary of the Outer Red Shell is where the biologically effective dose (BED) drops to the constraint dose. • The Red Shell is curved inward on the right side. • This is the result of careful planning to spare a critical serial organ (yellow) in near proximity. • As a result, the dose may need to protrude outward on the opposite side, generating a bigger Red Shell in that direction, at the ‘‘cost’’ of sparing the critical organ.
  38. 38. NCCN Guidelines Version 7.2019 Non-Small Cell Lung Cancer Maximum Dose Constraints for SABR OAR/Regimen 1 Fraction 3 Fractions 4 Fractions 5 Fractions Spinal cord 14 Gy 18 Gy (6 Gy/fx) 26 Gy (6.5 Gy/fx) 30 Gy (6 Gy/fx) Esophagus 15.4 Gy 27 Gy (9 Gy/fx) 30 Gy (7.5 Gy/fx) 105% of PTV prescription Brachial plexus 17.5 Gy 24 Gy (8 Gy/fx) 27.2 Gy (6.8 Gy/fx) 32 Gy (6.4 Gy/fx) Heart/ pericardium 22 Gy 30 Gy (10 Gy/fx) 34 Gy (8.5 Gy/fx) 105% of PTV prescription Great vessels 37 Gy NS 49 Gy (12.25 Gy/fx) 105% of PTV prescription Trachea & proximal bronchi 20.2 Gy 30 Gy (10 Gy/fx) 34.8 Gy (8.7 Gy/fx) 105% of PTV prescription Rib 30 Gy 30 Gy (10 Gy/fx) 40 Gy (10 Gy/fx) NS Skin 26 Gy 24 Gy (8 Gy/fx) 36 Gy (9 Gy/fx) 32 Gy (6.4 Gy/fx) Stomach 12.4 Gy NS 27.2 Gy (6.8 Gy/fx) NS *Based on constraints used in recent RTOG SABR trials (RTOG 0618, 0813, & 0915) ^for central tumor location. NS = not specified
  39. 39. Toxicity
  40. 40. Follow up Mandatory • Follow-up according to published guidelines • FDG-PET imaging in case of suspected local recurrence Recommended • Routine biopsy confirmation of imaging-defined local failure only in patients who are likely to undergo salvage therapy
  41. 41. Quality Assurance Mandatory • Intensified quality assurance (mechanical accuracy of 1.25 mm and a dosimetric accuracy of 3% in a lung phantom inside the treatment field) • Small field dosimetry detectors for commissioning • Quality assurance of in-room image-guidance systems and of the 4D- CT scanner • Weekly checks of the mechanical accuracy of the delivery system • Daily quality checks of the alignment of the IGRT system with the MV treatment beam
  42. 42. Evidences
  43. 43. A 7-year follow-up showed that overall survival rates were 55.7% at 5 years and 47.5% at 7 years. In 12 patients (18.5%), a second primary lung carcinoma developed after SABR at a median of 35 months (range, 5–67 months); 27% (18/65) had disease recurrence a median of 14.5 months (range, 4.3–71.5 months) after SABR. • In conventionally fractionated RT, • 3-year survival is only about 20% to 35% • Local failure rates of about 40% to 60% • In SBRT • Generally more than 85%, and about 60% at 3 years (median survival, 4 years), respectively In Medically inoperable patients
  44. 44. Indiana (Timmerman JCO 2006; Fakiris, IJROBP 2009) • n=70 • T1–3N0 (≤7 cm) • 60–66 Gy in 3 fx over 1–2 weeks. • Three-year LC 88%, CSS 82%, OS 43%, regional failure 9%, and distant failure 13%. • Patients with central tumors had increased risk of grade 3–5 toxicity (27% vs 10%). • Established “no-fly-zone” of 2 cm surrounding proximal bronchial tree for 3-fraction treatment.
  45. 45. Onishi (Cancer, 2004) • n=245 • T1–2N0 treated • 18–75 Gy in 1–22 fx • LF was 8% for BED ≥100 Gy vs 26% for BED <100 Gy. • Three-year OS was 88% for BED ≥100 Gy vs 69% for BED <100 Gy.
  46. 46. RTOG 0236 (Timmerman 2010) • T1–3N0 (≤5 cm), medically inoperable tumors >2 cm from proximal bronchial tree treated • SBRT 20 Gy × 3 over 1.5–2 weeks (54 Gy applying heterogeneity correction). • GTV = CTV. PTV = 0.5 cm axial margin and 1 cm superior/inferior margin. • 5-year LC 93%, LRC 62%, 31% DM, DFS 26%, OS 40%.
  47. 47. RTOG 0915 (Videtic IJROBP 2015) • Phase II randomized study of 34 Gy in 1 fraction vs 48 Gy in 4 fractions • Medically inoperable T1-3N0 (≤5 cm) NSCLC • Single fraction arm had lower risk of serious adverse events (10.3 vs 13.3%). • 2-year primary control, OS, and DFS were 97% vs 93%, 61% vs 77%, and 56% vs 71%, respectively.
  48. 48. RTOG 0618 (Timmerman ASCO 2013) • Medically operable T1-T3N0 (≤5 cm) NSCLC >2 cm from proximal bronchial tree • 60 Gy in 3 fractions (54 Gy with heterogeneity correction). • 2-year primary failure rate 7.8%, local failure (including ipsilateral lobe) 19.2%, OS 84%. 16% grade 3 toxicity
  49. 49. RTOG 0813 (Bezjak ASTRO 2016) • Phase I/II dose escalation trial for medically inoperable early- stage NSCLC with centrally located lesions (<2 cm from the bronchial tree) • Arm I- 57.5 Gy (n=38), Arm II-60 Gy (n=33). • Dose escalated from 50 Gy in 5 fractions to 60 Gy in 5 fractions. • 2 yr LC 88–89%, PFS 52–55%, OS 70–73%, grade 3 toxicity 6– 7%
  50. 50. VUMC (Senthi, Lancet Oncol 2012) • n=676 • PET+ clinical stage T1–2 N0 NSCLC • 2/5-yr LF 5/11%, regional failure 8/13%, DM 15/20%.
  51. 51. SBRT VS SURGERY Two randomized trials of surgery vs SBRT for operable early- stage NSCLC failed to accrue (STARS and ROSEL)
  52. 52. Combined ROSEL/STARS analysis (Chang Lancet Oncol 2015): • n=58 patients from two trials • T1-T2 (<4 cm) N0 medically operable NSCLC • SBRT (54 Gy in 3 fractions, 50 Gy in 4 fractions if central) vs lobectomy and mediastinal lymph node dissection. • 3-year OS improved for SBRT (95%) vs surgery (79%). Grade 3–4 toxicity 10% for SBRT vs 44% for surgery. SBRT VS SURGERY
  53. 53. • JoLT-Ca STABLE-MATES trial (NCT02468024) • VALOR (Veterans Affairs Lung cancer surgery Or stereotactic Radiotherapy trial, NCT02984761) • SABRTOOTH (NCT02629458) Trials under going SBRT VS SURGERY
  54. 54. Conclusion It is a form of high precision radiotherapy delivery technique • Needs to account for tumor motion • Needs to be accurate • Needs to have reproducible setup prior to treatment Indications • Stage I–II, inoperable, T1-3N0M0   Definitive SBRT not 3D • Medically inoperable • Operable disease who are high risk, elderly • Refuse surgery
  55. 55. SABR for Node-Negative Early-Stage NSCLC • BED ≥100 Gy are associated with significantly better local control and survival • For central and ultra-central tumors 4 to 10 fraction regimens are effective and safe • SABR is most commonly used for tumors up to 5 cm in size SBRT has a Developing role • Boost following definitive chemoradiation in management of LA-NSCLC • Re-irradiation of locally recurrent disease • Intrathoracic oligometastases from various primary histologies

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