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Radiosurgery for lung cancer short version


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Using radiosurgery (SBRT or SABR) to treat early stage lung cancer

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Radiosurgery for lung cancer short version

  1. 1. Radiosurgery for Lung Cancer Robert Miller MD
  2. 2. 0% 20% 40% 60% Local Regional Distant Stage Distribution for Lung Cancer 16% 22% 57% Very few are diagnosed at an early stage
  3. 3. 0% 20% 40% 60% Local Regional Distant 5 Year Survival for Lung Cancer 55% 28% 4% Cure rate is still poor even in early stages
  4. 4. Age Distribution at Diagnosis SEER Data 2009-2013
  5. 5. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 0 1 2 3 4 5 Stage 1 Stage 2 Stage 3 Stage 4 Observed Survival in the US (2003-2009) NSCL 51% 31% 14% 3%
  6. 6. Survival by Stage with Surgery Stage Clinical 5 Year Pathologic 5 Year IA 60 months 50% 119 month 73% IB 43 43% 81 58% IIA 34 36% 49 46 IIB 18 25% 31 36% IIIA 14 19% 22 24% IIIB 10 7% 13 9% IV 6 2% 17 13% J Thorac Oncol 2007; 2:706
  7. 7. Conventional Radiation for Stage I and II NSCL Years Over All Survival Cancer Specific Survival 2 years 22 – 72% 54 – 93% 5 years 0 – 42% 13 - 39% Cochrane Database Syst Rev. 2001
  8. 8. Stereotactic body radiation therapy (SBRT) is a technique that utilizes precisely targeted radiation to a tumor while minimizing radiation to adjacent normal tissue. This targeting allows treatment of small- or moderate-sized tumors in either a single or limited number of dose fractions. SBRT has been defined by the American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) as the use of very large doses per fraction SBRT
  9. 9. Stereotactic Ablative Radiotherapy (SABR) Radiation delivery to a demarcated tumor target using: optimal immobilization motion accounting many small fields accurate targeting heterogeneous target dose steep dose gradients outside targets large dose per treatment with ablative intent
  10. 10. May use motion control Upper Threshold Lower Threshold Playba ck Indicat or Breathing Signal Beam On / Off Indicator
  11. 11. Conformal High Dose
  12. 12. Techniques for Hitting the Tumor with a High Dose of Radiation Highly Targeted Conventional (traditional)
  13. 13. Large dose per fraction = greater BED (biologically effective dose) Assume an alpha/beta ratio of 10 / from RTOG 0915
  14. 14. Tomotherapy
  15. 15. T1 Adenocarcinoma / 10Gy X 5 with Tomotherapy Original CT Radiation Plan Original PET 1 Year PET
  16. 16. Squamous Cancer SBRT with Tomo PET 8 months later
  17. 17. Contour in the cancer (GTV) Use the CT and PET to identify the gross tumor volume (GTV) Or multiple scans to account for movement are combined to create ITV (internal target volume)
  18. 18. Add a margin around the target (PTV) Need to make the target a little bigger to account for movement or set up problems, but keep the PTV (planning target volume) as small as possible
  19. 19. Add a margin around the target (PTV) Review the images in all dimensions
  20. 20. Add in the other Organs to Measure the Radiation to Normal Structures Computer will track doses to ensure the normal structures are protected
  21. 21. PET before SBRT Target PET 2 months Later 80 yo man with adenocarcinoma LUL / Tomo 10Gy X 5
  22. 22. Cyberknife
  23. 23. Cyberknife for Lung Cancer
  24. 24. Complications from CT Needle Biopsy or Fiducial Placement
  25. 25. Cyberknife for Lung Cancer
  26. 26. Radiosurgery or SBRT for Early Stage Lung Cancer Are the results better than with conventional radiation? Are the results as good as conventional surgery?
  27. 27. Does it Work? • It’s better than doing nothing • It’s better than conventional radiation (3D conformal or daily radiation for 6 weeks) • It’s as good if not better that wedge resections or sub-lobar resections • It’s probably better than risking surgery in ‘high risk’ patients (old or poor medical status) • It may be as good as lobectomy
  28. 28. A Comparison of Stereotactic Body Radiation Therapy (SBRT) Versus No Treatment in Medically Inoperable Patients With Early-Stage Non-Small Cell Lung Cancer (NSCLC) From August, 2005 to June, 2013, 147 pts were treated with SBRT at a single institution. The thoracic RT consisted of 45-66 Gy/3 F delivered in 9 days. The control group of 43 untreated pts from Funen County, Denmark with early-stage NSCLC, from 2000 to 2012, was extracted from the Danish Lung Cancer Register. Jeppesen. IJROBP 2014;90:S642 SBRT No Rx Survival 40 months 9.9 months Survival/5y 37% 6% Lung Cancer cause of death 39% 77%
  29. 29. Conventional Radiation versus SBRT Therapy Local Control Survival/3 Y Conventional 30 – 40% 20 – 35% SBRT 97.6% 56% Timmerman RTOG 0236 / JAMA 2010;303:1070
  30. 30. Improved Local Control is Related to Improved Survival
  31. 31. Cause specific Survival Radiosurgery Results Robert Timmerman IJROBP 2009;75:677 Months
  32. 32. Years Radiosurgery Results – Stage I Cause Specific Survival Onishi IJROBP 2011;81:1352
  33. 33. 0236 A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I/II Non-Small Cell Lung Cancer 0618 A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Operable Stage I/II Non-Small Cell Lung Cancer 0813 Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients 0915 A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy (SBRT) Schedules for Medically Inoperable Patients with Stage I Peripheral Non-Small Cell Lung Cancer
  34. 34. Long-term Results of RTOG 0236: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I Non-Small Cell Lung Cancer Timmerman IJROBP 2014;90:S30 n = 55 / 18 Gy per fraction X 3 fractions (54 Gy total) 5-year primary tumor failure rate was 7% 5 year survival 40% / median of 4 years Grade 3 side effects in 27% . Grade 4 in 4% / no Grade 5
  35. 35. Timmerman JAMA 2010;303:1070 Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer RTOG 0236 18Gy X 3 OS 55.8% DFS 48%
  36. 36. RTOG 0618: Stereotactic body radiation therapy (SBRT) to treat operable early- stage lung cancer patients. The study opened December 2007 and closed May 2010 after accruing a total of 33 pts. Of 26 evaluable pts, 23 had T1, and 3 had T2 tumors. Median age was 72 years / dose 20Gy X 3 tumor failure rate of 7.7% / 2 years 2-year survival 84.4% J Clin Oncol 31, 2013 (suppl; abstr 7523)
  37. 37. 34Gy X1 12Gy X 4 Local Control/1y 97% 93% Survival/2y 61% 78% Side Effects 10% 13% RTOG 0915 IJROBP 2015;93:757 A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer
  38. 38. CyberKnife with tumor tracking: an effective treatment for high-risk surgical patients with stage I non-small cell lung cancer Chen Front. Onc. Feb 2012 N = 45 / 42-60Gy in 3 fx Local regional control at 3 years: 91% Overall survival at 3 years: 75% Overall Survival Years
  39. 39. Outcomes After Stereotactic Lung Radiotherapy or Wedge Resection for Stage I Non–Small-Cell Lung Cancer Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935. One hundred twenty-four patients with T1-2N0 NSCLC underwent wedge resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003 through August 2008. SBRT was volumetrically prescribed as 48 (T1) or 60 (T2) Gy in four to five fractions. SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P = .07). Overall survival (OS) was higher with wedge but cause-specific survival (CSS) was identical.
  40. 40. Local Regional Control Years SBRT Wedge Resection Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935.
  41. 41. Cause Specific Survival Years Grills Journal of Clinical Oncology 28, no. 6 (February 2010) 928-935. SBRT Wedge Resection
  42. 42. Lobectomy, Wedge Resection, or Stereotactic Radiotherapy (SBRT) for Stage I Non-small Cell Lung Cancer: Which Treatment Yields the Best Outcome? Lobectomy Wedge SBRT Local-regional recur/2y 2% 25% 9% Overall Survival/2y 85% 91% 72% Cause Specif Surv/2y 97% 96% 92% Welsh. IJROBP 2010;78:S180
  43. 43. Stereotactic ablative radiotherapy versus lobectomy for operable stage I non- small-cell lung cancer: a pooled analysis of two randomized trials Eligible patients in the STARS and ROSEL studies were those with clinical T1–2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling Chang in Lancet Oncology 16:630. June 2015
  44. 44. Outcome SABR Lobectomy OS/3y (overall survival) 95% 79% DFS/3y (progression free) 86% 80% Toxicity Grade 3 10% 44% Grade 4 0% 4% Stereotactic ablative radiotherapy versus lobectomy for operable stage I non- small-cell lung cancer: a pooled analysis of two randomized trials Chang in Lancet Oncology 16:630. June 2015
  45. 45. Outcomes of stereotactic body radiotherapy (SBRT) in 175 patients with stage I NSCLC aged 75 years and older Since 2003, 175 consecutive patients (67% male; 32% female) were treated with SBRT at a single center. The median age was 79 years, with 47% of patients aged 80 years or older. 56% of patients had T1 lesions and 44% T2 tumors. Risk-adapted SBRT schemes were used with the same total dose of 60 Gy in 3 (31%), 5 (53%) or 8 fractions (16%) depending upon risk for toxicity. Senan Journal of Clinical Oncology 27, no. 15S (May 2009) 9545-9545.
  46. 46. All patients completed planned SBRT and survival rates at 1 and 3 years were 85% and 46%. 60% of patients reported no early side effects, and fatigue (31%), cough (6%), dyspnea (5%), local chest wall pain (3%) and chest wall erythema (2%) were observed in others. Severe late toxicity was uncommon, with RTOG Grade 3 or higher radiation pneumonitis observed in 2%, radiation-induced rib fractures in 2%, chronic chest wall pain in 3%, and non-malignant pleural effusion in 2% of cases Senan Journal of Clinical Oncology 27, no. 15S (May 2009) 9545-9545. Outcomes of stereotactic body radiotherapy (SBRT) in 175 patients with stage I NSCLC aged 75 years and older
  47. 47. Survival With Stereotactic Body Radiation Therapy (SBRT) and Conventional Radiation Therapy (CRT) in Stage I Non-Small Cell Lung Cancer Patients in the Veterans Affairs System 2001 to 2010 along with increased SBRT utilization from 15.6% to 47.3%, and PET utilization from 12.0% to 69.4%. Boyer IJROBP 2016;96:S9 SBRT Conventional Overall Survival/4y 30% 19.2% DSS/ Survival / 4 y 54.7% 33.7%
  48. 48. Stereotactic Body Radiotherapy (SBRT) for Lung Lesions > 4 cm: Safety and Efficacy Woody. IJROBP 2011;81:S603 Cleveland Clinic Between 2005 and 2010, 51 lesions ranging from 4 to 7.2cm (20 > 5 cm) in 51 pts were treated. Forty (78%) were non small cell lung cancer (NSCLC) and 11 (22%) were oligometastatic disease. Local control at 12 and 24 months was 100 and 80.8% respectively. Loco-regional control at 12 and 24 months was 88% and 71% respectively. SBRT appears safe for lung lesions >4cm. Local control was excellent, with distant failure the primary form of failure. There appears to be an association between higher doses and tumor control.
  49. 49. 3 X 18 or 20 Gy 5 x 10Gy
  50. 50. Side Effects and Toxicity of SBRT for Lung Cancer
  51. 51. Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: Phase I study McGarry IJROBP 2005;63:1010 8.0 Gy/fraction for 3 fractions (total dose: 24 Gy / Radiation was given once daily with fractions separated by 2–3 days. The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy), but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis.
  52. 52. Excessive Toxicity When Treating Central Tumors in a Phase II Study of Stereotactic Body Radiation Therapy for Medically Inoperable Early-Stage Lung Cancer Timmerman JCO 2006:24:4833 staged T1 or T2 (≤ 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Patients treated for tumors in the peripheral lung had 2-year freedom from severe toxicity of 83% compared with only 54% for patients with central tumors.
  53. 53. Timmerman JCO 2006:24:4833 “No Fly Zone” Avoiding High Dose Centrally
  54. 54. What dose is safe for central cancer
  55. 55. Efficacy and Toxicity Analysis of NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiation Therapy (SBRT) for Centrally Located Non-Small Cell Lung Cancer (NSCLC) Bezjak IJROBP 2016;96:S8 PET staged T1-2 (<5 cm) N0M0 centrally located NSCLC (within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura) were successively accrued onto a dose-escalating 5 fraction SBRT schedule ranging from 10-12 Gy/fraction (fr) delivered over 1.5-2 weeks. Phase I data analysis revealed that maximum tolerated dose was the highest dose level allowed on the study, 12 Gy/fr x 5 fractions. Two-year OS rates of 70% in this medically inoperable group of elderly pts with comorbidities were comparable to pts with peripheral early stage tumors.
  56. 56. Author Local Control Rate Timmerman 95% Chang 57-100% Milano 73% Song 85% Haasbeek 93% Rowe 94-100% Nuyttens 76-85% Chang 97% Radiosurgery for Central Lesions Chang. IJROBP 2014;88:1120
  57. 57. Instead of 50Gy in 4 fractions they are using 70Gy in 10 fractions Results: Local Control (3y) WAS 96.5% and overall survival (3y) was 70.5% Conclusion: as long as lower dose constraints are used the outcome for central lesions is as good as peripheral Is it safe to use radiosurgery for central lesions?
  58. 58. Pulmonary VeinBronchus Esophagus Cord Skin Chestwall Lung Published dose limits for the normal structures near the target
  59. 59. Normal structures that need to be identified (contoured) so that the computer can keep track of the radiation exposure and ensure it stays in a safe range
  60. 60. Maximum Dose Constraints (to normal structures) for SABR (from Stablemates Trial)
  61. 61. RTOG 0236 Timmerman JAMA 2010:303:1070 Side Effects of SBRT
  62. 62. Rib Fractures After Stereotactic Body Radiation Therapy for Primary Non- small Cell Lung Cancer Oguir IJROBP 2012;84:S596 Between November 2001 and April 2009, 177 patients who had undergone SBRT were assessed for clinical symptoms and underwent follow-up thin-section computed tomography (CT). Forty-one patients were found to have rib fractures on follow-up thin- section CT. The frequency of rib fractures was 23.2%, appearing at a mean of 21.2 months (range, 4 -58 months) after completion of SBRT. The frequency of chest wall pain in patients with rib fractures was 34.1% (14/41), and was classified as Grade 1 or 2.
  63. 63. Limiting Chest Wall Toxicity by Adapting the Dose Schedule and Dose Constraints in Stereotactic Body Radiation Therapy for Early-Stage Lung Cancer IJROBP 2016:96:E457 60 Gy (range, 54 – 60). SBRT was delivered in 3 fractions for patients with a CW V30 of less than 30cc. If the CW V30 exceeded 30cc, 5 fractions were delivered and the SBRT plan was optimized on the biologically equivalent parameter of CW V30: CW V37 <30cc. Three hundred and eighty-one lesions were treated in a cohort of 363 patients with a median follow-up of 17 months (range, 1 - 62). Twenty patients (6%) had CW toxicity: 13 patients (4%) developed CW pain and 9 patients (3%) developed rib fractures.
  64. 64. Dose–effect analysis of radiation induced rib fractures after thoracic SBRT Barbara Stam N = 466 / Dose was 18 Gy X 3 Based on Max dose to ribs 37.5Gy = 50% <22.5Gy = < 5%
  65. 65. Side Effects of SBRT 80 yo 2.7 cm adenocarcinoma / 10Gy X 5 with Tomo Tomo Radiation CT CT 4 months later Note: mediastinal mass was thyroid goiter
  66. 66. Same patient, PET at 4 months, not hypermetabolic and assumed to be radiation fibrosis
  67. 67. Same patient, PET at 12 months, not hypermetabolic and assumed to be radiation fibrosis
  68. 68. Compare 3-year survival in high risk stage I NSCL between SAbR (18Gy X 3) and Sublobar resection
  69. 69. High-Risk = Minimum of 1 major or two minor criteria
  70. 70. • SABR/SBRT has achieved primary tumor control rates and survival , comparable to lobectomy and higher than 3D-CRT In non-randomized comparisons in medically inoperable or older patients • SBRT is an option if they cannot tolerate a lobectomy, with local control and survival comparable to wedge resections • In partially completed randomized trials found outcome similar to lobectomy with lower toxicity
  71. 71. • Intensive Regimens (BED >100Gy) have better local control and survival • For central lesions 4-10 fraction risk-adapted regimens appear to be safe and effective (while 54-60Gy/3 should be avoided) • For central lesions (from RTOG 0813) 50Gy in 5 fx appears safe • Most commonly used up to 5cm but larger lesions can be treated safely if the dose constraints are met
  72. 72. Comparable Survival Data for Stage I Lung Cancer