Radioterapia 4D

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4D Radiotherapy, Radioterapia 4D

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Radioterapia 4D

  1. 1. XXIII Corso Residenziale di Aggiornamento Moderna Radioterapia e Diagnostica per Immagini: dalla definizione dei volumi alla radioterapia «adaptive» Il glossario per il Corso: 4D-RT G.R. D’Agostino, M.M. Colangione, M. Ferro, A. Pacchiarotti, M.A. Tafuri
  2. 2. RADIOTERAPIA 1D Comas C, Prio A-Congres International Electrologie - 1905
  3. 3. 5D RT: Dose Painting by Numbers
  4. 4. Chen et al., JCO 2011
  5. 5. CONE BEAM - CT • Visualizzazione dei PARENCHIMI
  6. 6. Jiang SB, Semin Radiat Oncol 2006 Oct; 16(4):239-48.
  7. 7. Ποταμοῖς τοῖς αὐτοῖς ἐμβαίνομέν τε καὶ οὐκ ἐμβαίνομεν, εἶμέν τε καὶ οὐκ εἶμεν. Ἡράκλειτος ὁ Ἐφέσιος
  8. 8. 4D RADIOTHERAPY IMAGING 4D The explicit inclusion of the temporal changes in anatomy during the imaging, planning and delivery of radiotherapy. Acquisition of a sequence of CT IMAGE SETS over consecutive segments of a breathing cycle PLANNING 4D Designing treatment plans on CT image sets obtained for each segment of the breathing cycle DELIVERY 4D Continous delivery of the designed 4D treatment throughout the entire breathing cycle
  9. 9. A diagram showing a 4D CT acquisition process. Images are acquired and then sorted by the patient’s respiratory phase at the time the image was acquired to create 3D CT images at discrete phases of the respiratory cycle. Mageras G.S. Deep Inspiration Breath Hold and Respiratory Gating Strategies for Reducing Organ Motion in Radiation Treatment , 2004
  10. 10. • Respiratory motion can affect the delivered dose distribution – Especially in the thorax/abdominal region • Available solutions – INCREASED MARGINS • More dose will be delivered to the surrounding healthy tissue • Organs at risk must still be protected, which may be very difficult if they move near or into the desired target volume – GATED TREATMENT • Dose delivery is synchronized with respiratory motion • Potential for dose escalation, resulting in higher delivered dose to the tumor while healthy tissue is spared • The correlation between internal and external (surrogate) motion must be known • Mageras G.S. Deep Inspiration Breath Hold and Respiratory Gating Strategies for Reducing Organ Motion in Radiation Treatment , 2004
  11. 11. New radiotherapy technology True clinical benefit Improved tumour control Reduced toxicity Survival Quality of life
  12. 12. Breath-hold 4D Tracking Gating •Dose escalation •Reduction in PTV volume
  13. 13. BREATH-HOLD TECHNIQUES DIBH : DEEP INSPIRATION BREATH-HOLD Is generally performed in deep inspiration o Physiologically easier to mantain o Moves a significant amount of normal lung outside the treatment volume VOLUNTARY BREATH-HOLD A spirometer indicates in real-time the desired level of breath-hold and the level actually achieved.. The patient breathes freely for a certain numbers of cycles and then performed a modified manoeuvre inflate his lungs and mantain breath-hold in the desired zone, determined in collaboration with patient during a training session. The operator starts irradiation. ACTIVE BREATHING CONTROL (ABC) SYSTEM Breath-hold is not manteined voluntarily by the patient but is forced. When the patient enters the desidere breath breath-hold zone, a baloon a catheter or a valve completely closes the air inlet.
  14. 14. Patient intensive normal unregulated breathing regular breathing voluntary breath hold imposed breath hold sedation anaesthaesia
  15. 15. Patient intensive normal unregulated breathing real time tracking regular breathing voluntary breath hold predictive tracking imposed breath hold gating with free breathing or breath hold sedation anaesthaesia standard fixed delivery Technology intensive
  16. 16. Breathing-synchronized radiotherapy Treatment techniques in which the patient breathes freely and for which the linear accelerator delivers irradiation only during a given phase of respiratory cycle The radiation beam is turned on and off depending on the real-time position of target GATING The radiation beam is always turned on and follows the moving target TRACKING Giraud P, et al. Reduction of organ motion effect in IMRT and conformal 3D radiation delivery by using gating and tracking techniques. Cancer Radiothérapie 10, 269-282.
  17. 17. GATING RADIOTHERAPY A mechanism that SYNCHRONIZES imaging and dose delivery with a patient’s BREATHING CYCLE
  18. 18. 100% End exhale Gating window Amplitude End inhale 0% Giraud P, et al. Reduction of organ motion effect in IMRT and conformal 3D radiation delivery by using gating and tracking techniques. Cancer Radiothérapie 10, 269-282.
  19. 19. TRACKING RADIOTHERAPY Real time localization of a constantly moving tumor EXTERNAL TRACKING Tumor position is derived from SURROGATE BREATHING SIGNALS such as LUNG VOLUME or SKIN MOTION Disadvantages The short-term correlation between external surrogates and internal target position may be not stable during a long treatment fraction and over the treatment course
  20. 20. INTERNAL TRACKING • Implanting of FIDUCIAL MARKERS in the tumorbearing organs. The high radio-opacity of the markers makes them readily detectable in fluoroscopic images. • Markers can be implanted either PERCUTANEOUSLY or ENDOSCOPICALLY. • Disadvantages Invasive procedure Jiang et al, Seminars in Radiation Oncology 2006
  21. 21. Non-radiographic tumor tracking Real time 3D-US 1. Easy 2. Quick 3. Not invasive Svantaggi 1. operator-depending 2. Low quality of imaging Jiang et al, Seminars in Radiation Oncology 2006
  22. 22. OTHER STRATEGIES…. • A miniature, implantable RF coil has been developed by Seiler et al. that can be tracked magnetically in 3D from outside the patient. • A new technology currently under development at Calypso Medical Technologies, Seattle, using a small wireless transponders implanted in human tissue. Giraud P, et al. Reduction of organ motion effect in IMRT and conformal 3D radiation delivery by using gating and tracking techniques. Cancer Radiothérapie 10, 269-282.
  23. 23. Real-time beam adaptation to a constantly moving tumor The projected position of the planned (virtual) and actual (real) 3D coordinates of the marker can be seen on the corresponding fluoroscopic image. When the planned position and the actual position of the marker coincide within the permitted dislocation, the treatment beam is on. When the actual position of the marker is outside of the area of permitted dislocation, the treatment beam is off. Harada T., Cancer 2002
  24. 24. TC 4D Caratteristiche Tecniche
  25. 25. GE HiSpeed DX/i Spiral GE Optima CT 580 RT 65CM 80 CM
  26. 26. Ge HiSpeed DX/i Spiral Ge Optima CT 580 RT Detettori 1 16 Spessore Minimo (pitch) 1.25 mm 0.62 mm Intervallo 0.6 mm – 1 mm 0.3 mm Tempo Scansione 0.8 Sec. – 0.5 Sec 0.3 Sec – 0.4 Sec Tempo di Acquisizione 30 Sec. – 25 Sec. 15 Sec – 10 Sec. FOV 50 CM 65 CM
  27. 27. Accessori 4D • Marker riflettenti a 6 punti distanziati tra loro di 3 cm • Calibrazione prima di ogni simulazione e applicazione RT Telecamera ad infrarossi
  28. 28. SIMULAZIONE 4D
  29. 29. RPM : Simulazione Fase Forzata Fase Libera
  30. 30. RPM : Terapia RESPIRAZIONE LIBERA
  31. 31. RPM - Terapia RESPIRAZIONE FORZATA
  32. 32. Terapia IR
  33. 33. Respiratory Gating «A technique which allows collection of images or delivery of radiation only during certain time intervals, synchronous with the patient’s respiratory cycle.» Mageras G.S. Deep Inspiration Breath Hold and Respiratory Gating Strategies for Reducing Organ Motion in Radiation Treatment , 2004
  34. 34. Respiration-synchronized Radiotherapy Images acquisition • Prospective triggering • Retrospective correlation Radiation delivery
  35. 35. RPM system
  36. 36. Prospective triggering Inhale GATING WIDTH Exhale t X-Ray ON Scan in 1st couch position Scan in 2nd couch position Scan in 3rd couch position Scan in 4thcouch position Scan in 5th couch position
  37. 37. Prospective triggering Inhale GATING WIDTH Exhale t X-Ray ON Scan in 1st couch position Scan in Scan in Scan in 3rd couch position 4thcouch position 2nd couch position Scan in 5th couch position
  38. 38. Contouring
  39. 39. Treatment planning PTV Gating No gating Lung Heart
  40. 40. Treatment delivery
  41. 41. Retrospective correlation Inhale Exhale X-Ray ON t
  42. 42. Contouring Contouring different images CT data set, each related to one specific phase of respiratory cycle. 1° phase 2° phase
  43. 43. Contouring … in cine modality
  44. 44. Contouring MIP (Maximum Intensity Projection)
  45. 45. Contouring MIP (Maximum Intensity Projection)
  46. 46. Contouring MIP (Maximum Intensity Projection)
  47. 47. Contouring MIP (Maximum Intensity Projection)
  48. 48. Contouring MIP (Maximum Intensity Projection)
  49. 49. Contouring MIP (Maximum Intensity Projection)
  50. 50. Contouring MIP (Maximum Intensity Projection)
  51. 51. Treatment planning
  52. 52. Treatment delivery
  53. 53. 4D RT - Clinical applications • Tumor sites affected by respiratory motion • In particular thorax and abdominal regions • LUNG, BREAST and LIVER tumors
  54. 54. Respiratory motion • Anatomic excursion of 1-2 cm is common and larger for tumors close to the diaphragm • Intrafraction motion • Larger PTV  Increase volume normal tissue  Toxicity • Inadequate PTV  Underdose tumor  Target miss  No local control RESPIRATION GATING 4D RT P. Giraud et al. Cancer Radiotherapie 2006; 10:269-282
  55. 55. Motion with respiratory gating • Movements of the diaphragm in the CC are reduced (77%) by an average of 22,7 mm in free breathing to 5,1 mm with respiratory gating with a reduction of margin by 1 cm and allow an increase of dose of 20% Wagman R et al. Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):659-68
  56. 56. 4D RT IN LUNG CANCER
  57. 57. Motion in lung cancer A number of studies have investigated the magnitude of this motion M Dahele, J Cuijpers, and S Senan; Four-dimensional Radiation Therapy for Non-Small Cell Lung Cancer: A Clinical Perspective in: B. Jeremic´ (ed.), Advances in Radiation Oncology in Lung Cancer, Medical Radiology. Radiation Oncology, DOI: 10.1007/174_2011_284, Springer-Verlag Berlin Heidelberg 2011 • • Lung tumor motion is larger than 1 cm in CC direction in 33% of lung cancer Shirato H et al Cancer Sci. 2012 Jan;103(1):1-6. doi: 10.1111/j.1349-7006.2011.02114.x. Epub 2011 Nov 14. Review.
  58. 58. Lung tumor motion evaluated with 4DCT Korreman et al. Acta Oncologica, 2008; 47: 1390-1396
  59. 59. Resources that address important aspects of 4D RT in lung cancer 4D RT in conventional and stereotactic lung RT program M Dahele, J Cuijpers, and S Senan; Four-dimensional Radiation Therapy for Non-Small Cell Lung Cancer: A Clinical Perspective in: B. Jeremic´ (ed.), Advances in Radiation Oncology in Lung Cancer, Medical Radiology. Radiation Oncology,
  60. 60. Lung stereotactic 4DRT in stage I NSCLC SBRT needs ablative dose, small target, high BED but is related to a high risk of pneumonitis
  61. 61. Dosimetric comparison of SBRT using 4D CT • 4D CT reduces PTV and ITV resulting in smaller volume of normal lung irradiated and provides an excellent target coverage L. Wang et al. Radiot and Oncol 2009; 91:314-324
  62. 62. Lung stereotactic 4DRT in stage I NSCLC - clinical outcomes • On 130 patients with stage I NSCLC treated with 4D SBRT obtain 93% OS rate at 1 year, 65% at 3 year, a 2 year LC rate of 98 % and 0% of 4-5 grade toxicity. • 4D SBRT can achieve 90% local control when BED > 100 Gy with minimal side effect (< 3 grade) Chang et al. Radiation Oncology 2012,7:152
  63. 63. 4DRT in locally advanced lung cancer • Curative RT requires high radiation doses but the amount of normal lung in the high dose region is the dose limiting factor
  64. 64. V20 and outcomes in lung cancer The lung complications are correlated with mean lung dose and V20
  65. 65. 4DRT in locally advanced lung cancer There is a clinical evidence that 4DRT, which through safe PTV volume reduction will allow an increased dose to the tumor while sparing healthy tissue, can improve the balance between complication and cure Dose Van Meerbeeck JP et al. The Oncologist 2008;13:700–708
  66. 66. 4DRT in locally advanced lung cancer Outcomes for locally advanced non-small cell lung cancer (NSCLC), treated with today’s advanced technologies, comparated to those reported in the previous era demonstrate a decrease of pneumonities and an increase of OS M Dahele, J Cuijpers, and S Senan; Four-dimensional Radiation Therapy for Non-Small Cell Lung Cancer: A Clinical Perspective in: B. Jeremic´ (ed.), Advances in Radiation Oncology in Lung Cancer, Medical Radiology. Radiation Oncology, DOI: 10.1007/174_2011_284, Springer-Verlag Berlin Heidelberg 2011
  67. 67. 4D RT IN BREAST CANCER
  68. 68. Clinical outcomes in conventional BREAST CANCER • Patients with breast cancer have seen a decrease in recurrence after receiving breast RT. However, after being treated with breast radiotherapy patients have exhibited an increase in cardiac morbidities along with heart disease later in life. Qi XS et al Int J Radiat Oncol Biol Phys 2012:82(5):1605-1611
  69. 69. Heart disease in breast cancer RT • On 1601 patients, those who received left-sided breast cancer radiotherapy had a greater incidence of cardiovascular disease (16%) compared to those who had right-sided radiation (11.6%). Patients started experiencing heart disease 10 to 11 years after RT Borger et al. Int J Radiat Oncol Biol Phys. 2007;69(4)1131-1138 • Several studies show a radiation related microvascular damage in within 6 months after breast RT, particulary where the heart receives more than 25 Gy dose which could be related with 10 ys risk of mortality B. Jeremic´ (ed.), Advances in Radiation Oncology in Lung Cancer, Medical Radiology.Radiation Oncology, DOI: 10.1007/174_2011_284, Springer-Verlag Berlin Heidelberg 2011
  70. 70. Conventional breast RT • In conventional left breast irradiation there is a greater volume of heart included in the fields Harris EE. Cancer Control. 2008 Apr;15(2):120-9. Review • Breast moves only around 2-4 mm in AP direction but the heart moves up to several cm in CC direction Korreman et al. Acta Oncologica, 2008; 47: 1390-1396 • Breast irradiation, only during deep inspiration, reduces heart doses up to 80-90% and decreases cardiac mortality risk to 1‰ Korreman et al. Acta Oncologica, 2008; 47: 1390-1396
  71. 71. 4D RT for breast cancer The gated 4DRT at full inspiration (0%) reduces heart mean dose and ipsilateral lung doses while maintaing similar coverage for PTV and chest wall Sharon X. Et al. Radiat Oncol Biol Phis 2012; 82:1605-1611 4DRT provides a decrease in cardiac mortality and events of pneumonitis Korreman SS et al. Int J Radiat Oncol Biol Phys. 2006;65(5):1375-1380.
  72. 72. 4D RT IN LIVER CANCER
  73. 73. Motion for abdominal cancer • In the abdomen, the primary source of organ motion is respiration • There are critical organs adjacent to liver and pancreas tumors that may be over-irradiated Langen KM et al.. Int J Radiat Oncol Biol Phis 2001; 50:265-278
  74. 74. Motion of abdominal cancer • The liver tumor moves in CC of 10 mm more than pancreatic cancer (5 mm) and other abdominal organs Hallmann et al. Int J Radiat Oncol Biol Phis 2012; 83: 435-441
  75. 75. SBRT for abdominal cancer • Use of SBRT in patients with primary hepatocellular or metastatic liver tumor have shown high rates of local control Herfarth KK et al. J Clin Oncol. 2001 Jan 1;19(1):164-70 • High dose fraction  High precision needed • Important use of abdominal compression and respiratory gating
  76. 76. SBRT in abdominal cancer • Abdominal compression reduces tumor motion almost of 1 cm Heinzerling JH et al. Int J Radiat Oncol Biol Phys. 2008 Apr 1;70(5):1571-8. • A gating technique reduces the range of motion by almost a factor of 10 Hallmann et al. Int J Radiat Oncol Biol Phis 2012; 83: 435-441
  77. 77. 4D RT for liver cancer The PTV in 4D plan decresed by 20,5% The liver’s V30 e V40 were lower in 4D plan Liver complication decreased from 21,5% to 15,8 Gy The prescription dose was increased by 9,7% in 4D plan Xi M.et al. Chinese Journal of Cancer, 2007; 27:1-8
  78. 78. 4D RT for abdominal cancer • Respiratory gated 4D RT reduces target volume to spare more normal tissue and allows dose escalation especially for liver tumor mobility > 1 cm Xi M. Radiother Oncol 2007; 84: 272-8 • 4D CT simulation allows to precisely define the PTV and to tailor the treatment with a decrease of toxicity risk and an increase of LC De Bari et al. Cancer Radiother 2011; 15: 43-8
  79. 79. When using 4D RT? Gating techniques are reasonably time consuming and they may not be needed for every patient Investigate: • Patient comorbidities (heart desease, pneumonitis, CT) • Age and patient compliance • Tumor size (GTV< 100 cm3) (Starkscholt 2004) and tumor site • Respiratory phase optimizer (RPO), parameter to determine the optimal irradiation phase • Institute resources
  80. 80. Linee guida for 4D RT • Non ci sono ancora chiare indicazioni per l’utilizzo della 4D RT ma… La Radioterapia dei Tumori Gastrointestinali _ Indicazioni e Criteri Guida AIRO 2012

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