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Novel rt in sarc2017
- 1. IN THE NAME OF GOD
- 2. Novel radiotherapy techniques in sarcoma DR .MOHAMMAD GOURAN SAVADKOOHI RADIATION ONCOLOGIST EMAM ALI MEDICAL CENTER .(AUMS)
- 4. Type of radiation Therapy used in Sarcoma EBRT Brachytherapy systemic administration of radiopharmaceutical agents.
- 5. Patient positioning and Immobilization Volumetric Data acqusition Image Transfer to the TPS Target Volume Delineation 3D Model generation Forward Planning Inverse Planning Dose distribution Analysis Treatment QA Treatment Delivery
- 6. Advancements in radiotherapy Target delineation Treatment Planning & Delivery Combination with chemotherapy Enhancing The Response to Radiotherapy Radiation therapy
- 7. Target Volume delineation • GTV (Gross Target Volume) • CTV (Clinical Target Volume) • ITV (Internal Target Volume) • PTV (Planning Target Volume)
- 8. Target volumes in radiotherapy • GTV: Macroscopic extent of the tumor as defined by radiological and clinical investigations. • CTV: The GTV together with the surrounding microscopic extension of the tumor constitutes the CTV. The CTV also includes the tumor bed of a R0 resection (no residual). • ITV (ICRU 62): The ITV encompasses the GTV/CTV with an additional margin to account for physiological movement of the tumor or organs. It is defined with respect to a internal reference – most commonly rigid bony skeleton. • PTV: A margin given to above to account for uncertainities in patient setup and beam adjustment.
- 10. Target delineation advancements in sarcoma MRI fusion VS CT only USED FOR PLANNING ,PET 1 DEVELOPMENT OF CONSENSUS BY RTOG for treatment volumes 2 CT based atlas development 3
- 11. RTOG Sarcoma Consensus on The GTV For Preoperative Radiotherapy of Large High Grade Extremity Soft Tissue Sarcoma MRI T1 plus contrast images . Fusion of MRI and CT is recommended. IV contrast is recommended.
- 12. RTOG Sarcoma Consensus on The CTV For Preoperative Radiotherapy (CTV) CTV = GTV + 3 cm in longitudinal(proximal and distal) directions(no need to extend field out the compartment ). radial margin 1.5 cm including any portion of the tumor not confined by an intact fascial barrier, bone or skin surface.
- 13. CT ATLAS OF MSK ANATOMY FOR SARCOMADEVELOPMENT BY RTOG
- 15. Advancements in radiotherapy Target delineation Treatment Planning & Delivery Combination with chemotherapy Enhancing The Response to Radiotherapy Radiation therapy
- 16. Treatment Planning & Delivery advancements Better tumor deline ation Setup accuracy Daily localizati on Higher dose to tumor lower dose to normal tissue “
- 17. Treatment Planning & Delivery Advancements 1. dynamic multileaf collimators-->IMRT 2. volumetric-modulated arc therapy (VMAT), 3. Image Guided Radiation therapy (IGRT) 4. four-dimensional CT, Using planning images at multiple phases of the ventilatory cycle.(4DRT) respiratory gating possible 5. Tomotherapy 6. Stereotactic body radiotherapy high dose 7. Adaptive radiotherapy
- 20. Treatment Planning & Delivery Traditional radiation therapy consistent intensity of radiation across the treatment field. multi-leaf collimators •shape the radiation field •alter the intensity of radiation delivered to portions of the field •IMRT POSSIBLE
- 21. Treatment Planning & Delivery • multileaf collimators IMRT (intensity modulated radiotherapy) • ``
- 23. Treatment Planning & Delivery
- 24. Uniform Intensity Intensity Modulation Conventional RT vs. IMRT
- 25. IMRT3-D IMRT VS 3D SARCOMA % GTV PTV GTV PTV Hong et al Int J Rad Oncol Biol Phys, 2004
- 26. TRIAL RESULTS IMRT in SARCOMA
- 28. IGRT and ART •Image-guided radiation therapy serial imaging of patient setup prior to treatment so that appropriate positional adjustments can be made beforehand •adaptive radiation therapy :IF imaging during a course of treatment demonstrates changes in patient anatomy (e.g., due to weight loss) or changes in tumor shape, a second radiation plan can be developed to adapt to these new data
- 29. IGRT
- 34. SBRT • What is SBRT? Technical •Typically few-fraction (1 to 5) RT using large individual fraction doses •High dose conformality, i.e., “tight around target” • Rapid dose fall-off from target to surrounding normal tissue.
- 36. Trial results of SBRT
- 37. Advancements in radiotherapy Target delineation Treatment Planning & Delivery Combination with chemotherapy Enhancing The Response to Radiotherapy Radiation therapy
- 38. COMBINATION OF RADIOTHERAPY WITH CHEMOTHERAPY
- 39. COMBINATION OF RADIATION WITH CHEMO • Delaney TF, Spiro IJ, Suit HD, et al. Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas. Int J Radiat Oncol Biol Phys 2003;56:1117-1127. • Mullen JT, Kobayashi W, Wang JJ, et al. Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas. Cancer 2012;118:3758-- 3765. 22180344] • O'Sullivan B, Bell RS. Has "MAID" made it in the management of high- risk soft-tissue sarcoma? Int J Radiat Oncol Biol Phys 2003;56:915-- 916. • kraybill WG, Harris J, Spiro IJ, et al. Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514. Cance,2010;116:4613-4621
- 45. Alternative Radiation Modalities Neutrons: produce recoil protons, alpha-particles, and heavier nuclear fragments. Consequently, their biologic properties differ from those of X-rays: reduced OER, little or no repair of sublethal damage, and less variation of sensitivity through the cell cycle. Protons radiobiologic properties similar to those of X-rays; Negative π-mesons and heavy ions were introduced with the hope of combining the radiobiologic advantages attributed to neutrons with the dose distribution advantage characteristic of protons.
- 47. Carbon ion therapy Schulz-Ertner D, Nikoghosyan A, Hof H, et al. Carbon ion radiotherapy of skull base chondrosarcomas. Int J Radiat Oncol Biol Phys 2007;67(1):171–177. Kamada T, Tsujii H, Tsuji H, et al. Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas. J Clin Oncol 2002;20(22):4466–4471 Weber DC, Rutz HP, Pedroni ES, et al. Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys 2005;63(2):401–409 Proton therapy
- 48. Recent results of particle therapy in sarcoma
- 49. Advancements in radiotherapy Target delineation Treatment Planning & Delivery Combination with chemotherapy Enhancing The Response to Radiotherapy Radiation therapy
- 50. ENHANCING THE EFFECT OF RT • radiation-induced DNA damage is postulated to be the main source of cell death, the toxicity of radiotherapy is also modulated by molecular pathways and tumor microenvironmental factors
- 54. Antiangioginesis • Phase II studies in STS suggested that sorafenib is most active against angiosarcomas and Leiomyosarcomas Canter RJ, Borys D, Olusanya A, et al. Phase I Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity. Ann Surg Oncol. 2014;21(5):1616–16 Meyer JM, Perlewitz KS, Hayden JB, et al. Phase I trial of preoperative chemoradiation plus sorafenib for high-risk extremity soft tissue. sarcomas with dynamic contrast-enhanced MRI correlates. Clin Cancer Res. 2013;19(24):6902–6911.
- 55. Theoretically, angiogenesis inhibitors may improve the efficacy of radiotherapy either by normalizing tumor blood vessels to improve tumor oxygenation and reduce intratumoral pressure or by increasing the rate of tumor apoptosis through direct inhibition of cellular survival signals
- 56. Future of sarcoma treatment ? •Surgical resection of sarcoma ! Modification! •Increasing the effect of radiation therapy by implantation of devices after the resection of tumoral mass •Implantation of chemotherapy releasing materials in place of resected tumor •Multimodality treatment should be included in treatment of sarcoma •Better trial design should be considered
- 57. what are we working
Editor's Notes
- Work flow of radiation therapy 3D conformal radiation therapy 1.Patient positioning and Immobilization2. Volumetric Data acquisition 3.Target Volume Delineation
- Advancements in RT subdivided To 4 major categories as shown in The slide
- in order To understand the Advancement in Target delineation It is good To have a review on Target volumes in radiotherapy GTV: Macroscopic extent of the tumor as defined by radiological and clinical investigationsGTV: Macroscopic extent of the tumor as defined by radiological and clinical investigations. CTV: The GTV together with the surrounding microscopic extension of the tumor constitutes the CTV. The CTV also includes the tumor bed of a R0 resection (no residual). ITV (ICRU 62): physiological movement of the tumor or organs. It is defined with respect to a internal reference – most commonly rigid bony skeleton. PTV: uncertainities in patient setup and beam adjustment.
- MRI images used for Planning have increased Accuracy of Tumor delineationandnowit is recommended to use MRI with gd Contrast Tone images for volume delineation 2. Consensus development by RTOG 3.Ctscan Atlas for Anatomy of extremity by RTOG
- MRI T1 plus contrast images (MRI with contrast is required). Fusion of MRI and CT is recommended to delineate the GTV for radiotherapy planning. Intravenous contrast is recommended, particularly for upper extremity lesions,
- Clinical Target Volume (CTV) for intermediate-to-high grade sarcoma ≥ 5 cm: GTV+ Microscopic involvement Typically CTV = GTV plus 3 cm margins in the longitudinal(proximal and distal) directions.no need to extend field out the compartment . radial margin from the lesion should be 1.5 cm including any portion of the tumor not confined by an intact fascial barrier, bone or skin surface
- Advancements in Treatment Planning and delivery Second major Area which along with Torget delineation had improved the outcomes of Sarcoma
- 2.in which modulated treatments are delivered as the radiation treatment machine rotates in an arc around the patient, have both improved conformality (the ability to sculpt, or conform, the dose closely to the target) and reduced treatment times
- The Evolution of RT from 1960 from first LINAC Standard collimators to multileatcollimators MLC 3DCRt Possible by it
- Intensity modulation by IMRT at Right you see area that is in Field of RT but receives lower Dose Than other Parts
- IN THIS SLIDE WE CAN SEE THAT AT THE RIGHT SIDE HOW IMRT can spare large dose to normal tissue While it can provide enough dose to tumor
- Recent Trial results showing superiority of IMRT Both in Tumor Control Local Control better also Toxicity Lower
- serial imaging of patient setup prior to treatment so that appropriate positional adjustments can be made beforehand
- serial imaging of patient setup prior to treatment so that appropriate positional adjustments can be made beforehand if imaging during a course of treatment demonstrates changes in patient anatomy (e.g., due to weight loss) or changes in tumor shape, a second radiation plan can be developed to adapt to these new data
- here you Can see the imaging device by Red arrow and the Therapy Head with blue Arrow
- IGRT and reduction of tat Toxicity
- example of different Planning's methods
- Likelike sculpting A sculptor
- Method of Radiotherapy which delivers high dose of RT per fraction Usually 6-30 Gry Per fraction
- Stereotactic BODY Radiation therapy
- Robotic cyber knife for SBRT
- Particle beams such as protons and heavier ions (carbon ions) have more favorable physical and biologic characteristics than photons, which make them appealing for clinical use
- The early recognition that X-rays could produce local tumor control in some patients and not in others led to the notion that other forms of ionizing radiations might be superior.
- Bragg peak release of energy
- published data for treatment of chordomas and chondrosarcomas of the skull base as well as for paraspinal and sacral bone tumors.
- Radiation (RT)-induced cellular toxicity occurs through the production of double-stranded DNA break, which promptly activates a series of DNA damage response (DDR) that may repair the damage and rescue the cell from death through apoptosis, senescence, necrosis, mitotic catastrophe, and autophagy. Beyond DDR, the cell’s ability to survive from RT is also modulated by other biological pathways related to A) angiogenesis, B) cell cycle regulation, C) survival signaling, and D) cancer-host immune interaction. The activity of these pathways may be modulated by different targeted agents that in combination with RT may enhance the cytotoxicity of RT in soft-tissue sarcomas. DDR = DNA damage response; RT = radiotherapy.
- Figure 2. Tumor angiogenesis is frequently found in soft-tissue sarcomas (STSs), leading to high levels of aberrant vasculatures, acute and chronic hypoxia, and increased interstitial pressures within the STS microenvironment. Treatment of STS with angiogenesis inhibitors may renormalize the tumor vasculature. This would in turn increase tumor tissue oxygenation and reduce the interstitial pressure, thus increasing the sensitivity of the cells to radiotherapy. RT = radiotherapy.
- and determined the maximum tolerated dose of sorafenib to be 400 mg daily when combined with chemoradiation (epirubicin/ifosfamide and 28Gy/8 fractions) or radiotherapy (50Gy/25 fractions).