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Radiotherapy in ca esophagus

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RT Planning Techniques In Ca Oesophagus 2D,3D,IMRT,IGRT

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Radiotherapy in ca esophagus

  1. 1. RT Planning Techniques In Ca Oesophagus 2D,3D,IMRT,IGRT Presented by:Dr. Isha Jaiswal Moderated by:Dr Shagun Misra Date:18th April 2017
  2. 2. Radiation • Patients can be treated by • EBRT  Conventional:2D  3 D CRT  IMRT  IGRT • Brachytherapy (Intra-luminal, ILBT)
  3. 3. SIMULATION Extent of the disease should be known based on Barium swallow CT Endoscopy PET Radiographic simulation used in 2D era CT simulation preferred now
  4. 4. Positioning & Immobilisation Patient Positioning: • Cervical and upper thoracic Esophagus: Supine, arms by the side • Middle and Lower third: • Supine with arms above their head if AP – PA portals are being planned • Prone position may be considered if posterior obliques are being included. Esophagus is pulled anteriorly and spinal cord can be spared. • During simulation, the patient is positioned, straightened, and immobilized on the simulation table. • For cervical and upper thoracic lesions, an immobilization mask is used • Palpable neck disease should be marked with a radiopaque wire.
  5. 5. Image acquisition:  Need of contrast: • Iv contrast helps in delineation of mediastinal and abdominal vascular nodal basins • Also allow to discern normal vasculature from other adjacent normal structures, and potential adenopathy • oral contrast helps in better visualization of the esophageal lumen and define the extent of mucosal irregularity. • scan of the entire area of interest with margin is obtained. • At minimum, 3- to 5-mm slices should be used, allowing accurate tumor characterization, as well as improved quality of digitally reconstructed radiographs.
  6. 6. Advancement In Simulation Techniques OBJECTIVES: • to reduce target motion with respiration • Reduce margins as used in free breathing techniques • assess tumoral motion, facilitating appropriate margin placement TECHNIQUES: • breath-hold techniques • abdominal compression devices • respiratory gating • 4DCT scan
  8. 8. GROSS TUMOR VOLUME • accurate definition of primary and nodal gross disease is paramount in radiation esophageal cancer planning. • Barium swallow, EGD, EUS, and CT, as well as PET scan when available is used for GTV definition
  9. 9. CLINICAL TARGET VOLUME • Accurate delineation of CTV is critical in the effective management of Ca oesophagus using RT • improves the probability of local control and reduce the risk of complications. • no consistent standards on the margins added to the GTV • most precise method for delineating a reasonable CTV is to combine information from all diagnostic test • It allows the detection and prediction of subclinical lesions based on tumour characteristics such as the pathological type, differentiation, T disease, length and lymph node status
  10. 10. Subclinical lesions in ca esophagus: • CTV of esophageal carcinoma should cover the primary tumor and all detected secondary lesions • secondary lesions frequently include direct invasion (DI), intra-mural metastasis (IMM), multicentric occurrent lesions (MOL), vascular invasion(VI), microscopic lymph node metastasis (LNMM) isolated tumor cells (ITC) perineural invasion (PNI)
  11. 11. Subclinical lesions and the primary CTV (CTVp) CTVp includes GTVp + the following: • Direct invasion (DI) • Intra mural metastasis (IMM) • Multicentric occurent lesion (MOL) • vascular invasion (VI) • Peri neural invasion (PNI)
  12. 12. VASCULAR INVASION • defined as the infiltration of tumor cells into lymph and blood vessels, as well as tumor embolus formation. • The incidence of VI in early-stage ESCC was 13.89% (15/108) [14] and 39.1% (143/366) in advanced disease [15]. • The incidence of VI in esophageal adenocarcinoma was 49.9% (229/459) [16]. • All of these studies demonstrated that VI is an important prognostic factor; however, none of these studies assessed the distance of VI sites from the primary tumor 14. Amano T et al. Subepithelial extension of squamouscell carcinoma in the esophagus: histopathological study using D2-40 immunostaining for 108 superficial carcinomas. Pathol Int. 2007;57:759-64. 15. Brücher BL et al. Lymphatic vessel invasion is an independentprognostic factor in patients with a primary resected tumor withesophageal squamous cell carcinoma. Cancer. 2001;92:2228-33. 16. von Rahden BH, et al. Lymphatic vessel invasion as aprognostic factor in patients with primary resected adenocarcinomas of theesophagogastric junction. J Clin Oncol. 2005;23:874-9. 17. Koenig AM, et al. Strong impact of micrometastatictumor cell load in patients with esophageal carcinoma. Ann Surg Oncol.2009;16:454-62.
  13. 13. CTV for lymph nodes (CTVn) CTVn includes GTVn + the following: • Microscopic lymph node metastatis • Isolated tumor cells: skip metastasis
  14. 14. CTV for lymph nodes (CTVn) For upper thoracic esophageal carcinomas: • superior prophylactic nodal irradiation volume should include the cervical paraesophageal and supraclavicular lymph nodes, and the superior margin should include the subcarinal lymph nodes. For lower thoracic esophageal carcinomas: • superior margin should include the subcarinal lymph nodes, and the inferior margin should include the left gastric lymph nodes and common hepatic artery lymph nodes. For middle thoracic esophageal carcinomas: • prophylactic treatment volume should be customized depending on the clinical circumstances; more thorough coverage of the mediastinal lymph nodes should be considered, especially in patients who are generally in good condition
  16. 16. ELECTIVE NODAL IRRADIATION • PROS • High risk of micrometastasis • Skip metastasis • CONS • Increased risk of nodal failure • Large RT fields • Increased toxicity • No improvement in OS • Additional diagnostic test needed to accurately define involved nodes • Chemotherapy reduces micrometastasis
  17. 17. •In patients treated with 3D-CRT for esophageal SCC, the omission of elective nodal irradiation was not associated with a significant amount of failure in lymph node regions not included in the planning target volume. •Local failure and distant metastases remained the predominant problems. •A longitudinal margin of 3 cm from the GTV to the CTV1 is probably enough
  18. 18. Basis of omitting ENI Recurrence was with in GTV
  19. 19. 1. Recurrene pattern(in-field) Predominant failure pattern in with esophageal SCC was local in-field or distant failures. Regional nodal recurrence (out-of-field) was infrequent (8%) in the absence of elective node irradiation. 2. Biological behavior of the disease Esophageal cancer is characterized by a high rate of nodal involvement and its spread pattern is not always predictable. Also, skip node metastases are frequently observed. Thus the biological behavior of this disease makes it difficult to define in advance the extent of coverage of elective nodal irradiation. 3. Toxicities If distant lymph node areas were irradiated prophylactically, patients would then experience more severe radiation complications and have a poorer treatment tolerance.
  20. 20. In CRT for esophageal SqCC, ENI was effective for preventing regional nodal failure. TheUPPER THORACIC esophageal carcinomas had significantly more local recurrences than the middle or lower thoracic sites.
  21. 21. • Retrospective analysis • 79 patients with locally advanced ESCC underwent 3D-CRTor IMRT using IFI or elective nodal irradiation (ENI) according to the target volume. • The patterns of failure were defined as local/regional,in-field, out-of-field regional lymph node (LN) and distant failure. • With a median follow-up of 32.0 months, failures were observed in 66 (83.6%) patients.
  22. 22. Target definition • delineation of clinical target volume (CTV) was based on CT, barium esophagogram, and endoscopic examination. • Esophageal wall thickness of more than 0.5cm and • positive LNs were included in the gross tumor volume • (GTV) • LNs that were well vascularized, measuredmore than 8 mm in the short axes, and showed central necrosis or extracapsular extension in CT were considered malignant • The total dose of GTV was 58-66 Gy/29-33F. At the same time, the volume of CTV was appropriately adjusted on the basis of the human anatomic structure so that the maximum dosage in the spinal cord did not exceed 45 Gy.
  23. 23. ENI group • first clinical target volumes (CTV1) encompassed the primary tumor, the malignantLNs, and 3 cm proximal and distal margins; a 0.5-0.8 cm radial margin was added to the GTV. • The first planning target volumes (PTV1) encompassed 1 cm proximal and distal margins, 0.5 cm radial margin on the basis of CTV1, with a total dose of 54-60 Gy/29-33F. • The second CTV (CTV2) encompassed only 3-cm proximal and distal margins; a 0.5 cm radial margin was added to the GTV, and uninvolved regional LNs were encompassed in the CTV2 (Figure 1 A). • The second PTV (PTV2) encompassed 1-cm proximal and distal margins, 0.5 cm radial margin on the basis of CTV2, with a total dose of 50-54 Gy/29-33F.
  24. 24. IFI group • CTV only encompassed 3 cm proximal and distal margins and 0.5-0.8 cm radial margin on the basis of GTV. • Uninvolved regional LNs were not encompassed in the CTV • At the same time, the volume of CTV was appropriately adjusted on the basis of the human anatomic structure so that the maximum dosage in the spinal cord did not exceed 45Gy. • PTV encompassed 1 cm proximal and distal margins,0.5 cm radial margin on the basis of CTV, with a total dose of 50-56Gy/29-33F.
  25. 25. Pattern of failure • local/regional failure IFRT vs ENI (52.8 vs 55.8%) • distant failure (27.8 vs 32.6%) was lower in the ENI compared with the IFI group in 3 years, with no statistical significance (p=0.526 and 0.180, respectively). • The cumulative incidence of regional LN failure was 25.6% for the IFI group compared with 19.4% for the ENI group (p=0.215).
  26. 26. No global consensus on whether or not ENI should be performed.
  28. 28. ENLARGED RADIATION FIELDS • Enlarged fields (e.g., whole-esophagus or whole-mediastinum) have been used in past to to treat secondary lesions located far from the primary tumor.
  29. 29. Treatment Planning 2D Era – RTOG 8501 • RTOG 8501 compared CRT (50 Gy) to RT alone (64Gy) • Mid/Lower Esophageal Cancers • Initial Field was AP/PA to 30 Gy/15# • Extended from SCV region to GE junction • Omitted SCV nodes in lower esophageal tumors • Boost field was tumor + 5 cm sup/inf with a 3 field or opposed obliques to dose of 20 Gy in 10 fractions • Advantages • AP/PA limited lung dose • Replacing PA with oblique fields limited spinal cord dose • Disadvantages • For distal tumors, significant cardiac volume • Entire extent of the esophagus treated
  30. 30. ENLARGED RADIATION FIELDS RTOG 94-05 trial: • 5 cm margin beyond superior and Inferior extent of the primary tumor. lateral, anterior, and posterior borders of the field were ≥ 2 cm beyond the borders of the primary tumor • However, these studies did not demonstrate improved local control or survival despite causing intolerable toxicities • Rarely, individual lesions may be located distant from the primary tumor, therefore empirical irradiation of whole esophagus or mediastinum is likely unnecessary.
  31. 31. CONCLUSION: • A 3 cm margin proximally and distally would cover microscopic disease in 94% of all SCCs. • For GE junction tumours, a 3cm margin proximally and 5cm distally would allow similar coverage. • Most contemporary radiation trials used margins of 3 to 5 cm cranially and caudally on the GTV, along with a 2-2.5cm radial margin. LIMITATION: • investigators did not note the occurrence of each secondary lesion. • Small sample size
  32. 32. LIMITED FIELD TECHNIQUES • Most contemporary radiation trials used margins of 3 to 5 cm cranially and caudally on the GTV, along with an approximate 2-cm radial margin • With disease located at or above the carina (or middle/upper one-third of the esophagus), fields inclusive of the supraclavicular lymph node basins, whereas celiac axis nodal basin coverage was recommended for disease of the distal esophagus.
  33. 33. 2D RADIATIONTECHNIQUE • Field border defined on basis of anatomical landmarks
  34. 34. FIELD DESIGN: CERVICAL ESOPHAGUS • Challenging due to • changing contour from the neck to the thoracic inlet • Limited dose constrains of spinal cord
  35. 35. Cervical Esophagus FIELD DESIGN • lateral parallel opposed or oblique portals to the primary tumor and a single anterior field for the supraclavicular and superior mediastinal nodes • 2 anterior obliques and 1 posterior or 2 posterior obliques and 1 anterior field • AP – PA followed by opposed oblique pair. • 4 field box with soft tissue compensators followed by obliques. TARGET • Lesions in the upper cervical are treated from the laryngopharynx to the carina, depending on extent of disease. • Supraclavicular and superior mediastinal nodes are irradiated electively • Superior Border: C7 • Inferior Border: T4 (carina) • 2 cm lateral margins.
  36. 36. EBRT – Middle and Lower Third • Superior Border: 5 cm proximal to superior extent of disease. • Inferior Border: • Middle third - GEJ as visualised by Barium swallow • Lower third - Coeliac plexus (L1) to be included. • AP - PA followed by 1 Anterior and 2 Posterior oblique pairs • 4 Field: AP - PA & opposed laterals – for mid 1/3rd lesions. • AP - PA to deliver 36-44 Gy followed by posterior obliques to reach the full dose.
  37. 37. Treatment Planning – 3D Era Definitions • GTV – Gross Tumor Volume ( Tumor + grossly enlarged LN) • CTV – Clinical Target Volume – Includes microscopic disease • PTV – Planning Target Volume – accounts for setup error and intra-fraction motion
  38. 38. 3D CONFORMAL RT Advantages over 2D planning 3dimensional visualisation of target and OARs 3 dimensional reconstruction Creation of a “beam’s-eye” view of varying fields dose–volume histogram data can also be generated allowing improved conformality around target structures and improvements in normal-tissue sparing
  39. 39. Treatment Planning • 3D Treatment Planning (CT- based) • Start AP/PA • Treat to cord tolerance • 39.6 – 41.4 Gy • Then off-cord • 2 field or 3 field • AP/RAO/LAO for cervical/upper thoracic lesions • AP/RPO/LPO for lower lesions • RAO/LPO for distal esophagus lesions • Treat to total 50.4 – 54 Gy
  40. 40. 3D Planning Treatment Plan •3D-CRT •AP/PA to 36 Gy followed by 3-field boost to 45 Gy •Additional cone down (Boost PTV) to 50.4 Gy •Concurrent chemotherapy with carbo/taxol
  41. 41. Treatment Planning - Evaluation • Dose Volume Histograms • CT data allows to quantify dose received by tumor as well as organs at risk
  42. 42. Typical Radiation Field for Cervical or Upper Esophagus radiation
  43. 43. Typical Radiation Field for Middle Esophagus
  44. 44. Typical Radiation Field for Lower Esophagus
  45. 45. Typical Radiation Field for Lower Esophagus
  46. 46. Radiation Dose Guidelines PreOperative: 41.1 – 50.4Gy (1.8-2.0/day) PostOperative: 45 – 50.4Gy (1.8-2.0/day) Definitive: 50 – 50.4Gy (1.8-2.0/day) higher dose (60-66Gy) may be considered in cervical esophagus where surgery is not planned, but there is little evidence of benefit > 50.4Gy
  47. 47. IMRT
  48. 48. IMRT • Intensity Modulated Radiation Therapy • Clinical Rationale • Tumors arise from/within normal tissues • Normal tissues often limit the radiation doses that can be safely prescribed and delivered • Organs at risk in close proximity may have limited radiation tolerance • IMRT allows for the reduction of radiation dose delivered to normal tissue • Ability to maintain a high dose to the tumor
  49. 49. IMRT - Benefits • Normal Tissue sparing • Reduced late toxicities • Dose escalation • Dose painting • Ability to increase dose to areas of higher tumor burden • Re-irradiation
  50. 50. IMRT - Basics  Ability to break a large treatment port into multiple smaller subsets (field segments or pencil beams) • Through utilization of MLCs • A computer system to enable such field fragmentation  inverse treatment planning  Prescription dose and dose constraints are programmed into the radiation-planning software for generation of the radiation plan
  51. 51. IMRT in Esophageal Cancer • With the exception of a small series that used IMRT to treat patients with cervical esophageal primaries, most data regarding IMRT for esophageal malignancies has been limited to dosimetric analyses • found superior to 3dcrt in generating more conformal and homogeneous target coverage • Reducing dose to Spinal cord, Heart Lung
  52. 52. 3 D vs. IMRT
  53. 53. IMRT
  54. 54. IMRT
  55. 55. IMRT