Radiotherapy in ca esophagus

Isha Jaiswal
Isha JaiswalM.D RADIATION ONCOLOGY at Dr. Ram Manohar Lohia Institute Of Medical Sciences, Lucknow em Dr. Ram Manohar Lohia Institute Of Medical Sciences, Lucknow
RT Planning Techniques
In Ca Oesophagus
2D,3D,IMRT,IGRT
Presented by:Dr. Isha Jaiswal
Moderated by:Dr Shagun Misra
Date:18th April 2017
Radiation
• Patients can be treated by
• EBRT
 Conventional:2D
 3 D CRT
 IMRT
 IGRT
• Brachytherapy (Intra-luminal, ILBT)
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
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.
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.
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
TREATMENT PLANNING
TARGET DESIGN
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
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
Radiotherapy in ca esophagus
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)
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)
Radiotherapy in ca esophagus
Radiotherapy in ca esophagus
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.
CTV for lymph nodes (CTVn)
CTVn includes GTVn + the following:
• Microscopic lymph node metastatis
• Isolated tumor cells: skip metastasis
Radiotherapy in ca esophagus
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
ELECTIVE NODAL
IRRADIATION VS INVOLVED
FIELD RT
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
•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
Basis of omitting ENI
Recurrence was with in GTV
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.
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.
• 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.
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.
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.
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.
Radiotherapy in ca esophagus
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).
Radiotherapy in ca esophagus
No global consensus on whether or not ENI
should be performed.
RADIATION FIELD DESIGN
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.
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
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.
Radiotherapy in ca esophagus
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
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.
2D RADIATIONTECHNIQUE
• Field border defined on basis of anatomical
landmarks
FIELD DESIGN: CERVICAL
ESOPHAGUS
• Challenging due to
• changing contour from the neck to the thoracic inlet
• Limited dose constrains of spinal cord
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.
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.
Radiotherapy in ca esophagus
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
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
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
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
Treatment Planning - Evaluation
• Dose Volume Histograms
• CT data allows to quantify dose received by tumor as
well as organs at risk
Typical Radiation Field for Cervical or
Upper Esophagus
radiation
Typical Radiation Field for Middle
Esophagus
Typical Radiation Field for Lower Esophagus
Typical Radiation Field for Lower
Esophagus
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
IMRT
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
IMRT - Benefits
• Normal Tissue sparing
• Reduced late toxicities
• Dose escalation
• Dose painting
• Ability to increase dose to areas of higher tumor burden
• Re-irradiation
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
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
3 D vs. IMRT
IMRT
IMRT
IMRT
Radiotherapy in ca esophagus
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Radiotherapy in ca esophagus

  • 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. Radiation • Patients can be treated by • EBRT  Conventional:2D  3 D CRT  IMRT  IGRT • Brachytherapy (Intra-luminal, ILBT)
  • 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. 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. 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. 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. 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. 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
  • 11. 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)
  • 12. 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)
  • 15. 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.
  • 16. CTV for lymph nodes (CTVn) CTVn includes GTVn + the following: • Microscopic lymph node metastatis • Isolated tumor cells: skip metastasis
  • 18. 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
  • 19. ELECTIVE NODAL IRRADIATION VS INVOLVED FIELD RT
  • 20. 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
  • 21. •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
  • 22. Basis of omitting ENI Recurrence was with in GTV
  • 23. 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.
  • 24. 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.
  • 25. • 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.
  • 26. 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.
  • 27. 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.
  • 28. 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.
  • 30. 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).
  • 32. No global consensus on whether or not ENI should be performed.
  • 34. 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.
  • 35. 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
  • 36. 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.
  • 38. 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
  • 39. 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.
  • 40. 2D RADIATIONTECHNIQUE • Field border defined on basis of anatomical landmarks
  • 41. FIELD DESIGN: CERVICAL ESOPHAGUS • Challenging due to • changing contour from the neck to the thoracic inlet • Limited dose constrains of spinal cord
  • 42. 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.
  • 43. 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.
  • 45. 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
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. Treatment Planning - Evaluation • Dose Volume Histograms • CT data allows to quantify dose received by tumor as well as organs at risk
  • 50. Typical Radiation Field for Cervical or Upper Esophagus radiation
  • 51. Typical Radiation Field for Middle Esophagus
  • 52. Typical Radiation Field for Lower Esophagus
  • 53. Typical Radiation Field for Lower Esophagus
  • 54. 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
  • 55. IMRT
  • 56. 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
  • 57. IMRT - Benefits • Normal Tissue sparing • Reduced late toxicities • Dose escalation • Dose painting • Ability to increase dose to areas of higher tumor burden • Re-irradiation
  • 58. 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
  • 59. 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
  • 60. 3 D vs. IMRT
  • 61. IMRT
  • 62. IMRT
  • 63. IMRT

Notas do Editor

  1. The use of respiratory gating or breath-hold techniques may help to reduce target motion with respiration and, therefore, avoid normal-tissue irradiation associated with larger margins used in free-breathing approaches, particularly for lower esophageal cancers. Additional techniques to minimize physiologic motion include. Four-dimensional CT scan may be appropriate to assess tumoral motion, facilitating appropriate margin placement on the target volumes, particularly in lower esophageal tumors and/or disease involving the stomach. Treatment Planning
  2. barium swallow (when available), EGD, EUS, and CT, as well as PET scan.
  3. Lam KY, Ma LT, Wong J. Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning. J Clin Pathol. 1996;49:124-9. 14. Amano T, Matsumoto T, Hayashi T, et al. Subepithelial extension of squamous cell carcinoma in the esophagus: histopathological study using D2-40 immunostaining for 108 superficial carcinomas. Pathol Int. 2007;57:759-64. 15. Brücher BL, Stein HJ, Werner M, et al. Lymphatic vessel invasion is an independent prognostic factor in patients with a primary resected tumor with esophageal squamous cell carcinoma. Cancer. 2001;92:2228-33. 16. von Rahden BH, Stein HJ, Feith M, et al. Lymphatic vessel invasion as a prognostic factor in patients with primary resected adenocarcinomas of the esophagogastric junction. J Clin Oncol. 2005;23:874-9. 17. Koenig AM, Prenzel KL, Bogoevski D, et al. Strong impact of micrometastatic tumor cell load in patients with esophageal carcinoma. Ann Surg Oncol. 2009;16:454-62.
  4. For cervical primaries, patients are placed supine. Various field designs are possible and their choice depends on the geometry of the primary tumor in relation to the spinal cord. The ideal design is a three-field technique (two anterior obliques and a posterior). However, since the primary tumor is rarely limited to the midline, the most common approach is anteroposterior (AP)/posteroanterior (PA) to 39.6 to 41.4 Gy (Fig. 36-3) followed by a left or right opposed oblique pair with photons to 50.4 Gy (Fig. 36-4A-C). Since this technique will exclude the ipsilateral supraclavicular fossa, a separate electron field is added (commonly to a depth of 2 to 3 cm depending on the patient's anatomy) thereby bringing the total dose to 50.4 Gy. For cervical primaries, patients are placed supine. Various field designs are possible and their choice depends on the geometry of the primary tumor in relation to the spinal cord. The ideal design is a three-field technique (two anterior obliques and a posterior). However, since the primary tumor is rarely limited to the midline, the most common approach is anteroposterior (AP)/posteroanterior (PA) to 39.6 to 41.4 Gy (Fig. 36-3) followed by a left or right opposed oblique pair with photons to 50.4 Gy (Fig. 36-4A-C). Since this technique will exclude the ipsilateral supraclavicular fossa, a separate electron field is added (commonly to a depth of 2 to 3 cm depending on the patient's anatomy) thereby bringing the total dose to 50.4 Gy.