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1  sur  74
Role of radiation in carcinoma
rectum and colon
Dr Bharti Devnani
Moderator:- Dr Manoj K.Sharma
RT for rectal cancer was first introduced in the 1980s, in
an attempt to decrease rates of local recurrence in
patients with locally advanced rectal cancer.
One of the first RCTs to show decrease in local
recurrence with the use of adjuvant therapy was
published in 1985 by the Gastrointestinal Tumor Study
Group (USA)
In the United States, the first official recommendation
for the use of adjuvant chemoradiation in patients with
rectal cancer came from the National Institutes of
Health (NIH) consensus statement, published in 1990.
Set the standard of care for patients with stage II and III.
Although postoperative regimens were being
optimized in 1990s within United States, around
the same period investigators in Europe were
exploring the potential benefits of treatment
given in the preoperative setting (Neoadjuvant
RT).
Two different regimens of neoadjuvant RT were
being assessed:
long course RT, used mainly in the United
States; and short course RT, used mainly in
Europe
Benefit with addition of preop
RT to Surgery
Pre-op RT v/s chemoradiation
Preop CTRT v/s postop CTRT
German Rectal Cancer Study
N Eng J Med 351;17 october 21, 2004
T3/T4/N+
N=421
Preop CT+RT
50.4 Gy/28# with CI 5-
FU1000mg/m2(D1-D5) in 1st
&5th wk foll by Sx at 6 wks and
4 cycles of adjuvant chemo
N=402
Post op setting
–additional
boost of 5.4
Gy
Local recurrence 6%
v/s 13% (p=0.006)
NO OS benefit
Rate of sphincter preservation -39% v/s 19%-more than
double
Acute and long term toxicities are less
Arm No of
pts
Any grade
3-4 acute
toxicity
Grade 3-4
acute
diarrhea
Any grade
3-4 long
term
toxicity
Stricture at
anastomotic
site
Preop CT
RT
405 27% 12% 14% 4%
Postop CT
RT
394 40% 18% 24% 12%
‘p’ value 0.001 0.04 0.001 0.003
Preop CTRT improved local control with reduced toxicity
and more sphincter preservation rate
No OS benefitBenefit in local control persisted at 11 yrs
Update of german trial
ADVANTAGES OF PRE-OP
CHEMORADIATION
1.Tumor tissue is better oxygenated so irradiation
is more effective
2.Downstaging of the tumor leads to:-
More curative surgery
Conversion of APR to sphinctor preservation
(rate is doubled 39% v/s 19% in german study )
3.Local recurrence decreased
(6% v/s 13 % with a ‘p’ value of 0.006)
4. Compliance is better (Better tolerated)
With postop RT the soft tissues of the perineum
are at risk, for involvement after an APR because
of surgical manipulation and, need to be irradiated
with acute skin toxicity.
With postop RT, normal bowel is moved into the
pelvis for the anastomosis after a LAR & is
irradiated leading to late toxicity.
In the preoperative setting much of the
irradiated bowel is removed with the surgical
specimen and therefore is not at risk for
producing late bowel injury.
Avoidance of radiation to the neorectum.
Reduction in the risk of tumor seeding during
surgery.
Avoiding Tt. delays due to prolonged post-op
healing.
Higher pCR rates
Disadvantages
 Overtreatment of early stage tumors
(18 % in german study)
 Delay in surgery
 Wound healing problem
Indications of RT
Preoperative RT
For stage II-III resectable disease
Definitive treatment
Unresectable/unfit for surgery
Small rectal cancer
Palliative radiation
Advanced disease
For metastatic sites(liver SBRT etc)
IORT
Incomplete resection
Residual/recurrent disease
Preoperative setting
Preop CT RT for
Stage II –III disease
Stage II (T3 and
T4 disease)
&
Stage III that is
(any T with Nodal
positivity)
Postop Radiation
Synchronus metastasis
Techniques of Radiation
RT portals
1. Whole pelvic field:
PA/AP
 Lateral border - 1.5 cm
lateral to the widest bony
margin of the true pelvic
walls
 Distal border: 3 cm below
the primary tumor or at the
inferior aspect of obturator
foramina, whichever is the
most inferior
 Superior border: L5-S1
junction
RT portals
B: Lateral
 Posterior border: 1 to 1.5 cm
behind the anterior bony sacral
margin
 Anterior border:
1. T3 disease: post margin of
the symphysis pubis(to
treat only the internal iliac
nodes)
2. T4 disease: ant margin of
the symphysis pubis (to
include the external iliac
nodes)
T3
T4
RT portals
3. After an abdominoperineal
resection:
Wire the perineal scar
and create a 1.5 cm
margin beyond the wire
fields.
Bolus the perineal scar
every other day to bring
the dose to 100%
Methods to Decrease Radiation
Toxicity
RT technique
Physical maneuvers
Sequencing of RT and surgery
Surgical maneuvers in patients treated
postoperatively
Pharmacological approaches and radio
protectors
RT technique
 High-energy (>6 MV) linear accelerators.
 All fields should be treated each day.
 Shaped blocks and wedges on the lateral fields.
 A wire at the perineal scar after APR help to
guide field design.
 Small bowel contrast used to help Shielding of
small bowel.
 Rectal contrast :-Barium sulfate is injected with a
Foley catheter.
 Bladder protocol
 Computerised radiation dosimetery
 Multiple-field technique (3 or 4 field )
 3 field (PA + lat)rather than 4 field is preferred
in:-
 In males if the genitalia are in the treatment
field
 Colostomy is present
 For perineal scar coverage separate perineal
field should not be used(should be included in
the pelvic radiation field)
Physical Maneuvers
Prone position with abdominal wall
compression and bladder distension
Treatment in the prone position without
abdominal wall compression was not
consistently effective in displacing small bowel
and in some patients, most commonly
obese, the volume of small bowel increased.
Prone position with
Abd wall compression
and bladder distension
Immobilization molds
(belly boards)
Shanahan and colleagues reported that the
combination of the prone position and
immobilization molds decreased the mean
small-bowel volume in the radiation field by
66% compared with patients treated in the
supine position without the immobilization mold.
Sequencing of RT and surgery
Preop CTRT preferred :-
 Less acute and chronic toxicities
 Mobile small bowel
 Coverage of perinium not required
 Strictures at the anastomotic site reduced
Surgical maneuvers in patients
treated postoperatively
 Placing surgical clips
 Placement of an absorbable Dexon or Vicryl
mesh temporarily remove the small bowel from
the pelvis.
 Other methods:-
 Construction of omental pedical flap
 Small bowel displacement prosthesis
reconstruction of pelvic floor
 Retroversion of uterus
Pharmacological approaches
and radio protectors
 Sucralfate enemas
 Olsalazine
 Mesalazine
All of these trials
have been negative
Final Results of a Randomized Phase III Trial of
Chemoradiation treatment Amifostine in Patients with
Colorectal Cancer: Clinical Radiation Oncology Hellenic
Group
By Antonadou et al
Amifostine significantly reduced the incidence of grade 2
gastrointenstinal toxicity. There was no evidence of
compromised treatment efficacy.
Advantages with conformal
techniques
 Ability to plan and localise the target and
normal tissues.
 Less toxicites
 Obtaining DVH
 More conformal plans
Target delineation as per RTOG
contouring guidelines
Sites of recurrence
Short course v/s long course RT
Results of Polish trial
ARM SC LC
pCR(%) 1 16
Radial margin
positivity(%)
13 4
Sphinctor preservation(%) 58 NS 61
Early radiation toxicity 3 18
LC DFS & late toxicity NS
326 patients
radomaly
assigned
Long course
RT
50.4 Gy @ 1.8 in 5.5 wks with
CI 5-FU foll by Sx at 4-6 wks &
4 cycles adj CT
Short course
RT
RT 5x5 in 1 wk foll by early Sx & 6 cycle
adj CT
No difference in OS
Locoregional recurrence
No stastically significant
difference but
• Favouring long course
•pCR better with long course
•Long course better for distal
tumor (12.5% v/s 0%)
Endocavitory Radiation
(Papillon technique)
Papillon is the name of the
French professor
from Lyon who popularised this
technique.
Selection criteria
Early noninvasive tumors
For more advanced tumors (T2,T3) used in conjunction
with BT or XRT
G1-G2 tumors
Without deep ulceration
With in 10 cm from dentate line
Tumors with diameter <3 cm (size of the proctoscope is
3 cm)
Method
 Anus is dilated
 4-cm proctoscope
is introduced.
 low-energy x-ray
(50-kV x-rays) unit is placed
through the scope against
the tumor.
 Delivered at 30 Gy per fraction in three or four fractions
over 1 month.
Local control rates of 76% can be achieved at 10 years after
treatment with this technique
Lyon technique
Créteil technique
Template technique
Intra-operative Radiotherapy (IORT)
IOERT HDR-BT
Intra-operative Radiotherapy (IORT)
Tumor site accessible to IORT applicator
Locally advanced tumor
Recurrent tumor
Tumor not resected/Gross residual tumor
Positive surgical margin
Critical structures (dose limiting) are excluded
Advantages with IORT
Radiation can be delivered at the time of
surgery to the site with highest risk of
local failure
Normal tissue sparing
Very useful in recurrent setting
Dose
Ro resection:-7.5-10 Gy
R1 resection:-10-12.5 Gy
R2 resection:-15-20 Gy
Chances of local failure decreased
In margin negative cases from 15% 11%
After R1 resection 83% 32%
After R2 resection 83% 43%
Side effects and managment
Early complications
 Diarrhea
 Increased bowel frequency
 Dysuria
 Acute proctitis
 Malabsorption of fat,carbohydrate,protein and
bile salts
Mechanism:- depletion of actively dividing cells
Late complications
Small bowel obstruction
Bleeding
Persistent diarrhea
Scrotal/perineal tenderness
Urinary incontinence
Stricture
Second cancer
Role of RT in colon cancer
Treatment recommendations should be made on a
case-by-case basis with existing data in setting of an
informed consent.
Adj tumor bed RT with concurrent 5-FU based
chemo should be considered for pts with tumors
(a) invading adjoining structures
(b) those complicated by perforation or fistula
(c) Incomplete resection is performed
THANK YOU

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Role of radiation in carcinoma rectum and colon

  • 1. Role of radiation in carcinoma rectum and colon Dr Bharti Devnani Moderator:- Dr Manoj K.Sharma
  • 2. RT for rectal cancer was first introduced in the 1980s, in an attempt to decrease rates of local recurrence in patients with locally advanced rectal cancer. One of the first RCTs to show decrease in local recurrence with the use of adjuvant therapy was published in 1985 by the Gastrointestinal Tumor Study Group (USA) In the United States, the first official recommendation for the use of adjuvant chemoradiation in patients with rectal cancer came from the National Institutes of Health (NIH) consensus statement, published in 1990. Set the standard of care for patients with stage II and III.
  • 3. Although postoperative regimens were being optimized in 1990s within United States, around the same period investigators in Europe were exploring the potential benefits of treatment given in the preoperative setting (Neoadjuvant RT). Two different regimens of neoadjuvant RT were being assessed: long course RT, used mainly in the United States; and short course RT, used mainly in Europe
  • 4. Benefit with addition of preop RT to Surgery
  • 5.
  • 6.
  • 7. Pre-op RT v/s chemoradiation
  • 8.
  • 9.
  • 10. Preop CTRT v/s postop CTRT
  • 11. German Rectal Cancer Study N Eng J Med 351;17 october 21, 2004
  • 12. T3/T4/N+ N=421 Preop CT+RT 50.4 Gy/28# with CI 5- FU1000mg/m2(D1-D5) in 1st &5th wk foll by Sx at 6 wks and 4 cycles of adjuvant chemo N=402 Post op setting –additional boost of 5.4 Gy
  • 13. Local recurrence 6% v/s 13% (p=0.006) NO OS benefit
  • 14. Rate of sphincter preservation -39% v/s 19%-more than double
  • 15. Acute and long term toxicities are less Arm No of pts Any grade 3-4 acute toxicity Grade 3-4 acute diarrhea Any grade 3-4 long term toxicity Stricture at anastomotic site Preop CT RT 405 27% 12% 14% 4% Postop CT RT 394 40% 18% 24% 12% ‘p’ value 0.001 0.04 0.001 0.003 Preop CTRT improved local control with reduced toxicity and more sphincter preservation rate
  • 16. No OS benefitBenefit in local control persisted at 11 yrs Update of german trial
  • 18. 1.Tumor tissue is better oxygenated so irradiation is more effective 2.Downstaging of the tumor leads to:- More curative surgery Conversion of APR to sphinctor preservation (rate is doubled 39% v/s 19% in german study ) 3.Local recurrence decreased (6% v/s 13 % with a ‘p’ value of 0.006) 4. Compliance is better (Better tolerated)
  • 19. With postop RT the soft tissues of the perineum are at risk, for involvement after an APR because of surgical manipulation and, need to be irradiated with acute skin toxicity.
  • 20. With postop RT, normal bowel is moved into the pelvis for the anastomosis after a LAR & is irradiated leading to late toxicity. In the preoperative setting much of the irradiated bowel is removed with the surgical specimen and therefore is not at risk for producing late bowel injury. Avoidance of radiation to the neorectum.
  • 21. Reduction in the risk of tumor seeding during surgery. Avoiding Tt. delays due to prolonged post-op healing. Higher pCR rates
  • 22. Disadvantages  Overtreatment of early stage tumors (18 % in german study)  Delay in surgery  Wound healing problem
  • 24. Preoperative RT For stage II-III resectable disease Definitive treatment Unresectable/unfit for surgery Small rectal cancer Palliative radiation Advanced disease For metastatic sites(liver SBRT etc) IORT Incomplete resection Residual/recurrent disease
  • 25. Preoperative setting Preop CT RT for Stage II –III disease Stage II (T3 and T4 disease) & Stage III that is (any T with Nodal positivity)
  • 29. RT portals 1. Whole pelvic field: PA/AP  Lateral border - 1.5 cm lateral to the widest bony margin of the true pelvic walls  Distal border: 3 cm below the primary tumor or at the inferior aspect of obturator foramina, whichever is the most inferior  Superior border: L5-S1 junction
  • 30. RT portals B: Lateral  Posterior border: 1 to 1.5 cm behind the anterior bony sacral margin  Anterior border: 1. T3 disease: post margin of the symphysis pubis(to treat only the internal iliac nodes) 2. T4 disease: ant margin of the symphysis pubis (to include the external iliac nodes) T3 T4
  • 31. RT portals 3. After an abdominoperineal resection: Wire the perineal scar and create a 1.5 cm margin beyond the wire fields. Bolus the perineal scar every other day to bring the dose to 100%
  • 32. Methods to Decrease Radiation Toxicity RT technique Physical maneuvers Sequencing of RT and surgery Surgical maneuvers in patients treated postoperatively Pharmacological approaches and radio protectors
  • 34.  High-energy (>6 MV) linear accelerators.  All fields should be treated each day.  Shaped blocks and wedges on the lateral fields.  A wire at the perineal scar after APR help to guide field design.  Small bowel contrast used to help Shielding of small bowel.  Rectal contrast :-Barium sulfate is injected with a Foley catheter.  Bladder protocol  Computerised radiation dosimetery
  • 35.  Multiple-field technique (3 or 4 field )  3 field (PA + lat)rather than 4 field is preferred in:-  In males if the genitalia are in the treatment field  Colostomy is present  For perineal scar coverage separate perineal field should not be used(should be included in the pelvic radiation field)
  • 37. Prone position with abdominal wall compression and bladder distension Treatment in the prone position without abdominal wall compression was not consistently effective in displacing small bowel and in some patients, most commonly obese, the volume of small bowel increased.
  • 38. Prone position with Abd wall compression and bladder distension Immobilization molds (belly boards) Shanahan and colleagues reported that the combination of the prone position and immobilization molds decreased the mean small-bowel volume in the radiation field by 66% compared with patients treated in the supine position without the immobilization mold.
  • 39. Sequencing of RT and surgery
  • 40. Preop CTRT preferred :-  Less acute and chronic toxicities  Mobile small bowel  Coverage of perinium not required  Strictures at the anastomotic site reduced
  • 41. Surgical maneuvers in patients treated postoperatively
  • 42.  Placing surgical clips  Placement of an absorbable Dexon or Vicryl mesh temporarily remove the small bowel from the pelvis.  Other methods:-  Construction of omental pedical flap  Small bowel displacement prosthesis reconstruction of pelvic floor  Retroversion of uterus
  • 44.  Sucralfate enemas  Olsalazine  Mesalazine All of these trials have been negative Final Results of a Randomized Phase III Trial of Chemoradiation treatment Amifostine in Patients with Colorectal Cancer: Clinical Radiation Oncology Hellenic Group By Antonadou et al Amifostine significantly reduced the incidence of grade 2 gastrointenstinal toxicity. There was no evidence of compromised treatment efficacy.
  • 46.  Ability to plan and localise the target and normal tissues.  Less toxicites  Obtaining DVH  More conformal plans
  • 47. Target delineation as per RTOG contouring guidelines
  • 49.
  • 50.
  • 51.
  • 52.
  • 53.
  • 54. Short course v/s long course RT
  • 55.
  • 56. Results of Polish trial ARM SC LC pCR(%) 1 16 Radial margin positivity(%) 13 4 Sphinctor preservation(%) 58 NS 61 Early radiation toxicity 3 18 LC DFS & late toxicity NS
  • 57. 326 patients radomaly assigned Long course RT 50.4 Gy @ 1.8 in 5.5 wks with CI 5-FU foll by Sx at 4-6 wks & 4 cycles adj CT Short course RT RT 5x5 in 1 wk foll by early Sx & 6 cycle adj CT
  • 58. No difference in OS Locoregional recurrence No stastically significant difference but • Favouring long course •pCR better with long course •Long course better for distal tumor (12.5% v/s 0%)
  • 59. Endocavitory Radiation (Papillon technique) Papillon is the name of the French professor from Lyon who popularised this technique.
  • 60. Selection criteria Early noninvasive tumors For more advanced tumors (T2,T3) used in conjunction with BT or XRT G1-G2 tumors Without deep ulceration With in 10 cm from dentate line Tumors with diameter <3 cm (size of the proctoscope is 3 cm)
  • 61. Method  Anus is dilated  4-cm proctoscope is introduced.  low-energy x-ray (50-kV x-rays) unit is placed through the scope against the tumor.  Delivered at 30 Gy per fraction in three or four fractions over 1 month.
  • 62. Local control rates of 76% can be achieved at 10 years after treatment with this technique
  • 65. Intra-operative Radiotherapy (IORT) Tumor site accessible to IORT applicator Locally advanced tumor Recurrent tumor Tumor not resected/Gross residual tumor Positive surgical margin Critical structures (dose limiting) are excluded
  • 66. Advantages with IORT Radiation can be delivered at the time of surgery to the site with highest risk of local failure Normal tissue sparing Very useful in recurrent setting
  • 67. Dose Ro resection:-7.5-10 Gy R1 resection:-10-12.5 Gy R2 resection:-15-20 Gy
  • 68. Chances of local failure decreased In margin negative cases from 15% 11% After R1 resection 83% 32% After R2 resection 83% 43%
  • 69.
  • 70. Side effects and managment
  • 71. Early complications  Diarrhea  Increased bowel frequency  Dysuria  Acute proctitis  Malabsorption of fat,carbohydrate,protein and bile salts Mechanism:- depletion of actively dividing cells
  • 72. Late complications Small bowel obstruction Bleeding Persistent diarrhea Scrotal/perineal tenderness Urinary incontinence Stricture Second cancer
  • 73. Role of RT in colon cancer Treatment recommendations should be made on a case-by-case basis with existing data in setting of an informed consent. Adj tumor bed RT with concurrent 5-FU based chemo should be considered for pts with tumors (a) invading adjoining structures (b) those complicated by perforation or fistula (c) Incomplete resection is performed