Role of radiation in carcinoma rectum and colon Dr Bharti Devnani Moderator:- Dr Manoj K.Sharma
May 26, 2015
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=421Preop 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=402Post 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 lessArm No of
ptsAny 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 diseaseStage 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 withColorectal Cancer: Clinical Radiation Oncology Hellenic GroupBy Antonadou et al
Amifostine significantly reduced the incidence of grade 2 gastrointenstinal toxicity. There was no evidence ofcompromised 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
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