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

THANK YOU