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By
Dr Parneet Singh
Epidemiology
 Colorectal caner is the third most frequently diagnosed

cancer in the US men and women.

 108,070 new cas...
Incidence in Large Bowel
• Cecum

14 %

• Ascending colon

10 %

• Transverse colon

12 %

• Descending colon

7%

• Sigmo...
Clinical Anatomy
 12-15 cm from anal

verge.

 Diameter
 4 cm (upper part)
 Dilated (lower part)

 Posterior part of ...
Clinical Anatomy
.

 Ends at the anorectal

junction, 2-3 cm in front of
and a little below the coccyx

 Taenia of the s...
Rectum is divided into 3
portions
 3 distinct intraluminal

curves ( Valves of
Houston)

Lower rectum : 3 – 6 cm from

t...
Peritoneal Relations
 Superior 1/3rd of the rectum
 Covered by peritoneum on

the anterior
surfaces

and

lateral

 Mid...
Arterial Supply
 Superior rectal A – from

IMA; supplies upper
and middle rectum

 Middle rectal A- from

Internal iliac...
Venous Drainage
Superior rectal V- upper

& middle third rectum

Middle rectal V- lower

rectum and upper anal
canal

I...
Nerve supply
 Sympathetic: L1-

L3, Hypogastric plexus

 ParaSympathetic: S2-S4
Lymphatic drainage
 Upper and middle rectum
 Pararectal

lymph
nodes,
located directly on the muscle
layer of the rectum...
Lymphatic Drainage
Aetiology
 Etiological agents
 Environmental & dietary factors
 Chemical carcinogenesis.

 Associated risk factors
 M...
Symptoms
 Asymptomatic
 Blood PR(60%)
 Change in bowel habit(43%) (diarrhoea, constipation,








narrow stool,...
Acute Presentations
 Intestinal obstruction
 Perforation
 Massive bleeding
Signs
 Pallor
 Abdominal mass
 PR mass
 Jaundice

 Nodular liver
 Ascites
 Rectal metastasis travel along portal dr...
Signs

 Signs of primary cancer
 Abdominal tenderness and distension – large bowel obstruction
 Intra-abdominal mass

...
WHO Classification of
Rectal Carcinoma
 Adenocarcinoma in situ / severe dysplasia
 Adenocarcinoma
 Mucinous (colloid) a...
Dukes classification
Dukes A: Invasion into but not through the
bowel wall



 Dukes B: Invasion through the bowel wall ...
Modified astler coller
classification Stage A : Limited to mucosa

 Stage B1 : Extending into muscularis propria

penetr...
TX
T0
Tis
T1
T2

TNM Classification

Primary tumor cannot be assessed
No evidence of primary tumor
Carcinoma in situ: intr...
TNM Classification
Stage grouping
Stage
0
I
IIA
IIB

T
Tis
T1
T2
T3
T4

N
N0
N0
N0
N0
N0

M
M0
M0
M0
M0
M0

Dukes
A
A
B
B

MAC
A
B1
B2
B3

II...
Stage 0 Rectal Cancer
 Known as ―cancer in
situ,‖ meaning cancer
is located in the
mucosa.
Stage I Rectal Cancer
 The cancer has grown
through the mucosa
and invaded the
muscularis (muscular
coat)
Stage II Rectal Cancer
 The cancer has grown

beyond the muscularis
of the colon or rectum
but has not spread to
lymph no...
Stage III Rectal Cancer
 Cancer has spread to
the regional lymph
nodes (lymph nodes
near the colon and
rectum)
Stage IV Rectal Cancer
 Cancer has spread

outside of colon or
rectum to other areas of
the body
Prognostic factors
 Good prognostic

factors
 Old age
 Gender(F>M)
 Asymptomatic pts

 Polypoidal lesions
 Diploid

...
Stage and Prognosis
Stage

5-year Survival (%)

0,1

Tis,T1;No;Mo

> 90

I
II

T2;No;Mo
T3-4;No;Mo

80-85
70-75

III

T2;N...
Japanese Scientists train
Dogs to detect Colorectal
Cancer ( Gut, 2011)
Diagnostic Workup
 History—including family history of colorectal cancer
or polyps

 Physical examinations including DRE...
Diagnostic Evaluation

 General

Clinical features.
 Lab. Studies
Complete blood cell count
Blood chemistry profile
CEA
...
Colonoscopy or barium
enema
To evaluate remainder of large bowel to rule out
synchronous tumor or presence of polyp syndro...
Transrectal Ultrasound
 Used for clinical staging.
 80-95% accurate in tumor






staging
70-75%
accurate
in
mesore...
EUS : Accuracy
EUS CT
Depth of infiltration T staging

91% 71%

N staging

87% 76%
CT Scan
 Part of routine workup of patients
 Useful in identifying enlarged pelvic lymph-nodes and

metastasis outside t...
CT Scan
 Ability to detect pelvic and para-aortic lymph nodes

is higher than peri-rectal lymph nodes(75% to 87%
vs. 45%)...
Figure:
Rectal cancer with uterine
invasion. CT scan shows a large
heterogeneous rectal mass (M) with
compression and dire...
Magnetic Resonance
Imaging (MRI)
 Greater accuracy in defining extent of rectal cancer

extension and also location & sta...
Figure: Normal rectal and perirectal
anatomy on high-resolution T2-weighted
MRI. Rectal mucosa (M), submucosa
(SM), and mu...
PET with FDG
 Shows promise as the most sensitive

study for the detection of metastatic
disease in the liver and elsewhe...
Aims of treatment
 Local control

 Long-term survival
 Restoration of bowel continuity and Preservation
of anal sphinct...
Treatment

Surgery

Chemotherapy

Radiotherapy
Treatment Overview
 Sx mainstay of treatment.
 After curative resection the 5 year survival drops
from 80% in stage I to...
Principles of surgical
management
 Removal of primary tumor with adequate margin.
 T/t of draining LN.
 Restoration of ...
PELVIC SUBSITES
Five subsites :predominant areas at risk for local
recurrence:
 Mesorectal subsite (MS),
 Posterior pelv...
PATERN OF NODAL
RECURRENCE
 MS less common as it gets totally removed in
TME
 PPS most common site of nodal recurrence 2...
Surgical procedures for
Rectal ca

 APR ( abdomino-perineal resection).
 LAR ( Low ant. Resection)

Radical

 Proctecto...
Local excision

 For superficially invasive (T1) tumors with low







likelihood of LN metastases
Total biopsy, w...
Local Excision Techniques
 Transanal Excision.
 Post proctotomy.
 TEM
 Fulguration
 Endoscopic laser

 Staging of su...
LAR
 For tumors in upper/mid rectum allows
preservation of anal sphincter

 Join colon to low rectum
 Permanent colosto...
Abdomino-perineal
resection
 For tumors of distal rectum(lower 1/3rd) with distal edge

up to 6 cm from anal verge
 Asso...
Procedure

 Through combined abdominal and perineal
incisions, the anus, rectum, and sigmoid colon

are removed en bloc.
...
Heavy purse string suture
around anus to occlude it
Colon and Rectum are
delivered through the
perineal resection
Total mesorectal excision
 Local failures are most often due to inadequate surgical

clearance of radial margins.

 Conv...
TOTAL MESORECTAL
EXCISION
Total Mesorectal
Excision
Pelvic Exenteration
The surgeon removes the rectum as well as nearby organs such as the
bladder, prostate, or uterus if th...
Complications of Surgery
 Bleeding

 Infection
 Anastomotic Leakage
 Blood clots
 Anesthetic Risks
SUMMARY OF BOWEL FUNCTION IN THE 2 GROUPS
Non-Radiation
(59 Patients)
No. of bowel movements/day
Medican (range)
4
Cluster...
Adjuvant therapy

Chemotherapy

Radiation therapy
with or without
chemotherapy
Purpose of
Radio(chemo)therapy
 To lower local failure rates and improve
survival in resectable cancers
 To allow surger...
Chemotherapy agents







5Fu
Leucovorin
Oxaliplatin
Irinotecan
Bevacizumab
cetuximab

Combinations
 FOLFOX
 FOLF...
PREOPERATIVE CHEMORADIATION
 NSABP R-03 : improved DFS & OS
 German trial : improved locoregional control.
 REGIMENS :
...
POSTOPERATIVE CHEMORT :
 EORTC 22921 trial : improved DFS & OS.
 MOSAIC trial : Addition of oxaliplatin + 5- FU + leucov...
Role of Radiotherapy
 Neo-adjuvant/Adjuvant RT in resectable Ca Rectum

pre-op
post-op

 RT in locally advanced rectal c...
ADVANTAGES OF PRE
OP CT+RT

•

Down staging, hence increased resectability

•

Decreased risk of dissemination during surg...
TARGET VOLUME
 Site of local involvement

 spread to other organ - sacrum, vagina or
prostate
 Whole of the sacrum
 Po...
Positioning
 Prone position with belly

board

 Purpose is to displace

bowel superior and
anteriorly & bladder
anterior...
Treatment energy
 PA portal with 6MV to decrease bladder dose
 Lateral portal requires 10/15 MV to increase depth

dose ...
PA Borders – Pre Op
Case In most cases upper border


lies at L5-S1 junction to
cover Sacral promontary.
 Inferior margi...
Lateral portal
 Upper Border- L5-S1

 Lower Border 3-5 Cm below

inferior Tx extension

 Posterior border should be

at...
Issues in Postoperative RT
of Rectum
 Increased risk of bowel toxicity
Adhesions
Bowel sags in pelvic cavity
Large por...
PA Borders – Post Op
Case
 In case of APR, inferior border

should cover perineal scar
 8-30% scar recurrence if scar
no...
Lateral Borders – Post Op
Case
 In case of APR, inferior border

should cover perineal scar
Dose Distribution: 3
Fields / 30w
Dose Distribution: 3 Fields
/ 45w
DVH
3 Field / Open
Bilateral Portals
Portals- Two Fields : APPA
 Parallel opposing not commonly used
 High dose to bladder and bowel
 Used in palliative cas...
2 Fields AP / PA
DVH
Pre-Op radiotherapy
 Short course

25 Gy in 5 daily fractions of 5 Gy given in 1
week.
 Long course
 Phase 1
45 Gy in ...
Post-Op Radiotherapy
 Phase 1
 45 Gy in 25 daily fractions of 1.8 Gy given in 5 week

 Phase 2 (optional)
 5.4–9 Gy in...
Palliative radiotherapy
 Phase 1

 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.

 Phase 2 (optional)

 5.4–...
Dose limitations
 Small bowel- 45–50 Gy
 Femoral head and neck- 42 Gy
 Bladder -65 Gy
 Rectum- 60 Gy
CONTOURING
GUIDELINES
TARGET VOLUMES
 CTVA: Defined to be the regions that would always be

treated for rectal cancer
 Internal iliac
 Pre-sa...
GUIDELINES

 Lower Pelvis:

The caudal extent minimum of 2 cm caudal to
gross disease, including coverage of the entire m...
Mid pelvis
The posterior and lateral margins of CTVA should

extend to lateral pelvic sidewall musculature or, where
abse...
Upper pelvis:
 Superior extent - the rectosigmoid junction or 2 cm

proximal to the superior extent of macroscopic diseas...
Indications for elective
irradiation (CTVB+CTVC)
Elective coverage of the inguinal and external iliac regions

should be ...
OAR
The femoral head and neck should be avoidance

structures.

The small and large bowel are important structures to

c...
IORT radiation therapy (IORT) delivers a
 Intra-operative
concentrated dose of radiation therapy to a tumor
bed during su...
 Maximum effect, while minimizing recurrence
 Delivered immediately after tumor is removed,
helping to destroy the micro...
 A "boost" for traditional radiation pts.
 Patients who must receive additional radiation
therapy following surgery can ...
Endocavitary Radiation
 Propagated initially by Papillon and Sischy
 High doses low energy radiation delivered using
50 ...
Treatment Recommendations
Stage

Rectal cancer

~5-year LF/OS

I

• TME with APR or LAR.
• If pT1-2N0, no adj. treatment.
...
Stage

III
(T4/ Locally
unresectable
)

Rectal cancer

If obstructed, diverting colostomy or stent
placed  definitive tre...
Clinical Trials
Pre-op RT vs. surgery alone
Swedish Rectal Cancer Trial(NEJM 1997;336:980 ): 1168 patients
randomised to 25 Gy (5x5) PRT o...
Pre-op vs. post-op Chemo RT
Randomized trial of the German Rectal Cancer study Group (Sauer
R et al. N Engl J Med 2004;351...
• MRC CR07/NCIC-CTG C016 (Sebag-Montefiore et al.

2009): 1350 pt. with resectable rectal cancer randomized.
▫ 25 Gy/5# + ...
Polish Trial
• Polish Study (Br J Surg. 2006): 316 pts with resectable T3-

4 rectal cancer, no sphincter involvement, tum...
Post-op chemo, RT, and/or ChemoRT
 GITSG 7175 (Thomas and Lindblad, 1988): 227 patients with stage B2-C

rectal CA random...
Thank You !!
 Carcinoma rectum-radiotherapy perspective
 Carcinoma rectum-radiotherapy perspective
 Carcinoma rectum-radiotherapy perspective
 Carcinoma rectum-radiotherapy perspective
 Carcinoma rectum-radiotherapy perspective
 Carcinoma rectum-radiotherapy perspective
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Carcinoma rectum-radiotherapy perspective

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Christian Medical College and Hospital , Ludhiana

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Carcinoma rectum-radiotherapy perspective

  1. 1. By Dr Parneet Singh
  2. 2. Epidemiology  Colorectal caner is the third most frequently diagnosed cancer in the US men and women.  108,070 new cases of colon cancer and 40,740 new cases of rectal cancer in the US in 2008. Combined mortality for colorectal cancer 49,960 in 2008.  Worldwide approx. 1 million new cases p.a. are diagnosed, with 529,000 deaths.  Incidence rate in India is quite low about 2 to 8 per 100,000  Median age- 7th decade but can occur any time in adulthood  Lifetime risk   1 in 10 for men 1 in 14 for women
  3. 3. Incidence in Large Bowel • Cecum 14 % • Ascending colon 10 % • Transverse colon 12 % • Descending colon 7% • Sigmoid colon 25 % • Rectosigmoid junct 0.9 % • Rectum 23 %
  4. 4. Clinical Anatomy  12-15 cm from anal verge.  Diameter  4 cm (upper part)  Dilated (lower part)  Posterior part of the lesser pelvis and in front of lower three pieces of sacrum and the coccyx  Begins at the rectosigmoid junction, at level of third sacral vertebra
  5. 5. Clinical Anatomy .  Ends at the anorectal junction, 2-3 cm in front of and a little below the coccyx  Taenia of the sigmoid colon form a continuous outer longitudinal layer of smooth muscle  Fatty omental appendices are discontinued
  6. 6. Rectum is divided into 3 portions  3 distinct intraluminal curves ( Valves of Houston) Lower rectum : 3 – 6 cm from the anal verge Mid rectum: 6 cm to 8 -10cm from anal verge  Upper rectum: 8 cm to 12 -15cm from anal verge
  7. 7. Peritoneal Relations  Superior 1/3rd of the rectum  Covered by peritoneum on the anterior surfaces and lateral  Middle 1/3rd of the rectum  Covered by peritoneum on the anterior surface  Inferior 1/3rd of the rectum  Devoid of peritoneum  Close proximity to adjacent structure including boney pelvis.
  8. 8. Arterial Supply  Superior rectal A – from IMA; supplies upper and middle rectum  Middle rectal A- from Internal iliac A. (supplies lower rectum)  Inferior rectal A- from Internal pudendal A.
  9. 9. Venous Drainage Superior rectal V- upper & middle third rectum Middle rectal V- lower rectum and upper anal canal Inferior rectal vein- lower anal canal
  10. 10. Nerve supply  Sympathetic: L1- L3, Hypogastric plexus  ParaSympathetic: S2-S4
  11. 11. Lymphatic drainage  Upper and middle rectum  Pararectal lymph nodes, located directly on the muscle layer of the rectum  Inferior mesenteric lymph nodes, via the nodes along the superior rectal vessels  Lower rectum  Sacral group of lymph nodes or Internal iliac lymph nodes  NODAL GROUPS Perirectal Common iliac Internal iliac Paraortic
  12. 12. Lymphatic Drainage
  13. 13. Aetiology  Etiological agents  Environmental & dietary factors  Chemical carcinogenesis.  Associated risk factors  Male sex  Family history of colorectal cancer  Personal history of colorectal      cancer, ovary, endometrial, breast Excessive BMI Processed meat intake Excessive alcohol intake Low folate consumption Neoplastic polyps.  Hereditary Conditions (FAP, HNPCC)
  14. 14. Symptoms  Asymptomatic  Blood PR(60%)  Change in bowel habit(43%) (diarrhoea, constipation,       narrow stool, incomplete evacuation, tenesmus) Occult bleeding(23%) Abdominal discomfort (20%)(pain, fullness, cramps, bloating, vomiting) Weight loss, tiredness Back Pain Urinary symptoms Pelvic pain(5%) indicating nerve trunk involvement
  15. 15. Acute Presentations  Intestinal obstruction  Perforation  Massive bleeding
  16. 16. Signs  Pallor  Abdominal mass  PR mass  Jaundice  Nodular liver  Ascites  Rectal metastasis travel along portal drainage to liver via superior rectal vein as well as systemic drainage to lung via middle inferior rectal veins.
  17. 17. Signs  Signs of primary cancer  Abdominal tenderness and distension – large bowel obstruction  Intra-abdominal mass Digital rectal examination – most are in the lowest 12cm & reached by examining finger  Rigid sigmoidoscope  Signs of metastasis and complications  Signs of anaemia  Hepatomegaly (mets)  Monophonic wheeze  Bone pain
  18. 18. WHO Classification of Rectal Carcinoma  Adenocarcinoma in situ / severe dysplasia  Adenocarcinoma  Mucinous (colloid) adenocarcinoma (>50% mucinous)  Signet ring cell carcinoma (>50% signet ring cells)  Squamous cell (epidermoid) carcinoma  Adenosquamous carcinoma  Small-cell (oat cell) carcinoma  Medullary carcinoma  Undifferentiated Carcinoma
  19. 19. Dukes classification Dukes A: Invasion into but not through the bowel wall   Dukes B: Invasion through the bowel wall but not involving lymph nodes  Dukes C: Involvement of lymph nodes  Dukes D: Widespread metastases
  20. 20. Modified astler coller classification Stage A : Limited to mucosa  Stage B1 : Extending into muscularis propria penetrating through it; nodes not involved but not  Stage B2 : Penetrating through muscularis propria; nodes not involved  Stage C1 : Extending into muscularis propria but not penetrating through it. Nodes involved  Stage C2 : Penetrating through muscularis propria. Nodes involved  Stage D: Distant metastatic spread
  21. 21. TX T0 Tis T1 T2 TNM Classification Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ: intraepithelial or invasion of lamina propria Tumor invades submucosa Tumor invades muscularis propria T3 Tumor invades through the muscularis propria into pericolorectal tissues T4a Tumor penetrates to the surface of the visceral peritoneum T4b Tumor directly invades or is adherent to other organs or structures Tis T1 T2 T3 T4 Mucosa Muscularis mucosae Submucosa Muscularis propria Subserosa Serosa Extension to an adjacent organ
  22. 22. TNM Classification
  23. 23. Stage grouping Stage 0 I IIA IIB T Tis T1 T2 T3 T4 N N0 N0 N0 N0 N0 M M0 M0 M0 M0 M0 Dukes A A B B MAC A B1 B2 B3 IIIA IIIB IIIC IV T1-2 T3-4 Any T Any T N1 N1 N2 Any N M0 M0 M0 M1 C C C - C1 C2/C3 C1/C2/C3 D
  24. 24. Stage 0 Rectal Cancer  Known as ―cancer in situ,‖ meaning cancer is located in the mucosa.
  25. 25. Stage I Rectal Cancer  The cancer has grown through the mucosa and invaded the muscularis (muscular coat)
  26. 26. Stage II Rectal Cancer  The cancer has grown beyond the muscularis of the colon or rectum but has not spread to lymph nodes
  27. 27. Stage III Rectal Cancer  Cancer has spread to the regional lymph nodes (lymph nodes near the colon and rectum)
  28. 28. Stage IV Rectal Cancer  Cancer has spread outside of colon or rectum to other areas of the body
  29. 29. Prognostic factors  Good prognostic factors  Old age  Gender(F>M)  Asymptomatic pts  Polypoidal lesions  Diploid  Poor prognostic factors          Obstruction Perforation Ulcerative lesion Adjacent structures involvement Positive margins LVSI Signet cell carcinoma High CEA Tethered and fixed cancer
  30. 30. Stage and Prognosis Stage 5-year Survival (%) 0,1 Tis,T1;No;Mo > 90 I II T2;No;Mo T3-4;No;Mo 80-85 70-75 III T2;N1-3;Mo 70-75 III T3;N1-3;Mo 50-65 III IV T4;N1-2;Mo M1 25-45 <3
  31. 31. Japanese Scientists train Dogs to detect Colorectal Cancer ( Gut, 2011)
  32. 32. Diagnostic Workup  History—including family history of colorectal cancer or polyps  Physical examinations including DRE and complete pelvic examination in women: size, location, ulceration, mobile vs. tethered vs. fixed, distance from anal verge and sphincter functions.  Proctoscopy—including assessment of mobility, minimum diameter of the lumen, and distance from the anal verge  Biopsy of the primary tumor
  33. 33. Diagnostic Evaluation  General Clinical features.  Lab. Studies Complete blood cell count Blood chemistry profile CEA  Evaluation  Determination of Occult Blood Digital Rectal Examination Proctosigmoidoscopy Flexible Fibreoptic Sigmoidoscopy & Colonoscopy. Barium Enema • Urologic Evaluation • Other Imaging studies • CT, USG, MRI, Chest X-ray, FDG- PET scan, Endorectal U/S.
  34. 34. Colonoscopy or barium enema To evaluate remainder of large bowel to rule out synchronous tumor or presence of polyp syndrome. Figure: Carcinoma of the rectum. Doublecontrast barium enema shows a long segment of concentric luminal narrowing (arrows) along the rectum with minimal irregularity of the mucosal surface.
  35. 35. Transrectal Ultrasound  Used for clinical staging.  80-95% accurate in tumor     staging 70-75% accurate in mesorectal lymph node staging Very good at demonstrating layers of rectal wall Use is limited to lesion < 14 cm from anus, not applicable for upper rectum, for stenosing tumor Very useful in determining extension of disease into anal canal (imp to plan sphincter preserving surgery) Figure.Endorectal ultrasound of a T3 tumor of the rectum, extension through the muscularis propria, and into perirectal fat.
  36. 36. EUS : Accuracy EUS CT Depth of infiltration T staging 91% 71% N staging 87% 76%
  37. 37. CT Scan  Part of routine workup of patients  Useful in identifying enlarged pelvic lymph-nodes and metastasis outside the pelvis than the extent or stage of primary tumor  Limited utility in small primary cancer  Sensitivity 50-80%  Specificity 30-80%
  38. 38. CT Scan  Ability to detect pelvic and para-aortic lymph nodes is higher than peri-rectal lymph nodes(75% to 87% vs. 45%) Accuracy T stage 60-80% Accuracy N stage 60-75% Liver met. 70-79%
  39. 39. Figure: Rectal cancer with uterine invasion. CT scan shows a large heterogeneous rectal mass (M) with compression and direct invasion into the posterior wall of the uterus (U). Figure: Mucinous adenocarcinoma of the rectum. CT scan shows a large heterogeneous mass (M) with areas of cystic components. Note marked luminal narrowing of the rectum (arrow).
  40. 40. Magnetic Resonance Imaging (MRI)  Greater accuracy in defining extent of rectal cancer extension and also location & stage of tumor  Helpful in lateral extension of disease, critical in predicting circumferential margin for surgical excision.  Different approaches (body coils, endorectal MRI & phased array technique)
  41. 41. Figure: Normal rectal and perirectal anatomy on high-resolution T2-weighted MRI. Rectal mucosa (M), submucosa (SM), and muscularis propria (PM) are well discriminated. Mesorectal fascia appears as a thin, low-signal-intensity structure (arrowheads) and fuses with the remnant of urogenital septum making Denonvilliers fascia (arrows). Figure: Mucinous adenocarcinoma of the rectum. T2-weighted MRI shows high signal intensity (arrowheads) of the cancer lesion in right anterolateral side of the rectal wall.
  42. 42. PET with FDG  Shows promise as the most sensitive study for the detection of metastatic disease in the liver and elsewhere.  Sensitivity of 97% and specificity of 76% in evaluating for recurrent colorectal cancer. cancer rectum prostate Small bowel bladder pubic bone
  43. 43. Aims of treatment  Local control  Long-term survival  Restoration of bowel continuity and Preservation of anal sphincter.  Bladder and sexual function and maintenance or improvement in QOL.  Careful preoperative screening is crucial in determination of the location of lesion and its depth of invasion
  44. 44. Treatment Surgery Chemotherapy Radiotherapy
  45. 45. Treatment Overview  Sx mainstay of treatment.  After curative resection the 5 year survival drops from 80% in stage I to about 40% in stage III disease.  Local recurrence remains a major site of failure ranging from 5% in few selected series to about 40% in most reports.  LF associated with devastating symptoms that severely affects the QOL & difficult to salvage
  46. 46. Principles of surgical management  Removal of primary tumor with adequate margin.  T/t of draining LN.  Restoration of function  ―En bloc‖ resection if necessary
  47. 47. PELVIC SUBSITES Five subsites :predominant areas at risk for local recurrence:  Mesorectal subsite (MS),  Posterior pelvic subsite (PPS)  Lateral pelvic subsite (LPS)  Inferior pelvic subsite (IPS)  Anterior pelvic subsite (APS)
  48. 48. PATERN OF NODAL RECURRENCE  MS less common as it gets totally removed in TME  PPS most common site of nodal recurrence 22 to 49% in various series.  LPS around 21%  IPS around 3 to 11%  APS around 5 to17%
  49. 49. Surgical procedures for Rectal ca  APR ( abdomino-perineal resection).  LAR ( Low ant. Resection) Radical  Proctectomy & colo-anal anastomosis  Local excision    Transanal excision Post. Proctotomy Non-Radical Trans-anal endoscopic microsurgery(TEM).  Ablative procedures Endoscopic surgery Fulguration
  50. 50. Local excision  For superficially invasive (T1) tumors with low       likelihood of LN metastases Total biopsy, with further T/t based on pathology Tumors within 8 to 10 cm of anal verge, Encompass less than 40% of circumference of bowel wall, well or moderately well differentiated histology, No pathological evidence of venous or lymphatic vessel invasion on biopsy With unfavorable pathology patient should undergo total mesorectal excision with or without sphincterpreservation:  Positive margin (or <2 mm), lymphovascular invasion,  Poorly differentiated tumors, T2 lesion
  51. 51. Local Excision Techniques  Transanal Excision.  Post proctotomy.  TEM  Fulguration  Endoscopic laser  Staging of such lesions should be performed using EUS to minimize likelihood of doing a local excision for T3 tumors.
  52. 52. LAR  For tumors in upper/mid rectum allows preservation of anal sphincter  Join colon to low rectum  Permanent colostomy if tumor too low w  Reduced ability to define distant disease  Difficulty localizing lesion  OR time and costs
  53. 53. Abdomino-perineal resection  For tumors of distal rectum(lower 1/3rd) with distal edge up to 6 cm from anal verge  Associated with permanent colostomy and high incidence of sexual and genitourinary dysfunction
  54. 54. Procedure  Through combined abdominal and perineal incisions, the anus, rectum, and sigmoid colon are removed en bloc.  Also called Miles Resection  The proximal end of the bowel is exteriorized through a separate stab wound as a colostomy.  The distal end is pushed into the hollow of the sacrum and removed via perineum  Performed to treat cancer of the lower rectum—and diseases are too low for use of stapling devices
  55. 55. Heavy purse string suture around anus to occlude it
  56. 56. Colon and Rectum are delivered through the perineal resection
  57. 57. Total mesorectal excision  Local failures are most often due to inadequate surgical clearance of radial margins.  Conventional resection violates the mesorectal circumference during blunt dissection, leaving residual mesorectum.  Excision of fascia enveloping the fat pad around the rectum  TME involves precise dissection and removal of the entire rectal mesentery as an intact unit.  Local recurrence with conventional surgery averages approx. 25-30% vs. TME 4-7% by several groups (although several series have higher recurrence)
  58. 58. TOTAL MESORECTAL EXCISION
  59. 59. Total Mesorectal Excision
  60. 60. Pelvic Exenteration The surgeon removes the rectum as well as nearby organs such as the bladder, prostate, or uterus if the cancer has spread to these organs. A colostomy is needed after this operation. If the bladder is removed, a urostomy (opening to collect urine) is needed. High Anterior Resection 15 cm Low Anterior Resection Ultra-low Anterior Resection Abdominoperineal Resection (APR)
  61. 61. Complications of Surgery  Bleeding  Infection  Anastomotic Leakage  Blood clots  Anesthetic Risks
  62. 62. SUMMARY OF BOWEL FUNCTION IN THE 2 GROUPS Non-Radiation (59 Patients) No. of bowel movements/day Medican (range) 4 Clustering 5 Awoken at night for movement Incontinence None Occasional Frequent Wear a pad Perianal skin irritation Regularly use Lomotil ± Imodium Unable to differentiate stool from gas Liquid consistency (sometimes or always) Unable to defer defecation >15 min Need to defecate again within 30 min Bowel function different to preoperative 2 (1-7) 83% 3% 14% 14% – 93% 7% 0% 10% 12% 5% 15% 5% 19% 37% 61% Chemoradiotherapy (41 Patients) 7 (1-20) 22% 42% 37% 46% – 44% 39% 17% 41% 41% 58% 39% 29% 78% 88% 93% p Value <0.001 – – – <0.001 <0.001 – – – <0.001 <0.001 <0.001 0.009 0.001 <0.001 <0.001 0.001 JH012804
  63. 63. Adjuvant therapy Chemotherapy Radiation therapy with or without chemotherapy
  64. 64. Purpose of Radio(chemo)therapy  To lower local failure rates and improve survival in resectable cancers  To allow surgery in primarly inoperable cancers  To facilitate a sphincter-preserving procedure  To cure patients without surgery: very small cancer or very high surgical risk
  65. 65. Chemotherapy agents       5Fu Leucovorin Oxaliplatin Irinotecan Bevacizumab cetuximab Combinations  FOLFOX  FOLFIRI  Leucovorin/5FU  Capecitabine  NIGRO  Bevacizumab in combination with the above regimens.
  66. 66. PREOPERATIVE CHEMORADIATION  NSABP R-03 : improved DFS & OS  German trial : improved locoregional control.  REGIMENS :  5- FU : 225 mg/ m2 – daily continous infusion  Capecitabine : 825 mg/ m2 BD on days of radiation  5- FU : 400 mg / m2 IV bolus + leucovorin 20 mg /m2 IV bolus for 4 days : wk 1 & wk 5.
  67. 67. POSTOPERATIVE CHEMORT :  EORTC 22921 trial : improved DFS & OS.  MOSAIC trial : Addition of oxaliplatin + 5- FU + leucovorin . REGIMENS :  5-FU : bolus weekly regimen ( leucovorin 20 mg/m2 over 2 hrs : 5- FU 500 mg/ m2 bolus  if no neoadjuvant chemoRT :  Weekly Roswell Park regimen : 5-FU + leucovorin ( leucovorin 500 mg /m2 given over 2 hrs followed by 5-FU bolus ) : weekly over 6 wks then 2 wks rest .  mFOLFOX 6  Capecitabine 1000 – 1250 mg/ m2 from day 1-14 ( 21 day cycle )
  68. 68. Role of Radiotherapy  Neo-adjuvant/Adjuvant RT in resectable Ca Rectum pre-op post-op  RT in locally advanced rectal cancer pre-op for down staging IORT  Definitive RT unfit for surgery  Palliative RT – Pain, bleeding etc.
  69. 69. ADVANTAGES OF PRE OP CT+RT • Down staging, hence increased resectability • Decreased risk of dissemination during surgery. • Radiation more effective with tumour cells highly vascular. • Less serious bowel toxicity due to easy exclusion. • Possibility of increasing sphincter preservation in borderline cases.
  70. 70. TARGET VOLUME  Site of local involvement  spread to other organ - sacrum, vagina or prostate  Whole of the sacrum  Posterior margin should be beyond the sacrum  Anterior border 2-3 cm anterior to the promontry of sacrum to include common iliac LN
  71. 71. Positioning  Prone position with belly board  Purpose is to displace bowel superior and anteriorly & bladder anteriorly  Bladder distension  Blocks are used to spare the posterior muscle and soft tissues behind the sacrum and small bowel.
  72. 72. Treatment energy  PA portal with 6MV to decrease bladder dose  Lateral portal requires 10/15 MV to increase depth dose and decrease dose to hip joints  30 degree wedges improves distribution  Portals  4 fields (AP, PA, two lateral fields)  3 fields (PA, two lateral fields)  2 fields(AP,PA-rarely used)
  73. 73. PA Borders – Pre Op Case In most cases upper border  lies at L5-S1 junction to cover Sacral promontary.  Inferior margin should be 34 cm below inferior tumour extent on sigmoidoscopy.  For upper rectal Ca, inferior border upto dentate line( cover all mesorectum)  Lateral border -1.5 cm beyond the bony pelvic wall
  74. 74. Lateral portal  Upper Border- L5-S1  Lower Border 3-5 Cm below inferior Tx extension  Posterior border should be atleast 1 cm behind sacral convexity  Anterior border at pubic symphysis*(T3-T4)
  75. 75. Issues in Postoperative RT of Rectum  Increased risk of bowel toxicity Adhesions Bowel sags in pelvic cavity Large portals 1. 2. Anastomotic site in ANTERIOR RESECTION Perineal scar in APR
  76. 76. PA Borders – Post Op Case  In case of APR, inferior border should cover perineal scar  8-30% scar recurrence if scar not included in field  While only 2% reoccur if scar included in portal
  77. 77. Lateral Borders – Post Op Case  In case of APR, inferior border should cover perineal scar
  78. 78. Dose Distribution: 3 Fields / 30w
  79. 79. Dose Distribution: 3 Fields / 45w
  80. 80. DVH
  81. 81. 3 Field / Open
  82. 82. Bilateral Portals
  83. 83. Portals- Two Fields : APPA  Parallel opposing not commonly used  High dose to bladder and bowel  Used in palliative cases & when bladder or anterior wall involved
  84. 84. 2 Fields AP / PA
  85. 85. DVH
  86. 86. Pre-Op radiotherapy  Short course 25 Gy in 5 daily fractions of 5 Gy given in 1 week.  Long course  Phase 1 45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.  Phase 2 (optional) 5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. Fields)
  87. 87. Post-Op Radiotherapy  Phase 1  45 Gy in 25 daily fractions of 1.8 Gy given in 5 week  Phase 2 (optional)  5.4–9 Gy in 3–5 daily fractions of 1.8 Gy(2 lat. fields)
  88. 88. Palliative radiotherapy  Phase 1  45 Gy in 25 daily fractions of 1.8 Gy given in 5 weeks.  Phase 2 (optional)  5.4–14.4 Gy in 3–8 daily fractions of 1.8 Gy(2 lat fields)  A hypofractionated regimen can be used  30–36 Gy in 5–6 fractions of 6 Gy once weekly given in 5– 6 weeks.
  89. 89. Dose limitations  Small bowel- 45–50 Gy  Femoral head and neck- 42 Gy  Bladder -65 Gy  Rectum- 60 Gy
  90. 90. CONTOURING GUIDELINES
  91. 91. TARGET VOLUMES  CTVA: Defined to be the regions that would always be treated for rectal cancer  Internal iliac  Pre-sacral  Peri-rectal  CTVB:  External iliac nodal region  CTVC:  Inguinal nodal region
  92. 92. GUIDELINES  Lower Pelvis: The caudal extent minimum of 2 cm caudal to gross disease, including coverage of the entire mesorectum to the pelvic floor Extension of CTVA does not need to go more than a few millimeters beyond the levator muscles unless there is radiographic evidence of extension into the ischiorectal fossa For very advanced anal or rectal cancers, extending through the mesorectum or the levators, add ~1-2 cm margin up to bone wherever the cancer extends beyond the usual compartments An MRI and/or PET/CT scan is strongly recommended in such cases.
  93. 93. Mid pelvis The posterior and lateral margins of CTVA should extend to lateral pelvic sidewall musculature or, where absent, the bone. Anteriorly extend CTVA to ~1 cm into the posterior bladder, to account for day-to-day variation in bladder position. Include the posterior portion of the internal obturator vessels (which lie between the external and internal iliacs in the mid pelvis) with CTVA.
  94. 94. Upper pelvis:  Superior extent - the rectosigmoid junction or 2 cm proximal to the superior extent of macroscopic disease in the rectum/peri-rectal nodes.  This defines how much of the distal large bowel within CTVA.  Properly cover the internal iliac and pre-sacral regions.  The most cephalad aspect of CTVA - the common iliac vessels bifurcate into external/internal iliacs (landmark: sacral promontory).
  95. 95. Indications for elective irradiation (CTVB+CTVC) Elective coverage of the inguinal and external iliac regions should be routine for anal carcinoma. For rectal carcinomas extending into gynecologic or genitourinary structures, the external iliac region should be added (i.e. elective nodal coverage = CTVA + CTVB for these cases). Include the external iliacs for rectal cancers that extend into the anal canal. Electively irradiate the inguinal nodal region for rectal adenocarcinomas that extend to the anal verge or peri-anal
  96. 96. OAR The femoral head and neck should be avoidance structures. The small and large bowel are important structures to consider when planning treatment. The entire abdominal contents need to be contoured up to ~ 1 cm above the PTV. Absolute volume of bowel (in cc) is more important than relative volume (in %).
  97. 97. IORT radiation therapy (IORT) delivers a  Intra-operative concentrated dose of radiation therapy to a tumor bed during surgery  Dose range from 1250-2000cGy.  Patient must be a surgical candidate in order to be eligible for IORT  Reserved for pts. with early-stage disease.
  98. 98.  Maximum effect, while minimizing recurrence  Delivered immediately after tumor is removed, helping to destroy the microscopic tumor cells that may be left behind  The tumor site is typically at high risk for recurrence & traditional RT requires a recovery period after surgery, which leaves microscopic disease in the body for longer  Spares healthy tissues and organs  Shortened treatment times  IORT T/t itself takes about 4 to 5 min.
  99. 99.  A "boost" for traditional radiation pts.  Patients who must receive additional radiation therapy following surgery can receive a boost of radiation during IORT After they have recovered from the surgical procedure, they can continue with their RT with fewer complications.
  100. 100. Endocavitary Radiation  Propagated initially by Papillon and Sischy  High doses low energy radiation delivered using 50 KVp unit  Initially utilised applicator cones of 2.4 – 2.9 cm dia  Later intra-luminal catheters were used after development of after-loading techniques.  Dose at 1 cm depth = 1/3 rd of surface dose  Since, very small volume very high doses can be tolerated  Multiple treatment done till CR achieved
  101. 101. Treatment Recommendations Stage Rectal cancer ~5-year LF/OS I • TME with APR or LAR. • If pT1-2N0, no adj. treatment. • Local excision for favorable tumors (<3 cm size, <30% circumference, within 8 cm of anal verge, well-moderately differentiated; margin >3 mm, no LVSI/PNI).  favorable T1 lesions- observation.  T2 lesions - adjuvant 5-FU/RT <5% LF 90% OS II and III (locally resectabl e) • Pre-op 5-FU/RT LAR/APR adjuvant 5FU-based therapy × 3 cycles (preferred) • If surgery initially  then adjuvant 5-FU × 2 cycles  concurrent chemoRT  5-FU ×2 cycles T3N0 and T1-2N1: 5–10% LF 80% OS T4N0 and T3N1: 10–15% LF 60% OS T4N1 and T3/4N2: 15–20% LF 40% OS
  102. 102. Stage III (T4/ Locally unresectable ) Rectal cancer If obstructed, diverting colostomy or stent placed  definitive treatment. 5-FU/RT  resection if possible. Consider IORT for microscopic disease (after 50 Gy EBRT, give IORT 12.5–15 Gy) or brachytherapy for macroscopic disease  adjuvant 5-FU-based therapy* IV Individualized options, including combination 5-FU-based chemo alone, or chemo ± resection ± RT Recurrent Individualized options. If no prior RT, then chemoRT  surgery ± IORT or brachytherapy. If prior RT, then chemo surgery ± IORT or brachytherapy as appropriate. ~5-year LF/OS
  103. 103. Clinical Trials
  104. 104. Pre-op RT vs. surgery alone Swedish Rectal Cancer Trial(NEJM 1997;336:980 ): 1168 patients randomised to 25 Gy (5x5) PRT or no RT. Surgery alone Preop. RT Rate of local recurrence 27% 11% p<0.001 5-year overall survival 48% 58% p=0.004 Dutch Colorectal Cancer Group (Kapiteijn E. NEJM 2001;345:638): 1861 patients randomised TME vs PRT+TME TME PRT+TME Recurrence rate 2.4% 8.2% OS ns ns
  105. 105. Pre-op vs. post-op Chemo RT Randomized trial of the German Rectal Cancer study Group (Sauer R et al. N Engl J Med 2004;351:1731-40):  cT3 or cT4 or node-positive rectal cancer  50.4 Gy (1.8 Gy per day)  5-FU: 1000 mg/m2 per day (d1-5) during 1. and 5. week Preop CRT Patients 5 y. OS 5 y. local relapse G3,4 toxic effects Postop CRT N=415 76% 6% 27% N=384 74% p=0.8 13% p=0.006 40% p=0.001 • Increase in sphincter-preserving surgery with preop Th.
  106. 106. • MRC CR07/NCIC-CTG C016 (Sebag-Montefiore et al. 2009): 1350 pt. with resectable rectal cancer randomized. ▫ 25 Gy/5# + Surgery (TME) ▫ Surgery (TME) + (45 Gy & 5 FU) CRT 5 y. OS 5 y. local relapse DFS Preop RT 80.8% 4.4% 79.5% Postop 78.7% 10.6% 74.5%
  107. 107. Polish Trial • Polish Study (Br J Surg. 2006): 316 pts with resectable T3- 4 rectal cancer, no sphincter involvement, tumor palpable on DRE (1999-2002). – RT  short-course RT with 5 Gy/d x 5 days + Surgery (TME) – CRT  50.4 Gy (1.8 Gy /# over 5.5 weeks) + bolus 5-FU 325 mg/m²/d + LV x 5 days 1st and 5th wks of RT + Surgery (TME) Preop SCRT Preop LCRT 5 y. OS 5 y. local relapse DFS 67.2% 9.0% 58.4% 66.2% 14.2% 55.6%
  108. 108. Post-op chemo, RT, and/or ChemoRT  GITSG 7175 (Thomas and Lindblad, 1988): 227 patients with stage B2-C rectal CA randomized postoperatively to:  no adjuvant therapy vs.  chemo alone vs.  RT alone vs.  concurrent chemoRT. Result: Chemo-RT arm improved 5-year OS (54%) and LR(10%) over observational arm OS (27%) & LR (25%).  Mayo NCCTG 79-47-51 (NEJM 1991): 204 patients with T3/4 or LN+(B2-C) randomized to  post-op RT (45–50.4 Gy) vs.  chemoRT (bolus 5-FU concurrent). Result: Chemo-RT improved LF (25 14%), DFS, and OS (48 58%) vs. RT alone.
  109. 109. Thank You !!

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