locally advaced rectal cancer

1. MANAGEMENT OF LOCALLY
ADVANCED RECTAL CANCER
DR ABANI KANTA NANDA
3YR PG STUDENT
AHRCC., CUTTACK

2. DEFINITION
• The definition of locally advanced rectal cancer is variable.
• One definition of locally advanced disease encompasses, tumors that cannot be
resected without high likelihood of residual gross or microscopic disease secondary to
tumor fixation or adherence to adjacent structures. Perez……
• Hence Locally advanced rectal cancers may be defined as T4 or node-positive
lesions.

3. CLASSIFICATION OF LOCALLY ADVANCED RECTAL CANCER
• Locally advanced cancers can be divided into following groups based on
management, approaches and outcomes: (Rectal Cancer International
Perspectives on Multimodality Management)
1. Isolated, resectable pelvic disease  define as a resectable case as one in which
we anticipate achieving a negative (R0) microscopic resection margin with
acceptable risk and morbidity to the patient.
2. Isolated, unresectable pelvic disease  tumors for which the likelihood of
resection with negative margin is extremely low or zero, without incurring
unacceptable patient risk or morbidity

4. DIAGNOSIS / WORK UP
• CBC, LFT, RFT
• Baseline CEA preoperatively for
1. Assessment of prognosis (>5ng/ml worse prognosis)
2. Presence of persistence disease after resection

5. • Digital rectal examination (DRE): To know
 How far the tumor begins from the anal verge
 Mobility of the tumor
 Early tumors (T1-2) are typically mobile.
 Tumors that have penetrated through the muscularis propria into the
perirectal tissue (T3) feel tethered
 Tumors that invade adjacent structures such as the pelvic sidewall (T4) will
feel firm and fixed
 Sphincter function

6. • Rigid Proctoscopy
 Assess primary tumor and biopsy
• Sigmoidoscopy
 Allows the surgeon to see the tumor and more accurately assess its location
 Assessment of tumor distance from the anal verge.
• Full Colonoscopy
 Should always be performed to rule out synchronous tumors.

7. • CT scan (chest, abdomen, and pelvis): To assess the primary tumor and the status of
the regional lymph nodes
• Endorectalultrasound (ERUS): to determine
Depth of invasion of the primary tumor
To assess the lymph node status
• MRI: to determine
Invasion of tumor into the mesorectal fat (T3) and into adjacent organs
(T4)
To assess lymph node status
Verify distance from the anal verge
To assess operability with negative margins
• Both ERUS and MRI are accurate in predicting T stage
• PET scan is accurate in identifying nodal disease, though not routinely indicated.

8. BIOPSY
• Colorectal Cancers According to the WHO Classification :
 Adenocarcinoma
 Mucinous adenocarcinoma
 Signet-ring cell carcinoma
 Adenosquamous carcinoma
 Squamous cell carcinoma
 Undifferentiated carcinoma
• [Most rectal cancers (95%) are adenocarcinomas]

9. TNM STAGING STAGING (2017)
T category:
• TX- Primary tumor cannot be assessed
• T0- No evidence of primary tumor
• Tis- Carcinoma in situ, intramucosal carcinoma
• T1 Tumor invades the submucosa (through the muscularis
mucosa but not into the muscularis propria)
• T2- Tumor invades the muscularis propria
• T3- Tumor invades through the muscularis propria into pericolorectal tissue
• T4a- Tumor invades through the visceral peritoneum (including gross perforation of
the bowel through tumor and continuous invasion of tumor through areas of
inflammation to the surface of the visceral peritoneum)
• T4b- Tumor directly invades or adheres to adjacent organs or structures

10. N Category:
• NX Regional lymph nodes cannot be assessed
• N0- No regional lymph node metastasis
• N1a- 1 regional lymph node is positive
• N1b- 2-3 regional lymph nodes are positive
• N1c- No regional lymph nodes are positive, but there are tumor deposits in the
• subserosa
• mesentery
• or nonperitonealized pericolic, or perirectal/ mesorectal tissues.
• N2a- 4-6 regional lymph nodes are positive
• N2b- ≥7 regional lymph nodes are positive
M Category:
• M0- No evidence of tumor in distant sites or organs
• M1a- Metastasis to 1 site or organ is identified without peritoneal metastastis
• M1b- Metastasis to ≥2 sites or organs is identified without peritoneal metastasis
• M1c- Metastasis to the peritoneal surface is identified alone or with other site or organ
metastases

11. TNM GROUPING AND STAGING
Node -ve No Metastasis Stage I or II
Node +ve No Metastasis Stage III
Any Node Metastasis Stage IV
NODE -ve T1 T2 Stage I
T3 T4 Stage II T3 Stage IIA
T4a Stage IIB
T4b Stage IIC
ADJACENT ORGAN
INVOLVEMENT (T4b)
Node -ve Stage IIC
Node +ve Stage IIIC

12. N1 1-3 nodes
or N1c
T1 T2 Stage IIIA
T3 T4a Stage IIIB
T4b Stage IIIC
N2a 4-6
nodes
T1 Stage IIIA
T2 T3 Stage IIIB
T4 Stage IIIC
N2b ≥7
nodes
T1 T2 Stage IIIB
T3 T4 Stage IIIC

13. DUKE’S CLASSIFICATION-
• Dukes A: Limited to bowel wall (T1,T2-N0-M0)  Stage I
• Dukes B: Spread outside the bowel wall (T3, T4-N0-M0)  Stage II
• Dukes C: Involvement of lymph nodes (Any T- N1,N2-M0)  Stage III
• Dukes D: Widespread metastases (Any T- any N – M1)  Stage IV
Modified astler coller classification (modified Duke’s) –
• Stage A : Limited to mucosa (T1-N0-M0)
• Stage B1 : Infiltration into muscularis propria (T2-N0-M0)
• Stage B2 : Infiltration beyond muscularis propria into serosa (T3-N0-M0)
• Stage C1 : Lymph node involvement but did not penetrate the entire bowel wall
(T1,T2- N1,N2- M0)
• Stage C2 : Tumors that invaded lymph nodes and did penetrate the entire wall
(T3-N1,N2-M0)
• Stage D: Distant metastatic spread (Any T- any N- M1)

14. TREATMENT RECOMMENDATIONS
• Stage II/ III Pre-op
 Pre-op chemoRT (50.4 Gy/28 fx + capecitabine or infusional 5-FU) → LAR/APR →
adjuvant 5-FU-based therapy (FOLFOX or CAPEOX preferred)
 Pre-op RT (25 Gy/5 fx) → LAR/APR → adjuvant 5-FU-based therapy (FOLFOX or
CAPEOX preferred)
 Pre-op chemo and then chemoRT (FOLFOX or CAPEOX → chemoRT) → LAR or
APR (J NCCN 2014;12:513-519;Andrea Cercek et al.)
• Ongoing clinical trials (PROSPECT) are investigating neoadjuvant chemotherapy
alone for patients with high tumors with intermediate risk for LR, as well nonoperative
management for patients who would be ineligible for sphincter preservation.
• Stage II/ III post-op
 Adjuvant FOLFOX or CAPEOX x 2 cycles → chemoRT (50.4-55.8 Gy + capecitabine
or infusional 5-FU) → additional FOLFOX or CAPEOX x 2 cycles

15. • T4 unresectable
 Consider diverting colostomy if near or total obstruction
 Consider induction FOLFOX
 ChemoRT (55.8 – 59.4 Gy + capecitabine or 5-FU) → resection (if possible)
 At the time of resection, consider IORT or brachytherapy boost for gross residual
disease
 All patients should receive adjuvant FOLFOX or CAPEOX as tolerated.

16. CRITERIA OF UNRESECTABILITY
1. Broad, diffuse involvement of the proximal sacrum (S1 or higher)
2. Diffuse circumferential pelvic sidewall involvement
3. Extension through the sciatic foramina
4. Encasement of the sciatic nerve
5. Encasement of external iliac vessels
6. Encasement of bilateral ureter

17. ALGORITHM FOR MANAGEMENT OF T4 RECTAL CANCER

18. PRE-OP RT + SURGERY VS SURGERY ALONE
• Resectable rectal cancer
Plan for Surgery with TME Plan for Surgery with out TME
Dutch TME study (Kapiteijn NEJM 2001, Peeters JCO 2005,
Peeters Ann Surg 2007, van Gijn Lancet Oncol 2011):
Swedish Rectal Cancer Trial (NEJM 1997; Folkesson
JCO 2005)
• Phase III trial, 1861 patients
• pre-op RT (25 Gy in 5 fx)
• Pre-op RT improved 5-year LR (5.6% vs 10.9%) and 10-
year LR (5% vs 11%).
• Pre-op RT had no effect on overall survival (OS).
• Toxicity At 5 years, RT increased fecal incontinence
(62% vs 38%), pad wearing (56% vs 33%), bleeding (11%
vs 3%), and mucous discharge (27% vs 15%).
• Phase III trial, 1168 patients
• pre-op RT (25 Gy in 5 fx)
• Pre-op RT improved 5-year LR (11% vs 27%) and 13-
year LR (9% vs 26%).
• Pre-op RT improves 5-year OS (58% vs 48%) and 13-
year OS (38% vs 30%)

19. PRE-OP SHORT-COURSE VS PRE-OP LONG-COURSE CHEMORT
• Most of the trials failed to show a significant difference between short coarse vs long coarse
chemoRT as these trials had modest sample sizes.
• But in the USA, long-course chemoRT remains favored due to
 Their ability to give concurrent Chemotherapy
 Improved sphincter preservation
 Tumor regression
• Polish (Bujko Br J Surg 2006, Pietrzak Radiother Oncol 2007): Phase III trial
 312 patients
 With T3/4 resectable rectal CA randomized to pre-op RT (25 Gy/5fx) + surgery
vs pre-op chemoRT (50.4 Gy with bolus 5-FU and leucovorin) + surgery.
 Early toxicity was higher in the chemoRT group (18.2% vs 3.2%).
 ChemoRT did not increase OS, LC, or late toxicity compared to short-course RT alone.
 Patients treated with chemoRT were likely to have higher pCR rates and lower pathologic
stage and had lower rates of radial margin involvement.

20. • Polish (Bujko Ann Onc 2016): Phase III. 515 patients
• Randomized to pre-op sequential short-course RT (25 Gy/5 fx) + FOLFOX4
vs pre-op long-course chemoRT (50.4 Gy/28 fx with 5-FU).
• Short-course RT-FOLFOX was associated with
 lower rates of acute toxicity (75% vs 83%; driven by grade I–II toxicity)
 higher rates of R0 resection (77% vs 71%, p = 0.07)
 pCR rates were 16% vs 12% (p = 0.17)
 3-year OS higher with short-course RT (73% vs 65%, p = 0.046);
• DFS, LR, and DM were not different.
• Post-op complication and late complication were not different.

21. • TROG 01.04 (Ngan JCO 2012): Phase III. 326 patients
• T3N0-2 low rectal cancer randomized between shortcourse RT
vs long-course chemoRT.
• 3-year LR rates were nonsignificantly reduced with long-course CRT (7.5% vs 4.4%, p
= 0.24).
• There was no difference in distant recurrence or overall survival.
• Stockholm III (Pettersson BJS 2010, BJS 2015): Phase III. 303 patients
• Randomized to short-course RT (25 Gy/5 fx) and early surgery (within 1 week),
short-course and delayed surgery (after 4–8 weeks),
and long-course RT (50 Gy/2 fx).
• The post-op complication rates were 46%, 40%, and 32% for the arms, respectively (p
= 0.164).
• Among patients receiving short-course RT, patients in the delayed surgery arm had
lower ypT stages, higher rates of pCR (11.8% vs 1.7%), and higher likelihood of tumor
regression (10.1% vs 1.7%).

22. PRE-OP RT VS PRE-OP CHEMORT
French FFCD 9203 (Gerard,
JCO 2006)
EORTC 22921 (Bosset,
JCO 2005, NEJM 2006,
Lancet Oncol 2014)
No. of patients 733 1011
Eligible patients T3-4 N0 resectable T3/4 resectable
Randomisation 1. Pre-op RT (45 Gy/25 fx)
2. pre-op concurrent RT +
bolus 5-FU and LV d1–5
weeks 1 and 5.
All patients had adjuvant 4c of
FU-LV chemo
randomized in 2x2 fashion
to pre-op RT vs pre-op
chemoRT,
adjuvant chemo vs
observation
Favours ChemoRT with Increase pCR, LC, Toxicity Decrease 5yr LRR
Increase pCR
No difference Sphinctor saving surgery, OS DFS, OS

23. PRE-OP VS POST-OP CHEMORT
German Rectal Cancer Study Group
(Sauer NEJM 2004, JCO 2012)
MRC CR07/NCIC-CTG C016
(Sebag-Montefiore Lancet 2009,
Quirke Lancet 2009)
No. of patients 823 patients 1350 patients
Eligible patients T3/4 or N+ Resectable rectal CA
Randomisation 1. pre-op chemoRT (50.4 Gy + 5 FU)
2. post-op chemoRT (54 Gy + 5-FU).
• All patients received an additional
4 cycles of bolus 5-FU
1. Short-course pre-op RT (25
Gy/5fx) + surgery
2. surgery + selective post-op
chemoRT (45 Gy and 5-FU)
Fovours preop RT 1. Improve 5-year LR rate (6% vs
13%)
2. Increased sphincter preservation
(39% vs19%)
3. Decreased grade 3–4 acute and
late toxicity
4. late anastomotic strictures.
1. Reduced 3-year LR (4.4% vs
10.6%)
No difference OS OS

24. POST-OP CHEMO, RT, AND/OR CHEMORT
GITSG 7175 (Thomas
Radiother Oncol
1988)
NSABP R01 (Fisher JNCI 1988) NSABP R02 (Wolmark JNCI
2000)
No. of patients 227 patients 555 patients 694 patients
Eligible patients Dukes’ B2-C Dukes’ B–C (II–III) Dukes’ B–C (II–III)
Post-Op
Randomisation
1. No adjuvant
therapy
2. Chemo alone
3. RT alone
4. Concurrent CTRT.
1. No adjuvant therapy
2. RT (46–47 Gy) alone
3. Chemo (5-FU, semustine,
vincristine)(=MOF) alone
1. Chemo (5-FU/LV vs MOF)
2. CTRT
Fovours 1. CTRT arm
improved 5-year
DFS and OS
1. RT improved LF (16% vs 25%)
2. CT improved DFS (42% vs 30%)
and OS (53% vs 53%) compared
with observation.
1. RT reduced 5-year LF
(8% vs 14%)
2. 5-FU/LV improved DFS
but not OS compared with
MOF.
No difference RT did not improve DFS or OS RT-no difference in DFS or
OS

25. POST-OP CHEMO, RT, AND/OR CHEMORT ,,, CONTINUE….
NCCTG 79-47-51
(Krook NEJM 1991)
Intergroup/NCCTG
(O’Connell NEJM 1994)
Pooled analysis (Gunderson, JCO 2004):
Analysis on NCCTG trials, Int 0144,
NSABP R01, and R02
No. of patients 204 patients 660 patients 3791 patients
Eligible patients T3/4 or LN+ (B2-C) stage II or III
Post-Op
Randomisation
1. RT (45–50.4 Gy)
2. ChemoRT (bolus 5-
FU).
2x2 randomization of bolus
vs infusional 5-FU during
radiation and 5-FU ±
semustine.
• Increasing T and N stage negatively
impacted survival
• But N stage alone does not determine
survival.
• For intermediate-risk patients,Post-op
chemo improve OS after surgery (to ~85%),
similar to post-op chemoRT.
• For moderately high-risk and highrisk
patients, DFS, OS, and LF tended to be
better with chemoRT than with chemo
alone.
Fovours CTRT improved LF (14%
vs 25%), DM, DFS, and
OS (58% vs 48%) vs RT
alone.
1. Infusional 5-FU
improved 4-year OS
(70% vs 60%) and
relapse-free rate (63%
vs 53%).
2. No benefit with
Semustine

26. DATA FROM THE RECTAL CANCER POOLED ANALYSES
(GUNDERSON, JCO 2004)
• Substaging for TNM stage III patients
• Three separate prognostic subgroups of lesions exist
1. Intermediate risk T1-2N1
2. Moderately high risk T1-2N2 and T3N1
3. High risk T3N2 and T4N1-2

27. SURGERY
• Goal of curative intent surgery is complete resection of the tumor and rectum en bloc
with any involved organs or structures, with preservation of at least reasonable
function and quality of life.
• Most significant predictive factors associated with improved survival in locally
advanced patients are
 Absence of distant metastatic disease
 Ability to achieve an R0 resection margin.
• For nodal sampling to be accurate, it is important to obtain and examine at least 12
lymph nodes in radical colon and rectum resections in patients who undergo surgery
for cure.

28. TME (TOTAL MESORECTAL EXCISION)
• The historic local recurrence rate for T3-4 or N1 rectal cancer is ~25%.
• This is improved with better surgery (i.e., total mesorectal excision [TME], 10year LR 11% [Dutch
TME study]).
• TME got its wide spread attention after herald’s article A new approach to rectal cancer.
(Heald RJ, Br J Hosp Med. 1979 Sep; 22(3):277-81.)
• Goal of this surgery-
1. En bloc resection of the rectal cancer with a complete pararectal lymph node dissection as
contained in the mesorectum.
2. Any additional lymphadenopathy may also be dealt with depending on the stage of the
tumor.
• To reach this goal, the lateral dissection of the rectum must not breech the fascia propria of the
rectum, which stays outside the mesorectum.

29. • In TME the mesorectal fascia (MRF) is the resection plane and it has to be tumor-free.
• A distance of the tumor to the mesorectal fascia of ⩽1 mm is regarded as not suitable for
TME and is called an Involved MRF.
• This means that the tumor has to be downstaged before TME is possible.

30. THE BEYOND TME COLLABORATIVE
• Commonly involved structures or organs can include the genitourinary organs, pelvic
sidewall or sacrum, pelvic floor or anal musculature, and small bowel.
• Multiple organs are involved in approximately 25% of the cases.
• Primary rectal cancer beyond total mesorectal excision planes (PRC-bTME) and
locally recurrent rectal cancer (RRC) require exenterative-type surgical resection
beyond conventional total mesorectal excision (TME) planes.

31. LAR VS APR
• Abdominoperineal resection (APR) (Miles’ operation): tumoral tissue +
entire rectum + Anal canal are dissected and a permanent colostomy is opened.
• Lower anterior resection (LAR): tumoral tissue + the upper parts of the rectum
are dissected and a permanent colostomy is not opened.
• Studies by Paty et al and Vernava and Moran et al suggest that there is no difference in
survival or recurrence rates with a < 2-cm distal margin as compared with a > 2-cm
margin.
• Study by Vernava and Moran clearly demonstrated reduced survival rates and increased
rates of anastomotic recurrence with distal margins ≤ 8 mm,
• Several series have shown that the distal intramural spread of cancer is rarely > 1 cm
(Kirwan et al, Williams et al, and Grinnell).
• Recommendation if the estimated distal margin of resection is < 1 cm from the sphincter
mechanism, then APR should be chosen to avoid leaving residual disease behind.
• Also, patients who have problems with incontinence should undergo an abdominoperineal
resection (APR).

32. CONVENTIONAL RADIOTHERAPY PLANNING
• Simulation is performed in either the supine or the prone position.
• The prone position with a full bladder may decrease the small intestinal dose.
• Rectal and vaginal markers are useful during simulation.
• The perineal scar should be wired after APR.
• Portals:
 4 fields (AP, PA, two lateral fields)
 3 fields (PA, two lateral fields)
 2 fields (AP,PA)

33. ANTERIOR–POSTERIOR FIELDS:
• Superior: between levels L5 and S1
• Inferior: preoperative, tumor + 3 cm; If LARbelow obturator foramen or tumor + 3 cm
If APR includes perineal scar
• Lateral: bony pelvis +2 cm
Lateral fields:
• Superior– Inferior: same as anterior–posterior fields
• Anterior: ≤T3 tumors, posterior to pubic symphysis
T4 tumors, anterior to pubic symphysis
• Posterior: Includes sacrum
Boost field →
• Tumor/tumor bed + 2–3 cm. Sacral concavity should be included in lateral fields.

35. DOSE:
• Preoperative radiotherapy:
 Short course: 25 Gy in 5 daily fractions of 5 Gy given in 1 week.
 Long course:
1. Phase 1
 45 Gy in 25 fractions, 1.8 Gy per fraction per day, given in 5 weeks.
2. Phase 2 (optional)
 5.4Gy in 3 fractions, 1.8 Gy per fraction per day
• Postoperative radiotherapy:
1. Phase 1
 45 Gy in 25 fractions, 1.8 Gy per fraction per day, given in 5 weeks.
2. Phase 2 (optional)
 5.4-9 Gy in 3-5 fractions, 1.8 Gy per fraction per day

36. CONFORMAL TREATMENT PLANNING
• Simulation and Daily Localization:
• Most patients are to be treated with standard 3D conformal radiotherapy To
simulate in the prone position with the use of a belly board for anterior displacement
of the bowel.
• If IMRT is planned Supine position in a body mold or other immobilization device
To ensure more accurate setup reproducibility.
• A radiopaque marker should be placed on the anus.
• CT simulation with ≤3 mm thickness with IV contrast  To delineate the pelvic blood
vessels and gross tumor volume.
• Oral contrast may be helpful To identify the small bowel  Important organ at risk
• If PET/CT is available, a PET/CT fusion should be obtained to aid in target volume
delineation.

37. • For patients that underwent preoperative MRI, MR fusion could also aide with
treatment planning.
• Bladder filling/emptying may be considered, especially if IMRT is used.
• A full bladder may keep bowel from migrating into the pelvis. But an empty bladder
may be more reproducible.
• Daily orthogonal kilovoltage images and weekly cone beam CT scans to be done 
(to assess soft tissue) to verify alignment during treatment.
• Cone beam CTs may be done more frequently if there is significant variation in
bladder and/or rectal filling.

38. ORGAN AT RISK CONSTRAINTS:
• Peritoneal cavity /bowel bag
V45<195cc
• Femoral head V40 < 40%
• Bladder V40 < 40%
Plan Assessment:
• Ideally, at least 95 % of each PTV should
receive 100 % of the prescription dose.
• The maximum dose in the PTV should be
<110 %.

39. TARGET VOLUMES IN PRE OP SETTING
• GTV
 Primary (GTV-P): All gross disease on physical examination and imaging
 Regional nodes (GTV-N): all visible perirectal and involved iliac nodes (include any lymph
node in doubt as GTV in the absence of a biopsy)
• CTV-high risk (CTV-HR)
 CTV-HR should cover the GTV-P and GTV-N with 1.5–2-cm superior and inferior margin
 But exclude the uninvolved bone, muscle, or air.
 Include the entire rectum, mesorectum, and presacral space. Any visible mesorectal
nodes on CT and PET should also be included.
 A 1–2-cm margin around gross tumor invasion into adjacent organs should be added.
 Anteriorly, a margin of 1–1.5 cm should be added into bladder to account for changes in
bladder and rectal. (Myerson et al. 2009 ; Daly et al. 2011 )

40. • CTV-standard risk (CTV-SR)
 Should cover the entire mesorectum
 Right and left internal iliac lymph nodes for T3 tumors.
 Right and left external iliac lymph nodes for T4 tumors with anterior organ involvement
should also be included.
 A 1–2-cm margin in adjacent organs with gross tumor invasion should be added for
T4 lesions
 Superiorly, the entire rectum and mesorectum should be included (usually up to
L5/S1) and at least 2-cm margin superior to gross disease, whichever is most
cephalad
 Inferiorly, the CTV should extend to the pelvic floor or at least 2 cm below the gross
disease, whichever is most caudal

41. • CTV-standard risk (CTV-SR) continue…
 To cover the iliac lymphatics, a 0.7-cm margin around the internal iliac vessels should be
drawn (excluding the muscle and bone) (Myerson et al. 2009 ; Taylor et al. 2005 )
 To cover the external iliac nodes (for T4 lesions), an additional 1-cm margin anterolaterally
around the vessels is needed.
Any adjacent small nodes should be included. (Myerson et al. 2009 ; Taylor et al. 2005 )
 Anteriorly, a margin of 1–1.5 cm should be added into bladder to account for changes in
bladder and rectal filling. (Myerson et al. 2009 ; Daly et al. 2011 )
 A 1.8-cm-wide volume between the external and internal iliac vessels is needed to cover
the obturator nodes. (Taylor et al. 2005 )
• Planning target volume (PTV)
 Each CTV should be expanded by 0.5–1 cm, depending on the physician’s comfort level
with setup accuracy, frequency of imaging, and the use of IGRT

42. A patient with T3N1 rectal adenocarcinoma.

45. 00
T4N0 rectal adenocarcinoma

48. • In the preoperative setting
 the most common prescription dose is 1.8 Gy/fraction to 45 Gy to the PTV-SR
 1.8 Gy/fraction to 50.4 Gy to the PTV-HR

49. TARGET VOLUME IN POST OP SETTING
• Target volume delineation in the postoperative setting is similar to the preoperative
setting.
• However, in the case of an abdominoperineal resection, the entire surgical bed
extending inferiorly to the level of the perineal scar needs to be included.
• CTV (positive margin or gross disease)
Should include
 area of known microscopically involved margin, or
 macroscopic residual disease
 plus a 1–2-cm margin
(exclude the uninvolved bone, muscle, or air)
• CTV-high risk (CTV-HR)
 Should include the entire remaining rectum (if applicable), mesorectal bed, and
presacral space
 Exclude uninvolved bone, muscle, or air.
 Coverage of the entire presacral space and mesorectum should be considered

50. • CTV-standard risk (CTV-SR)
 Should cover the entire mesorectum and right and left internal iliac lymph nodes for
T3 tumors.
 The right and left external iliac lymph nodes for T4 tumors with anterior organ
involvement should also be included
 Superiorly, the entire remaining rectum and mesorectum should be included (usually
up to L5/S1) and at least 1-cm margin superior to the anastomosis, whichever is most
cephalad
 Inferiorly, the CTV should extend to the pelvic fl oor or at least 1 cm below the
anastomosis or rectal stump, whichever is most caudad.
 If patient is status post an abdominoperineal resection, the surgical bed extending
down to the perineal scar should be included.
 The scar should be outlined with a radiopaque marker.

51. • CTV-standard risk (CTV-SR) continue..
 To cover the iliac lymphatics, a 0.7-cm margin around the internal iliac vessels should be
drawn (excluding muscle and bone) (Myerson et al. 2009 ; Taylor et al. 2005 )
 To cover the external iliac nodes (for T4 lesions), an additional 1-cm margin anterolaterally
around the vessels is needed.
Any adjacent small nodes should be included (Myerson et al. 2009 ; Taylor et al. 2005 )
 Anteriorly, a margin of 1–1.5 cm should be added into bladder to account for changes in
bladder and rectal filling (Myerson et al. 2009 ; Daly et al. 2011 )
 A 1.8-cm-wide volume between the external and internal iliac vessels is needed to cover
the obturator nodes (Taylor et al. 2005 )
 For tumors that extend inferiorly to or inferior to the dentate line, the bilateral inguinal
nodes should be included
• Planning target volume (PTV) 
 Each CTV should be expanded by 0.5–1 cm, depending on the physician’s comfort level
with setup accuracy, frequency of imaging, and the use of IGRT

52. THE RTOG ANORECTAL CONTOURING ATLAS (MYERSON ET
AL. 2009 )
• It provides a detailed consensus contouring descriptions of three elective CTVs that should
be considered in patients with rectal and anal cancers.
• CTV-A includes the perirectal, presacral, and internal iliac regions
(should be covered in all patients with rectal cancer)
• CTV-B includes the external iliac nodes
(covered only in rectal cancer cases with T4 disease or for primary rectal tumors that
extend inferiorly into the distal anal canal).
• CTV-C includes the inguinal region
(should be considered in rectal cancer cases that extend into the distal anal canal).

53. TARGET VOLUMES: CTVA
• Inferior
 At least 2 cm caudad to gross disease, including coverage of the entire mesorectum
to the pelvic floor
• Posterior and lateral
 Lateral pelvic sidewall musculature or, where absent, the bone
• Anterior
 ~1 cm into the posterior bladder and the posterior portion of the internal obturator
vessels
• Superior
 Primary: the rectosigmoid junction or 2 cm proximal to the superior extent of
macroscopic disease
 LN: where the common iliac vessels bifurcate into external/internal iliacs (approximate
boney landmark: sacral promontory)

55. 3DCRT IMRT
GI toxicity 62% 32%
Diarrhoea 48% 23%
Enteritis 30% 10%
No difference in pCR rates

56. CHEMO DURING RADIATION
• Concurrent infusional 5-FU-based therapy is given as 5-FU 225 mg/m2 over 24 hrs 7
days/week during RT. (IJROBP 1998 Sep 1;42(2):319-24; Videtic GM et al.)
• The recommended doses for single-agent capecitabine as part of chemoradiation
regimens are:
 825 mg/m2 twice daily given continuously (i.e. 7 days/week)
 900 mg/m2 twice daily given on weekdays (i.e. 5 days/week).
• When combined with oxaliplatin (130 mg/m2 days 1 and 29), the recommended dose
of capecitabine is
 625 mg/m2 twice daily given continuously (i.e. 7 days/week)
 825 mg/m2 twice daily given on weekdays (i.e. 5 days/week).
(Annals of Oncology, Volume 17, Issue 3, 1 March 2006, Pages 361–371)

57. INTERPRETATION:
 Capecitabine could replace fluorouracil in adjuvant or neoadjuvant
chemoradiotherapy regimens for patients with locally advanced rectal cancer.

58. CHEMOTHERAPY IN RECTAL CANCER
• Some drugs commonly used for colorectal cancer include:
1. 5-Fluorouracil (5-FU)
2. Capecitabine (Xeloda), which is in pill form. Once in the body, it is changed to 5-FU
when it gets to the tumor site.
3. Irinotecan (Camptosar)
4. Oxaliplatin (Eloxatin)
5. Trifluridine and Tipiracil (Lonsurf), a combination drug in pill form
6. Leucovorin
• In most cases, 2 or more of these drugs are combined, which makes them work
better.
• Most are given along with targeted therapy, can often help people with advanced
colon or rectal cancers live longer.

59. TARGETED THERAPY
• Anti-VEGF VEGF is a protein that helps tumors for Angiogenesis
1. Bevacizumab (Avastin)
2. Ramucirumab (Cyramza)
3. Ziv-aflibercept (Zaltrap)
• Drugs that target cells with EGFR 
 EGFR is a protein that helps cancer cells grow.
 These drugs don't work in colorectal cancers that have mutations (defects) in
the KRAS, NRASor BRAF gene.
1. Cetuximab (Erbitux)
2. Panitumumab (Vectibix)

60. • Other targeted therapy drugs
1. Regorafenib (Stivarga)  a kinase inhibitor.
 Kinases are proteins on or near the surface of a cell that carry important signals to the
cell’s control center.
 Regorafenib blocks several kinase proteins that either help tumor cells grow or help
form new blood vessels to feed the tumor.
 Blocking these proteins can help stop the growth of cancer cells.
 This drug is used to treat advanced colorectal cancer, typically when other drugs are
no longer helpful.
 It's taken as a pill.

61. IORT
• Intra-operative radiation therapy (IORT) delivers a concentrated dose of radiation
therapy to a tumor bed during surgery.
• Patient must be a surgical candidate in order to be eligible for IORT.
• 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.

62. IORT
• Dose:
 Ro resection:- 7.5-10 Gy
 R1 resection:- 10-12.5 Gy
 R2 resection:- 15-20 Gy

63. PREOPERATIVE RT
Advantages:
• Large and advanced tumors may be downsized during radiation and the chances of
resection may also increase.
• Tumor cells that may be implanted into the surgical region are eradicated.
• Tumor cells that may enter circulation are eradicated and distant metastatic risk
decreases.
• Tumor cells are more oxic before surgery and sensitive to radiation.
Disadvantages:
• Overtreatment of early or metastatic tumors
• Delayed surgery and risk of stage advancement
• Postoperative perineal complications may increase

64. POSTOPERATIVE RT
Advantages:
• There is no overtreatment with radiation due to pathological confirmation of exact
stage.
• RT field is accurately designed since tumoral extension is known.
Disadvantages:
• RT efficacy may decrease due to hypoxic medium after surgery.
• Postoperative adhesions may increase intestinal side effects of RT.
• Field size increases after APR due to the inclusion of the perineal scar in the RT portal.

65. TAKE HOME MESSAGE
• Locally advanced rectal cancers may be defined as T4 or node-positive lesions.
• Baseline CEA preoperatively is necessary.
• DRE is an important part in Ca Rectum to determine distance of tumor from anal
verge and sphincter function.
• Both ERUS and MRI are accurate in predicting T stage.
• Treatment of Rectal cancer is based on multi-modality management.
• In resectable stage II and III rectal cancer, pre operative CTRT should be consider in
all patients, which has improved LC as compare to pre-op RT alone or post-op CTRT.
• Stage II and III post op rectal cancer can be treated with chemotherapy CTRT
chemotherapy

66. • TME is better than NON-TME surgery
• Trials failed to show a significant difference between short coarse vs long coarse RT,
but long coarse CTRT may be prefered.
• It is important to obtain and examine at least 12 lymph nodes in radical colon and
rectum resections.
• IMRT is better than 3DCRT due to low toxicity. But pCR are similar.
• Dose of capecitabine in CTRT 825 mg/m2 twice daily given continuously (i.e. 7
days/week)
• Intra-operative radiation therapy (IORT) delivers a concentrated dose of radiation
therapy to a tumor bed during surgery.

67. Thank You