1. Which preoperative regimen in rectal cancer?
Karin Haustermans

4. Initial staging of rectal cancer
Parameter
Method of choice
1° choice
equivalent (if 1°choice is not available)
2° choice
location
MRI
rigid protoscopy
flexible endoscopy
T-stage T1
ERUS T2 T3 T4
(ERUS)
multidect. CT (high and mid rectum)
sphincter infiltration
mesorectal fascia involvement
N-stage
multidect. CT
Full colonoscopy
CT scan of the thorax and the abdomen
ESMO guidelines 2011

5. Location of the primary tumor
Rigid proctoscopy
MRI
low
up to 5 cm
up to 4 cm
mid
from > 5 to 10 cm
from > 4 to 8 cm
high
from > 10 up to 15 cm
from > 8 up to 12 cm
reference level
anal verge
anorectal junction
ESMO guidelines 2011

6. Parameters defining treatment strategy
Local tumor extension
Location of the tumor
N-stage
MRF involvement
Extra-mural invasion
Venous invasion

7. Tailor treatment according to
Initial staging
MRF involvement
Treatment decision by a multidisciplinary team

8. Treatment strategy in rectal cancer
Resectable
Very early
T1sm1, sm2
Resectable
Non resectable

9. Early rectal cancer: risk assessment
Low-risk early rectal cancer
High-risk early rectal cancer
Well or moderately differentiated
Poorly differentiated
No V or LV invasion
Signet ring
Kikuchi Sm1, possibly Sm2
Kikuchi Sm3, possibly Sm2
Haggitt 1-3
Positive resection margin
Stalk (steel) pedunculated, sessile polyps Kikuchi classification
1 to 3 % risk of LN 8%
23%

10. ESMO guidelines 2012 rectal cancer (M0) follow up
postop CT analogue colon cancer
(6months)
risk factors
(crm+, N+, perforation) no
yes
≤T4a
optional
postop (C)RT
cT1 sm3 – T2
localization very low rectum/ APR probably required
postop CT (4.5-6months) or post-op CRT
T3/4 MRF+ positive lateral LN
preop CRT
postop CRT
T4b
>cT1 sm2 N0
preop (C)RT
localization upper
third of rectum
Nothing or preop RT (5x5) or CRT
T3a/b N0, MRF-
resection (TME)
preop RT (5x5) or CRT
localization middle/lower third of rectum
>T3b MRF-
local excision (TEM) no
resection (TME)
(or CRT)
yes
cT1 sm1/2 N0
poor prognostic factors
(>sm2, >G1, PNI, V1)
ESMO guidelines 2012

11. Treatment strategy in rectal cancer
Resectable
Very early
T1sm1, sm2
Resectable
Non resectable
In non resectable rectal cancer, CRT is the standard
Preoperative CRT

12. rectal cancer (M0)
follow up
postop CT analog colon cancer
(6months)
risk factors
(crm+, N+, perforation) no
yes
local excision (TEM)
resection (TME)
(or CRT)
≤T4a
optional
postop (C)RT
Nothing or preop RT (5x5) or CRT
T3a/b N0 MRF-
cT1 sm3 – T2
preop RT (5x5) or CRT
postop CT (4.5-6months) ior post-op CRT
>T3b MRF-
postop CRT
cT1 sm1/2 N0
T4b
>cT1 sm2 N0
preop (C)RT
localization upper
third of rectum
poor prognostic factors
(>sm2, >G1, PNI, V1)
resection (TME)
localization middle/lower third of rectum
localization very low rectum/ APR probably required
T3/4 MRF+ positive lateral LN
preop CRT
T3 rectal cancer grouped by mesorectal extension depth (T3a, <1 mm; T3b, 1-5 mm; T3c, 5-15 mm; T3d, >15 mm).
ESMO guidelines 2012

13. Treatment strategy in rectal cancer
Resectable
Very early
T1sm1, sm2
Resectable
Non resectable
Preoperative (C) RT?

14. Resectable rectal cancer: high
SURGERY
PME at least 5 cm below the lower tumor border
(tumor deposits) OR
TME
The cornerstone of upper rectal cancer treatment remains surgery. Because tumor deposits can occur up to 5 cm below the primary tumor, this resection should be extended to this level. Concerning perioperative treatment recommendations for stage II or III upper third rectal cancers differ widely because of insufficient data.

15. Resectable rectal cancer: high
Swedish Rectal Cancer Trial
Local recurrence rates according to tumor height
RT + surgery
surgery alone
Tumor height (cm)
N° pts/total %
p value
≤ 5.0
14/136 10
39/146 27
0.003
6 – 10
16/185 9
51/198 26
<0.001
≥ 11
10/133 8
13/10-10 12
0.3
Follow-up analyses of the Swedish rectal cancer trial in which patients were randomized to surgery with or without preop RT, demonstrated that preoperative RT 5 x5Gy reduced the number of LR al all three tumor heights, but no statistically significant effect was seen for upper rectal tumors.
Abstract
PURPOSE:
To evaluate the long-term effects on survival and recurrence rates of preoperative radiotherapy in the treatment of curatively operated rectal cancer patients.
PATIENTS AND METHODS:
Of 1,168 randomly assigned patients in the Swedish Rectal Cancer Trial between 1987 and 1990, 908 had curative surgery; 454 of these patients had surgery alone, and 454 were administered preoperative radiotherapy (25 Gy in 5 days) followed by surgery within 1 week. Follow-up was performed by matching against three Swedish nationwide registries (the Swedish Cancer Register, the Hospital Discharge Register, and the Cause of Death Register).
RESULTS:
Median follow-up time was 13 years (range, 3 to 15 years). The overall survival rate in the irradiated group was 38% v 30% in the nonirradiated group (P = .008). The cancer-specific survival rate in the irradiated group was 72% v 62% in the nonirradiated group (P = .03), and the local recurrence rate was 9% v 26% (P < .001), respectively. The reduction of local recurrence rates was observed at all tumor heights, although it was not statistically significant for tumors greater than 10 cm from the anal verge.
CONCLUSION:
Preoperative radiotherapy with 25 Gy in 1 week before curative surgery for rectal cancer is beneficial for overall and cancer-specific survival and local recurrence rates after long-term follow-up.
Folkesson et al, JCO 2005
Preop RT did not benefit in upper rectal cancer  R/ colon cancer ?

16. Resectable rectal cancer: high
Dutch TME trial
Univariate analysis of 5-year LRR among 1748 eligible patients who underwent TME
RT +TME
TME alone
Distance from
anal verge (cm)
N° at risk
LR at 5y
p value
≥ 10.1
262
3.7
271
6.2
0.122
372
350
13.7
<0.001
≤ 5.0
237
10.7
253
12.0
0.578
In the Dutch TME trial, the preoperative radiotherapy group had a lower local recurrence rate at 5 years compared with the surgery-alone group (5,6 vs 10,9%);
In a subanalysis, preop RT did not benefit the subset of patients with upper rectal cancer. This is an argument to treat rectal cancers of the upper third like colon cancers.
Follow-up analyses of the Swedish Rectal Cancer trial in which patients were randomized to surgery with or without preoperative RT (5x5Gy), demonstrated that preoperative RT reduced the number at all three tumour heights although the difference was not statistically significant for tumors in the upper third of the rectum.
OBJECTIVE:
To investigate the efficacy of preoperative short-term radiotherapy in patients with mobile rectal cancer undergoing total mesorectal excision (TME) surgery.
SUMMARY BACKGROUND DATA:
Local recurrence is a major problem in rectal cancer treatment. Preoperative short-term radiotherapy has shown to improve local control and survival in combination with conventional surgery. The TME trial investigated the value of this regimen in combination with total mesorectal excision. Long-term results are reported after a median follow-up of 6 years.
METHODS:
One thousand eight hundred and sixty-one patients with resectable rectal cancer were randomized between TME preceded by 5 x 5 Gy or TME alone. No chemotherapy was allowed. There was no age limit. Surgery, radiotherapy, and pathologic examination were standardized. Primary endpoint was local control.
RESULTS:
Median follow-up of surviving patients was 6.1 year. Five-year local recurrence risk of patients undergoing a macroscopically complete local resection was 5.6% in case of preoperative radiotherapy compared with 10.9% in patients undergoing TME alone (P < 0.001). Overall survival at 5 years was 64.2% and 63.5%, respectively (P = 0.902). Subgroup analyses showed significant effect of radiotherapy in reducing local recurrence risk for patients with nodal involvement, for patients with lesions between 5 and 10 cm from the anal verge, and for patients with uninvolved circumferential resection margins.
CONCLUSIONS:
With increasing follow-up, there is a persisting overall effect of preoperative short-term radiotherapy on local control in patients with clinically resectable rectal cancer. However, there is no effect on overall survival. Since survival is mainly determined by distant metastases, efforts should be directed towards preventing systemic disease.
Peeters et al, Ann Surg 2007

17. LR by distance from the anal verge: MRC trial
3yr 5yr
HR (95%CI)
Distance from anal verge
Events/N
PRE
POST
0-5cm
29/444 6% 7%
10%
17%
2.0
(0.97,4.15)
>5-10cm
39/674 5%
16%
2.14
(1.14,4.02)
>10-15cm
15/204 1%
19%
4.94
(1.79,13.64)

18. Resectable rectal cancer: mid
No benefit in LC comparing 5x5 Gy to CRT
Abstract
PURPOSE To compare the local recurrence (LR) rate between short-course (SC) and long-course (LC) neoadjuvant radiotherapy for rectal cancer. PATIENTS AND METHODS Eligible patients had ultrasound- or magnetic resonance imaging-staged T3N0-2M0 rectal adenocarcinoma within 12 cm from anal verge. SC consisted of pelvic radiotherapy 5 × 5 Gy in 1 week, early surgery, and six courses of adjuvant chemotherapy. LC was 50.4 Gy, 1.8 Gy/fraction, in 5.5 weeks, with continuous infusional fluorouracil 225 mg/m(2) per day, surgery in 4 to 6 weeks, and four courses of chemotherapy. Results Three hundred twenty-six patients were randomly assigned; 163 patients to SC and 163 to LC. Median potential follow-up time was 5.9 years (range, 3.0 to 7.8 years). Three-year LR rates (cumulative incidence) were 7.5% for SC and 4.4% for LC (difference, 3.1%; 95% CI, -2.1 to 8.3; P = .24). For distal tumors (< 5 cm), six of 48 SC patients and one of 31 LC patients experienced local recurrence (P = .21). Five-year distant recurrence rates were 27% for SC and 30% for LC (log-rank P = 0.92; hazard ratio [HR] for LC:SC, 1.04; 95% CI, 0.69 to 1.56). Overall survival rates at 5 years were 74% for SC and 70% for LC (log-rank P = 0.62; HR, 1.12; 95% CI, 0.76 to 1.67). Late toxicity rates were not substantially different (Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer G3-4: SC, 5.8%; LC, 8.2%; P = .53). CONCLUSION Three-year LR rates between SC and LC were not statistically significantly different; the CI for the difference is consistent with either no clinically important difference or differences in favor of LC. LC may be more effective in reducing LR for distal tumors. No differences in rates of distant recurrence, relapse-free survival, overall survival, or late toxicity were detected.
Ngan et al, JCO 2012

19. Resectable rectal cancer: low
1. 5x5 Gy or CRT
2. TME (low anterior) or
APR if
- no adequate distal clearance
- poor sphincter function
- “difficult” pelvic anatomy
“difficult pelvic anatomy”= IBD, narrow pelvis, obese patients
Sphincter preservation?

20. Preoperative RCT Preoperative 5 x 5Gy (+) + (+)
Biologic effective dose
Combination with CT
Downsizing
Acute toxicity
Late toxicity
Compliance
Costs +
(+)

21. Resectable rectal cancer: low
Sphincter preservation?
Polish Trial
Resectable T3-T4
Inferior tumoral margin palpable
5 x 5 Gy
n=155 (%)
50.4 Gy + CT
n = 157 (%)
Sphincter preserving resection
95 (61)
91 (58)
Abdomino)perineal resection
50 (32)
56 (36)
Laparatomy, no resection
8 (5)
5 (3)
No surgery
2 (1)
p = 0.57
Polish trial
No statistically significant difference in sphincter preservation rate despite significant downsizing. Surgeons did not perform more sphincter sparing surgery in the RCT group.
Explanation: more patients with lower tumors randomized in CRT arm by chance OR surgeons violated the rule that the decision on sphincter preservation had to be based on the tumor status at the time of surgery, not on the pretreatment volume.
BACKGROUND AND PURPOSE:
The aim was to verify whether preoperative conventionally fractionated chemoradiation offers an advantage in sphincter preservation in comparison with preoperative short-term irradiation.
PATIENTS AND METHODS:
Patients with resectable T3-4 rectal carcinoma without sphincters' infiltration and with a lesion accessible to digital rectal examination were randomised into: preoperative 5x5Gy short-term irradiation with subsequent total mesorectal excision (TME) performed within 7 days or chemoradiation to a total dose of 50.4Gy (1.8Gy per fraction) concomitantly with two courses of bolus 5-fluorouracil and leucovorin followed by TME after 4-6 weeks. Surgeons were obliged to base the type of operation on the tumour status at the time of surgery.
RESULTS:
Between 1999 and 2002, 316 patients from 19 institutions were enrolled. The sphincter preservation rate was 61% in the 5x5Gy arm and 58% in the radiochemotherapy arm, P = The tumour was on average 1.9 cm smaller (P < 0.001) among patients treated with chemoradiation compared with short-term schedule. For patients who underwent sphincter-preserving procedure, the surgeons generally followed the rule of tailoring the resection according to tumour downsizing; the median distal bowel margin was identical (2 cm) for both randomised groups. However, in the chemoradiation group, five patients underwent abdominoperineal resection despite clinical complete response.
CONCLUSIONS:
Despite significant downsizing, chemoradiation did not result in increased sphincter preservation rate in comparison with short-term preoperative radiotherapy. The surgeons' decisions were subjective and based on pre-treatment tumour volume at least in clinical complete responders.
Bujko et al, Radiother Oncol 2004
No statistically significant difference in sphincter preservation rate p= 0.57
despite significant tumor downsizing (26 vs 45 mm, p= <0.001)

22. Resectable rectal cancer: low
Sphincter preservation?
Lyon R96-02 trial
88 pts
T2-T3 lower rectal
EBRT
39 Gy/3 Gy
EBRT
39 Gy/3 Gy +
CXRT boost 85 Gy in 3 fr.
10-year results of the Lyon R96-02 trial
There was a significant higher rate of colostomy in patients without the contact radiotherapy boost. Ten year local recurrence, DFS and OS was not statistically different.
PURPOSE:
To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial.
METHODS AND MATERIALS:
A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months.
RESULTS:
The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in the EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR ≥ 50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR ≥ 50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR ≥ 50%, and 77% for patients with CR <50% (p = 0.014).
CONCLUSION:
In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.
Ortholan et al, IJROBP 2012

23. rectal cancer (M0)
follow up
postop CT analogue colon cancer
(6months)
risk factors
(crm+, N+, perforation) no
yes
local excision (TEM)
resection (TME)
(or CRT)
≤T4a
optional
postop (C)RT
cT1 sm3 – T2
localization very low rectum/ APR probably required
postop CT (4.5-6months) or post-op CRT
T3/4 MRF+ positive lateral LN
preop CRT
postop CRT
cT1 sm1/2 N0
T4b
>cT1 sm2 N0
preop (C)RT
localization upper
third of rectum
poor prognostic factors
(>sm2, >G1, PNI, V1)
Nothing or preop RT (5x5) or CRT
T3a/b N0 MRF-
resection (TME)
preop RT (5x5) or CRT
localization middle/lower third of rectum
>T3b MRF-
T3 rectal cancer grouped by mesorectal extension depth (T3a, <1 mm; T3b, 1-5 mm; T3c, 5-15 mm; T3d, >15 mm).
ESMO guidelines 2012

24. Response to pre-op CRT
Good responders
~30% pCR after CRT
Organ preservation ?
Poor responders
Standard CRT insufficient
Treatment-intensification
Is there a role for treatment intensification in rectal cancer?
Pre-op chemoRT results in a reduction of local recurrences, with no or a minor improvement in progression free and overall survival.
In an attempt to improve outcome, many investigators have explored different strategies: varying the method of 5-FU administration (bolus, intermittent or continous and oral fluoropyrimidines), radiotherapy dose-escalation and the addition of a second chemotherapeutic.
pCR = pathological complete response, defined as the absence of cancer cell sin the resected specimen, has been used as early end point to assess the efficacy of the schedule. However, it should be noted that only a few reports on long-term outcome are available and there are no large prospective randomized control trials comparing such approaches

25. Different cytotoxic drugs
STAR-01
ACCORD 12/0405
CAO/ARO/AIO-04
PETACC-6
Year
11/2003-
08/2008
11/2005-
07/2008
07/2006-
02/2010
11/2008-
9/2011
Number of patients
747
598
1265
1094
Primary endpoint OS
pCR
DFS
3y DFS
Preop CRT
5-FU 225mg/m² Gy vs
5-FU 225mg/m²
OX 60mg/m²weekly Gy
Cape 1600mg/m² + 45 Gy
Cape 1600mg/m²
OX 50mg/m²weekly + 50 Gy
5-FU Gy
5-FU/OX
Cape 1650mg/m² Gy
Cape 1650mg/m² + OX 50mg/m²weekly Gy
Cum OX preop
360mg/m²
250mg/m²
200mg/m²

26. Different cytotoxic drugs
STAR-01
ACCORD 12/0405
CAO/ARO/AIO-04
PETACC-6
Adjuvant chemo
5-FU based
Center’s preference
mFOLFOX
Cape 2000mg/m² d1-15 q3w vs
Cape 2000mg/m² + OX 130mg/m² q3w
Main (first) results
pCR not improved
More toxcicity with OX
pCR n.s. improved
More toxciity with OX
pCR improved
No more toxicity
pCR, R0, sphincter preservation not improved
Compliance OX preop
66% received all OX cycles
Dose mod in 59%
80% vs 85%
27% <90% of the dose
Full dose RT
92% vs 84%
100% vs 87%
95% vs 94%
98% vs 96%

27. RAPIDO trial
Rectal Cancer And Pre-operative Induction Therapy Followed by Dedicated Operation trial
Randomized multicentre Phase III study
Pts with primary high risk rectal cancer
N = 885
Arm A = control
 Long course chemo-RT
(5 weeks)
Surgery
(adjuvant chemo)
Arm B = exp
 5 x 5Gy
 6 cycles of capecitabine + oxaliplatin
Surgery
Start date: June 2011 – currently recruiting
Estimated Primary Completion Date: June 2016 (final data collection date for primary outcome measure)
Primary outcome measure: DFS (time frame: 3y)
Secondary outcome measures: OS, CRM negative rate, pCR rate, short and long-term toxicity, surgical complications, QoL
Estimated enrollment n = 885
Estimated completion date: June 2019
Collaborators: UMC Groningen, Karolinska UH, Leiden UMC, Uppsala UH
Patients will be randomized between an experimental arm (B) in which short course 5 x 5Gy radiation scheme is followed by six cycles of combination chemotherapy (capecetabine and oxaliplatin) and surgery and a control group (A) with long course chemoRT followed by surgery. In arm A adjuvant chemotherapy is allowed according to the local protocol of the institution. In both groups the rectal tumor will be removed by TME surgery or more extensive surgery if required because of tumor extent.

28. RT dose escalation Danish Colorectal Cancer Group
Dose-escalation randomized phase III trial
Pts with resectable T3 and T4 tumors; CRM ≤ 5mm on MRI
Standard CRT (50Gy in 28fx)
N = 123
(T3: 102; T4: 21)
Standard CRT + HDR brachy boost (10Gy in 2fx)
N = 120
(T3: 120; T4: 18)
Abstract :Jakobsen A et al Dose-effect relationship in CRT for LARC: a randomized trial comparing 2 radiation doses.
PURPOSE:
Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation.
METHODS AND MATERIALS:
The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of ≤5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m(2) and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0).
RESULTS:
The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04).
CONCLUSIONS:
This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.
Fig. 2. Comparison of major response, grade 3 toxicity (Common Toxicity Criteria), and surgical complications in T3
tumors with biologic equivalent dose. Bars indicate SD; solid lines, TRG 1 and 2; dashed lines, postoperative complications; and dotted, dashed lines, grade 3 toxicity.
Jakobsen et al. IJROBP 2012

29. RT dose-escalation T3 tumors
TRG 1 and 2
Post-op complications
Grade 3 toxicity
T3 tumors
Jakobsen A et al Dose-effect relationship in CRT for LARC: a randomized trial comparing 2 radiation doses.
PURPOSE:
Locally advanced rectal cancer represents a major therapeutic challenge. Preoperative chemoradiation therapy is considered standard, but little is known about the dose-effect relationship. The present study represents a dose-escalation phase III trial comparing 2 doses of radiation.
METHODS AND MATERIALS:
The inclusion criteria were resectable T3 and T4 tumors with a circumferential margin of ≤5 mm on magnetic resonance imaging. The patients were randomized to receive 50.4 Gy in 28 fractions to the tumor and pelvic lymph nodes (arm A) or the same treatment supplemented with an endorectal boost given as high-dose-rate brachytherapy (10 Gy in 2 fractions; arm B). Concomitant chemotherapy, uftoral 300 mg/m(2) and L-leucovorin 22.5 mg/d, was added to both arms on treatment days. The primary endpoint was complete pathologic remission. The secondary endpoints included tumor response and rate of complete resection (R0).
RESULTS:
The study included 248 patients. No significant difference was found in toxicity or surgical complications between the 2 groups. Based on intention to treat, no significant difference was found in the complete pathologic remission rate between the 2 arms (18% and 18%). The rate of R0 resection was different in T3 tumors (90% and 99%; P=.03). The same applied to the rate of major response (tumor regression grade, 1+2), 29% and 44%, respectively (P=.04).
CONCLUSIONS:
This first randomized trial comparing 2 radiation doses indicated that the higher dose increased the rate of major response by 50% in T3 tumors. The endorectal boost is feasible, with no significant increase in toxicity or surgical complications.
Fig. 2. Comparison of major response, grade 3 toxicity (Common Toxicity Criteria), and surgical complications in T3
tumors with biologic equivalent dose. Bars indicate SD; solid lines, TRG 1 and 2; dashed lines, postoperative complications; and dotted, dashed lines, grade 3 toxicity.
Higher radiation dose increases the rate of major response by 50% in T3 tumors
Endorectal boost is feasible, with no significant increase in toxicity or surgical complications
Jakobsen et al. IJROBP 2012

30. FUTURE
Patient Tailored Treatment