rectal cancer treatment updates in simple way and the advances in the molecular techniques .the role of the neo adjuvant chemoradiotherapy and the state of the art in the management by each stage.radiotherapy role and technique by using the RTOG guidance in target definition

1. HIGHLIGHTS IN THE
TREATMENT OF RECTAL
CANCER
MONA NAFEA
M.D

2. OUTLINE
•
Global incidence of colorectal cancer
•
anatomy and molecular basics
•
diagnosis
•
Treatment outline

3. GLOBAL CANCER
FIGURE
•
As the third most common
malignancy and the second
most deadly cancer, colorectal
cancer (CRC) induces
estimated 1.9 million incidence
cases and 0.9 million deaths
worldwide in 2020. The
incidence of CRC is higher in
highly developed countries, and
it is increasing in middle- and
low-income countries due to
westernization.

4. GLOBAL
FIG.CONT
•
Globally, 60% of cases are diagnosed at ages 50–
74 years, and almost 10% occur in adults under
50. By 2040, the number of cases of colorectal
cancer is predicted to increase to 3.2 million new
cases and 1.6 million deaths

5. WORLD HEALTH
ORGANIZATION
RELEASES LATEST
GLOBAL CANCER
DATA

6. ANATOMY OF
RECTUM

7. RECTAL CANCER
TREATMENT UPDATES
Progress in MULTIMODAL THERAPY of
Rectal Cancer is one of the BEST
examples of success of Clinical Research
in the last 2 decades.

8. RECTAL
CARCINOMA –
RECENT
ADVANCES --
OVERALL
1.SPHINCTER SAVING PROCEDURES – UP FROM
15% TO 50% -- NO COLOSTOMY (IMPROVED
QOL)
2. OVERALL FIVE YR SURVIVAL – UP FROM 30%
60%
3. DEPTH OF INVASION – DECREASED BY 40%-
60% WITH ADJUVANT RTP
4. LYMPH NODE STATUS AND REC. FREE

9. RECENT ADVANCES
1. MOLECULAR BIOLOGY 2. SURGERY
3. IMAGING – MRI, CT
AND PET
4.
CHEMO/RADIOTHERAPY

10. MOLECULAR
BIOLOGY
DNA chip technique DNA
sequence checked
-- APC Gene – FAP gene mutation
-- mismatch repair gene -HNPCC
SUCH PTS.(5%) Put on surveillance
program .prophylactic surgery

11. • Pathology review
• 1 ●CEA●
• Complete MSI analysis●
• Proctoscopy evaluation by surgeon●
• High-resolution rectal staging MRI
• CT of chest/abdomen/pelvis (with and without contrast) or MRI with
abdomen/pelvis●
• Colonoscopy (with biopsy if no pathology or pathology non diagnostic)●
• Lifestyle risk assessment2
• diagnosis in
glance

13. II USE OF CH/RT
(NEOADJUVANT/ADJUVANT)

PTS WITH POOR HISTOLOGY

PTS WITH EXTRA MURAL SPREAD (MRI)

PTS WITH INVOLVED NODES (ERUS)
The concept of neo-
adjuvant treatment

14. :
stage I
Resectable
primary,no
metastasis
TAE or TAMIS/TEM3
Treatment guide

15. Stage I not eligible
for TAE or
TAMIS/TEM
resection3
Radical surgical resection: LAR,
CAA or APR, with or without
temporary fecal diversion
(ileostomy)

16. Unresectable primary, no
metastasis
Consider chemoradiation therapy

17. Stage II and
Stage III
Neoadjuva
nt therapy Radical surgical
resection
Consider adjuvant
chemotherapy

18. Metastatic
disease, intact
primary
Are primary
tumor and
metastases
resectable

19. .
.
in Europe short-
term
radiotherapy is
increasingly used
in the primary
management of
rectal cancer
In united states
postoperative
chemoradiotherapy
is the standard
treatment of choice.

22. LOW
ANTERIOR
RESECTION

24. • 1-Abdominoperineal Resection
• ● Tumors located in the distal rectum requiring an
abdominoperineal resection are at an increased risk for
circumferential resection margin positivity. ●
• In addition to the TME principles as outlined above, the
division of the pelvic floor (levator muscles) should be
wide around the level of tumor to avoid narrowing or
coning of the resection.
• .

25. • For anterior or posterior tumors, this could require
en bloc resection of the adjacent structure such as the
vagina or coccyx in order to ensure a clear margin.
• ● The approach to the pelvic floor may be
• trans-abdominal (from above) or
• trans-perineal (from below) in either a lithotomy or
prone position as long as a complete resection with clear
margins can be achieved.
• . ● Prior resection does not preclude re-resection in
selected patients

26. • II-Liver ● Hepatic resection is the treatment of choice for resectable
liver metastases from colorectal cancer.
• Complete resection or ablative therapy must be feasible based on
anatomic grounds and extent of disease. Maintenance of normal hepatic
function is required.
•
• A- ● Resectable extrahepatic sites of metastases do not preclude
curative hepatic resection.
• ● Re-evaluation for resection can be considered in otherwise
unresectable patients after neoadjuvant therapy. All original sites of
disease must be resectable.

27. PRINCIPLES
OF RECTAL
SURGERY
● Ablative techniques may be
considered in conjunction with resection
in otherwise unresectable patients. ●
Primary tumor should be resected with
curative intent (R0).
Consider completion with radical
lymphadenectomy at time of liver
resection if synchronous metastasis at
presentation and a non-oncologic
resection of the primary was performed

28. PRINCIPLES OF
RECTAL SURGERY
III Lung Surgery
● Complete resection must
be feasible based on
anatomic grounds and the
extent of disease.
Maintenance of adequate
residual pulmonary function
is required.
● Resectable extrapulmonary
metastases do not preclude
resection.

29. IV Other sites
Primary tumor should be resected with curative intent (R0).
● Prior resection does not preclude a subsequent resection in selected patients. Other Sites
(other than liver or lung)
● Resection of isolated metastasis outside of the liver or lung may be considered if complete
resection can be performed, but treatment should be individualized and based on a
multidisciplinary treatment plan.

30. • V Peritoneal carcinomatosis
• ○ Cytoreductive surgery with or without intra-peritoneal hyperthermic chemotherapy
may be considered in the setting of a clinical trial.
PRINCIPLES OF
RECTAL SURGERY

31. Three major indications for
radiotherapy can be
identified: -
- downstaging
of the tumor
in primary
irresectable
tumors
reduction of
local
recurrences
in mobile
rectal cancer,
RADIATION THERAPY

32. ,
The Swedish Rectal Cancer Trial was one of the first major studies
in which a significant benefit of neoadjuvant irradiation
compared to surgery alone was found. By preoperatively
applying a short-course radiotherapy (SC-RT) of 5 × 5 Gy, the
overall survival (OS) was significantly improved from 30 to 38%
(p = 0.008), and the local recurrence rate (LRR) decreased from
26 to 9% (p < 0.001).
Evidenced based clinical practice”

33. In a Dutch trial, the addition of preoperative SC-RT to TME surgery reduces LRR from 11 to 5%
(p < 0.0001) but did not result in a better OS (49 vs. 48%; p = 0.86)
Evidenced based practice cont”

34. In the MRC CR07 trial, preoperative SC-RT was tested against selective
adjuvant chemoradiation for high-risk patients with a positive
circumferential resection margin (CRM+). TME was not obligatory but
equably balanced between both treatment arms. Though selective
postoperative treatment did not influence OS after 3 years (76.7 vs.
74.4%; p = 0.04), LRR was remarkably higher with 10.6% compared to
preoperative SC-RT with 4.4% (p < 0.0001)
Evidenced based practice cont

35. EVIDENCED
BASED
PRACTICE CONT
• Alternatively to SC-RT, the combination of norm fractionated
irradiation with radiation doses between 45 and 50.4 Gy and
simultaneous application of chemotherapy was established as long
course chemoradiotherapy (LC-CRT).
• The German CAO/ARO/ AIO-94 trial introduced a 5-
fluorouracil(5-FU)-based CRT approach and demonstrated an
advantage of preoperative over postoperative application in terms of
10-year LRR (7.1 vs. 10.1%; p = 0.048) but not in OS
• Omitting the chemotherapeutic component in preoperative long-
course treatment does not affect OS negatively but results in a worse
LRR as Gérard et al. [9] were able to demonstrate. Alternatively to 5-
FU-based approaches, capecitabine can be used in preoperative LC-
CRT

36. With two available neoadjuvant concepts, SC-RT and LC-CRT, the question arose
whether one of them is superior to the other and should thus be used preferably in
daily practice. Several works addressed this topic,
Evidenced based practice cont.”

37. ]
Evidenced based Practice cont.
The Trans-Tasman Radiation Oncology Group presented comparable
prognostic results in 2012 for both strategies, with a 5-year OS of 74 versus
70% (p = 0.62) and a 3-year LRR of 7.5 versus 4.4% (p = 0.24) for SC-RT
versus LC-CRT.

39.  From a clinical point of view,
 SC-RT and LC-CRT are not competing but complementary strategies with a separate scope of use and
partly different therapeutic goals: concordantly, both strategies aim to reduce the risk of local relapse. But
as reflected in the major clinical guidelines
 SC-RT is commonly recommended in early T3 stage without lymph node involvement,
 LC-CRT is indicated for advanced T3 and T4 tumors with positive clinical circumferential resection margin
(cCRM+) and/or positive lymph nodes to additionally downsize the tumor.

40. The downsize effect aims at increasing the probability of R0 resection and in special
cases to preserve the sphincter muscle.
Adjuvant chemoradiation should be avoided by thorough diagnostic work-up before treatment
onset. Further, the management of proximal rectal cancer, i.e. 12–16 cm from the anal verge, is
debated controversially due to the anatomical setting und the underrepresentation in the mentioned
studies.

41. A detailed overview of the relevant, major randomized trials for neoadjuvant SC-RT
or LC-CRT Toxicity
late side effects of neoadjuvant radiotherapy in rectal cancer deserve special
attention due to the functional sensitivity of concerned structures like the anal
sphincter or the urinary tract.

42. Long-term follow-up data from the Dutch trial or Swedish cohorts suggested high rates of fecal
and urinary incontinence after SC-RT compared to surgery alone, thus impairing quality of life.
However, from today’s perspective, old radiation techniques were used in these trials.
More recent toxicity data from the British MRC CR07 trial also showed increased fecal incontinence
rates associated with SC-RT; however, in most of the affected patients changes were reported on a
low-grade level with rather minor impact on the quality of life.

43. ,
but incidence rates of late side effects do not show significant differences .
Gender-specific analyses of toxicity showed a significantly higher rate of hematologic and acute
organ toxicity for female patients in the cohort of the German CAO/ARO/ AIO-94 trial and an
increased rate of dyspareunia and vaginal dryness

44. Protocol of Radiotherapy for Rectal Cancer
Indication of radiotherapy
(1) Clinical stage II, III
(2) Lower rectum clinical stage I disease for organ preservation. (RT +/- C/T) (optional)
(1) Pathological StageⅡ,Ⅲ
(2) After local excision, pT1Nx with high risk factors (close/positive margin, LVI,
PNI, and poorly differentiated, or sm3 invasion), pT2Nx

45. Simulation and Treatment Planning:
 Use of CT simulation and 3D/IMRT/VMAT treatment planning is required to
ensure adequate target volume coverage and avoid normal tissue irradiation.
When clinically appropriate, use of IV and/or oral contrast for CT simulation may
be used to aid in target localization.
 Use of an immobilization device (such as vacuum cushion or ankle holder) is
strongly recommended for reproducibility of daily set-up.
 Patients could be simulated and treated either in the supine or prone position.
 Positioning and other techniques to minimize the volume of small bowel in the
field should be encouraged.
 • Full bladder filling is not compulsorily necessary.

46. Radiation Treatment Fields (CTV)
• Radiation therapy fields should include the tumor or tumor bed and mesorectum
with an adequate margin, the pre-sacral nodes, and the internal iliac nodes.
• nodes should also be included for T4 tumors involving anterior
structures.
• should also be included for lower tumors involving the anal
canal or the anal margin or advanced disease with lower third vaginal involvement.
contours: 7 mm around vessels, carving out bowel, bladder and
bone. (based by RTOG consensus)
• The ischial fossa should be included RT field if tumor invasion to this area.
• For postoperative patients treated by , the perineal
wound should be included within the fields.
• Different CTV to create PTV should be considered for motion target
(rectum) and motionless target (pelvis nodal) (5~20 mm),

47. Radiation dose
• Once daily, 5-6 fractions per week.
• For resectable cancers, after 45 Gy to pelvis, a tumor bed boost with an adequate
margin of 5.4 Gy in 3 fractions could be considered for preoperative radiation (for
T4 disease, total dose 54 Gy may be considered) and 5.4-9.0 Gy in 3-5 fractions
for postoperative radiation.
• For patients with very close or positive margins after resection, especially for
patients with T4 or recurrent cancers, as an additional boost, 10-20 Gy external
beam radiation (IMRT) to a limited volume could be considered soon after surgery,
prior to adjuvant chemotherapy.
• For unresectable cancers, doses higher than 54 Gy may be required, if technically
feasible.
• Short-course radiation therapy (25 Gy in 5 fractions) with surgery within 1 week of
completion of therapy or delayed 6-8 weeks can also be considered if clinically
necessary

48. Group consensus contours: Brown = CTVA (peri-rectal, pre-sacral, internal
iliac), Blue = CTVB (external iliac), Red = CTVC (inguinal). An RTOG
Consensus Panel Contouring Atlas - SEOR