1. Colorectal Cancer A Multidisciplinary Approach to Individualized Patient Care
1st Lebanese Oncology Forum Mount Lebanon Hospital Gharios Medical Center

2. Professor of Medical Oncology
Session 2: Enhancing Colorectal Cancer Care - How does a tumor’s location impact the surgical treatment and long- term outcomes for patients with colorectal cancer - Colorectal Cancer A Multidisciplinary Approach to Individualized Patient Care
Fadi Farhat, MD, MHHM
Professor of Medical Oncology

3. 1. Introduction
Because treatment options for cancer care have increased rapidly in recent decades, establishing an multidisciplinary team - MDT is crucial to fulfilling the requirement of multimodal treatments in current practice in cancer treatment
Establishing MDTs for treating various cancers is encouraged in some countries and is considered a standard of quality control in cancer care
Here, we present a review that focuses on the influence of MDTs in colorectal cancer treatment through the literatue review

4. Group of people of different healthcare disciplines
MDT is
Pathologist &
Radiologist
Group of people of different healthcare disciplines
The first set of ESMO consensus guidelines for metastatic colorectal guidelines was published in 2012.
In 2014, an international panel of experts in the management of patients with CRC was convened to update the existing ESMO Consensus Guidelines for the management of patients with CRC
A set of pre-formulated topics was prepared and three working groups convened in the areas of:

5. Radiologist & Radio-Oncologist
MDT is
Radiologist & Radio-Oncologist
Pathologist &
Radiologist
Which meets together at a given time “whether physically in one place, or by video or teleconferencing”

6. ESMO consensus guidelines
to discuss a given case
Radio-Oncologist & Palliative Sp
Pathologist &
Radiologist
Set of pre-formulated topics; 3 working groups convened in areas:
Molecular pathology and biomarkers [1-9]
Local and ablative treatment (LAT) (including surgery and the management of patients with oligometastatic disease) [10-17]
The treatment of metastatic disease [18-…]

7. ESMO consensus guidelines
Oncological Surgeon
Medical Oncologist
ESMO consensus guidelines
Radio-Oncologist & Palliative Sp
Pathologist &
Radiologist
Set of pre-formulated topics; 3 working groups convened in areas:
Molecular pathology and biomarkers [1-9]
Local and ablative treatment (LAT) (including surgery and the management of patients with oligometastatic disease) [10-17]
The treatment of metastatic disease [18-…]
who are each able to contribute independently to the diagnostic and treatment decisions about the case”.1

8. 2. Definition of MDTs
In general, the composition of an MDT for cancer care includes specialists from
Medical, surgical Oncology

9. 2. Definition of MDTs
In general, the composition of an MDT for cancer care includes specialists from
Medical, surgical Oncology
Radiologist & Radiation oncology

10. 2. Definition of MDTs
In general, the composition of an MDT for cancer care includes specialists from
Medical, surgical Oncology
Radiologist & Radiation oncology
Pathology, & palliative care,
nursing professionals, & nutritionists2

11. 2. Definition of MDTs
In general, the composition of an MDT for cancer care includes specialists from
Medical, surgical Oncology
Radiologist & Radiation oncology
Pathology, & palliative care,
nursing professionals, & nutritionists2
Through regular meetings and discussions within MDTs, healthcare professionals can improve communication, cooperation, and decision-making regarding cancer treatment
The composition of an MDT may vary depending on the cancer type*

12. The composition of an MDT may vary depending on the cancer type
At Taipei Veterans General Hospital, Taipei, Taiwan an MDT for CRC was established in October 2008
The core members are surgeons, medical oncologists, radiation oncologists, pathologists, diagnostic and interventional radiologists, nurse specialists, and coordinators
Initially, the group included colorectal & hepatobiliary surgeons as team members, and because of an increase in treatment demands for pulmonary metastatic lesions, thoracic surgeons have been included since October 2011

13. 3. MDTs in cancer care
1996: UK issued National standards & guidance for cancer care; establishment of MDTs - consistent recommendation 2-5
MDTs - now widely accepted as a model of various approaches to cancer care in many other countries
USA,6,- 8 Canada,9 Australia,10-11, some in Europe12-13 & Asia.14
Effect of MDTs on more favorable patient selection & improved patient survival - demonstrated in patients with esophageal,15-16 gastric,16 pancreatic,17 lung,13-18 breast,7 & gynecological cancers.14, 19-20

14. Primary care physician
3. MDTs in cancer care
The cancer-specific outcome is considered more favorable when patients are managed under MDT care
MRC Patient Journey
MDTs Improve Patient Outcomes by Combining Specialist Knowledge to Identify Individual Diagnostic & Treatment Options
Primary care physician
Gastro-enterologist
Radiologist
Meical Oncologist
Pathologist
Surgeon
Patient
Cedars-Sinai: : accessed 1 October 2010

15. 3. MDTs in cancer care
The cancer-specific outcome is considered more favorable when patients are managed under MDT care.
MDTs can improve clinical decision-making, outcomes & experiences of patients with various cancers.6, 15,21
Retrospective study of Australian patients NET m+ (n = 49)
Median Survival for pts managed at medical oncology unit- longer than elsewhere (112 vs.53 mos)
Treatment differed between oncology unit compared to other sites
120
100 80 60
Median Survival (months) 40 20
Specialty Multidisciplinary Center
Community Care
Townsend A, et al. J Clin Gastroenterol 2009.

16. 3. MDTs in cancer care
The cancer-specific outcome is considered more favorable when patients are managed under MDT care.
MDTs can improve clinical decision-making, outcomes & experiences of patients with various cancers.6, 15,21
Validating the specific effects of MDTs on patient outcomes is challenging because most studies on MDTs are observational or retrospective2 and 22
Initiate RCT trial validating effects of MDTs- impossible.

17. Before The Era of Chemotherapy
4. MDTs in CRC treatment
Diagnosis & treatment of CRC - rapidly developed in the past decade.
Before The Era of Chemotherapy 35 30 25 20 15 10 5
Months
Best supportive care 17

18. Chemotherapy Has Improved Survival
4. MDTs in CRC treatment
Diagnosis & treatment of CRC - rapidly developed in the past decade.
Managing through a single treatment is difficult.
Chemotherapy Has Improved Survival 35 30 25 20 15 10 5
Months
5-FU 18

19. Improved CRC Survival But More To Be Done
Drug development & Multidiscplinary approach 35 30 25 20 15 10 5
Irinotecan
Capecitabine
Oxaliplatin
Months
mCRC = metastatic colorectal cancer; 5-FU = 5-fluorouracil; MoAbs = monoclonal antibodies; OS = overall survival 19

20. Targeted Therapy Improved CRC Survival Bevacizumab, Cetuximab, Panitumumab, Aflibercept, etc…
MDT
Chemotherapy
MoAb 35 30 25 20 15 10 5
Months 20

21. 4. MDTs in CRC treatment
Although some limitations regarding MDTs are emphasized in the literature,24, 25 and 26 such as debates
On decision-making within MDTs
On the costs of MDTs (extra hours & workload for members attending MDT meetings, unnecessary discussion in routine cases)
On the limitation of discussion regarding elective cancer patients
MDTs have been incorporated into government policies and guidelines.

22. 4. MDTs in CRC treatment
USA- the American College of Surgeons Commission on Cancer has included MDTs as a key program requirement for CRC care
German Cancer Society- has provided certification for oncological care institutions since 2003 and the numbers of pre and postoperative case presentations at MDT conferences are evaluation indicators for CRC care28
Taiwan- certification program on the quality of cancer care in hospitals initiated by the National Health Research Institutes in
Establishing MDTs for cancer care is required for certification30
Results of certification - available on a website for public access & influence national health insurance payments by the government

23. 4.1. Decision-making Ryan and Faragher25
Prospectively
assessed 197 consecutive cases presented to a CRC MDT
Compared plans made using routine care pathways vs. made at MDT meetings
Routine cases of colon cancer: authors demonstrated that discussing rarely changed management (3.4%)
Complex cases: conversely, management changed in 50%

24. 4.1. Decision-making Topics that commonly generated useful discussion:
Preoperative management of rectal cancer
Metastatic or recurrent disease’s management
Malignant polyps management
Deviation from the proposed treatment
Only 4% of all cases
Because of complex patient factors
Poor prognostic features
Patient age
Medical comorbidity.25

25. 4.1. Decision-making
These findings highlight the need of information on the general health status of patients and their preference for treatment, which should be available at MDT meetings.
Typically, MDT decisions are made by physician members according to biomedical information and patient choice is seldom considered in the decision-making process.31
Nurses should attend MDT meetings because they can offer the views of patients and the psychosocial aspects of care to the meetings.
When nurses are actively involved, the performance of an MDT is apparently higher.3

26. 4.2. Preoperative workup under the care of MDT
Evidence has shown that implementing an MDT approach for managing CRC can result in more complete preop evaluations as well as higher rates of access to multimodal therapies33-34
When the preop tests prescribed by the NCCN guidelines were considered, the proportion of patients with colon cancer who underwent complete preoperative tests was significantly higher under MDT care (91.7% vs. 27.5%, p < 0.001)
Trend observed in patients with rectal cancer (84.0% vs. 15.3%, p < 0.001).
Differences - observed in the rates of
Chest CT (95.0% vs. 37.1%, p < 0.001)
CEA (100% vs. 63.8%, p < 0.001)
Transrectal US for rectal cancer (88.0% vs. 37.7%, p < 0.001). 34
carcinoembryonic antigen testing

27. 4.2. Preoperative workup under the care of MDT
Another study - significantly more patients underwent CT TNM staging (81.3% vs. 41.1%, p < 0.001). 35
Population-based study in The Netherlands
MRI more used (p = 0.001)
TNM staging - more complete (p < 0.001)36
Staging accuracy improves after MDT approach
Radiological TNM staging according to CT scans was compared with the final pathological stage between the periods before and after the establishment of an MDT approach
CT TNM staging
more accurate in MDT group
64.0% vs. 45.9%, p = 

28. ESMO 2014 : Patient groups and treatment strategy
Not R0-resectable liver
Lung metastases only
may become resectable after induction CT
Maximum tumor shrinkage
Upfront most active combination
Multiple metastases,sites
Rapid progression Tumor-related symptoms
Clinically relevant tumor shrinkage ASAP Control progression
Upfront active combination: at least doublet
Multiple metastases/sites with no option for resection and/or initially asymptomatic, less aggressive disease
Prevent further progression, low toxicity
Watchful waiting or sequential approach (triplet regimens only in selected patients)
Clinical presentation
Treatment goal
Treatment strategy
Van Custem E. et al. Ann Oncol 2014;25(Supplement 3):iii1–iii9

29. ESMO 2014 : Patient groups and treatment strategy
Decreasing treatment intensity
Not R0-resectable liver
Lung metastases only
May become resectable after induction CT
Maximum tumor shrinkage
Upfront most active combination
Multiple metastases & sites
Rapid progression
Tumor-related symptoms
Clinically relevant tumor shrinkage ASAP Control progression
Upfront active combination: at least doublet
Multiple metastases/sites
No option for resection
Initially asymptomatic
Less aggressive disease
Prevent further progression, low toxicity
Watchful waiting or sequential approach (triplet regimens only in selected patients)
Group 1
Group 2
Group 3
Van Custem E. et al. Ann Oncol 2014;25(Supplement 3):iii1–iii9

30. The main components of rectal cancer treatment include
4.3. Access to multimodal therapy for rectal cancer MDTs are crucial for treating patients with rectal Ca
The main components of rectal cancer treatment include
Total mesorectal excision
Assessment of the quality of surgery by pathologists
Identification of patients at a high risk of local recurrence through imaging techniques
Use of effective neoadjuvant and adjuvant therapies, including radiotherapy and chemotherapy
MDT approach that identifies, coordinates, delivers, and monitors the ideal treatment on an individual basis27

31. 4.3. Access to multimodal therapy for rectal cancer MDTs are crucial for treating patients with rectal Ca
According to an international survey, regular MDT meetings significantly influence decisions on the choice of
staging modality
neoadjuvant treatment
several other critical factors in the preop planning of rectal cancer treatment33
MDT approach enables distinguishing between patients who should first be treated surgically and those who should be offered neoadjuvant therapy.37

32. 4.3. Access to multimodal therapy for rectal cancer MDTs are crucial for treating patients with rectal Ca
Are more often discussed by MDTs.36
Advanced disease (cT3 or N+)
Distal tumors
Preoperative chemo-radiotherapy
International survey involving
123 colorectal cancer centers
North America, Europe, and Asia, departments with regular MDT
More likely to use MRI to determine local staging
More likely to encourage patients with threatened circumferential resection margins to undergo neoadjuvant treatment.33

33. 4.3. Access to multimodal therapy for rectal cancer
Neoadjuvant treatment, MDT meetings, reduced positive circumferential resection margin rate, lowered rate of local recurrence, and more favorable OS38
Burton 38- higher positive rate (26%) of the circumferential resection margin observed in 62 patients surgery alone without MRI-based MDT discussion vs. surgery with MRI-based MDT discussion (1%)
Positive circumferential resection margin rate decreased to 7% overall at 1 year of follow-up after compulsory MDT discussion in 96% of patients with rectal cancer.38

34. 4.4. Quality of pathology reports
MDTs significantly affected the quality of pathology reports (RR = 4.85, 95% CI = 1.34–17.46, p = 0.01) in one study, 33 (circumferential resection margin in millimeters)
# LN examined in an MDT group - significantly higher than that in a pre-MDT group (8.5 vs. 13.7, p < 0.001)35
MSI analysis - more likely to be performed under care of MDT (29.6% vs. 10.6%, p < 0.001)34 ***

35. MSI analysis - more likely to be performed under care of MDT (29.6% vs. 10.6%, p < 0.001)34
The past: One size fits all
The future: Individualized treatment
MMR/MSI
RAS
BRAF
Better identification of patient subgroups
Dynamic monitoring of therapeutic effect and resistance

36. Stage II Colon Cancer - MSI Status is Prognostic Correlation with Adjuvant Chemotherapy (5 FU-based)
MSS/MSI-L
MSI-H 36

37. 4.4. Quality of pathology reports
MDTs significantly affected the quality of pathology reports (RR = 4.85, 95% CI = 1.34–17.46, p = 0.01) in one study, 33 (circumferential resection margin in millimeters)
# LN examined in an MDT group - significantly higher than that in a pre-MDT group (8.5 vs. 13.7, p < 0.001)35
MSI analysis - more likely to be performed under care of MDT (29.6% vs. 10.6%, p < 0.001)34
Suggest that MDT meetings & discussions encourage pathologists to improve their reports to fulfill guidelines & provide more information for diagnosis and decision-making regarding treatment planning

38. 4.5. Adjuvant chemotherapy
MDTs - suitable recommendations for adjuvant chemo for CRC
MacDermid40 significantly > patients adjuvant chemotherapy after the implementation of MDT approach (31.3% vs. 13.0%, p < 0.001; Dukes' B, p = 0.002; Dukes' C, p = 0.004)
Survey in Netherlands: Stage III colon cancer in MDT meetings > adjuvant chemotherapy (OR = 1.33, 95% CI = 1.15–1.55, p < 0.05)23
Ye et al35 revealed that significantly fewer patients with Stages I & IIA disease - adjuvant chemotherapy after the implementation of MDT approach (64% vs. 0%, p < 0.001; 82% vs. 12%, p < 0.001)
No significant differences in the prescription of adjuvant chemotherapy to Stages IIB & III between pre-MDT & MDT groups

39. MOSAIC: OS - stage II & III patients
1.0
0.8
0.6
0.4
0.2
p=0.996
0.1%
p=0.029
4.4%
Probability
FOLFOX4 stage II
LV5FU2 stage II
FOLFOX4 stage III
LV5FU2 stage III
HR (95% CI)
Stage II (0.71–1.42)
Stage III (0.66–0.98)
Overall survival (months)
De Gramont A, et al. J Clin Oncol 2007;25 (Suppl. 18)165s (Abstract 4007)
Data cut-off: January 2007

40. 4.5. Adjuvant chemotherapy
MDTs - suitable recommendations for adjuvant chemo for CRC
MacDermid40 significantly > patients adjuvant chemotherapy after the implementation of MDT approach (31.3% vs. 13.0%, p < 0.001; Dukes' B, p = 0.002; Dukes' C, p = 0.004)
Survey in Netherlands: Stage III colon cancer in MDT meetings > adjuvant chemotherapy (OR = 1.33, 95% CI = 1.15–1.55, p < 0.05)23
Ye et al35 revealed that significantly fewer patients with Stages I & IIA disease - adjuvant chemotherapy after the implementation of MDT approach (64% vs. 0%, p < 0.001; 82% vs. 12%, p < 0.001)
No significant differences in the prescription of adjuvant chemotherapy to Stages IIB & III between pre-MDT & MDT groups

41. 4.6. Chemotherapy for metastatic disease
For patients with metastatic disease, MDTs
Significantly influenced the use of new chemotherapy regimens if liver metastases were present (relative risk = 6.41, CI = 1.34–30.64, p = 0.02)33
However, no difference was observed in the number of patients who were prescribed palliative chemotherapy before and after the implementation of an MDT approach (p = 0.750 and p = 0.431, respectively) 35-40

42. Many patients present with metastatic CRC
All patients with CRC1
~25% of patients present with mCRC1
~50% of patients will develop metastases1
The liver is the most common organ site for CRC metastases2
1. Van Cutsem E, et al. Ann Oncol 2010; 21 (Suppl. 5): v93–v DiSibio G, French SW. Arch Pathol Lab Med 2008; 132: 931–939

43. mCRC: Liver Metastases Resectability Profile
80% non-resectable
20% resectable
Active therapy
80% remain non-resectable/20% might shift
Resection
Potential for cure!
The liver is the most common organ site for CRC metastases2
1. Van Cutsem E, et al. Ann Oncol 2010; 21 (Suppl. 5): v93–v DiSibio G, French SW. Arch Pathol Lab Med 2008; 132: 931–939

44. Resection for CRC Liver Metastases
MSKCC
p<0.01
N=563
( )
Probability
N=1036
( )
Disease-specific survival (months)
Improvements in survival over time
Better chemotherapy
Better imaging
Better patient selection

45. Variance in Multidisciplinary Consultation
Setting: In untreated patients with liver-only colorectal cancer, I generally;
Always consult with my surgeon to determine resectability
Only consult with my surgeon if there are fewer than 3 lesions that appear resectable to me
Key points:
The extent to which multidisciplinary consultation is a reality varies considerably across different care settings in the US
In a 2006 NMCR Challenging Casessm survey, medical oncologists were asked whether they habitually consulted with a surgeon upon seeing a previously untreated patient with liver-only colorectal metastases
More academics than community oncologists consulted with a surgeon as a matter of course regarding such patients
Community oncologists were more likely than academics to decline to refer patients with 3 or more lesions for a surgical consultation
Data on file, sanofi-aventis. © Network for Medical Communication and Research, LLC.
Generally do not consult with my surgeon as these patients are best treated with systemic chemotherapy alone
Network for Medical Communication and Research (NMCR), Challenging Casessm 2006 is a nationwide forum for peer-to-peer market research for oncology practitioners.
Data on file, sanofi-aventis. Network for Medical Communication and Research (NMCR), Challenging Casessm 2006.

46. 4.6. Chemotherapy for metastatic disease
For patients with metastatic disease, MDTs
Significantly influenced the use of new chemotherapy regimens if liver metastases were present (relative risk = 6.41, CI = 1.34–30.64, p = 0.02)33
However, no difference was observed in the number of patients who were prescribed palliative chemotherapy before and after the implementation of an MDT approach (p = 0.750 and p = 0.431, respectively) 35-40

47. 4.7. Patient survival
Most studies have confirmed + effect of MDTs on survival
Observational or retrospective MDTs - effects of multiple concurrent changes in cancer treatment & care should always be considered when study results are interpreted (+MDTs)
Morris4 - population-based retrospective survey - 25%
3% reduction risk of death all CRC [HR = 0.97, 95% p = 0.01]
Survey Netherlands: mortality < in MDT group (HR = 0.97, 95% p < 0.05), not rectal cancer (HR = 0.96, 95% CI = 0.92–1.01) 23
MacDermid40 single institution- independent predictor of survival (HR = 0.73, 95% CI = 0.54–0.98, p = 0.044)

48. Summary : mCRC is an interesting disease Every patient is different !
Summary – Every Patient is different, every disease is different
Don’t put all mCRC patients into one bag
Biological presentation - Molecular profile
Clinical presentation - Burden of the disease
Choice of the treatment Goal
Resectable disease or not?
Sequence of Treatment
Explore different strategies to prolong survival

49. 5. Conclusion Establishing MDTs for CRC care can lead to
more complete preoperative evaluation
higher rates of access to multimodal therapies
Moreover, MDTs can
improve the quality of pathology reports
provide suitable recommendations for adjuvant chemotherapy
increase overall survival in patients with CRC
To enhance the quality of cancer care, hospitals should encourage establishing MDTs