“mCRC” Do we need the oncologist?
Mohamed Abdulla M.D.Prof. of Clinical Oncology
Cairo University
Gastrohep – 2016Cairo Conrad Hotel09/12/2016
Member of Advisory Board, Consultant, and Speaker for:• Amgen, Astellas, AstraZeneca, Hoffman la Roche, Janssen Cilag,
Merck Serono, Novartis, Pfizer, Mundipharma, MSD• The content of this presentation does not relate to any product of a
commercial interest
Speaker Disclosures:
Management of Met. CRC:Playing a Strategic Game:
The King Should SURVIVE
SURVIVAL
What You Have to Play?
Surgery, Pharmaceuticals, Interventional Radiology, …
How to Play?Sequence and Treatment Lines
Try to be Creative Research
Colon Cancer:Basic Facts & Figures:
• 2nd & 3rd most common cancers in females and males.• 9% of cancer related deaths.• 90% occurring around the age of 40 – 50 years.• OAS for entire patients = 65%.• Metastatic disease: 5-year OAS = 10%.• Organ limited metastatic disease: 5-year OAS > 40%• Median survival of metastatic disease > 24 - 30 months.• Improved OAS with exposure to all available drugs.• Unified global ideal treatment algorhytm is still
controversial.
Colorectal Cancer: “Not only one scenario”
Operable M0
Metastatic
Resection +/-Adjuvant
Resectable
Convertible
Beyond Conversion OAS & QoL
Intervention
Metastatic
Non Metastatic
Resectable NAT Surgery
Advanced TNAT Surgery
Gold Standard of Practice Principles :
Surgery is the cornerstone in curative management of Gastrointestinal Malignancies
However,
Who Should Receive Adjuvant Th:
60 m 30 m 0 month Stage% Survival % Survival % Survival
93.2 96.1 100 I84.7 91.0 100 IIa72.2 80.2 100 IIb83.4 91.4 100 IIIa64.1 77.3 100 IIIb52.3 67.1 100 IIIc43.0 57.3 100 IIId26.8 43.1 100 IIIe8.1 17.3 100 IV
O’ConnellJB, Maggard MA, Ko CY: Colon Cancer Survival Rates with The New American Joint Committee on Cancer, Sixth Edition Staging. J Natl Cancer Inst 2004;96:1423.
LNs = > 12
Curves showing significant improvement in overall survival in arm A [open diamonds, 5-fluorouracil (5-FU)/leucovorin] compared with arm B (filled squares, 5-FU/levamisole) (P =
0.0035).
H. T. Arkenau et al. Ann Oncol 2003;14:395-399
Adjuvant 5-Fu
Surgery
MOSAIC Study: 6-Y OAS; by Treatment Arm:
J Clin Oncol. 2009,27:3109-3116
Median OSMonths
1980s 1990s 2000sBSC
5-FUIrinotecan1
Capecitabine2
Oxaliplatin3
Bevacizumab4
Cetuximab5,6
Panitumumab7
Aflibercept8
Regorafenib9
30
25
20
15
10
5
0
1. Cunningham D, et al. Lancet. 1998;352(9138):1413-1418. 2. Van Cutsem E, et al. Br J Cancer. 2004;90(6):1190-1197. 3. Rothenberg M, et al. J Clin Oncol. 2003;21(11):2059-2069.4. Hurwitz H, et al. N Engl J Med. 2004;350(23):2335-2342. 5. Cunningham D, et al. N Engl J Med. 2004;351(4):337-345. 6. Van Cutsem E, et al. N Engl J Med. 2009;360(14):1408-1417.7. Van Cutsem E, et al. J Clin Oncol. 2007;25(13):1658-6164. 8. Van Cutsem E et al. J Clin Oncol.2012;30(28):3499-3506. 9. Grothey A, et al. Lancet. 2013;381(9863):303-312.
Choice of Systemic Therapy in M1 disease::
Local Recurrence in Rectal Cancer Following Surgery Alone:
Clinical Colorectal Cancer, Vol. 4, No. 4, 233-240, 2004
Adjuvant Radiation Therapy in Rectal Cancer:
Clinical Colorectal Cancer, Vol. 4, No. 4, 233-240, 2004
Neoadjuvant Therapy: The German Study: A Shifting Concept
N Engl J Med 2004;351:1731-40.
Radiation & Medical Oncologist
It is also Important
Local Recurrence: Better Insight:
Circumferential Margins
Number Local Recurrence Rate
P
> 2 mm 987 3.3% < 0.0001
1 – 2 mm 100 8.5% 0.02
< 1 mm 227 13.1 0.08
Int. J. Radiation Oncology Biol. Phys., Vol. 55, No. 5, pp. 1311–1320, 2003
CRM or LNs:
MURCERY Trial:
Fiona et al. JCO. 2014:1(32). 34-46.
Radiologist
Welcome on Board
Cuthbert Dukes 1932: Nodes as a prognostic factor
Limitations of the TNM – T3 category forms 80% of rectal cancers
Understanding of Molecular Events:
Epidermal Growth Factor Family of Receptors
Biological Cascade of Proliferation
Angiogenesis
Invasion, Progression & Metastases
Pathologist
Very Crucial.
MDT: Definition
Individual Specialties Together Either Physically or Virtually Discussing Therapeutic Strategy of a Given Patient
It’s MANDATORY! Greater accuracy of staging Fewer treatment delays Better outcome!
Fleissing A, et al. Lancet Oncol. 2006; 7(11): 935 – 943; Du CZ, et al. Worl J Gastroenterol. 2011;17(15):2013-2018;MacDermid E, et al. Colorectal Dis. 2009;11(3):291-295; Viganò L, et al. Ann Surg Oncol. 2013 Mar;20(3):938-45
MDT: Benefits
Met. CRC: Different Presentations, Aims & Outcomes
Potentially resectable
LLD of mCRC
Resectable 15-20%
Unresectable 80-85%
Resection
Cure 30-40%
Potentially Resectable 10-
30%
Unresectable 70-90%
Cth +/- Others
OASQ0L
mCRC with LLD: Key Players
Systemic Therapies Alone
Cures 1 – 2% of Patients
Surgery Alone
Cures > 30% of Patients
Don’t Miss Surgical Intervention
The Race Toward More Responses
Results of Hepatic Resection for Patients with mCRC:
Survival (%)Author (year) No. Patients Mortality,% Median Survival 1-year 5-year
Hughes et al (86) 607 --- --- --- 33
Gayowski et al (94) 204 0 33 mo 91 32
Scheele et al (95) 469 4 40 mo 83 39
Fong et al (95) 577 4 40 mo 85 35
Jamison et al (97) 280 4 33 mo 84 27
Fong et al (99) Choti et al (02) Pawlik et al (05)
1001226557
311
42 mo46 mo74 mo
--- 9697
364058
Hughes KS, et al. Surgery. 1986;100(2):278-284. Gayowski TJ, et al. Surgery. 1994;116(4):703-710. Scheele J, et al. World J Surg. 1995;19(1):59-71. Fong Y, et al. Ann Surg. 1995;222(4):426-434.; Jamison RL, et al. Arch Surg. 1997;132:505–510. Fong Y, et al. Ann Surg 1999;230:309-318; Choti MA, et al. Ann Surg. 2002;235(6):759-766; Pawlik TM, et al. Ann Surg. 2005;241(5):715-722.
MDT Outcome:
Take Home Message:
• mCRC is a real burden in daily practice.• Surgical resection of organ limited disease
Cure “The Race Toward Surgery”.• Changing landscape of disease Cure of
advancing & metastatic diseasebecame possible.
• Routine practice of MDT should be encouraged to get the beneficial outcome.
Thank You