Hotel Sonesta, Bogotá, 29.07.2017

1. Tratamiento multimodal de cáncer de recto: visión del
oncólogo
Mauricio Lema Medina MD
Clínica de Oncología Astorga / Clínica SOMA, Medellín, Colombia
Hotel Sonesta
Bogotá, 29.07.2017
1er Simposiso de Cáncer
Gastrointestinal - ACHO

2. Rectal
cancer
Stage I Surgery
Stage
IVb
Palliative CT
Stage
II-IVa
XRT
CT
Surgery
Combined-
modality

3. XRT
CT
Surgery
SurgeryXRT
SurgeryCRT
CRTSurgery
Surgery
SurgeryXRT
SurgeryCRT
CRTSurgery
XRT
CT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long RT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

5. Presented By Al Benson at 2017 ASCO Annual Meeting

6. XRT
CT
TME
TMEXRT
TMECRT
CRTTME
TME
TMEXRT
TMECRT
CRTTME
XRT
CT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long RT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

7. Preoperative or postoperative irradiation in adenocarcinoma of the
rectum: final treatment results of a randomized trial and an
evaluation of late secondary effects.
Frykholm, G. J., Glimelius, B., & Påhlman, L. (1993). Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final
treatment results of a randomized trial and an evaluation of late secondary effects. Diseases of the Colon and Rectum, 36(6), 564–
72. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8500374
Short-RT Surgery
25.5 Gy in 5d
Surgery Long-RT
60 Gy in 6-7 weeks
Stage II/III
Rectal cancer
Variable Pre-Op XRT Post-Op XRT p
Local recurrence
rate
11 % 22 % 0.02

8. Preoperative Radiotherapy Combined with Total Mesorectal
Excision for Resectable Rectal Cancer
Kapiteijn, E., Marijnen, C. A. M., Nagtegaal, I. D., Putter, H., Steup, W. H., Wiggers, T., … van de Velde, C. J. H. (2001). Preoperative
Radiotherapy Combined with Total Mesorectal Excision for Resectable Rectal Cancer. New England Journal of Medicine, 345(9),
638–646. https://doi.org/10.1056/NEJMoa010580
Short-RT TME
25.5 Gy in 5d
TME
Resectable
rectal cancer (15
cm)
(n=1861)
Variable Pre-Op XRT TME alone p
Local recurrence
rate
2.4 % 8.2 % 1E+00

9. XRT
CT
Surgery
TMEShort XRT
TMECRT
CRTTME
Surgery
CRTTME
TMECRT
CRTTME
XRT
CT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long RT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

10. Preoperative versus postoperative chemoradiotherapy for rectal
cancer.
Sauer, R., Becker, H., Hohenberger, W., Rödel, C., Wittekind, C., Fietkau, R., … German Rectal Cancer Study Group. (2004).
Preoperative versus Postoperative Chemoradiotherapy for Rectal Cancer. New England Journal of Medicine, 351(17), 1731–1740.
https://doi.org/10.1056/NEJMoa040694
Chemo-RT (CRT) TME
5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5
TME Chemo-RT (CRT)
Rectal cancer
(16 cm)
(n=421)
Variable Pre-Op CRT Post-Op CRT p
Local recurrence
rate
6 % 13 % 6E+00
5040 cGy, FU 5000 mg/m2 continuous infusion 120 h, week 1 and 5

11. http://clinicaloptions.com/onco
Summary of Study Design
Sauer R, et al. N Engl J Med, 2004;351:1731-1740.
Arm A*
(n = 415)
Arm B†
(n = 384)
Locally
advanced
rectal cancer,
T3, T4, or node
positive
(N = 823)
*Arm A: Preoperative chemoradiotherapy: 28 fractions (180 cGy/day, 5 x/wk) radiotherapy plus
fluoropyrimidine agent
Postoperative chemotherapy: bolus 5-FU (500 mg/m2 5 x/wk) every 4 wks for 4 cycles
†Arm B: Chemotherapy: bolus 5-FU (500 mg/m2/day) for 5 days, every 4 wks for 4 cycles
Follow-up
every 3 mos for
2 yrs,
then every 6
mos for 3 yrs
Surgery
Wk 12
Preoperative
chemoradiotherapy
(6 wks)
Wk 0
Postoperative
chemotherapy
Wk 16
Wk 0
Surgery
Wk 16
Postoperative + 540 cGy boost
chemotherapy

12. http://clinicaloptions.com/onco
Key Conclusions
 Compared with postoperative chemotherapy,
preoperative chemoradiotherapy in patients with
locally advanced rectal cancer:
– Improves
» Local control
» Treatment compliance
» Rates of sphincter preservation
– Reduces long-term toxicity
– Does not improve overall survival or disease-free survival
 Preoperative chemoradiotherapy should be
considered first-line therapy for patients with
locally advanced rectal cancer
Sauer R, et al. N Engl J Med, 2004;351:1731-1740.

13. Timing of Chemo-XRT
Presented By Al Benson at 2017 ASCO Annual Meeting

14. XRT
CT
Surgery
TMEShort XRT
TMECRT
CRTTME
Surgery
CRTTME
TMECRT
CRTTME
XRT
CT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long CRT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

15. Postoperative adjuvant chemotherapy in rectal cancer operated for
cure
Petersen, S. H., Harling, H., Kirkeby, L. T., Wille-Jørgensen, P., & Mocellin, S. (2012). Postoperative adjuvant chemotherapy in rectal
cancer operated for cure. In S. H. Petersen (Ed.), Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons,
Ltd. https://doi.org/10.1002/14651858.CD004078.pub2

16. XRT
CT
Surgery
TMEShort XRT
TMECRT
CRTTME
Surgery
CRTTME
TMECRT
CRTTME
XRT
CT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long CRT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

17. Chemoradiotherapy with capecitabine versus fluorouracil for locally
advanced rectal cancer: a randomised, multicentre, non-inferiority,
phase 3 trial.
Hofheinz, R.-D., Wenz, F., Post, S., Matzdorff, A., Laechelt, S., Hartmann, J. T., … Hochhaus, A. (2012). Chemoradiotherapy with
capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. The
Lancet Oncology, 13(6), 579–588. https://doi.org/10.1016/S1470-2045(12)70116-X
CRT
(Capec)
TME
Two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by
chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three
cycles of capecitabineT
Stage II/III
Rectal cancer
(n=401)
Variable FOLFOX FULV p
5-yr OS 76 % 67 %
Significant (post-
hoc)
Capec.
x3-5
Caepec.
x2
CRT
(FULV)
TME
two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by
chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two
cycles of bolus fluorouracil
FULV.
x2-4
FULV.
x2

18. XRT
CT
Surgery
TMEShort XRT
TMECRT
CRTTME
Surgery
CRTTME
TME
CRT (FULV or
Capec)
CRTTME
XRT
CT
FULV
orCapec.
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long CRT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin

19. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant
chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy
(ADORE): an open-label, multicentre, phase 2, randomised controlled trial.
Hong, Y. S., Nam, B.-H., Kim, K., Kim, J. E., Park, S. J., Park, Y. S., … Kim, T. W. (2014). Oxaliplatin, fluorouracil, and leucovorin
versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy
(ADORE): an open-label, multicentre, phase 2, randomised controlled trial. The Lancet Oncology, 15(11), 1245–1253.
https://doi.org/10.1016/S1470-2045(14)70377-8
CRT TME
FU/Capecitabine + RT
CRT TME
Stage II/III
Rectal cancer
(n=321)
Variable FOLFOX FULV p
3-yr DFS 71.6 % 62.9 % Significant
FU/Capecitabine + RT
FOLFOX
(4 mo)
FU/LV
(4 mo)

20. XRT
CT
Surgery
TMEShort XRT
TMECRT
CRTTME
Surgery
CRTTME
CRTTME
XRT
CT
CT
Modality sequence
in stage II-IVa
rectal cancer
Short, or Long CRT
FU, or Capecitabine
Oxaliplatin vs no-oxaliplatin
TME
CRT (FULV or
Capec)
FOLFOX or
CAPOX

21. Non-standard

22. Cercek, Proc ASCO, 2017

23. Cercek, Proc ASCO, 2017

24. Total neoadjuvant therapy TNT
+/- TME
CRT (FULV or
Capec)
FOLFOX or
CAPOX
% Surgery % No surgery
TNT 78.2 21.8
Conventional 94.0 6.0
Cercek, Proc ASCO, 2017
RETROSPECTIVE

25. Gu, J. Proc ASCO, 2017

26. Gu, J. Proc ASCO, 2017