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CANCER GÁSTRICO
TRATAMIENTO ADYUVANTE
MARIANA SERRANO CARDOSO
R4 MEDICINA ONCOLÓGICA – INEN
MAYO, 2017
I: 12.1 por cada 100 000 hab
M: 8.9 por cada 100 000 hab
EPIDEMIOLOGÍA
INCIDENCIA: 5to lugar
MORTALIDAD: 2da causa
•> incidencia: Este de Asia, Sudamérica, Europa Oriental
•< Incidencia: EUA, Europa occidental.
https://www.inei.gob.pe/media/MenuRecursivo/publicaciones_digitales/Est/Lib1251/Libro.pdf
EPIDEMIOLOGÍA
17 trials (3838 patients), median follow-up > 7 years
OS was 4.9 years in CX / 7.8 years in ADY QT
5 years CX ALONE 49.6%/ ADY QT 55.3%
10 years CX ALONE 37,5%/ ADY QT 44.9%
Absolute benefits were 5.8%
SG & SLE (HR 0.82)
18% reduction of risk of death with ADY QT
DFS The absolute benefit at 5 years was 5.3%, from 48.7% to 54.0%
JAMA, May 5, 2010—Vol 303, No. 17
Estimated 3-year DFS ADY CHEMO was 75%
DFS OBSERV was 60%
Estimated 5-year DFS ADY CHEMO was 68%
DFS OBSERV was 53%
Estimated 5-year SG ADY CHEMO was 78%
SG OBSERV was 69%
.
Lancet Oncol 2014; 15: 1389–96
ADY QT; DFS (HR 0.58)
ADY QT; SG (HR 0.66)
A randomised Phase III Trial
1035 patients, EC II, IIIA – IIIB, ECOG O – 2
D2 resection within 6 w before randomisation
END POINT: SLE a los 3 años, SG
Absolute benefits 15%
Absolute benefits 9%
34% reduction of risk of death
42% reduction of risk of recurrence disease
A randomised Phase III Trial
556 patients
ECOG O - 2
Histologically: Adenocarcinoma
R0 – D0 – D1 – D2 (10%)
EC: IB through IVM0
T 1–4
NODES 0, 1–3, >3
END POINT: SG, SLR
CHEMO (5FU 425 mg/m2/d and leucovorin, 20 mg/m2/d for 5
days): Days 1 - 5 after 28 days: CT_RT x 25 days
CHEMO-RT: 4500 cGy of radiation at 180 cGy/d 5 days/week for
5 weeks + 5FU 400 mg/m2/d and leucovorin, 20 mg/m2/d: Days
1 – 4 and 26 – 28 of RT
1 m after the completion of RT, 2 cycles of 5-day of 5FU (425
mg/m2/d) and leucovorin (20 mg/m2/d)
MacDonaldJS, et al. N EnglJ Med2001;345:725–730
CT+ CT-RT + CT
NO TREATMENT
SURGERY
SURGICAL PROCEDURES
54 (10%): D2 dissection.
199 (36%): D1 dissection
299 (54%): D0 dissection.
SLR 3y 48% VS 31%
SG 3y 50% VS 41%
THE ROLE OF RADIATION IN THE POSTOPERATIVE
SETTING: ADJUVANT
Absolute benefits 17% y 9%
Stephen R. Smalley J Clin Oncol 30. © 2012 by American Society of Clinical Oncology
ADJUVANT CHEMORADIOTHERAPY FOR GASTRIC CANCER AFTER
SURGERY VERSUS SURGERY ALONE: LONG TERM DATA OF A
RANDOMISED PHASE III TRIAL
The HR for OS after CRT compared with surgery alone was 1.32 (p =
0.004) and 1.51 for recurrence-free survival (p < 0.001).
The XP/XRT/XP arm:
2 cycles of XP followed
45-Gy XRT (Capecitabine
1,650 mg/m2/day for 5
weeks)
Then 2 cycles of XP.
6 cycles of XP
(capecitabine
2g/m2/day 1 to 14
and CDDP 60 mg/m2
on day 1)
repeated c/3 weeks
458 korean patients
GASTRIC CA IB – IV (M0)
18 years or older.
ECOG 0, 1
R0 gastrectomy
D2 lymph node
Dissection
END POINT: SLE
ARTIST 10 years
THE ROLE OF RADIATION IN THE POSTOPERATIVE SETTING
ADJUVANT CISPLATIN AND CAPECITABINE VERSUS
CHEMORADIATION FOR GASTRIC CANCER AFTER SURGERY
Se Hoon Park. J Clin Oncol 33. © 2015 by American Society of Clinical Oncology
Se Hoon Park. J Clin Oncol 33. © 2015 by American Society of Clinical Oncology
In 396 patients with node-positive disease, 3-year DFS was
significantly different (72% in XP arm v 76% in XPRT arm; P .04).
In 163 patients with intestinal-type GC, 3-year DFS rates were
83% and 94% in the XP and XPRT arms, respectively (P.01).
FOREST PLOT OF HAZARD RATIOS (HRS)
AND 95% CIS FOR DISEASE-FREE SURVIVAL.
PROGNOSTIC VALUE OF THE METASTATIC LYMPH NODE (N) RATIO IN THE ADJUVANT CHEMORADIOTHERAPY IN
STOMACH TUMORS (ARTIST) PHASE III TRIAL
The proportion between metastatic and examined
lymph nodes (N ratio): independent prognostic
factor in gastric cancer (GC) patients.
Methods: We retrospectively reviewed the data of
458 ARTIST patients who underwent D2 gastrectomy
followed by adjuvant chemotherapy with
capecitabine plus cisplatin (XP, n = 228) or
chemoradiotherapy (XPRT, n = 230).
Four N ratio categories (0% v 1-9% v 10-25% v >
25%) were employed, and statistical analysis was
performed using adjusted Cox regression and
stratified survival analysis.
Soonil Lee, Se Hoon Park, Jeeyun Lee, Won Ki Kang; Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea; Samsung Medical
Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Samsung Medical Center, Seoul, Korea, The Republic of; Division of Hematology-Oncology, Department of Medicine, Samsung
Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
ASCO, 2016 (suppl; abstr 4038)
Results:
At multivariate analysis, N ratio was retained as an
independent prognostic factor for DFS: HR for N ratio 0%, 1; N
ratio 1-9%, 1.061; N ratio 10-25%, 1.202; and N ratio > 25%,
3.571.
In patients with N ratio > 25%, the 5-year DFS was 55% v 28%
for XPRT and XP arms, respectively (HR, 0.527; 95% CI, 0.307
to 0.904; P = 0.020).
PHASE III trial,
788 patients, GASTRIC CA IB – III, ECOG 0, 1
D1 + lymph node dissection
END POINT: SG, SLE, toxicity profile and quality of life
Control arm: ECC x 3
Experimental arm: QT-RT x 5 weeks.
Capecitabine: 575 mg/m2 bid from Mon to Frid
Cisplatin 20 mg/m2 intravenously weekly.
Epirubicin 50 mg/m2 day 1
Cisplatin 60 mg/m2 day 1
Capecitabine 1000 mg/m2 bid for 14 d
every 3 weeks
Dikken et al. BMC Cancer 2011, 11:329
CONCLUSIONES
PACIENTES CANDIDATOS A QUIMIOTERAPIA
- RADIOTERAPIA CONCURRENTE
 Cirugías insuficientes: D1
 Ratio ganglionar: > 25%
 Según clasificación de Lauren: Adenocarcinomas de
Tipo intestinal
 Grupo Molecular: CIN.
¿ PORQUE ELIGIRÍA ADYUVANCIA COMO OPCION TERAPEUTICA ?
STATUS PERFORMANCE INADECUADO PARA NEOADYUVANCIA
PACIENTES CANDIDATOS A
QUIMIOTERAPIA SISTEMICA
 Cirugías D2, R0

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Cancer gastrico adyuvancia

  • 1. CANCER GÁSTRICO TRATAMIENTO ADYUVANTE MARIANA SERRANO CARDOSO R4 MEDICINA ONCOLÓGICA – INEN MAYO, 2017
  • 2. I: 12.1 por cada 100 000 hab M: 8.9 por cada 100 000 hab EPIDEMIOLOGÍA INCIDENCIA: 5to lugar MORTALIDAD: 2da causa •> incidencia: Este de Asia, Sudamérica, Europa Oriental •< Incidencia: EUA, Europa occidental.
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  • 6. 17 trials (3838 patients), median follow-up > 7 years OS was 4.9 years in CX / 7.8 years in ADY QT 5 years CX ALONE 49.6%/ ADY QT 55.3% 10 years CX ALONE 37,5%/ ADY QT 44.9% Absolute benefits were 5.8% SG & SLE (HR 0.82) 18% reduction of risk of death with ADY QT DFS The absolute benefit at 5 years was 5.3%, from 48.7% to 54.0% JAMA, May 5, 2010—Vol 303, No. 17
  • 7. Estimated 3-year DFS ADY CHEMO was 75% DFS OBSERV was 60% Estimated 5-year DFS ADY CHEMO was 68% DFS OBSERV was 53% Estimated 5-year SG ADY CHEMO was 78% SG OBSERV was 69% . Lancet Oncol 2014; 15: 1389–96 ADY QT; DFS (HR 0.58) ADY QT; SG (HR 0.66) A randomised Phase III Trial 1035 patients, EC II, IIIA – IIIB, ECOG O – 2 D2 resection within 6 w before randomisation END POINT: SLE a los 3 años, SG Absolute benefits 15% Absolute benefits 9% 34% reduction of risk of death 42% reduction of risk of recurrence disease
  • 8. A randomised Phase III Trial 556 patients ECOG O - 2 Histologically: Adenocarcinoma R0 – D0 – D1 – D2 (10%) EC: IB through IVM0 T 1–4 NODES 0, 1–3, >3 END POINT: SG, SLR CHEMO (5FU 425 mg/m2/d and leucovorin, 20 mg/m2/d for 5 days): Days 1 - 5 after 28 days: CT_RT x 25 days CHEMO-RT: 4500 cGy of radiation at 180 cGy/d 5 days/week for 5 weeks + 5FU 400 mg/m2/d and leucovorin, 20 mg/m2/d: Days 1 – 4 and 26 – 28 of RT 1 m after the completion of RT, 2 cycles of 5-day of 5FU (425 mg/m2/d) and leucovorin (20 mg/m2/d) MacDonaldJS, et al. N EnglJ Med2001;345:725–730 CT+ CT-RT + CT NO TREATMENT SURGERY SURGICAL PROCEDURES 54 (10%): D2 dissection. 199 (36%): D1 dissection 299 (54%): D0 dissection. SLR 3y 48% VS 31% SG 3y 50% VS 41% THE ROLE OF RADIATION IN THE POSTOPERATIVE SETTING: ADJUVANT Absolute benefits 17% y 9%
  • 9. Stephen R. Smalley J Clin Oncol 30. © 2012 by American Society of Clinical Oncology ADJUVANT CHEMORADIOTHERAPY FOR GASTRIC CANCER AFTER SURGERY VERSUS SURGERY ALONE: LONG TERM DATA OF A RANDOMISED PHASE III TRIAL The HR for OS after CRT compared with surgery alone was 1.32 (p = 0.004) and 1.51 for recurrence-free survival (p < 0.001).
  • 10. The XP/XRT/XP arm: 2 cycles of XP followed 45-Gy XRT (Capecitabine 1,650 mg/m2/day for 5 weeks) Then 2 cycles of XP. 6 cycles of XP (capecitabine 2g/m2/day 1 to 14 and CDDP 60 mg/m2 on day 1) repeated c/3 weeks 458 korean patients GASTRIC CA IB – IV (M0) 18 years or older. ECOG 0, 1 R0 gastrectomy D2 lymph node Dissection END POINT: SLE ARTIST 10 years THE ROLE OF RADIATION IN THE POSTOPERATIVE SETTING ADJUVANT CISPLATIN AND CAPECITABINE VERSUS CHEMORADIATION FOR GASTRIC CANCER AFTER SURGERY Se Hoon Park. J Clin Oncol 33. © 2015 by American Society of Clinical Oncology
  • 11. Se Hoon Park. J Clin Oncol 33. © 2015 by American Society of Clinical Oncology In 396 patients with node-positive disease, 3-year DFS was significantly different (72% in XP arm v 76% in XPRT arm; P .04). In 163 patients with intestinal-type GC, 3-year DFS rates were 83% and 94% in the XP and XPRT arms, respectively (P.01). FOREST PLOT OF HAZARD RATIOS (HRS) AND 95% CIS FOR DISEASE-FREE SURVIVAL.
  • 12. PROGNOSTIC VALUE OF THE METASTATIC LYMPH NODE (N) RATIO IN THE ADJUVANT CHEMORADIOTHERAPY IN STOMACH TUMORS (ARTIST) PHASE III TRIAL The proportion between metastatic and examined lymph nodes (N ratio): independent prognostic factor in gastric cancer (GC) patients. Methods: We retrospectively reviewed the data of 458 ARTIST patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with capecitabine plus cisplatin (XP, n = 228) or chemoradiotherapy (XPRT, n = 230). Four N ratio categories (0% v 1-9% v 10-25% v > 25%) were employed, and statistical analysis was performed using adjusted Cox regression and stratified survival analysis. Soonil Lee, Se Hoon Park, Jeeyun Lee, Won Ki Kang; Department of Internal Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan, South Korea; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Samsung Medical Center, Seoul, Korea, The Republic of; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea ASCO, 2016 (suppl; abstr 4038) Results: At multivariate analysis, N ratio was retained as an independent prognostic factor for DFS: HR for N ratio 0%, 1; N ratio 1-9%, 1.061; N ratio 10-25%, 1.202; and N ratio > 25%, 3.571. In patients with N ratio > 25%, the 5-year DFS was 55% v 28% for XPRT and XP arms, respectively (HR, 0.527; 95% CI, 0.307 to 0.904; P = 0.020).
  • 13. PHASE III trial, 788 patients, GASTRIC CA IB – III, ECOG 0, 1 D1 + lymph node dissection END POINT: SG, SLE, toxicity profile and quality of life Control arm: ECC x 3 Experimental arm: QT-RT x 5 weeks. Capecitabine: 575 mg/m2 bid from Mon to Frid Cisplatin 20 mg/m2 intravenously weekly. Epirubicin 50 mg/m2 day 1 Cisplatin 60 mg/m2 day 1 Capecitabine 1000 mg/m2 bid for 14 d every 3 weeks Dikken et al. BMC Cancer 2011, 11:329
  • 14. CONCLUSIONES PACIENTES CANDIDATOS A QUIMIOTERAPIA - RADIOTERAPIA CONCURRENTE  Cirugías insuficientes: D1  Ratio ganglionar: > 25%  Según clasificación de Lauren: Adenocarcinomas de Tipo intestinal  Grupo Molecular: CIN. ¿ PORQUE ELIGIRÍA ADYUVANCIA COMO OPCION TERAPEUTICA ? STATUS PERFORMANCE INADECUADO PARA NEOADYUVANCIA PACIENTES CANDIDATOS A QUIMIOTERAPIA SISTEMICA  Cirugías D2, R0