Transcript Guidelines for Upper G.I. Carcinomas

MANAGEMENT OF
ESOPHAGEAL CANCER
Elshami Elamin, MD
Medical Oncologist
Central Care Cancer Center
www.cccancer.com
Newton, KS - USA
ESOPHAGEAL CANCER
 Risk factors
 Alcohol / Tobacco
 Head / neck cancer
 High fat, low protein & calories
 Barrett’s
 Tylosis
 Plummer Vinson syndrome (Paterson-Brown-
kelly Synd)
 Achalasia
Symptoms & Signs
 Dysphagia
 Wt. Loss
 Cough
 Pain
 Hoarseness
 Malig pleural effusion, Ascites
 Hypercalcemia
Work-Up
Locoregional
H&P
EGD
CBC, CMP
CT chest/abd
I-III/IVA
No Mets:
Bronchoscopy
*Tumor at or above Carina
EUS
Laparoscopy (GEJ)
PET/CT
IVB
INTRODUCTION
 Surgery has been the raditional management
of patients with localised esophageal cancer
 Survival is poor, and many pts develop mets or
locoregional recurrence soon after surgery
Treatment modalities
 Esophagectomy:
 Resectable esophageal cancer:
 >5 cm from cricopharyngeus
 Cervical and cervicothoracic cancer i.e <5 cm
from cricopharyngeus should be treated
with definitive chemoradiation.
 R.T.
 Chemotherapy
 BSC
•Medically Fit
•Resectable
(>5cm from
cricopharyngeus)
Locoregional
I-III/IVA
•Multidisiplinary
Eval
•Nutritional
Assessment
(NGT, J-Tube, PEG
not recommended)
IVB
Salvage
Therapy
•Inresectable: T4
•Medically unfit
 GEJ: Celiac nodal involvement may not exclude
combined modality therapy
 Resectable stage IVA:
 Distal esophageal cancer with resectable celiac node
 No involvement of aorta or other organ
 No involvement of celiac artery
 ReseInvctable T4:
 Involvement of
 Pericardium
 Pleura
 Diaphragm
•Medically Fit
•Resectable disease
•Endoscopic mucosal resection OR
•Esophagectomy
•Esophagectomy
•Medically Fit
•Resectable
•T1b,N0-1
(preferred for
noncervical)
Preop Chemo for adeno
of distal Esoph or GEJ
(ECF)
•T1b, N1
•T2-4, N0-1,Nx
•M1a (IVA)
Definitive
ChemoRT
Preop ChemoRT
RT 50-50.4 Gy
Preop Chemo for
adeno
of distal Esoph or GEJ
Definitive
ChemoRT
Preop ChemoRT
RT 50-50.4 Gy
Esophagectomy
PET-CT/CT
*EGD
PET-CT/CT
*EGD
•*EGD > 5 wks with biopsy or brushings
See
Surgical
outcome
Salvage
esophagectomy
for local residual
disease
NED
•Esophagectomy (preferred)
•Observe
See
Surgical
outcome
Preop
ChemoRT
RT 50-50.4 Gy
•PET-CT/CT
•*EGD
Persistent
local dis
unresectable
Mets
•*EGD > 5 wks with biopsy or brushings
•Esophagectomy
(preferred)
•paliative/ (chemo)
Surgical outcomes
•Tis, T1, N0: observe
•adeno
•N -
R0
•T2,N0: observe or chemoRT
•T3,N0: chemoRT *ECF if given preop (categ 1)
•Squamous
•N+
*ECF if given preop (categ 1)
•Adeno prox or mid
•Adeno distal or GEJ
•Observe
•Observe or chemoRT
•chemoRT *ECF if given preop (categ 1)
R1
•chemoRT
R2
•chemoRT or palliative
•Medically Unfit
•Unresectable dis.
•Endoscopic mucosal resection OR
•ChemoRT
•Medically unfit
•unresectable
•Medically unfit
•Chemo is tolerable
•Unresectable: T4/IVA
•ChemoRT
•Chemo
•RT
•BSC
•Palliative RT
•BSC
ANY SCEINTIFIC EVIDENCE TO
SUPPORT THE USE OF
CHEMOTHERAPY/R.T. IN LOCALLY
ADVANCED OPERABLE
ESOPHAGEAL/GASTRIC CANCER
?
LITRETURE
REVIEW
ADJUVANT THERAPY
 Adj RT, chemo, or chemoRT
 Mixed results and disappointing
 Because trials were small and lacked statistical power
 Adj treatment based on 2 or 3-year survival rates
 chemoRT and chemo have similar benefits
NEOADJUVANT THERAPY
 Due to sig postop complication rate, focus
has turned to neoadj treatment.
 Currently, there is no evidence to support the use of
neoadj RT alone
Any role for Chemo/RT
 <30% of locally advanced Gastric/GEJ adeno
could be cure with surgery alone
 Previous adj chemo failed to show clinical
benefit
INT-0116
(SWOG 9008)
 Randomized lll Trial:
•Adj
Option
 Resectable adeno of stomach
 GEJ (lB-IVA)
 5-FU/LVx5d--> RT+5-FU/LV during first 4d and last
3d of RT --> 2cycles of 5-FU/LVx5d
 postop CT/RT improve DFS&OS in R0
(resected locally advanced)
 [standard of care]
•Macdonald et al; N Engl J Med. 2001 Sep 6;345(10):725-30.
The MAGIC Trial
The Medical Research Council Adjuvant
Gastric Infusional Chemotherapy
 Operable adeno of the stomach, the lower
third of the esophagus, and the GEJ ( 74% of
pts had tumors in the stomach)
 ECFx3->surg->ECFx3 (250 pts) vs Surgery
alone (253 pts):
 5Y survival: 36% vs 23%
 Chemo sig. improves resectability,
PFS and OS
•D. Cunningham, et al ; N Engl J Med. 2006 Jul 6;355(1):11-20.
•Periop.
option
Preoperative Chemotherapy vs
Surgery Alone
 FNLCC ACCORD 07-FFCD 9703, multicenter,
randomized
trial indicated benefit of preoperative
chemotherapy vs surgery alone for resectable
adenocarcinoma of stomach and lower
esophagus[1]
 Higher rate of R0 resection (87% vs 74%; P = .04)
 Higher 5-yr OS (38% vs 24%; P = .021)
 No increase in postoperative morbidity or mortality
Boige V, et al. ASCO 2007; Abstract 4510.
Preoperative Chemotherapy vs
Surgery Alone
 Meta-analysis also demonstrated benefit for
preoperative chemotherapy in resectable
esophageal cancer[2]
 5-yr OS benefit of 4.3% (P = .003)
 5-yr DFS benefit of 4.4% (P = .0001)
Thirion P, et al. ASCO 2007. Abstract 4512.
CALGB 9781
 Only 56 pt with stage I-III
 Preop-chemo/RT vs surgery
alone
 MS 4.5y vs 1.8y
 Trimodality imroves survival
Survival benefits from neoadjuvant
chemoradiotherapy or
chemotherapy in oesophageal carcinoma
(meta-analysis)
Val Gebski, Bryan Burmeister, B Mark Smithers, Kerwyn Foo, John Zalcberg,
John Simes, for the Australasian Gastro-Intestinal Trials Group
Lancet Oncol 2007; 8: 226–34
Meta-analysis
 MEDLINE, Cancerlit, and EMBASE
databases from major scientific
meetings (1980-2006)
 Pts with local operable esophageal
ca
 10 randomised trials of neoadjuvant
chemoRT vs surgery (n=1209)
 SCC = 6, adeno =1, both = 3
 8 of neoradjuvant chemo vs surgery (n=1724)
with comparisons
 SCC = 7, both = 2
Meta-analysis
Findings
 The hazard ratio for all-cause mortality with
neoadj chemoRT vr surgery
 0·81 (95% CI 0·70–0·93; p=0·002)
 corresponding to a 13% absolute difference in survival at
2 years
 0·84 (0·71–0·99; p=0·04) for SCC
 0·75 (0·59–0·95; p=0·02) for adeno
 The hazard ratio for neoadj chemo was 0·90
(0·81–1·00;p=0·05)
 2-year absolute survival benefit of 7%
 No sig effect on all-cause mortality of chemo for SCC
(hazard ratio 0·88 [0·75–1·03]; p=0·12)
 Sig benefit for adeno (0·78 [0·64–0·95]; p=0·014)
NEOADJ CHEMO
 For SCC, neoadj chemo did not have a
survival benefit
 hazard ratio for mortality 0・88 [0・75–1・03]
 p = 0・12
 For adeno, neoadj chemo showed sig survival
benefit (UK Medical Research Council MRC trial)
 hazard ratio for mortality 0・78 [0・64–0・95]
 P = 0・014
Long term results of the MRC OEO2 randomized
trial of surgery with or without preoperative
chemotherapy in resectable esophageal cancer
 Conclusions: Long term follow-up confirms
that preoperative chemotherapy improves
survival in operable esophageal cancer and
should be considered as a standard of care.
 2002 (Lancet 2002; 359: 1727-33)
NEOADJUVANT CHEMO/RT
 Neoadj chemoRT vs surgery
 sign benefit over surgery for both histological types
 0・84 (0・71–0・99); p = 0・04 for SCC
 0・75 (0・59–0・95); p = 0・02 for adeno
Sequential vs Concurrent chemoRT
 No survival benefit of sequential chemoRT in
SCC
 hazard ratio for mortality 0・90 [0・72–1・03]; p=0
・18)
 similar to SCC treated with neoadj chemo
 Concurrent chemoRT had sig benefit for both
histological types
 hazard ratios 0・76 and 0・75 for SCC and adeno,
respectively
Meta-analysis
Interpretation
 A signifi cant survival benefi t was evident
for preoperative chemoradiotherapy and,
to a lesser extent, for chemotherapy in
patients with adenocarcinoma of the
oesophagus.
Cumulative Survival
Probability
MDACC study: Salvage Resection
for Esophageal Carcinoma: OS
OS
Planned surgery
1.0
0.8
Salvage
0.6
 5-year survival 46% for
salvage vs 42% for
planned resection
0.4
0.2 P = .125
0.0
0
10
 No difference in OS
between salvage and
planned resection
20
30
40
50
60
Months
Median follow-up: 24 months
Hofstetter WL, et al. GI Cancers Symposium 2009. Abstract 7.
THANKS