Guidelines for Upper G.I. Carcinomas
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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