management of esophageal cancer elshami elamin, md medical oncologist central care cancer center ...
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Elshami Elamin, MD Medical Oncologist
Central Care Cancer Centerwww.cccancer.comNewton, 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-UpWork-Up
H&PH&PEGDEGDCBC, CMPCBC, CMPCT chest/abdCT chest/abd
No Mets:No Mets: BronchoscopyBronchoscopy *Tumor at or above Carina*Tumor at or above Carina
EUSEUS Laparoscopy Laparoscopy (GEJ)(GEJ)
PET/CTPET/CT
Locoregional I-III/IVA
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
Locoregional I-III/IVA
IVB
SalvageTherapy
•Medically Fit•Resectable(>5cm from cricopharyngeus)
•Inresectable: T4•Medically unfit
•Multidisiplinary Multidisiplinary EvalEval
•NutritionalNutritionalAssessmentAssessment
(NGT, J-Tube, PEG (NGT, J-Tube, PEG not recommended)not recommended)
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
•Esophagectomy (preferred for noncervical)
•Tis, T
1a
Tis, T
1a
•Medically Fit•Resectable
•T1b,N0-1T1b,N0-1
•T1b, N1•T2-4, N0-1,Nx•M1a (IVA)
•Endoscopic mucosal resection OR•Esophagectomy
•T1b, N1•T2-4, N0-1,Nx•M1a (IVA)
Preop Chemo for adeno Preop Chemo for adeno
of distal Esoph or GEJof distal Esoph or GEJ
(ECF)(ECF)
PreopPreop ChemoRTChemoRT
RT 50-50.4 GyRT 50-50.4 Gy
Definitive Definitive ChemoRTChemoRT
Preop Chemo for Preop Chemo for adeno adeno
of distal Esoph or of distal Esoph or GEJGEJ
PreopPreop ChemoRTChemoRT
RT 50-50.4 GyRT 50-50.4 Gy
Definitive Definitive ChemoRTChemoRT
PET-CT/CTPET-CT/CT
*EGD*EGD
Salvage Salvage esophagectomesophagectom
y for local y for local residual residual diseasedisease
EsophagectomyEsophagectomy
PET-CT/CTPET-CT/CT
*EGD*EGD
See See SurgicSurgic
al al outcooutco
meme
•*EGD *EGD >> 5 wks with biopsy or brushings 5 wks with biopsy or brushings
PreopPreop ChemoRTChemoRT
RT 50-50.4 GyRT 50-50.4 GyPersistent Persistent
local dislocal dis
NEDNED
unresectableunresectable
MetsMets
See See SurgicSurgic
al al outcooutco
meme
•PET-CT/CTPET-CT/CT•*EGD*EGD
•Esophagectomy (preferred)Esophagectomy (preferred)•ObserveObserve
•Esophagectomy Esophagectomy
(preferred)(preferred)•paliative/ (chemo)paliative/ (chemo)
•*EGD *EGD >> 5 wks with biopsy or brushings 5 wks with biopsy or brushings
RR00
Surgical outcomesSurgical outcomes
RR11RR22
•N -N -
•N+N+
•adenoadeno
•Tis, T1, N0: observeTis, T1, N0: observe
•T2,N0: observe or chemoRT T2,N0: observe or chemoRT *ECF if given *ECF if given preop (categ 1)preop (categ 1)
•T3,N0: chemoRT *T3,N0: chemoRT *ECF if given ECF if given preop (categ 1)preop (categ 1)
•Observe or Observe or chemoRTchemoRT
•SquamousSquamous •ObserveObserve
•Adeno prox or midAdeno prox or mid
•Adeno distal or GEJAdeno distal or GEJ •chemoRT *chemoRT *ECF if given preop ECF if given preop (categ 1)(categ 1)
•chemoRT chemoRT
•chemoRT or palliativechemoRT or palliative
•Medically Unfit•Unresectable dis.
•ChemoRT•Chemo•RT•BSC
•Tis, T
1a
Tis, T
1a
•Medically unfit•unresectable
•Medically unfit•Chemo is tolerable•Unresectable: T4/IVA
•Endoscopic mucosal resection OR•ChemoRT
•Medically unfit•Chemo is not tolerable •Palliative Palliative RTRT•BSCBSC
ANY SCEINTIFIC EVIDENCE TO ANY SCEINTIFIC EVIDENCE TO SUPPORT THE USE OF SUPPORT THE USE OF CHEMOTHERAPY/R.T. IN CHEMOTHERAPY/R.T. IN
LOCALLY ADVANCED OPERABLE LOCALLY ADVANCED OPERABLE ESOPHAGEAL/GASTRIC CANCERESOPHAGEAL/GASTRIC CANCER
??
LITRETULITRETURE RE
REVIEWREVIEW
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: 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]
•Adj Option
•Macdonald et al; N Engl J Med. 2001 Sep 6;345(10):725-30.
The MAGIC TrialThe MAGIC TrialThe Medical Research Council The Medical Research Council Adjuvant Gastric Infusional Adjuvant Gastric Infusional
Chemotherapy 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
•Periop. option•D. Cunningham, et al ; N Engl J Med. 2006 Jul 6;355(1):11-20.
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
mortalityBoige 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
Lancet Oncol 2007; 8: 226–34
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
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-analysisFindings
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-analysisInterpretation
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.
MDACC study: Salvage Resection for Esophageal
Carcinoma: OS No difference in OS between salvage and planned resection
5-year survival 46% for salvage vs 42% for planned resection
Hofstetter WL, et al. GI Cancers Symposium 2009. Abstract 7.
OS
Cu
mu
lati
ve S
urv
ival
Pro
bab
ilit
y
Months
P = .125
Median follow-up: 24 months
Salvage
Planned surgery
0.0
0.2
0.4
0.6
0.8
1.0
0 10 20 30 40 50 60
THANKS