Guidelines for Upper G.I. Carcinomas

1
(No Transcript)
2
MANAGEMENT OF ESOPHAGEAL CANCER

• Elshami Elamin, MD
• Medical Oncologist
• Central Care Cancer Center
• www.cccancer.com
• Newton, KS - USA

3
ESOPHAGEAL CANCER

• Risk factors
• Alcohol / Tobacco
• Head / neck cancer
• High fat, low protein calories
• Barretts
• Tylosis
• Plummer Vinson syndrome (Paterson-Brown-kelly
  Synd)
• Achalasia

4
Symptoms Signs

• Dysphagia
• Wt. Loss
• Cough
• Pain
• Hoarseness
• Malig pleural effusion, Ascites
• Hypercalcemia

5
Work-Up HP EGD CBC, CMP CT chest/abd No Mets
Bronchoscopy Tumor at or above Carina
EUS Laparoscopy (GEJ) PET/CT
Locoregional I-III/IVA
IVB
6
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

7
Treatment modalities

• Esophagectomy
• Resectable esophageal cancer
• gt5 cm from cricopharyngeus
• Cervical and cervicothoracic cancer i.e lt5 cm
  from cricopharyngeus should be treated with
  definitive chemoradiation.
• R.T.
• Chemotherapy
• BSC

8

• Medically Fit
• Resectable
• (gt5cm from cricopharyngeus)

• Multidisiplinary
• Eval
• Nutritional
• Assessment
• (NGT, J-Tube, PEG
• not recommended)

Locoregional I-III/IVA
IVB
Salvage Therapy

• Inresectable T4
• Medically unfit

9

• 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

10

• Medically Fit
• Resectable disease

11

• Endoscopic mucosal resection OR
• Esophagectomy

• Tis, T1a

• Medically Fit
• Resectable

• Esophagectomy (preferred for noncervical)

• T1b,N0-1

• T1b, N1
• T2-4, N0-1,Nx
• M1a (IVA)

12
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
13
Preop Chemo for adeno of distal Esoph or GEJ
See Surgical outcome
Esophagectomy
Salvage esophagectomy for local residual disease
PET-CT/CT EGD
Definitive ChemoRT
Preop ChemoRT RT 50-50.4 Gy
PET-CT/CT EGD

• EGD gt 5 wks with biopsy or brushings

14
NED

• Esophagectomy (preferred)
• Observe

See Surgical outcome
Preop ChemoRT RT 50-50.4 Gy

• Esophagectomy
• (preferred)
• paliative/ (chemo)

Persistent local dis

• PET-CT/CT
• EGD

unresectable Mets

• EGD gt 5 wks with biopsy or brushings

15
Surgical outcomes

• Tis, T1, N0 observe

• adeno

• T2,N0 observe or chemoRT ECF if given preop
  (categ 1)

• N -

• T3,N0 chemoRT ECF if given preop (categ 1)

• Squamous

R0

• Observe

• Adeno prox or mid

• N

• Observe or chemoRT

• Adeno distal or GEJ

• chemoRT ECF if given preop (categ 1)

R1

• chemoRT

R2

• chemoRT or palliative

16

• Medically Unfit
• Unresectable dis.

17

• Endoscopic mucosal resection OR
• ChemoRT

• Tis, T1a

• Medically unfit
• unresectable

• ChemoRT
• Chemo
• RT
• BSC

• Medically unfit
• Chemo is tolerable
• Unresectable T4/IVA

• Medically unfit
• Chemo is not tolerable

• Palliative RT
• BSC

18
ANY SCEINTIFIC EVIDENCE TO SUPPORT THE USE OF
CHEMOTHERAPY/R.T. IN LOCALLY ADVANCED OPERABLE
ESOPHAGEAL/GASTRIC CANCER ?
19
LITRETURE REVIEW
20
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

21
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

22
Any role for Chemo/RT

• lt30 of locally advanced Gastric/GEJ adeno could
  be cure with surgery alone
• Previous adj chemo failed to show clinical
  benefit

23
INT-0116 (SWOG 9008)

• Adj Option

• Randomized lll Trial
• Resectable adeno of stomach
• GEJ (lB-IVA)
• 5-FU/LVx5d--gt RT5-FU/LV during first 4d and last
  3d of RT --gt 2cycles of 5-FU/LVx5d
• postop CT/RT improve DFSOS in R0 (resected
  locally advanced)
• standard of care

• Macdonald et al N Engl J Med. 2001 Sep
  6345(10)725-30.

24
The MAGIC TrialThe 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-gtsurg-gtECFx3 (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
  6355(1)11-20.

25
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
  esophagus1
• 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.
26
Preoperative Chemotherapy vs Surgery Alone

• Meta-analysis also demonstrated benefit for
  preoperative chemotherapy in resectable
  esophageal cancer2
• 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.
27
CALGB 9781

• Only 56 pt with stage I-III
• Preop-chemo/RT vs surgery alone
• MS 4.5y vs 1.8y
• Trimodality imroves survival

28
Survival benefits from neoadjuvant
chemoradiotherapy orchemotherapy 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 22634

29
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 (n1209)
• SCC 6, adeno 1, both 3
• 8 of neoradjuvant chemo vs surgery (n1724) with
  comparisons
• SCC 7, both 2

30
Meta-analysisFindings

• The hazard ratio for all-cause mortality with
  neoadj chemoRT vr surgery
• 081 (95 CI 070093 p0002)
• corresponding to a 13 absolute difference in
  survival at 2 years
• 084 (071099 p004) for SCC
• 075 (059095 p002) for adeno
• The hazard ratio for neoadj chemo was 090
  (081100p005)
• 2-year absolute survival benefit of 7
• No sig effect on all-cause mortality of chemo for
  SCC (hazard ratio 088 075103 p012)
• Sig benefit for adeno (078 064095 p0014)

31
NEOADJ CHEMO

• For SCC, neoadj chemo did not have a survival
  benefit
• hazard ratio for mortality 088 075103
• p 012
• For adeno, neoadj chemo showed sig survival
  benefit (UK Medical Research Council MRC trial)
• hazard ratio for mortality 078 064095
• P 0014

32
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)

33
NEOADJUVANT CHEMO/RT

• Neoadj chemoRT vs surgery
• sign benefit over surgery for both histological
  types
• 084 (071099) p 004 for SCC
• 075 (059095) p 002 for adeno

34
Sequential vs Concurrent chemoRT

• No survival benefit of sequential chemoRT in SCC
• hazard ratio for mortality 090 072103
  p018)
• similar to SCC treated with neoadj chemo
• Concurrent chemoRT had sig benefit for both
  histological types
• hazard ratios 076 and 075 for SCC and adeno,
  respectively

35
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.

36
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

OS
1.0
Planned surgery
0.8
Salvage
0.6
Cumulative Survival Probability
0.4
P .125
0.2
0.0
60
0
30
50
10
20
40
Months
Median follow-up 24 months
Hofstetter WL, et al. GI Cancers Symposium 2009.
Abstract 7.
37
THANKS