Preoperative Chemo Versus Chemoradiotherapy for Regionally Advanced Esophageal Adenocarcinoma


Study

Histology

Treatment

No. of patients

% pCR

Treatment related mortality (%)

Survival

Quality of evidence

Kelsen et al. [2]

SCC 59.7 %

CDDP + 5FU + S

213

2.5

6.4

23 % at 3 years

Moderate

S

227
 
4

26 % at 3 years

MRC OEO2 [3]

SCC 31 %

CDDP + 5FU + S

434

4

N/A

23 % at 5 years

Moderate

S

437
 
N/A

17 % at 5 years

Cunningham et al. (MAGIC) [4]

ACA 100 %

Perioperative ECF + S

250
  
36.3 % at 5 years

Low

S

253
  
23 % at 5 years

Ychou et al. [5]

ACA 100 %

Perioperative CDDP + 5FU + S

113
 
4.6

38 % at 5 years

Moderate

S

111
 
4.5

24 % at 5 years

Ancona et al. [6]

SCC 100 %

CDDP + 5FU + S

48

12.8

4.2

22 % at 5 years

Moderate

S

48
 
4.2

34 % at 5 years

Boonstra et al. [7]

SCC 100 %

CDDP + etoposide + S

85

7

5

26 % at 5 years

Moderate

S

84
 
4

17 % at 5 years


Rows in italics indicate a statistically significant difference in outcomes

Abbreviations: ACA adenocarcinoma, CDDP cisplatin, ECF epirubicin, cisplatin, 5-fluoruracil, MRC OE2 Medical Research Council Oesophageal Cancer working party, pCR complete pathologic response, S surgery, SCC squamous cell carcinoma, 5FU 5-fluorouracil




Table 23.2
Selected meta-analysis of surgery with or without neoadjuvant therapy









































































































Study

Treatment

No. of patients

Treatment related mortality (95%CI)a

Overall survival (95%CI)a

Neoadjuvant chemotherapy and surgery versus surgery only

Urschel et al. [8]

CS

NS

0.94

1 year: 1.00 (0.76–1.3; p = 0.98)

(0.66–1.35, p = 0.76)

2 year: 0.88 (0.62–1.24; p = 0.45)

3 year: 0.77 (0.37–1.59; p = 0.48)

S

NS

Kaklamanos et al. [9]

CS

845

Difference in mortality 1.7 % (–0.9 to 4.3, p = 0.38)b

ARR for mortality at 2 years by 4.4 % (0.3–8.5; p = 0.07)b

S

838

Neoadjuvant chemoradiation and surgery versus surgery only

Sjouquist et al. [10]

CS

1,046

Not stated

0.87 (0.790.96; p = 0.005)

S

1,016

Urschel et al. [19]

CRS

NS

1.72 (0.963.07; p = 0.07)

1 year: 0.79 (0.591.06; p = 0.12)

2 year: 0.77 (0.561.05; p = 0.1)

3 year: 0.66 (0.470.92 p = 0.016)

S

NS

Kaklamanos et al. [9]

CRS

289

Difference in mortality 3.4 % (95%CI −0.1 to 7.3; p = 0.2)b

ARR for mortality at 2 years by 6.4 % (95%CI 1.2–14.0; p = 0.86)b

S

280

Fiorica et al. [20]

CRS

385

2.10 (1.183.73; p = 0.01)

0.53 (0.320.89; p = 0.02)

S

379

Jin et al. [21]

CRS

659

1.68 (1.032.73, p = 0.04)

1 year 1.28 (1.011.64, p = .05)

3 year 1.78 (1.22.66 p = 0.02)

5 year 1.46 (1.071.99, p = 0.02)

S

649

Sjouquist et al. [10]

CS

980

Not stated

0.78 (0.700.88; p < 0.0001).

S

952


Rows in italics indicate a statistically significant difference in outcomes

Abbreviations: ARR absolute risk reduction, CRS neoadjuvant chemoradiation and surgery, CS neoadjuvant chemotherapy and surgery, HR hazard ratio, NS not stated, S surgery, 95%CI 95 % confidence interval

aHazard ratio (95 % confidence interval [95%CI]; P value), expressed as chemotherapy and surgery versus surgery alone (treatment versus control; values <1 favor neoadjuvant therapy-surgery arm)

bResults from the meta-analysis by Kaklamanos et al. are stated in absolute percentage difference in survival at 2 years. No odds ratio or hazard ration values were given


The United Kingdom Medical Research Council (MRC) OEO2 trial was published in 2002 and subsequently was updated in 2009. This trial is the largest single trial addressing neoadjuvant chemotherapy published (802 patients) to date [3]. Patients with esophageal tumors of the upper, middle or lower third of the esophagus, including tumors of the cardia, were enrolled. Almost two thirds of the patients had adenocarcinoma, whereas 31 % has squamous cell carcinoma (SCC) and 3 % had undifferentiated histology. The study group included patients that received two cycles of preoperative cisplatin (CDDP) and 5-fluorouracil (5FU) followed by surgery versus the control group that underwent surgery only. There were 434 patients in the study group versus 437 patients in the control group. Two-year survival was significantly better in the chemotherapy arm at 43 % versus 34 % in the surgery only group. In a later update, this advantage extended to 5- years, with an overall survival rate of 23 % in the chemotherapy group versus 17 % in the surgery group. Progression-free survival was also improved in the chemotherapy arm. One major peculiarity about this trial is the exclusion of 69 patients from one site due to unclear reasons.

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Dec 30, 2016 | Posted by in CARDIOLOGY | Comments Off on Preoperative Chemo Versus Chemoradiotherapy for Regionally Advanced Esophageal Adenocarcinoma
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