Clinical Trials Evaluating Chemotherapy with or without radiotherapy in addition to surgery in Locally Advanced Esophageal and GEJ Cancer.

Table 1: Clinical Trials Evaluating Chemotherapy with or without radiotherapy in addition to surgery in Locally Advanced Esophageal and GEJ Cancer.

Trial	Treatment Arms	Patients (N)	Histology	GEJ tumors (%)	pCR Rate	Rate of R0 resection	Survival	Loco-regional Failure	Comments
Kelsen et al. [18]	Preop Chemo (5-FU + Cis) à Surgery	213	Adeno 54% Epidermoid Carcinoma 46%	Included, Number not specified	Data not available	62%	mOS: 14.9 mo 2-yr OS: 35%	32%	Preoperative chemotherapy was tolerable. No increase in operative morbidity or mortality.
Kelsen et al. [18]	Surgery	227	Adeno 54% Epidermoid Carcinoma 46%	Included, Number not specified	Data not available	59%	mOS: 16.1 mo 2-yr OS: 37%	31%
RTOG 8501 [21,22]	CRT (5-FU + Cis + 50Gy radiation)	100	Adeno 16% SCC 84%	Only patients with thoracic esophagus tumors included	NA	NA	mOS: 12.5 mo 5-yr OS: 26%	39%	Severe and life threatening side effects in 44% and 20% of patients receiving CRT vs 25% and 3% in patients who underwent XRT alone.
RTOG 8501 [21,22]	Radiation alone (64 Gy)	100	Adeno 16% SCC 84%	Only patients with thoracic esophagus tumors included	NA	NA	mOS: 8.9 mo 5-yr OS: 0%	52%
Urba et al. [20]	Preop CRT (5-FU + Cis + Vinblastine + 45Gy) à Surgery	50	Adeno 75% SCC 25%	GEJ tumor patients included Number not specified	Adeno: 24% SCC: 38%	Gross total resection: 96%	mOS: 16.9 mo 3-yr OS: 30%	19%	Grade 3/4 hematologic toxicity 78% in multimodality arm.
Urba et al. [20]	Surgery	50	Adeno 75% SCC 25%	GEJ tumor patients included Number not specified	NA	Gross total resection: 90%	mOS: 17.6 mo 3-yr OS: 16%	42%	Grade 3/4 hematologic toxicity 78% in multimodality arm.
CROSS [23,24]	Preop CRT (Carbo + Paclitaxel +41.4 Gy) à Surgery	178	Adeno 75% SCC 23% Large-cell Undifferentiated Carcinoma 2%	23% among the adenocarcinoma patients had GEJ tumor	29%	92%	mOS: 49.4 mo 5-yr OS: 47%	22%	Grade 3 and 4 hematologic toxicity: 7% and 1% respectively in multimodality group.
CROSS [23,24]	Surgery	188		23% among the adenocarcinoma patients had GEJ tumor	NA	69%	mOS: 24 mo 5-yr OS: 33%	38%
Walsh et al. [25]	Preop CRT (5-FU + Cis + 40Gy) à Surgery	58	Adeno 100%	38% patients with tumors of the cardia	25%	Data not available	mOS: 16 mo 3-yr OS: 32%	Data not available	-
Walsh et al. [25]	Surgery	55	Adeno 100%	38% patients with tumors of the cardia	NA	Data not available	mOS: 11 mo 3-yr OS: 6%	Data not available	-
CALGB 9781 (Tepper et al.) [26]	Preop CRT (5-FU + Cis + 50.4 Gy) à Surgery	30	Adeno 75% SCC 25%	Patients with GEJ tumor included, number not specified	40%	Data not available	mOS: 4.48 yr 5-yr OS: 39%	Data not available	Trend towards improved OS in trimodality group. Trial closed early because of poor accrual.
CALGB 9781 (Tepper et al.) [26]	Surgery	26	Adeno 75% SCC 25%	Patients with GEJ tumor included, number not specified	NA	Data not available	mOS: 1.79yr 5-yr OS: 16%	Data not available
Burmeister et al. [28]	Preop CRT (5-FU + Cis + 35 Gy) à Surgery	128	Adeno 62% SCC 37% Mixed 1%	Patients with tumors of the cardia with predominant esophageal involvement were allowed but the number not stated	SCC 27% Adeno 9%	80%	mOS: 22.2 mo	15%	16% patients developed Grade 3-4 esophagitis, other grade 3-4 toxicity <5%
Burmeister et al. [28]	Surgery	128			NA	59%	mOS: 19.3 mo	19%
FFCD 9901 [27]	Preop CRT (5-FU + Cis + 45 Gy) à Surgery	98	Only stage I and II disease included Adeno30% SCC 70%	Data not available	33.3%	93.8%	mOS: 31.8 mo 5-yr OS: 41.1%	15.3%	No improvement in OS or R0 resection, likely because most of the patients had stage I or IIA disease. Closed early because of futility. Higher perioperative morbidity and mortality in trimodality group.
FFCD 9901 [27]	Surgery	97	Only stage I and II disease included Adeno30% SCC 70%	Data not available	NA	92.1%	mOS: 41.2 mo 5-yr OS: 33.8%	28.9%
POET [40]	Induction chemo à Surgery	59	Adeno only	GEJ only	2%	69.5%	mOS: 21.1 mo 3-yr OS: 27.7%	Data not available	Study closed early because of poor accrual
POET [40]	Chemotherapy à CRT à Surgery	60	Adeno only		15.6%	72%	mOS: 33.1 mo 3-yr OS: 47.4%	Data not available	Study closed early because of poor accrual
MAGIC [5]	Preop chemo (Epirubicin + Cis + 5-FU) à Surgery à Postop chemo (same regimen)	250	All adeno 75% Gastric 14% Esophageal 11% GEJ	11%	Data not available	Data not available	5-yr OS: 36%	Data not available	Improved OS and PFS with perioperative chemotherapy Rate of post-op complications similar between the 2 groups
MAGIC [5]	Surgery	253	All adeno 75% Gastric 14% Esophageal 11% GEJ	11%	Data not available	Data not available	5-yr OS: 23%	Data not available

pCR: Pathologic Complete Response; CRT: Chemoradiation; XRT: Radiotherapy; 5-FU: 5-fluorouracil; Cis: Cisplatin; OS: Overall Survival; SCC: Squamous Cell Carcinoma; Adeno: Adenocarcinoma; Carbo: Carboplatin; pCR: Pathologic Complete Response; GEJ: Gastroesophageal Junction.