CROSS TRIAL

Question 1

metodos

Answer 1

1. criterios de inclusion:
   * potentially curable squamous-cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction
   * The upper border of the tumor had to be at least 3 cm below the upper esophageal sphincter.
   * siewert 3 excluidos
   * The length and width of the tumor could not exceed 8 cm and 5 cm, respectively
   * clinical stage T1N1 or T2-3N0-1 no Mt
   * no older 75 yr
   * ECOG o PS < de 2

Question 2

treatment

Answer 2

QT = days 1, 8, 15, 22, and 29
* carboplatin (AUC 2 mg/mm/min) // paclitaxel at a dose of 50 mg
RT:
* 41.4 Gy was given in 23 fractions of 1.8 Gy each, with 5 fractions admin- istered per week
* starting on the first day of the first chemotherapy cycle
* all EBRT
Surgery:
* within 4 to 6 weeks
* patients in the surgery group were treated as soon as possible after randomization.
* transthoracic approach= 1/3 distal under the carina
* transhiatal= esophagogastric junction, a transhiatal resection was preferred
* Gastric-tube reconstruction with a cervical anastomosis was the preferred technique for re- storing the continuity of the digestive tract
PATHOLOGICAL ANALYSIS:
* grade 1, no evidence of vital residual tumor cells (pathological complete response);
* grade 2, less than 10% vital residual tumor cells
* grade 3, 10 to 50%
* grade 4, more than 50%
* vital tumor was present at 1 mm or less from the proximal, distal, or circumferential resection margin = R1

FOLLOW-UP:
* 1er año cada 3 meses
* 2do año cada 6 meses hasta los 5 años

Question 3

analisis estadistico

Answer 3

• The primary end point was overall survival. All other described outcomes were secondary end points.
• Survival was calculated from the date of randomization until death.

Question 4

resultados

Answer 4

**analisis estadistico
From March 2004 through December 2008
we enrolled 368 patients
Of whom 180 were randomly assigned to the chemoradiotherapy–surgery group, and 188 to the surgery group, 2 pts of CRT withdrew consent and were not included in the analysis
* Fueron 178 pts. del brazo de crt y cirugía y 188 pts. del brazo cirugía sola
Tenían una media de edad de 60 años, con un rango de 36-79 y de 36-73 para ambos
La mayoría fueron ADC 75 % en ambos brazos y 23 % de escamosos
Tamaño tumoral tenían una media de 4 cm y rango intercuantil de 3-6
De acuerdo a la localización fueron más frecuentes de esófago distal y del UGE con 58 % y 57 % para ambos brazos y de UGE 22 % y 26 % respectivamente, hubo un 14 y 13 de esófago medio, y 2 % de esófago proximal
En su mayoría era T3 (84 y 78 %) N1 (65 y 64 %)
PS 0 (81 y 87 %) y PS 1 (19 13 %)

DELIVERY AND TOXIC EFFECTS OF CHEMORADIOTHERAPY
Seven patients (4%) in the chemoradiotherapy– surgery group did not receive any chemoradio- therapy: 5 because of disease progression before commencing therapy
91% received the full treatment regimen of five cycles of chemoradiotherapy, and 92% received the full dose of radiotherapy.
trombocitopenia fue la causa mas frecuente por la cual no recibieron todos los ciclos de QT
12 pts in the QRT arm —grade 3 hematologic toxic effects were observed; a grade 4 hematologic toxic effect and neutropenic fever developed in 1 patient
1 pts complete QRT an dead waiting surgery
during qt most frecuent sintom were : anorexia, constipaction, y diarrea, fatiga nauseas
SURGERY
168 patients (94%) underwent surgery, as compared with 186 (99%) in the surgery group (P = 0.01)
disease progression during treatment (7 in the chemoradiotherapy–surgery group and 1 in the surgery group), diagnosis of a second cancer before surgery (1 in the surgery group), and death before surgery due to toxic effects of chemoradiotherapy (1)
The median time between randomization and surgery was 97 days in the chemoradiotherapy– surgery group and 24 days in the surgery group
7 of 168 patients (4%) in the chemoradiotherapy–surgery group, a resection was not possible because the primary tumor or lymph nodes were identified during surgery as unresectable, as compared with 25 of 186 patients (13%) in the surgery group (P=0.002)
Six of 168 patients (4%) in the chemoradiotherapy–surgery group died in the hospital, as did 8 of 186 (4%) in the surgery group (P = 0.70)
4 pts (2%) in the chemoradio- therapy–surgery group died within 30 days after surgery, as compared with 5 (3%) in the surgery group (P=0.85)
PATHOLOGICAL ASSESSMENT
An R0 resection was achieved (92%) in the chemoradiotherapy–surgery group, as compared with (69%) in the surgery group (P<0.001)
complete response dn 29 % in the QRT group, and (23%) ADC versus squamous-cell (49%) (P = 0.008)
no diferfence in the linfadenectomy 15 vs 18 Nodos
1 o mores lymph nodes positiove in (31%) in the chemoradiotherapy–surgery group, as compared with (75%)