Department of Radiation Oncology, University of Amsterdam,, The Netherlands.

Purpose: To analyse the treatment results of neo-adjuvant chemoradiation combined with regional hyperthermia in patients with resectable esophageal cancer.

Patients and methods: Between August 2003 and December 2004, 28 patients entered a phase II study combining chemoradiation over a 4.5-week period with five sessions of regional hyperthermia. Chemotherapy consisted of carboplatin (AUC = 2) and paclitaxel (50 mg/m(2)) and radiotherapy of 41.4 Gy in 1.8 Gy daily fractions. Locoregional hyperthermia was applied using the AMC phased array of four 70 MHz antennas, aiming at a stable tumor temperature of 41 degrees C for one hour. Carboplatin was infused during the hyperthermia session. Esophageal resection was planned at 6-8 weeks after the end of radiotherapy. The majority of the patients had a T3 tumor (86%) and were cN+ (64%). Median follow-up for survivors was 37 months (range 31-46).

Results: Twenty-five patients (89%) completed the planned neo-adjuvant treatment and acute toxicity was generally mild. Twenty-six patients were operated on. A pathologically CR, PRmic, PR and SD were seen in 19%, 27%, 31% and 23% respectively. All patients had a R0 resection. In-field locoregional control during follow up for the operated patients was 100%. Quality of life was good for patients without disease progression. Survival rates at one, two and three years were 79%, 57% and 54% respectively.

Conclusion: Neo-adjuvant chemoradiation combined with regional hyperthermia followed by esophageal resection for patients with esophageal cancer resulted in good locoregional control and overall survival.

PMID: 19219704 [PubMed - as supplied by publisher]

1: Am J Surg. 2003 Jun;185(6):538-43. Links

A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer.

Department of Surgery, McMaster University, Hamilton, Ontario, Canada. jurschel@caregroup.harvard.edu

BACKGROUND: Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer.

METHODS: Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response.

RESULTS: Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values <1 favor chemoradiation-surgery arm), was 0.79 (0.59, 1.06; P = 0.12) for 1-year survival, 0.77 (0.56, 1.05; P = 0.10) for 2-year survival, 0.66 (0.47, 0.92; P = 0.016) for 3-year survival, 2.50 (1.05, 5.96; P = 0.038) for rate of resection, 0.53 (0.33, 0.84; P = 0.007) for rate of complete resection, 1.72 (0.96, 3.07; P = 0.07) for operative mortality, 1.63 (0.99, 2.68; P = 0.053) for all treatment mortality, 0.38 (0.23, 0.63; P = 0.0002) for local-regional cancer recurrence, 0.88 (0.55, 1.41; P = 0.60) for distant cancer recurrence, and 0.47 (0.16, 1.45; P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiation occurred in 21% of patients. The 3-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR 0.45, 95% CI 0.26 to 0.79, P = 0.005) instead of sequentially (OR 0.82, 95% CI 0.54 to 1.25, P = 0.36).

CONCLUSIONS: Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.

PMID: 12781882 [PubMed - indexed for MEDLINE]

1: Ann Thorac Surg. 2008 Apr;85(4):1217-23; discussion 1223-4. Links

Neoadjuvant chemoradiation versus chemotherapy for patients undergoing esophagectomy for esophageal cancer.

Section of General Thoracic Surgery, Department of General Surgery, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

BACKGROUND: Neoadjuvant chemoradiation followed by esophagectomy is currently the standard of care for locally advanced esophageal cancer. This intense preoperative regimen delays definitive resection and increases perioperative risks. With the improvement of chemotherapy agents, chemotherapy alone may be better suited for patients awaiting esophagectomy because of shorter preoperative treatment time and less associated perioperative complications. No recent study has compared chemoradiation to chemotherapy alone before esophageal resection with respect to operative morbidity and mortality and overall survival.

METHODS: A retrospective review was performed of all patients (281) who underwent an esophagectomy for cancer at our institution from July 1995 through June 2005; 122 patients (43%) had neoadjuvant treatment and form the basis of this study.

RESULTS: Preoperative chemoradiation (CR) was administered in 64 patients and chemotherapy only (CO) in 58 patients. Operative mortality was 6% (4 patients) in the CR group and 0% in the CO group (p = 0.12). Overall postoperative complications rate was 48% in CR patients and 33% in CO patients (p = 0.09). Complete pathologic response occurred in 11 CR patients (17%) and in 2 CO patients (4%; p = 0.02). There was no difference in recurrences between the two groups (p = 0.43). Median survival was 17 months in the CR patients and 21 months in the CO patients (p = 0.14). One-, 3-, and 5-year survivals were 76%, 46%, and 41%, respectively, in the CR patients and 70%, 40%, and 31%, respectively, in the CO patients (p = 0.31).

CONCLUSIONS: Although neoadjuvant chemoradiation resulted in a significantly better complete pathologic response rate when compared with chemotherapy alone, that did not translate into a long-term survival advantage. Chemotherapy alone may be the preferred neoadjuvant modality to expedite resection, decrease operative mortality and postoperative complications, and improve survival in patients with locally advanced esophageal cancer.

PMID: 18355499 [PubMed - indexed for MEDLINE]