Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

[Palliative treatment of esophageal cancer with dysphagia: more favourable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomised study]. / Palliatieve behandeling voor slokdarmkanker met passageklachten: gunstiger uitkomsten van eenmalige inwendige brachytherapie dan van plaatsing van een zelfexpanderende stent; multicentrisch, gerandomiseerd onderzoek.

OBJECTIVE: To compare the results of single-dose internal irradiation (brachytherapy) and self-expanding metal stent placement in the palliation of oesophageal obstruction due to cancer of the oesophagus. DESIGN: Randomised trial. METHOD: In the period from December 1999-Jun 2002, 209 patients with dysphagia due to inoperable carcinoma of the oesophagus were randomised to placement of an Ultraflex stent (n = 108) or single-dose (12 Gy) brachytherapy (n = 101). Primary outcome was relief of dysphagia; secondary outcomes were complications, persistent or recurrent dysphagia, health-related quality of life, and costs. Patients were followed up by monthly home visits from a specialised nurse. RESULTS: Dysphagia improved more rapidly after stent placement than after brachytherapy, but long-term relief of dysphagia was better after brachytherapy. Stent placement resulted in more complications than did brachytherapy (36/108 (33%) versus 21/101 (21%); p = 0.02), due mainly to an increased incidence of late haemorrhage in the stent group (14 versus 5; p = 0.05). The groups did not differ with regard to the incidence of persistent or recurrent dysphagia or median survival (p > 0.20). In the long term, quality-of-life scores were higher in the brachytherapy group. Total medical costs were also similar for both treatments: Euro 8,215 for stent placement and Euro 8,135 for brachytherapy. CONCLUSION: Brachytherapy provided better long-term relief of dysphagia than did stent placement and also produced fewer complications. Brachytherapy is therefore recommended as the preferred treatment for the palliation of dysphagia due to oesophageal cancer.

Ischemic heart disease after mantlefield irradiation for Hodgkin's disease in long-term follow-up.

BACKGROUND AND PURPOSE: In patients with Hodgkin's disease treated by radiotherapy with a moderate total dose and a low (mean) fraction dose to the heart, the risk of ischemic heart disease was investigated during long-term follow-up. MATERIALS AND METHODS: The medical records of 258 patients treated in the period 1965-1980 with radiotherapy alone as the primary treatment were reviewed. The median follow-up was 14.2 years (range 0.7-26.2). The mean total dose and fraction dose to the heart were 37.2 Gy (SD 2.9) and 1.64 Gy (SD 0.09), respectively. The impact on the development of ischemic heart disease of treatment-related parameters, such as the applied (fraction) dose, irradiation technique (one or two fields per day), and chemotherapy in case of a relapse, was investigated. The incidence of ischemic heart disease in this patient population was compared with the expected incidence based on gender, age and calendar period-specific data for the Dutch population. RESULTS: Thirty-one patients (12%) experienced ischemic heart disease (actuarial risk at 20-25 years: 21.2% (95% C.I. 15-30). Twenty-five of them were hospitalized. When compared with the expected incidence, the relative risk (RR) of hospital admission for ischemic heart disease was 2.7 (95% C.I. 1.7-4.0). There were 12 deaths (4.7%) due to ischemic myocardial or sudden death (actuarial risk at 25 years: 10.2% (95% C.I. 5.3-19), compared to 2.3 cases that were expected to have died from these causes, yielding a standardized mortality ratio (SMR) of 5.3 (95% C.I. 2.7-9.3). Gender (male), pretreatment cardiac medical history and increasing age appeared to be the only significant factors for the development of ischemic heart disease. CONCLUSIONS: Despite the moderate total dose and the low (mean) fraction dose to the heart, the observed incidence of ischemic heart disease is high, especially after long follow-up periods. Treatment related cardiac disease in patients treated for Hodgkin's disease has only been reported for doses above 30 Gy. Although the optimum curative dose is still under debate, some studies recommend a dose as low as 32.5 Gy. The observed high rate of severe heart complications in this study advocates a dose reduction to this level, particularly in the regions where the coronary arteries are located.