Treatment For Resectable Esophageal Cancer Research Articles

Progress in multidisciplinary treatment of resectable esophageal cancer

In recent years, there has been a gradual increase in treatment options for patients with esophageal cancer. While surgery remains to be the primary treatment, neoadjuvant and adjuvant therapy, both preoperatively and postoperatively, have become more important in the multidisciplinary treatment of resectable esophageal cancer. Definitive concomitant chemo-radiotherapy may replace surgery as the primary treatment for resectable esophageal cancer. Cisplatin combined with 5-fluorouracil remains the backbone regimen for neoadjuvant and adjuvant therapy. Intense researches are underway to investigate new cytotoxic drugs such as taxanes and topoisomerase inhibitor, and new regimens for perioperative treatment of resectable esophageal cancer. Key words: Esophageal neoplasms; Combined modality therapy; Neoadjuvant therapy

QS313. Chemoradiation and Salvage Esophagectomy for Treatment of Resectable Esophageal Cancer

QS313. Chemoradiation and Salvage Esophagectomy for Treatment of Resectable Esophageal Cancer

Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer

Esophagectomy is underused as treatment for resectable stage I, II, and III esophageal cancers. Retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare linked database. We used the Surveillance, Epidemiology, and End Results database to identify persons 65 years or older who were not enrolled in a health maintenance organization and who were diagnosed as having stage I, II, or III esophageal cancer between January 1, 1997, and December 31, 2002 (N = 2386). The rate of surgical intervention was compared across varying patient characteristics, including age, race, comorbidity score, sex, tumor stage, and socioeconomic region. Survival was compared between patients who received surgery and those who did not using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression. Statistical analysis was performed using the chi2 test and multiple logistic regression. The overall rate of surgical intervention in this cohort was 34.1%. In all, 36.8% of white patients underwent surgical treatment of their disease, whereas only 19.2% of nonwhite patients did. Patients residing in areas with high poverty rates were 27% less likely to have surgery. Older age and higher comorbidity scores were also associated with lower rates of surgery. Patients who received surgical treatment for their disease experienced significantly longer survival than did patients who did not undergo surgical resection. There seems to be significant underuse of esophagectomy as treatment for potentially resectable stage I, II, and III esophageal cancers across all patient groups. In nonwhite and low socioeconomic patient cohorts, the underuse is even more pronounced.

Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer—Invited Critique

Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer—Invited Critique

Neoadjuvant chemoradiation therapy for the treatment of esophageal carcinoma

An esophagectomy with three-field lymph node dissection is the standard therapy for esophageal cancer in many countries, including Japan. However, the results of esophagectomy are still unsatisfactory in comparison to the results of surgical treatment for gastric cancer or colon cancer. On the other hand, definitive chemoradiation therapy has recently shown progress as a treatment modality for resectable esophageal cancer, with data indicating the potential efficacy of combination therapy with chemoradiation and an esophagectomy. In fact, preoperative chemoradiotherapy for resectable esophageal cancer is becoming a standard therapy in Europe and North America. The latest metaanalysis concerning neoadjuvant chemoradiotherapy for resectable esophageal cancer concluded that a significant survival benefit was evident with preoperative chemoradiotherapy. However, there are still no supportive data for neoadjuvant chemoradiation and surgery from a well-designed large-scale randomized control trial (RCT). A well-designed large-scale RCT is needed to determine the utility of neoadjuvant chemoradiation. Future trials based on precise diagnosis and surgical procedures are required for the adequate interpretation of the results of treatment for resectable esophageal cancer. Of course, quality control of the operation is a very important factor, because operative mortality influences these results.

Iatrogenic Dissection of Esophagus During a Transesophageal Echocardiogram

Esophageal cancer is usually detected in the advanced stage due to its anatomical characteristics. Recently, early esophageal cancers are detected more frequently with the nationwide screening of digestive tract cancer and development of new endoscopic technology in Korea. From the treatment view point, esophageal cancer can be categorized into early, locally advanced resectable, locally advanced unresectable, and metastatic esophageal cancer. Traditionally, surgery has been the mainstay of treatment for resectable esophageal cancer. However, endoscopic resection can be another therapeutic option in selected early esophageal cancer cases. Although most studies with preoperative chemoradiotherapy and subsequent surgery in locally advanced resectable cancer could not demonstrate definite survival benefit, many authorities prefer this multimodality approach to surgery alone. Best supportive care is always necessary for those with unresectable esophageal cancer, and palliation for dysphagia can be considered according to the patients' status. For the best management of esophageal cancer, the development of diagnostic method for more accurate staging should be followed.

Survival After Neoadjuvant Therapy Compared with Surgery Alone for Resectable Esophageal Cancer in a Population‐based Study

Esophagectomy remains the standard treatment for resectable esophageal cancer, but the cure rate is low. Neoadjuvant therapy has been tried in attempts to prolong survival and reduce tumor recurrence. The aim of this study was to assess the surgical outcomes with and without neoadjuvant treatment for resectable esophageal cancer in a population-based setting. All 1,155 patients treated with esophagectomy for esophageal cancer in Sweden in 1987 through 2000 with or without neoadjuvant therapy were identified and followed up in nationwide registers up to 18 October 2004. Tumor characteristics and response to neoadjuvant treatment were obtained from histopathological reports. Hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for potential confounding factors were calculated by a Cox proportional hazards regression model. Overall survival was similar in the groups with and without neoadjuvant therapy (adjusted HR 0.99, 95% CI 0.86-1.16). The 3-year survival rates were 34.6% and 32.0%, respectively. Survival was better among the 27.6% of the neoadjuvant group with a complete histopathological response (HR 0.71, 95% CI 0.53-0.94) compared with the surgery only group. Patients without complete response to neoadjuvant therapy had seemingly poorer survival (HR 1.10, 95% CI 0.94-1.29). Surgical outcomes with and without neoadjuvant therapy were equivalent. Only patients with a complete histopathological response after neoadjuvant treatment had better survival.

A randomized clinical study of surgery versus radiotherapy in the treatment of resectable esophageal cancer

4013 Background: To compare the treatment results between radical surgery and late-course accelerated hyperfractionation radiotherapy (LCAHFR) for patients with resectable thoracic segment esophageal cancer. Methods: From June 1998 to September 2002, 269 patients with resectable thoracic esophageal cancer were randomized into two groups. 135 were with surgery and 134 with late-course accelerated hyperfractionated (LCAF) radiotherapy. Chemotherapy only for clinical recurrence and salvage therapy. Results: The 1-, 3- and 5- year overall survival rate were 88.6%, 56.2% and 34.7% in the surgery group and 93.3%, 61.5% and 36.9% in the radiotherapy group. There was no statistical difference between the two groups (P =0.58). Median survival was 28.5 months and 30.5 months respectively. The 1-, 3-and 5-year progression-free survival rate was 73.3%, 39.7% and 20.6% in the surgery group and 75.9%, 43.7% and 23.1% in the radiotherapy group (P =0.65) . There was no difference between the two groups in survival rates including different location and length (P > 0.05). The incidence of failure by hematogenous metastasis and distant lymphatic metastasis in the radiotherapy group (16.6% and 13.3% respectively ) was lower than in the surgery group ( 25.3% and 20.3 % respectively ), there was no significance between them. The incidence of local failure in the radiotherapy and surgery group was 57.3% and 27.8% respectively (P = 0.001) The incidence of death by local reasons was higher than in the surgery group (P = 0.02 ). The incidence of death by distant metastasis was lower than in the surgery group (P = 0.02 ). Conclusion: The treatment results between radical surgery and LCAHFR with conformal radiotherapy for patients with resectable thoracic esophageal cancer were comparable. No significant financial relationships to disclose.

Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer

Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer. Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy. Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery. The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.

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

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.

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

Background: Esophagectomy is often considered the standard treatment for resectable esophageal cancer but the rate of cure is low. Combining neoadjuvant chemotherapy with surgery has theoretical appeal and some clinical evidence suggests a benefit. We performed a meta-analysis of randomized controlled trials (RCTs) that compared neoadjuvant chemotherapy and surgery with surgery alone for esophageal cancer. Methods: Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemotherapy and surgery to surgery alone for esophageal cancer. The selection process was inclusive; no trials were excluded. Trial validity assessment was done and a trial quality score was assigned. Outcomes assessed by meta-analysis included 1-, 2-, and 3-year survival, rate of resection, rate of complete resection, operative mortality, anastomotic leaks, postoperative pulmonary complications, all treatment mortality, local-regional cancer recurrence, distant cancer recurrence, and all cancer recurrence. A random-effects model was used and odds ratio was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemotherapy treatment group (clinical response, pathological complete response, and chemotherapy mortality). Results: Eleven RCTs, which included 1,976 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 chemotherapy and surgery versus surgery alone (treatment versus control; values <1 favor chemotherapy-surgery arm), was 1.00 (0.76, 1.30; P = 0.98) for 1-year survival, 0.88 (0.62, 1.24; P = 0.45) for 2-year survival, 0.77 (0.37, 1.59; P = 0.48) for 3-year survival, 1.71 (1.22, 2.40; P = 0.002) for rate of resection, 0.71 (0.58, 0.87; P = 0.001) for rate of complete resection, 0.94 (0.66, 1.35; P = 0.76) for operative mortality, 1.08 (0.45, 2.60; P = 0.87) for anastomotic leaks, 1.31 (0.77, 2.23; P = 0.32) for postoperative pulmonary complications, 1.36 (0.83, 2.25; P = 0.22) for all treatment mortality, 0.71 (0.36, 1.42; P = 0.33) for local-regional cancer recurrence, 0.79 (0.57, 1.10; P = 0.16) for distant cancer recurrence, and 0.63 (0.28, 1.41; P = 0.26) for all cancer recurrence. A clinical response to chemotherapy was observed in 31% of patients and 5% had a complete pathological response. Chemotherapy mortality (before surgery) was 1.6%. Conclusions: Compared with surgery alone, neoadjuvant chemotherapy and surgery is associated with a lower rate of esophageal resection but a higher rate of complete (R0) resection. It does not increase treatment related mortality. This meta-analysis did not demonstrate a survival benefit for the combination of neoadjuvant chemotherapy and surgery.

Neoadjuvant chemoradiotherapy for esophageal cancer: is it worthwhile?

With promising results from several institutions, many centers began treating patients with esophageal cancer with neoadjuvant chemoradiotherapy (NC) followed by esophagectomy. This approach is demanding for the patient and has not been proved to be better than esophagectomy alone. To assess survival time and measures of quality of life associated with NC. A retrospective review during 1990 to 1996. The 3 tertiary academic hospitals affiliated with the University of Massachusetts Medical School, Worcester. All patients (N=51) with cancer of the middle or lower esophagus who were treated with NC followed by esophagectomy during this period. Median and 1-, 2-, and 3-year survival times; median preoperative treatment time (first office visit for surgical consultation before beginning NC to the date of surgery), median hospital stay, and postoperative swallowing function. The median survival time of all patients was 16.3 months; 1-, 2-, and 3-year overall survival rates were 67%, 46%, and 39%, respectively. The median hospital stay was 12 days. The median postoperative treatment time was 3.3 months, which was 20% of the median survival time. Of the 51 patients, 19 were alive with a median follow-up time of 2.5 years. Twenty-nine percent of the patients had a complete pathological response with median and 1-, 2-, and 3-year survival rates of 17.5 months, 73%, 57%, and 57%, respectively. Palliation of dysphagia was excellent, with 44 (93%) of 47 operative survivors taking either a soft diet (18 [38%]) or a regular (26 [55%]) diet by the first postoperative visit. Median survival time with NC followed by esophagectomy for resectable cancer of the esophagus does not appear to be significantly better than that reported for esophagectomy alone. Further, treatment time with NC consumed 20% of survival time. Examining only these outcome variables suggests that NC is not worth-while. However, examining a longer-term outcome survival variable, such as 3-year survival time, suggests that NC followed by esophagectomy may result in greater long-term survival than that reported for esophagectomy alone. We conclude that further randomized, controlled studies are necessary before NC followed by esophagectomy is considered superior to esophagectomy alone for the treatment of resectable esophageal cancer.