Health-related quality of life in a randomized trial of neoadjuvant chemotherapy or chemoradiotherapy plus surgery in patients with oesophageal cancer (NeoRes trial).

BACKGROUND: There are few data comparing health-related quality of life (HRQoL) after neoadjuvant chemotherapy alone (nCT) compared with neoadjuvant chemoradiotherapy (nCRT) in patients with oesophageal cancer. METHODS: In the NeoRes trial, patients were assigned randomly in a 1 : 1 ratio to receive either cisplatin 100 mg/m2 on day 1 and an infusion of 750 mg per m2 5-fluorouracil over 24 h on days 1-5 in three 21-day cycles (nCT) or the same chemotherapy regimen, but with the addition of 40 Gy radiotherapy (nCRT). HRQoL data were collected at baseline, after neoadjuvant therapy and at 1, 3 and 5 years after surgery. The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease-specific modules were used. RESULTS: Of 181 patients randomized, 165 were included in the analysis of HRQoL. In a direct comparison between the allocated treatments, odynophagia after completion of neoadjuvant therapy but before surgery (P = 0·047) and troublesome coughing at 3 years' follow-up (P = 0·011) were more pronounced in the nCRT arm. In the longitudinal analyses within each treatment arm, a large deterioration in HRQoL was noted at 1 year. Some recovery was seen in both arms over time but, after 3 and 5 years, patients in the nCRT arm reported more symptoms compared with baseline than patients in the nCT arm. CONCLUSION: HRQoL after multimodal treatment for cancer of the oesophagus or gastro-oesophageal junction was impaired and more pronounced in patients who underwent nCRT, with only partial recovery over time.

ANTECEDENTES: Se dispone de poca información sobre la calidad de vida relacionada con la salud (health-related quality of life, HRQOL) en pacientes con cáncer de esófago después de quimioterapia neoadyuvante sola en comparación con quimiorradioterapia neoadyuvante. MÉTODOS: En el ensayo NeoRes, los pacientes fueron asignados de forma aleatoria 1:1 a tratamiento con cisplatino 100 mg/m2 en el día uno y 5-Fluorouracilo 750 mg/m2 /infusión de 24 horas en los días 1-5 en tres ciclos de 21 días (nCT) o al mismo régimen de quimioterapia, pero con la adición de radioterapia 40 Gy (nCRT). Los datos de HRQOL se recogieron al inicio, tras el tratamiento neoadyuvante y al cabo de 1, 3 y 5 años tras la cirugía. Se utilizaron los cuestionarios QLQ-C30 de la European Organisation for Research and Treatment of Cancer (EORTC) y los módulos específicos para la enfermedad. RESULTADOS: De 181 pacientes aleatorizados, 165 fueron incluidos en el análisis de la HRQOL. En la comparación directa entre los tratamientos asignados, la odinofagia tras terminar nCRT pero antes de la cirugía (P = 0,047) y la tos molesta a los 3 años de seguimiento (P = 0,011), fueron más acentuadas en el brazo de nCRT. En el análisis longitudinal dentro de cada rama de tratamiento hubo un fuerte deterioro en la HRQOL al año. Se observó cierta recuperación en ambas ramas con el tiempo, pero a los 3 y 5 años de seguimiento, los pacientes de la rama de nCRT describieron más síntomas en comparación con la situación de inicio que los pacientes de la rama de nCT. CONCLUSIÓN: La HRQOL después del tratamiento multimodal del cáncer de esófago o de la unión gastroesofágica se ve afectada, siendo dicha afectación más pronunciada en pacientes que recibieron nCRT, recuperándose solo parcialmente con el tiempo.

National guidelines may reduce socioeconomic disparities in treatment selection for esophageal cancer.

The 2011 National Comprehensive Cancer Network guidelines first incorporated the results of the landmark CROSS trial, establishing induction therapy (chemotherapy ± radiation) and surgery as the treatment standard for locoregional esophageal cancer in the United States. The effect of guideline publication on socioeconomic status (SES) inequalities in cancer treatment selection remains unknown. Patients diagnosed with Stage II/III esophageal cancer between 2004 and 2013 who underwent curative treatment with definitive chemoradiation or multimodality treatment (induction and surgery) were identified from the Surveillance, Epidemiology and End Results (SEER)-Medicare registry. Clinicopathologic characteristics were compared between the two therapies. Multivariable regression analysis was used to adjust for known factors associated with treatment selection. An interaction term with respect to guideline publication and SES was included Of the 2,148 patients included, 1,478 (68.8%) received definitive chemoradiation and 670 (31.2%) induction and surgery. Guideline publication was associated with a 16.1% increase in patients receiving induction and surgery in the low SES group (21.4% preguideline publication vs. 37.5% after). In comparison, a 4.5% increase occurred during the same period in the high SES status group (31.8% vs. 36.3%). After adjusting for factors associated with treatment selection, guideline publication was associated with a 78% increase in likelihood of receiving induction and surgery among lower SES patients (odds ratio 1.78; 95% confidence interval (CI): 1.05,3.03). Following the new guideline publication, patients living in low SES areas were more likely to receive optimal treatment. Increased dissemination of guidelines may lead to increased adherence to evidence-based treatment standards.

A comparative study of the iron status of patients with oesophageal adenocarcinoma to determine suitability for a clinical trial of iron chelation therapy.

INTRODUCTION: The incidence of oesophageal adenocarcinoma (OAC) is rising dramatically and overall survival remains extremely poor. Iron has been shown to potentiate tumourigenesis in OAC, and iron chelation therapy demonstrates promise in vivo as an adjunct to neoadjuvant and palliative chemotherapy. OAC, however, has traditionally been associated with iron deficiency anaemia. The aim of this study was therefore to formally quantify the iron status of OAC patients in order to guide the design of future clinical trials involving iron chelation therapy. METHODS: Demographic and cancer specific data were collected prospectively from all patients presenting with OAC and gastric adenocarcinoma (GAC). Patients had haemoglobin, serum iron, serum ferritin and serum transferrin receptor (sTfR) levels measured to assess systemic iron status. In addition, the sTfR/log ferritin (sTfR-F) index was calculated. RESULTS: Average haemoglobin, serum iron, serum ferritin, sTfR and sTfR-F index values for all patients presenting with OAC were within normal sex specific reference ranges. No statistical difference in iron status was observed between OAC patients presenting with resectable and advanced OAC. Patients with OAC are relatively iron replete compared with those presenting with GAC. Iron parameters were not significantly altered by standard neoadjuvant chemotherapy. CONCLUSIONS: Patients presenting with resectable or advanced OAC could be considered as candidates for a clinical trial of iron chelation therapy as an addition to standard neoadjuvant or palliative treatments.

[Esophageal cancer: outcome according to therapeutic strategy]. / Évolution des cancers de l'œsophage : impact de la stratégie thérapeutique.

PURPOSE: To assess the outcome of esophageal cancer according to therapeutic strategy. PATIENTS AND METHODS: One-hundred and twenty patients with esophageal cancer treated by an association of radiotherapy and chemotherapy and possibly surgery, between 2004 and 2010, were retrospectively studied. The first site of relapse was classified as follows: local (tumour), locoregional (tumour and/or nodal: celiac, mediastinal, sus-clavicular) or metastatic. RESULTS: With a 15.7-months (1.4-62) median follow-up, there were 89 deaths and 79 recurrences. Three types of treatments were performed: 50Gy exclusive chemoradiotherapy (47 patients) or 50 to 65Gy exclusive chemoradiotherapy (44 patients) or chemoradiotherapy followed by surgery (27 patients). The local first relapse was as much frequent as distant relapse (50 patients). With a-5cm margin up and down to the tumour, there was only one nodal relapse. Two-year survival was 39.5% (95% confidence interval [IC]: 30.5-40.8) and relapse-free survival was 26.5% (CI: 18.6-35). Multivariate analysis revealed that treatment type and disease stage had a significant impact on survival, relapse-free survival and locoregional control. Compared to exclusive chemoradiotherapy, surgery improved locoregional control (40.2 versus 8.7 months, P=0.0004) but in a younger population. Despite postoperative mortality, the gain was maintained for distance relapse-free survival (40.2 versus 10 months, P=0.0147) and overall survival (29.3 versus 14.2 months, P=0.0088). Compared to 50Gy chemoradiotherapy, local control was improved if high dose chemoradiotherapy was performed (13.8 versus 7.5 months, P=0.05) but not overall survival (14.0 versus 15.4 months, P=0.24). CONCLUSION: More than one-third relapse is local. Locoregional control is better with high dose chemoradiotherapy. In this study, surgery performed in selected patients only, improved locoregional control, relapse-free disease and overall survival.

Centralization of esophageal cancer surgery: does it improve clinical outcome?

BACKGROUND: The volume-outcome relationship for complex surgical procedures has been extensively studied. Most studies are based on administrative data and use in-hospital mortality as the sole outcome measure. It is still unknown if concentration of these procedures leads to improvement of clinical outcome. The aim of our study was to audit the process and effect of centralizing oesophageal resections for cancer by using detailed clinical data. METHODS: From January 1990 until December 2004, 555 esophagectomies for cancer were performed in 11 hospitals in the region of the Comprehensive Cancer Center West (CCCW); 342 patients were operated on before and 213 patients after the introduction of a centralization project. In this project patients were referred to the hospitals which showed superior outcomes in a regional audit. In this audit patient, tumor, and operative details as well as clinical outcome were compared between hospitals. The outcome of both cohorts, patients operated on before and after the start of the project, were evaluated. RESULTS: Despite the more severe comorbidity of the patient group, outcome improved after centralizing esophageal resections. Along with a reduction in postoperative morbidity and length of stay, mortality fell from 12% to 4% and survival improved significantly (P = 0.001). The hospitals with the highest procedural volume showed the biggest improvement in outcome. CONCLUSION: Volume is an important determinant of quality of care in esophageal cancer surgery. Referral of patients with esophageal cancer to surgical units with adequate experience and superior outcomes (outcome-based referral) improves quality of care.

[Surgical volume. An American perspective]. / Chirurgische Fallzahl. Die amerikanische Perspektive.

Due to an increasing interest in patient safety and quality health care, many studies attempt to show a relationship between procedural volume at the institutional and individual level and patient outcome. Despite the correlation between number of surgeons and institutional volume in major operative procedures such as coronary artery bypass graft, pancreatic resection, and esophagectomy, these parameters are likely to be proxy for individual factors such as experience and structural aspects. In general the relationship between case numbers and results is more convincing in cancer surgery than for cardiovascular procedures, and risk adjustment may play an important role for interpreting results of the various studies. Exact thresholds cannot be determined and thus remain speculative. It appears difficult to implement practical changes based on the observations, because the etiology and causality of the relationship between volume and outcome are still not understood. The simple focus on volume does not apply to measurements of quality but can be a starting point for further studies to identify more specific factors associated with surgical quality.

Factors affecting postoperative course and survival after en bloc resection for esophageal carcinoma.

BACKGROUND: To identify factors affecting postoperative course and survival after esophagectomy for cancer and reasons for improved survival over time. METHODS: Complete esophageal resection was attempted for middle and lower third esophageal carcinomas in 386 consecutive patients between January 1982 and January 2002. Two study periods were analyzed: 1982 to 1993 and 1994 to 2002. Prognostic factors were identified by multivariate analysis and the two periods compared. RESULTS: Hospital mortality rate decreased from 5.4% to 2.9% (p = 0.245). Both anastomotic leakage and pulmonary complications rates decreased from 9.8% to 2.2% (p = 0.001) and 24.1% to 19.3% (p = 0.295), respectively. An increased proportion of patients had R0 resection in the latter period, 78.5% versus 67.0%, (p = 0.028). Five-year survival rate after R0 resection increased from 29% to 46% (p = 0.001), with a decreased recurrence rate from 65.8% to 44.3% (p = 0.002). Three favorable prognostic factors were identified: low pT stage, pN0 stage, and operation during the 1994 to 2002 study period. CONCLUSIONS: Short-term outcome and survival of patients with resected esophageal cancer have improved over time. Advances in perioperative technique, staging methods, and surgical management combined with higher patient selection and use of neoadjuvant chemoradiation may be responsible for this progress.

Differences in operative mortality between high- and low-volume hospitals in Ontario for 5 major surgical procedures: estimating the number of lives potentially saved through regionalization.

BACKGROUND: Previous research has shown that persons undergoing certain high-risk surgical procedures at high-volume hospitals (HVHs) have a lower risk of postoperative death than those undergoing surgery at low-volume hospitals (LVHs). We estimated the absolute number of operative deaths that could potentially be avoided if 5 major surgical procedures in Ontario were restricted to HVHs. METHODS: We collected data on all persons who underwent esophagectomy (613), colon or rectal resection for colorectal cancer (18 898), pancreaticoduodenectomy (686), pulmonary lobectomy or pneumonectomy for lung cancer (5156) or repair of an unruptured abdominal aortic aneurysm (AAA) (6279) in Ontario from Apr. 1, 1994, to Mar. 31, 1999. We calculated the excess number of operative deaths (defined as deaths in the period from the day of the operation to 30 days thereafter), adjusted for age, sex and comorbidity, among the 75% of persons treated in LVHs, as compared with the 25% treated in the highest-volume quartile of hospitals. Bootstrap methods were used to estimate 95% confidence intervals (CIs). RESULTS: Of the 31 632 persons undergoing any of the 5 procedures, 1341 (4.24%) died within 30 days of surgery. If the 75% of persons treated at the LVHs had instead been treated at the HVHs, the annual number of lives potentially saved would have been 4 (95% CI, 0 to 9) for esophagectomy, 6 (95% CI, 1 to 11) for pancreaticoduodenectomy, 1 (95% CI, -10 to 13) for major lung resection and 14 (95% CI, 1 to 25) for repair of unruptured AAA. For resection of colon or rectum, the regionalization strategy would not have saved any lives, and 17 lives (95% CI, 36 to -3) would potentially have been lost. INTERPRETATION: A small number of operative deaths are potentially avoidable by performing 4 of 5 complex surgical procedures only at HVHs in Ontario. In determining health policy, the most compelling argument for regionalizing complex surgical procedures at HVHs may not be the prevention of a large number of such deaths.

Current trends in the surgical treatment of esophageal and cardia adenocarcinoma.

Since adenocarcinoma of the esophagus and cardia is increasing at an alarming rate, major efforts are currently oriented to identify patients who may benefit from extensive resection. Between November 1992 and May 1998, 218 patients with histologically proven adenocarcinoma of the distal esophagus or cardia were referred to our Department. In six patients (10.2%) with Barrett's adenocarcinoma, cancer was discovered during endoscopic surveillance program for Barrett's metaplasia. Overall, one hundred-forty-seven patients (67%) underwent resection. Fifty-one underwent an extended mediastinal lymphadenectomy. Median cumulative survival was 25.9+/-3.1 months in patients undergoing resection, and 7+/-1.3 months in patients having palliation (p<0.01). Survival was significantly longer in patients with negative nodes than in those with lymph node metastases (54+/-12.9 versus 17+/-2.8 months, p<0.01). Six of the 51 patients (11.8%) undergoing extended lymphadenectomy had metastatic upper mediastinal nodes. Additional serial sections and immunohistochemistry were performed in 46 patients. In 6 of 18 patients (33.3%) with negative nodes at conventional hematoxylin-eosin examination, immunohistochemistry demonstrated micrometastases in the lesser curve, paracardial, peripancreatic, or lower mediastinal nodes. Early diagnosis remains the prerequisite for curative treatment of adenocarcinoma of the esophagus and cardia. When a curative resection is attempted, extended lymphadenectomy improves tumor staging and may prevent local recurrences. Serial sections and immunohistochemistry provide additional accuracy in the staging of the disease and may prove useful to select patients for adjuvant therapy.