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  • Klevebro, F., et al. (författare)
  • Association between time interval from neoadjuvant chemoradiotherapy to surgery and complete histological tumor response in esophageal and gastroesophageal junction cancer : a national cohort study
  • 2020
  • Ingår i: Diseases of the Esophagus. - : Oxford University Press. - 1120-8694 .- 1442-2050. ; 33:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal time interval from neoadjuvant therapy to surgery in the treatment of esophageal cancer is not known. The aim of this study was to investigate if a prolonged interval between completed neoadjuvant chemoradiotherapy and surgery was associated with improved histological response rates and survival in a population-based national register cohort. The population-based cohort study included patients treated with neoadjuvant chemoradiotherapy and esophagectomy due to cancer in the esophagus or gastroesophageal junction. Patients were divided into two groups based on the median time from completed neoadjuvant treatment to surgery. The primary outcome was complete histological response. Secondary outcomes were lymph node tumor response, postoperative complications, R0 resection rate, 90-day mortality, and overall survival. In total, 643 patients were included, 344 (54%) patients underwent surgery within 49 days, and 299 (47%) after 50 days or longer. The groups were similar concerning baseline characteristics except for a higher clinical tumor stage (P = 0.009) in the prolonged time to surgery group. There were no significant differences in complete histological response, R0 resection rate, postoperative complications, 90-day mortality, or overall survival. Adjusted odds ratio for ypT0 in the prolonged time to surgery group was 0.99 (95% confidence interval: 0.64-1.53). Complete histological response in the primary tumor (ypT0) was associated with significantly higher overall survival: adjusted hazard ratio: 0.55 (95% CI 0.41-0.76). If lymph node metastases were present in these patients, the survival was, however, significantly lower: adjusted hazard ratio for ypT0N1: 2.30 (95% CI 1.21-4.35). In this prospectively collected, nationwide cohort study of esophageal and junctional type 1 and 2 cancer patients, there were no associations between time to surgery and histological complete response, postoperative outcomes, or overall survival. The results suggest that it is safe for patients to postpone surgery at least 7 to 10 weeks after completed chemoradiotherapy, but no evidence was seen in favor of recommending a prolonged time to surgery after neoadjuvant chemoradiotherapy for esophageal cancer. A definitive answer to this question requires a randomized controlled trial of standard vs. prolonged time to surgery.
  • Klevebro, F., et al. (författare)
  • Morbidity and mortality after surgery for cancer of the oesophagus and astro-oesophageal junction : a randomized clinical trial of neoadjuvant hemotherapy vs. neoadjuvant chemoradiation
  • 2015
  • Ingår i: European Journal of Surgical Oncology. - 0748-7983 .- 1532-2157. ; 41:7, s. 920-926
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare the incidence and severity of postoperative omplications after oesophagectomy for carcinoma of the oesophagus and astro-oesophageal junction (GOJ) after randomized accrual to eoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT). ackground: Neoadjuvant therapy improves long-term survival after esophagectomy. To date, evidence is insufficient to determine whether ombined nCT, or nCRT alone, is the most beneficial. ethods: Patients with carcinoma of the oesophagus or GOJ, resectable ith a curative intention, were enrolled in this multicenter trial onducted at seven centres in Sweden and Norway. Study participants re andomized to nCT or nCRT followed by surgery with two-field ymphadenectomy. Three cycles of cisplatin/5-fluorouracil was dministered in all patients, while 40 Gy of concomitant radiotherapy as administered in the nCRT group. esults: Of the randomized 181 patients, 91 were assigned to nCT and 90 o nCRT. One-hundred-and-fifty-five patients, 78 nCT and 77 nCRT, nderwent resection. There was no statistically significant difference etween the groups in the incidence of surgical or nonsurgical omplications (P-value = 0.69 and 0.13, respectively). There was no 0-day mortality, while the 90-day mortality was 3% (2/78) in the nCT roup and 6% (5/77) in the nCRT group (P = 0.24). The median lavien-Dindo complication severity grade was significantly higher in he nCRT. group (P = 0.001). onclusion: There was no significant difference in the incidence of omplications between patients randomized to nCT and nCRT. However, omplications were significantly more severe after nCRT. Registration rial database: The trial was registered in the Clinical Trials tabase registration number NCT01362127). 
  • Klevebro, F., et al. (författare)
  • Outcome of neoadjuvant therapies for cancer of the oesophagus or gastro-oesophageal junction based on a national data registry
  • 2016
  • Ingår i: British Journal of Surgery. - : Oxford University Press. - 0007-1323 .- 1365-2168. ; 103:13, s. 1864-1873
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Randomized trials have shown that neoadjuvant treatment improves survival in the curative treatment of oesophageal and gastro-oesophageal junction cancer. Results from population-based observational studies are, however, sparse and ambiguous. Methods: This prospective population-based cohort study included all patients who had oesophagectomy for cancer in Sweden, excluding clinical T1 N0, recorded in the National Register for Oesophageal and Gastric Cancer, 2006–2014. Patients were stratified into three groups: surgery alone, neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy. Results: Neoadjuvant treatment was given to 521 patients (51·1 per cent) and 499 (48·9 per cent) received surgery alone. Neoadjuvant chemotherapy increased the risk of postoperative surgical complications compared with surgery alone (adjusted odds ratio 2·01, 95 per cent c.i. 1·24 to 3·25; P = 0·005). Postoperative mortality was significantly increased after neoadjuvant chemoradiotherapy compared with surgery alone (odds ratio 2·37, 1·06 to 5·29; P = 0·035). Survival improved in patients with squamous cell carcinoma after neoadjuvant chemotherapy, whereas after neoadjuvant chemoradiotherapy survival was significantly improved only in the subgroup with the highest performance status and without known co-morbidity. In adenocarcinoma there was a trend towards improved overall survival after neoadjuvant chemotherapy, but neoadjuvant chemoradiotherapy did not offer a survival benefit. Stratified analysis including only patients with adenocarcinoma in the highest performance category without known co-morbidity showed a strong trend towards improved survival after neoadjuvant chemotherapy compared with surgery alone (adjusted hazard ratio 0·47, 0·21 to 1·04; P = 0·061). Conclusion: For patients with squamous cell carcinoma of the oesophagus or gastro-oesophageal junction, neoadjuvant treatments seemed to increase long-term survival, but also the risk of postoperative morbidity and mortality, compared with surgery alone. Neither neoadjuvant treatment option seemed to improve survival significantly among patients with adenocarcinoma, compared with surgery alone.
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