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Sökning: WFRF:(Klevebro Fredrik)

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1.
  • Elliott, Jessie A, et al. (författare)
  • An International Multicenter Study Exploring Whether Surveillance After Esophageal Cancer Surgery Impacts Oncological and Quality of Life Outcomes (ENSURE).
  • 2022
  • Ingår i: Annals of Surgery. - 0003-4932 .- 1528-1140.
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To determine the impact of surveillance on recurrence pattern, treatment, survival and health-related quality-of-life (HRQL) following curative-intent resection for esophageal cancer.SUMMARY BACKGROUND DATA: Although therapies for recurrent esophageal cancer may impact survival and HRQL, surveillance protocols after primary curative treatment are varied and inconsistent, reflecting a lack of evidence.METHODS: European iNvestigation of SUrveillance after Resection for Esophageal cancer was an international multicenter study of consecutive patients undergoing surgery for esophageal and esophagogastric junction cancers (2009-2015) across 20 centers (NCT03461341). Intensive surveillance (IS) was defined as annual computed tomography for 3 years postoperatively. The primary outcome measure was overall survival (OS), secondary outcomes included treatment, disease-specific survival, recurrence pattern, and HRQL. Multivariable linear, logistic, and Cox proportional hazards regression analyses were performed.RESULTS: Four thousand six hundred eighty-two patients were studied (72.6% adenocarcinoma, 69.1% neoadjuvant therapy, 45.5% IS). At median followup 60 months, 47.5% developed recurrence, oligometastatic in 39%. IS was associated with reduced symptomatic recurrence (OR 0.17 [0.12-0.25]) and increased tumor-directed therapy (OR 2.09 [1.58-2.77]). After adjusting for confounders, no OS benefit was observed among all patients (HR 1.01 [0.89-1.13]), but OS was improved following IS for those who underwent surgery alone (HR 0.60 [0.47-0.78]) and those with lower pathological (y)pT stages (Tis-2, HR 0.72 [0.58-0.89]). IS was associated with greater anxiety ( P =0.016), but similar overall HRQL.CONCLUSIONS: IS was associated with improved oncologic outcome in select cohorts, specifically patients with early-stage disease at presentation or favorable pathological stage post neoadjuvant therapy. This may inform guideline development, and enhance shared decision-making, at a time when therapeutic options for recurrence are expanding.
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2.
  • Holmén, Anders, et al. (författare)
  • Nutritional jejunostomy in esophagectomy for cancer, a national register-based cohort study of associations with postoperative outcomes and survival
  • 2021
  • Ingår i: Langenbeck's archives of surgery (Print). - : Springer. - 1435-2443 .- 1435-2451. ; 406:5, s. 1415-1423
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: Insertion of a nutritional jejunostomy in conjunction with esophagectomy is performed with the intention to decrease the risk for postoperative malnutrition and improve recovery without adding significant catheter-related complications. However, previous research has shown no clear benefit and there is currently no consensus of practice.METHODS: All patients treated with esophagectomy due to cancer during the period 2006-2017 reported in the Swedish National Register for Esophageal and Gastric Cancer were included in this register-based cohort study from a national database. Patients were stratified into two groups: esophagectomy alone and esophagectomy with jejunostomy.RESULTS: A total of 847 patients (45.27%) had no jejunostomy inserted while 1024 patients (54.73%) were treated with jejunostomy. The groups were comparable, but some differences were seen in histological tumor type and tumor stage between the groups. No significant differences in length of hospital stay, postoperative surgical complications, Clavien-Dindo score, or 90-day mortality rate were seen. There was no evidence of increased risk for significant jejunostomy-related complications. Patients in the jejunostomy group with anastomotic leaks had a statistically significant lower risk for severe morbidity defined as Clavien-Dindo score ≥ IIIb (adjusted odds ratio 0.19, 95% CI: 0.04-0.94, P = 0.041) compared to patients with anastomotic leaks and no jejunostomy.CONCLUSION: A nutritional jejunostomy is a safe method for early postoperative enteral nutrition which might decrease the risk for severe outcomes in patients with anastomotic leaks. Nutritional jejunostomy should be considered for patients undergoing curative intended surgery for esophageal and gastro-esophageal junction cancer.
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3.
  • Klevebro, Fredrik (författare)
  • Aspects of neoadjuvant therapy in the curative treatment of cancer in the esophagus or gastroesophageal junction
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Malignant esophageal tumors are among the most severe cancers. Only about 30% of the patients are suitable for curative treatment at diagnosis. The treatment is extremely demanding and unfortunately has disappointing results. The staging of disease and the treatment for cancer of the esophagus and gastroesophageal junction need to be improved. It is currently well established that neoadjuvant therapy, either with chemotherapy or with combined chemo- and radiotherapy, followed by surgery, offers a better chance for a cure in stage II and III esophageal and gastroesophageal junction cancer, than surgery alone. Data directly comparing neoadjuvant chemotherapy and chemoradiotherapy are scarce and it is debatable which of these neoadjuvant treatment concepts offers the best chance for long-term survival. This thesis aims to improve the knowledge about neoadjuvant treatment in the curative treatment of esophageal cancer. Papers I and III were based on the Neoadjuvant Chemotherapy versus Chemoradiotherapy in Resectable Cancer of the Esophagus and Gastric Cardia (NeoRes) trial, which was performed in Norway and Sweden during the period 2006– 2013. Patients with resectable squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction were randomized to either preoperative chemotherapy or preoperative combined chemoradiotherapy followed by surgical resection. Paper I showed an increased risk for severe postoperative complications after chemoradiotherapy compared to chemotherapy. In paper III we found that neoadjuvant chemoradiotherapy significantly increases the proportion of complete histological response, increases the occurrence of N0 lymph-node status, and increases the R0 resection rate, but there was no difference in overall survival compared to neoadjuvant chemotherapy. Paper II is a retrospective cohort study of patients with cancer of the esophagus or gastro- esophageal junction, who was reconstructed with cervical anastomosis. The planned radiation dose to the site of the cervical anastomosis on the gastric fundus was estimated for each patient. This study suggests that nCRT exposes the future anastomotic site to doses of radiation that may impair healing of the subsequent cervical anastomosis. Our data further suggest that nCRT may increase the severity of cervical anastomotic complications. Paper IV is a prospective population-based cohort study including all patients who underwent an esophagectomy operation due to cancer in Sweden, excluding T1N0, recorded in the Swedish National Register for Esophageal and Gastric Cancer, 2006-2014. The results showed that neoadjuvant chemoradiotherapy increases local tumor control, represented by increased R0 resection rates and pathological node-negative disease both compared to surgery alone and chemotherapy. For patients with the histological subtype squamous cell carcinoma, neoadjuvant treatment increases long-term survival but also increases the risk of postoperative morbidity and mortality compared to surgery alone. Neither of the two neoadjuvant treatment options seem to improve survival in adenocarcinomas, compared to surgery alone, in an unselected population of patients.
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4.
  • Nilsson, Klara, et al. (författare)
  • Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial : Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.
  • 2020
  • Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 272:5, s. 684-689
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate if prolonged TTS after completed nCRT improves postoperative outcomes for esophageal and esophagogastric junction cancer.SUMMARY OF BACKGROUND DATA: TTS has traditionally been 4-6 weeks after completed nCRT. However, the optimal timing is not known.METHODS: A multicenter clinical trial was performed with randomized allocation of TTS of 4-6 or 10-12 weeks. The primary endpoint of this sub-study was overall postoperative complications defined as Clavien-Dindo grade II-V. Secondary endpoints included complication severity according to Clavien-Dindo grade IIIb-V, postoperative 90-day mortality, and length of hospital stay. The study was registered in Clinicaltrials.gov (NCT02415101).RESULTS: In total 249 patients were randomized. There were no significant differences between standard TTS and prolonged TTS with regard to overall incidence of complications Clavien-Dindo grade II-V (63.2% vs 72.6%, P = 0.134) or regarding Clavien-Dindo grade IIIb-V complications (31.6% vs 34.9%, P = 0.603). There were no statistically significant differences between standard and prolonged TTS regarding anastomotic leak (P = 0.596), conduit necrosis (P = 0.524), chyle leak (P = 0.427), pneumonia (P = 0.548), and respiratory failure (P = 0.723). In the standard TTS arm 5 patients (4.3%) died within 90 days of surgery, compared to 4 patients (3.8%) in the prolonged TTS arm (P = 1.0). Median length of hospital stay was 15 days in the standard TTS arm and 17 days in the prolonged TTS arm (P = 0.234).CONCLUSION: The timing of surgery after completed nCRT for carcinoma of the esophagus or esophagogastric junction, is not of major importance with regard to short-term postoperative outcomes.
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5.
  • Nilsson, Magnus, et al. (författare)
  • Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed : The Study Protocol for the Randomized Controlled NEEDS Trial
  • 2022
  • Ingår i: Frontiers in Oncology. - : Frontiers Media S.A.. - 2234-943X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC.Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up.
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6.
  • Tsekrekos, Andrianos, et al. (författare)
  • Impact of Laparoscopic Gastrectomy on the Completion Rate of the Perioperative Chemotherapy Regimen in Gastric Cancer : A Swedish Nationwide Study
  • 2023
  • Ingår i: Annals of Surgical Oncology. - 1068-9265. ; 30:1112, s. 7196-7205
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Omission of prescheduled chemotherapy following surgery for gastric cancer is a frequent clinical problem. This study examined whether laparoscopic gastrectomy (LG) had a positive impact on compliance with adjuvant chemotherapy compared with open (OG). Methods: Patients with cT2-4aN0-3M0 adenocarcinoma treated with gastrectomy and perioperative chemotherapy between 2015 and 2020 were identified in the Swedish national register. Additional information regarding chemotherapy was retrieved from medical records. Regression models were used to investigate the association between surgical approach and the following outcomes: initiation of adjuvant chemotherapy, modification, and time interval from surgery to start of treatment. Results: A total of 247 patients were included (121 OG and 126 LG, conversion rate 11%), of which 71.3% had performance status ECOG 0 and 77.7% clinical stage II/III. In total, 86.2% of patients started adjuvant chemotherapy, with no significant difference between the groups (LG 88.1% vs OG 84.3%, p = 0.5). Reduction of chemotherapy occurred in 37.4% of patients and was similar between groups (LG 39.4% vs OG 35.1%, p = 0.6), as was the time interval from surgery. In multivariable analysis, LG was not associated with the probability of starting adjuvant chemotherapy (OR 1.36, p = 0.4) or the need for reduction (OR 1.29, p = 0.4). Conversely, major complications had a significant, negative impact on both outcomes. Conclusions: This nationwide study demonstrated a high rate of adjuvant chemotherapy initiation after curative intended surgery for gastric cancer. A beneficial effect of LG compared with OG on the completion rate was not evident.
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