Impact on postoperative complications of changes in skeletal muscle mass during neoadjuvant chemotherapy for gastro-oesophageal cancer.
ABSTRACT: BACKGROUND:Risk assessment is relevant to predict postoperative outcomes in patients with gastro-oesophageal cancer. This cohort study aimed to assess body composition changes during neoadjuvant chemotherapy and investigate their association with postoperative complications. METHODS:Consecutive patients with gastro-oesophageal cancer undergoing neoadjuvant chemotherapy and surgery with curative intent between 2016 and 2019 were identified from a specific database and included in the study. CT images before and after neoadjuvant chemotherapy were used to assess the skeletal muscle index, sarcopenia, and subcutaneous and visceral fat index. RESULTS:In a cohort of 199 patients, the mean skeletal muscle index decreased during neoadjuvant therapy (from 51·187 to 49·19?cm2 /m2 ; P?
Project description:Background:Neoadjuvant chemotherapy or chemoradiotherapy is used widely before tumour resection in cancer of the gastro-oesophageal junction (GOJ). Strategies to improve treatment tolerability are warranted. This study examined the safety and feasibility of preoperative exercise training during neoadjuvant treatment in these patients. Methods:Patients were allocated to a standard-care control group or an exercise group, who were prescribed standard care plus twice-weekly high-intensity aerobic exercise and resistance training sessions. The primary endpoint was the incidence of serious adverse events (SAEs) that prevented surgery, including death, disease progression or physical deterioration. Preoperative hospital admission, postoperative complications, changes in patient-reported quality of life and pathological treatment response were also recorded. In the exercise group, adherence to exercise and changes in aerobic fitness, muscle strength and body composition were measured. Results:The incidence of SAEs was not increased in the exercise group. The risk of failure to reach surgery was 5 versus 21 per cent in the control group (risk ratio (RR) 0·23, 95 per cent c.i. 0·04 to 1·29), the risk of preoperative hospital admission was 15 versus 38 per cent respectively (RR 0·39, 0·12 to 1·23) and the risk of postoperative complications was 58 versus 57 per cent (RR 1·06, 0·61 to 1·73). The exercise group attended a mean of 17·5 sessions, and improved fitness, muscle strength and Functional Assessment of Cancer Therapy - Esophageal (FACT-E) total score compared with the baseline level. Conclusion:Preoperative exercise training during neoadjuvant treatment in patients with GOJ cancer is safe and feasible, with improvements in fitness, strength and quality of life. Preoperative exercise training may be associated with a lower risk of critical SAEs that preclude surgery or result in hospitalization.
Project description:BACKGROUND:Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS:Patients with stage I-III GOJ cancer were allocated to 12?weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS:Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P =?0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P =?0·839) for exercise and usual care respectively. CONCLUSION:Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).
Project description:BACKGROUND:In patients who undergo curative treatment for oesophageal cancer, risk estimates of venous thromboembolism (VTE), arterial thromboembolism and bleeding are needed to guide decisions about thromboprophylaxis. METHODS:This was a single-centre, retrospective cohort study of patients with stage I-III oesophageal cancer who received neoadjuvant chemoradiation followed by oesophagectomy. The outcomes VTE, arterial thromboembolism, major bleeding, clinically relevant non-major bleeding and mortality were analysed for four consecutive cancer treatment stages (from diagnosis to neoadjuvant chemoradiotherapy, during neoadjuvant treatment, 30-day postoperative period, and up to 6?months after postoperative period). RESULTS:Some 511 patients were included. The 2-year survival rate was 67·3 (95 per cent c.i. 63·2 to 71·7) per cent. During the 2-year follow-up, 50 patients (9·8 per cent) developed VTE, 20 (3·9 per cent) arterial thromboembolism, 21 (4·1 per cent) major bleeding and 30 (5·9 per cent) clinically relevant non-major bleeding. The risk of these events was substantial at all treatment stages. Despite 30-day postoperative thromboprophylaxis, 17 patients (3·3 per cent) developed VTE after surgery. Patients with VTE had worse survival (time-varying hazard ratio 1·81, 95 per cent c.i. 1·25 to 2·64). Most bleeding events occurred around the time of medical intervention, and approximately one-half during concomitant use of prophylactic or therapeutic anticoagulation. CONCLUSION:Patients with oesophageal cancer undergoing neoadjuvant chemoradiotherapy and surgery are at substantial risk of thromboembolic and bleeding events throughout all stages of treatment. Survival is worse in patients with thromboembolic events during follow-up.
Project description:Background:Benchmarking on an international level might lead to improved outcomes at a national level. The aim of this study was to compare treatment and surgical outcome data from the Swedish National Register for Oesophageal and Gastric Cancer (NREV) and the Dutch Upper Gastrointestinal Cancer Audit (DUCA). Methods:All patients with primary oesophageal or gastric cancer who underwent a resection and were registered in NREV or DUCA between 2012 and 2014 were included. Differences in 30-day mortality were analysed using case mix-adjusted multivariable logistic regression. Results:In total, 4439 patients underwent oesophagectomy (2509 patients) or gastrectomy (1930 patients). Estimated resection rates were comparable. Swedish patients were older but had less advanced disease and less co-morbidity than Dutch patients. Neoadjuvant treatment rates were lower in Sweden than in the Netherlands, both for patients who underwent oesophagectomy (68·6 versus 90·0 per cent respectively; P?<?0·001) and for those having gastrectomy (38·3 versus 56·6 per cent; P?<?0·001). In Sweden, transthoracic oesophagectomy was performed in 94·7 per cent of patients, whereas in the Netherlands, a transhiatal approach was undertaken in 35·8 per cent. Higher annual procedural volumes per hospital were observed in the Netherlands. Adjusted 30-day and/or in-hospital mortality after gastrectomy was statistically significantly lower in Sweden than in the Netherlands (odds ratio 0·53, 95 per cent c.i. 0·29 to 0·95). Conclusion:For oesophageal and gastric cancer, there are differences in patient, tumour and treatment characteristics between Sweden and the Netherlands. Postoperative mortality in patients with gastric cancer was lower in Sweden.
Project description:BACKGROUND:Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS:Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS:A total of 812 patients were included. The recurrence rate at less than 1?year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION:The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.
Project description:Background:Oesophagectomy has a high risk of postoperative morbidity. The impact of postoperative complications on overall survival of oesophageal cancer remains unclear. This meta-analysis addressed the impact of complications on long-term survival following oesophagectomy. Methods:A search of PubMed and Cochrane Library databases was undertaken for systematic review of papers published between January 1995 and August 2016 that analysed the relation between postoperative complications and long-term survival. In the meta-analysis, data were pooled. The main outcome was overall survival (OS). Secondary endpoints included disease-free (DFS) and cancer-specific (CSS) survival. Results:A total of 357 citations was reviewed; 21 studies comprising 11 368 patients were included in the analyses. Overall, postoperative complications were associated with significantly decreased 5-year OS (hazard ratio (HR) 1·16, 95 per cent c.i. 1·06 to 1·26; P = 0·001) and 5-year CSS (HR 1·27, 1·09 to 1·47; P = 0·002). Pulmonary complications were associated with decreased 5-year OS (HR 1·37, 1·16 to 1·62; P < 0·001), CSS (HR 1·60, 1·35 to 1·89; P < 0·001) and 5-year DFS (HR 1·16, 1·00 to 1·33; P = 0·05). Patients with anastomotic leakage had significantly decreased 5-year OS (HR 1·20, 1·10 to 1·30; P < 0·001), 5-year CSS (HR 1·81, 1·11 to 2·95; P = 0·02) and 5-year DFS (HR 1·13, 1·02 to 1·25; P = 0·01). Conclusion:Postoperative complications after oesophagectomy, including pulmonary complications and anastomotic leakage, decreased long-term survival.
Project description:<h4>Background</h4>Effects of postmastectomy radiotherapy (PMRT) on autologous breast reconstruction (BRR) are controversial regarding surgical complications, cosmetic appearance and quality of life (QOL). This systematic review evaluated these outcomes after abdominal free flap reconstruction in patients undergoing postoperative adjuvant radiotherapy (PMRT), preoperative radiotherapy (neoadjuvant radiotherapy) and no radiotherapy, aiming to establish evidence-based optimal timings for radiotherapy and BRR to guide contemporary management.<h4>Methods</h4>The study was registered on PROSPERO (CRD42017077945). Embase, MEDLINE, Google Scholar, CENTRAL, Science Citation Index and ClinicalTrials.gov were searched (January 2000 to August 2018). Study quality and risk of bias were assessed using GRADE and Cochrane's ROBINS-I respectively.<h4>Results</h4>Some 12 studies were identified, involving 1756 patients (350 PMRT, 683 no radiotherapy and 723 neoadjuvant radiotherapy), with a mean follow-up of 27·1 (range 12·0-54·0)?months for those having PMRT, 16·8 (1·0-50·3)?months for neoadjuvant radiotherapy, and 18·3 (1·0-48·7)?months for no radiotherapy. Three prospective and nine retrospective cohorts were included. There were no randomized studies. Five comparative radiotherapy studies evaluated PMRT and four assessed neoadjuvant radiotherapy. Studies were of low quality, with moderate to serious risk of bias. Severe complications were similar between the groups: PMRT versus no radiotherapy (92 versus 141 patients respectively; odds ratio (OR) 2·35, 95 per cent c.i. 0·63 to 8·81, P?=?0·200); neoadjuvant radiotherapy versus no radiotherapy (180 versus 392 patients; OR 1·24, 0·76 to 2·04, P?=?0·390); and combined PMRT plus neoadjuvant radiotherapy versus no radiotherapy (272 versus 453 patients; OR 1·38, 0·83 to 2·32, P?=?0·220). QOL and cosmetic studies used inconsistent methodologies.<h4>Conclusion</h4>Evidence is conflicting and study quality was poor, limiting recommendations for the timing of autologous BRR and radiotherapy. The impact of PMRT and neoadjuvant radiotherapy appeared to be similar.
Project description:The impact of body composition on the short- or long-term outcomes of patients with surgically treated advanced rectal cancer after neoadjuvant chemoradiotherapy remains unclear. This study examined the correlation between low skeletal muscle mass and morbidity and survival in patients with advanced lower rectal cancer.We enrolled 144 clinical stage II/III patients with advanced lower rectal cancer who underwent neoadjuvant chemoradiotherapy followed by curative resection between 2004 and 2011. The cross-sectional skeletal muscle area at the third lumbar vertebra (L3) level was evaluated by computed tomography before chemoradiotherapy, and this was normalized by the square of the height to obtain the skeletal muscle index. Low skeletal muscle mass was defined as the sex-specific lowest quartile of the L3 skeletal muscle index. The association between low skeletal muscle mass and morbidity, relapse-free survival, or overall survival was assessed.Low skeletal muscle mass was identified in 37 (25.7%) patients. Age and body mass index were associated with low skeletal muscle mass. By multivariate analysis, we found that low skeletal muscle mass was independently associated with poor overall survival (hazard ratio = 2.93; 95%CI: 1.11-7.71; p = 0.031) and relapse-free survival (hazard ratio = 2.15; 95%CI: 1.06-4.21; p = 0.035), but was not associated with the rate of postoperative complications.Low skeletal muscle mass is an independent negative prognostic factor for relapse-free and overall survival in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy.
Project description:<h4>Background</h4>There is currently conflicting evidence surrounding the effects of obesity on postoperative outcomes. Previous studies have found obesity to be associated with adverse events, but others have found no association. The aim of this study was to determine whether increasing body mass index (BMI) is an independent risk factor for development of major postoperative complications.<h4>Methods</h4>This was a multicentre prospective cohort study across the UK and Republic of Ireland. Consecutive patients undergoing elective or emergency gastrointestinal surgery over a 4-month interval (October-December 2014) were eligible for inclusion. The primary outcome was the 30-day major complication rate (Clavien-Dindo grade III-V). BMI was grouped according to the World Health Organization classification. Multilevel logistic regression models were used to adjust for patient, operative and hospital-level effects, creating odds ratios (ORs) and 95 per cent confidence intervals (c.i.).<h4>Results</h4>Of 7965 patients, 2545 (32·0 per cent) were of normal weight, 2673 (33·6 per cent) were overweight and 2747 (34·5 per cent) were obese. Overall, 4925 (61·8 per cent) underwent elective and 3038 (38·1 per cent) emergency operations. The 30-day major complication rate was 11·4 per cent (908 of 7965). In adjusted models, a significant interaction was found between BMI and diagnosis, with an association seen between BMI and major complications for patients with malignancy (overweight: OR 1·59, 95 per cent c.i. 1·12 to 2·29, P = 0·008; obese: OR 1·91, 1·31 to 2·83, P = 0·002; compared with normal weight) but not benign disease (overweight: OR 0·89, 0·71 to 1·12, P = 0·329; obese: OR 0·84, 0·66 to 1·06, P = 0·147).<h4>Conclusion</h4>Overweight and obese patients undergoing surgery for gastrointestinal malignancy are at increased risk of major postoperative complications compared with those of normal weight.
Project description:<h4>Background</h4>Although cytoreductive surgery has been shown to be beneficial in carefully selected patients with metastatic gastrointestinal stromal tumours (GISTs) treated with tyrosine kinase inhibitors (TKIs), factors predictive of postoperative morbidity have not been investigated previously.<h4>Methods</h4>A surgical complexity score for GIST metastasectomy (GM-SCS) composed of patient-related and surgical factors was assigned retrospectively to patients with metastatic GIST treated with TKI therapy and surgery at two institutions between 2002 and 2014. The ability of clinicopathological factors and GM-SCS to predict postoperative morbidity was assessed by means of a multivariable logistic regression model. Postoperative complications were categorized using the Clavien-Dindo classification.<h4>Results</h4>Some 400 operations on 323 patients with metastatic GIST on TKIs were included. Complications were observed following 110 operations (27·5 per cent) including 70 major complications (grade III-V) (17·5 per cent of 400 operations). Patients were divided into low (5 points or less; 100 patients, 25·0 per cent), intermediate (6-9 points; 191, 47·8 per cent) and high (at least 10 points; 109, 27·3 per cent) complexity scoring groups based on the GM-SCS. An intermediate (odds ratio (OR) 2·88; P = 0·008) and high (OR 5·40; P < 0·001) GM-SCS were independent predictors of overall complications, whereas only a high GM-SCS was independently predictive of a major complication (OR 3·65; P = 0·018). Metastatic mitotic index was also an independent predictor of overall complications (OR 2·55; P = 0·047). GM-SCS did not predict progression-free or overall survival.<h4>Conclusion</h4>A gastrointestinal stromal tumour metastastectomy surgical complexity score can predict morbidity, which may help in preoperative risk stratification and optimal treatment planning.