scholarly journals P01.08 Sarcopenia as biomarker for immunotherapy outcomes and immune-related adverse events – a systematic review and meta-analysis

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A7.1-A7
Author(s):  
S Günther ◽  
P Trinkner ◽  
M von Bergwelt ◽  
D Cordas dos Santos ◽  
S Theurich
Keyword(s):  
Systematic Review ◽  
Skeletal Muscle ◽  
Risk Factor ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Lumbar Vertebrae ◽  
Psoas Muscle ◽  
Skeletal Muscle Index ◽  
The Impact

BackgroundSarcopenia is an established risk factor for oncologic treatments like surgical interventions and conventional chemotherapy. However, the impact of sarcopenia on treatment and immune-related adverse events (irAEs) of cancer patients treated with immune checkpoint inhibitors (ICIs) continues to be debated. Therefore, we performed a systematic review and meta-analysis of all published articles evaluating the effects of sarcopenia on survival outcomes and irAEs of patients undergoing ICI treatment.Materials and MethodsIn analogy to the Cochrane guidelines for systematic reviews, we performed a systematic literature search including all published articles in PubMed until February 2021 for the key terms ‘sarcopenia’ or ‘sarcopenic obesity’ in combination with several terms for ICI treatments, irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included defined cut-offs for sarcopenia. Reported outcomes included progression-free survival (PFS), overall survival (OS) and the frequency of irAEs. For the random effects meta-analysis, we used Hazard Ratios (HR) for OS and PFS and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 15 studies with 1,428 patients were selected to be eligible for meta-analysis. To evaluate muscle mass, all studies used CT-derived body composition parameters at the third lumbar vertebrae level and defined sarcopenia by using skeletal muscle index (SMI), psoas muscle index (PMI) or skeletal muscle density (SMD). Sarcopenic patients showed an inferior survival compared to non-sarcopenic patients with a combined HR for PFS with 1.53 (95%CI 1.23-1.91, p= 0.0001) and for OS with 1.6 (95% CI 1.23-2.09, p= 0,0005). Frequency of irAEs did not differ between sarcopenic and non-sarcopenic patients regardless of irAE grade (irAEs of grade≥3: OR 1.14, 95%CI 0.65-2.01, p = 0.64, irAEs of any grade: OR 0.96, 95%CI 0.65-1.42, p = 0.85).ConclusionsThis is the first meta-analysis that assessed sarcopenia in a mixed cohort of cancer patients. It revealed that sarcopenia is an adverse risk factor for survival of patients undergoing ICI treatment without affecting the risk of developing irAEs. Future studies may address sarcopenia as a patient-derived risk factor emphasizing the importance of nutrition and physical activity interventions.Disclosure InformationS. Günther: None. P. Trinkner: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

scholarly journals P01.06 Overweight and obesity as biomarkers for survival outcomes and immune related adverse events undergoing immunotherapy – a systematic review and meta-analysis

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A5.2-A6
Author(s):  
P Trinkner ◽  
S Günther ◽  
M von Bergwelt ◽  
D Cordas dos Santos ◽  
S Theurich
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Obese Patients ◽  
Increased Risk ◽  
Underweight Patients ◽  
The Impact

BackgroundThe impact of overweight/obesity in cancer patients treated with immune checkpoint inhibitors (ICIs) is controversial. To further contribute to this debate, we performed a systematic review and meta-analysis of published articles evaluating the effects of overweight/obesity on survival and immune-related adverse events (irAEs).Materials and MethodsIn analogy to Cochrane recommendations, systematic literature searches included all published articles in PubMed until February 2021 with key terms ‘obesity’ and ‘overweight’ and ICI treatment irrespective of cancer entity and ICI used. Further selection criteria for meta-analysis included WHO cut-offs for overweight/obesity. For the random effects meta-analysis, we used Hazard Ratios (HR) for overall and progression-free survival (OS, PFS) and Odds Ratios (OR) for occurrence of irAEs with corresponding 95% confidence intervals (95%CI), respectively.ResultsA total of 30 studies (12,895 patients, 38% female) selected for meta-analysis revealed a superior survival of overweight/obese patients (PFS: HR 0.9, 95%CI 0.77-1.04, p = 0.11; OS: 0.74, 95%CI 0.63-0.92, p = 0.0005) compared to normal weight patients. In subgroup analyses based on sex, overweight/obese male patients showed increased survival (PFS: HR 0.79, 95%CI 0.63-1.00, p = 0.05; OS: 0.71, 95%CI 0.58-0.86, p = 0.0005), whereas overweight/obese female patients had similar survival probabilities compared to their normal weight counterparts (PFS: HR 1.01, 95%CI 0.69-1.47, p = 0.96; OS: HR 0.73, 95%CI 0.48-1.10, p = 0.13). Underweight patients showed inferior survival (PFS: HR 1.48, 95%CI 1.07-2.04, p = 0.02; OS: HR 1.86, 95%CI 1.13-3.04, p = 0.01). In addition, overweight/obese patients had a higher risk of developing irAEs with grade ≥ 3 (OR 1.91, 95%CI 1.18-3.10, p = 0.008).ConclusionsOur meta-analysis revealed that overweight/obesity is a beneficial factor for PFS and OS in a mixed cohort of cancer patients undergoing ICI treatment accompanied by an increased risk of severe irAEs. The differences between overweight/obese males and overweight/obese females might point to sex specific adipose distribution patterns and interactions of sex steroids on a molecular level. A significant number of studies included underweight patients into normal weight control groups which led to a compromised interpretation of the data and should be addressed in future studies.Disclosure InformationP. Trinkner: None. S. Günther: None. M. von Bergwelt: None. D. Cordas dos Santos: None. S. Theurich: None.

Antifungal Prophylaxis in Cancer Patients After Chemotherapy or Hematopoietic Stem-Cell Transplantation: Systematic Review and Meta-Analysis

2007 ◽  
Vol 25 (34) ◽  
pp. 5471-5489 ◽  
Author(s):  
Eyal Robenshtok ◽  
Anat Gafter-Gvili ◽  
Elad Goldberg ◽  
Miriam Weinberger ◽  
Moshe Yeshurun ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Adverse Events ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Antifungal Prophylaxis ◽  
Hematopoietic Stem ◽  
All Cause Mortality ◽  
Related Mortality

Purpose To evaluate the effect of antifungal prophylaxis on all-cause mortality as primary outcome, invasive fungal infections (IFIs), and adverse events. Many studies have evaluated the role of antifungal prophylaxis in cancer patients, with inconsistent conclusions. Methods We performed a systematic review and meta-analysis of randomized, controlled trials comparing systemic antifungals with placebo, no intervention, or other antifungal agents for prophylaxis in cancer patients after chemotherapy. The Cochrane Library, MEDLINE, conference proceedings, and references were searched. Two reviewers independently appraised the quality of trials and extracted data. Results Sixty-four trials met inclusion criteria. Antifungal prophylaxis decreased all-cause mortality significantly at end of follow-up compared with placebo, no treatment, or nonsystemic antifungals (relative risk [RR], 0.84; 95% CI, 0.74 to 0.95). In allogeneic hematopoietic stem-cell transplantation (HSCT) recipients, prophylaxis reduced all-cause mortality (RR, 0.62; 95% CI, 0.45 to 0.85), fungal-related mortality, and documented IFI. In acute leukemia patients, there was a significant reduction in fungal-related mortality and documented IFI, whereas the difference in mortality was only borderline significant (RR, 0.88; 95% CI, 0.74 to 1.06). Prophylaxis with itraconazole suspension reduced documented IFI when compared with fluconazole, with no difference in survival, and at the cost of more adverse events. On the basis of two studies, posaconazole prophylaxis reduced all-cause mortality (RR, 0.74; 95% CI, 0.56 to 0.98), fungal-related mortality, and IFI when compared with fluconazole. Conclusion Antifungal prophylaxis decreases all-cause mortality significantly in patients after chemotherapy. Antifungal prophylaxis should be administered to patients undergoing allogeneic HSCT, and should probably be administered to high-risk acute leukemia patients.

Pretreatment skeletal muscle depletion as an adverse prognostic factor in metastatic gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 161-161
Author(s):  
Hiroko Hasegawa ◽  
Kazumasa Fujitani ◽  
Yusuke Yamaoka ◽  
Motohiro Hirao ◽  
Shoichi Nakazuru ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Skeletal Muscle ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Gastric Cancer ◽  
First Line ◽  
Skeletal Muscle Index ◽  
Pre Treatment ◽  
The Impact

161 Background: Body composition has emerged as an important prognostic factor in cancer patients. Especially, skeletal mass depletion has been associated with poor performance status, toxicity of chemotherapy and shortened survival in cancer patients. However, the impact of pre-treatment skeletal muscle index on survival or toxicity in metastatic gastric cancer patients remains uncertain. Methods: In this retrospective study, we reviewed 98 metastatic gastric cancer (mGC) patients who received S-1 based combination chemotherapy as first-line treatment from April 2006 to March 2013. Pre-treatment skeletal muscle mass was quantified by CT cross sectional area at the third lumbar vertebrae and evaluated as lumbar skeletal muscle index (SMI) (cm2/m2) after normalization for stature (m2). Patients were categorized into 2 groups depending on initial SMI: 35 patients with SMI ≤ 40 and 63 patients with SMI > 40. Results: Median overall survival was significantly shorter in the SMI ≤ 40 group than in the SMI >40 group (439 days versus 565 days; p= 0.03). Progression free survival was also better in the SMI> 40 group without statistical significance (175 days versus 151 days; p= 0.17). Toxicity (grade 3 or 4) was more common in the SMI ≤ 40 group than in the SMI >40 group. (41.1% versus 11.1%; p=0.001). In multivariate analysis, performance status of 2 (HR 4.711, 95%CI 1.065 to 20.832, p=0.04), presence of primary tumor (HR 2.322, 95%CI 1.007 to 5.357, p=0.04) and pre-treatment SMI (HR 2.525, 95%CI 1.145 to 5.568, p=0.02) were independent prognostic factors for OS. Conclusions: The present study suggests that skeletal muscle depletion at the initiation of first-line chemotherapy might be an independent prognostic factor for mGC patients.

scholarly journals Prone Positioning of Non-intubated Patients with COVID-19 - A Systematic Review and Meta-analysis

2020 ◽  
Author(s):  
Mallikarjuna Reddy PONNAPA REDDY ◽  
Ashwin SUBRAMANIAM ◽  
Zheng Jie LIM ◽  
Alexandr ZUBAREV ◽  
Afsana AFROZ ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Prone Positioning ◽  
Serious Adverse Events ◽  
Lack Of Control ◽  
The Impact ◽  
Substantial Heterogeneity ◽  
Major Adverse Events

Abstract Purpose: Several studies have reported adopting prone positioning (PP) in non-intubated patients with COVID-19-related hypoxaemic respiratory failure. This systematic review and meta-analysis evaluated the impact of PP on oxygenation and clinical outcomes.Methods: We searched PubMed, Embase and the COVID-19 living systematic review from December 1, 2019 to July 23, 2020. We included studies that reported using PP in hypoxaemic, non-intubated adult patients with COVID-19. Primary outcome measureed was the weighted mean difference (MD) in oxygenation parameters (PaO2/FiO2, PaO2 or SpO2) pre and post-PP. Results: Fifteen single arm observational studies reporting PP in 449 patients were included. Substantial heterogeneity was noted in terms of, location within hospital where PP was instituted, respiratory supports during PP, and frequency and duration of PP. Significant improvement in oxygenation was reported post-PP: PaO2/FiO2 (MD 37.6, 95% CI 18.8-56.5); PaO2 (MD 30.4 mmHg, 95% CI 10.9 to 49.9); and SpO2 (MD 5.8%, 95% CI 3.7 to 7.9). Patients with a pre-PP PaO2/FiO2 ≤150 experienced greater oxygenation improvements compared with those with a pre-PP PaO2/FiO2 >150 (MD 40.5, 95% CI -3.5 to 84.6) vs. 37, 95% CI 17.1 to 56.9). Respiratory rate decreased post-PP (MD -2.9, 95% CI -5.4 to -0.4). Overall intubation and mortality rates were 21% (90/426) and 26% (101/390) respectively. There were no major adverse events reported. Conclusions: Despite the significant variability in frequency and duration of PP and respiratory supports applied, PP was associated with improvements in oxygenation parameters without any reported serious adverse events. The results are limited by lack of control arm and adjustment for confounders. Clinical trials are required to determine the effect of awake PP on patient-centred outcomes.Systematic review registration: Registration/protocol in PROSPERO (CRD42020194080).

scholarly journals Effectiveness of trauma centre verification: a systematic review and meta-analysis

2021 ◽  
Vol 64 (1) ◽  
pp. E25-E38
Author(s):  
Brice Batomen ◽  
Lynne Moore ◽  
Mabel Carabali ◽  
Pier-Alexandre Tardif ◽  
Howard Champion
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Resource Use ◽  
Meta Analysis ◽  
The United States ◽  
Trauma Centre ◽  
Trauma Centres ◽  
Processes Of Care ◽  
Injured Patients ◽  
The Impact

Background: There is a growing trend toward verification of trauma centres, but its impact remains unclear. This systematic review aimed to synthesize available evidence on the effectiveness of trauma centre verification. Methods: We conducted a systematic search of the CINAHL, Embase, HealthStar, MEDLINE and ProQuest databases, as well as the websites of key injury organizations for grey literature, from inception to June 2019, without language restrictions. Our population consisted of injured patients treated at trauma centres. The intervention was trauma centre verification. Comparison groups comprised nonverified trauma centres, or the same centre before it was first verified or re-verified. The primary outcome was in-hospital mortality; secondary outcomes included adverse events, resource use and processes of care. We computed pooled summary estimates using random-effects meta-analysis. Results: Of 5125 citations identified, 29, all conducted in the United States, satisfied our inclusion criteria. Mortality was the most frequently investigated outcome (n = 20), followed by processes of care (n = 12), resource use (n = 12) and adverse events (n = 7). The risk of bias was serious to critical in 22 studies. We observed an imprecise association between verification and decreased mortality (relative risk 0.74, 95% confidence interval 0.52 to 1.06) in severely injured patients. Conclusion: Our review showed mixed and inconsistent associations between verification and processes of care or patient outcomes. The validity of the published literature is limited by the lack of robust controls, as well as any evidence from outside the US, which precludes extrapolation to other health care jurisdictions. Quasiexperimental studies are needed to assess the impact of trauma centre verification. Systematic reviews registration: PROSPERO no. CRD42018107083

scholarly journals Efficaciousness of dexmedetomidine in children undergoing cleft lip and palate repair: a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e046798
Author(s):  
Dengfeng Liu ◽  
Li Pan ◽  
Yin Gao ◽  
Jiefan Liu ◽  
Feng Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Adverse Events ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Meta Analysis ◽  
Cochrane Review ◽  
Random Effect Model ◽  
Control Group ◽  
Paediatric Patients ◽  
The Impact

ObjectiveTo systematically assess the efficacy and safety of dexmedetomidine as an anaesthesia adjuvant for cleft lip and palate (CLP) repair in children.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang (up to October 2020). Studies in languages other than English and Chinese were excluded.Eligibility criteria for selecting studiesRandomised controlled trials (RCTs) evaluating the impact of dexmedetomidine on emergence agitation (EA), the need for postoperative rescue analgesics, postoperative nausea and vomiting (PONV), and other adverse events in paediatric patients during CLP repair.Data extraction and synthesisThe quality of evidence was assessed by using the Cochrane Review Methods and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were screened, extracted and assessed by two independent authors. Outcomes were reported as a risk ratio (RR) with a 95% CI. A random-effect model was used when heterogeneity was detected.ResultsThirteen studies including 1040 children met the inclusion criteria. The incidence of EA was significantly decreased in the dexmedetomidine group (RR, 0.19; 95% CI 0.10 to 0.36; p<0.00001; I2=56%) as compared with the control group. Paediatric patients receiving dexmedetomidine had lower postoperative analgesic requirements (RR, 0.27; 95% CI 0.10 to 0.73; p=0.01; I2=84%) and a lower incidence of respiratory adverse events (RR, 0.49; 95% CI 0.31 to 0.78; p=0.003; I2=0%). There were no significant differences in the risk of PONV and cardiovascular adverse events.ConclusionsThere was a lack of high-quality studies in this field. Perioperative administration of dexmedetomidine reduced the need for postoperative rescue analgesics and the incidence of EA in children without side effects undergoing CLP repair. However, further verification with larger samples and higher-quality RCTs is needed.

Systematic review of histamine type 2 receptor antagonists as an adjunct to curative surgical resection in gastrointestinal malignancies

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15085-e15085
Author(s):  
S. Deva ◽  
M. B. Jameson
Keyword(s):  
Systematic Review ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Risk Ratio ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Cochrane Collaboration ◽  
Curative Intent ◽  
Gastrointestinal Malignancies ◽  
The Impact

e15085 Background: H2RAs have induced regression in a number of malignancies. The mechanisms that may contribute to this effect include inhibition of T-suppressor lymphocytes, increased tumor infiltrating lymphocytes and blockade of histamine-induced tumor proliferation and angiogenesis. Unique to cimetidine is its ability to inhibit vascular endothelial expression of the cell adhesion molecule E-selectin, to which many GI tumor cells adhere via carbohydrate antigen ligands. The optimal use of H2RAs in cancer patients could therefore be as adjuvant therapy rather than for metastatic disease. Methods: This systematic review examines the impact of H2RAs on the overall survival of patients when used as an adjunct to curative surgical resection for a GI malignancy. Using a sensitive search strategy, randomized controlled trials were identified in relevant databases. Criteria for study selection included: patients with colorectal or gastric cancer surgically resected with curative intent; H2RAs used i) at any dose, ii) for any length of time, iii) with any other treatment modality and iv) in the pre-, peri- or post-operative period. The results were stratified for both the type of malignancy and the H2RA used and analyzed by meta-analysis using Cochrane Collaboration software. Results: Of 350 trials identified, 8 were eligible for inclusion and had sufficient data for analysis, including a total of 1461 patients. Meta-analysis revealed a risk ratio for mortality of 0.86 (95% CI 0.76–0.99, p = 0.03) for patients randomised to H2RAs. Trials of colorectal cancer patients where cimetidine was the H2RA being evaluated demonstrated a significant survival advantage, risk ratio 0.53 (95% CI 0.33–0.84, p = 0.007). All other subgroups demonstrated a non-significant trend favouring H2RAs. Conclusions: H2RAs, and cimetidine in particular, appear to confer a survival benefit when given as an adjunct to curative surgical resection of GI cancers. The trial designs were heterogeneous and further large studies are warranted. No significant financial relationships to disclose.

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