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Journal of Cachexia, Sarcopenia and... Apr 2022Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of... (Review)
Review
Cancer cachexia is an unmet clinical need that affects more than 50% of patients with cancer. The systemic inflammatory response, which is mediated by a network of cytokines, has an established role in the genesis and maintenance of cancer as well as in cachexia; yet, the specific role of the cytokine milieu in cachexia requires elucidation. This systematic review aims to examine the relationship between cytokines and the cachexia syndrome in patients with incurable cancer. The databases MEDLINE, EMBASE, CINAHL, CENTRAL, PsycINFO, and Web of Science were searched for studies published between 01/01/2004 and 06/01/2020. Included studies measured cytokines and their relationship with cachexia and related symptoms/signs in adults with incurable cancer. After title screening (n = 5202), the abstracts (n = 1264) and the full-text studies (n = 322) were reviewed independently by two authors. The quality assessment of the selected papers was conducted using the modified Downs and Black checklist. Overall, 1277 patients with incurable cancer and 155 healthy controls were analysed in the 17 eligible studies. The mean age of the patients was 64 ± 15 (mean ± standard deviation). Only 34% of included participants were female. The included studies were assessed as moderate-quality to high-quality evidence (mean quality score: 7.8; range: 5-10). A total of 31 cytokines were examined in this review, of which interleukin-6 (IL-6, 14 studies) and tumour necrosis factor-α (TNF-α, 12 studies) were the most common. The definitions of cachexia and the weight-loss thresholds were highly variable across studies. Although the data could not be meta-analysed due to the high degree of methodological heterogeneity, the findings were discussed in a systematic manner. IL-6, TNF-α, and IL-8 were greater in cachectic patients compared with healthy individuals. Also, IL-6 levels were higher in cachectic participants as opposed to non-cachectic patients. Leptin, interferon-γ, IL-1β, IL-10, adiponectin, and ghrelin did not demonstrate any significant difference between groups when individuals with cancer cachexia were compared against non-cachectic patients or healthy participants. These findings suggest that a network of cytokines, commonly IL-6, TNF-α, and IL-8, are associated with the development of cachexia. Yet, this relationship is not proven to be causative and future studies should opt for longitudinal designs with consistent methodological approaches, as well as adequate techniques for analysing and reporting the results.
Topics: Aged; Cachexia; Cytokines; Female; Humans; Interleukin-6; Male; Middle Aged; Neoplasms; Tumor Necrosis Factor-alpha
PubMed: 35080147
DOI: 10.1002/jcsm.12912 -
Journal of Cachexia, Sarcopenia and... Dec 2022Sarcopenia measured through body composition analysis is emerging as an important prognosticator among various malignancies, including oesophageal cancer. Skeletal... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia measured through body composition analysis is emerging as an important prognosticator among various malignancies, including oesophageal cancer. Skeletal muscle index (SMI) as determined by the third lumbar vertebrae on cross-sectional CT images has been demonstrated as a predictor of overall survival in oesophageal cancer, using pre-defined cut off values for sarcopenia. However, this is largely within the setting of resectable disease. The primary objective of this systematic review and meta-analysis was to determine the effect of sarcopenia defined by SMI on overall-survival in patients with unresectable oesophageal cancer. On 30 January 2021, a systematic search of the literature was conducted to identify the role of SMI among patients with unresectable oesophageal cancer, with overall survival as the primary outcome. Databases included MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library. Inclusion criteria included age >18, diagnosis of oesophageal cancer, and non-operative management. A meta-analysis was conducted using RevMan 5.4.1 using an inverse variance, random effects model. After the removal of duplicates, 2755 unique search results were obtained. Manual screening of titles and abstracts resulted in 287 full text articles that were reviewed. Of these, five studies met the inclusion criteria with data evaluating the effect of sarcopenia defined by SMI on overall survival. A total of 783 patients, the majority of which were male (n = 638, 81%), with a mean age of 68 ± 2.3 years were included. 641 (82%) patients were diagnosed with squamous cell carcinoma. Sarcopenia, as determined by SMI using pre-defined cut-off values, was reported in 517 patients (66%). Meta-analysis demonstrated decreased overall survival in the sarcopenia group compared with the non-sarcopenia group (HR = 1.51; 95% CI 1.21-1.89; P = 0.0003; I = 0%; Figure 1). No significant publication bias was noted on assessment of funnel plot and Egger's test (P = 0.295). Sarcopenia as defined by SMI is predictive of overall survival among patients with nonoperative oesophageal cancer. Further analysis on the effect of sarcopenia on treatment related adverse effects and complications, particularly related to chemotherapy, radiotherapy, and oesophageal stenting, is needed to identify the degree of prognostication offered by body composition analysis. Studies on the modifiability of sarcopenia will help determine the utility of nutritional interventions.
Topics: Humans; Male; Female; Aged; Prognosis; Sarcopenia; Esophageal Neoplasms; Muscle, Skeletal; Body Composition
PubMed: 36151845
DOI: 10.1002/jcsm.13082 -
Annals of Medicine 2023The optimal cycle of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) remains controversial. This study aimed to compare the efficacy of three... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The optimal cycle of neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) remains controversial. This study aimed to compare the efficacy of three and four cycles of NAC in the treatment of MIBC through a systematic review and meta-analysis of the literature.
MATERIALS AND METHODS
Relevant studies were systematically collected and reviewed in PubMed, Medline, Embase, Web of Science Databases, and the Cochrane Library. Relative ratios (RRs), Hazard ratios (HRs) and their 95% confidence intervals (CIs) were used to estimate outcome measures. Studies comparing the pathological response and prognosis of three versus four cycles of NAC for MIBC were included.
RESULTS
Five studies were included in this meta-analysis, including 2190 patients, of whom 1016 underwent three cycles of NAC and 1174 underwent four cycles of NAC. All studies were retrospective cohort studies. We found that 4 cycles of NAC had significantly better cancer-specific survival than 3 cycles (HR = 1.31, 95%CI,1.03-1.67, = 0.029). There was no significant difference in overall survival between patients who received 3 and 4 cycles of chemotherapy (HR = 1.18, 95%CI = 0.83-1.69, = 0.345). Similarly, no significant difference was observed in pathological objective response (RR = 0.95, 95%CI= 0.81-1.11, = 0.515) and complete response rates (RR = 0.87, 95%CI = 0.69-1.11, = 0.256) in MIBC after 3 or 4 cycles of NAC.
CONCLUSIONS
Three and four cycles of NAC had similar pathological responses and prognosis for MIBC, although the cancer-specific survival rate of four cycles was better than that of three cycles.
Topics: Humans; Neoadjuvant Therapy; Retrospective Studies; Chemotherapy, Adjuvant; Urinary Bladder Neoplasms; Muscles
PubMed: 37963224
DOI: 10.1080/07853890.2023.2281654 -
Systematic Reviews Nov 2023Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery....
BACKGROUND
Prehabilitation programs focusing on exercise training as the main component are known as a promising alternative for improving patients' outcomes before cancer surgery. This systematic review determined the benefits and harms of prehabilitation programs compared with usual care for individuals with cancer.
METHODS
We searched CENTRAL, MEDLINE, and EMBASE from inception to June 2022, and hand searched clinical trial registries. We included randomized-controlled trials (RCTs) in adults, survivors of any type of cancer, that compared prehabilitation programs that had exercise training as the major component with usual care or other active interventions. Outcome measures were health-related quality of life (HRQL), muscular strength, postoperative complications, average length of stay (ALOS), handgrip strength, and physical activity levels. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias and the certainty of the evidence.
RESULTS
Twenty-five RCTs (2682 participants) published between 2010 and 2022 met our inclusion criteria. Colorectal and lung cancers were the most common diagnoses. The studies had methodological concerns regarding outcome measurement, selective reporting, and attrition. Five prehabilitation programs were compared to usual care (rehabilitation): combined training, aerobic training, respiratory muscle training plus aerobic training, respiratory muscle training plus resistance training, and pelvic floor training. The studies provided no clear evidence of an effect between groups. We assessed the overall certainty of the evidence as very low, downgraded due to serious study limitations and imprecision.
CONCLUSION
Prehabilitation programs focusing on exercise training may have an effect on adults with cancer, but the evidence is very uncertain. We have very little confidence in the results and the true effect is likely to be substantially different from these. Further research is needed before we can draw a more certain conclusion.
SYSTEMATIC REVIEW REGISTRATION
CRD42019125658.
Topics: Adult; Humans; Preoperative Exercise; Exercise; Exercise Therapy; Neoplasms; Resistance Training; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 37978411
DOI: 10.1186/s13643-023-02373-4 -
Journal of Cachexia, Sarcopenia and... Dec 2019Sarcopenia is the loss of skeletal muscle mass and function that occurs with advancing age and certain diseases. It is thought to have a negative impact on survival in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sarcopenia is the loss of skeletal muscle mass and function that occurs with advancing age and certain diseases. It is thought to have a negative impact on survival in cancer patients. Routine computed tomography imaging is often used to quantify skeletal muscle in cancer patients. Sarcopenia is defined by a low skeletal muscle index (SMI). Skeletal muscle radiation attenuation (SMRA) is used to define muscle quality. The primary aim of this meta-analysis was to study the association between sarcopenia or SMRA and overall survival (OS) or complications in patients with ovarian cancer.
METHODS
Medline, Embase, CINAHL, and PEDro databases were searched from inception to 15 February 2019. Studies evaluating the prognostic effect of SMI and SMRA on ovarian cancer survival or surgical complications were included. Risk of bias and study quality were evaluated with the Quality in Prognosis Studies Instrument (QUIPS) according to the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.
RESULTS
The search strategy yielded 4262 hits in all four databases combined. Ten and eight studies were included for qualitative and quantitative analysis, respectively. Meta-analysis revealed a significant association between the SMI and OS [0.007; hazard ratio (HR): 1.11, 95% confidence interval (CI): 1.03-1.20]. SMRA was also significantly associated with OS (P < 0.001; HR: 1.14, 95% CI: 1.08-1.20). Association between the SMI and surgical complications had borderline statistical significance (0.05; HR: 1.23, 95% CI: 1.00-1.52). The risk of bias assessed with QUIPS was high in all studies. The quality of the evidence was very low.
CONCLUSIONS
Whereas our meta-analysis indicated that a low SMI and low SMRA are associated with survival in ovarian cancer patients, the low quality of the source data precludes drawing definitive conclusions.
Topics: Aged; Aged, 80 and over; Female; Humans; Middle Aged; Ovarian Neoplasms; Prognosis; Sarcopenia; Survival Analysis; Tomography, X-Ray Computed
PubMed: 31389674
DOI: 10.1002/jcsm.12468 -
Minerva Urology and Nephrology Apr 2023Radical cystectomy represents the standard of care for localized muscle invasive or high-grade non-muscle invasive BCG unresponsive bladder cancer. Several randomized... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Radical cystectomy represents the standard of care for localized muscle invasive or high-grade non-muscle invasive BCG unresponsive bladder cancer. Several randomized control trials have been published comparing open (ORC) with robot-assisted radical cystectomy (RARC). We aimed to summarize evidence in this setting with a systematic review and meta-analysis.
EVIDENCE ACQUISITION
All published randomized prospective trials that compared ORC with RARC were retrieved through a systematic search according to PRISMA guidelines. Outcomes investigated were the risks of overall complications, high grade (Clavien-Dindo ≥3) complications, positive surgical margins, the number of lymph nodes removed, estimated blood loss, operative time, length of hospital stay, quality of life, overall survival (OS) and progression-free survival. A random effect model was applied. Subgroup analysis on the basis of the urinary diversion was also performed.
EVIDENCE SYNTHESIS
Seven trials enrolling 974 patients were included. No differences in terms of major oncological and perioperative outcomes between RARC and ORC were observed. However, length of hospital stay was significantly shorter (MD -0.95; 95%CI -1.32, -0.58) and estimated blood loss lower (MD -296.66; 95%CI -462.59, -130.73) for RARC. Operative time was overall shorter for ORC (MD 89.52; 95%CI 55.88, 123.16), however no difference emerged between ORC and RARC with intracorporeal urinary diversion.
CONCLUSIONS
Despite several limitations due to heterogeneity and possible unaddressed confounding in included trials, we concluded that ORC and RARC represent equally valid options for the surgical treatment of patients with advanced bladder cancer.
Topics: Humans; Cystectomy; Prospective Studies; Quality of Life; Robotics; Treatment Outcome; Robotic Surgical Procedures; Postoperative Complications; Urinary Bladder Neoplasms
PubMed: 36999835
DOI: 10.23736/S2724-6051.23.05065-6 -
Archives of Gynecology and Obstetrics Feb 2023Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Uterine leiomyosarcoma (uLMS) may show loss of expression of B-cell lymphoma-2 (Bcl-2) protein. It has been suggested that Bcl-2 loss may both be a diagnostic marker and an unfavorable prognostic marker in uLMS.
OBJECTIVE
To define the diagnostic and prognostic value of Bcl-2 loss in uLMS through a systematic review and meta-analysis.
METHODS
Electronic databases were searched from their inception to May 2020 for all studies assessing the diagnostic and prognostic value of Bcl-2 loss of immunohistochemical expression in uLMS. Data were extracted to calculate odds ratio (OR) for the association of Bcl-2 with uLMS vs leiomyoma variants and smooth-muscle tumors of uncertain malignant potential (STUMP), and hazard ratio (HR) for overall survival; a p value < 0.05 was considered significant.
RESULTS
Eight studies with 388 patients were included. Loss of Bcl-2 expression in uLMS was not significantly associated with a diagnosis of uLMS vs leiomyoma variants and STUMP (OR = 2.981; p = 0.48). Bcl-2 loss was significantly associated with shorter overall survival in uLMS (HR = 3.722; p = 0.006). High statistical heterogeneity was observed in both analyses.
CONCLUSION
Loss of Bcl-2 expression appears as a significant prognostic but not diagnostic marker in uLMS. The high heterogeneity observed highlights the need for further research and larger studies.
Topics: Female; Humans; Leiomyosarcoma; Prognosis; Uterine Neoplasms; Leiomyoma; Pelvic Neoplasms
PubMed: 35344084
DOI: 10.1007/s00404-022-06531-2 -
Scientific Reports May 2023Head and Neck Cancer (HNC) is a globally rare cancer that includes a variety of tumors affecting the upper aerodigestive tract. It presents with difficulty breathing or... (Meta-Analysis)
Meta-Analysis
Head and Neck Cancer (HNC) is a globally rare cancer that includes a variety of tumors affecting the upper aerodigestive tract. It presents with difficulty breathing or swallowing and is mainly treated with radiation therapy, chemotherapy, or surgery for tumors that have spread locally or throughout the body. Alternatively, exercise can be used during cancer treatment to improve function, including pain relief, increase range of motion and muscle strength, and reduce cancer-related fatigue, thereby enhancing quality of life. Although existing evidence suggests the adjunctive use of exercise in other cancer types, no previous studies have examined the effects on HNC survivors. The aim of this meta-analysis was to quantify the effect of exercise-based rehabilitation on functionality and quality of life in HNC survivors who underwent surgery and/or chemoradiotherapy. A systematic review and meta-analysis were carried out following PRISMA statement and registered in PROSPERO (CRD42023390300). The search was performed in MEDLINE (PubMED), Cochrane Library, CINAHL and Web of Science (WOS) databases from inception to 31st December 2022 using the terms "cancer", "head and neck neoplasms", "exercise", "rehabilitation", "complications", "muscle contraction", "muscle stretching exercises" combining with booleans "AND"/"OR". PEDro scale, Cochrane Risk of Bias Tool and GRADE were used to assess methodological quality, risk of bias and grade of recommendation of included studies respectively. 18 studies (n = 1322) were finally included which 1039 (78.6%) were men and 283 (21.4%) were women. In patients who underwent radio-chemotherapy, overall pain [SMD = - 0.62 [- 4.07, 2.83] CI 95%, Z = 0.35, p = 0.72] and OP [SMD = - 0.07 [- 0.62, 0.48] CI 95%, Z = 0.25, p = 0.81] were slightly reduced with exercise in comparison to controls. Besides, lower limb muscle strength [SMD = - 0.10 [- 1.52, 1.32] CI 95%, Z = 0.14, p = 0.89] and fatigue [SMD = - 0.51 [- 0.97, - 0.057] CI 95%, Z = 2.15, p < 0.01] were also improved in those who receive radio-chemoradiation. In HNC survivors treated with neck dissection surgery, exercise was superior to controls in overall pain [SMD = - 1.04 [- 3.31, 1.23] CI 95%, Z = 0.90, p = 0.37] and, in mid-term, on shoulder pain SMD = - 2.81 [- 7.06, 1.43] CI 95%, Z = 1.76, p = 0.08]. No differences in quality of life were found at any of the follow-up periods. There is evidence of fair to good methodological quality, low to moderate risk of bias, and weak recommendations supporting the use of exercise-based rehabilitation to increase functionality. However, no evidence was found in favor of the use of this modality for improving the quality of life of HNC survivors who underwent chemoradiotherapy or surgery.
Topics: Male; Humans; Female; Quality of Life; Head and Neck Neoplasms; Survivors; Fatigue; Pain
PubMed: 37237097
DOI: 10.1038/s41598-023-35503-y -
Journal of Cachexia, Sarcopenia and... Oct 2023In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function...
In cancer cachexia trials, measures of physical function are commonly used as endpoints. For drug trials to obtain regulatory approval, efficacy in physical function endpoints may be needed alongside other measures. However, it is not clear which physical function endpoints should be used. The aim of this systematic review was to assess the frequency and diversity of physical function endpoints in cancer cachexia trials. Following a comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2021), records were retrieved. Eligible trials met the following criteria: adults (≥18 years), controlled design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a physical function endpoint. Physical function measures were classified as an objective measure (hand grip strength [HGS], stair climb power [SCP], timed up and go [TUG] test, 6-min walking test [6MWT] and short physical performance battery [SPPB]), clinician assessment of function (Karnofsky Performance Status [KPS] or Eastern Cooperative Oncology Group-Performance Status [ECOG-PS]) or patient-reported outcomes (physical function subscale of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaires [EORTC QLQ-C30 or C15]). Data extraction was performed using Covidence and followed PRISMA guidance (PROSPERO registration: CRD42022276710). A total of 5975 potential studies were examined and 71 were eligible. Pharmacological interventions were assessed in 38 trials (54%). Of these, 11 (29%, n = 1184) examined megestrol and 5 (13%, n = 1928) examined anamorelin; nutritional interventions were assessed in 21 trials (30%); and exercise-based interventions were assessed in 6 trials (8%). The remaining six trials (8%) assessed multimodal interventions. Among the objective measures of physical function (assessed as primary or secondary endpoints), HGS was most commonly examined (33 trials, n = 5081) and demonstrated a statistically significant finding in 12 (36%) trials (n = 2091). The 6MWT was assessed in 12 trials (n = 1074) and was statistically significant in 4 (33%) trials (n = 403), whereas SCP, TUG and SPPB were each assessed in 3 trials. KPS was more commonly assessed than the newer ECOG-PS (16 vs. 9 trials), and patient-reported EORTC QLQ-C30 physical function was reported in 25 trials. HGS is the most commonly used physical function endpoint in cancer cachexia clinical trials. However, heterogeneity in study design, populations, intervention and endpoint selection make it difficult to comment on the optimal endpoint and how to measure this. We offer several recommendations/considerations to improve the design of future clinical trials in cancer cachexia.
Topics: Humans; Cachexia; Hand Strength; Neoplasms; Quality of Life; Research Design
PubMed: 37671529
DOI: 10.1002/jcsm.13321 -
Journal of Cachexia, Sarcopenia and... Oct 2021Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia, which is characterized by a decrease in muscle quantity or quality, is commonly observed in patients with cancer. Recent research has reported contradictory results on the association between sarcopenia and the efficacy of immune checkpoint inhibitors (ICIs). We conducted a systematic review and meta-analysis to investigate this discrepancy. We systematically searched three electronic databases to identify articles reporting on the association between sarcopenia and treatment outcomes in patients with solid cancers who received ICIs. The outcomes assessed were hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for objective response rate (ORR), disease control rate (DCR), and toxicity. Pooled estimates and their 95% confidence intervals (CIs) were calculated. A total of 2501 patients from 26 studies were analysed. Sarcopenia was observed in 44.7% (95% CI: 38.2-51.3) of the patients and was significantly associated with poor survival (HR = 1.55, 95% CI = 1.32-1.82 for OS and HR = 1.61, 95% CI = 1.35 to 1.93 for PFS). The HRs (95% CIs) for OS according to the diagnostic measures used were 1.97 (0.88-4.41) for psoas muscle index (PMI), 1.41 (0.87-2.28) for skeletal muscle density (SMD), and 1.43 (1.23-1.67) for skeletal mass index (SMI). The HRs (95% CIs) for PFS were 1.86 (1.08-3.21) for PMI, 1.27 (0.94-1.71) for SMD, and 1.38 (1.11-1.71) for SMI. Poor radiological response to ICI therapy was observed in patients with sarcopenia (OR = 0.52, 95% CI = 0.34-0.80 for ORR and OR = 0.45, 95% CI = 0.30-0.67 for DCR). The ORs for ORR (95% CIs) were 0.56 (0.15-2.05) for PMI and 0.78 (0.56-1.09) for SMI. The oncologic outcomes associated with melanoma and non-small cell lung cancer (NSCLC) were comparable with those observed overall (HR for OS = 2.02, 95% CI = 1.26-3.24 for melanoma and HR for OS = 1.61, 95% CI = 1.19-2.18 for NSCLC). In contrast, the occurrence of severe toxicity was not associated with sarcopenia (OR = 1.13, 95% CI = 0.51-2.52). Poor survival and poor response in patients with sarcopenia indicate a negative association between sarcopenia and efficacy of ICIs. Sarcopenia's predictive ability is consistent across various tumour types. For the selection of patients who may respond to ICIs pre-therapeutically, the presence of sarcopenia should be assessed in clinical practice.
Topics: Carcinoma, Non-Small-Cell Lung; Humans; Immune Checkpoint Inhibitors; Lung Neoplasms; Progression-Free Survival; Sarcopenia
PubMed: 34337889
DOI: 10.1002/jcsm.12755