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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... 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 -
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 -
Cancer Mar 2016There is uncertainty regarding the use of bladder-sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal... (Review)
Review
There is uncertainty regarding the use of bladder-sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal chemotherapeutic regimens. This study was conducted to systematically review the benefits and harms of bladder-sparing therapies, lymph node dissection, and systemic chemotherapy for patients with clinically localized muscle-invasive bladder cancer. Systematic literature searches of MEDLINE (from 1990 through October 2014), the Cochrane databases, reference lists, and the ClinicalTrials.gov Web site were performed. A total of 41 articles were selected for review. Bladder-sparing therapies were found to be associated with worse survival compared with radical cystectomy, although the studies had serious methodological shortcomings, findings were inconsistent, and only a few studies evaluated currently recommended techniques. More extensive lymph node dissection might be more effective than less extensive dissection at improving survival and decreasing local disease recurrence, but there were methodological shortcomings and some inconsistency. Six randomized trials found cisplatin-based combination neoadjuvant chemotherapy to be associated with a decreased mortality risk versus cystectomy alone. Four randomized trials found adjuvant chemotherapy to be associated with decreased mortality versus cystectomy alone, but none of these trials reported a statistically significant effect. There was insufficient evidence to determine optimal chemotherapeutic regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Cystectomy; Evidence-Based Medicine; Humans; Lymph Node Excision; Neoadjuvant Therapy; Neoplasm Invasiveness; Organ Sparing Treatments; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 26773572
DOI: 10.1002/cncr.29843 -
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 -
Nutrition (Burbank, Los Angeles County,... Aug 2023Sarcopenia has been identified as a prognostic factor among certain types of cancer. However, it is unclear whether there is prognostic value of temporalis muscle... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia has been identified as a prognostic factor among certain types of cancer. However, it is unclear whether there is prognostic value of temporalis muscle thickness (TMT), a potential surrogate for sarcopenia, in adults patients with brain tumors. Therefore, we searched the Medline, Embase, and PubMed to systematically review and meta-analyze the relationship between TMT and overall survival, progression-free survival, and complications in patients with brain tumors and the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) were evaluated. The quality in prognostic studies (QUIPS) instrument was employed to evaluate study quality. Nineteen studies involving 4570 patients with brain tumors were included for qualitative and quantitative analysis. Meta-analysis revealed thinner TMT was associated with poor overall survival (HR, 1.72; 95% CI, 1.45-2.04; P < 0.01) in patients with brain tumors. Sub-analyses showed that the association existed for both primary brain tumors (HR, 2.02; 95% CI, 1.55-2.63) and brain metastases (HR, 1.39; 95% CI, 1.30-1.49). Moreover, thinner TMT also was the independent predictor of progression-free survival in patients with primary brain tumors (HR, 2.88; 95% CI, 1.85-4.46; P < 0.01). Therefore, to improve clinical decision making it is important to integrate TMT assessment into routine clinical settings in patients with brain tumors.
Topics: Adult; Humans; Prognosis; Sarcopenia; Temporal Muscle; Brain Neoplasms
PubMed: 37236042
DOI: 10.1016/j.nut.2023.112077 -
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 -
World Journal of Urology Jul 2023To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC)... (Meta-Analysis)
Meta-Analysis
PURPOSE
To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.
METHODS
Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.
RESULTS
Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.
CONCLUSIONS
OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
Topics: Female; Male; Humans; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Neoplasm Recurrence, Local; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Kidney; Adjuvants, Immunologic; Kidney Neoplasms
PubMed: 37209143
DOI: 10.1007/s00345-023-04412-0 -
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