Androgen-deprivation therapy alone versus combined with radiation therapy or chemotherapy for nonlocalized prostate cancer: a systematic review and meta-analysis

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy (ADT) alone versus combined with radiation therapy (RT) or chemotherapy for locally advanced and metastatic prostate cancer (PCa). A literature search was performed using OvidSP. Randomized controlled trials (RCTs) that met the following criteria were included: including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT (n = 2344) and one compared ADT versus ADT plus docetaxel–estramustine (n = 413) in locally advanced PCa; two compared ADT versus ADT plus docetaxel (n = 1175) and two compared ADT versus ADT plus estramustine (n = 114) in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio (OR) of overall survival (OS) was 1.43 (95% confidence interval 1.20–1.71) when compared ADT plus RT with ADT alone (P < 0.0001). For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe (pooled OR of OS: 1.29 [1.01–1.65]: P = 0.04). In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.     

Postoperative chemoradiotherapy for advanced squamous cell carcinoma of the head and neck: a systematic review with meta-analysis

BACKGROUND: This systematic review evaluates the use of postoperative chemoradiotherapy for patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck at a high risk of recurrence. METHODS: The literature was systematically searched for eligible randomized controlled trials (RCTs). RESULTS: Of 4 RCTs identified, 3 reported improvements in locoregional control, 3 reported improved disease-free or progression-free survival, and 3 reported improved overall survival with chemoradiotherapy compared with radiotherapy alone. Pooling trials confirmed the benefit for chemoradiotherapy in locoregional recurrence (relative risk [RR] = 0.59; 95% confidence interval [CI] = 0.47-0.75; p < .00001) and overall survival (RR = 0.80; 95% CI = 0.71-0.90; p = .0002). More frequent and severe acute mucosal toxicity was reported with combined treatment. CONCLUSIONS: Postoperative adjuvant chemoradiotherapy is superior to radiotherapy alone. Because chemoradiotherapy is associated with significantly increased toxicity, further investigations to identify patients most likely to benefit or toxicity reduction strategies are warranted.     

Cerebrospinal fluid drainage to prevent paraplegia during thoracic and thoracoabdominal aortic aneurysm surgery: a systematic review and meta-analysis

OBJECTIVES: We undertook a quantitative systematic review of randomized controlled trials (RCTs) and observational studies to determine the effectiveness of cerebrospinal fluid (CSF) drainage to prevent paraplegia in thoracic aneurysm (TA) and thoracoabdominal aortic aneurysm (TAAA) surgery. METHODS: We included RCTs and cohort studies that met the following criteria: elective or emergent aneurysm surgery involving the thoracic or thoracoabdominal aorta, documentation of postoperative neurologic deficits, and patient age older than 18 years. We excluded studies that reported results in 10 or fewer patients and duplicate publications. We identified eligible studies by searching computerized databases, our own files, and the reference lists of relevant articles and review articles. Database searching, eligibility decisions, relevance and method quality assessments, and data extraction were performed in duplicate with prespecified criteria. RESULTS: Of 372 publications identified in our search, 14 met our eligibility criteria. Three RCTs reported 289 patients with type I or type II TAAA. Lower limb neurologic deficits occurred in 12% of patients who underwent CSF drainage and 33% of control subjects (number needed to treat, 9; 95% confidence interval [CI], 5-50). The pooled odds ratio (OR) for development of paraplegia in patients in the CSF drainage group was 0.35 (P =.05; 95% CI, 0.12-0.99). Similar results were found in five cohort studies with a control group (pooled OR, 0.26; P =.0002; 95% CI, 0.13-0.53). When all studies were considered together the pooled OR of TA and TAAA was 0.3 (95% CI, 0.17-0.54). There was no statistical heterogeneity among studies included in the meta-analysis. In six cohort studies without a control group, the incidence of paraplegia in high-risk TA and TAAA was 7.6%. CONCLUSIONS: Evidence from randomized and nonrandomized trials and from cohort studies support the use of CSF drainage as an adjunct to prevent paraplegia when this adjunct is used in centers with large experience in the management of TAAA.     

Systematic review of the benefits and harms of calcitriol and alfacalcidol for fractures and falls

Our objective was to conduct a systematic review on the benefits and harms of calcitriol and alfacalcidol in the reduction of fracture and fall risk. Randomized controlled trials (RCTs) comparing these agents to placebo or calcium and reporting fracture and fall incidence were retrieved from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Two reviewers independently determined study eligibility, assessed trial quality, and extracted data. Twenty-three RCTs were included (2139 participants), and 16 trials had sufficient data for meta-analysis. Vertebral fractures were not significantly reduced based on the combined results of 13 trials; however, subgroup analyses demonstrated a significant reduction with alfacalcidol [odds ratio (OR) = 0.50, 95% confidence interval (CI), 0.25–0.98], but not with calcitriol. There was a significant reduction in nonvertebral fractures (six trials, OR = 0.51, 95% CI, 0.30–0.88), and falls (two trials, OR = 0.66, 95% CI, 0.44–0.98). There was an increased risk of hypercalcemia (OR = 3.63, 95% CI, 1.51–8.73) and a trend toward an increased risk of hypercalciuria. There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. Hypercalcemia and hypercalciuria are potential side effects.     

Immediate surgery or conservative treatment for complicated acute appendicitis in children? A meta-analysis

PurposeThis study carried out a meta-analysis to compare immediate surgery (IS) with conservative treatment (CT) of complicated acute appendicitis (CAA) in children.MethodsSystematic literature research was performed for relevant studies published from 1969 to date. Trials of IS compared with CT were included. Outcomes of interest were postoperative morbidity and length of hospital stay (LOS).ResultsFifteen trials were studied (1.243 patients). CT achieved better rates of any complication type (odds ratio [OR] 0.22, [95% confidence interval (CI): 0.14, 0.38], p = 0.001) and wound infection (OR: 0.40 [95% CI: 0.17, 0.96], p = 0.041). Neither intraabdominal abscess (OR: 1.03 [95% CI: 0.31, 3.37], p = 0.958) nor postoperative ileus (OR: 0.29 [95% CI: 0.06, 1.44], p = 0.130) was affected by the treatment option. The polled difference in LOS showed a trend for shorter LOS in the IS group (standard mean difference [SMD]: 0.25 [95% CI: 0.07, ? 0.43], p = 0.007).ConclusionsIS was associated with shorter LOS, while overall complication rates and wound infection declined significantly with CT. The development of intraabdominal abscess and postoperative ileus was not affected by the treatment of choice. The heterogeneity of most studies depicts the need for randomized controlled trials (RCTs) to discover safe management of CAA in children.Level of evidence: IIIType of study: Meta-analysis.     

Open Reduction and Internal Fixation Versus Primary Arthrodesis for the Treatment of Acute Lisfranc Injuries: A Systematic Review and Meta-analysis

This study aims to compare outcomes of open reduction and internal fixation (ORIF) and primary arthrodesis in management of Lisfranc injuries. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, a systematic review was carried out. MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials were searched to identify both randomised controlled trials (RCTs) and nonrandomised studies comparing the outcomes of ORIF and primary arthrodesis for Lisfranc injuries. Random- and fixed-effect statistical models were applied to calculate the pooled outcome data. Two RCTs and 3 observational studies were identified, compiling a total of 187 subjects with acute Lisfranc injuries and a mean follow-up duration of 62.3 months. Our results demonstrate that ORIF is associated with a significantly higher need for revision surgery (odds ratio [OR] 6.37, 95% confidence interval [CI] 2.68 to 15.11, p < .0001) and a significantly higher rate of persistent pain (OR 6.29, 95% CI 1.07 to 36.89, p?=?.04) compared with primary arthrodesis. However, we found no significant difference between the groups in terms of visual analogue scale pain score, American Orthopaedic Foot & Ankle Society functional score, or rates of infection. Separate analysis of RCTs showed that ORIF was associated with a more frequent need for revision surgery (OR 17.56, 95% CI 5.47 to 56.38, p < .00001), higher visual analogue scale pain score (mean difference 2.90, 95% CI 2.84 to 2.96, p < .00001), and lower American Orthopaedic Foot & Ankle Society score (mean difference –29.80, 95% CI –39.82 to –19.78, p < .00001). The results of the current study suggest that primary arthrodesis may be associated with better pain and functional outcomes and lower need for revision surgery compared with ORIF. The available evidence is limited and is not adequately robust to make explicit conclusions. The current literature requires high-quality and adequately powered RCTs.     

Effects of levosimendan on mortality in patients undergoing cardiac surgery: A systematic review and meta‐analysis

Purpose

We sought to determine the impact of levosimendan on mortality following cardiac surgery based on large‐scale randomized controlled trials (RCTs).

Methods

We searched PubMed, Web of Science, Cochrane databases, and ClinicalTrials.gov for RCTs published up to December 2017, on levosimendan for patients undergoing cardiac surgery.

Results

A total of 25 RCTs enrolling 2960 patients met the inclusion criteria; data from 15 placebo‐controlled randomized trials were included for meta‐analysis. Pooled analysis showed that the all‐cause mortality rate was 6.4% (71 of 1106) in the levosimendan group and 8.4% (93 of 1108) in the placebo group (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.55‐1.04; P = 0.09). There were no significant differences between the two groups in the rates of myocardial infarction (OR: 0.91; 95% CI, 0.68‐1.21; P = 0.52), serious adverse events (OR: 0.84; 95% CI, 0.66‐1.07; P = 0.17), hypotension (OR: 1.69; 95% CI, 0.94‐3.03; P = 0.08), and low cardiac output syndrome (OR: 0.47; 95% CI, 0.22‐1.02; P = 0.05).

Conclusion

Levosimendan did not result in a reduction in mortality in adult cardiac surgery patients. Well designed, adequately powered, multicenter trials are necessary to determine the role of levosimendan in adult cardiac surgery.     

Effects and safety of atmospheric low‐temperature plasma on bacterial reduction in chronic wounds and wound size reduction: A systematic review and meta‐analysis

The use of atmospheric low‐temperature plasma (AP) on chronic wounds and its effect on microbial bioburden in open wounds has not been explored with a systematic review and meta‐analysis. PRISMA guidelines were followed and PubMed, Embase, CENTRAL, and CINAHL databases searched for randomised controlled trials (RCTs), which compared AP with no AP for the management of open, chronic wounds. The primary outcomes of reduction of bioburden or wound size were included. Meta‐analyses were performed; odds ratio (OR) and 95% confidence intervals (CIs) were extracted and pooled in a random effects model. Four RCTs investigated the effect of AP on chronic wound healing. Chronic wounds treated with AP did not show a significant improvement in healing (AP vs control: OR = 1.46; 95% CI = 0.89‐2.38; P = 0.13). Five further RCTs investigated the reduction of bioburden in wounds, but AP demonstrated no significant reduction of bioburden (AP vs control: OR = 0.85; 95% CI = 0.45‐1.62; P = 0.63). All nine RCTs recorded the presence of any severe adverse events (SAEs) in the 268 patients studied, with only one unrelated SAE identified in each group (AP vs control: OR = 1.00; 95% CI = 0.05‐19.96; P = 1.00). Use of AP in wound care is safe, but the retrieved evidence and meta‐analysis show that there is no clinical benefit of AP in chronic open wounds using currently available AP device settings.     

Interventions for steroid-resistant nephrotic syndrome: a systematic review

In a systematic review and meta-analysis of randomized controlled trials (RCT), we aimed to evaluate the benefits and harms of all interventions for children with steroid-resistant nephrotic syndrome (SRNS). Nine RCTs involving 225 children were included. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission [3 trials, 49 children, relative risk (RR) for persistent nephrotic syndrome 0.64, 95% confidence intervals (CI), 0.47–0.88]. There was no significant difference in the number of children who achieved complete remission between oral cyclophosphamide with prednisone and prednisone alone [2 trials, 91 children, RR 1.01, 95% CI 0.74–1.36], between intravenous cyclophosphamide and oral cyclophosphamide [1 study, 11 children, RR 0.09, 95% CI 0.01–1.39], and between azathioprine with prednisone and prednisone alone [1 trial, 31 children, RR 1.01, 95% CI 0.77–1.32]. No RCTs were identified comparing combination regimens comprising high-dose steroids, alkylating agents or cyclosporin with single agents, placebo, or no treatment. Further adequately powered and well-designed RCTs are needed to confirm the efficacy of cyclosporin and to evaluate regimens of high-dose steroids with alkylating agents or cyclosporin for SRNS.     

Partial Breast Irradiation or Whole Breast Radiotherapy for Early Breast Cancer: A Meta‐Analysis of Randomized Controlled Trials

Abstract: The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast‐radiation therapy (WBRT). We conducted a systematic review and meta‐analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674–1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506–1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396–3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p < 0.0001) compared with whole breast‐radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast‐radiation. Nevertheless the issue of loco‐regional recurrence needs to be further addressed.     

Pharmacologic myocardial protection in patients undergoing noncardiac surgery: a quantitative systematic review

A number of drugs have been tested in clinical trials to decrease cardiac complications in patients undergoing noncardiac surgery. To compare the results of these studies, we conducted a quantitative systematic review. Medline, Embase, and Cochrane databases were searched for randomized trials that assessed myocardial ischemia, myocardial infarction, 30-day cardiac mortality, and adverse effects. Data were combined using a fixed-effect model and expressed as Peto odds ratios (OR) with 95% confidence interval (CI) and as numbers-needed-to-treat/harm (NNT/H). Twenty-one trials involving 3646 patients were included: 11 trials using beta-blockers (6 drugs; 866 patients), 6 clonidine or mivazerol (614 patients), 3 diltiazem or verapamil (121 patients), and 1 nitroglycerin (45 patients). All trials had an inactive control; there were no direct comparisons. beta-blockers decreased ischemic episodes during surgery (7.6% versus 20.2% with placebo; OR 0.32 [95% CI, 0.17-0.58]; NNT 8) and after surgery (15.2% versus 27.9% with control; OR 0.46 [95% CI, 0.26-0.81]; NNT 8). alpha(2)-agonists decreased ischemia during surgery only (19.4% versus 32.8%; OR 0.47 [95% CI, 0.33-0.68]; NNT 7). beta-blockers reduced the risk of myocardial infarction (0.9% versus 5.2%; OR 0.19 [95% CI, 0.08-0.48]; NNT 23) but only when 2 trials with high-risk patients were included. The effect of alpha(2)-agonists on myocardial infarction was not significant (6.1% versus 7.3%; OR 0.85 [95% CI, 0.62-1.14]). beta-blockers significantly decreased the risk of cardiac death from 3.9% to 0.8% (OR 0.25 [95% CI, 0.09-0.73], NNT 32). alpha(2)-agonists significantly decreased the risk of cardiac death from 2.3% to 1.1% (OR 0.50 [95% CI, 0.28-0.91], NNT 83). For calcium channel blockers and nitroglycerin, evidence of any benefit was lacking. The most common adverse effect was bradycardia, which occurred in 24.5% of patients receiving a beta adrenergic blocker versus 9.1% of controls (OR 3.76 [95% CI, 2.45-5.77], NNH 6).     

中筒弹力袜预防下肢深静脉血栓效果的Meta分析

目的：综合评价中筒弹力袜在预防下肢深静脉血栓形成（DVT）中应用价值。 方法：检索多个中外文数据库上关于医用弹力袜预防下肢DVT的随机对照试验（RCT）。按照纳入排除标准筛选和提取文献,并采用RevMan 5.2软件进行统计学分析。 结果：最终纳入12个随机对照试验,共6 049例患者。Meta分析结果显示,在高危长途飞行乘客中,中筒弹力袜组较无袜对照组发生下肢DVT的风险明显降低（OR=0.08,95% CI=0.03~0.22,P<0.00001）;在住院患者中,中筒弹力袜组与长筒弹力袜在预防下肢DVT方面差异无统计学意义（OR=1.47,95% CI=0.69~3.13,P=0.32）;将住院患者及高危长途飞行的乘客合并分析,中筒弹力袜组发生下肢DVT的风险较无袜及长筒弹力袜组明显降低（OR=0.32,95% CI=0.11~0.92,P=0.03）。 结论：中筒弹力袜可减少高危长途飞行乘客与住院患者发生下肢DVT的风险,且效果优于长筒弹力袜,但仍需大样本、高质量的临床随机对照试验来验证。     

Changing practice patterns of adjuvant radiation among elderly women with early stage breast cancer in the United States from 2004 to 2014

Randomized controlled trials (RCTs) have challenged the need for routine radiation therapy (RT) in women ≥ age 70 with favorable early stage breast cancer (BC) due to modest improvement in local control and no survival benefit. We studied practice patterns in RT among elderly women in the United States. We analyzed data from the National Cancer Database (NCDB) of women ≥age 70 diagnosed with T1 or T2 and N0 invasive BC treated with breast conservation surgery (BCS) between 2004 and 2014. Patients were divided into four groups: (1) no RT, (2) partial breast irradiation (PBI); (3) hypofractionation (HF); and (4) conventional whole breast RT (CWBI). Univariable and multivariable analyses (MVA) were performed to compare characteristics among the four RT groups. A subgroup analysis of women with favorable disease (T1N0 ER + HER2‐) was also performed with similar statistical comparisons. Of the 66,126 meeting eligibility, 9,570 (14.5%) had PBI, 16,340 (24.7%) had HF, and 40,117 (60.7%) had CWBI. Only 99 patients (0.15%) had RT omitted. Omission of RT increased marginally from 0.04% in 2004 to 0.24% in 2014. MVA identified older age (OR 1.18, CI 1.08‐1.28), more comorbidities (Charlson‐Deyo Score of 1) (OR 3.36, CI 1.29‐8.72), and no hormone therapy (OR 22.07, CI 5.79‐84.07) as more likely to have RT omitted. The use of HF increased from 3.9% to 47.0%, P < .001 with a concomitant decrease in CWBI from 88% to 41%, P < .001. MVA identified older age, treatment location, and omission of chemotherapy as associated with HF. No significant differences from the larger cohort were found among the T1N0 subgroup analysis. Despite RCT evidence, omission of RT was rare in the United States, suggesting that more effective outreach methods to disseminate clinical guideline information may be needed.     

进展期直肠癌新辅助放疗与化放疗联合TME随机对照试验的Meta分析

目的评价新辅助放疗组与新辅助化放疗组联合全直肠系膜切除术(TME)治疗局部进展期直肠癌的安全性与疗效。 方法检索2002年至2017年PubMed、OVID、Cochrane图书馆、中国生物医学文献数据库(CBM)、中国知网全文数据库(CNKI)、万方数据库关于新辅助治疗联合TME手术治疗局部进展期直肠癌的文献,对符合纳入标准的文献进行质量评价,采用Revman5.0软件检验异质性,进行meta分析。 结果共4个随机对照试验共2 272例直肠癌患者纳入研究,新辅助放疗组1 133例患者,新辅助化放疗组1 139例患者。与新辅助化放疗组相比,单纯新辅助放疗组的完全病理缓解率更低(OR＝0.32, 95%CI: 0.22～0.44, P<0.05),5年局部复发率更高(OR＝2.13, 95%CI: 1.62～2.79, P<0.05),严重不良反应更少(OR＝0.38, 95%CI: 0.17～0.82, P＝0.01),差异有统计学意义。但保肛率、术后并发症发病率、5年无病生存率和总生存率差异无统计学意义。 结论新辅助化放疗总体上优于单纯新辅助放疗治疗进展期直肠癌,但临床应用中仍需要根据患者的耐受情况选择合适的新辅助治疗方案。     

Meta analyses in treatment of spontaneous supratentorial intracerebral haematoma

Summary Background. None of the randomized controlled trials (RCT) on treatment of Intracerebral haematoma (ICH), definitely shows surgery to be beneficial over conservative treatment alone. Systematic reviews that pooled these RCTs were also inconclusive. This systematic review updates previous meta-analyses, using an alternative manner of reviewing with a criteria list constructed specifically for this type of disease and related interventions. Methods. RCTs and quasi-RCTs (q-RCT) published in English were identified with a systematic literature search. They were evaluated with disease/intervention-specific criteria on comparability between intervention and control group concerning prognostic factors, co-interventions and effect measurement. The resulting selection of studies was compared with those of two earlier systematic reviews. In a meta-analysis selected studies were statistically pooled. Findings. The meta-analysis of surgery versus conservative treatment failed to show a statistically significant reduction in the odds of death (OR: 0.84, 95% CI: 0.67–1.07) in surgically treated patients. Conclusions. Like previous reviews, our disease/intervention-specific methodological evaluation showed no reduction in mortality. Sensitivity analysis demonstrates that the manner in which studies are methodologically evaluated in a systematic review has a great impact on its conclusions.     

Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis

PURPOSETyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC.MATERIALS AND METHODSThe MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade.RESULTSFive trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81–0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83–1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10–6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22–12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity.CONCLUSIONSThe findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.     

Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years

OBJECTIVE: The Early Prostate Cancer (EPC) programme is evaluating the efficacy and tolerability of bicalutamide following standard care (radiotherapy, radical prostatectomy or watchful waiting) in patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N + ) non-metastatic prostate cancer. Herein we report the latest findings after a median follow-up period of 7.1 years from the Scandinavian Prostate Cancer Group (SPCG)-6 study, one of three trials in the EPC programme. MATERIAL AND METHODS: A total of 1218 patients were randomized on a 1:1 basis to either bicalutamide 150 mg/day (n=607) or placebo (n=611) following standard care; 81.4% were followed conservatively (watchful waiting). The primary endpoints were objective progression-free survival (PFS) and overall survival (OS). RESULTS: In patients with localized disease there was no significant difference in PFS [hazard ratio (HR) 0.85; 95% CI 0.69-1.06; p=0.15] and a trend towards decreased OS with bicalutamide plus standard care compared with standard care alone (HR 1.23; 95% CI 0.96-1.58; p=0.11). In patients with locally advanced disease, bicalutamide significantly improved PFS, reducing the risk of progression by 53% compared with standard care alone (HR 0.47; 95% CI 0.37-0.59; p<0.001). The median time to progression was 8.8 years for bicalutamide plus standard care and 7.1 years for standard care alone. There was a significant improvement in OS with bicalutamide plus standard care, with a reduction in the risk of death of 35% versus standard care alone (HR 0.65; 95% CI 0.50-0.85; p=0.001). CONCLUSION: This analysis of the SPCG-6 study showed that bicalutamide plus standard care offers significant PFS and OS benefits for patients with locally advanced disease, but not for those with localized disease.     

A Systematic Review and Meta-analysis of the Randomized Controlled Trials on Adjuvant Intraperitoneal Chemotherapy for Resectable Gastric Cancer

Background The purpose of this systematic review and meta-analysis was to determine the effectiveness and safety of adjuvant intraperitoneal chemotherapy for patients with locally advanced resectable gastric cancer. Methods Studies eligible for this systematic review included those in which patients with gastric cancer were randomly assigned to receive surgery combined with intraperitoneal chemotherapy versus surgery without intraperitoneal chemotherapy. There were no language restrictions. After independent quality assessment and data extraction, data were pooled for meta-analysis. Results Thirteen reports of randomized controlled trials (RCTs) were included for quality appraisal and data extraction. Ten reports were judged to be of fair quality and subjected to meta-analysis. A significant improvement in survival was associated with hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) alone (hazard ratio [HR] = 0.60; 95% CI = 0.43 to 0.83; p = 0.002) or HIIC combined with early postoperative intraperitoneal chemotherapy (EPIC) (HR = 0.45; 95% CI = 0.29 to 0.68; p = 0.0002). There was a trend towards survival improvement with normothermic intraoperative intraperitoneal chemotherapy (p = 0.06), but this was not significant with either EPIC alone or delayed postoperative intraperitoneal chemotherapy. Intraperitoneal chemotherapy was also found to be associated with higher risks of intra-abdominal abscess (RR = 2.37; 95% CI = 1.32 to 4.26; p = 0.003) and neutropenia (RR = 4.33; 95% CI = 1.49 to 12.61; p = 0.007). Conclusions The present meta-analysis indicates that HIIC with or without EPIC after resection of advanced gastric primary cancer is associated with improved overall survival. However, increased risk of intra-abdominal abscess and neutropenia are also demonstrated.     

Inclusion of premenopausal women in breast cancer clinical trials

BackgroundPatients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.MethodsUsing ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.ResultsOf 170 breast cancer RCTs identified, 131 (77.1%) included PMBC patients. Sixty-five (38.2%) trials analyzed patients with hormone-receptor-positive (HR+) and HER2-negative (HER2-) breast cancer, of which 31 (47.7%) allowed for enrollment of PMBC patients. Lower rates of PMBC inclusion were seen in trials that studied HR+/HER2-patients (47.7% PMBC inclusion in HR+/HER2-trials vs. 94.3% in non-HR+/HER2-trials, aOR 0.07 [95% CI: 0.02–0.19], p < 0.001) and in trials that randomized or mandated ET (44.4% in ET trials vs. 83.2% in non-ET trials, aOR 0.21 [95% CI: 0.10–0.83], p = 0.02). Trials studying chemotherapy (CT) were associated with inclusion of PMBC patients (100% in CT trials vs. 70.5% in non-CT trials, a OR 14.02 [95% CI: 1.54–127.91], p = 0.01). All surgical and radiation therapy clinical trials allowed for the inclusion of PMBC patients in their eligibility criteria.ConclusionsBreast cancer clinical trials should carefully select their enrollment criteria and consider inclusion of premenopausal patients when appropriate.     

Inotropes,vasopressors, and mechanical circulatory support for treatment of cardiogenic shock complicating myocardial infarction: a systematic review and network meta-analysis

Purpose

To compare the relative efficacy of supportive therapies (inotropes, vasopressors, and mechanical circulatory support [MCS]) for adult patients with cardiogenic shock complicating acute myocardial infarction.

Source

We conducted a systematic review and network meta-analysis and searched six databases from inception to December 2021 for randomized clinical trials (RCTs). We evaluated inotropes, vasopressors, and MCS in separate networks. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework to rate the certainty in findings. The critical outcome of interest was 30-day all-cause mortality.

Principal findings

We included 17 RCTs. Among inotropes (seven RCTs, 1,145 patients), levosimendan probably reduces mortality compared with placebo (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.33 to 0.87; moderate certainty), but primarily in lower severity shock. Milrinone (OR, 0.52; 95% CI, 0.19 to 1.39; low certainty) and dobutamine (OR, 0.67, 95% CI, 0.30 to 1.49; low certainty) may have no effect on mortality compared with placebo. With regard to MCS (eight RCTs, 856 patients), there may be no effect on mortality with an intra-aortic balloon pump (IABP) (OR, 0.94; 95% CI, 0.69 to 1.28; low certainty) or percutaneous MCS (pMCS) (OR, 0.96; 95% CI, 0.47 to 1.98; low certainty), compared with a strategy involving no MCS. Intra-aortic balloon pump use was associated with less major bleeding compared with pMCS. We found only two RCTs evaluating vasopressors, yielding insufficient data for meta-analysis.

Conclusion

The results of this systematic review and network meta-analysis indicate that levosimendan reduces mortality compared with placebo among patients with low severity cardiogenic shock. Intra-aortic balloon pump and pMCS had no effect on mortality compared with a strategy of no MCS, but pMCS was associated with higher rates of major bleeding.

Study registration

Center for Open Science (https://osf.io/ky2gr); registered 10 November 2020