Despite major advances in therapy, cancer continues to be a leading cause of mortality. In addition, toxicities of traditional therapies pose a significant challenge to tolerability and adherence. ...TTFields, a noninvasive anticancer treatment modality, utilizes alternating electric fields at specific frequencies and intensities to selectively disrupt mitosis in cancerous cells. TTFields target proteins crucial to the cell cycle, leading to mitotic arrest and apoptosis. TTFields also facilitate an antitumor immune response. Clinical trials of TTFields have proven safe and efficacious in patients with glioblastoma multiforme (GBM), and are FDA approved for use in newly diagnosed and recurrent GBM. Trials in other localized solid tumors are ongoing.
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Background
Please see Appendix 4 for a glossary of terms.
The outcome of patients with esophageal cancer is generally poor. Although multimodal therapy is standard, there is conflicting evidence ...regarding the addition of esophagectomy to chemoradiotherapy.
Objectives
To compare the effectiveness and safety of chemoradiotherapy plus surgery with that of chemoradiotherapy alone in people with nonmetastatic esophageal carcinoma.
Search methods
We performed a computerized search for relevant studies, up to Feburary 2017, on the CENTRAL, MEDLINE, and Embase databases using MeSH headings and keywords. We searched five online databases of clinical trials, handsearched conference proceedings, and screened reference lists of retrieved papers.
Selection criteria
We included randomized controlled trials (RCTs) comparing chemoradiotherapy plus esophagectomy with chemoradiotherapy alone for localized esophageal carcinoma. We excluded RCTs comparing chemotherapy or radiotherapy alone with esophagectomy.
Data collection and analysis
Two authors independently selected studies, extracted data, and assessed risk of bias and the quality of the evidence, using standardized Cochrane methodological procedures. The primary outcome was overall survival (OS), estimated with Hazard Ratio (HR). Secondary outcomes, estimated with risk ratio (RR), were local and distant progression‐free survival (PFS), quality of life (QoL), treatment‐related mortality and morbidity, and use of salvage procedures for dysphagia. Data were analyzed using a random effects model in Review Manager 5.3 software.
Main results
From 2667 references, we identified two randomized studies, in six reports, that included 431 participants. All participants were clinically staged to have at least T3 and/or node positive thoracic esophageal carcinoma, 93% of which was squamous cell histology. The risk of methodological bias of the included studies was low to moderate.
High‐quality evidence found the addition of esophagectomy had little or no difference on overall survival (HR 0.99, 95% CI 0.79 to 1.24; P = 0.92; I² = 0%; two trials). Neither study reported PFS, therefore, freedom from loco‐regional relapse was used as a proxy. Moderate‐quality evidence suggested that the addition of esophagectomy probably improved freedom from locoregional relapse (HR 0.55, 95% CI 0.39 to 0.76; P = 0.0004; I² = 0%; two trials), but low‐quality evidence suggested it may increase the risk of treatment‐related mortality (RR 5.11, 95% CI 1.74 to 15.02; P = 0.003; I² = 2%; two trials).
The other pre‐specified outcomes (quality of life, treatment‐related toxicity, and use of salvage procedures for dysphagia) were reported by only one study, which found very low‐quality evidence that use of esophagectomy was associated with reduced short‐term QoL (MD 0.93, 95% CI 0.24 to 1.62), and low‐quality evidence that it reduced use of salvage procedures for dysphagia (HR 0.52, 95% CI 0.36 to 0.75). Neither study compared treatment‐related morbidity between treatment groups.
Authors' conclusions
Based on the available evidence, the addition of esophagectomy to chemoradiotherapy in locally advanced esophageal squamous cell carcinoma, provides little or no difference on overall survival, and may be associated with higher treatment‐related mortality. The addition of esophagectomy probably delays locoregional relapse, however, this end point was not well defined in the included studies. It is undetermined whether these results can be applied to the treatment of adenocarcinomas, tumors involving the distal esophagus and gastro‐esophageal junction, and to people with poor response to chemoradiation.
Background
Electromechanical‐ and robotic‐assisted gait‐training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first ...published in 2007.
Objectives
To investigate the effects of automated electromechanical‐ and robotic‐assisted gait‐training devices for improving walking after stroke.
Search methods
We searched the Cochrane Stroke Group Trials Register (last searched 9 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 8), MEDLINE in Ovid (1950 to 15 August 2016), Embase (1980 to 15 August 2016), CINAHL (1982 to 15 August 2016), AMED (1985 to 15 August 2016), Web of Science (1899 to 16 August 2016), SPORTDiscus (1949 to 15 September 2012), the Physiotherapy Evidence Database (PEDro) (searched 16 August 2016), and the engineering databases COMPENDEX (1972 to 16 November 2012) and Inspec (1969 to 26 August 2016). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists, and contacted authors in an effort to identify further published, unpublished, and ongoing trials.
Selection criteria
We included all randomised controlled trials and randomised controlled cross‐over trials in people over the age of 18 years diagnosed with stroke of any severity, at any stage, in any setting, evaluating electromechanical‐ and robotic‐assisted gait training versus normal care.
Data collection and analysis
Two review authors independently selected trials for inclusion, assessed methodological quality and risk of bias, and extracted the data. The primary outcome was the proportion of participants walking independently at follow‐up.
Main results
We included 36 trials involving 1472 participants in this review update. Electromechanical‐assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 1.94, 95% confidence interval (CI) 1.39 to 2.71; P < 0.001; I² = 8%; moderate‐quality evidence) but did not significantly increase walking velocity (mean difference (MD) 0.04 m/s, 95% CI 0.00 to 0.09; P = 0.08; I² = 65%; low‐quality evidence) or walking capacity (MD 5.84 metres walked in 6 minutes, 95% CI ‐16.73 to 28.40; P = 0.61; I² = 53%; very low‐quality evidence). The results must be interpreted with caution because 1) some trials investigated people who were independent in walking at the start of the study, 2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and 3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggested that people in the acute phase may benefit, but people in the chronic phase may not benefit from electromechanical‐assisted gait training. Post hoc analysis showed that people who are non‐ambulatory at intervention onset may benefit, but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity.
Authors' conclusions
People who receive electromechanical‐assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that seven patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase III trials undertaken to address specific questions about the most effective frequency and duration of electromechanical‐assisted gait training as well as how long any benefit may last.
Background
This is an updated version of the original review published in Issue 4, 2004. The use of concurrent chemotherapy and radiotherapy in non‐small cell lung cancer (NSCLC) might be seen as a ...way of increasing the effectiveness of radical radiotherapy at the same time as reducing the risks of metastatic disease.
Objectives
To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to overall survival, tumour control and treatment‐related morbidity. To determine the effectiveness of concurrent versus sequential chemoradiotherapy.
Search methods
For this update we ran a new search in October 2009, using a search strategy adapted from the design in the original review. We searched: CENTRAL (accessed through The Cochrane Library, 2009, Issue 4), MEDLINE (accessed through PubMed), and EMBASE (accessed through Ovid).
Selection criteria
Randomised trials of patients with stage I‐III NSCLC undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy.
Data collection and analysis
Study selection, data extraction and assessment of risk of bias was performed independently by two authors. Pooled hazard ratios and relative risks were calculated according to a random‐effects model.
Main results
Nineteen randomised studies (2728 participants) of concurrent chemoradiotherapy versus radiotherapy alone were included. Chemoradiotherapy significantly reduced overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; I2 0%; 1607 participants) and overall progression‐free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I2 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation.
Six trials (1024 patients) of concurrent versus sequential chemoradiation were included. A significant benefit of concurrent treatment was shown in overall survival (HR 0.74, 95% CI 0.62 to 0.89; I2 0%; 702 participants). This represented a 10% absolute survival benefit at 2 years. More treatment‐related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; I2 0%; 950 participants). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95%CI 2.17 to 11.37; I2 66%; 947 participants).
Authors' conclusions
This update of the review published in 2004 incorporates additional trials and more mature data. It demonstrates the benefit of concurrent chemoradiation over radiotherapy alone or sequential chemoradiotherapy. Patient selection is an important consideration in view of the added toxicity of concurrent treatment. Uncertainty remains as to how far this is purely due to a radiosensitising effect and whether similar benefits could be achieved by using modern radiotherapy techniques and more dose intensive accelerated and/ or hyperfractionated radiotherapy regimens.
The incidence of brain metastases has markedly increased in the past 20 years owing to progress in the treatment of malignant solid tumours, earlier diagnosis by MRI and an ageing population. ...Although local therapies remain the mainstay of treatment for many patients with brain metastases, a growing number of systemic options are now available and/or are under active investigation. HER2-targeted therapies (lapatinib, neratinib, tucatinib and trastuzumab emtansine), alone or in combination, yield a number of intracranial responses in patients with HER2-positive breast cancer brain metastases. New inhibitors are being investigated in brain metastases from ER-positive or triple-negative breast cancer. Several generations of EGFR and ALK inhibitors have shown activity on brain metastases from EGFR and ALK mutant non-small-cell lung cancer. Immune-checkpoint inhibitors (ICIs) hold promise in patients with non-small-cell lung cancer without druggable mutations and in patients with triple-negative breast cancer. The survival of patients with brain metastases from melanoma has substantially improved after the advent of BRAF inhibitors and ICIs (ipilimumab, nivolumab and pembrolizumab). The combination of targeted agents or ICIs with stereotactic radiosurgery could further improve the response rates and survival but the risk of radiation necrosis should be monitored. Advanced neuroimaging and liquid biopsy will hopefully improve response evaluation.
Within the past decade, the field of immunotherapy has revolutionized the treatment of many cancers with the development and regulatory approval of various immune-checkpoint inhibitors and chimeric ...antigen receptor T cell therapies in diverse indications. Another promising approach to cancer immunotherapy involves the use of personalized vaccines designed to trigger de novo T cell responses against neoantigens, which are highly specific to tumours of individual patients, in order to amplify and broaden the endogenous repertoire of tumour-specific T cells. Results from initial clinical studies of personalized neoantigen-based vaccines, enabled by the availability of rapid and cost-effective sequencing and bioinformatics technologies, have demonstrated robust tumour-specific immunogenicity and preliminary evidence of antitumour activity in patients with melanoma and other cancers. Herein, we provide an overview of the complex process that is necessary to generate a personalized neoantigen vaccine, review the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses. In addition, we discuss the current status of clinical studies testing personalized neoantigen vaccines in patients with cancer and considerations for future clinical investigation of this novel, individualized approach to immunotherapy.
Background:
Men with locally advanced prostate cancer (LAPCa) or regionally advanced prostate cancer (RAPCa) are at high risk for death from their disease. Clinical guidelines support multimodal ...approaches, which include radical prostatectomy (RP) followed by radiotherapy (XRT) and XRT plus androgen deprivation therapy (ADT). However, there are limited data comparing these substantially different treatment approaches. Using Surveillance, Epidemiology, and End Results (SEER)–Medicare data, this study compared survival outcomes and adverse effects associated with RP plus XRT versus XRT plus ADT in these men.
Methods:
SEER‐Medicare data were queried for men with cT3‐T4N0M0 (LAPCa) or cT3‐T4N1M0 (RAPCa) prostate cancer. Propensity score methods were used to balance cohort characteristics between the treatment arms. Survival analyses were analyzed with the Kaplan‐Meier method and Cox proportional hazards models.
Results:
From 1992 to 2009, 13,856 men (≥65 years old) were diagnosed with LAPCa or RAPCa: 6.1% received RP plus XRT, and 23.6% received XRT plus ADT. At a median follow‐up of 14.6 years, there were 2189 deaths in the cohort, of which 702 were secondary to prostate cancer. Regardless of the tumor stage or the Gleason score, the adjusted 10‐year prostate cancer–specific survival and 10‐year overall survival favored men who underwent RP plus XRT over men who underwent XRT plus ADT. However, RP plus XRT versus XRT plus ADT was associated with higher rates of erectile dysfunction (28% vs 20%; P = .0212) and urinary incontinence (49% vs 19%; P < .001).
Conclusions:
Men with LAPCa or RAPCa treated initially with RP plus XRT had a lower risk of prostate cancer–specific death and improved overall survival in comparison with those men treated with XRT plus ADT, but they experienced higher rates of erectile dysfunction and urinary incontinence.
Clinical practice guidelines support multimodal therapeutic approaches for men with locally advanced or regionally advanced prostate cancer. This comparative effectiveness study using population‐based data demonstrates more favorable survival outcomes in these men who received radical prostatectomy with adjuvant radiotherapy when compared to those who received radiotherapy plus androgen deprivation therapy
Summary Ischaemic stroke is one of the leading causes of death and disability worldwide, and intravenous alteplase is the only proven effective treatment in the acute setting. Hypothermia has been ...shown to improve neurological outcomes after global ischaemia–hypoxia in comatose patients who have had cardiac arrest, and is one of the most extensively studied and powerful therapeutic strategies in acute ischaemic stroke. The protective mechanisms of therapeutic hypothermia affect the ischaemic cascade across several parallel pathways and, when coupled with reperfusion strategies, might yield synergistic benefits for patients who have had a stroke. Technological advances have allowed hypothermia to be induced rapidly, and the treatment has been used safely in acute stroke patients. Conclusive efficacy trials assessing therapeutic hypothermia combined with reperfusion therapies in acute ischaemic stroke are ongoing.
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Corona virus disease (COVID-19) has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of ...Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as “Integrated Medicine”) to COVID-19. We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses with the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, both of which were demonstrated in effect size and 95% confidence intervals (CI). A total of 11 studies were included. Four were RCTs and seven were CCSs. The sample size of including studies ranged from 42 to 200 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (e.g. Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate RR = 1.230, 95%CI (1.113, 1.359), P = 0.000, cure rate RR = 1.604, 95%CI (1.181, 2.177), P = 0.002, severity illness rate RR = 0.350, 95%CI (0.154, 0.792), P = 0.012, and hospital stay WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002 of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients’ fever, and fatigue time (P < 0.05). This review found that Integrated Medicine had better effects and did not increase adverse drug reactions for COVID-19. More high-quality RCTs are needed in the future.
Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the ...Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs 95% CIs) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC.
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