To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer.
ASCO convened an Expert Panel to conduct a ...systematic review of the more recently published literature (1999-2019) on therapy options for patients with locally advanced esophageal cancer and provide recommended care options for this patient population.
Seventeen randomized controlled trials met the inclusion criteria. Where possible, data were extracted separately for squamous cell carcinoma and adenocarcinoma.
Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended. For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered. For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered. Additional subgroup considerations are provided to assist with implementation of these recommendations. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
Background
Gestational diabetes mellitus (GDM) is associated with a wide range of adverse health consequences for women and their infants in the short and long term. With an increasing prevalence of ...GDM worldwide, there is an urgent need to assess strategies for GDM prevention, such as combined diet and exercise interventions. This is an update of a Cochrane review that was first published in 2015.
Objectives
To assess the effects of diet interventions in combination with exercise interventions for pregnant women for preventing GDM, and associated adverse health consequences for the mother and her infant/child.
Search methods
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (27 November 2016) and reference lists of retrieved studies.
Selection criteria
We included randomised controlled trials (RCTs) and cluster‐RCTs, comparing combined diet and exercise interventions with no intervention (i.e. standard care), that reported on GDM diagnosis as an outcome. Quasi‐RCTs were excluded. Cross‐over trials were not eligible for inclusion. We planned to include RCTs comparing two or more different diet/exercise interventions, however none were identified.
Data collection and analysis
Two review authors independently assessed study eligibility, extracted data, assessed the risk of bias of the included trials and assessed quality of evidence for selected maternal and infant/child outcomes using the GRADE approach. We checked data for accuracy.
Main results
In this update, we included 23 RCTs (involving 8918 women and 8709 infants) that compared combined diet and exercise interventions with no intervention (standard care). The studies varied in the diet and exercise programs evaluated and health outcomes reported. None reported receiving funding from a drug manufacturer or agency with interests in the results. Overall risk of bias was judged to be unclear due to the lack of methodological detail reported. Most studies were undertaken in high‐income countries.
For our primary review outcomes, there was a possible reduced risk of GDM in the diet and exercise intervention group compared with the standard care group (average risk ratio (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.01; 6633 women; 19 RCTs; Tau² = 0.05; I² = 42%; P = 0.07; moderate‐quality evidence). There was also a possible reduced risk of caesarean section (RR 0.95, 95% CI 0.88 to 1.02; 6089 women; 14 RCTs; moderate‐quality evidence). No clear differences were seen between groups for pre‐eclampsia (RR 0.98, 95% CI 0.79 to 1.22; 5366 participants; 8 RCTs; low‐quality evidence), pregnancy‐induced hypertension and/or hypertension (average RR 0.78, 95% CI 0.47 to 1.27; 3073 participants; 6 RCTs; Tau² = 0.19; I² = 62%; very low‐quality evidence), perinatal mortality (RR 0.82, 95% CI 0.42 to 1.63; 3757 participants; 2 RCTs; low‐quality evidence) or large‐for‐gestational age (RR 0.93, 95% CI 0.81 to 1.07; 5353 participants; 11 RCTs; low‐quality evidence). No data were reported for infant mortality or morbidity composite.
Subgroup analyses (based on trial design, maternal body mass index (BMI) and ethnicity) revealed no clear differential treatment effects. We were unable to assess the impact of maternal age, parity and specific features of the diet and exercise interventions. Findings from sensitivity analyses (based on RCT quality) generally supported those observed in the main analyses. We were not able to perform subgroup analyses based on maternal age, parity or nature of the exercise/dietary interventions due to the paucity of information/data on these characteristics and the inability to meaningfully group intervention characteristics.
For most of the secondary review outcomes assessed using GRADE, there were no clear differences between groups, including for perineal trauma (RR 1.27, 95% CI 0.78 to 2.05; 2733 participants; 2 RCTs; moderate‐quality evidence), neonatal hypoglycaemia (average RR 1.42, 95% CI 0.67 to 2.98; 3653 participants; 2 RCTs; Tau² = 0.23; I² = 77%; low quality evidence); and childhood adiposity (BMI z score) (MD 0.05, 95% CI ‐0.29 to 0.40; 794 participants; 2 RCTs; Tau² = 0.04; I² = 59%; low‐quality evidence). However, there was evidence of less gestational weight gain in the diet and exercise intervention group compared with the control group (mean difference (MD) ‐0.89 kg, 95% CI ‐1.39 to ‐0.40; 5052 women; 16 RCTs; Tau² = 0.37; I² = 43%;moderate‐quality evidence). No data were reported for maternal postnatal depression or type 2 diabetes; childhood/adulthood type 2 diabetes, or neurosensory disability.
Authors' conclusions
Moderate‐quality evidence suggests reduced risks of GDM and caesarean section with combined diet and exercise interventions during pregnancy as well as reductions in gestational weight gain, compared with standard care. There were no clear differences in hypertensive disorders of pregnancy, perinatal mortality, large‐for‐gestational age, perineal trauma, neonatal hypoglycaemia, and childhood adiposity (moderate‐ tovery low‐quality evidence).
Using GRADE methodology, the evidence was assessed as moderate to very low quality. Downgrading decisions were predominantly due to design limitations (risk of bias), and imprecision (uncertain effect estimates, and at times, small sample sizes and low event rates), however two outcomes (pregnancy‐induced hypertension/hypertension and neonatal hypoglycaemia), were also downgraded for unexplained inconsistency (statistical heterogeneity).
Due to the variability of the diet and exercise components tested in the included studies, the evidence in this review has limited ability to inform practice. Future studies could describe the interventions used in more detail, if and how these influenced behaviour change and ideally be standardised between studies. Studies could also consider using existing core outcome sets to facilitate more standardised reporting.
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. ...Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor microenvironment. Programmed-death-1 (PD-1) is a surface receptor expressed on activated and exhausted T cells, which mediate T cell inhibition upon binding with its ligand PD-L1, expressed on many tumor types including human GBMs. We tested the combination of anti-PD-1 immunotherapy with stereotactic radiosurgery in a mouse orthotopic GBM model.
We performed intracranial implantation of mouse glioma cell line GL261 transfected with luciferase into C57BL/6 mice. Mice were stratified into 4 treatment groups: (1) control; (2) radiation only; (3) anti-PD-1 antibody only; and (4) radiation plus anti-PD-1 antibody. Overall survival was quantified. The mice were killed on day 21 after implantation to assess immunologic parameters in the brain/tumor, cervical lymph nodes, and spleen.
Improved survival was demonstrated with combination anti-PD-1 therapy plus radiation compared with either modality alone: median survival was 25 days in the control arm, 27 days in the anti-PD-1 antibody arm, 28 days in the radiation arm, and 53 days in the radiation plus anti-PD-1 therapy arm (P<.05 by log-rank Mantle-Cox). Long-term survival was seen only in the combined treatment arm, with a fraction (15%-40%) of animals alive at day 180+ after treatment. Immunologic data on day 21 after implantation showed increased tumor infiltration by cytotoxic T cells (CD8+/interferon-γ+/tumor necrosis factor-α+) and decreased regulatory T cells (CD4+/FOXP3) in the combined treatment group compared with the single modality arms.
The combination of PD-1 blockade and localized radiation therapy results in long-term survival in mice with orthotopic brain tumors. These studies provide strong preclinical evidence to support combination trials in patients with GBM.
Introduction
Melanoma is the most serious form of skin cancer causing most of the skin cancer-related deaths. The incidence of melanoma has risen so dramatically over past few years that no other ...solid or blood malignancy comes close to it in terms of increased incidence. The main problem associated with the treatment of melanoma is low response rate to the existing treatment modalities, which in turn is due to the incomplete response by chemotherapeutic agents and inherent resistance of melanoma cells.
Materials and Methods
Conventional therapeutic strategies, as well as, recent literature on melanoma have been thoroughly studied. This review summarizes the base of anti-melanoma treatment with conventional chemotherapeutic drugs, followed by an account of recent studies which explored the potential of nanotechnology and newer strategies and agents in melanoma treatment.
Conclusion
Although melanoma is curable if detected in its early localized form, metastatic melanoma continues to be a therapeutic challenge. Metastatic melanoma has a very poor prognosis and conventional therapies have not improved the outcomes of the treatment so far. For this reason, newer combinations of anti-melanoma drugs and newer strategies utilizing nanotechnology have been constantly explored.
Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as ...a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.
The Faculty of Intensive Care Medicine and Intensive Care Society Guideline Development Group have used GRADE methodology to make the following recommendations for the management of adult patients ...with acute respiratory distress syndrome (ARDS). The British Thoracic Society supports the recommendations in this guideline. Where mechanical ventilation is required, the use of low tidal volumes (<6 ml/kg ideal body weight) and airway pressures (plateau pressure <30 cmH2O) was recommended. For patients with moderate/severe ARDS (PF ratio<20 kPa), prone positioning was recommended for at least 12 hours per day. By contrast, high frequency oscillation was not recommended and it was suggested that inhaled nitric oxide is not used. The use of a conservative fluid management strategy was suggested for all patients, whereas mechanical ventilation with high positive end-expiratory pressure and the use of the neuromuscular blocking agent cisatracurium for 48 hours was suggested for patients with ARDS with ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF) ratios less than or equal to 27 and 20 kPa, respectively. Extracorporeal membrane oxygenation was suggested as an adjunct to protective mechanical ventilation for patients with very severe ARDS. In the absence of adequate evidence, research recommendations were made for the use of corticosteroids and extracorporeal carbon dioxide removal.
Background
Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad‐spectrum beta‐lactams have been introduced as single treatment, and classically, a ...combination of a beta‐lactam with an aminoglycoside has been used.
Objectives
To compare beta‐lactam monotherapy versus beta‐lactam‐aminoglycoside combination therapy for cancer patients with fever and neutropenia.
Search methods
The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of s of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies.
Selection criteria
Randomised controlled trials (RCTs) comparing any beta‐lactam antibiotic monotherapy with any combination of a beta‐lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed.
Data collection and analysis
Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super‐infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention‐to‐treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors.
Main results
Seventy‐one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same beta‐lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different beta‐lactams－usually a broad‐spectrum beta‐lactam compared with a narrower‐spectrum beta‐lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same beta‐lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different beta‐lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super‐infections occurred with equal frequency, and fungal super‐infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open‐label. No correlation was noted between mortality and failure rates and these trials.
Authors' conclusions
Beta‐lactam monotherapy is advantageous compared with beta‐lactam‐aminoglycoside combination therapy with regard to survival, adverse events and fungal super‐infections. Treatment failure should not be regarded as the primary outcome in open‐label trials, as it reflects mainly treatment modifications.
Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a ...growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents.
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