This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for ...limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease.
The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest.
Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality.
PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.
Systematic review of outcomes of three treatments for osteoarthritis (OA) of the knee: intra-articular viscosupplementation; oral glucosamine, chondroitin or the combination; and arthroscopic lavage ...or debridement.
We abstracted data from: 42 randomized, controlled trials (RCTs) of viscosupplementation, all but one synthesized among six meta-analyses; 21 RCTs of glucosamine/chondroitin, 16 synthesized among 6 meta-analyses; and 23 articles on arthroscopy. The search included foreign-language studies and relevant conference proceedings.
The review methods were defined prospectively in a written protocol. We sought systematic reviews, meta-analyses, and RCTs published in full or in abstract. Where randomized trials were few, we sought other study designs. We independently assessed the quality of all primary studies.
Viscosupplementation trials generally report positive effects on pain and function scores compared to placebo, but the evidence on clinical benefit is uncertain, due to variable trial quality, potential publication bias, and unclear clinical significance of the changes reported. The Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a large (n=1,583), high-quality, National Institutes of Health-funded, multicenter RCT showed no significant difference compared to placebo. Glucosamine sulfate has been reported to be more effective than glucosamine hydrochloride, which was used in GAIT, but the evidence is not sufficient to draw conclusions. Clinical studies of glucosamine effect on glucose metabolism are short term, or if longer (e.g., 3 years), excluded patients with metabolic disorders. The best available evidence for arthroscopy, a single sham-controlled RCT (n=180), showed that arthroscopic lavage with or without debridement was equivalent to placebo. The main limitations of this trial are the use of a single surgeon and enrollment of patients at a single Veterans Affairs Medical Center. No studies reported separately on patients with secondary OA of the knee. The only comparative study was an underpowered, poor-quality trial comparing viscosupplementation to arthroscopy with debridement.
Osteoarthritis of the knee is a common condition. The three interventions reviewed in this report are widely used in the treatment of OA of the knee, yet the best available evidence does not clearly demonstrate clinical benefit. Uncertainty regarding clinical benefit can be resolved only by rigorous, multicenter RCTs. In addition, given the public health impact of OA of the knee, research on new approaches to prevention and treatment should be given high priority.
Increasingly, clinicians advocate the use of nonmyeloablative allogeneic stem-cell transplants (NM-allo-SCTs, "mini-transplants") to manage hematologic malignancies. They hypothesize that NM-allo-SCT ...is equally efficacious to standard allo-SCT but produces less regimen-related toxicity.
To analyze available evidence on the benefits and harms of "mini-transplants," we identified 23 manuscripts, 1 abstract, and 1 letter that reported the outcome of mini-transplants in hematologic malignancies.
Data were compiled on 603 treated patients, with 118 transplants using stem cells from matched unrelated donors. All studies were small prospective case series, and most lacked concurrent or historical controls. Outcomes of interest were not uniformly reported. The studies were heterogeneous and used different patient selection criteria, conditioning regimens, and timing of transplant with respect to disease status. The transplant-related mortality rate was 32%, the relapse rate was 15%, and toxicities included acute and chronic graft-vs-host disease and veno-occlusive disease. The aggregate rate of complete remission was 45%. Survival at 1 year or longer ranged from 30% to 60% at 1 to 5 years of follow-up. All studies reported successful chimerism.
Disease-specific studies with longer follow-up are needed to evaluate this potentially promising therapy.
Systematic review of trastuzumab outcomes among breast cancer patients who have negative, equivocal, or discordant HER2 assay results; use of HER2 assay results to predict outcomes of chemotherapy or ...hormonal therapy regimen for breast cancer; use of serum HER2 to monitor treatment response or disease progression in breast cancer patients; and use of HER2 testing to manage patients with lung, ovarian, prostate, or head and neck tumors. Also, narrative review of concordance of HER2 assays.
We abstracted data from: three articles plus one conference abstract on negative, equivocal, or discordant HER2 results; 26 studies on selection of chemotherapy or hormonal therapy; 15 studies on serum HER2; and 26 studies on ovarian, lung, prostate, or head and neck tumors. Foreign-language studies were included.
We sought randomized trials or single-arm series (prospective or retrospective) of identically treated patients that presented relevant outcome data associated with HER2 status.
HER2 assay results are influenced by multiple biologic, technical, and performance factors. Many aspects of HER2 assays were standardized only recently, so inconsistencies confound the literature comparing different methods. The evidence is weak on outcomes of trastuzumab added to chemotherapy for HER2-equivocal, -discordant, or -negative patients. Evidence comparing chemotherapy outcomes in HER2-positive and HER2-negative patient subgroups may generate hypotheses, but is too weak to test hypotheses. Only a rigorous test can resolve whether HER2-positive patients (but not HER2-negative patients) benefit from an anthracycline regimen. Evidence is available only from uncontrolled series on whether HER2 status predicts complete pathologic response to neoadjuvant chemotherapy. Evidence also is weak regarding differences by HER2 status for outcomes of chemotherapy for advanced or metastatic disease; with most studies lacking statistical power. Data from studies of tamoxifen and aromatase inhibitors suggest that future studies should examine whether HER2 status predicts response to specific hormonal therapies among estrogen-receptor-positive patients. The evidence is weak on whether serum HER2 predicts outcome after treatment with any regimens in any setting, as is the evidence on use of serum or tissue HER2 testing for malignancies of lung, ovary, head and neck, or prostate.
Overall, few studies directly investigated the key questions of this systematic review. Going forward, cancer therapy trial protocols should incorporate elements to facilitate robust analyses of the use of HER2 status and other biomarkers for managing treatment.
This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for ...limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease.
The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest.
Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality.
PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.
Management of small cell lung cancer Seidenfeld, Jerome; Samson, David J; Bonnell, Claudia J ...
Evidence report/technology assessment (Full report)
143
Journal Article
This is a systematic review of evidence on issues in managing small cell lung cancer (SCLC). Key questions addressed are: the sequence, timing, and dosing characteristics of primary thoracic ...radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second- and subsequent-line treatment for relapsed/progressive disease.
MEDLINE, EMBASE, and the Cochrane Register
The review methods were defined prospectively in a written protocol. We sought randomized controlled trials that compared the interventions of interest. Where randomized trials were limited or nonexistent, we sought additional studies. We performed meta-analysis of studies that compared early and late TRTx.
The strongest evidence available for this report is a patient-level meta-analysis showing that PCI improves survival of SCLC patients who achieved complete response following primary therapy from 15.3 percent to 20.7 percent (p=0.01). No other question yielded evidence so robust. The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Our meta-analysis did not find significant reductions in 2- and 3-year mortality for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. For other questions (i.e., management of mixed histology disease; surgery for early limited SCLC), relevant comparative studies were nonexistent. PET may be more sensitive in detecting disease outside the brain than conventional staging modalities, but studies were of poor quality and reliable estimates of performance are not possible.
PCI improves survival among those with a complete response to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components. PET for staging may be useful, but its role awaits clarification by rigorous studies. No relevant evidence was available to address management of mixed histology disease or surgery for early limited SCLC.
During a 10-week period prior to the 1997 Kyoto conference on climate change, two parallel studies were conducted: Study 1 examined media portrayals of global warming and the certainty with which ...information was reported (percentage of 'hedging'); Study 2 was a telephone survey to assess public knowledge about key topics in global climate change, people's certainty about their information, trust in the media, and willingness to take action on global warming. Media reports were found to be scarce, and about half of the references to global warming were found to be hedged. More hedging was evident in the New York Times than in other print media and national television reports, and economic impacts of climate change were reported with the greatest certainty. The audience (N = 139 adults, average age 36-45, with at least a high school education) reported trusting their media sources more than 50% of the time. They were collectively fairly knowledgeable and certain about global warming information (9.1 on a scale of - 20 to + 20), and they appeared to be willing to adopt a range of responsible behaviors seen to be useful in countering global warming (average response 3.0 out of 4). The knowledge/certainty factor was described as 'attitude under uncertainty', and was significantly related to media trust (r = 0.325, p < 0.01) and willingness to act responsibly (r = 0.400, p < 0.01). Comparing Study 1 with Study 2, the research does not support a hypothesis that media hedging is related to uncertainty. Implications for environmental communicators are discussed.
The politics of history in comparative perspective Kammen, Michael; Lebow, Richard Ned; Bonnell, Andrew ...
The Annals of the American Academy of Political and Social Science,
05/2008, Letnik:
617, Številka:
1
Journal Article
Using the Atacama Large Millimetre/submillimeter Array (ALMA) and the Karl G. Jansky Very Large Array (VLA), we observed the Extended Green Object (EGO) G19.01\(-\)0.03 with sub-arcsecond resolution ...from 1.05 mm to 5.01 cm wavelengths. Our \(\sim0.4''\sim1600\) AU angular resolution ALMA observations reveal a velocity gradient across the millimetre core MM1, oriented perpendicular to the previously known bipolar molecular outflow, that is consistently traced by 20 lines of 8 molecular species with a range of excitation temperatures, including complex organic molecules (COMs). Kinematic modelling shows the data are well described by models that include a disc in Keplerian rotation and infall, with an enclosed mass of \(40-70 \mathrm{M}_{\odot}\) (within a 2000 AU outer radius) for a disc inclination angle of \(i=40^{\circ}\), of which \(5.4-7.2 \mathrm{M}_{\odot}\) is attributed to the disc. Our new VLA observations show that the 6.7 GHz Class II methanol masers associated with MM1 form a partial ellipse, consistent with an inclined ring, with a velocity gradient consistent with that of the thermal gas. The disc-to-star mass ratio suggests the disc is likely to be unstable and may be fragmenting into as-yet-undetected low mass stellar companions. Modelling the centimetre--millimetre spectral energy distribution of MM1 shows the ALMA 1.05 mm continuum emission is dominated by dust, whilst a free-free component, interpreted as a hypercompact HII region, is required to explain the VLA \(\sim\)5 cm emission. The high enclosed mass derived for a source with a moderate bolometric luminosity (\(\sim\)10\(^{4} \mathrm{L}_{\odot}\)) suggests that the MM1 disc may feed an unresolved high-mass binary system.
PDF
