Background
It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its ...effectiveness.
Purpose
To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis.
Methods
Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (
β
) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran
χ
2
statistic and the
I
2
statistic. Potential publication bias was investigated using standard error-based funnel plots.
Results
Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01–1.08) and random-effects model (RR 1.08; 95 % CI, 1.01–1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias.
Conclusions
Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.
We present 10 high‐speed video images that depict the bottom 150 m of a downward‐negative, dart‐stepped leader in a rocket‐and‐wire triggered flash, recorded at 240 kiloframes per second (4.17 μs ...frame integration time), along with correlated measurements of the X‐ray emission at 50 m, electric field derivative (dE/dt) at 80 m, and the rocket‐launch‐tower current beneath the leader. We observed discrete segments of secondary channel that exhibited luminosity above that of the surrounding corona streamers and were distinctly separate and beneath the downward‐extending leader channel. These segments appear similar to the space stems or space leaders that have been imaged in long negative laboratory sparks. Multiple simultaneous pulses in X‐ray emission, dE/dt, and launch tower current were recorded during the time that the leader steps were imaged. The leader extended at an average downward speed between 2.7 × 106 and 3.4 × 106 m s−1.
Pancreatic cancer is the seventh leading cause of cancer deaths worldwide, accounting for 4.7% of all cancer deaths, and is expected to climb significantly over the next decade. The purpose of this ...systematic review and guidance document was to synthesize the evidence surrounding the role of adjuvant treatment (chemotherapy and chemoradiation therapy CRT, and stereotactic body radiation therapy SBRT) in resected pancreatic ductal adenocarcinoma (PDAC). Systematic literature searches of MEDLINE, EMBASE, and 11 guideline databases were conducted. Both direct and indirect comparisons indicate adjuvant chemotherapy offers a survival advantage over surgery alone. The optimal regimens recommended are mFOLFIRINOX with alternative options of gemcitabine plus capecitabine, gemcitabine alone, or S-1 (which is not available in North America). Trials comparing a CRT strategy to modern chemotherapy regimens are lacking. However, current evidence demonstrates that the addition of CRT to chemotherapy does not result in a survival advantage over chemotherapy alone and is therefore not recommended. Trials evaluating SBRT in PDAC are also lacking. SBRT should only be used within a clinical trial or multi-institutional registry.
Sunitinib is a multitargeted receptor tyrosine kinase inhibitor. We conducted a two-stage phase II study to evaluate the objective response rate of oral sunitinib in recurrent epithelial ovarian ...cancer.
Eligibility required measurable disease and one or two prior chemotherapies, at least one platinum based. Platinum-sensitive or -resistant disease was allowed. Initial dose schedule was sunitinib 50 mg daily, 4 of 6 weeks. Observation of fluid accumulations during off-treatment periods resulted in adoption of continuous 37.5 mg daily dosing in the second stage of accrual.
Of 30 eligible patients, most had serous histology (67%), were platinum sensitive (73%) and had two prior chemotherapies (60%). One partial response (3.3%) and three CA125 responses (10%) were observed, all in platinum-sensitive patients using intermittent dosing. Sixteen (53%) had stable disease. Five had >30% decrease in measurable disease. Overall median progression-free survival was 4.1 months. Common adverse events included fatigue, gastrointestinal symptoms, hand–foot syndrome and hypertension. No gastrointestinal perforation occurred.
Single-agent sunitinib has modest activity in recurrent platinum-sensitive ovarian cancer, but only at the 50 mg intermittent dose schedule, suggesting that dose and schedule may be vital considerations in further evaluation of sunitinib in this cancer setting.
In a prospective, randomized trial involving patients with resected pancreatic cancer, adjuvant combination chemotherapy with FOLFIRINOX resulted in a median disease-free survival of 21.6 months, as ...compared with 12.8 months with gemcitabine therapy. Overall survival was also longer with FOLFIRINOX.
We present observations of a rocket‐and‐wire triggered lightning flash obtained with high‐speed video cameras recording 5400 and 50000 frames per second (frame times 185 μs and 20 μs) with ...time‐synchronized current and electric field measurements. Transient leader channels were observed with precursor current pulses occurring before the development of the sustained upward positive leader that initiated the initial continuous current. The sustained upward positive leader stepped with a constant speed of 5.6 × 104 m s−1 over its initial 100 m. The wire destruction occurred discontinuously over a time of 7 ms about 45 ms after sustained upward leader inception, with a small change in channel current. Downward leaders, upward connecting leaders, and filamentary streamers were imaged in the bottom 50 m of the channel. We present the first images of a negative step forming in lightning, apparently involving a space stem similar to steps in meter‐length negative laboratory sparks.
We present 63 high‐speed video frames (108 kilo‐frames per second (kfps), 9.26 µs per frame) showing the development of the downward negative stepped leader in the initial stage of an ...altitude‐triggered flash. The downward negative stepped leader initiated from the bottom of the triggering wire at a height of about 128 m above ground and, 553 µs later, it struck a lightning rod located at a distance of about 50 m from the launch tower. During the leader's development, electric field derivative pulses were detected associated with leader stepping. The interpulse intervals ranged from 3 to 27 µs with a mean value of 13 µs. Distinct segments of luminosity were observed ahead of the main leader channel that appear similar to space leaders were observed in the high‐speed video frames. A total of eight luminous segments were observed that were 1 m to 6 m in length and were centered at distances from the main leader channel ranging from 3 m to 8 m. The new leader steps that appeared in the frames following the luminous segments were 5 m to 8 m in length. Two of the observed segments apparently never connected to the leader channel and thus failed to produce a new leader step.
Key Points
Lightning negative leaders stepping processes observed
Observations are similar to other reported observations
Altitude triggered lightning good source to study leader stepping processes
Background To determine the role of liver resection in patients with liver and extrahepatic colorectal cancer metastases and the role of chemotherapy in patients in conjunction with liver resection. ...Methods MEDLINE and EMBASE databases were searched for articles published between 1995 and 2010, along with hand searching. Results A total of 4875 articles were identified, and 83 were retained for inclusion. Meta-analysis was not performed because of heterogeneity and poor quality of the evidence. Outcomes in patients who had liver and lung metastases, liver and portal node metastases, and liver and other extrahepatic disease were reported in 14, 10, and 14 studies, respectively. The role of perioperative chemotherapy was assessed in 30 studies, including 1 randomized controlled trial and 1 pooled analysis. Ten studies assessed the role of chemotherapy in patients with initially unresectable disease, and 5 studies assessed the need for operation after a radiologic complete response. Conclusion The review suggests that: (1) select patients with pulmonary and hepatic CRC metastases may benefit from resection; (2) perioperative chemotherapy may improve outcome in patients undergoing a liver resection; (3) patients whose CRC liver metastases are initially unresectable may benefit from chemotherapy to identify a subgroup who may benefit later from resection; (4) after radiographic complete response (RCR), lesions should be resected if possible.
We present a detailed evaluation of performance characteristics of the U.S. National Lightning Detection Network (NLDN) using, as ground truth, Florida rocket‐triggered lightning data acquired in ...2004–2012. The overall data set includes 78 flashes containing both the initial stage and leader/return‐stroke sequences and 2 flashes composed of the initial stage only. In these 80 flashes, there are a total of 326 return strokes (directly measured channel‐base currents are available for 290 of them) and 173 kiloampere‐scale (≥1 kA) superimposed pulses, including 58 initial continuous current pulses and 115 M components. All these events transported negative charge to the ground. The NLDN detected 245 return strokes and 9 superimposed pulses. The resultant NLDN flash detection efficiency is 94%, return‐stroke detection efficiency is 75%, and detection efficiency for superimposed pulses is 5% for peak currents ≥1 kA and 32% for peak currents ≥5 kA. For return strokes, the median location error is 334 m and the median value of absolute peak current estimation error is 14%. The percentage of misclassified events is 4%, all of them being return strokes. The median value of absolute event‐time mismatch (the difference in times at which the event is reported to occur by the NLDN and recorded at the lightning triggering facility) for return strokes is 2.8 µs. For two out of the nine superimposed pulses detected by the NLDN, we found optical evidence of a reilluminated branch (recoil leader) coming in contact with the existing grounded channel at an altitude of a few hundred meters above ground.
Key Points
Flash and stroke detection efficiencies of the NLDN are 94% and 75%, respectivelyMedian location error of the NLDN is 334 mMedian value of absolute peak current estimation error is 14%
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