Background
The unsurpassed sensitivity of intracranial electroencephalography (icEEG) and the growing interest in understanding human brain networks and ongoing activities in health and disease have ...make the simultaneous icEEG and functional magnetic resonance imaging acquisition (icEEG-fMRI) an attractive investigation tool. However, safety remains a crucial consideration, particularly due to the impact of the specific characteristics of icEEG and MRI technologies that were safe when used separately but may risk health when combined. Using a clinical 3-T scanner with body transmit and head-receive coils, we assessed the safety and feasibility of our icEEG-fMRI protocol.
Methods
Using platinum and platinum-iridium grid and depth electrodes implanted in a custom-made acrylic-gel phantom, we assessed safety by focusing on three factors. First, we measured radio frequency (RF)-induced heating of the electrodes during fast spin echo (FSE, as a control) and the three sequences in our icEEG-fMRI protocol. Heating was evaluated with electrodes placed orthogonal or parallel to the static magnetic field. Using the configuration with the greatest heating observed, we then measured the total heating induced in our protocol, which is a continuous 70-min icEEG-fMRI session comprising localizer, echo-planar imaging (EPI), and magnetization-prepared rapid gradient-echo sequences. Second, we measured the gradient switching-induced voltage using configurations mimicking electrode implantation in the frontal and temporal lobes. Third, we assessed the gradient switching-induced electrode movement by direct visual detection and image analyses.
Results
On average, RF-induced local heating on the icEEG electrode contacts tested were greater in the orthogonal than parallel configuration, with a maximum increase of 0.2°C during EPI and 1.9°C during FSE. The total local heating was below the 1°C safety limit across all contacts tested during the 70-min icEEG-fMRI session. The induced voltage was within the 100-mV safety limit regardless of the configuration. No gradient switching-induced electrode displacement was observed.
Conclusion
We provide evidence that the additional health risks associated with heating, neuronal stimulation, or device movement are low when acquiring fMRI at 3 T in the presence of clinical icEEG electrodes under the conditions reported in this study. High specific absorption ratio sequences such as FSE should be avoided to prevent potential inadvertent tissue heating.
A phase III study was performed to determine whether concurrent or sequential treatment with radiotherapy (RT) and chemotherapy (CT) improves survival in unresectable stage III non-small-cell lung ...cancer (NSCLC).
Patients were assigned to the two treatment arms. In the concurrent arm, chemotherapy consisted of cisplatin (80 mg/m(2) on days 1 and 29), vindesine (3 mg/m(2) on days 1, 8, 29, and 36), and mitomycin (8 mg/m(2) on days 1 and 29). RT began on day 2 at a dose of 28 Gy (2 Gy per fraction and 5 fractions per week for a total of 14 fractions) followed by a rest period of 10 days, and then repeated. In the sequential arm, the same CT was given, but RT was initiated after completing CT and consisted of 56 Gy (2 Gy per fraction and 5 fractions per week for a total of 28 fractions).
Three hundred twenty patients were entered onto the study. Pretreatment characteristics were well balanced between the treatment arms. The response rate for the concurrent arm was significantly higher (84. 0%) than that of the sequential arm (66%) (P =.0002). The median survival duration was significantly superior in patients receiving concurrent therapy (16.5 months), as compared with those receiving sequential therapy (13.3 months) (P =.03998). Two-, 3-, 4-, and 5-year survival rates in the concurrent group (34.6%, 22.3%, 16.9%, and 15.8%, respectively) were better than those in the sequential group (27.4%, 14.7%, 10.1%, and 8.9%, respectively). Myelosuppression was significantly greater among patients on the concurrent arm than on the sequential arm (P =.0001).
In selected patients with unresectable stage III NSCLC, the concurrent approach yields a significantly increased response rate and enhanced median survival duration when compared with the sequential approach.
Abstract
Background
This study evaluated the efficacy and safety of the combination chemotherapy of docetaxel plus S‐1 in patients with previously treated non‐small cell lung cancer (NSCLC) compared ...to docetaxel alone.
Methods
Patients with previously treated NSCLC were randomly assigned to docetaxel alone (arm A) or a combination of docetaxel and S‐1 (arm B) for a maximum of four cycles. The primary endpoint was overall survival (OS).
Results
The study was terminated early because of poor accrual. The number of patients evaluated were 74 and 77 in arm A and arm B, respectively. The median OS was 9.8 months (95% confidence interval CI: 6.8–15.2) and 12.3 months (95% CI: 9.2–14.5) in arms A and B, respectively. In arms A and B, the median progression‐free survival was 3.5 months (95% CI: 2.7–4.0) and 4.1 months (95% CI: 3.2–4.7), respectively. No statistically significant difference was observed in OS (hazard ratio HR: 0.984, 95% CI: 0.682–1.419,
p
= 0.4569) or progression‐free survival (HR: 0.823, 95% CI: 0.528–1.282,
p
= 0.0953). The major toxicity was myelosuppression. The incidence of grade 3 or more neutropenia was higher in arm A than in arm B (44.6% vs. 35.1%). However, the incidence of grade 3 or more febrile neutropenia and infection with neutropenia (12.2% vs. 22.1%) was more frequently observed in arm B.
Conclusions
The prematurely terminated study did not show the benefit of two cytotoxic agents over single‐agent therapy for previously treated NSCLC patients.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Percutaneous coronary intervention for the treatment of a severe calcified lesion is still one of the most technically challenging areas of interventional cardiology. Calcified lesions are a cause of ...stent underexpansion, which significantly increases the subsequent risks of in-stent restenosis and thrombosis, even when drug-eluting stents are used. In this report, we describe the usefulness of prolonged inflations using a scoring balloon catheter (Scoreflex) for severe calcified lesions. Prolonged inflation using a scoring balloon enables an adequate dilation for treatment of a severe calcified plaque that was unresponsive to conventional technique with or without rotational atherectomy.
Background
Nab‐paclitaxel (nab‐PTX) has better transfer to tumor tissue than cremophor‐based paclitaxel. It suggests that the optimum dose of nab‐PTX might be lower than the dose and schedule that is ...widely used. We designed a randomized phase II trial to examine the clinical utility and safety of nab‐PTX in patients with previously treated advanced non‐small cell lung cancer (NSCLC).
Methods
Patients were randomly allocated (1:1) to receive nab‐PTX monotherapy at 100 mg/m2 (group A) or 70 mg/m2 (group B). The primary endpoint was progression‐free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs).
Results
Finally, 81 patients were randomized. Similar results were observed in both groups for PFS (3.75 vs. 3.71 months), OS (13.50 vs. 16.13 months), or ORR (20.5% vs. 23.1%). The incidences of grade 3 or worse AEs were 57.5% in group A and 41.5% in group B. The proportion of serious side effects was 10.0% in group A and 4.9% in group B.
Conclusion
Both standard dose and low dose of nab‐PTX monotherapy are active for previously treated NSCLC patients with better safety profile. Therefore, nab‐PTX 70 mg/m2 dose and schedule in the trial would be a reasonable option.
In this phase 2 randomized clinical trial to examine activity and safety, and to determine optimum dose of nab‐PTX in patients with previously treated stage IIIB/IV or postoperative relapsed NSCLC, both 100 and 70 mg/m2 of nab‐PTX monotherapy were active in patients with previously treated advanced NSCLC. Since the 70 mg/m2 dose has a better safety profile and numerically favored median overall survival, 70 mg/m2 on days 1, 8, and 15 every 4 weeks would be the optimal dose and schedule for nab‐PTX during treatment of NSCLC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A water soluble derivative of camptothecin, irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC), as well as non-SCLC and gastrointestinal cancers. This extended review of recently ...concluded and ongoing studies focuses on irinotecan in the treatment of limited (LD) and extensive (ED) SCLC specifically considering the safety of patients. Irinotecan-induced diarrhoea is pervasive, and can be severe and life-threatening especially in combination with neutropenia. It can have a significant impact on patient quality of life, negatively influencing compliance with therapy and dose-intensity. For LD SCLC, irinotecan can be administered with radiotherapy concurrently or sequentially. In a Phase III study for ED SCLC comparing etoposide and cisplatin (EP) and irinotecan and cisplatin (IP) regimens, severe myelosuppression was more frequent in the EP arm than in the IP arm, and conversely severe or life-threatening diarrhoea was more frequent in the IP arm than in the EP arm. IP resulted in significantly higher response rates and overall survival in Japan, and confirmatory Phase III studies are ongoing. Irinotecan should not be administered to patients with any degree of ongoing diarrhoea above their baseline. Irinotecan can be administered with relative safety for patients with SCLC only through careful patient monitoring, especially regarding diarrhoea and myelosuppression.
Background
Gefitinib (G) is a recommended molecular‐targeted agent for elderly patients with epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer (NSCLC). Docetaxel (Doc) and ...pemetrexed (Pem) have similar efficacies, and either is often used as the sole agent during treatment. The efficacy of continuing G after progressive disease (PD) develops has been reported. It remains unclear whether the continuation of G in combination with a single cytotoxic agent beyond PD is beneficial for elderly patients. Here, we conducted a randomized phase II study to assess the efficacy and safety of cytotoxic chemotherapy with G for elderly patients with progressive EGFR‐mutant NSCLC.
Methods
Elderly patients with EGFR‐mutant NSCLC with PD previously treated with G were enrolled. Patients received Pem 500 mg/m or Doc 60 mg/m every 21 days and were randomly assigned to receive chemotherapy with 250 mg G (G+ Doc/Pem arm) or without G (Doc/Pem arm) until further disease progression or unacceptable toxicity.
Results
This trial was terminated early owing to slow accrual. A group of 22 patients underwent analysis. The primary endpoint, progression‐free survival (PFS), was significantly longer in the G + Doc/Pem arm (median: 1.6 months vs. 5.6 months, hazard ratio = 0.40, 95% CI: 0.16–0.99, p = 0.0391). Adverse events ≥ grade 3 were more frequent in the G + Doc/Pem arm (45.5% vs. 90.9%, p = 0.032).
Conclusions
Patients on G and Pem or Doc beyond PD showed a longer PFS than those on single‐agent chemotherapy; however, it was associated with increased toxicity.
We conducted a randomized phase II study to assess the efficacy and safety of cytotoxic chemotherapy with gefitinib for elderly patients with progressive EGFR‐mutant NSCLC. PFS was significantly longer in the gefitinib with chemotherapy arm (median: 1.6 months vs. 5.6 months, HR = 0.40, 95% CI: 0.16–0.99, p = 0.0391). Adverse events ≥ grade 3 were more frequent in the gefitinib with chemotherapy arm (45.5% vs. 90.9%, p = 0.032). Based on our results, combination chemotherapy with continuing gefitinib beyond PD may have potential benefit in limited elderly NSCLC without information on acquired resistance to gefitinib.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary Background Platinum-containing two-drug combinations improve survival and cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). However, survival benefit is ...modest and platinum-containing regimens cause substantial toxic effects. We did a prospective randomised open-label phase III study to compare an experimental platinum-free, triplet, sequential regimen of vinorelbine plus gemcitabine followed by docetaxel with the standard platinum-containing, doublet regimen paclitaxel plus carboplatin in patients with advanced NSCLC. Methods Between March, 2001, and April, 2005, patients with stage IIIB (positive pleural effusion) or IV NSCLC, performance status 0 to 1, and adequate organ function, were randomly assigned to experimental treatment or to standard treatment. Randomisation was done centrally by use of a dynamic balancing algorithm. Patients were stratified by weight loss, lactate dehydrogenase concentration, and disease stage. Patients in the experimental group were scheduled to receive intravenous vinorelbine (25 mg/m2 ) plus gemcitabine (1000 mg/m2 ) on days 1 and 8 every 21 days for three cycles, followed by intravenous docetaxel (60 mg/m2 ) on day 1 every 21 days for three cycles. Patients in the standard group were scheduled to receive intravenous paclitaxel (225 mg/m2 ) plus carboplatin (area under the curve=6) for 3 h on day 1, every 21 days for six cycles. The primary endpoint was overall survival, and secondary endpoints were progression-free survival, response, and toxic effects. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00079287. Findings Of the 401 patients enrolled and randomised in the trial, five patients in the experimental group and three in the standard group were ineligible for analysis; thus 196 patients in the experimental group and 197 in the standard group were included in analyses. Patient characteristics were well-balanced between the two groups with regard to major prognostic factors. Median overall survival was 13·6 months (range 12·0–16·4) in the experimental group versus 14·1 months (11·9–17·5) in the standard group (p=0·97). 49 of 196 patients (25%) in the experimental group had a partial response compared with 73 of 197 patients (37%) in the standard group (p=0·012). There were no complete responses. Median progression-free survival was 5·5 months (95% CI 4·9–6·3) in the experimental group compared with 5·8 months (5·3–6·1) in the standard group (p=0·74). The incidence of grade 3 and 4 neutropenia, neuropathy, arthralgia, and myalgia was lower in the experimental group than in the standard group, although the incidence of pulmonary toxic effects was higher. Interpretation Although platinum-containing regimens remain the standard treatment for advanced NSCLC, non-platinum regimens could provide equivalent efficacy with a different toxicity profile. Funding Japan Multi-National Trial Organisation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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