Hazard ratio

Intrarenal Resistive Index after Renal Transplantation.

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BACKGROUND

The intrarenal resistive index is routinely measured in many renal–transplantation centers for assessment of renal-allograft status, although the value of the resistive index remains unclear.

METHODS

In a single-center, prospective study involving 321 renal-allograft recipients, we measured the resistive index at baseline, at the time of protocol-specified renal-allograft biopsies (3, 12, and 24 months after transplantation), and at the time of biopsies performed because of graft dysfunction. A total of 1124 renal-allograft resistive-index measurements were included in the analysis. All patients were followed for at least 4.5 years after transplantation.

RESULTS

Allograft recipients with a resistive index of at least 0.80 had higher mortality than those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 5.20 [95% confidence interval {CI}, 2.14 to 12.64; P<0.001]; 3.46 [95% CI, 1.39 to 8.56; P=0.007]; and 4.12 [95% CI, 1.26 to 13.45; P=0.02], respectively). The need for dialysis did not differ significantly between patients with a resistive index of at least 0.80 and those with a resistive index of less than 0.80 at 3, 12, and 24 months after transplantation (hazard ratio, 1.95 [95% CI, 0.39 to 9.82; P=0.42]; 0.44 [95% CI, 0.05 to 3.72; P=0.45]; and 1.34 [95% CI, 0.20 to 8.82; P=0.76], respectively). At protocol-specified biopsy time points, the resistive index was not associated with renal-allograft histologic features. Older recipient age was the strongest determinant of a higher resistive index (P<0.001). At the time of biopsies performed because of graft dysfunction, antibody-mediated rejection or acute tubular necrosis, as compared with normal biopsy results, was associated with a higher resistive index (0.87±0.12 vs. 0.78±0.14 [P=0.05], and 0.86±0.09 vs. 0.78±0.14 [P=0.007], respectively).

CONCLUSIONS

The resistive index, routinely measured at predefined time points after transplantation, reflects characteristics of the recipient but not those of the graft.

 

Souirce: NEJM

 

 

Glasgow Prognostic Score as a useful prognostic factor after hepatectomy for hepatocellular carcinoma.

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Abstract

Background

Several previous studies have revealed that the Glasgow Prognostic Score (GPS) is a clinically useful scoring system to predict the prognosis of patients with various kinds of advanced cancers. However, there have been few reports on the relationship between the GPS and prognosis after hepatectomy for hepatocellular carcinoma (HCC). Therefore, we performed an analysis of the relationship between the GPS and prognosis after hepatectomy for HCC.

Methods

Between January 2005 and December 2009, 352 HCC patients underwent hepatectomy at Kumamoto University Hospital. Nineteen clinicopathologic factors were analyzed, using univariate and multivariate analyses.

Results

Univariate analysis showed that significant risk factors for poor survival included serum albumin level (<3.5 g/dL), tumor size (>35 mm), presence of ascites, portal vein invasion, operation time (>400 min), blood loss (>360 mL), requirement for blood transfusion, and GPS. Multivariate analysis revealed that tumor size [hazard ratio (HR) 3.355; p = 0.003], operation time (HR 2.634; p = 0.006), portal vein invasion (HR 2.419; p = 0.009), and GPS (HR 3.796; p < 0.001) were independent factors for poor prognosis.

Conclusion

The GPS was demonstrated to be a statistically significant prognostic factor after hepatectomy for HCC.

Source: International Journal of Clinical Oncology

Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension.

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Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.

METHODS

We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension.

RESULTS

A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P=0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia.

CONCLUSIONS

Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study.

Source: NEJM

 

Lenalidomide plus Dexamethasone for High-Risk Smoldering Multiple Myeloma.

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BACKGROUND

For patients with smoldering multiple myeloma, the standard of care is observation until symptoms develop. However, this approach does not identify high-risk patients who may benefit from early intervention.

METHODS

In this randomized, open-label, phase 3 trial, we randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. Patients in the treatment group received an induction regimen (lenalidomide at a dose of 25 mg per day on days 1 to 21, plus dexamethasone at a dose of 20 mg per day on days 1 to 4 and days 12 to 15, at 4-week intervals for nine cycles), followed by a maintenance regimen (lenalidomide at a dose of 10 mg per day on days 1 to 21 of each 28-day cycle for 2 years). The primary end point was time to progression to symptomatic disease. Secondary end points were response rate, overall survival, and safety.

RESULTS

After a median follow-up of 40 months, the median time to progression was significantly longer in the treatment group than in the observation group (median not reached vs. 21 months; hazard ratio for progression, 0.18; 95% confidence interval [CI], 0.09 to 0.32; P<0.001). The 3-year survival rate was also higher in the treatment group (94% vs. 80%; hazard ratio for death, 0.31; 95% CI, 0.10 to 0.91; P=0.03). A partial response or better was achieved in 79% of patients in the treatment group after the induction phase and in 90% during the maintenance phase. Toxic effects were mainly grade 2 or lower.

CONCLUSIONS

Early treatment for patients with high-risk smoldering myeloma delays progression to active disease and increases overall survival.

Source: NEJM

 

 

Dual-Maintenance Therapy for Advanced Non–Small-Cell Lung Cancer.

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Progression-free survival was superior with bevacizumab plus pemetrexed versus bevacizumab alone after induction with bevacizumab, cisplatin, and pemetrexed.
Maintenance therapy has been shown to improve survival in patients with non–small-cell lung cancer (NSCLC). Recently, maintenance with single-agent pemetrexed versus placebo was associated with improved progression-free survival (PFS) and overall survival . To test a dual-maintenance strategy in this setting, investigators conducted an industry-supported, phase III, multicenter, randomized, open-label trial (AVAPERL) of maintenance bevacizumab with or without pemetrexed.

A total of 376 patients with advanced, nonsquamous NSCLC received induction therapy with intravenous bevacizumab (7.5 mg/kg), cisplatin (75 mg/m2), and pemetrexed (500 mg/m2) every 3 weeks for 4 cycles. The 253 responding patients were randomized to maintenance bevacizumab every 3 weeks or combination bevacizumab (7.5 mg/kg) plus pemetrexed (500 mg/m2) every 3 weeks.

At a median follow-up of 8.1 months, PFS from time of randomization (the primary endpoint) was superior with combination bevacizumab plus pemetrexed versus bevacizumab alone (median, 7.4 vs. 3.7 months; hazard ratio, 0.48; P<0.0001), as was PFS from time of induction (10.2 vs. 6.6 months; HR, 0.50; P<0.001). OS favored combination therapy but did not reach statistical significance. No new safety signals were identified, but toxicity was greater with combination therapy.

COMMENT

At ASC0 2013, updated results from the AVAPERL trial (Abstract 8014) indicated that OS also failed to reach statistical significance (median OS from randomization, 17.1 vs. 13.2 months; HR 0.87; P=0.29 and median OS from induction, 19.8 vs. 15.9 months; HR 0.88; P=0.32). The AVAPERL trial thus suggests that adding pemetrexed to maintenance bevacizumab improves PFS with a trend towards OS benefit. However, other randomized, phase III data presented at ASCO 2013 (Abstract 8004) indicate that dual maintenance provides no OS benefit. At present, the issue of optimal maintenance therapy in unselected nonsquamous NSCLC patients remains unknown. Treatment decisions are currently based on eligibility for bevacizumab treatment and patient preference for toxicity profiles.

Source: NEJM

A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1–4 vs ≥ 5 tumors.

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Abstract

OBJECT

Although stereotactic radiosurgery (SRS) alone for patients with 4–5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors’ aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1–4 tumors.

METHODS

This institutional review board–approved retrospective cohort study used the authors’ database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1–4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death–free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications.

RESULTS

The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0–8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2–7.8 months], HR 1.176 [95% CI 1.039–1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death–free survival intervals (HR 0.945, 95% CI 0.636–1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312–1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910–1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608–1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490–2.496, p = 0.81).

In the authors’ cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm3, controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups.

CONCLUSIONS

This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1–4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.

Source: JNS