Independent Poor Prognostic Factors for True Progression after Radiation Therapy and Concomitant Temozolomide in Patients with Glioblastoma: Subependymal Enhancement and Low ADC Value

BACKGROUND AND PURPOSE:Subependymal enhancement and DWI have been reported to be useful MR imaging markers for identifying true progression. Our aim was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with glioblastoma multiforme treated with concurrent chemoradiotherapy by using temozolomide.MATERIALS AND METHODS:Forty-two patients with glioblastoma multiforme with newly developed or enlarged enhancing lesions on the first follow-up MR images obtained within 2 months of concurrent chemoradiotherapy completion were included. Subependymal enhancement was analyzed for the presence, location, and pattern (local or distant relative to enhancing lesions). The mean ADC value and the fifth percentile of the cumulative ADC histogram were determined. A multiple logistic regression analysis was performed to identify independent factors associated with true progression.RESULTS:Distant subependymal enhancement (ie, extending >1 cm or isolated from the enhancing lesion) was significantly more common in true progression (n = 24) than in pseudoprogression (n = 18) (P = .042). The fifth percentile of the cumulative ADC histogram was significantly lower in true progression than in pseudoprogression (P = .014). Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were independent factors associated with true progression (P = .041 and P = .033, respectively). Sensitivity and specificity for the diagnosis of true progression were 83% and 67%, respectively, by using both factors.CONCLUSIONS:Both the distant subependymal enhancement and the fifth percentile of the cumulative ADC histogram were significant independent factors predictive of true progression.

Glioblastoma multiforme (GBM) is the most common form of malignant primary brain tumor in adults,¹ which is notorious for its intrinsic aggressiveness and a dismal prognosis.^2,3 The current standard treatment for GBM is maximal safe tumor resection followed by radiation therapy with concurrent temozolomide (TMZ) and adjuvant TMZ.⁴Recently, the criteria for assessing therapeutic responses in high-grade gliomas have been updated by the Response Assessment in Neuro-Oncology (RANO) Working Group to address the limitations of the previous guideline.⁵ For instance, contrast enhancement, which has been regarded as a surrogate marker for tumor progression, has been reassessed as a nonspecific finding merely reflecting the passage of contrast material across a disrupted blood-tumor barrier.^6–11 In particular, radiologists and clinicians have increasingly recognized the occurrence of progressive MR imaging lesions immediately after completion of concurrent chemoradiotherapy (CCRT) with TMZ, which spontaneously improved without further treatment other than the adjuvant TMZ.^12–14 The treatment-related reaction is termed pseudoprogression and has received attention as a potential pitfall in the response evaluation. At present, owing to the lack of established findings in conventional contrast-enhanced MR imaging for the differential diagnosis of true progression from pseudoprogression,^9,10 RANO stresses that the diagnosis of true progression can be made within the first 12 weeks after completion of radiation therapy only if most of the new enhancement is located outside the radiation field or if there is pathologic confirmation of progressive disease.⁵During the past few decades, there has been extensive effort to identify imaging biomarkers for tumor progression. Among the many parameters derived from advanced MR imaging techniques, DWI has been consistently reported to be helpful in differentiating tumor progression from treatment-related changes or necrosis.^15–22 Meanwhile, most previous studies pertaining to the role of conventional MR imaging have not shown promising results.^9,23 Nevertheless, a recent study focusing on the conventional MR imaging findings has proposed subependymal enhancement as a useful MR imaging marker for differentiating true progression from pseudoprogression.²⁴ To our knowledge, however, no previous studies have conducted in-depth analysis of the subependymal enhancement, and its potential as an independent predictor for true progression remains elusive.The purpose of the present study was to determine whether the subependymal enhancement pattern and ADC can differentiate true progression from pseudoprogression in patients with GBM treated with radiation therapy and concomitant TMZ.     

Quadriceps neural alterations in anterior cruciate ligament reconstructed patients: A 6‐month longitudinal investigation

The purpose of this investigation was to evaluate differences in quadriceps corticospinal excitability, spinal‐reflexive excitability, strength, and voluntary activation before, 2 weeks post and 6 months post‐anterior cruciate ligament reconstruction (ACLr). This longitudinal, case‐control investigation examined 20 patients scheduled for ACLr (11 females, 9 males; age: 20.9 ± 4.4 years; height:172.4 ± 7.5 cm; weight:76.2 ± 11.8 kg) and 20 healthy controls (11 females, 9 males; age:21.7 ± 3.7 years; height: 173.7 ± 9.9 cm; weight: 76.1 ± 19.7 kg). Maximal voluntary isometric contractions (MVIC), central activation ratio (CAR), normalized Hoffmann spinal reflexes, active motor threshold (AMT), and normalized motor‐evoked potential (MEP) amplitudes at 120% of AMT were measured in the quadriceps muscle at the specific time points. ACLr patients demonstrated bilateral reductions in spinal‐reflexive excitability compared with controls before surgery (P = 0.02) and 2 weeks post‐surgery (P ≤ 0.001). ACLr patients demonstrated higher AMT at 6 months post‐surgery (P ≤ 0.001) in both limbs. No MEP differences were detected. Quadriceps MVIC and CAR were lower in both limbs of the ACLr group before surgery and 6 months post‐surgery (P ≤ 0.05) compared with controls. Diminished excitability of spinal‐reflexive and corticospinal pathways are present at different times following ACLr and occur in combination with clinical deficits in quadriceps strength and activation. Early rehabilitation strategies targeting spinal‐reflexive excitability may help improve postoperative outcomes, while later‐stage rehabilitation may benefit from therapeutic techniques aimed at improving corticospinal excitability.     

The Extended Rapid Response System: 1-Year Experience in a University Hospital

The rapid response system (RRS) is an innovative system designed for in-hospital, at-risk patients but underutilization of the RRS generally results in unexpected cardiopulmonary arrests. We implemented an extended RRS (E-RRS) that was triggered by actively screening at-risk patients prior to calls from primary medical attendants. These patients were identified from laboratory data, emergency consults, and step-down units. A four-member rapid response team was assembled that included an ICU staff, and the team visited the patients more than twice per day for evaluation, triage, and treatment of the patients with evidence of acute physiological decline. The goal was to provide this treatment before the team received a call from the patient''s primary physician. We sought to describe the effectiveness of the E-RRS at preventing sudden and unexpected arrests and in-hospital mortality. Over the 1-yr intervention period, 2,722 patients were screened by the E-RRS program from 28,661 admissions. There were a total of 1,996 E-RRS activations of simple consultations for invasive procedures. After E-RRS implementation, the mean hospital code rate decreased by 31.1% and the mean in-hospital mortality rate was reduced by 15.3%. In conclusion, the implementation of E-RRS is associated with a reduction in the in-hospital code and mortality rates.

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