Wait-and-Scan management in sporadic Koos grade 4 vestibular schwannomas:A longitudinal volumetric study

BackgroundVolumetric natural history studies specifically on large vestibular schwannomas (VSs), commonly classified as Koos grade 4, are lacking. The aim of the current study is to present the volumetric tumor evolution in sporadic Koos grade 4 VSs and possible predictors for tumor growth.MethodsVolumetric tumor measurements and tumor evolution patterns from serial MRI studies were analyzed from selected consecutive patients with Koos grade 4 VS undergoing initial wait-and-scan management between January 2001 and July 2020. The significant volumetric threshold was defined as a change in volume of ≥10%.ResultsAmong 215 tumors with a median size (IQR) of 2.7cm3 (1.8-4.2), 147 tumors (68%) demonstrated growth and 75 tumors (35%) demonstrated shrinkage during follow-up. Growth-free survival rates (95% CI) at 1, 2, 5, and 10 years were 55% (48-61), 36% (29-42), 29% (23-36), and 28% (21-34), respectively and did not significantly differ in tumors >20 mm (Chi-square=.40; P-value=.53). Four tumor evolution patterns (% of total) were observed: continued growth (60); initial growth then shrinkage (7); continued shrinkage (27); and stability (5). Good hearing (adjusted HR 2.21, 95% CI 1.48-3.30; P<.001) and peritumoral edema (adjusted HR 2.22, 95% CI 1.18-4.13; P.01) at diagnosis were significantly associated with an increased likelihood of growth.ConclusionsKoos grade 4 VSs show a wide variety in size and growth. Due to variable growth patterns, an initial wait-and-scan strategy with short scan intervals may be an acceptable option in selected tumors, if no significant clinical symptoms of mass effect that warrant treatment are present

Agreement between oral contraceptive users and prescribers: implications for case-control studies

Case-control studies examining the effects of oral contraceptives (OC) are prone to misclassification bias due to errors in assessment of OC use. Concern about inaccurate exposure histories has increased since current studies require women to recall OC use over prolonged periods of time. In preparation for a case-control study of breast cancer and OC use, an investigation was carried out to assess agreement between women's lifetime histories of OC use (covering a period of up to 20 years) and prescribers' records. OC histories were obtained during personal interview with 218 women who had used OC at some point in their lives (127 breast cancer patients, 91 controls). Recall was aided by an album with color photographs of all OC marketed in the Netherlands from 1962 onwards (n = 65), and a calendar that covered the women's life span from date of birth to menopause. The participants were asked for the names of all physicians who prescribed OC for them. The rate of response from the prescribers was high (94%), but only half of the forms provided useful information. Patient-prescriber agreement on brand names (including dosage) was 70%. About half of the women agreed with their prescribers on starting dates to within less than a year's difference. Approximately the same percentage of agreement was found for stopping dates. Multiple linear regression indicated that agreement on brand names and dates of usage was lower for women of low socioeconomic status, for healthy women (as compared to breast cancer patients) and for periods of pill use that had to be recalled from the more distant past. Agreement on total duration of use was high enough to permit testing of a moderately strong duration-response relationship in a case-control study

Zeniplatin in patients with advanced ovarian cancer, a phase II study with a third generation platinum complex

25 patients with residual or recurrent ovarian cancer were treated with the new platinum complex zeniplatin (CL 286,558) and 23 patients were evaluable for response. Responses were achieved in 4 patients, 1 complete and 3 partial remissions (16%). 7 patients had stable disease and 12 patients had tumour progression. At a median follow-up of 12 months, the median progression-free survival in responding patients was 11 months and overall survival 81%. The median overall survival of progressive patients amounted to 9 months, indicating the advanced stage of disease in most patients. Renal function was monitored by isotope clearance studies. There was no significant change in effective renal plasma flow (ERPF) or glomerular filtration rate (GFR) in 10 patients who completed six cycles of treatment. 1 patient with a marginal creatinine clearance at baseline suffered from sudden and severe renal failure during the first cycle. Zeniplatin may be active in relapsing, platinum-pretreated patients, and has no direct effects on renal function as measured by isotope clearance. Despite these findings, occasional nephrotoxicity may occur in patients with compromised kidney function, even with prophylactic hydration, and thus limit the application of this new analogue

Admission Blood Pressure in Relation to Clinical Outcomes and Successful Reperfusion After Endovascular Stroke Treatment

BACKGROUND AND PURPOSE: Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and clinical outcomes and successful reperfusion after EVT. METHODS: We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, an observational, prospective, nationwide cohort study of patients with ischemic stroke treated with EVT in routine clinical practice in the Netherlands. Baseline systolic BP (SBP) and diastolic BP (DBP) were recorded on admission. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2B-3), symptomatic intracranial hemorrhage, and 90-day mortality. Multivariable logistic and linear regression were used to assess the associations of SBP and DBP with outcomes. The relations between BPs and outcomes were tested for nonlinearity. Parameter estimates were calculated per 10 mm Hg increase or decrease in BP. RESULTS: We included 3180 patients treated with EVT between March 2014 and November 2017. The relations between admission SBP and DBP with 90-day modified Rankin Scale scores and mortality were J-shaped, with inflection points around 150 and 81 mm Hg, respectively. An increase in SBP above 150 mm Hg was associated with poor functional outcome (adjusted common odds ratio, 1.09 [95% CI, 1.04-1.15]) and mortality at 90 days (adjusted odds ratio, 1.09 [95% CI, 1.03-1.16]). Following linear relationships, higher SBP was associated with a lower probability of successful reperfusion (adjusted odds ratio, 0.97 [95% CI, 0.94-0.99]) and with the occurrence of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.06 [95% CI, 0.99-1.13]). Results for DBP were largely similar. CONCLUSIONS: In patients with acute ischemic stroke treated with EVT, higher admission BP is associated with lower probability of successful reperfusion and with poor clinical outcomes. Further research is needed to investigate whether these patients benefit from BP reduction before EVT

Influence of pretreatment growth rate on Gamma Knife treatment response for vestibular schwannoma: a volumetric analysis

OBJECTIVE The aim of this study was to gain insight into the influence of the pretreatment growth rate on the volumetric tumor response and tumor control rates after Gamma Knife radiosurgery (GKRS) for incidental vestibular schwannoma (VS). METHODS All patients treated with GKRS at the Gamma Knife Center, ETZ Hospital, who exhibited a confirmed radiological progression of their VS after an initial observation period were included. Pre- and posttreatment MRI scans were volumetrically evaluated, and the volume doubling times (VDTs) prior to treatment were calculated. Posttreatment volumes were used to create an objective mathematical failure definition: 2 consecutive significant increases in tumor volume among 3 consecutive follow-up MRI scans. Spearman correlation, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were used to determine the influence of the VDT on the volumetric treatment response. RESULTS The resulting patient cohort contained 311 patients in whom the VDT was calculated. This cohort had a median follow-up time of 60 months after GKRS. Of these 311 patients, 35 experienced loss of tumor control after GKRS. The pretreatment growth rate and the relative volume changes, calculated at 6 months and 1, 2, and 3 years following treatment, showed no statistically significant correlation. Kaplan-Meier analysis revealed that slow-growing tumors, with a VDT equal to or longer than the median VDT of 15 months, had calculated 5- and 10-year control rates of 97.3% and 86.0%, respectively, whereas fast-growing tumors, with a VDT less than the median growth rate, had control rates of 85.5% and 67.6%, respectively (log-rank, p = 0.001). The influence of the VDT on tumor control was also determined by employing the Cox regression analysis. The resulting model presented a significant (p = 0.045) effect of the VDT on the hazard rates of loss of tumor control. CONCLUSIONS By employing a unique, large database with long follow-up times, the authors were able to accurately investigate the influence of the pretreatment VS growth rate on the volumetric GKRS treatment response. The authors have found a predictive model that illustrates the negative influence of the pretreatment VS growth rate on the efficacy of radiosurgery treatment. The resulting tumor control rates confirm the high efficacy of GKRS for slow-growing VS. However, fast-growing tumors showed significantly lower control rates. For these cases, different treatment strategies may be considered

Correlation between pre-treatment growth rate and tumor control of vestibular schwannomas after gamma knife radiosurgery in the dutch database

Introduction: Prognostic factors of tumor control after Gamma Knife Radiosurgery (GKRS) for vestibular schwannoma (VS) are largely unknown. Recently, it has been reported that the growth rate of VS before treatment is indicative of the chance that radiosurgery achieves tumor control. Such findings may have important implications for treatment strategies and may lead to advise for either microsurgery or higher marginal doses for fast growing tumors. However, studies on this important aspect are limited and show conflicting results. Moreover, the available studies are hampered by methodological limitations such as limited patient numbers and followup and two-dimensional assessment of tumor size. The objective of this study is to identify a possible correlation between pre-treatment growth rate and tumor control after GKRS in a large database with sufficient follow-up and volumetric tumor assessments. Methods: In the prospectively collected database of the Gamma Knife Center Tilburg, 445 patients with VS, treated between 2002 and 2014, that showed documented growth before treatment and who have had a minimum follow-up of 2 years after treatment, were identified. Tumor volumes before, at and after treatment were assessed. GKRS was performed in a uniform way, with a dose of 12-13Gy prescribed to the isodose line covering 90-99% of the target. Failures were defined as tumor progression on 2 consecutive MRI’s beyond 2 years after GKRS, or as judged by the radiosurgical team. Volume doubling times (VDT) before treatment were correlated with the observed tumor control rates and volumetric responses after treatment. Results: Until now 266 of the 445 patients with documented pre-treatment tumor growth have been analyzed. 25 Patients were lost to follow-up. The median follow-up was 4 years. 25 Patients showed a radiological failure. The 5- and 10-year actuarial control rates were 91% and 78% respectively. VDT varied from 3 to 344 months, with a median of 16 months. Using the Mann-Whitney-U test, the VDT of tumors that showed tumor control is significantly higher than those that failed (p=0.01). After stratifying for VDT at the median, slow growing tumors showed a 5- and 10-year actuarial control rate of 97% and 89%, where the fast growing tumors had a 5- and 10-year control rate of 85% and 68% (p=0.009). Conclusion: This study clearly shows that the pretreatment growth rate correlates with the observed tumor control after GKRS. Fast growing tumors are less likely to show tumor control. This finding might justify alterations in the management of VS