Paal‐Henning Pedersen

OBJECTIVE: To conduct a prospective, open, nonrandomized study of treatment-associated morbidity in patients undergoing microsurgery or gamma knife radiosurgery (GKRS) for vestibular schwannomas. METHODS: Ninety-one patients with vestibular schwannomas with a maximum tumor diameter of 25 mm in the cerebellopontine angle were treated according to a prospective protocol either by GKRS (63 patients) or open microsurgery (28 patients) using the suboccipital approach. Primary end points included hearing function, according to the Gardner-Robertson scale, and facial nerve function, according to the House-Brackmann scale at 2 years. Clinical data included a balance platform test, score for tinnitus and vertigo using a visual analog scale, and working ability. Patients responded to the quality-of-life questionnaires Short-Form 36 and Glasgow Benefit Inventory. RESULTS: Three elderly GKRS patients withdrew; all remaining patients were followed for 2 years. Both primary end points were highly significant in favor of GKRS (P < 0.001). Evidence of reduced facial nerve function (House-Brackmann grade 2 or poorer) at 2 years was found in 13 of 28 open microsurgery patients and 1 of 60 GKRS patients. Thirteen of 28 patients who underwent surgery had serviceable hearing (Gardner-Robertson grade A or B) preoperatively, but none had serviceable hearing postoperatively. Twenty-five of 60 GKRS patients had serviceable hearing before treatment, and 17 (68%) of them had serviceable hearing 2 years after treatment. The tinnitus and vertigo visual analog scale score, as well as balance platform tests, did not change significantly after treatment, and working status did not differ between the groups at 2 years. Quality of life was significantly better in the GKRS group at 2 years, based on the Glasgow Benefit Inventory questionnaire. One GKRS patient required operative treatment within the 2-year study period. CONCLUSION: This is the second prospective study to demonstrate better facial nerve and hearing outcomes from GKRS than from open surgery for small- and medium-sized vestibular schwannomas.

BACKGROUND: Radiosurgery is the main alternative to microsurgical resection for benign meningiomas. OBJECTIVE: To assess the long-term efficacy and safety of radiosurgery for meningiomas with respect to tumor growth and prevention of associated neurological deterioration. Medium- to long-term outcomes have been widely reported, but no large multicenter series with long-term follow-up have been published. METHODS: From 15 participating centers, we performed a retrospective observational analysis of 4565 consecutive patients harboring 5300 benign meningiomas. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author (A.S.). RESULTS: Median tumor volume was 4.8 cm³, and median dose to tumor margin was 14 Gy. All tumors with imaging follow-up < 24 months were excluded. Detailed results from 3768 meningiomas (71%) were analyzed. Median imaging follow-up was 63 months. The volume of treated tumors decreased in 2187 lesions (58%), remained unchanged in 1300 lesions (34.5%), and increased in 281 lesions (7.5%), giving a control rate of 92.5%. Only 84 (2.2%) enlarging tumors required further treatment. Five- and 10-year progression-free survival rates were 95.2% and 88.6%, respectively. Tumor control was higher for imaging defined tumors vs grade I meningiomas (P < .001), for female vs male patients (P < .001), for sporadic vs multiple meningiomas (P < .001), and for skull base vs convexity tumors (P < .001). Permanent morbidity rate was 6.6% at the last follow-up. CONCLUSION: Radiosurgery is a safe and effective method for treating benign meningiomas even in the medium to long term.

OBJECT: The optimal treatment for sporadic vestibular schwannoma (VS) is highly controversial. To date, the majority of studies comparing treatment modalities have focused on a narrow scope of technical outcomes including facial function, hearing status, and tumor control. Very few publications have investigated health-related quality of life (HRQOL) differences between individual treatment groups, and none have used a disease-specific HRQOL instrument. METHODS: All patients with sporadic small- to medium-sized VSs who underwent primary microsurgery, stereotactic radiosurgery (SRS), or observation between 1998 and 2008 were identified. Subjects were surveyed via postal questionnaire using the 36-Item Short Form Health Survey (SF-36), the 10-item Patient-Reported Outcomes Measurement Information System short form (PROMIS-10), the Glasgow Benefit Inventory (GBI), and the Penn Acoustic Neuroma Quality-of-Life (PANQOL) scale. Additionally, a pool of general population adults was surveyed, providing a nontumor control group for comparison. RESULTS: A total of 642 respondents were analyzed. The overall response rate for patients with VS was 79%, and the mean time interval between treatment and survey was 7.7 years. Using multivariate regression, there were no statistically significant differences between management groups with respect to the PROMIS-10 physical or mental health dimensions, the SF-36 Physical or Mental Component Summary scores, or the PANQOL general, anxiety, hearing, or energy subdomains. Patients who underwent SRS or observation reported a better total PANQOL score and higher PANQOL facial, balance, and pain subdomain scores than the microsurgical cohort (p < 0.02). The differences in scores between the nontumor control group and patients with VS were greater than differences observed between individual treatment groups for the majority of measures. CONCLUSIONS: The differences in HRQOL outcomes following SRS, observation, and microsurgery for VS are small. Notably, the diagnosis of VS rather than treatment strategy most significantly impacts quality of life. Understanding that a large number of VSs do not grow following discovery, and that intervention does not confer a long-term HRQOL advantage, small- and medium-sized VS should be initially observed, while intervention should be reserved for patients with unequivocal tumor growth or intractable symptoms that are amenable to treatment. Future studies assessing HRQOL in VS patients should prioritize use of validated disease-specific measures, such as the PANQOL, given the significant limitations of generic instruments in distinguishing between treatment groups and tumor versus nontumor subjects.

Spheroids initiated directly from human primary gliomas were used to investigate the effects of EGF, bFGF, NGF and PDGF(bb) on cell proliferation, migration and invasion into foetal rat brain tissue. EGF increased tumour spheroid volume in 10 of 13 glioblastomas studied, whereas 5 of 11 tumours responded to bFGF. NGF increased the spheroid volume in 2 of 5 tumours. In 8 tumours, PDGF(bb) had no effect on tumour spheroid volume. An increase in BUdR-labelling indices confirmed that cell proliferation was responsible for the volume increase observed in stimulated spheroids. EGF stimulated cell migration in 5 and bFGF in 3 of 8 tumours studied. NGF stimulated cell migration in 1 of 5 glioblastomas, whereas 1 of 3 glioblastomas responded to PDGF(bb). The effects of growth factors on the invasion of spheroids prepared from the glioblastoma biopsy specimens were also studied in vitro using foetal rat brain aggregates as target tissue. EGF stimulated invasion in 7 of 8 glioblastomas studied, whereas bFGF stimulated invasion in 2 of these tumours. NGF or PDGF(bb) did not increase the invasiveness of the glioblastoma tissue. Our results represent the net effect of the growth factors on a complex tumour-cell population. We conclude that exogenously administered growth factors, EGF in particular, increase the cell proliferation as well as migratory and invasive capacities of cultured primary brain tumour biopsies in vitro.