Abstract BACKGROUND Meningioma is typically benign and is occasionally detected during examinations due to other reasons (e.g. suspected stroke, trauma). Reported incidence figures usually come from various registers, and most reported prevalence figures are estimations derived from incidence figures and survival data. The Region Örebro County meningioma project aims to gain a better understanding of the incidence and prevalence of meningioma in the population. With these preliminary data, we seek to ascertain the practical feasibility of our proposed search method. MATERIAL AND METHODS In the Swedish county of Örebro with 302,252 inhabitants (2019), all radiology departments are within the public healthcare system. The electronic radiology archive (ERA) includes all patients who have undergone any type of radiological examination in the region since its introduction in 1996. To determine the number of individuals with meningioma in the region and when they were diagnosed, we conducted free-text searches for the word “meningioma” with various spelling variations in ERA and included all patients where the word appears in ERA referrals or responses. Subsequently, using data from the region’s electronic medical records (EMR), we excluded all patients not residing within the region. We then manually reviewed these patients’ referrals, written reports and radiology examinations, to determine whether they have meningioma, the date of diagnosis, whether it was an incidental finding, and presence of multiple meningioma. RESULTS We identified 3,428 patients, of which 3,064 have been included in this study (being residents of the region). In a preliminary review, we have been able to identify 1,663 (55 %) patients with likely meningioma. Of the 1,663 patients, 5 % had a diagnosis date before the introduction of ERA. The median age was 73 (IQR 61-82) years. There were 24 % males and 76 % females. Multiple meningioma were found in 9 % of the patients. In the preliminary review 64 % were incidental findings, while 21 % and 15 % were classified as non-incidental and indeterminate, respectively. CONCLUSION Performing free-text ERA/EMR searches is a potential avenue to achieve better coverage when investigating incidence and prevalence of a disease such as meningioma in a public healthcare setting. In our initial review, it is evident that the method identifies and can retrieve meningioma patients from the ERA. Gender distribution, median age and multiple meningioma numbers are comparable to other reported meningioma populations. Based on our experience with this dataset, it is not advisable to rely solely on simple automated searches. Projects akin to this would likely be well suited for future automated image analysis (volumetric measurement, meningioma identification, etc.).

The Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG) conducted the SAKK 35/14 randomized phase-2 trial (NCT02451111) to evaluate the safety and efficacy of frontline treatment with ibrutinib plus rituximab compared to rituximab plus placebo in adult patients (pts) with advanced follicular lymphoma in need of therapy. Ibrutinib was administered orally (560 mg once a day) for 24 months (104 weeks), while rituximab was given intravenously (375 mg/m2) on day 1 of weeks 1, 2, 3, and 4, and subsequently every 2 months for 12 maintenance administrations, given either intravenous (375 mg/m2) or subcutaneous (1400 mg flat dose) based on local policy. The primary endpoint was the complete remission (CR) rate at 24 months after randomization determined on PET/CT scans by an independent review panel. In total, 192 pts were randomized (98 in arm A rituximab + placebo; 94 in arm B rituximab + ibrutinib) with stratification by rituximab maintenance route, lymphoma grade, follicular lymphoma international prognostic index, and bulky (≥6 cm) disease. The CR rate at 24 months was 36% (95% CI, 26%–46%) in arm A and 40% (95% CI, 30%–51%) in arm B with an odds ratio (OR) of 0.80 (95% CI, 0.44–1.46; p = 0.233). At a median follow-up of 42 months, the 3-year progression-free survival (PFS) rate was 36% in arm A (95% CI, 19%–54%) and 45% (95% CI, 25%–64%) in arm B, with a hazard ratio (HR) of 1.63 (95% CI, 0.99–2.7; p = 0.056). At 3 years after randomization, 45% (95% CI, 36%–56%) of pts in arm A and 39% (95% CI, 30%–50%) in arm B had already required a new treatment, with a HR of 1.47 (95% CI, 0.93–2.32; p = 0.099). The 3-year overall survival rate (OS) approximated 96% in both arms (95% CI, ∼89%–99%) with a HR of 1.02 (95% CI, 0.29–3.55; p = 0.979). The percentage of pts experiencing at least one adverse event (AE) was similar in the two arms (100% and 99%). However, 29% of pts experienced at least one AE of grade ≥3 in arm A while this was the case for 49% of pts in arm B. The percentage of pts experiencing AEs related to trial treatment was also lower in arm A (67%) than in arm B (84%). A total of 93 SAEs were reported, 42 in arm A, affecting 26% of pts, and 51 in arm B, involving 39% of pts. A total of 7 SUSARS occurred, 1 in arm A and 6 in arm B. The most frequent AEs of grade ≥3 during treatment were neutropenia (8% in arm A and 14% in arm B), lymphocytosis (5% in arm A and 10% in arm B), hypertension (5% in each arm), and maculo-papular skin rash (not observed in arm A, 11% in arm B). The SAKK35/14 study was partly funded by Janssen Cilag AG, Roche Pharma (Schweiz) AG, and the Hubacher Fonds. Keywords: immunotherapy, indolent non-Hodgkin lymphoma, molecular Targeted Therapies Conflicts of interests pertinent to the abstract A. Stathis Consultant or advisory role: Janssen, Roche Research funding: Abbvie, ADC Therapeutics, Amgen, AstraZeneca, Bayer, Cellestia, Incyte, LoxoOncology, Merck, Novartis, Pfizer, Philogen, Roche Educational grants: AstraZeneca Other remuneration: Expert testimonies: Bayer, Eli/Lilly F. Hitz Consultant or advisory role: Takeda, Abbvie, Roche E. Zucca Consultant or advisory role: BeiGene, BMS/Celgene, Celltion Healthcare, Curis, Eli/Lilly, Incyte, Ipsen, Janssen, Kyte (a Gilead Company), Merck, Roche Research funding: AstraZeneca, BMS/Celgene, Incyte, Janssen, Merck, Roche Educational grants: Abbvie, BeiGene, Janssen, Roche.

The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.

Background Although high grade gliomas largely affect older patients, current evidence on neurosurgical complications is mostly based on studies including younger study populations. We aimed to investigate the risk for postoperative complications after neurosurgery in a population-based cohort of older patients with high grade gliomas, and explore changes over time. Methods In this retrospective study we have used data from the Swedish Brain Tumour Registry and included patients in Sweden age 65 years or older, with surgery 1999–2017 for high grade gliomas. We analysed number of surgical procedures per year and which factors contribute to postoperative morbidity and mortality. Results The study included 1998 surgical interventions from an area representing 60% of the Swedish population. Over time, there was an increase in surgical interventions in relation to the age specific population ( p < 0.001). Postoperative morbidity for 2006–2017 was 24%. Resection and not having a multifocal tumour were associated with higher risk for postoperative morbidity. Postoperative mortality for the same period was 5%. Increased age, biopsy, and poor performance status was associated with higher risk for postoperative mortality. Conclusions This study shows an increase in surgical interventions over time, probably representing a more active treatment approach. The relatively low postoperative morbidity- and mortality-rates suggests that surgery in older patients with suspected high grade gliomas can be a feasible option. However, caution is advised in patients with poor performance status where the possible surgical intervention would be a biopsy only. Further, this study underlines the need for more standardised methods of reporting neurosurgical complications.

Background Meningioma is the most common primary CNS tumour. Most meningiomas are benign, and most patients are 65 years or older. Surgery is usually the primary treatment option. Most prior studies on early surgical outcomes in older patients with meningioma are small, and there is a lack of larger population-based studies to guide clinical decision-making. We aimed to explore the risks for perioperative mortality and morbidity in older patients with meningioma and to investigate changes in surgical incidence over time. Methods In this retrospective population-based study on patients in Sweden, 65 years or older with surgery 1999–2017 for meningioma, we used data from the Swedish Brain Tumour Registry. We analysed factors contributing to perioperative mortality and morbidity and used official demographic data to calculate yearly incidence of surgical procedures for meningioma. Results The final study cohort included 1676 patients with a 3.1% perioperative mortality and a 37.6% perioperative morbidity. In multivariate analysis, higher age showed a statistically significant association with higher perioperative mortality, whereas larger tumour size and having preoperative symptoms were associated with higher perioperative morbidity. A numerical increased rate of surgical interventions after 2012 was observed, without evidence of worsening short-term surgical outcomes. Conclusions Higher mortality with increased age and higher morbidity risk in larger and/or symptomatic tumours imply a possible benefit from considering surgery in selected older patients with a growing meningioma before the development of tumour-related symptoms. This study further underlines the need for a standardized method of reporting and classifying complications from neurosurgery.

Background: Meningioma surgery is often considered, even at a high age, and is regarded an acceptable practice in patients without severe health problems even though there is much that is not yet k ...

Background: Disulfiram (DSF) is a well-tolerated, inexpensive, generic drug that has been in use to treat alcoholism since the 1950s. There is now independent preclinical data that supports DSF as an anticancer agent, and experimental data suggest that copper may increase its anti-neoplastic properties. There is also some clinical evidence that DSF is a promising anticancer agent in extracranial cancers. In glioblastoma, DSF induced O6-methylguanine methyltransferase (MGMT) inhibition may increase response to alkylating chemotherapy. A recent phase I study demonstrated the safety of DSF in glioblastoma patients when DSF was administered at doses below 500 mg/day together with chemotherapy. We plan to assess the effects of DSF combined with nutritional copper supplement (DSF-Cu) as an adjuvant to alkylating chemotherapy in glioblastoma treatment. Methods: In an academic, industry independent, multicenter, open label randomized controlled phase II/III trial with parallel group design (1:1) we will assess the efficacy and safety of DSF-Cu in glioblastoma treatment. The study will include 142 patients at the time of first recurrence of glioblastoma where salvage therapy with alkylating chemotherapy is planned. Patients will be randomized to treatment with or without DSF-Cu. Primary end-point is survival at 6 months. Secondary end-points are overall survival, progression free survival, quality of life, contrast enhancing tumor volume and safety. Discussion: There is a need to improve the treatment of recurrent glioblastoma. Results from this randomized controlled trial with DSF-Cu in glioblastoma will serve as preliminary evidence of the future role of DSF-Cu in glioblastoma treatment and a basis for design and power estimations of future studies. In this publication we provide rationale for our choices and discuss methodological issues. Trial registration: The study underwent registration in EudraCT 2016-000167-16 (Date: 30.03.2016,) and Clinicaltrials.gov NCT02678975 (Date: 31.01.2016) before initiating the study.

There is a trend in brain tumor treatments over time to treat patients at a higher age and to perform more advanced and radical surgery. Despite this little is known about the perioperative morbidity and mortality after intracranial tumor surgery, especially regarding the elderly. The Swedish brain tumor registry has collected data since 1999 with good coverage and is considered population based. Among the parameters registered are perioperative complications such as postoperative hematoma and thromboembolism as well as newly diagnosed epilepsy, new focal neurologic deficit and date of death. Data from the registry has been collected and analyzed in this retrospective population based study. This study includes patients in the registry at age 65 or older, with high grade glioma (GBM, astrocytoma grIII), low grade glioma (astrocytoma grI-II, oligodendroglioma grII-III and gangliogliomas) registered from 1999 to 2015. Formation of diagnose groups are in conjunction with suggestions from the Swedish National Brain Tumor Trialist Group. From this data we have excluded patients that have not undergone surgery, where surgery (or not) cannot be determined and where data on complications is unavailable. Only the national regions with a high enough coverage are included. The material contains 1467 evaluable patients. High grade gliomas were 1277 (male 59%, female 41%), median age at surgery 71 (range 65 to 86), women not older (72 VS 71; NS). 17,5% (male 16,4%, female 20,0%; NS) had WHO/ECOG-PS >2. Perioperative mortality was 7,8% (male 9,2%, female 5,9%; p=0,03), associated with WHO/ECOG-PS >2 (p<0,0001). 15,7% (male 17,3%, female 13,5%; NS) had perioperative complications. The most common complication was worsening of neurologic function (7,6%, male 8,4%, female 6,5%; NS) and most patients (10,8%, male 12,8%, female 8,0%; NS) had one recorded complication. The mortality and morbidity remains consistent regardless of year of surgery. Low grade gliomas were 190 (male 55% VS female 45%), median age 70 (65 to 83), men not significantly older (71 VS 69; NS). 16,8% (male 15,7%, female 19,5%; NS) had WHO/ECOG-PS >2. Perioperative mortality was 5,3% (male 6,7%, female 3,5%; NS). 20,0% (male 21%, female 18,8%; NS) had perioperative complications. As with high grade gliomas the most common complication was worsening of neurologic function (13,7%, male 15,2%, female 11,8%; NS) and the mortality and morbidity remains without significant changes regardless of year of surgery. In this material we can conclude that the perioperative mortality as well as morbidity is higher than in published younger patient materials for gliomas. We cannot see an increase in perioperative mortality or morbidity with higher age within the material but this could be from lack of power and we hope to be able to get a clearer view in a later comparison with the younger patients in the registry.