First-line palliative systemic therapy alternated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for unresectable colorectal peritoneal metastases: A single-arm phase II trial (CRC-PIPAC-II).

BACKGROUND: Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy. METHODS: This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m2) with intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS). RESULTS: Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval [CI] 8.0-13.0) and median OS was 17.5 months (95 % CI 13.0-not reached). CONCLUSIONS: Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy.

The additional value of 68Ga-PSMA PET/CT SUVmax in predicting ISUP GG ≥ 2 and ISUP GG ≥ 3 prostate cancer in biopsy.

BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.

Automated pelvic MRI measurements associated with urinary incontinence for prostate cancer patients undergoing radical prostatectomy.

BACKGROUND: Pelvic morphological parameters on magnetic resonance imaging (MRI), such as the membranous urethral length (MUL), can predict urinary incontinence after radical prostatectomy but are prone to interobserver disagreement. Our objective was to improve interobserver agreement among radiologists in measuring pelvic parameters using deep learning (DL)-based segmentation of pelvic structures on MRI scans. METHODS: Preoperative MRI was collected from 167 prostate cancer patients undergoing radical prostatectomy within our regional multicentric cohort. Two DL networks (nnU-Net) were trained on coronal and sagittal scans and evaluated on a test cohort using an 80/20% train-test split. Pelvic parameters were manually measured by three abdominal radiologists on raw MRI images and with the use of DL-generated segmentations. Automated measurements were also performed for the pelvic parameters. Interobserver agreement was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: The DL models achieved median Dice similarity coefficient (DSC) values of 0.85-0.97 for coronal structures and 0.87-0.98 for sagittal structures. When radiologists used DL-generated segmentations of pelvic structures, the interobserver agreement for sagittal MUL improved from 0.64 (95% confidence interval 0.28-0.83) to 0.91 (95% CI 0.84-0.95). Furthermore, there was an increase in ICC values for the obturator internus muscle from 0.74 (95% CI 0.42-0.87) to 0.86 (95% CI 0.75-0.92) and for the levator ani muscle from 0.40 (95% CI 0.05-0.66) to 0.61 (95% CI 0.31-0.78). CONCLUSIONS: DL-based automated segmentation of pelvic structures improved interobserver agreement in measuring pelvic parameters on preoperative MRI scans. RELEVANCE STATEMENT: The implementation of deep learning segmentations allows for more consistent measurements of pelvic parameters by radiologists. Standardized measurements are crucial for incorporating these parameters into urinary continence prediction models. KEY POINTS: • DL-generated segmentations improve interobserver agreement for pelvic measurements among radiologists. • Membranous urethral length measurement improved from substantial to almost perfect agreement. • Artificial intelligence enhances objective pelvic parameter assessment for continence prediction models.

Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Active Surveillance for Prostate Cancer Trial (PASPoRT).

BACKGROUND: The use of clinical parameters, including prebiopsy magnetic resonance imaging (MRI), to decide between active surveillance (AS) and active therapy for prostate cancer (PCa) leads to imperfect selection. Additional prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging may improve risk stratification. OBJECTIVE: To study risk stratification and patient selection for AS with the addition of PSMA PET/CT to standard practice. DESIGN, SETTING, AND PARTICIPANTS: A single-centre prospective cohort study (NL69880.100.19) enrolled patients recently diagnosed with PCa who started AS. At diagnosis, all participants had undergone prebiopsy MRI and targeted biopsy for visualised lesions. Patients underwent an additional [68Ga]-PSMA PET/CT and targeted biopsy of all PSMA lesions with a maximum standardised uptake value (SUVmax) of ≥4 not covered by previous biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number needed to scan (NNS) to detect one patient with upgrading. The study was powered to detect an NNS of 10. Regarding secondary outcomes, univariate logistic regressions analyses were performed on all patients and on the patients who received additional PSMA targeted biopsies on the likelihood of upgrading. RESULTS AND LIMITATIONS: A total of 141 patients were included. Additional PSMA targeted biopsies were performed in 45 (32%) patients. In 13 (9%) patients, upgrading was detected: nine grade group (GG) 2, two GG 3, one GG 4, and one GG 5. The NNS was 11 (95% confidence interval 6-18). Of all participants, PSMA PET/CT and targeted biopsies yielded upgrading most frequently in patients with negative MRI (Prostate Imaging Reporting and Data System [PI-RADS] 1-2). Of patients who received additional PSMA targeted biopsies, upgrading was most frequently found in those with higher prostate-specific antigen density and negative MRI. Limitations included the lack of comparison with standard repeat biopsy, no central review of MRI, and possibility of biopsy sampling error. CONCLUSIONS: PSMA PET/CT can further improve PCa risk stratification and selection for AS patients diagnosed after MRI and targeted biopsies. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography/computed tomography and additional targeted prostate biopsies can identify more aggressive prostate cancer cases previously missed in patients recently started with expectant management for favourable-risk prostate cancer.

The Development and External Validation of Artificial Intelligence-Driven MRI-Based Models to Improve Prediction of Lesion-Specific Extraprostatic Extension in Patients with Prostate Cancer.

Adequate detection of the histopathological extraprostatic extension (EPE) of prostate cancer (PCa) remains a challenge using conventional radiomics on 3 Tesla multiparametric magnetic resonance imaging (3T mpMRI). This study focuses on the assessment of artificial intelligence (AI)-driven models with innovative MRI radiomics in predicting EPE of prostate cancer (PCa) at a lesion-specific level. With a dataset encompassing 994 lesions from 794 PCa patients who underwent robot-assisted radical prostatectomy (RARP) at two Dutch hospitals, the study establishes and validates three classification models. The models were validated on an internal validation cohort of 162 lesions and an external validation cohort of 189 lesions in terms of discrimination, calibration, net benefit, and comparison to radiology reporting. Notably, the achieved AUCs ranged from 0.86 to 0.91 at the lesion-specific level, demonstrating the superior accuracy of the random forest model over conventional radiological reporting. At the external test cohort, the random forest model was the best-calibrated model and demonstrated a significantly higher accuracy compared to radiological reporting (83% vs. 67%, p = 0.02). In conclusion, an AI-powered model that includes both existing and novel MRI radiomics improves the detection of lesion-specific EPE in prostate cancer.

Outcomes of a Diagnostic Pathway for Prostate Cancer Based on Biparametric MRI and MRI-Targeted Biopsy Only in a Large Teaching Hospital.

BACKGROUND: Diagnostic pathways for prostate cancer (PCa) balance detection rates and burden. MRI impacts biopsy indication and strategy. METHODS: A prospectively collected cohort database (N = 496) of men referred for elevated PSA and/or abnormal DRE was analyzed. All underwent biparametric MRI (3 Tesla scanner) and ERSPC prostate risk-calculator. Indication for biopsy was PIRADS ≥ 3 or risk-calculator ≥ 20%. Both targeted (cognitive-fusion) and systematic cores were combined. A hypothetical full-MRI-based pathway was retrospectively studied, omitting systematic biopsies in: (1) PIRADS 1-2 but risk-calculator ≥ 20%, (2) PIRADS ≥ 3, receiving targeted biopsy-cores only. RESULTS: Significant PCa (GG ≥ 2) was detected in 120 (24%) men. Omission of systematic cores in cases with PIRADS 1-2 but risk-calculator ≥ 20%, would result in 34% less biopsy indication, not-detecting 7% significant tumors. Omission of systematic cores in PIRADS ≥ 3, only performing targeted biopsies, would result in a decrease of 75% cores per procedure, not detecting 9% significant tumors. Diagnosis of insignificant PCa dropped by 52%. PCa undetected by targeted cores only, were ipsilateral to MRI-index lesions in 67%. CONCLUSIONS: A biparametric MRI-guided PCa diagnostic pathway would have missed one out of six cases with significant PCa, but would have considerably reduced the number of biopsy procedures, cores, and insignificant PCa. Further refinement or follow-up may identify initially undetected cases. Center-specific data on the performance of the diagnostic pathway is required.

The Diagnostic Accuracy of Abdominal Computed Tomography in Diagnosing Internal Herniation Following Roux-en-Y Gastric Bypass Surgery: A Systematic Review and Meta-analysis.

OBJECTIVE: To analyze the diagnostic accuracy of abdominal computed tomography (CT) in diagnosing internal herniation (IH) following Rouxen-Y gastric bypass (RYGB) surgery. SUMMARY OF BACKGROUND DATA: IH is one of the most important and challenging complications following RYGB. Therefore, early and adequate diagnosis of IH is necessary. Currently, exploratory surgery is considered the gold standard in diagnosing IH. Although CT scans are frequently being used, the true diagnostic accuracy in diagnosing IH remains unclear. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for relevant articles describing the diagnostic accuracy of abdominal CT in diagnosing IH after RYGB. Data were extracted, recalculated, and pooled to report on the overall diagnostic accuracy of CT in diagnosing IH, and the diagnostic accuracy of specific radiological signs. RESULTS: A total of 20 studies describing 1637 patients were included. seventeen studies provided data regarding the overall diagnostic accuracy: pooled sensitivity of 82.0%, specificity of 84.8%, positive predictive value of 82.7%, and negative predictive value of 85.8% were calculated. Eleven studies reported on specific CT signs and their diagnostic accuracy. The radiological signs with the highest sensitivity were the signs of venous congestion, swirl, and mesenteric oedema (sensitivity of 78.7%, 77.8%, and 67.2%, respectively). CONCLUSIONS: This meta-analysis demonstrates that CT is a reliable imaging modality for the detection of IH. Therefore, abdominal CT imaging should be added to the diagnostic work-up for RYGB patients who present themselves with abdominal pain suggestive of IH to improve patient selection for explorative surgery.

Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effectiveness of endovascular therapy in patients with stroke caused by basilar-artery occlusion has not been well studied. METHODS: We randomly assigned patients within 6 hours after the estimated time of onset of a stroke due to basilar-artery occlusion, in a 1:1 ratio, to receive endovascular therapy or standard medical care. The primary outcome was a favorable functional outcome, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 to 6, with 0 indicating no disability, 3 indicating moderate disability, and 6 indicating death) at 90 days. The primary safety outcomes were symptomatic intracranial hemorrhage within 3 days after the initiation of treatment and mortality at 90 days. RESULTS: A total of 300 patients were enrolled (154 in the endovascular therapy group and 146 in the medical care group). Intravenous thrombolysis was used in 78.6% of the patients in the endovascular group and in 79.5% of those in the medical group. Endovascular treatment was initiated at a median of 4.4 hours after stroke onset. A favorable functional outcome occurred in 68 of 154 patients (44.2%) in the endovascular group and 55 of 146 patients (37.7%) in the medical care group (risk ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.50). Symptomatic intracranial hemorrhage occurred in 4.5% of the patients after endovascular therapy and in 0.7% of those after medical therapy (risk ratio, 6.9; 95% CI, 0.9 to 53.0); mortality at 90 days was 38.3% and 43.2%, respectively (risk ratio, 0.87; 95% CI, 0.68 to 1.12). CONCLUSIONS: Among patients with stroke from basilar-artery occlusion, endovascular therapy and medical therapy did not differ significantly with respect to a favorable functional outcome, but, as reflected by the wide confidence interval for the primary outcome, the results of this trial may not exclude a substantial benefit of endovascular therapy. Larger trials are needed to determine the efficacy and safety of endovascular therapy for basilar-artery occlusion. (Funded by the Dutch Heart Foundation and others; BASICS ClinicalTrials.gov number, NCT01717755; Netherlands Trial Register number, NL2500.).

First-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy (oxaliplatin) for isolated unresectable colorectal peritoneal metastases: protocol of a multicentre, single-arm, phase II study (CRC-PIPAC-II).

INTRODUCTION: Despite its increasing use, first-line palliative systemic therapy alternated with electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX), hereinafter referred to as first-line bidirectional therapy, has never been prospectively investigated in patients with colorectal peritoneal metastases (CPM). As a first step to address this evidence gap, the present study aims to assess the safety, feasibility, antitumour activity, patient-reported outcomes, costs and systemic pharmacokinetics of first-line bidirectional therapy in patients with isolated unresectable CPM. METHODS AND ANALYSIS: In this single-arm, phase II study in two Dutch tertiary referral centres, 20 patients are enrolled. Key eligibility criteria are a good performance status, pathologically proven isolated unresectable CPM, no previous palliative systemic therapy for colorectal cancer, no (neo)adjuvant systemic therapy ≤6 months prior to enrolment and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC). Patients receive three cycles of bidirectional therapy. Each cycle consists of 6 weeks first-line palliative systemic therapy at the medical oncologists' decision (CAPOX-bevacizumab, FOLFOX-bevacizumab, FOLFIRI-bevacizumab or FOLFOXIRI-bevacizumab) followed by ePIPAC-OX (92 mg/m2) with an intraoperative bolus of intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Study treatment ends after the third ePIPAC-OX. The primary outcome is the number of patients with-and procedures leading to-grade ≥3 adverse events (Common Terminology Criteria for Adverse Events V.5.0) up to 4 weeks after the last procedure. Key secondary outcomes include the number of bidirectional cycles in each patient, treatment-related characteristics, grade ≤2 adverse events, tumour response (histopathological, cytological, radiological, biochemical, macroscopic and ascites), patient-reported outcomes, systemic pharmacokinetics of oxaliplatin, costs, progression-free survival and overall survival. ETHICS AND DISSEMINATION: This study is approved by the Dutch competent authority, a medical ethics committee and the institutional review boards of both study centres. Results will be submitted for publication in peer-reviewed medical journals and presented to patients and healthcare professionals. TRIAL REGISTRATION NUMBER: NL8303.

Comparison of risk-calculator and MRI and consecutive pathways as upfront stratification for prostate biopsy.

PURPOSE: In biopsy naïve men suspected for prostate cancer (PCa), it is uncertain how a risk-calculator and bi-parametric (bp) MRI should be combined to decide on prostate biopsy, balancing cancer detection rates and diagnostic burden. METHODS: Prospective, single centre cohort study (August 2018-April 2019). All patients referred with serum PSA ≥ 3 ng/ml or abnormal digital rectal examination received bpMRI and risk for PCa was calculated using the ERSPC risk-calculator. Men with either PI-RADS ≥ 3 or calculator risk-score > 20% were recommended to undergo systematic biopsy (SB) and targeted biopsy (TB) of any visible lesion (reference pathway). Eight different derived diagnostic pathways were compared to the reference pathway regarding cancer detection, number of biopsies and bpMRIs performed. RESULTS: Of 496 patients; 233 (47%) had a risk-calculator score of > 20%; 201 (41%) had PI-RADS score ≥ 3. The reference pathway detected PCa in 32.1%, clinically significant (cs) PCa in 19.4%, with 41% avoided biopsies, but 0% avoided bpMRI. Stratification with only risk-calculator: 76% csPCa diagnosed, 53% avoided biopsies and 100% avoided bpMRI. Stratification with only bpMRI: 97% csPCa diagnosed, 59% avoided biopsies, but 0% avoided bpMRI. A pathway with risk-calculator first, followed only with bpMRI when high-risk: 81% csPCa diagnosed, 72% avoided biopsies and 53% avoided bpMRI. CONCLUSION: Upfront bpMRI as a risk stratification tool outperforms risk-calculator in detecting significant disease. Applying the risk-calculator first to decide on performing an MRI, avoids 1 out of 2 MRIs, but up to 1 out of 5 significant cancers are missed.

Additional diagnostic value of computed tomography perfusion for detection of acute ischemic stroke in the posterior circulation.

BACKGROUND AND PURPOSE: Detection of acute infarction in the posterior circulation is challenging. We aimed to determine the additional value of tomograpy (CT) perfusion to noncontrast CT and CT angiography source images for infarct detection and localization in patients suspected of acute ischemic posterior circulation stroke. METHODS: Patients with suspected acute ischemic posterior circulation stroke were selected from the Dutch acute Stroke Trial (DUST) study. Patients underwent noncontrast CT, CT angiography, and CT perfusion within 9 hours after stroke onset and CT or MRI on follow-up. Images were evaluated for signs and location of ischemia. Discrimination of 3 hierarchical logistic regression models (noncontrast CT [A], added CT angiography source images [B], and CT perfusion [C]) was compared with C-statistics. RESULTS: Of 88 patients, 76 (86%) had a clinical diagnosis of ischemic stroke on discharge and 42 patients (48%) showed a posterior circulation infarct on follow-up imaging. Model C (area under the curve from the receiver operating characteristic curve=0.86; 95% confidence interval, 0.77-0.94) predicted an infarct in the posterior circulation territory better than models A (area under the curve from the receiver operating characteristic curve=0.64; 95% confidence interval, 0.53-0.76; P(C versus A)<0.001) and B (area under the curve from the receiver operating characteristic curve=0.68; 95% confidence interval, 0.56-0.79; P(C versus B)<0.001). CONCLUSIONS: CT perfusion has significant additional diagnostic values to noncontrast CT and CT angiography source images for detecting ischemic changes in patients suspected of acute posterior circulation stroke.

Vertebral artery stenosis in the Basilar Artery International Cooperation Study (BASICS): prevalence and outcome.

We assessed the prevalence of vertebral artery (VA) stenosis or occlusion and its influence on outcome in patients with acute basilar artery occlusion (BAO). We studied 141 patients with acute BAO enrolled in the Basilar Artery International Cooperation Study (BASICS) registry of whom baseline CT angiography (CTA) of the intracranial VAs was available. In 72 patients an additional CTA of the extracranial VAs was available. Adjusted risk ratios (aRRs) for death and poor outcome, defined as a modified Rankin Scale score ≥4, were calculated with Poisson regression in relation to VA occlusion, VA occlusion or stenosis ≥50 %, and bilateral VA occlusion. Sixty-six of 141 (47 %) patients had uni- or bilateral intracranial VA occlusion or stenosis ≥50 %. Of the 72 patients with intra- and extracranial CTA, 46 (64 %) had uni- or bilateral VA occlusion or stenosis ≥50 % and 9 (12 %) had bilateral VA occlusion. Overall, VA occlusion or stenosis ≥50 % was not associated with the risk of poor outcome. Patients with intra- and extracranial CTA and bilateral VA occlusion had a higher risk of poor outcome than patients without bilateral VA occlusion (aRR, 1.23; 95 % CI 1.02-1.50). The risk of death did not depend on the presence of unilateral or bilateral VA occlusion or stenosis ≥50 %. In conclusion, in patients with acute BAO, unilateral VA occlusion or stenosis ≥50 % is frequent, but not associated with an increased risk of poor outcome or death. Patients with BAO and bilateral VA occlusion have a slightly increased risk of poor outcome.

Diagnostic and Prognostic Impact of pc-ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study.

BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-APECTS) applied to CT angiography source images (CTA-SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc-ASPECTS applied to perfusion CT (CTP) in the BASICS registry population. METHODS: We applied pc-ASPECTS to CTA-SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA-SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal. RESULTS: CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%-99%), compared with 78% (58%-91%) for CTA-SI and CBF, and 46% (27%-67%) for CBV (P < .001). All 3 patients with a CBV pc-ASPECTS < 8 compared to 6/23 patients with a CBV pc-ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9-7.6). CONCLUSION: CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc-ASPECTS < 8 may indicate patients with high case fatality.

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial.

BACKGROUND: Despite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials.Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely. DESIGN: BASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0-3. DISCUSSION: The BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755).