The HER2 flip-HER2 amplification of tumor cells in the cerebrospinal fluid of breast cancer patients with leptomeningeal disease: implications for treating the LM tumor with anti-HER2 therapy.

Introduction: CNSide is a platform that detects and characterizes tumor cells in the cerebrospinal fluid (CSF) of patients with leptomeningeal disease (LMD). The platform was validated per College of American Pathologists (CAP) and Clinical Laboratories Improvement Amendment (CLIA) guidelines and run as a commercial Laboratory Developed Test (LDT) at Biocept in San Diego, CA. The platform allows CSF tumor cell (CSF-TC) enumeration and biomarker characterization by fluorescent in situ hybridization (FISH). Methods: We performed a multicenter retrospective chart review of HER2 FISH CNSide test results that were commercially ordered on 26 patients by physicians for LMD breast cancer patients between April 2020 and October 2022. Results: We show that HER2 is amplified on CSF tumor cells in 62% (16/26) of LMD breast cancer patients. 10/26 (38%) patients had discordant HER2-positivity between the primary tumor tissue and CSF-TC; of these, 35% (9/26) of the patients displayed HER2 amplification on the CSF-TCs, however were categorized as HER2 negative on the primary tumor. Of the 27% (7/26) patients with a HER2 positive primary tumor, one patient showed a HER2 negative LMD tumor. Two patients, 8% (2/26) had a HER2 equivocal primary tumor; of these, one demonstrated a HER2 negative, and one a HER2 positive LMD tumor. Serial analysis (at least 4 longitudinal tests) of HER2 status of the CSF-TC throughout therapy was available for 14 patients and demonstrated that HER2 status of the LMD changed in 29% (4/14) during their treatment course and impacted care decisions. Conclusions: Our data suggests that CSF-TC HER2 FISH analysis in LMD breast cancer patients may be discordant to the primary tumor sample and the discovery of HER2 positivity in the CSF may open doors to anti-HER2 targeted therapy options for LMD patients.

Extraneural metastatic ependymoma: distant metastasis to the pleura, lungs, lymph nodes and bone.

Ependymomas are neuroepithelial tumours arising from ependymal cells surrounding the cerebral ventricles that rarely metastasise to extraneural structures. This spread has been reported to occur to the lungs, lymph nodes, liver and bone. We describe the case of a patient with recurrent CNS WHO grade 3 ependymoma with extraneural metastatic disease. He was treated with multiple surgical resections, radiation therapy and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space and lymph nodes.

The Population-level Prevalence of Exocrine Pancreas Insufficiency and the Subsequent Risk of Pancreatic Cancer.

OBJECTIVES: To study the prevalence of exocrine pancreas insufficiency (EPI) at a population level and the subsequent risk of pancreatic ductal adenocarcinoma (PDAC). METHODS: Using TriNetX (a database of over 79 million US residents), we included patients ≥18 years with EPI (identified via ICD-10 codes) and continuous follow-up from 2016-2022. Patients with prior pancreas resection and PDAC before an EPI diagnosis were excluded. The primary outcome was EPI prevalence. Secondary outcomes included imaging utilization, PDAC risk and, pancreas enzyme replacement therapy (PERT) utilization. We performed 1:1 propensity score matching of patients with EPI vs. patients without an EPI diagnosis. Adjusted odds ratio (aOR) and hazard ratios (aHR) with 95% confidence intervals were reported. RESULTS: The population prevalence of EPI was 0.8% (n = 24,080) with a mean age of 55.6 years at diagnosis. After propensity score matching, PDAC risk among patients with EPI was twice as high compared to patients without EPI (AHR 1.97, 95% confidence interval [CI] 1.66-2.36). This risk persisted even after excluding patients with a history of acute or chronic pancreatitis (aOR: 4.25, 95% CI 2.99-6.04). Only 58% (n = 13, 390) of patients with EPI received PERT with a mean treatment duration of 921 days. No difference was observed in PDAC risk between patients with EPI treated with PERT vs. those that did not receive PERT (AHR 1.10, 95% CI 0.95-1.26, p = 0.17). CONCLUSIONS: Despite a low prevalence, patients with EPI may have a higher risk of PDAC and many of these patients with EPI were not on PERT. PERT did not appear to impact incident PDAC risk after an EPI diagnosis.

Endoscopic submucosal dissection (ESD) outcomes in T1B esophageal cancer: a retrospective study.

BACKGROUND AND AIMS: The role of submucosal endoscopic dissection (ESD) in management of invasive esophageal cancer (EC) remains unclear. In this case series, we evaluate the clinical and technical outcomes of patients who underwent ESD with pathologically staged T1b EC. METHODS: This retrospective study included patients who underwent ESD between December 2016 and April 2023 with pathologically staged T1b EC. Patient demographics, tumor characteristics, and ESD technical outcomes were analyzed. Patients were followed to determine disease-free survival and tumor recurrence rates. RESULTS: Sixteen patients with a total of 17 pathologically staged T1b ECs were included in this case series with a median follow-up time of 28 months [range 3-75]. ESD had high en-bloc (100%) and R0 (82.3%) resection rates. 16/17 patients (94.1%) were discharged the same day, and there were no immediate perioperative complications. 4/17 patients (23.5%) had curative ESD resections with no tumor recurrence. Among those with non-curative resections (n = 13), 5 patients had ESD only, 6 had ESD + surgery, and 2 underwent ESD + chemoradiation. In the ESD only group, 2/5 patients (40%) had tumor recurrence. In the ESD + surgery group, one patient died from a surgical complication, and 1/5 (20%) had tumor recurrence at follow-up. There was no tumor recurrence among patients who had ESD + chemoradiation. CONCLUSION: ESD is safe with high en-bloc and R0 resection rates in T1b EC. Recurrence rates are low but patients need close monitoring. Larger-scale studies are needed to determine the long-term clinical efficacy of ESD in T1b EC.

Creating Health Equity in Cancer Screening: Developing Outreach Strategies for Under-Screened Populations through Community Engagement.

Inequities in cancer screening were identified in Calgary, AB, by correlating low screening participation with higher material deprivation. This initiative sought to understand awareness of and barriers to breast, cervical and colorectal cancer screening to inform the co-design and implementation of an outreach strategy to increase screening awareness. Online focus groups with community members (n = 69) identified five themes, and interviews with community health workers (n = 21) identified four themes. The engagement phase led to a multi-component outreach strategy including a multilingual video series, a media campaign leveraging partner channels and a health worker information package with resources to assist with hosting community-based education sessions.

A nationwide study of liver disease hospitalizations during the coronavirus pandemic in the United States.

BACKGROUND AND AIM: The impact of the Coronavirus disease-2019 (COVID-19) pandemic on patients with liver disease is not well described at the population level in the United States. We used the largest, nationwide inpatient dataset to describe inpatient liver disease outcomes in the United States during the first year of the pandemic (2020) using 2018 and 2019 as comparator years. METHODS: Using the National Inpatient Sample (2018-2020), we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality for liver-related complications including cirrhosis, alcohol-associated liver disease (ALD) and alcoholic hepatitis using regression modeling. We reported relative change (RC) in the study period. RESULTS: Decompensated cirrhosis hospitalizations decreased in 2020 compared with 2019 (RC: -2.7%, P < 0.001) while all-cause mortality increased by 15.5% (P < 0.001). Hospitalizations for ALD increased compared with pre-pandemic years (RC: 9.2%, P < 0.001) with a corresponding increase in mortality in 2020 (RC 25.2%, P = 0.002). We observed an increase in liver transplant surgery mortality during the peak months of the pandemic. Importantly, mortality from COVID-19 was higher among patients with decompensated cirrhosis (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] [1.53-1.94]), Native Americans (OR 1.76, 95% CI [1.53-2.02]), and patients from lower socioeconomic groups. CONCLUSIONS: Cirrhosis hospitalizations decreased in 2020 compared with pre-pandemic years but were associated with higher all-cause mortality rates particularly in the peak months of the COVID-19 pandemic. In-hospital COVID-19 mortality was higher among Native Americans, patients with decompensated cirrhosis, chronic illnesses, and those from lower socioeconomic groups.

Acute Pancreatitis as a First Presentation of Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is a rare necrotizing antineutrophil cytoplasmic antibody-associated vasculitis characterized by inflammation in small-sized arteries. Gastrointestinal involvement is exceedingly rare in GPA. Here, we present a case of recurrent acute pancreatitis as the initial presentation of GPA. The diagnosis was made based on radiological and pathological findings of acute pancreatitis in conjunction with positive anti-PR3 antibody which is strongly associated with GPA. Systemic vasculitides are rare but important to consider in cases of idiopathic acute pancreatitis. Early diagnosis and therapy allow for high rates of remission and improved survival rates.

Impact of CDKN2A/B, MTAP, and TERT Genetic Alterations on Survival in IDH Wild Type Glioblastomas.

PURPOSE: Poor outcomes in IDH wild-type (IDHwt) glioblastomas indicate the need to determine which genetic alterations can indicate poor survival and guidance of patient specific treatment options. We sought to identify the genetic alterations in these patients that predict for survival when adjusting particularly for treatments and other genetic alterations. METHODS: A cohort of 167 patients with pathologically confirmed IDHwt glioblastomas treated at our institution was retrospectively reviewed. Next generation sequencing was performed for each patient to determine tumor genetic alterations. Multivariable cox proportional hazards analysis for overall survival (OS) was performed to control for patient variables. RESULTS: CDKN2A, CDKN2B, and MTAP deletion predict for worse OS independently of other genetic alterations and patient characteristics (hazard ratio [HR] 2.192, p = 0.0017). Patients with CDKN2A copy loss (HR 2.963, p = 0.0037) or TERT mutated (HR 2.815, p = 0.0008) glioblastomas exhibited significant associations between radiation dose and OS, while CDKN2A and TERT wild type patients did not. CDKN2A deleted patients with NF1 mutations had worse OS (HR 1.990, p = 0.0540), while CDKN2A wild type patients had improved OS (HR 0.229, p = 0.0723). Patients with TERT mutated glioblastomas who were treated with radiation doses < 45 Gy (HR 3.019, p = 0.0010) but not those treated with ≥ 45 Gy exhibited worse OS compared to those without TERT mutations. CONCLUSION: In IDHwt glioblastomas, CDKN2A, CDKN2B, and MTAP predict for poor prognosis. TERT and CDKN2A mutations are associated with worse survival only when treated with lower radiation doses, thus potentially providing a genetic marker that can inform clinicians on proper dose-fractionation schemes.

Neutrophilia and post-radiation thrombocytopenia predict for poor prognosis in radiation-treated glioma patients.

Introduction: Poor outcomes in glioma patients indicate a need to determine prognostic indicators of survival to better guide patient specific treatment options. While preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) have been suggested as prognostic systemic inflammation markers, the impact of post-radiation changes in these cell types is unclear. We sought to identify which hematologic cell measurements before, during, or after radiation predicted for patient survival. Methods: A cohort of 182 patients with pathologically confirmed gliomas treated at our institution was retrospectively reviewed. Patient blood samples were collected within one month before, during, or within 3 months after radiation for quantification of hematologic cell counts, for which failure patterns were evaluated. Multivariable cox proportional hazards analysis for overall survival (OS) and progression-free survival (PFS) was performed to control for patient variables. Results: Multivariable analysis identified pre-radiation NLR > 4.0 (Hazard ratio = 1.847, p = 0.0039) and neutrophilia prior to (Hazard ratio = 1.706, p = 0.0185), during (Hazard ratio = 1.641, p = 0.0277), or after (Hazard ratio = 1.517, p = 0.0879) radiation as significant predictors of worse OS, with similar results for PFS. Post-radiation PLR > 200 (Hazard ratio = 0.587, p = 0.0062) and a percent increase in platelets after radiation (Hazard ratio = 0.387, p = 0.0077) were also associated with improved OS. Patients receiving more than 15 fractions of radiation exhibited greater post-radiation decreases in neutrophil and platelet counts than those receiving fewer. Patients receiving dexamethasone during radiation exhibited greater increases in neutrophil counts than those not receiving steroids. Lymphopenia, changes in lymphocyte counts, monocytosis, MLR, and changes in monocyte counts did not impact patient survival. Conclusion: Neutrophilia at any time interval surrounding radiotherapy, pre-radiation NLR, and post-radiation thrombocytopenia, but not lymphocytes or monocytes, are predictors of poor patient survival in glioma patients.

EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.

The epidermal growth factor receptor (EGFR) is a prime oncogene that is frequently amplified in glioblastomas. Here we demonstrate a new tumour-suppressive function of EGFR in EGFR-amplified glioblastomas regulated by EGFR ligands. Constitutive EGFR signalling promotes invasion via activation of a TAB1-TAK1-NF-κB-EMP1 pathway, resulting in large tumours and decreased survival in orthotopic models. Ligand-activated EGFR promotes proliferation and surprisingly suppresses invasion by upregulating BIN3, which inhibits a DOCK7-regulated Rho GTPase pathway, resulting in small hyperproliferating non-invasive tumours and improved survival. Data from The Cancer Genome Atlas reveal that in EGFR-amplified glioblastomas, a low level of EGFR ligands confers a worse prognosis, whereas a high level of EGFR ligands confers an improved prognosis. Thus, increased EGFR ligand levels shift the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastomas by suppressing invasion. The tumour-suppressive function of EGFR can be activated therapeutically using tofacitinib, which suppresses invasion by increasing EGFR ligand levels and upregulating BIN3.

Pure White Cell Aplasia and Immune Thrombocytopenia after Thymoma Resection: A Case Report and Review of the Literature.

We report a case of pure white cell aplasia (PWCA) postthymoma resection in a 74-year-old male presenting with a 2-week history of fevers, night sweats, and severe febrile neutropenia. His pure white cell aplasia was treated with intravenous immunoglobulin (IVIg), granulocyte colony-stimulating factor (G-CSF), prednisone, and cyclosporine with a mixed response. He also developed immune thrombocytopenia, which responded well to a short course of eltrombopag. With continued cyclosporine treatment, his platelet counts were stable after stopping eltrombopag. The patient's cyclosporine treatment was complicated by renal failure, resulting in cessation of cyclosporine. His PWCA and immune thrombocytopenia significantly worsened after stopping cyclosporine, and unfortunately, he died from multiorgan failure and sepsis.

Distance traveled to glioblastoma treatment: A measure of the impact of socioeconomic status on survival.

BACKGROUND: Previous studies have shown improved post-surgical outcomes in patients who travel farther for glioblastoma treatment. This study investigates socioeconomic and facility factors that may influence this relationship. METHODS: Overall survival was calculated and compared by distance to treatment facility using univariate and multivariate survival models. The analysis was stratified by facility type, income quartile and insurance status and the association re-evaluated. Kaplan-Meier survival curves were created to analyze the relationship between overall survival and distance group. RESULTS: Individuals who traveled less than 5 miles to treatment had the shortest overall survival (11.8 months), while those who traveled greater than 50 miles had the longest survival (12.9 months). Stratification by income quartile failed to demonstrate an association between distance traveled and survival for those making less than $63,000 (adjusted hazard ratio range: 0.94-1.01). There was no association between survival and distance traveled for patients treated at a community cancer center, comprehensive community cancer center or an integrated network cancer program (adjusted hazard ratio range: 0.86-1.04). CONCLUSION: Financial strain, rather than distance traveled to treatment, may be associated with glioblastoma survival.

IDH mutation status and the development of venous thromboembolism in astrocytoma patients.

BACKGROUND: Venous thromboembolism (VTE) is a very common adverse event for astrocytoma patients, but validation of proposed risk biomarkers has been elusive. We examine whether the status of the isocitrate dehydrogenase (IDH) gene is a risk factor for the development of venous thromboembolism (VTE) in astrocytoma patients. METHODS: We conducted a retrospective chart review of 282 astrocytoma patients enrolled in the PROACTIVE (Prospective Assessment of Correlative Biomarker) study at MD Anderson Cancer Center (MDACC) from 9/1/2000 until 12/31/2013. RESULTS: We identified 282 astrocytoma patients consisting of 49 IDH mutant astrocytomas and 233 IDH wildtype astrocytomas. Glioblastoma was the initial histopathologic diagnosis in 30 (61.2%) of the IDH mutated astrocytomas compared to 227(97.4%) of the IDH wild type astrocytomas. VTE was identified in 52 (18.4%) of patients. VTE was diagnosed in 7 (14.3%) of the IDH mutated astrocytomas compared to 45(19.3%) of the IDH wild type astrocytoma s (p = 0.4094). Median time to VTE from diagnosis was 2.71 months. Median time to VTE from diagnosis was 2.6 months for IDH mutated astrocytomas compared to 3.06 months for the IDH wild type astrocytomas (p = 0.8663). CONCLUSIONS: IDH gene status did not appear as a significant risk factor for the development of venous thromboembolism (VTE) in our cohort of astrocytoma patients. Further research into potential biomarkers for VTE may be warranted.

Paraneoplastic syndromes in small cell lung cancer.

Paraneoplastic syndromes can commonly occur due to lung cancer, especially small cell lung cancer. Frequently paraneoplastic syndromes can precede the diagnosis of the neoplasm or present with limited stage disease. However, these syndromes can also occur at the time of recurrence or metastasis of disease. This review focuses on the epidemiology, pathogenesis, clinical features, and current management of the most common paraneoplastic syndromes encountered in patients with small cell lung cancer. Manifestations of paraneoplastic syndromes in small cell lung cancer include endocrine syndromes with secretion of excess hormones, and neurologic syndromes due to the production of antibodies causing an autoimmune condition. Recent advances have allowed for greater understanding of these syndromes and for the development of improved diagnostic as well as therapeutic tools. Awareness of paraneoplastic syndromes in small cell lung cancer can lead to an earlier diagnosis and recognition of both the condition and in some cases the disease potentially improving the overall survival and prognosis for patients. Further research examining effective methods to improve recovery from neurologic deficits in patients with a paraneoplastic neurologic illness is warranted.

Treatment strategies for glioblastoma in older patients: age is just a number.

BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Surgery of malignant motor-eloquent gliomas guided by sodium-fluorescein and navigated transcranial magnetic stimulation: a novel technique to increase the maximal safe resection.

BACKGROUND: Maximal safe resection is the goal of modern surgical treatment of high-grade gliomas (HGGs) located close to the motor cortex (M1) and/or the corticospinal tract (CST). Preoperative planning based on navigated transcranial magnetic stimulation (nTMS) and fluorescence-guided resection (FGR) using sodium-fluorescein have been separately described to increase the extent of resection (EOR) while preserving the motor pathway. We assessed the efficacy of the combination of these techniques for surgery of motor-eloquent HGGs. METHODS: We enrolled patients with motor-eloquent HGGs operated at the Departments of Neurosurgery of the University of Messina, Italy, and of the Charitè Universitatsmedizin Berlin, Germany, between 2016 and 2019. All patients underwent nTMS mapping of M1, and nTMS-based DTI tractography of CST. Tumor resection was guided by intraoperative neurophysiological mapping (IONM) supported by sodium-fluorescein fluorescence and by intraoperative visualization of the nTMS-based information through neuronavigation. EOR and new permanent motor deficits were compared with a historical control group of patients operated exclusively with IONM guidance. RESULTS: Seventy-nine patients were enrolled, while 55 patients were included as controls. The gross total resection (GTR) rate was significantly higher in patients operated using nTMS + FGR compared with controls (64.5% vs. 47.2%, P=0.04). As well, postoperative new permanent motor deficits were reduced in the study group vs. controls (11.4% vs. 20%). CONCLUSIONS: In this series, the combination of sodium-fluorescein FGR with nTMS-based planning improved surgical treatment of motor-eloquent HGGs. It represents a valuable support to IONM-guided resection, increasing the GTR rate while reducing the occurrence of permanent motor deficits.

Recurrent Papillary Glioneuronal Tumor.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are rare World Health Organization grade I neoplasms that are characterized by a benign course and excellent response to surgical resection. A few reports exist of tumors with more aggressive clinical and histologic features. In this report we detail the case of an unusually aggressive PGNT in a 67-year-old woman. CASE DESCRIPTION: The patient had a 3-year history of seizures and was diagnosed with a frontoparietal mass on imaging. She underwent subtotal resection with a histologic diagnosis of PGNT. Less than a year after surgery, the patient experienced recurrence of disease and underwent reresection and adjuvant radiation treatment. The patient's disease continued to progress despite radiation treatment, so adjuvant temozolomide was initiated. Molecular testing was performed and revealed a TERT promotor mutation, an FGFR3-TACC3 oncogenic fusion, and a copy number loss in CDKN2A/CDKN2B. CONCLUSIONS: PGNTs, while typically benign, can rarely recur after surgery. Molecular testing should be performed on all PGNTs to help possibly identify more aggressive tumors and potentially reveal novel treatment options.

Effect of health disparities on overall survival of patients with glioblastoma.

BACKGROUND: Examine the potential effects of health disparities in survival of glioblastoma (GB) patients. METHODS: We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS). RESULTS: We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.

Trochleoplasty provides good clinical outcomes and an acceptable complication profile in both short and long-term follow-up.

PURPOSE: The purpose of this study is to report on the global distribution and clinical outcomes of published articles related to trochleoplasty. METHODS: The online databases OVID Medline, OVID EMBASE, and the Cochrane Library were searched for the literature assessing trochleoplasty performed for lateral patellofemoral instability (LPI). Study data were abstracted looking at global trends in the literature, as well as clinical and patient-reported outcomes following this technique. RESULTS: For the assessment of global distribution, 29 studies including 998 patients met the inclusion criteria. The majority of the studies were conducted in Europe (93%) and most used an open thin flap technique (52%). For the secondary analysis of clinical outcomes, 21 studies were included with significant heterogeneity in patient selection, reporting on the degree of trochlear dysplasia, and patient-reported outcomes. All trochleoplasty techniques showed statistically significant improvement in clinical outcomes at average 50 months (range 3-228 months) post-operative, with most patients being satisfied with their procedure. Re-dislocation and complication rates were low. CONCLUSIONS: European centers have published majority of data on trochleoplasty surgery, which has been shown to be an acceptable procedure for patients with high-grade trochlear dysplasia and LPI. Trochleoplasty has demonstrated good clinical outcomes, a low re-dislocation rate, and an acceptable complication profile in both short and long-term follow-up. This study highlights the difficulty in reporting outcomes in this group of patients due to heterogeneity in patient selection, grading of trochlear dysplasia, and the lack of disease-specific outcome measures. LEVEL OF EVIDENCE: IV.

Highlighting the need for reliable clinical trials in glioblastoma.

INTRODUCTION: Several recent phase III studies have attempted to improve the dismal survival seen in glioblastoma patients, with disappointing results despite prior promising phase II data. Areas covered: A literature review of prior phase II and phase III studied in glioblastoma was performed to help identify possible areas of concern. Numerous issues in previous phase II trials for glioblastoma were found that may have contributed to these discouraging outcomes and discordant results. Expert commentary: These concerns include the improper selection of therapeutics warranting investigation in a phase III trial, suboptimal design of phase II studies (often lacking a control arm), absence of molecular data, the use of imaging criteria as a surrogate endpoint, and a lack of pharmacodynamic testing. Hopefully, by recognizing prior phase II trial limitations that contributed to failed phase III trials, we can adapt quickly to improve our ability to accurately discover survival-prolonging treatments for glioblastoma patients.