Margaret O. Johnson

The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial (NCT03299309) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targeting pp65 in individuals (3–35 years old) with recurrent HGG or medulloblastoma. Thirty-six individuals with HGG received PEP-CMV. The mean age was 22.75 ± 9.34 years. The primary outcome, percentage of unacceptable toxicity, was met. The maximum-grade adverse events (AE) related to PEP-CMV were 17 grade 1 AEs, 15 grade 2 AEs, 1 grade 3 AE (pyramidal tract syndrome) and 1 grade 4 AE (cerebral edema). As a secondary outcome, in 21 individuals with evaluable data, T cell reactivity, measured as change in baseline interferon-γ pp65 enzyme-linked immunospot assay reactivity, had an estimated increase of 46 spots (95% confidence interval (95% CI): 8, 194) after treatment with PEP-CMV. As exploratory endpoints, the median progression-free survival was 2.5 months (95% CI: 2.2, 3.2), and median overall survival was 6.5 months (95% CI: 4.6, 8.4). PEP-CMV is well tolerated and elicits an antigen-specific immune response in individuals with multiply recurrent HGG. Only two individuals with medulloblastoma were enrolled, showing one grade 3 encephalopathy possibly related to PEP-CMV, while neither had postvaccine immune assessments due to progression-free survival and overall survival less than 2 months.

Introduction: Distress is common among cancer patients, especially those undergoing surgery. However, no study has systematically analyzed distress trends in this population. The purpose of this study was to systematically review perioperative rates of distress, as well as differences across cancer types, in cancer patients undergoing surgical intervention.Methods: A systematic review was conducted using PubMed, EMBASE, Scopus, and APA PsycINFO (searched until July 17, 2023). Included studies were clinical studies of cancer patients undergoing surgery reporting distress measured by the National Comprehensive Cancer Network (NCCN) distress thermometer (DT). Data on study and patient characteristics, and preoperative and postoperative distress rates were extracted. Results were pooled, and overall distress rates were calculated as weighted means. Subanalysis by cancer type was performed. Three meta‐analyses were conducted: (1) preoperative distress, (2) postoperative distress, and (3) change in distress.Results: Fifty‐seven studies including 13,410 cancer patients were reviewed. Most patients were female (67.4%), White (77.8%), and married/partnered (72.2%), with an average age of 59.2 years. The most common cancers were breast (14 studies), brain (8), and colorectal (7). Weighted mean pre‐ and postoperative distress scores were 5.1 and 4.5, respectively. Distress remained high through 30 days postoperatively, then declined thereafter. Brain cancer patients reported the highest postoperative distress (5.1), followed by breast cancer patients (4.9).Conclusion: The perioperative phase is a critical period of elevated distress in cancer patients. Preoperatively, patients experience moderate to severe levels of distress, which persist throughout the early postoperative phase, gradually declining from the 1‐month postoperative mark onwards.

Background: Primary brain tumors (PBTs) pose a significant health challenge, affecting patients and their caregivers. While early integration of palliative care (PC) has shown benefits in advanced cancer, its integration for PBT patients, particularly glioblastoma (GBM) patients, remains complex. We hypothesized that our previous PC integration efforts may have failed due to knowledge-gaps and misconceptions among patients, caregivers, and providers. Objective: This study aimed to identify knowledge gaps and misconceptions about PC among patients with primary brain tumors (PBTs), their caregivers, and their medical providers. Method: An electronic survey was distributed to PBT patients, caregivers, and medical providers, that included questions regarding PC from the Health Information National Trends Survey (HINTS). Survey responses were analyzed; comparisons were made between the 3 groups as well as the general population. Results: Of 141 respondents (59 patients, 57 caregivers, and 25 providers), each group held perspectives on PC differing from the general population. While all groups had an improved understanding of PC’s role in symptom management, uncertainty persisted among patients and caregivers regarding life-prolonging treatment and certain PC goals like caregiver support or end-of-life care. Conclusion: Understanding gaps in knowledge and perceptions of PC among PBT patients and caregivers is crucial for effective intervention, with caregivers playing a vital role in advocating for PC. Future research should explore factors influencing these perceptions and development of targeted education to improve early PC referrals for patients with PBTs.

Glioblastoma (GBM) is a fatal brain tumor with limited treatment options. O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is the central molecular biomarker linked to both the response to temozolomide, the standard chemotherapy drug employed for GBM, and to patient survival. However, MGMT status is captured on tumor tissue which, given the difficulty in acquisition, limits the use of this molecular feature for treatment monitoring. MGMT protein expression levels may offer additional insights into the mechanistic understanding of MGMT but, currently, they correlate poorly to promoter methylation. The difficulty of acquiring tumor tissue for MGMT testing drives the need for non-invasive methods to predict MGMT status. Feature selection aims to identify the most informative features to build accurate and interpretable prediction models. This study explores the new application of a combined feature selection (i.e., LASSO and mRMR) and the rank-based weighting method (i.e., MGMT ProFWise) to non-invasively link MGMT promoter methylation status and serum protein expression in patients with GBM. Our method provides promising results, reducing dimensionality (by more than 95%) when employed on two large-scale proteomic datasets (7k SomaScan^® panel and CPTAC) for all our analyses. The computational results indicate that the proposed approach provides 14 shared serum biomarkers that may be helpful for diagnostic, prognostic, and/or predictive operations for GBM-related processes, given further validation.

Atypical teratoid rhabdoid tumors (AT/RT) are rare and highly malignant CNS neoplasms primarily affecting children. Adult cases are extremely uncommon, with only approximately 92 reported. Spinal A... Plain language summary Atypical teratoid rhabdoid tumors (AT/RT) are rare and serious cancers that affect the brain and spine, and mostly occur in children. AT/RT are rare in adults, with only abou... Tweetable abstract Rare spinal AT/RT case in a 50-year-old adult initially misdiagnosed as ependymoma. Recurrence led to reclassification. Highlights SMARCB1 mutations and treatment with surgery, r...

Purpose: Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan. Experimental Design: Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy. Results: Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice. Conclusions: This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.

Background: Collaborative relationships between academic oncology and industry (pharmaceutical, biotechnology, “omic,” and medical device companies) are essential for therapeutic development in oncology; however, limited research on engagement in and perceptions of these relationships has been done.Methods: Survey questions were developed to evaluate relationships between academic oncology and industry. An electronic survey was delivered to 1000 randomly selected members of the American Society of Clinical Oncology, a professional organization for oncologists, eliciting respondents' views around oncology‐industry collaborations. The responses were analyzed according to prespecified plans.Results: There were 225 survey respondents. Most were from the United States (70.0%), worked at an academic institution (60.1%), worked in medical oncology (81.2%), and had an active relationship with industry (85.8%). One quarter (26.7%) of respondents reported difficulty establishing a relationship with industry collaborators, and most respondents (75%) did not report having had mentorship in developing these relationships. The majority (85.3%) of respondents considered these collaborations important to their careers. Respondents generally thought that scientific integrity was preserved (92%), and most respondents (95%) had little concern over the quality of the collaborative product. Many (60%) shared concerns over potential conflict of interest if an individual with a compensated relationship promoted an industry product for clinical care/research, yet most respondents (67%) stated these relationships did not shape their interactions with patients.Conclusions: This study provides novel data characterizing the nature of collaborative relationships between clinicians, researchers, and industry in oncology. Although respondents considered these collaborations an important part of clinical and academic oncology, formal education or mentorship around these relationships was rare. Conflicting findings around conflict of interest highlight the importance of more dedicated research in this area.Plain Language Summary: Business enterprises in health care play a central role in cancer research and care, driving the development of new medical testing, drugs, and devices. Effective working relationships among clinicians, researchers, and these industry partners can promote innovative research and enhance patient care. Study of these collaborations has been limited to date. Through distribution of a questionnaire to cancer clinicians and researchers, we found that most participants consider these relationships valuable, though they find establishing such relationships challenging partly because of gaps in educational programs in this area. Our findings also highlight the need for further policy around the potential bias these relationships can introduce.