Editorial: Precision Medicine in Spinal Oncology.

This special focus issue from the 2023-2024 AOSpine Knowledge Forum Tumor represents a culmination of years of experience devoted to advancing the care of patients with both metastatic and primary spinal tumors. We have learned much since the fundamental assessments of instability that led to the Spinal Instability Neoplastic Score (SINS), the grading of epidural disease utilizing the Epidural Spinal Cord Compression Scale (aka Bilsky grade), as well as the development of tumor-specific health related quality of life assessments such as the Spine Oncology Study Group Outcome Questionnaire (SOSGOQ). These tools have enabled us to make several prior recommendations for the appropriate use of advanced surgical techniques such as en bloc resection and the use of stereotactic body radiotherapy (SBRT) to optimize patient care.

Latest Developments in Targeted Biological Therapies in the Management of Chordoma and Chondrosarcoma.

Study Design: Systematic review.

Objectives: The objective of this review paper was to summarize targeted molecular therapy options for spinal chordoma and chondrosarcoma, and to provide an update on the relevant clinical trials open for recruitment.

Methods: A systematic review of the current literature was performed, according to PRISMA guidelines, to summarize the latest developments in non-surgical molecular treatment options for low grade malignant primary spinal tumours.

What is the Optimal Management of Metastatic Spine Patients With Intermediate Spinal Instability Neoplastic Scores: To Operate or Not to Operate?

Study Design: Systematic review.

Objective: In patients with extradural metastatic spine disease, we sought to systematically review the outcomes and complications of patients with intermediate Spinal Instability Neoplastic Score (SINS) lesions undergoing radiation therapy, percutaneous interventions, minimally invasive surgeries, or open spinal surgeries.

Methods: Following PRISMA guidelines for systematic reviews, MEDLINE, EMBASE, Web of Science, the Cochrane Database of Systematic Reviews and the Cochrane Center Register of Controlled Trials were queried for studies that reported on SINS intermediate patients who underwent: 1) radiotherapy, 2) percutaneous intervention, 3) minimally invasive, or 4) open surgery.

Role of Posterior Carbon Fiber Implants in Spine Tumor Surgery.

Study Design: Narrative Review.

Objective: The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability.

Infections Due to Corynebacterium kroppenstedtii With Focus on Granulomatous Lobular Mastitis for Tissue Specificity, Pathogenesis, Bacteriologic Workup, and Treatment.

Objective.—: To report the isolation and significance of C kroppenstedtii, features of patients with GLM, pathologic findings and mechanism, bacteriologic workup, and optimal treatment.

Design.

Empathy Unmasked: Patient Perception of Physician Empathy in an Oncologic Emergency Setting. A Randomized Controlled Trial Comparing Personal Protective Equipment Wear versus Unmasked Video Communication.

Background: Amidst the COVID-19 pandemic, telemedicine emerged as an important option that supports and facilitates clinical practice, however, its usefulness in emergency settings that treat patients with cancer is unclear.

Objective: To evaluate patient perception of physician empathy in an emergency oncology setting, comparing video interaction to an in-person with personal protective equipment (PPE) approach.

Methods: In this single-center, prospective, cross-sectional, survey-based randomized controlled trial, patients were randomized 1:1 for the concluding conversation done in-person which included either interacting with physicians wearing PPE or video interaction with physicians without PPE (virtual).

Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.

There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas.

Content and quality of consumer websites providing information about human papillomavirus infection in patients with systemic lupus erythematosus: An environmental scan.

Objective: We aimed to evaluate the content and quality of websites for consumers providing information about human papillomavirus (HPV) risks in patients with systemic lupus erythematosus (SLE).

Methods: We conducted an environmental scan of websites for patients and the general public with information about HPV and SLE. We searched Google from inception to June 2023, using the terms "HPV" and "lupus".

Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain.

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes past the left.

Impact of comorbidities on the mortality benefits of lung cancer screening: a post-hoc analysis of PLCO and NLST trials.

Hypothesis: To evaluate how comorbidities affect mortality benefits of lung cancer screening (LCS) with low-dose computed-tomography (LDCT).

Methods: We developed a comorbidity index (PLCO-ci) using LCS-eligible participants' data from the Prostate Lung Colorectal and Ovarian (PLCO) trial (training set) and the National Lung Screening Trial (NLST) (validation set). PLCO-ci predicts 5-year non-lung cancer (LC) mortality using a regularized Cox model; with performance evaluated by the area under the ROC curve (ROC).

Integrating CTLA-4/PD-1 blockade into cervical cancer management: Results of COMPASSION-16.

Although there is anti-tumor efficacy of dual CTLA-4/PD-1 blockade in advanced/recurrent cervical cancer, it is unclear whether combination with chemotherapy is synergistic. In COMPASSION-16, Wu et al. demonstrated improved survival outcomes of cadolinimab plus chemotherapy compared to chemotherapy alone for first-line systemic therapy for advanced/recurrent cervical cancer, suggesting a potential role of bispecific CTLA-4/PD-1 inhibitors in the frontline setting.

An examination of ambulatory care code specificity utilization in ICD-10-CM compared to ICD-9-CM: implications for ICD-11 implementation.

Objective: The ICD-10-CM classification system contains more specificity than its predecessor ICD-9-CM. A stated reason for transitioning to ICD-10-CM was to increase the availability of detailed data. This study aims to determine whether the increased specificity contained in ICD-10-CM is utilized in the ambulatory care setting and inform an evidence-based approach to evaluate ICD-11 content for implementation planning in the United States.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

FT538, iPSC-derived NK cells, enhance AML cell killing when combined with chemotherapy.

Induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells offer an opportunity for a standardized, off-the-shelf treatment with the potential to treat a wider population of acute myeloid leukaemia (AML) patients than the current standard of care. FT538 iPSC-NKs express a high-affinity, noncleavable CD16 to maximize antibody dependent cellular cytotoxicity, a CD38 knockout to improve metabolic fitness, and an IL-15/IL-15 receptor fusion preventing the need for cytokine administration, the main source of adverse effects in NK cell-based therapies. Here, we sought to evaluate the potential of FT538 iPSC-NKs as a therapy for AML through their effect on AML cell lines and primary AML cells.

Predictive Value of FDG Uptake on PET for Future Immune Checkpoint Inhibitor-Mediated Colitis: A Case Series.

: Immune-mediated colitis (IMC) is a common immune-related adverse event during immune checkpoint inhibitor (ICI) therapy. This case series and review aimed to highlight atypical cases of IMC and explore the potential of PET/CT to predict imminent ICI colitis. : Through a descriptive, retrospective study at a tertiary cancer center, we identified adult patients receiving ICIs for any cancer between 2010 and 2022 who also underwent PET/CT for routine cancer surveillance during this time.

GrB-Fc-KS49, an anti-EMP2 granzyme B fusion protein therapeutic alters immune cell infiltration and suppresses breast cancer growth.

Background: Granzyme B (GrB) is a key effector molecule, delivered by cytotoxic T lymphocytes and natural killer cells during immune surveillance to induce cell death. Fusion proteins and immunoconjugates represent an innovative therapeutic approach to specifically deliver a deadly payload to target cells. Epithelial membrane protein-2 (EMP2) is highly expressed in invasive breast cancer (BC), including triple-negative BC (TNBC), and represents an attractive therapeutic target.

Exploring Quantitative MRI Biomarkers of Head and Neck Post-Radiation Lymphedema and Fibrosis: Post Hoc Analysis of a Prospective Trial.

Background: Quantifying head and neck lymphedema and fibrosis (HN-LEF) is crucial in the investigation and management of treatment sequelae in head and neck cancer (HNC).

Methods: The T1- and T2-weighted MRI signal intensity (SI) was examined in relation to HN-LEF categories per physical/tactile examination (No-LEF, A-B = edema, C = edema + fibrosis, D = fibrosis), and MRI structural volumes were examined in relation to a novel 10-point HN-LEF score in the intraoral and submental regions.

Results: We identified differences in ranks among HN-LEF categories in relation to the MRI SI (A-B and C are higher than D and No-LEF for T2 SI, and A-B is the highest for T1).

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial.

We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics.

Lead time trajectory of blood-based protein biomarkers for detection of pancreatic cancer based on repeat testing.

In the current study, we assessed whether repeated measurements of a panel of protein biomarkers with relevance to pancreatic ductal adenocarcinoma (PDAC) improves lead time performance for earlier detection over a single timepoint measurement. Specifically, CA125, CEA, LRG1, REG3A, THBS2, TIMP1, TNRFSF1A as well as CA19-9 were assayed in serially collected pre-diagnostic plasma from 242 PDAC cases and 242 age- and sex-matched non-case control participants in the PLCO cohort. We compared performance estimates of a parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history, to that of a single-threshold (ST) method.