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Study Design: Literature review with clinical recommendation. Objective: A concise curation of the latest spine literature exploring the relationship between expectations and satisfaction for patients with metastatic spinal disease (MSD). Deliver recommendations to practicing clinicians regarding interpretation and utilisation of this evidence. Methods: The latest spine literature in the topic of factors affecting the expectations of patients with MSD was reviewed and clinical recommendations were formulated. Recommendations are graded as strong or Conditional. Results: 5 articles were selected. Article 1: risk factors for the development of dissatisfaction from a cohort of 362 MSD patients. Strong recommendation to incorporate risk factor assessment when considering treatment. Article 2: systematic review assessing the relationship between pre-operative patient expectations and subsequent satisfaction in allied disciplines. Conditional recommendation to optimize patient expectation to positively modify patient satisfaction. Article 3: qualitative study of how clinicians, from different specialties, counsel patients with MSD pre-treatment. Strong recommendation to use a multidisciplinary approach. Article 4 qualitative study of how MSD patients experience their pre-treatment counselling and how that affected their appreciation of treatment success. Conditional recommendation to furnish patients with tailored, expected outcomes in the context of systemic progression. Article 5 Design and validation of a pre-treatment questionnaire specific to MSD. A conditional recommendation to incorporate this questionnaire in clinical and research MSD practice. Conclusion: Patients with MSD are approaching end of life care and high levels of treatment satisfaction are crucial at this juncture. The role of expectation management and comprehensive counselling is critical. [ABSTRACT FROM AUTHOR]

The goal of adjuvant (post-surgery) radiation therapy (RT) for breast cancer (BC) is to eliminate residual cancer cells, leading to better local tumor control and thus improving patient survival. However, radioresistance increases the risk of tumor recurrence and negatively affects survival. Recent evidence shows that breast cancer stem cells (BCSCs) are radiation-resistant and that relatively differentiated BC cells can be reprogrammed into induced BCSCs (iBCSCs) via radiation-induced re-expression of the stemness genes. Here we show that in irradiation (IR)-treated mice bearing syngeneic mammary tumors, IR-induced stemness correlated with increased spontaneous lung metastasis (51.7%). However, IR-induced stemness was blocked by targeting the NF-κB- stemness gene pathway with disulfiram (DSF)and Copper (Cu2+). DSF is an inhibitor of aldehyde dehydrogenase (ALDH) and an FDA-approved drug for treating alcoholism. DSF binds to Cu2+ to form DSF-Cu complexes (DSF/Cu), which act as a potent apoptosis inducer and an effective proteasome inhibitor, which, in turn, inhibits NF-κB activation. Treatment of mice with RT and DSF significantly inhibited mammary primary tumor growth (79.4%) and spontaneous lung metastasis (89.6%) compared to vehicle treated mice. This anti-tumor efficacy was associated with decreased stem cell properties (or stemness) in tumors. We expect that these results will spark clinical investigation of RT and DSF as a novel combinatorial treatment for breast cancer.

PDGFR is an important target for novel anticancer therapeutics because it is overexpressed in a wide variety of malignancies. Recently, however, several anticancer drugs that inhibit PDGFR signaling have been associated with clinical heart failure. Understanding this effect of PDGFR inhibitors has been difficult because the role of PDGFR signaling in the heart remains largely unexplored. As described herein, we have found that PDGFR-β expression and activation increase dramatically in the hearts of mice exposed to load-induced cardiac stress. In mice in which Pdgfrb was knocked out in the heart in development or in adulthood, exposure to load-induced stress resulted in cardiac dysfunction and heart failure. Mechanistically, we showed that cardiomyocyte PDGFR-β signaling plays a vital role in stress-induced cardiac angiogenesis. Specifically, we demonstrated that cardiomyocyte PDGFR-β was an essential upstream regulator of the stress-induced paracrine angiogenic capacity (the angiogenic potential) of cardiomyocytes. These results demonstrate that cardiomyocyte PDGFR-β is a regulator of the compensatory cardiac response to pressure overload-induced stress. Furthermore, our findings may provide insights into the mechanism of cardiotoxicity due to anticancer PDGFR inhibitors., Introduction PDGF receptors and/or ligands are overexpressed in a wide variety of malignancies (1-4). In the past decade, a number of inhibitors of receptor tyrosine kinases (RTKs) whose targets include [...]

Background: Current functional assessment tools for orthopaedic oncology are long surveys that contribute to patients' survey fatigue and yet lack the ability to discern meaningful differences in a patient population that is often mobile but unable to perform strenuous activities. We sought to determine whether a shorter, novel tool based on existing, validated surveys could better capture differences in a sample of orthopaedic oncology patients., Questions/purposes: (1) Can a concise fixed-item functional tool derived from the 50 items in the Toronto Extremity Salvage Score for the lower extremity (TESS LE) and the Lower Extremity Functional Scale (LEFS) demonstrate similar responsiveness in terms of sensitivity and specificity? (2) What is the precision and accuracy of the concise tool compared with the TESS LE and LEFS?, Methods: Functional outcome data were collected and maintained in a longitudinally maintained database at a single institution. Patients were included in the study if (1) they had undergone a tumor excision or a nononcologic orthopaedic procedure (for example, arthroplasty for osteoarthritis) for a bone or soft tissue tumor affecting lower extremity function, and (2) they had completed the LEFS, TESS LE, and Patient-Reported Outcomes Measurement Information System (PROMIS) global health tool on at least two clinic visits. Between September 2014 and April 2022, we treated 14,234 patients for primary bone or soft tissue sarcoma, metastatic disease to bone, or orthopaedic sequelae of chronic cancer care. Approximately 6% (854 of 14,234) were excluded due to the need of a language translator. Approximately 2% (278 of 13,380) refused or were unable to participate. Seventy-two percent (9433 of 13,102) of the patients had an operation on a lower extremity. Of these, 4% (339 of 9433) of the patients completed the TESS LE, LEFS, and Item 3 of the PROMIS global health tool on ≥ 2 clinic visits. Of the patients in the current study, 49% (167 of 339) were women, and 27% (93 of 339) had metastatic carcinoma. Twelve percent (41 of 339) of the patients died before the end of the study period. Spearman rank-order correlation, principal component analysis (PCA), and item response theory (IRT) modeling identified 14 highly discriminating items from the TESS LE and LEFS. Multiple linear stepwise regression (MLSR) was performed with the dependent variable being the summary score of the 14 items derived from the TESS LE and LEFS and standardized to a percentage of 100. The beta coefficient from the MLSR was used to derive a weight for each of the 14 items. Evaluation of the model with 10 to 17 variables was performed to ensure that the model with the 14 items met the most criteria for fit with the PCA, the receiver operating characteristic (ROC) curve, and the IRT modeling criteria. The responsiveness (sensitivity and specificity) of the change scores in the shortened 14-item survey, the 30-item TESS LE, and the 20-item LEFS as compared with the dichotomized changes in Item 3 of the PROMIS global health tool was evaluated using ROCs. The concordance (accuracy and precision) of the 14 items derived from the LEFS and TESS LE was evaluated., Results: The responsiveness (sensitivity and specificity) of the shortened 14-item survey, the TESS LE, and the LEFS to the criterion target of the PROMIS global health tool (Item 3) was similar, with areas under the curve (AUCs) ranging from 0.62 to 0.65 for the ROC curves. The responsiveness of the 14-item survey to the TESS LE showed sensitivity of 96% and specificity of 90%, with an AUC of 0.98 (p < 0.001). The responsiveness of the 14 items to the LEFS showed sensitivity of 95% and specificity of 86%, with an AUC of 0.96. The validity of the 14 items to the TESS LE was measured by concordance, with a precision of 0.98 and an accuracy of 0.97. Concordance of the 14 items to the LEFS showed a precision of 0.98 and accuracy of 0.83., Conclusion: The concise 14 items derived from patient-reported responses in the TESS LE and LEFS outcome measures showed similar responsiveness (sensitivity and specificity) as the original TESS LE and LEFS for cancer patients after lower extremity orthopaedic surgery performed for oncologic and nononcologic indications. The concise 14 items have a similar ability to the TESS LE and LEFS to tell the clinician or patient how they are functioning compared with other patients. These 14 items are shorter than the combined 50 items of the TESS LE and LEFS while retaining the capacity to describe a broad range of lower extremity function for orthopaedic oncology patients. We have named the 14-item survey the Lower Extremity Oncology Functional Assessment Tool.Level of Evidence Level II, diagnostic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 by the Association of Bone and Joint Surgeons.)

Introduction: Pelvic metastasis is a common presentation among patients presenting with skeletal metastasis. Image-guided percutaneous cementation of these lesions is becoming increasingly popular for the treatment of these lesions. The objective of this study was to conduct a systematic review that investigates clinical outcomes after percutaneous cementation for pelvic metastasis., Methods: A systematic review was registered with International Prospective Register of Systematic Reviews and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed, SCOPUS, and Ovid MEDLINE databases. All level I to IV clinical studies published in the English language investigating the clinical outcomes after percutaneous cementation for pelvic metastasis were included., Results: Fourteen studies with 579 patients (278 men, 301 women) and 631 metastatic pelvic lesions were included in the study. The mean follow-up range was 0.7 to 26.4 months. Percutaneous cementation alone was performed in 441 patients (76.2%). Supplemental ablative procedures were performed in 77 patients (13.3%), and supplemental internal fixation using cannulated screws was performed in 107 patients (18.5%). Twelve studies with 430 patients (74.2%) reported pain-related and/or functional outcome scores, of which all studies reported overall clinically notable improvement at short-term follow-up. All studies reported periprocedural complications. Local cement leakage was the most common complication (162/631 lesions, 25.7%) followed by transient local pain (25/579 patients, 4.3%). There were no reported cases of major complications. Seven patients (1.2%) underwent re-intervention for persistent symptoms., Conclusions: Percutaneous cementation may be an effective method for treating pain and function related to pelvic metastasis. The most common complication was cement leakage surrounding the lesion. The rates of major complications were low, and most complications appeared minor and transient. Additional prospective studies are needed to further assess the efficacy of this procedure., Level of Evidence: IV, systematic review of level I to IV therapeutic studies., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)