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Background: Stratification of the fracture risk is an important treatment component for patients with multiple myeloma, which is associated with up to an 80% risk of pathologic fracture. The Mirels score, which is commonly used to estimate the fracture risk for patients with osseous lesions, was evaluated in a cohort in which fewer than 15% of lesions were caused by multiple myeloma. The behavior of multiple myeloma lesions often differs from that of lesions caused by metastatic disease, and accurate risk stratification is critical for effective care. To our knowledge, the Mirels score has not been validated specifically for multiple myeloma.Questions/purposes: Our purpose was: (1) To develop a novel scoring system for the prediction of pathologic fracture in patients with long-bone lesions from multiple myeloma; and (2) to compare the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) area under curve (AUC) between the novel scoring system and the Mirels system.Methods: Between 2003 and 2017, 763 patients at one center with the diagnosis of multiple myeloma were reviewed, of whom 174 presented with long-bone disease involvement. Of those, 5% (nine of 174) were missing data or radiographs at a minimum of 1 year and had not reached an endpoint (fracture or surgery) before that time and were therefore excluded. Many patients have more than one lesion; consequently, we used the largest lesion in each patient, resulting in 163 lesions in as many patients. Ten percent (16 of 163) of these patients eventually developed a fracture and 4% (six of 163) underwent prophylactic stabilization (excluded from analysis because of outcome uncertainty). During the study period, prophylactic stabilization was performed at the discretion of the orthopaedic oncologist. Fifty-one percent (83 of 163) of patients were female, and the mean (± SD) age was 60 ± 10 years at radiographic lesion identification. All lesions were characterized before determining whether the patient underwent pathologic fracture. We identified variables associated with pathologic fracture on univariate analysis. Variables independently significant on logistic regression analysis were used to generate scoring algorithms at varying weights and scoring cutoffs for comparison via ROC curves. We then selected a novel score based on ROC performance, and compared the sensitivity, specificity, PPV, and NPV of that scoring system to that of Mirels score. ROC AUCs were compared after bootstrapping 100,000 iterations. Alpha was set at 0.05.Results: After controlling for potential confounders, such as age, sex, and duration of myeloma diagnosis, we found the following factors were independently associated with the occurrence of pathologic fracture: larger lesion size (area, cm2) (log odds 0.17; p = 0.03), longer lesion latency (years from diagnosis to lesion identification) (log odds 0.25; p = 0.03), presence of pain (relative risk [RR] 2.9; p = 0.04), and metaphyseal location (RR 3.2, compared with epiphyseal or diaphyseal; p = 0.003). These variables were used to formulate a novel scoring system. Compared with the Mirels system, the novel system was more sensitive (69% [95% CI 61 to 76] versus 38% [95% CI 30 to 46]; p < 0.05) but not different in terms of specificity (87% [95% CI 80 to 91] versus 87% [95% CI 81 to 92]; p > 0.05), PPV (37% [95% CI 29 to 45] versus 25% [95% CI 19 to 33]; p > 0.05), NPV (96% [95% CI 91 to 99] versus 92% [95% CI 87 to 96]; p > 0.05), or AUC (0.85 [95% CI 0.74 to 0.92] versus 0.67 [95% CI 0.51 to 0.81]; p > 0.05).Conclusion: The novel scoring system was found to be more sensitive than the Mirels system for predicting pathologic fracture in our retrospective cohort of patients with multiple myeloma-related bone disease. Specificity, PPV, NPV, and ROC AUC were not different with the numbers available. Thus, the novel scoring system may serve as a more effective screening tool to determine which patients with multiple myeloma would benefit from further radiologic or orthopaedic evaluation based on a skeletal survey.Level Of Evidence: Level III, diagnostic study. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced fibrosis is a long-term adverse effect of external beam radiation therapy for cancer treatment that can cause pain, loss of function, and decreased quality of life. Transforming growth factor beta (TGF-β) is believed to be critical to the development of radiation-induced fibrosis, and TGF-β inhibition decreases the development of fibrosis. However, no treatment exists to prevent radiation-induced fibrosis. Therefore, we aimed to mitigate the development of radiation-induced fibrosis in a mouse model by inhibiting TGF-β.Question/purposes: Does TGF-β inhibition decrease the development of muscle fibrosis induced by external beam radiation in a mouse model?Methods: Twenty-eight 12-week-old male C57BL/6 mice were assigned randomly to three groups: irradiated mice treated with TGF-βi, irradiated mice treated with placebo, and control mice that received neither irradiation nor treatment. The irradiated mice received one 50-Gy fraction of radiation to the right hindlimb before treatment initiation. Mice treated with TGF-c (n = 10) received daily intraperitoneal injections of a small-molecule inhibitor of TGF-β (1 mg/kg) in a dimethyl sulfoxide vehicle for 8 weeks (seven survived to histologic analysis). Mice treated with placebo (n = 10) received daily intraperitoneal injections of only a dimethyl sulfoxide vehicle for 8 weeks (10 survived to histologic analysis). Control mice (n = 8) received neither radiation nor TGF-β treatment. Control mice were euthanized at 3 months because they were not expected to exhibit any changes related to treatment. Mice in the two treatment groups were euthanized 9 months after radiation, and the quadriceps of each thigh was sampled. Masson's trichome stain was used to assess muscle fibrosis. Slides were viewed at 10 × magnification using bright-field microscopy, and in a blinded fashion, five representative images per mouse were used to quantify fibrosis. The mean ± SD fibrosis pixel densities in the TGF-βi and radiation-only groups were compared using Mann-Whitney U tests. The ratio of fibrosis to muscle was calculated using the mean fibrosis per slide in the TGF-βi group to standardize measurements. Alpha was set at 0.05.Results: The mean (± SD) percentage of fibrosis per slide was greater in the radiation-only group (1.2% ± 0.42%) than in the TGF-βi group (0.14% ± 0.09%) (odds ratio 0.12 [95% CI 0.07 to 0.20]; p < 0.001). Among control mice, mean fibrosis was 0.05% ± 0.02% per slide. Mice in the radiation-only group had 9.1 times the density of fibrosis as did mice in the TGF-βi group.Conclusion: Our study provides preliminary evidence that the fibrosis associated with radiation therapy to a quadriceps muscle can be reduced by treatment with a TGF-β inhibitor in a mouse model.Clinical Relevance: If these observations are substantiated by further investigation into the role of TGF-β inhibition on the development of radiation-induced fibrosis in larger animal models and humans, our results may aid in the development of novel therapies to mitigate this complication of radiation treatment. [ABSTRACT FROM AUTHOR]

In this article I use Angie Thomas's popular young-adult novel The Hate U Give as a lens through which to explore how young adult fiction, produced by African American writers, can serve to facilitate social activism and change. In the novel, Thomas's Black teenage protagonist, Starr Carter, undergoes a transformation from victim and witness to activist after she sees her Black male friend murdered by a white police officer. As I will demonstrate, the novel is guided and shaped by the ideologies of the Black Lives Matter Movement as it explores the complexities of Blackness in both post-racial and communal spaces. By drawing on these ideologies and employing the perspective of a Black teenage girl, Thomas engages her Black female readers in a readerly process in which they reflect on how Starr's narrative relates to their own lives. In doing so, I argue, she encourages these readers to explore ways in which their own narratives can be used to instigate social activism and change. [ABSTRACT FROM AUTHOR]

• Only 7.7 % of patients with osseous metastases are prescribed antiresorptive therapy. • 7.3 % of patients with osseous metastases sustain a pathologic fracture. • Younger and male patients are less likely to receive treatment. Antiresorptive therapies are commonly utilized to mitigate and prevent skeletal-related-events in patients with metastatic osseous disease. However, limited data exists on the incidence or factors associated with prescription of antiresorptives or their effects on the incidence of pathologic fractures in patients with osseous metastatic disease. The aims of this study were to determine 1) the proportion of patients with osseous metastasis who receive antiresorptive therapy and sustain a pathologic fracture within 2-years of a new diagnosis, 2) factors associated with sustaining a pathologic fracture, and 3) factors are associated with the likelihood of receiving antiresorptive therapy. Between January 2010 and October 2021, 1,492,301 patients with a new diagnosis of osseous metastasis were captured in the Mariner dataset of the PearlDiver database. Patients were identified using International Classification of Disease (ICD) 10 codes for osseous metastasis. We excluded patients with a prior diagnosis of osseous metastasis and if they had less than two-years of follow-up. There were 696,459 patients (46.7 %) included for analysis. Of these patients, 63 % (N = 437,716) were over the age of 65, 46 % were women, and 5.6 % had Medicaid insurance. We identified patients who were prescribed antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis. Cox proportional hazard ratio models were created to predict factors associated with 1) pathologic fracture and 2) receiving antiresorptive therapy within 2-years of a new diagnosis of osseous metastasis, respectively. The incidence of antiresorptive therapy prescription was 7.7 % in our cohort. The incidence of pathologic fracture within 2-years of a new diagnosis was 7.3 %. The risk of sustaining a pathologic fracture was higher for patients aged 35–44 (HR 1.27 [95 % CI 1.08–1.51]; p = 0.004), those with primary kidney cancer (HR 1.78 [95 % CI 1.71–1.85]; p < 0.001), p = 0.005), multiple myeloma (HR 2.49 [95 % CI 2.39–2.59]; p < 0.001), and Medicaid insurance (HR 1.17 [95 % CI 1.13–1.21]; p < 0.001). The risk of sustaining a pathologic fracture was lower for patients on antiresorptive therapy (HR 0.71 [95 % CI 0.66–0.83]; p < 0.001). Increasing age was an independent predictor for antiresorptive therapy prescription (HR 1.77–16.38, all p < 0.05). Male sex as well as diagnosis of primary prostate, lung, or kidney cancer and Medicaid insurance were negative predictors for antiresorptive prescription (HR 0.15–0.87, all p < 0.001). The utilization of antiresorptive therapy in patients with osseous metastases remains unacceptably low, with only 7.7% patients being prescribed these therapies, despite shown efficacy in reduction of pathologic fractures incidences. This study identified younger patients, males, and those diagnosed with primary prostate, kidney, and lung cancers to be at increased risk of not being prescribed antiresorptive therapy, suggesting possible bias in prescription patterns. Greater efforts are needed by providers who care for this vulnerable population to increase the utilization and reduce disparities of prescribing antiresorptive therapy. [ABSTRACT FROM AUTHOR]

Case: A 20-year-old woman presented with hip pain related to an osteocartilaginous lesion arising within the cotyloid fossa. She also had a lesion along the inferior femoral neck. Resection of both lesions was performed with surgical hip dislocation through a modified Hardinge approach. Conclusions: This unusual location for an osteocartilaginous lesion can lead to substantial pain and disability. Surgical dislocation through a modified Hardinge approach is an excellent option to concurrently resect these benign lesions of the cotyloid fossa and femoral neck without the need for trochanteric osteotomy. [ABSTRACT FROM AUTHOR]

Background: Metastatic carcinoma to skeletal muscle and/or subcutaneous fat is a rare event. Only 27 cases of esophageal cancer to soft tissue have been described in the English-language literature.Purpose: Our goal was to describe the prevalence and clinical characteristics of soft-tissue metastasis among patients with primary esophageal cancer at a single institution.Methods: We performed a retrospective review of all patients with primary esophageal cancer. Data points analyzed included histologic subtype, anatomic location, metastasis pattern, treatment, and survival. Kaplan-Meier curves were used to estimate survival time, and log-rank tests were used for comparisons. For all analyses, P < 0.05 was considered significant.Results: Of 1341 patients with primary esophageal cancer, 25 (1.9%) had metastases to soft tissue. Soft-tissue metastases were diagnosed at a median age of 64 years, a median 9.6 months after esophageal cancer diagnosis. Adenocarcinoma was the predominant histopathological type, and soft-tissue metastasis was most common in the lower extremity. Local intervention was used for 10 symptomatic patients with favorable prognoses. Chemotherapy was the only treatment modality in 18 patients. Median survival time after diagnosis of soft-tissue metastasis was 8.9 months and was longer in patients with metastasis in soft tissue only (24.6 months, P = 0.007) and in those who received local intervention (11.1 months vs those who did not, P = 0.020).Conclusion: We estimate the prevalence of soft-tissue metastasis to be 1.9% among patients with esophageal cancer. Local intervention may be beneficial for patients in otherwise good health with symptomatic soft-tissue lesions. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. Materials and Methods: Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. Results: Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. Conclusion: Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection. [ABSTRACT FROM AUTHOR]

Significant advancements have been made in the molecular mechanisms of myelomagenesis, diagnostic methods, prognostication, and the treatment options in multiple myeloma (MM) over the last decade. Despite these, MM remains a heterogeneous disease with differing outcomes. As myeloma treatment landscape continues to expand, personalized treatment that provides maximum benefit to a specific patient becomes more important. In the last few years, serum monoclonal proteins including the serum-free light chain assays, imaging, and cytogenetics have been used to predict the outcomes of MM patients receiving different types of therapies. With the development of novel technologies, more sensitive detection of residual disease using flow cytometry and next-generation sequencing has been possible. In addition, liquid biopsies using circulating tumor cells, tumor DNA, and novel immune biomarkers are potentially being investigated. These novel potential biomarkers not only accurately detect the mutational landscape of different cancers compared to standard methods but also serve as prognostic and predictive biomarkers for disease relapse and response to therapy. It is likely that we will be able to offer more targeted and risk-adapted therapeutic approach to patients with MM at different stages of their disease guided by these potential biomarkers. [ABSTRACT FROM AUTHOR]