Prophylactic Radiotherapy for Prevention of Heterotopic Ossification After Periacetabular Fractures: A Review of Efficacy and Associated Conditions.

Prophylactic radiotherapy (XRT) is a commonly used treatment to decrease heterotopic ossification (HO) in patients with traumatic hip injuries. We conducted a retrospective review of patients at risk for HO who underwent XRT. Of the patients reviewed, 27.3% developed radiographic HO, 11.2% developed symptoms, and 2.0% required resection surgery. Patients were divided into primary (n = 71) and secondary prophylaxis (n = 27) cohorts. In the primary group, 25.0% developed radiographic HO, 5.6% developed symptoms, and 0 required surgery. In the secondary cohort, 33.3% of patients developed new radiographic HO, and 25.9% were symptomatic: four had a Brooker score of 3, and three had a score of 4 (p = 0.03), and 7.4% required surgical resection. (Journal of Surgical Orthopaedic Advances 31(2):113-118, 2022).

Patient and physician attitudes towards salvage stereotactic radiosurgery or radiotherapy for brain metastases.

Background: The experience of patients with brain metastases treated with stereotactic radiosurgery (SRS) may shape attitudes towards salvage therapy. Furthermore, physician attitudes towards salvage therapy may differ based on specialty and experience. Our objective is to compare physician attitudes and patient experiences with SRS. Methods: Eligible patients with brain metastases treated with one course of SRS or fractionated stereotactic radiotherapy (FSRT) without whole brain radiotherapy (WBRT) in the definitive or postoperative setting at a single institution were surveyed from 11/2021 to 11/2022 regarding their perspectives on salvage therapy. A separate 11-question multi-disciplinary physician survey was distributed to residents, fellows and attendings at seven additional academic institutions in the US. Chi-square test and Mann-Whitney U test were used to assess differences. Results: A total of 30 patients and 88 physicians were surveyed. Most patients reported being satisfied or very satisfied with initial SRS/FSRT (90%). When given an option between WBRT or SRS for salvage treatment, all patients favored SRS. The physicians consisted of radiation oncologists (69.3%), neurosurgeons (19.3%), medical oncologists (8.0%), and neuro-oncologists (3.4%). Most physicians were confident or very confident in their ability to discuss the risks and benefits of SRS for brain metastases (78.9%), but this was significantly lower if the patient had received prior SRS (56.6%, P<.001). In these cases, there were significant differences in response by medical specialty and confidence level (P<0.05). Conclusions: Patients and physicians view tumor control followed by long-term toxicity as the most important factors for salvage therapy after initial SRS for brain metastases.

Musculoskeletal Metastasis From Soft-tissue Sarcomas: A Review of the Literature.

Soft-tissue sarcomas are a rare and extremely heterogeneous group of cancers, representing <1% of all human malignancies. The lungs are the most common site of distant metastasis, followed by the bone, lymph nodes, liver, brain, and subcutaneous tissue. Clinical experience suggests that skeletal metastasis is part of the natural history affecting the prognosis and quality of life in these patients. Approximately 2.2% of patients have skeletal metastasis at diagnosis. However, up to 10% will develop skeletal metastasis after a mean interval of 21.3 months. Although systemic therapy with conventional chemotherapy remains the primary treatment modality for those with metastatic sarcoma, increased survival has been achieved in selected patients who receive multimodality therapy, including surgery, for their metastatic disease. The 5-year overall survival of patients with isolated bone metastases was 41.2% (26.9% to 54.9%), which decreased to 32.9% (21.2% to 45.1%) in the setting of combined bone and lung metastases. Moreover, the resection of the primary soft-tissue sarcoma is a predictor of survival, resulting in a 58% decrease in mortality after surgery (hazard ratio, 0.42, P = 0.013). Understanding the effect of these metastases on patient survival may influence imaging, surveillance, and treatment decisions.

Genomic alterations predictive of poor clinical outcomes in pan-cancer.

BACKGROUND: Genomic alterations are highly frequent across cancers, but their prognostic impact is not well characterized in pan-cancer cohorts. Here, we use pan-cancer cohorts from TCGA and MSK-IMPACT to evaluate the associations of common genomic alterations with poor clinical outcome. MATERIALS AND METHODS: Genomic alterations in commonly altered genes were extracted from Pan-Cancer TCGA and MSK-IMPACT cohorts. Multivariable Cox regression analyses stratified by cancer type defined adjusted hazard ratios (AHRs) for disease-specific survival (DSS), progression-free survival (PFS) and overall survival (OS). RESULTS: Using TCGA we identified 32 mutated genes, and 15 copy number (CN) genes with frequency >= 4% in 9,104 patients across 28 cancers. On UVA, having a TP53-mutations or any mutation in the 31 genes (mut31) were associated with worse PFS (HR: 1.22, p < 0.0001 and HR: 1.1, p = 0.04, respectively) and DSS (HR: 1.38, p < 0.0001, and HR: 1.16, p = 0.03, respectively). CDKN2A, PTEN deletions, and MYC-amplifications were associated with PFS and DSS (p < 0.05 for all). On MVA, including TP53-mutations, mut31, CDKN2A-deletion, PTEN-deletion, and MYC-amplification, all five alterations were independently prognostic of poor PFS and DSS. Similar results were observed in an independent cohort from MSK-IMPACT (n = 7,051) where TP53 was associated with poor OS independent of mut31 and CN alterations in CDKN2A, PTEN, and MYC in primary tumors (p < 0.0001). CONCLUSIONS: TP53-mutations, CDKN2A-deletion, PTEN-deletion, and MYC-amplification are independent pan-cancer prognostic genomic alterations.

Bone Marrow Suppression during Postoperative Radiation for Bladder Cancer and Comparative Benefit of Proton Therapy-Phase 2 Trial Secondary Analysis.

PURPOSE: For patients with high-risk bladder cancer (pT3+ or N+), local regional failure remains a challenge after chemotherapy and cystectomy. An ongoing prospective phase 2 trial (NCT01954173) is examining the role of postoperative photon radiation therapy for high-risk patients using volumetric modulated arc therapy. Proton beam therapy (PBT) may be beneficial in this setting to reduce hematologic toxicity. We evaluated for dosimetric relationships with pelvic bone marrow (PBM) and changes in hematologic counts before and after pelvic radiation therapy and explored the potential of PBT treatment plans to achieve reductions in PBM dose. MATERIALS AND METHODS: All enrolled patients were retrospectively analyzed after pelvic radiation per protocol with 50.4 to 55.8 Gy in 28 to 31 fractions. Comparative PBT plans were generated using pencil-beam scanning and a 3-beam multifield optimization technique. Changes in hematologic nadirs were assessed using paired t test. Correlation of mean nadirs and relative PBM dose levels were assessed using the Pearson correlation coefficient (CC). RESULTS: Eighteen patients with a median age of 70 were analyzed. Mean cell count values after radiation therapy decreased compared with preradiation therapy values for white blood cells (WBCs), absolute neutrophil count (ANC), absolute lymphocyte count (all P < .001), and platelets (P = .03). Increased mean PBM dose was associated with lower nadirs in WBC (Pearson CC -0.593, P = .02), ANC (Pearson CC -0.597, P = .02), and hemoglobin (Pearson CC -0.506, P = .046), whereas the PBM V30 to V40 correlated with lower WBC (Pearson CC -0.512 to -0.618, P < .05), and V20 to V30 correlated with lower ANC (Pearson CC -0.569 to -0.598, P < .04). Comparative proton therapy plans decreased the mean PBM dose from 26.5 Gy to 16.1 Gy (P < .001) and had significant reductions in the volume of PBM receiving doses from 5 to 40 Gy (P < .001). CONCLUSION: Increased PBM mean dose and V20 to V40 were associated with lower hematologic nadirs. PBT plans reduced PBM dose and may be a valuable strategy to reduce the risk of hematologic toxicity in these patients.

Primary Versus Secondary Radiotherapy for Heterotopic Ossification Prevention About the Elbow.

OBJECTIVES: To examine the efficacy and safety of radiotherapy for the prevention of heterotopic ossification (HO) about the elbow. DESIGN: Retrospective chart review. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred and twenty-nine patients who received prophylactic radiotherapy (XRT) over a 15-year period were identified. Patients were included if they received XRT to the elbow joint and had at least 12 weeks of follow-up after XRT. Fifty-four patients were ultimately included. INTERVENTION: All patients were treated with a single dose of 7 Gy. Ninety-eight percentage of patients received XRT within 24 hours after surgery, and all patients received XRT within 72 hours after surgery. MAIN OUTCOMES MEASUREMENTS: The primary study measures evaluated were the presence or absence of clinically symptomatic HO and the presence of radiographic HO after XRT to the elbow joint. RESULTS: Eighteen patients were treated with XRT after a traumatic injury requiring surgery (primary prophylaxis), and 36 were treated with XRT after excision surgery to remove HO which had already formed (secondary prophylaxis). In the primary cohort, 16.7% developed symptomatic HO after XRT and 11.1% required surgery to resect the heterotopic bone. In the secondary cohort, 11.1% developed symptomatic HO after surgery and XRT and 5.5% required resection surgery. No secondary malignancies were identified. CONCLUSIONS: Our findings suggest that XRT for elbow HO may be safe and effective for both primary and secondary HO. XRT for HO was not shown to be associated with radiation-induced sarcoma in this series, at least in the short term. Further study in a large patient population with extended follow-up is required to better characterize populations at high risk for development of HO and secondary malignancy. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Chromodomain-helicase-DNA binding protein 5, 7 and pronecrotic mixed lineage kinase domain-like protein serve as potential prognostic biomarkers in patients with resected pancreatic adenocarcinomas.

Pancreatic cancer is one of the deadliest cancers with a very poor prognosis. Recently, there has been a significant increase in research directed towards identifying potential biomarkers that can be used to diagnose and provide prognostic information for pancreatic cancer. These markers can be used clinically to optimize and personalize therapy for individual patients. In this review, we focused on 3 biomarkers involved in the DNA damage response pathway and the necroptosis pathway: Chromodomain-helicase-DNA binding protein 5, chromodomain-helicase-DNA binding protein 7, and mixed lineage kinase domain-like protein. The aim of this article is to review present literature provided for these biomarkers and current studies in which their effectiveness as prognostic biomarkers are analyzed in order to determine their future use as biomarkers in clinical medicine. Based on the data presented, these biomarkers warrant further investigation, and should be validated in future studies.