Valerae O. Lewis

The University of Texas MD Anderson Cancer Center

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Patrick P. Lin

The University of Texas MD Anderson Cancer Center

Bryan S. Moon

The University of Texas MD Anderson Cancer Center

Justin E. Bird

The University of Texas MD Anderson Cancer Center

Shreyaskumar Patel

The University of Texas MD Anderson Cancer Center

Wei‐Lien Wang

The University of Texas MD Anderson Cancer Center

Alexander J. Lazar

The University of Texas MD Anderson Cancer Center

Robert L. Satcher

The University of Texas MD Anderson Cancer Center

Christina L. Roland

The University of Texas MD Anderson Cancer Center

Robert S. Benjamin

The University of Texas MD Anderson Cancer Center

Anthony P. Conley

The University of Texas MD Anderson Cancer Center

Cooperative Institutions

The University of Texas MD Anderson Cancer Center

451

The University of Texas Health Science Center at Houston

110

Baylor College of Medicine

Harvard University

Memorial Sloan Kettering Cancer Center

Creative Commons

Scripps MD Anderson Cancer Center

Massachusetts General Hospital

WinnMed

Brigham and Women's Hospital

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Single-fraction radiation retreatment for bone metastases: role of a rapid access clinic

BMJ Supportive & Palliative Care (2024)

Minsoo Kim J. Alberto Maldonado Prasamsa Pandey Molly B. El Alam Ramez Kouzy

Objectives This study investigates retreatment rates in single-fraction radiation therapy (SFRT) for painful bone metastasis in patients with limited life expectancy. We compared retreatment-free survival (RFS) in patients from a rapid access bone metastases clinic (RABC) and non-RABC patients, identifying factors associated with retreatment. Methods In this observational study, we analysed RABC patients who received SFRT between April 2018 and November 2019, using non-RABC SFRT patients as a comparison group. Patients with prior or perioperative radiation therapy (RT) were excluded. The primary endpoint was same-site and any-site retreatment with RT or surgery. Patient characteristics were compared using χ 2 and Student’s t-tests, with RFS estimates based on a multistate model considering death as a competing risk using Aalen-Johansen estimates. Results We identified 151 patients (79 RABC, 72 non-RABC) with 225 treatments (102 RABC, 123 non-RABC) meeting eligibility criteria. Of the 22 (10.8%) same-site retreatments, 5 (22.7%) received surgery, 14 (63.6%) received RT and 3 (13.6%) received both RT and surgery. We found no significant differences in any-site RFS (p=0.97) or same-site RFS (p=0.11). Conclusions RFS is high and similar comparable in the RABC and non-RABC cohorts. Retreatment rates are low, even in patients with low Eastern Cooperative Oncology Group scores.

Clinical endpoint

10.1136/spcare-2023-004497

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Combined Radiation Therapy and Surgery Results in Improved Local Control for Patients with Extraskeletal Myxoid Chondrosarcomas Which Translates into Lower Risk of Distant Metastases

International Journal of Radiation Oncology*Biology*Physics (2019)

Andrew J. Bishop Justin E. Bird Anthony P. Conley Christina L. Roland Bryan S. Moon

10.1016/j.ijrobp.2019.06.2498

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Preliminary results of a phase II study of neoadjuvant checkpoint blockade for surgically resectable undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS).

Journal of Clinical Oncology (2020)

Christina L. Roland Emily Z. Keung Alexander J. Lazar Keila E. Torres Wei‐Lien Wang

11505 Background: is a randomized, phase II non-comparative trial evaluating the efficacy of neoadjuvant checkpoint blockade [nivolumab (N) or ipilimumab/ nivolumab (I/N)] in patients (pts) with surgically resectable retroperitoneal DDLPS or extremity/truncal UPS treated with concurrent neoadjuvant radiation therapy (RT, UPS only). Methods: Primary endpoint was pathologic (path) response. Secondary endpoints were safety, RECIST response, recurrence-free survival, overall survival and patient-reported outcomes. Biospecimens (tumor, blood, fecal microbiome) at baseline, on therapy, and at time of surgery were collected and will be assessed for immune-based prognostic biomarkers. We assessed correlation between radiographic and pathologic response by linear regression. Correlative analyses includes assessment of tumor PD-L1 expression, characterization of tumor immune infiltrates by multiplex immunohistochemistry, and transcriptomic and genomic analyses. Results: Of the 25 pts enrolled; 24 are evaluable for response (14 DDLPS, 9 UPS). Clinical activity was variable by histologic subtype and treatment with RT. Median path response in the UPS cohort was 95% [95% CI 85–99] and was similar between the N/RT and I/N/RT groups (Table). Median path response in the DDLPS cohort was 22.5% [95% CI 85–99; Table]. Median change in tumor size (radiographic response) was -4% and +9% in the UPS and DDLPS cohorts, respectively. There was no correlation between path response and radiographic response (R 2 0.0309; p = 0.43). Of 8 pts with path response ≥ 85%, there was 1 partial response, 5 stable disease and 2 progressive disease by RECIST criteria. There was 1 delay to surgery due to grade 3 hyperbilirubinemia (Arm B). There was no difference in toxicity between N/RT and I/N/RT. Conclusions: N/RT and I/N/RT have significant clinical activity in UPS; more than expected compared to historic controls. Toxicity profiles were as expected and the majority of patients underwent resection without delay. Larger studies evaluating N/RT in UPS are warranted given the significant path response in this cohort. RECIST was not associated with path response and better markers of on-treatment clinical activity are needed. Correlative analyses that may guide combination strategies are ongoing and will be presented at the meeting. Clinical trial information: NCT03307616 .

Clinical endpoint

Neoadjuvant Therapy

10.1200/jco.2020.38.15_suppl.11505

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Data from The Interleukin-11 Receptor α as a Candidate Ligand-Directed Target in Osteosarcoma: Consistent Data from Cell Lines, Orthotopic Models, and Human Tumor Samples

Valerae O. Lewis Michael G. Ozawa Michael T. Deavers Guiying Wang Tomo Shintani

<div>Abstract<p>The interleukin-11 receptor α (IL-11Rα) is a functional target in bone metastasis. However, its role in primary bone tumors has not been established. As such, here, we evaluated IL-11Rα as a candidate target in primary and metastatic human osteosarcoma. First, in an orthotopic mouse model, we showed that IL-11Rα protein is markedly expressed in primary osseus and pulmonary metastatic osteosarcoma but absent from control normal tibia and lung. Moreover, systemic administration of an IL-11Rα–targeting phage displaying the cyclic nonapeptide CGRRAGGSC resulted in strong and selective accumulation of IL-11Rα–homing phage particles in the osteosarcoma but not in several control organs. Finally, IL-11Rα expression in a large panel of human primary and metastatic osteosarcoma samples was remarkably consistent with the observations in the orthotopic mouse model. These data establish IL-11Rα as a candidate target in human osteosarcoma and provide leads for the development of novel imaging and therapeutic agents for the management of this malignant tumor. [Cancer Res 2009;69(5):1995–9]</p></div>

10.1158/0008-5472.c.6499802

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Reply to the Comment on “The binding energy of Ni+ · (N2O)”

Chemical Physics Letters (1995)

D. Bellert T. Buthelezi Valerae O. Lewis K. Dezfulian P.J. Brucat

Opposition (politics)

10.1016/s0009-2614(95)01258-3

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Enchondroma with secondary aneurysmal bone cyst

Skeletal Radiology (2012)

Justin E. Bird Wei‐Lien Wang Michael T. Deavers John E. Madewell Valerae O. Lewis

Enchondroma

Aneurysmal Bone Cyst

Presentation (obstetrics)

Bone cyst

Long bone

10.1007/s00256-012-1418-1

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BMTP-11 is active in preclinical models of human osteosarcoma and a candidate targeted drug for clinical translation

Proceedings of the National Academy of Sciences (2017)

Valerae O. Lewis Eswaran Devarajan Marina Cardó‐Vila Dafydd G. Thomas Eugenie S. Kleinerman

Osteosarcoma occurs predominantly in children and young adults. High-grade tumors require multidisciplinary treatment consisting of chemotherapy in the neoadjuvant and adjuvant settings, along with surgical intervention. Despite this approach, death from respiratory failure secondary to the development and progression of pulmonary metastases remains a significant problem. Here, we identify the IL-11 receptor α subunit (IL-11Rα) as a cell surface marker of tumor progression that correlates with poor prognosis in patients with osteosarcoma. We also show that both IL-11Rα and its ligand, IL-11, are specifically up-regulated in human metastatic osteosarcoma cell lines; engagement of this autocrine loop leads to tumor cell proliferation, invasion, and anchorage-independent growth in vitro. Consistently, IL-11Rα promotes lung colonization by human metastatic osteosarcoma cells in vivo in an orthotopic mouse model. Finally, we evaluate the IL-11Rα-targeted proapoptotic agent bone metastasis-targeting peptidomimetic (BMTP-11) in preclinical models of primary intratibial osteosarcomas, observing marked inhibition of both tumor growth and lung metastases. This effect was enhanced when BMTP-11 was combined with the chemotherapeutic drug gemcitabine. Our combined data support the development of approaches targeting IL-11Rα, and establish BMTP-11 as a leading drug candidate for clinical translation in patients with high-risk osteosarcoma.

Peptidomimetic

10.1073/pnas.1704173114

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Management of Radiation-associated Fractures

Journal of the American Academy of Orthopaedic Surgeons (2008)

Christopher P. Cannon Patrick P. Lin Valerae O. Lewis Alan W. Yasko

High-dose radiation is injurious to bone and is a known risk factor for the development of late fracture. Management of radiation-induced fractures is generally thought to be difficult, with prolonged healing times and a high nonunion rate. There is a relative paucity of literature to guide treatment. Fractures of the long bones typically should be managed with intramedullary nailing. A low threshold should exist for supplemental bone grafting, and a vascularized fibula graft should be considered for persistent nonunion. To prevent refracture, fixation should be left in situ indefinitely. Resection of the fracture site and reconstruction with an oncologic endoprosthesis is an effective salvage procedure. Periarticular fractures should be treated with joint arthroplasty, which allows early mobilization and avoids prolonged healing times. Fractures of expendable bones, primarily the clavicle, typically should be managed with débridement or resection.

Bone grafting

10.5435/00124635-200809000-00006

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Extraskeletal Myxoid Chondrosarcomas

American Journal of Clinical Oncology (2019)

Andrew J. Bishop Justin E. Bird Anthony P. Conley Christina L. Roland Bryan S. Moon

Objective: We evaluated our experience treating patients with localized extraskeletal myxoid chondrosarcomas (EMCs) to evaluate outcomes and relapse rates in order to better inform treatment decisions for these rare soft tissue sarcomas. Materials and Methods: We reviewed the records of 41 consecutive patients with localized EMC treated at our institution from 1990 to 2016. Most patients (n=33, 80%) received combined modality therapy with surgery and radiation therapy, whereas only 8 (20%) underwent surgery alone. The Kaplan-Meier method was used to estimate rates of overall survival, disease-specific survival, local control (LC), and distant metastatic-free survival (DMFS). Results: Median follow-up time was 94 months (range, 8 to 316). The 10-year LC, DMFS, disease-specific survival, and overall survival rates were 90%, 69%, 85%, and 66%, respectively. There were 5 patients (12%) with local relapse at a median time of 75 months (range, 13 to 176). On univariate analysis, the only significant factor associated with poorer LC was the use of surgery alone (10 y LC, 63% vs. 100% for combined modality therapy, P =0.004), which remained the only factor also significant on the multivariable analysis ( P =0.02; hazard ratio [HR], 12.7; 95% confidence interval [CI], 1.4-115.3). In total, 13 patients (32%) developed distant metastatic at a median time of 28 months (range, 3 to 154). Interestingly, local recurrence was the only factor associated with poorer DMFS on multivariate analysis ( P =0.04; HR, 3.9; 95% CI, 1.1-14.7). Conclusions: For patients with EMC, surgery alone was associated with a higher risk of local recurrence. Therefore, we recommend optimal local therapeutic strategies upfront with both surgery and radiation therapy to reduce the risk of local and ultimately distant recurrence.

Univariate analysis

10.1097/coc.0000000000000590

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Clinico-Genomic Profiling of Conventional and Dedifferentiated Chondrosarcomas Reveals TP53 Mutation to Be Associated with Worse Outcomes

Clinical Cancer Research (2023)

Ryan A. Denu Richard K. Yang Alexander J. Lazar Shalin S. Patel Valerae O. Lewis

Abstract Purpose: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes. Experimental Design: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas. Results: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising in the extremities, associated with higher age at diagnosis, and more common in dedifferentiated chondrosarcomas compared with grades 1–3 conventional chondrosarcoma. There was no difference in survival based on IDH mutation in univariate and multivariate analyses. TP53 mutation was the next most prevalent (41.9%) and is associated with worse overall survival and metastasis-free survival in both univariate and multivariate analyses. TP53 mutation was also associated with higher risk of recurrence following curative-intent surgery and worse survival among patients that presented with de novo metastatic disease. Conclusions: IDH mutations are prevalent in chondrosarcoma though were not associated with survival outcomes in this cohort. TP53 mutations were the next most common alteration and were associated with worse outcomes.

IDH2

Isocitrate dehydrogenase

Univariate analysis

10.1158/1078-0432.ccr-23-1703

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