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The Impact of Targetable Mutations on Clinical Outcomes of Metastatic Epidural Spinal Cord Compression in Patients With Non-Small-Cell Lung Cancer Treated With Hybrid Therapy (Surgery Followed by Stereotactic Body Radiation Therapy)
Chakravarthy, Vikram B; Schachner, Benjamin; Amin, Anubhav G; Reiner, Anne S; Yamada, Yoshiya; Schmitt, Adam; Higginson, Daniel S; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:In treatment of metastatic epidural spinal cord compression (MESCC), hybrid therapy, consisting of separation surgery, followed by stereotactic body radiation therapy, has become the mainstay of treatment for radioresistant pathologies, such as non-small-cell lung cancer (NSCLC). OBJECTIVE:To evaluate clinical outcomes of MESCC secondary to NSCLC treated with hybrid therapy and to identify clinical and molecular prognostic predictors. METHODS:This is a single-center, retrospective study. Adult patients (≥18 years old) with pathologically confirmed NSCLC and spinal metastasis who were treated with hybrid therapy for high-grade MESCC or nerve root compression from 2012 to 2019 are included. Outcome variables evaluated included overall survival (OS) and progression-free survival, local tumor control in the competing risks setting, surgical and radiation complications, and clinical-genomic correlations. RESULTS:One hundred and three patients met inclusion criteria. The median OS for this cohort was 6.5 months, with progression of disease noted in 5 (5%) patients at the index tumor level requiring reoperation and/or reirradiation at a mean of 802 days after postoperative stereotactic body radiation therapy. The 2-year local control rate was 94.6% (95% CI: 89.8-99.3). Epidermal growth factor receptor (EGFR) treatment-naïve patients who initiated EGFR-targeted therapy after hybrid therapy had significantly longer OS (hazard ratio 0.47, 95% CI 0.23-0.95, P = .04) even after adjusting for smoking status. The presence of EGFR exon 21 mutation was predictive of improved progression-free survival. CONCLUSION/CONCLUSIONS:Hybrid therapy in NSCLC resulted in 95% local control at 2 years after surgery. EGFR treatment-naïve patients initiating therapy after hybrid therapy had significantly improved survival advantage. EGFR-targeted therapy initiated before hybrid therapy did not confer survival benefit.
PMID: 36477376
ISSN: 1524-4040
CID: 5383082
Long Term Clinical Outcomes of Patients with Colorectal Cancer with Metastatic Epidural Spinal Cord Compression treated with Hybrid Therapy (Surgery followed by Stereotactic Body Radiation Therapy)
Chakravarthy, Vikram B; Schachner, Ben; Amin, Anubhav; Reiner, Anne S; Yamada, Yoshiya; Schmitt, Adam; Higginson, Daniel S; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:"Hybrid-therapy", consisting of separation-surgery followed by stereotactic body radiation therapy (SBRT) has become the mainstay treatment for radioresistant spinal metastases. Histology-specific outcomes for hybrid therapy are scarce. In clinical practice, colorectal cancer (CRC) is particularly thought to have poor outcomes regarding spinal metastases. The goal of this study is to evaluate clinical outcomes for patients treated with hybrid therapy for spinal metastases from CRC. METHODS:This is a retrospective study performed at a tertiary cancer center. Adult patients with CRC spinal metastasis who were treated with hybrid-therapy for high-grade epidural spinal cord or nerve root compression from 2005-2020 were included. Outcome variables evaluated included patient demographics, overall survival (OS) and progression-free survival (PFS), surgical and radiation complications, and clinical-genomic correlations. RESULTS:Fifty patients met inclusion criteria. Progression of disease occurred in 7 (14%) patients at the index-level requiring reoperation and/or reirradiation at a mean of 400 days after surgery. Postoperative complications occurred in 16% of patients, with 3 (6%) requiring intervention. Adenomatous polyposis coli (APC) exon 14 and 16 mutations were found in 15 of 17 patients tested and in all 3 of 7 local failures tested. Twenty patients (40%) underwent further radiation due to disease progression at another spinal levels. CONCLUSIONS:Hybrid-therapy in CRC patients resulted in 86.7% local control at two years after surgery, with limited complications. APC mutations are commonly present in CRC patients with spine metastases and may suggest worse prognosis. Patients with CRC spinal metastases commonly progress outside the index treatment level.
PMID: 36272727
ISSN: 1878-8769
CID: 5360662
Stereotactic body radiation therapy for an unresectable FGF23-secreting tumor of the cervical spine: A case report and literature review
Hockemeyer, Kathryn; Purswani, Juhi M; Kim, Joseph K; Givi, Babak; Zan, Elcin; Pacione, Donato; Shapiro, Maksim; Laufer, Ilya; Feffer, Jill B; Silverman, Joshua S
We present the case of a 65-year-old male with tumor-induced osteomalacia (TIO) caused by an FGF23-secreting phosphaturic tumor of C2 treated definitively with stereotactic body radiation therapy (SBRT) and kyphoplasty. The patient exhibited notable reduction in FGF23 6 weeks following radiotherapy. He also received a dose of the FGF23 monoclonal antibody, burosumab. We discuss the case with emphasis on radiation in the management of TIO. This case demonstrates SBRT as a well-tolerated local treatment option for the management of unresectable FGF23-producing tumors.
PMCID:10322171
PMID: 37416336
ISSN: 2156-4647
CID: 5892262
Integration of an enhanced recovery after surgery program for patients undergoing pituitary surgery
Flukes, Stephanie; Laufer, Ilya; Cracchiolo, Jennifer; Geer, Eliza; Lin, Andrew L; Brallier, Jess; Tsui, Van; Afonso, Anoushka; Tabar, Viviane; Cohen, Marc A
Evidence-based enhanced recovery after surgery (ERAS) programs aim to improve patient outcomes and shorten hospital stays. The objective of this study is to describe the development, implementation, and evolution of an ERAS protocol to optimize the perioperative management for patients undergoing endoscopic skull base surgery for pituitary tumors. A systematic review of the literature was performed, best practices were discussed with stakeholders, and institutional guidelines were established and implemented. Key performance indicators (KPI) were measured and patient-reported outcome surveys were collected. The ERAS protocol was introduced successfully at our institution. We describe the process of initiation of the program and the perioperative management of our patients. We demonstrated the feasibility of integration of ERAS protocols for pituitary tumors with multidisciplinary engagement, with a particular emphasis on the use of data informatics and metrics to monitor outcomes. We expect that this approach will translate to improved quality of care for these often-complex patients.
PMCID:9714042
PMID: 36474665
ISSN: 2589-1081
CID: 5892252
Attitudes and trends in the use of radiolucent spinal implants: A survey of the North American Spine Society section of spinal oncology
Zavras, Athan G; Schoenfeld, Andrew J; Patt, Joshua C; Munim, Mohammed A; Goodwin, C Rory; Goodwin, Matthew L; Lo, Sheng-Fu Larry; Redmond, Kristin J; Tobert, Daniel G; Shin, John H; Ferrone, Marco L; Laufer, Ilya; Saifi, Comron; Buchowski, Jacob M; Jennings, Jack W; Ozturk, Ali K; Huang-Wright, Christina; Mesfin, Addisu; Steyn, Chris; Hsu, Wesley; Soliman, Hesham M; Krishnaney, Ajit A; Sciubba, Daniel M; Schwab, Joseph H; Colman, Matthew W
BACKGROUND/UNASSIGNED:In spinal oncology, titanium implants pose several challenges including artifact on advanced imaging and therapeutic radiation perturbation. To mitigate these effects, there has been increased interest in radiolucent carbon fiber (CF) and CF-reinforced polyetheretherketone (CFR-PEEK) implants as an alternative for spinal reconstruction. This study surveyed the members of the North American Spine Society (NASS) section of Spinal Oncology to query their perspectives regarding the clinical utility, current practice patterns, and recommended future directions of radiolucent spinal implants. METHODS/UNASSIGNED:In February 2021, an anonymous survey was administered to the physicians of the NASS section of Spinal Oncology. Participation in the survey was optional. The survey contained 38 items including demographic questions as well as multiple-choice, yes/no questions, Likert rating scales, and short free-text responses pertaining to the "clinical concept", "efficacy", "problems/complications", "practice pattern", and "future directions" of radiolucent spinal implants. RESULTS/UNASSIGNED:Fifteen responses were received (71.4% response rate). Six of the participants (40%) were neurosurgeons, eight (53.3%) were orthopedic surgeons, and one was a spinal radiation oncologist. Overall, there were mixed opinions among the specialists. While several believed that radiolucent spinal implants provide substantial benefits for the detection of disease recurrence and radiation therapy options, others remained less convinced. Ongoing concerns included high costs, low availability, limited cervical and percutaneous options, and suboptimal screw and rod designs. As such, participants estimated that they currently utilize these implants for 27.3% of anterior and 14.7% of all posterior reconstructions after tumor resection. CONCLUSION/UNASSIGNED:A survey of the NASS section of Spinal Oncology found a lack of consensus with regards to the imaging and radiation benefits, and several ongoing concerns about currently available options. Therefore, routine utilization of these implants for anterior and posterior spinal reconstructions remains low. Future investigations are warranted to practically validate these devices' theoretical risks and benefits.
PMCID:8967730
PMID: 35368717
ISSN: 2666-5484
CID: 5892242
Hybrid Therapy (Surgery and Radiosurgery) for the Treatment of Renal Cell Carcinoma Spinal Metastases
Hussain, Ibrahim; Goldberg, Jacob L; Carnevale, Joseph A; Hanz, Samuel Z; Reiner, Anne S; Schmitt, Adam; Higginson, Daniel S; Yamada, Yoshiya; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:The management of spinal metastatic renal cell carcinoma (mRCC) is controversial regarding extent of resection and radiation dosing. OBJECTIVE:To determine outcomes in patients treated with hybrid therapy (separation surgery plus adjuvant stereotactic body radiation therapy [SBRT]) for mRCC. METHODS:A retrospective study of a prospectively collected cohort of patients undergoing hybrid therapy for mRCC between 2003 and 2017 was performed. SBRT was delivered as high-dose single-fraction, high-dose hypofractionated, or low-dose hypofractionated. Extent of disease, clinical and operative outcomes, and complications data were collected, and associations with overall survival (OS) and progression-free survival were determined. RESULTS:Ninety patients with mRCC with high-grade epidural spinal cord compression (ESCC grades 2 and 3) were treated. Metastases were widespread, oligometastatic, and solitary in 56%, 33%, and 11% of patients, respectively. SBRT delivered was high-dose single-fraction, high-dose hypofractionated, and low-dose hypofractionated in 24%, 56%, and 20% of patients, respectively. The 1-yr cumulative incidence of major complications was 3.4% (95% confidence interval [CI]: 0.0%-7.2%). The median follow-up was 14.2 mo for the entire cohort and 38.3 mo for survivors. The 1-yr cumulative incidence of progression was 4.6% (95% CI: 0.2%-9.0%), which translates to a local control rate of 95.4% (95% CI: 91.0%-99.8%) 1 yr after surgery. The median OS for the cohort was 14.8 mo. CONCLUSION:These data support the use of hybrid therapy as a safe and effective strategy for the treatment of renal cell spine metastases.
PMID: 35023875
ISSN: 1524-4040
CID: 5892232
Patient outcomes following implementation of an enhanced recovery after surgery pathway for patients with metastatic spine tumors
Chakravarthy, Vikram B; Laufer, Ilya; Amin, Anubhav G; Cohen, Marc A; Reiner, Anne S; Vuong, Cindy; Persaud, Petal-Ann S; Ruppert, Lisa M; Puttanniah, Vinay G; Afonso, Anoushka M; Tsui, Van S; Brallier, Jess W; Malhotra, Vivek T; Bilsky, Mark H; Barzilai, Ori
BACKGROUND:Metastatic spine tumor surgery consists of palliative operations performed on frail patients with multiple medical comorbidities. Enhanced recovery after surgery (ERAS) programs involve an evidence-based, multidisciplinary approach to improve perioperative outcomes. This study presents clinical outcomes of a metastatic spine tumor ERAS pathway implemented at a tertiary cancer center. METHODS:The metastatic spine tumor ERAS program launched in April 2019, and data from January 2018 to May 2020 were reviewed. Measured outcomes included the following: hospital length of stay (LOS), time to ambulation, urinary catheter duration, time to resumption of diet, intraoperative fluid intake, estimated blood loss (EBL), and intraoperative and postoperative day 0-5 cumulative opioid use (morphine milligram equivalent [MME]). RESULTS:A total of 390 patients were included in the final analysis: 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program and 213 consecutive pre-ERAS patients. Although the mean case durations were similar in the ERAS and pre-ERAS cohorts (265 vs. 274 min; p = .22), the ERAS cohort had decreased EBL (157 vs. 215 ml; p = .003), decreased postoperative day 0-5 cumulative mean opioid use (178 vs. 396 MME; p < .0001), earlier ambulation (mean, 34 vs. 57 h; p = .0001), earlier discontinuation of urinary catheters (mean, 36 vs. 56 h; p < .001), and shorter LOS (5.4 vs. 7.5 days; p < .0001). CONCLUSIONS:The implementation of a multidisciplinary ERAS program designed for metastatic spine tumor surgery led to improved clinical quality metrics, including shorter hospitalizations and significant reductions in opioid consumption.
PMID: 36219485
ISSN: 1097-0142
CID: 5352002
Influence of Healthcare Disparities on Outcomes for Spinal Metastasis Patients [Meeting Abstract]
Ashayeri, K; McLaughlin, L; Khan, H; Kurland, D; Shin, W; Sales, J; Lau, D; Frempong-Boadu, A; Laufer, I; Pacione, D
Introduction: The objective of this analysis was to compare sociodemographic characteristics and outcomes between cohorts of patients receiving separation surgery for spinal metastases at two neighboring institutions, one private and one public, affiliated with a major academic medical center in a large metropolitan area.
Method(s): Patients who received separation surgery for spinal metastases between 2013 and 2021 were included in this analysis. Sociodemographic factors, treatment characteristics, and outcomes were compared between those treated at a private hospital and those treated at a neighboring public hospital using Rao-Scott chi square tests.
Result(s): Compared to those treated at our private hospital, patients treated at our public hospital were more often younger (p=0.005), of Black or Hispanic race (70% vs. 14.9%, p<0.001), and insured via Medicaid or Emergency Medicaid (48.6% vs. 3.2%, p<0.001). They more frequently presented with ESCC grade 3 compression (81.6% vs. 49.2%), potentially unstable or unstable lesions as denoted by SINS >7 (64.1% vs. 37.7%), and increased neurologic impairment as denoted by ASIA Impairment Scale scores of A, B, or C (35% vs. 7.9%). Local progression was less frequently observed in patients treated at our public hospital (28.2% vs. 54.7%, p=0.001), although this is likely due to poorer clinical and radiographic follow-up amongst this cohort. Median survival was significantly lower in patients treated at our public hospital (Median [Range]: 81 [11-1,873] days vs. 264 [0-3,092] days, p<0.001), although this is also likely confounded by lower rates of follow-up.
Conclusion(s): This study highlights substantial disparities amongst patients treated for spinal metastases at neighboring institutions affiliated with a major academic medical center. Further work is needed to identify reasons for these disparities and create avenues by which to mitigate them
EMBASE:638336457
ISSN: 1933-0693
CID: 5292372
Responder Analysis of Pain Relief After Surgery for the Treatment of Spinal Metastatic Tumors
Rothrock, Robert J; Reiner, Anne S; Barzilai, Ori; Kim, Nora C; Ogilvie, Shahiba Q; Lis, Eric; Gulati, Amitabh; Yamada, Yoshiya; Bilsky, Mark H; Laufer, Ilya
BACKGROUND:Central tendency analysis studies demonstrate that surgery provides pain relief in spinal metastatic tumors. However, they preclude patient-specific probability of treatment outcome. OBJECTIVE:To use responder analysis to study the variability of pain improvement. METHODS:In this single-center, retrospective analysis, 174 patients were studied. Logistic regression modeling was used to associate preoperative characteristics with rating the Brief Pain Inventory (BPI) worst pain item 0 to 4. Linear regression modeling was used to associate preoperative characteristics with minimal clinically important improvement (MCI) in physical functioning defined by a 1-point decrease in the BPI Interference Construct score from preoperative baseline to 6 months postoperatively. RESULTS:Patient-level analysis revealed that 60% of patients experienced an improvement in pain. At least half experienced a decrease in pain resulting in MCI in physical functioning. Cutpoint analysis revealed that 48% were responders. Increasing scores on the preoperative pain intensity BPI items, the MD Anderson Symptom Inventory (MDASI) Core Symptom Severity Construct, the MDASI Spine Tumor-Specific Construct, the presence of preoperative neurologic deficits, and postoperative complications were associated with lower probability of treatment success while increasing severity in all BPI pain items, and MDASI constructs were associated with increased probability of MCI in physical function. Significant mortality and loss to follow-up intrinsic to this patient population limit the strength of these data. CONCLUSION/CONCLUSIONS:Although patients with milder preoperative symptoms are likely to achieve better pain relief after surgery, patients with worse preoperative symptom also benefit from surgery with adequate pain relief with an improvement in physical function.
PMID: 35856981
ISSN: 1524-4040
CID: 5279122
Development and external validation of predictive algorithms for 6-week mortality in spinal metastasis using 4304 Patients from 5 Institutions
Karhade, Aditya V; Fenn, Brian; Groot, Olivier Q; Shah, Akash A; Yen, Hung-Kuan; Bilsky, Mark H; Hu, Ming-Hsiao; Laufer, Ilya; Park, Don Y; Sciubba, Daniel M; Steyerberg, Ewout W; Tobert, Daniel G; Bono, Christopher M; Harris, Mitchel B; Schwab, Joseph H
BACKGROUND CONTEXT/BACKGROUND:Historically, spine surgeons used expected postoperative survival of 3-months to help select candidates for operative intervention in spinal metastasis. However, this cutoff has been challenged by the development of minimally invasive techniques, novel biologics, and advanced radiotherapy. Recent studies have suggested that life expectancy of 6 weeks may be enough to achieve significant improvements in postoperative health-related quality of life. PURPOSE/OBJECTIVE:The purpose of this study was to develop a model capable of predicting 6-week mortality in patients with spinal metastases treated with radiation or surgery. STUDY DESIGN/SETTING/METHODS:Retrospective review was conducted at five large tertiary centers in the United States and Taiwan. PATIENT SAMPLE/METHODS:The development cohort consisted of 3,001 patients undergoing radiotherapy and/or surgery for spinal metastases from one institution. The validation institutional cohort consisted of 1,303 patients from four independent, external institutions. OUTCOME MEASURES/METHODS:The primary outcome was six-week mortality METHODS: Five models were considered to predict six-week mortality, and the model with the best performance across discrimination, calibration, decision-curve analysis, and overall performance was integrated into an open access web-based application. RESULTS:The most important variables for prediction of 6-week mortality were albumin, primary tumor histology, absolute lymphocyte, three or more spine metastasis, and ECOG score. The elastic-net penalized logistic model was chosen as the best performing model with AUC 0.84 on evaluation in the independent testing set. On external validation in the 1,303 patients from the four independent institutions, the model retained good discriminative ability with an area under the curve of 0.81. The model is available here: https://sorg-apps.shinyapps.io/spinemetssurvival/. CONCLUSIONS:While this study does not advocate for the use of 6-week life expectancy as a criteria for considering operative management, the algorithm developed and externally validated in this study may be helpful for preoperative planning, multidisciplinary management, and shared decision making in spinal metastasis patients with shorter life expectancy.
PMID: 35843533
ISSN: 1878-1632
CID: 5278782