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AO Spine Clinical Practice Recommendations: Current Systemic Oncological Treatments with the Largest Impact on Patients with Metastatic Spinal Disease
Czyz, Marcin; Wensink, Emerens G; Coimbra, Brian; Galgano, Michael; Patel, Shreyaskumar; Redmond, Kristin; Rutges, Joost; Tan, Jiong Hao Jonathan; Barzilai, Ori; Dea, Nicolas; Gasbarrini, Alessandro; Laufer, Ilya; Lazary, Aron; Netzer, Cordula; Reynolds, Jeremy J; Rhines, Laurence D; Sahgal, Arjun; Fisher, Charles G; Verlaan, Jorrit-Jan
Study DesignLiterature review with clinical recommendation.ObjectiveTo provide the readers with a concise curation of the latest literature in recent advances in systemic oncological therapies and their implications for decision-making in patients with metastatic spinal disease. This review aims to enhance spine specialist's understanding of modern oncological treatments to facilitate optimal timing and planning of local interventions.MethodsThe latest literature in the topic of advances in oncology was reviewed by a multidisciplinary group of experts in metastatic spinal disease and clinical recommendations were formulated. The recommendations were dichotomously graded into strong and conditional (weak) based on the integration of scientific methodology and content expert opinion. This opinion considered experience and practical issues such as risks, burdens, costs, patient values, and circumstances.ResultsFour high-impact studies were reviewed, demonstrating significant advancements in systemic treatments for metastatic cancers commonly affecting the spine. These studies showed improved survival outcomes and efficacy across breast cancer, colorectal cancer, prostate cancer, and renal cell carcinoma. The findings have important implications for surgical/radiotherapy planning, including considerations for timing of interventions, wound healing, and the potential for extended survival affecting construct durability requirements.ConclusionsRecent advances in systemic oncological treatments have important implications for managing metastatic spinal disease. Understanding these developments is crucial for spine specialists to optimize decision-making through a multidisciplinary approach, particularly regarding timing of local interventions, strategy of the surgical approach and reconstruction.[Formula: see text].
PMID: 40153520
ISSN: 2192-5682
CID: 5817582
Frontline Voice: AO Spine Member Survey Regarding Spine Oncology Knowledge Generation and Translation Needs
Goodwin, Matthew L; Loomans, Janneke I; Barzilai, Ori; Dea, Nicolas; Gasbarrini, Alessandro; Lazáry, Aron; Netzer, Cordula; Reynolds, Jeremy; Rhines, Laurence; Sahgal, Arjun; Verlaan, Jorrit-Jan; Fisher, Charles G; Laufer, Ilya; On Behalf Of Ao Spine Knowledge Forum Tumor,
STUDY DESIGN/METHODS:cross-sectional survey. OBJECTIVES/OBJECTIVE:To evaluate AO Spine members' practices and comfort in managing metastatic and primary spine tumors, explore the use of decision-support and patient assessment tools, and identify knowledge gaps and future needs in spine oncology. METHODS:An online survey was distributed to AO Spine members to query comfort levels with key decisions in spinal oncology management, utilization of decision frameworks and spine oncology-specific instruments, and educational material preferences. RESULTS:Responses were obtained from 381 members across 82 countries. Most respondents were orthopedic spine surgeons (62%) or neurosurgeons (36%), with 42% performing 100-200 spine surgeries per year. Extradural primary and metastatic tumors were managed by 84% and 95% of respondents, respectively, with survival and frailty assessment tools used for both. While most surgeons felt comfortable determining when emergency surgery was needed (81% for primary and 82% for metastatic tumors), nuanced decisions about surgical timing were more challenging. Surgeons also noted challenges in tailoring the oncologic surgical plan to what the patient could safely tolerate. There was a strong desire for guidelines on tumor-related spinal pain (85%), treatment timing (85%), stabilization (85%), and glucocorticoid use for symptomatic extradural metastatic tumors (77%). Interest was high for classification systems for spine tumor pain (65%) and stabilization decisions (80%). CONCLUSIONS:Additional support is needed in decision-making regarding surgical timing, patient selection, and tailoring treatment invasiveness to life expectancy and frailty. Surgeons seek further guidance to prevent neurologic deterioration and optimize recovery. Guidelines and classification systems were highly coveted for daily practice.
PMCID:11773503
PMID: 39868544
ISSN: 2192-5682
CID: 5780592
Overview of Molecular Prognostication for Common Solid Tumor Histologies - What the Surgeon Should Know
Goodwin, C Rory; De la Garza Ramos, Rafael; Bettegowda, Chetan; Barzilai, Ori; Shreyaskumar, Patel; Fehlings, Michael G; Laufer, Ilya; Sahgal, Arjun; Rhines, Laurence D; Reynolds, Jeremy J; Lazary, Aron; Gasbarrini, Alessandro; Dea, Nicolas; Verlaan, Jorrit-Jan; Sullivan, Patricia Zadnik; Gokaslan, Ziya L; Fisher, Charles G; Boriani, Stefano; Shin, John H; Hornicek, Francis J; Weber, Michael H; Goodwin, Matthew L; Charest-Morin, Raphaële; ,
STUDY DESIGN/METHODS:Narrative Literature review. OBJECTIVE:To provide a general overview of important molecular markers and targeted therapies for the most common neoplasms (lung, breast, prostate and melanoma) that metastasize to the spine and offer guidance on how to best incorporate them in the clinical setting. METHODS:A narrative review of the literature was performed using PubMed, Google Scholar, Medline databases, as well as the histology-specific National Comprehensive Cancer Network guidelines to identify relevant articles limited to the English language. Relevant articles were reviewed for commonly described molecular mutations or targeted therapeutics, as well as associated clinical outcomes, and surgery-related risks. RESULTS:Molecular markers and targeted therapies have dramatically improved the survival of cancer patients. The increasing importance of prognostic molecular markers and targeted therapies provides rationale for their incorporation into clinical decision-making for patients diagnosed with metastatic spine disease. In this review, we discuss the molecular markers/mutations and targeted therapies associated with the most common malignancies that metastasize to the spine and provide a framework that the surgeon can utilize when evaluating patients for potential intervention. Finally, we provide case examples that highlight the importance of molecular prognostication and therapies in surgical decision-making. CONCLUSION/CONCLUSIONS:An integrated understanding of the implications of surgery, radiation, molecular markers and targeted therapies that guide prognostication and treatment is warranted in order to achieve the most favorable outcomes for patients with metastatic spine disease.
PMCID:11726510
PMID: 39801124
ISSN: 2192-5682
CID: 5776062
Defining Spine Cancer Pain Syndromes: A Systematic Review and Proposed Terminology
Pahuta, Markian; Laufer, Ilya; Lo, Sheng-Fu Larry; Boriani, Stefano; Fisher, Charles; Dea, Nicolas; Weber, Michael H; Chou, Dean; Sahgal, Arjun; Rhines, Laurence; Reynolds, Jeremy; Lazary, Aron; Gasbarrinni, Alessandro; Verlaan, Jorrit-Jan; Gokaslan, Ziya; Bettegowda, Chetan; Sarraj, Mohamed; Barzilai, Ori; ,
STUDY DESIGN/METHODS:Systematic Review. OBJECTIVES/OBJECTIVE:Formalized terminology for pain experienced by spine cancer patients is lacking. The common descriptors of spine cancer pain as mechanical or non-mechanical is not exhaustive. Misdiagnosed spinal pain may lead to ineffective treatment recommendations for cancer patients. METHODS:We conducted a systematic review of pain terminology that may be relevant to spinal oncology patients. We provide a comprehensive and unbiased summary of the existing evidence, not limited to the spine surgery literature, and subsequently consolidate these data into a practical, clinically relevant nomenclature for spine oncologists. RESULTS:Our literature search identified 3515 unique citations. Through title and abstract screening, 3407 citations were excluded, resulting in 54 full-text citations for review. Pain in cancer patients is typically described as nociceptive pain (somatic vs visceral), neurologic pain and treatment related pain. CONCLUSIONS:We consolidate the terminology used in the literature and consolidated into clinically relevant nomenclature of biologic tumor pain, mechanical pain, radicular pain, neuropathic pain, and treatment related pain. This review helps standardize terminology for cancer-related pain which may help clinicians identify pain generators.
PMCID:11726517
PMID: 39801118
ISSN: 2192-5682
CID: 5775962
Radiation Myelitis Risk After Hypofractionated Spine Stereotactic Body Radiation Therapy
Jackson, Christopher B; Boe, Lillian A; Zhang, Lei; Apte, Aditya; Ruppert, Lisa M; Haseltine, Justin M; Mueller, Boris A; Schmitt, Adam M; Yang, Jonathan T; Newman, W Christopher; Barzilai, Ori; Bilsky, Mark H; Yamada, Yoshiya; Jackson, Andrew; Lis, Eric; Higginson, Daniel S
IMPORTANCE/UNASSIGNED:Stereotactic body radiation therapy (SBRT) for spinal metastases improves symptomatic outcomes and local control compared to conventional radiotherapy. Treatment failure most often occurs within the epidural space, where dose is constrained by the risk of radiation myelitis (RM). Current constraints designed to prevent RM after spine SBRT are derived from limited data. OBJECTIVE/UNASSIGNED:To characterize the risk of RM after spine SBRT and to update the dosimetric constraints for preventing it. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted in a single tertiary cancer care center with patients treated for spinal metastases from 2014 to 2023. All included participants had undergone spine SBRT, had a minimum of 1-month follow-up with magnetic resonance imaging (MRI), a maximal cord dose to a voxel (Dmax) greater than 0 Gy, and no overlapping prior radiotherapy. In all, 2051 patients received SBRT to 2835 spinal metastases (levels C1-L2) during the study period. EXPOSURES/UNASSIGNED:Three-fraction spine SBRT to a prescription dose of 27 to 36 Gy. MAIN OUTCOMES AND MEASURES/UNASSIGNED:RM defined as radiographic evidence of spinal cord injury in the treatment field, classified as grade (G) 1 to G4 or G3 to G4 per the Common Terminology Criteria for Adverse Events, version 5.0. Multiple dosimetric parameters of the true spinal cord structure were assessed for an association with risk of RM to determine the important covariates associated with this toxicity. RESULTS/UNASSIGNED:The analysis included 1423 patients (mean [SD] age, 61.6 [12.9] years; 695 [48.8%] females and 728 [51.1%] males) who received SBRT for 1904 spinal metastases. Among them, 30 cases of RM were identified, 19 of which were classified as G3 to G4. Two years after SBRT, the rate of G1 to G4 RM was 1.8% (95% CI, 1.2%-2.5%) and the rate of G3 to G4 RM was 1.1% (95% CI, 0.7%-1.7%). The minimum dose to the 0.1 cm3 of spinal cord receiving the greatest dose (D0.1cc) was the most important covariate on univariable cause-specific hazards regression for RM (for G3 to G4: hazard ratio, 2.14; 95% CI, 1.68-2.72; P < .001). A true cord D0.1cc of 19.1 Gy and Dmax of 20.8 Gy estimated a 1.0% risk (95% CI, 0.3%-1.6% and 0.4%-1.6%, respectively) of G3 to G4 RM 2 years after SBRT. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this cohort study indicate that a cord (myelogram or MRI-derived) D0.1cc constraint of 19.1 Gy and a Dmax constraint of 20.8 Gy correspond with a 1.0% risk of G3 to G4 RM at 2 years.
PMID: 39699884
ISSN: 2374-2445
CID: 5771512
40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy
Moore, Assaf; Zhang, Zhigang; Fei, Teng; Zhang, Lei; Accomando, Laura; Schmitt, Adam M; Higginson, Daniel S; Mueller, Boris A; Zinovoy, Melissa; Gelblum, Daphna Y; Yerramilli, Divya; Xu, Amy J; Brennan, Victoria S; Guttmann, David M; Grossman, Craig E; Dover, Laura L; Shaverdian, Narek; Pike, Luke R G; Cuaron, John J; Dreyfuss, Alexandra; Lis, Eric; Barzilai, Ori; Bilsky, Mark H; Yamada, Yoshiya
BACKGROUND AND PURPOSE/OBJECTIVE:A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. METHODS:We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. RESULTS:Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. CONCLUSION/CONCLUSIONS:In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.
PMID: 38456696
ISSN: 1524-4040
CID: 6014572
Radiation therapy, radiosurgery, chemotherapy and targeted therapies for metastatic spine tumors: WFNS Spine committee recommendations
Sekar, Vashisht; Walsh, Jamie; Pearson, Luke H; Barzilai, Ori; Sharif, Salman; Zileli, Mehmet
OBJECTIVE:This review aims to formulate the most current, evidence-based recommendations regarding radiation therapy, radiosurgery, and chemotherapy for patients with metastatic spine tumors. METHODS:A systematic literature using PRISMA methodology was performed from 2010-2023 using the search terms "radiosurgery," "radiation therapy," "external beam radiation therapy," or "stereotactic body radiation therapy" in conjunction with "spinal," "spine," "metastasis," "metastases," or "metastatic." RESULTS:Spinal metastases should be managed in a multidisciplinary team consisting of spine surgeons, radiation oncologists, radiologists and oncologists. Patients identified as potential candidates for SRS/EBRT using internationally recognized frameworks and criteria should be assessed by surgeons to see if surgical cyto-reduction/ separation surgery can be achieved. Choices for treatment of recurrence include re-irradiation with SBRT vs EBRT, surgical debulking, additional chemotherapy or palliative care. There is a lack of current clinical evidence to support the routine use of targeted therapies in the management of metastatic spinal tumors. CONCLUSIONS:Improving the management of spinal metastasis will lead to increased quality of life and improved survival. This review provides current, evidence-based guidelines on radiation therapy, radiosurgery, and chemotherapy for patients with metastatic spine tumors.
PMID: 39739070
ISSN: 1437-2320
CID: 6014622
Compliance With Federal Price Transparency Rules and Cost Estimation at United States Hospitals With Neurosurgical Training Programs
Giantini-Larsen, Alexandra; Pandey, Abhinav; Abou-Mrad, Zaki; Tata, Nalini; Barzilai, Ori; Bilsky, Mark; Newman, W Christopher
BACKGROUND AND OBJECTIVES/OBJECTIVE:The Centers for Medicare & Medicaid Services implemented federal requirements on January 1, 2021, under the Public Health Service Act that require hospitals to provide a list of payer-negotiated prices or "standard charges" in a machine-readable file and in a patient-friendly online estimator for standard services. We sought to assess compliance by United States hospitals associated with neurosurgical training programs with these federal requirements for 11 common neurosurgical procedures. METHODS:We performed a cross-sectional analysis in March 2023 of 116 United States hospitals associated with a neurosurgical training program to assess compliance with the new federal requirements to have a machine-readable, downloadable file with standard charges and a patient-friendly online estimator for two spinal procedures. RESULTS:A total of 110/114 (96.5%) hospitals were compliant with the requirement for a machine-readable file with payer-negotiated prices. A total of 47/110 hospitals (42.7%) were compliant with downloadable machine-readable files and reported at least one payer-negotiated price for 1 of the 11 common neurosurgical procedures. A total of 45/110 (40.9%) used bundled Diagnosis-Related Group codes, and 18/110 (16.4%) did not contain any price information for neurosurgical procedures. For neurosurgical procedures, the percent difference between the average negotiated private insurance and Medicare price per procedure ranged from 17.5% to 77.6%. Medicare and private insurance data for each procedure were available on average for 10.3 states (SD = 3.8) and 15.6 states (SD = 4.8), respectively. CONCLUSION/CONCLUSIONS:While hospital compliance with federal requirements for machine-readable files with payer-negotiated prices was high, availability of payer-negotiated prices for 4 major insurance types across 11 common neurosurgical procedures based on Current Procedural Terminology codes was sparce. Consequently, meaningful conclusions on procedure-related charges for elective procedures are difficult for patients to make because of the unintelligible format of data and a lack of reporting of charges per Current Procedural Terminology code in a comprehensive manner.
PMID: 38345364
ISSN: 1524-4040
CID: 6014562
Management of Refractory Cancer Pain with Intrathecal Drug Delivery and Spinal Cord Stimulation
Bulat, Evgeny; Crowther, Jason E; Chakravarthy, Vikram; Laufer, Ilya; Barzilai, Ori; Gulati, Amitabh
BACKGROUND/UNASSIGNED:Intrathecal pumps (ITPs) are indicated for refractory cancer pain and decrease systemic opioid requirements. While not yet indicated for cancer pain, spinal cord stimulators (SCSs) are used off-label for cancer pain, with increasing evidence of their efficacy. MATERIALS AND METHODS/UNASSIGNED:A retrospective chart review was conducted of patients who underwent both ITP and at least SCS trial for cancer pain. Primary outcomes were pain numeric rating scale (NRS) and daily morphine equivalents (MEQs). RESULTS/UNASSIGNED:Seventeen patients were identified. Both ITP and SCS were associated with significant decreases in pain ratings at the 3-month follow-up, but this decrease became nonsignificant subsequently. ITP, but not SCS, was associated with a significant decrease in MEQ. CONCLUSIONS/UNASSIGNED:ITP and SCS may both provide efficacy for cancer pain, but the opioid-sparing effects of SCS may be limited. ITP and SCS may potentially be complementary in their ability to provide relief from cancer-related pain.
PMCID:11319851
PMID: 39144131
ISSN: 2689-2820
CID: 5892282
Safety and Efficacy of Surgical Implantation of Intrathecal Drug Delivery Pumps in Patients With Cancer With Refractory Pain
Winston, Graham M; Zimering, Jeffrey H; Newman, Christopher W; Reiner, Anne S; Manalil, Noel; Kharas, Natasha; Gulati, Amitabh; Rakesh, Neal; Laufer, Ilya; Bilsky, Mark H; Barzilai, Ori
BACKGROUND AND OBJECTIVES/OBJECTIVE:Pain management in patients with cancer is a critical issue in oncology palliative care as clinicians aim to enhance quality of life and mitigate suffering. Most patients with cancer experience cancer-related pain, and 30%-40% of patients experience intractable pain despite maximal medical therapy. Intrathecal pain pumps (ITPs) have emerged as an option for achieving pain control in patients with cancer. Owing to the potential benefits of ITPs, we sought to study the long-term outcomes of this form of pain management at a cancer center. METHODS:We retrospectively reviewed medical records of all adult patients with cancer who underwent ITP placement at a tertiary comprehensive cancer center between 2013 and 2021. Baseline characteristics, preoperative and postoperative pain control, and postoperative complication rate data were collected. RESULTS:A total of 193 patients were included. We found that the average Numerical Rating Scale (NRS) score decreased significantly by 4.08 points (SD = 2.13, P < .01), from an average NRS of 7.38 (SD = 1.64) to an average NRS of 3.27 (SD = 1.66). Of 185 patients with preoperative and follow-up NRS pain scores, all but 9 experienced a decrease in NRS (95.1%). The median overall survival from time of pump placement was 3.62 months (95% CI: 2.73-4.54). A total of 42 adverse events in 33 patients were reported during the study period. The 1-year cumulative incidence of any complication was 15.6% (95% CI: 10.9%-21.1%) and for severe complication was 5.7% (95% CI: 3.0%-9.7%). Eleven patients required reoperation during the study period, with a 1-year cumulative incidence of 4.2% (95% CI: 2.0%-7.7%). CONCLUSION/CONCLUSIONS:Our study demonstrates that ITP implantation for the treatment of cancer-related pain is a safe and effective method of pain palliation with a low complication rate. Future prospective studies are required to determine the optimal timing of ITP implantation.
PMID: 38700319
ISSN: 1524-4040
CID: 5734282