Editorial. Assessing treatment response following stereotactic body radiotherapy for spinal metastases

Steven G. RothDepartment of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee

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Lola B. ChamblessDepartment of Neurosurgery, Vanderbilt University Medical Center, Nashville, Tennessee

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Although the exact prevalence of spinal column metastases is unclear, encountering these lesions is an increasingly frequent clinical scenario due to both an aging population and improving survival rates for primary malignancies.1 Spinal column metastases frequently manifest as pain, or less commonly, with neurological deficit secondary to metastatic epidural spinal cord compression (MESCC).2 Treatment-related decisions require multidisciplinary collaboration due to the significant complexity of disease in these patients, taking into consideration the primary pathology, performance status, disease extent, and the presence of MESCC or instability.1 The overarching goal is the enhancement of patient outcomes while concurrently limiting treatment-related morbidity.

Stereotactic body radiotherapy (SBRT), with or without separation surgery to mitigate the risk of radiation myelopathy, is an established treatment modality available in the armamentarium against spinal column metastases. SBRT is particularly valuable in oligometastatic disease,3,4 as well as for pathologies previously considered radioresistant.5 SBRT as a technique is well described and has been validated in terms of safety, symptomatic relief, and local disease control.6 The literature reflects the fact that local control of spinal column metastases following SBRT ranges from 82% to 96%;7 however, studies suffer from a lack of consistency in how treatment response is evaluated.

Objective solid-tumor treatment response is assessed radiographically using several methodologies. Each uses differing metrics to assign treatment responses to one of four categories: complete response, partial response, stable disease, or progressive disease. The bidimensional WHO criteria, developed in 1979 prior to the widespread availability of CT, involves measuring the largest tumor diameter and multiplying this by the largest perpendicular diameter.8 The unidimensional Response Evaluation Criteria in Solid Tumors (RECIST) criteria, developed in 2000, involve trending only the largest measurable tumor diameter.9 Although not initially applicable to bony lesions, a 2009 update, RECIST 1.1, expanded the criteria to include mixed and osteolytic lesions with 10 mm of soft-tissue extension.10 RECIST 1.1 is still not applicable to osteoblastic lesions and those without 10 mm of soft-tissue extension. The University of Texas MD Anderson Cancer Center criteria were developed specifically for bony metastases and include both quantitative and qualitative assessment metrics.11 The MD Anderson Cancer Center system is limited in that it can only be used in conjunction with other response criteria or in individuals with no other measurable disease. Importantly, each system possesses its own limitations, and importantly, none were specifically designed for spinal column metastases.

The Spine Response Assessment in Neuro-Oncology (SPINO) group published the results of an international survey of experts that demonstrated the challenges of standardizing imaging-based assessment of local control for spinal metastases following SBRT.12 Heterogeneity between centers was noted in imaging selection for initial treatment planning—with CT, CT myelography, MRI with or without contrast, and FDG-PET all being used. Also, although MRI was the most frequently used imaging study for serial tumor assessment, follow-up imaging schedules varied greatly. Last, radiographic tumor response criteria were not standardized.12 The authors propose that local control be defined as absence of progression on serial imaging obtained 6–8 weeks apart and that local progression should be defined as follows: 1) gross unequivocal increase in volume or linear dimension; 2) any new or progressive disease within the epidural space; or 3) neurological deterioration attributable to MESCC.12

The paper by Harel and colleagues in this edition of Neurosurgical Focus addresses the need for a simple, reproducible, quantitative method of assessing local treatment response derived from widely available imaging modalities.13 They sought to validate and compare the WHO and RECIST tumor response criteria for spinal column metastases following SBRT by using traditional MRI. Their cohort included 59 patients with spinal column metastases representing 111 diseased vertebral bodies treated with SBRT at 81 isocenters.13 They described a straightforward technique of measuring pretreatment tumor dimensions in three orthogonal planes: anterior-posterior, transverse, and cranial-caudal. The largest of these measurements was used for RECIST criteria, and the two largest were used to calculate WHO criteria. They observed local control rates of 95% and 98% using WHO and RECIST criteria, respectively, at a median follow-up of 10.8 months, and demonstrated a statistically significant agreement between the two methods.13 Due to simplicity in obtaining unidimensional measurement, they favored adopting RECIST as a uniform strategy for assessing treatment response for spinal column metastases following SBRT. They posit that standardization will benefit data integration and have positive downstream effects on clinical trials and outcomes.13

The inherently complex nature of the spinal column and its associated tumors as well as the level of variability present in MRI technique serves to complicate current anatomical assessment methods. The use of detailed volumetric analysis, the standard for evaluating certain other pathologies such as intracranial tumors, is in its infancy for use with spinal column metastases.14 Harel et al. concede that although volumetric analysis may be the ideal method for assessing local control, they also identify several challenges limiting widespread implementation. These include a lack of imaging standardization between centers, the labor-intensive nature of tumor contouring, and the present difficulty in developing software to effectively resolve issues related to spinal instrumentation.13

The role of advanced imaging modalities is also of interest in evaluating tumor progression. A novel method of assessing treatment response, PERCIST (PET Response Criteria in Solid Tumors) is not based on anatomical response but rather on changes in tumor metabolic activity as measured on FDG-PET.15 While potentially invaluable, this technique is not consistently applied at most centers and its use is restricted to FDG-avid lesions. Initial studies on dynamic contrast-enhanced MRI demonstrate promise in detecting early treatment response; however, this technique is not yet widely used or available.16 Last, the potential application of artificial intelligence and machine learning techniques to the fields of spinal column metastases and SBRT treatment has not yet been explored in detail, and may prove to be a source of innovation.17

Disclosures

The authors report no conflict of interest.

References

  • 1

    Wewel JT, O’Toole JE. Epidemiology of spinal cord and column tumors. Neurooncol Pract. 2020;7(suppl 1):i5i9.

  • 2

    Sciubba DM, Pennington Z, Colman MW, et al. Spinal metastases 2021: a review of the current state of the art and future directions. Spine J. 2021;21(9):14141429.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol. 2020;38(25):28302838.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Chen H, Louie AV, Higginson DS, Palma DA, Colaco R, Sahgal A. Stereotactic radiosurgery and stereotactic body radiotherapy in the management of oligometastatic disease. Clin Oncol (R Coll Radiol). 2020;32(11):713727.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Ghia AJ, Chang EL, Bishop AJ, et al. Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials. J Neurosurg Spine. 2016;24(5):829836.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021;22(7):10231033.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Soltys SG, Grimm J, Milano MT, et al. Stereotactic body radiation therapy for spinal metastases: tumor control probability analyses and recommended reporting standards. Int J Radiat Oncol Biol Phys. 2021;110(1):112123.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    World Health Organization. WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization;1979.

  • 9

    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205216.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228247.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT. Bone imaging in metastatic breast cancer. J Clin Oncol. 2004;22(14):29422953.

  • 12

    Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol. 2015;16(16):e595e603.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Harel R, Kaisman-Elbaz T, Emch T, et al. A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology. Neurosurg Focus. 2022;53(5):E10.

    • Search Google Scholar
    • Export Citation
  • 14

    Jabehdar Maralani P, Tseng CL, Baharjoo H, et al. The initial step towards establishing a quantitative, magnetic resonance imaging-based framework for response assessment of spinal metastases after stereotactic body radiation therapy. Neurosurgery. 2021;89(5):884891.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(suppl 1):122S150S.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Kumar KA, Peck KK, Karimi S, et al. A pilot study evaluating the use of dynamic contrast-enhanced perfusion MRI to predict local recurrence after radiosurgery on spinal metastases. Technol Cancer Res Treat. 2017;16(6):857865.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Galbusera F, Casaroli G, Bassani T. Artificial intelligence and machine learning in spine research. JOR Spine. 2019;2(1):e1044.

  • Collapse
  • Expand
  • 1

    Wewel JT, O’Toole JE. Epidemiology of spinal cord and column tumors. Neurooncol Pract. 2020;7(suppl 1):i5i9.

  • 2

    Sciubba DM, Pennington Z, Colman MW, et al. Spinal metastases 2021: a review of the current state of the art and future directions. Spine J. 2021;21(9):14141429.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3

    Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol. 2020;38(25):28302838.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4

    Chen H, Louie AV, Higginson DS, Palma DA, Colaco R, Sahgal A. Stereotactic radiosurgery and stereotactic body radiotherapy in the management of oligometastatic disease. Clin Oncol (R Coll Radiol). 2020;32(11):713727.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5

    Ghia AJ, Chang EL, Bishop AJ, et al. Single-fraction versus multifraction spinal stereotactic radiosurgery for spinal metastases from renal cell carcinoma: secondary analysis of Phase I/II trials. J Neurosurg Spine. 2016;24(5):829836.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Sahgal A, Myrehaug SD, Siva S, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021;22(7):10231033.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Soltys SG, Grimm J, Milano MT, et al. Stereotactic body radiation therapy for spinal metastases: tumor control probability analyses and recommended reporting standards. Int J Radiat Oncol Biol Phys. 2021;110(1):112123.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    World Health Organization. WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization;1979.

  • 9

    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92(3):205216.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228247.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT. Bone imaging in metastatic breast cancer. J Clin Oncol. 2004;22(14):29422953.

  • 12

    Thibault I, Chang EL, Sheehan J, et al. Response assessment after stereotactic body radiotherapy for spinal metastasis: a report from the SPIne response assessment in Neuro-Oncology (SPINO) group. Lancet Oncol. 2015;16(16):e595e603.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Harel R, Kaisman-Elbaz T, Emch T, et al. A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology. Neurosurg Focus. 2022;53(5):E10.

    • Search Google Scholar
    • Export Citation
  • 14

    Jabehdar Maralani P, Tseng CL, Baharjoo H, et al. The initial step towards establishing a quantitative, magnetic resonance imaging-based framework for response assessment of spinal metastases after stereotactic body radiation therapy. Neurosurgery. 2021;89(5):884891.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: evolving considerations for PET response criteria in solid tumors. J Nucl Med. 2009;50(suppl 1):122S150S.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Kumar KA, Peck KK, Karimi S, et al. A pilot study evaluating the use of dynamic contrast-enhanced perfusion MRI to predict local recurrence after radiosurgery on spinal metastases. Technol Cancer Res Treat. 2017;16(6):857865.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Galbusera F, Casaroli G, Bassani T. Artificial intelligence and machine learning in spine research. JOR Spine. 2019;2(1):e1044.

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