Metastatic Spinal Cord Compression Secondary to Lung Cancer: Comparison
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Please note this is a comparison between Version 2 by Catherine Yang and Version 1 by Stergios Boussios.

Metastatic spinal cord compression (MSCC) is characterised by the compression of the spinal cord due to direct or metastatic spread to the vertebrae, potentially leading to neurological deficits. This condition constitutes an urgent situation in oncology, demanding swift diagnosis and immediate intervention due to the considerable risk of spinal cord damage and irreversible neurological repercussions. Spinal tumours resulting from the metastasis of lung cancer are particularly connected with an unfavourable prognosis, often displaying rapid advancement and limited survival. Treatment approaches encompass a combination of radiotherapy and potential surgery, which are tailored to each patient’s situation. Within this retrospective study, our goal was to pinpoint prognostic elements that impact the survival rates of lung cancer patients experiencing MSCC. Identifying such prognostic factors associated with shorter or longer survival subsequent to MSCC could contribute to tailoring distinct, more or less intensive therapeutic strategies for these individuals.

  • metastatic spinal cord compression
  • lung cancer
  • survivor
  • prognostic factors

1. Introduction

MSCC is an oncological emergency for which early detection and prompt management are critical to preserving patients’ neurological function. Lung cancer represents the most common tumour type among patients presenting with MSCC, overall representing approximately 20% of cases [20,21,22,23][1][2][3][4]. Several studies have shown that the MSCC sequela of lung cancer has worse survival compared to other solid tumours such as prostate and breast cancer [24,25,26,27][5][6][7][8]. Weigel et al. reported that the survival time of lung cancer patients presenting with MSCC was 2.1 months in comparison to 7.3 months in prostate cancer patients and 21.2 months in breast cancer patients [28][9]. In this study, wthe researchers showed that the median survival of lung cancer patients presenting with MSCC was 5.5 months, and the six-month survival rate was 29.7%.
In the entire lung cancer cohort, the weresearchers identified two prognostic factors that demonstrated a statistically significant impact on patient survival with NSCLC and one to two affected vertebrae. In the NSCLC subgroup, the following factors were associated with improved overall survival: EGFR molecular alterations, ambulatory patients, and the ECOG performance status of 1–2. The early development of motor deficits (≤10 days) was associated with worsened OS in both the entire lung cancer cohort and the NSCLC subgroup.
There are several scoring systems available to predict survival in patients with spinal metastasis. The Tokuhashi score comprises six factors that are deemed influential for prognosis, encompassing overall health status, the count of bone metastases apart from spinal involvement, the number of spinal metastases, primary lesion type, the presence of major organ metastases, and paralysis status [8][10]. Survival durations were projected based on the cumulative score utilising prognostic benchmarks. The survival period was up to 6 months for a total score of 0–8, over 6 months for a total score of 9–11, and over 1 year for a total score of 12 or more. The Tokuhashi score did not incorporate any element in relation to treatment interventions and allowed for an adaptable application. Furthermore, the Spine Oncology Study Group (SOSG) developed the Spinal Instability Neoplastic Score (SINS) in 2010 [29][11]. This scoring system evaluates and assigns scores to 6 variables—lesion location, pain characteristics, bony lesion type, spinal alignment on radiographs, the extent of vertebral body destruction, and involvement of posterolateral spinal elements. The individual scores for each variable were summed to yield a final score ranging from a minimum of 0 to a maximum of 18. A score between 0 and 6 indicates stability, a score between 7 and 12 suggests uncertain (potentially impending) instability and a score between 13 and 18 signifies instability. For scores exceeding 7, it is advisable to seek surgical consultation. However, none of the known scoring systems are particularly tailored to lung cancer patients, despite a few studies focusing on the analysis of prognostic variables in MSCC secondary to lung cancer [30,31][12][13]. Nevertheless, many parameters assessed by these scoring systems were also identified in the present study, including the number of vertebrae affected by spinal metastasis.
From a histological perspective, SCLC behaves more aggressively than NSCLC histology, exhibiting early dissemination to distant sites and rapid growth [32][14]. The distinction between these two types of lung cancer was clearly evident in ourthe study, where, at any given time, SCLC patients were 82% more likely to die compared to NSCLC patients. This aligns with previous studies showing the survival rate of SCLC ranging from 6 days to 20 months [33,34][15][16]. Another independent negative prognostic factor noted in ourthe study was the involvement of more than two vertebrae, with patients being 64% more likely to die compared to those with two or fewer vertebra involved. This is also seen in the literature with studies evaluating the number of vertebrae involved as a factor of advanced disease; in univariate analysis, a positive association with survival was noted when one or two vertebrae were involved [21,35][2][17].

2. The treatment of  Metastatic Spinal Cord Compression

The treatment of MSCC includes corticosteroids, radiotherapy, and surgery used either alone or in combination [22,35,36,37,38,39][3][17][18][19][20][21]. Irrespective of the palliative nature of this treatment approach, treatment objectives encompass local tumour and pain management, as well as enhancing neurological functions to enhance overall quality of life. However, within this study, wthe researchers faced limitations when isolating and individually addressing each of these goals. OurThe study, however, has shown that having decompressive laminectomy, either less or equal to 6 days from confirmed MSCC, confers a significant impact on survival. This is also supported by a recent study by Meyer et al., who found that early surgery within 16 h, or even 12 h in certain cases, could significantly increase the chances for better functional recovery without increasing the risk of complications [40][22]. Therefore, referring patients with MSCC to surgery as early as possible is critical in the management of these patients. Younsi et al. reported that after decompressive laminectomy, 61% of 101 neurologically impaired MSCC patients were able to walk at discharge [41][23]. According to their findings, the better the pre-operative ambulatory function of the patient, the higher the survival rates, which is in line with the literature and the data of ourthe study [42,43,44,45][24][25][26][27].
The molecular screening of NSCLC is vital to guiding the most appropriate therapies, with studies reporting the dysregulation of several receptor tyrosine kinases (RTK) as common tumorigenic mechanisms in NSCLC [46,47,48][28][29][30]. In this study, wthe researchers investigated for the first time, to the best of our knowledge, the prognostic effect of EGFR mutations, including ALK and KRAS rearrangements, in patients with NSCLC and MSCC. We found thPat patients with EGFR mutations (20/50; 40%) were 90% less likely to die from MSCC in comparison to patients with KRAS (12/50, 24%) and ALK (2/50, 4%) rearrangements or with an undetermined genetic status (16/50, 32%). Importantly, we also reported that patatients who received targeted molecular therapy for NSCLC had a higher survival rate than patients who did not receive targeted molecular therapy and developed MSCC. Therefore, future research should incorporate the genetic status of patients with MSCC secondary to NSCLC when assessing the prognostic variables affecting survival so that a decision about a patient’s tailored course of treatment can be supported by scientific evidence.
OurThe study has several limitations (retrospective analysis, single-centre experience, small sample size and heterogenous patient populations) and larger scale prospective studies must be conducted for the provision of the best evidence-based information for the management of MSCC in patients with lung cancer.
The major role of radiotherapy in MSCC patients is clearly demonstrated either as a post-operative treatment after urgent surgical decompression and stabilisation or upfront for patients who are not eligible or not fit for surgery. Guidelines on the management of complicated bone metastases have been recently published, and the importance of these scoring systems to predict survival after radiotherapy for MSCC has been highlighted [49][31]. Indeed, the prognosis (at least functional) is different if there is a deformation of the dural sac, contact without the spinal cord, or compression with or without cerebrospinal fluid visualization [50][32]. This is another limitation of the current retrospective study that such categorization was not available. Furthermore, the elements of the Tokuhashi score and the SINS criteria have not all been considered due to their absence from the Electronic Patient Record (EPR) system. This presents an added constraint within our study, considering the valuable predictive importance of these parameters. Overall, further work is required to better include these scoring systems into treatment algorithms in cohorts of NSCLC patients and validate our findings in an independent cohort.

References

  1. Shah, S.; Kutka, M.; Lees, K.; Abson, C.; Hadaki, M.; Cooke, D.; Neill, C.; Sheriff, M.; Karathanasi, A.; Boussios, S. Management of Metastatic Spinal Cord Compression in Secondary Care: A Practice Reflection from Medway Maritime Hospital, Kent, UK. J. Pers. Med. 2021, 11, 110.
  2. Morgen, S.S.; Lund-Andersen, C.; Larsen, C.F.; Engelholm, S.A.; Dahl, B. Prognosis in patients with symptomatic metastatic spinal cord compression: Survival in different cancer diagnosis in a cohort of 2321 patients. Spine 2013, 38, 1362–1367.
  3. Tang, Y.; Qu, J.; Wu, J.; Li, S.; Zhou, Y.; Xiao, J. Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients. J. Bone Joint. Surg. Am. 2015, 97, 1418–1425.
  4. Gao, X.; Zhang, K.; Cao, S.; Hou, S.; Wang, T.; Guo, W.; Wu, Z.; Jia, Q.; Liu, T.; Xiao, J. Surgical Treatment of Spinal Cord Compression Caused by Metastatic Small Cell Lung Cancer: Ten Years of Experience in a Single Center. Cancer Manag. Res. 2020, 12, 3571–3578.
  5. da Silva, G.T.; Bergmann, A.; Santos Thuler, L.C. Prognostic factors in patients with metastatic spinal cord compression secondary to lung cancer: A systematic review of the literature. Eur. Spine J. 2015, 24, 2107–2113.
  6. Rades, D.; Weber, A.; Karstens, J.H.; Schild, S.E.; Bartscht, T. Prognostic role of the number of involved extraspinal organs in patients with metastatic spinal cord compression. Clin. Neurol. Neurosurg. 2014, 118, 12–15.
  7. Conway, R.; Graham, J.; Kidd, J.; Levack, P. Scottish Cord Compression Group. What happens to people after malignant cord compression? Survival, function, quality of life, emotional well-being and place of care 1 month after diagnosis. Clin. Oncol. 2007, 19, 56–62.
  8. Tabouret, E.; Cauvin, C.; Fuentes, S.; Esterni, B.; Adetchessi, T.; Salem, N.; Madroszyk, A.; Gonçalves, A.; Casalonga, F.; Gravis, G. Reassessment of scoring systems and prognostic factors for metastatic spinal cord compression. Spine J. 2015, 15, 944–950.
  9. Weigel, B.; Maghsudi, M.; Neumann, C.; Kretschmer, R.; Müller, F.J.; Nerlich, M. Surgical management of symptomatic spinal metastases. Postoperative outcome and quality of life. Spine 1999, 24, 2240–2246.
  10. Tokuhashi, Y.; Matsuzaki, H.; Oda, H.; Oshima, M.; Ryu, J. A revised scoring system for preoperative evaluation of metastatic spine tumor prognosis. Spine 2005, 30, 2186–2191.
  11. Fisher, C.G.; DiPaola, C.P.; Ryken, T.C.; Bilsky, M.H.; Shaffrey, C.I.; Berven, S.H.; Harrop, J.S.; Fehlings, M.G.; Boriani, S.; Chou, D.; et al. A novel classification system for spinal instability in neoplastic disease: An evidence-based approach and expert consensus from the Spine Oncology Study Group. Spine 2010, 35, E1221–E1229.
  12. Tokuhashi, Y.; Uei, H.; Oshima, M.; Ajiro, Y. Scoring system for prediction of metastatic spine tumor prognosis. World J. Orthop. 2014, 5, 262–271.
  13. Leithner, A.; Radl, R.; Gruber, G.; Hochegger, M.; Leithner, K.; Welkerling, H.; Rehak, P.; Windhager, R. Predictive value of seven preoperative prognostic scoring systems for spinal metastases. Eur. Spine J. 2008, 17, 1488–1495.
  14. Park, S.J.; Lee, C.S.; Chung, S.S. Surgical results of metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC): Analysis of functional outcome, survival time, and complication. Spine J. 2016, 16, 322–328.
  15. Rades, D.; Douglas, S.; Veninga, T.; Bajrovic, A.; Stalpers, L.J.; Hoskin, P.J.; Rudat, V.; Schild, S.E. Metastatic spinal cord compression in non-small cell lung cancer patients. Prognostic factors in a series of 356 patients. Strahlenther. Onkol. 2012, 188, 472–476.
  16. Bakar, D.; Tanenbaum, J.E.; Phan, K.; Alentado, V.J.; Steinmetz, M.P.; Benzel, E.C.; Mroz, T.E. Decompression surgery for spinal metastases: A systematic review. Neurosurg. Focus 2016, 41, E2.
  17. Tancioni, F.; Navarria, P.; Pessina, F.; Attuati, L.; Mancosu, P.; Alloisio, M.; Scorsetti, M.; Santoro, A.; Baena, R.R. Assessment of prognostic factors in patients with metastatic epidural spinal cord compression (MESCC) from solid tumor after surgery plus radiotherapy: A single institution experience. Eur. Spine J. 2012, 21, S146–S148.
  18. Rades, D.; Lange, M.; Veninga, T.; Stalpers, L.J.; Bajrovic, A.; Adamietz, I.A.; Rudat, V.; Schild, S.E. Final results of a prospective study comparing the local control of short-course and long-course radiotherapy for metastatic spinal cord compression. Int. J. Radiat. Oncol. Biol. Phys. 2011, 79, 524–530.
  19. Chaichana, K.L.; Pendleton, C.; Sciubba, D.M.; Wolinsky, J.P.; Gokaslan, Z.L. Outcome following decompressive surgery for different histological types of metastatic tumors causing epidural spinal cord compression. Clinical article. J. Neurosurg. Spine 2009, 11, 56–63.
  20. Silva, G.T.; Bergmann, A.; Thuler, L.C. Incidence, associated factors, and survival in metastatic spinal cord compression secondary to lung cancer. Spine J. 2015, 15, 1263–1269.
  21. Ogihara, S.; Seichi, A.; Hozumi, T.; Oka, H.; Ieki, R.; Nakamura, K.; Kondoh, T. Prognostic factors for patients with spinal metastases from lung cancer. Spine 2006, 31, 1585–1590.
  22. Meyer, H.S.; Wagner, A.; Raufer, A.; Joerger, A.K.; Gempt, J.; Meyer, B. Surgery in Acute Metastatic Spinal Cord Compression: Timing and Functional Outcome. Cancers 2022, 14, 2249.
  23. Younsi, A.; Riemann, L.; Scherer, M.; Unterberg, A.; Zweckberger, K. Impact of decompressive laminectomy on the functional outcome of patients with metastatic spinal cord compression and neurological impairment. Clin. Exp. Metastasis 2020, 37, 377–390.
  24. Helweg-Larsen, S.; Sørensen, P.S.; Kreiner, S. Prognostic factors in metastatic spinal cord compression: A prospective study using multivariate analysis of variables influencing survival and gait function in 153 patients. Int. J. Radiat. Oncol. Biol. Phys. 2000, 46, 1163–1169.
  25. Lei, M.; Li, J.; Liu, Y.; Jiang, W.; Liu, S.; Zhou, S. Who are the Best Candidates for Decompressive Surgery and Spine Stabilization in Patients with Metastatic Spinal Cord Compression? A New Scoring System. Spine 2016, 41, 1469–1476.
  26. Lei, M.; Liu, Y.; Liu, S.; Wang, L.; Zhou, S.; Zhou, J. Individual strategy for lung cancer patients with metastatic spinal cord compression. Eur. J. Surg. Oncol. 2016, 42, 728–734.
  27. Lei, M.; Liu, Y.; Yan, L.; Tang, C.; Yang, S.; Liu, S. A validated preoperative score predicting survival and functional outcome in lung cancer patients operated with posterior decompression and stabilization for metastatic spinal cord compression. Eur. Spine J. 2016, 25, 3971–3978.
  28. Reinmuth, N.; Meister, M.; Muley, T.; Steins, M.; Kreuter, M.; Herth, F.J.; Hoffmann, H.; Dienemann, H.; Thomas, M. Molecular determinants of response to RTK-targeting agents in nonsmall cell lung cancer. Int. J. Cancer. 2006, 119, 727–734.
  29. Carper, M.B.; Claudio, P.P. Clinical potential of gene mutations in lung cancer. Clin. Transl. Med. 2015, 4, 33.
  30. Chen, X.; Xu, B.; Li, Q.; Xu, X.; Li, X.; You, X.; Yu, Z. Genetic profile of non-small cell lung cancer (NSCLC): A hospital-based survey in Jinhua. Mol. Genet. Genom. Med. 2020, 8, e1398.
  31. Oldenburger, E.; Brown, S.; Willmann, J.; van der Velden, J.M.; Spałek, M.; van der Linden, Y.M.; Kazmierska, J.; Menten, J.; Andratschke, N.; Hoskin, P. ESTRO ACROP guidelines for external beam radiotherapy of patients with complicated bone metastases. Radiother. Oncol. 2022, 173, 240–253.
  32. Bilsky, M.H.; Laufer, I.; Fourney, D.R.; Groff, M.; Schmidt, M.H.; Varga, P.P.; Vrionis, F.D.; Yamada, Y.; Gerszten, P.C.; Kuklo, T.R. Reliability analysis of the epidural spinal cord compression scale. J. Neurosurg. Spine 2010, 13, 324–328.
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