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16 pages, 3577 KiB

Open AccessArticle

SBRT of Spinal Metastases Using a Simultaneous Integrated Boost Concept in Oligometastatic Cancer Patients Is Safe and Effective

by Maria Waltenberger, Christian Strick, Marco M. E. Vogel, Christian Diehl and Stephanie E. Combs

Cancers 2023, 15(24), 5813; https://doi.org/10.3390/cancers15245813 - 12 Dec 2023

Cited by 1 | Viewed by 1360

Abstract

(1) Purpose: To assess the safety and effectivity of stereotactic body radiotherapy (SBRT) on spinal metastases utilizing a simultaneous integrated boost (SIB) concept in oligometastatic cancer patients. (2) Methods: 62 consecutive patients with 71 spinal metastases received SIB–SBRT between 01/2013 and 09/2022 at [...] Read more.

(1) Purpose: To assess the safety and effectivity of stereotactic body radiotherapy (SBRT) on spinal metastases utilizing a simultaneous integrated boost (SIB) concept in oligometastatic cancer patients. (2) Methods: 62 consecutive patients with 71 spinal metastases received SIB–SBRT between 01/2013 and 09/2022 at our institution. We retrospectively analyzed toxicity, local tumor control (LC), and progression-free (PFS) and overall survival (OS) following SIB–SBRT and assessed possible influencing factors (Kaplan–Meier estimator, log-rank test and Cox proportional-hazards model). (3) Results: SIB–SBRT was delivered in five fractions, mostly with 25/40 Gy (n = 43; 60.56%) and 25/35 Gy (n = 19, 26.76%). Estimated rates of freedom from VCF were 96.1/90.4% at one/two years. VCF development was significantly associated with osteoporosis (p < 0.001). No ≥ grade III acute and one grade III late toxicity (VCF) were observed. Estimated LC rates at one/two years were 98.6/96.4%, and histology was significantly associated with local treatment failure (p = 0.039). Median PFS/OS was 10 months (95% CI 6.01–13.99)/not reached. Development of metastases ≥ one year after initial diagnosis and Karnofsky Performance Score ≥ 90% were predictors for superior PFS (p = 0.038) and OS (p = 0.012), respectively. (4) Conclusion: Spinal SIB–SBRT yields low toxicity and excellent LC. It may be utilized in selected oligometastatic patients to improve prognosis. To the best of our knowledge, we provide the first clinical data on the toxicity and effectivity of SIB–SBRT in spinal metastases in a larger patient cohort. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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8 pages, 391 KiB

Open AccessArticle

Local Recurrence and Development of Spinal Cord Syndrome during Follow-Up after Surgical Treatment of Metastatic Spine Disease

by Peter Knöll, Moritz Lenschow, Maximilian Lenz, Volker Neuschmelting, Niklas von Spreckelsen, Sergej Telentschak, Sebastian Olbrück, Maximilian Weber, Johannes Rosenbrock, Peer Eysel and Sebastian G. Walter

Cancers 2023, 15(19), 4749; https://doi.org/10.3390/cancers15194749 - 27 Sep 2023

Cited by 1 | Viewed by 862

Abstract

Background: Surgical decompression (SD), with or without posterior stabilization followed by radiotherapy, is an established treatment for patients with metastatic spinal disease with epidural spinal cord compression (ESCC). This study aims to identify risk factors for occurrence of neurological compromise resulting from local [...] Read more.

Background: Surgical decompression (SD), with or without posterior stabilization followed by radiotherapy, is an established treatment for patients with metastatic spinal disease with epidural spinal cord compression (ESCC). This study aims to identify risk factors for occurrence of neurological compromise resulting from local recurrence. Methods: All patients who received surgical treatment for metastatic spinal disease at our center between 2011 and 2022 were included in this study. Cases were evaluated for tumor entity, surgical technique for decompression (decompression, hemilaminectomy, laminectomy, corpectomy) neurological deficits, grade of ESCC, time interval to radiotherapy, and perioperative complications. Results: A total of 747 patients were included in the final analysis, with a follow-up of 296.8 days (95% CI (263.5, 330.1)). During the follow-up period, 7.5% of the patients developed spinal cord/cauda syndrome (SCS). Multivariate analysis revealed prolonged time (>35 d) to radiation therapy as a solitary risk factor (p < 0.001) for occurrence of SCS during follow-up. Conclusion: Surgical treatment of spinal metastatic disease improves patients’ quality of life and Frankel grade, but radiation therapy needs to be scheduled within a time frame of a few weeks in order to reduce the risk of tumor-induced neurological compromise. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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12 pages, 274 KiB

Open AccessArticle

The Management of Metastatic Spinal Cord Compression in Routine Clinical Practice

by Luis Alberto Pérez-Romasanta, Estanislao Arana, Francisco M. Kovacs and Ana Royuela

Cancers 2023, 15(10), 2821; https://doi.org/10.3390/cancers15102821 - 18 May 2023

Cited by 3 | Viewed by 1945

Abstract

(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in [...] Read more.

(1) Background: Whether clinical management of spinal metastatic disease (SMD) matches evidence-based recommendations is largely unknown. (2) Patients and Methods: A questionnaire was distributed through Spanish Medical Societies, exploring routine practice, interpretation of the SINS and ESCC scores and agreement with items in the Tokuhashi and SINS scales, and NICE guideline recommendations. Questionnaires were completed voluntarily and anonymously, without compensation. (3) Results: Eighty specialists participated in the study. A protocol for patients with SMD existed in 33.7% of the hospitals, a specific multidisciplinary board in 33.7%, 40% of radiological reports included the ESCC score, and a prognostic scoring method was used in 73.7%. While 77.5% of the participants were familiar with SINS, only 60% used it. The different SINS and ESCC scores were interpreted correctly by 57.5–70.0% and 30.0–37.5% of the participants, respectively. Over 70% agreed with the items included in the SINS and Tokuhashi scores and with the recommendations from the NICE guideline. Differences were found across private/public sectors, hospital complexity, number of years of experience, number of patients with SMD seen annually and especially across specialties. (4) Conclusions: Most specialists know and agree with features defining the gold standard treatment for patients with SCC, but many do not apply them. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

17 pages, 3668 KiB

Open AccessArticle

Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328

by Helena Järemo, Julius Semenas, Sofia Halin Bergström, Marie Lundholm, Elin Thysell, Anders Widmark, Sead Crnalic, Erik Bovinder Ylitalo, Anders Bergh, Maria Brattsand and Pernilla Wikström

Cancers 2023, 15(9), 2437; https://doi.org/10.3390/cancers15092437 - 24 Apr 2023

Cited by 1 | Viewed by 1833

Abstract

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation [...] Read more.

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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9 pages, 972 KiB

Open AccessArticle

The Identification of Risk Factors for Symptomatic Spinal Metastasis Onset: A Prospective Cohort Study of 128 Asymptomatic Spinal Metastasis Patients

by Kenichiro Kakutani, Yutaro Kanda, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Kohei Kuroshima, Naotoshi Kumagai, Yoshiaki Hiranaka, Shinya Hayashi, Yuichi Hoshino, Hitomi Hara, Yoshitada Sakai and Ryosuke Kuroda

Cancers 2023, 15(4), 1251; https://doi.org/10.3390/cancers15041251 - 16 Feb 2023

Cited by 4 | Viewed by 1714

Abstract

Background: Symptomatic spinal metastasis (SSM) decreases the activities of daily living (ADL) and quality of life of cancer patients. However, the risk factors for SSM onset remain unclear. This prospective cohort study aimed to statistically analyze the significant risk factors. Methods: From 2016 [...] Read more.

Background: Symptomatic spinal metastasis (SSM) decreases the activities of daily living (ADL) and quality of life of cancer patients. However, the risk factors for SSM onset remain unclear. This prospective cohort study aimed to statistically analyze the significant risk factors. Methods: From 2016 to 2018, 210 consecutive patients with spinal metastases were prospectively registered. Patients with SSM at the first consultation and those who were unable to be followed-up owing to poor general condition were excluded. The demographic factors (age, sex, primary cancer, performance status, and ADL), clinical factors (radiation therapy, chemotherapy, molecularly targeted drugs, and bone-modifying agents (BMAs)), and Spinal Neoplastic Instability Score (SINS) were evaluated. Multivariate analysis was performed to identify the risk factors for SSM onset. Furthermore, the threshold was calculated from the receiver operating characteristic curve using the Youden index. Results: Thirty-nine patients who presented with SSM at the first consultation and 43 patients who were unable to be followed-up owing to poor general condition were excluded. Finally, 128 asymptomatic patients were included. Thirty-seven patients (28.9%) developed SSM during the follow-up period. The total SINS (OR: 1.739; 95% CI: 1.345–2.250) was identified as the most significant factor. The cut-off value of the SINS was 9.5 (sensitivity: 67.6%; specificity: 83.5%). Twenty-five (62.5%) of the forty patients with a SINS ≥ 10 developed SSM within a mean of 5.5 months (95% CI: 1.17–9.83). Furthermore, all patients with a SINS ≥ 13 developed SSM (n = 5) within a mean of 1.37 months (95% CI: 0.0–3.01). Conclusions: This study identified the significant risk factors for SSM onset and the threshold of the SINS. If long-term survival is expected, patients with a SINS ≥ 10 should be considered for intervention to prevent SSM. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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9 pages, 536 KiB

Open AccessArticle

Role of Decompressive Surgery in Neurologically Intact Patients with Low to Intermediate Intraspinal Metastatic Tumor Burden

by Niklas von Spreckelsen, Julian Ossmann, Maximilian Lenz, Lukas Nadjiri, Moritz Lenschow, Sergej Telentschak, Johanna Meyer, Julia Keßling, Peter Knöll, Peer Eysel, Roland Goldbrunner, Moritz Perrech, Max Scheyerer, Eren Celik, Kourosh Zarghooni and Volker Neuschmelting

Cancers 2023, 15(2), 385; https://doi.org/10.3390/cancers15020385 - 6 Jan 2023

Cited by 1 | Viewed by 1456

Abstract

Background: Surgical decompression (SD) followed by radiotherapy (RT) is superior to RT alone in patients with metastatic spinal disease with epidural spinal cord compression (ESCC) and neurological deficit. For patients without neurological deficit and low- to intermediate-grade intraspinal tumor burden, data on whether [...] Read more.

Background: Surgical decompression (SD) followed by radiotherapy (RT) is superior to RT alone in patients with metastatic spinal disease with epidural spinal cord compression (ESCC) and neurological deficit. For patients without neurological deficit and low- to intermediate-grade intraspinal tumor burden, data on whether SD is beneficial are scarce. This study aims to investigate the neurological outcome of patients without neurological deficit, with a low- to intermediate-ESCC, who were treated with or without SD. Methods: This single-center, multidepartment retrospective analysis includes patients treated for spinal epidural metastases from 2011 to 2021. Neurological status was assessed by Frankel grade, and intraspinal tumor burden was categorized according to the ESCC scale. Spinal instrumentation surgery was only considered as SD if targeted decompression was performed. Results: ESCC scale was determined in 519 patients. Of these, 190 (36.6%) presented with no neurological deficit and a low- to intermediate-grade ESCC (1b, 1c, or 2). Of these, 147 (77.4% were treated with decompression and 43 (22.65%) without. At last follow-up, there was no difference in neurological outcome between the two groups. Conclusions: Indication for decompressive surgery in neurologically intact patients with low-grade ESCC needs to be set cautiously. So far, it is unclear which patients benefit from additional decompressive surgery, warranting further prospective, randomized trials for this significant cohort of patients. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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11 pages, 1003 KiB

Open AccessArticle

A New Survival Score for Patients ≥65 Years Assigned to Radiotherapy of Bone Metastases

by Dirk Rades, Cansu Delikanli, Steven E. Schild, Charlotte Kristiansen, Søren Tvilsted and Stefan Janssen

Cancers 2022, 14(19), 4679; https://doi.org/10.3390/cancers14194679 - 26 Sep 2022

Cited by 4 | Viewed by 1348

Abstract

Survival scores are important for personalized treatment of bone metastases. Elderly patients are considered a separate group. Therefore, a specific score was developed for these patients. Elderly patients (≥65 years) irradiated for bone metastases were randomly assigned to the test (n = [...] Read more.

Survival scores are important for personalized treatment of bone metastases. Elderly patients are considered a separate group. Therefore, a specific score was developed for these patients. Elderly patients (≥65 years) irradiated for bone metastases were randomly assigned to the test (n = 174) or validation (n = 174) cohorts. Thirteen factors were retrospectively analyzed for survival. Factors showing significance (p < 0.05) or a trend (p < 0.06) in the multivariate analysis were used for the score. Based on 6-month survival rates, prognostic groups were formed. The score was compared to an existing tool developed in patients of any age. In the multivariate analysis, performance score, tumor type, and visceral metastases showed significance and gender was a trend. Three groups were designed (17, 18–25 and 27–28 points) with 6-month survival rates of 0%, 51%, and 100%. In the validation cohort, these rates were 9%, 55%, and 86%. Comparisons of prognostic groups between both cohorts did not reveal significant differences. In the test cohort, positive predictive values regarding death ≤6 and survival ≥6 months were 100% with the new score vs. 80% and 88% with the existing tool. The new score was more accurate demonstrating the importance of specific scores for elderly patients. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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13 pages, 2805 KiB

Open AccessArticle

Diagnostic Accuracy of CT for Metastatic Epidural Spinal Cord Compression

by James Thomas Patrick Decourcy Hallinan, Shuliang Ge, Lei Zhu, Wenqiao Zhang, Yi Ting Lim, Yee Liang Thian, Pooja Jagmohan, Tricia Kuah, Desmond Shi Wei Lim, Xi Zhen Low, Ee Chin Teo, Nesaretnam Barr Kumarakulasinghe, Qai Ven Yap, Yiong Huak Chan, Jiong Hao Tan, Naresh Kumar, Balamurugan A. Vellayappan, Beng Chin Ooi, Swee Tian Quek and Andrew Makmur

Cancers 2022, 14(17), 4231; https://doi.org/10.3390/cancers14174231 - 31 Aug 2022

Cited by 7 | Viewed by 5577

Abstract

Background: Early diagnosis of metastatic epidural spinal cord compression (MESCC) is vital to expedite therapy and prevent paralysis. Staging CT is performed routinely in cancer patients and presents an opportunity for earlier diagnosis. Methods: This retrospective study included 123 CT scans from 101 [...] Read more.

Background: Early diagnosis of metastatic epidural spinal cord compression (MESCC) is vital to expedite therapy and prevent paralysis. Staging CT is performed routinely in cancer patients and presents an opportunity for earlier diagnosis. Methods: This retrospective study included 123 CT scans from 101 patients who underwent spine MRI within 30 days, excluding 549 CT scans from 216 patients due to CT performed post-MRI, non-contrast CT, or a gap greater than 30 days between modalities. Reference standard MESCC gradings on CT were provided in consensus via two spine radiologists (11 and 7 years of experience) analyzing the MRI scans. CT scans were labeled using the original reports and by three radiologists (3, 13, and 14 years of experience) using dedicated CT windowing. Results: For normal/none versus low/high-grade MESCC per CT scan, all radiologists demonstrated almost perfect agreement with kappa values ranging from 0.866 (95% CI 0.787–0.945) to 0.947 (95% CI 0.899–0.995), compared to slight agreement for the reports (kappa = 0.095, 95%CI −0.098–0.287). Radiologists also showed high sensitivities ranging from 91.51 (95% CI 84.49–96.04) to 98.11 (95% CI 93.35–99.77), compared to 44.34 (95% CI 34.69–54.31) for the reports. Conclusion: Dedicated radiologist review for MESCC on CT showed high interobserver agreement and sensitivity compared to the current standard of care. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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10 pages, 600 KiB

Open AccessArticle

Prognosis after Palliative Surgery for Patients with Spinal Metastasis: Comparison of Predicted and Actual Survival

by Hideaki Nakajima, Shuji Watanabe, Kazuya Honjoh, Yuya Izubuchi, Yumiko Watanabe, Takaaki Tanaka and Akihiko Matsumine

Cancers 2022, 14(16), 3868; https://doi.org/10.3390/cancers14163868 - 10 Aug 2022

Cited by 5 | Viewed by 1794

Abstract

Prediction of prognosis is a key factor in therapeutic decision making due to recent the development of therapeutic options for spinal metastases. The aim of the study was to examine predictive scoring systems and identify prognostic factors for 6–month mortality after palliative surgery. [...] Read more.

Prediction of prognosis is a key factor in therapeutic decision making due to recent the development of therapeutic options for spinal metastases. The aim of the study was to examine predictive scoring systems and identify prognostic factors for 6–month mortality after palliative surgery. The participants were 75 patients with spinal metastases who underwent palliative surgery and had a minimum follow–up period of 1 year. Associations of actual survival with categories based on the revised Tokuhashi score and new Katagiri score were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors for 6–month mortality after palliative surgery. The median actual survival period was longer than those predicted using the scoring systems. However, 21.3% of patients died of cancers within 6 months after surgery. A higher CRP/albumin ratio (odds ratio: 0.39; cut–off 0.409) and absence of postoperative adjuvant therapy (odds ratio: 7.15) were independent risk factors for 6–month mortality. There was no association of mortality with primary site, severity of sarcopenia, or other biomarkers. These results suggest that careful consideration is needed to determine whether palliative surgery is the best option for patients with a high preoperative CRP/albumin ratio and/or absence of postoperative adjuvant therapy, regardless of predictions made from scoring systems. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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12 pages, 761 KiB

Open AccessArticle

A New Clinical Instrument for Estimating the Ambulatory Status after Irradiation for Malignant Spinal Cord Compression

by Dirk Rades, Ahmed Al-Salool, Christian Staackmann, Florian Cremers, Jon Cacicedo, Darejan Lomidze, Barbara Segedin, Blaz Groselj, Natalia Jankarashvili, Antonio J. Conde-Moreno, Raquel Ciervide, Charlotte Kristiansen and Steven E. Schild

Cancers 2022, 14(15), 3827; https://doi.org/10.3390/cancers14153827 - 7 Aug 2022

Cited by 3 | Viewed by 1851

Abstract

Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from [...] Read more.

Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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14 pages, 2077 KiB

Open AccessArticle

Overall Survival Improvement in Patients with Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer and Bone Metastasis Treated with Denosumab

by How-Wen Ko, Chi-Tsun Chiu, Chih-Liang Wang, Tsung-Ying Yang, Chien-Ying Liu, Chih-Teng Yu, Li-Chuan Tseng, Chih-Hsi Scott Kuo, Chin-Chou Wang, Muh-Hwa Yang and Cheng-Ta Yang

Cancers 2022, 14(14), 3470; https://doi.org/10.3390/cancers14143470 - 17 Jul 2022

Cited by 5 | Viewed by 2636

Abstract

The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated [...] Read more.

The impact of an initial skeletal-related event (SRE) and denosumab adjuvant treatment on the survival outcome of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with bone metastasis remains unclear. This retrospective study included 400 metastatic EGFR-mutated NSCLC patients. Among 190 bone metastasis patients, 61 had initial SREs and 73 received denosumab. We analyzed patient characteristics, SRE-free survival (SRE-FS), and overall survival (OS). In metastatic EGFR-mutated NSCLC, bone metastasis was associated with a poorer OS (21.7 vs. 33.0 months; p < 0.001). Bone metastasis patients with initial SREs at diagnosis had an even shorter OS, compared with those without initial SRE (15.4 vs. 23.6 months; p = 0.026). Denosumab reduced SRE incidence (hazard ratio (HR) 0.57 (95% confidence interval (CI) 0.34–0.94; p = 0.027) and was associated with improved OS (26.6 vs. 20.1 months; p = 0.015). A multivariate analysis demonstrated that denosumab treatment was correlated with a lower incidence of SRE (HR 0.61 (95% CI 0.37–0.98); p = 0.042) and better OS (HR 0.60 (95% CI 0.41–0.88); p = 0.008). In subgroup analyses, denosumab prolonged SRE-FS (HR 0.36 (95% CI 0.19–0.79); p = 0.009) in patients without initial SREs and was related to a better OS (25.3 vs. 12.9 months; p = 0.016) in patients with initial or pre-existing SREs. Osteonecrosis of the jaw was diagnosed in two patients (2.74%) receiving denosumab. Our study confirmed the association between initial SREs and a worse outcome and provided novel evidence of the survival benefit of denosumab for EGFR-mutated NSCLC patients with bone metastasis. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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15 pages, 2158 KiB

Open AccessArticle

Deep Learning Model for Grading Metastatic Epidural Spinal Cord Compression on Staging CT

by James Thomas Patrick Decourcy Hallinan, Lei Zhu, Wenqiao Zhang, Tricia Kuah, Desmond Shi Wei Lim, Xi Zhen Low, Amanda J. L. Cheng, Sterling Ellis Eide, Han Yang Ong, Faimee Erwan Muhamat Nor, Ahmed Mohamed Alsooreti, Mona I. AlMuhaish, Kuan Yuen Yeong, Ee Chin Teo, Nesaretnam Barr Kumarakulasinghe, Qai Ven Yap, Yiong Huak Chan, Shuxun Lin, Jiong Hao Tan, Naresh Kumar, Balamurugan A. Vellayappan, Beng Chin Ooi, Swee Tian Quek and Andrew Makmur Show full author list Hide full author list

Cancers 2022, 14(13), 3219; https://doi.org/10.3390/cancers14133219 - 30 Jun 2022

Cited by 8 | Viewed by 4578

Abstract

Background: Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy. Deep learning (DL) models for automatic MESCC classification on staging CT were developed to aid earlier diagnosis. Methods: This retrospective study included 444 CT staging studies from 185 patients [...] Read more.

Background: Metastatic epidural spinal cord compression (MESCC) is a disastrous complication of advanced malignancy. Deep learning (DL) models for automatic MESCC classification on staging CT were developed to aid earlier diagnosis. Methods: This retrospective study included 444 CT staging studies from 185 patients with suspected MESCC who underwent MRI spine studies within 60 days of the CT studies. The DL model training/validation dataset consisted of 316/358 (88%) and the test set of 42/358 (12%) CT studies. Training/validation and test datasets were labeled in consensus by two subspecialized radiologists (6 and 11-years-experience) using the MRI studies as the reference standard. Test sets were labeled by the developed DL models and four radiologists (2–7 years of experience) for comparison. Results: DL models showed almost-perfect interobserver agreement for classification of CT spine images into normal, low, and high-grade MESCC, with kappas ranging from 0.873–0.911 (p < 0.001). The DL models (lowest κ = 0.873, 95% CI 0.858–0.887) also showed superior interobserver agreement compared to two of the four radiologists for three-class classification, including a specialist (κ = 0.820, 95% CI 0.803–0.837) and general radiologist (κ = 0.726, 95% CI 0.706–0.747), both p < 0.001. Conclusion: DL models for the MESCC classification on a CT showed comparable to superior interobserver agreement to radiologists and could be used to aid earlier diagnosis. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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14 pages, 2017 KiB

Open AccessArticle

Medium to Long-Term Clinical Outcomes of Spinal Metastasectomy

by Satoshi Kato, Satoru Demura, Hideki Murakami, Kazuya Shinmura, Noriaki Yokogawa, Ryohei Annen, Motoya Kobayashi, Yohei Yamada, Satoshi Nagatani, Norio Kawahara and Hiroyuki Tsuchiya

Cancers 2022, 14(12), 2852; https://doi.org/10.3390/cancers14122852 - 9 Jun 2022

Cited by 2 | Viewed by 2427

Abstract

The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated [...] Read more.

The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated spinal metastases (2006–2018) with a postoperative follow-up for a minimum of 3 years. The findings present information on patient demographics (i.e., performance status, location of non-spinal metastases, and history of systemic therapy) and postoperative outcomes, including perioperative complications, disease progression of non-operated metastases, and additional excisional surgeries. Additionally, postoperative survival, local tumor control in the operated spine, and maintenance of spinal reconstruction without instrumentation failure were determined using Kaplan–Meier analyses. The primary malignancy was kidney and thyroid cancer in 51 and 14 patients, respectively, low-grade sarcoma and lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. We found that patients with thyroid cancer had the best survival results, with local tumor recurrence and instrumentation failure at 10% and 22%, respectively. These findings suggest that for certain patients with isolated and removable spine metastases, metastasectomy can improve function and survival. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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11 pages, 245 KiB

Open AccessArticle

Prognostic Value of Preclinical Markers after Radiotherapy of Metastatic Spinal Cord Compression—An Additional Analysis of Patients from Two Prospective Trials

by Dirk Rades, Jon Cacicedo, Darejan Lomidze, Ahmed Al-Salool, Barbara Segedin, Blaz Groselj and Steven E. Schild

Cancers 2022, 14(10), 2547; https://doi.org/10.3390/cancers14102547 - 22 May 2022

Cited by 2 | Viewed by 1847

Abstract

For optimal personalization of treatment for metastatic spinal cord compression (MSCC), the patient’s survival prognosis should be considered. Estimation of survival can be facilitated by prognostic factors. This study investigated the prognostic value of pre-treatment preclinical markers, namely hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte [...] Read more.

For optimal personalization of treatment for metastatic spinal cord compression (MSCC), the patient’s survival prognosis should be considered. Estimation of survival can be facilitated by prognostic factors. This study investigated the prognostic value of pre-treatment preclinical markers, namely hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), and c-reactive protein (CRP), in 190 patients from two prospective trials who had poor or intermediate survival prognoses and were irradiated for MSCC with motor deficits. In addition, clinical factors including radiation regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, visceral metastases, other bone metastases, time developing motor deficits, ambulatory status, sensory function, and sphincter function were evaluated. On univariate analyses, NLR (p = 0.033), LDH (p < 0.001), CRP (p < 0.001), tumor type (p < 0.001), pre-radiotherapy ambulatory status (p < 0.001), and sphincter function (p = 0.011) were significant. In the subsequent Cox regression analysis, LDH (p = 0.007), CRP (p = 0.047), tumor type (p = 0.003), and ambulatory status (p = 0.010) maintained significance. In addition to clinical factors, preclinical markers may help in estimating the survival of patients irradiated for MSCC. Additional prospective trials are warranted. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

11 pages, 648 KiB

Open AccessArticle

Surgery in Acute Metastatic Spinal Cord Compression: Timing and Functional Outcome

by Hanno S. Meyer, Arthur Wagner, Alessandra Raufer, Ann-Kathrin Joerger, Jens Gempt and Bernhard Meyer

Cancers 2022, 14(9), 2249; https://doi.org/10.3390/cancers14092249 - 30 Apr 2022

Cited by 15 | Viewed by 3038

Abstract

Background: Patients with metastatic spinal cord compression (MSCC) may experience long-term functional impairment. It has been established that surgical decompression improves neurological outcomes, but the effect of early surgery remains uncertain. Our objective was to evaluate the impact of early versus late surgery [...] Read more.

Background: Patients with metastatic spinal cord compression (MSCC) may experience long-term functional impairment. It has been established that surgical decompression improves neurological outcomes, but the effect of early surgery remains uncertain. Our objective was to evaluate the impact of early versus late surgery for acute MSCC due to spinal metastases (SM). Methods: We retrospectively reviewed a consecutive cohort of all patients undergoing surgery for SMs at our institution. We determined the prevalence of acute MSCC; the time between acute neurological deterioration as well as between admission and surgery (standard procedure: decompression and instrumentation); and neurological impairment graded by the ASIA scale upon presentation and discharge. Results: We screened 693 patients with surgery for spinal metastasis; 140 patients (21.7%) had acute MSCC, defined as neurological impairment corresponding to ASIA grade D or lower, acquired within 72 h before admission. Non-MSCC patients had surgery for SM-related cauda equina syndrome, radiculopathy and/or spinal instability. Most common locations of the SM in acute MSCC were the thoracic (77.9%) and cervical (10.7%) spine. Per standard of care, acute MSCC patients underwent surgery including decompression and instrumentation, and the median time from admission to surgery was 16 h (interquartile range 10–22 h). Within the group of patients with acute MSCC, those who underwent early surgery (i.e., before the median 16 h) had a significantly higher rate of ASIA improvement by at least one grade at discharge (26.5%) compared to those who had late surgery after 16 h (10.1%; p = 0.024). Except for a significantly higher sepsis rate in the late surgery group, complication rates did not differ between the late and early surgery subgroups. Conclusions: We report data on the largest cohort of patients with MSCC to date. Early surgery is pivotal in acute MSCC, substantially increasing the chance for neurological improvement without increasing complication rates. We found no significant impact when surgery was performed later than 24 h after admission. These findings will provide the framework for a much-needed prospective study. Until then, the treatment strategy should entail the earliest possible surgical intervention. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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10 pages, 225 KiB

Open AccessArticle

Radiotherapy with or without Decompressive Surgery for Metastatic Spinal Cord Compression: A Retrospective Matched-Pair Study Including Data from Prospectively Evaluated Patients

by Dirk Rades, Jan Küchler, Lena Graumüller, Abdulkareem Abusamha, Steven E. Schild and Jan Gliemroth

Cancers 2022, 14(5), 1260; https://doi.org/10.3390/cancers14051260 - 28 Feb 2022

Cited by 10 | Viewed by 2149

Abstract

In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data [...] Read more.

In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data from prospective cohorts treated after 2005. Seventy-nine patients receiving radiotherapy alone were matched to 79 patients assigned to surgery plus radiotherapy (propensity score method) for age, gender, performance score, tumor type, affected vertebrae, other bone or visceral metastases, interval tumor diagnosis to MSCC, time developing motor deficits, and ambulatory status. Improvement of motor function by ≥1 Frankel grade occurred more often after surgery plus radiotherapy (39.2% vs. 21.5%, p = 0.015). No significant differences were found for post-treatment ambulatory rates (59.5% vs. 67.1%, p = 0.32), local progression-free survival (p = 0.47), overall survival (p = 0.51), and freedom from in-field recurrence of MSCC (90.1% vs. 76.2% at 12 months, p = 0.58). Ten patients (12.7%) died within 30 days following radiotherapy alone and 12 patients (15.2%) died within 30 days following surgery (p = 0.65); 36.7% of surgically treated patients did not complete radiotherapy as planned. Surgery led to significant early improvement of motor function and non-significantly better long-term control. Patients scheduled for surgery must be carefully selected considering potential benefits and risk of perioperative complications. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

Review

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17 pages, 1049 KiB

Open AccessReview

Novel Therapeutic Targets on the Horizon: An Analysis of Clinical Trials on Therapies for Bone Metastasis in Prostate Cancer

by Wenhao Zhou, Wei Zhang, Shi Yan, Kaixuan Zhang, Han Wu, Hongyu Chen, Minfeng Shi and Tie Zhou

Cancers 2024, 16(3), 627; https://doi.org/10.3390/cancers16030627 - 31 Jan 2024

Cited by 5 | Viewed by 3406

Abstract

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients’ well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often [...] Read more.

In the absence of early detection and initial treatment, prostate cancer often progresses to an advanced stage, frequently spreading to the bones and significantly impacting patients’ well-being and healthcare resources. Therefore, managing patients with prostate cancer that has spread to the bones often involves using bone-targeted medications like bisphosphonates and denosumab to enhance bone structure and minimize skeletal complications. Additionally, researchers are studying the tumor microenvironment and biomarkers to understand the mechanisms and potential treatment targets for bone metastases in prostate cancer. A literature search was conducted to identify clinical studies from 2013 to 2023 that focused on pain, performance status, or quality of life as primary outcomes. The analysis included details such as patient recruitment, prior palliative therapies, baseline characteristics, follow-up, and outcome reporting. The goal was to highlight the advancements and trends in bone metastasis research in prostate cancer over the past decade, with the aim of developing strategies to prevent and treat bone metastases and improve the quality of life and survival rates for prostate cancer patients. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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26 pages, 1062 KiB

Open AccessReview

Multidisciplinary Approach to Spinal Metastases and Metastatic Spinal Cord Compression—A New Integrative Flowchart for Patient Management

by Miguel Esperança-Martins, Diogo Roque, Tiago Barroso, André Abrunhosa-Branquinho, Diogo Belo, Nuno Simas and Luis Costa

Cancers 2023, 15(6), 1796; https://doi.org/10.3390/cancers15061796 - 16 Mar 2023

Cited by 12 | Viewed by 6746

Abstract

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms [...] Read more.

Metastatic spine disease (MSD) and metastatic spinal cord compression (MSCC) are major causes of permanent neurological damage and long-term disability for cancer patients. The development of MSD is pathophysiologically framed by a cooperative interaction between general mechanisms of bone growth and specific mechanisms of spinal metastases (SM) expansion. SM most commonly affects the thoracic spine, even though multiple segments may be affected concomitantly. The great majority of SM are extradural, while intradural-extramedullary and intramedullary metastases are less frequently seen. The management of patients with SM is particularly complex and challenging, with multiple factors—such as the spinal stability status, primary tumor radio and chemosensitivity, cancer biological burden, patient performance status and comorbidities, and patient’s oncological prognosis—influencing the clinical decision-making process. Different frameworks were developed in order to systematize and support this process. A multidisciplinary, personalized approach, enriched by the expertise of each involved specialty, is crucial. We reviewed the most recent evidence and proposed an updated algorithmic approach to patients with MSD according to the clinical scenario of each patient. A flowchart-based approach offers an evidence-based management of MSD, providing a valuable clinical decision tool in a context of high uncertainty and quick-acting need. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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32 pages, 1918 KiB

Open AccessReview

Biological and Clinical Aspects of Metastatic Spinal Tumors

by Jakub Litak, Wojciech Czyżewski, Michał Szymoniuk, Leon Sakwa, Barbara Pasierb, Joanna Litak, Zofia Hoffman, Piotr Kamieniak and Jacek Roliński

Cancers 2022, 14(19), 4599; https://doi.org/10.3390/cancers14194599 - 22 Sep 2022

Cited by 15 | Viewed by 4786

Abstract

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to [...] Read more.

Spine metastases are a common life-threatening complication of advanced-stage malignancies and often result in poor prognosis. Symptomatic spine metastases develop in the course of about 10% of malignant neoplasms. Therefore, it is essential for contemporary medicine to understand metastatic processes in order to find appropriate, targeted therapeutic options. Thanks to continuous research, there appears more and more detailed knowledge about cancer and metastasis, but these transformations are extremely complicated, e.g., due to the complexity of reactions, the variety of places where they occur, or the participation of both tumor cells and host cells in these transitions. The right target points in tumor metastasis mechanisms are still being researched; that will help us in the proper diagnosis as well as in finding the right treatment. In this literature review, we described the current knowledge about the molecular pathways and biomarkers engaged in metastatic processes involving the spine. We also presented a current bone-targeted treatment for spine metastases and the emerging therapies targeting the discussed molecular mechanisms. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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33 pages, 4784 KiB

Open AccessReview

State-of-the-Art Imaging Techniques in Metastatic Spinal Cord Compression

by Tricia Kuah, Balamurugan A. Vellayappan, Andrew Makmur, Shalini Nair, Junda Song, Jiong Hao Tan, Naresh Kumar, Swee Tian Quek and James Thomas Patrick Decourcy Hallinan

Cancers 2022, 14(13), 3289; https://doi.org/10.3390/cancers14133289 - 5 Jul 2022

Cited by 15 | Viewed by 5646

Abstract

Metastatic Spinal Cord Compression (MSCC) is a debilitating complication in oncology patients. This narrative review discusses the strengths and limitations of various imaging modalities in diagnosing MSCC, the role of imaging in stereotactic body radiotherapy (SBRT) for MSCC treatment, and recent advances in [...] Read more.

Metastatic Spinal Cord Compression (MSCC) is a debilitating complication in oncology patients. This narrative review discusses the strengths and limitations of various imaging modalities in diagnosing MSCC, the role of imaging in stereotactic body radiotherapy (SBRT) for MSCC treatment, and recent advances in deep learning (DL) tools for MSCC diagnosis. PubMed and Google Scholar databases were searched using targeted keywords. Studies were reviewed in consensus among the co-authors for their suitability before inclusion. MRI is the gold standard of imaging to diagnose MSCC with reported sensitivity and specificity of 93% and 97% respectively. CT Myelogram appears to have comparable sensitivity and specificity to contrast-enhanced MRI. Conventional CT has a lower diagnostic accuracy than MRI in MSCC diagnosis, but is helpful in emergent situations with limited access to MRI. Metal artifact reduction techniques for MRI and CT are continually being researched for patients with spinal implants. Imaging is crucial for SBRT treatment planning and three-dimensional positional verification of the treatment isocentre prior to SBRT delivery. Structural and functional MRI may be helpful in post-treatment surveillance. DL tools may improve detection of vertebral metastasis and reduce time to MSCC diagnosis. This enables earlier institution of definitive therapy for better outcomes. Full article

(This article belongs to the Special Issue Treatment of Bone Metastases including Metastatic Spinal Cord Compression)

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