Spinal Chordoma and Chondrosarcoma Treatment Experiences - A 20-Year Retrospective Study from Databases of Two Medical Centers

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Among the 48 patients studied (39 chordoma and 9 chondrosarcoma cases), the average age was 53.9 ± 15.8 years, with a range of 17 to 86 years. Out of these patients, 43 underwent excision surgery and were categorized based on tumor margin into negative (R0) or microscopically positive (R1) margin (n = 14) and macroscopically positive (R2) margin (n = 29) groups. The mean overall survival (OS) for R0/R1 and R2 groups was 156.5 ± 19.3 and 79.2 ± 11.9 months, respectively ( p value = 0.012). The mean progression-free survival (PFS) for R0/R1 and R2 was 112.9 ± 24.4 and 25.5 ± 5.5 months ( p value < 0.001). The study showed that regardless of whether patients in the R0/R1 or R2 groups received radiation therapy (RT) or not, there was no significant improvement in OS or PFS. Specifically, the OS and PFS for the RT only group were 75.9 ± 16.6 and 73.3 ± 18.0 months. In conclusion, the recommended treatment approach for spinal chordoma and chondrosarcoma remains en bloc resection surgery with an appropriate margin. Patients who are unsuitable for or decline surgery may find a beneficial disease control rate with traditional external beam photon/proton therapy. Biological sciences/Cancer Health sciences/Oncology spinal chordoma spinal chondrosarcoma en bloc resection radiation therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Spinal chordoma and chondrosarcoma are classified as low to intermediate grade primary malignant tumors of the vertebrae 1 , 2 . While chordoma constitutes a relatively small fraction (1.4%) of primary malignant tumors overall 3 , they notably represent over half of all primary sacral tumors 4 , 5 . Moreover, they comprise 15 to 20% of primary tumors in the mobile spine 6 , 7 , but are exceedingly rare (0.2%) in the skull base 8 . Chondrosarcoma constitutes a significant portion, approximately 27%, of all primary bone tumors 9 , with spinal chondrosarcoma estimated to account for about 26% of primary malignant tumors in the vertebrae 10 , 11 . These tumors predominantly arise in the thoracic and lumbar regions 10 . Both chordoma and chondrosarcoma present a spectrum of symptoms, including back pain, neurological deficits, muscle atrophy, urinary and bowel dysfunction, and potential reductions in life expectancy 11 – 13 . Crafting comprehensive treatment strategies is paramount in optimizing patients' quality of life and improving their overall survival (OS) outlook. Chordoma emerges from the remnants of the notochord and typically grows slowly, yet malignantly 14 – 16 . Spinal chondrosarcoma can emerge spontaneously or as a result of preexisting cartilage lesions such as osteochondroma or enchondroma 13 , 17 , 18 . Despite their resistance to radiotherapy and chemotherapy, total en bloc resection is necessary to enhance local control rates 5 , 19 – 23 . The preferred treatment for both chordoma and spinal chondrosarcoma is wide local excision, sometimes accompanied by adjuvant radiotherapy 24 , 25 . However, many patients experience complications post-surgery. The extent of surgical removal is directly linked to improved OS 26 . Neurological involvement and disability are common and significant side effects, varying in severity based on the tumor's extent or location 23 . For patients with positive margins or those with unfavorable local tumor characteristics, an aggressive radiotherapy (RT) approach incorporating techniques like intraoperative dural plaques brachytherapy and high-dose photon/proton therapy may achieve regional control 17 , 27 , 28 . When achieving negative margins is challenging, RT utilizing the heavy charged particle carbon ion, known for its sharper lateral penumbra, is seen as a promising treatment option 29 – 31 . Additionally, hypofractionated stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) are under consideration as potential therapies for unresectable vertebral chordoma and chondrosarcoma due to advancements in geometric accuracy 32 – 34 . Since spinal chordoma and chondrosarcoma exhibit several overlapping characteristics, this study collected cases of both conditions and investigated how different treatment methods influenced patient outcomes, aiming to anticipate the development of standardized therapeutic guidelines. Results Patients The patient characteristics are displayed in Table 1 . The average age at diagnosis among the 48 patients was 53.9 ± 15.8 (ranging from 17 to 86) years, with 34 males and 14 females. Of these, 39 had vertebral chordoma and 9 had chondrosarcoma, all classified as 1B according to the Enneking classification. None of the patients exhibited lymph node or distant metastasis. Based on the AJCC 8th edition staging, there were 3, 21, 3, and 21 patients with T1, T2, T3, and T4 stages, respectively. Distribution across spinal regions was as follows: three in the cervical spine, five in the thoracic region, four in the lumbar spine, and thirty-six in the sacrum. The majority (n = 43) underwent tumor removal surgery, among which seven had negative margin (R0), seven had microscopically positive margin (R1), and 29 had macroscopically positive margin (R2). Among the R0 cases, two opted for adjuvant radiotherapy (RT), while five did not. Among the R1 cases, two chose RT, and five did not. Within the R2 cases, fourteen patients underwent RT, while 15 did not. Additionally, five patients received RT as a palliative measure instead of surgery. The follow-up period was computed starting on the date of treatment completion, including surgery and RT. At the last follow-up, 28 out of 48 individuals were alive, with an average follow-up duration of 58.1 ± 44.9 months. The Differences in Results between R0/R1 and R2 Margin Patients who underwent excision surgery were divided into two groups based on histological findings: R0/R1 (n = 14) and R2 (n = 29) tumor margin. Figure 1 illustrates the OS curve. The mean OS for R0/R1 and R2 groups was 156.5 ± 19.3 and 79.2 ± 11.9 months, respectively ( p value = 0.012). Both groups had estimated 5-year survival rates of 100.0% and 67.7 ± 9.8%, and estimated 10-year survival rates of 80.0 ± 17.9% and 15.1 ± 9.6%, respectively. Figure 2 shows the progression-free survival curve curve. The mean PFS for R0/R1 and R2 groups was 112.9 ± 24.4 and 25.5 ± 5.5 months, respectively ( p value < 0.001). The Implications of Adjuvant Radiation on People with R0/R1 Margin Four out of the fourteen patients with negative or microscopically positive margin underwent RT, while ten did not. Figure 3 depicts the OS curve. Both groups had estimated 5-year survival rates of 100%, while the projected 10-year survival rates were 100% and 66.7 ± 27.2%, respectively. The average OS could not be calculated due to insufficient OS data. The PFS curve is shown in Fig. 4 . The mean PFS for R0/R1 patients with and without RT was 94.0 ± 21.9 and 111.0 ± 27.3 months, respectively ( p value = 0.901). The Effect of Adjuvant Radiation on Patients with R2 Margin Fourteen out of the twenty-nine cases with R2 margin opted for RT, while 15 did not. The OS curve is depicted in Fig. 5 . The estimated 5-year survival rates were 51.6 ± 17.8% and 78.0 ± 11.4%, and the estimated 10-year survival rates were 51.6 ± 17.8% and 9.8 ± 9.2%, respectively. For R2 patients with and without RT, the average OS was 105.5 ± 26.2 and 76.0 ± 9.2 months ( p value = 0.734). The PFS curve is shown in Fig. 6 . The mean PFS for R2 patients with and without RT was 27.1 ± 6.4 and 22.9 ± 7.8 months ( p value = 0.513), respectively. The Results for Patients with R0/R1 Margin, with R2 Margin, and with RT Only The outcomes following therapy were compared among patients with R0/R1 margin, individuals with R2 margin, and those who received only RT to assess whether RT could be beneficial for those unwilling or unable to undergo resection surgery. Figure 7 illustrates the OS curve. The estimated 5-year survival rates for each group were 100.0%, 67.7 ± 9.8%, and 60.0 ± 21.9%, while the estimated 10-year survival rates were 80.0 ± 17.9%, 15.1 ± 9.6%, and 30.0 ± 23.9%, respectively. The average OS for the three groups was 156.5 ± 19.3, 79.2 ± 11.9, and 75.9 ± 16.6 months ( p value = 0.046). Figure 8 presents the PFS curve. The PFS for the three groups was 112.9 ± 24.4, 25.5 ± 5.5, and 73.3 ± 18.0 months, respectively ( p value < 0.001). Treatment-Related Complications Complications arising from surgery and adjuvant RT were documented according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 and are outlined in Table 2 and Table 3 . Among the forty-three participants who underwent surgery in our study, twelve experienced grade 2 surgical complications. Of these, eight presented with neurological deficits, including dysuria or urinary incontinence, constipation or fecal incontinence, and decreased mobility. One case involved hematoma formation, two had wound infection, and one required tracheostomy care. Additionally, seven patients experienced grade 3 surgical complications, all of which were categorized as sepsis or deep wound infection. Among patients with R0/R1 and R2 margins, surgical complications ≥ CTCAE grade 2 occurred in 8 (57.1%) and 11 (37.9%) cases, respectively ( p value = 0.235). Furthermore, 3 (21.4%) and 4 (13.8%) patients experienced surgical complications graded higher than CTCAE grade 3 ( p value = 0.665), respectively. Twenty-three patients in our study opted for either palliative or adjuvant radiotherapy. Among them, twelve (52.2%) experienced acute CTCAE grade 2 RT-related complications, while one (4.3%) had acute CTCAE grade 3 complications. Additionally, one (5.3%), one (5.3%), and one (5.3%) patient experienced CTCAE grade 2, 3, and 4 late-onset RT toxicity, respectively. Discussion Primary vertebral neoplasms are uncommon in adulthood, with chordoma and chondrosarcoma comprising the majority. These tumors exhibit aggressive behavior and are prone to local recurrence 25 . The primary goal of treatment is excision surgery aiming for a negative or microscopically positive margin, which enhances local control and improves survival prospects for patients 5 , 19 – 22 , 26 . Nonetheless, surgical procedures often lead to complications due to delayed diagnosis and the tumors' proximity to vital structures like arteries, viscera, and neural tissue 24 , 35 . En bloc resection of chordoma and spinal chondrosarcoma remains particularly challenging considering the potential postoperative side effects and functional impairments 24 . For instance, data from Maggiore Hospital in Bologna, Italy, indicated that only 20% of 52 patients treated over a 50-year period until 2002 achieved adequate margins post-surgery, with many experiencing local recurrence within 56–94 months 36 . In our investigation, fourteen out of the 43 patients who opted for surgery achieved a negative or microscopically positive margin, demonstrating notably superior outcomes in terms of OS and PFS compared to those with a macroscopically positive margin The efficacy of therapy was found to be significantly influenced by complete surgical resection, corroborating findings from previous studies 5 , 19 – 22 , 26 , 37 , 38 . Previous clinical series have consistently highlighted that a negative surgical margin stands out as the most critical predictor of tumor recurrence rates and long-term survival 1 , 4 . While total excision is considered the optimal treatment approach, it is essential to weigh the risks of perioperative complications, including damage to nearby structures, neurological impairments, wound complications such as dehiscence or infection, medical morbidity stemming from surgical trauma, and potential long-term device failure 39 , 40 . Li et al. carried out a systematic review of perioperative complications in 824 cases undergoing total en bloc resection, revealing various rates: 12.7% for neurological damage, 12.1% for hardware failure, 10.6% for dural tear and cerebrospinal fluid leakage, 7.6% for wound-related complications with nearly half necessitating revision, and 7.3% for vascular injury and bleeding 41 . Additionally, mortality rates due to surgical complications were reported at 1.2%. 41 . In our dataset, among patients undergoing surgery, 55.8% (24/43) experienced complications graded as CTCAE 0 or 1, 27.9% (12/43) had grade 2 complications, and 16.3% (7/43) had grade 3 adverse events. Of those with complications grade 2 or higher, ten were related to wound issues, and eight were neurological. Besides, one patient succumbed to severe sepsis within a month after surgery, leading to the exclusion from our study. Assessing the efficacy of radiation therapy can be challenging due to the limited patient pool and ongoing technological advancements in radiation therapy. Research strongly supports the effectiveness of conventional photon or proton dosages for chordoma treatment 30 , 42 . Studies have indicated that radical surgery combined with conventional radiation at doses below 60 Gy yields poor local control rates (ranging from 0–50%) for spinal and sacral chordoma 43 – 45 . Nonetheless, the maximum feasible dose of traditional photon radiation typically administered to spinal tumors is around 50 Gy, a level associated with minimal risk of paralysis, determined by the tolerance of the spinal cord 46 . Proton therapy presents a promising option for treating spinal malignancies due to its potential for reduced or delayed toxicity. In a study by Hug et al., employing combined photon-proton radiotherapy with an average dose of 73.9 Gy/CGE, 5-year local control rates of 53% and 100% were observed for chordoma and chondrosarcoma of the axial skeleton, respectively 47 . Another phase II clinical study at Massachusetts General Hospital administered radiation doses of 70.2 Gy/CGE for microscopic positive resection and 77.4 Gy/CGE for gross disease, with long-term results revealing a 74% local control rate after eight years 48 , 49 . In our investigation, four out of the 14 individuals having R0/R1 resection received adjuvant RT, with only one of them receiving photon/proton therapy at a dosage exceeding 60 Gy/CGE. The OS and PFS were not significantly influenced by the administration of RT in the R0/R1 group. Among the 29 patients with R2 margin in our study, fourteen opted for adjuvant RT, while fifteen did not. Concerning toxicity, nine of the fourteen patients received cumulative doses exceeding 60 Gy/CGE, while five received low-dose RT, with dosages ranging from 30 to 74 Gy/CGE. There was no discernible difference in therapeutic outcomes between R2 margin patients who underwent RT and those who did not. For individuals with unresectable tumors, conventional photon beam radiation therapy administered at doses exceeding 60 Gy, although high and often associated with toxicity, may exhibit therapeutic efficacy 44 , 50 , 51 . A retrospective study by Chen et al. demonstrated that proton therapy, with a median total dose of 77.4 Gy, resulted in OS rates of 91.7% and 78.1%, as well as PFS rates of 90.4% and 79.8% at 3 and 5 years, respectively 51 . In our study, only 5 out of the 48 people did not undergo tumor resection surgery due to considerations of adverse effects, unresectable tumor location or size, or both factors combined. Among these, three patients received high-dose photon therapy, one received low-dose photon therapy, and one patient's record was misplaced. The results indicated no significant difference between patients with R2 margin and those undergoing RT alone. In other words, RT served as an alternative option for these particular individuals, potentially offering benefits to those who were unwilling or unsuitable candidates for excision surgery. Furthermore, the analysis confirmed that patients with R0/R1 margin had significantly longer PFS than others, consistent with findings from numerous previous studies 5 , 19 – 22 , 26 . Radiation therapy has the potential to induce damage to cellular DNA, leading to both therapeutic effects on neoplasms and the occurrence of acute and late-onset toxicities 52 , 53 . Acute RT complications typically manifest within 3 months post-treatment and are sometimes unavoidable but typically self-limiting 52 , 54 . Following conventional photon RT (5500 cGy in 22 fractions) over sacrococcygeal area, one patient experienced cystitis with gross hematuria. The RT course was thus terminated. Conversely, late-onset complications usually emerge three months post-RT and are often deemed irreversible and progressive over time 52 . Fuller et al. documented a case series of 25 patients undergoing RT for gross residual spinal or cranial chordoma, with only one severe complication reported, involving skin and sacral necrosis occurring in a patient receiving EBRT at 70 Gy in 35 fractions 19 . In another study involving 24 patients with spinal chordoma receiving conventional EBRT after biopsy or partial resection, two cases experienced late skin necrosis following RT retreatment for recurrence 44 . In our study, three cases experienced late-onset RT complications exceeding grade 2. Among them, one patient developed lower limb soreness and weakness two years post-RT, while two patients suffered from severe soft tissue necrosis. None of these cases underwent resection surgery or reirradiation, receiving RT with photon beam at doses ranging from 6250 to 7450 cGy delivered in 25 to 37 fractions. Presently, experts are actively pursuing the development of SBRT, which holds promise for curative treatment while minimizing adverse effects. Hypofractionated SBRT leverages advancements in radiation technology, such as micro-multileaf collimators, robotic systems, cone beam computed tomography scans, and real-time image guidance. This approach enables the delivery of ablative radiation doses to target tissues and spares neighboring normal tissues from excessive radiation exposure 55 . Jin et al. conducted a study where they utilized surgery and/or single-fraction SBRT (18–24 Gy) to treat 35 patients with de novo chordoma of the sacrum and mobile spine. The 3- and 5-year OS rates were reported as 90.0% and 84.3%, respectively, with corresponding local control rates of 86.2% and 80.5% 33 . Sherry et al. reported results from a study involving 15 patients with chordoma or chondrosarcoma affecting the sacrum or mobile spine, who were treated with a single fraction of SBRT (24 Gy); the OS rates at 2 and 5 years were 86% and 62%, while 2- and 5-year local control rates were 100% and 90%, respectively 56 . The acute toxicity associated with spinal SBRT is minimal and exceedingly rare, with reported incidence rates of serious adverse effects (CTCAE grade 3 or higher) at 5% or lower 57 – 60 . However, a relatively common late-onset toxicity attributed to SBRT is vertebral compression fracture (VCF), with estimated risks ranging from 11–39% 61–63 . Evidence suggests that VCF risk increases when the dosage exceeds 20 Gy per fraction 64 . Radiation-induced myelopathy, a feared late effect, is exceptionally rare with the advent of modern SBRT techniques. Besides, separation surgery, where the tumor is excised to decompress the spinal cord, leaving a space for safe SBRT delivery, serves as a viable treatment option preceding SBRT 65 . Currently, it is widely acknowledged that chemotherapy lacks efficacy against the majority of chordoma and chondrosarcoma cases, with no approved medications specifically indicated for their treatment 66 – 69 . However, Frezza et al. demonstrated that adjuvant therapy might confer a survival benefit for mesenchymal chondrosarcoma, a relatively rare and aggressive histologic subtype of chondrosarcoma 70 . In our study, only one out of the 48 patients diagnosed with chondrosarcoma received chemotherapy in 2002. Notably, immunotherapy was not administered to any case in this study. Numerous ongoing clinical trials hold the potential to yield promising therapeutic options for chordoma and chondrosarcoma in the future 71 . Our study investigated the outcomes of individuals diagnosed with vertebral chordoma and chondrosarcoma who underwent either surgery or radiotherapy. However, several limitations of our investigation should be considered when interpreting the findings. One limitation is its retrospective nature, which can introduce challenges and biases such as selection bias and confounding factors. Additionally, the small sample size poses another constraint, as it can be challenging to recruit an adequate number of participants due to the rarity of these tumors. Furthermore, our research did not document data regarding post-treatment symptom improvement, which is crucial for assessing the overall quality of life of patients. Moreover, the study did not delve deeply into the specific surgical strategies employed in the treatment, making it difficult to accurately evaluate the success rates of different surgical methods. Another limitation is the relatively short follow-up period for many cases, which may result in an overestimation or underestimation of treatment effectiveness due to the lack of consideration for long-term effects. Consequently, the findings of the study should be interpreted with caution and cannot be extrapolated to larger populations without further investigation. Despite these limitations, the study offers valuable insights and contributes to the existing body of knowledge on the subject. To enhance the robustness and validity of future findings, researchers should aim to address these limitations by utilizing more diverse and up-to-date data sources. Methods Study Design Patients diagnosed with primary spinal chordoma or chondrosarcoma were identified through a search of the databases of two medical centers in Taiwan spanning from 2001 to 2023. Only individuals who underwent tumor resection surgery or radiotherapy at these institutions and whose histology was confirmed were included in the study. General patient information collected for the study included age at diagnosis, gender, tumor types and subtypes, primary lesion location, Enneking classification, American Joint Committee on Cancer (AJCC) 8th edition TNM staging, surgical margin (R classification), RT and chemotherapy regimens, post-intervention complications, duration of follow-up, status at last follow-up, OS, as well as PFS. The project received approval from the Institutional Review Boards of both medical centers (IRB No.202400714B0) and (IRB No.202403144RIND). All research were performed in accordance with the relevant guidelines and regulations, as well as the Declaration of Helsinki. Due to the retrospective nature of the study, both Chang Gung Medical Foundation Institutional Review Board and National Taiwan University Hospital Institutional Review Board waived the need of obtaining informed consent. Patients with tumors located in the spine or pelvis were retrospectively reviewed from 2001 to 2023. The study excluded individuals with non-spinal pelvic tumors, untreated patients, those presenting with distant metastasis or recurrence of the original tumor at their initial visit, individuals with tumors originating in the bone marrow, and patients diagnosed with reticuloendothelial system or germ cell cancers. Additionally, those who were not followed up for more than three months after completing therapy, as well as patients with diagnoses other than chondrosarcoma or chordoma, such as osteosarcoma or Ewing's sarcoma, were excluded. Pediatric patients, defined as those under 16 years old, were also excluded. Ultimately, the study included 39 cases of spinal chordoma and 9 cases of chondrosarcoma. Comparison of the outcomes after various treatment We compared OS and PFS among patients with different surgical margins (i.e., R0/R1, R2). Within each subgroup defined by surgical margin, we analyzed whether adjuvant radiotherapy (RT) contributed to OS and PFS. Additionally, we compared OS and PFS between patients who only received RT and those with R0/R1 or R2 margins. These analyses were conducted to assess the effectiveness of various treatment approaches. Recurrence, disease progression, or distant metastasis were identified by an increase in tumor size observed on magnetic resonance imaging (MRI) or computed tomography (CT), the onset of neurological deficits due to tumor enlargement, or worsening symptoms attributed to tumor growth. Treatment-related complications were documented following CTCAE version 5.0. Surgical complications among different surgical margin groups were also compared. Statistical analysis IBM SPSS Statistics (Version 25) was employed for the statistical analysis. Fisher’s exact test and one-way ANOVA were utilized for analyzing patient baseline characteristics, while treatment results were assessed using the Kaplan-Meier technique and the log-rank test. In addition, Chi-square test or Fisher’s exact test was utilized in order to compare the surgical complication rates among different groups. All continuous variables were deemed statistically significant at a p value of 0.05, which were showed as mean ± standard deviation. Conclusion Our study findings corroborated the hypothesis that excision surgery with a suitable margin stands as the gold standard treatment. Additionally, our research revealed that photon/proton radiation holds promise for achieving a favorable disease control rate in patients who are either unwilling or unable to undergo surgery. Declarations Declaration of Conflicting Interests The authors declare no competing interests. Data availability statement The accompanying author can provide the data supporting the results of the research upon reasonable request with the appropriate ethical and legal approvals. To gain access to the data, researchers with an interest can contact [email protected] . Author Contribution P.L.K. and Y.C.Y. conceived the study and drafted the main manuscript. P.L.K., Y.C.Y., and F.Y.T. conducted the analyses and developed the methods. K.C. and T.T.T. collected the study data. P.L.L. and F.Y.T. were involved in the study design and oversaw the analyses. All authors participated in interpreting the results and provided critical revisions to the manuscript. References Sciubba, D. M., Chi, J. H., Rhines, L. D. & Gokaslan, Z. L. Chordoma of the spinal column. Neurosurgery Clinics of North America 19 , 5-15 (2008). McLoughlin, G. S., Sciubba, D. M. & Wolinsky, J.-P. 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Predictors for surgical complications of en bloc resections in the spine: review of 220 cases treated by the same team. Eur Spine J 25 , 3932-3941, doi:10.1007/s00586-016-4463-y (2016). Charest-Morin, R. et al. Perioperative adverse events following surgery for primary bone tumors of the spine and en bloc resection for metastases. J Neurosurg Spine , 1-8, doi:10.3171/2019.6.Spine19587 (2019). Li, Z. et al. A Systematic Review of Perioperative Complications in en Bloc Resection for Spinal Tumors. Global Spine Journal 13 , 812-822, doi:10.1177/21925682221120644 (2022). Kim, Y.-J. et al. The volumetric change and dose-response relationship following hypofractionated proton therapy for chordomas. Acta Oncologica 53 , 563-568 (2014). Rich, T. A., Schiller, A., Suit, H. D. & Mankin, H. J. Clinical and pathologic review of 48 cases of chordoma. Cancer 56 , 182-187 (1985). Cummings, B. J., Hodson, D. I. & Bush, R. S. Chordoma: the results of megavoltage radiation therapy. 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Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. J Surg Oncol 110 , 115-122, doi:10.1002/jso.23617 (2014). Catton, C. et al. Chordoma: long-term follow-up after radical photon irradiation. Radiotherapy and Oncology 41 , 67-72 (1996). Chen, Y.-L. et al. Definitive High-Dose Photon/Proton Radiotherapy for Unresected Mobile Spine and Sacral Chordomas. Spine 38 , E930-E936, doi:10.1097/BRS.0b013e318296e7d7 (2013). De Ruysscher, D. et al. Radiotherapy toxicity. Nat Rev Dis Primers 5 , 13, doi:10.1038/s41572-019-0064-5 (2019). Wang, K. & Tepper, J. E. Radiation therapy-associated toxicity: Etiology, management, and prevention. CA Cancer J Clin 71 , 437-454, doi:10.3322/caac.21689 (2021). Brown, S., Kirkbride, P. & Marshall, E. Radiotherapy in the acute medical setting. Clin Med (Lond) 15 , 382-387, doi:10.7861/clinmedicine.15-4-382 (2015). Redmond, K. J. et al. Radiotherapy for Mobile Spine and Sacral Chordoma: A Critical Review and Practical Guide from the Spine Tumor Academy. Cancers 15 , 2359 (2023). Sherry, A. D. et al. Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery. Journal of Neuro-Oncology 164 , 377-386, doi:10.1007/s11060-023-04432-1 (2023). Al-Omair, A. et al. Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy. Neuro-oncology 15 , 1413-1419 (2013). Laufer, I. et al. Local disease control for spinal metastases following “separation surgery” and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients. Journal of Neurosurgery: Spine 18 , 207-214 (2013). Bate, B. G., Khan, N. R., Kimball, B. Y., Gabrick, K. & Weaver, J. Stereotactic radiosurgery for spinal metastases with or without separation surgery. Journal of Neurosurgery: Spine 22 , 409-415 (2015). Folkert, M. R. et al. Outcomes and toxicity for hypofractionated and single-fraction image-guided stereotactic radiosurgery for sarcomas metastasizing to the spine. International Journal of Radiation Oncology* Biology* Physics 88 , 1085-1091 (2014). Cunha, M. V. R. et al. Vertebral Compression Fracture (VCF) After Spine Stereotactic Body Radiation Therapy (SBRT): Analysis of Predictive Factors. International Journal of Radiation Oncology*Biology*Physics 84 , e343-e349, doi:https://doi.org/10.1016/j.ijrobp.2012.04.034 (2012). Boehling, N. S. et al. Vertebral compression fracture risk after stereotactic body radiotherapy for spinal metastases. Journal of Neurosurgery: Spine 16 , 379-386 (2012). Rose, P. S. et al. Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. Journal of Clinical Oncology 27 , 5075 (2009). Lee, S.-H. et al. Can the spinal instability neoplastic score prior to spinal radiosurgery predict compression fractures following stereotactic spinal radiosurgery for metastatic spinal tumor?: a post hoc analysis of prospective phase II single-institution trials. Journal of Neuro-Oncology 126 , 509-517, doi:10.1007/s11060-015-1990-z (2016). Gerszten, P. C. Spine metastases: from radiotherapy, surgery, to radiosurgery. Neurosurgery 61 , 16-25 (2014). Diaz, R. J. & Cusimano, M. D. The biological basis for modern treatment of chordoma. Journal of neuro-oncology 104 , 411-422 (2011). Italiano, A. et al. Advanced chondrosarcomas: role of chemotherapy and survival. Annals of oncology 24 , 2916-2922 (2013). Stacchiotti, S. & Sommer, J. Building a global consensus approach to chordoma: a position paper from the medical and patient community. The lancet oncology 16 , e71-e83 (2015). Stacchiotti, S. et al. Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group. Annals of Oncology 28 , 1230-1242 (2017). Frezza, A. M. et al. Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. European journal of cancer 51 , 374-381 (2015). Traylor, J. I., Pernik, M. N., Plitt, A. R., Lim, M. & Garzon-Muvdi, T. Immunotherapy for chordoma and chondrosarcoma: Current evidence. Cancers 13 , 2408 (2021). Tables Table 1. Patient characteristics Total R0/R1 margin R2 margin RT only p value Patient number 48 14 29 5 - Age (years old) 53.9 ± 15.8 (17-86) 56.6 ± 10.2 (39-78) 52.0 ± 16.2 (21-86) 57.6 ± 26.1 (17-83) 0.587* Gender Male 34 11 21 2 0.300⸸ Female 14 3 8 3 Pathology Chordoma 39 12 23 4 1.000⸸ Chondrosarcoma 9 2 6 1 Location Cervical 3 0 3 0 0.604⸸ Thoracic 5 2 3 0 Lumbar 4 0 4 0 Sacral 36 12 19 5 Enneking classification 1B 48 14 29 5 - AJCC TNM stage T1N0M0 3 1 2 0 0.231⸸ T2N0M0 21 10 9 2 T3N0M0 3 0 3 0 T4N0M0 21 3 15 3 Radiotherapy (+) 23 4 14 5 0.024⸸ (-) 25 10 15 0 Follow-up time (months) 58.1 ± 44.9 (3-193) 63.3 ± 58.8 (3-193) 54.5 ± 39.2 (3-179) 63.3 ± 58.8 (27-119) 0.794* * One-way ANOVA ⸸ Fisher’s exact test Age and follow-up time were presented as mean ± standard deviation (minimum-maximum). Abbreviations: AJCC: American Joint Committee on Cancer R0/R1 margin: negative or microscopically positive margin R2 margin: macroscopically positive margin RT: radiation therapy Table 2. Surgical complications Surgical complication (CTCAE grade) Total (n=48) R0/R1 margin (n=14) R2 margin (n=29) Toxicity Grade 0 14 (32.6%) 5 (35.7%) 9 (31.0%) None Grade 1 10 (23.3%) 1 (7.1%) 9 (31.0%) Transient urinary retention; transient constipation; wound dehiscence; limb numbness, soreness, or anesthesia; neck/back numbness or soreness; unilateral drop foot Grade 2 12 (27.9%) 5 (35.7%) 7 (24.1%) Wound infection; hematoma formation; constant urinary incontinence or dysuria; constant stool incontinence/constipation; tracheostomy care; impaired mobility Grade 3 7 (16.3%) 3 (21.4%) 4 (13.8%) Deep wound infection; sepsis Grade 4 0 (0.0%) 0 (0.0%) 0 (0.0%) - Grade 5 0 (0.0%) 0 (0.0%) 0 (0.0%) - No surgical intervention 5 - - - Abbreviations: CTCAE: Common Terminology Criteria for Adverse Events R0/R1 margin: negative or microscopically positive margin R2 margin: macroscopically positive margin Table 3: Radiotherapy complications Acute-onset RT complication (CTCAE grade) Total (n=48) Toxicity Grade 0 3 (13.0%) None Grade 1 7 (30.4%) Dermatitis; myositis; esophagitis; diarrhea; paresthesia; fatigue; dysuria; mild taste impairment Grade 2 12 (52.2%) Dermatitis; myositis; xerostomia; pharyngeal mucositis; diarrhea; urinary incontinence; paresthesia; fatigue Grade 3 1 (4.3%) Cystitis with gross hematuria Grade 4 0 (0.0%) - Grade 5 0 (0.0%) - No RT 25 - Late-onset RT complication (CTCAE grade) Total (n=48) Toxicity Grade 0 20 (87.0%) None Grade 1 0 (0.0%) - Grade 2 1 (4.3%) Lower limb soreness and weakness Grade 3 1 (4.3%) Soft-tissue necrosis Grade 4 1 (4.3%) Secondary founier's gangrene Grade 5 0 (0.0%) - No RT 25 - Abbreviations: CTCAE: Common Terminology Criteria for Adverse Events R0/R1 margin: negative or microscopically positive margin R2 margin: macroscopically positive margin RT: radiation therapy Additional Declarations No competing interests reported. Supplementary Files 20240606Tablesver.1.docx Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 23 Jul, 2024 Reviews received at journal 20 Jul, 2024 Reviews received at journal 20 Jul, 2024 Reviewers agreed at journal 17 Jul, 2024 Reviewers agreed at journal 15 Jul, 2024 Reviews received at journal 09 Jul, 2024 Reviewers agreed at journal 04 Jul, 2024 Reviewers invited by journal 04 Jul, 2024 Editor assigned by journal 04 Jul, 2024 Editor invited by journal 10 Jun, 2024 Submission checks completed at journal 10 Jun, 2024 First submitted to journal 06 Jun, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4540904","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":317950224,"identity":"36189dca-5211-43f5-88b2-43318bf0170e","order_by":0,"name":"Pin-Lin Kuo","email":"","orcid":"","institution":"Linkou Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Pin-Lin","middleName":"","lastName":"Kuo","suffix":""},{"id":317950225,"identity":"03711301-07e4-4728-bb86-ed5906a71574","order_by":1,"name":"Yu-Cheng Yeh","email":"","orcid":"","institution":"Linkou Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yu-Cheng","middleName":"","lastName":"Yeh","suffix":""},{"id":317950226,"identity":"0108354c-c3ed-4427-972f-2076a76aa3a2","order_by":2,"name":"Koping Chang","email":"","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Koping","middleName":"","lastName":"Chang","suffix":""},{"id":317950227,"identity":"1bf82f96-2977-4aef-9832-d8f9a37b9b71","order_by":3,"name":"Tsung-Ting Tsai","email":"","orcid":"","institution":"Linkou Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tsung-Ting","middleName":"","lastName":"Tsai","suffix":""},{"id":317950228,"identity":"9298712b-ff2f-4828-95f6-d34abafc3bbc","order_by":4,"name":"Po-Liang Lai","email":"","orcid":"","institution":"Linkou Chang Gung Memorial Hospital","correspondingAuthor":false,"prefix":"","firstName":"Po-Liang","middleName":"","lastName":"Lai","suffix":""},{"id":317950229,"identity":"28182bd3-bfef-4bde-b832-bb47fd0823a7","order_by":5,"name":"Fon-Yih Tsuang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYPACOQZ+EJVQQIRaHghlzCDZANJiQIoWgwMgmhgt9vxnDD8X/DJI3Hx+deKHBwYM8vxiBwjYIpFjLD2zzyBx2423myWADjOcOTuBkBYeA2nenj9ALWc3gLQkGNwmpIX/jPFv3h6gw2ac3fyDOC0MOWbSPD8MEjfw924j0pYbaWXWvA0GxjNu8G6zSDCQIOwX9v7Dm2/z/DGQ7e8/u/nmjwobeX5pAlrAgLGNwbFBAqxSggjlYPCHwZ6B/wCxqkfBKBgFo2CkAQB+6EON95f7FwAAAABJRU5ErkJggg==","orcid":"","institution":"National Taiwan University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Fon-Yih","middleName":"","lastName":"Tsuang","suffix":""}],"badges":[],"createdAt":"2024-06-06 14:00:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4540904/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4540904/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-74317-4","type":"published","date":"2024-10-03T15:57:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":59434685,"identity":"97890ced-b229-49dc-a3ff-241ff3d784c4","added_by":"auto","created_at":"2024-07-01 19:04:34","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120167,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival (OS) of Patients with R0/R1 and R2 margin. For R0/R1 and R2 group, the mean OS was 156.5±19.3 and 79.2±11.9 months, respectively (\u003cem\u003ep\u003c/em\u003e value=0.012). The anticipated 5-year and 10-year survival rates for both groups were 100.0% and 67.7±9.8%, and 15.1±9.6% and 80.0±17.9%, respectively.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/56f854fa256f4c4bd547e409.jpg"},{"id":59434684,"identity":"1e5c26ed-0f77-46ed-afc9-69d2fef0be19","added_by":"auto","created_at":"2024-07-01 19:04:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120329,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) of Patients with R0/R1 and R2 margin. For individuals with R0/R1 and R2 margin, the average PFS was 112.9±24.4 and 25.5±5.5 months, respectively (\u003cem\u003ep\u003c/em\u003e value \u0026lt; 0.001).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/5da7a9972631217e5f65387d.jpg"},{"id":59434082,"identity":"0b7e002c-6615-42db-af95-96f3310479d1","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":113234,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival (OS) between R0/R1-margined Patients with or without radiation therapy (RT). Due to insufficient OS data, the average OS could not be calculated. However, the estimated 5-year survival rate was both 100%. Predicted 10-year survival rates were 66.7±27.2% and 100%, respectively.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/2b9a28fab970d12f027fafe1.jpg"},{"id":59434086,"identity":"48a26d37-d5e1-4aa1-a0ef-ac40fa600959","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":119363,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) between R0/R1-margined Patients with or without radiation therapy (RT). Among R0/R1 patients, the mean PFS was 94.0±21.9 months for those undergoing RT and 111.0±27.3 months for those who did not (\u003cem\u003ep\u003c/em\u003e value=0.901).\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/f2cdf78583c9302830649b5f.jpg"},{"id":59434083,"identity":"466197c3-139d-49cf-ab92-17c25adaec5e","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":118639,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival (OS) between R2-margined Patients with or without radiation therapy (RT). The mean OS for R2 patients, with and without RT, was 105.5±26.2 and 76.0±9.2 months, respectively (\u003cem\u003ep\u003c/em\u003e value = 0.734). The predicted 5-year survival rates for each group were 51.6±17.8% and 78.0±11.4%, while the anticipated 10-year survival rates were 51.6±17.8% and 9.8±9.2%.\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/6d4676d5f31d8c702d119978.jpg"},{"id":59434088,"identity":"f3001dc2-6751-4b2e-bca5-28c649703872","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":104939,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) between R2-margined Patients with or without radiation therapy (RT). Among R2 patients, the mean PFS was 27.1±6.4 months for those who underwent RT and 22.9±7.8 months for those who did not (\u003cem\u003ep\u003c/em\u003e value=0.513).\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/0351d4f004a3661b8ba094a6.jpg"},{"id":59434087,"identity":"53ccf950-e98a-4f8f-b319-510dad522372","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":129529,"visible":true,"origin":"","legend":"\u003cp\u003eOverall Survival (OS) between patients with R0/R1 margin, with R2 margin, or with radiation therapy (RT) only. The predicted 5-year survival rates for each group were 100.0%, 67.7±9.8%, and 60.0±21.9%, respectively, while the expected 10-year survival rates were 80.0±17.9%, 15.1±9.6%, and 30.0±23.9%. The OS for the three groups was 156.5±19.3, 79.2±11.9, and 75.9±16.6 months (\u003cem\u003ep\u003c/em\u003e value=0.046).\u003c/p\u003e","description":"","filename":"Figure7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/c01fba99a8746bf810fb4ff7.jpg"},{"id":59434687,"identity":"3d2a7408-674d-4e3f-9992-aaf040468725","added_by":"auto","created_at":"2024-07-01 19:04:34","extension":"jpg","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":133915,"visible":true,"origin":"","legend":"\u003cp\u003eProgression-Free Survival (PFS) between patients with R0/R1 margin, with R2 margin, or with radiation therapy (RT) only. The PFS of the 3 groups was 112.9±24.4, 25.5±5.5, and 73.3±18.0 months (\u003cem\u003ep\u003c/em\u003e value\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"Figure8.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/1d716a38b6726a10b4d2f6ef.jpg"},{"id":66097440,"identity":"bab90235-9ed0-4ef3-855a-d7b635001b36","added_by":"auto","created_at":"2024-10-07 16:14:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1736716,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/ed165671-377a-405f-80c5-d76c5ddddeb4.pdf"},{"id":59434079,"identity":"2fc0f7fa-3039-45e5-a405-8969592d7fac","added_by":"auto","created_at":"2024-07-01 18:56:34","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":19611,"visible":true,"origin":"","legend":"","description":"","filename":"20240606Tablesver.1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4540904/v1/ce575ee541dd19c857c176b6.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Spinal Chordoma and Chondrosarcoma Treatment Experiences - A 20-Year Retrospective Study from Databases of Two Medical Centers","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSpinal chordoma and chondrosarcoma are classified as low to intermediate grade primary malignant tumors of the vertebrae\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. While chordoma constitutes a relatively small fraction (1.4%) of primary malignant tumors overall\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, they notably represent over half of all primary sacral tumors\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Moreover, they comprise 15 to 20% of primary tumors in the mobile spine\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, but are exceedingly rare (0.2%) in the skull base\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Chondrosarcoma constitutes a significant portion, approximately 27%, of all primary bone tumors\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, with spinal chondrosarcoma estimated to account for about 26% of primary malignant tumors in the vertebrae\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. These tumors predominantly arise in the thoracic and lumbar regions\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Both chordoma and chondrosarcoma present a spectrum of symptoms, including back pain, neurological deficits, muscle atrophy, urinary and bowel dysfunction, and potential reductions in life expectancy\u003csup\u003e\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Crafting comprehensive treatment strategies is paramount in optimizing patients' quality of life and improving their overall survival (OS) outlook.\u003c/p\u003e \u003cp\u003eChordoma emerges from the remnants of the notochord and typically grows slowly, yet malignantly\u003csup\u003e\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Spinal chondrosarcoma can emerge spontaneously or as a result of preexisting cartilage lesions such as osteochondroma or enchondroma\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Despite their resistance to radiotherapy and chemotherapy, total en bloc resection is necessary to enhance local control rates\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR20 CR21 CR22\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. The preferred treatment for both chordoma and spinal chondrosarcoma is wide local excision, sometimes accompanied by adjuvant radiotherapy\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. However, many patients experience complications post-surgery. The extent of surgical removal is directly linked to improved OS\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Neurological involvement and disability are common and significant side effects, varying in severity based on the tumor's extent or location\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eFor patients with positive margins or those with unfavorable local tumor characteristics, an aggressive radiotherapy (RT) approach incorporating techniques like intraoperative dural plaques brachytherapy and high-dose photon/proton therapy may achieve regional control\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. When achieving negative margins is challenging, RT utilizing the heavy charged particle carbon ion, known for its sharper lateral penumbra, is seen as a promising treatment option\u003csup\u003e\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e. Additionally, hypofractionated stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) are under consideration as potential therapies for unresectable vertebral chordoma and chondrosarcoma due to advancements in geometric accuracy\u003csup\u003e\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e Since spinal chordoma and chondrosarcoma exhibit several overlapping characteristics, this study collected cases of both conditions and investigated how different treatment methods influenced patient outcomes, aiming to anticipate the development of standardized therapeutic guidelines.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003ePatients\u003c/h2\u003e\n \u003cp\u003eThe patient characteristics are displayed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The average age at diagnosis among the 48 patients was 53.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8 (ranging from 17 to 86) years, with 34 males and 14 females. Of these, 39 had vertebral chordoma and 9 had chondrosarcoma, all classified as 1B according to the Enneking classification. None of the patients exhibited lymph node or distant metastasis. Based on the AJCC 8th edition staging, there were 3, 21, 3, and 21 patients with T1, T2, T3, and T4 stages, respectively. Distribution across spinal regions was as follows: three in the cervical spine, five in the thoracic region, four in the lumbar spine, and thirty-six in the sacrum. The majority (n\u0026thinsp;=\u0026thinsp;43) underwent tumor removal surgery, among which seven had negative margin (R0), seven had microscopically positive margin (R1), and 29 had macroscopically positive margin (R2). Among the R0 cases, two opted for adjuvant radiotherapy (RT), while five did not. Among the R1 cases, two chose RT, and five did not. Within the R2 cases, fourteen patients underwent RT, while 15 did not. Additionally, five patients received RT as a palliative measure instead of surgery. The follow-up period was computed starting on the date of treatment completion, including surgery and RT. At the last follow-up, 28 out of 48 individuals were alive, with an average follow-up duration of 58.1\u0026thinsp;\u0026plusmn;\u0026thinsp;44.9 months.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n \u003ch2\u003eThe Differences in Results between R0/R1 and R2 Margin\u003c/h2\u003e\n \u003cp\u003ePatients who underwent excision surgery were divided into two groups based on histological findings: R0/R1 (n\u0026thinsp;=\u0026thinsp;14) and R2 (n\u0026thinsp;=\u0026thinsp;29) tumor margin. Figure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the OS curve. The mean OS for R0/R1 and R2 groups was 156.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.3 and 79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 months, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.012). Both groups had estimated 5-year survival rates of 100.0% and 67.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8%, and estimated 10-year survival rates of 80.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9% and 15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6%, respectively. Figure \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e shows the progression-free survival curve curve. The mean PFS for R0/R1 and R2 groups was 112.9\u0026thinsp;\u0026plusmn;\u0026thinsp;24.4 and 25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 months, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003eThe Implications of Adjuvant Radiation on People with R0/R1 Margin\u003c/h2\u003e\n \u003cp\u003eFour out of the fourteen patients with negative or microscopically positive margin underwent RT, while ten did not. Figure \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e depicts the OS curve. Both groups had estimated 5-year survival rates of 100%, while the projected 10-year survival rates were 100% and 66.7\u0026thinsp;\u0026plusmn;\u0026thinsp;27.2%, respectively. The average OS could not be calculated due to insufficient OS data. The PFS curve is shown in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. The mean PFS for R0/R1 patients with and without RT was 94.0\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9 and 111.0\u0026thinsp;\u0026plusmn;\u0026thinsp;27.3 months, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.901).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eThe Effect of Adjuvant Radiation on Patients with R2 Margin\u003c/h2\u003e\n \u003cp\u003eFourteen out of the twenty-nine cases with R2 margin opted for RT, while 15 did not. The OS curve is depicted in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. The estimated 5-year survival rates were 51.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8% and 78.0\u0026thinsp;\u0026plusmn;\u0026thinsp;11.4%, and the estimated 10-year survival rates were 51.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8% and 9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2%, respectively. For R2 patients with and without RT, the average OS was 105.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.2 and 76.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2 months (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.734). The PFS curve is shown in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e. The mean PFS for R2 patients with and without RT was 27.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 and 22.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8 months (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.513), respectively.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003eThe Results for Patients with R0/R1 Margin, with R2 Margin, and with RT Only\u003c/h2\u003e\n \u003cp\u003eThe outcomes following therapy were compared among patients with R0/R1 margin, individuals with R2 margin, and those who received only RT to assess whether RT could be beneficial for those unwilling or unable to undergo resection surgery. Figure \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e illustrates the OS curve. The estimated 5-year survival rates for each group were 100.0%, 67.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8%, and 60.0\u0026thinsp;\u0026plusmn;\u0026thinsp;21.9%, while the estimated 10-year survival rates were 80.0\u0026thinsp;\u0026plusmn;\u0026thinsp;17.9%, 15.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6%, and 30.0\u0026thinsp;\u0026plusmn;\u0026thinsp;23.9%, respectively. The average OS for the three groups was 156.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.3, 79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9, and 75.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 months (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.046). Figure \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e presents the PFS curve. The PFS for the three groups was 112.9\u0026thinsp;\u0026plusmn;\u0026thinsp;24.4, 25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5, and 73.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0 months, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eTreatment-Related Complications\u003c/h2\u003e\n \u003cp\u003eComplications arising from surgery and adjuvant RT were documented according to Common Terminology Criteria for Adverse Events (CTCAE) version 5 and are outlined in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Among the forty-three participants who underwent surgery in our study, twelve experienced grade 2 surgical complications. Of these, eight presented with neurological deficits, including dysuria or urinary incontinence, constipation or fecal incontinence, and decreased mobility. One case involved hematoma formation, two had wound infection, and one required tracheostomy care. Additionally, seven patients experienced grade 3 surgical complications, all of which were categorized as sepsis or deep wound infection. Among patients with R0/R1 and R2 margins, surgical complications\u0026thinsp;\u0026ge;\u0026thinsp;CTCAE grade 2 occurred in 8 (57.1%) and 11 (37.9%) cases, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.235). Furthermore, 3 (21.4%) and 4 (13.8%) patients experienced surgical complications graded higher than CTCAE grade 3 (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.665), respectively. Twenty-three patients in our study opted for either palliative or adjuvant radiotherapy. Among them, twelve (52.2%) experienced acute CTCAE grade 2 RT-related complications, while one (4.3%) had acute CTCAE grade 3 complications. Additionally, one (5.3%), one (5.3%), and one (5.3%) patient experienced CTCAE grade 2, 3, and 4 late-onset RT toxicity, respectively.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003ePrimary vertebral neoplasms are uncommon in adulthood, with chordoma and chondrosarcoma comprising the majority. These tumors exhibit aggressive behavior and are prone to local recurrence\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. The primary goal of treatment is excision surgery aiming for a negative or microscopically positive margin, which enhances local control and improves survival prospects for patients\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Nonetheless, surgical procedures often lead to complications due to delayed diagnosis and the tumors' proximity to vital structures like arteries, viscera, and neural tissue\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e. En bloc resection of chordoma and spinal chondrosarcoma remains particularly challenging considering the potential postoperative side effects and functional impairments\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. For instance, data from Maggiore Hospital in Bologna, Italy, indicated that only 20% of 52 patients treated over a 50-year period until 2002 achieved adequate margins post-surgery, with many experiencing local recurrence within 56–94 months\u003csup\u003e\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our investigation, fourteen out of the 43 patients who opted for surgery achieved a negative or microscopically positive margin, demonstrating notably superior outcomes in terms of OS and PFS compared to those with a macroscopically positive margin The efficacy of therapy was found to be significantly influenced by complete surgical resection, corroborating findings from previous studies\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e,\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u003c/sup\u003e. Previous clinical series have consistently highlighted that a negative surgical margin stands out as the most critical predictor of tumor recurrence rates and long-term survival\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhile total excision is considered the optimal treatment approach, it is essential to weigh the risks of perioperative complications, including damage to nearby structures, neurological impairments, wound complications such as dehiscence or infection, medical morbidity stemming from surgical trauma, and potential long-term device failure\u003csup\u003e\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e,\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e\u003c/sup\u003e. Li et al. carried out a systematic review of perioperative complications in 824 cases undergoing total en bloc resection, revealing various rates: 12.7% for neurological damage, 12.1% for hardware failure, 10.6% for dural tear and cerebrospinal fluid leakage, 7.6% for wound-related complications with nearly half necessitating revision, and 7.3% for vascular injury and bleeding\u003csup\u003e\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e\u003c/sup\u003e. Additionally, mortality rates due to surgical complications were reported at 1.2%.\u003csup\u003e41\u003c/sup\u003e. In our dataset, among patients undergoing surgery, 55.8% (24/43) experienced complications graded as CTCAE 0 or 1, 27.9% (12/43) had grade 2 complications, and 16.3% (7/43) had grade 3 adverse events. Of those with complications grade 2 or higher, ten were related to wound issues, and eight were neurological. Besides, one patient succumbed to severe sepsis within a month after surgery, leading to the exclusion from our study.\u003c/p\u003e \u003cp\u003eAssessing the efficacy of radiation therapy can be challenging due to the limited patient pool and ongoing technological advancements in radiation therapy. Research strongly supports the effectiveness of conventional photon or proton dosages for chordoma treatment\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u003c/sup\u003e. Studies have indicated that radical surgery combined with conventional radiation at doses below 60 Gy yields poor local control rates (ranging from 0–50%) for spinal and sacral chordoma\u003csup\u003e\u003cspan additionalcitationids=\"CR44\" citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e–\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e\u003c/sup\u003e. Nonetheless, the maximum feasible dose of traditional photon radiation typically administered to spinal tumors is around 50 Gy, a level associated with minimal risk of paralysis, determined by the tolerance of the spinal cord\u003csup\u003e\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e\u003c/sup\u003e. Proton therapy presents a promising option for treating spinal malignancies due to its potential for reduced or delayed toxicity. In a study by Hug et al., employing combined photon-proton radiotherapy with an average dose of 73.9 Gy/CGE, 5-year local control rates of 53% and 100% were observed for chordoma and chondrosarcoma of the axial skeleton, respectively\u003csup\u003e\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u003c/sup\u003e. Another phase II clinical study at Massachusetts General Hospital administered radiation doses of 70.2 Gy/CGE for microscopic positive resection and 77.4 Gy/CGE for gross disease, with long-term results revealing a 74% local control rate after eight years\u003csup\u003e\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e,\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our investigation, four out of the 14 individuals having R0/R1 resection received adjuvant RT, with only one of them receiving photon/proton therapy at a dosage exceeding 60 Gy/CGE. The OS and PFS were not significantly influenced by the administration of RT in the R0/R1 group. Among the 29 patients with R2 margin in our study, fourteen opted for adjuvant RT, while fifteen did not. Concerning toxicity, nine of the fourteen patients received cumulative doses exceeding 60 Gy/CGE, while five received low-dose RT, with dosages ranging from 30 to 74 Gy/CGE. There was no discernible difference in therapeutic outcomes between R2 margin patients who underwent RT and those who did not.\u003c/p\u003e \u003cp\u003eFor individuals with unresectable tumors, conventional photon beam radiation therapy administered at doses exceeding 60 Gy, although high and often associated with toxicity, may exhibit therapeutic efficacy\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e,\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e,\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e. A retrospective study by Chen et al. demonstrated that proton therapy, with a median total dose of 77.4 Gy, resulted in OS rates of 91.7% and 78.1%, as well as PFS rates of 90.4% and 79.8% at 3 and 5 years, respectively\u003csup\u003e\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn our study, only 5 out of the 48 people did not undergo tumor resection surgery due to considerations of adverse effects, unresectable tumor location or size, or both factors combined. Among these, three patients received high-dose photon therapy, one received low-dose photon therapy, and one patient's record was misplaced. The results indicated no significant difference between patients with R2 margin and those undergoing RT alone. In other words, RT served as an alternative option for these particular individuals, potentially offering benefits to those who were unwilling or unsuitable candidates for excision surgery. Furthermore, the analysis confirmed that patients with R0/R1 margin had significantly longer PFS than others, consistent with findings from numerous previous studies\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e–\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRadiation therapy has the potential to induce damage to cellular DNA, leading to both therapeutic effects on neoplasms and the occurrence of acute and late-onset toxicities\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e\u003c/sup\u003e. Acute RT complications typically manifest within 3 months post-treatment and are sometimes unavoidable but typically self-limiting\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e,\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e\u003c/sup\u003e. Following conventional photon RT (5500 cGy in 22 fractions) over sacrococcygeal area, one patient experienced cystitis with gross hematuria. The RT course was thus terminated. Conversely, late-onset complications usually emerge three months post-RT and are often deemed irreversible and progressive over time\u003csup\u003e\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e\u003c/sup\u003e. Fuller et al. documented a case series of 25 patients undergoing RT for gross residual spinal or cranial chordoma, with only one severe complication reported, involving skin and sacral necrosis occurring in a patient receiving EBRT at 70 Gy in 35 fractions\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In another study involving 24 patients with spinal chordoma receiving conventional EBRT after biopsy or partial resection, two cases experienced late skin necrosis following RT retreatment for recurrence\u003csup\u003e\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e\u003c/sup\u003e. In our study, three cases experienced late-onset RT complications exceeding grade 2. Among them, one patient developed lower limb soreness and weakness two years post-RT, while two patients suffered from severe soft tissue necrosis. None of these cases underwent resection surgery or reirradiation, receiving RT with photon beam at doses ranging from 6250 to 7450 cGy delivered in 25 to 37 fractions.\u003c/p\u003e \u003cp\u003ePresently, experts are actively pursuing the development of SBRT, which holds promise for curative treatment while minimizing adverse effects. Hypofractionated SBRT leverages advancements in radiation technology, such as micro-multileaf collimators, robotic systems, cone beam computed tomography scans, and real-time image guidance. This approach enables the delivery of ablative radiation doses to target tissues and spares neighboring normal tissues from excessive radiation exposure\u003csup\u003e\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e\u003c/sup\u003e. Jin et al. conducted a study where they utilized surgery and/or single-fraction SBRT (18–24 Gy) to treat 35 patients with de novo chordoma of the sacrum and mobile spine. The 3- and 5-year OS rates were reported as 90.0% and 84.3%, respectively, with corresponding local control rates of 86.2% and 80.5%\u003csup\u003e33\u003c/sup\u003e. Sherry et al. reported results from a study involving 15 patients with chordoma or chondrosarcoma affecting the sacrum or mobile spine, who were treated with a single fraction of SBRT (24 Gy); the OS rates at 2 and 5 years were 86% and 62%, while 2- and 5-year local control rates were 100% and 90%, respectively\u003csup\u003e\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe acute toxicity associated with spinal SBRT is minimal and exceedingly rare, with reported incidence rates of serious adverse effects (CTCAE grade 3 or higher) at 5% or lower\u003csup\u003e\u003cspan additionalcitationids=\"CR58 CR59\" citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e–\u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e\u003c/sup\u003e. However, a relatively common late-onset toxicity attributed to SBRT is vertebral compression fracture (VCF), with estimated risks ranging from 11–39%\u003csup\u003e61–63\u003c/sup\u003e. Evidence suggests that VCF risk increases when the dosage exceeds 20 Gy per fraction\u003csup\u003e\u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e\u003c/sup\u003e. Radiation-induced myelopathy, a feared late effect, is exceptionally rare with the advent of modern SBRT techniques. Besides, separation surgery, where the tumor is excised to decompress the spinal cord, leaving a space for safe SBRT delivery, serves as a viable treatment option preceding SBRT\u003csup\u003e\u003cspan citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCurrently, it is widely acknowledged that chemotherapy lacks efficacy against the majority of chordoma and chondrosarcoma cases, with no approved medications specifically indicated for their treatment\u003csup\u003e\u003cspan additionalcitationids=\"CR67 CR68\" citationid=\"CR66\" class=\"CitationRef\"\u003e66\u003c/span\u003e–\u003cspan citationid=\"CR69\" class=\"CitationRef\"\u003e69\u003c/span\u003e\u003c/sup\u003e. However, Frezza et al. demonstrated that adjuvant therapy might confer a survival benefit for mesenchymal chondrosarcoma, a relatively rare and aggressive histologic subtype of chondrosarcoma\u003csup\u003e\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e\u003c/sup\u003e. In our study, only one out of the 48 patients diagnosed with chondrosarcoma received chemotherapy in 2002. Notably, immunotherapy was not administered to any case in this study. Numerous ongoing clinical trials hold the potential to yield promising therapeutic options for chordoma and chondrosarcoma in the future\u003csup\u003e\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur study investigated the outcomes of individuals diagnosed with vertebral chordoma and chondrosarcoma who underwent either surgery or radiotherapy. However, several limitations of our investigation should be considered when interpreting the findings. One limitation is its retrospective nature, which can introduce challenges and biases such as selection bias and confounding factors. Additionally, the small sample size poses another constraint, as it can be challenging to recruit an adequate number of participants due to the rarity of these tumors. Furthermore, our research did not document data regarding post-treatment symptom improvement, which is crucial for assessing the overall quality of life of patients. Moreover, the study did not delve deeply into the specific surgical strategies employed in the treatment, making it difficult to accurately evaluate the success rates of different surgical methods. Another limitation is the relatively short follow-up period for many cases, which may result in an overestimation or underestimation of treatment effectiveness due to the lack of consideration for long-term effects. Consequently, the findings of the study should be interpreted with caution and cannot be extrapolated to larger populations without further investigation. Despite these limitations, the study offers valuable insights and contributes to the existing body of knowledge on the subject. To enhance the robustness and validity of future findings, researchers should aim to address these limitations by utilizing more diverse and up-to-date data sources.\u003c/p\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e \u003c/div\u003e \u003c/div\u003e "},{"header":"Methods","content":"\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003ePatients diagnosed with primary spinal chordoma or chondrosarcoma were identified through a search of the databases of two medical centers in Taiwan spanning from 2001 to 2023. Only individuals who underwent tumor resection surgery or radiotherapy at these institutions and whose histology was confirmed were included in the study. General patient information collected for the study included age at diagnosis, gender, tumor types and subtypes, primary lesion location, Enneking classification, American Joint Committee on Cancer (AJCC) 8th edition TNM staging, surgical margin (R classification), RT and chemotherapy regimens, post-intervention complications, duration of follow-up, status at last follow-up, OS, as well as PFS. The project received approval from the Institutional Review Boards of both medical centers (IRB No.202400714B0) and (IRB No.202403144RIND). All research were performed in accordance with the relevant guidelines and regulations, as well as the Declaration of Helsinki. Due to the retrospective nature of the study, both Chang Gung Medical Foundation Institutional Review Board and National Taiwan University Hospital Institutional Review Board waived the need of obtaining informed consent.\u003c/p\u003e\u003cp\u003ePatients with tumors located in the spine or pelvis were retrospectively reviewed from 2001 to 2023. The study excluded individuals with non-spinal pelvic tumors, untreated patients, those presenting with distant metastasis or recurrence of the original tumor at their initial visit, individuals with tumors originating in the bone marrow, and patients diagnosed with reticuloendothelial system or germ cell cancers. Additionally, those who were not followed up for more than three months after completing therapy, as well as patients with diagnoses other than chondrosarcoma or chordoma, such as osteosarcoma or Ewing's sarcoma, were excluded. Pediatric patients, defined as those under 16 years old, were also excluded. Ultimately, the study included 39 cases of spinal chordoma and 9 cases of chondrosarcoma.\u003c/p\u003e\u003ch2\u003eComparison of the outcomes after various treatment\u003c/h2\u003e\u003cp\u003eWe compared OS and PFS among patients with different surgical margins (i.e., R0/R1, R2). Within each subgroup defined by surgical margin, we analyzed whether adjuvant radiotherapy (RT) contributed to OS and PFS. Additionally, we compared OS and PFS between patients who only received RT and those with R0/R1 or R2 margins. These analyses were conducted to assess the effectiveness of various treatment approaches. Recurrence, disease progression, or distant metastasis were identified by an increase in tumor size observed on magnetic resonance imaging (MRI) or computed tomography (CT), the onset of neurological deficits due to tumor enlargement, or worsening symptoms attributed to tumor growth. Treatment-related complications were documented following CTCAE version 5.0. Surgical complications among different surgical margin groups were also compared.\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eIBM SPSS Statistics (Version 25) was employed for the statistical analysis. Fisher’s exact test and one-way ANOVA were utilized for analyzing patient baseline characteristics, while treatment results were assessed using the Kaplan-Meier technique and the log-rank test. In addition, Chi-square test or Fisher’s exact test was utilized in order to compare the surgical complication rates among different groups. All continuous variables were deemed statistically significant at a \u003cem\u003ep\u003c/em\u003e value of 0.05, which were showed as mean ± standard deviation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study findings corroborated the hypothesis that excision surgery with a suitable margin stands as the gold standard treatment. Additionally, our research revealed that photon/proton radiation holds promise for achieving a favorable disease control rate in patients who are either unwilling or unable to undergo surgery.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDeclaration of Conflicting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe accompanying author can provide the data supporting the results of the research upon reasonable request with the appropriate ethical and legal approvals. To gain access to the data, researchers with an interest can contact [email protected].\u0026nbsp;\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eP.L.K. and Y.C.Y. conceived the study and drafted the main manuscript. P.L.K., Y.C.Y., and F.Y.T. conducted the analyses and developed the methods. K.C. and T.T.T. collected the study data. P.L.L. and F.Y.T. were involved in the study design and oversaw the analyses. All authors participated in interpreting the results and provided critical revisions to the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSciubba, D. M., Chi, J. H., Rhines, L. D. \u0026amp; Gokaslan, Z. L. Chordoma of the spinal column. \u003cem\u003eNeurosurgery Clinics of North America\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 5-15 (2008).\u003c/li\u003e\n\u003cli\u003eMcLoughlin, G. S., Sciubba, D. M. \u0026amp; Wolinsky, J.-P. Chondroma/chondrosarcoma of the spine. \u003cem\u003eNeurosurgery Clinics of North America\u003c/em\u003e \u003cstrong\u003e19\u003c/strong\u003e, 57-63 (2008).\u003c/li\u003e\n\u003cli\u003eHealey, J. \u0026amp; Lane, J. 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Predictors for surgical complications of en bloc resections in the spine: review of 220 cases treated by the same team. \u003cem\u003eEur Spine J\u003c/em\u003e \u003cstrong\u003e25\u003c/strong\u003e, 3932-3941, doi:10.1007/s00586-016-4463-y (2016).\u003c/li\u003e\n\u003cli\u003eCharest-Morin, R.\u003cem\u003e et al.\u003c/em\u003e Perioperative adverse events following surgery for primary bone tumors of the spine and en bloc resection for metastases. \u003cem\u003eJ Neurosurg Spine\u003c/em\u003e, 1-8, doi:10.3171/2019.6.Spine19587 (2019).\u003c/li\u003e\n\u003cli\u003eLi, Z.\u003cem\u003e et al.\u003c/em\u003e A Systematic Review of Perioperative Complications in en Bloc Resection for Spinal Tumors. \u003cem\u003eGlobal Spine Journal\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 812-822, doi:10.1177/21925682221120644 (2022).\u003c/li\u003e\n\u003cli\u003eKim, Y.-J.\u003cem\u003e et al.\u003c/em\u003e The volumetric change and dose-response relationship following hypofractionated proton therapy for chordomas. \u003cem\u003eActa Oncologica\u003c/em\u003e \u003cstrong\u003e53\u003c/strong\u003e, 563-568 (2014).\u003c/li\u003e\n\u003cli\u003eRich, T. A., Schiller, A., Suit, H. D. \u0026amp; Mankin, H. J. Clinical and pathologic review of 48 cases of chordoma. \u003cem\u003eCancer\u003c/em\u003e \u003cstrong\u003e56\u003c/strong\u003e, 182-187 (1985).\u003c/li\u003e\n\u003cli\u003eCummings, B. J., Hodson, D. I. \u0026amp; Bush, R. S. Chordoma: the results of megavoltage radiation therapy. \u003cem\u003eInternational Journal of Radiation Oncology* Biology* Physics\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 633-642 (1983).\u003c/li\u003e\n\u003cli\u003eBjornsson, J., Wold, L. E., Ebersold, M. J. \u0026amp; Laws, E. R. Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients. \u003cem\u003eCancer\u003c/em\u003e \u003cstrong\u003e71\u003c/strong\u003e, 735-740 (1993).\u003c/li\u003e\n\u003cli\u003eSchultheiss, T., Kun, L., Ang, K. \u0026amp; Stephens, L. Radiation response of the central nervous system. \u003cem\u003eInternational Journal of Radiation Oncology* Biology* Physics\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 1093-1112 (1995).\u003c/li\u003e\n\u003cli\u003eHug, E. B., Fitzek, M. M., Liebsch, N. J. \u0026amp; Munzenrider, J. E. Locally challenging osteo-and chondrogenic tumors of the axial skeleton: results of combined proton and photon radiation therapy using three-dimensional treatment planning. \u003cem\u003eInternational journal of radiation oncology, biology, physics\u003c/em\u003e \u003cstrong\u003e31\u003c/strong\u003e, 467-476 (1995).\u003c/li\u003e\n\u003cli\u003eDeLaney, T. F.\u003cem\u003e et al.\u003c/em\u003e Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. \u003cem\u003eInternational Journal of Radiation Oncology* Biology* Physics\u003c/em\u003e \u003cstrong\u003e74\u003c/strong\u003e, 732-739 (2009).\u003c/li\u003e\n\u003cli\u003eDeLaney, T. F.\u003cem\u003e et al.\u003c/em\u003e Long-term results of Phase II study of high dose photon/proton radiotherapy in the management of spine chordomas, chondrosarcomas, and other sarcomas. \u003cem\u003eJ Surg Oncol\u003c/em\u003e \u003cstrong\u003e110\u003c/strong\u003e, 115-122, doi:10.1002/jso.23617 (2014).\u003c/li\u003e\n\u003cli\u003eCatton, C.\u003cem\u003e et al.\u003c/em\u003e Chordoma: long-term follow-up after radical photon irradiation. \u003cem\u003eRadiotherapy and Oncology\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 67-72 (1996).\u003c/li\u003e\n\u003cli\u003eChen, Y.-L.\u003cem\u003e et al.\u003c/em\u003e Definitive High-Dose Photon/Proton Radiotherapy for Unresected Mobile Spine and Sacral Chordomas. \u003cem\u003eSpine\u003c/em\u003e \u003cstrong\u003e38\u003c/strong\u003e, E930-E936, doi:10.1097/BRS.0b013e318296e7d7 (2013).\u003c/li\u003e\n\u003cli\u003eDe Ruysscher, D.\u003cem\u003e et al.\u003c/em\u003e Radiotherapy toxicity. \u003cem\u003eNat Rev Dis Primers\u003c/em\u003e \u003cstrong\u003e5\u003c/strong\u003e, 13, doi:10.1038/s41572-019-0064-5 (2019).\u003c/li\u003e\n\u003cli\u003eWang, K. \u0026amp; Tepper, J. E. Radiation therapy-associated toxicity: Etiology, management, and prevention. \u003cem\u003eCA Cancer J Clin\u003c/em\u003e \u003cstrong\u003e71\u003c/strong\u003e, 437-454, doi:10.3322/caac.21689 (2021).\u003c/li\u003e\n\u003cli\u003eBrown, S., Kirkbride, P. \u0026amp; Marshall, E. Radiotherapy in the acute medical setting. \u003cem\u003eClin Med (Lond)\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 382-387, doi:10.7861/clinmedicine.15-4-382 (2015).\u003c/li\u003e\n\u003cli\u003eRedmond, K. J.\u003cem\u003e et al.\u003c/em\u003e Radiotherapy for Mobile Spine and Sacral Chordoma: A Critical Review and Practical Guide from the Spine Tumor Academy. \u003cem\u003eCancers\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 2359 (2023).\u003c/li\u003e\n\u003cli\u003eSherry, A. D.\u003cem\u003e et al.\u003c/em\u003e Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery. \u003cem\u003eJournal of Neuro-Oncology\u003c/em\u003e \u003cstrong\u003e164\u003c/strong\u003e, 377-386, doi:10.1007/s11060-023-04432-1 (2023).\u003c/li\u003e\n\u003cli\u003eAl-Omair, A.\u003cem\u003e et al.\u003c/em\u003e Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy. \u003cem\u003eNeuro-oncology\u003c/em\u003e \u003cstrong\u003e15\u003c/strong\u003e, 1413-1419 (2013).\u003c/li\u003e\n\u003cli\u003eLaufer, I.\u003cem\u003e et al.\u003c/em\u003e Local disease control for spinal metastases following \u0026ldquo;separation surgery\u0026rdquo; and adjuvant hypofractionated or high-dose single-fraction stereotactic radiosurgery: outcome analysis in 186 patients. \u003cem\u003eJournal of Neurosurgery: Spine\u003c/em\u003e \u003cstrong\u003e18\u003c/strong\u003e, 207-214 (2013).\u003c/li\u003e\n\u003cli\u003eBate, B. G., Khan, N. R., Kimball, B. Y., Gabrick, K. \u0026amp; Weaver, J. Stereotactic radiosurgery for spinal metastases with or without separation surgery. \u003cem\u003eJournal of Neurosurgery: Spine\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 409-415 (2015).\u003c/li\u003e\n\u003cli\u003eFolkert, M. R.\u003cem\u003e et al.\u003c/em\u003e Outcomes and toxicity for hypofractionated and single-fraction image-guided stereotactic radiosurgery for sarcomas metastasizing to the spine. \u003cem\u003eInternational Journal of Radiation Oncology* Biology* Physics\u003c/em\u003e \u003cstrong\u003e88\u003c/strong\u003e, 1085-1091 (2014).\u003c/li\u003e\n\u003cli\u003eCunha, M. V. R.\u003cem\u003e et al.\u003c/em\u003e Vertebral Compression Fracture (VCF) After Spine Stereotactic Body Radiation Therapy (SBRT): Analysis of Predictive Factors. \u003cem\u003eInternational Journal of Radiation Oncology*Biology*Physics\u003c/em\u003e \u003cstrong\u003e84\u003c/strong\u003e, e343-e349, doi:https://doi.org/10.1016/j.ijrobp.2012.04.034 (2012).\u003c/li\u003e\n\u003cli\u003eBoehling, N. S.\u003cem\u003e et al.\u003c/em\u003e Vertebral compression fracture risk after stereotactic body radiotherapy for spinal metastases. \u003cem\u003eJournal of Neurosurgery: Spine\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, 379-386 (2012).\u003c/li\u003e\n\u003cli\u003eRose, P. S.\u003cem\u003e et al.\u003c/em\u003e Risk of fracture after single fraction image-guided intensity-modulated radiation therapy to spinal metastases. \u003cem\u003eJournal of Clinical Oncology\u003c/em\u003e \u003cstrong\u003e27\u003c/strong\u003e, 5075 (2009).\u003c/li\u003e\n\u003cli\u003eLee, S.-H.\u003cem\u003e et al.\u003c/em\u003e Can the spinal instability neoplastic score prior to spinal radiosurgery predict compression fractures following stereotactic spinal radiosurgery for metastatic spinal tumor?: a post hoc analysis of prospective phase II single-institution trials. \u003cem\u003eJournal of Neuro-Oncology\u003c/em\u003e \u003cstrong\u003e126\u003c/strong\u003e, 509-517, doi:10.1007/s11060-015-1990-z (2016).\u003c/li\u003e\n\u003cli\u003eGerszten, P. C. Spine metastases: from radiotherapy, surgery, to radiosurgery. \u003cem\u003eNeurosurgery\u003c/em\u003e \u003cstrong\u003e61\u003c/strong\u003e, 16-25 (2014).\u003c/li\u003e\n\u003cli\u003eDiaz, R. J. \u0026amp; Cusimano, M. D. The biological basis for modern treatment of chordoma. \u003cem\u003eJournal of neuro-oncology\u003c/em\u003e \u003cstrong\u003e104\u003c/strong\u003e, 411-422 (2011).\u003c/li\u003e\n\u003cli\u003eItaliano, A.\u003cem\u003e et al.\u003c/em\u003e Advanced chondrosarcomas: role of chemotherapy and survival. \u003cem\u003eAnnals of oncology\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 2916-2922 (2013).\u003c/li\u003e\n\u003cli\u003eStacchiotti, S. \u0026amp; Sommer, J. Building a global consensus approach to chordoma: a position paper from the medical and patient community. \u003cem\u003eThe lancet oncology\u003c/em\u003e \u003cstrong\u003e16\u003c/strong\u003e, e71-e83 (2015).\u003c/li\u003e\n\u003cli\u003eStacchiotti, S.\u003cem\u003e et al.\u003c/em\u003e Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group. \u003cem\u003eAnnals of Oncology\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 1230-1242 (2017).\u003c/li\u003e\n\u003cli\u003eFrezza, A. M.\u003cem\u003e et al.\u003c/em\u003e Mesenchymal chondrosarcoma: prognostic factors and outcome in 113 patients. A European Musculoskeletal Oncology Society study. \u003cem\u003eEuropean journal of cancer\u003c/em\u003e \u003cstrong\u003e51\u003c/strong\u003e, 374-381 (2015).\u003c/li\u003e\n\u003cli\u003eTraylor, J. I., Pernik, M. N., Plitt, A. R., Lim, M. \u0026amp; Garzon-Muvdi, T. Immunotherapy for chordoma and chondrosarcoma: Current evidence. \u003cem\u003eCancers\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 2408 (2021).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Patient characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"604\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eR0/R1 margin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eR2 margin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRT only\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePatient number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAge (years old)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e53.9 \u0026plusmn; 15.8 (17-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e56.6 \u0026plusmn; 10.2 (39-78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e52.0 \u0026plusmn; 16.2 (21-86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e57.6 \u0026plusmn; 26.1 (17-83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.587*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.300⸸\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePathology\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eChordoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e1.000⸸\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eChondrosarcoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eLocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCervical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e0.604⸸\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eThoracic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eLumbar\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSacral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEnneking classification\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1B\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAJCC TNM stage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eT1N0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\"\u003e\n \u003cp\u003e0.231⸸\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eT2N0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eT3N0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eT4N0M0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRadiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e(+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e0.024⸸\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e(-)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFollow-up time (months)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e58.1 \u0026plusmn; 44.9 (3-193)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e63.3 \u0026plusmn; 58.8 (3-193)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e54.5 \u0026plusmn; 39.2 (3-179)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003e63.3 \u0026plusmn; 58.8 (27-119)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.794*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*\u0026nbsp;One-way ANOVA\u003c/p\u003e\n\u003cp\u003e⸸\u0026nbsp;Fisher\u0026rsquo;s exact test\u003c/p\u003e\n\u003cp\u003eAge and follow-up time were presented as mean \u0026plusmn; standard deviation (minimum-maximum).\u003c/p\u003e\n\u003cp\u003eAbbreviations:\u003c/p\u003e\n\u003cp\u003eAJCC: American Joint Committee on Cancer\u003c/p\u003e\n\u003cp\u003eR0/R1 margin: negative or microscopically positive margin\u003c/p\u003e\n\u003cp\u003eR2 margin: macroscopically positive margin\u003c/p\u003e\n\u003cp\u003eRT: radiation therapy\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Surgical complications\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eSurgical complication (CTCAE grade)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003eTotal (n=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003eR0/R1 margin (n=14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003eR2 margin (n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e14 (32.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e5 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e9 (31.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e10 (23.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e1 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e9 (31.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003eTransient urinary retention; transient constipation; wound dehiscence; limb numbness, soreness, or anesthesia; neck/back numbness or soreness; unilateral drop foot\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e12 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e5 (35.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e7 (24.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003eWound infection; hematoma formation; constant urinary incontinence or dysuria; constant stool incontinence/constipation; tracheostomy care; impaired mobility\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e7 (16.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e3 (21.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e4 (13.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003eDeep wound infection; sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eNo surgical intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.403880070546737%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"49.91181657848325%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations:\u003c/p\u003e\n\u003cp\u003eCTCAE:\u0026nbsp;Common Terminology Criteria for Adverse Events\u003c/p\u003e\n\u003cp\u003eR0/R1 margin: negative or microscopically positive margin\u003c/p\u003e\n\u003cp\u003eR2 margin: macroscopically positive margin\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Radiotherapy complications\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"566\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eAcute-onset RT complication (CTCAE grade)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003eTotal (n=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e3 (13.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e7 (30.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003eDermatitis; myositis; esophagitis; diarrhea; paresthesia; fatigue; dysuria; mild taste impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e12 (52.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003eDermatitis; myositis; xerostomia; pharyngeal mucositis; diarrhea; urinary incontinence; paresthesia; fatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003eCystitis with gross hematuria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eGrade 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\" valign=\"bottom\"\u003e\n \u003cp\u003eNo RT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\" valign=\"bottom\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\" valign=\"bottom\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eLate-onset RT complication (CTCAE grade)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003eTotal (n=48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eToxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e20 (87.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eLower limb soreness and weakness\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eSoft-tissue necrosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e1 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003eSecondary founier\u0026apos;s gangrene\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eGrade 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"13.227513227513228%\"\u003e\n \u003cp\u003eNo RT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.052910052910052%\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"76.71957671957672%\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations:\u003c/p\u003e\n\u003cp\u003eCTCAE:\u0026nbsp;Common Terminology Criteria for Adverse Events\u003c/p\u003e\n\u003cp\u003eR0/R1 margin: negative or microscopically positive margin\u003c/p\u003e\n\u003cp\u003eR2 margin: macroscopically positive margin\u003c/p\u003e\n\u003cp\u003eRT: radiation therapy\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"spinal chordoma, spinal chondrosarcoma, en bloc resection, radiation therapy","lastPublishedDoi":"10.21203/rs.3.rs-4540904/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4540904/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe research retrospectively analyzed cases of spinal chordoma and chondrosarcoma involving patients who received treatment at the two hospitals between 2001 and 2023. Among the 48 patients studied (39 chordoma and 9 chondrosarcoma cases), the average age was 53.9\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8 years, with a range of 17 to 86 years. Out of these patients, 43 underwent excision surgery and were categorized based on tumor margin into negative (R0) or microscopically positive (R1) margin (n\u0026thinsp;=\u0026thinsp;14) and macroscopically positive (R2) margin (n\u0026thinsp;=\u0026thinsp;29) groups. The mean overall survival (OS) for R0/R1 and R2 groups was 156.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.3 and 79.2\u0026thinsp;\u0026plusmn;\u0026thinsp;11.9 months, respectively (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;=\u0026thinsp;0.012). The mean progression-free survival (PFS) for R0/R1 and R2 was 112.9\u0026thinsp;\u0026plusmn;\u0026thinsp;24.4 and 25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 months (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The study showed that regardless of whether patients in the R0/R1 or R2 groups received radiation therapy (RT) or not, there was no significant improvement in OS or PFS. Specifically, the OS and PFS for the RT only group were 75.9\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 and 73.3\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0 months. In conclusion, the recommended treatment approach for spinal chordoma and chondrosarcoma remains en bloc resection surgery with an appropriate margin. Patients who are unsuitable for or decline surgery may find a beneficial disease control rate with traditional external beam photon/proton therapy.\u003c/p\u003e","manuscriptTitle":"Spinal Chordoma and Chondrosarcoma Treatment Experiences - A 20-Year Retrospective Study from Databases of Two Medical Centers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-01 18:56:29","doi":"10.21203/rs.3.rs-4540904/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-23T04:34:51+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-21T02:55:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-20T05:51:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191301903041599876685598393005148490620","date":"2024-07-17T04:07:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"262543987205209256500948139708539239455","date":"2024-07-15T16:26:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-09T13:15:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"59357289994542303828350343753114587295","date":"2024-07-04T15:28:47+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-04T14:41:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-04T14:17:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-10T07:48:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-06-10T05:38:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-06-06T13:59:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"702f0699-77a5-4a43-bcd6-19df70d70e9d","owner":[],"postedDate":"July 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":33617200,"name":"Biological sciences/Cancer"},{"id":33617201,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2024-10-07T16:08:33+00:00","versionOfRecord":{"articleIdentity":"rs-4540904","link":"https://doi.org/10.1038/s41598-024-74317-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-10-03 15:57:58","publishedOnDateReadable":"October 3rd, 2024"},"versionCreatedAt":"2024-07-01 18:56:29","video":"","vorDoi":"10.1038/s41598-024-74317-4","vorDoiUrl":"https://doi.org/10.1038/s41598-024-74317-4","workflowStages":[]},"version":"v1","identity":"rs-4540904","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4540904","identity":"rs-4540904","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}