Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?

BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.

Advances in the multidisciplinary surgical approach to primary spinal sarcomas: insights from a retrospective case series on outcomes and survival.

INTRODUCTION: The management of spinal sarcomas is complex, given their widespread involvement and high recurrence rates. Despite consensus on the need for a multidisciplinary approach with surgery at its core, there is a lack of definitive guidelines for clinical decision-making. This study examines a case series of primary spinal sarcomas, focusing on the surgical strategies, clinical results, and survival data to inform and guide therapeutic practices. METHODS: We conducted a retrospective analysis of patients who underwent surgical resection for primary spinal sarcomas between 2005 and 2022. The study focused on gathering data on patient demographics, surgical details, postoperative complications, overall hospital stay, and mortality within 90 days post-surgery. RESULTS: The study included 14 patients with a primary diagnosis of spinal sarcoma, with an average age of 48.6 ± 12.6 years. Chondrosarcoma emerged as the most common tumor type, representing 57.1% of cases, followed by Ewing sarcoma at 35.7%, and synovial sarcoma at 7.1%. Patients with chondrosarcoma were treated with en-bloc resection, while the patient with synovial sarcoma underwent intra-lesional excision and those with Ewing sarcoma received decompression and tumor debulking. Postoperative assessments revealed significant improvements in neurological conditions. Notably, functional status as measured by the Karnofski Performance Index (KPI), improved substantially post-surgery (from 61.4 to 80.0%) The mean follow-up was 34.9 ± 9.2 months. During this time period one patient experienced fatal bleeding after en-bloc resection complications involving the vena cava. None of the patient needed further surgery. CONCLUSIONS: Our 16-year study offers vital insights into managing primary spinal sarcomas, showcasing the effectiveness of surgical intervention, particularly en-bloc resection. Despite their rarity and complexity, our multidisciplinary treatment approach yields improved outcomes and highlights the potential for refined surgical strategies to become standardized care in this challenging domain.

Relevance of the combination of external beam radiotherapy with the hypoxia-activated prodrug ICF05016 in an experimental model of extraskeletal myxoid chondrosarcoma.

Currently, there is no gold standard treatment for Extraskeletal Myxoid Chondrosarcomas (EMC) making wide margin surgical resection the most effective alternative treatment. Nevertheless, in previous preclinical studies our lab demonstrated the potential of the hypoxia-activated prodrug (HAP) ICF05016 on EMC murine model inoculated with the H-EMC-SS human cell line. The aim of this study was to assess, in vivo, the relevance of the combination of this HAP with External Beam Radiotherapy (EBR). Firstly EMC-bearing mice were treated with 6 Gy or 12 Gy of EBR (single 6 MV photon). Then for combination of HAP and EBR, animals received 6 doses of ICF05016 (46.8 µmol/kg, intravenously) at 4-day intervals, with 6 Gy EBR performed 24 h after the 3rd dose of HAP. Animals were monitored throughout the study for clinical observations (tumour growth, side effects) and survival studies were performed. From tumour samples, PCNA, Ki-67 and p21 expressions were used as markers of proliferation and cell cycle arrest. Statistical significances were determined using Kruskall-Wallis and log rank tests. The radiosensitivity of the EMC model was demonstrated at 12 Gy with significant inhibition of tumour growth. Then, the HAP strategy potentiated EBR efficacy at a lower dose (6 Gy) by improving survival without generating side effects. Thus, results of this study showed the potential interest of ICF05016 for the combination with EBR in the management of EMC.

Diagnoses, treatment, and oncologic outcomes in patients with calcaneal malignances: Case series, systematic literature review, and pooled cohort analysis.

BACKGROUND AND OBJECTIVES: Malignant tumors of the calcaneus are rare but pose a treatment challenge. AIMS: (1) describe the demographics of calcaneal malignancies in a large cohort; (2) describe survival after amputation versus limb-salvage surgery for high-grade tumors. METHODS: Study group: a "pooled" cohort of patients with primary calcaneal malignancies treated at two cancer centers (1984-2015) and systematic literature review. Kaplan-Meier analyses described survival across treatment and diagnostic groups; proportional hazards modeling assessed mortality after amputation versus limb salvage. RESULTS: A total of 131 patients (11 treated at our centers and 120 patients from 53 published studies) with a median 36-month follow-up were included. Diagnoses included Ewing sarcoma (41%), osteosarcoma (30%), and chondrosarcoma (17%); 5-year survival rates were 43%, 73% (70%, high grade only), and 84% (60%, high grade only), respectively. Treatment involved amputation in 52%, limb salvage in 27%, and no surgery in 21%. There was no difference in mortality following limb salvage surgery (vs. amputation) for high-grade tumors (HR 0.38; 95% CI 0.14-1.05), after adjusting for Ewing sarcoma diagnosis (HR 5.15; 95% CI 1.55-17.14), metastatic disease at diagnosis (HR 3.88; 95% CI 1.29-11.64), and age (per-year HR 1.04; 95% CI 1.02-1.07). CONCLUSIONS: Limb salvage is oncologically-feasible for calcaneal malignancies.

Risk stratification for central conventional chondrosarcoma of bone: A novel system predicting risk of metastasis and death in the Cancer Registry of Norway cohort.

BACKGROUND AND OBJECTIVES: Interobserver variability in histological grading of central conventional chondrosarcoma (CCCS) limits the quality of patient information and research progression. We aim to quantify known and new prognostic variables and propose a risk stratification model. METHOD: We selected 149 cases from the Cancer Registry of Norway. Cox proportional hazard models were estimated. Based on these results a dichotomous risk classification was proposed and presented by Kaplan-Meier estimates for rates of local recurrence, metastasis, and disease-specific survival. RESULTS: The influence of axial skeletal location (Hazard ratio [HR] = 19.06), a soft tissue component ≥1 cm (HR = 13.45), and histological grade 3 (HR = 16.46) are all significant in predicting the rate of metastasis. The creation of a variable combining axial skeletal location and a soft tissue component ≥1 cm strongly predicts the risk of metastasis (HR = 14.02; P < .001) and death (HR = 2.74; P = .030) at multivariate analysis, making the histological grade insignificant. Together with metastasis at diagnosis (HR = 285.65; P < .001), this forms the basis of our proposed risk stratification, producing a small high-risk group (39 cases with 33% risk of metastasis) and a large low-risk group (103 cases with 2% risk of metastasis) without a histological grade. CONCLUSION: Axial skeletal location and a soft tissue component ≥1 cm combined divides a CCCS cohort into low- and high-risk groups without a histological grade.

Advancing patient age is associated with worse outcomes in low- and intermediate-grade primary chondrosarcoma of the pelvis.

BACKGROUND: Conventional primary pelvic chondrosarcoma often presents as a low- or intermediate-grade tumor in older patients. Although this is the most common variant of pelvic chondrosarcoma, studies examining treatment outcomes are lacking. The purpose of this study was to evaluate patients with these tumors to determine their outcomes of treatment. METHODS: Seventy-three patients (grade I [n = 19, 26%] and grade II [n = 54, 74%]) were reviewed including 55 (75%) males and 18 (25%) females, with a mean age of 51 (range, 17-81) years and follow-up of 9 ± 5 years. RESULTS: The 10-year disease-specific survival was 71%. Grade II disease (hazard ratio [HR], 6.74; P = .04) and age ≥50 years (HR, 3.97; P = .02) was associated with death due to disease. The 10-year local recurrence- and metastatic-free survival were 79% and 72%. Of the patients with a local recurrence (n = 11), 7 (64%) recurred at a higher histological grade. Patient age ≥50 years was associated with local recurrence (HR, 10.03; P = .02) and metastatic disease (HR, 4.20; P = .02). CONCLUSION: Advancing patient age was an independent risk factor for worse survival and disease recurrence. Tumors often recurred locally at a higher grade and as such wide local excision remains the treatment of choice for these tumors.

Extraskeletal myxoid chondrosarcoma: A high incidence of metastatic disease to lymph nodes.

BACKGROUND: Extraskeletal myxoid chondrosarcoma (ESMC) is a rare type of soft-tissue sarcoma with limited series reporting outcome of treatment. Currently there is limited data on the incidence and impact on patient outcome in those with metastatic disease to lymph nodes in ESMC. METHODS: Thirty (21 males, 9 females) patients, mean age 50 ± 16 years, with ESMC were reviewed. The tumors were most commonly located in the lower extremity (n = 23, 77%) and the mean tumor size and volume were 9 ± 5 cm and 490 ± 833 cm3 . Mean follow up was 7 ± 4 years. RESULTS: Six (20%) patients either presented (n = 3, 10%) or developed (n = 3, 10%) lymph node metastatic disease. When comparing patients without, with lymph node metastasis and metastasis elsewhere, patients with lymph nodes metastasis had worse survival than those without metastasis, however better 10-year disease specific survival than those with metastasis elsewhere (100% vs 62% vs 0%; P < .001). CONCLUSION: There is a high incidence of lymph node metastatic disease in patients with ESMC. Although survival in these patients is worse compared to those without metastasis, their survival is better than those with metastasis elsewhere. Due to the high incidence of lymph node metastatic disease, preoperative staging of the lymph node should be considered.

How Does the Skeletal Oncology Research Group Algorithm's Prediction of 5-year Survival in Patients with Chondrosarcoma Perform on International Validation?

BACKGROUND: The Skeletal Oncology Research Group (SORG) machine learning algorithm for predicting survival in patients with chondrosarcoma was developed using data from the Surveillance, Epidemiology, and End Results (SEER) registry. This algorithm was externally validated on a dataset of patients from the United States in an earlier study, where it demonstrated generally good performance but overestimated 5-year survival. In addition, this algorithm has not yet been validated in patients outside the United States; doing so would be important because external validation is necessary as algorithm performance may be misleading when applied in different populations. QUESTIONS/PURPOSES: Does the SORG algorithm retain validity in patients who underwent surgery for primary chondrosarcoma outside the United States, specifically in Italy? METHODS: A total of 737 patients were treated for chondrosarcoma between January 2000 and October 2014 at the Italian tertiary care center which was used for international validation. We excluded patients whose first surgical procedure was performed elsewhere (n = 25), patients who underwent nonsurgical treatment (n = 27), patients with a chondrosarcoma of the soft tissue or skull (n = 60), and patients with peripheral, periosteal, or mesenchymal chondrosarcoma (n = 161). Thus, 464 patients were ultimately included in this external validation study, as the earlier performed SEER study was used as the training set. Therefore, this study-unlike most of this type-does not have a training and validation set. Although the earlier study overestimated 5-year survival, we did not modify the algorithm in this report, as this is the first international validation and the prior performance in the single-institution validation study from the United States may have been driven by a small sample or non-generalizable patterns related to its single-center setting. Variables needed for the SORG algorithm were manually collected from electronic medical records. These included sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location. By inputting these variables into the algorithm, we calculated the predicted probabilities of survival for each patient. The performance of the SORG algorithm was assessed in this study through discrimination (the ability of a model to distinguish between a binary outcome), calibration (the agreement of observed and predicted outcomes), overall performance (the accuracy of predictions), and decision curve analysis (establishment on the ability of a model to make a decision better than without using the model). For discrimination, the c-statistic (commonly known as the area under the receiver operating characteristic curve for binary classification) was calculated; this ranged from 0.5 (no better than chance) to 1.0 (excellent discrimination). The agreement between predicted and observed outcomes was visualized with a calibration plot, and the calibration slope and intercept were calculated. Perfect calibration results in a slope of 1 and an intercept of 0. For overall performance, the Brier score and the null-model Brier score were calculated. The Brier score ranges from 0 (perfect prediction) to 1 (poorest prediction). Appropriate interpretation of the Brier score requires comparison with the null-model Brier score. The null-model Brier score is the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for every patient. A decision curve analysis was performed to compare the potential net benefit of the algorithm versus other means of decision support, such as treating all or none of the patients. There were several differences between this study and the earlier SEER study, and such differences are important because they help us to determine the performance of the algorithm in a group different from the initial study population. In this study from Italy, 5-year survival was different from the earlier SEER study (71% [319 of 450 patients] versus 76% [1131 of 1487 patients]; p = 0.03). There were more patients with dedifferentiated chondrosarcoma than in the earlier SEER study (25% [118 of 464 patients] versus 8.5% [131 of 1544 patients]; p < 0.001). In addition, in this study patients were older, tumor size was larger, and there were higher proportions of high-grade tumors than the earlier SEER study (age: 56 years [interquartile range {IQR} 42 to 67] versus 52 years [IQR 40 to 64]; p = 0.007; tumor size: 80 mm [IQR 50 to 120] versus 70 mm [IQR 42 to 105]; p < 0.001; tumor grade: 22% [104 of 464 had Grade 1], 42% [196 of 464 had Grade 2], and 35% [164 of 464 had Grade 3] versus 41% [592 of 1456 had Grade 1], 40% [588 of 1456 had Grade 2], and 19% [276 of 1456 had Grade 3]; p ≤ 0.001). RESULTS: Validation of the SORG algorithm in a primarily Italian population achieved a c-statistic of 0.86 (95% confidence interval 0.82 to 0.89), suggesting good-to-excellent discrimination. The calibration plot showed good agreement between the predicted probability and observed survival in the probability thresholds of 0.8 to 1.0. With predicted survival probabilities lower than 0.8, however, the SORG algorithm underestimated the observed proportion of patients with 5-year survival, reflected in the overall calibration intercept of 0.82 (95% CI 0.67 to 0.98) and calibration slope of 0.68 (95% CI 0.42 to 0.95). The Brier score for 5-year survival was 0.15, compared with a null-model Brier of 0.21. The algorithm showed a favorable decision curve analysis in the validation cohort. CONCLUSIONS: The SORG algorithm to predict 5-year survival for patients with chondrosarcoma held good discriminative ability and overall performance on international external validation; however, it underestimated 5-year survival for patients with predicted probabilities from 0 to 0.8 because the calibration plot was not perfectly aligned for the observed outcomes, which resulted in a maximum underestimation of 20%. The differences may reflect the baseline differences noted between the two study populations. The overall performance of the algorithm supports the utility of the algorithm and validation presented here. The freely available digital application for the algorithm is available here: https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE: Level III, prognostic study.

Is Surgical Resection of the Primary Site Associated with an Improved Overall Survival for Patients with Primary Malignant Bone Tumors Who Have Metastatic Disease at Presentation?

BACKGROUND: The management of primary malignant bone tumors in patients with metastatic disease at presentation remains a challenge. Although surgical resection has been a mainstay in the management of nonmetastatic malignant bone tumors, there is a lack of large-scale evidence-based guidance on whether surgery of the primary site/tumor improves overall survival in malignant bone tumors with metastatic disease at presentation. QUESTIONS/PURPOSES: (1) Is surgical resection of the primary tumor associated with improved overall survival in patients with primary malignant bone tumors who have metastatic disease at presentation? (2) What other factors are associated with improved and/or poor overall survival? METHODS: The 2004 to 2016 National Cancer Database (NCDB), a national registry containing data from more than 34 million cancer patients in the United States, was queried using International Classification of Diseases, 3rd Edition, topographical codes to identify patients with primary malignant bone tumors of the extremities (C40.0-C40.3, C40.8, and C40.9) and/or pelvis (C41.4). The NCDB was preferred over other national cancer registries (that is, the Surveillance, Epidemiology, and End Results database) because it includes a specific variable that codes for patients who received additional surgeries at metastatic sites. Patients with malignant bone tumors of the head or skull, trunk, and spinal column were excluded because these patients are not routinely encountered and treated by orthopaedic oncologists. Histologic codes were used to categorize the tumors into the following groups: osteosarcomas, chondrosarcomas, and Ewing sarcomas. Patients whose tumors were classified as Stage 1, 2, or 3 based on American Joint Commission of Cancer guidelines were excluded. Only patients who presented with metastatic disease were included in the final study sample. The study sample was divided into two distinct groups: those who underwent surgical resection of the primary tumor and those who did not receive any operation for the primary tumor. A total of 2288 patients with primary malignant bone tumors (1121 osteosarcomas, 345 chondrosarcomas, and 822 Ewing sarcomas) with metastatic disease at presentation were included, of whom 46% (1053 of 2288) underwent surgical resection of the primary site. Thirty-three percent (348 of 1053) of patients undergoing surgical resection of the primary site also underwent additional resection of metastases. Patients undergoing surgical resection of the primary site typically were younger than 18 years, lived further from a facility, had tumors involving the upper or lower extremity, had a diagnosis of osteosarcoma or chondrosarcoma, and had a greater tumor size and higher tumor grade at presentation. To account for baseline differences within the patient population and to adjust for additional confounding variables, multivariate Cox regression analyses were used to assess whether undergoing surgical resection of the primary tumor was associated with improved overall survival, after controlling for differences in baseline demographics, tumor characteristics (grade, location, histologic type, and tumor size), and treatment patterns (resection of distant or regional metastatic sites, positive or negative surgical margins, and use of radiation therapy or chemotherapy). Additional sensitivity analyses, stratified by histologic type for osteosarcomas, chondrosarcomas, and Ewing sarcomas, were used to assess factors associated with overall survival for each tumor type. RESULTS: After controlling for differences in baseline demographics, tumor characteristics, and treatment patterns, we found that surgical resection of the primary site was associated with reduced overall mortality compared with those who did not have a resection of the primary site (hazard ratio 0.42 [95% confidence interval 0.36 to 0.49]; p < 0.001). Among other factors, in the stratified analysis, radiation therapy was associated with improved overall survival for patients with Ewing sarcoma (HR 0.71 [95% CI 0.57 to 0.88]; p = 0.002) but not for those with osteosarcoma (HR 1.14 [95% CI 0.91 to 1.43]; p = 0.643) or chondrosarcoma (HR 1.0 [95 % CI 0.78 to 1.50]; p = 0.643). Chemotherapy was associated with improved overall survival for those with osteosarcoma (HR 0.50 [95% CI 0.39 to 0.64]; p < 0.001) and those with chondrosarcoma (HR 0.62 [95% CI 0.45 to 0.85]; p = 0.003) but not those with Ewing sarcoma (HR 0.7 [95% CI 0.46 to 1.35]; p = 0.385). CONCLUSIONS: Surgical resection of the primary site was associated with an overall survival advantage in patients with primary malignant bone tumors who presented with metastatic disease. Further research, using more detailed data on metastatic sites (such as, size, location, number, and treatment), chemotherapy regimen and location of radiation (primary or metastatic site) is warranted to better understand which patients will have improved overall survival and/or a benefit in the quality of life from resecting their primary malignant tumor if they present with metastatic disease at diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Chondrosarcoma in Norway 1990-2013; an epidemiological and prognostic observational study of a complete national cohort.

BACKGROUND: Knowledge of chondrosarcoma (CS) of bone to date is based on institutional reports and registry publications with limits in reporting, detail and quality of data. METHOD: We have performed a retrospective search of CS of bone in the National Cancer Registry in Norway from 1990-2013, cross checked against local tumor databases with further quality control and supplementation of all data from clinical files. The time period is defined by the routine use of axial imaging in clinical practice. A total of 311 cases are included. We performed 108 pathological reviews and 223 radiological reviews. The manuscript was prepared according to the STROBE checklist for strengthening of observational studies. We performed uni-/multivariate cox analyses to define independent prognostic variables from the main cohort of central CS of bone. RESULTS: The incidence of CS of bone in Norway is 2.85/million/yr. for both sexes overall, rising to 3.45/million/yr. in the last 5-year period. There is an increase in the most common central CS subtype, stronger for women than for men. Central CS had, in general 10-15% local recurrence rates, all evident by 5 years while metastasis rate increases with location and grade. Exceptions are extremity grade 1 CS which displayed no metastatic events and axial grade-3 disease with high rates (50%) of both local and metastatic relapse. Peripheral CS had limited metastatic potential (2%), but rates of local relapse (13%) continue to appear towards 10 years of follow up. Malignancy grade 3 independently predicts rate of metastasis and presence of soft tissue component predicts local recurrence, metastasis and survival. CONCLUSION: Rates of local recurrence, metastasis and disease specific survival follow clear patterns depending on subtype, location and grade allowing better tailoring of follow-up regimes. Malignancy grade 3 and the presence of a soft tissue component independently predict behavior for central CS of bone.

Intralesional treatment versus wide resection for central low-grade chondrosarcoma of the long bones.

BACKGROUND: Grade I or low-grade chondrosarcoma (LGCS) is a primary bone tumour with low malignant potential. Historically, it was treated by wide resection, since accurate pre-operative exclusion of more aggressive cancers can be challenging and under-treatment of a more aggressive cancer could negatively influence oncological outcomes. Intralesional surgery for LGCS has been advocated more often in the literature over the past few years. The potential advantages of less aggressive treatment are better functional outcome and lower complication rates although these need to be weighed against the potential for compromising survival outcomes. OBJECTIVES: To assess the benefits and harms of intralesional treatment by curettage compared to wide resection for central low-grade chondrosarcoma (LGCS) of the long bones. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 4), MEDLINE and Embase up to April 2018. We extended the search to include trials registries, reference lists of relevant articles and review articles. We also searched 'related articles' of included studies suggested by PubMed. SELECTION CRITERIA: In the absence of prospective randomised controlled trials (RCTs), we included retrospective comparative studies and case series that evaluated outcome of treatment of central LGCS of the long bones. The primary outcome was recurrence-free survival after a minimal follow-up of 24 months. Secondary outcomes were upgrading of tumour; functional outcome, as assessed by the Musculoskeletal Tumor Society (MSTS) score; and occurrence of complications. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recognised by Cochrane. We conducted a systematic literature search using several databases and contacted corresponding authors, appraised the evidence using the ROBINS-I risk of bias tool and GRADE, and performed a meta-analysis. If data extraction was not possible, we included studies in a narrative summary. MAIN RESULTS: We included 18 studies, although we were only able to extract participant data from 14 studies that included a total of 511 participants; 419 participants were managed by intralesional treatment and 92 underwent a wide resection. We were not able to extract participant data from four studies, including 270 participants, and so we included them as a narrative summary only. The evidence was at high risk of performance, detection and reporting bias.Meta-analysis of data from 238 participants across seven studies demonstrated little or no difference in recurrence-free survival after intralesional treatment versus wide resection for central LGCS in the long bones (risk ratio (RR) 0.98; 95% confidence interval (CI) 0.92 to 1.04; very low-certainty evidence). MSTS scores were probably better after intralesional surgery (mean score 93%) versus resection (mean score 78%) with a mean difference of 12.69 (95% CI 2.82 to 22.55; P value < 0.001; 3 studies; 72 participants; low-certainty evidence). Major complications across six studies (203 participants) were lower in cases treated by intralesional treatment (5/125 cases) compared to those treated by wide resection (18/78 cases), with RR 0.23 (95% CI 0.10 to 0.55; low-certainty evidence). In four people (0.5% of total participants) a high-grade (grade 2 or dedifferentiated) tumour was found after a local recurrence. Two participants were treated with second surgery with no evidence of disease at their final follow-up and two participants (0.26% of total participants) died due to disease. Kaplan-Meier analysis of data from 115 individual participants across four studies demonstrated 96% recurrence-free survival after a maximum follow-up of 300 months after resection versus 94% recurrence-free survival after a maximum follow-up of 251 months after intralesional treatment (P value = 0.58; very low-certainty evidence). Local recurrence or metastases were not reported after 41 months in either treatment group. AUTHORS' CONCLUSIONS: Only evidence of low- and very low-certainty was available for this review according to the GRADE system. Included studies were all retrospective in nature and at high risk of selection and attrition bias. Therefore, we could not determine whether wide resection is superior to intralesional treatment in terms of event-free survival and recurrence rates. However, functional outcome and complication rates are probably better after intralesional surgery compared to wide resection, although this is low-certainty evidence, considering the large effect size. Nevertheless, recurrence-free survival was excellent in both groups and a prospective RCT comparing intralesional treatment versus wide resection may be challenging for both practical and ethical reasons. Future research could instead focus on less invasive treatment strategies for these tumours by identifying predictors that help to stratify participants for surgical intervention or close observation.

Development and validation of a nomogram containing the prognostic determinants of chondrosarcoma based on the Surveillance, Epidemiology, and End Results database.

BACKGROUND: We aimed to develop and validate a reliable nomogram for predicting the disease-specific survival (DSS) of chondrosarcoma patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 2004 to 2015 to identify cases of histologically confirmed chondrosarcoma. Multivariate Cox regression analysis was performed to identify independent prognostic factors and construct a nomogram for predicting the 3- and 5-year DSS rates. Predictive values were compared between the new model and the American Joint Committee on Cancer (AJCC) staging system using concordance indexes (C-indexes), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA). RESULTS: Multivariate Cox regression identified 1180 patients, who were used to establish a nomogram based on a new model containing the predictive variables of age, socioeconomic status, tumor size, surgery status, chemotherapy status, and AJCC staging. In the nomogram, age at diagnosis is the factor with the highest risk, followed by AJCC stage IV and tumor size > 100 mm. Both the C-index and the calibration plots demonstrated the good performance of the nomogram. Moreover, both NRI and IDI were improved compared to the AJCC staging system, and also DCA demonstrated that the nomogram is clinically useful. CONCLUSION: We have developed a reliable nomogram for determining the prognosis and treatment outcomes of chondrosarcoma patients that is superior to the traditional AJCC staging system.

Clinical significance of traditional clinical parameters and inflammatory biomarkers for the prognosis of patients with spinal chondrosarcoma: a retrospective study of 150 patients in a single center.

BACKGROUND: To investigate the clinical significance of five inflammatory biomarkers and conventional clinical parameters in prognostic prediction of spinal chondrosarcoma. METHODS: Univariate and multivariate analyses were performed to investigate independent prognostic factors for recurrence and death of patients with spinal chondrosarcoma. Disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier curve, and differences were analyzed by log-rank test. The optimal cutoff values for NLR, PLR, LMR, and CAR were determined by X-tile program. RESULTS: The optimal cutoff value for NLR, PLR, LMR, AGR, and CAR was 2.7, 200, 3.0, 1.5, and 0.2, respectively. Of the 150 patients included, recurrence was detected in 105 patients, and death occurred in 78 patients. Multivariate analysis indicated that Tomita I-III, total resection, and CAR < 0.2 were significantly associated with longer DFS. Meanwhile, preoperative Frankel score D-E, total resection, and CAR < 0.2 were favorable prognostic factors for OS. Subtype analysis showed that only total resection was an independent prognostic factor for DFS of recurrent spinal chondrosarcoma. CONCLUSION: Total resection could significantly reduce the recurrence rate of spinal chondrosarcoma and improve OS of chondrosarcoma patients. Tomita classification I-III was a favorable factor for DFS, and preoperative Frankel score A-C was an adverse prognostic factor for OS. CAR was the most robust prognostic indicator with a discriminatory ability as compared with other inflammatory indicators. These slides can be retrieved under Electronic Supplementary Material.

Does the SORG Algorithm Predict 5-year Survival in Patients with Chondrosarcoma? An External Validation.

BACKGROUND: We developed a machine learning algorithm to predict the survival of patients with chondrosarcoma. The algorithm demonstrated excellent discrimination and calibration on internal validation in a derivation cohort based on data from the Surveillance, Epidemiology, and End Results (SEER) registry. However, the algorithm has not been validated in an independent external dataset. QUESTIONS/PURPOSES: Does the Skeletal Oncology Research Group (SORG) algorithm accurately predict 5-year survival in an independent patient population surgically treated for chondrosarcoma? METHODS: The SORG algorithm was developed using the SEER registry, which contains demographic data, tumor characteristics, treatment, and outcome values; and includes approximately 30% of the cancer patients in the United States. The SEER registry was ideal for creating the derivation cohort, and consequently the SORG algorithm, because of the high number of eligible patients and the availability of most (explanatory) variables of interest. Between 1992 to 2013, 326 patients were treated surgically for extracranial chondrosarcoma of the bone at two tertiary care referral centers. Of those, 179 were accounted for at a minimum of 5 years after diagnosis in a clinical note at one of the two institutions, unless they died earlier, and were included in the validation cohort. In all, 147 (45%) did not meet the minimum 5 years of followup at the institution and were not included in the validation of the SORG algorithm. The outcome (survival at 5 years) was checked for all 326 patients in the Social Security death index and were included in the supplemental validation cohort, to also ascertain validity for patients with less than 5 years of institutional followup. Variables used in the SORG algorithm to predict 5-year survival including sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location were collected manually from medical records. The tumor characteristics were collected from the postoperative musculoskeletal pathology report. Predicted probabilities of 5-year survival were calculated for each patient in the validation cohort using the SORG algorithm, followed by an assessment of performance using the same metrics as used for internal validation, namely: discrimination, calibration, and overall performance. Discrimination was calculated using the concordance statistic (or the area under the Receiver Operating Characteristic (ROC) curve) to determine how well the algorithm discriminates between the outcome, which ranges from 0.5 (no better than a coin-toss) to 1.0 (perfect discrimination). Calibration was assessed using the calibration slope and intercept from a calibration plot to measure the agreement between predicted and observed outcomes. A perfect calibration plot should show a 45° upwards line. Overall performance was determined using the Brier score, ranging from 0 (excellent prediction) to 1 (worst prediction). The Brier score was compared with the null-model Brier score, which showed the performance of a model that ignored all the covariates. A Brier score lower than the null model Brier score indicated greater performance of the algorithm. For the external validation an F1-score was added to measure the overall accuracy of the algorithm, which ranges between 0 (total failure of an algorithm) and 1 (perfect algorithm).The 5-year survival was lower in the validation cohort than it was in the derivation cohort from SEER (61.5% [110 of 179] versus 76% [1131 of 1544] ; p < 0.001). This difference was driven by higher proportion of dedifferentiated chondrosarcoma in the institutional population than in the derivation cohort (27% [49 of 179] versus 9% [131 of 1544]; p < 0.001). Patients in the validation cohort also had larger tumor sizes, higher grades, and nonextremity tumor locations than did those in the derivation cohort. These differences between the study groups emphasize that the external validation is performed not only in a different patient cohort, but also in terms of disease characteristics. Five-year survival was not different for both patient groups between subpopulations of patients with conventional chondrosarcomas and those with dedifferentiated chondrosarcomas. RESULTS: The concordance statistic for the validation cohort was 0.87 (95% CI, 0.80-0.91). Evaluation of the algorithm's calibration in the institutional population resulted in a calibration slope of 0.97 (95% CI, 0.68-1.3) and calibration intercept of -0.58 (95% CI, -0.20 to -0.97). Finally, on overall performance, the algorithm had a Brier score of 0.152 compared with a null-model Brier score of 0.237 for a high level of overall performance. The F1-score was 0.836. For the supplementary validation in the total of 326 patients, the SORG algorithm had a validation of 0.89 (95% CI, 0.85-0.93). The calibration slope was 1.13 (95% CI, 0.87-1.39) and the calibration intercept was -0.26 (95% CI, -0.57 to 0.06). The Brier score was 0.11, with a null-model Brier score of 0.19. The F1-score was 0.901. CONCLUSIONS: On external validation, the SORG algorithm retained good discriminative ability and overall performance but overestimated 5-year survival in patients surgically treated for chondrosarcoma. This internet-based tool can help guide patient counseling and shared decision making. LEVEL OF EVIDENCE: Level III, prognostic study.

Regional Lymph Node Involvement Is Associated With Poorer Survivorship in Patients With Chondrosarcoma: A SEER Analysis.

BACKGROUND: Regional lymph node involvement is thought to be rare in patients with chondrosarcoma, but its actual prevalence is unclear. Additionally, it is often not considered when prognostic factors are analyzed in patients with chondrosarcoma. However, it has been well established that lymph node involvement is a poor prognostic marker in patients with many types of bone and soft tissue sarcoma, including rhabdomyosarcoma, osteosarcoma, and Ewing's sarcoma. Although lymph node metastases are rare among all sarcoma types, it is important to consider whether lymph node metastases should be assessed in patients with chondrosarcoma because these metastases may impact survival. QUESTIONS/PURPOSES: (1) What is the reported prevalence of regional lymph node involvement in patients with chondrosarcoma? (2) Do patients who have chondrosarcomas with regional lymph node involvement have different clinicopathologic presentations and survival than patients without regional lymph node involvement? (3) Is regional lymph node involvement independently associated with prognosis in patients with chondrosarcoma? METHODS: The data of patients with chondrosarcoma registered in the Surveillance Epidemiology and End Results database (SEER) (1988-2015) were analyzed for the reported prevalence of regional lymph node involvement and its relationship with clinicopathologic features and the 5-year overall survival rate. From 1988 to 2015, 5528 patients with chondrosarcoma were registered in the SEER database. After screening by the inclusion criterion-chondrosarcoma as the first primary tumor, diagnosis with histology confirmation, patients with active followup and available information about regional node status-3374 patients met the inclusion criteria and were analyzed. Demographics and clinicopathologic data were compared using chi-square or Fisher's exact tests. Logistic regression analysis was used to assess the adjusted odds ratio. The overall survival rate was estimated with Kaplan-Meier curves and log-rank tests. Univariate and multivariate analyses of overall survival were performed with Cox proportional hazard models. In addition, a series of sensitivity analyses were performed to assess the robustness of the final Cox proportional hazard model. RESULTS: Forty-four patients (1.3%) were recorded in the database as having regional lymph node involvement at the time of the primary diagnosis. Lymph node metastases were more likely to be reported in an extraskeletal primary site (3% [13 of 426] versus 1% [31 of 2948], adjusted odds ratio [OR] = 2.9, 95% CI, 1.5-5.8; p = 0.003) for bone primary sites and tumors with maximum diameter ≥ 8 cm (2% [26 of 1045] versus 1% [10 of 1075], adjusted OR = 2.9, 95% CI, 1.3-6.3; p = 0.008) and poorer differentiation (4% [24 of 608] versus 1% [14 of 2308], adjusted OR = 4.0, 95% CI, 2.0-8.2; p < 0.001), and in those with distant metastases (7% [14 of 203] versus 1% [30 of 3148], adjusted OR = 3.5, 95% CI, 1.7-7.1, p = 0.001). The 5-year overall survival rates of patients with and without regional lymph node involvement were 28% (95% CI, 15-42%) and 77% (95% CI, 75-78%), respectively (p < 0.001). After controlling for age, sex, race, grade, metastatic status, size, and histologic subtype, the presence of regional lymph node involvement was associated with poorer survival (hazard ratio, 2.20; 95% CI, 1.50-3.24; p < 0.001); this finding was confirmed in several sensitivity analyses. CONCLUSION: The prevalence of regional lymph node involvement in patients with chondrosarcoma was 1.3% in the SEER database. Although chondrosarcomas are rare, patients with chondrosarcomas who have regional node metastases have a poorer prognosis than those who have not reported to have them. This may underrepresent the true proportion of patients with lymph node metastases given the inaccuracies of reporting in this database, but we believe these findings indicate that clinicians should examine patients more carefully for chondrosarcoma with lymph node metastases. Future studies are needed to assess potential treatment strategies to improve the prognosis of these patients. LEVEL OF EVIDENCE: Level III, prognostic study.

Is the Width of a Surgical Margin Associated with the Outcome of Disease in Patients with Peripheral Chondrosarcoma of the Pelvis? A Multicenter Study.

BACKGROUND: We attempted to resect peripheral chondrosarcoma of the pelvis with clear margins. Because of the proximity of vessels or organs, there is still concern that narrow surgical margins may have an adverse effect on disease outcomes. Although current guidelines recommend resection of histologic Grade II or Grade III chondrosarcomas with a "wide" margin, there are no specific recommendations for the adequate width of a surgical margin. QUESTIONS/PURPOSES: (1) What is the disease-specific and local recurrence-free survival of patients with peripheral chondrosarcoma of the pelvis treated with resection or amputation? (2) Is the width of a surgical margin associated with the outcome of disease in patients with peripheral chondrosarcoma of the pelvis? (3) Does the histologic grade as determined with a preoperative biopsy correlate with the final grade after resection? (4) What are surgical complications in these patients? METHODS: We retrospectively reviewed records from three international collaborating hospitals. Between 1983 and 2017, we resected 262 pelvic chondrosarcomas of all types. After reviewing the pathologic reports of these patients, we included 52 patients with peripheral chondrosarcomas of the pelvis who had an osteochondroma-like lesion at the base of the tumor and a cartilage cap with malignant cells in resected specimens. To be eligible for this study, a patient had to have a minimum of 1 year of follow-up. Two patients were excluded because they had less than 1 year of follow-up, leaving 50 patients for inclusion in this study. The median follow-up duration was 7.0 years (interquartile range 2.1-10 years). The median age was 37 years (IQR 29-54 years). The ilium was the most frequently affected bone (in 36 of 50 patients; 72%). The histologic status of the surgical margin was defined as microscopically positive (0 mm), negative < 1 mm, or negative ≥ 1 mm. Thirteen of the 50 patients (26%) had local recurrence. Seven of 34 patients had Grade I tumors, five of 13 had Grade II tumors, and one of three had a Grade III tumor. Nine of 16 patients had multiple local recurrences. Two patients with Grade I tumors and two with Grade II tumors died because of pressure effects caused by local recurrence. RESULTS: The 10-year disease-specific and local recurrence-free survival rates were 90% (95% confidence interval, 70-97) and 69% (95% CI, 52-81), respectively. A surgical margin ≥ 1 mm (n = 16) was associated with a better local recurrence-free survival rate than a surgical margin < 1 mm (n = 17) or 0 mm (n = 11) (10-year local recurrence-free survival: resection margin ≥ 1 mm = 100% versus < 1 mm = 52% [95% CI, 31 to 70]; p = 0.008). No patients with a surgical margin ≥ 1 mm had local recurrence, metastasis, or disease-related death, irrespective of tumor grade. Patients with local recurrence (n = 13) showed worse disease-specific survival than those without local recurrence (n = 37) (10-year disease-specific survival: local recurrence [+] = 59% [95% CI, 16 to 86] versus local recurrence [-] = 100%; p=0.001]). The preoperative biopsy results correctly determined the tumor grade in 15 of 41 patients (37%). The most frequent complication after surgery was local recurrence (13 of 50 patients, 26%). Deep infection was the most frequent nononcologic complication (four patients). CONCLUSIONS: We found a high local recurrence rate after surgical treatment of a peripheral pelvic chondrosarcoma, which was related to the width of the surgical margin. These local recurrences led to inoperable recurrent tumors and death. The tumor grade as determined by preoperative biopsy was inaccurate in 2/3 of patients compared with the final histologic assessment. Therefore, we believe every attempt should be made to achieve a negative margin during the initial resection to lessen the likelihood of local recurrence of peripheral chondrosarcoma of the pelvis of all grades. A margin of 1 mm or more appeared to be sufficient in these patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Does Resection of the Primary Tumor Improve Survival in Patients With Metastatic Chondrosarcoma?

BACKGROUND: Although surgical resection or amputation has been the mainstay of localized chondrosarcoma management for many decades, its efficacy in patients with metastatic chondrosarcoma remains unknown, and likewise we do not know whether there are any tumor- or patient-related factors associated with better survival after surgery for metastatic chondrosarcoma. QUESTIONS/PURPOSES: (1) Is resection of the primary tumor associated with improved survival in patients with metastatic chondrosarcoma? (2) Which subgroups of patients with chondrosarcoma benefit more from resection in terms of survival? METHODS: We identified 200 of 222 patients with metastatic chondrosarcoma in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2014 based on the exclusion criteria. Among those patients, 107 (53.5%) underwent primary tumor resection or amputation. Patient information, including demographics (patient age, gender, race, year of diagnosis), tumor characteristics (primary site, histologic subtype, tumor grade, tumor size), and treatment (record of operation and radiation), was collected and included in the study. Kaplan-Meier analyses, log-rank tests, competing risks framework, multivariable Cox regression modeling, and interaction tests were conducted to assess the association of primary tumor resection and survival in the overall cohort and subgroups. RESULTS: Resection of the primary tumor was associated with improved overall survival (hazard ratio [HR], 0.481; 95% confidence interval [CI], 0.340-0.680; p < 0.001) and cancer-specific survival (HR, 0.493; 95% CI, 0.343-0.709; p < 0.001) after controlling for confounding variables. After controlling further for age, histologic subtype, and grade, primary tumor resection was associated with a survival advantage in patients with conventional subtype and Grade II chondrosarcoma (conventional subtype: HR, 0.403; 95% CI, 0.260-0.623 for overall survival and HR, 0.396; 95% CI, 0.250-0.627 for cancer-specific survival). However, primary tumor resection was not associated with increased survival in patients with metastatic chondrosarcoma who had the dedifferentiated subtype and Grade III malignancy. CONCLUSIONS: The present study demonstrates a possible favorable association between primary tumor resection and survival in some patients with metastatic chondrosarcoma at initial diagnosis. Specifically, patients with conventional subtypes and Grade II malignancies who underwent primary tumor resection had better survival compared with those patients who did not have primary tumor resection. Thus, there might be a benefit from primary tumor resection in these patients, but given the limitations of this database, further prospective studies or randomized trials are needed to confirm our findings. In the meantime, this information might be helpful to consider when discussing surgical options with patients who have conventional, Grade 2 metastatic chondrosarcoma at diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.

Are Limb-sparing Surgical Resections Comparable to Amputation for Patients With Pelvic Chondrosarcoma? A Case-control, Propensity Score-matched Analysis of the National Cancer Database.

BACKGROUND: Chondrosarcoma is the second most frequent primary sarcoma of bone and frequently occurs in the pelvis. Surgical resection is the primary treatment with the two main operative modalities being limb-sparing resection and amputation. Contemporary management has trended toward limb-sparing procedures; however, whether this approach has an adverse effect on long-term survival is unclear. QUESTIONS/PURPOSES: (1) What are the 5- and 10-year survival rates after limb-sparing surgery and amputation? (2) What factors are associated with survival after contemporary surgical management of pelvic chondrosarcoma? METHODS: The 2004-2014 National Cancer Database, a nationwide registry that includes approximately 70% of all new cancers in the United States with requirement for 90% followup, was reviewed for patients diagnosed with pelvic chondrosarcoma who had undergone limb-sparing surgery or amputation. To compare survival, patient demographics, tumor attributes, and treatment characteristics were used to generate one-to-one propensity score-matched cohorts. Other factors associated with survival were determined through multivariable Cox regression. Three hundred eighty-five patients (75%) underwent limb-sparing surgery and 131 (25%) underwent amputation. Propensity score matching resulted in two balanced cohorts of 131 patients. RESULTS: With the numbers available, we could not demonstrate a difference in overall survival between limb-sparing procedures and amputation. The 5-year survivorship was 70% (95% confidence interval [CI], 62%-79%) for limb-sparing surgery versus 70% (95% CI, 62%-79%) for amputation. The 10-year survivorship was 60% (95% CI, 48%-75%) for limb-sparing surgery versus 59% (95% CI, 48%-72%) for amputation. Kaplan-Meier survival analysis did not demonstrate a difference in survival (p = 0.9). Older age (hazard ratio [HR] = 1.029, p < 0.001), higher Charlson/Deyo comorbidity score (HR = 3.039, p = 0.004), higher grade (HR = 2.547, p = 0.005 for Grade 2; HR = 7.269, p < 0.001 for Grade 3; HR = 10.36, p < 0.001 for Grade 4), and positive surgical margins (HR = 1.61, p = 0.039) were associated with decreased survival. CONCLUSIONS: Our findings support the trend toward increased use of limb-sparing surgery for patients with pelvic chondrosarcoma. Orthopaedic oncologists may use our results when counseling their patients regarding treatment options. However, the choice of limb-sparing surgery versus amputation for these challenging patients should still be a highly individualized decision with careful discussion between the patient and the surgeon. LEVEL OF EVIDENCE: Level III, therapeutic study.

Survival and prognostic factors in conventional G1 chondrosarcoma.

BACKGROUND: Chondrosarcoma is the second most frequent malignant bone tumor. Grade I chondrosarcoma (syn.: atypical cartilaginous tumor) is classified as an intermediately and locally aggressive neoplasm and typically is treated less aggressively (i.e., by intralesional curettage). Does the data regarding local recurrence (LR) and metastatic disease justify this? METHODS: From 1982 to 2014, 37 consecutive patients with G1 chondrosarcoma had been resected or curetted. The margin was defined as R0 (wide resection) or R1 (marginal resection). All patients were followed for evidence of local recurrence or metastatic disease. Overall and recurrence-free survival were calculated, and various potentially prognostic factors were evaluated. RESULTS: In 23 patients (62%), the tumor was widely (R0) resected, whereas in 14 patients, (38%) the resection was marginal (R1). Overall survival was 97% after 5 years, 92% after 10 years, and 67% after 20 years. Five-year local recurrence-free survival was 96%. Ten-year local recurrence-free survival was 83%. Local recurrence-free survival showed a significant correlation to margin status but no correlation to location or age. None of the patients with local recurrence died during the follow-up. One patient had metastatic disease at initial presentation, and a further five patients developed metastatic disease during follow-up. Metastatic disease proofed to be a highly significant factor for survival but was not correlated to local recurrence. CONCLUSIONS: There was no significant correlation between the outcome and the primary tumor location. Marginal resection was a risk factor for LR, but there was no significant difference in the overall survival in patients with or without LR. Metastatic disease (16%) was more common than expected from the literature and a significant predictor for poor overall survival.

High control rates of proton- and carbon-ion-beam treatment with intensity-modulated active raster scanning in 101 patients with skull base chondrosarcoma at the Heidelberg Ion Beam Therapy Center.

BACKGROUND: The current study compares the results of irradiation with protons and irradiation with carbon ions via a raster scan technique in patients with G1 and G2 skull base chondrosarcomas. METHODS: Between 2009 and 2014, a total of 101 patients (40 men and 61 women) with a median age of 44 years (range, 19-77 years) were irradiated with carbon ions (79 patients) or protons (22 patients) via a raster scan technique at the Heidelberg Ion Beam Therapy Center. The median total dose was 60 Gy (relative biological effectiveness [RBE]) at 3 Gy per fraction for carbon ions and 70 Gy (RBE) at 2 Gy per fraction for protons. The median boost planning target volume was 38 cm3 (range, 8-133 cm3 ). Overall survival (OS) and local control (LC) were evaluated with the Kaplan-Meier method. RESULTS: The median follow-up period was 40 months (range, 0.8-78.1 months). At the start of the irradiation, all patients had residual macroscopic tumors. Five patients (5%) developed a local recurrence during the follow-up. The 1-, 2-, and 4-year LC rates were 100%, 100%, and 100%, respectively, for protons and 98.6%, 97.2%, and 90.5%, respectively, for carbon ions. The OS rates during the same periods of time were 100%, 100%, and 100%, respectively, for protons and 100%, 98.5%, and 92.9%, respectively, for carbon ions. An age ≤ 44 years was associated with a trend for a better outcome. No toxicity worse than Common Toxicity Criteria grade 3 was observed after treatment. CONCLUSIONS: No significant difference between carbon ions and protons in the therapy of skull base chondrosarcoma could be detected in these initial retrospective results. Cancer 2018;124:2036-44. © 2018 American Cancer Society.