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Advances in Bone Tumor and Sarcoma

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 19460

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Dr. Michael J. Wagner

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Guest Editor

Division of Medical Oncology, University of Washington, Seattle, WA 98195, USA
Interests: bone and soft tissue sarcoma

Special Issue Information

Dear Colleagues,

Bone tumors span from “benign” neoplasms, such as giant cell tumors of bone, to aggressive sarcomas including osteosarcoma, Ewing sarcoma, and chondrosarcoma. In spite of revolutionary breakthroughs in other cancer types over the past several decades, the management of most aggressive bone sarcomas has remained relatively unchanged. Most of the large clinical trials recently completed for osteosarcoma and Ewing sarcoma have refined the multi-agent chemotherapy regimens. No studies have identified an effective systemic treatment for chondrosarcoma.

A better understanding of bone and tumor biology has led to insights into potential paths forward for treating these rare diseases. New targets are being identified in the laboratory, with translational work and early stage trials ongoing. Improvements in surgery and radiation techniques promise to improve local control and functional outcomes for patients with bone tumors. Increased collaboration in database efforts and multi-institutional interventional trials has allowed for more rapid accumulation of data and for larger, high-quality studies on these rare bone diseases.

This Special Issue will highlight the spectrum of bone neoplasms, and cover preclinical and clinical advances that improve our understanding of these complex tumors and inform future clinical management.

Dr. Michael J. Wagner
Guest Editor

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Keywords

sarcoma
bone sarcoma
osteosarcoma
Ewing sarcoma
chondrosarcoma
giant cell tumor
TGCT

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Published Papers (9 papers)

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Research

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14 pages, 2990 KiB

Open AccessArticle

Clinical Outcome after Surgical Treatment of Sacral Chordomas: A Single-Center Retrospective Cohort of 27 Patients

by Stavros Goumenos, Georgios Kakouratos, Ioannis Trikoupis, Panagiotis Gavriil, Pavlos Gerasimidis, Konstantinos Soultanis, Pavlos Patapis, Vasileios Kontogeorgakos and Panayiotis Papagelopoulos

Cancers 2024, 16(5), 973; https://doi.org/10.3390/cancers16050973 - 28 Feb 2024

Cited by 2 | Viewed by 2146

Abstract

Introduction: The aims of our study were (1) to determine disease-specific and disease-free survival after the en-bloc resection of sacral chordomas and (2) to investigate potential risk factors for tumor recurrence and major postoperative wound-related complications. Methods: We retrospectively analyzed 27 consecutive patients with sacral chordomas who were surgically treated in our institution between 2004 and 2022. Three patients (11.1%) had a recurrent tumor and four patients (14.8%) had history of a second primary solid tumor prior to or after their sacral chordoma. A combined anterior and posterior approach, colostomy, plastic reconstruction, and spinopelvic instrumentation were necessitated in 51.9%, 29.6%, 37%, and 7.4% of cases, respectively. The mean duration of follow-up was 58 ± 41 months (range= 12–170). Death-related-to-disease, disease recurrence, and major surgical site complications were analyzed using Kaplan–Meier survival analysis, and investigation of the respective risk factors was performed with Cox hazard regression. Results: The estimated 5-year and 10-year disease-specific survival was 75.3% (95% CI = 49.1–87.5%) and 52.7% (95% CI = 31–73.8%), respectively. The estimated 1-year, 5-year, and 10-year disease-free survival regarding local and distant disease recurrence was 80.4% (95% CI = 60.9–91.1%), 53.9% (95% CI = 24.6–66.3%), and 38.5% (95% CI = 16.3–56.2%), respectively. The mean survival of the recurred patients was 61.7 ± 33.4 months after their tumor resection surgery. Conclusions: Despite the high relapse rates and perioperative morbidity, long-term patient survival is not severely impaired. Positive or less than 2 mm negative resection margins have a significant association with disease progression. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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12 pages, 1424 KiB

Open AccessArticle

Changes in Health-Related Quality of Life following Surgery in Patients with High-Grade Extremity Soft-Tissue Sarcoma: A Prospective Longitudinal Study

by Anouk A. Kruiswijk, Michiel A. J. van de Sande, Cornelis Verhoef, Yvonne M. Schrage, Rick L. Haas, Marc H. A. Bemelmans, Robert J. van Ginkel, Johannes J. Bonenkamp, Arjen J. Witkamp, M. Elske van den Akker-van Marle, Perla J. Marang-van de Mheen and Leti van Bodegom-Vos

Cancers 2024, 16(3), 547; https://doi.org/10.3390/cancers16030547 - 26 Jan 2024

Cited by 1 | Viewed by 1325

Abstract

Introduction: Changes in health-related quality of life (HRQoL) during the diagnostic and treatment trajectory of high-grade extremity soft-tissue sarcoma (eSTS) has rarely been investigated for adults (18–65 y) and the elderly (aged ≥65 y), despite a potential variation in challenges from diverse levels of physical, social, or work-related activities. This study assesses HRQoL from time of diagnosis to one year thereafter among adults and the elderly with eSTS. Methods: HRQoL of participants from the VALUE-PERSARC trial (n = 97) was assessed at diagnosis and 3, 6 and 12 months thereafter, utilizing the PROMIS Global Health (GH), PROMIS Physical Function (PF) and EQ-5D-5L. Results: Over time, similar patterns were observed in all HRQoL measures, i.e., lower HRQoL scores than the Dutch population at baseline (PROMIS-PF:46.8, PROMIS GH-Mental:47.3, GH-Physical:46.2, EQ-5D-5L:0.76, EQ-VAS:72.6), a decrease at 3 months, followed by an upward trend to reach similar scores as the general population at 12 months (PROMIS-PF:49.9, PROMIS GH-Physical:50.1, EQ-5D-5L:0.84, EQ-VAS:81.5), except for the PROMIS GH-Mental (47.5), where scores remained lower than the general population mean (T = 50). Except for the PROMIS-PF, no age-related differences were observed. Conclusions: On average, eSTS patients recover well physically from surgery, yet the mental component demonstrates no progression, irrespective of age. These results underscore the importance of comprehensive care addressing both physical and mental health. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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11 pages, 2314 KiB

Open AccessArticle

Chondrosarcoma of the Femur: Is Local Recurrence Influenced by the Presence of an Extraosseous Component?

by Minna K. Laitinen, Michael C. Parry, Guy V. Morris, Robert J. Grimer, Vaiyapuri Sumathi, Jonathan D. Stevenson and Lee M. Jeys

Cancers 2024, 16(2), 363; https://doi.org/10.3390/cancers16020363 - 15 Jan 2024

Cited by 3 | Viewed by 1357

Abstract

Background: Chondrosarcoma (CS) is the second most common surgically treated primary malignancy of the bone. The current study explored the effect of the margin and extraosseous tumor component in CS in the femur on local recurrence (LR), LR-free survival (LRFS), and disease-specific survival (DSS). Methods: Among 202 patients, 115 were in the proximal extremity of the femur, 4 in the corpus of the femur, and 83 in the distal extremity of femur; 105 patients had an extraosseous tumor component. Results: In the Kaplan–Meier analysis, factors significant for decreased LRFS were the extraosseous tumor component (p < 0.001), extraosseous tumor component arising from the superior aspect (p < 0.001), histological grade (p = 0.031), and narrow surgical margin < 3 mm (p < 0.001). Factors significantly affecting DSS were the histological grade (p < 0.001), extraosseous component (p < 0.001), LR (p < 0.001), metastases (p < 0.001), and surgical margin (p < 0.001). Conclusions: In CS of the femur, the presence of an extraosseous tumor component has a predictive role in LRFS, and extraosseous tumor component arising from the superior aspect was significant for decreased LRFS. Wide margins were more commonly achieved when the tumor had only an intraosseous component, and the rate of LR was significantly higher in cases with an extraosseous tumor component. When the extraosseous component arose from the superior aspect of the femur, LR occurred more frequently despite achieving adequate margins. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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10 pages, 1482 KiB

Open AccessArticle

Distal Humeral Replacement in Patients with Primary Bone Sarcoma: The Functional Outcome and Return to Sports

by Kristian Nikolaus Schneider, Moritz Ellerbrock, Georg Gosheger, Lucia Maria Westphal, Niklas Deventer, Sebastian Klingebiel, Carolin Rickert and Christoph Theil

Cancers 2023, 15(13), 3534; https://doi.org/10.3390/cancers15133534 - 7 Jul 2023

Cited by 1 | Viewed by 1388

Abstract

Distal humeral replacement (DHR) is a limb-salvage option for the endoprosthetic reconstruction of bone defects following the resection of a primary bone sarcoma. As primary bone sarcomas are only occasionally located around the distal humerus, there is a paucity of information regarding postoperative function, and patients’ resumption of sporting activities. With advances in diagnostics and in surgical and oncological treatment leading to an increased patient life expectancy and higher quality of life, patients’ functional outcome and return to sports activities are of increasing interest. Between 1997 and 2021, a total of 24 patients underwent DHR with a single-design modular implant at a tertiary sarcoma center. A total of 14 patients who died of their disease were excluded, leaving a study cohort of 10 patients, with a median age of 30 years on the day of surgery (IQR 20–37). At the last follow-up, after a median of 230 months (IQR 165–262), the median MSTS was 19 (IQR 13–24), the median TESS was 79 (IQR 66–87), the median SEV was 38% (IQR 24–53), the median TS was 6 (IQR 4–7), and the median WAS was 3 (IQR 1–8). Among the variables of gender, surgery on the dominant extremity, intraoperative nerve resection, extra-articular tumor resection, chemotherapy, radiotherapy, and revision surgeries, none were associated with a better/lower functional outcome score or return to sports activities. However, a higher level of sports performance prior to diagnosis (WAS > 10) was associated with a higher level of sports performance postoperatively (p = 0.044). Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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14 pages, 2577 KiB

Open AccessArticle

Midterm Results of High-Dose-Rate Intraoperative Brachytherapy in the Treatment of Soft Tissue Sarcomas

by Dietmar Dammerer, Johannes Neugebauer, Matthias Braito, Moritz Wagner, Markus Neubauer, Lukas Moser, Markus Süß, Michael Liebensteiner and David Putzer

Cancers 2023, 15(10), 2854; https://doi.org/10.3390/cancers15102854 - 21 May 2023

Cited by 1 | Viewed by 1575

Abstract

Introduction: According to the literature only sparse data are available on the use of high-dose-rate intraoperative brachytherapy (IOHDR-BT) as a boost to external-beam irradiation (EBRT) in combination with a wide resection in patients with high-grade soft tissue sarcomas (STS). Materials and Methods: Applying a retrospective study design, we investigated all patients who between 2010 and 2016 underwent marginal resection of a high-grade STS and intraoperative radiotherapy, followed by EBRT. We included only patients with a traceable follow-up time of at least two years. Of 89 patients, 35 met our inclusion criteria and showed an average follow-up of four years. Results: We found an overall 2-year local control rate of 94.3%. The local recurrence rate for R0 resections was 6%, whereas recurrences occurred in 13% of R1 resections and in 100% of R2 resections. One affected patient received only intraoperative radiotherapy. The recurrence rate by tumour entity was 36% for LPS, 11% for myxofibrosarcoma and 17% for undifferentiated pleomorphic sarcoma. Conclusion: The treatment regimen consisting of limb-preserving surgery, IORT and pre- or postoperative radiotherapy consistently shows excellent local control rates. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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9 pages, 1069 KiB

Open AccessArticle

A Retrospective Multi-Institutional Cohort Analysis of Clinical Characteristics and Outcomes in Dedifferentiated Chondrosarcoma

by Nam Bui, Hilary Dietz, Sheima Farag, Angela C. Hirbe, Michael J. Wagner, Brian A. Van Tine, Kristen Ganjoo, Robin L. Jones, Vicki L. Keedy and Elizabeth J. Davis

Cancers 2023, 15(9), 2617; https://doi.org/10.3390/cancers15092617 - 5 May 2023

Cited by 5 | Viewed by 2464

Abstract

Background: Dedifferentiated chondrosarcoma (DDCS) is a rare subset of chondrosarcoma. It is an aggressive neoplasm characterized by a high rate of recurrent and metastatic disease with overall poor outcomes. Systemic therapy is often used to treat DDCS; however, the optimal regimen and timing are not well defined, with current guidelines recommending following osteosarcoma protocols. Methods: We conducted a multi-institutional retrospective analysis of clinical characteristics and outcomes of patients with DDCS. Between 1 January 2004 and 1 January 2022, the databases from five academic sarcoma centers were reviewed. Patient and tumor factors, including age, sex, tumor size, site, location, the treatments rendered, and survival outcomes, were collected. Results: Seventy-four patients were identified and included in the analysis. Most patients presented with localized disease. Surgical resection was the mainstay of therapy. Chemotherapy was used predominantly in the metastatic setting. Partial responses were low (n = 4; 9%) and occurred upon treatment with doxorubicin with cisplatin or ifosfamide and single-agent pembrolizumab. For all other regimens, stable disease was the best response. Prolonged stable disease occurred with the use of pazopanib and immune checkpoint inhibitors. Conclusions: DDCS has poor outcomes and conventional chemotherapy has limited benefit. Future studies should focus on defining the possible role of molecularly targeted therapies and immunotherapy in the treatment of DDCS. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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11 pages, 1673 KiB

Open AccessArticle

Chondrosarcoma of the Proximal Humerus: Does the Margin Affect Survival?

by Gilber Kask, Minna K. Laitinen, Michael C. Parry, Jose I. Albergo, Jonathan D. Stevenson, German Farfalli, Luis Aponte-Tinao, Robert Grimer, Vaiyapuri Sumathi and Lee M. Jeys

Cancers 2023, 15(8), 2337; https://doi.org/10.3390/cancers15082337 - 17 Apr 2023

Cited by 2 | Viewed by 1605

Abstract

Chondrosarcoma (CS) is the second most common primary malignant bone tumour and, in the absence of reliable chemotherapy and radiotherapy, is effectively a surgical disease. Overall disease specific survival (DSS) is affected by tumour grade, whilst resection margin contributes to local recurrence free survival (LRFS). The aim of this study was to investigate factors that affect the local and systemic prognoses for conventional central CSs arising from the proximal humerus. A multi-centre, retrospective study from three international collaborative sarcoma centres identified 110 patients between 1995 and 2020 undergoing treatment for a conventional central CS of the proximal humerus; 58 patients (53%) had a grade 1 tumour, 36 (33%) had a grade 2 tumour, and 16 patients (13%) had a grade 3 CS. The mean age of patients was 50 years (range 10–85). The incidence of local recurrence (LR) was 9/110 (8.2%), and the disease specific mortality was 6/110 (5.5%). The grade was a statistically significant factor for LRFS (p < 0.001). None of the grade 1 tumours developed LR. The DSS was affected by the grade (p < 0.001) but not by the LR (p = 0.4). Only one patient with a grade 2 tumour died from the disease. The proximal humeral grade 1 CS behaved as a benign tumour, having no cases of LR nor death due to disease. Grade 2 CSs of the proximal humerus behaved in a more indolent way when compared with comparable grade tumours elsewhere in the appendicular skeleton, being locally aggressive with a higher LR rate than grade 1 CSs but still having very low mortality and a high rate of DSS. The LR in grade 2 CSs did not affect the DSS; therefore, surgical management in proximal humeral grade 2 CSs should have a greater emphasis on preserving function whilst maintaining an adequate margin for resection. The proximal humeral grade 3 CS was, as elsewhere in the skeleton, an aggressive, high-grade tumour. Therefore, surgical management should include en bloc resection with clear margins to avoid LR. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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Review

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23 pages, 26979 KiB

Open AccessReview

Diffuse-Type Tenosynovial Giant Cell Tumor: What Are the Important Findings on the Initial and Follow-Up MRI?

by Woo Suk Choi, Seul Ki Lee, Jee-Young Kim and Yuri Kim

Cancers 2024, 16(2), 402; https://doi.org/10.3390/cancers16020402 - 17 Jan 2024

Cited by 1 | Viewed by 3471

Abstract

Tenosynovial giant cell tumor (TSGCT) is a rare soft tissue tumor that involves the synovial lining of joints, bursae, and tendon sheaths, primarily affecting young patients (usually in the fourth decade of life). The tumor comprises two subtypes: the localized type (L-TSGCT) and the diffuse type (D-TSGCT). Although these subtypes share histological and genetic similarities, they present a different prognosis. D-TSGCT tends to exhibit local aggressiveness and a higher recurrence rate compared to L-TSGCT. Magnetic resonance imaging (MRI) is the preferred diagnostic tool for both the initial diagnosis and for treatment planning. When interpreting the initial MRI of a suspected TSGCT, it is essential to consider: (i) the characteristic findings of TSGCT—evident as low to intermediate signal intensity on both T1- and T2-weighted images, with a blooming artifact on gradient-echo sequences due to hemosiderin deposition; (ii) the possibility of D-TSGCT—extensive involvement of the synovial membrane with infiltrative margin; and (iii) the resectability and extent—if resectable, synovectomy is performed; if not, a novel systemic therapy involving colony-stimulating factor 1 receptor inhibitors is administered. In the interpretation of follow-up MRIs of D-TSGCTs after treatment, it is crucial to consider both tumor recurrence and potential complications such as osteoarthritis after surgery as well as the treatment response after systemic treatment. Given its prevalence in young adult patents and significant impact on patients’ quality of life, clinical trials exploring new agents targeting D-TSGCT are currently underway. Consequently, understanding the characteristic MRI findings of D-TSGCT before and after treatment is imperative. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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15 pages, 1291 KiB

Open AccessReview

Osteosarcoma in Pediatric and Adult Populations: Are Adults Just Big Kids?

by Caleb Kim, Lara E. Davis, Catherine M. Albert, Brian Samuels, Jesse L. Roberts and Michael J. Wagner

Cancers 2023, 15(20), 5044; https://doi.org/10.3390/cancers15205044 - 19 Oct 2023

Cited by 10 | Viewed by 2977

Abstract

Malignant bone tumors are commonly classified as pediatric or adolescent malignancies, and clinical trials for these diseases have generally focused on these populations. Of primary bone cancers, osteosarcoma is among the most common. Osteosarcoma has a bimodal age distribution, with the first peak occurring in patients from 10 to 14 years old, and the second peak occurring in patients older than 65, with about 25% of cases occurring in adults between 20 and 59 years old. Notably, adult osteosarcoma patients have worse outcomes than their pediatric counterparts. It remains unclear whether age itself is a poor prognostic factor, or if inherent differences in tumor biology exist between age groups. Despite these unknowns, current treatment strategies for adults are largely extrapolated from pediatric studies since the majority of clinical trials for osteosarcoma treatments are based on younger patient populations. In light of the different prognoses observed in pediatric and adult osteosarcoma, we summarize the current understanding of the molecular etiology of osteosarcoma and how it may differ between age groups, hypothesizing why adult patients have worse outcomes compared to children. Full article

(This article belongs to the Special Issue Advances in Bone Tumor and Sarcoma)

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