Giant cell tumour of bone (GCTB) is a benign, locally aggressive primary bone neoplasm that represents 5% of all bone tumours. The principal treatment approach is surgery. Although generally GCTB is considered only a locally aggressive disease, it can metastasise, and lung metastases occur in 1–9% of patients. To date, only the use of denosumab has been approved as medical treatment for GCTB. Even more rarely, GCTB undergoes sarcomatous transformation into a malignant tumour (4% of all GCTB), but history of this malignant transformation is unclear and unpredictable. Considering the rarity of the event, the data in the literature are few. In this review, we summarise published data of GCTB malignant transformation and we analyse three cases of malignant transformation of GCTB, evaluating histopathology, genetics, and radiological aspects. Despite the rarity of this event, we conclude that a strict follow up is recommended to detect early malignant transformation.

Background: Undifferentiated soft-tissue sarcomas (USTS) are one of the most common sarcoma histotypes in adults. The standard of care is surgical excision plus adjuvant radiotherapy, while the use of perioperative chemotherapy is still controversial. The aim of this study was to investigate the value of pre-treatment [18F]FDG PET/CT conventional metrics and textural features in predicting disease-free survival (DFS) and overall survival (OS) in patients with USTS of the limbs and trunk. Methods: [18F]FDG PET/CT scans of 51 consecutive patients with locally advanced USTS were retrospectively evaluated. Conventional and textural PET parameters were analysed and tested as predictive factors for DFS and OS. Results: During a median follow up of 50.7 months, 23 (45.1%) and 29 (56.9%) patients had death or disease progression, respectively. Univariate analysis revealed a significant association for perioperative treatment, PET volumetric parameters and the textural feature GLCM_correlation with DFS and OS. In multivariate analysis, perioperative treatment and GLCM_correlation were the only independent factors, allowing stratification of the population into three different prognostic classes. Conclusion: GLCM_correlation can identify USTS at high risk of relapse and death, thus helping to optimize the perioperative treatment of patients.

Background: The COVID-19 pandemic led to a rapid reorganization of healthcare activities, leading to reduced access to clinics, interruption of screenings, and treatment schedule modifications in several cancer types. Few data are available on sarcomas. We analyzed COVID-19-related diagnostic delay in a sarcoma referral center in Italy.Methods: We retrospectively enrolled in this study patients with histological diagnosis of soft tissue or bone sarcoma and aggressive benign musculoskeletal diseases obtained during the first year of the pandemic (Covid group) or the year before (Control group) and followed at the Regina Elena National Cancer Institute in Rome. The primary endpoint was the time from the first symptom to histological diagnosis.Results: We evaluated 372 patients, 185 of whom were eligible for primary endpoint analysis (92 patients in the Control group and 93 patients in the Covid group). The patients were affected by soft tissue sarcoma in most cases (63.0% and 66.7% in Covid and Control groups, respectively). We observed a diagnostic delay in the Covid group with a median time from the first symptom to the definitive histological diagnosis of 103.00 days (95% CI 92.77–113.23) vs. 90.00 days (95% CI 69.49–110.51) in the Control group (p = 0.024), but not a delay in treatment beginning (151 days, 95% CI 132.9–169.1 vs. 144 days, 95% CI 120.3–167.7, respectively, p = 0.208). No differences in stage at diagnosis were observed (12% vs. 16.5% of patients with metastatic disease at diagnosis in the Covid and Control groups, respectively, p = 0.380). Progression-free survival (p = 0.897) and overall survival (p = 0.725) were comparable in the subgroup of patients affected by soft tissue sarcoma.Conclusions: A delay in sarcoma diagnosis but not in starting treatment has been observed during the first year of the COVID-19 pandemic. Nevertheless, no difference in stage at diagnosis or in terms of survival has been observed.

Background: Trabectedin is an antineoplastic drug approved for patients (pts) with advanced soft tissue sarcomas (STS). Interestingly, the radiological evaluation of response during trabectedin therapy is peculiar.Methods: The aim of this single-center retrospective study is to analyze the concordance of response assessment according to RECIST compared with Choi criteria in patients with STS treated with trabectedin between 2009 and 2020 at Regina Elena National Cancer Institute in Rome.Results: We present the preliminary data collected in the last 2 months (mos) on 37 pts who received the diagnosis between 2015 and 2020, with a median age of 52.5 years (range 32–78). The median number of trabectedin cycles administered was four (range 2–50) for a median follow up of 5.83 months (range 1–60). Histological subtypes of STS were five (13.5%) leiomyosarcoma, 14 (37.8%) liposarcoma, nine (24.3%) undifferentiated pleomorphic sarcoma, three (8.1%) synovial sarcoma, and six (16.2%) other rare histological subtypes. Eight pts (21.6%) received trabectedin in the first line setting, 21 (56.8%) in the second line, and seven (18.9%) received it in subsequent lines. One pt received trabectedin as neoadjuvant therapy in a clinical trial (ISG-STS 1001). Median progression-free survival was 3.6 months (CI95% 2.7–4.6); median overall survival was 34.3 months (CI95% 0–75.4). The radiological responses were evaluated with both RECIST and Choi criteria; responses matched in 33 pts (89.2%) but not in four (10.8%). The best responses obtained according to RECIST criteria were two (5.4%) partial response (PR), 13 (35.1%) stable disease (SD), and 22 (59.5%) progressive disease (PD). Instead, two (5.4%), 13 (35.1%), and 22 (59.5%) pts obtained PR, SD, and PD respectively, according to Choi criteria. Cohen’s kappa coefficient of concordance was 0.792 (p-value <0.002). A specialized radiologist performed all imaging examinations using a dedicated workstation in the same center.Conclusion: In this first analysis, the concordance between RECIST and Choi assessments demonstrates no statistically significant difference. Responses did not match for four pts. We are expanding the analysis to all pts included in the original cohort to confirm or deny these initial results.

Background: With the rapid progress of molecular medicine, new target therapies for solid tumors have become available, leading to the creation of molecular tumor boards (MTBs) designated to evaluate potential individualized treatment options. Unlike other solid or liquid tumors, there is no standard and customized tool to analyze sarcoma. We analyzed the organization of MTB in referral centers for sarcomas treatment in Italy. Materials and methods: A 30-question survey was designed in 2021 by the Regina Elena National Cancer Institute and distributed among Italian referral centers for pediatric and adult sarcomas. This survey was developed as part of Alliance Against Cancer (Alleanza Contro il Cancro, ACC) project to provide a descriptive analysis of the availability and organization of MTBs as well as the propensity to offer genomic profiling to sarcoma patients. Results: A total of 6 out of 10 centers contacted answered the survey, and all stating centers declared to have an MTB. The composition of MTB was variable, with a dedicated oncologist in 83% of centers, although all cases discussed required the presence of the oncologist. 83% of centers met the ACC criteria for eligibility at MTB discussion. In 83% of cases both the primary and the metastases were analyzed, while in 17% only the metastasis were analyzed. The type of analysis available were target panel sequencing and whole exome sequencing (WES) in 100% of centers, whole genome sequencing (WGS) in 83%, RNA sequencing in 53%. Bioinformatics analysis software used were Illumina pipeline in 50% of centers; Ion Reporter (Thermo Fisher Scientific), QIAGEN CLC Genomics Variant Reporter and Archer Analysis in 33%, 17% and 33% of centers respectively. The knowledge base software for variant interpretation in precision oncology were Oncomine Reporter and Sophia, both in 17%. Other specific tools (e.g., CibersortX, GATK suite, and DEseq2) were used in 33% of centers. The time required for the analysis was ≤ 10 days in 33% of centers and > 10 days in 67%. In 83% of centers results are stored locally, and a database with clinical data and follow-up was recorded. Conclusion: MTBs were present in most sarcoma referral centers that answered the survey, albeit with different organizational arrangements. Although this survey should be regarded merely as a descriptive analysis of the early stages of MTB use in sarcomas, and is not representative of the national landscape as a whole, it highlights the clinical need to develop expertise in using MTB for rare cancers and to standardize the process and may serve as a basis for future larger-scale, prospective efforts aimed at harmonizing MTB practices across Italian sarcoma centers.

Giant cell tumor of bone (GCTB) is a benign but locally aggressive neoplasm that can rarely undergo malignant transformation, with a poor prognosis. The most frequent histotypes of the sarcomatous transformation of GCTB are osteosarcoma, fibrosarcoma, and undifferentiated pleomorphic sarcoma, and the treatment approach mirrors that of high-grade sarcomas. This case report describes the malignant transformation of a maxillary GCTB treated with standard systemic treatments for bone tumors and local treatment, resulting in a progression of disease until the patient’s death. Nevertheless, a marked radiological and clinical response was achieved with local carbon ion therapy. This case highlights the diagnostic and therapeutic challenges of malignant transformation of GCTB, emphasizing the importance of a multidisciplinary approach at specialized centers and the potential role of local therapies in selected cases.