The Impact of Expert Pathology Review and Molecular Diagnostics on the Management of Sarcoma Patients: A Prospective Study of the Hellenic Group of Sarcomas and Rare Cancers.

Precise classification of sarcomas is crucial to optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC), we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on the diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was performed on all samples using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed in the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary, molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas.

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes.

Multimodality treatment of primary cardiac angiosarcoma: A systematic literature review.

BACKGROUND: Primary cardiac angiosarcoma (PCA) is the most prevalent histological type of cardiac sarcoma but its rarity poses a challenge for standardizing treatment protocols. Moreover, published studies are limited by small patient numbers and lack of randomization, making it challenging to establish evidence-based treatment strategies. This systematic review aims to consolidate the heterogeneous published data and identify factors related to the treatment outcome of PCA patients. METHODS: The PubMed and Scopus bibliographic databases were systematically searched for original articles reporting clinical, treatment and outcome data for PCA patients. Kaplan-Meier analysis was used to calculate the time to progression and survival. The Log-Rank test was used to compare progression-free and overall survival data. The Cox proportional hazards regression model was used for univariate and multivariate analysis of survival data. RESULTS: A total of 127 studies containing data for 162 patients were analyzed. The median age of the patient cohort was 45 years, with males being 1.5 times more frequently affected than females. Tumors were primarily located on the right side of the heart, with a median size of 6 cm. Median progression-free and overall survival of 5 months and 12 months, respectively, were calculated. Age, sex, and resection margins did not have a significant impact on PCA survival, as determined by both univariate and multivariate analyses. The presence of metastases at diagnosis was associated with lower overall survival in univariate analysis, although this effect was not significant in multivariate analysis. Multimodality treatment that incorporated surgery and adjuvant chemo-radiotherapy was associated with a statistically significant survival benefit. Median overall survival increased from 6 months with surgery alone to 13 months and 27 months with adjuvant chemotherapy and chemo-radiotherapy, respectively. CONCLUSION: Multimodality treatment including surgery and chemo-radiotherapy was found to offer the greatest survival benefit for PCA patients.

Treatment of an unresectable cardiac angiosarcoma using paclitaxel and image guided radiotherapy: Case report and literature review.

Primary cardiac angiosarcomas (PCAs) are rare tumors that are typically found in the right atrium between the third and the fifth decade of life. While surgical removal of the tumor combined with adjuvant chemotherapy and/or radiotherapy is the treatment of choice, most of the patients present with unresectable tumors and metastatic disease carrying a dismal prognosis with a median survival of less than 1 year. Doxorubicin and ifosfamide based chemotherapy combined with radiotherapy is currently employed in these patients, but no standardized treatment algorithms exist. In this report, we present the management of a patient with an unresectable PCA treated using weekly paclitaxel (120 mg) combined with radiotherapy (60 Gy in 30 fractions) delivered by a helical TomoTherapy system. Follow-up imaging studies showed a remarkable tumor regression which allowed for surgical excision of the tumor 10 months post treatment. Histopathological examination of the resected mass showed no viable tumor cell. On the latest follow-up study, 12 months post treatment, no sign of disease progression (local or distant) was found, and the patient is in good clinical condition.

Case report: skeletal muscle metastasis from follicular thyroid carcinoma presenting as synovial sarcoma.

Differentiated thyroid carcinomas tend to remain localized and usually are of slow progression with excellent long-term survival. The major sites of distant metastases are cervical lymph nodes, lungs and bones and the minor sites include the brain, liver, pericardium, skin, kidney, pleura and muscle. Skeletal muscle metastases from differentiated thyroid carcinoma, are exceedingly rare. In this report, a 42-year-old woman with follicular thyroid cancer that had had a total thyroidectomy and radioiodine ablation nine years ago was presented with a painful right thigh mass and negative PET/CT scan. The patient had also lung metastases during the follow-up period which were treated with surgery, chemotherapy and radiation therapy. An MRI scan of the right thigh showed a deep-seated lobulated mass with cystic regions, bleeding elements and strong heterogeneous post contrast administration enhancement. Due to the similarities in clinical manifestations and imaging features between soft tissue tumors and skeletal muscle metastases, the case was initially misdiagnosed in favor of synovial sarcoma. Histopathological, immunohistochemistry and molecular analysis of the soft tissue mass confirmed to be a thyroid metastasis and, as a result, a final diagnosis of skeletal muscle metastasis was provided. Even though the probability of a skeletal muscle metastasis from thyroid cancer approaches zero, this study aims to raise the awareness to the medical community that these events do in fact occur in the clinical setting and should be considered in the differential diagnosis of patients with thyroid carcinomas.

Brain Metastases from Adult Sarcomas: A Retrospective Cohort Study from the Hellenic Group of Sarcomas and Rare Cancers (HGSRC).

Brain metastases are rare events in patients with sarcoma and the available information is relatively limited. We retrospectively reviewed medical records of patients with sarcoma who developed brain metastases between April 2010 and April 2020 in six centers. Thirty-four adult patients were included with a median age at brain metastases diagnosis of 55.5 years (range, 18-75). The primary sarcomas originated either from soft tissue (n = 27) or bone (n = 7) and the most common subtypes were leiomyosarcoma (n = 8), Ewing sarcoma/peripheral neuroectodermal tumor (PNET) (n = 7) and osteosarcoma (n = 3). Most primary tumors were of high grade and located mainly in the extremities (n = 18). The vast majority of patients at the time of brain metastasis diagnosis already had extracranial metastatic disease (n = 26). The median time from sarcoma diagnosis to cerebral metastasis diagnosis was 16 months (range, 1-136). Treatment modalities for brain metastatic disease included whole-brain radiation therapy (WBRT) (n = 22), chemotherapy (n = 17), exclusive palliative care (n = 5), surgery (n = 9), targeted therapy (n = 6) or stereotactic radiosurgery (n = 2). Most patients experienced a progression of brain metastases (n = 11). The median overall survival from brain metastasis diagnosis was 3 months (range, 0-80). OS was significantly influenced by time-to-brain metastases (p = 0.041), WBRT (p = 0.018), surgery (p = 0.002) and chemotherapy (p = 0.006). In a multivariate analysis, only the localization of the primary (p = 0.047) and WBRT (p = 0.038) were associated with survival with statistical significance. Patients with sarcoma brain metastases have a particularly poor prognosis and an appropriate therapeutic approach is yet to be defined.