Cancers

Editorial

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Open AccessEditorial

Personalized Therapy of Sarcomas

by Ingrid M. E. Desar and Christian Rothermundt

Cancers 2023, 15(20), 5110; https://doi.org/10.3390/cancers15205110 - 23 Oct 2023

Viewed by 748

Abstract

Sarcomas are a group of rare malignant mesenchymal tumors [...] Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

Research

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19 pages, 4343 KiB

Open AccessArticle

SHARPIN Enhances Ferroptosis in Synovial Sarcoma Cells via NF-κB- and PRMT5-Mediated PGC1α Reduction

by Hironari Tamiya, Naoko Urushihara, Kazuko Shizuma, Hisataka Ogawa, Sho Nakai, Toru Wakamatsu, Satoshi Takenaka and Shigeki Kakunaga

Cancers 2023, 15(13), 3484; https://doi.org/10.3390/cancers15133484 - 04 Jul 2023

Cited by 2 | Viewed by 1410

Abstract

Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron uptake protein, was expressed at higher levels in sarcoma cell lines than [...] Read more.

Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, compared to non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression was significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promoted the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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11 pages, 1889 KiB

Open AccessArticle

Measuring Tumour Imatinib Concentrations in Gastrointestinal Stromal Tumours: Relevant or Redundant?

by Eline L. Giraud, Loek A. W. de Jong, Erik van den Hombergh, Suzanne E. J. Kaal, Nielka P. van Erp and Ingrid M. E. Desar

Cancers 2023, 15(11), 2875; https://doi.org/10.3390/cancers15112875 - 23 May 2023

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Abstract

Imatinib plasma trough concentrations are associated with efficacy for patients treated for advanced or metastatic KIT-positive gastrointestinal stromal tumours (GISTs). This relationship has not been studied for patients treated in the neoadjuvant setting, let alone its correlation with tumour drug concentrations. In this [...] Read more.

Imatinib plasma trough concentrations are associated with efficacy for patients treated for advanced or metastatic KIT-positive gastrointestinal stromal tumours (GISTs). This relationship has not been studied for patients treated in the neoadjuvant setting, let alone its correlation with tumour drug concentrations. In this exploratory study we aimed to determine the correlation between plasma and tumour imatinib concentrations in the neoadjuvant setting, investigate tumour imatinib distribution patterns within GISTs, and analyse its correlation with pathological response. Imatinib concentrations were measured in both plasma and in three regions of the resected primary tumour: the core, middle part, and periphery. Twenty-four tumour samples derived from the primary tumours of eight patients were included in the analyses. Imatinib tumour concentrations were higher compared to plasma concentrations. No correlation was observed between plasma and tumour concentrations. Interpatient variability in tumour concentrations was high compared to interindividual variability in plasma concentrations. Although imatinib accumulates in tumour tissue, no distribution pattern of imatinib in tumour tissue could be identified. There was no correlation between imatinib concentrations in tumour tissue and pathological treatment response. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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11 pages, 1865 KiB

Open AccessArticle

The Prognostic Relevance of MRI Characteristics in Myxofibrosarcoma Patients Treated with Neoadjuvant Radiotherapy

by Stefan G. van Ravensteijn, Maikel J. L. Nederkoorn, Tom C. P. Wal, Yvonne M. H. Versleijen-Jonkers, Pètra M. Braam, Uta E. Flucke, Johannes J. Bonenkamp, Bart H. W. Schreuder, Carla M. L. van Herpen, Johannes H. W. de Wilt, Ingrid M. E. Desar and Jacky W. J. de Rooy

Cancers 2023, 15(10), 2843; https://doi.org/10.3390/cancers15102843 - 19 May 2023

Cited by 3 | Viewed by 1934

Abstract

To improve local control, neoadjuvant radiotherapy (nRT) followed by surgery is the standard of care in myxofibrosarcoma (MFS) because of its infiltrative growth pattern. Nevertheless, local recurrence rates are high. Data on prognostic factors for poor clinical outcomes are lacking. This retrospective study [...] Read more.

To improve local control, neoadjuvant radiotherapy (nRT) followed by surgery is the standard of care in myxofibrosarcoma (MFS) because of its infiltrative growth pattern. Nevertheless, local recurrence rates are high. Data on prognostic factors for poor clinical outcomes are lacking. This retrospective study thus investigates the prognostic relevance of magnetic resonance imaging (MRI) characteristics before and after nRT in 40 MFS patients, as well as their association with disease-free survival (DFS) and overall survival (OS). A vascular pedicle, defined as extra-tumoral vessels at the tumor periphery, was observed in 12 patients (30.0%) pre-nRT and remained present post-nRT in all cases. Patients with a vascular pedicle had worse DFS (HR 5.85; 95% CI 1.56–21.90; p = 0.009) and OS (HR 9.58; 95% CI 1.91–48.00; p = 0.006). An infiltrative growth pattern, referred to as a tail sign, was observed in 22 patients (55.0%) pre-nRT and in 19 patients (47.5%) post-nRT, and was associated with worse DFS post-nRT (HR 6.99; 95% CI 1.39–35.35; p = 0.019). The percentage of tumor necrosis estimated by MRI was increased post-nRT, but was not associated with survival outcomes. The presence of a tail sign or vascular pedicle on MRI could support the identification of patients at risk for poor clinical outcomes after nRT. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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14 pages, 287 KiB

Open AccessArticle

Fear of Cancer Recurrence in Sarcoma Survivors: Results from the SURVSARC Study

by Ilaria Pellegrini, Cas Drabbe, Dirk J. Grünhagen, Michiel A. J. Van de Sande, Jacco J. de Haan, Kristien B.M.I. Keymeulen, Johannes J. Bonenkamp, Winette T. A. Van der Graaf and Olga Husson

Cancers 2022, 14(24), 6099; https://doi.org/10.3390/cancers14246099 - 11 Dec 2022

Cited by 2 | Viewed by 1229

Abstract

Fear of cancer recurrence (FCR) is often reported as an unmet concern by cancer patients. The aim of our study was to investigate (1) the prevalence of FCR in sarcoma survivors; (2) the factors associated with a higher level of FCR; the relationship [...] Read more.

Fear of cancer recurrence (FCR) is often reported as an unmet concern by cancer patients. The aim of our study was to investigate (1) the prevalence of FCR in sarcoma survivors; (2) the factors associated with a higher level of FCR; the relationship between (3) FCR and global health status and (4) FCR and use of follow-up care. Methods: A cross-sectional study was conducted among sarcoma survivors 2 to 10 years after diagnosis. Patients completed the Cancer Worry Scale (CWS), the global health status subscale of the EORTC QLQ-C30 and a custom-made questionnaire on follow-up care. Results: In total, 1047 patients were included (response rate 55%). The prevalence of high FCR was 45%. Factors associated with high FCR were female sex with 1.6 higher odds (95% CI 1.22–2.25; p = 0.001); having ≥1 comorbidities and receiving any treatment other than surgery alone with 1.5 (95% CI 1.07–2.05; p = 0.017) and 1.4 (95% CI 1.06–1.98; p = 0.020) higher odds, respectively. Patients on active follow-up had 1.7 higher odds (95% CI 1.20–2.61; p = 0.004) and patients with higher levels of FCR scored lower on the global health status scale (72 vs. 83 p ≤ 0.001). Conclusions: Severe FCR is common in sarcoma survivors and high levels are related to a decreased global health status. FCR deserves more attention in sarcoma survivorship, and structured support programs should be developed to deliver interventions in a correct and time adequate environment. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

14 pages, 1998 KiB

Open AccessArticle

Immunological and Genomic Analysis Reveals Clinically Relevant Distinctions between Angiosarcoma Subgroups

by Stefan G. van Ravensteijn, Yvonne M. H. Versleijen-Jonkers, Melissa H. S. Hillebrandt-Roeffen, Marije E. Weidema, Maikel J. L. Nederkoorn, Kalijn F. Bol, Mark A. J. Gorris, Kiek Verrijp, Leonie I. Kroeze, Tessa J. J. de Bitter, Richarda M. de Voer, Uta E. Flucke and Ingrid M. E. Desar

Cancers 2022, 14(23), 5938; https://doi.org/10.3390/cancers14235938 - 30 Nov 2022

Cited by 4 | Viewed by 1396

Abstract

Angiosarcomas (AS) are extremely rare and aggressive vascular malignancies subdivided in de novo primary AS (pAS) and secondary AS (sAS). We hypothesize that the combination of immunological and genomic profiles significantly differs between primary and secondary AS, with potential impact on treatment strategies [...] Read more.

Angiosarcomas (AS) are extremely rare and aggressive vascular malignancies subdivided in de novo primary AS (pAS) and secondary AS (sAS). We hypothesize that the combination of immunological and genomic profiles significantly differs between primary and secondary AS, with potential impact on treatment strategies and a role for immunotherapy. Tumor-infiltrating lymphocytes were analyzed using multiplex immunohistochemistry from 79 pAS and 178 sAS. Median cell density was significantly higher in sAS for CD3⁺ T-cells (p < 0.001), CD8⁺ cytotoxic T-cells (p = 0.033), CD4⁺ T-helper cells (p < 0.001) and FoxP3⁺ T-regulatory cells (p < 0.001). CD20⁺ B-cell density was comparable (p = 0.417). Comprehensive genomic profiling was performed in 25 pAS and 25 sAS. A (likely) pathogenic mutation was detected in 80% of pAS vs. 88% of sAS (p = 0.702). Amplifications were found in 15% of pAS vs. 84% of sAS (p < 0.001). DNA damage response (DDR) pathway mutations (p = 0.021) and MYC amplifications (p < 0.001) were predominantly seen in sAS. In conclusion we observed a clear and clinical relevant distinction in immune infiltration and genomic profiles between pAS and sAS. The T-cell infiltrated tumor microenvironment and frequent DDR gene mutations, especially in sAS, warrant clinical trials with immunotherapy. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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Review

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25 pages, 7423 KiB

Open AccessReview

Diagnostics and Treatment of Extrameningeal Solitary Fibrous Tumors

by Anna Maria Janik, Anna Terlecka, Mateusz J. Spałek, Kjetil Boye, Bartłomiej Szostakowski, Paulina Chmiel, Anna Szumera-Ciećkiewicz, Klaudia Bobak, Tomasz Świtaj, Piotr Rutkowski and Anna M. Czarnecka

Cancers 2023, 15(24), 5854; https://doi.org/10.3390/cancers15245854 - 15 Dec 2023

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Abstract

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms that account for less than 2% of all soft tissue masses. In the latest WHO 2020 Classification of Soft Tissue Tumors, extrameningeal SFT was listed as intermediate (rarely metastasizing) or malignant neoplasms. Due to the [...] Read more.

Solitary fibrous tumors (SFT) are rare mesenchymal neoplasms that account for less than 2% of all soft tissue masses. In the latest WHO 2020 Classification of Soft Tissue Tumors, extrameningeal SFT was listed as intermediate (rarely metastasizing) or malignant neoplasms. Due to the lack of characteristic clinical features, their diagnosis and treatment remain challenging. The pathogenesis of SFT is often associated with the presence of fusions of the NAB2-STAT6 gene on the 12q13 chromosome. Cytoplasmic CD34 positive staining is considerably characteristic for most SFTs; less frequently, factor XII, vimentin, bcl-2, and CD99 are present. A key factor in the diagnosis is the prevalent nuclear location of STAT6 expression. Radical resection is the mainstay of localized SFTs. In the case of unresectable disease, only radiotherapy or radio-chemotherapy may significantly ensure long-term local control of primary and metastatic lesions. To date, no practical guidelines have been published for the treatment of advanced or metastatic disease. Classical anthracycline-based chemotherapy is applicable. The latest studies suggest that antiangiogenic therapies should be considered after first-line treatment. Other drugs, such as imatinib, figitumumab, axitinib, and eribulin, are also being tested. Definitive radiotherapy appears to be a promising therapeutic modality. Since standards for the treatment of advanced and metastatic diseases are not available, further investigation of novel agents is necessary. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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20 pages, 519 KiB

Open AccessReview

Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours

by Marin Golčić, Robin L. Jones, Paul Huang and Andrea Napolitano

Cancers 2023, 15(16), 4081; https://doi.org/10.3390/cancers15164081 - 13 Aug 2023

Cited by 4 | Viewed by 1353

Abstract

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Surgical treatment is recommended for the majority of localised GIST, while systemic treatment is the cornerstone of management for metastatic or unresectable disease. While a three-year regimen of imatinib [...] Read more.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract. Surgical treatment is recommended for the majority of localised GIST, while systemic treatment is the cornerstone of management for metastatic or unresectable disease. While a three-year regimen of imatinib is the standard of care in the adjuvant setting, there is no precise recommendation for the duration of neoadjuvant treatment, where imatinib is usually given between 4 and 12 months. Continuous treatment with imatinib at a dose of 400 mg once per day is recommended for most patients with unresectable or metastatic GIST in the first line. An exception is represented by patients with tumours harbouring the imatinib-insensitive PDGFRA D842V mutation who would be better treated with avapritinib. Targeted therapies are also recommended in the presence of NTRK rearrangements and BRAF mutations, although limited data are available. While an increase in the dose of imatinib to 800 mg is an option for the second line, sunitinib is usually considered the standard of care. Similar outcomes were reported for ripretinib in patients with tumours harbouring KIT exon 11 mutation, with significantly fewer side effects. Regorafenib and ripretinib are the standards of care in the third and fourth lines, respectively. The recent development of various systemic treatment options allows for a more personalised approach based on the molecular profile of the GIST, patient characteristics, and the profile of medications’ adverse events. A multidisciplinary approach is paramount since combining systemic treatment with locoregional treatment options and supportive care is vital for long-term survival. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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Other

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2 pages, 189 KiB

Open AccessReply

Reply to Chen, A.; Zhang, X. Comment on “Golčić et al. Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. Cancers 2023, 15, 4081”

by Marin Golčić, Robin L. Jones, Paul Huang and Andrea Napolitano

Cancers 2023, 15(23), 5619; https://doi.org/10.3390/cancers15235619 - 28 Nov 2023

Cited by 1 | Viewed by 460

Abstract

We appreciate the comment made by Chen et al. on our manuscript evaluating the systemic treatment options for gastrointestinal stromal tumours (GIST) [...] Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

2 pages, 187 KiB

Open AccessComment

Comment on Golčić et al. Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours. Cancers 2023, 15, 4081

by Anni Chen and Xinhua Zhang

Cancers 2023, 15(23), 5618; https://doi.org/10.3390/cancers15235618 - 28 Nov 2023

Cited by 1 | Viewed by 379

Abstract

We carefully read the article written by Golčić et al. “Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours” [...] Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

27 pages, 2162 KiB

Open AccessSystematic Review

Telemedicine in Care of Sarcoma Patients beyond the COVID-19 Pandemic: Challenges and Opportunities

by Christos Tsagkaris, Nikolaos Trygonis, Vasiliki Spyrou and Andreas Koulouris

Cancers 2023, 15(14), 3700; https://doi.org/10.3390/cancers15143700 - 21 Jul 2023

Cited by 2 | Viewed by 1365

Abstract

Background: The COVID-19 pandemic has created a challenging environment for sarcoma patients. Most oncology societies published guidelines or recommendations prioritizing sarcoma patients and established telehealth as an efficient method of approaching them. The aim of this review is the assessment of current evidence [...] Read more.

Background: The COVID-19 pandemic has created a challenging environment for sarcoma patients. Most oncology societies published guidelines or recommendations prioritizing sarcoma patients and established telehealth as an efficient method of approaching them. The aim of this review is the assessment of current evidence regarding the utilization of telemedicine in diagnosis, treatment modalities, telerehabilitation and satisfaction among sarcoma patients and healthcare providers (HP). Methods: This systematic review was carried out using the databases PubMed and Ovid MEDLINE according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: The application of telemedicine to the management of sarcoma has yielded improved clinical and psychological outcomes. Specifically, significant progress has been demonstrated in the areas of tele-oncology and telerehabilitation during the last decade, and the COVID-19 outbreak has accelerated this transition toward them. Telehealth has been proven efficient in a wide spectrum of applications from consultations on physical therapy and psychological support to virtual care symptom management. Both HP and patients reported satisfaction with telehealth services at levels comparable to in-person visits. Conclusions: Telehealth has already unveiled many opportunities in tailoring individualized care, and its role in the management of sarcoma patients has been established in the post-COVID-19 era, as well. Full article

(This article belongs to the Special Issue Personalized Therapy of Sarcomas)

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