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14 pages, 4138 KiB

Open AccessArticle

Inhibiting Endothelin Receptors with Macitentan Strengthens the Bone Protective Action of RANKL Inhibition and Reduces Metastatic Dissemination in Osteosarcoma

by Javier Muñoz-Garcia, Jorge William Vargas-Franco, Bénédicte Brounais-Le Royer, Denis Cochonneau, Jérôme Amiaud, Marie-Françoise Heymann, Dominique Heymann and Frédéric Lézot

Cancers 2022, 14(7), 1765; https://doi.org/10.3390/cancers14071765 - 30 Mar 2022

Cited by 3 | Viewed by 2087

Abstract

Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone [...] Read more.

Current treatments for osteosarcoma, combining conventional polychemotherapy and surgery, make it possible to attain a five-year survival rate of 70% in affected individuals. The presence of chemoresistance and metastases significantly shorten the patient’s lifespan, making identification of new therapeutic tools essential. Inhibiting bone resorption has been shown to be an efficient adjuvant strategy impacting the metastatic dissemination of osteosarcoma, tumor growth, and associated bone destruction. Unfortunately, over-apposition of mineralized matrix by normal and tumoral osteoblasts was associated with this inhibition. Endothelin signaling is implicated in the functional differentiation of osteoblasts, raising the question of the potential value of inhibiting it alone, or in combination with bone resorption repression. Using mouse models of osteosarcoma, the impact of macitentan, an endothelin receptor inhibitor, was evaluated regarding tumor growth, metastatic dissemination, matrix over-apposition secondary to RANKL blockade, and safety when combined with chemotherapy. The results showed that macitentan has no impact on tumor growth or sensitivity to ifosfamide, but significantly reduces tumoral osteoid tissue formation and the metastatic capacity of the osteosarcoma. To conclude, macitentan appears to be a promising therapeutic adjuvant for osteosarcoma alone or associated with bone resorption inhibitors. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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15 pages, 3646 KiB

Open AccessArticle

Evaluation of NAB2-STAT6 Fusion Variants and Other Molecular Alterations as Prognostic Biomarkers in a Case Series of 83 Solitary Fibrous Tumors

by Carmen Salguero-Aranda, Paula Martínez-Reguera, David Marcilla, Enrique de Álava and Juan Díaz-Martín

Cancers 2021, 13(20), 5237; https://doi.org/10.3390/cancers13205237 - 19 Oct 2021

Cited by 13 | Viewed by 3233

Abstract

Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this [...] Read more.

Risk stratification of solitary fibrous tumor (SFT) patients based on clinicopathological features has limited efficacy, especially in predicting late relapse or metastasis. The hallmark alteration of SFT is the gene fusion NAB2-STAT6, whose prognostic value remains controversial. As biological knowledge of this entity has increased in recent years, new molecular alterations have emerged that could be helpful to refine current risk models. Here, we evaluated NAB2-STAT6 fusion variants and other molecular alterations in a series of 83 SFTs that are enriched in progressing cases. Gene fusion variants were identified by targeted RNA-seq in the whole series, whereas TERT promoter (pTERT) mutations were inspected by Sanger sequencing in a subset of 18 cases. Immunohistochemical assays were performed to assess BCOR and NTRK expression as well as P53 mutation status in 45, 44, and 44 cases, respectively. While confirming the associations of gene fusion variants with clinicopathological parameters, our results do not prove their prognostic value. Pan-TRK immunoexpresion correlated with recurrence/progression, P53 staining associated with higher mitotic counts, and pTERT mutations were enriched in cases with fatal outcome. An intriguing correlation was found for BCOR protein expression with gene fusion variants, size, and tumor location. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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11 pages, 2460 KiB

Open AccessArticle

Midterm MRI Follow-Up of Untreated Enchondroma and Atypical Cartilaginous Tumors in the Long Bones

by Claudia Deckers, Jacky W. J. de Rooy, Uta Flucke, H. W. Bart Schreuder, Edwin F. Dierselhuis and Ingrid C. M. van der Geest

Cancers 2021, 13(16), 4093; https://doi.org/10.3390/cancers13164093 - 13 Aug 2021

Cited by 20 | Viewed by 3981

Abstract

Management of atypical cartilaginous tumors (ACTs) in the long bones is shifting towards active surveillance to avoid unnecessary surgeries. The frequency and duration of active surveillance for these tumors is unclear as there is little knowledge of its biological behavior. In this retrospective [...] Read more.

Management of atypical cartilaginous tumors (ACTs) in the long bones is shifting towards active surveillance to avoid unnecessary surgeries. The frequency and duration of active surveillance for these tumors is unclear as there is little knowledge of its biological behavior. In this retrospective study, we examined the natural course of enchondroma and ACTs through active surveillance. A total of 128 central cartilaginous tumors, located in the long bones, with a minimum interval of 24 months between baseline and last MRI were included. MRI characteristics (e.g., size, scalloping, fat entrapment) were scored and tumors were classified according to the changes between MRIs. Mean follow-up of this study was 50 months, range = 25–138 months. The majority of the cartilaginous tumors (87%) remained stable (n = 65) or showed regression (n = 46) on MRI. A total of 87% of the cases that developed tumor regression presented with entrapped fat at diagnosis. Only 13% (n = 17) showed some progression on MRI, although none of the tumors developed characteristics of high-grade chondrosarcoma. Based on our results, active surveillance is considered safe for enchondroma and ACTs of the long bones. We propose active surveillance for all asymptomatic enchondroma or ACTs in the long bones irrespective of tumor size, and follow-up schemes should be tailored on natural course. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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13 pages, 2433 KiB

Open AccessArticle

Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study

by Hisaki Aiba, Kunihiro Ikuta, Kunihiro Asanuma, Katsuhisa Kawanami, Satoshi Tsukushi, Akihiko Matsumine, Daisuke Ishimura, Akihito Nagano, Yoji Shido, Eiji Kozawa, Kenji Yamada, Junji Wasa, Hiroaki Kimura, Takao Sakai, Hideki Murakami, Tomohisa Sakai, Tomoki Nakamura and Yoshihiro Nishida

Cancers 2021, 13(15), 3901; https://doi.org/10.3390/cancers13153901 - 2 Aug 2021

Cited by 3 | Viewed by 2438

Abstract

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions [...] Read more.

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail-like lesions. This study indicated that the shrinkage of tail-like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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11 pages, 537 KiB

Open AccessArticle

Pleuropneumonectomy as Salvage Therapy in Children Suffering from Primary or Metastatic Sarcomas with Pleural Localizations

by Frédéric Hameury, Perrine Marec-Berard, Mathilde Eymery, Marc H. W. Wijnen, Niels van der Kaaij, Pierre-Yves Mure, François Tronc, Franck Chotel, Clara Libbrecht, Wim Jan P. van Boven and Lianne M. Haveman

Cancers 2021, 13(15), 3655; https://doi.org/10.3390/cancers13153655 - 21 Jul 2021

Cited by 3 | Viewed by 2245

Abstract

Pediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to obtain local control. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent salvage PP for [...] Read more.

Pediatric sarcoma patients with pleuropulmonary lesions have a dismal prognosis because the impossibility to obtain local control. The aim of this study was to determine if pleuropneumonectomy (PP) could be a therapeutic option. We retrospectively reviewed nine patients who underwent salvage PP for pleuropulmonary localization of primary localized sarcoma or metastatic recurrence. Surgery and complications were analyzed, pulmonary function tests were conducted, and quality of life was determined with EORTC-QLQ-C30 questionnaire. At the time of PP age was between 9–17 years. Underlying disease included metastatic osteosarcoma (n = 5), Ewing sarcoma (two metastatic, one primary), and one primary undifferentiated sarcoma. Early complications occurred in three patients. Mean postoperative hospitalization stay was 14.5 days. Pulmonary function test showed 19–66% reduction of total lung capacity which led to mild exercise intolerance but did not affect daily life. Four patients died of multi-metastatic relapse <14 months after PP, one patient had a local recurrence, and four patients are in complete remission between 1.5 and 12 years after PP. In conclusion, in this small patient group treated with a pleuropneumonectomy for primary or metastatic lesions, outcome is variable; however, this extended surgical technique was generally quite well tolerated. Postoperative lung function seems well preserved, and it seems to lead to at least an extension of life with good quality and therefor can be considered as salvage therapy. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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11 pages, 2185 KiB

Open AccessArticle

A Radiological Scoring System for Differentiation between Enchondroma and Chondrosarcoma

by Shinji Miwa, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Kentaro Igarashi, Kaoru Tada, Hirotaka Yonezawa, Sei Morinaga, Yoshihiro Araki, Yohei Asano, Shiro Saito, Miho Okuda, Junichi Taki, Hiroko Ikeda, Takayuki Nojima and Hiroyuki Tsuchiya

Cancers 2021, 13(14), 3558; https://doi.org/10.3390/cancers13143558 - 16 Jul 2021

Cited by 9 | Viewed by 2204

Abstract

Background: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. Methods: To evaluate the diagnostic usefulness of radiological findings, correlations between various [...] Read more.

Background: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. Methods: To evaluate the diagnostic usefulness of radiological findings, correlations between various radiological findings and final diagnoses were investigated in a cohort of 81 patients. Furthermore, a new radiological scoring system was developed by combining radiological findings. Results: Periosteal reaction on X-ray (p = 0.025), endosteal scalloping (p = 0.010) and cortical defect (p = 0.002) on CT, extraskeletal mass (p < 0.001), multilobular lesion (p < 0.001), abnormal signal in adjacent tissue (p = 0.004) on MRI, and increased uptake in bone scan (p = 0.002) and thallium scan (p = 0.027) was significantly correlated with final diagnoses. Based on the correlations between each radiological finding and postoperative histological diagnosis, a radiological scoring system combining these findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and ACTs/chondrosarcomas were 88%, 89%, and 88%, respectively (p = 0.003). Conclusion: Radiological assessment with combined radiological findings is recommended to differentiate between enchondromas and ACT/chondrosarcomas. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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13 pages, 1413 KiB

Open AccessArticle

Impact of Surgical Resection and Reasons for Poor Prognosis of Pelvic Osteosarcoma Based on the Bone Tumor Registry in Japan

by Satoshi Takenaka, Hironari Tamiya, Toru Wakamatsu, Sho Nakai, Yoshinori Imura, Hidetatsu Outani, Toshinari Yagi and Akira Kawai

Cancers 2021, 13(13), 3320; https://doi.org/10.3390/cancers13133320 - 1 Jul 2021

Cited by 10 | Viewed by 2239

Abstract

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the [...] Read more.

Pelvic osteosarcoma has a poor prognosis compared to osteosarcomas in other locations, and the reasons for this remain unknown. Surgical resection of pelvic osteosarcoma is technically demanding and often results in dysfunction and complications. In this study, we investigated the reasons underlying the poor prognosis of pelvic osteosarcoma by comparing it to femoral osteosarcoma using data from the Bone Tumor Registry in Japan. We used propensity score analysis to determine whether surgical resection of pelvic osteosarcoma improved its prognosis. We demonstrated that pelvic osteosarcoma had a poor prognosis because it occurred more often in the elderly, often had larger tumor size, and had metastasis at presentation more often in comparison to femoral osteosarcoma. These three factors were also associated with the non-surgical treatment of pelvic osteosarcoma, which also led to a poor outcome. The overall survival rate was only comparable in pelvic osteosarcoma and femoral osteosarcoma in cases treated with surgical resection. Propensity score analysis revealed that surgical treatment improved the prognosis of pelvic osteosarcoma. As such, we propose that surgical resection should be considered based on tumor stage and patient age in order to improve the prognosis of pelvic osteosarcoma. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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34 pages, 17704 KiB

Open AccessArticle

Data-Driven Mathematical Model of Osteosarcoma

by Trang Le, Sumeyye Su, Arkadz Kirshtein and Leili Shahriyari

Cancers 2021, 13(10), 2367; https://doi.org/10.3390/cancers13102367 - 14 May 2021

Cited by 22 | Viewed by 3729

Abstract

As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance [...] Read more.

As the immune system has a significant role in tumor progression, in this paper, we develop a data-driven mathematical model to study the interactions between immune cells and the osteosarcoma microenvironment. Osteosarcoma tumors are divided into three clusters based on their relative abundance of immune cells as estimated from their gene expression profiles. We then analyze the tumor progression and effects of the immune system on cancer growth in each cluster. Cluster 3, which had approximately the same number of naive and M2 macrophages, had the slowest tumor growth, and cluster 2, with the highest population of naive macrophages, had the highest cancer population at the steady states. We also found that the fastest growth of cancer occurred when the anti-tumor immune cells and cytokines, including dendritic cells, helper T cells, cytotoxic cells, and IFN-

γ

, switched from increasing to decreasing, while the dynamics of regulatory T cells switched from decreasing to increasing. Importantly, the most impactful immune parameters on the number of cancer and total cells were the activation and decay rates of the macrophages and regulatory T cells for all clusters. This work presents the first osteosarcoma progression model, which can be later extended to investigate the effectiveness of various osteosarcoma treatments. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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Review

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28 pages, 724 KiB

Open AccessEditor’s ChoiceReview

Origin and Therapies of Osteosarcoma

by Brice Moukengue, Morgane Lallier, Louise Marchandet, Marc Baud’huin, Franck Verrecchia, Benjamin Ory and Francois Lamoureux

Cancers 2022, 14(14), 3503; https://doi.org/10.3390/cancers14143503 - 19 Jul 2022

Cited by 39 | Viewed by 5122

Abstract

Osteosarcoma (OS) is the most frequent primary bone tumor, mainly affecting children and young adults. Despite therapeutic advances, the 5-year survival rate is 70% but drastically decreases to 20–30% for poor responders to therapies or for patients with metastasis. No real evolution of [...] Read more.

Osteosarcoma (OS) is the most frequent primary bone tumor, mainly affecting children and young adults. Despite therapeutic advances, the 5-year survival rate is 70% but drastically decreases to 20–30% for poor responders to therapies or for patients with metastasis. No real evolution of the survival rates has been observed for four decades, explained by poor knowledge of the origin, difficulties related to diagnosis and the lack of targeted therapies for this pediatric tumor. This review will describe a non-exhaustive overview of osteosarcoma disease from a clinical and biological point of view, describing the origin, diagnosis and therapies. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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27 pages, 2898 KiB

Open AccessReview

Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review

by Adrian Emilian Bădilă, Dragoș Mihai Rădulescu, Adelina-Gabriela Niculescu, Alexandru Mihai Grumezescu, Marius Rădulescu and Adrian Radu Rădulescu

Cancers 2021, 13(16), 4229; https://doi.org/10.3390/cancers13164229 - 23 Aug 2021

Cited by 43 | Viewed by 13170

Abstract

In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, [...] Read more.

In the last decades, the treatment of primary and secondary bone tumors has faced a slow-down in its development, being mainly based on chemotherapy, radiotherapy, and surgical interventions. However, these conventional therapeutic strategies present a series of disadvantages (e.g., multidrug resistance, tumor recurrence, severe side effects, formation of large bone defects), which limit their application and efficacy. In recent years, these procedures were combined with several adjuvant therapies, with different degrees of success. To overcome the drawbacks of current therapies and improve treatment outcomes, other strategies started being investigated, like carrier-mediated drug delivery, bone substitutes for repairing bone defects, and multifunctional scaffolds with bone tissue regeneration and antitumor properties. Thus, this paper aims to present the types of bone tumors and their current treatment approaches, further focusing on the recent advances in new therapeutic alternatives. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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15 pages, 462 KiB

Open AccessReview

Immunotherapy for Chordoma and Chondrosarcoma: Current Evidence

by Jeffrey I. Traylor, Mark N. Pernik, Aaron R. Plitt, Michael Lim and Tomas Garzon-Muvdi

Cancers 2021, 13(10), 2408; https://doi.org/10.3390/cancers13102408 - 17 May 2021

Cited by 28 | Viewed by 5318

Abstract

Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. [...] Read more.

Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. In chordoma, brachyury has been identified as a prominent biomarker and potential molecular immunotherapy target as well as PD-1 inhibition. While studies on immunotherapy in chondrosarcoma are sparse, there is emerging evidence and ongoing clinical trials for PD-1 as well as IDH inhibitors. This review highlights potential biomarkers and targets for immunotherapy in chordoma and chondrosarcoma, as well as current clinical evidence and ongoing trials. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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37 pages, 6493 KiB

Open AccessReview

Chondrosarcoma-from Molecular Pathology to Novel Therapies

by Agnieszka E. Zając, Sylwia Kopeć, Bartłomiej Szostakowski, Mateusz J. Spałek, Michał Fiedorowicz, Elżbieta Bylina, Paulina Filipowicz, Anna Szumera-Ciećkiewicz, Andrzej Tysarowski, Anna M. Czarnecka and Piotr Rutkowski

Cancers 2021, 13(10), 2390; https://doi.org/10.3390/cancers13102390 - 14 May 2021

Cited by 44 | Viewed by 11201

Abstract

Chondrosarcoma (CHS) is the second most common primary malignant bone sarcoma. Overall survival and prognosis of this tumor are various and often extreme, depending on histological grade and tumor subtype. CHS treatment is difficult, and surgery remains still the gold standard due to [...] Read more.

Chondrosarcoma (CHS) is the second most common primary malignant bone sarcoma. Overall survival and prognosis of this tumor are various and often extreme, depending on histological grade and tumor subtype. CHS treatment is difficult, and surgery remains still the gold standard due to the resistance of this tumor to other therapeutic options. Considering the role of differentiation of CHS subtypes and the need to develop new treatment strategies, in this review, we introduced a multidisciplinary characterization of CHS from its pathology to therapies. We described the morphology of each subtype with the role of immunohistochemical markers in diagnostics of CHS. We also summarized the most frequently mutated genes and genome regions with altered pathways involved in the pathology of this tumor. Subsequently, we discussed imaging methods and the role of currently used therapies, including surgery and the limitations of chemo and radiotherapy. Finally, in this review, we presented novel targeted therapies, including those at ongoing clinical trials, which can be a potential future target in designing new therapeutics for patients with CHS. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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11 pages, 639 KiB

Open AccessStudy Protocol

Front-Line Window Therapy with Temozolomide and Irinotecan in Patients with Primary Disseminated Multifocal Ewing Sarcoma: Results of the ISG/AIEOP EW-2 Study

by Sebastian Dorin Asaftei, Nadia Puma, Anna Paioli, Marco Petraz, Carlo Morosi, Marta Podda, Angela Tamburini, Emanuela Palmerini, Luca Coccoli, Giovanni Grignani, Carla Manzitti, Rossella Bertulli, Francesco De Leonardis, Marco Rabusin, Anna Campello, Elisa Tirtei, Piero Picci, Arcangelo Prete, Alessandra Longhi, Franca Fagioli and Roberto Luksch Show full author list Hide full author list

Cancers 2021, 13(12), 3046; https://doi.org/10.3390/cancers13123046 - 18 Jun 2021

Cited by 9 | Viewed by 2475

Abstract

Purpose: The main objective was to evaluate the activity and tolerability of TEMIRI as a front-line treatment in primary disseminated Ewing sarcoma (PDMES) using the RECIST 1.1 criteria. The secondary objectives included the assessment of toxicity and the performance status/symptom changes. Methods: Between [...] Read more.

Purpose: The main objective was to evaluate the activity and tolerability of TEMIRI as a front-line treatment in primary disseminated Ewing sarcoma (PDMES) using the RECIST 1.1 criteria. The secondary objectives included the assessment of toxicity and the performance status/symptom changes. Methods: Between 2012 and 2018, patients with PDMES received two courses of temozolomide 100 mg/sqm/day + irinotecan 50 mg/sqm/day for 5 days every 3 weeks as an amendment to the Italian Sarcoma Group/Associazione Italiana EmatoIogia ed Oncologia Pediatrica (ISG/AIEOP) EW-2 protocol (EUDRACT#2009-012353-37, Vers. 1.02). Results: Thirty-four patients were enrolled. The median age at diagnosis was 19 years (range 3–55). After TEMIRI, the RECIST response was as follows: a partial response in 20 (59%) patients, stable disease in 11 (32%), and disease progression in 3 (9%). The ECOG/Lansky score was improved in 25/34 (73.5%) cases, and a reduction or disappearance of pain was observed in 31/34 patients (91%). The incidence of grade 3–4 toxicity was 3%. The 3-year event-free survival (EFS) and overall survival (OS) were 21% (95% CI 6–35%) and 36% (95% CI: 18–54%), respectively. Conclusion: the smooth handling and encouraging activity demonstrated by up-front TEMIRI did not change the EFS in PDMES, so this result suggests the need for the further evaluation of the efficacy of TEMIRI in combination with conventional treatments in non-metastatic patients. Full article

(This article belongs to the Special Issue Diagnosis and Treatment for Bone Tumor and Sarcoma)

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