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Sarcoma and Bone Cancer Awareness Month

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (1 July 2023) | Viewed by 22606

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Dr. Shinji Miwa

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Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa-shi, Ishikawa-ken 920-8641, Japan
Interests: cancer therapy; oncology; osteosarcoma; surgical oncology; orthopedic surgery; bone tumor
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Dear Colleagues,

Sarcomas are malignant tumors commonly arise from bone and soft-tissue such as muscle, fat, and nerves. Bone sarcomas include osteosarcoma, chondrosarcoma, and Ewing's sarcoma, and soft-tissue sarcomas include liposarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, synovial sarcoma, leiomyosarcoma, and rhabdomyosarcoma. The characteristics of sarcoma are its rarity (low frequency of occurrence) and diversity (various histological types). The frequency of sarcoma is extremely low compared to carcinoma such as lung cancer and colon cancer, and sarcoma account for only 1% of all malignant tumors.

Due to the rarity and variety of sarcoma, it is difficult to make diagnosis and treat the disease appropriately. In addition, many patients are referred to cancer center after receiving unplanned excision.

Recently, July is designated as "Sarcoma Awareness Month", with the yellow ribbon as a symbol, and various activities are done to raise awareness of this rate cancer for research support and development in the treatment in all over the world.

We would like to take this opportunity to appreciate all the researchers who have contributed to the fight against this disease. In particular, we would like to highlight several researches in this field, which cover mechanisms in tumor microenvironment, early detection, promising therapeutic target, and new therapeutic strategies. We hope this special issue will provide useful information for clinical practice.

Dr. Shinji Miwa
Guest Editor

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Published Papers (10 papers)

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Research

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16 pages, 1969 KiB

Open AccessArticle

Patients’ Experiences of a Sarcoma Diagnosis: A Process Mapping Exercise of Diagnostic Pathways

by Sam Martin, Sigrún Eyrúnardóttir Clark, Craig Gerrand, Katie Gilchrist, Maria Lawal, Laura Maio, Ana Martins, Lesley Storey, Rachel M. Taylor, Mary Wells, Jeremy S. Whelan, Rachael Windsor, Julie Woodford, Cecilia Vindrola-Padros and Lorna A. Fern

Cancers 2023, 15(15), 3946; https://doi.org/10.3390/cancers15153946 - 3 Aug 2023

Cited by 2 | Viewed by 1788

Abstract

Patients with sarcoma often report prolonged time to diagnosis, which is attributed to the rarity of sarcoma and the low awareness of pre-diagnostic signs and symptoms. Aims: To describe patients’ experiences of pre-diagnostic signs/symptoms and pathways to diagnosis, including where help was sought, and the processes involved. Methods: Mixed methods involving quantitative, qualitative and inductive thematic analyses using novel process mapping of patient journey data, as reported by the patients. We examined the time from symptom onset to first professional presentation (patient interval, PI), first consultation to diagnostic biopsy, first consultation to diagnosis (diagnostic interval) and first presentation to diagnosis (total interval). Results: A total of 87 interviews were conducted over 5 months in 2017. Of these, 78 (40 males/38 females) were included. The sarcoma subtypes were bone (n = 21), soft tissue (n = 41), head and neck (n = 9) and gastro-intestinal (GIST; n = 7). Age at diagnosis was 13–24 (n = 7), 25–39 (n = 23), 40–64 (n = 34) and 65+ (n = 14) years. The median PI was 13 days (1–4971) and similar between sarcoma subtypes, with the exception of GIST (mPI = 2 days, (1–60). The longest mPI (31 days, range 4–762) was for those aged 13–24 years. The median diagnostic interval was 87.5 (range 0–5474 days). A total of 21 patients were misdiagnosed prior to diagnosis and symptoms were commonly attributed to lifestyle factors. Conclusions: Prolonged times to diagnosis were experienced by the majority of patients in our sample. Further research into the evolution of pre-diagnostic sarcoma symptoms is required to inform awareness interventions. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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17 pages, 2033 KiB

Open AccessArticle

Intramedullary Nailing with and without the Use of Bone Cement for Impending and Pathologic Fractures of the Humerus in Multiple Myeloma and Metastatic Disease

by Andriy Kobryn, Patrick Nian, Joydeep Baidya, Tai L. Li and Aditya V. Maheshwari

Cancers 2023, 15(14), 3601; https://doi.org/10.3390/cancers15143601 - 13 Jul 2023

Cited by 2 | Viewed by 1986

Abstract

Although intramedullary nailing (IMN) is considered the standard of care for the surgical management of most femur metastatic diseases, the optimal treatment of metastatic humeral impending and/or pathologic fractures is still debatable. Moreover, the use of cemented humeral nails has not been thoroughly studied, and only a few small series have compared their results with uncemented nails. The purpose of this study was to compare the (1) survivorship, (2) functional outcomes, and (3) perioperative complications in patients receiving cemented versus uncemented humerus IMN for impending or complete pathologic fractures resulting from metastatic disease or multiple myeloma. We retrospectively reviewed 100 IMNs in 82 patients, of which 53 were cemented and 47 were uncemented. With a mean survival of 10 months (Cemented: 8.3 months vs. Uncemented: 11.6 months, p = 0.34), the mean Musculoskeletal Tumor Society (MSTS) scores increased from 42.4% preoperatively (Cemented: 40.2% vs. Uncemented: 66.7%, p = 0.01) to 89.2% at 3 months postoperatively (Cemented: 89.8% vs. Uncemented: 90.9%, p = 0.72) for the overall group (p < 0.001). Both cohorts yielded comparable complication rates (overall [22.6% vs. 19.1%)], surgical ([11.3% vs. 4.3%], and medical [13.2% vs. 14.9%], all p > 0.05), but estimated blood loss was significantly higher in the cemented group (203 mL vs. 126 mL, p = 0.003). Thus, intramedullary nailing, with and without cement augmentation in select patients, is a relatively safe and effective therapeutic modality for metastatic humeral disease with similar clinical outcomes and acceptable complication rates. While controlling for possible selection bias, larger-scale, higher-level studies are warranted to validate our results. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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13 pages, 757 KiB

Open AccessArticle

Single-Stage versus Multi-Stage Intramedullary Nailing for Multiple Synchronous Long Bone Impending and Pathologic Fractures in Metastatic Bone Disease and Multiple Myeloma

by Aditya V. Maheshwari, Andriy Kobryn, Juhayer S. Alam and Mikhail Tretiakov

Cancers 2023, 15(4), 1227; https://doi.org/10.3390/cancers15041227 - 15 Feb 2023

Cited by 3 | Viewed by 2050

Abstract

Purpose: Determine whether perioperative outcomes differ between patients who have undergone single or multi-stage IMN procedures for impending or completed pathologic fractures. Methods: Patients were classified into single-stage single-bone (SSSB), single-stage multiple-bone (SSMB), and multi-stage multiple-bone (MSMB) based on procedure timing and number of bones involved. Outcome variables compared included length of stay (LOS), in-hospital mortality and survival, initiation of rehabilitation and adjuvant therapy, and perioperative complications. Results: There were 272 IMNs placed in 181 patients (100 males, 81 females, 55.2% and 44.8%, respectively) with a mean age of 66.3 ± 12.1 years. MSMB had significantly longer LOS (24.3 ± 14.2 days) and rehabilitation initiation (3.4 ± 2.5 days) compared to SSSB (8.5 ± 7.7 and 1.8 ± 1.6 days) and SSMB (11.5 ± 7.6 and 2.0 ± 1.6 days) subjects, respectively (both; p < 0.01). Although total perioperative complication rates in SSMB and MSMB were comparable (33.3% vs. 36.0%), they were significantly higher than SSSB (18%) (p = 0.038). MSMB had significantly more (20%) cardiopulmonary complications than SSMB (11.1%) and SSSB (4.5%) (p = 0.027). All groups exhibited comparative survivorship (8.1 ± 8.6, 7.1 ± 7.2, and 11.4 ± 11.8 months) and in-hospital mortality (4.5%, 8.9%, and 4.0%) (all; p > 0.05). Conclusion: In comparison to MSMB, SSMB intramedullary nailing did not result in higher perioperative complication or in-hospital mortality rates in select patients with synchronous long-bone metastases but led to earlier postoperative discharge and initiation of rehabilitation. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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20 pages, 4682 KiB

Open AccessArticle

Characterizing the Ablative Effects of Histotripsy for Osteosarcoma: In Vivo Study in Dogs

by Lauren N. Ruger, Alayna N. Hay, Elliana R. Vickers, Sheryl L. Coutermarsh-Ott, Jessica M. Gannon, Hannah S. Covell, Gregory B. Daniel, Paul F. Laeseke, Timothy J. Ziemlewicz, Katharine R. Kierski, Brittany J. Ciepluch, Eli Vlaisavljevich and Joanne L. Tuohy

Cancers 2023, 15(3), 741; https://doi.org/10.3390/cancers15030741 - 25 Jan 2023

Cited by 7 | Viewed by 4125

Abstract

Osteosarcoma (OS) is a malignant bone tumor treated by limb amputation or limb salvage surgeries and chemotherapy. Histotripsy is a non-thermal, non-invasive focused ultrasound therapy using controlled acoustic cavitation to mechanically disintegrate tissue. Recent ex vivo and in vivo pilot studies have demonstrated the ability of histotripsy for ablating OS but were limited in scope. This study expands on these initial findings to more fully characterize the effects of histotripsy for bone tumors, particularly in tumors with different compositions. A prototype 500 kHz histotripsy system was used to treat ten dogs with suspected OS at an intermediate treatment dose of 1000 pulses per location. One day after histotripsy, treated tumors were resected via limb amputation, and radiologic and histopathologic analyses were conducted to determine the effects of histotripsy for each patient. The results of this study demonstrated that histotripsy ablation is safe and feasible in canine patients with spontaneous OS, while offering new insights into the characteristics of the achieved ablation zone. More extensive tissue destruction was observed after histotripsy compared to that in previous reports, and radiographic changes in tumor size and contrast uptake following histotripsy were reported for the first time. Overall, this study significantly expands our understanding of histotripsy bone tumor ablation and informs future studies for this application. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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13 pages, 928 KiB

Open AccessArticle

Does Aggressive Surgery Mean Worse Quality of Life and Functional Capacity in Retroperitoneal Sarcoma Patients?—A Retrospective Study of 161 Patients from China

by Aobo Zhuang, Yuan Fang, Lijie Ma, Hua Yang, Weiqi Lu, Yuhong Zhou, Yong Zhang and Hanxing Tong

Cancers 2022, 14(20), 5126; https://doi.org/10.3390/cancers14205126 - 19 Oct 2022

Cited by 3 | Viewed by 1425

Abstract

The mainstay of treatment for primary retroperitoneal sarcoma (RPS) is surgery. However, whether multiple visceral resection (MVR) affects patients’ quality of life compared with simple tumor resection has not been reported. Patients with primary RPS who underwent radical resection between 2009 and 2021 were included. Patients who were alive at the last follow-up were asked to complete the European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). The primary endpoint of the study was the global health (GH) score. A total of 161 patients were included, including 77 in the MVR group and 84 in the non-MVR group. When comparing EORTC scores on functional domains and symptom scales between MVR and non-MVR groups, only constipation scores differed (p = 0.011). Comparing GH scores within 6 months after surgery between the two groups, GH was better in non-MVR patients (58.3 vs. 76.4, p = 0.082). However, patients with longer postoperative intervals in the MVR group had higher scores (p < 0.001), and patients with postoperative intervals of more than one year scored similar to those in the non-MVR group (64.7 vs. 59.2, p = 0.522). As the postoperative interval increased, there was an improvement in all indicators in MVR patients, while there was no significant improvement in non-MVR patients. Aggressive surgical approaches impair quality of life within 6 months postoperatively, but the long-term quality of life is similar to that of patients undergoing simple tumor resection. This should be factored into RPS treatment decisions. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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17 pages, 5840 KiB

Open AccessArticle

Astragaloside IV Inhibits the Proliferation of Human Uterine Leiomyomas by Targeting IDO1

by Tiantian Qiu, Donghua Li, Yu Liu, Hui Ren, Xuan Yang and Wenting Luo

Cancers 2022, 14(18), 4424; https://doi.org/10.3390/cancers14184424 - 12 Sep 2022

Cited by 4 | Viewed by 2243

Abstract

Astragaloside IV (AS-IV) is a chemical found in traditional Chinese medicine called Astragalus membranaceus (Fisch.) Bunge that has antitumor properties. However, the roles and mechanisms of AS-IV in uterine leiomyomas (ULMs) are unclear. The immunosuppressive enzyme indoleamine-2,3-dioxygenase-1 (IDO1) is involved in tumor formation. IDO1 is a new and reliable prognostic indicator for several cancers. In this work, AS-IV was applied to ULM cells in various concentrations. CCK-8, immunofluorescence, and flow cytometry were used to examine the proliferation and apoptosis of ULM cells caused by AS-IV. After lentiviral vector transduction with IDO1 short hairpin RNA (shRNA), the knockdown and overexpression of IDO1 were stable in ULM cells. To verify the antitumor effect of AS-IV in vivo, we established a rat model of uterine leiomyoma. HE staining, Masson staining, and transmission electron microscopy were used to observe pathological changes in the uterus, and the levels of serum sex hormones were measured by radio immune assay (RIA). The levels of CD3+T, CD4+T, and CD25+ Foxp3+Treg in rat peripheral blood were detected by flow cytometry. Western blotting and immunohistochemistry were used to examine protein expression. We found that AS-IV dramatically increased the apoptotic rate of ULM cells and reduced viability in a time- and dosage-dependent manner. After sh-IDO1 lentiviral transfection, we discovered that knocking down IDO1 reversed the effects of AS-IV on ULM cell proliferation and autophagy. We also found that AS-IV can effectively inhibit the growth of ULMs in vivo. AS-IV may promote apoptosis and autophagy in ULMs by activating PTEN/PI3K/AKT signaling through inhibition of IDO1. These findings imply that AS-IV exerts antifibroid effects, and the underlying mechanism may be IDO1, which is involved in proliferation, apoptosis, and autophagy. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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Review

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27 pages, 5700 KiB

Open AccessReview

Breast Sarcomas, Phyllodes Tumors, and Desmoid Tumors: Turning the Magnifying Glass on Rare and Aggressive Entities

by Miguel Esperança-Martins, Cecília Melo-Alvim, Sara Dâmaso, Raquel Lopes-Brás, Tânia Peniche, Gonçalo Nogueira-Costa, Catarina Abreu, Helena Luna Pais, Rita Teixeira de Sousa, Sofia Torres, Lina Marcela Gallego-Paez, Marta Martins, Leonor Ribeiro and Luís Costa

Cancers 2023, 15(15), 3933; https://doi.org/10.3390/cancers15153933 - 2 Aug 2023

Cited by 2 | Viewed by 2505

Abstract

Breast sarcomas (BSs), phyllodes tumors (PTs), and desmoid tumors (DTs) are rare entities that arise from connective tissue. BSs can be classified as either primary or secondary, whether they develop de novo or after radiation exposure or lymphedema. PIK3CA seems to play an important common role in different BS. Malignant PTs show similar behavior to BSs, while DTs are locally aggressive but rarely metastasize. BSs usually present as unilateral, painless, rapidly growing masses with rare nodal involvement. The diagnosis should be based on magnetic resonance imaging and a core needle biopsy. Staging should comprise a chest computed tomography (CT) scan (except for benign PT and DT), while abdominal and pelvic CT scans and bone scans should be added in certain subtypes. The mainstay of treatment for localized BS is surgery, with margin goals that vary according to subtype. Radiotherapy and chemotherapy can be used as neoadjuvant or adjuvant approaches, but their use in these settings is not standard. Advanced BS should be treated with systemic therapy, consistent with recommendations for advanced soft tissue sarcomas of other topographies. Given the rarity and heterogeneity of these entities, multidisciplinary and multi-institutional collaboration and treatment at reference centers are critical. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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12 pages, 1033 KiB

Open AccessReview

RUNX Family as a Promising Biomarker and a Therapeutic Target in Bone Cancers: A Review on Its Molecular Mechanism(s) behind Tumorigenesis

by Selvaraj Vimalraj and Saravanan Sekaran

Cancers 2023, 15(12), 3247; https://doi.org/10.3390/cancers15123247 - 19 Jun 2023

Cited by 4 | Viewed by 1960

Abstract

The transcription factor runt-related protein (RUNX) family is the major transcription factor responsible for the formation of osteoblasts from bone marrow mesenchymal stem cells, which are involved in bone formation. Accumulating evidence implicates the RUNX family for its role in tumor biology and cancer progression. The RUNX family has been linked to osteosarcoma via its regulation of many tumorigenicity-related factors. In the regulatory network of cancers, with numerous upstream signaling pathways and its potential target molecules downstream, RUNX is a vital molecule. Hence, a pressing need exists to understand the precise process underpinning the occurrence and prognosis of several malignant tumors. Until recently, RUNX has been regarded as one of the therapeutic targets for bone cancer. Therefore, in this review, we have provided insights into various molecular mechanisms behind the tumorigenic role of RUNX in various important cancers. RUNX is anticipated to grow into a novel therapeutic target with the in-depth study of RUNX family-related regulatory processes, aid in the creation of new medications, and enhance clinical efficacy. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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12 pages, 308 KiB

Open AccessReview

Surgical Site Infection after Bone Tumor Surgery: Risk Factors and New Preventive Techniques

by Shinji Miwa, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Kentaro Igarashi and Hiroyuki Tsuchiya

Cancers 2022, 14(18), 4527; https://doi.org/10.3390/cancers14184527 - 19 Sep 2022

Cited by 11 | Viewed by 2249

Abstract

The management of malignant bone tumors requires multidisciplinary interventions including chemotherapy, radiation therapy, and surgical tumor resection and reconstruction. Surgical site infection (SSI) is a serious complication in the treatment of malignant bone tumors. Compared to other orthopedic surgeries, the surgical treatment of malignant bone tumors is associated with higher rates of SSIs. In patients with SSIs, additional surgeries, long-term administrations of antibiotics, extended hospital stays, and the postponement of scheduled adjuvant treatments are required. Therefore, SSI may adversely affect functional and oncological outcomes. To improve surgical outcomes in patients with malignant bone tumors, preoperative risk assessments for SSIs, new preventive techniques against SSIs, and the optimal use of prophylactic antibiotics are often required. Previous reports have demonstrated that age, tumor site (pelvis and tibia), extended operative time, implant use, body mass index, leukocytopenia, and reconstruction procedures are associated with an increased risk for SSIs. Furthermore, prophylactic techniques, such as silver and iodine coatings on implants, have been developed and proven to be efficacious and safe in clinical studies. In this review, predictive factors of SSIs and new prophylactic techniques are discussed. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

Other

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22 pages, 997 KiB

Open AccessSystematic Review

Safety and Efficacy of a Single-Stage versus Two-Stage Intramedullary Nailing for Synchronous Impending or Pathologic Fractures of Bilateral Femur for Oncologic Indications: A Systematic Review

by Patrick P. Nian, Vanathi Ganesan, Joydeep Baidya, Ryan S. Marder, Krish Maheshwari, Andriy Kobryn and Aditya V. Maheshwari

Cancers 2023, 15(17), 4396; https://doi.org/10.3390/cancers15174396 - 2 Sep 2023

Viewed by 1211

Abstract

Although intramedullary nail (IMN) fixation is the standard of care for most impending and/or complete pathologic fractures of the femur, the optimal timing/sequence of the IMN in cases of synchronous bilateral femoral disease in advanced cancer is not well established. Thus, we compared the outcomes of single-stage (SS) vs. two-stage (TS) IMN of the bilateral femur with a systematic review of the literature on this topic. Bilateral SS and TS IMN cases were identified from 14 studies extracted from four databases according to PRISMA guidelines. Safety (complications, reoperations, mortality, survival, blood loss, and transfusion) and efficacy (length of stay [LOS], time to start rehabilitation and adjuvant therapy, functional scores, and cost) were compared between the groups. A total of 156 IMNs in 78 patients (36 SS and 42 TS) were analyzed. There were one surgical (infection in TS requiring reoperation; p = 0.860) and fifteen medical complications (five in SS, ten in TS; p = 0.045), with SS being associated with lower rates of total and medical complications. Survival, intraoperative mortality, and postoperative same-admission mortality were similar. No cases of implant failure were reported. Data on LOS, rehabilitation, and adjuvant therapy were scarcely reported, although one study favored SS over TS. No study compared cost or functional scores. Our study is the largest and most comprehensive of its kind in supporting the safety and efficacy of a SS bilateral femur IMN approach in these select patients. Further investigations with higher levels of evidence are warranted to optimize treatment protocols for this clinical scenario. Full article

(This article belongs to the Special Issue Sarcoma and Bone Cancer Awareness Month)

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