| 1. |
- Arroyo, Vidal M., et al.
(author)
-
Soft tissue sarcoma clinical presentation, treatment, and survival in adolescents and young adults compared to older adults : A report from the Scandinavian Sarcoma Group
- 2018
-
In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 78:13
-
Journal article (other academic/artistic)abstract
- Background: Five-year survival rates for those diagnosed with soft tissue sarcoma (STS) have improved significantly among children and older adults (OAs), but these same trends have not been observed for adolescents and young adults (AYAs). While these disparities could be due to differences in biology or treatment, few studies have evaluated STS occurrence and outcome in AYAs. Therefore, the purpose of this study was to evaluate differences between adolescents and young adults (AYAs) and older adults (OAs) diagnosed with STS by stratifying analysis by: (1) clinical presentation; (2) treatment; and (3) survival.Methods: Data were obtained from the Scandinavian Sarcoma Group (SSG) Central Register, which includes information on 5,747 patients from Sweden and Norway, diagnosed with a STS during 1986-2011. Variables included: age at diagnosis, metastasis at diagnosis, tumor size, histology, adjuvant treatment, date of death or last follow-up. AYAs were defined as those diagnosed ages 15-39 years. Categorical variables were analyzed using chi-square tests, and continuous variables were analyzed using t-tests. Overall survival (OS) and recurrence-free survival (RFS) were compared between AYAs and OAs using Kaplan-Meier estimates and log-rank tests. All analyses were conducted overall and by common STS subtypes.Results: Overall and by STS subtype, there were significant differences between AYAs and OAs on presentation, treatment, and survival. The distribution of STS subtypes was different between OAs and AYAs. For example, OAs were more likely to be diagnosed with leiomyosarcoma compared to AYAs (18% vs. 10%, p<0.001), whereas AYAs were more likely to be diagnosed with malignant peripheral nerve sheath tumor (MPNST, 9% vs. 4%, p<0.001). OAs were also more likely to have larger tumors (>5 cm, 67% vs. 52%, p<0.001) and higher malignancy grade (grade IV, 45% vs. 31%, p<0.001). Interestingly, AYAs were more likely to be treated with radiotherapy and chemotherapy compared to OAs (12% vs. 5%, p<0.001). There were also differences within STS subtypes. For example, OAs were more likely to have metastasis compared to AYAs if diagnosed with leiomyosarcoma (18% vs. 10%, p=0.04). In most scenarios AYAs had significantly better OS and RFS compared to OAs, other than for MPNST (OS: p=0.19, RFS: p=0.28).Conclusions: There were several differences between AYAs and OAs on STS presentation, treatment, and outcome. AYAs not only had differences in terms of STS subtypes but also tumor size and malignancy grade within subtypes. Additional work is needed to characterize the biology underlying these differences, which will inform future treatment strategies for both AYAs and OAs with STS.
|
|
| 2. |
- Difilippo, Valeria, et al.
(author)
-
Osteosarcomas With Few Chromosomal Alterations or Adult Onset Are Genetically Heterogeneous
- 2024
-
In: Laboratory investigation; a journal of technical methods and pathology. - 1530-0307. ; 104:1
-
Journal article (peer-reviewed)abstract
- Osteosarcoma is the most common primary bone malignancy, often detected in children and adolescents and commonly associated with TP53 alterations along with a high number of chromosomal rearrangements. However, osteosarcoma can affect patients of any age, and some tumors display less genetic complexity. Besides TP53 variants, data on key driving mutations are lacking for many osteosarcomas, particularly those affecting adults. To detect osteosarcoma-specific alterations, we screened transcriptomic and genomic sequencing and copy number data from 150 bone tumors originally diagnosed as osteosarcomas. To increase the precision in gene fusion detection, we developed a bioinformatic tool denoted as NAFuse, which extracts gene fusions that are verified at both the genomic and transcriptomic levels. Apart from the already reported genetic subgroups of osteosarcoma with TP53 structural variants, or MDM2 and/or CDK4 amplification, we did not identify any recurrent genetic driver that signifies the remaining cases. Among the plethora of mutations identified, we found genetic alterations characteristic of, or similar to, those of other bone and soft tissue tumors in 8 cases. These mutations were found in tumors with relatively few other genetic alterations or in adults. Due to the lack of clinical context and available tissue, we can question the diagnosis only on a genetic basis. However, our findings support the notion that osteosarcomas with few chromosomal alterations or adult onset seem genetically distinct from conventional osteosarcomas of children and adolescents.
|
|
| 3. |
- Geijer, Mats, et al.
(author)
-
Fetthaltiga mjukdelstumörer i rörelseapparaten ofta godartade.
- 2014
-
In: Läkartidningen. - 0023-7205. ; 111
-
Journal article (peer-reviewed)abstract
- Most musculoskeletal soft tissue tumors are benign, lipoma being the most common. Malignant soft tissue tumors may be difficult to clinically distinguish from benign.Scandinavian recommendations are that all lesions suspicious for sarcoma be referred to a sarcoma center. This has led to improved tumor control and less post-operative functional deficits.Magnetic resonance imaging (MRI) can reliably diagnose lipomas, and further work-up is not necessary. Lipomas can be treated at the local hospital.All deep seated musculoskeletal tumors (under the muscle fascia) not unequivocally lipomas should be referred to a sarcoma center.All superficial (subcutaneous) musculoskeletal tumors larger than 5 cm and not unequivocally lipomas should be referred to a sarcoma center.
|
|
| 4. |
- Hesla, Asle Charles, et al.
(author)
-
Ewing sarcoma of the mobile spine; predictive factors for survival, neurological function and local control. A Scandinavian sarcoma group study with a mean follow-up of 12 years
- 2019
-
In: Journal of Bone Oncology. - : Elsevier BV. - 2212-1374 .- 2212-1366. ; 14
-
Journal article (peer-reviewed)abstract
- Object: Many patients with Ewing sarcoma (ES) of the mobile spine present with neurologic symptoms leading to emergency decompressive surgery. Only rarely is optimal treatment involving neo-adjuvant chemotherapy followed by en bloc excision possible. The purpose of this study was to study treatment, neurologic and oncologic outcome in patients with ES of the mobile spine. Methods: Twenty-four patients diagnosed between 1986 and 2012 were identified through the Scandinavian Sarcoma Group registry. Charts were reviewed in order to assess details in patient characteristics, neurologic status, treatment and outcome. Prognostic factors were analyzed with respect to local control, disease-free survival and overall survival. Results: Neurologic symptoms were frequently observed at presentation, being present in 19/23 patients with documented neurologic status. Most (13/19) patients had a complete neurologic recovery regardless of whether or not emergency decompressive surgery was performed. The majority (18/24) of patients were treated with definitive radiotherapy. However, only 9/17 received the recommended dose of ≥ 50.4 Gy. The disease-free and overall survival rates were 48% and 57% at 5 and 10 years, respectively. The local recurrence rates were 19% and 27% at 5 and 10 years, respectively. Only year of diagnosis, categorized into periods with significant changes in chemotherapy protocols, was a significant factor for local recurrence, but there was a trend (p = 0.06) for an increased risk of a local recurrence if emergency decompressive surgery was performed. Conclusion: Patients with ES of the mobile have a relatively favorable prognosis. Nonetheless, local recurrence rate is high for this group of patients for which local treatment mainly relies on definitive radiotherapy. Emergency decompressive surgery may increase the risk for local recurrence.
|
|
| 5. |
- Liu, Yang, et al.
(author)
-
Bone mineral : A trojan horse for bone cancers. Efficient mitochondria targeted delivery and tumor eradication with nano hydroxyapatite containing doxorubicin
- 2022
-
In: Materials Today Bio. - : Elsevier BV. - 2590-0064. ; 14
-
Journal article (peer-reviewed)abstract
- Efficient systemic pharmacological treatment of solid tumors is hampered by inadequate tumor concentration of cytostatics necessitating development of smart local drug delivery systems. To overcome this, we demonstrate that doxorubicin (DOX), a cornerstone drug used for osteosarcoma treatment, shows reversible accretion to hydroxyapatite (HA) of both nano (nHA) and micro (mHA) size. nHA particles functionalized with DOX get engulfed in the lysosome of osteosarcoma cells where the acidic microenvironment causes a disruption of the binding between DOX and HA. The released DOX then accumulates in the mitochondria causing cell starvation, reduced migration and apoptosis. The HA+DOX delivery system was also tested in-vivo on osteosarcoma bearing mice. Locally delivered DOX via the HA particles had a stronger tumor eradication effect compared to the controls as seen by PET-CT and immunohistochemical staining of proliferation and apoptosis markers. These results indicate that in addition to systemic chemotherapy, an adjuvant nHA could be used as a carrier for intracellular delivery of DOX for prevention of tumor recurrence after surgical resection in an osteosarcoma. Furthermore, we demonstrate that nHA particles are pivotal in this approach but a combination of nHA with mHA could increase the safety associated with particulate nanomaterials while maintaining similar therapeutic potential.
|
|
| 6. |
- Papworth, Karin E., 1964-, et al.
(author)
-
Soft-tissue sarcoma in adolescents and young adults compared with older adults : a report among 5000 patients from the Scandinavian Sarcoma Group Central Register
- 2019
-
In: Cancer. - : American Cancer Society. - 0008-543X .- 1097-0142. ; 125:20, s. 3595-3602
-
Journal article (peer-reviewed)abstract
- Background: In recent years, there has been growing awareness of the distinct characteristics of adolescents and young adults (AYA) diagnosed with cancer. Soft-tissue sarcoma (STS) accounts for approximately 1% of all cancers diagnosed in adults and 8% of cancers diagnosed in AYA. To the best of our knowledge, only a few sarcoma registers include data regarding histological subtype, age at diagnosis, and detailed clinical information. Therefore, little is known regarding clinical presentation and outcomes in AYA diagnosed with STS.Methods: Using the Scandinavian Sarcoma Group Central Register, data were obtained regarding 4977 patients who were diagnosed with STS for the period between 1986 and 2011. AYA (those aged 18-39 years) were compared with older adults (OA; those aged 40-80 years) with respect to clinical presentation, treatment, and outcome.Results: There were 868 AYA and 4109 OA. Overall and by STS subtype, there were significant differences noted between AYA and OA with regard to presentation, treatment, and survival. The distribution of STS subtypes was different between OA and AYA (eg, OA were more likely to be diagnosed with malignant fibrous histiocytoma compared with AYA [34% vs 16%; P < .001]). OA also were more likely to have tumors measuring >= 5 cm (68% vs 56%; P < .001) and a higher malignancy grade (75% vs 67%; P < .001). In the majority of STS subtypes AYA had significantly better overall survival and less disease recurrence compared with OA, but this finding was not true for those with malignant peripheral nerve sheath tumors.Conclusions: There are several differences between AYA and OA with STS with regard to presentation, treatment, and survival, and such differences must be taken into consideration when designing clinical trials. Additional work also is needed to characterize the potential biological mechanisms underlying these differences.
|
|
| 7. |
- Saba, Karim H., et al.
(author)
-
Disruption of the TP53 locus in osteosarcoma leads to TP53 promoter gene fusions and restoration of parts of the TP53 signalling pathway
- 2024
-
In: Journal of Pathology. - 0022-3417. ; 262:2, s. 147-160
-
Journal article (peer-reviewed)abstract
- TP53 is the most frequently mutated gene in human cancer. This gene shows not only loss-of-function mutations but also recurrent missense mutations with gain-of-function activity. We have studied the primary bone malignancy osteosarcoma, which harbours one of the most rearranged genomes of all cancers. This is odd since it primarily affects children and adolescents who have not lived the long life thought necessary to accumulate massive numbers of mutations. In osteosarcoma, TP53 is often disrupted by structural variants. Here, we show through combined whole-genome and transcriptome analyses of 148 osteosarcomas that TP53 structural variants commonly result in loss of coding parts of the gene while simultaneously preserving and relocating the promoter region. The transferred TP53 promoter region is fused to genes previously implicated in cancer development. Paradoxically, these erroneously upregulated genes are significantly associated with the TP53 signalling pathway itself. This suggests that while the classical tumour suppressor activities of TP53 are lost, certain parts of the TP53 signalling pathway that are necessary for cancer cell survival and proliferation are retained. In line with this, our data suggest that transposition of the TP53 promoter is an early event that allows for a new normal state of genome-wide rearrangements in osteosarcoma.
|
|
| 8. |
- Saba, Karim H., et al.
(author)
-
Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma
- 2020
-
In: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 6:4, s. 231-237
-
Journal article (peer-reviewed)abstract
- Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.
|
|
| 9. |
- Seinen, Jojanneke, et al.
(author)
-
Delays in the management of retroperitoneal sarcomas.
- 2010
-
In: Sarcoma. - : Hindawi Limited. - 1357-714X .- 1369-1643. ; 2010
-
Journal article (peer-reviewed)abstract
- Retroperitoneal sarcomas are rare and treatment should optimally be centralized. Despite successful centralization with 90% of the patients referred prior to surgery, delays occur, which led us to assess lead times in a population-based series. Method. Patients diagnosed with retroperitoneal sarcoma in the southern Sweden health care region 2003-2009 were eligible for the study. Data on referrals and diagnostic investigations were collected from clinical files from primary health care, local hospitals, and from the sarcoma centre. Lead times were divided into patient delays and health care delays caused by primary health care, local hospitals, or procedures at the sarcoma centre. Results. Complete data were available from 33 patients and demonstrated a median patient delay of 23 days (0-17 months) and median health care delay of 94 days (1-40 months) with delays of median 15 days at the general practitioner, 36 days at local hospitals, and 55 days at the sarcoma centre. Conclusion. Centralization per se is not sufficient for optimized and efficient management. Our findings suggest that delays can be minimized by direct referral of patients from primary health care to sarcoma centers and indicate that development of coordinated diagnostic packages could shorten delays at the sarcoma centre.
|
|
| 10. |
- Seinen, Jojanneke M., et al.
(author)
-
Radiation-Associated Angiosarcoma After Breast Cancer: High Recurrence Rate and Poor Survival Despite Surgical Treatment with R0 Resection
- 2012
-
In: Annals of Surgical Oncology. - : Springer Science and Business Media LLC. - 1534-4681 .- 1068-9265. ; 19:8, s. 2700-2706
-
Journal article (peer-reviewed)abstract
- Secondary angiosarcoma of the breast is a rare but severe long-term complication of breast cancer treated with breast-conserving surgery and radiotherapy. We characterized a population-based cohort of patients with secondary angiosarcomas from two tertiary hospitals to investigate this complication with respect to surgical treatment and outcome. We identified 35 patients with a history of radiation for breast cancer that developed angiosarcoma in the irradiated field from 1990 to 2009. Of these, 31 underwent surgery and were included for analysis. Angiosarcoma developed after median 7 years (range 3-25 years). R0 resection was obtained in 23 of 31 patients after primary treatment. Local recurrence developed in 19 patients after median 6 months (range 1-89 months). Regional and distant metastases occurred in 13 patients after median 17 months (range 2-50 months); nine which also had local recurrence. Patients whose local recurrence could be operated on had a better survival after treatment than those who were not considered for surgical treatment, median 34 months (range 6-84 months) compared with 6 months (range 5-24 months). The median disease-free survival and disease-specific survival was 16 and 37 months, respectively. Despite R0 resection, two-thirds of the patients developed a local recurrence. Survival among those with local recurrence was better if the patient could be treated with surgery. Overall, the prognosis was dismal and median DSS was just over 3 years.
|
|
