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2.  Reliability of Margin Assessment after Surgery for Extremity Soft Tissue Sarcoma: The SSG Experience 
Sarcoma  2012;2012:290698.
Surgery remains the mainstay of soft tissue sarcoma (STS) treatment and has been the primary treatment for the majority of patients in Scandinavia during the last 30 years although the use of adjuvant radiotherapy has increased. Patient and treatment characteristics have been recorded in the Scandinavian Sarcoma Group (SSG) Register since 1987. When the effect of new radiotherapy guidelines from 1998 was evaluated, the reliability of surgical margin assessments among different Scandinavian institutions was investigated. Margins were reevaluated by a panel of sarcoma surgeons, studying pathology and surgical reports from 117 patients, randomly selected among 470 recorded patients treated between 1998–2003. In 80% of cases, the panel agreed with the original classification. Disagreement was most frequent when addressing the distinction between marginal and wide margins. Considered the element of judgment inherent in all margin assessment, we find this reliability acceptable for using the Register for studies of local control of STS.
doi:10.1155/2012/290698
PMCID: PMC3385668  PMID: 22761544
3.  Radiation-Associated Angiosarcoma After Breast Cancer: High Recurrence Rate and Poor Survival Despite Surgical Treatment with R0 Resection 
Annals of Surgical Oncology  2012;19(8):2700-2706.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1245/s10434-012-2310-x
PMCID: PMC3404270  PMID: 22466664
4.  Delays in the Management of Retroperitoneal Sarcomas 
Sarcoma  2010;2010:702573.
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.
doi:10.1155/2010/702573
PMCID: PMC2964909  PMID: 21048999
5.  Happy birthday, Acta! 
Acta Orthopaedica  2010;81(1):1-2.
doi:10.3109/17453671003685392
PMCID: PMC2856195  PMID: 20175644
6.  New format, Open Access, and online pre-publication 
Acta Orthopaedica  2009;80(1):1.
doi:10.1080/17453670902804406
PMCID: PMC2823245  PMID: 19301447
7.  Genetic Profiling Differentiates Second Primary Tumors from Metastases in Adult Metachronous Soft Tissue Sarcoma 
Sarcoma  2009;2008:431019.
Purpose. Patients with soft tissue sarcomas (STS) are at increased risk of second primary malignancies, including a second STS, but distinction between metastases and a second primary STS is difficult. Patients and Methods. Array-based comparative genomic hybridization (aCGH) was applied to 30 multiple STS of the extremities and the trunk wall from 13 patients. Different histotypes were present with malignant fibrous histiocytomas/undifferentiated pleomorphic sarcomas being the predominant subtype. Results. aCGH profiling revealed genetic complexity with multiple gains and losses in all tumors. In an unsupervised hierarchical cluster analysis, similar genomic profiles and close clustering between the first and subsequent STS were identified in 5 cases, suggesting metastatic disease, whereas the tumors from the remaining 8 patients did not cluster and showed only weak pairwise correlation, suggesting development of second primary STS. Discussion. The similarities and dissimilarities identified in the first and second STS suggest that genetic profiles can be used to distinguish soft tissue metastases from second primary STS. The demonstration of genetically different soft tissue sarcomas in the same patient suggests independent tumor origin and serves as a reminder to consider development of second primary STS, which has prognostic and therapeutic implications.
doi:10.1155/2008/431019
PMCID: PMC2634844  PMID: 19197386
8.  Diagnostic and prognostic gene expression signatures in 177 soft tissue sarcomas: hypoxia-induced transcription profile signifies metastatic potential 
BMC Genomics  2007;8:73.
Background
Soft tissue sarcoma (STS) diagnosis is challenging because of a multitude of histopathological subtypes, different genetic characteristics, and frequent intratumoral pleomorphism. One-third of STS metastasize and current risk-stratification is suboptimal, therefore, novel diagnostic and prognostic markers would be clinically valuable. We assessed the diagnostic and prognostic value of array-based gene expression profiles using 27 k cDNA microarrays in 177, mainly high-grade, STS of 13 histopathological subtypes.
Results
Unsupervised analysis resulted in two major clusters – one mainly containing STS characterized by type-specific genetic alterations and the other with a predominance of genetically complex and pleomorphic STS. Synovial sarcomas, myxoid/round-cell liposarcomas, and gastrointestinal stromal tumors clustered tightly within the former cluster and discriminatory signatures for these were characterized by developmental genes from the EGFR, FGFR, Wnt, Notch, Hedgehog, RAR and KIT signaling pathways. The more pleomorphic STS subtypes, e.g. leiomyosarcoma, malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma, were part of the latter cluster and were characterized by relatively heterogeneous profiles, although subclusters herein were identified. A prognostic signature partly characterized by hypoxia-related genes was identified among 89 genetically complex pleomorphic primary STS and could, in a multivariate analysis including established prognostic markers, independently predict the risk of metastasis with a hazard ratio of 2.2 (P = 0.04).
Conclusion
Diagnostic gene expression profiles linking signaling pathways to the different STS subtypes were demonstrated and a hypoxia-induced metastatic profile was identified in the pleomorphic, high-grade STS. These findings verify diagnostic utility and application of expression data for improved selection of high-risk STS patients.
doi:10.1186/1471-2164-8-73
PMCID: PMC1839099  PMID: 17359542
9.  Focus on the Tumour Periphery in MRI Evaluation of Soft Tissue Sarcoma: Infiltrative Growth Signifies Poor Prognosis 
Sarcoma  2006;2006:21251.
Purpose. Infiltrative microscopical peripheral growth of soft tissue sarcomas (STS) has been shown to be of prognostic importance and preoperative risk stratification could individualize neoadjuvant treatment. Patients and methods. We assessed peripheral tumour growth pattern on preoperative MRI from 78 STS. The findings were correlated to histopathology and to outcome. Results. The MRI-based peripheral tumour growth pattern was classified as pushing in 34 tumours, focally infiltrative in 25, and diffusely infiltrative in 19. All tumours with diffuse infiltration on MRI also showed microscopical infiltration, whereas MRI failed to identify infiltration in two-thirds of the microscopically infiltrative tumours. Diffusely infiltrative growth on MRI gave a 2.5 times increased risk of metastases (P = .01) and a 3.7 times higher risk of local recurrence (P = .02). Discussion. Based on this observation we suggest that MRI evaluation of STS should focus on the peripheral tumour growth pattern since it adds prognostic information of value for decisions on neoadjuvant therapies.
doi:10.1155/SRCM/2006/21251
PMCID: PMC1779504  PMID: 17496992
10.  Should tumor depth be included in prognostication of soft tissue sarcoma? 
BMC Cancer  2003;3:17.
Background
Most staging systems for soft tissue sarcoma are based on histologic malignancy-grade, tumor size and tumor depth. These factors are generally dichotomized, size at 5 cm. We believe it is unlikely that tumor depth per se should influence a tumor's metastatic capability. Therefore we hypothesized that the unfavourable prognostic importance of depth could be explained by the close association between size and depth, deep-seated tumors on average being larger than the superficial ones. When tumor size is dichotomized, this effect should be most pronounced in the large size (>5 cm) group in which the size span is larger.
Methods
We analyzed the associations between tumor size and depth and the prognostic importance of grade, size and depth in a population-based series of 490 adult patients with soft tissue sarcoma of the extremity or trunk wall with complete, 4.5 years minimum, follow-up.
Results
Multivariate analysis showed no major prognostic effect of tumor depth when grade and size were taken into account. The mean size of small tumors was the same whether superficial or deep but the mean size of large and deep-seated tumors were one third larger than that of large but superficial tumors. Tumor depth influenced the prognosis in the subset of high-grade and large tumors. In this subset deep-seated tumors had poorer survival rate than superficial tumors, which could be explained by the larger mean size of the deep-seated tumors.
Conclusion
Most of the prognostic value of tumor depth in soft tissue sarcomas of the extremity or trunk wall can be explained by the association between tumor size and depth.
doi:10.1186/1471-2407-3-17
PMCID: PMC161793  PMID: 12769830
prognosis; soft tissue sarcoma; staging; tumor depth
11.  Chest Wall Sarcoma: Outcome in 22 Patients After Resection Requiring Thoracic Cage Reconstruction 
Sarcoma  1998;2(3-4):143-147.
Purpose. To evaluate the outcome after resection of malignant chest wall sarcoma, requiring reconstruction of the chest wall.
Subjects. Twenty-two patients, 15 with primary tumours, were operated on in our institution between 1983 and 1996. Four patients underwent surgery after a previous intralesional or marginal excision and three patients because of a local recurrence.
Methods. The tumour was resected ‘en bloc’, including skin, muscle and thoracic skeleton. When necessary, adjacent organs invaded by the tumour, such as lung, pericardium and diaphragm, were also removed to obtain a wide margin. Reconstruction of the chest wall was performed with Marlex mesh (n=9), methylmethacrylate cement (n=2) or a Marlex methylmethacrylate ‘sandwich’ (n=11).
Results. The median tumour size was 9.5 (2–20) cm. The most common type of tumour was chondrosarcoma (12 cases). No patient died in hospital. Five patients required reoperation because of complications, two patients because of loosening of the acrylate prosthesis, two because of necrosis of soft tissue coverage and one was reoperated because of bleeding. Four patients died of generalized tumour disease between 5 and 77 months after surgery and one patient died of a local recurrence 32 months after the primary operation. Seventeen patients are alive, with a median follow-up of 36 (4–162) months. Microscopic radicality (negative margin) was achieved in 17 patients but 5 of these had local recurrences. Two of five patients with positive margins had a local recurrence of the tumour. Of the seven patients with local recurrences, two also developed metastases.
Discussion. Large chest wall sarcomas can be successfully resected and the chest wall reconstructed with low morbidity and mortality.
doi:10.1080/13577149877894
PMCID: PMC2395395  PMID: 18521246
12.  Improving the management of soft tissue sarcoma 
BMJ : British Medical Journal  1998;317(7151):93-94.
PMCID: PMC1113522  PMID: 9657781

Results 1-12 (12)