European Journal of Cancer’s Biennial report on soft tissue and visceral sarcomas or the rapid evolution of treatment concepts in sarcomas

Soft tissue and visceral sarcoma gather a large group of rare to very rare cancers and locally aggressive connective tissue tumours. Novel concepts on histological and molecular classification, optimal management of patients, systemic adjuvant and neoadjuvant treatment have been emerging in the last 5 years. In the present publication, we review and summarise significant changes which impact on disease management in this group of rare cancers.     

Should tumor depth be included in prognostication of soft tissue sarcoma?

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.     

What is the role of routine follow-up for localised limb soft tissue sarcomas? A retrospective analysis of 174 patients

Background:

There are neither prospective data nor agreement on the optimal routine follow-up procedures in patients treated for soft tissue sarcoma of the limb.

Methods:

Data on 174 consecutive patients with a soft tissue sarcoma of the limb undergoing follow-up by oncologists at a single centre from 2003 to 2009 were included in this analysis. The rate and site of recurrence and mode of detection were analysed. Outcome of the patients was assessed.

Results:

Eighty-two patients (47%) experienced relapse of any type. Isolated local recurrence occurred in 26 patients and local relapse with synchronous pulmonary metastases in five patients. Local recurrences were detected clinically in 30 of these 31 patients; magnetic resonance imaging identified only one local recurrence. Twenty-eight patients developed isolated lung metastases; in nine patients these were amenable to resections, seven of whom are currently free of disease after treatment. Lung metastases were detected by chest x-ray (CXR) in 19 patients, computed tomography scanning in 3 patients, and clinically in 11 patients. Twenty-three patients developed non-pulmonary metastases. More than 80% of relapses occurred in the first 2 years of follow-up; however, later recurrences were also observed.

Conclusions:

Routine follow-up CXR can detect lung metastases suitable for surgical resection, although the optimal interval of imaging has yet to be defined. Local relapse is almost always detected by patients or physicians, and routine scanning of the primary site is of doubtful benefit. Patient and physician education to detect local relapse may be helpful. Prospective evaluation of follow-up is recommended.     

Chemotherapy in alveolar soft part sarcomas. What do we know?

Alveolar soft part sarcoma (ASPS) is a rare tumour. Published series about treatment and outcome are scarce. Conclusive data about the response to chemotherapy are not available. The aim of this study was to analyse the efficacy of palliative chemotherapeutic treatment options and the incidence and mode of presentation of brain metastases. We retrospectively analysed our own sarcoma data-base and reviewed the literature. From our registry containing 757 patients, we identified 8 patients with ASPS. From the literature, 47 cases of adult patients and 13 children with sufficient data about chemotherapy were identified. Response to first-line chemotherapy in 68 patients was: complete remission (CR) 4%, partial remission (PR) 3%, stable disease (SD) 41%, progressive disease (PD) 51%. 285 patients with stage IV disease were evaluable for the analysis of metastatic sites. The incidence of brain metastases was 30.5% (87/285). Brain metastases were detected at a median interval of 48 months (range 0-396 months) after the primary diagnosis. Median survival after the diagnosis of brain metastases was 12 months. The median survival for patients with stage IV disease treated by chemotherapy was 36+ months (range 10-132 months) (31 patients evaluable) with a median follow-up of 46 months (range 10-135 months). ASPS shows a high incidence of brain metastases, at least 3 times higher than that of other soft tissue sarcomas. Chemotherapeutic regimens used for the treatment of other soft tissue sarcomas lack efficacy in ASPS. Staging investigations for ASPS should routinely include imaging of the brain. ASPS patients should not be treated with chemotherapy outside of controlled clinical trials. New targets for specific biologically-directed therapies need to be developed.     

Treatment of patients with advanced soft tissue sarcoma: disappointment or challenge?

PURPOSE OF REVIEW: We give an overview on the emerging compounds for patients with soft tissue sarcoma. Included are recent developments in targeted therapy, focusing on the following: antiangiogenic and immunomodulatory drugs (e.g. anti-cytotoxic T lymphocyte associated antigen-4 monoclonal antibody), Bcl-2 antisense therapy, raf kinase and mammalian target of rapamycin inhibition, heat shock protein modulators, minor groove binders and other agents being developed. RECENT FINDINGS: Soft tissue sarcomas are a heterogeneous group of tumours that arise predominantly from the embryonic mesoderm. They account for fewer than 1% of all adult malignancies. The prognosis of patients with advanced metastatic soft tissue sarcoma remains poor, with disease-free survival at 5 years below 10%. Complete resection remains the only potentially curative treatment option. Only few chemotherapeutic agents have been identified to be active, with reported response rates for doxorubicin and ifosfamide of around 20%. New strategies are urgently needed to improve outcomes. SUMMARY: Understanding of the molecular biology and pathogenesis of soft tissue sarcomas has been enhanced, and in the near future this should translate into molecular tumour characterization and development of new therapeutic strategies.     

Routine bone scintigraphy in primary staging of soft tissue sarcoma; Is it worthwhile?

BACKGROUND: The incidence of bone metastases in soft tissue sarcoma (STS) patients seems to be low but has not been studied separately. In this study, the authors aimed to determine the value of routine radionuclide bone scanning in preoperative staging of STS patients. METHODS: Preoperative bone scans were evaluated retrospectively in 109 consecutive patients (median age, 44 years; range, 1-86) with intermediate or high grade STS. Scans were scored in 3 categories: 1, metastases very likely; 2, equivocal; and 3, normal or benign lesions. RESULTS: Category 1 scans were found in 8 of 109 patients (7%); in all 8 patients, bone metastases were confirmed. Six of these eight patients reported pain, and all had additional lung, bone marrow, or lymph node metastases. The highest rate (17%) was found in the rhabdomyosarcoma subgroup (n = 18). Category 2 (equivocal) scans were present in 12 of 109 patients (11%), in all of which bone metastases were excluded through additional investigations. Category 3 (normal) scans were found in 81%. Bone metastases were at least as frequent as lung metastases (4%) and were the single site of systemic disease in 4%. The rate of bone metastases was 55% in patients with bone pain versus 2% in patients without pain. CONCLUSIONS: Bone metastases in primary STS patients are rare (7%) yet in this study at least as frequent as lung metastases. The low rate in asymptomatic patients versus the high rate in symptomatic patients supports the use of bone scanning in symptomatic patients only. The yield of routine bone scanning is low.     

Caveolin-1 in sarcomas: friend or foe?

Sarcomas represent a heterogeneous group of tumors with a complex and difficult reproducible classification. Their pathogenesis is poorly understood and there are few effective treatment options for advanced disease. Caveolin-1 is a multifunctional scaffolding protein with multiple binding partners that regulates multiple cancer-associated processes including cellular transformation, tumor growth, cell death and survival, multidrug resistance, angiogenesis, cell migration and metastasis. However, ambiguous roles have been ascribed to caveolin-1 in signal transduction and cancer, including sarcomas. In particular, evidence indicating that caveolin-1 function is cell context dependent has been repeatedly reported. Caveolin-1 appears to act as a tumor suppressor protein at early stages of cancer progression. In contrast, a growing body of evidence indicates that caveolin-1 is up-regulated in several multidrug-resistant and metastatic cancer cell lines and human tumor specimens. This review is focused on the role of caveolin-1 in several soft tissue and bone sarcomas and discusses the use of this protein as a potential diagnostic and prognostic marker and as a therapeutic target.