Prognostic Factors In Soft Tissue Sarcoma Research Articles

Finding the Common Thread in Rare Diseases

Soft-tissue sarcomas are extremely rare, with an estimated 11 930newcases in theUnitedStates in2015, representing less than 1% of all new cancer cases.1 They are a heterogeneous group of diseases with more than 80 different histologic types and subtypes that have widely different clinical behaviors andoutcomes.2 Leiomyosarcomas involving the inferiorvenacava (IVC)are the rarest of the rare; even at tertiary referral centers, no more than approximately 1 case per year is seen.3 In this issue of JAMA Surgery, Roland et al4 describe one of the largest singleinstitution reviews of leiomyosarcomas arising from the IVC and other vessels, adding to our very limited understanding of these rare diseases. For all surgeonswho resect retroperitoneal neoplasms, an important take-home point is preoperative recognition and preparation.5 Consider the possibility of a leiomyosarcoma in the IVCwhen imagingshowsaright-sidedretroperitonealmass abutting the IVC (especially if no lumen is present at the site of contact) or an intraluminal IVC mass,6 and anticipate the complex surgical issuespotentially necessary for removal (eg, ligation, patch, or graft of IVC;managementof renal veins; hepatectomy; or cardiopulmonary bypass). A complete resection, performed safely, is the only chance for long-term survival.3 However, local and distant recurrences are common, so better adjuvant therapies are needed. Site is an important prognostic factor for soft-tissue sarcomas.2 The series of patients in Roland et al4 includes patientswith leiomyosarcomas arising fromthe IVC (n = 42) and patientswith leiomyosarcomas arising fromother vessels, includingsaphenous, femoral, renal,andupper-extremityveins.4 Certainly, the surgical complexity of resecting a leiomyosarcoma in the IVC is much greater than the surgical complexity of resecting one arising from an upper-extremity vein. Other factors, suchasunique tumorbiology,mayalso affect theoutcomes of patients with leiomyosarcomas arising from different vessels, so it may not be appropriate to lump all these heterogeneous sites together. Nevertheless, Roland et al4 should be applauded for their immunohistochemical studies seeking to identify the specificmolecular alterations thatmaybedriving tumorprogression and thatmay serve aspotential targets for therapy.4 Leiomyosarcomas arising from various vessels may share key signaling pathways that drive other forms of cancer. As new therapies targeting these signaling pathways are developed, there is the hope of improving the outcome of patients with cancer, including those patients with extremely rare types of cancer that share these molecular alterations.

Prognostic factors in soft-tissue sarcomas: what have we learnt?

John Abernethy (1764–1831) first introduced the term ‘sarcoma’, which in Greek means a fleshy excrescence, to describe a circumscribed neoplasm consisting of malignant fat cells occurring principal...

Outcomes for Soft-Tissue Sarcoma in 8249 Cases from a Large State Cancer Registry

To date, outcome reports for soft-tissue sarcoma (STS) have largely been limited to single or paired institutional series. To more accurately elucidate population-based outcomes and prognostic factors associated with STS, a large cancer registry was examined. STS arising in the Florida Cancer Data System were examined (1981-2004). A total of 8249 patients were identified, the calculated annual incidence of sarcoma being approximately 38 cases per million in 2003. The tumor histologies among these patients were leiomyosarcoma and gastrointestinal stromal tumor (LMS/GIST) (43.5%), malignant fibrous histiocytoma (MFH) (31.5%), liposarcoma (19.0%), and fibrosarcoma (6.0%). Tumors were situated in the extremities (30.7%), truncal or visceral locations (50.4%), retroperitoneum (11.7%), and head or neck (7.2%). Thirty-three percent of lesions were over 10 cm in greatest dimension, while 50.2% were classified as high grade. Median overall survival was 25 months. Superior survival was observed for liposarcomas and fibrosarcomas as compared to MFH and LMS/GIST (P < 0.001). Retroperitoneal and truncal sarcomas had a more ominous prognosis than did other sites (P < 0.001). Multivariate analysis of pretreatment variables demonstrated that increasing age, male gender, non-Caucasian race, advanced stage, and a truncal or retroperitoneal location were each independently associated with lower survival. Histological subtype was also an independent predictor of outcome. Surgical resection and radiation therapy were the only treatment variables shown to improve survival. Histological subtype, tumor site, and stage are independent prognostic factors in STS. Surgical resection and radiotherapy are unique among treatment modalities in association with a significant survival benefit.

P20: Outcomes for soft tissue sarcoma in 8249 cases from a large state cancer registry

Introduction: To date, outcome reports for soft tissue sarcoma (STS) have largely been limited to single or paired institutional series. To more accurately elucidate population-based outcomes and prognostic factors associated with STS, a large cancer registry was examined. Methods: STS arising in the Florida Cancer Data System were examined (1981 - 2004). Results: A total of 8249 patients were identified, the calculated annual incidence of sarcoma being approximately 38 cases per million in 2003. The tumor histologies among these patients were leiomyosarcoma and GIST (LMS/GIST) (43.5%), malignant fibrous histiocytoma (MFH) (31.5%), liposarcoma (19.0%) and fibrosarcoma (6.0%). Tumors were situated in the extremities (30.7%), truncal or visceral locations (50.4%), retroperitoneum (11.7%), and head or neck (7.2%). Thirty-three percent of lesions were over 10 cm in greatest dimension, while 50.2% were classified as high grade. Metastatic disease was present in 16.3% of patients at the time of diagnosis. Median overall survival for the cohort was 25 months. Superior survival was observed for liposarcomas and fibrosarcomas as compared to MFH and LMS/GIST (p < 0.001). Retroperitoneal and truncal sarcomas had a more ominous prognosis than did other sites (p < 0.001). Multivariate analysis of pre-treatment variables demonstrated that increasing age, male gender, non-Caucasian race, advanced stage and a truncal or retroperitoneal location were each independently associated with lower survival. Histological subtype was also an independent predictor of outcome. Surgical resection and radiation therapy were the only treatment variables shown to improve survival. Conclusions: Histological subtype, tumor site and stage are independent prognostic factors in STS. Surgical resection and radiotherapy are unique among treatment modalities in association with a significant survival benefit.

Expression of hypoxia-inducible factor (HIF)-1α as a biomarker of outcome in soft-tissue sarcomas

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that supports the adaptation of human cancer cells to hypoxia and tumor growth and progression. The overexpression of HIF-1alpha protein has been reported to be associated with a worse prognosis in various cancers. However, the expression of HIF-1alpha in soft-tissue sarcomas has not yet been characterized. The expression of HIF-1alpha protein was immunohistochemically determined in 49 specimens of soft-tissue sarcomas including malignant fibrous histiocytoma (29 patients), synovial sarcoma (12 patients), leiomyosarcoma (four patients), and malignant peripheral nerve sheath tumors (four patients). The 49 samples consisted of 40 primary lesions and nine local recurrences. An immunohistochemical analysis showed the nuclear accumulation of HIF-1alpha protein in 35 (71.4%) samples. The expression of HIF-1alpha was negative in 14 (28.6%) cases, weak in nine (18.4%), moderate in 17 (35.4%), and strong in nine (18.4%). The patients with a strong or moderate expression of HIF-1alpha had a significantly shorter overall survival rate in comparison with those with a weak or negative expression in a univariate analysis (P = 0.029; log-rank test) and multivariate analysis (P = 0.018). This is the first report that demonstrated an overexpression of HIF-1alpha protein to be an independent prognostic factor for soft-tissue sarcomas.

An assessment of prognostic factors in soft-tissue sarcoma of the head and neck.

This study evaluates the outcome, patterns of failure, and prognostic factors in head and neck soft-tissue sarcoma in the adult. A retrospective evaluation of 73 patients treated recently for this rare disease. The minimum follow-up for all patients was 3 years with the living patients having a mean follow-up of 4.6 years. All patients were treated between January 1980 and December 1988, at the Princess Margaret Hospital-Ontario Cancer Institute, Toronto, the major sarcoma referral center for a population in excess of 3 million. PATIENTS OR PARTICIPANTS AND INTERVENTIONS: Fifty-two patients were treated with curative intent: 10 by surgery without radiotherapy and 42 with surgery and radiotherapy. Twelve patients received adjuvant chemotherapy. Five-year cause-specific survival, local relapse, and distant failure rates were calculated by the product limit method. Comparisons between survival curves were carried out by the log-rank statistic and Cox regression analysis was performed to assess the influence of prognostic factors. The 5-year cause-specific survival was 62%, with a local relapse rate of 41% and distant relapse rate of 31%. Extension to adjacent structures, high grade, and large lesion size were associated with poorer survival. Gross residual tumor also was associated with high local failure (75% failure) despite the addition of radiation therapy. Those with clear surgical margins or only microscopic involvement fared much more favorably and had similar local control rates (26% and 30% failure, respectively) provided adjuvant radiotherapy was given. However, 68% of patients dying as a result of their sarcoma had uncontrolled local disease because of the high incidence (27%) of gross residuum following surgery in this series. This series highlights the absolute necessity for resection of all overt disease with planned adjunctive radiotherapy and appropriate reconstruction in most cases. This is achieved more easily in the setting of a specialized sarcoma treatment unit.

Nuclear immunoreaction of p53 protein in soft tissue sarcomas. A possible prognostic factor

Tumor suppressor gene p53, located on the short arm of chromosome 17, frequently mutates in various types of cancers and plays a critical role in the multiple stages of carcinogenesis. However, there is little information about the clinicopathologic significance of alterations of the p53 gene in soft tissue sarcomas (STS). Because it is known that nuclear accumulation of p53 protein correlates closely with the presence of mutations in the p53 gene, immunohistochemical detection of this protein was performed. A polyclonal antibody (RSP-53) raised against synthetic human p53 peptide was used to detect nuclear accumulation of the protein. Pathologic specimens of 96 patients with STS were collected from the surgical pathology files of the National Cancer Center Hospital and examined. Nuclear accumulation of p53 protein was detected in 31 (32.3%) patients. The percentage of patients with a positive immunoreaction was high in patients with malignant schwannoma (100%), rhabdomyosarcoma (71.4%), and synovial sarcoma (50.0%), whereas it was low in patients with liposarcoma (13.6%) and 0% in those with fibrosarcoma. It was closely associated with the histologic grade of malignancy (grade 1, 12.0%; grade 2, 30.8%; grade 3, 44.4%) and the patient's age (younger than 40 years, 46.9%; 40 years of age or older, 25.0%). Both overall and metastasis-free survival rates were significantly lower for patients with a nuclear p53 immunoreaction than for those without it. The nuclear p53 immunoreaction is considered a marker of tumor aggressiveness and appears to be a useful prognostic factor for STS.

Prognostic significance of mast cells in soft tissue sarcoma.

We counted the number of toluidine blue positive mast cells within and around the tumor in 44 patients with soft tissue sarcomas (STS). Irrespective of their histologic types, these cases were broadly divided into the following two groups: (1) low count (less than 20 mast cells/10 high-power fields [HPF]) and (2) high count (greater than or equal to 20 mast cells/10 HPF). The patients with a high mast cell count showed a significantly better 5-year survival rate than those with a low count (85.9% versus 30.5%; P less than 0.01). Five patients with distant metastases at first admission all belonged to the low count group. These results suggest that the number of mast cells within and around the tumor is a useful prognostic factor for STS.

Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system.

The pathological features of 155 adult patients with soft-tissue sarcomas were studied retrospectively, in an attempt to set up a grading system for these tumors. As the first step, seven histological criteria (tumor differentiation, cellularity, importance of nuclear atypia, presence of malignant giant cells, mitosis count, pattern of tumor necrosis and presence of vascular emboli) were evaluated in a monofactorial analysis. Five of these (tumor differentiation, cellularity, mitosis count, tumor necrosis, and vascular emboli) were correlated with the advent of metastases and with survival. A multivariate analysis, using a Cox model, selected a minimal set of three factors (tumor differentiation, mitosis count, and tumor necrosis) the combination of which was necessary and sufficient to retain all the prognostic information. A grading system was elaborated, which turned out to be correlated with the advent of metastasis and with patients' survival. A second multivariate analysis introducing clinical prognostic features showed that the histological grade was the most important prognostic factor for soft-tissue sarcomas. Thus, this grading system appears to be highly interesting because of its prognostic value and the facility of its elaboration. However, its reproducibility should be tested.