Adherence to treatment guidelines for primary sarcomas affects patient survival: a side study of the European CONnective TIssue CAncer NETwork (CONTICANET).

BACKGROUND: The impact of adherence to clinical practice guidelines (CPGs) for loco-regional treatment (i.e. surgery and radiotherapy) and chemotherapy on local disease control and survival in sarcoma patients was investigated in a European study conducted in an Italian region (Veneto). PATIENTS AND METHODS: The completeness of the adherence to the Italian CPGs for sarcomas treatment was assessed by comparing the patient's charts and the CPGs. Propensity score-adjusted multivariate survival analysis was used to assess the impact of CPGs adherence on patient clinical outcomes. RESULTS: A total of 151 patients were included. Adherence to CPGs for loco-regional therapy and chemotherapy was observed in 106 out of 147 (70.2%) and 129 out of 139 (85.4%) patients, respectively. Non-adherence to CPGs for loco-regional treatment was independently associated with AJCC stage III disease [odds ratio (OR) 1.77, P = 0.011] and tumor-positive excision margin (OR 3.55, P = 0.003). Patients not treated according to the CPGs were at a higher risk of local recurrence [hazard ratio (HR) 5.4, P < 0.001] and had a shorter sarcoma-specific survival (HR 4.05, P < 0.001), independently of tumor stage. CONCLUSIONS: Incomplete adherence to CPGs for loco-regional treatment of sarcomas was associated with worse prognosis in patients with non-metastatic tumors.

Prognostic significance of bone or cartilage invasion of locally advanced head and neck cancers.

PURPOSE/OBJECTIVE(S): Locally advanced squamous cell cancers of the head and neck with bone and cartilage invasion (BCI) traditionally have been treated with resection followed up with radiotherapy or less commonly definitive chemoradiotherapy (CRT). However, it is unclear whether bone or cartilage invasion confers a worse prognosis in comparison with each other. MATERIALS/METHODS: T4N0-3M0 squamous cell cancers of the head and neck patients underwent CRT or radical resection followed up with postoperative CRT. Oral cavity, oropharynx, laryngeal and hypopharyngeal squamous cell cancers were included. Radiotherapy ranged from 59.4 to 72 Gy. Concurrent chemotherapy was platinum based. RESULTS: Forty-six patients with BCI were treated. When treated with CRT, 5-year local control was 55% and 43% for BCI, respectively (P = 0.23). Five-year overall survival for these patients was 54% and 29% for BCI, respectively (P = 0.99). When treated with upfront resection, 5-year local control was not significantly different (P = 0.60) nor was 5-year overall survival (P = 0.15). CONCLUSIONS: This study suggests similar outcomes between patients with bone or cartilage invasion treated with upfront CRT or resection followed by CRT. Concurrent CRT may be viable alternative to resection in patients with either bone or cartilage invasion.

Functional outcomes and complications of reconstruction of the proximal humerus after intra-articular tumor resection.

OBJECTIVE: To evaluate functional outcomes and complications of reconstruction of the proximal humerus after intra-articular tumor resection. METHODS: Twenty-five patients who underwent Malawer I type resection and reconstruction of the proximal humerus for treatment of malignant or invasive benign tumors from August 1999 to August 2005 were evaluated. A variety of reconstructive procedures, including modular tumor prosthesis, osteoarticular allograft, and allograft-prosthetic composite (APC), were performed after resection of tumor. Oncological and radiographic parameters were evaluated. The modified Musculoskeletal Tumor Society (MSTS) evaluation system was used to assess limb functional outcome. RESULTS: The study group consisted of 10 male and 15 female patients, among which there were 20 malignant and 5 benign tumors. Restoration of shoulder function was achieved with a prosthesis in 6 patients, osteoarticular allograft in 12, and allograft-prosthesis composite in 7. At a mean of 48 months follow-up, 2 patients had died of disease. Two patients had local recurrence and 2 had metastatic disease. On the basis of the modified MSTS functional evaluation, the mean scores were 22.50 in the modular prosthesis group, 24.58 in the osteoarticular allograft group, and 27.00 in APC group, respectively. Joint instability and subluxation were serious complications affecting shoulder function in 10 patients. CONCLUSION: Reconstruction of the proximal humerus is an option that provides good relief of pain and preserves manual dexterity. Functional outcomes are better for APC and allograft than for modular prosthesis, due to retention of the rotation cuff. Complications in the APC group were less than in the allograft one.

The classic prognostic factors tumor stage, tumor size, and tumor grade are the strongest predictors of outcome in synovial sarcoma: no role for SSX fusion type or ezrin expression.

BACKGROUND: The aim of this study was to investigate prognostic factors influencing the survival of synovial sarcoma, including the debated role of SYT-SSX fusion type and the newly suggested immunohistochemical marker ezrin. PATIENTS AND METHODS: From 1984 to 2005, 45 patients-25 men (56%) and 20 women (44%) with a median age of 31 (range: 2 to 81) years-were diagnosed with a synovial sarcoma. Age at diagnosis, tumor site, tumor size, tumor histology (biphasic vs. monophasic), mitotic count, necrosis, histologic grade, SYT-SSX fusion type, and ezrin immunostaining were analyzed for influence on survival by univariate and multivariate methods. RESULTS: The median follow-up for all patients was 55 (range: 2 to 238) months. Five patients had metastatic disease at the time of presentation. Five-year disease-specific survivals (DSS) were 67% overall and 72% for the 40 patients presenting with localized disease at diagnosis. Nineteen patients (48%) developed metastases during follow-up. Five-year metastasis-free survival (MFS) for the 40 patients with localized disease at diagnosis was 60% and the 10-year MFS was 52%. Disease stage at presentation, tumor size >5 cm, and histologic grade 3 were univariate significant factors associated with a worse DSS. Age >or=30 years, tumor size >5 cm, necrosis, and histologic grade were univariate significant factors associated with a worse MFS. In multivariate analysis, tumor size and tumor grade remained significant prognostic factors for DSS and MFS. A role of SYT-SSX fusion type could not be confirmed in our patient group. Ezrin showed high expression in glandular and nonglandular epithelioid components in biphasic synovial sarcoma. Variable expression was found in the mesenchymal component of monophasic and biphasic synovial sarcoma. Low versus high ezrin expression levels in monophasic and/or biphasic synovial sarcoma did not correlate with patient outcome. CONCLUSIONS: Disease stage at presentation, tumor size, and tumor grade were significant predictors of survival in synovial sarcoma. SYT-SSX fusion type was not correlated with survival in our series. Ezrin expression levels were not discriminative in predicting outcome.

The diagnosis and prognosis of synovial tumors in dogs: 35 cases.

Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.

Alterations of cell cycle regulators in localized synovial sarcoma: A multifactorial study with prognostic implications.

Genetic alterations of cell cycle regulators are thought to represent uncommon and possible secondary events in sarcomas characterized by recurrent chromosomal translocations. The present study investigates this hypothesis on synovial sarcoma (SS), assessing the frequency of expression and possible clinical implications of detecting alterations in critical cell cycle regulatory proteins. A homogeneous cohort of 49 patients with localized SS, restricted to the extremity and with available long-term follow-up information, was selected from our files. We focused our study on molecules involved in the G1 checkpoint and G1-S transition, including cyclins D1 and E, p21(WAF1), p27(Kip1), mdm2, p53, and Ki67. A cutoff point of 10% immunoreactive tumor cell nuclei was selected to define a positive phenotype for any given marker, except for Ki67. High Ki67 proliferative index was considered when >/=20% tumor cells displayed nuclear immunoreactivity. Biphasic SS were analyzed, taking into account separately the expression of these proteins in the spindle and glandular components. Disease specific survival was modeled using the Kaplan-Meier method with log rank test and Cox regression. The cohort of patients analyzed included 23 females and 26 males, and the histological type distribution was 35 monophasic and 14 biphasic SS. The median follow-up for survivors was 53 months, with a 5-year disease-specific survival of 63% and a metastatic disease-free survival of 40%. The positive phenotypes identified for the different markers studied were as follows: cyclin D1, 59%; cyclin E, 29%; p21, 51%; p27, 69%; mdm2, 59%; p53, 16%; and Ki67, 59%. We observed that positive p53, cyclin E, and high Ki67 proliferative index were correlated with survival, but only Ki67 and p53 were independent variables for prognostication. The present study suggests that alterations of cell cycle regulators are more common events in SS than originally thought. p53 overexpression could be of use as a marker together with a high Ki67 proliferative index, in identifying a subset of SS patients with increased risk of tumor relapse.

KIT mutation portends poor prognosis in gastrointestinal stromal/smooth muscle tumors.

Gastrointestinal stromal/smooth muscle tumors (GISTs) are uncommon neoplasms for which current criteria for the diagnosis of malignancy (location, size, and mitotic index) do not always reliably predict patient outcome. Recently, mutation of KIT oncogene exon 11 has been observed in some of these tumors, but the relationship between mutation and clinical outcome has not yet been determined. DNA was obtained from the formalin-fixed, paraffin-embedded tissue of 35 gastric GISTs. A segment of exon 11 was amplified by PCR and sequenced on an ABI 377 sequencer. The relationship between the presence or absence of mutation, tumor size, and mitotic index was investigated using correlation analysis, and the relationship between mutation and outcome was investigated using Kaplan-Meier plots, the Cox-Mantel statistic, and the Cox regression model. Exon 11 deletion mutations were identified in 10 cases, and point mutations were identified in an additional 3 cases; 22 cases demonstrated no KIT mutations. KIT mutation was associated with decreased survival (p = 0.001), with fewer than 30% of patients surviving more than 3 years, compared with over 65% survival for patients whose tumors did not bear the mutation. KIT mutation did not correlate with either the mitotic index or the tumor size. In conclusion, KIT mutation is associated with poor prognosis in patients with gastrointestinal stromal tumors. Whether the KIT mutation will prove to be an independent prognostic factor awaits the completion of larger studies.

DNA content and morphological parameters in synovial sarcoma and synovioma.

By using image analysis technique with 6 normal synovial tissue specimens as controls, nuclear DNA content and morphological parameters in specimens from 51 synovial sarcomas and 15 synovioma were examined quantitatively. The DNA content in synovial sarcoma and synovioma was significantly different (P < 0.01), and that of synovioma and normal synovial tissue was also different (P < 0.05). Morphological parameters including nuclear areas and perimeters differed significantly among the above three groups (P < 0.01). There was no correlation between the DNA content of synovial sarcoma and its histologic type (P > 0.05), but the DNA content greatly differed between its higher and lower differentiated grade in each type (P < 0.01). The DNA content in synovial sarcoma IIA stage, according to Enneking's staging system was lower than that in IIB, IIIA and IIIB (P < 0.05). The 5-year survival rate of synovial sarcoma with diploid/nearly diploid (D/ND) pattern was higher than that of aneuploid (AN) pattern (P = 0.028). The study suggests that analysis of the DNA content and morphological parameters of tumor cells is helpful in the diagnosis and pathologic grading of synovial sarcoma. It also provides a guide to clinical operation and estimation of the prognosis. Although synovioma is usually a well-differentiated and benign lesion, this investigation also suggested that increased DNA content may be an indication of poor prognosis for this neoplasm.

Epidemiology of cancer of the connective tissue in Canada during the period 1950-1985.

Canadian patterns of morbidity and mortality from malignancies of the connective tissue were examined for the periods 1970-1982 and 1950-1985, respectively. Age-standardized morbidity rates have risen significantly during 1970-1982 in males (P = 0.005), whereas the increase noted in females was of borderline significance (P = 0.055). Examination of age-specific morbidity rates during this period revealed that rates for the eight age groups studied in males have increased, with rates of increase for males aged 65-74 attaining statistical significance (P = 0.0006), whereas increases for males aged 0-24 and 75-84 years were of borderline significance (P less than 0.08). Age-standardized mortality rates during 1950-1985 have risen significantly for both males (0.013 additional new deaths per 100,000 population per year; P less than 0.0001) and females (0.008 additional new deaths per 100,000 population per year; P less than 0.0001). Significant rates of increase were noted in age-specific mortality rates for seven of the eight age groups studied in males (P less than 0.03) and for five of the eight age groups studied in females (P less than 0.04). The rate of increase for women aged 35-44 years was of borderline significance (P = 0.06). Rates of increase in age-specific mortality rates were greatest in males and females aged 75-84 years at 0.113 and 0.059 additional new deaths per 100,000 population per year, respectively.

[Surgical therapy of malignant soft tissue tumors]. / Chirurgische Therapie maligner Weichteiltumoren.

Soft-tissue sarcomas are rare neoplasms originating from the extraskeletal connective tissues of the body. The GTNM-system is recommended for clinical staging. The most effective treatment are radical surgery and the combination of limited surgical removal and high-dose irradiation. In the management of soft-tissue sarcomas of the extremities the isolated hyperthermic perfusion is a successful adjuvant to excision for saving a tumour bearing limb.