Low-grade fibromyxoid sarcoma: A report of the Cooperative Weichteilsarkom Studiengruppe (CWS).

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft-tissue tumor with benign histologic appearance, though fully malignant behavior is possible. METHODS: Patients with LGFMS <21 years registered in Cooperative Weichteilsarkom Studiengruppe trials until 2017 were analyzed. Firstline treatment consisted of complete surgical resection whenever possible. RESULTS: Median age of 31 patients was 10.9 years (first month to 17.1 years). Twenty-six tumors were confirmed to the tissue of origin (T1), four invaded contiguous structures (T2), one was TX. Eight were >5 cm. The best surgical result was resection with free margins (R0) in 24 and microscopic residuals (R1) in seven. Five-year event-free (EFS), 5-year local-relapse-free (LRFS), and 5-year overall-survival were 71 ± 18.6% confidence interval (CI) 95%, 76 ± 17.6% CI 95%, and 100%, respectively. Six patients suffered local relapse in a median of 1 year, one combined within 1.3 year and one metastatic relapse with lesions in the lung, back muscles, and thigh discovered in whole-body imaging 6 years after the first diagnosis. In univariate analysis, T status correlated with EFS (T1 79.6 ± 18.6%, T2 50.0 ± 49.0%, P = .038). Resection with free margins tends to be associated with better LRFS (R0 82.4 ± 18.6%, R1 53.6 ± 39.4%, P = .053). Among 24 patients with R0 resection, five (21%) suffered relapse, thereof three local, one metastatic, and one combined. Among seven patients with R1-resection, three (43%) suffered local relapse. CONCLUSION: Special caution is advisable in T2 tumors. The metastatic potential with lesions in unusual sites indicates that affected patients need to be informed. If long-term follow-up with whole-body imaging is beneficial, it may be addressed in larger intergroup analyses. Further research in disease biology is essential for optimal treatment and follow-up care.

Localized synovial sarcoma of the foot or ankle: A series of 32 Cooperative Weichteilsarkom Study Group patients.

BACKGROUND: Synovial sarcoma of the foot/ankle is rare. Mutilating surgery is often discussed. METHODS: Patients registered from 1981 to 2013 were analyzed. Cooperative Weichteilsarkom Studiengruppe (CWS) protocols recommend chemotherapy for all synovial sarcoma patients. RESULTS: Thirty-two of 330 patients with localized synovial sarcoma had their tumor at the foot/ankle. Eleven of thirty-two tumors were >5 cm. Twenty were T1, 11 T2, and one TX, respectively. Eight (25%) patients underwent primary complete resection with free margins (Intergroup Rhabdomyosarcoma Study [IRS] I), 12 of 32 (38%) primary complete resection with positive margins (IRS II), and 12 of 32 (38%) had macroscopic residuals (IRS III). The best surgical result at any time was R0 in 19, R1 in 10 and R2 in one patient, and missing in two. Mutilation was documented in 14 of 32 (44%). Radiotherapy was conducted in 20 patients. All patients achieved a first complete remission. Five-year-event-free survival and overall survival rates were 80% and 86%, respectively. Four patients suffered local and four other metastatic recurrences. IRS and the best surgical result at any time did not correlate with survival. There was no prognostic difference between R0- and R1-resection. CONCLUSION: Survival expectancies for patients with localized synovial sarcomas of the foot/ankle compare favorably to that of those with other affected sites. DISCUSSION: Further studies are needed to set the limits of minimally required aggressiveness of local therapies.

Extraskeletal osteosarcoma of the breast in an adolescent girl.

Extraskeletal osteosarcoma (ESOS) is a rare malignancy, usually arising in older adults. We were unable to find reports of children or adolescents affected by an ESOS of the breast. Here, we present the case of a high-grade osteosarcoma arising in the breast of a 16-year-old girl. The tumor was treated with breast-conserving resections and adjuvant multiagent chemotherapy, based on a regimen of doxorubicin, high-dose methotrexate, cisplatin, and ifosfamide. At last follow-up, the patient was in first complete remission, 29 months after initial diagnosis.

Cooperative trial CWS-91 for localized soft tissue sarcoma in children, adolescents, and young adults.

PURPOSE: To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting. PATIENTS AND METHODS: Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy. RESULTS: At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% +/- 4% and 73% +/- 4%, respectively (all survival rates in this abstract are calculated and displayed with +/-95% CI). EFS/OS rates by histology were 60% +/- 5%/72% +/- 5% in rhabdomyosarcoma, 62% +/- 10%/69% +/- 10% for Ewing tumors of soft tissues, 84% +/- 12%/90% +/- 10% for synovial sarcoma, and 67% +/- 38%/83% +/- 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% +/- 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% +/- 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis. CONCLUSION: Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.

Full-thickness resection with myocutaneous flap reconstruction for locally recurrent breast cancer.

BACKGROUND: Despite available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. This retrospective study presents the possibilities and results of complete, full-thickness chest wall resection. METHODS: Between 1985 and 2006, 63 women (mean age, 58 years) with local recurrence of breast cancer invading the chest wall underwent chest wall resection with myocutaneous flap coverage and are included in this study. Adequate lung, cardiovascular, renal, and hepatic functions were additional eligibility requirements for inclusion. Preoperative known extrapulmonary metastases, pleural dissemination, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4 were exclusion criteria. Survival rates were calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analysis was used for relative risk factors. RESULTS: The median interval between operation for the primary tumor and of the local recurrence was 89 months, with median follow-up at 28 months. In the total collective, cumulative 5-, 10- and 15-year survival rates were 46%, 29%, and 22%, respectively, with a median survival of 56 months. R0 resection was associated with a 5-year survival of 50.4%. Prognostic factors were patient age at the time of the primary operation and tumor invasion of bony structures. Mortality was 1.6% and morbidity was 25%. CONCLUSIONS: Full-thickness chest wall resection of locally recurrent breast cancer performed by a team of thoracic and plastic surgeons provides the best survival rates, with low mortality and morbidity. An earlier application of this method may lead to further improvement of these results.

Symptom-oriented follow-up of early breast cancer is not inferior to conventional control. Results of a prospective multicentre study.

BACKGROUND: The homogeneity of the schemes for follow-up care after curative surgical treatment of early breast cancer is still a matter of debate in Germany. We investigated whether symptom-oriented follow-up is equivalent in terms of survival rates to conventional surveillance based on scheduled tests. PATIENTS AND METHODS: In a prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent a conventional follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both branches. 1,108 patients did not participate in the project. They represent 'real world patients', unaffected by the implications of a study. RESULTS: The symptom-oriented follow- up group produced results not inferior to those of the intensive one (p < 0.05) in terms of overall and relapse-free survival. Furthermore, no difference was indicated in terms of overall survival between study participants and the 'real world patients' (p = 0.316). CONCLUSION: The results confirm that regular imaging and laboratory tests have no relevant effect on overall survival of patients after curative primary therapy of early breast cancer and support the implementation of a symptom-oriented routine follow-up.

Full-thickness chest wall resection for locally recurrent breast cancer.

AIM: In spite of available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. In a retrospective study, the possibilities and results of complete, full-thickness chest wall resection are presented. METHODS: Between 1985 and 2004, 51 women underwent complete, full-thickness chest wall resection with primary coverage. Primary surgical therapy of breast cancer had been mastectomy in 88%. Median age of patients undergoing surgery for a local recurrence was 57 (29 - 81) years. The median interval between surgery of the primary tumour and of the local recurrence was 70.3 (10.7 - 327.2) months; median follow-up was 29.4 (1.8 - 230.9) months. 40 (78.4%) patients required rib resections, 15 (29.4%) of them in combination with partial sternal resection. In 4 (7.8%) patients complete and in 7 (13.7%) patients partial sternal resection without additional rib resection were performed.Coverage was mainly realized using latissimus dorsi myocutaneous flaps (n=44; 86.3%). Survival rates were calculated by means of the Kaplan-Meier method, the relative risk using univariate and multivariate Cox-regression analysis. RESULTS: In the total collective, cumulative 5-, 10- and 15-year survival (YS) rates were 39%, 31% and 23%, respectively, median survival 46.4 months. R0 resection was associated with a 5-YS of 42%. Prognostic factors were age at the time of primary surgery, disease-free interval and tumour invasion of bony structures. Mortality was 2%, morbidity 35%. CONCLUSION: Full-thickness chest wall resection of locally recurrent breast cancer is possible in almost any patient when performed by a team of thoracic and plastic surgeons. Only radical resection provides good long-term results with low mortality and morbidity.

Similar insulin secretory response to a gastric inhibitory polypeptide bolus injection at euglycemia in first-degree relatives of patients with type 2 diabetes and control subjects.

Insulin secretion following the intravenous infusion of gastric inhibitory polypeptide (GIP) is diminished in patients with type 2 diabetes and at least a subgroup of their first-degree relatives at hyperglycemic clamp conditions. Therefore, we studied the effects of an intravenous bolus administration of GIP at normoglycemic conditions in the fasting state. Ten healthy control subjects were studied with an intravenous bolus administration of placebo, and of 7, 20, and 60 pmol GIP/kg body weight (BW), respectively. Forty-five first-degree relatives of patients with type 2 diabetes and 33 matched control subjects were studied with (1) a 75-g oral glucose tolerance test (OGTT) and (2) an intravenous bolus injection of 20 pmol GIP/kg BW with blood samples drawn over 30 minutes for determination of plasma glucose, insulin, C-peptide, and GIP. Statistical analysis applied repeated-measures analysis of variance (ANOVA) and Duncan's post hoc tests. Insulin secretion was stimulated after the administration of 20 and of 60 pmol GIP/kg BW in the dose-response experiments (P <.0001). GIP administration (20 pmol/kg BW) led to a significant rise of insulin and C-peptide concentrations in the first-degree relatives and control subjects (P <.0001), but there was difference between groups (P =.64 and P =.87, respectively). Also expressed as increments over baseline, no differences were apparent (Delta(insulin), 7.6 +/- 1.2 and 7.6 +/- 1.6 mU/L, P =.99; Delta(C-peptide), 0.35 +/- 0.06 and 0.38 +/- 0.08 ng/mL, P =.75). Integrated insulin and C-peptide responses after GIP administration significantly correlated with the respective insulin and C-peptide responses after glucose ingestion (insulin, r = 0.78, P <.0001; C-peptide, r = 0.35, P =.0015). We conclude that a reduced insulinotropic effect of GIP in first-degree relatives of patients with type 2 diabetes cannot be observed at euglycemia. Therefore, a reduced GIP-induced insulin secretion in patients with type 2 diabetes and their first-degree relatives at hyperglycemia is more likely due to a general defect of B-cell function than to a specific defect of the GIP action.