Pathology and genetics of tumors of soft tissue and bone

PURPOSE: To define prognostic factors for response and long-term outcome for a wide spectrum of osteosarcomas, extending well beyond those of the typical young patient with seemingly localized extremity disease. PATIENTS AND METHODS: A total of 1,702 consecutive newly diagnosed patients with high-grade osteosarcoma of the trunk or limbs registered into the neoadjuvant studies of the Cooperative Osteosarcoma Study Group before July 1998 were entered into an analysis of demographic, tumor-related, and treatment-related variables, response, and survival. The intended therapeutic strategy included preoperative and postoperative chemotherapy with multiple agents as well as surgery of all operable lesions. RESULTS: Axial tumor site, male sex, and a long history of symptoms were associated with poor response to chemotherapy in univariate and multivariate analysis. Actuarial 10-year overall and event-free survival rates were 59.8% and 48.9%. Among the variables assessable at diagnosis, patient age (actuarial 10-y...

Prognostic Factors in High-Grade Osteosarcoma of the Extremities or Trunk: An Analysis of 1,702 Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

https://www.unitypoint.org/desmoines/filesimages/Cancer%20Education/Oncology%20Nursing%20Conference/2015/2014%20NCCN%20Clin%20Pract%20Guidelines%20Male%20Sex%20Dysf.pdf

Clinical practice guidelines in oncology

PURPOSEThis randomized, prospective study assesses the impact of postoperative external-beam radiation therapy on local recurrence (LR), overall survival (OS), and quality of life after limb-sparing resection of extremity sarcomas.PATIENTS AND METHODSPatients with extremity tumors and a limb-sparing surgical option were randomized to receive or not receive postoperative adjuvant external-beam radiotherapy. Patients with high-grade sarcomas received postoperative adjuvant chemotherapy whereas patients with low-grade sarcomas or locally aggressive nonmalignant tumors were randomized after surgery alone.RESULTSNinety-one patients with high-grade lesions were randomized; 47 to receive radiotherapy (XRT) and 44 to not receive XRT. With a median follow-up of 9.6 years, a highly significant decrease (P2 = .0028) in the probability of LR was seen with radiation, but no difference in OS was shown. Of 50 patients with low-grade lesions (24 randomized to resection alone and 26 to resection and postoperative XRT), th...

Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity.

This study was performed to explore the relationship between tumor oxygenation and treatment outcome in human soft tissue sarcoma. Twenty-two patients with nonmestastatic, high-grade, soft tissue sarcomas underwent preoperative irradiation and hyperthermia and pretreatment measurement of tumor oxygenation. The 18-month actuarial disease-free survival was 70% for patients with tumor median oxygen pressure (pO2) values of >10 mm Hg but only 35% for those with median pO2 values of <10 mm Hg (P=0.01). There were eight treatment failures; the first site of recurrence was lung in all patients. Median pO2 was 7.5 mm Hg for metastasizing tumors versus 20 mm Hg for nonmetastasizing tumors (P=0.03). Potential mechanisms and implications for clinical trial design are discussed.

https://cancerres.aacrjournals.org/content/canres/56/5/941.full.pdf

Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma.

PURPOSETo evaluate the benefit of adjuvant chemotherapy in adult patients with soft tissue sarcomas. The principal end points were freedom from local recurrence and/or metastases and overall survival.PATIENTS AND METHODSBetween January 1977 and June 1988, 468 patients entered this randomized study and 317 were considered eligible. Following complete surgical resection with or without radiotherapy, outcome in 145 eligible patients receiving cyclophosphamide 500 mg/m2 intravenously (IV) bolus on day 1, vincristine 1.4 mg/m2 IV bolus on day 1, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH) 50 mg/m2 IV bolus on day 1, and dacarbazine (DTIC) 400 mg/m2 by 1-hour infusion on days 1 to 3 (CYVADIC) cycles repeated every 28 days for eight courses was compared with that in 172 control patients.RESULTSWith a median follow-up duration of 80 months (range, 39 to 165), actuarial percentage survival figures at 7 years were compared. Relapse-free survival rates were higher for CYVADIC, 56% versus 43% (P = .007...

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

Two hundred forty‐six adults with advanced progressive soft tissue sarcoma received combination chemotherapy with cyclophosphamide, vincristine, Adriamycin (doxorubicin), and DTIC. They were randomly allocated to receive the four drugs simultaneously every 4 weeks (S1: CYVADIC), or pairs of drugs (S2: ADIC‐CYV) alternating at 4 weekly intervals. One hundred sixty‐two patients completed 8 weeks of chemotherapy, and were considered to be evaluable for response. There were 18 complete remissions and 25 partial remissions, an overall response rate of 26%, with a highly significant difference between the two arms in favor of S1 (38% versus 14%, P = 0.001). There were no significant differences between S1 and S2 in terms of median duration of remissions (62 versus 39 weeks), and median survival of responders (85 versus 80 weeks) and of all evaluable patients (43 versus 45 weeks). Karnofsky index (KI) was the single most important prognostic factor. Patients with KI 90–100 showed a remission rate of 41% (56% on the S1 regimen) in contrast with 14% in those with KI 50–80. No patient with a KI of 50 responded to chemotherapy. The main toxicities were nausea, vomiting, anorexia, alopecia and myelosuppression, but did not differ significantly between the two regimens. Our findings suggest that stratification according to KI is essential for studies on chemotherapy for advanced soft tissue sarcomas in order to make a valuable comparison of treatment results. Copyright © 1984 American Cancer Society

Cyvadic in advanced soft tissue sarcoma: A randomized study comparing two schedules: A study of the EORTC soft tissue and bone sarcoma group

High-dose DTIC in advanced soft-tissue sarcomas in the adult

High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group.

The European Organization for Research on Treatment of Cancer (EORTC) trial 20781, concerning osteosarcoma of the limbs is reported. After definitive treatment of the primary tumor with amputation or irradiation, adjuvant treatment was given, randomized into either 9 months of chemotherapy according to a modified Rosen schedule, or elective bilateral lung irradiation of 20 Gy, or 3 months of chemotherapy followed by lung irradiation. The 4-year disease-free survival and total survival were 24% and 43%, respectively, with no difference between the treatment arms. In the radiotherapy arms the lung metastases were more frequently suitable for surgical treatment. The survival of patients with either tibia localizations or higher age was somewhat better. Local recurrences occurred in 16% of patients, 50% of them with distant metastases. The trial was executed from 1978 to 1983; 205 patients were evaluable and eligible, and three toxic deaths occurred in the chemotherapy arms. Elective lung irradiation provided the same survival as the adjuvant chemotherapy given in that time.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819880301%2961%3A5%3C1024%3A%3AAID-CNCR2820610528%3E3.0.CO%3B2-P

Osteosarcoma of the limbs: report of the EORTC-SIOP 03 trial 20781 investigating the value of adjuvant treatment with chemotherapy and/or prophylactic lung irradiation

T. Wagener

Papers

Adjuvant CYVADIC chemotherapy for adult soft tissue sarcoma--reduced local recurrence but no improvement in survival: a study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

Cyvadic in advanced soft tissue sarcoma: A randomized study comparing two schedules: A study of the EORTC soft tissue and bone sarcoma group

High-dose DTIC in advanced soft-tissue sarcomas in the adult

High-dose DTIC in advanced soft-tissue sarcomas in the adult. A phase II study of the E.O.R.T.C. Soft Tissue and Bone Sarcoma Group.

Osteosarcoma of the limbs: report of the EORTC-SIOP 03 trial 20781 investigating the value of adjuvant treatment with chemotherapy and/or prophylactic lung irradiation