Pathologic Complete Response and Clinical Outcomes in Patients With Localized Soft Tissue Sarcoma Treated With Neoadjuvant Chemoradiotherapy or Radiotherapy: The NRG/RTOG 9514 and 0630 Nonrandomized Clinical Trials.

Importance: Pathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).

Objective: We sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.

Design, Setting, And Participants: RTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS.

Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.

Background: Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection.

Methods: Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation.

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas.

Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue.

Final trial report of sentinel-node biopsy versus nodal observation in melanoma.

Background: Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial.

Methods: We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.

miR-29 acts as a decoy in sarcomas to protect the tumor suppressor A20 mRNA from degradation by HuR.

In sarcoma, the activity of NF-κB (nuclear factor κB) reduces the abundance of the microRNA (miRNA) miR-29. The tumor suppressor A20 [also known as TNFAIP3 (tumor necrosis factor-α-induced protein 3)] inhibits an upstream activator of NF-κB and is often mutated in lymphomas. In a panel of human sarcoma cell lines, we found that the activation of NF-κB was increased and, although the abundance of A20 protein and mRNA was decreased, the gene encoding A20 was rarely mutated.

The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors.

Metastasectomy for distant metastatic melanoma: analysis of data from the first Multicenter Selective Lymphadenectomy Trial (MSLT-I).

Background: For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery with or without SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial.

Methods: Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation.

Prognostic factors and staging for soft tissue sarcomas: an update.

Soft tissue sarcoma (STS) staging is a constantly evolving process. Grading is still of utmost importance and has been adapted into a three-tier system. The STS most difficult to categorize are those with uncertain malignant potential, such as solitary fibrous tumors, gastrointestinal stromal tumors, and glomus tumors, some of which have developed completely separate staging systems and may not even be considered sarcomas.

Patient surveillance after treatment for soft-tissue sarcoma.

About 1% of all cancers are soft tissue sarcomas (STS); about 60% of these occur in the extremities. Post-treatment surveillance programs are designed to identify recurrence, new primary cancers, and complications of therapy early enough to increase survival duration and quality of life. The intensity of surveillance varies among surgeons.

Long-term results of a phase 2 study of neoadjuvant chemotherapy and radiotherapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

Background: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (≥5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy.

Methods: Patients with high-grade soft tissue sarcoma≥8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine).

Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans.

Objectives: Dermatofibrosarcoma protuberans (DFSP) is a spindle cell tumor with a high local recurrence rate. Wide excision (WE) has been the standard treatment, but ideal margin width is poorly defined and Mohs micrographic surgery (MMS) has emerged as an alternative procedure. This study examines the use of WE versus MMS for the treatment of primary DFSP at a single institution.

The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma.

Background: The objective of this study was to evaluate the impact of adjuvant radiation therapy (RT) on regional recurrence and survival after therapeutic lymphadenectomy (TL) for clinically advanced, lymph node-metastatic melanoma.

Methods: Six hundred fifteen patients who had clinically advanced, regional lymph node-metastatic disease underwent TL. All patients were appropriate potential candidates for adjuvant RT (enlarged or multiple positive lymph nodes, extracapsular extension) because of a high risk for regional recurrence regardless of whether or not they received RT.

Soft tissue sarcomas: current management and future directions.

This article reviews the current state of diagnosis and treatment of soft tissue sarcomas. Etiology, staging, imaging, tissue sampling, and current treatment are all reviewed using updated references. Current standards for surgical treatment are emphasized and the future directions of treatment addressed.

The treatment and outcome of patients with soft tissue sarcomas and synchronous metastases.

Introduction: There is a strong association between poor overall survival and a short disease-free interval for patients with soft tissue sarcomas (STS) and metastatic disease. Patients with STS and synchronous metastases should have a very dismal prognosis.The role of surgery in this subgroup of patients with STS has not been defined.

Fever-range whole body hyperthermia increases the number of perfused tumor blood vessels and therapeutic efficacy of liposomally encapsulated doxorubicin.

Purpose: Two major questions were addressed: (1) Can fever-range whole body hyperthermia (FR-WBH) affect the number of perfused tumor blood vessels? (2) Can pre-treatment with FR-WBH improve accumulation or anti-tumor efficacy of doxorubicin or DOXIL (liposomal doxorubicin)?

Materials And Methods: Perfused blood vessels were visualized by intravenous injection of the fluorescent dye (DiOC7(3)) and the number of labeled vessels in tumors and normal organs of unheated mice and those previously heated to 39.5 degrees C for 6 hours were compared. Using three animal tumor models (one syngeneic murine model and two human tumor xenografts in SCID mice) we also compared tumor growth and amount of intratumoral doxorubicin (given as free drug or as DOXIL) in control mice or those given pre-treatment with FR-WBH.

Adjuvant therapy for extremity sarcomas.

Extremity soft tissue sarcomas (STS) represent a rare, heterogeneous malignancy. Surgery is the primary treatment for patients with no evidence of metastatic disease, and for small low-grade superficial tumors in which adequate margins can be obtained, it may be the only therapy indicated. For large, deep tumors or tumors that are close to important neurovascular structures or bone, the addition of radiotherapy to resection has improved local control and increased limb salvage without affecting overall survival.

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

Purpose: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma.

Patients And Methods: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status.

Phase II study of neoadjuvant chemotherapy and radiation therapy in the management of high-risk, high-grade, soft tissue sarcomas of the extremities and body wall: Radiation Therapy Oncology Group Trial 9514.

Purpose: On the basis of a positive reported single-institution pilot study, the Radiation Therapy Oncology Group initiated phase II trial 9514 to evaluate its neoadjuvant regimen in a multi-institutional Intergroup setting.

Patients And Methods: Eligibility included a high-grade soft tissue sarcoma > or = 8 cm in diameter of the extremities and body wall. Patients received three cycles of neoadjuvant chemotherapy (CT; modified mesna, doxorubicin, ifosfamide, and dacarbazine [MAID]), interdigitated preoperative radiation therapy (RT; 44 Gy administered in split courses), and three cycles of postoperative CT (modified MAID).

American Joint Committee on Cancer clinical stage as a selection criterion for sentinel lymph node biopsy in thin melanoma.

Background: A significant proportion of newly diagnosed melanomas are thin lesions (< or = 1.00 mm). Because tumor thickness correlates with the risk for nodal metastases, sentinel lymph node (SLN) biopsy in this subset is controversial.

Developments in the management of extremity soft tissue sarcomas.

Soft tissue sarcomas, a rare and extremely low prevalence tumor, has no uniform treatment recommendation because there have been few randomized prospective trials to guide management. Recently, there have been surgical, medical, biologic, and genetic advances toward improved treatment. A multidisciplinary approach at specialized treatment centers should be sought because the skill set necessary to implement these advances can be provided and outcomes improved.