Length of symptoms before referral: prognostic variable for high-grade soft tissue sarcoma?

BACKGROUND: It is commonly assumed patients with high-grade soft tissue sarcomas who are diagnosed and treated quickly after the first onset of symptoms fare better than those with longer symptoms before treatment. The literature contains no substantive data to support this assumption for soft tissue sarcomas, particularly for high-grade lesions. QUESTIONS/PURPOSES: We examined selected potential prognostic factors for high-grade soft tissue sarcoma and determined whether the time from first symptom to diagnosis has an impact on survival or disease-free survival and whether subcutaneous sarcomas are diagnosed more quickly than deep sarcomas. METHODS: We retrospectively reviewed 381 consecutive patients treated for high-grade soft tissue sarcoma between 1992 and 2007. Each patient's time from first symptom (pain and/or palpable mass) was prospectively entered into a surgical oncology database. The patients were followed for disease recurrence and survival. We compared length of symptoms with disease-free survival, overall survival, metastases at diagnosis, tumor size, and patient age. Minimum followup was 1 month (mean, 57 months; range, 1-201 months). RESULTS: The overall 5-year survival was 64.7% and disease-free survival was 54.5%. Tumor size and metastatic disease correlated with overall survival and disease-free survival but not length of symptoms. Length of symptoms did not correlate with overall survival or disease-free survival. CONCLUSIONS: Our data do not support the assumption that longer length of symptoms before diagnosis predicts worse overall survival, disease-free survival, or metastatic disease at diagnosis. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.

Biopsy of soft tissue masses: evidence-based medicine for the musculoskeletal tumor society.

UNLABELLED: The literature contains a number of controversies regarding key questions: (1) When is a biopsy indicated? (2) How should the biopsy be placed? (3) How should the biopsy be performed and which has the greatest diagnostic accuracy? (4) Who should perform the biopsy? (5) What clinical parameters present the greatest diagnostic difficulty? Using PubMed and Google Scholar we performed English-language literature searches of clinical studies reporting biopsy of soft tissue masses. Thirty-two studies met the inclusion criteria but were only able to address three of the five questions the authors had hoped to evaluate. Available evidence suggests open biopsy has the highest diagnostic accuracy over core needle biopsy, which was higher than fine needle aspiration. There was no evidence to address who is best suited to perform the biopsy (general surgeon, orthopaedic surgeon, radiologist, pathologist) in terms of accuracy of diagnosis. Frozen section at the time of biopsy may improve diagnostic accuracy. Diagnostic difficulty was associated with myxoid and round cell neoplasms, infections, and tumors located in the paraspinal region. The limited number of references addressing these issues demonstrated the need for more Level I research in the area of biopsy of soft tissue masses. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Diagnosis and treatment of joint-related tumors that mimic sports-related injuries.

Tumors involving the joint or having symptoms in the joint are rare. Both joint-related tumors and sports-related injuries can affect young, active patients, and their symptoms often overlap. Sports medicine specialists rarely encounter synovial conditions, so expertise in this area is difficult to establish. Orthopaedic oncologists often see only patients with an advanced condition. The clinical presentation of a soft-tissue sarcoma may be similar to that of a common lesion such as a synovial cyst. Some benign or malignant bone tumors cause referred pain to distant joints, possibly leading to a delay in diagnosis or inappropriate initial surgery. For example, a hip or proximal femoral bone tumor commonly causes isolated knee pain. Conversely, because the symptoms of some sports-related conditions or pseudotumors (such as a rectus femoris tear, fascial herniation, myositis ossificans, an avulsion injury, an avulsive cortical irregularity, femoral diaphyseal periostitis, or pseudotumor deltoideus) are similar to symptoms of a sarcoma, overtreatment is possible. A sports medicine physician should be familiar with these conditions to facilitate accurate and expedient diagnosis with appropriate treatment.

Tumors masquerading as hematomas.

Suboptimal patient management can occur when malignant soft tissue tumors with internal hemorrhage masquerade as simple hematomas. We retrospectively reviewed 31 patients with malignancies who had diagnostic delays averaging 6.7 months (range, 1.0-49.3 months). The diagnoses included soft tissue sarcomas (27), metastatic cancers (three), and lymphoma (one). History of subcutaneous ecchymosis was positive in only five patients (three of whom had trauma), negative in 18, and unknown in eight. Ecchymosis was present in two patients, absent in 20, and unknown in nine. Previous treatments included observation and reassurance (21), aspiration (11), incision and drainage (10), unplanned resections (seven), physical therapy (seven), medication administration (six), and arthroscopy (one). Interpretations of initial MRI (21) and ultrasound (four) did not raise suspicion of underlying cancers. Traumatic hemorrhage usually causes subcutaneous ecchymosis. However, intratumoral hemorrhage often is contained by a pseudocapsule, which prevents fascial plane tracking and subcutaneous ecchymosis, thus providing a diagnostic clue. Magnetic resonance imaging and ultrasound studies may not accurately diagnose questionable lesions. Diagnostic delay or inappropriate treatment may result if patients do not receive appropriate followup, biopsy (usually open), or referral whenever the diagnosis is in doubt.

Does length of symptoms before diagnosis of sarcoma affect patient survival?

It generally is accepted that earlier diagnosis of sarcoma is associated with a better disease-free survival. Because the legal community is convinced this is true, a delay in cancer diagnosis is a frequent source of medical malpractice lawsuits. We asked whether symptom duration before diagnosis affected sarcoma outcome. We compiled prospective data from 624 consecutive patients with sarcoma treated from 1992 to 2003. The data included length of symptoms before diagnosis, tumor size and grade, presence of metastatic disease at diagnosis, anatomic location, disease-free survival, overall survival, and local recurrence. Length of symptoms did not predict presence of metastatic disease at diagnosis, survival, or disease-free survival. We found no correlation between the length of a patient's symptoms and the tumor size or anatomic site of disease (axial, proximal, and distal). Tumors were larger at diagnosis in axial and proximal locations than in more peripheral locations, despite no difference in length of symptoms before diagnosis. Patients with sarcoma with long-standing symptoms did not have a worse prognosis than those with a shorter length of symptoms before diagnosis in terms of disease-free survival, overall survival, and presence of metastatic disease at diagnosis.

Indeterminate pulmonary nodules in patients with sarcoma affect survival.

We prospectively studied 331 sarcoma patients treated between April 1999 and December 2004 to see if small, indeterminate pulmonary nodules are of prognostic significance. Seventy-one (21%) had indeterminate pulmonary nodules on initial spiral CCT. Twenty of 71 (28%) patients with indeterminate nodules progressed with metastatic disease. Metastatic disease developed in 18/20 (90%) in the area of the original indeterminate nodule. The presence of tiny (<5 mm) indeterminate nodules was not a prognostic variable, however, the presence of nodules > or =5 mm was associated with worse 3 year disease-free survival compared to those with no nodules or tiny nodules (81% versus 49%) but better than those with definite metastatic disease at presentation (49% versus 5%). Because patients with pulmonary nodules > or =5 mm are at increased risk for metastatic disease compared to patients with normal CCT or those with <5 mm nodules but better survival than patients with Stage IV disease, we believe a new staging system of these patients should be considered and recommend careful followup.

Multifocality and multifocal postradiation sarcomas.

UNLABELLED: Hypothetically, any site in a radiation portal has potential for late malignant transformation. Secondary malignant neoplasms may occur after almost any index cancer has been treated with radiation and/or chemotherapy. The incidence of secondary malignant neoplasms, histopathology, time delay, radiation dose, cytotoxic agents, age and type of initial malignancy, and outcome all negatively impact cancer survivors. We highlight the new concept of multifocality, defined as greater than two noncontiguous second malignant neoplasms that develop in a prior radiation port. We identified 48 patients with postradiation sarcomas from three prospectively collected databases. Fifteen of these patients (31%) had evidence of multifocal postradiation sarcomas. Five of 10 women had multifocal postradiation sarcomas after breast-conserving surgery for carcinoma. The longer the time interval between the index cancer and post-radiation sarcoma, the greater the likelihood of multifocal malignant transformation occurring. LEVEL OF EVIDENCE: Therapeutic study, level III.

The impact of previous surgical manipulation of subcutaneous sarcoma on oncologic outcome.

UNLABELLED: We prospectively followed 106 consecutive patients referred for surgical treatment of nonmetastatic subcutaneous soft tissue sarcoma to assess whether prior surgical manipulation had an impact on local control and/or disease-free survival. 10 patients had no previous surgical treatment; 11 had only a previous biopsy, 75 had a previous attempted excision, and 10 were referred after the tumor had recurred locally. Histologic grade was inversely associated with overall survival and disease-free survival. Of the 75 patients with previous attempted excision, 22 (29%) had gross residual disease, 27 (36%) had microscopic residual disease, and 26 (35%) had no identifiable residual disease. The 5-year metastasis-free survival was 88%. Local control was obtained in 100% of patients without previous surgical manipulation, 89% of those with previous surgery, and 60% of those who were referred after a local relapse had been recognized. Cox proportional hazards analysis revealed that larger tumor size negatively impacted disease-free survival in those patients who were treated with previous attempted excision. Of those patients with tumors 4 cm or larger and a previous unplanned sarcoma excision, disease-free survival was lower than in those patients referred without previous attempted excision. LEVEL OF EVIDENCE: Prognostic study, Level I-2 (prospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Bone graft alternatives in the treatment of benign bone tumors.

Most bone grafting procedures are done during spinal fusion and to treat patients with skeletal trauma. Very few studies have addressed the bone grafting of skeletal defects after benign bone tumor excision. Contained defects have been treated with autogenous bone grafts, fresh-frozen allografts, freeze-dried allografts, demineralized bone matrix, and ceramic materials. Additionally, bone morphogenetic proteins may provide a future treatment option for bone tumor reconstruction.

Soft-tissue lumps and bumps.

Soft-tissue masses of the extremities and torso are a common problem encountered by the orthopaedic surgeon. Although these soft-tissue masses are often benign, the orthopaedic surgeon must be able to recognize the features key to differentiating benign and malignant masses. An understanding of the epidemiology and clinical presentation of soft-tissue masses is needed in order to outline a practical approach to evaluation and surgical management.

Evaluation of the patient with carcinoma of unknown origin metastatic to bone.

Metastatic carcinoma to bone of uncertain primary origin is a common clinical diagnostic scenario. I present a simple and effective staging system to identify primary malignancies. The role of clinical history, physical examination, laboratory studies, and limited radiographic studies are critical to the success of this diagnostic strategy. Needle or open biopsy frequently is needed yet usually is more effective as a confirmatory study for carcinoma or to rule out primary bone sarcomas. Patients who present with a displaced pathologic fracture require an urgent diagnostic and treatment plan that does not compromise future treatment options and provides durable skeletal reconstruction.

Treatment of active unicameral bone cysts with percutaneous injection of demineralized bone matrix and autogenous bone marrow.

BACKGROUND: The treatment of unicameral bone cysts varies from open bone-grafting procedures to percutaneous injection of corticosteroids or bone marrow. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous injection of a mixture of demineralized bone matrix and autogenous bone marrow for the treatment of simple bone cysts. METHODS: Twenty-three patients with an active unicameral bone cyst were treated with trephination and injection of allogeneic demineralized bone matrix and autogenous bone marrow. The patients were followed for an average of fifty months (range, thirty to eighty-one months), at which time pain, function, and radiographic signs of resolution of the cyst were assessed. RESULTS: The average time until the patients had pain relief was five weeks, and the average time until the patients returned to full, unrestricted activities was six weeks. Bone-healing at the site of the injection was first seen radiographically at three to six months. No patient had a pathologic fracture during this early bone-healing stage. Cortical remodeling was seen radiographically by six to nine months, and after one year the response was usually complete, changing very little from then on. Five patients required a second injection because of recurrence of the cyst, and all five had a clinically and radiographically quiescent cyst after an average of thirty-six additional months of follow-up. Seven of the twenty-three patients had incomplete healing manifested by small, persistent radiolucent areas within the original cyst. None of these cysts increased in size or resulted in pain or fracture. CONCLUSIONS: Percutaneous injection of allogeneic demineralized bone matrix and autogenous bone marrow is an effective treatment for unicameral bone cysts.

Karnofsky performance score as a predictor of survival in soft tissue sarcoma.

Forty-six consecutive patients with nonmetastatic, large, high-grade soft tissue sarcomas were treated with surgical resection and radiation therapy but no adjuvant chemotherapy. Clinical and radiographic followup ranged from 36 to 90 months (mean, 50 months). One patient died of unrelated causes 10 months after the completion of radiation and surgery, leaving the oncologic outcome of 45 patients to be evaluated. Twenty-seven of 45 patients (60%) survived with an average followup of 50 months. The limb salvage rate was 91% and local control was obtained in 43 of 45 patients (96%). During the time of the study, 73% of patients could have been offered chemotherapy. However, only 53% of patients who died of their disease would have been candidates for chemotherapy trials because of medical comorbidities. More importantly, patients with a Karnofsky performance score of 80 or more had a significantly better survival rate than patients with a Karnofsky performance score less than 80 without the use of chemotherapy. Current chemotherapy trials that exclude patients because of medical comorbidities are introducing bias toward improved survival that may not be attributable to the chemotherapy. If a real survival benefit of adjuvant chemotherapy exists, it would be most evident in the largest (> 15 cm) high-grade tumors. Aggressive metastasectomy seems to be most beneficial for patients with isolated nodules.