Oncology—Bone and Soft Tissue Tumors

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Figure 1: A male patient with isolated distal left femoral osseous lymphoma. A. MRI demonstrates a heterogeneous abnormality involving the distal left femoral bone marrow. B. PET sows relatively intense hypermetabolism corresponding to the MRI lesion.

Oncology—Bone and Soft Tissue Tumors

I. BONE TUMORS

The malignant tumors of the bone include osteosarcoma, Ewing’s sarcoma, lymphoma, chondrosarcoma, and parosteal osteosarcoma. Central osteosarco- ma is the most common primary bone malignancy in childhood and at all ages if multiple myeloma is excluded. The lesion is usually metaphyseal and most frequently involves the distal femur and proximal tibia. The natural history of osteosarcoma involves a rapid enlargement of the primary tumor with propen- sity for metastatic disease in the lungs, other bones, and lymph nodes. Long- term survival has improved with the introduction of multidrug adjuvant and neoadjuvant chemotherapy.

The principal traditional imaging findings demonstrate a productive lesion with bone disruption and production, soft tissue component, and marked tumor accumulation of bone-seeking radiotracers. Skeletal scintigraphy occa- sionally demonstrates extraosseous (e.g., lung) metastases due to osteoid pro- duction by the metastatic deposits. MRI is used to define the local extent of osteosarcoma in bone and soft tissue. However, signal abnormalities caused by peritumoral edema can result in an overestimation of tumor extension. Due to nonspecific appearance of viable tumor on MRI, variable results have been reported for assessing chemotherapeutic response in planning for limb salvage surgery. Scintigraphy with Tl-201 and Tc-99m MIBI have been shown to be useful for assessing therapeutic response in osteosarcoma.

The exact role of FDG PET in bone tumors is unclear (Fig. 1). However, cur-

rent experience suggests that in patients with bone sarcomas, FDG PET may play

an important role in guiding biopsy, detecting local recurrence in amputation

stumps, evaluating patients with suspected metastatic disease, monitoring response to therapy, and assessing for prognosis (Fig. 2).

There appears to be a statistically significant difference in SUV between benign and malignant lesions. However, lesions such as giant cell tumors and fibrous dysplasias may not display statistically significant difference in SUV compared with osteosarcomas. Therefore, FDG PET may be limited in distin- guishing accurately malignant from benign bone tumors due to the high accu- mulation of FDG in some benign bone lesions. FDG-PET SUV analysis may, however, be useful in histologic grading and guiding biopsy toward the most metabolically active regions of large masses.

FDG PET may have some limitation in detecting local recurrence in the amputation stump. Focal hypermetabolism may be associated with pressure areas and skin breakdown without evidence of disease recurrence. For detecting lung metastases, FDG PET may not be as sensitive as CT (50% vs. 75%), although due to the high specificity of FDG PET (98% vs. 100%), a positive FDG PET result can be used to confirm abnormalities seen on CT as metastat- ic disease. Similarly FDG PET may miss some osseous metastases of osteo- sarcoma in comparison to skeletal scintigraphy.

FDG PET has been reported to be useful in evaluating treatment response

in patients with osteosarcoma. A ratio of post-therapy SUV to pre-treatment

Figure 2: An 18-year-old male with osteogenic carcinoma of the left distal femur treated

with chemotherapy. PET-CT shows a large bulky extensive primary tumor with

post-treatment central necrosis and some extension within the diaphysis superiorly and

along the medial condylar cortical surface.

SUV less than about 40% predicts a favorable histologic response to chemotherapy (defined as ≥90% necrosis). The prognostic utility of FDG PET in osteosarcoma has also been investigated. Overall and event-free survivals are significantly better in patients with tumors that display low FDG uptake in comparison to those patients with tumors that demonstrate high FDG accumulation.

II. SOFT TISSUE TUMORS

Soft tissue sarcomas compose a diverse group of solid malignancies with varied morphologic and anatomic characteristics. The most common sites of initial presentation are the extremities, followed in decreasing order of frequency by retroperitoneum, abdominal, trunk, genitourinary tract, viscera, and head and

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Figure 3: A 24-year-old woman with a monophasic synovial sarcoma anterolateral to

mid-right tibia. PET-CT shows a hypermetabolic soft tissue mass.

neck. Retroperitoneal and visceral sarcomas are more likely to metastasize than the extremity tumors. High-grade lesions and tumors larger than 5 cm are also more likely to metastasize. The predominant tumor subtypes include lipo- sarcoma, leiomyosarcoma, malignant fibrous histiocytoma (MFH), and fibro- sarcoma. Management of soft tissue sarcomas usually involves aggressive tumor resection for local control. For extremity sarcomas, limb sparing surgery is cur- rently the goal of therapy.

Functional imaging with FDG PET has been shown to be useful in direct- ing biopsy, differentiating benign from malignant soft tissue masses, predicting tumor grade, staging, restaging, and prognosis (Figs. 3–7). Sarcomas in general tend to be highly FDG-avid, although significant heterogeneity in glucose metabolism may be evident. FDG PET has been used to direct biopsy to the most metabolically active area of the lesion in order to improve the diagnostic yield. FDG PET has also been used in characterizing soft tissue masses with

Figure 4: A 25-year-old man with left lower extremity rhabdomyosarcoma. PET shows

hypermetabolic disease crossing the left knee joint.

reported sensitivity of 95% and specificity of 75% in diagnosing sarcoma. FDG PET may also identify unexpected sites of metastases.

A systematic review and meta-analysis of 29 clinical studies on the diag- nostic utility of FDG-PET in soft tissue and bone sarcomas reported a pooled sensitivity of 91%, specificity of 85%, and accuracy of 88% in detecting sarco- mas. The differences between the mean SUV in malignant and benign tumors and that between low- and high-grade sarcomas were statistically significant.

Another meta-analysis reviewed the diagnostic performance of FDG PET in grading of soft-tissue sarcomas in 15 clinical studies encompassing 441 soft- tissue lesions (227 malignant, 214 benign). For diagnosis of malignant versus benign lesions, typical pairs of sensitivity and specificity estimates from the summary receiver operating characteristic curves were 92% and 73% for qual- itative visualization, 87% and 79% for SUV of 2.0, 70% and 87% for SUV of 3.0. Diagnostic performance was similar for both primary and recurrent lesions. Although FDG PET may be helpful in tumor grading, low-grade tumors and benign lesions may not be adequately discriminated.

An important diagnostic utility of FDG PET has been in the prediction and evaluation of therapy response in soft tissue sarcoma). In one example, FDG PET has been shown to be a sensitive method for evaluating an early

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B

Figure 5: A 60-year-old man with metastatic angiosarcoma of the pelvis. A. Coronal

inversion recovery sequence MRI of the sacrum demonstrates tumor foci in right sacral

ala and the left posterior ilium. B. PET shows hyermetabolism in these same lesions and

also demonstrated a left lower paralumbar metastatic retroperitoneal lymph node.

response to imatinib mesylate (Gleevec/Glivec) treatment in gastrointestinal stromal tumors (GISTs), which are soft tissue sarcomas of the gastrointestinal tract originating from mesenchymal cells. Successful treatment results in a decline in tumor glucose metabolism in comparison to the high level of glucose metabolism in the tumor prior to therapy. Other studies have demonstrated the diagnostic utility of FDG PET in distinguishing viable tumor from changes caused by therapy in areas associated with equivocal MRI findings. However, occasionally prominent FDG accumulation may be observed in benign thera- py-related fibrous tissue presumably due to local inflammation and healing.

Despite this potential limitation, the ability to differentiate postoperative changes from local recurrence may impact the clinical management of patients with sarcoma. Additionally, pre-therapy FDG PET may be helpful in predicting overall and disease-free survivals. A multivariate analysis has shown that SUV(max) is a statistically significant independent predictor of patient survival such that tumors with larger SUV(max) have a significantly poorer prognosis.

In conclusion, the published literature suggests that FDG PET may have an

important role in the imaging evaluation of patients with bone and soft tissue

Figure 6: A 50-year-old male with newly diagnosed sarcoma of the left thigh. PET-CT

shows relatively heterogeneous hypermetabolism in the anterior left proximal thigh soft

tissue mass compatible with a mixture of viable tumor and necrosis.

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B

C

Figure 7: A 39-year-old female with malignant fibrous histiocytoma of the right thigh diagnosed by incisional biopsy. A. MRI shows a heterogeneous soft tissue mass in the right medial thigh. B. Pre-treatment PET shows an intensely hypermetabolic tumor.

C. PET scan after cryoablation shows nodular residual disease in the upper anterolateral

aspect of the lesion in combination with extensive subtotal necrosis surrounded by a rim

of hypermetabolism which may represent reactive inflammation and residual tumor. The

surgical specimen demonstrated 90% tumor necrosis with several areas of residual

cancer.

sarcoma. Prospective studies with large patient groups are essential further to evaluate the cost-effectiveness and the short-term and long-term benefits of FDG-PET in these patients.

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