Jonathan Landa

Phase II Trial of the CDK4 Inhibitor PD0332991 in Patients With Advanced CDK4-Amplified Well-Differentiated or Dedifferentiated Liposarcoma

PURPOSE CDK4 is amplified in > 90% of well-differentiated (WDLS) and dedifferentiated liposarcomas (DDLS). The selective cyclin-dependent kinase 4 (CDK4)/CDK6 inhibitor PD0332991 inhibits growth and induces senescence in cell lines and xenografts. In a phase I trial of PD0332991, several patients with WDLS or DDLS experienced prolonged stable disease. We performed an open-label phase II study to determine the safety and efficacy of PD0332991 in patients with advanced WDLS/DDLS. PATIENTS AND METHODS Patients age ≥ 18 years experiencing disease progression while receiving systemic therapy before enrollment received PD0332991 200 mg orally once per day for 14 consecutive days in 21-day cycles. All were required to have CDK4 amplification by fluorescence in situ hybridization and retinoblastoma protein (RB) expression by immunohistochemistry (≥ 1+). The primary end point was progression-free survival (PFS) at 12 weeks, with 12-week PFS of ≥ 40% considered promising and ≤ 20% not promising. If ≥ nine of 28 patients were progression free at 12 weeks, PD0332991 would be considered active. RESULTS We screened 48 patients (44 of 48 had CDK4 amplification; 41 of 44 were RB positive). Of those, 30 were enrolled, and 29 were evaluable for the primary end point. Grade 3 to 4 events included anemia (17%), thrombocytopenia (30%), neutropenia (50%), and febrile neutropenia (3%). At 12 weeks, PFS was 66% (90% CI, 51% to 100%), significantly exceeding the primary end point. The median PFS was 18 weeks. There was one partial response. CONCLUSION Treatment with the CDK4 inhibitor PD0332991 was associated with a favorable progression-free rate in patients with CDK4-amplified and RB-expressing WDLS/DDLS who had progressive disease despite systemic therapy.

Percutaneous CT-Guided Bone Biopsy: Diagnosis of Malignancy in Lesions With Initially Indeterminate Biopsy Results and CT Features Associated With Diagnostic or Indeterminate Results

OBJECTIVE The purpose of our study was to determine the proportion of bone lesions with indeterminate results after initial percutaneous CT-guided bone biopsy that ultimately are found to be malignant and whether CT features are associated with diagnostic outcomes. MATERIALS AND METHODS The results of 800 consecutive percutaneous CT-guided bone biopsies performed at a tertiary cancer center were reviewed. The initial histopathologic diagnosis was classified as diagnostic or indeterminate. On the basis of follow-up information, indeterminate results were subcategorized as benign, malignant, or persistently indeterminate. Two readers independently analyzed the CT images. RESULTS Initial percutaneous CT-guided bone biopsy was diagnostic in 69% and indeterminate in 31%. Malignancy was diagnosed in 90% of initially diagnostic results. In lesions with initially indeterminate results, a diagnosis was subsequently made in 62%; 39% of subsequent diagnoses were malignant as of the last available follow-up. CT features associated with diagnostic results included cortical destruction and large extraosseous mass (p < 0.05). More lesional sclerosis and presence of fat were associated with indeterminate results (p < 0.001). CT features associated with malignant results included less-extensive sclerosis and lesser sclerotic rim (p < 0.05). Increased age, female sex, and a cancer history were associated with higher risk of malignancy among patients with diagnostic results at initial biopsy. CONCLUSION Bone lesions that initially yield indeterminate results at percutaneous CT-guided bone biopsy often are subsequently shown to be malignant; vigorous pursuit of a diagnosis is recommended if initial results are indeterminate. Lesions showing fat or more sclerosis are more likely to be indeterminate; lesions with less sclerosis or smaller sclerotic rim are more likely to yield malignant results.

Imaging findings, prevalence and outcome of de novo and secondary malignant fibrous histiocytoma of bone

ObjectiveTo evaluate the radiographic and magnetic resonance (MR) imaging features of primary and secondary malignant fibrous histiocytoma in bone and determine the demographics, prevalence and outcome of patients with this tumor.Materials and methodsA retrospective search of files from two institutions identified 28 patients with malignant fibrous histiocytoma (MFH) of bone. Microscope slides were reviewed to confirm diagnosis and identify any pre-existing lesions. Medical records were reviewed with respect to patients’ demographic characteristics and outcomes.ResultsRadiographic features demonstrated an aggressive osteolytic lesion with a permeative pattern of bone destruction. Periosteal reaction was seen in three of 13 lesions. T1-weighted images (T1WIs) demonstrated signal intensity iso- to slightly hyperintense to muscle. T2-weighted images (T2WIs) demonstrated mildly higher signal intensity than that of muscle. The 5-year survival rate was 53%. The tumor arose secondarily in pre-existing lesions in 43% of patients. Metastases occurred in 46% of patients during the course of the disease, with pulmonary and osseous metastases being the most common.ConclusionSecondary MFH of bone was slightly less common than primary MFH and had a prognosis similar to that of primary MFH of bone. MR imaging showed variable and somewhat unusual low to intermediate T2 signal characteristics for a radiographically malignant osteolytic lesion.

Contemporary Imaging in Sarcoma

Sarcomas are a heterogeneous group of >50 subtypes of neoplasm. It is imperative to obtain appropriate imaging of these tumors in order to adequately assess, characterize, and stage bone and soft tissue sarcomas. Anatomic imaging such as radiographs, computed tomography, and magnetic resonance imaging (MRI) remain the foundation for both biopsy planning and postoperative evaluation of these neoplasms. However, anatomic imaging may not be entirely accurate in the evaluation of treatment response. Newer techniques, such (18)F-fluorodeoxyglucose positron emission tomography, are being used to evaluate distant metastases. Newer radiopharmaceuticals, such as (18)F-fluorodeoxythymidine, are being developed to assist in the differentiation between benign and low-grade malignant neoplasms. Newer functional imaging techniques, such as dynamic contrast-enhanced MRI and diffusion-weighted imaging, among others, are being developed to evaluate treatment response.

Combined Whole Body and Multiparametric Prostate Magnetic Resonance Imaging as a 1-Step Approach to the Simultaneous Assessment of Local Recurrence and Metastatic Disease after Radical Prostatectomy

Purpose: We report our initial experience with whole body and dedicated prostate magnetic resonance imaging as a single examination to assess local recurrence and metastatic disease in patients with suspected recurrent prostate cancer after radical prostatectomy. Materials and Methods: In this institutional review board approved, retrospective, single center study 76 consecutive patients with clinically suspected recurrent prostate cancer following radical prostatectomy underwent combined whole body and dedicated prostate magnetic resonance imaging at a single session from October 2014 to January 2016. Scans were evaluated to detect disease in the prostate bed and regional nodes, and at distant sites. Comparison was made to other imaging tests, and prostate bed, node and bone biopsies performed within 90 days. Results: Whole body and dedicated prostate magnetic resonance imaging was completed successfully in all patients. Median prostate specific antigen was 0.36 ng/ml (range less than 0.05 to 56.12). Whole body and dedicated prostate magnetic resonance imaging identified suspected disease recurrence in 16 of 76 patients (21%), including local recurrence in the radical prostatectomy bed in 6, nodal metastases in 3, osseous metastases in 4 and multifocal metastatic disease in 3. In 43 patients at least 1 standard staging scan was done in addition to whole body and dedicated prostate magnetic resonance imaging. Concordance was demonstrated between the imaging modalities in 36 of 43 cases (84%). All metastatic lesions detected by other imaging tests were detected on magnetic resonance imaging. In addition, the magnetic resonance imaging modality detected osseous metastases in 4 patients with false‐negative findings on other imaging tests, including 2 bone scans and 3 computerized tomography scans. It also excluded osseous disease in 1 patient with positive 18F‐fluorodeoxyglucose positron emission tomography/computerized tomography and subsequent negative bone biopsy. Conclusions: Combined whole body and dedicated prostate magnetic resonance imaging is feasible in a clinical practice setting. It can provide incremental information compared to standard imaging in men with suspected prostate cancer recurrence after radical prostatectomy.

Musculoskeletal tumours and tumour-like conditions: common and avoidable pitfalls at imaging in patients with known or suspected cancer: Part B: malignant mimics of benign tumours.

A wide range of musculoskeletal tumours and tumour-like conditions may be encountered when patients undergo radiological examinations. Some malignant musculoskeletal lesions may mimic benign tumours at imaging, being confused with benign cystic lesions or haematomas. Also, inappropriately selected magnetic resonance (MR) image sequences or computed tomography (CT) display windows can lead to misdiagnosis. Many orthopaedic surgeons interpret radiological images themselves, and therefore need to be as aware of these issues as radiologists are. This review describes and illustrates a number of such errors that commonly occur, and provides suggestions for avoiding these pitfalls.

Biopsy of suspicious bone lesions in patients with a single known malignancy: prevalence of a second malignancy.

OBJECTIVE The probability that a suspicious bone lesion in a patient with one known malignancy is actually due to a second, previously unknown primary malignancy has been reported to be 2-8%. We sought to determine this prevalence as well as that of benign diagnoses in a larger number of patients in a tertiary cancer center. MATERIALS AND METHODS The medical records of 482 consecutive patients (254 women and 228 men) with only one known primary malignancy each (excluding nonmelanoma skin cancer) and who underwent biopsy of a suspicious bone lesion were retrospectively reviewed. The results of bone biopsy were classified as benign, metastasis of the known primary malignancy, due to a second primary malignancy, or nondiagnostic or indeterminate. RESULTS In 103 of 482 (21%) patients, bone biopsy results were benign, 316 (66%) were due to metastases of the known malignancy, 15 (3%) were due to a second malignancy, and 48 (10%) were nondiagnostic or indeterminate. Second malignancies included osteosarcoma (n = 4); soft-tissue sarcoma (n = 2); lymphoma (n = 2); plasma cell malignancy (n = 2); and lung cancer, thyroid cancer, renal cancer, chondrosarcoma, and carcinoma of unknown primary (n = 1 each). CONCLUSION In 3% of patients with one known malignancy and a suspicious bone lesion, the lesion was due to a previously unknown second malignancy; in 21% of patients, the lesion was benign. Bone biopsy is recommended in the management of patients with one known cancer and a suspicious bone lesion only if the presence of a second malignancy would alter clinical management.

Imaging Techniques in Desmoid Tumors

From an imaging perspective, desmoid tumors are best classified as extra-abdominal, abdominal wall, and intra-abdominal. MRI is the imaging modality of choice for extra-abdominal desmoids, demonstrating a lesion that can be well-defined, has infiltrative margins, or a combination of both. The lesions are low in T1 signal, while T2 signal is variable, depending upon the stage of evolution. During their early growth stage, desmoid tumors are highly cellular with relatively less collagen. As a result, they are predominantly high in T2 signal with small foci of low T2 signal, and demonstrate avid contrast enhancement. As they evolve over time, the tumors become less cellular and more densely collagenous, with a resultant decrease in T2 signal intensity and enhancement, and often with a concomitant decrease in size. Radiation and medical therapy can also result in these signal changes, suggesting treatment response even in the absence of decreases in size. Abdominal wall desmoid tumors can best be imaged with MRI or CT, while intra-abdominal desmoid tumors are best imaged with CT. CT demonstrates a mass which is nearly isodense to muscle on noncontrast images and which demonstrates mild-to-moderate enhancement with intravenous contrast. CT is superior to MRI in distinguishing intra-abdominal desmoids from adjacent bowel loops, although vascular involvement can be accurately assessed with either CT or MRI. MRI is sometimes desirable to CT for imaging of intra-abdominal desmoids, particularly in patients who cannot receive iodinated contrast material, either because of allergies or impaired renal function, or in patients in whom radiation exposure is a major concern. In patients with severe renal dysfunction, intravenous contrast should not be used with MRI either because of the risk of developing nephrogenic systemic sclerosis.