Katherine Zukotynski

Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin

PURPOSE Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities. PATIENTS AND METHODS We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy. RESULTS Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mutation status (7 of 13 or 54% KIT mutated v 0% KIT amplified only). There were no statistical differences in rates of progression or survival by mutation status or by melanoma site. The overall disease control rate was 50% but varied significantly by KIT mutation status (77% mutated v 18% amplified). Four patients harbored pretreatment NRAS mutations, and one patient acquired increased KIT amplification after treatment. CONCLUSION Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.

Sonography for assessment of haemophilic arthropathy in children: a systematic protocol

Summary.  Radiological imaging of joints in children with haemophilia is important to detect abnormalities, grade their severity and monitor the effects of treatment. Scoring systems for staging haemophilic arthropathy have been developed based on plain film or magnetic resonance imaging (MRI) findings. Radiographs alone may be inadequate for evaluating joint disease in children with haemophilia on prophylaxis while MRI may be difficult to access and require the child to be sedated. Sonography can be a useful complementary modality in the evaluation of haemophilic arthropathy that is readily available and does not require the child to be sedated. In this paper, we briefly review the current imaging scales available for the assessment of haemophilic arthropathy and present a systematic protocol for sonographic assessment of the knee and ankle in haemophilic children along with examples of findings in joint effusion/hemarthrosis, synovial hypertrophy and cartilage loss. Also, we correlate the ultrasound findings with the corresponding MRI images demonstrating the anatomic planes used for imaging acquisition. Sonography is a promising technique for the assessment of soft tissue changes which are the earliest findings in haemophilic arthropathy. Further investigation is required for evaluation of osteochondral changes given limitations of sonography in this regard and in minimizing operator dependency, especially if applied in multicentric clinical trials.

End-of-treatment but not interim PET scan predicts outcome in nonbulky limited-stage Hodgkin’s lymphoma

BACKGROUND Early interim positron emission tomography (PET) scans appear powerfully predictive of outcome in Hodgkins lymphoma (HL), particularly in advanced-stage disease where it has been predominantly studied. The prognostic value of interim PET in limited-stage patients with nonbulky disease has not been well established. PATIENTS AND METHODS Ninety-six patients with nonbulky limited-stage HL were identified who had interim and end-of-treatment PET scans. Response rate, overall survival (OS), and progression-free survival (PFS) were calculated. RESULTS Four-year PFS and OS for the entire cohort were 88% and 97%, respectively. Interim PET did not predict outcome, with PFS in positive and negative patients 87% versus 91% (P=0.57), respectively. End-of-treatment PET result was predictive of outcome, with PFS of 94% in end PET-negative patients versus 54% in end PET-positive patients (P<0.0001). Four-year OS was 100% in end PET-negative patients and 84% in end PET-positive patients (P<0.0001). CONCLUSIONS Interim PET scans were not predictive of outcome, compared with scans carried out at completion of therapy. End-of-treatment PET was highly predictive of PFS and OS, regardless of interim PET result. In this low-risk patient population, even patients with interim positive PET scans show a favorable prognosis.

Pneumatosis Intestinalis and Bowel Perforation Associated With Molecular Targeted Therapy: An Emerging Problem and the Role of Radiologists in Its Management

OBJECTIVE The purpose of this article is to study the imaging features, management, and outcome of pneumatosis intestinalis and bowel perforation associated with molecular targeted therapy. MATERIALS AND METHODS In this retrospective study, 48 patients with cancer who developed pneumatosis or intestinal perforation were found by searching a radiology database. Of these patients, 24 patients (13 women and 11 men; mean age, 61 years; range, 39-83 years) receiving molecular targeted therapy without any confounding factors for pneumatosis or perforation were selected. Initial and follow-up CT scans were evaluated by two radiologists; medical records were reviewed to note clinical features, management, and outcome. RESULTS Seventeen (70.8%) patients were asymptomatic. Colorectal cancer (n = 10) and renal cell carcinoma (n = 5) were the most common malignancies; bevacizumab (n = 14) and sunitinib (n = 6) were the most common associated drugs. Imaging findings included intestinal perforation (20 sites in 18 patients), pneumatosis (n = 10), ascites (n = 8), pneumoperitoneum (n = 7), fistula formation (n = 7), and fluid collections (six collections in five patients). Fifteen (62.5%) patients were treated conservatively, seven (29.2%) underwent surgery, and two (8.3%) underwent percutaneous drainage. Molecular targeted therapy was discontinued in 22 of 24 patients; findings resolved in 19 patients, remained stable in one, and worsened in one. One patient died after surgery. In both instances where the drug was continued, the abnormality worsened. Findings recurred in three of four patients in whom the drug was restarted after initial resolution. CONCLUSION Radiologists should be aware of intestinal complications associated with molecular targeted therapy, including pneumatosis, bowel perforation, and fistula formation. Most patients can be treated conservatively after discontinuation of molecular targeted therapy. Continuing or restarting molecular targeted therapy can cause worsening or recurrent pneumatosis or perforation.

Imaging of liposarcoma: classification, patterns of tumor recurrence, and response to treatment.

OBJECTIVE The purpose of this study was to illustrate the subtypes of liposarcoma (LPS) and the significance of the nonlipomatous tumor components using multiple imaging modalities. CONCLUSION The subtypes of LPS with greater nonlipomatous soft-tissue components on imaging studies tend to show less differentiation and are usually more aggressive both histologically and clinically. Imaging plays an important role in the diagnosis, surveillance, and response assessment of LPS.

Evaluation of 18F-FDG PET and MRI Associations in Pediatric Diffuse Intrinsic Brain Stem Glioma: A Report from the Pediatric Brain Tumor Consortium

The purpose of this study was to assess 18F-FDG uptake in children with a newly diagnosed diffuse intrinsic brain stem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS), and MRI indices. Methods: Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: phase I/II study of gefitinib; PBTC-014: phase I/II study of tipifarnib). Baseline brain 18F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus between 2 PET experts for intensity and uniformity of tracer uptake. Associations of 18F-FDG uptake intensity and uniformity with both PFS and OS, as well as associations with tumor MRI indices at baseline (tumor volume on fluid-attenuated inversion recovery, baseline intratumoral enhancement, diffusion and perfusion values), were evaluated. Results: In most of the children, BSG 18F-FDG uptake was less than gray-matter uptake. Survival was poor, irrespective of intensity of 18F-FDG uptake, with no association between intensity of 18F-FDG uptake and PFS or OS. However, hyperintense 18F-FDG uptake in the tumor, compared with gray matter, suggested poorer survival rates. Patients with 18F-FDG uptake in 50% or more of the tumor had shorter PFS and OS than did patients with 18F-FDG uptake in less than 50% of the tumor. There was some evidence that tumors with higher 18F-FDG uptake were more likely to show enhancement, and when the diffusion ratio was lower, the uniformity of 18F-FDG uptake appeared higher. Conclusion: Children with BSG for which 18F-FDG uptake involves at least half the tumor appear to have poorer survival than children with uptake in less than 50% of the tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors, compared with gray matter, suggests decreased survival. Higher 18F-FDG uptake within the tumor was associated with enhancement on MR images. Increased tumor cellularity as reflected by restricted MRI diffusion may be associated with increased 18F-FDG uniformity throughout the tumor.

Nuclear Medicine in the First Year of Life

Nuclear medicine has an important role in the care of newborns and children less than 1 y old. Patients in this age group present with a spectrum of diseases different from those of older children or adults. These patients can benefit from the full range of nuclear medicine studies. In these young children, nuclear medicine studies are more likely to be used to evaluate a wide range of congenital conditions but also can be helpful for evaluating acquired conditions such as infection, cancer, and trauma. This review first will cover the general aspects of nuclear medicine practice with these patients, including the special considerations that can help achieve successful diagnostic imaging. These topics will include clinical indications, imaging technology, instrumentation, software, positioning and immobilization, sedation, local and general anesthesia, radiopharmaceutical doses, radiation risk, and dose reduction. The review then will discuss the specific nuclear medicine studies that typically are obtained in patients in this age group. With extra care and attention to the special needs of this population, nuclear medicine departments can successfully study patients less than 1 y old.

MRI for evaluation of myeloid sarcoma in adults: a single-institution 10-year experience.

OBJECTIVE The purpose of this study was to evaluate the utilization and role of MRI in the management of myeloid sarcoma in adults. MATERIALS AND METHODS A retrospective study of 69 patients with pathologically proven myeloid sarcoma included 25 patients (16 men, nine women; mean age, 55 years; range, 22-78 years) who underwent pretreatment MRI at our institution from January 2001 to October 2011. A total of 71 MRI examinations were evaluated by two radiologists in consensus. RESULTS A total of 41 sites of involvement of myeloid sarcoma were noted, most commonly bone (13/25, 52%), muscle (7/25, 28%), CNS (6/25, 24%), and head and neck (6/25, 24%). Nineteen sites were noted on MR images obtained for evaluation of a new sign or symptom, most commonly musculoskeletal (11 sites) and CNS (six sites). Fifteen sites were noted on MR images obtained for further evaluation of a previously detected abnormality, most commonly in the abdomen and pelvis (seven sites). Seven lesions were incidentally found on MR images obtained for other myeloid sarcoma-related indications, most commonly in the head and neck (three lesions) and musculoskeletal system (three lesions). The mean size of measurable lesions was 5.6 cm (range, 1-20 cm). Compared with muscle, the lesions were isointense (31/41, 75.6%) or hypointense (10/41, 24.4%) on T1-weighted images and mildly hyperintense (39/41, 95.1%) on T2-weighted images and had homogeneous enhancement (29/38, 76.3%). CONCLUSION In our experience, MRI was most often used for evaluation of bone, muscle, the CNS, and the head and neck region. MRI is useful for evaluation of new musculoskeletal and CNS findings and for further evaluation of known abdominopelvic masses. Incidental findings are often musculoskeletal or in the soft tissues of the head and neck.

Anal carcinoma: FDG PET/CT in staging, response evaluation, and follow-up

The role of FDG PET/CT in anal cancer is becoming increasingly important. At the time of initial staging, FDG PET/CT can detect the primary site of disease more frequently than CT, is sensitive for nodal and metastatic spread and alters staging in a significant number of patients. Indeed, the NCCN guidelines for anal cancer published in April 2012 recommend FDG PET/CT for therapy planning. Metabolic activity of primary anal cancer at presentation is a potential biomarker for predicting prognosis, treatment response and survival. More intensely FDG-avid primary malignancy is associated with a higher incidence of disease spread. Metabolic response following chemoradiotherapy is associated with improved survival. The aim of this paper is to provide an up-to-date pictorial review of FDG PET/CT in anal cancer at the time of staging and to illustrate its utility for determining response to therapy and detecting recurrent disease.

Pheochromocytoma and paraganglioma: imaging characteristics

Abstract The accurate diagnosis of adult pheochromocytoma and paraganglioma necessitates a multidisciplinary approach that includes clinical history, biochemical testing, and multimodality imaging such as computed tomography, magnetic resonance imaging, and nuclear medicine studies. This review illustrates the different imaging characteristics of primary adult pheochromocytomas as well as both sympathetic and parasympathetic paragangliomas. The review also describes known genetic associations and shows common metastatic patterns. Knowledge of the diverse appearance of pheochromocytomas and paragangliomas can result in early initial diagnosis or detection of disease recurrence thereby affecting patient management and prognosis.