Jyothi P. Jagannathan

Major Response to Imatinib Mesylate in KIT-Mutated Melanoma

addition, this is the first reported case of a synchronous malignant melanoma and a small-cell lung cancer metastasizing to the same anatomic location. This case illustrates the necessity of proper pathologic evaluation in a brain lesion assumed to be a metastasis. In this case, had the patient’s performance status improved after her motor vehicle accident, she would have been offered systemic chemotherapy for her extensive-stage smallcell lung cancer, which can markedly improve survival, even in advanced disease. If this brain lesion had proven to be solely melanoma, it is unlikely that any systemic treatment would have been offered.

Revised RECIST Guideline Version 1.1: What Oncologists Want to Know and What Radiologists Need to Know

OBJECTIVE The objectives of this article are to review the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1, highlighting the major changes in the new version compared with the original RECIST guideline (version 1.0), and to present case examples with representative imaging. CONCLUSION Familiarity with the revised RECIST is essential in day-to-day oncologic imaging practice to provide up-to-date service to oncologists and their patients. Some of the changes in the revised RECIST affect how radiologists select, measure, and report target lesions.

Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma.

BACKGROUND Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome. OBJECTIVE To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT). DESIGN, SETTING, AND PARTICIPANTS Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31-223 d). MEASUREMENTS Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria. RESULTS AND LIMITATIONS Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p=0.02) and OS (32.5 vs 15.8 mo; p=0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations. CONCLUSIONS In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.

Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial

BACKGROUND Few treatment options remain for patients with metastatic or unresectable gastrointestinal stromal tumours (GIST) after objective progression on approved tyrosine-kinase inhibitors. We aimed to assess efficacy of imatinib rechallenge in these patients. METHODS In our prospective, randomised, double-blind trial, we enrolled adults (≥18 years) who had previously benefited from first-line imatinib (initial response or stable disease for ≥6 months) but whose metastatic or unresectable GIST had progressed on at least imatinib and sunitinib. We randomly allocated participants in a 1:1 ratio, with a centralised computer-generated allocation procedure (random permuted blocks of two, four, and six) and stratified by previous treatment and Eastern Cooperative Oncology Group performance status, to receive best supportive care with imatinib 400 mg per day or matched placebo. Crossover to open-label imatinib was allowed after investigator-adjudicated disease progression. The primary endpoint was progression-free survival (PFS), as determined by a masked external radiological review. All analyses were done for all patients who received at least one dose of study drug. FINDINGS Between July 20, 2010, and Jan 17, 2013, we randomly allocated 41 patients to the imatinib group and 40 patients to the placebo group. After a median follow-up of 5·2 months (IQR 3·4-9·4), median PFS was 1·8 months (95% CI 1·7-3·6) with imatinib compared with 0·9 months (0·9-1·7) with placebo (hazard ratio for progression or death 0·46, 95% CI 0·27-0·78; p=0·005). 37 (93%) patients in the placebo group crossed over to open-label imatinib after progression. The most common grade 3 or worse adverse events were anaemia (12 [29%] of 41 patients in the imatinib group vs three [8%] of 40 in the placebo group), fatigue (four [10%] vs none), and hyperbilirubinaemia (three [7%] vs one [3%]). INTERPRETATION In patients with GIST that is refractory to treatment with all standard tyrosine-kinase inhibitors, the disease continues to harbour many clones that are sensitive to kinase inhibitors. Continued kinase suppression might slow, although not halt, disease progression.

Pneumonitis associated with mTOR inhibitors therapy in patients with metastatic renal cell carcinoma: Incidence, radiographic findings and correlation with clinical outcome

BACKGROUND Mammalian target of rapamycin (mTOR) inhibitors are approved for use in patients with metastatic renal cell carcinoma (mRCC) and are under investigation in several other malignancies. We assessed the incidence, clinical presentation and computed tomography (CT) findings of pneumonitis associated with mTOR inhibitors in mRCC. Correlation between radiological findings of pneumonitis and clinical outcome was also determined. METHODS We retrospectively reviewed the clinical data and serial CT scans from patients with mRCC treated with either temsirolimus or everolimus. Serial chest CT scans were reviewed in consensus, read by two independent radiologists for the presence of pneumonitis, and corresponding clinical data were reviewed for symptoms and clinical outcome. The baseline and follow up CTs were reviewed to assess outcome to therapy. RESULTS The study population consisted of 46 pts, 21 treated with temsirolimus and 25 with everolimus (M:F 2.5:1; median 63 years, range 31-79 years). CT evidence of pneumonitis was seen in 14/46 pts (30%), at a median of 56days on mTOR inhibitor treatment (range 31-214 days). Respiratory symptoms at the time of radiographically detected pneumonitis, were observed in 7pts. Stable disease (SD) by Response Evaluation Criteria in Solid Tumours (RECIST) was achieved in 12/14 pts (86%) who developed radiographic pneumonitis compared to 14/32 (44%) without pneumonitis (p=0.01) The mean change of tumour long axis size for target lesions by RECIST, normalised for 30 days on therapy was -2.9% in the pneumonitis group and +4.3% in the non-pneumonitis group (p=.002). CONCLUSIONS Preliminary data suggest that pneumonitis may be a marker of stable disease by RECIST and therefore, of therapeutic benefit. Careful patient assessment should be undertaken before the drug is discontinued.

Metastatic Pattern of Bladder Cancer: Correlation With the Characteristics of the Primary Tumor

OBJECTIVE The purpose of this study was to evaluate the metastatic pattern of muscle-invasive bladder cancer and to correlate the findings with the characteristics of the primary tumor. MATERIALS AND METHODS From a clinic population of 392 patients with muscle-invasive (pT2-4) bladder cancer seen at our institution from January 2004 through December 2009, we studied the cases of 150 consecutively registered patients with pathologically proven metastatic disease. The metastasis-free intervals and metastatic patterns of different T categories were compared by Kruskal-Wallis test and Freeman-Halton extension of Fishers exact test. Patients were divided into two histologic categories, those with transitional cell carcinoma and those with atypical histologic features. The metastasis-free interval and metastatic pattern of these two groups were compared by Mann-Whitney test and Fishers exact test. RESULTS The study group consisted of 150 patients (116 men [77%], 34 women [23%]; median age, 64 years). The transitional cell carcinoma group consisted of 94 (63%) patients and the atypical histologic features group of 56 (37%) patients. The most common metastatic sites were lymph nodes (104 patients, 69%), bone (71 patients, 47%), lung (55 patients, 37%), liver (39 patients, 26%), and peritoneum (24 patients, 16%). Patients with tumors of a more advanced T category had shorter metastasis-free intervals (p = 0.001, df = 2). There was no significant difference in the metastatic patterns of tumors in the different T categories. Patients with atypical histologic features had a shorter median metastasis-free interval (3 months; range, 0-29 months) than patients with transitional cell carcinoma (12 months; range, 0-192 months) (p = 0.0001). Patients with atypical histologic features had a significantly higher incidence of peritoneal metastasis (p < 0.0002). CONCLUSION Lymph nodes, bones, lung, liver, and peritoneum are the most common sites of metastasis from bladder cancer. Tumors in a more advanced T category and those with atypical histologic features metastasize earlier. Tumors with atypical histologic features also have a higher frequency of peritoneal metastasis.

A to Z of Desmoid Tumors

OBJECTIVE The purpose of this article is to illustrate the common locations of desmoid tumors (deep fibromatosis), complications of intra- and extraabdominal desmoids, and treatment-related changes in their imaging appearance. CONCLUSION Desmoids are locally aggressive fibrous tumors with a tendency to recur. Desmoids can be intraabdominal, in the abdominal wall, or extraabdominal. Complications, such as compression or invasion of adjacent structures, and abscess formation can occur. Treatment options include observation, local treatment (surgery, radiotherapy), or systemic therapy (conventional chemotherapy, molecular targeted agents).

Ipilimumab-Associated Colitis: CT Findings

OBJECTIVE The purpose of this article is to describe the CT findings of ipilimumab-associated colitis. MATERIALS AND METHODS In this retrospective study, 16 patients diagnosed with ipilimumab-associated colitis and available CT scans obtained at the time of symptoms were found by a search through the electronic medical record database. Two radiologists reviewed the CT images in consensus for the presence of bowel wall thickening, bowel mucosal enhancement, bowel distention, pneumatosis, pericolic fat stranding, and mesenteric vessel engorgement. Medical records were reviewed to note clinical features, management, and outcome. RESULTS The common CT findings of ipilimumab-associated colitis were mesenteric vessel engorgement (13/16 [81.3%]) followed by bowel wall thickening (12/16 [75%]) and fluid-filled colonic distention (4/16 [25%]). None of the patients had pneumatosis or halo or target signs. Two distinct CT patterns of ipilimumab-associated colitis were observed: first, the diffuse colitis pattern (n = 12), which is characterized by mesenteric vessel engorgement with mild diffuse bowel wall thickening or fluid-filled distended colon; and, second, the segmental colitis associated with diverticulosis (SCAD) pattern (n = 4), which is characterized by segmental moderate wall thickening and associated pericolic fat stranding in a segment of preexisting diverticulosis. Clinical features and management also differed according to the CT pattern. Patients with the diffuse colitis pattern presented with watery diarrhea and were treated with steroids, whereas the patients with the SCAD pattern presented with mixed watery and bloody diarrhea and cramping pain and were treated with steroids and antibiotics. CONCLUSION Two different radiologic and clinical manifestations of ipilimumab-associated colitis were observed: the diffuse colitis pattern and the SCAD pattern.

Uterine Sarcomas: Then and Now

OBJECTIVE The purpose of this article is to provide an updated review of uterine sarcomas. The traditionally described neoplasms are reviewed as well as several recently characterized entities in terms of their imaging and clinical aspects. We attempt to provide a longitudinal imaging overview, from initial presentation to follow-up. Imaging features are also described of response to traditional therapeutic agents and newer targeted agents. CONCLUSION A greater understanding of the pathogenesis has improved our ability to image and treat uterine sarcomas, both at initial staging and on follow-up. Targeted therapy is assuming an increasingly important role in the management of these lesions. It is imperative for radiologists to be aware of response characteristics and potential complications of these agents as well as conventional chemotherapeutic agents.

Venous thromboembolism: indirect CT venography during CT pulmonary angiography--should the pelvis be imaged?

PURPOSE To retrospectively determine the relative contribution of pelvic and lower-extremity indirect computed tomographic (CT) venography to the diagnosis of venous thromboembolism (VTE) in patients undergoing CT for pulmonary embolism (PE). MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board, and informed consent was waived. The records of 2074 consecutive patients (890 men, 1184 women; mean age, 59 years; age range, 15-97 years) suspected of having PE who underwent combined CT pulmonary angiography and CT venography between May 2005 and March 2006 were reviewed. CT venograms from the iliac crests to the popliteal fossae were reviewed for presence and location of thrombi. Radiology reports were reviewed for CT pulmonary angiographic results. Thrombus detection rates with and without pelvic CT venography were compared by using the chi(2) test. Separate effective radiation doses for CT venography of pelvis and lower extremities were calculated. RESULTS On CT images of the 2074 patients, VTE was detected in 283 (13.6%) patients; PE, in 237 (11.4%); and deep vein thrombosis (DVT), in 121 (5.8%). Forty-six patients had DVT but no PE. Addition of CT venography to CT pulmonary angiography increased the detection of VTE by 19.4% (46 of 237). Isolated pelvic DVT was seen in two (0.1%) patients. There was no difference in the detection of VTE whether or not the pelvis was included (P = .92). Effective radiation dose for CT venography was 5.2 mSv +/- 0.5 (standard deviation) for the pelvis and 0.6 mSv +/- 0.2 for the lower extremities. CONCLUSION CT venography of the pelvis during CT pulmonary angiography does not significantly improve the detection of VTE. CT venography may be limited to the lower extremities, thus reducing radiation dose.