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PDF file - 82K, Response kinetics in treated patients. Baseline tumor measurements are standardized to zero. A. Entire treatment population (cohorts 1-4). B. Cohort 2 patients (MTD). Horizontal line PD = progressive disease representing 20% increase. Horizontal line PR represents 30% decrease from baseline. Filled in circle depicts radiographic development of new sites of disease.

PDF file - 68K, A. Axial CT section of the chest at baseline demonstrates two nodules in the right lung, the dominant one in the lower lobe (white arrows). B. Follow-up CT 3 months after start of treatment demonstrates resolution of one of the nodules and no change in the other nodule. C. Axial CT section 8 months after start of treatment demonstrates complete resolution of the dominant lung nodule.

PDF file - 74K, High-power H&E and CD31 stained post treatment biopsy of intratumoral vessels. The endothelial cells appear morphologically columnar. CD31 staining is concentrated at the interendothelial junctions (arrows).

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PDF file - 64K, Illustrations of the variation in pathologic responses to treatment. Examples of intermediate and no response.

PDF file - 76K, CONSORT Diagram.

PDF file - 125K, Individual response of CCR7+CD45RO+ and CCD7-CD45RO+ of CD4+ and CD8+ T cells in melanoma patients treated with ipilimumab (3mg/kg), ipilimumab (3mg/kg) plus bevacizumab, or ipilimumab (10mg/kg) plus bevacizumab.

PDF file - 39K, Summary of grade 3 and grade 4 events incidence at each dose level for all events and those events possibly, probably, or definitively related.

PDF file - 111K, Patient Demographics.

PDF file - 59K, Kaplan-Meier estimates for time-to-progression in the entire treated population (A) and by treatment cohort (B). Kaplan-Meier estimates for overall survival in the entire treated population (C) and by treatment cohort (D).

PDF file - 139K, Worst grade adverse event for individual patients that occurred within the first twelve weeks of treatment (induction dose-limiting toxicity period). Adverse events recorded multiple times for any patient are reported only once according to the worst grade.

PDF file - 43K, Best overall response in ipilimumab plus bevacizumab treated patients per RECIST criteria by treatment cohort.

Supplemental Table 1. Adverse events observed and adjudicated as possibly, probably or definitely related to therapy (n = 19).

Purpose: Although durable responses can be achieved with tyrosine kinase inhibitors such as imatinib in melanomas harboring KIT mutations, the efficacy of alternative inhibitors after progression to imatinib and the activity of these agents on brain metastases are unknown.Experimental Design: We conducted a phase II study of nilotinib 400 mg twice a day in two cohorts of patients with melanomas harboring KIT mutations or amplification: (A) those refractory or intolerant to a prior KIT inhibitor; and (B) those with brain metastases. The primary endpoint was 4-month disease control rate. Secondary endpoints included response rate, time-to-progression (TTP), and overall survival (OS). A Simon two-stage and a single-stage design was planned to assess for the primary endpoint in cohorts A and B, respectively.Results: Twenty patients were enrolled and 19 treated (11 in cohort A; 8 in cohort B). Three patients on cohort A [27%; 95% confidence interval (CI), 8%–56%] and 1 on cohort B (12.5%; 90% CI, 0.6%–47%) achieved the primary endpoint. Two partial responses were observed in cohort A (18.2%; 90% CI, 3%–47%); none were observed in cohort B. The median TTP and OS was 3.3 (90% CI, 2.1–3.9 months) and 9.1 months (90% CI, 4.3–14.2 months), respectively, in all treated patients.Conclusions: Nilotinib may achieve disease control in patients with melanoma harboring KIT alterations and whose disease progressed after imatinib therapy. The efficacy of this agent in KIT-altered melanoma with brain metastasis is limited. Clin Cancer Res; 21(10); 2289–96. ©2015 AACR.

Dysphagia, or a disorder of swallowing, is very common and is reported in 1 out of 25 adults with approximately 1 million new cases per year in the United States alone. This also disproportionately impacts elderly patients, with a prevalence of 17%. Patients with dysphagia may have severe clinical complications such as starvation, dehydration, and airway obstruction- which may further increase mortality. Hence, timely and accurate diagnosis of dysphagia is hence crucial in management considerations. The gold standard for evaluating and diagnosing dysphagia is a modified barium swallow study (MBSS). The study is typically performed as a collaborative effort between a speech language pathologist (SLP) and a radiologist, who bring their individual skill sets to the table. Current MBSS reporting involves separately dictated and interpreted reports from the SLP and radiologist. In this paper, we elucidate our experience in a multi-institutional healthcare system wherein we have devised a single, integrated report for MBSS, which involves collaborative effort between SLP and the radiologist. We weight the advantages and disadvantages of unified reporting, the challenges of implementing it in a large healthcare system, and note how it can help improve efficiency and deliver unified patient care. We hope that this would be a template for other institutions as well as improve standardization of reporting techniques.

The radiology report is the primary work product of the diagnostic radiologist. Its quality is a direct reflection of his or her knowledge, experience, and confidence. Certain factors hindering one's ability to deliver a diagnostically accurate and concise report are sometimes unavoidable (e.g., study limitations and insufficient history); however, radiologists who routinely produce deficient reports not only erode their credibility and reputation amongst colleagues, they magnify their risk of litigation.This article is directed toward radiology residents to help facilitate the adoption of effective reporting habits.Up to 92% of referring physicians and 95% of radiologists agree that learning to report should be an "obligatory and well-structured" component of radiology residency education as discussed by Bosmans JM, Weyler JJ, De Schepper AM, and Parizel PM. Unfortunately, this remains the exception rather than the rule. This article is written with the following objectives: (1) to identify strategies that improve the value of radiology reporting, (2) to define the features of a high-quality radiology report, (3) to instill trust and respect from referring clinicians through clear, accurate, and effective communication, and (4) to understand and avoid potential medicolegal ramifications of deficient radiology reports.

OBJECTIVE. The objective of this article is to illustrate examples of radiologic immune-related response criteria and toxicity in patients with advanced melanoma treated with the immunotherapeutic agent ipilimumab. CONCLUSION. Novel immune-related tumor response criteria should be applied to patients undergoing therapy with ipilimumab for advanced melanoma. Ipilimumab also produces a spectrum of immune-related adverse effects that can be recognized radiologically.

Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known.The authors performed a single-arm phase 2 study of the aromatase inhibitor letrozole at a dose of 2.5 mg daily in patients with unresectable ULMS with ER and/or PR expression confirmed by immunohistochemistry. Tumor assessments were performed at baseline, 6 weeks, 12 weeks, and every 8 weeks thereafter. Toxicity was monitored throughout treatment. The primary endpoint was the progression-free survival at 12 weeks.A total of 27 patients was accrued, with a median of 2 prior treatment regimens (range, 0-9 treatment regimens). The median duration of protocol treatment was 2.2 months (range, 0.4 months-9.9 months). The 12-week progression-free survival rate was 50% (90% confidence interval, 30%-67%). The best response was stable disease in 14 patients (54%; 90% CI, 36%-71%). Three patients, all of whom had tumors expressing ER and PR in90% of tumor cells, continued to receive letrozole for24 weeks. The most common reason for treatment discontinuation was disease progression (85%). Letrozole was found to be well tolerated.Letrozole met protocol-defined criteria as an agent with activity in patients with advanced ULMS. Patients with the longest progression-free survival rate were those whose tumors strongly and diffusely expressed ER and PR.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed.

Malignant primary chest wall neoplasms (MCWN) are uncommon. Although benign chest wall neoplasms are most commonly asymptomatic, MCWN typically manifest as painful, fast growing masses. While the imaging features of malignant masses can be nonspecific, knowledge of the typical radiologic manifestations of MCWN may suggest a specific diagnosis. We review imaging features of the most common MCWN with images collected at an outpatient academic oncologic center. Objective While the imaging features of patients with malignant masses can be nonspecific, knowledge of the typical radiologic manifestations of MCWN may suggest a specific diagnosis. We review distinguishing imaging features of the most common MCWN, including epithelial and mesenchymal malignancies, with images collected at an outpatient oncologic center. Conclusion Chest wall neoplasms encompass 5% of all thoracic tumors, with nearly half of chest wall neoplasms being malignant. Out of these malignant neoplasms, 50% are primary and the commonest one is chondrosarcoma. Although distinguishing imaging features may suggest a specific diagnosis in the majority of MCWN, most affected patients undergo biopsy for a definitive diagnosis.

LBA10502 Background: To palliate and prolong disease control after failure of all available treatment in advanced GIST, resumption of IM dosing has been commonly practiced based on evidence of rapid GIST progression after discontinuation of all TKIs. We evaluated the efficacy of IM rechallenge in pts with advanced GIST following failure of all TKIs. Methods: Eligible pts had metastatic and/or unresectable GIST with prior benefit from first-line IM (defined as disease control for > 6 months), progressive disease (PD) on first-line IM, PD on or intolerance to SU, and ECOG performance status 0-3. Pts were randomized 1:1 to receive best supportive care with either IM 400 mg po once daily or PL. At the time of PD, pts were unblinded and allowed to cross-over to open-label IM. The primary endpoint was progression-free survival (PFS) determined by blinded external radiology review according to RECIST v1.0. Secondary endpoints included overall survival (OS), time to progression, disease control rate (DCR) at 12 weeks, and safety. Results: Between July 2010 and January 2013, 81 pts were randomized (IM: 41, PL: 40) at a single Korean center. All baseline characteristics were balanced between the arms and 40% of pts received ≥ 3 prior TKIs. The planned final analysis in March 2013 demonstrated that the primary endpoint was met, with significantly greater PFS for pts randomized to IM vs. PL : 1.8 vs. 0.9 months, respectively (p=0.002), hazard ratio (HR) 0.45 (95% CI, 0.27-0.76). DCR at 12 weeks was 32% for IM vs. 5% for PL (p=0.003). With 92.5 % of PL pts rapidly crossing over to IM, median OS was 8.2 months for IM vs. 7.5 months for PL (HR of 0.99, p=0.982). The most common treatment-emergent AEs (> grade 3) during double-blind period in the IM arm included anemia (29%), fatigue (10%), and hyperbilirubinemia (7%). Conclusions: Rechallenge of IM significantly improves PFS and DCR in pts with advanced GIST after failure of at least IM and SU, likely by continuous kinase inhibition of the bulk of disease clones which retain IM sensitivity. However, TKI-resistant clones continue to progress leading to relatively brief duration of benefit. Clinical trial information: NCT01151852.