Randomized Phase 2 Trial of Tremelimumab and Durvalumab in Combination Versus Sequentially in Recurrent Platinum-Resistant Ovarian Cancer

BACKGROUND: Single-agent immune checkpoint inhibitors (ICIs) have demonstrated limited responses in recurrent ovarian cancer; however, 30%-40% of patients achieve stable disease. The primary objective was to estimate progression-free survival (PFS) after sequential versus combination cytotoxic T-lymphocyte antigen 4 and programmed death ligand 1 ICIs in patients with platinum-resistant high-grade serous ovarian cancer (HGSOC). METHODS: Patients were randomized to a sequential arm (tremelimumab followed by durvalumab on progression) or a combination arm (tremelimumab plus durvalumab, followed by durvalumab) via a Bayesian adaptive design that made it more likely for patients to be randomized to the more effective arm. The primary end point was immune-related PFS (irPFS). RESULTS: Sixty-one subjects were randomized to sequential (n = 38) or combination therapy (n = 23). Thirteen patients (34.2%) in the sequential arm received durvalumab. There was no difference in PFS in the sequential arm (1.84 months; 95% CI, 1.77-2.17 months) compared with the combination arm (1.87 months; 95% CI, 1.77-2.43 months) (p = .402). In the sequential arm, no responses were observed, although 12 patients (31.6%) demonstrated stable disease. In the combination arm, two patients (8.7%) had partial response, whereas one patient (4.4%) had stable disease. Adverse events were consistent with those previously reported for ICIs. Patient-reported outcomes were similar in both arms. CONCLUSIONS: There was no difference in irPFS for combination tremelimumab plus durvalumab compared to tremelimumab alone (administered as part of a sequential treatment strategy) in a heavily pretreated population of patients with platinum-resistant HGSOC. Response rates were comparable to prior reports, although the combination regimen did not add significant benefit, as has been previously described

Imaging Features of Rare Hepatic Tumors

Hepatic lesions are commonly encountered in radiology practice. Lesions with classic imaging findings such as hepatocellular carcinoma, cholangiocarcinoma, hemangiomas, focal nodular hyperplasia, and adenomas are well described in literature and easily diagnosed by most experienced radiologists. In the appropriate context, metastases, which are one of the most common lesions encountered by radiologists who practice in predominantly cancer care settings, are also easily diagnosed. However, one may encounter rarer neoplasms which may be challenging to diagnose and manage. Often, these lesions have overlapping imaging features with those of the common lesions mentioned above. Diagnosis of these rarer tumors would require not only interpreting the images in the context of patient's demographics and clinical presentation but also recognizing the unique imaging features of these tumors. The literature is sparse in describing the radiological appearances of these tumors. Diagnosis based solely on imaging criteria is not advised in these instances. Histological confirmation or other prudent follow-up strategies are necessary for confirmation of imaging findings and interpretation. In this article, we will describe known imaging features of a few rarer primary malignant and benign neoplasms in the liver

Visualization and Quantification of Intraperitoneal Tumors by In Vivo Computed Tomography Using Negative Contrast Enhancement Strategy in a Mouse Model of Ovarian Cancer

Small animal computed tomography (CT) has poor intrinsic soft tissue contrast, limiting evaluation of intra-abdominal structures. Using standard intravascular-extracellular intravenous contrast (IE-IV) alone is theoretically limited by long acquisition times of traditional small animal scanners that may result in equilibration. We assessed whether a negative contrast strategy of enhancing normal tissue surrounding tumor, instead of the tumor itself, can visualize and quantify intraperitoneal (IP) cancer in a mouse model. Two and a half weeks after IP injection of Hey A8 cells, four groups of three animals each were administered serial dilutions of IV Fenestra LC (RES-IV), oral Gastroview, and IP Optiray 320. Another group of three animals was administered IV Optiray 320 (IE-IV), oral Gastroview, and IP Optiray 320 in successive combinations. Both groups were imaged by CT. Tumor and organ Hounsfield units were measured, and visualization was assessed. With increasing contrast amount, the Hounsfield unit of organs generally increased, whereas that of tumor remained essentially stable. The visualization of abdominal organs and tumor also generally increased with increasing contrast amount. Visualization of tumor and its margins adjacent to liver, spleen, and stomach was significantly better on administering RES-IV. However, for tumor adjacent to bladder, both IE-IV and RES-IV were equivalent. In vivo CT-derived tumor weights correlated highly with ex vivo tumor weights (r = 0.96, P < .0001, n = 15). Thus, CT using negative contrast enhancement strategy allows visualization and quantification of IP tumors. Such a strategy will also enable anatomic localization of functional signal for combination/molecular imaging

Abdominal and pelvic complications of nonoperative oncologic therapy.

Oncologic patients are treated with a combination of chemotherapy, radiation therapy, and surgery. Advances in therapeutic options have greatly improved the survival of patients with cancer. Examples of these advances are newer chemotherapeutic agents that target the cell receptors and advanced radiation therapy delivery systems. It is imperative that radiologists be aware of the variety of imaging findings seen after therapy in patients with cancer. Complications may occur with classic cytotoxic therapies (eg, 5-fluorouracil), usually at higher or prolonged doses or when administered to radiosensitive areas. Newer targeted systemic agents, such as bevacizumab and imatinib, have associated characteristic toxicities because their effects on cells do not depend on dose. Radiation may induce early and late effects in local normal tissues that may be seen at imaging. Imaging findings after chemotherapy include fatty liver, pseudocirrhosis, hepatic veno-occlusive disease, and splenic rupture. Complications of radiation therapy include large and small bowel strictures and radiation-induced hepatitis and tumors. Awareness of the various therapeutic options and knowledge of the spectrum of posttherapeutic complications allows radiologists to provide a comprehensive report that may impact patient management

Lexicon for renal mass terms at CT and MRI: a consensus of the society of abdominal radiology disease-focused panel on renal cell carcinoma

PurposeThere is substantial variation in the radiologic terms used to characterize renal masses, leading to ambiguity and inconsistency in clinical radiology reports and research studies. The purpose of this study was to develop a standardized lexicon to describe renal masses at CT and MRI.Materials and methodsThis multi-institutional, prospective, quality improvement project was exempt from IRB oversight. Thirteen radiologists belonging to the Society of Abdominal Radiology (SAR) disease-focused panel on renal cell carcinoma representing nine academic institutions participated in a modified Delphi process to create a lexicon of terms used to describe imaging features of renal masses at CT and MRI. In the first round, members voted on terms to be included and proposed definitions; subsequent voting rounds and a teleconference established consensus. One non-voting member developed the questionnaire and consolidated responses. Consensus was defined as ≥ 80% agreement.ResultsOf 37 proposed terms, 6 had consensus to be excluded. Consensus for inclusion was reached for 30 of 31 terms (13/14 basic imaging terms, 8/8 CT terms, 6/6 MRI terms and 3/3 miscellaneous terms). Despite substantial initial disagreement about definitions of 'renal mass,' 'necrosis,' 'fat,' and 'restricted diffusion' in the first round, consensus for all was eventually reached. Disagreement remained for the definition of 'solid mass.'ConclusionsA modified Delphi method produced a lexicon of preferred terms and definitions to be used in the description of renal masses at CT and MRI. This lexicon should improve clarity and consistency of radiology reports and research related to renal masses