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Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7-52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide-rituximab is associated with prolonged response duration.

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The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

To evaluate colorectal cancer hepatic metastasis detection and characterization between reduced radiation dose (RD) and standard dose (SD) contrast material-enhanced CT of the abdomen and to qualitatively compare between filtered back projection (FBP) and iterative reconstruction algorithms. Materials and Methods:In this prospective study (from May 2017 through November 2017), 52 adults with biopsy-proven colorectal cancer and suspected hepatic metastases at baseline CT underwent two portal venous phase CT scans: SD and RD in the same breath hold. Three radiologists, blinded to examination details, performed detection and characterization of 2-15-mm lesions on the SD FBP and RD adaptive statistical iterative reconstruction (ASIR)-V 60% series images. Readers assessed overall image quality and lesions between SD FBP and seven different iterative reconstructions. Two nonblinded consensus reviewers established the reference standard using the picture archiving and communication system lesion marks of each reader, multiple comparison examinations, and clinical data.Results: RD CT resulted in a mean dose reduction of 54% compared with SD. Of the 260 lesions (233 metastatic, 27 benign), 212 (82%; 95% confidence interval [CI]: 76%, 86%) were detected with RD CT, whereas 252 (97%; 95% CI: 94%, 99%) were detected with SD (P , .001); per-lesion sensitivity was 79% (95% CI: 74%, 84%) and 94% (95% CI: 90%, 96%) (P , .001), respectively. Mean qualitative scores ranked SD images as higher quality than RD series images, and ASIR-V ranked higher than ASIR and Veo 3.0. Conclusion:CT evaluation of colorectal liver metastases is compromised with modest radiation dose reduction, and the use of iterative reconstructions could not maintain observer performance.

Adaptive statistical iterative reconstruction-V 30% and ASIR-V 60% provided the best combination of qualitative and quantitative performance. Adaptive statistical iterative reconstruction 80% was equivalent qualitatively, but demonstrated inferior spatial resolution and LCD.