Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer.

BACKGROUND: This trial evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients with metastatic triple-negative breast cancer (mTNBC). METHODS: Eligibility criteria were mTNBC, RECIST 1.1 measurable disease, no prior use of platinum for metastatic disease (Arms A and B), and no prior exposure to immune checkpoint inhibitor (Arm C). Primary endpoints were safety and RP2D. Secondary endpoints were progression-free survival (PFS), response rate, and overall survival. RESULTS: RP2D for Arm A (n = 10) was ipatasertib 300 mg daily, carboplatin AUC2, and paclitaxel 80 mg m-2 days 1, 8, and 15 every 28 days. RP2D for Arm B (n = 12) was ipatasertib 400 mg daily and carboplatin AUC2 days 1, 8, and 15 every 28 days. RP2D for Arm C (n = 6) was likely ipatasertib 300 mg 21 days on 7 days off, capecitabine 750 mg m-2, twice a day, 7 days on 7 days off, and atezolizumab 840 mg days 1 and 15 every 28 days. The most common (≥10%) grade 3-4 AEs at RP2D for Arm A (N = 7 at RP2D) were neutropenia (29%), diarrhea (14%), oral mucositis (14%), and neuropathy (14%); Arm B had diarrhea (17%) and lymphopenia (25%); and Arm C had anemia, fatigue, cognitive disturbance, and maculopapular rash (17% each). Overall responses at RP2D were 29% Arm A, 25% Arm B, and 33% Arm C. PFS was 4.8, 3.9, and 8.2 months for patients on Arms A, B, and C, respectively. CONCLUSIONS: Continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated. Further study is warranted in understanding the role of AKT inhibition in treatment of TNBCs. TRIAL REGISTRATION: NCT03853707.

Preoperative Computed Tomography Assessment for Perinephric Fat Invasion: Comparison With Pathological Staging.

OBJECTIVE: The aim of this study was to assess the accuracy of computed tomography (CT) imaging in diagnosing perinephric fat (PNF) invasion in patients with renal cell carcinoma. METHODS: We retrospectively reviewed the medical records and preoperative CT images of 161 patients (105 men and 56 women) for pT1-pT3a renal cell carcinoma. We analyzed the predictive accuracy of CT criteria for PNF invasion stratified by tumor size. We determined the predictive value of CT findings in diagnosing PNF invasion using logistic regression analysis. RESULTS: The overall accuracy of perinephric (PN) soft-tissue stranding, peritumoral vascularity, increased density of the PNF, tumoral margin, and contrast-enhancing soft-tissue nodule to predict PNF invasion were 56%, 59%, 35%, 80%, and 87%, respectively. Perinephric soft-tissue stranding and peritumoral vascularity showed high sensitivity but low specificity regardless of tumor size. A contrast-enhancing soft-tissue nodule showed low sensitivity but high specificity in predicting PNF invasion. Among tumors 4 cm or less, PN soft-tissue stranding showed 100% sensitivity and 70% specificity, and tumor margin showed 100% sensitivity and 98% specificity. Among CT criteria for PNF invasion, PN soft-tissue stranding was chosen as the only significant factor for assessing PNF invasion by logistic regression analysis. CONCLUSIONS: Computed tomography does not seem to reliably predict PNF invasion. However, PN soft-tissue stranding was shown to be the only significant factor for predicting PNF invasion, which showed good accuracy with high sensitivity and high specificity in tumors 4 cm or less.

Duplex Doppler Imaging of Dialysis Fistulae and Grafts.

Arteriovenous fistulae and grafts for hemodialysis access are a lifeline in patients with end-stage renal disease. A significant cause of morbidity and mortality in this population is dialysis access dysfunction. Duplex ultrasound imaging is an excellent modality to evaluate arteriovenous fistulae and grafts, the 2 main types of long-term hemodialysis access. This review provides a detailed Doppler ultrasound protocol for evaluation of fistulae or grafts to familiarize imagers with their normal appearance, highlighting common dialysis access complications.

Comparison of Renal Parenchymal Volume Preservation Between Partial Nephrectomy, Cryoablation, and Radiofrequency Ablation Using 3D Volume Measurements.

PURPOSE: Small renal masses (SRM) can be managed via a variety of nephron-sparing procedures (NSPs), but the association between choice of NSP and renal parenchymal volume (RPV) preservation is not well understood. We sought to examine RPV preservation after partial nephrectomy (PN) performed via open, robotic, or laparoscopic approaches and thermal ablation (TA) performed via cryoablation (CA) or radiofrequency ablation (RFA). PATIENTS AND METHODS: The study was a retrospective review of three institutional databases of patients with a SRM <4 cm treated via one of the five NSPs (open PN, laparoscopic PN, robotic PN, percutaneous CA, or percutaneous RFA). The 30 most recent consecutive cases treated via each NSP were selected to obtain a total of 150 cases for analysis. Patient characteristics were obtained via manual chart review, and tumor characteristics were assessed via the R.E.N.A.L. nephrometry score. Using three-dimensional rendering software, preoperative and postoperative RPV was calculated for the tumor-bearing kidney, excluding the tumor itself (for preoperative images) or the postsurgical/ablative defect (for postoperative images). The percent change in RPV was compared between the procedure types. RESULTS: One hundred fifty cases were included in the final analysis, with 30 cases from each NSP category. While preoperative tumors were larger in the PN group, there was no difference in the mean nephrometry score between groups. The TA group was found to have a lower mean RPV loss (-8.1% vs -16.5%, p<0.005). There was no difference in the RPV loss between modalities of TA (CA vs RFA) or between approaches to PN (open, laparoscopic, robotic). Matched-pair analysis based on the tumor size and multivariate analysis indicated TA vs PN was independently associated with less RPV loss. CONCLUSIONS: TA is associated with less RPV loss than PN in the management of SRM, but there is no difference between modalities of TA (CA vs RFA) or between approaches to PN.

Overview of migraine treatment.

SUMMARY Migraine is ranked as the 19th top cause of disability worldwide by WHO. Despite advancements in migraine-specific acute treatment, only a minority of patients utilize these medications. Specific pharmacologic treatments consist of the ergot alkaloids and triptans (serotonin 5-HT1B/1D receptor agonists). Both classes are regarded as relatively safe and effective; however, there is a greater concern for vasoconstrictive effects with the ergots, which limits their use. Triptans transformed migraine therapy, setting in motion revolutionary research that heightened our understanding of migraine mechanisms. However, one in three migraineurs may be triptan nonresponders and there is a group of migraine patients that remains 'refractory' to conventional pharmacologic migraine therapy. This article discusses the approach to migraine management, reviews currently available acute and preventive pharmacologic and nonpharmacologic treatment options for migraine headache, as well as briefly focuses on novel and upcoming medicines presently under investigation.

Migraine pathophysiology.

SUMMARY Our understanding of migraine pathophysiology is a work in progress, largely because of the absence of any identifiable cephalic pathology. There are currently two main theories on the genesis of migraine pain. One hypothesizes that the origin is in the periphery, requiring the activation of primary afferent nociceptive neurons that innervate cephalic tissue. The other theorizes that the origin of migraine pain is in the CNS, as a result of abnormal processing of sensory signals, rather than the activation of nociceptors. After briefly reviewing the clinical presentation and diagnosis of migraine, this article focuses on explaining the traditional and current theories of migraine pathogenesis.