The accumulation of immune-suppressive myeloid cells is a critical determinant of resistance to anti–programmed death-1 (PD-1) therapy in advanced clear cell renal cell carcinoma (ccRCC). In preclinical models, the tyrosine kinase inhibitor sitravatinib enhanced responses to anti–PD-1 therapy by modulating immune-suppressive myeloid cells. We conducted a phase 1-2 trial to choose an optimal sitravatinib dose combined with a fixed dose of nivolumab in 42 immunotherapy-naïve patients with ccRCC refractory to prior antiangiogenic therapies. The combination demonstrated no unexpected toxicities and achieved an objective response rate of 35.7% and a median progression-free survival of 11.7 months, with 80.1% of patients alive after a median follow-up of 18.7 months. Baseline peripheral blood neutrophil-to-lymphocyte ratio correlated with response to sitravatinib and nivolumab. Patients with liver metastases showed durable responses comparable to patients without liver metastases. In addition, correlative studies demonstrated reduction of immune-suppressive myeloid cells in the periphery and tumor microenvironment following sitravatinib treatment. This study provides a rationally designed combinatorial strategy to improve outcomes of anti–PD-1 therapy in advanced ccRCC.

Objectives Real-time magnetic resonance imaging (MRI)–guided cryoablation has been investigated in open MRI systems with low magnetic fields (0.2–0.5 T). More advanced imaging techniques and faster imaging rates are possible at higher magnetic fields, which often require a closed-bore magnet design. However, there is very little experience with real-time interventions in closed-bore 1.5-T MRI units. Herein, we report our initial experience with real-time MRI-guided cryoablation of small renal tumors using a prototype balanced steady-state free precession imaging sequence in a closed-bore 1.5-T MRI system. Materials and Methods From August 2008 to April 2012, 18 patients underwent MRI-guided cryoablation of small renal tumors. A 1.5-T cylindrical MRI scanner with a 125 cm × 70 cm bore and a prototype balanced steady-state free precession sequence (BEAT interactive real-time tip tracking) were used to guide the placement of 17-gauge cryoprobes in real time. Ice ball formation was monitored every 3 minutes in 1 or more imaging planes. Each ablation consisted of 2 freeze-thaw cycles. Contrast-enhanced MRI was performed after the second active thaw period. Follow-up consisted of clinical evaluation and renal protocol computed tomography (CT) or MRI performed at 1, 6, 12, 18, and 24 months and annually thereafter. Results During the study period, we successfully ablated 18 tumors in 18 patients in 18 sessions. The mean tumor size was 2.2 cm (median, 2 cm; range, 1.2–4.4 cm). The number of cryoprobes used per patient was determined based on tumor size. The mean number of cryoprobes used per patient was 3 (median, 3 cryoprobes; range, 2–4 cryoprobes). Fifty-six cryoprobes, 9 biopsy needles, and 2 hydrodissection needles were successfully placed under real-time MRI guidance using BEAT interactive real-time tip tracking sequence. Hydrodissection under MRI guidance was successfully performed in 4 patients. In each patient, contrast-enhanced MRI performed after the second active thaw period revealed a sharply defined avascular zone surrounding the targeted tumor, which confirmed complete ablation of the tumor with adequate margins. Although contrast media slowly accumulated in the targeted tumor in 9 patients immediately after the procedure, follow-up imaging studies performed at a mean of 16.7 months revealed no contrast enhancement within the ablation zone in these patients. Disease-specific, metastasis-free, and local recurrence-free survival rates were all 100%. Conclusions Real-time placement and manipulation of cryoprobes during MRI-guided cryoablation of small renal tumors in a closed-bore, high–magnetic field scanner are feasible. Technical and clinical success rates are similar to those of patients who undergo CT-guided radiofrequency ablation or cryoablation of small renal tumors. Our findings suggest that MRI-guided ablation has several advantages over CT-guided ablation, including real-time guidance for probe placement, multiplanar imaging, exquisite soft tissue contrast, and lack of ionizing radiation.

To report our experience with computed tomography (CT)-guided coaxial needle biopsy of intrathoracic lesions by using the transsternal approach.Medical records of 37 consecutive patients who underwent CT-guided transsternal biopsy of intrathoracic lesions were evaluated retrospectively. A coaxial needle technique was used in all patients; an 18-gauge needle was used for transsternal penetration, through which a 22-gauge needle was passed to obtain fine-needle aspirates. Five patients also underwent core-needle biopsy with a coaxially introduced 20-gauge needle. Medical records were reviewed for lesion size and location, needle path, number of needle penetrations, reasons for failure, biopsy results, and complications.The transsternal approach was used in mediastinal (n = 32) or intrapulmonary (n = 5) lesions. Transsternal needle sampling of the target lesion was successful in 35 patients. In the remaining two, adequate angling of the transsternal needle could not be achieved. Extrapleural access to the mediastinal lesions was achieved in all but one patient in whom the 22-gauge needle traversed the lung. Major vessels were avoided in most patients; the 22-gauge needle was safely passed through the brachiocephalic vein in one patient with a retrotracheal mass. Thirty-two (91%) of the 35 biopsies yielded diagnostic specimens. No major complications were encountered. Minor complications were pneumothorax in one patient and mediastinal hematoma in another.The CT-guided transsternal approach for coaxial core-needle biopsy allows safe access to masses in various locations in the mediastinum and anteromedial lung.