Eric Wehrenberg-Klee

Impact on renal function of percutaneous thermal ablation of renal masses in patients with preexisting chronic kidney disease.

PURPOSE To examine the effect of percutaneous thermal ablation of renal masses on renal function among patients with baseline chronic kidney disease (CKD). MATERIALS AND METHODS Patients with baseline CKD (initial glomerular filtration rate [GFR] < 60 mL/min/1.73 m(2)) who underwent percutaneous cryoablation or radiofrequency (RF) ablation of renal masses were reviewed. RESULTS A total of 48 patients with a GRF of 60 mL/min/1.73 m(2) or lower were treated with renal cryoablation or RF ablation and had follow-up GFR measurement 1 month afterward. Mean patient age was 73 years (range, 47-89 y). Cryoablation was performed in 22 patients and RF ablation was performed in 26. Mean tumor diameter was 3.4 cm (range, 0.9-10.2 cm). Mean overall GFRs were 39.8 mL/min/1.73 m(2) at baseline and 39.7 mL/min/1.73 m(2) at 1 month after ablation (P = .85). A total of 38 patients had 1-year follow-up GFR measurement (cryoablation, n = 18; RF ablation, n = 20), and their mean GFR was 40.9 mL/min/1.73 m(2) ± 11.4 (SD), compared with a preablation GFR of 41.2 mL/min/1.73 m(2)(P = .79). In the cryoablation group, mean GFRs at 1 month and 1 year were 41.4 mL/min/1.73 m(2) and 44.4 mL/min/1.73 m(2), compared with respective baseline GFRs of 41.1 mL/min/1.73 m(2) and 42.1 mL/min/1.73 m(2) (P = .75 and P = .19, respectively). In the RF ablation group, mean GFRs at 1 month and 1 year were 38.2 mL/min/1.73 m(2) and 37.8 mL/min/1.73 m(2), compared with respective baseline GFRs of 38.7 mL/min/1.73 m(2) and 40.4 mL/min/1.73 m(2) (P = .58 and P = .09, respectively). CONCLUSIONS Independent of ablation modality, percutaneous renal mass ablation does not appear to affect renal function among patients with CKD.

Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response

While cancer immunotherapy can produce dramatic responses, only a minority of patients respond to treatment. Reliable response biomarkers are needed to identify responders, and conventional imaging modalities have not proved adequate. Here, we provide a preclinical proof of concept for the use of granzyme B, a downstream effector of tumoral cytotoxic T cells, as an early biomarker for tumors responding to immunotherapy. We designed novel PET imaging probes for the murine and human granzyme B isoforms that specifically and quantitatively bind granzyme B. Immunotherapy-treated mice were imaged prior to therapy-induced tumor volume reduction. Imaging distinguished treated responders from nonresponders with excellent predictive ability. To assess the clinical value of a granzyme B imaging paradigm, biopsy specimens from melanoma patients on checkpoint inhibitor therapy were analyzed. A marked differential in granzyme B expression was observed between treated responders and nonresponders. Additionally, our human probe was able to specifically detect granzyme B expression in human samples, providing a clear candidate for clinical application. Overall, our results suggest granzyme B PET imaging can serve as a quantitatively useful predictive biomarker for efficacious responses to cancer immunotherapy. Cancer Res; 77(9); 2318-27. ©2017 AACR.

Percutaneous Computed Tomography–guided Renal Mass Radiofrequency Ablation versus Cryoablation: Doses of Sedation Medication Used

PURPOSE To compare the amount of sedation medication administered during radiofrequency (RF) ablation versus cryoablation of small renal masses. MATERIALS AND METHODS Records were retrospectively reviewed in patients who underwent percutaneous computed tomography-guided RF ablation and cryoablation of small renal masses from January 2002 to June 2011 for patient and tumor characteristics, amount of medications used for moderate sedation, and complications. Sedation was performed by giving patients titrated doses of midazolam and fentanyl. Additional medications were given if the desired level of sedation was not achieved. RESULTS There were 116 patients who underwent 136 ablation procedures; 71 patients underwent RF ablation, and 65 patients underwent cryoablation. RF ablation was associated with a significantly higher mean dose of fentanyl (mean dose for RF ablation, 236.43 μg; mean dose for cryoablation, 172.27 μg; P<.001). RF ablation was also associated with a higher mean dose of midazolam (mean dose for RF ablation, 4.5 mg; mean dose for cryoablation, 3.27 mg; P<.001). In the RF ablation group, two patients required additional sedation with droperidol. As a result of oversedation, two patients in the RF ablation cohort required sedation reversal with naloxone and flumazenil. None of the patients who underwent cryoablation required sedation reversal. No other sedation-related complications occurred. CONCLUSIONS Cryoablation of small renal masses was performed with less sedation medication than RF ablation. This finding suggests renal cryoablation is less painful than RF ablation; however, prospective studies with validated pain scales are needed to confirm these results.

Inferior vena cava filters for primary prophylaxis: when are they indicated?

Over the past several years there has been a rapid increase in the number of inferior vena cava (IVC) filters placed for primary thromboprophylaxis. Increased use has occurred in settings where other methods of thromboprophylaxis are viewed to be inadequate, technically challenging, or that place patients at an unacceptably high bleeding risk. These clinical services include trauma, bariatric surgery, neurosurgery, cancer, intensive care unit populations, and patients with a relative contraindication to anticoagulation. We review the studies to date addressing filter placement for these indications. Although preliminary data are promising, the patient populations most likely to benefit from prophylactic IVC filter placement have not been well defined, and randomized studies demonstrating efficacy have not been conducted. Moving forward, it will be critical to accomplish these two tasks if IVC filters are to continue to have a role in primary thromboprophylaxis.

Differential Receptor Tyrosine Kinase PET Imaging for Therapeutic Guidance.

Inhibitors of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway hold promise for the treatment of breast cancer, but resistance to these treatments can arise via feedback loops that increase surface expression of the receptor tyrosine kinases (RTK) epidermal growth factor receptor 1 (EGFR) and human epidermal growth factor receptor 3 (HER3), leading to persistent growth pathway signaling. We developed PET probes that provide a method of imaging this response in vivo, determining which tumors may use this escape pathway while avoiding the need for repeated biopsies. Methods: Anti-EGFR-F(ab′)2 and anti-HER3-F(ab′)2 were generated from monoclonal antibodies by enzymatic digestion, conjugated to DOTA, and labeled with 64Cu. A panel of breast cancer cell lines was treated with increasing concentrations of the AKT inhibitor GDC-0068 or the PI3K inhibitor GDC-0941. Pre- and posttreatment expression of EGFR and HER3 was compared using Western blot and correlated to probe accumulation with binding studies. Nude mice xenografts of HCC-70 or MDA-MB-468 were treated with either AKT inhibitor or PI3K inhibitor and imaged with either EGFR or HER3 PET probe. Results: Changes in HER3 and EGFR PET probe accumulation correlate to RTK expression change as assessed by Western blot (R2 of 0.85–0.98). EGFR PET probe PET/CT imaging of HCC70 tumors shows an SUV of 0.32 ± 0.03 for vehicle-, 0.50 ± 0.01 for GDC-0941–, and 0.62 ± 0.01 for GDC-0068–treated tumors, respectively (P < 0.01 for both comparisons to vehicle). HER3 PET probe PET/CT imaging of MDAMB468 tumors shows an SUV of 0.35 ± 0.02 for vehicle- and 0.73 ± 0.05 for GDC-0068–treated tumors (P < 0.01). Conclusion: Our imaging studies, using PET probes specific to EGFR and HER3, show that changes in RTK expression indicative of resistance to PI3K and AKT inhibitors can be seen within days of therapy initiation and are of sufficient magnitude as to allow reliable clinical interpretation. Noninvasive PET monitoring of these RTK feedback loops should help to rapidly assess resistance to PI3K and AKT inhibitors and guide selection of an appropriate combinatorial therapeutic regimen on an individual patient basis.

CT-Guided Percutaneous Needle Biopsy of Retroperitoneal and Pelvic Lymphadenopathy: Assessment of Technique, Diagnostic Yield, and Clinical Value

PURPOSE To assess the technical success rate, diagnostic yield, and clinical value of computed tomography (CT)-guided percutaneous needle biopsy (PNB) for retroperitoneal and pelvic lymphadenopathy. MATERIALS AND METHODS This retrospective study included 344 patients evaluated for safety and technique and 334 patients evaluated for diagnostic yield and clinical analyses. PNBs were performed with fine-needle aspiration (FNA) in 315 patients and with core biopsy in 333 patients. Follow-up analyses, including repeat biopsy, open surgery, imaging, and clinical indicators, were conducted for 94 patients who had nonspecific malignant or benign results. Diagnostic yields were calculated based on biopsy and follow-up results. Factors associated with final diagnoses were compared and modeled by multivariate analysis. RESULTS Technical success rate was 99.7%. Thirty-nine patients (11.3%) had minor complications. From biopsy results and follow-up analyses, final malignant diagnoses were determined for 281 patients (84.1%). Overall sensitivity, specificity, and accuracy rates of PNB were 91.5%, 100%, and 92.8%, respectively. For patients with a history of malignancy, the likelihood of nodal involvement was 84.6% and that of a new, different malignancy was 3.7%. Older age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.00-1.05), history of malignancy (OR, 3.44; 95% CI, 1.71-6.92), multiple lymph nodes (LNs; OR, 2.65; 95% CI, 1.38-5.09), and new or enlarging LNs (OR, 2.62; 95% CI, 1.25-5.48) were independent risk factors for malignancy diagnosis. CONCLUSIONS CT-guided PNB is a safe, effective procedure that can achieve high diagnostic yields for patients with retroperitoneal and pelvic lymphadenopathy.

Y-90 Radioembolization Combined with a PD-1 Inhibitor for Advanced Hepatocellular Carcinoma

Nivolumab has recently received approval by the Food and Drug Administration for treatment of advanced hepatocellular carcinoma (HCC) in patients previously treated with sorafenib. Nivolumabs’ overall response rate of 20% (El-Khoueiry et al. in Lancet 389:2492–2502, 2017) is a step forward for these patients, but there is significant room for improvement. We describe a case of combining Y-90 radioembolization with nivolumab for treatment of angioinvasive HCC, which successfully bridged patient to partial hepatectomy. Surgical pathology showed negative margins with complete pathological response. With the introduction of immunotherapy for HCC, combining Y-90 radioembolization with immunotherapy may enhance the anti-tumoral immune response of checkpoint inhibitors.