Thiel, David D.

ObjectiveTo validate the Martini nomogram predicting the decline in estimated glomerular filtration rate after robotic‐assisted partial nephrectomy.MethodsEstimated glomerular filtration rate of 406 patients from a single surgeon series was calculated before robotic‐assisted partial nephrectomy and at postoperative intervals. To determine the risk group, we calculated the total score and corresponding risk of significant estimated glomerular filtration rate reduction at 15 months using the Martini nomogram. The primary outcome was a reduction in estimated glomerular filtration rate of ≥25% from preoperative levels between 1 and 12 months after surgery.ResultsThe median length of follow up for this study was 12 months (interquartile range 6–12 months). Overall, 134 (33%) patients were in the low‐, 143 (35%) in the intermediate‐, 119 (29%) in the high‐ and 10 (2%) in the very high‐risk groups. The Kaplan–Meier estimates for the probability of significant estimated glomerular filtration rate reduction by 12 months after robotic‐assisted partial nephrectomy was 12.9% in the low‐risk group, 24.0% in the intermediate‐risk group, 49.7% in the high‐risk group and 40.0% in the very high‐risk group. Harrell’s C‐index for discriminating between those with and without a significant reduction in estimated glomerular filtration rate 1–12 months after robotic‐assisted partial nephrectomy was 0.73 (95% confidence interval 0.68–0.78).ConclusionsThe risk groups proposed by the Martini nomogram are accurate in predicting those at higher risk for a >25% decline in postoperative estimated glomerular filtration rate after robotic‐assisted partial nephrectomy at 12 months.

Abstract Background: The Circulating Cell-free Genome Atlas study (NCT02889978) is a multi-center, case-control, observational study with longitudinal follow-up (n=15,254; 56% cancer, 44% non-cancer) to support development of a cell-free DNA (cfDNA) multi-cancer early detection test. Previously, we reported that a targeted methylation assay detected and localized >20 cancer types at >99% specificity in individuals with cancer.1,2 Here, we report prediction of cancer (presence/absence) and tissue of origin (TOO) in individuals enrolled with clinical suspicion of cancer but without pathologic diagnosis or treatment at time of enrollment. Methods: Plasma cfDNA from blood samples collected prior to clinical diagnosis was subjected to targeted methylation sequencing. Samples were divided into a training set and an independent validation set to train and validate a machine learning classifier to assess cancer and predict TOO. Performance was assessed in a subset of participants enrolled with suspicion of cancer; subsequently, cancer was confirmed by evaluating a pathologic specimen. Results: Participants being evaluated for suspicion of cancer were classified as confirmed cancer (>20 cancer types; n=164 in training, n=75 in validation) or confirmed non-cancer (n=49 training, n=15 validation). In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer (100% specificity). In the confirmed cancer group, cancer detection across all stages was 40.2% (66/164; 95% confidence interval [CI], 32.7-48.2%) in training and 46.7% (35/75; 95% CI, 35.1-58.6%) in validation. Excluding stage I renal cancers (where detection/tumor fraction is low in plasma and which comprised 20% of participants in this subset) detection across stages was 50.4% (66/131; 95% CI, 41.5-59.2%) and 59.3% (35/59; 95% CI, 45.7-71.9%), respectively. In stages II and above, detection was 70.7% (58/82; 95% CI, 59.6-80.3%) and 78.9% (30/38; 95% CI, 62.7-90.4%), respectively. For detected cancers, TOO was predicted in 93.9% (62/66) samples in training and 100% (35/35) in validation. Of those with a TOO call, accuracy was 85.5% (53/62; 95% CI, 74.2-93.1%) and 97.1% (34/35; 95% CI, 85.1-99.9%), respectively. Conclusion: A cfDNA multi-cancer detection test has shown the potential to predict cancer and TOO in individuals with suspicion of cancer ahead of histologic diagnosis with performance comparable to those with confirmed cancer at the time of blood collection. This was achieved with high specificity and TOO accuracy. The high specificity suggests that the false positive rate could be comparable in populations with average versus higher risk (suspicion) of cancer. These findings suggest that a cfDNA multi-cancer detection test could accelerate the diagnostic resolution of suspicion of cancer. References: 1. Oxnard GR, et al. ASCO Breakthrough Meeting 2019; Abstract 44. 2. Oxnard GR, et al. ESMO Annual Meeting 2019; Abstract 5639. Citation Format: David D. Thiel, Xiaoji Chen, Kathryn N. Kurtzman, Jessica Yecies, Tony Wu, Quan Zhang, Hai Liu, Nan Zhang, Eric T. Fung, Michael V. Seiden, Minetta C. Liu, Geoffrey R. Oxnard, Earl Hubbell, Alexander M. Aravanis, Anne-Renee Hartman, Eric A. Klein. Prediction of cancer and tissue of origin in individuals with suspicion of cancer using a cell-free DNA multi-cancer early detection test [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT021.

AbstractBackgroundRenal tumor scoring systems, such as the contact surface area value, aim to assist in predicting outcomes following robotic‐assisted partial nephrectomy. The aim of this study is to identify associations between specific postoperative outcomes and the contact surface area of renal masses.MethodsWe analyzed 332 consecutive robotic‐assisted partial nephrectomies and calculated contact surface area for renal tumors with the contact surface area formula (CSA = 2πrd), where π ≈ 3.14, r = greatest tumor radius (cm), and d = greatest tumor depth (cm).ResultsHigher contact surface area was associated with longer warm ischemia time (P < .001), higher estimated blood loss (P < .001), and longer length of hospital stay (LOS) (P < .001). Higher contact surface area was significantly associated with decreased renal function at 1 day, 1 month, and 6 months following robotic‐assisted partial nephrectomy.ConclusionsContact surface area is associated with certain outcomes following robotic‐assisted partial nephrectomy and may be a useful predictive tool.

Multinucleate Giant Cell (GC) reaction is a biological response that occurs secondary to infection, an implanted foreign body, tissue injury, or inflammation. In rare instances GC reactions have been reported following tissue ablation. Multinucleate GC reactions and tumefactive fat necrosis both have the ability to mimic cancer recurrence or metastasis and can appear as enhancing masses. We discuss a case of a surgically resected retroperitoneal perinephric mass thought to be recurrent renal cell carcinoma (RCC) that was pathologically confirmed as tumefactive fat necrosis with multinucleate GC reaction 2 years following percutaneous cryoablation of a small renal mass.