Hong, Kelvin K.

Management of patients with advanced sarcoma has been evolving in recent decades, from a one-fit-all perspective to a more refined, personalized, and multidisciplinary approach. In parallel, the evolution of local therapies (radiotherapy, surgical and interventional radiology techniques) has contributed to the improvement of survival of patients with advanced sarcoma. In this article, we review the evidence regarding local treatments in advanced sarcoma, as well as its integration with systemic therapies, to provide the reader a wider and deeper perspective on the management of patients with metastatic sarcoma.

BACKGROUNDThis study evaluated the 2‐year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non–small cell lung cancer (NSCLC) undergoing computed tomography (CT)–guided radiofrequency ablation (RFA) in a prospective, multicenter trial.METHODSFifty‐four patients (25 men and 29 women) with a median age of 76 years (range, 60‐89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy‐proven stage IA NSCLC and were deemed medically inoperable by a board‐certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed.RESULTSThe overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence–free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re‐treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years.CONCLUSIONSRFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2‐year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. Cancer 2015;121:3435–43. © 2015 American Cancer Society.

The angiotensin II subtype 1 receptor (AT 1 R) has been linked to the development and progression of renovascular hypertension. In this study we applied a pig model of renovascular hypertension to investigate the AT 1 R in vivo with positron-emission tomography (PET) and in vitro with quantitative autoradiography. AT 1 R PET measurements were performed with the radioligand [ 11 C]KR31173 in 11 control pigs and in 13 pigs with hemodynamically significant renal artery stenosis; 4 were treated with lisinopril for 2 weeks before PET imaging. The radioligand impulse response function was calculated by deconvolution analysis of the renal time-activity curves. Radioligand binding was quantified by the 80-minute retention of the impulse response function. Median values and interquartile ranges were used to illustrate group statistics. Radioligand retention was significantly increased ( P =0.044) in hypoperfused kidneys of untreated (0.225; range: 0.150 to 0.373) and lisinopril-treated (0.237; range:0.224 to 0.272) animals compared with controls (0.142; range:0.096 to 0.156). Increased binding of [ 11 C]KR31173 documented by PET in vivo was confirmed by in vitro autoradiography. Both in vivo and in vitro binding measurements showed that the effect of renal artery stenosis on the AT 1 R was not abolished by lisinopril treatment. These studies provide insight into kidney biology as the first in vivo/in vitro experimental evidence about AT 1 R regulation in response to reduced perfusion of the kidney. The findings support the concept of introducing AT 1 R PET as a diagnostic biomarker of renovascular disease.