Developing strategies to inflame tumors is critical for increasing response to immunotherapy. Here, we report that low-dose radiotherapy (LDRT) of murine tumors promotes T-cell infiltration and enables responsiveness to combinatorial immunotherapy in an IFN-dependent manner. Treatment efficacy relied upon mobilizing both adaptive and innate immunity and depended on both cytotoxic CD4+ and CD8+ T cells. LDRT elicited predominantly CD4+ cells with features of exhausted effector cytotoxic cells, with a subset expressing NKG2D and exhibiting proliferative capacity, as well as a unique subset of activated dendritic cells expressing the NKG2D ligand RAE1. We translated these findings to a phase I clinical trial administering LDRT, low-dose cyclophosphamide, and immune checkpoint blockade to patients with immune-desert tumors. In responsive patients, the combinatorial treatment triggered T-cell infiltration, predominantly of CD4+ cells with Th1 signatures. Our data support the rational combination of LDRT with immunotherapy for effectively treating low T cell–infiltrated tumors. Significance: Low-dose radiation reprogrammed the tumor microenvironment of tumors with scarce immune infiltration and together with immunotherapy induced simultaneous mobilization of innate and adaptive immunity, predominantly CD4+ effector T cells, to achieve tumor control dependent on NKG2D. The combination induced important responses in patients with metastatic immune-cold tumors. This article is highlighted in the In This Issue feature, p. 1

OBJECTIVE. We describe the rates and potential risk factors of complications of radiofrequency ablation of hepatic tumors.SUBJECTS AND METHODS. Over a 5-year period, 312 patients underwent 350 sessions of radiofrequency ablation (124 intraoperative and 226 percutaneous) for treatment of 582 liver tumors including 115 hepatocellular carcinomas and 467 metastatic tumors. The chi-square test was used for a group-to-group comparison of the occurrence of adverse events.RESULTS. Thirty-seven (10.6%) adverse events and five (1.4%) deaths were related to radiofrequency treatment. The deaths were caused by liver insufficiency (n = 1), colon perforation (n = 1), and portal vein thrombosis (n = 3). Portal vein thrombosis was significantly (p < 0.00001) more frequent in cirrhotic livers (2/5) than in noncirrhotic livers (0/54) after intraoperative radiofrequency ablation performed during a Pringle maneuver. Liver abscess (n = 7) was the most common complication. Abscess occurred significantly (p < 0.00001) more frequ...

Purpose: To compare the respective sensitivity of somatostatin receptor scintigraphy (SRS), computed tomography (CT), and magnetic resonance imaging (MRI) in the detection of liver metastases from well-differentiated gastroenteropancreatic endocrine tumor (WDGEP ET) patients. To define predictive factors for “high-sensitivity SRS.” Patients and Methods: Sixty-four patients with WDGEP ET underwent SRS with abdominal single-photon emission computed tomography (SPECT), spiral CT, and 1.5-T MRI within a 15-day interval, the order of which was randomized. Two readers analyzed images of each modality, blindly and independently. Results: Hepatic metastases were present in 40 of the 64 patients and confirmed by pathology after liver biopsy or surgery in 32 and eight patients, respectively. SRS, CT, and MRI detected a total of 204, 325, and 394 metastases, respectively. The number of detected metastases was significantly higher with MRI than with CT (P = .02) and SRS (P < 10⁻⁴) and higher with CT than with SRS (P < 10⁻⁴). SRS was negative in seven patients with a positive CT and/or MRI. More lesions were detected in 10 patients by SPECT compared with static views. The median metastasis size was significantly correlated (P = .04) with the sensitivity of SRS. Conclusion: MRI seems to have an edge over CT and SRS for the detection of liver metastases from endocrine tumors. We recommend the systematic performance of liver MRI at WDGEP ET initial staging and before major therapeutic events. The low performance of SRS was mainly explained by the impact of the metastasis size on the detection capacity of SRS.

To prospectively evaluate the local efficacy of radiofrequency (RF) ablation of lung neoplasms, with a minimum follow-up period of 1 year. Sixty patients (34 men and 26 women; age range, 27-81 years; mean age, 66 years) with 100 lung tumors gave written informed consent to be enrolled in a prospective study that was approved by the local ethics committee. There were five or fewer tumors per patient, each with a diameter of less than 40 mm (mean +/- standard deviation, 17 mm +/- 10). RF ablation was performed in tumors by using computed tomographic (CT) guidance. Follow-up CT studies were obtained within 48 hours after treatment and at 2, 4, 6, 9, and 12 months thereafter to evaluate treatment outcome and complications. Lung spirometry measurements were obtained before and 4 weeks after RF ablation. Ninety-seven of 100 targeted tumors were treated and required 163 RF ablations (1.68 per tumor), each lasting 14 minutes +/- 8, delivered during 74 procedures. The 18-month estimated rate of incomplete local treatment at CT was 7% (95% confidence interval: 3%, 14%) per tumor and 12% (95% confidence interval: 5%, 23%) per patient. An ablation area at least four times larger than the initial tumor was predictive of complete ablation treatment (P = .02). There was a trend toward better efficacy for tumors smaller than 2 cm in diameter (P = .066). Overall survival and lung disease-free survival at 18 months were 71% and 34%, respectively. The main adverse event was a pneumothorax, which occurred in 54% of procedures, but a chest tube was required in only 9% of the procedures. No modification of respiratory function was found when spirometry measurements obtained before and within 2 months after RF ablation were compared (P = .51). RF ablation has a high local efficacy and is well tolerated.

OBJECTIVE. The objective of our study was to evaluate the efficacy and safety of radiofrequency ablation of hepatic metastases performed either percutaneously for treatment of hepatic metastases in patients deemed ineligible for surgery or intraoperatively during partial hepatectomy to destroy unresectable metastases.SUBJECTS AND METHODS. Sixty-eight patients with 121 hepatic metastases (<5 metastases per patient) that were mainly colorectal in origin underwent 76 sessions of radiofrequency ablation with cooled-needle electrodes under sonographic guidance. Twenty-one patients with 33 metastases of 5-20 mm in diameter (mean ± SD,13 ± 7 mm) underwent intraoperative radiofrequency ablation. Forty-seven patients with 88 metastases of 10 to 42 mm in diameter (mean ± SD, 26 ± 9 mm) were treated with percutaneous radiofrequency ablation. Procedure efficacy was evaluated with dynamic enhanced CT and MR imaging performed 2, 4, and 6 months after treatment and then every 3 months.RESULTS. Radiofrequency ablation al...