Summary Tumours respond differently to immunotherapies compared with chemotherapeutic drugs, raising questions about the assessment of changes in tumour burden—a mainstay of evaluation of cancer ...therapeutics that provides key information about objective response and disease progression. A consensus guideline—iRECIST—was developed by the RECIST working group for the use of modified Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) in cancer immunotherapy trials, to ensure consistent design and data collection, facilitate the ongoing collection of trial data, and ultimate validation of the guideline. This guideline describes a standard approach to solid tumour measurements and definitions for objective change in tumour size for use in trials in which an immunotherapy is used. Additionally, it defines the minimum datapoints required from future trials and those currently in development to facilitate the compilation of a data warehouse to use to later validate iRECIST. An unprecedented number of trials have been done, initiated, or are planned to test new immune modulators for cancer therapy using a variety of modified response criteria. This guideline will allow consistent conduct, interpretation, and analysis of trials of immunotherapies.
To evaluate the accuracy and source of errors using a two-dimensional (2D)/three-dimensional (3D) fusion road map for endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm.
A rigid 2D/3D ...road map was tested in 16 patients undergoing EVAR. After 3D/3D manual registration of preoperative multidetector computed tomography (CT) and cone beam CT, abdominal aortic aneurysm outlines were overlaid on live fluoroscopy/digital subtraction angiography (DSA). Patient motion was evaluated using bone landmarks. The misregistration of renal and internal iliac arteries were estimated by 3 readers along head-feet and right-left coordinates (z-axis and x-axis, respectively) before and after bone and DSA corrections centered on the lowest renal artery. Iliac deformation was evaluated by comparing centerlines before and during intervention. A score of clinical added value was estimated as high (z-axis < 3 mm), good (3 mm ≤ z-axis ≤ 5 mm), and low (z-axis > 5 mm). Interobserver reproducibility was calculated by the intraclass correlation coefficient.
The lowest renal artery misregistration was estimated at x-axis = 10.6 mm ± 11.1 and z-axis = 7.4 mm ± 5.3 before correction and at x-axis = 3.5 mm ± 2.5 and z-axis = 4.6 mm ± 3.7 after bone correction (P = .08), and at 0 after DSA correction (P < .001). After DSA correction, residual misregistration on the contralateral renal artery was estimated at x-axis = 2.4 mm ± 2.0 and z-axis = 2.2 mm ± 2.0. Score of clinical added value was low (n = 11), good (n= 0), and high (n= 5) before correction and low (n = 5), good (n = 4), and high (n = 7) after bone correction. Interobserver intraclass correlation coefficient for misregistration measurements was estimated at 0.99. Patient motion before stent graft delivery was estimated at x-axis = 8 mm ± 5.8 and z-axis = 3.0 mm ± 2.7. The internal iliac artery misregistration measurements were estimated at x-axis = 6.1 mm ± 3.5 and z-axis = 5.6 mm ± 4.0, and iliac centerline deformation was estimated at 38.3 mm ± 15.6.
Rigid registration is feasible and fairly accurate. Only a partial reduction of vascular misregistration was observed after bone correction; minimal DSA acquisition is still required.
To evaluate the efficacy and safety of percutaneous renal artery embolization (RAE) of iatrogenic vascular kidney injuries and the effects of RAE on renal function and arterial blood pressure (BP).
...Over a 12-year period, 50 consecutive patients with severe hemorrhage after iatrogenic arterial kidney injuries underwent RAE. Technical success was defined as occlusion of the bleeding site, and clinical success was defined as complete bleeding cessation. The effects on renal function and arterial BP were assessed by comparing the estimated glomerular filtration rate (eGFR), renal function stage (National Kidney Foundation scale), systolic BP, and BP stage (European Society of Hypertension classification) before and after RAE.
RAE was technically successful in 49 patients (98%). Two patients were lost to follow-up after RAE. Clinical success was obtained in 40 (83%), 45 (94%), and 47 patients (98%), respectively, at 24, 48, and 96 hours after RAE. Three patients (6%) had minor complications, and one patient (2%) died within 30 days after RAE. Follow-up renal function data (mean, 4 mo) were available for 33 patients (66%). No statistically significant differences in eGFR (P = .186) or renal function stage (P = .183) were apparent after RAE. Follow-up BP data (mean, 3 mo) were available for 28 patients (56%). There were no significant differences in systolic BP (P = .233) or BP stage (P = .745) after RAE.
Embolization of iatrogenic renal artery injuries is safe and associated with high technical and clinical success rates. It is not associated with a significant worsening of renal function or increase in BP.
Objective The objective of this study was to evaluate the safety and efficacy of external beam radiation (EBR) in preventing restenosis after superficial femoral artery (SFA) stenting in comparison ...with a control group treated with SFA stenting only. Methods In this Institutional Review Board-approved study, patients who provided written informed consent were randomly assigned to 0 Gy or 14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point was the angiographic binary restenosis rate 2 years after stenting. Categorical and continuous end points were respectively analyzed using logistic regression models and Wilcoxon tests. End points expressed as time to event were analyzed using a log-rank test. Results The study included 155 patients, 46 women and 109 men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2 years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group and in 33% (25/77) of the 14 Gy group ( P = .003). Target lesion revascularization at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group ( P = .56). There were no significant differences in total walking distances change from baseline to 2 years (46 ± 100 and 26 ± 79 m, respectively, in the 0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no major amputations. Conclusions A single 14 Gy dose of EBR to the SFA stenting site did not prevent in-stent restenosis.
To evaluate the impact of cone-beam computed tomography (CT) during sclerotherapy of low-flow vascular malformations.
Eighty-seven cone-beam CT examinations were acquired during 81 sclerotherapy ...treatments of low-flow malformations in 48 patients: 81 were performed to evaluate sclerosing agent diffusion and six were performed to evaluate needle or catheter positioning before injection of therapeutic agent. Image quality was rated by two observers. Clinical impact of cone-beam CT in the assessment of therapeutic agent diffusion, needle or catheter positioning, subsequent treatment planning, and complication detection was evaluated. The κ-statistic was used to assess interobserver reliability and proportions, with associated 95% confidence intervals (CIs).
All cone-beam CT images were successfully acquired. Image quality was rated as excellent or good for the majority of studies, with substantial interobserver reliability (κ = 0.648). Cone-beam CT studies improved assessment of therapeutic agent diffusion in 83% of cases (67 of 81; 95% CI, 75%-91%) for observer 1, who had access to ultrasound, fluoroscopic, and digital subtraction angiographic (DSA) imaging, and in 95% of cases (77 of 81; 95% CI, 90%-100%) for observer 2, who had access to only stored fluoroscopic spot radiographs and DSA images. Cone-beam CT impacted planning of the next treatment session in 49% of cases (40 of 81; 95% CI, 38%-60%). In 7% of cases (six of 81; 95% CI, 1%-13%), complications such as migration of therapeutic agent or compression of upper airways were detected that were not seen with other imaging.
Cone-beam CT can be a useful adjunctive imaging tool, providing information to help decision-making during percutaneous sclerotherapy and ongoing management of low-flow vascular malformations.
Summary Background Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial ...progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. Methods In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov , number NCT00480025. Findings Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 38·1 months (IQR 27·9–48·4) in the MAGE-A3 group and 39·5 months (27·9–50·4) in the placebo group. In the overall population, median disease-free survival was 60·5 months (95% CI 57·2–not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7–not reached) for the placebo group (hazard ratio HR 1·02, 95% CI 0·89–1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6–not reached) in those in the MAGE-A3 group and 56·9 months (44·4–not reached) in the placebo group (HR 0·97, 95% CI 0·80–1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 16% of 1515 patients in the MAGE-A3 group and 122 16% of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 2% in the MAGE-A3 group and 19 3% in the placebo group), vascular disorders (30 2% vs 17 3%), and neoplasm (benign, malignant, and unspecified (29 2% vs 16 2%). Interpretation Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped. Funding GlaxoSmithKline Biologicals SA.
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