Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Thermal ablation of colorectal liver metastases: a position paper by an international panel of ablation experts, The Interventional Oncology Sans Frontières meeting 2013.

OBJECTIVES: Previous attempts at meta-analysis and systematic review have not provided clear recommendations for the clinical application of thermal ablation in metastatic colorectal cancer. Many authors believe that the probability of gathering randomised controlled trial (RCT) data is low. Our aim is to provide a consensus document making recommendations on the appropriate application of thermal ablation in patients with colorectal liver metastases. METHODS: This consensus paper was discussed by an expert panel at The Interventional Oncology Sans Frontières 2013. A literature review was presented. Tumour characteristics, ablation technique and different clinical applications were considered and the level of consensus was documented. RESULTS: Specific recommendations are made with regard to metastasis size, number, and location and ablation technique. Mean 31 % 5-year survival post-ablation in selected patients has resulted in acceptance of this therapy for those with technically inoperable but limited liver disease and those with limited liver reserve or co-morbidities that render them inoperable. CONCLUSIONS: In the absence of RCT data, it is our aim that this consensus document will facilitate judicious selection of the patients most likely to benefit from thermal ablation and provide a unified interventional oncological perspective for the use of this technology. KEY POINTS: • Best results require due consideration of tumour size, number, volume and location. • Ablation technology, imaging guidance and intra-procedural imaging assessment must be optimised. • Accepted applications include inoperable disease due to tumour distribution or inadequate liver reserve. • Other current indications include concurrent co-morbidity, patient choice and the test-of-time approach. • Future applications may include resectable disease, e.g. for small solitary tumours.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes.

Image-guided tumor ablation: standardization of terminology and reporting criteria--a 10-year update.

Image-guided tumor ablation has become a well-established hallmark of local cancer therapy. The breadth of options available in this growing field increases the need for standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison among treatments that use different technologies, such as chemical (eg, ethanol or acetic acid) ablation, thermal therapies (eg, radiofrequency, laser, microwave, focused ultrasound, and cryoablation) and newer ablative modalities such as irreversible electroporation. This updated consensus document provides a framework that will facilitate the clearest communication among investigators regarding ablative technologies. An appropriate vehicle is proposed for reporting the various aspects of image-guided ablation therapy including classification of therapies, procedure terms, descriptors of imaging guidance, and terminology for imaging and pathologic findings. Methods are addressed for standardizing reporting of technique, follow-up, complications, and clinical results. As noted in the original document from 2003, adherence to the recommendations will improve the precision of communications in this field, leading to more accurate comparison of technologies and results, and ultimately to improved patient outcomes. Online supplemental material is available for this article .

Outcome after radiofrequency ablation of sarcoma lung metastases.

PURPOSE: Resection is the mainstay of management in patients with sarcoma lung metastases, but there is a limit to how many resections can be performed. Some patients with inoperable disease have small-volume lung metastases that are amenable to thermal ablation. We report our results after radiofrequency ablation (RFA). METHODS: This is a retrospective study of patients treated from 2007 to 2012 in whom the intention was to treat all sites of disease and who had a minimum CT follow-up of 4 months. Treatment was performed under general anesthesia/conscious sedation using cool-tip RFA. Follow-up CT scans were analyzed for local control. Primary tumor type, location, grade, disease-free interval, prior resection/chemotherapy, number and size of lung tumors, uni- or bilateral disease, complications, and overall and progression-free survival were recorded. RESULTS: Twenty-two patients [15 women; median age 48 (range 10-78) years] with 55 lung metastases were treated in 30 sessions. Mean and median tumor size and initial number were 0.9 cm and 0.7 (range 0.5-2) cm, and 2.5 and 1 (1-7) respectively. Median CT and clinical follow-up were 12 (4-54) and 20 (8-63) months, respectively. Primary local control rate was 52 of 55 (95 %). There were 2 of 30 (6.6 %) Common Terminology Criteria grade 3 complications with no long-term sequelae. Mean (median not reached) and 2- and 3-year overall survival were 51 months, and 94 and 85 %. Median and 1- and 2-year progression-free survival were 12 months, and 53 and 23 %. Prior disease-free interval was the only significant factor to affect overall survival. CONCLUSION: RFA is a safe and effective treatment for patients with small-volume sarcoma metastases.

Radiologists' leading position in image-guided therapy.

Image-guided diagnostic and therapeutic procedures are related to, or performed under, some kind of imaging. Such imaging may be direct inspection (as in open surgery) or indirect inspection as in endoscopy or laparoscopy. Common to all these techniques is the transformation of optical and visible information to a monitor or the eye of the operator. Image-guided therapy (IGT) differs by using processed imaging data acquired before, during and after a wide range of different imaging techniques. This means that the planning, performing and monitoring, as well as the control of the therapeutic procedure, are based and dependent on the "virtual reality" provided by imaging investigations. Since most of such imaging involves radiology in the broadest sense, there is a need to characterise IGT in more detail. In this paper, the technical, medico-legal and medico-political issues will be discussed. The focus will be put on state-of-the-art imaging, technical developments, methodological and legal requisites concerning radiation protection and licensing, speciality-specific limitations and crossing specialty borders, definition of technical and quality standards, and finally to the issue of awareness of IGT within the medical and public community. The specialty-specific knowledge should confer radiologists with a significant role in the overall responsibility for the imaging-related processes in various non-radiological specialties. These processes may encompass purchase, servicing, quality management, radiation protection and documentation, also taking responsibility for the definition and compliance with the legal requirements regarding all radiological imaging performed by non-radiologists.

Survival after radiofrequency ablation in 122 patients with inoperable colorectal lung metastases.

PURPOSE: To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. METHODS: Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, and factors were compared by log rank test. RESULTS: The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. CONCLUSION: Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.

Ablation of lung tumours.

Radiofrequency, laser, microwave and cryotherapy have all been used for the ablation of lung tumours. However, radiofrequency ablation (RFA) and microwave ablation are the most widely used technologies. RFA has been successfully applied to tumour measuring from <3 to 3.5 cm, either primary or secondary. Lung function usually recovers to pre-ablation values following an initial reduction and the complication profile is well understood.

Tumour ablation: current role in the kidney, lung and bone.

The last few years have seen a rapid expansion in the use and availability of ablation techniques with hundreds of papers published. Radiofrequency remains the front-runner in terms of cost, ease of set-up, versatility and flexibility but other techniques are catching up. Ablation with cryotherapy and microwave, which were previously only available at open laparotomy due to the large size of the probes, are now readily performed percutaneously, with a predictable reduction in morbidity. Ablation is now accepted as the first line of treatment in patients with limited volume hepatocellular carcinoma who are not candidates for transplantation. There is continuing debate in most other areas but the evidence is increasing for an important role in liver metastases, renal carcinoma, inoperable lung tumours and some bone tumours.

Image-guided tumor ablation: standardization of terminology and reporting criteria.

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.

Tumour ablation: current role in the liver, kidney, lung and bone.

The last few years have seen a rapid expansion in the use and availability of ablation techniques with hundreds of papers published. Radiofrequency remains the front-runner in terms of cost, ease of set-up, versatility and flexibility but other techniques are catching up. Ablation with cryotherapy and microwave, which were previously only available at open laparotomy due to the large size of the probes, are now readily performed percutaneously, with a predictable reduction in morbidity. Ablation is now accepted as the first line of treatment in patients with limited volume hepatocellular carcinoma who are not candidates for transplantation. There is continuing debate in most other areas but the evidence is increasing for an important role in liver metastases, renal carcinoma, inoperable lung tumours and some bone tumours.

Response to radiofrequency ablation of pulmonary tumours: a prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study).

BACKGROUND: Radiofrequency ablation is an accepted treatment for non-surgical patients with liver cancer. The purpose of this study was to identify the feasibility, safety, and effectiveness of percutaneous radiofrequency ablation of malignant lung tumours. METHODS: Between July 1, 2001, and Dec 10, 2005, a series of 106 patients with 183 lung tumours that were 3.5 cm in diameter or smaller (mean 1.7 cm [SD 1.3]) were enrolled in a prospective, intention-to-treat, single-arm, multicentre clinical trial from seven centres in Europe, the USA, and Australia. Proof of malignancy was obtained by biopsy in all patients. Diagnoses included non-small-cell lung cancer (NSCLC) in 33 patients, metastasis from colorectal carcinoma in 53 patients, and metastasis from other primary malignancies in 20 patients. All patients were considered by the treating physician to be unsuitable for surgery and unfit for radiotherapy or chemotherapy. Patients underwent radiofrequency ablation in accordance with standard rules for CT-guided lung biopsy and were then followed for up to 2 years. Primary endpoints were technical success (defined as correct placement of the ablation device into all tumour targets with completion of the planned ablation protocol), safety (including identification of treatment-related complications and changes in pulmonary function), and confirmed complete response of tumours (according to modified Response Evaluation Criteria in Solid Tumors). Secondary endpoints were overall survival, cancer-specific survival, and quality of life. This trial is registered with ClinicalTrials.gov, number NCT00690703. FINDINGS: Correct placement of the ablation device into the target tumour with completion of the planned treatment protocol was feasible in 105 (99%) of 106 patients. The technical failure in one patient was caused by the inability to place the device inside a small tumour. No procedure-related deaths occurred in any of the 137 ablation procedures. Major complications consisted of pneumothorax (n=27) or pleural effusion (n=4), which needed drainage. No significant worsening of pulmonary function was noted. A confirmed complete response of target tumours lasting at least 1 year was shown in 75 (88%) of 85 assessable patients. No differences in response were noted between patients with NSCLC or lung metastases. Overall survival was 70% (95% CI 51-83%) at 1 year and 48% (30-65%) at 2 years in patients with NSCLC, 89% (76-95%) at 1 year and 66% (53-79%) at 2 years in patients with colorectal metastases, and 92% (65-99%) at 1 year and 64% (43-82%) at 2 years in patients with other metastases. Cancer-specific survival was 92% (78-98%) at 1 year and 73% (54-86%) at 2 years in patients with NSCLC, 91% (78-96%) at 1 year and 68% (54-80%) at 2 years in patients with colorectal metastases, and 93% (67-99%) at 1 year and 67% (48-84%) at 2 years in patients with other metastases. Patients with stage I NSCLC (n=13) had a 2-year overall survival of 75% (45-92%) and a 2-year cancer-specific survival of 92% (66-99%). INTERPRETATION: Percutaneous radiofrequency ablation yields high proportions of sustained complete responses in properly selected patients with pulmonary malignancies, and is associated with acceptable morbidity. Randomised controlled trials comparing radiofrequency ablation with standard non-surgical treatment options are warranted.

Five-year survival following radiofrequency ablation of small, solitary, hepatic colorectal metastases.

PURPOSE: Radiofrequency (RF) ablation is an increasingly accepted treatment for nonsurgical candidates with a limited number of colorectal hepatic metastases. RF ablation is most effective in tumors smaller than 4.0 cm. This report describes 5-year survival in patients with single tumors with a maximum diameter of 4 cm. MATERIALS AND METHODS: Forty of 291 patients (14%; 24 men, 16 women; mean age, 67 years; age range, 34-86 y) with no or treated extrahepatic disease were identified who were not candidates for resection and who had a minimum follow-up of 6 months. Sixteen had undergone hepatic resection and two had undergone lung resection and lung ablation. Thirty-two (80%) received chemotherapy. Thirty-five were treated under general anesthesia and five under conscious sedation. Our standard ablation protocol used internally water-cooled electrodes introduced percutaneously with ultrasonography and computed tomography guidance and monitoring. Follow-up data were obtained from primary care physicians or oncologists. RESULTS: Mean tumor diameter was 2.3 cm (range, 0.8-4.0 cm). There were two successfully treated systemic complications: a chest infection and an exacerbation of asthma. There were no local complications. Mean follow-up was 38 months (range, 6-132 months). The median survival duration and 1-, 3-, and 5-year survival rates were 59 months and 97%, 84%, 40%, respectively, after ablation; and 63 months, 100%, 88%, and 54%, respectively, from the diagnosis of liver metastases. History of liver resection did not impact survival. CONCLUSIONS: RF ablation of solitary liver metastases 4 cm or smaller can be performed with minimal morbidity and results in excellent long-term survival, approaching that of surgical resection, even in patients who are not surgical candidates.

Correlation of MRCP quantification (MRCPQ) with conventional non-invasive pancreatic exocrine function tests.

PURPOSE: To correlate MRCP quantification (MRCPQ) of pancreatic fluid output following secretin with steatorrhoea, urinary pancreo-lauryl (PL) or fecal elastase 1 (FE1) tests. METHODS AND MATERIALS: Sixty-one patients, 36 male, median age 51 years (23-78) with known or suspected pancreatic disease who had undergone both MRCPQ and FE1 or PL were included. Twenty-nine patients had chronic pancreatitis, five acute pancreatitis, seven normal, five pancreas divisum, four pancreatic atrophy, three pancreatic duct obstruction, two post-surgical and six miscellaneous diagnoses. Clinical assessment of steatorrhoea was available in 29. MRCP was performed before and at 2 min intervals after 0.1 ml/kg IV Secretin. Changes in signal intensity in the imaging volume were plotted against time and the flow rate derived from the gradient. Scatter plots, Pearson correlation coefficient, and the Fisher Exact test were performed. RESULTS: MRCPQ was significantly different (p = 0.012) between those with/without steatorrhoea; mean +/- SD (95% CI) were 4.0 +/- 1.5 (3.1:4.9, n = 16) and 6.3 +/- 2.9 (4.7:7.8, n = 13). Fifty-one paired FE1-MRCPQ and 24 PL-MRCPQ data sets were analysed. Both the Pearson correlation coefficient (FE1 p = 0.001 and %TK p = 0.003) and the Fisher Exact test were significant (FE1 p = 0.016 and %T/K 0.03). CONCLUSIONS: MRCPQ correlated with steatorrhoea, PL and FE1.

Radiofrequency ablation of lung metastases: factors influencing success.

This paper analyses the factors associated with successful radiofrequency ablation (RFA) of lung metastases. The study group comprised 37 patients [19 female, mean age 61 (34-83)] with 72 metastases who had follow-up CT scans available for analysis and for those with no recurrence >6 months follow-up. Internally cooled electrodes were used in 64 and expandable electrodes in 8. The tumour size and location, electrode type, number of ablations, duration of ablation, year of treatment and tumour contact with vessels larger than 3 mm were recorded. The mean tumour diameter was 1.8 cm (0.4-6.6 cm). Mean follow-up in those without recurrence was 13.1 months (6-48). Recurrence was common in larger tumours, occurring in 7/7 (100%) tumours >3.5 cm compared with 18/65 (28%) < or = 3.5 cm (P < 0.01). Recurrence occurred in 14/24 (58%) tumours in direct contact with large vessels compared with 11/48 (23%) of the remainder (P = 0.04). On multivariate analysis, size was the dominant feature (P = 0.013); vessel contact and peripheral location did not reach significance (P = 0.056 and 0.054 respectively). Peripheral tumours less than 3.5 cm with no large vessel contact are the optimal tumours for RFA.

Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series.

OBJECTIVE: Most cases of autoimmune pancreatitis (AIP) have been reported from Japan. We present data on a UK series, including clinical and radiological features at presentation, and longitudinal response to immunosuppression. METHODS: Over an 18-month period, all patients diagnosed in our center with AIP were studied. Endoscopic biliary stenting was performed as required, and patients were treated with prednisolone, with response assessed longitudinally. In cases of disease relapse following steroid reduction, azathioprine was instituted. RESULTS: Eleven patients met diagnostic criteria for AIP. Diffuse pancreatic enlargement was seen in eight patients (73%), and pancreatic duct strictures in all. Seven patients required biliary stents. Extrapancreatic involvement occurred in all, including intrahepatic stricturing and renal disease. Eight weeks after starting steroids, the median serum bilirubin level had fallen from 38 mumol/L to 11 mumol/L (P= 0.001), and ALT from 97 IU/L to 39 IU/L (P= 0.002). Stents were removed in all cases, with no recurrence of jaundice. Improvements in mass lesions and pancreaticobiliary stricturing occurred in all patients. During a median 18-month follow-up, six patients relapsed, four of whom responded to azathioprine. Two patients discontinued steroids and remained well. CONCLUSIONS: Extrapancreatic disease was an important feature of AIP in this UK series. Initial response to immunosuppressive therapy was excellent, but disease relapse was common. Optimal long-term management remains to be established.

Prospective comparison of secretin-stimulated magnetic resonance cholangiopancreatography with manometry in the diagnosis of sphincter of Oddi dysfunction types II and III.

BACKGROUND: In sphincter of Oddi dysfunction (SOD), sphincter of Oddi manometry (SOM) predicts the response to sphincterotomy, but is invasive and associated with complications. AIM: To evaluate the role of secretin-stimulated magnetic resonance cholangiopancreatography (ss-MRCP) in predicting the results of SOM in patients with suspected type II or III SOD. METHODS: MRCP was performed at baseline and at 1, 3, 5 and 7 min after intravenous secretin. SOD was diagnosed when the mean basal sphincter pressure at SOM was >40 mm Hg. Long-term outcome after SOM, with or without endoscopic sphincterotomy, was assessed using an 11-point (0-10) Likert scale. RESULTS: Of 47 patients (male/female 9/38; mean age 46 years; range 27-69 years) referred for SOM, 27 (57%) had SOD and underwent biliary and/or pancreatic sphincterotomy. ss-MRCP was abnormal in 10/16 (63%) type II and 0/11 type III SOD cases. The diagnostic accuracy of ss-MRCP for SOD types II and III was 73% and 46%, respectively. During a mean follow-up of 31.6 (range 17-44) months, patients with normal SOM and SOD type II experienced a significant reduction in symptoms (mean Likert score 8 vs 4; p = 0.03, and 9 vs 1.6; p = 0.0002, respectively), whereas in patients with SOD type III, there was no improvement in pain scores. All patients with SOD and an abnormal ss-MRCP (n = 12) reported long-term symptom improvement (mean Likert score 9.2 v 1.2, p<0.001). CONCLUSIONS: ss-MRCP is insensitive in predicting abnormal manometry in patients with suspected type III SOD, but is useful in selecting patients with suspected SOD II who are most likely to benefit from endotherapy.

Image-guided tumor ablation: standardization of terminology and reporting criteria.

The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy.