Is There a Role for Percutaneous Ablation for Early Stage Lung Cancer? What Is the Evidence?

PURPOSE OF REVIEW: For patients with early stage non-small-cell lung cancer (NSCLC), thermal ablation (TA) has become in the least two decades an option of treatment used worldwide for patients with comorbidities who are not surgical candidates. Here, we review data published with different TA techniques: radiofrequency ablation (RFA), microwave ablation (MWA) and cryoablation. This paper reviews also the comparison that has been made between TA and stereotactic radiotherapy (SBRT). RECENT FINDINGS: A majority of retrospective studies, the absence of comparative studies, and the variety of techniques make difficult to get evident data. Nevertheless, these stand-alone techniques have demonstrated local efficacy for tumors less than 3 cm and good tolerance on fragile patients. Many recent reviews and database analyses show that outcomes after TA (mainly RFA and MWA) are comparable to SBRT in terms of survival rates. For patients who are unfit for surgery, TA has demonstrated interesting results for safety, benefits in overall survival, and acceptable local control.

Contrast-enhanced intra-operative ultrasound as a clinical decision making tool during surgery for colorectal liver metastases: The ULIIS study.

BACKGROUND: Detecting more colorectal liver metastases (CRLMs) during surgery may help optimise strategy and improve outcomes. Our objective was to determine clinical utility (CU) of contrast-enhanced intra-operative ultrasound (CE-IOUS) using sulphur hexafluoride microbubbles during CRLM surgery. METHOD: A prospective phase II trial performed at two comprehensive cancer research centres. Patients operated for CRLMs were eligible and assessable if intra-operative ultrasound (IOUS) and CE-IOUS had been performed and pathological results were available and/or 3-month imaging. CU was defined as the justified change in planned surgical strategy or procedure using CE-IOUS. RESULTS: Out of the 68 patients enrolled, 54 were eligible and assessable. 43 patients underwent pre-operative chemotherapy. The median number of CRLMs was 2 (range, 1-11). Pre-operative staging was performed using MRI. IOUS allowed identification of 45 new CRLMs in 13 (24.7%) patients. Compared to IOUS, CE-IOUS allowed identification of 10 additional CRLMs in 9 (16.7%) patients. Surgery was altered and justified in 4 patients only, leading to a CU rate of 7.70% (95 CI, [3.2, 18.6]). No missing CRLMs were identified by CE-IOUS. CONCLUSIONS: Although the primary endpoint was not met for one protocol violation, secondary endpoints indicate that CE-IOUS has an intermediate added-value for surgeons treating CRLMs. TRIAL REGISTRATION: NCT01880554 (https://clinicaltrials.gov/).

Radiofrequency ablation of stage IA non-small cell lung cancer in patients ineligible for surgery: results of a prospective multicenter phase II trial.

BACKGROUND: A prospective multicenter phase II trial to evaluate the survival outcomes of percutaneous radiofrequency ablation (RFA) for patients with stage IA non-small cell lung cancer (NSCLC), ineligible for surgery. METHODS: Patients with a biopsy-proven stage IA NSCLC, staging established by a positron emission tomography-computed tomography (PET-CT), were eligible. The primary objective was to evaluate the local control of RFA at 1-year. Secondary objectives were 1- and 3-year overall survival (OS), 3-year local control, lung function (prior to and 3 months after RFA) and quality of life (prior to and 1 month after RFA). RESULTS: Of the 42 patients (mean age 71.7 y) that were enrolled at six French cancer centers, 32 were eligible and assessable. Twenty-seven patients did not recur at 1 year corresponding to a local control rate of 84.38% (95% CI, [67.21-95.72]). The local control rate at 3 years was 81.25% (95% CI, [54.35-95.95]). The OS rate was 91.67% (95% CI, [77.53-98.25]) at 1 year and 58.33% (95% CI, [40.76-74.49]) at 3 years. The forced expiratory volume was stable in most patients apart from two, in whom we observed a 10% decrease. There was no significant change in the global health status or in the quality of life following RFA. CONCLUSION: RFA is an efficient treatment for medically inoperable stage IA NSCLC patients. RFA is well tolerated, does not adversely affect pulmonary function and the 3-year OS rate is comparable to that of stereotactic body radiotherapy, in similar patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01841060 registered in November 2008.

Percutaneous thermal ablation of lung tumors - Radiofrequency, microwave and cryotherapy: Where are we going?

Main indications of percutaneous pulmonary thermal ablation are early stage non-small cell lung carcinoma (NSCLC) for patients who are not amenable to surgery and slow-evolving localized metastatic disease, either spontaneous or following a general treatment. Radiofrequency ablation (RFA) is the most evaluated technique. This technique offers a local control rate ranging between 80 and 90% for tumors <3cm in diameter. Other more recently used ablation techniques such as microwaves and cryotherapy could overcome some limitations of RFA. One common characteristic of these techniques is an excellent tolerance with very few complications. This article reviews the differences between these techniques when applied to lung tumors, indications, results and complications. Future potential associations with immunotherapy will be discussed.

Precision of manual two-dimensional segmentations of lung and liver metastases and its impact on tumour response assessment using RECIST 1.1.

BACKGROUND: Response evaluation criteria in solid tumours (RECIST) has significant limitations in terms of variability and reproducibility, which may not be independent. The aim of the study was to evaluate the precision of manual bi-dimensional segmentation of lung, liver metastases, and to quantify the uncertainty in tumour response assessment. METHODS: A total of 520 segmentations of metastases from six livers and seven lungs were independently performed by ten physicians and ten scientists on CT images, reflecting the variability encountered in clinical practice. Operators manually contoured the tumours, firstly independently according to the RECIST and secondly on a preselected slice. Diameters and areas were extracted from the segmentations. Mean standard deviations were used to build regression models and 95% confidence intervals (95% CI) were calculated for each tumour size and for limits of progressive disease (PD) and partial response (PR) derived from RECIST 1.1. RESULTS: Thirteen aberrant segmentations (2.5%) were observed without significant differences between the physicians and scientists; only the mean area of liver tumours (p = 0.034) and mean diameter of lung tumours (p = 0.021) differed significantly. No difference was observed between the methods. Inter-observer agreement was excellent (intra-class correlation >0.90) for all variables. In liver, overlaps of the 95% CI with the 95% CI of limits of PD or PR were observed for diameters above 22.7 and 37.9 mm, respectively. An overlap of 95% CIs was systematically observed for area. No overlaps were observed in lung. CONCLUSIONS: Although the experience of readers might not affect the precision of segmentation in lung and liver, the results of manual segmentation performed for tumour response assessment remain uncertain for large liver metastases.

Percutaneous thermal ablation of primary lung cancer.

Percutaneous ablation of small-size non-small-cell lung cancer (NSCLC) has demonstrated feasibility and safety in nonsurgical candidates. Radiofrequency ablation (RFA), the most commonly used technique, has an 80-90% reported rate of complete ablation, with the best results obtained in tumors less than 2-3cm in diameter. The highest one-, three-, and five-year overall survival rates reported in NSCLC following RFA are 97.7%, 72.9%, and 55.7% respectively. Tumor size, tumor stage, and underlying comorbidities are the main predictors of survival. Other ablation techniques such as microwave or cryoablation may help overcome the limitations of RFA in the future, particularly for large tumors or those close to large vessels. Stereotactic ablative radiotherapy (SABR) has its own complications and carries the risk of fiducial placement requiring multiple lung punctures. SABR has also demonstrated significant efficacy in treating small-size lung tumors and should be compared to percutaneous ablation.

Temperature monitoring during microwave ablation in ex vivo porcine livers.

OBJECTIVE: The aim of the present study was to assess the temperature map and its reproducibility while applying two different MWA systems (915 MHz vs 2.45 GHz) in ex vivo porcine livers. MATERIALS AND METHODS: Fifteen fresh pig livers were treated using the two antennae at three different settings: treatment time of 10 min and power of 45 W for both systems; 4 min and 100 W for the 2.45 GHz system. Trends of temperature were recorded during all procedures by means of fiber optic-based probes located at five fixed distances from the antenna, ranging between 10 mm and 30 mm. Each trial was repeated twice to assess the reproducibility of temperature distribution. RESULTS: Temperature as function of distance from the antenna can be modeled by a decreasing exponential trend. At the same settings, temperature obtained with the 2.45 GHz system was higher than that obtained with the 915 MHz thus resulting into a wider area of ablation (diameter 17 mm vs 15 mm). Both systems showed good reproducibility in terms of temperature distribution (root mean squared difference for both systems ranged between 2.8 °C and 3.4 °C). CONCLUSIONS: When both MWA systems are applied, a decreasing exponential model can predict the temperature map. The 2.45 GHz antenna causes higher temperatures as compared to the 915 MHz thus, resulting into larger areas of ablation. Both systems showed good reproducibility although better results were achieved with the 2.45 GHz antenna.

Over ten years of single-institution experience in percutaneous image-guided treatment of bone metastases from differentiated thyroid cancer.

OBJECTIVE: Percutaneous image-guided treatments (PIGT) are performed by interventional radiologists with a minimally invasive approach. Currently, very little published data on their outcomes are available and conclusions regarding their application are cautious. The aim of the present study was to review our experience in PIGT of bone metastases from thyroid cancer. MATERIALS AND METHODS: Institutional databases were reviewed to identify patients with differentiated thyroid cancer and bone metastases who received PIGT between October 2001 and April 2014. Complications, local evolution of the treated lesions, and overall survival (OS) were investigated. RESULTS: Twenty-five patients (12 male, 13 female) underwent 49 PIGT sessions consisting of cementoplasty (77.5%), cryoablation (14.3%) or radiofrequency ablation (8.2%). Most of the treated lesions (50/54, 92.6%) were symptomatic at the time of PIGT. Median follow-up after PIGT was 4.6 years. Local complete remission rate was 55.6%. Two complications (one major and one minor) were noted, but none of these were consistent with fractures or nervous system injuries. OS after PIGT was 71.6%, 66.8% and 60.1% at 1, 2 and 3 years, respectively. A difference in survival was observed between patients with metastatic bone involvement only at the time of first PIGT compared to those with multi-organ involvement (P = 0.03). CONCLUSIONS: Patients with bone metastases from differentiated thyroid cancer may benefit from PIGT. Although patients are usually referred for PIGT due to their symptomatic status, a more relevant "curative" role may exist for PIGT. Further prospective studies are needed to confirm this perception.

Interventional Radiologist's perspective on the management of bone metastatic disease.

Bone metastases can be treated by interventional radiologists with a minimally invasive approach. Such treatments are performed percutaneously under radiological imaging guidance. Different interventional techniques can be applied with curative or palliative intent depending on lesions and patients' status. In the whole, available interventional techniques are distinguished into "ablative" and "consolidative". Ablative techniques achieve bone tumor necrosis by dramatically increasing or decreasing intra-tumoral temperature. This option can be performed in order to alleviate pain or to eradicate the lesion. On the other hand, consolidative techniques aim at obtaining bone defect reinforcement mainly to alleviate pain and prevent pathological fractures. We herein present evidence supporting the application of each different interventional technique, as well as common strategies followed by interventional radiologists while approaching bone metastases.

Radiofrequency ablation is a valid treatment option for lung metastases: experience in 566 patients with 1037 metastases.

BACKGROUND: Minimal invasive methods are needed as an alternative to surgery for treatment of lung metastases. PATIENTS AND METHODS: The prospective database of two cancer centers including all consecutive patients treated with radiofrequency ablation (RFA) for lung metastasis over 8 years was reviewed. RFA was carried out under general anesthesia, with computed tomography guidance using a 15-gauge multitined expandable electrodes RF needle. RESULTS: Five hundred sixty-six patients including 290 men (51%), 62.7 ± 13.2 years old with primary tumor to the colon (34%), rectum (18%), kidney (12%), soft tissue (9%) and miscellaneous (27%) received 642 RFA for 1037 lung metastases. Fifty-three percent of patients had 1 metastasis, 25% had 2, 14% had 3, 5% had 4 and 4% had 5-8. Metastases were unilateral (75%), or bilateral (25%). The median diameter [extremes] of metastases was 15 mm (4-70). Twenty-two percent of patients had extrapulmonary disease amenable to local therapy including 49 liver, 16 bone and 60 miscellaneous metastases. Median follow-up was 35.5 months. Median overall survival (OS) was 62 months. Four-year local efficacy was 89%. Four-year lung disease control rate was 44.1%, with patient retreated safely up to four times. Primary origin, disease-free interval, size and number of metastases were associated with OS in multivariate analysis. Progression at RFA site was associated with poor OS [P = 0.011, hazard ratio (HR): 1.69 (95% confidence interval 1.13-2.54)]. In the 293 colorectal cancer metastases, size >2 cm (HR = 2.10, P = 0.0027) and a number of metastases ≥3 (HR = 1.86, P = 0.011) remained significantly associated with OS. A prognostic score made of three groups based on the four above-mentioned prognostic factors demonstrated 3-year OS rates of respectively 82.2%, 69.5% and 53.6% (log-rank test, P ≤ 0.0001) among the three groups in the overall population, and of 81.3%, 72.8% and 57.9% (log-rank test, P = 0.005) in the colorectal cancer patients. CONCLUSION: Radiofrequency is an option for treatment of small size lung metastases, namely the ones below 2-3 cm.

Local treatment of metastases from differentiated thyroid cancer.

OBJECTIVES: To study the various local treatments available for thyroid cancer metastases, investigate techniques and assess their advantages and limitations and roles in the overall treatment strategy for metastatic disease. RESULTS: We investigated metastases surgery, external radiation therapy, embolization, chemoembolization, cementoplasty, radiofrequency ablation and cryotherapy, describing techniques, advantages and drawbacks and possible complications. Indications were reviewed according to metastases location, and the roles of the various techniques are discussed in the overall treatment strategy for thyroid cancer metastases. Despite the advent of new targeted therapies, local treatment still has an important role to play: either palliative or, in oligometastatic involvement, curative. Even in extensive disease, it may allow postponement of tyrosine kinase inhibitor therapy, which, once initiated, has to be continued life-long, is expensive and is not free of side-effects.

Hepar lobatum carcinomatosum associated with liver metastases from breast cancer: report of five cases.

BACKGROUNDS AND AIMS: Hepar lobatum carcinomatosum (HLC) is an exceptional acquired hepatic distortion which consists in irregularly lobulated hepatic contours seen in patients with known liver metastases, usually from breast carcinoma. We aimed to describe and analyze five similar cases of HLC resulting from metastatic mammary carcinoma in the liver and associated with rapid hepatic failure. METHODS: Five cases of HLC were investigated. Medical (including blood liver tests), radiological and histological data (2 cases) were collected and retrospectively analyzed. All patients were followed up for metastatic invasive ductal carcinoma of the breast and had a common pattern of treatment with combination of targeted therapies (bevacizumab, AVASTIN) and chemotherapy (paclitaxel, TAXOL). RESULTS: All the patients showed rapid hepatic failure after a mean of 9 courses of bevacizumab/paclitaxel. In all cases, liver imaging revealed liver capsule retraction and an irregular lobular margin. An apparent tumor regression of all liver metastases was showed in two cases. Biopsies were consistent with sinusoidal obstruction syndrome (SOS) and, surprisingly, no tumoral cells were found. CONCLUSION: Although rare, such an unusual pattern of liver metastasis may mimick acute cirrhosis and cause rapid hepatic failure in patients, despite possible apparent tumor regression on imaging. The etiology of this pathology is unclear, and may involve multiple pathogenic factors. Direct or indirect vascular injury plays an important role in the development of HLC.

Pulmonary aspergilloma in a cavity formed after percutaneous radiofrequency ablation.

We report two cases of pulmonary aspergilloma (PA) in a cavity formed after percutaneous radiofrequency ablation (PRFA), a rare complication that has only been described once in the literature. The first patient was a 59-year-old white woman treated for a secondary lung nodule of an advanced hepatocellular carcinoma. One month after PRFA, a consolidation of a cavity was noticed with an "air crescent sign," and aspergilloma serology was highly positive. A bisegmentectomy was performed due to the proximity of the lesion to mediastinal vessels and the absence of significant regression after antifungal treatment. Histological examination confirmed the diagnosis of PA. The second patient was a 61-year-old white man followed-up for a non-small-cell lung cancer. A cavitation with thick margins in the ablation zone was noticed 6 months after PRFA. A biopsy was performed, and aspergilloma was diagnosed. Medical treatment with itraconazole was administered for 13 months, and there was significant regression.

In vivo mathematical modeling of tumor growth from imaging data: soon to come in the future?

The future challenges in oncology imaging are to assess the response to treatment even earlier. As an addition to functional imaging, mathematical modeling based on the imaging is an alternative, cross-disciplinary area of development. Modeling was developed in oncology not only in order to understand and predict tumor growth, but also to anticipate the effects of targeted and untargeted therapies. A very wide range of these models exist, involving many stages in the progression of tumors. Few models, however, have been proposed to reproduce in vivo tumor growth because of the complexity of the mechanisms involved. Morphological imaging combined with "spatial" models appears to perform well although functioning imaging could still provide further information on metabolism and the micro-architecture. The combination of imaging and modeling can resolve complex problems and describe many facets of tumor growth or response to treatment. It is now possible to consider its clinical use in the medium term. This review describes the basic principles of mathematical modeling and describes the advantages, limitations and future prospects for this in vivo approach based on imaging data.

Radiologically guided percutaneous cryotherapy for soft tissue tumours: A promising treatment.

Studies of percutaneous cryotherapy in the treatment of benign or malignant soft tissue tumours are rare and mainly involve small populations. Nevertheless, results show cryotherapy's potential in terms of local control of tumours, analgesic efficacy, reduced intra- and postoperative complications, and reduction in the length of convalescence after the procedure. The objective of this update is to set out the short-term prospects for this technique in the treatment of soft tissue tumours, so that it may be more widely offered in these indications.

Percutaneous cryotherapy of vascular malformation: initial experience.

The present report describes a case of percutaneous cryotherapy in a 36-year-old woman with a large and painful pectoral venous malformation. Cryoablation was performed in a single session for this 9-cm mass with 24 h hospitalisation. At 2- and 6-month follow-up, the pain had completely disappeared, and magnetic resonance imaging demonstrated a significant decrease in size. Percutaneous cryoablation shows promise as a feasible and apparently safe method for local control in patients with symptomatic venous vascular malformations.

Radiofrequency ablation of bone tumours.

The indications for radiofrequency bone ablation in the case of benign tumours (osteoid osteoma, osteoblastoma) are curative, whereas for bone metastases, the prime aim is palliative analgesia. The failure rate for osteoid osteomas is low (<15%), and 70 to 90% of patients with metastases experience considerable relief, but if the treatment fails, it can be offered again. In the spine, heating can damage neighboring nerve structures, which means they need to be protected (CO(2) dissection). Radiofrequency ablation may be combined with an injection of cement. The osteonecrosis resulting from heating is painful and justifies performing the procedure under general anesthesia.

[Is there a curative treatment for oligometastases? Lung radiofrequency ablation]. / Oligométastases : prise en charge thérapeutique à visée curative ? Radiofréquence pulmonaire.

Percutaneous ablation allows to treat tumours with temperature modifications. These non-invasive techniques are useful to treat metastatic lung tumours in patients with a slowly evolving disease, which requires multiple local treatment. Ablation is therefore proposed as a locoregional treatment because it has a minimal impact on the lung. Other advantages are its efficacy and a low morbidity. Limits may be the tumour size and its location.

Imaging benign inflammatory syndromes.

Benign mastitis is a rare disease and its management is difficult. The diagnostic challenge is to distinguish it from carcinomatous mastitis. We make a distinction between acute mastitis secondary to an infection, to inflammation around a benign structure or to superficial thrombophlebitis, and chronic, principally plasma cell and idiopathic granulomatous mastitis. Imaging is often non-specific but we need to know and look for certain ultrasound, mammogram or magnetic resonance imaging (MRI) signs to give a pointer as early as possible towards a benign aetiology. A biopsy should be undertaken systematically where there is the slightest diagnostic doubt, to avoid failing to recognise a carcinomatous mastitis.