Long-Term Treatment of Unresectable Pseudomyxoma Peritonei with Multiple Treatments of Intratumoural Bromelain and Acetylcysteine (BromAc®): A Case Report.

Pseudomyxoma peritonei is a rare peritoneal malignancy characterized by the progressive accumulation of mucinous material and tumour within the abdomen and pelvis. Percutaneous drainage of mucin may be a non-surgical option for relief of symptoms; however, it remains difficult due to the high viscosity of mucin, with numerous case reports reporting difficulty removing material through medium-bore catheters alone. BromAc is a therapy currently undergoing development which dissolves mucinous tumour masses and allows for extraction. This report describes the case of a patient who has had multiple treatments with BromAc over 4 years.

Comparison of Microwave and Radiofrequency Ablation in the Treatment of Pulmonary Metastasis of Colorectal Cancer.

BACKGROUND/AIM: Radiofrequency ablation (RFA) for colorectal cancer pulmonary metastases (CRCPulM) has been shown to be safe. Microwave ablation (MWA) has emerged in the treatment for CRCPulM. However, short to long-term efficacy of both modalities have yet to be understood. PATIENTS AND METHODS: This is a retrospective study of 203 patients who received RFA and MWA from 2000-2018 at a major tertiary hospital in Australia. RESULTS: A total of 161 patients underwent RFA and 42 MWA. Median ablation size and time was 4 (range=3-5 cm) vs. 3.5 cm (range=3-4 cm; p=0.0395) and 49 (range=26-65 min) vs. 8 min (5-13 min) in the RFA and MWA groups, respectively (p<0.001). The complication rate was 112 (55%) and 40 (74%) in the RFA and MWA group, respectively (p=0.011). Life-threatening pulmonary haemorrhage occurred in 1 (0.5%) and 4 (7.4%) patients in the RFA and MWA group, respectively (p=0.007). Local recurrences detected after discharge were similar in both groups [28% (p<0.001)]. However, the MWA group demonstrated higher survival rate and less recurrence rate than RFA in the first 24 months of follow up. CONCLUSION: RFA and MWA are competitive treatment methods for CRCPulM. Although MWA has significantly higher complication rate than RFA, it can be performed in a much shorter time and lead to a shorter length of hospital stay.

Long term survival after multiple microwave ablations for colorectal cancer lung metastases: A case report.

Colorectal cancer is one of the leading causes of cancer-associated morbidity and mortality in the world, with lower survival rates when metastases are present. We present a case of a 69-year-old man, diagnosed with metastatic rectal cancer to the lungs in 2015. Over the course of 5 years, he was treated with 4 microwave ablation procedures to both his lungs. Despite this, he does not have any local recurrence or any symptoms since he was first diagnosed 7 years ago. This case highlights the potential for microwave ablation to be used for curative intent in pulmonary metastases in colorectal cancer as an alternative to more invasive and complex procedures such as metastasectomies or lung resection, as well as the benefit of using microwave ablation for disease control to improve patients' quality of life.

Surgical Removal of an Unusual Massive Mediastinal Tumour Preceded by Interventional Embolisation.

Massive mediastinal tumours are rare in clinical practice and complete surgical resection may be associated with serious complications. Preoperative angiography and embolisation are valuable adjuncts in the management of giant tumours to decrease perioperative blood loss, provide a clear operative field and facilitate complete resection. We report the safe use of preoperative embolisation which facilitated excision via clamshell incision, of a highly vascular massive anterior mediastinal tumour with an unusual final diagnosis.

Evaluation of carcinoembryonic antigen (CEA) density as a prognostic factor for percutaneous ablation of pulmonary colorectal metastases.

OBJECTIVES: To evaluate the prognostic value of carcinoembryonic antigen (CEA) density and other clinicopathological factors for percutaneous ablation of pulmonary metastases from colorectal cancer. METHODS: CEA density was calculated as: "absolute serum CEA pre-ablation/volume of all lung metastases [mm3]". Median CEA density was the cut-off for high and low groups. Cox-regression was used to determine prognostic factors for survival. RESULTS: A total of 85 patients (102 ablation sessions) were followed for a median of 27 months. High CEA density was significantly associated with worse overall survival compared to low CEA density (adjusted HR: 2.12; 95 % CI: 1.22-3.70, p=0.002; median survival: 25.7 vs. 44.3 months). The interval between primary resection of the colorectal carcinoma and first ablation was also a prognostic factor, a duration >24 months being associated with better survival compared to a shorter interval (0-24 months) (adjusted HR: 0.55; 95 % CI: 0.31-0.98, p=0.04). Moreover, a disease-free interval >24 months was significantly associated with low CEA density compared to a shorter interval (0-24 months) (adjusted OR: 0.29; 95 % CI: 0.11-0.77, p=0.01). CONCLUSIONS: Serum CEA density and interval between primary resection of a colorectal carcinoma and pulmonary ablation are independent prognostic factors for overall survival. In two patients with identical CEA serum levels, the patient with the lower/smaller pulmonary tumour load would have a worse prognosis than the one with the higher/larger pulmonary metastases. KEY POINTS: • CEA density is an independent prognostic factor for colorectal pulmonary metastases. • A lower CEA density is associated with better overall survival. • CEA may play a functional role in tumour progression. • High CEA density is associated with smaller tumours. • Interval between pulmonary ablation and primary colorectal carcinoma is a prognostic factor.

A Differential Diagnosis of Haematuria following a Motor Vehicle Collision: Nutcracker Syndrome.

A young female presented to the emergency department following a motor vehicle collision. She complained of left flank pain and was found to have haematuria. After investigation no trauma related injuries were identified. However, an incidental finding of nutcracker phenomenon/syndrome was made. Nutcracker phenomenon is a rare cause of haematuria resulting from nontraumatic compression of the left renal vein between the superior mesenteric artery and the aorta. It affects females more than males and its presentation can range from asymptomatic to debilitating haematuria, pelvic congestion in females, varicosities in males, and pain. No validated diagnostic criteria exist and treatment is usually surgical in those with debilitating symptoms or refractory anaemia.

Radiofrequency ablation of concomitant and recurrent pulmonary metastases after surgery for colorectal liver metastases.

BACKGROUND: To evaluate our experience of radiofrequency ablation (RFA) of pulmonary metastases in patients with resected colorectal liver metastases who had concomitant or recurrent pulmonary metastases. METHODS: Clinical and treatment variables of patients undergoing RFA were collected, and their association with survival was examined. Survival analysis was performed by the Kaplan-Meier method. RESULTS: RFA was performed as concomitant sequential treatment of extrahepatic pulmonary metastases after hepatectomy in 19 patients (30%) and as salvage treatment for pulmonary recurrences after hepatectomy in 45 patients (70%). Patients undergoing sequential treatment had a median survival of 31 (95% confidence interval [CI] 21.8-40.6) months compared to 59 (95% CI 35.0-82.0) months in the salvage treatment group (P = 0.142). The disease-free survival (DFS) was 9 (95% CI 1.0-18.8) months in the sequential treatment group and 16 (95% CI 8.1-23.1) months in the salvage treatment group (P = 0.023). Liver metastases occurring within 12 months of the primary tumor negatively influenced overall survival (OS) and DFS in the sequential treatment group (P = 0.003 and P = 0.091). Poorly differentiated tumor (P = 0.001) was associated with a poorer OS, and prehepatectomy carcinoembryonic antigen > 200 ng/ml (P = 0.017) and bilateral pulmonary metastases (P = 0.030) were associated with a shorter DFS in the salvage treatment group. CONCLUSIONS: The DFS and OS of patients undergoing sequential RFA of extrahepatic pulmonary metastases after hepatectomy appeared shorter when compared to patients who underwent RFA as salvage treatment for pulmonary recurrences after hepatectomy. It nonetheless remains better than the historical results of chemotherapy alone and thus supports the use of RFA as an ablative technology to achieve tumor control.

Determining the association between preoperative computed tomography findings and postoperative outcomes after cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei.

BACKGROUND: This study evaluates the accuracy of computed tomography (CT) scoring of the peritoneal cancer index (PCI) and examines its association with surgical morbidity and outcomes in pseudomyxoma peritonei. METHODS: Forty-seven patients with pseudomyxoma peritonei had preoperative evaluation of CT scans and were treated with cytoreductive surgery and perioperative intraperitoneal chemotherapy. Their radiological PCI and intraoperative PCI were scored for determination of accuracy and for correlation with morbidity and outcomes. RESULTS: Accuracy in detecting peritoneal lesions regardless of size ranged from 51% to 85% in the abdominopelvic regions and 21% to 25% in the small intestinal regions. The sensitivity of CT detection of peritoneal implants ranged from 67% to 84% in the abdominopelvic regions and from 56% to 57% in the small intestinal regions. The specificity of CT detection of peritoneal lesions was 100% in all regions. Preoperative CT identification of larger peritoneal lesions in the right upper quadrant (P = 0.016), epigastrium (P = 0.003), left upper quadrant (P = 0.019), proximal jejunum (P = 0.022), distal jejunum (P = 0.022), and proximal ileum (P = 0.022) predicted development of severe complications. Similarly, larger peritoneal lesions in the right upper quadrant (P = 0.039), epigastrium (P = 0.024), right flank (P = 0.005), and right lower quadrant (P = 0.034) were negatively associated with disease-free survival, and the right upper quadrant (P = 0.037) was negatively associated with overall survival. CONCLUSIONS: Preoperative CT scan depicting extensive upper abdominal and small bowel disease predicts the presence of severe complications after cytoreduction. Extensive disease in the right upper quadrant seems to be associated with a poorer survival outcome.

Hepatic resection with or without adjuvant iodine-131-lipiodol for hepatocellular carcinoma: a comparative analysis.

BACKGROUND: Resection of hepatocellular carcinoma (HCC) is potentially curative; however, recurrence is common. To date, few or no effective adjuvant therapies have been adequately investigated. This study evaluates the efficacy of adjuvant iodine-131-lipiodol after hepatic resection through the experience of a single-center hepatobiliary service of managing this disease. PATIENTS AND METHODS: All patients who underwent hepatic resection for HCC and received adjuvant iodine-131-lipiodol between January 1991 and August 2009 were selected for inclusion into the experimental group. A group composed of patients treated during the same time period without adjuvant iodine-131-lipiodol was identified through the unit's HCC surgery database for comparison. The endpoints of this study were disease-free survival and overall survival. RESULTS: Forty-one patients who received adjuvant iodine-131-lipiodol after hepatic resection were compared with a matched group of 41 patients who underwent hepatic resection only. The median disease-free and overall survival were 24 versus 10 months (P = 0.032) and 104 versus 19 months (P = 0.001) in the experimental and control groups, respectively. Rates of intrahepatic-only recurrences (73 vs. 37%; P = 0.02) and surgical and nonsurgical treatments for recurrences (84 vs. 56%; P = 0.04) were higher in the experimental group compared to the control group. CONCLUSION: The finding of this study corroborates the current evidence from randomized and nonrandomized trials that adjuvant iodine-131-lipiodol improves disease-free and overall survival in patients with HCC after hepatic resection. The lengthened disease-free survival after adjuvant iodine-131-lipiodol allows for further disease-modifying treatments to improve the overall survival.

Intra-arterial iodine-131-lipiodol for unresectable hepatocellular carcinoma.

BACKGROUND: Hepatic artery administration of iodine-131-Lipiodol serves as a modality that delivers targeted radiation therapy to hepatocellular carcinoma. Its efficacy has been promising according to trials conducted in the adjuvant setting after hepatic resection. Further investigation of its role in the palliative setting is warranted. METHODS: A retrospective review of 72 patients with unresectable hepatocellular carcinoma treated with iodine-131-Lipiodol and followed up by the St. George Hospital Sydney's hepatobiliary service was conducted. Efficacy of treatment was determined based on progression-free and overall survival as the endpoints using the Kaplan-Meier method. RESULTS: Sixty men and 12 women with a mean age of 65 years (standard deviation = 11) underwent iodine-131-Lipiodol treatment. Chronic viral hepatitis was present in 29 (41%) patients. Fifty (69%) patients were Child-Pugh class A. Median progression-free survival was 6 months, and overall survival was 14 months; the 1-, 2-, and 3-year survival rates were 52%, 33% and 20%, respectively. Factors associated with survival include the American Joint Committee on Cancer stage (P = .03), Barcelona Clinic Liver Cancer stage (P = .05), Cancer of the Liver Italian Program score (P = .008), tumor size (P = .01), extrahepatic disease (P < .001), previous surgery (P = .02), and response to treatment (P < .001). The response to treatment was identified through a multivariate analysis as the single independent predictor for survival (hazard ratio, 3.5; 95% confidence interval, 2.2-5.4; P < .001). CONCLUSIONS: Encouraging survival outcomes may be derived through administration of iodine-131-Lipiodol in patients with unresectable hepatocellular carcinoma. The overall success of treatment may be determined by the response to treatment.

Radiofrequency ablation as an adjunct to systemic chemotherapy for colorectal pulmonary metastases.

BACKGROUND: Radiofrequency ablation (RFA) is an alternative to local treatment for pulmonary metastases in patients who are nonsurgical candidates. Based on previously documented efficacy of this treatment, the authors retrospectively studied the prognostic factors for long-term survival. METHODS: One hundred patients with unresectable colorectal pulmonary metastases underwent percutaneous RFA. Clinical and treatment variables were collected and evaluated using univariate and multivariate analyses with overall survival as the primary endpoint. RESULTS: At a median follow-up period of 23 (range, 1 to 96) months from the time of RFA treatment, 49 patients have died. The median overall survival after RFA treatment was 36 months and 5-year overall survival rates of 30%. Univariate analyses demonstrated that histopathological grade (p < .001), time to RFA treatment (p = .017), response to treatment (p < .001), repeat RFA treatments (p = .001), presence of extrapulmonary metastases (p < .001), presence of mediastinal lymphadenopathy (p = .007), and adjunct systemic chemotherapy (p < .001) were associated with overall survival. Multivariate analyses demonstrated that response to RFA treatment (p < .001), repeat RFA treatment (p = .002), presence of extrapulmonary metastases (p = .008), and use of adjunct systemic chemotherapy (p = .05) were independent predictors for survival. CONCLUSIONS: Radiofrequency ablation for colorectal pulmonary metastases represents a step forward towards a nonsurgical option of combining systemic and local treatment for metastatic disease and is a safe treatment with a low risk profile.

Systematic review of neoadjuvant transarterial chemoembolization for resectable hepatocellular carcinoma.

Resection of hepatocellular carcinoma (HCC) offers the only hope for cure. However, in patients undergoing resection, recurrences, in particular, intrahepatic recurrence are common. The effectiveness of transarterial chemoembolization (TACE) as a neoadjuvant therapy for unresectable HCC was exploited by numerous liver units and employed preoperatively in the setting of resectable HCC with an aim to prevent recurrence and prolong survival. A systematic literature search of databases (Medline and PubMed) to identify published studies of TACE administered preoperatively as a neoadjuvant treatment for resectable HCC was undertaken. A systematic review by tabulation of the results was performed with disease-free survival (DFS) as the primary endpoint. Overall survival (OS), rate of pathological response, impact on surgical morbidity and mortality and pattern of recurrences were secondary endpoints of this review. Eighteen studies; three randomized trials and 15 observational studies were evaluated. This comprised of 3927 patients, of which, 1293 underwent neoadjuvant TACE. The median DFS in the TACE and non-TACE group ranged from 10 to 46 and 8 to 52 months, respectively, with 67% of studies reporting similar DFS between groups despite higher extent of tumour necrosis from the resected specimens indicating a higher rate of pathological response (partial TACE 27-72% vs. non-TACE 23-52%; complete TACE 0-28% vs. non-TACE zero), with no difference in surgical morbidity and mortality outcome. No conclusion could be drawn with respect to OS. Both randomized and non-randomized trials suggest the use of TACE preoperatively as a neoadjuvant treatment in resectable HCC is a safe and efficacious procedure with high rates of pathological responses. However, it does not appear to improve DFS.

Feasibility of ablation as an alternative to surgical metastasectomy in patients with unresectable sarcoma pulmonary metastases.

Percutaneous radiofrequency ablation (RFA) is an alternate treatment modality for pulmonary metastasis in non-surgical candidates. Four patients not suitable for surgery underwent percutaneous RFA for pulmonary metastases from leiomyosarcoma. Success of RFA was assessed with computed tomography (CT). The median length from the radiographic diagnosis of metastatic pulmonary disease (CT-scan) from the primary tumor diagnosis was 67.0 months with a range of 15.0-81.0 months. The median disease free interval following RFA was 19.0 months with a range of 4.0-35.0 months. Three of four patients underwent the procedure uneventfully. RFA is a safe and minimally invasive intervention in non-surgical candidates with sarcoma pulmonary metastases.

Use of percutaneous radiofrequency ablation in pulmonary metastases from renal cell carcinoma.

BACKGROUND: Surgical resection of pulmonary metastases from renal cell carcinoma (RCC) has been demonstrated in recent studies to produce good long-term survival outcomes. Radiofrequency ablation (RFA) may offer an alternative treatment option for this group of patients, especially for those who are unable to have surgery. METHODS: Nine patients had a total of 23 pulmonary metastases treated with percutaneous RFA under fluoro-computed tomography (CT) guidance. Patients underwent routine overnight hospitalization and monitoring for other potential complications. CT scans were performed at 1 month after the procedure and at 3-monthly intervals. RESULTS: A total of 25 ablations were performed to 23 pulmonary metastases for our nine patients in 12 RFA sessions. No patient died within 30 days of the procedure. Five of the 12 procedures resulted in a pneumothorax (42%) and 3 required insertion of a Pleurocath. One patient had a bronchopulmonary fistula with an associated small pleural effusion and one patient had pneumonia. Of the 25 ablations, 14 lesions had decreased in size (56%), 1 was stable in size (4%), and 9 had increased in size (36%). One patient had deceased before adequate follow-up. Of the nine patients, two are alive and free of disease (mean survival time of 74 months), two are alive with disease (mean survival time of 16 months), and five have died of disease (mean survival time of 26.2 months). CONCLUSION: RFA offers a treatment alternative for local tumor control, particularly in selected patients with multiple, small lesions who are unsuitable for pulmonary resections.

Radiofrequency ablation of lung tumors: feasibility and safety.

BACKGROUND: Percutaneous image-guided radiofrequency ablation is being promoted as a novel technique with a low morbidity rate in the treatment of inoperable lung tumors. The purpose of this study was to assess the incidence and risk factors of various complications after radiofrequency ablation of pulmonary neoplasms. METHODS: The clinical and treatment-related data regarding 129 consecutive percutaneous radiofrequency ablation treatment sessions for 100 patients with inoperable lung tumors were collected prospectively. Univariate and multivariate analyses were conducted to identify significant risk factors associated with postprocedural overall morbidity, pleuritic chest pain, hemoptysis, pneumothorax, pleural effusions, and chest drain requirement. RESULTS: There was no postprocedural mortality. The overall morbidity rate was 43% (n = 55 of 129). The most common adverse effect was pneumothorax, occurring in 32% (n = 41 of 129) of treatment sessions. Other significant complications included pleuritic chest pain (18%, n = 23 of 129), hemoptysis (7%, n = 9 of 129), pleural effusions (12%, n = 15 of 129), and chest drain insertion (20%, n = 26 of 129). Both univariate and multivariate analyses identified more than two lesions ablated per session as a significant risk factor for overall morbidity, pneumothorax, and chest drain insertion, but not for pleuritic pain, hemoptysis, and pleural effusions. Length of the ablation probe trajectory greater than 3 cm was an additional independent risk factor for overall morbidity and pneumothorax. Hilar location of lung tumor/s was the only independent risk factor associated with the increased incidence of hemoptysis. CONCLUSIONS: Radiofrequency ablation for lung tumors can be considered as a safe and technically feasible procedure with acceptable incidence of complications.

Extending the limits for curative liver resections by portal vein embolization.

The optimal chance of long-term survival for patients with liver metastasis and large hepatocellular carcinoma is curative liver resections. One of the major limiting factors in performing curative liver resections is the necessity of leaving enough functional parenchyma to avoid postoperative liver failure. The preoperative ipsilateral embolization of the portal vein (PVE) was introduced to produce compensatory hypertrophy of the future liver remnant. In this report, we compare the postoperative hepatic function of patients who had preoperative PVE to those with similar resections who did not have preoperative embolization. Also, for the first time, we report the outcome of those patients who were embolized but did not undergo liver resection because of extrahepatic disease identified at laparotomy.

Evaluation of preoperative computed tomography in estimating peritoneal cancer index in colorectal peritoneal carcinomatosis.

Peritoneal Cancer Index (PCI) has been recognized as an independent prognostic indicator for long-term outcomes. It also influences the likelihood of complete cytoreduction, another principal determinant of long-term survival. The objective of this study was to evaluate the utility of preoperative CT in estimating PCI during the patient selection process. The efficacy of CT in demonstrating peritoneal disease was evaluated by comparing the radiological and intraoperative lesion size and PCI scores using the Wilcoxon signed-rank test. Tumor distribution was assessed in each abdominopelvic region as tumor present versus absent. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated in each abdominopelvic region. Overall, where CT identifies the presence of disease, it portrayed lesion size accurately in 60%, underestimated in 33%, and overestimated in 7% of cases. Analysis of individual abdominopelvic regions demonstrated a statistically significant difference between radiologically and intraoperatively visualized lesion sizes (P < 0.05) except in the epigastrium, left upper, and left flank regions. The sensitivity of CT in detecting peritoneal implants was influenced by lesion size. Small nodules (<0.5 cm) were visualized on CT with only a sensitivity of 11%, which is in contrast to 94% with nodules exceeding 5 cm. Radiological PCI scores significantly underestimated intraoperative PCI (P < 0.001). This study demonstrated that the sensitivity of CT in detecting peritoneal implants was influenced by lesion size and CT PCI significantly underestimated clinical PCI. The role of CT in refining patient selection and improving prognosis remains to be closely evaluated.

Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases.

BACKGROUND: There are limited effective treatment options available and a poor 5-year survival for patients with inoperable neuroendocrine liver metastases (NETLMs). In this study, the authors prospectively assessed the safety and efficacy of treatment with yttrium 90 ((90)Y) radioactive microspheres for patients with unresectable NETLMs. METHODS: Radioactive (90)Y resin microspheres (selective internal radiation [SIR-Spheres]) were administered through a temporarily placed percutaneous hepatic artery catheter concomitantly with a 7-day systemic infusion of 5-fluorouracil to patients with progressive, unresectable NETLMs. Patients were monitored prospectively, and the response to treatment was measured by using cancer markers and tumor size on computed tomography imaging studies. RESULTS: Thirty-four patients (22 men) with a mean age 61 years (range, 32-79 years) who had unresectable NETLMs were treated between December 2003 and December 2005. The mean (+/-standard error) follow-up was 35.2 +/- 3.2 months. The site of the primary neuroendocrine tumor was the bronchus in 1 patient, the medullary thyroid in 2 patients, gastrointestinal in 15 patients, the pancreas in 8 patients, and of unknown origin in 8 patients. The tumors were classified as vipoma (1 tumor), somatostatinoma (1 tumor), glucagonoma (2 tumors), large cell (3 tumors), carcinoid (25 tumors), and of unknown origin (2 tumors). Complications after (90)Y radioembolization included abdominal pain, which was mild to severe; nausea and fever; and lethargy that lasted from 1 week to 1 month. Two patients developed biopsy-proven radiation gastritis, 1 patient developed a duodenal ulcer, and there was 1 early death from liver dysfunction and pneumonia. Subjective changes from recorded baseline hormone symptoms were reported every 3 months. Symptomatic responses were observed in 18 of 33 patients (55%) at 3 months and in 16 of 32 patients (50%) at 6 months. Radiologic liver responses were observed in 50% of patients and included 6 (18%) complete responses and 11 (32%) partial responses, and the mean overall survival was 29.4 +/- 3.4 months). In patients who had evaluable chromogranin A (CgA) marker levels, there was a fall in CgA marker levels after (90)Y radioembolization in 19 patients (26%) at 1 month, in 19 patients (41%) at 3 months, in 15 patients (43%) at 6 months, in 11 patients (42%) at 12 months, in 8 patients (38%) at 24 months, and in 3 patients (46%) at 30 months. CONCLUSIONS: In this open study of 34 patients, the results demonstrated that radioembolization with (90)Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs.

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.