Midterm outcomes in patients with intermediate‐sized hepatocellular carcinoma

BACKGROUND:

To improve the efficacy of radiofrequency ablation (RFA) for the treatment of intermediate‐sized hepatocellular carcinomas (HCCs), the authors compared RFA combined with transcatheter arterial chemoembolization (TACE) to RFA alone.

METHODS:

The authors randomly assigned 37 patients with solitary HCCs (diameter, 3.1‐5.0 cm in the greatest dimension) to 2 groups: the TACE‐RFA group, in which the patients received TACE followed by RFA on the same day, and the RFA group, in which the patients received only RFA.

RESULTS:

Technical success was achieved after 1.4 ± 0.5 RFA sessions in the RFA group and after 1.1 ± 0.2 RFA sessions in the TACE‐RFA group (P < .01). The mean diameters of the longer and shorter axes of the RFA‐induced ablated areas were 50 ± 8.0 mm and 41 ± 7.1 mm, respectively, in the RFA group and 58 ± 13.2 mm and 50 ± 11.3 mm, respectively, in the TACE‐RFA group; the mean diameters of the shorter axes were significantly different (P = .012). The rates of local tumor progression at the end of the third year in the RFA and TACE‐RFA groups were 39% and 6%, respectively (P = .012). The 3‐year survival rates of the patients in the RFA and TACE‐RFA groups were 80% and 93%, respectively (P = .369).

CONCLUSIONS:

In patients with intermediate‐sized HCCs, RFA combined with TACE is more effective than RFA alone for extending the ablated area in fewer treatment sessions and for decreasing the local tumor progression rate. Cancer 2010. © 2010 American Cancer Society.     

Durable oncologic outcomes after radiofrequency ablation

BACKGROUND:

Long‐term oncologic outcomes for renal thermal ablation are limited. The authors of this report present their experience with radiofrequency ablation (RFA) therapy for 243 small renal masses (SRMs) over the past 7.5 years.

METHODS:

The authors' institutional, prospectively maintained RFA database was reviewed to determine intermediate and long‐term oncologic outcomes for patients with SRMs (generally <4 cm) who underwent RFA. Particular attention was placed on patients who had a minimum 3 years of follow‐up. Patients were excluded from the analysis if they had received previous treatment for renal cell carcinoma (RCC) on the ipsilateral kidney or if they did not have at least 1 imaging study available for follow‐up.

RESULTS:

Two hundred eight patients (with 243 SRMs) who had no evidence of previous ipsilateral renal cancer treatment underwent RFA and had follow‐up imaging studies available for review. Overall, tumor size averaged 2.4 cm, and follow‐up ranged from 1.5 months to 90 months (mean, 27 months). Of the 227 tumors (93%) that underwent preablation biopsy, RCC was confirmed in 79%. The initial treatment success rate was 97%, and the overall 5‐year recurrence‐free survival rate was 93% (90% for 160 patients who had biopsy‐proven RCC). During follow‐up, 3 patients developed metastatic disease, and 1 patient died of RCC, yielding 5‐year actuarial metastasis‐free and cancer‐specific survival rates of 95% and 99%, respectively.

CONCLUSIONS:

RFA provided successful treatment of SRMs and produced a low rate of recurrence as well as prolonged metastasis‐free and cancer‐specific survival rates at 5 years after treatment. Although longer term follow‐up of RFA will be required to determine late recurrence rates, the current results indicated a minimal risk of disease recurrence in patients who are >3 years removed from RFA. Cancer 2010. © 2010 American Cancer Society.     

Percutaneous radiofrequency ablation of painful osseous metastases

BACKGROUND:

The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease.

METHODS:

The single‐arm prospective trial included patients with a single painful bone metastasis with unremitting pain with a score >50 on a pain scale of 0‐100. Percutaneous computed tomography‐guided RFA of the bone metastasis to temperatures >60°C was performed. Endpoints were the toxicity and pain effects of RFA before and at 2 weeks, 1 month, and 3 months after RFA.

RESULTS:

Fifty‐five patients completed RFA. Grade 3 toxicities occurred in 3 of 55 (5%) patients. RFA reduced pain at 1 and 3 months for all pain assessment measures. The average increase in pain relief from pre‐RFA to 1‐month follow‐up is 26.3 (95% confidence interval [CI], 17.7‐34.9; P < .0001), and the increase from pre‐RFA to 3‐month follow‐up is 16.38 (95% CI, 3.4‐29.4; P = .02). The average decrease in pain intensity from pre‐RFA to 1‐month follow‐up was 26.9 (P < .0001) and 14.2 for 3‐month follow‐up (P = .02). The odds of lower pain severity at 1‐month follow‐up were 14.0 (95% CI, 2.3‐25.7; P < .0001) times higher than at pre‐RFA, and the odds at 3‐month follow‐up were 8.0 (95% CI, 0.9‐15.2; P < .001) times higher than at pre‐RFA. The average increase in mood from pre‐RFA to 1‐month follow‐up was 19.9 (P < .0001) and 14.9 to 3‐month follow‐up (P = .005).

CONCLUSIONS:

This cooperative group trial strongly suggests that RFA can safely palliate pain from bone metastases. Cancer 2010. © 2010 American Cancer Society     

Lung radiofrequency ablation in patients with pulmonary metastases from musculoskeletal sarcomas

BACKGROUND:

The authors retrospectively evaluated the impact of lung radiofrequency (RF) ablation on survival in patients with lung metastases from musculoskeletal sarcomas.

METHODS:

Lung RF ablation was done under the real‐time computed tomography (CT) fluoroscopy. Safety, local tumor progression, and survival were evaluated in 2 institutions.

RESULTS:

Lung RF ablation was performed in 20 consecutive patients. The mean maximum tumor diameter was 14 ± 9 mm (range, 5‐40 mm) and the mean tumor number 7 ± 6 (range, 1‐18) per patient. Pneumothorax requiring chest tube placement developed in 24 of 63 RF sessions (38%). During the mean follow‐up period of 18 months (range, 7 months to 54 months), 9 of 20 patients died of lung tumor progression. The 1‐ and 3‐year survival rates from RF ablation were 58% (95% confidence interval [CI], 33.3‐82.6%) and 29% (95% CI, 0‐59.9%) with a median survival time of 12.9 months in all patients. Ablation of all lung tumors was the only significantly better prognostic factors in both the univariate analysis and the multivariate analyses. The 1‐ and 3‐year survival rates were 88.9% (95% CI, 69.3%‐100%) and 59.2% (95% CI, 10.2%‐100%) in 11 patients with complete tumor ablation.

CONCLUSIONS:

Lung RF ablation is a safe and useful therapeutic option for selected patients. (R#1) Prognostic factors identified in our study will help to stratify those patients who may benefit from lung RF ablation. Cancer 2009. © 2009 American Cancer Society.     

Chemoembolization of colorectal liver metastases with cisplatin,doxorubicin, mitomycin C,ethiodol, and polyvinyl alcohol

BACKGROUND:

Unresectable colorectal liver metastases have a 1‐ and 2‐year survival of 55% and 33% with current systemic therapies. The authors evaluated response and survival after transarterial chemoembolization.

METHODS:

Chemoembolization with cisplatin, doxorubicin, mitomycin C, ethiodized oil, and polyvinyl alcohol particles was performed at monthly intervals for 1 to 4 sessions. Cross‐sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle was performed for intrahepatic recurrence. Toxicity was assessed using National Cancer Institute's Common Toxicity Criteria version 3.0. Response was evaluated using Response Evaluation Criteria in Solid Tumors criteria. Progression and survival were estimated with Kaplan‐Meier analysis.

RESULTS:

A total of 245 treatments were performed over 141 cycles on 121 patients. Ninety‐five of 141 treatment cycles were evaluable for response: 2 (2%) partial response, 39 (41%) stable disease, and 54 (57%) progression. Median time to disease progression (TTP) in the treated liver was 5 months, and median TTP anywhere was 3 months. Median survival was 33 months from diagnosis of the primary colon cancer, 27 months from development of liver metastases, and 9 months from chemoembolization. Survival was significantly better when chemoembolization was performed after first‐ or second‐line systemic therapy (11‐12 months) than after third‐ to fifth‐line therapies (6 months) (P = .03). Presence of extrahepatic metastases did not adversely affect survival (P = .48).

CONCLUSIONS:

Chemoembolization provided local disease control of hepatic metastases after 43% of treatment cycles. Median survival was 27 months overall, and 11 months when initiated for salvage after failure of second‐line systemic therapy. Cancer 2011. © 2010 American Cancer Society.     

Transcatheter arterial chemoembolization plus radiofrequency ablation therapy for early stage hepatocellular carcinoma

BACKGROUND:

Radiofrequency ablation (RFA) is becoming a well‐known local therapy for hepatocellular carcinoma (HCC). Transcatheter arterial chemoembolization (TACE) is expected to enhance the effects of subsequent RFA by reducing arterial blood flow. However, the long‐term efficacy of this combined therapy has not been elucidated. In this study, the survival rates of patients who received TACE combined with RFA (TACE + RFA) were compared with those of patients treated surgically.

METHODS:

The study included consecutive patients who received TACE + RFA or surgical resection as the initial curative treatment for HCC between 2000 and 2005 at Tokai University Hospital. Inclusion criteria were a single HCC ≤50 mm or up to 3 HCCs ≤30 mm, presence of cirrhosis classified as Child‐Pugh class A, no vascular invasion, and no extrahepatic metastasis.

RESULTS:

Sixty‐two patients (23 women, 39 men; aged 67.5 ± 8.4 years [mean ± standard deviation]) received TACE + RFA, and 55 patients (15 women, 40 men; aged 66.1 ± 8.4 years) underwent surgical resection. Median follow‐up periods were similar (50 months in the TACE + RFA group vs 49 months in the resection group). The probabilities of overall survival at 1, 3, and 5 years in the TACE + RFA group (100%, 94.8%, and 64.6%, respectively) were similar (P = .788) to those in the resection group (92.5%, 82.7%, and 76.9%, respectively). Two major RFA‐related complications were observed (1.5%).

CONCLUSIONS:

RFA combined with TACE is an efficient and safe treatment that provides overall survival rates similar to those achieved with surgical resection. Cancer 2010. © 2010 American Cancer Society.     

A phase 1/pilot study of radiofrequency ablation for the treatment of recurrent pediatric solid tumors

BACKGROUND:

This prospective study was designed to be the first to evaluate the toxicity of radiofrequency ablation (RFA) in patients with recurrent pediatric solid tumors.

METHODS:

From 2003 through 2008, a phase 1/pilot study of RFA for recurrent pediatric solid tumors was conducted. A multidisciplinary cancer management team selected appropriate candidates for the study. Imaging‐guided RFA was performed percutaneously. Repeat RFA was performed for recurrences when appropriate. Toxicity and imaging response was assessed at 1 month and 3 months prospectively. Accrual stopped in 2006, and data collection stopped in 2008.

RESULTS:

Sixteen patients (ages 4 years‐33 years; median age, 15 years) and 56 tumor sites were treated in 37 RFA sessions including 38 pulmonary, 11 musculoskeletal, and 7 hepatic lesions (82 lesion‐treatments). Postprocedural pain was moderate (median 5 on a scale from 1 to 10) and lasted a median of 9 days. Prolonged hospitalization (beyond 1 day) occurred 17 times (range, 2 days‐25 days; median, 3 days). Hypoxia supported by supplemental oxygen occurred in 8 of 16 patients and resolved within 1 month after each RFA. No patient had tumor lysis syndrome but myoglobinuria/hemoglobinuria occurred in 6 of 16 patients, all without renal damage. Serious complications from pulmonary RFA included 2 diaphragmatic hernias. Of 82 lesions imaged, 24 (29%) remained ablated at the end of the study.

CONCLUSIONS:

The toxicity from RFA of recurrent pediatric solid tumors was real but limited, and RFA may offer a local tumor control alternative in carefully selected cases. Cancer 2009. © 2009 American Cancer Society.     

Cryoablation or radiofrequency ablation of the small renal mass : a meta-analysis

BACKGROUND.

The incidence of renal cell carcinoma is rising because of incidental detection of small renal masses (SRMs). Although surgical resection remains the standard of care, cryoablation and radiofrequency ablation (RFA) have emerged as minimally invasive treatment alternatives. The authors of this report performed a comparative meta‐analysis evaluating cryoablation and RFA as primary treatment for SRMs.

METHODS.

A search of the MEDLINE database was performed reviewing the world literature for clinically localized renal masses treated by cryoablation or RFA.

RESULTS.

Forty‐seven studies representing 1375 kidney lesions treated by cryoablation or RFA were analyzed. No differences were detected between ablation modalities with regard to mean patient age (P = .17), tumor size (P = .12), or duration of follow‐up (P = .53). Pretreatment biopsy was performed more often for cryoablated lesions (82.3%) than for RFA (62.2%; P < .0001). Unknown pathology occurred at a significantly higher rate for SRMs that underwent RFA (40.4%) versus cryoablation (24.5%; P < .0001). Repeat ablation was performed more often after RFA (8.5% vs 1.3%; P < .0001), and the rates of local tumor progression were significantly higher for RFA (12.9% vs 5.2%; P < .0001) compared with cryoablation. The higher incidence of local tumor progression was found to be correlated significantly with treatment by RFA on univariate analysis (P = .001) and on multivariate regression analysis (P = .003). Metastasis was reported less frequently for cryoablation (1.0%) versus RFA (2.5%; P = .06). Cryoablation usually was performed laparoscopically (65%), whereas 94% of lesions that were treated with RFA were approached percutaneously.

CONCLUSIONS.

Ablation of SRMs is a viable strategy based on short‐term oncologic outcomes. Although extended oncologic efficacy remains to be established for ablation modalities, the current data suggest that cryoablation results in fewer retreatments and improved local tumor control, and it may be associated with a lower risk of metastatic progression compared with RFA. Cancer 2008. © 2008 American Cancer Society.     

Results of liver resection in combination with radiofrequency ablation for hepatic malignancies

Introduction

Liver tumors should be surgically treated whenever possible. In the case of bilobar disease or coexisting liver cirrhosis, surgical options are limited. Radiofrequency ablation (RFA) has been successfully used for irresectable liver tumors. The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with liver metastases and hepatocellular carcinoma (HCC).

Patients and methods

RFA was performed with two different monopolar devices using ultrasound guidance. Intraoperative use of RFA for the treatment of liver metastases or HCC was limited to otherwise irresectable tumors during open surgical procedures including hepatic resections. Irresectability was considered if bilobar disease was treated, the functional hepatic reserve was impaired or appraised marginal for allowing further resection.

Results

Ten patients with both liver metastases and HCC, and two patients with cholangiocellular carcinoma were treated. Complete initial tumor clearance was achieved in all patients. Two patients of the metastases group and five patients of the HCC group suffered from local recurrence after a median of 12 months (1–26) (local recurrence rate 32%). Five patients of the metastases group and six patients of the HCC group developed recurrent tumors in different areas of the ablation site after a median time of 4 months (2–18) (distant intrahepatic recurrence in 55%). Survival at 31 months was 36%.

Conclusion

RFA extends the scope of surgery in some candidates with intraoperatively found irresectability.     

CT-guided percutaneous microwave ablation of adrenal malignant carcinoma: preliminary results

BACKGROUND:

Microwave ablation has recently been developed as a safe and effective treatment for a variety of tumors. The authors evaluated the safety and efficacy of computed tomography (CT)‐guided percutaneous microwave ablation of adrenal malignant tumors.

METHODS:

Nine patients between 41 and 83 years of age (average age, 54 years) with adrenal carcinoma (a total of 10 lesions) received CT‐guided percutaneous water‐cooled microwave ablation. The 9 cases included 1 primary adrenocortical carcinoma and 8 metastatic carcinomas (4 from lung cancer, 2 from hepatocellular carcinoma, 1 from intrahepatic cholangiocarcinoma, and 1 from left tibial osteosarcoma). Of the 8 metastatic cases, 7 were unilateral, and 1 was bilateral. All cases were pathologically confirmed by aspiration biopsy or postsurgical biopsy. The tumor diameters ranged from 2.1 cm to 6.1 cm (average, 3.8 cm). The average number of ablation sites was 1.5 sites (1‐3 sites), and the average accumulated ablation time was 7.7 minutes (4‐15 minutes). The procedures were performed using a cooled‐shaft antenna.

RESULTS:

The patients were followed for 3‐37 months, with an average of 11.3 months. Nine of 10 lesions were completely necrotized after first treatment. The other lesion was completely necrotized after 2 treatments. One of the patients experienced hypertensive crisis during treatment. No patient experienced recurrent tumor at the treated site, and this lack of recurrence indicated effective local control. All patients had progression of metastatic disease at extra‐adrenal sites.

CONCLUSIONS:

CT‐guided percutaneous water‐cooled microwave ablation is a minimally invasive and effective method for the treatment of adrenal carcinoma. Cancer 2011;. © 2011 American Cancer Society.     

Percutaneous CT-guided radiofrequency ablation for patients with extrahepatic oligometastases of hepatocellular carcinoma: long-term results

Background: The aim of this study was to evaluate the therapeutic outcome of percutaneous computed tomography (CT)-guided radiofrequency ablation (RFA) for extrahepatic oligometastases of hepatocellular carcinoma (HCC).

Methods: Institutional review board approval was obtained for this retrospective study, and all patients provided written informed consent. Between April 2004 and December 2015, 116 oligometastases (diameter, 5–50?mm; 20.3?±?10.4) in 79 consecutive HCC patients (73 men and 6 women; average age, 50.3?years ±13.0) were treated with RFA. We focussed on patients with 1–3 extrahepatic metastases (EHM) confined to 1–2 organs (including the lung, adrenal gland, bone, lymph node and pleura/peritoneum) who were treated naïve with curative intent. Survival, technical success and safety were evaluated. The log-rank test and Cox proportional hazards regression models were used to analyse the survival data.

Results: No immediate technical failure occurred, and at 1 month, the technique effectiveness rate was determined to be 95.8%. After a median follow-up time of 28.0 months (range, 6–108 months), the 1-, 2- and 3-year overall survival (OS) rates were 91, 70 and 48%, respectively, with a median survival time of 33.5 months. Time to unoligometastatic progression (TTUP) of less than 6 months (p?p?=?0.001) were significant indicators of shorter OS. The 1-, 2- and 3-year disease free survival (DFS) rates were 34, 21 and 8%, respectively, with a median DFS time of 6.8 months. DFS was better for those with lung metastases (p?=?0.006). Major complication occurred in nine (9.5%, 9/95) RFA sessions without treatment-related mortality.

Conclusions: CT-guided RFA for oligometastatic HCC may provide favourable efficacy and technical success with a minimally invasive approach.     

Percutaneous CT-guided radiofrequency ablation for unresectable hepatocellular carcinoma pulmonary metastases

Purpose: This study aimed to evaluate the safety and efficacy of percutaneous CT-guided radiofrequency ablation (RFA) for unresectable hepatocellular carcinoma pulmonary metastases (HCCPM) and to identify the prognostic factors for survival.

Materials and methods: We reviewed the medical records of 320 patients with HCCPM treated between January 2005 and January 2012. Among them, 29 patients with 68 lesions of unresectable HCCPM underwent 56 RFA sessions. Safety, local efficacy, survival and prognostic factors were evaluated. Survival was analysed using the Kaplan-Meier method. Univariate analyses were evaluated by the log-rank test.

Results: Pneumothorax requiring chest tube placement occurred in five (8.9%, 5/56) RFA sessions. During the median follow-up period of 23 months (range 6–70), 18 patients (62.1%, 18/29) died of tumour progression and 11 (37.9%, 11/29) were alive. The 1-, 2- and 3-year overall survival rates were 73.4%, 41.1% and 30%, respectively. The median progression-free survival was 18 months (95% confidence interval (CI) 9.8–26.2) and the median overall survival time was 21 months (95%CI, 9.7–32.3). The maximum tumour diameter ≤3?cm (p?=?0.002), the number of pulmonary metastases ≤3 (p?=?0.014), serum AFP level ≤400?ng/mL (p?=?0.003), and the controlled status of intrahepatic tumour after lung RFA (p?=?0.001) were favourable prognostic factors for overall survival.

Conclusions: Our study indicates that percutaneous CT-guided RFA, as an alternative treatment procedure to pulmonary metastasectomy, can be a safe and effective therapeutic option for unresectable HCCPM.     

Proliferative rate in endoscopic ultrasound fine‐needle aspiration of pancreatic endocrine tumors

BACKGROUND:

The objectives of this study were to evaluate the role of endoscopic ultrasonography (EUS)‐guided fine‐needle aspiration (FNA) in the preoperative diagnosis of pancreatic endocrine tumors (PETs) and to investigate whether the Ki‐67 index determined on cytologic material could help predict their behavior.

METHODS:

The study included 10 men and 5 women (ratio of men to women, 2:1) with a mean age of 62.4 years (range, 40‐79 years). Diff‐Quik‐ and Papanicolaou‐stained FNA samples were analyzed retrospectively, and immunocytochemical stains were performed for chromogranin A, synaptophysin, vimentin, α‐1‐antitrypsin, and Ki‐67 on cell block sections. The Ki‐67 index was evaluated by using digital image‐analysis software and was correlated with follow‐up (mean, 21.5 months; range, 2‐43 months).

RESULTS:

The overall survival was rate 86.7% (13 of 15 patients). Seven of 15 patients (46.7%) patients developed lymph node and/or hematogenous metastases. The Ki‐67 index in PETs with no metastases was lower (mean, 6.3%; range, 2%‐13%) than in clinically aggressive (metastatic) tumors (mean, 7.7%; range, 3%‐27%; P = .03). None of the tumors that had a Ki‐67 index ≤2% were metastatic. Both patients who died of disease had a Ki‐67 index of 4%.

CONCLUSIONS:

Although tumors with metastatic potential tended to exhibit a slightly higher Ki‐67 index, there was a significant overlap with nonmetastatic tumors, and PETs that had a very low proliferative rate still could behave aggressively; therefore, the authors concluded that the Ki‐67 index does not predict the risk of disease progression in patients with PETs. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Pulmonary metastases in patients with recurrent, treatment-resistant meningioma: prognosis and identification by ¹¹¹Indium-octreotide imaging

BACKGROUND:

Meningioma is the most common extra‐axial primary intracranial tumor in adults that rarely metastasizes outside of the central nervous system (CNS). Among recognized sites of metastases, the lung is the most common, but the importance of lung metastases relative to prognosis is unknown. ¹¹¹Indium (¹¹¹In)‐octreotide scintigraphy (octreotide scanning) is a valuable imaging modality with which to evaluate intracranial meningiomas and their response to treatment with somatostatin analogues and has the potential to identify extracranial metastatic disease.

METHODS:

In this retrospective multicenter study, adult patients treated for recurrent meningioma were identified. These patients underwent ¹¹¹In‐octreotide positron emission tomography/computed tomography imaging (octreotide scintigraphy) and were found to have positive octreotide uptake in their lungs.

RESULTS:

Six cases were identified with recurrent meningioma (after surgery, radiotherapy, and at least 1 chemotherapy agent) and pulmonary lesions by octreotide scintigraphy. Biopsy of a pulmonary lesion in 1 patient confirmed the diagnosis of metastatic meningioma. Patients with metastatic pulmonary involvement identified by ¹¹¹In‐octreotide scintigraphy in this case series had an overall survival of 6 months, which is less than that reported from previously published series of patients with unknown systemic disease status.

CONCLUSIONS:

¹¹¹In‐octreotide scintigraphy is useful for assessing both CNS disease and extracranial metastases. The presence of pulmonary metastases appears to negatively affect survival in patients with recurrent meningioma. The usefulness of ¹¹¹In‐octreotide scintigraphy should be considered in staging patients with recurrent meningioma who are considered for further treatment. A prospective study to confirm this finding is warranted. Cancer 2011;. Published 2011 by the American Cancer Society.     

Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas

BACKGROUND:

The authors report on the local control and toxicity of stereotactic body radiotherapy (SBRT) for patients with unresectable pancreatic adenocarcinoma.

METHODS:

Seventy‐seven patients with unresectable adenocarcinoma of the pancreas received 25 gray (Gy) in 1 fraction. Forty‐five patients (58%) had locally advanced disease, 11 patients (14%) had medically inoperable disease, 15 patients (19%) had metastatic disease, and 6 patients (8%) had locally recurrent disease. Nine patients (12%) had received prior chemoradiotherapy. Sixteen patients (21%) received between 45 to 54 Gy of fractionated radiotherapy and SBRT. Various gemcitabine‐based chemotherapy regimens were received by 74 patients (96%), but 3 patients (4%) did not receive chemotherapy until they had distant failure.

RESULTS:

The median follow‐up was 6 months (range, 3‐31 months) and, among surviving patients, it was 12 months (range, 3‐31 months). The overall rates of freedom from local progression (FFLP) at 6 months and 12 months were 91% and 84%, respectively. The 6‐ and 12‐month isolated local recurrence rates were 5% and 5%, respectively. There was no difference in the 12‐month FFLP rate based on tumor location (head/uncinate, 91% vs body/tail, 86%; P = .52). The progression‐free survival (PFS) rates at 6 months and 12 months were 26% and 9%, respectively. The PFS rate at 6 months was superior for patients who had nonmetastatic disease versus patients who had metastatic disease (28% vs 15%; P = .05). The overall survival (OS) rates at 6 months and 12 months from SBRT were 56% and 21%, respectively. Four patients (5%) experienced grade ≥2 acute toxicity. Three patients (4%) experienced grade 2 late toxicity, and 7 patients (9%) experienced grade ≥3 late toxicity. At 6 months and 12 months, the rates of grade ≥2 late toxicity were 11% and 25%, respectively.

CONCLUSIONS:

SBRT for pancreatic adenocarcinoma was effective for local control with associated risk of toxicity and should be used with rigorous attention to quality assurance. Efforts to reduce complications are warranted. Distant metastases account for the vast majority of disease‐related mortality. Cancer 2009. © 2008 American Cancer Society.     

A phase 2 study of estramustine,docetaxel, and bevacizumab in men with castrate‐resistant prostate cancer

BACKGROUND:

The use of docetaxel prolongs survival for patients with castrate‐resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the antitumor effect of docetaxel and estramustine in patients with CRPC.

METHODS:

This cooperative group trial enrolled men with CRPC. Patients received oral estramustine 280 mg 3 times daily on Days 1 through 5 of every cycle plus 70 mg/m² docetaxel and 15 mg/kg bevacizumab on Day 2 every 3 weeks. Prostate‐specific antigen (PSA) values were monitored every cycle, and imaging studies were obtained every 3 cycles. The primary endpoint was progression‐free survival (PFS), and the secondary objectives were safety, PSA decline, measurable disease response, and overall survival.

RESULTS:

Seventy‐nine patients were enrolled; and 77 patients received a median of 8 cycles and were evaluable. A 50% PSA decline was observed in 58 patients (75%). Twenty‐three of 39 patients with measurable disease had a partial response (59%). The median PFS was 8 months, and the overall median survival was 24 months. Neutropenia without fever (69%), fatigue (25%), and thrombosis/emboli (9%) were the most common severe toxicities. Twenty‐four of 77 patients were removed from protocol treatment because of disease progression, 35 of 77 patients were removed because of a physician or patient decision, and 15 patients were removed secondary to toxicity.

CONCLUSIONS:

The combination of docetaxel, estramustine, and bevacizumab was tolerable but complicated by toxicity. Although the endpoint of PFS did not meet the desired level, encouraging antitumor activity and overall survival were observed. Further phase 3 evaluation of the role of bevacizumab in CRPC is ongoing. Cancer 2011. © 2010 American Cancer Society.     

Treatment of Pulmonary Colorectal Metastases by Radiofrequency Ablation

BackgroundRadiofrequency ablation has emerged as a potential, lung function-preserving treatment of colorectal lung metastases.Patients and MethodsForty-five patients with colorectal pulmonary metastases underwent computed tomography-guided RFA from December 2004 to June 2010. A baseline posttreatment scan was obtained 4-6 weeks after RFA and follow-up imaging studies every 3 months thereafter were obtained and compared to evaluate the tumor progression at site of ablation or elsewhere. The primary end points were LTP-free survival and overall survival from RFA procedure. The Kaplan–Meier method was used to analyze the end points. A Cox proportional hazard model with robust inference was used to estimate the associations between baseline factors and survival end points.ResultsSixty-nine metastases were ablated in 45 patients. Tumor size ranged from 0.4 to 3.5 cm. The median number of metastases ablated per patient was 1 (range, 1-3). Median follow-up after RFA was 18 months. Median survival from the time of RFA was 46 months (95% confidence interval [CI], 27.8-47.3). One-, 2- and 3-year overall survival rates from the time of RFA were 95% (95% CI, 82%-99%), 72% (95% CI, 52%-85%), and 50% (95% CI, 26%-71%), respectively. Nine of 69 lesions (13%) progressed and 4 were retreated with no progression after second RFA. Median time to progression was not reached. LTP-free survival from RFA was 92% (95% CI, 82%-97%) at 1 year, 77% (95% CI, 58%-88%) at 2 years, and 77% (95% CI, 58%-88%) at 3 years.ConclusionRadiofrequency ablation of lung metastases is an effective minimally invasive, parenchymal-sparing technique that has very good local control rates in patients with pulmonary metastases from colorectal cancer, with LTP-free survival of 77% at 3 years.     

Phase 2 trial of irinotecan and thalidomide in adults with recurrent anaplastic glioma

BACKGROUND:

Therapeutic options for patients with anaplastic gliomas (AGs) are limited despite better insights into glioma biology. The authors previously reported improved outcome in patients with recurrent glioblastoma treated with thalidomide and irinotecan compared with historical controls. Here, results of the AG arm of the study are reported, using this drug combination.

METHODS:

Adults with recurrent AG previously treated with radiation therapy, with Karnofsky performance score ≥70, adequate organ function and not on enzyme‐inducing anticonvulsants were enrolled. Treatment was in 6‐week cycles with irinotecan at 125 mg/m² weekly for 4 weeks followed by 2 weeks off, and thalidomide at 100 mg daily increased to 400 mg/day as tolerated. The primary endpoint was progression‐free survival rate at 6 months (PFS‐6), and the secondary endpoints were overall survival (OS) and response rate (RR).

RESULTS:

In 39 eligible patients, PFS‐6 for the intent‐to‐treat population was 36% (95% confidence interval [CI] = 21%, 53%), median PFS was 13 weeks (95% CI = 6%, 28%) and RR was 10%(95% CI = 3%, 24%). Radiological findings included 2 complete and 2 partial responses and 17 stable disease. Median OS from study registration was 62 weeks, (95% CI = 51, 144). Treatment‐related toxicities (grade 3 or higher) included neutropenia, diarrhea, nausea, and fatigue; 6 patients experienced venous thromboembolism. Four deaths were attributable to treatment‐related toxicities: 1 from pulmonary embolism, 2 from colitis, and 1 from urosepsis.

CONCLUSIONS:

The combination of thalidomide and irinotecan did not achieve sufficient efficacy to warrant further investigation against AG, although a subset of patients experienced prolonged PFS/OS. A trial of the more potent thalidomide analogue, lenalidomide, in combination with irinotecan against AG is currently ongoing. Cancer 2012;3599–3606. © 2011 American Cancer Society.     

Progression-free survival as a predictor of overall survival in metastatic renal cell carcinoma treated with contemporary targeted therapy

BACKGROUND.

The majority of metastatic renal cell carcinoma (mRCC) clinical trials that examined targeted agents used progression‐free survival (PFS) as the primary endpoint. Whether PFS can be used as a predictor of overall survival (OS) is unknown.

METHODS.

Patients from 12 cancer centers who received targeted therapy for mRCC were identified. Landmark analyses for progression at 3 months and 6 months after drug initiation were performed to minimize lead‐time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS.

RESULTS.

In total, 1158 patients were included. The median follow‐up was 30.6 months, the median age was 60 years, and the median Karnofsky performance status was 80%. For the entire cohort, the median PFS was 7.6 months, and the median OS was 19.7 months. In the landmark analysis, the median OS for patients who progressed at 3 months was 7.8 months compared with 23.6 months for patients who did not progress (log‐rank test; P < .0001). Similarly, for patients who progressed at 6 months, the median OS was 8.6 months compared with 26 months for patients who did not progress (P < .0001). Compared with those who did not progress, for the patients who progressed at 3 months and at 6 months, the hazard ratios for death adjusted for adverse prognostic factors were 3.05 (95% confidence interval, 2.42‐3.84) and 2.96 (95% confidence interval, 2.39‐3.67), respectively. Similar results were demonstrated with landmark analyses at 9 months and at 12 months and in the bootstrap validation. Kendall tau rank correlation and a Fleischer model demonstrated a statistically significant dependent correlation.

CONCLUSIONS.

PFS at 3 months and at 6 months predicted OS, and the current results indicated that PFS may be a meaningful intermediate endpoint for OS in patients with mRCC who receive treatment with novel agents. Cancer 2011;. © 2010 American Cancer Society.     

Sarcoma metastases to the skin: a clinicopathologic study of 65 patients

BACKGROUND:

Sarcoma metastases to the skin are relatively rare, because most involve the lung, liver, or deep soft tissues. The authors of this report examined the distribution and clinical significance of cutaneous and superficial subcutaneous sarcoma metastases.

METHODS:

Sixty‐five patients with histologically confirmed dermal and superficial subcutaneous sarcoma metastases were identified in pathology files from more than 25,000 patients with sarcoma who were evaluated at The University of Texas M. D. Anderson Cancer Center from 1989 to 2009. Pathology slides and clinical and radiological information were evaluated.

RESULTS:

Cutaneous metastases were documented histologically in <0.25% of patients. The mean patient age was 49 years (range, 16‐79 years), and there was an equivalent ratio of men to women. The most common source of metastasis was leiomyosarcoma (28 of 65 patients; 43%). The most common region of first skin metastasis was head and neck (33 patients; 51%), and the scalp predominated (25 patients; 38%). The mean time from primary tumor diagnosis to skin metastasis was 48 months (range, 0‐166 months). Fifty‐three patients (81%) had multiple metastases (skin and other). Among the patients who had complete clinical information available, 31 patients (62%) had other metastases diagnosed before skin involvement, 17 patients (34%) had skin metastases diagnosed first, and 2 patients (4%) had simultaneous presentation. The following clinical outcomes were documented: Twenty‐nine patients (45%) died of disease, 24 patients (37%) remained alive with disease, and 12 patients were lost to follow‐up. The mean time to death was 80 months (range, 9‐224 months) after primary diagnosis, 45 months (range, 5‐94 months) after the first metastasis to any site, and 27 months (range, 5‐65 months) after the first skin metastasis.

CONCLUSIONS:

Sarcoma metastases to the skin are rare. In this large study, leiomyosarcoma was the most common source, and the scalp was the most frequent site. The majority of patient with skin metastases harbored metastases elsewhere. However, skin was the initial site of metastasis in approximately 1 in 3 patients. Thus, clinical correlation is needed before establishing a diagnosis of primary cutaneous sarcoma, particularly leiomyosarcoma of scalp. Finally, the current results indicated that skin metastasis usually is a late event in sarcoma clinical progression and heralds a poor prognosis. Cancer 2011. © 2011 American Cancer Society.