Surgical resection criteria and neoadjuvant therapies for intrahepatic cholangiocarcinoma.

The staging of intrahepatic cholangiocarcinoma (ICC) is complex, and there is no consensus among international cancer groups on how to most appropriately select candidates with nonmetastatic disease for surgical resection. Factors contributing to a higher stage of disease include larger tumor size, multiple tumors, vascular invasion (either portal venous or arterial), biliary invasion, involvement of local hepatic structures, serosal invasion, and regional lymph node metastases. For patients selected to undergo surgery, it is well-documented that R0 resection translates to a survival benefit. Estimating the risk of post-hepatectomy liver failure and post-surgical residual liver function is vital and may preclude some patients with significant tumor burden from undergoing surgery. Numerous serum and biliary biomarkers of the disease can help detect recurrence in patients undergoing surgical resection. Systemic and locoregional neoadjuvant treatments to facilitate better surgical outcomes have yielded mixed results regarding improving resectability and overall survival. Additional research is needed to identify optimal neoadjuvant treatment approaches and to evaluate which patients will benefit most from these strategies. Therapies targeting genetic mutations and protein aberrations found by tumor molecular profiling may offer additional options for future neoadjuvant treatment.

Bridging and downstaging with TACE in early and intermediate stage hepatocellular carcinoma: Predictors of receiving a liver transplant.

Background and Aims: In patients with surgically unresectable early and intermediate stage hepatocellular carcinoma (HCC), only liver transplant (LT) offers a cure. Locoregional therapies, such as transarterial chemoembolization (TACE), are widely used to bridge patients waiting for an LT or downstage tumors beyond Milan Criteria (MC). However, there are no formal guidelines on the number of TACE procedures patients should receive. Our study explores the extent to which repeated TACE might offer diminishing gains toward LT. Approach: We retrospectively analyzed 324 patients with BCLC stage A and B HCC who had received TACE with the intention of disease downstaging or bridging to LT. In addition to baseline demographics, we collected data on LT status, survival, and the number of TACE procedures. Overall survival (OS) rates were estimated using the Kaplan-Meier method, and correlative studies were calculated using chi-square or Fisher's exact test. Results: Out of 324 patients, 126 (39%) received an LT, 32 (25%) of whom had responded favorably to TACE. LT significantly improved OS: HR 0.174 (0.094-0.322, P < .001). However, the LT rate significantly decreased if patients received ≥3 vs < 3 TACE procedures (21.6% vs 48.6%, P < .001). If their cancer was beyond MC after the third TACE, the LT rate was 3.7%. Conclusions: An increased number of TACE procedures may have diminishing returns in preparing patients for LT. Our study suggests that alternatives to LT, such as novel systemic therapies, should be considered for patients whose cancers are beyond MC after three TACE procedures.

Oncologic Interventions: Periprocedural Medications.

Significant advances in ablative and endovascular therapies have allowed interventional radiology to play a substantial role in the management of patients with malignant neoplasms. The evolution of these procedures and the optimization of patient outcomes and experience must take into account various elements of the periprocedural period. Some of the most important considerations within the periprocedural period are the pharmacologic agents used to avoid infectious complications, decrease pain, and manage side effects. In this article, we discuss some of the most commonly used medications in interventional oncology procedures including antibiotics, narcotics, sedatives, antiemetics, and others.

An Unsuccessful Randomized Trial of Percutaneous vs Endoscopic Drainage of Suspected Malignant Hilar Obstruction.

Percutaneous transhepatic biliary drainage (PTBD) and endoscopic retrograde cholangiopancreatography (ERCP) are widely accepted but competing approaches for the management of malignant obstruction at the hilum of the liver. ERCP is favored in the United States on the basis of high success rates for non-hilar indications, the perceived safety and superior tissue sampling capability of ERCP relative to PTBD, and the avoidance of external drains that are undesirable to patients. A recent randomized controlled trial (RCT) comparing the 2 modalities in patients with resectable hilar cholangiocarcinoma was terminated prematurely because of higher mortality in the PTBD group.1 In contrast, most observational data suggest that PTBD is superior for achieving complete drainage.2-6 Because the preferred procedure remains uncertain, we aimed to compare PTBD and ERCP as the primary intervention in patients with cholestasis due to malignant hilar obstruction (MHO).

Safety and Tolerability of Topotecan-Eluting Radiopaque Microspheres for Hepatic Chemoembolization in a Rabbit Preclinical Model.

PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70-150 µm, DC Bead LUMI™, Biocompatibles UK Ltd-Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post-TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076-0.105 mL) and 1.99 mg/kg (1.51-2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within 2 weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m2) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Neutrophil/Lymphocyte Ratio Predicts Increased Risk of Immediate Progressive Disease following Chemoembolization of Hepatocellular Carcinoma.

PURPOSE: To demonstrate that patients with hepatocellular carcinoma (HCC) and elevated baseline neutrophil/lymphocyte ratio (NLR) have a significantly greater risk of progressive disease following initial transarterial chemoembolization. MATERIALS AND METHODS: A total of 190 HCC patients (149 male/41 female) treated with transarterial chemoembolization between July 2013 and July 2017 were reviewed. Mean patient age was 62. Child-Pugh grades were 132 A, 61 B, and 4 C. Tracked criteria included etiology of cirrhosis, tumor number, Barcelona Clinic Liver Cancer score, diameter of the largest 2 tumors, and presence of portal vein thrombosis. Complete blood count with differential before the procedure was used for NLR calculation. Follow-up imaging was performed 2 months after treatment. The modified response evaluation criteria in solid tumors were used to assess response. The association between baseline NLR and tumor response (ordinal modified response evaluation criteria in solid tumors categories) on 2-month follow-up imaging was evaluated using the proportional odds logistic regression model. RESULTS: A total of 194 patients (76.6%) patients had a preprocedural NLR <3.5, and 59 (23%) patients had a preprocedural NLR ≥3.5. There was a statistically significant association between baseline NLR and immediate progression on 2-month follow-up imaging (mean NLR 4.10, 2.76, 2.72, and 2.48 for progressive and stable disease and partial and complete response, respectively; odds ratio 2.1, P = .04). NLR (P = .021) and tumor multiplicity (P = .011) predicted progressive disease at 2-month imaging. CONCLUSIONS: Elevated baseline NLR is associated with higher rates of HCC tumor progression at 2-month follow-up imaging after transarterial chemoembolization.

PET/CT-guided biopsy with respiratory motion correction.

PURPOSE: Given the ability of positron emission tomography (PET) imaging to localize malignancies in heterogeneous tumors and tumors that lack an X-ray computed tomography (CT) correlate, combined PET/CT-guided biopsy may improve the diagnostic yield of biopsies. However, PET and CT images are naturally susceptible to problems due to respiratory motion, leading to imprecise tumor localization and shape distortion. To facilitate PET/CT-guided needle biopsy, we developed and investigated the feasibility of a workflow that allows to bring PET image guidance into interventional CT suite while accounting for respiratory motion. METHODS: The performance of PET/CT respiratory motion correction using registered and summed phases method was evaluated through computer simulations using the mathematical 4D extended cardiac-torso phantom, with motion simulated from real respiratory traces. The performance of PET/CT-guided biopsy procedure was evaluated through operation on a physical anthropomorphic phantom. Vials containing radiolabeled 18F-fluorodeoxyglucose were placed within the physical phantom thorax as biopsy targets. We measured the average distance between target center and the simulated biopsy location among multiple trials to evaluate the biopsy localization accuracy. RESULTS: The computer simulation results showed that the RASP method generated PET images with a significantly reduced noise of 0.10 ± 0.01 standardized uptake value (SUV) as compared to an end-of-expiration image noise of 0.34 ± 0.04 SUV. The respiratory motion increased the apparent liver lesion size from 5.4 ± 1.1 to 35.3 ± 3.0 cc. The RASP algorithm reduced this to 15.7 ± 3.7 cc. The distances between the centroids for the static image lesion and two moving lesions in the liver and lung, when reconstructed with the RASP algorithm, were 0.83 ± 0.72 mm and 0.42 ± 0.72 mm. For the ungated imaging, these values increased to 3.48 ± 1.45 mm and 2.5 ± 0.12 mm, respectively. For the ungated imaging, this increased to 1.99 ± 1.72 mm. In addition, the lesion activity estimation (e.g., SUV) was accurate and constant for images reconstructed using the RASP algorithm, whereas large activity bias and variations (± 50%) were observed for lesions in the ungated images. The physical phantom studies demonstrated a biopsy needle localization error of 2.9 ± 0.9 mm from CT. Combined with the localization errors due to respiration for the PET images from simulations, the overall estimated lesion localization error would be 3.08 mm for PET-guided biopsies images using RASP and 3.64 mm when using ungated PET images. In other words, RASP reduced the localization error by approximately 0.6 mm. The combined error analysis showed that replacing the standard end-of-expiration images with the proposed RASP method in PET/CT-guided biopsy workflow yields comparable lesion localization accuracy and reduced image noise. CONCLUSION: The RASP method can produce PET images with reduced noise, attenuation artifacts and respiratory motion, resulting in more accurate lesion localization. Testing the PET/CT-guided biopsy workflow using computer simulation and physical phantoms with respiratory motion, we demonstrated that guided biopsy procedure with the RASP method can benefit from improved PET image quality due to noise reduction, without compromising the accuracy of lesion localization.

Are prophylactic antibiotics necessary prior to transarterial chemoembolization for hepatocellular carcinoma in patients with native biliary anatomy?

BACKGROUND AND OBJECTIVES: Prophylactic antibiotics are frequently administered for transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). In patients without previous biliary instrumentation, infection risk from TACE is low. We hypothesized that there is a negligible rate of infection in these patients without prophylactic antibiotics. METHODS: We reviewed consecutive patients undergoing TACE between 7/1/2013-6/15/2016. All patients had an intact Sphincter of Oddi, received no peri-procedural antibiotics, and had 30+ days follow-up. Level of arterial selection was recorded. Baseline Child-Pugh (CP) and Barcelona Clinic Liver Cancer (BCLC) scores were recorded. The primary outcome measure was the absence of clinical or imaging findings of hepatic abscess within 30 days. RESULTS: A total of 171 patients underwent 235 TACE procedures. CP scores were A (n = 109), B (n = 47), and C (n = 15). BCLC scores were 0 (n = 1), A (n = 108), B (n = 47), and C (n = 15). TACE was performed segmentally (n = 208) or lobar (n = 27). Three patients died of non-infectious causes before 30 days. No hepatic abscesses developed in evaluable patients: 0/232 infusions. CONCLUSIONS: In patients with HCC and an intact Sphincter of Oddi, TACE was performed safely without prophylactic antibiotics. The majority of the patients were BCLC and CP A/B. Additional study of BCLC and CP C patients is warranted.

Percutaneous transhepatic vs. endoscopic retrograde biliary drainage for suspected malignant hilar obstruction: study protocol for a randomized controlled trial.

BACKGROUND: The optimal approach to the drainage of malignant obstruction at the liver hilum remains uncertain. We aim to compare percutaneous transhepatic biliary drainage (PTBD) to endoscopic retrograde cholangiography (ERC) as the first intervention in patients with cholestasis due to suspected malignant hilar obstruction (MHO). METHODS: The INTERCPT trial is a multi-center, comparative effectiveness, randomized, superiority trial of PTBD vs. ERC for decompression of suspected MHO. One hundred and eighty-four eligible patients across medical centers in the United States, who provide informed consent, will be randomly assigned in 1:1 fashion via a web-based electronic randomization system to either ERC or PTBD as the initial drainage and, if indicated, diagnostic procedure. All subsequent clinical interventions, including crossover to the alternative procedure, will be dictated by treating physicians per usual clinical care. Enrolled subjects will be assessed for successful biliary drainage (primary outcome measure), adequate tissue diagnosis, adverse events, the need for additional procedures, hospitalizations, and oncological outcomes over a 6-month follow-up period. Subjects, treating clinicians and outcome assessors will not be blinded. DISCUSSION: The INTERCPT trial is designed to determine whether PTBD or ERC is the better initial approach when managing a patient with suspected MHO, a common clinical dilemma that has never been investigated in a randomized trial. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03172832 . Registered on 1 June 2017.

Outpatient Transarterial Chemoembolization of Hepatocellular Carcinoma: Review of a Same-Day Discharge Strategy.

PURPOSE: To test the hypothesis that same-day discharge of selected transarterial chemoembolization patients would not increase 30-day readmission rate compared with overnight observation. MATERIALS AND METHODS: With institutional review board approval, 193 hepatocellular carcinoma patients who underwent transarterial chemoembolization from July 2013 to June 2016 were reviewed. Treatment was conventional/lipiodol transarterial chemoembolization with 50 mg doxorubicin/10 mg mitomycin-c/particles or drug-eluting embolics transarterial chemoembolization with 50-75 mg doxorubicin/vial. At 3 hours, patients tolerating oral intake and not requiring intravenous analgesics were considered for discharge. The primary outcome measure was 30-day readmission for observation versus discharge using chi-squared (χ2) analysis. The secondary aim was to identify baseline or treatment variables independently associated with readmission, including Child-Pugh class, medically managed encephalopathy or ascites, patient age (<65 vs ≥65), tumor number (1 or >1), and level of embolization (segmental vs lobar). RESULTS: Patients underwent 261 transarterial chemoembolization procedures. The 30-day readmission rate was not significantly different between observed patients (n = 179, 9.0%) and discharged patients (n = 82, 13.8%; P = .33). Readmission was not related to the selected agent (conventional/lipiodol-transarterial chemoembolization, 11.0% vs drug-eluting embolics transarterial chemoembolization, 7.5%; P = .36). Baseline variables associated with readmission were Child-Pugh B/C (χ2 = 7.9, P < .01), history of encephalopathy (χ2 = 15.4, P < 0.01), and ascites (χ2 = 4.4, P < .05). Patient age (<65 vs ≥65), tumor number (1 vs >1), and level of embolization (segmental vs lobar) were not predictive of readmission (all P > .05). CONCLUSIONS: Same-day discharge after transarterial chemoembolization does not increase the risk of 30-day readmission. Child-Pugh B/C patients, as well as those with ascites or encephalopathy, have the highest risk of readmission.

Procedural Impact of a Dedicated Interventional Oncology Service Line in a National Cancer Institute Comprehensive Cancer Center.

PURPOSE: We tested the hypothesis that establishing a dedicated interventional oncology (IO) clinical service line would increase clinic visits and procedural volumes at a single quaternary care academic medical center. METHODS: Two time periods were defined: July 2012 to June 2013 (pre-IO clinic) and July 2013 to June 2014 (first year of dedicated IO service). Staff was recruited, and clinic space was provided in the institution's comprehensive cancer center. Clinic visits and procedure numbers were documented using the institution's electronic medical record and billing forms. IO procedures included were transarterial chemoembolization, Y-90 radioembolization, perfusion mapping for Y-90, portal vein embolization, and bland embolization. We compared changes in clinic visit and procedure numbers using paired t tests. Changes after IO initiation were compared to 1-year changes in the Medicare 5% Limited Data Set by cross-referencing Current Procedure Terminology and International Classification of Diseases codes in 2012 and 2013. RESULTS: Clinic visits increased from 9 to 204 (P = .003, t = 8.89, df = 3). Procedures increased from 60 to 239 (P = .018, t = 3.85, df = 4). Procedural volumes increased at least 150% for each subtype. The volumes in the 5% Limited Data Set did not change significantly over the 2-year period (443 to 385, P > .05). CONCLUSIONS: The establishment of a dedicated IO service significantly increased clinic visits and procedural volumes. National trends were unchanged, suggesting that the impact of our program was not part of a sudden increase of IO procedures.

Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3(+)) and cytotoxic (CD8(+)) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3(+) and CD8(+) cells and clinical outcome. High densities of both CD3(+) and CD8(+) T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3(+) and CD8(+) cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3(+) and 3.9 (95% CI, 1.1-14.1) for CD8(+) Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419-30. ©2016 AACR.

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma.

PURPOSE: We sought to report outcomes and toxicity in patients with hepatocellular carcinoma (HCC) who received resin yttrium-90 selective internal radiation therapy ((90)Y-SIRT) and to identify factors associated with declining liver function. METHODS: Patients treated with (90)Y-SIRT were retrospectively evaluated. Radiographic response was assessed using RECIST 1.1. Median liver progression-free survival (LPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Bivariate analysis was used to examine associations between change in Child-Pugh (CP) score/class and patient characteristics and treatment parameters. RESULTS: Twenty-seven patients with unresectable HCC underwent SIRT, 52% were CP Class A, 48% were Class B, 11% were BCLC stage B, and 89% were stage C. Forty-four percent of patients had portal vein thrombus at baseline. One-third of patients received bilobar treatment. Median activity was 32.1 mCi (range 9.18-43.25) and median--absorbed dose to the liver was 39.6 Gy (range 13.54-67.70). Median LPFS and OS were 2.5 and 11.7 months, respectively. Three-month disease control rate was 63 and 52% in the target lesions and whole liver, respectively. New onset or worsened from baseline clinical toxicities were confined to Grade 1-2 events. However, new or worsened Grade 3-4 laboratory toxicities occurred in 38% of patients at 3 months and 43% of patients at 6 months following SIRT (six had lymphocytopenia, three had hypoalbuminemia, and two had transaminasemia). After 3 months, six patients had worsened in CP score and five had worsened in class from baseline. After 6 months, four patients had worsened in CP score and one had worsened in class from baseline. Pretreatment bilirubinemia was associated with a 2+ increase in CP score within 3 months (P = 0.001) and 6 months (P = 0.039) of (90)Y-SIRT. Pretreatment transaminasemia and bilirubinemia were associated with increased CP class within 3 months of SIRT (P = 0.021 and 0.009, respectively). CONCLUSION: (90)Y-SIRT was well-tolerated in patients with unresectable HCC, with no Grade 3-4 clinical toxicities. However, Grade 3-4 laboratory toxicities and worsened CP scores were more frequent. HCC patients with pretreatment bilirubinemia or transaminasemia may be at higher risk of experiencing a decline in liver function following (90)Y-SIRT.

Effect of multimodality treatment on overall survival for patients with metastatic or recurrent HPV-positive head and neck squamous cell carcinoma.

BACKGROUND: The optimal treatment for patients with recurrent human papillomavirus (HPV)-positive head and neck cancer is poorly understood. METHODS: We investigated treatments and outcomes in patients with recurrent head and neck cancer. Treatments included salvage neck surgery, metastasectomy, hypofractionated reirradiation, chemoembolization, and chemotherapy. Treatment outcomes were compared based on HPV status. RESULTS: A total of 37 patients were identified (12 HPV positive and 25 HPV negative). Demographics were similar. Overall, there was a trend toward a higher number of total treatment interventions in patients with HPV-positive disease (4.5 vs 2.6), but this was statistically insignificant (p=.066). After a mean follow-up of 21 months, median survival in HPV-negative patients was 10.6 months, whereas the median survival had not been reached for HPV-positive patients. Of the 12 HPV-positive patients, 7 were still alive (58%) after a mean follow-up period of 33 months. CONCLUSION: Multimodality aggressive therapy may improve overall survival in patients with recurrent HPV-positive disease. Further prospective research is warranted.

Treatment planning and image guidance for radiofrequency ablation of large tumors.

This article addresses the two key challenges in computer-assisted percutaneous tumor ablation: planning multiple overlapping ablations for large tumors while avoiding critical structures, and executing the prescribed plan. Toward semiautomatic treatment planning for image-guided surgical interventions, we develop a systematic approach to the needle-based ablation placement task, ranging from preoperative planning algorithms to an intraoperative execution platform. The planning system incorporates clinical constraints on ablations and trajectories using a multiple objective optimization formulation, which consists of optimal path selection and ablation coverage optimization based on integer programming. The system implementation is presented and validated in both phantom and animal studies. The presented system can potentially be further extended for other ablation techniques such as cryotherapy.

Experimental Evaluation of a Deformable Registration Algorithm for Motion Correction in PET-CT Guided Biopsy.

Positron emission tomography computed tomography (PET-CT) images are increasingly being used for guidance during percutaneous biopsy. However, due to the physics of image acquisition, PET-CT images are susceptible to problems due to respiratory and cardiac motion, leading to inaccurate tumor localization, shape distortion, and attenuation correction. To address these problems, we present a method for motion correction that relies on respiratory gated CT images aligned using a deformable registration algorithm. In this work, we use two deformable registration algorithms and two optimization approaches for registering the CT images obtained over the respiratory cycle. The two algorithms are the BSpline and the symmetric forces Demons registration. In the first optmization approach, CT images at each time point are registered to a single reference time point. In the second approach, deformation maps are obtained to align each CT time point with its adjacent time point. These deformations are then composed to find the deformation with respect to a reference time point. We evaluate these two algorithms and optimization approaches using respiratory gated CT images obtained from 7 patients. Our results show that overall the BSpline registration algorithm with the reference optimization approach gives the best results.

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases.

Standard treatment for operable patients with single peripheral lung metastases is metastasectomy. We report mature CyberKnife outcomes for high-risk surgical patients with biopsy proven single peripheral lung metastases. Twenty-four patients (median age 73 years) with a mean maximum tumor diameter of 2.5 cm (range, 0.8-4.5 cm) were treated over a 6-year period extending from September 2004 to September 2010 and followed for a minimum of 1 year or until death. A mean dose of 52 Gy (range, 45-60 Gy) was delivered to the prescription isodose line in three fractions over a 3-11 day period (mean, 7 days). At a median follow-up of 20 months, the 2-year Kaplan-Meier local control and overall survival rates were 87 and 50%, respectively. CyberKnife with fiducial tracking is an effective treatment for high-risk surgical patients with single small peripheral lung metastases. Trials comparing CyberKnife with metastasectomy for operable patients are necessary to confirm equivalence.

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer.

Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21-111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3-13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12-72 months) follow-up, the 3 year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1-2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

Resolution of hydronephrosis after uterine artery embolization for fibroids.

PURPOSE: To determine the prevalence, predisposing factors, and resolution of hydronephrosis among patients undergoing uterine artery embolization (UAE) for fibroids. MATERIALS AND METHODS: From October 2004 to May 2008, 1,114 patients underwent UAE at an academic medical center. Hydronephrosis was found on angiographic images in 101 patients. In 34 of these patients, 3-month ultrasound follow-up was available. The angiographic images were graded for hydronephrosis severity by three interventional radiologist reviewers. The degree of residual hydronephrosis was obtained from ultrasound images or reports in 3-month follow-up imaging. Descriptive statistics summarizing outcomes and interobserver agreement regarding hydronephrosis grade were calculated. In a parallel assessment, prospectively gathered baseline data available from 776 patients undergoing UAE were analyzed to identify predisposing factors to hydronephrosis. RESULTS: Among the 34 patients with hydronephrosis and appropriate follow-up, resolution occurred in 28 of 34 (82%) patients. Among the entire study group, 9.0% (101 of 1,114) of patients had unilateral or bilateral hydronephrosis. Hydronephrosis was less frequent in left kidneys (4.5% [35 of 776]) than right kidneys (6.3% [49 of 776]; P = .013). The mean uterine volume in the group with hydronephrosis was greater than in the group without hydronephrosis (1,041 cm(3) vs 609 cm(3); P < .0001), and the mean dominant fibroid volume was also greater (233 cm(3) vs 147 cm(3); P < .0001). CONCLUSIONS: These results suggest that UAE may result in resolution of hydronephrosis in a notable number of cases. Large uterine size and dominant fibroid size was associated with hydronephrosis.

CyberKnife radiosurgery for inoperable stage IA non-small cell lung cancer: 18F-fluorodeoxyglucose positron emission tomography/computed tomography serial tumor response assessment.

OBJECTIVE: To report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC). METHODS: Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUV(max)) was recorded for each time point. RESULTS: Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUV(max) before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUV(max) remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUV(max) levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUV(max) for controlled tumors was 2.0, with a narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUV(max) of 8.4. CONCLUSION: Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUV(max) are likely related to radiation-induced pneumonitis. Tumor SUV(max) values return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study.