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 relapse-free survival (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% CI 1.6-21.8) for CD3+, and 3.9 (95% CI 1.1-14.1) for CD8+. Positive PD-L1 staining 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.

PURPOSE-To assess the feasibility of the use of preprocedural imaging for guide wire, catheter, and needle navigation with electromagnetic tracking in phantom and animal models. MATERIALS AND METHODS-An image-guided intervention software system was developedbased on open-source software components. Catheters, needles, and guide wires were constructed with small position and orientation sensors in the tips. A tetrahedral-shaped weak electromagnetic field generator was placed in proximity to an abdominal vascular phantom or three pigs on the angiography table. Preprocedural computed tomographic (CT) images of the phantom or pig were loaded into custom-developed tracking, registration, navigation, and rendering software. Devices were manipulated within the phantom or pig with guidance from the previously acquired CT scan and simultaneous real-time angiography. Navigation within positron emission tomography (PET) and magnetic resonance (MR) volumetric datasets was also performed. External and endovascular fiducials were used for registration in the phantom, and registration error and tracking error were estimated. RESULTS-The CT scan position of the devices within phantoms and pigs was accurately determined during angiography and biopsy procedures, with manageable error for some applications. Preprocedural CT depicted the anatomy in the region of the devices with real-time position updating and minimal registration error and tracking error (<5 mm). PET can also be used with this system to guide percutaneous biopsies to the most metabolically active region of a tumor.CONCLUSIONS-Previously acquired CT, MR, or PET data can be accurately codisplayed during procedures with reconstructed imaging based on the position and orientation of catheters, guide wires, or needles. Multimodality interventions are feasible by allowing the real-time updated display of previously acquired functional or morphologic imaging during angiography, biopsy, and ablation.Address correspondence to B.J.W.; E-mail: bwood@nih.gov. B.J.W. and K.C. are coinventors on related US Patent Application #10/377,528, "Interstitial Magnetic Position Sensor System and Needle for Surgical and Image-guided Therapy Navigation." B.J.W. and N.G. are coinventors on US Patent Application: "Design for Guiding and Electromagnetic Tracking of Radiofrequency Ablation Needle" (US Provisional Patent Application # 60/625,186). Philips owns intellectual property and has market interest in this area. J.K., J.B., and S.K. are salaried employees of Philips Electronics. The mention of commercial devices or products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the National Institutes of Health, the Department of Health and Human Services, or the Public Health Service. N.G. is President and a major shareholder of Traxtal, Inc. DEVICE navigation in angiography and interventional radiology has traditionally relied on real-time imaging to monitor anatomic position...

Background: Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors.

ObjectiveCurative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective.MethodsInoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42–60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment.ResultsTwenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 – 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 – 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression.ConclusionRadical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study.

This article reviews the published efforts to characterize hepatic motion secondary to respiration, with the specific goal of defining the limitations and potential applications of image-guided systems in percutaneous liver interventions (computer assisted interventions). Hepatic motion and deformation due to respiration remain obstacles to applying stereotactic localization techniques to the liver. Respiratory-associated hepatic motion is complex. Nine studies using diagnostic imaging or modeling are reviewed, and their findings are tabulated herein. The significant variations in their findings are discussed, including cranio-caudal translation, anterior-posterior and lateral translation, movement secondary to tissue deformation, and motion with respect to surrounding tissue. Techniques for correcting for hepatic respiratory motion are then described, including gating techniques, modeling approaches, real-time liver tracking, and magnetic tracking technology.