Faculty Bibliography

OBJECTIVES: The aim of this study was to evaluate the prognostic value of pretreatment F-fluorodeoxyglucose PET/computed tomography (CT), particularly in the assessment of metabolic tumor burden markers such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), with respect to clinical outcomes in stage I non-small-cell lung cancer (NSCLC) patients undergoing stereotactic body radiation therapy (SBRT). METHODS: This retrospective study evaluated 50 patients who underwent SBRT for stage I NSCLC from May 2007 to December 2012. The maximum standardized uptake value (SUVmax), average SUV (SUVavg), MTV, and TLG were measured from the PET/CT scan. The study population was dichotomized at the median into high and low groups. Kaplan-Meier log-rank tests were then used to compare high with low PET/CT parameter groups, and univariate Cox proportional hazards regression analysis was carried out to identify predictors of overall survival. RESULTS: The 2-year local control rate was 93.7%. After a median follow-up of 25.1 months, the 2-year overall survival was 79.3%. Eight patients (16%) had disease recurrence. There were three local failures (6%), three mediastinal failures (6%), and six cases of distant metastases (12%). Both Kaplan-Meier actuarial analysis and Cox proportional hazards regression found no correlation between SUVmax, SUVavg, MTV, and TLG and overall survival. CONCLUSION: Standard PET/CT measures, such as SUVmax, as well as newer measures of metabolic tumor burden, such as MTV and TLG, were not correlated with overall survival in our study population of stage I NSCLC patients undergoing SBRT. Larger studies with longer follow-up periods are needed to confirm these results.

BACKGROUND: CT-guided needle biopsy of lung nodules requires breath holding during needle placement, and is thus inapplicable to patients with difficulty in holding breath. METHODS: A robotic needle biopsy technique is introduced, adapting to the patient respiratory pattern and using a robot manipulator to drive the needle towards a moving lung nodule. Based on the nodule respiratory motion model, needle placement is planned to follow an optimal timing and path, and is triggered based on the respiratory phase tracking. An experimental system has been created to study robotic needle placement. RESULTS: Preliminary phantom tests were conducted based on three representative clinically-collected lung nodule motion paths, using an 18-gauge coaxial needle set. 300 needle paths were implemented. Robotic needle driving was accomplished within 0.4 s (a typical respiratory phase), and resulted in a needle placement accuracy of 0.5 mm with a standard deviation about 0.1 mm over the non-resistance paths. CONCLUSION: The proposed robotic needle placement technique is promising for accurately biopsying lung nodules under respiratory motion and those with very small sizes.

Increased public and regulatory scrutiny of imaging-related radiation exposure requires familiarity with current dose-monitoring techniques and best practices. CT-related ionizing radiation exposure has been cited as the largest and fastest growing source of population-wide iatrogenic ionizing radiation exposure. Upcoming federal regulations require imaging centers to familiarize themselves with available dose-monitoring techniques and implement comprehensive strategies to track patient dose, with particular emphasis on CT. Because of institution-specific and vendor-specific technologies, there are significant barriers to adoption and implementation. In this article, the authors outline the core components of a universal dose-monitoring strategy and detail a few of the many available commercial platforms. In addition, the authors introduce a cloud-based hybrid model dose-tracking system with the goal of rapid implementation, multicenter scalability, real-time dose feedback for technologists, cumulative dose monitoring, and optional dose communication to patients and into the record; doing so results in improved patient loyalty, referring physician satisfaction, and opportunity for repeat business.

(18)F-FDG PET/CT was compared with non-contrast chest CT in monitoring for recurrence 1-year after lobectomy of stage 1 non-small-cell lung cancer (NSCLC). For surveillance after treatment with curative intent, current (April 2012) National Comprehensive Cancer network guidelines recommend chest CT with or without contrast every 6-12 months for 2 years, then non-contrast chest CT annually. PET/CT is not currently indicated for routine follow-up. One hundred patients receiving surveillance PET/CT 1-year after lobectomy for the treatment of stage 1a or 1b NSCLC were included in the study. Exclusion criteria included the presence or interval diagnosis of a second malignancy, or surgical treatment more radical than single lobectomy. The non-contrast CT obtained from the 1-year PET/CT was interpreted by an experienced chest radiologist blinded to the PET/CT for evidence of recurrence using the following findings: pulmonary nodule, pleural effusion, pleural mass, adenopathy, and extrathoracic mass. The ecision about recurrence was made solely from the non-contrast CT without PET/CT findings. This was compared with the determination made with PET/CT. The reference standard for determination of recurrence was the multi-disciplinary tumor board who had access to all imaging and clinical data. Recurrence at 1 year was documented in 16 of 90 patients. All 16 recurrences were documented with PET/CT and 9 were found with non-contrast CT. Five of the 7 recurrences missed with non-contrast CT were extrathoracic metastases. Sensitivity of CT and PET/CT for recurrence was 56.3% and 100%, respectively (p = 0.015). Specificity of CT and PET/CT for recurrence was 95.9% and 93.2%, respectively (p = 0.62).

LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along with bioavailability studies. To determine the antiangiogenic activity of LP-261, both in vitro and ex vivo experiments were performed. Human umbilical vein endothelial cells (HUVECs) were incubated with LP-261 at 50 nM to 10 μM. LP-261 was also tested in a rat aortic ring assay, from 20 nM to 10 μM. Multiple mouse xenograft studies were performed to assess in vivo antitumor activity. LP-261 was tested as a single agent in colon adenocarcinoma (SW620) and prostate cancer (LNCaP and PC3) xenografts, evaluating several different dosing schedules. LP-261 was also used in combination with bevacizumab in the SW620 xenograft model. LP-261 also exhibited high oral bioavailability and apparent lack of efflux by intestinal transporters such as ABCB1. LP-261 is a very potent inhibitor of angiogenesis, preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell proliferation at nanomolar concentrations. Complete inhibition of tumor growth was achieved in the PC3 xenograft model and shown to be schedule dependent. Excellent inhibition of tumor growth in the SW620 model was observed, comparable with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to significantly improved tumor inhibition. Oral LP-261 is very effective at inhibiting tumor growth in multiple mouse xenograft models and is well tolerated.

BACKGROUND: Percutaneous irreversible electroporation (IRE) of lung tumors is a new minimally invasive technique which has recently been used in the treatment of soft tissue tumors. CASE REPORTS: The case histories are presented of two patients with unresectable malignancies in the lung, who underwent irreversible electroporation as a treatment attempt. The procedure was performed under CT guidance and was uneventful. CONCLUSIONS: At follow up 6 months later, the tumors both appeared to have recurred. To our knowledge, no similar cases have previously been reported in the literature.

Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy ((1)HMRS). Together with neurocognitive testing, (1)HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the concentration of tumor-necrosis factor alpha ([TNF-alpha]) was positively correlated to the metabolic activity of the lung tumor as defined by the 2-deoxy-2-((18)F)fluoro-D-glucose ((18)FDG) positron emission tomography (PET) derived maximal standardized uptake values (SUV(max)). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate [NAA] in the occipital cortex was negatively associated with [TNF-alpha]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed even prior to treatment. In addition, the association between inflammatory cytokines, SUV(max) and [NAA] points towards interactions between the cancer's inherent metabolic activity, systemic subclinical inflammation and brain function.

PURPOSE: Administration of radioactive iodine to a pregnant woman for thyroid ablation has been shown to affect neonatal thyroid levels. Thus, there is a theoretical risk in affecting a neonate's thyroid level upon birth with prior administration of intravenous contrast containing iodine to a pregnant woman during a computed tomographic scan. However, there is no literature to support this theoretical risk. This study attempted to determine if there is any effect on a newborn's thyroid levels after exposure to this type of contrast material in utero. MATERIALS AND METHODS: The medical charts of 96 pregnant women during the years 2004 through 2009 on whom computed tomographic scans were performed were reviewed. A total of 29 charts were excluded secondary to missing neonatal records, missed abortions, and intrauterine fetal demise. The rest were subdivided into those who received intravenous (IV) +/- oral contrast material and those who did not. The medical records of the newborns of these patients were also reviewed. The subject group consisted of 61 pregnant women who received IV +/- oral contrast and their 64 neonates. The control group consisted of 6 pregnant patients who did not receive IV contrast and their 6 neonates. RESULTS: Of the 64 neonates in the subject group, only one neonate was found to have a low thyroxine level with a normal thyroid stimulating hormone level. This infant was severely premature, being born at the 25th week of gestation, and developed respiratory distress syndrome and sepsis, which were potential confounding factors. All of the 6 neonates in the control group had normal thyroid levels. CONCLUSION: This study concludes that there is no significant adverse clinical risk of thyroid function abnormalities to the fetus after IV iodinated contrast material to their mothers.

PURPOSE: Surgical resection remains the standard of care for operable early-stage non-small-cell lung cancer (NSCLC). However, some patients are not fit for surgery because of comorbidites such as chronic obstructive pulmonary disease (COPD) and other medical conditions. We aimed to evaluate pulmonary function and tumor volume before and after stereotactic body radiotherapy (SBRT) for patients with and without COPD in early-stage lung cancer. METHODS AND MATERIALS: A review of prospectively collected data of Stage I and II lung cancers, all treated with SBRT, was performed. The total SBRT treatment was 60 Gy administered in three 20 Gy fractions. The patients were analyzed based on their COPD status, using their pretreatment pulmonary function test cutoffs as established by the American Thoracic Society guidelines (forced expiratory volume [FEV]%