Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors.

Background: Development of acquired resistance limits the utility of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) for the treatment of EGFR-mutant lung cancers. There are no accepted targeted therapies for use after acquired resistance develops. Metastasectomy is used in other cancers to manage oligometastatic disease.

Role of FDG-PET scans in staging, response assessment, and follow-up care for non-small cell lung cancer.

The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC.

Predictors for locoregional recurrence for clinical stage III-N2 non-small cell lung cancer with nodal downstaging after induction chemotherapy and surgery.

Purpose: Pathologic downstaging following chemotherapy for stage III-N2 NSCLC is a well-known positive prognostic indicator. However, the predictive factors for locoregional recurrence (LRR) in these patients are largely unknown.

Methods: Between 1998 and 2008, 153 patients with clinically or pathologically staged III-N2 NSCLC from two cancer centers in the United States were treated with induction chemotherapy and surgery.

A novel four-dimensional radiotherapy planning strategy from a tumor-tracking beam's eye view.

To investigate the feasibility of four-dimensional radiotherapy (4DRT) planning from a tumor-tracking beam's eye view (ttBEV) with reliable gross tumor volume (GTV) delineation, realistic normal tissue representation, high planning accuracy and low clinical workload, we propose and validate a novel 4D conformal planning strategy based on a synthesized 3.5D computed tomographic (3.5DCT) image with a motion-compensated tumor.

A study of respiration-correlated cone-beam CT scans to correct target positioning errors in radiotherapy of thoracic cancer.

Purpose: There is increasingly widespread usage of cone-beam CT (CBCT) for guiding radiation treatment in advanced-stage lung tumors, but difficulties associated with daily CBCT in conventionally fractionated treatments include imaging dose to the patient, increased workload and longer treatment times. Respiration-correlated cone-beam CT (RC-CBCT) can improve localization accuracy in mobile lung tumors, but further increases the time and workload for conventionally fractionated treatments. This study investigates whether RC-CBCT-guided correction of systematic tumor deviations in standard fractionated lung tumor radiation treatments is more effective than 2D image-based correction of skeletal deviations alone.

Reduction of irregular breathing artifacts in respiration-correlated CT images using a respiratory motion model.

Purpose: Respiration-correlated CT (RCCT) images produced with commonly used phase-based sorting of CT slices often exhibit discontinuity artifacts between CT slices, caused by cycle-to-cycle amplitude variations in respiration. Sorting based on the displacement of the respiratory signal yields slices at more consistent respiratory motion states and hence reduces artifacts, but missing image data (gaps) may occur. The authors report on the application of a respiratory motion model to produce an RCCT image set with reduced artifacts and without missing data.

SU-E-J-119: Comparative Evaluation of Respiratory Motion-Corrected Cone-Beam CT Images Derived from Treatment-Day Vs. Simulation-Day Respiration-Correlated CT Scans.

Purpose: Respiration-induced motion artifacts in cone-beam CT (CBCT) can be corrected using a model of patient motion obtained from respiration-correlated CT (RCCT). This approach assumes that respiration-induced organ deformations at simulation, when RCCT scans are normally acquired, are still valid at treatment. The purpose of this study is to compare lung tumor image quality in motion-corrected CBCT images derived from treatment-day RCCT(tx) to simulation-day RCCT(sim) patient images.

SU-E-J-121: A New 4D Radiotherapy Planning Strategy Using Synthesized Tumor-Motion-Compensated Computed Tomography.

Purpose: To validate a four-dimensional radiotherapy (4DRT) planning based on a synthesized CT image compensating for tumor motion, accounting for tumor rotation, deformation and distortion due to motion artifacts, and producing realistic normal tissue density in motion-tracking beam eye view.

Methods: 4D computed tomography (4DCT) images of six patients with peripheral lung lesions in mid or lower lobs (motion range: 0.5-3.

SU-E-J-67: A Potential New Technique to Measure Respiratory Tidal Volume Using Optical Surface Imaging: A Geometric and Deformable Phantom Study.

Purpose: To develop a new method for accurate measurement of dynamic respiratory tidal volume, we investigate the feasibility of measuring torso volume change using optical surface imaging (OSI).

Methods: Based on a validated volume conservation theory, the tidal volume is equal to the volume change of the torso during quiet respiration (Li et al, PMB, 54:1693, 2009). A clinical OSI system was employed to acquire surface images of seven geometric phantoms and two 'deformable' torso phantoms.

SU-E-T-595: Comparison of Volumetric Modulated Arc Therapy (VMAT) and Static Intensity Modulated Radiotherapy (IMRT) for Malignant Pleural Mesothelioma in Patients with Intact Lungs/Post Pleurectomy.

Purpose: This planning study compares VMAT and static gantry, sliding window IMRT for malignant pleural mesothelioma for post pleurectomy.

Methods: We compared plans for a left sided (L) and a right sided case (R). Plans used clinically approved planning target volumes (PTVs) and critical organ contours.

Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma.

Purpose: In patients with malignant pleural mesothelioma who are unable to undergo pneumonectomy, it is difficult to deliver tumoricidal radiation doses to the pleura without significant toxicity. We have implemented a technique of using intensity-modulated radiotherapy (IMRT) to treat these patients, and we report the feasibility and toxicity of this approach.

Methods And Materials: Between 2005 and 2010, 36 patients with malignant pleural mesothelioma and two intact lungs (i.

Multidisciplinary management of thymic carcinoma.

Thymic carcinomas represent approximately 10% of thymic tumors. In our approach to patients with thymic carcinoma, we emphasize multimodality treatment with close communication between the pathologist, thoracic surgeon, medical oncologist, and radiation oncologist. Given the paucity of high-quality clinical research data, treatment decisions are guided by a small amount of prospective trial data, retrospective reports, and clinical experience.

Mitochondrial ceramide-rich macrodomains functionalize Bax upon irradiation.

Background: Evidence indicates that Bax functions as a "lipidic" pore to regulate mitochondrial outer membrane permeabilization (MOMP), the apoptosis commitment step, through unknown membrane elements. Here we show mitochondrial ceramide elevation facilitates MOMP-mediated cytochrome c release in HeLa cells by generating a previously-unrecognized mitochondrial ceramide-rich macrodomain (MCRM), which we visualize and isolate, into which Bax integrates.

Methodology/principal Findings: MCRMs, virtually non-existent in resting cells, form upon irradiation coupled to ceramide synthase-mediated ceramide elevation, optimizing Bax insertion/oligomerization and MOMP.

Breast cancer methylomes establish an epigenomic foundation for metastasis.

Cancer-specific alterations in DNA methylation are hallmarks of human malignancies; however, the nature of the breast cancer epigenome and its effects on metastatic behavior remain obscure. To address this issue, we used genome-wide analysis to characterize the methylomes of breast cancers with diverse metastatic behavior. Groups of breast tumors were characterized by the presence or absence of coordinate hypermethylation at a large number of genes, demonstrating a breast CpG island methylator phenotype (B-CIMP).

MicroRNA-335 inhibits tumor reinitiation and is silenced through genetic and epigenetic mechanisms in human breast cancer.

Post-transcriptional regulators have emerged as robust effectors of metastasis and display deregulated expression through unknown mechanisms. Here, we reveal that the human microRNA-335 locus undergoes genetic deletion and epigenetic promoter hypermethylation in every metastatic derivative obtained from independent patients' malignant cell populations. Genetic deletion of miR-335 is a common event in human breast cancer, is enriched for in breast cancer metastases, and also correlates with ovarian cancer recurrence.

Influence of compartmental involvement on the patterns of morbidity in soft tissue sarcoma of the thigh.

Background: The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb-sparing surgery and postoperative radiation therapy (RT).

Methods: A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982-2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins.

Palliative radiation for lung cancer metastases to the breast: two case reports.

Metastases from non-small cell lung cancer to the breast represent an unusual diagnosis. We present two cases of metastatic lung cancer to the breast that were treated with palliative radiation with achievement of good local control and symptom relief. We suggest the use of palliative radiation therapy as an effective and simple treatment modality for metastatic disease to the breast.

Relevance and mechanism of oxysterol stereospecifity in coronary artery disease.

Cholesterol oxidation products (oxysterols) are markers for in vitro LDL oxidation. They are potent inducers of programmed cell death and are also found in high concentrations inside atherosclerotic lesions. Among physiologically occurring oxysterols, 7beta-OH-cholesterol suggests an increase of lipid peroxidation in vivo.

Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma.

Interactions of CD70, a tumor necrosis factor-related cell surface ligand and its receptor, CD27, are thought to play an important role for T-, B-, and natural killer-cell activation. However, ligation of CD27 can also induce apoptosis. Human glioblastoma is paradigmatic for cancer-associated immunosuppression.

BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells.

Radiotherapy is the standard treatment for glioblastoma. Here, we assessed the radiosensitivity of 12 human malignant glioma cell lines in vitro and correlated these data with irradiation-induced cell cycle changes, chemosensitivity profiles and BCL-2 family protein expression. Irradiation at 3 Gy failed to cause major cell cycle perturbations.

Identification by suppression subtractive hybridization of p21 as a radio-inducible gene in human glioma cells.

Background: Radio-gene therapy involves the delivery, to tumor cells, of a therapeutic transgene whose expression is controlled by irradiation.

Materials And Methods: Here, we sought to identify novel radio-inducible transcripts in U87MG human malignant glioma cells using suppression subtractive hybridization (SSH).

Results: Of 998 clones from a subtracted library of irradiated U87MG cells, 24 candidate clones were identified by dot blot and 3 clones were confirmed as having been induced by irradiation by Northern blot analysis.

Sublethal irradiation promotes migration and invasiveness of glioma cells: implications for radiotherapy of human glioblastoma.

Human malignant gliomas are highly lethal neoplasms. Involved-field radiotherapy is the most important therapeutic measure. Most relapses originate from the close vicinity of the irradiated target field.

"Allograft-inflammatory-factor-1 is upregulated in microglial cells in human cerebral infarctions".

Allograft inflammatory factor-1 (AIF-1) is a 17-kDa-peptide identified in rat cardiac allografts undergoing chronic rejection and in activated microglial cells in inflammatory autoimune disease of the CNS. We have investigated the expression of AIF-1 in 18 autopsy cases of human focal cerebral infarction. AIF-1-positive cells show the morphology of microglia and are CD68- but not GFAP-positive.

Allograft-inflammatory-factor-1 is upregulated in microglial cells in human cerebral infarctions.

Allograft inflammatory factor-1 (AIF-1) is a 17-kDa-peptide identified in rat cardiac allografts undergoing chronic rejection and in activated microglial cells in inflammatory autoimune disease of the CNS. We have investigated the expression of AIF-1 in 18 autopsy cases of human focal cerebral infarction. AIF-1-positive cells show the morphology of microglia and are CD68- but not GFAP-positive.