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The incorporation of sensors onto the stapling platform has been investigated to overcome the disconnect in our understanding of tissue handling by surgical staplers. The goal of this study was to explore the feasibility of in vivo porcine tissue differentiation using bioimpedance data and machine learning methods. In vivo electrical impedance measurements were obtained in 7 young domestic pigs, using a logarithmic sweep of 50 points over a frequency range of 100 Hz to 1 MHz. Tissues studied included lung, liver, small bowel, colon, and stomach, which was further segmented into fundus, body, and antrum. The data was then parsed through MATLAB's classification learner to identify the best algorithm for tissue type differentiation. The most effective classification scheme was found to be cubic support vector machines with 86.96% accuracy. When fundus, body and antrum were aggregated together as stomach, the accuracy improved to 88.03%. The combination of stomach, small bowel, and colon together as GI tract improved accuracy to 99.79% using fine k nearest neighbors. The results suggest that bioimpedance data can be effectively used to differentiate tissue types in vivo. This study is one of the first that combines in vivo bioimpedance tissue data across multiple tissue types with machine learning methods.

The incorporation of sensors onto the stapling platform has been investigated to overcome the disconnect in our understanding of tissue handling by surgical staplers. The goal of this study was to explore the feasibility of in vivo porcine tissue differentiation using bioimpedance data and machine learning methods. In vivo electrical impedance measurements were obtained in 7 young domestic pigs, using a logarithmic sweep of 50 points over a frequency range of 100 Hz to 1 MHz. Tissues studied included lung, liver, small bowel, colon, and stomach, which was further segmented into fundus, body, and antrum. The data was then parsed through MATLAB's classification learner to identify the best algorithm for tissue type differentiation. The most effective classification scheme was found to be cubic support vector machines with 86.96% accuracy. When fundus, body and antrum were aggregated together as stomach, the accuracy improved to 88.03%. The combination of stomach, small bowel, and colon together as GI tract improved accuracy to 99.79% using fine k nearest neighbors. The results suggest that bioimpedance data can be effectively used to differentiate tissue types in vivo. This study is one of the first that combines in vivo bioimpedance tissue data across multiple tissue types with machine learning methods.

BackgroundMurine model suggests programmed cell death-1 (PD-1), an immune checkpoint not only plays role in tumor escape but is also a tumor suppressor for T-cells. But until, no reports of secondary T-cell lymphoma postuse of immune checkpoint inhibitors (ICIs) has been reported. Herein, we present a hitherto unreported phenomenon of secondary T-cell lymphoma when PD-1 inhibitor was used in a patient diagnosed with a tumor of epithelial origin.Case reportA man in mid-70s presented with biopsy-proven metastatic tumor of epithelial origin. Patient received carboplatin in combination with paclitaxel for four cycles leading to partial remission. The patient was subsequently switched to pembrolizumab due to persistent disease in the mediastinum. After four cycles of PD-1 inhibitor, patient presented with progression of disease and was diagnosed with biopsy-proven peripheral T-cell lymphoma-not otherwise specified. Based on the reported tumor suppressor function of PD-1 in murine models, we hypothesized that the use of PD-1 inhibitor caused clonal proliferation of abnormal T-cell clone leading to T-cell lymphoma. T-cell receptor (TCR) sequencing was performed by TCRβ sequencing and T-cell clones from pre-ICI treatment specimen were compared with post-ICI treatment specimens. We show that one of the T-cell clones present in pre-ICI treatment specimen at a low frequency of had massive expansion to become most dominant clone in post-ICI treatment specimens leading to lymphoma. Moreover, targeted exome sequencing revealed a new TET2 mutation in the clone representing the lymphoma.Next, we retrospectively reviewed the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), the pharmacovigilance database from 2012 to 2018 to find the reported incidence of this phenomenon and calculated the reporting OR (ROR) for disproportionality analysis for risk of T-cell lymphoma due to checkpoint inhibitors compared with other drugs. In FAERS, the incidence of T-cell lymphoma post-ICIs (pembrolizumab, nivolumab and ipilimumab) was found to be 0.02% with 17% mortality. The ROR probability of risk of T-cell lymphoma compared with other drugs in pharmacovigilance database was increased at 1.91.ConclusionsT-cell lymphoma is a rare sequela of ICIs with high mortality. Larger studies with long-term follow-up of patients receiving ICIs is needed.

The liver is a common site for metastatic disease for many cancers. Radiation therapy is one means of treatment for liver metastases, especially for patients unable to undergo surgery or ineligible for systemic chemotherapy. In particular, stereotactic body radiotherapy (SBRT) has become an important option in the treatment of metastatic disease in the liver. SBRT delivers ablative doses of radiation in relatively few fractions. As such, precise and clear imaging plays an important role in maximizing disease control while minimizing normal tissue toxicity. We present a case that highlights the importance of using multiple imaging modalities for target volume delineation in stereotactic radiation treatment of liver metastases.

Small conductance Ca2+-activated potassium (SK) channels play a key role in the regulation of neuronal excitability. Positive modulation of potassium ion channels has been suggested as a potential therapeutic strategy to normalize the excitability of neurons, in movement disorders such as ataxia and Amyotrophic Lateral Sclerosis (ALS). Riluzole is the only FDA approved drug for ALS, although its therapeutic effects are only modest. Riluzole positively modulates SK channels, which contributes to its neuroprotective effects. With crystallography, we discovered the binding pocket of riluzole in SK2 channels. This binding pocket was further validated through combined techniques including site directed mutagenesis and electrophysiological recordings. These data suggest that the binding pocket identified by crystallography is indeed the functional binding pocket through which riluzole exerts the positive modulation of channel activity.

Renal cell carcinoma (RCC) metastases have been reported in almost every organ. The most common involved organs are the lungs, liver, kidneys, bones, and brain.1,2 Autopsy series have reported RCC adrenal metastases rates ranging from 7% to 19%.2-4 Contralateral adrenal involvement is rare. In one study the incidence was 2.5%.5 In addition contralateral adrenal metastases from RCC can present late, even after 23 years from primary tumor resection.4,6 Such unusual delay in presentation, infrequent occurrence, and confusing clinical presentation can lead to misdiagnosis, delayed diagnosis, or failure to treat promptly.3 Herein a case of RCC involving the contralateral adrenal gland that was successfully treated with SBRT is reported. The patient had right nephrectomy and right adrenalectomy 12 years earlier. His resulting adrenal

Stereotactic ablative radiotherapy (SABR), also named stereotactic body radiation therapy, entails the delivery of individual ablative doses of radiation to the tumor volume with a very steep dose gradient beyond the tumor volume using highly conformal techniques and has been used to treat primary and metastatic lung tumors with promising results achieved. As a result of the delivery of individual ablative doses to the lung, the resulting inflammatory (acute) and fibrotic (late) reactions are more intense, rendering interpretation of post-SABR imaging changes difficult. Different early and late injury patterns have been described based on computerized tomography (CT) by various groups of researchers. Although the data on post-SABR imaging changes are emerging, there are still challenges distinguishing between post-treatment changes and tumor progression. The necessity for evaluation based on serial imaging cannot be overemphasized. Controversies still exist as to whether CT or positron emission tomography (PET) should be used for follow-up. Since CT and PET are the most commonly used imaging modalities for follow-up after SABR, they will be the foci of this review article.

Purpose To determine how the incorporation of PET-CT changes radiotherapy treatment in pediatric Hodgkin lymphoma. Procedure Fifty-three Hodgkin lymphoma patients with a median age of 14 years (6–21 years) underwent multiagent chemotherapy followed by involved field radiotherapy (IFRT) to initial sites of disease. All patients had conventional staging which included CT scan of the neck, chest, abdomen and pelvis, bone marrow biopsy ± MRI, Gallium scan and bone scan. All had an initial 18-F-fluoro-deoxy-D-glucose (FDG) PET-CT. When there was discordance between conventional staging and PET-CT staging, true sites of disease were determined either by biopsy or response to multiagent chemotherapy. Results In 19 of 53 (35.8%) patients, there was discordance between conventional staging and PET-CT findings. The most common location for the 23 sites of discordance were the spleen in 6 (26.1%), neck in 3 (13%), inguinal nodes in 3 (13%) and mediastinum in 3 (13%). A change in stage occurred in 5 (9.4%) as a result of PET-CT imaging. A change in IFRT fields occurred in 9 (17%); eight were more extensive while one was less extensive. For PET-CT, the specificity, sensitivity, positive predictive value and accuracy were 99.5%, 96.3%, 97.9%, and 98.9%. Conclusion Incorporation of PET-CT information was found to influence IFRT design in 17% of patients, with most having more extensive radiotherapy fields. Pediatr Blood Cancer 2012; 58: 860–864. © 2011 Wiley Periodicals, Inc.

182 Background: In the treatment of gastroesophageal junction (GEJ) cancer, trimodality treatment with preoperative chemoradiation followed by surgery is the standard of care. However, predicting patient survival outcomes remains difficult. One possible means of predicting outcomes is comparing pre-treatment PET-CT with post-treatment PET-CT to see if a favorable response on imaging correlates with survival outcomes. Methods: We conducted a retrospective chart review of locally advanced GEJ cancer patients who underwent preoperative chemoradiotherapy followed by esophagectomy with negative margins. All patients underwent two PET-CT scans (before and after preoperative chemoradiation). We compared PET-CT imaging results and pathology results with survival outcomes. Values such as pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, complete response on PET-CT, and pathologic complete response were analyzed for potential impacts on recurrence rates and survival outcomes. Results: Forty patients had sufficient data to be included in our study. The median follow-up was 22.5 months. The majority of patients were male (82.5%), Caucasian (84.2%) and had adenocarcinoma histology (97.5%). Altogether, 75% of patients had stage III disease and 67.5% had locoregional nodal involvement. The majority (90%) of patients received some form of taxane and platinum based chemotherapy. Pre-treatment max SUV, post-treatment max SUV, change in max SUV, percent residual max SUV, and complete response on PET-CT were not associated with local recurrence, regional recurrence, disease-free survival, or overall survival. Pathologic complete response was associated with a decrease in the rate of distant metastasis ( P= 0.021) but not disease-free survival ( P= 0.411) or overall survival ( P= 0.878). Conclusions: Response on PET-CT after preoperative chemoradiation is not a predictive factor for recurrence, disease-free survival, or overall survival. Pathologic complete response predicted for a decrease in the rate of distant metastasis but not disease-free survival or overall survival.

To prospectively demonstrate the feasibility of using indocyanine green, a near-infrared (NIR) fluorophore at the minimum dose needed for noninvasive optical imaging of lymph nodes (LNs) in breast cancer patients undergoing sentinel lymph node mapping (SLNM).Informed consent was obtained from 24 women (age range, 30-85 years) who received intradermal subcutaneous injections of 0.31-100 microg indocyanine green in the breast in this IRB-approved, HIPAA-compliant, dose escalation study to find the minimum microdose for imaging. The breast, axilla, and sternum were illuminated with NIR light and the fluorescence generated in the tissue was collected with an NIR-sensitive intensified charged-coupled device. Lymphoscintigraphy was also performed. Resected LNs were evaluated for the presence of radioactivity, blue dye accumulation, and fluorescence. The associations between the resected LNs that were fluorescent and (a) the time elapsed between NIR fluorophore administration and resection and (b) the dosage of NIR fluorophores were tested with the Spearman rank and Pearson product moment correlation tests, respectively.Lymph imaging consistently failed with indocyanine green microdosages between 0.31 and 0.77 microg. When indocyanine green dosages were 10 microg or higher, lymph drainage pathways from the injection site to LNs were imaged in eight of nine women; lymph propulsion was observed in seven of those eight. When propulsion in the breast and axilla regions was present, the mean apparent velocities ranged from 0.08 to 0.32 cm/sec, the time elapsed between "packets" of propelled fluid varied from 14 to 92 seconds. In patients who received 10 microg of indocyanine green or more, a weak negative correlation between the fluorescence status of resected LNs and the time between NIR fluorophore administration and LN resection was found. No statistical association was found between the fluorescence status of resected LNs and the dose of NIR fluorophore.NIR fluorescence imaging of lymph function and LNs is feasible in humans at microdoses that would be needed for future molecular imaging of cancer-positive LNs.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) programs to treat brain tumors were implemented when we first acquired the Brainlab Novalis system in 2003. Two years later, we started an extra-cranial stereotactic radio-ablation or more appropriately a stereotactic body radiation therapy (SBRT) program using the Brainlab Novalis image-guided system at The Methodist Hospital in Houston, Texas. We hereby summarize our initial experience with this system in delivering image-guided SBRT to a total of 80 patients during our first year of clinical implementation, from February 2005 to January 2006. Over 100 lesions in more than 20 distinct anatomical sites were treated. These include all levels of spine from cervical, thoracic, lumbar, and sacral lesions. Spinal lesions encompass intramedullary, intradural, extradural, or osseous compartments. Also treated were lesions in other bony sites including orbit, clavicle, scapula, humerus, sternum, rib, femur, and pelvis (ilium, ischium, and pubis). Primary or metastatic lesions located in the head and neck, supraclavicular region, axilla, mediastinum, lung (both central and peripheral), abdominal wall, liver, kidney, para-aortic lymph nodes, prostate, and pelvis were also treated. In addition to primary radiotherapy, SBRT program using the Brainlab Novalis system allows re-irradiation for recurrence and “boost” after conventional treatment to various anatomical sites. Treating these sites safely and efficaciously requires knowledge in radiation tolerance, fraction size, total dose, biologically equivalent dose (BED), prior radiotherapy, detailed dose volume histograms (DVH) of normal tissues, and the radiosensitive/radioresistant nature of the tumor. Placement of radio-opaque markers (Visicoil, Radiomed) in anatomical sites not in close proximity to bony landmarks (e.g., kidney and liver) helps in measuring motion and providing image guidance during each treatment fraction. Tumor/organ motion data obtained using 4D-CT while the patient is immobilized in the body cast aids in planning treatment margin and determining the need for respiratory motion control, e.g., abdominal compressor, gating, or active breathing control. The inclusion of PET/CT to the Brainlab treatment planning system further refines the target delineation and possibly guides differential fraction size prescription and delivery. The majority of the patients tolerated the SBRT treatment well despite the longer daily treatment time when compared to that of conventional treatment. All patients achieved good pain relief after SBRT. Compared to conventional standard radiotherapy of lower daily fraction size, we observed that the patients achieved faster pain relief and possibly more durable symptom control. Very high local control with stable disease on imaging was observed post SBRT. Our initial experience shows that the Brainlab Novalis system is very versatile in delivering image-guided SBRT to various anatomical sites. This SBRT approach can be applied to either primary or metastatic lesions in the primary, “boost,” or re-irradiation settings. The understanding of fraction size, total dose, BED, and DVH of normal tissues is very important in the treatment planning. Appropriate use of immobilization devices, radio-opaque markers for image-guidance, 4D-CT for tumor/organ motion estimates, and fusion of planning CT scans with biological/functional imaging will further improve the planning and delivery of SBRT, hopefully leading to better treatment outcome.

To describe urodynamic study (UDS) findings in middle-aged and older women with various lower urinary tract symptoms (LUTS) who were found to have a normal study interpretation.Following institutional review board approval, UDS tracings of non-neurogenic women who were tested for various LUTS and whose study was interpreted as normal were reviewed. Demographic data, indications for UDS, and UDS parameter findings were extracted. UDS was conducted according to an established protocol using a 6F dual-lumen catheter (ICS guidelines) with a Laborie system and interpreted with a pre-existing template to standardize each reading. The fill-void study was frequently repeated during the same UDS session to confirm normal findings. Study interpretation was done by a neutral reviewer with UDS expertise.From 2000-2012, 42 middle-aged women, who had been coded as having a normal study, were retrospectively reviewed from a database of over 2200 studies. The majority were Caucasian, with mean age 63 (range 42-85), mean body mass index 24.5 (20-37), mean parity 2 (0-4), and 67% were post-menopausal. Of the 42 patients, 28 underwent a second fill-void study. UDS findings were reported based on clinical indication for UDS: 1) incontinence, 2) pelvic organ prolapse, or 3) other LUTS symptoms. UDS findings were consistent between first and second studies.UDS parameters from a cohort of middle-aged and older women with normal findings could serve as reference values when interpreting urodynamic studies or for designing an age-comparable nomogram.

Nuclear medicine studies have a role in the evaluation of drug induced osteonecrosis of the jaw (DIONJ). In this article, we discuss the current and future applications within nuclear medicine appropriate for evaluation of DIONJ. The emphasis of this article is positron emission tomography (PET) imaging, specifically, with 18F-fluoro-deoxy-glucose (FDG).

Sarcoidosis is a systemic, granulomatous disorder that affects the lungs and mediastinal lymph nodes in most patients. Areas affected by sarcoidosis can exhibit F-fluoro2-deoxy-D-glucose avidity on positron emission tomography (PET). We report the case of a 47-year-old woman with T2N0 cancer of the right breast who was initially diagnosed as stage IV because of multiple areas of mediastinal and supraclavicular PET-positive lymphadenopathy. Biopsy of a supraclavicular lymph node showed noncaseating granulomas, consistent with sarcoidosis, leading to appropriate treatment for her stage IIA disease. The imaging characteristics of sarcoidosis and its possible implications in staging and diagnosis of malignancy, more specifically in breast cancer patients, are discussed herein.

The distinction between treatment effect and recurrent brain malignancy has been a controversial topic for quite some time, with various proponents and opponents for the various cross-sectional neuroimaging modalities. The goal of this manuscript is to provide the latest information on positron emission tomography (PET) molecular imaging, offer other options within the realm of molecular imaging, and to let the reader’s ultimate decision regarding follow-up imaging be made on a case-by-case basis based upon available resources and user experience. Delineation between treatment effect and tumor recurrence is an exceedingly important decision in the era of more focused, targeted therapy, whether anti-angiogenic, immunologic, or radiotherapy. The consequences of an incorrect assessment are obvious, leading to unnecessary treatment and morbidity, delayed treatment, or shortened survival. Various modalities have been proposed to follow such lesions after initial treatment: MRI, MRS, brain PET, and brain single photon emission computed tomography (SPECT). Only molecular imaging (PET and SPECT) will be discussed in this article. Molecular imaging is distinguished from anatomical imaging in that it requires intact intraand extra-cellular architecture, whereas anatomical imaging only requires an intact structure. Cancer begins at a cellular level, and thusly, microscopic changes precede macroscopic changes. No imaging modality can replace a microscopic diagnosis, but current technology attempts to model a microscopic process non-invasively. This has inherent implications of: 1. A radiographically negative scan cannot exclude microscopic disease. 2. Molecular imaging depends on specific substrate metabolism by tumors. If the particular tumor cannot metabolize or concentrate the substrate, false negative scans will occur. 3. False positive scans can occur when substrates are metabolized or concentrated by cells related to non-neoplastic processes, such as inflammation or infection. These implications lead to the paradigmof follow up imaging after initial diagnosis and treatment: how to separate cases of residual/recurrent disease from treatment response. The optimal imaging algorithm has not been clearly delineated.

Department of Radiation Oncology, The Methodist Hospital, Research Institute, ouston, TX Department of Radiation Oncology, The Methodist Hospital, Houston, TX Department of Radiology and Radiation Oncology, Kitasato University School of edicine, Sagamihara, Kanagawa, Japan Department of Radiation Oncology, Cancer Hospital (Institute), Chinese Academy f Medical Sciences, Peking Union Medical College, Beijing, China Department of Radiology, The Methodist Hospital, Houston, TX Medical Branch, The University of Texas, Houston, TX Division of Oncology, The University of Texas, Health Science Center, Memorial ermann Cancer Center, Houston, TX

Purpose Brain metastases from renal cell carcinoma (RCC) have been successfully treated with stereotactic radiosurgery (SRS). Metastases to extra-cranial sites may be treated with similar success using stereotactic body radiation therapy (SBRT), where image-guidance allows for the delivery of precise high-dose radiation in a few fractions. This paper reports the authors' initial experience with image-guided SBRT in treating primary and metastatic RCC. Materials and methods The image-guided Brainlab Novalis stereotactic system was used. Fourteen patients with 23 extra-cranial metastatic RCC lesions (orbits, head and neck, lung, mediastinum, sternum, clavicle, scapula, humerus, rib, spine and abdominal wall) and two patients with biopsy-proven primary RCC (not surgical candidates) were treated with SBRT (24-40 Gy in 3-6 fractions over 1-2 weeks). All patients were immobilised in body cast or head and neck mask. Image-guidance was used for all fractions. PET/CT images were fused with simulation CT images to assist in target delineation and dose determination. SMART (simultaneous modulated accelerated radiation therapy) boost approach was adopted. 4D-CT was utilised to assess tumour/organ motion and assist in determining planning target volume margins. Results Median follow-up was nine months. Thirteen patients (93%) who received SBRT to extra-cranial metastases achieved symptomatic relief. Two patients had local progression, yielding a local control rate of 87%. In the two patients with primary RCC, tumour size remained unchanged but their pain improved, and their renal function was unchanged post SBRT. There were no significant treatment-related side effects. Conclusion Image-guided SBRT provides excellent symptom palliation and local control without any significant toxicity. SBRT may represent a novel, non-invasive, nephron-sparing option for the treatment of primary RCC as well as extra-cranial metastatic RCC.

Fully three-dimensional (3-D) reconstruction algorithms have the potential to better utilize PET data acquired in true 3-D acquisition modes, as compared to 2-D approaches involving data reduction through rebinning procedures followed by a 2-D or 2.5-D reconstruction. Our previous studies, involving simulated and real phantom data from PET scanners working purely in 3-D acquisition mode, showed that the fully 3-D reconstruction approaches bring appreciable improvement on physical measures and visual image quality as well. Reconstruction procedures utilized in those studies were based upon the row action maximum likelihood algorithm (RAMLA) implemented on our clinical scanners. The purpose of this study was to investigate if the fully 3-D RAMLA reconstruction software brings an appreciable improvement in clinical image quality and reader confidence.Ninety patient scans acquired on the Philips CPET scanner at our institution were reconstructed using 2.5-D RAMLA and 3-D RAMLA with differing reconstruction parameters. These scans were blindly presented to four experienced PET scan readers who graded various aspects of image quality.Our study concluded that 3-D RAMLA on the CPET scanner reduces artifacts and image noise and improves clinical confidence in interpreting PET images.This study led to the routine use of 3-D RAMLA reconstruction on the CPET scanner at our institution.

The aim of this study was to determine the accuracy of (18)F-FDG PET in detecting recurrent melanoma.PET findings were compared with those obtained by standard diagnostic clinical procedures (CP) to establish the role of PET in the management of patients with melanoma. From 156 patients with confirmed melanoma and recurrence suspected by clinical examination, 184 PET scans were retrospectively reviewed. Histology or clinical follow-up was used for final diagnosis.The sensitivity and specificity of PET for detecting lesions on an individual-patient basis were 74% and 86%, respectively, compared with respective values of 58% and 45% for CP alone. The overall accuracy for PET was 81%, compared with 52% for other methods. PET was more accurate (91% vs. 67%) than CP in detecting locoregional disease and distant metastases (85% vs. 55%), and PET results led to a change in the planned clinical management of 36% of patients included in this study. PET was more accurate than CT in detecting skin lesions, malignant lymph nodes, and metastases to the abdomen, liver, and bone. In the assessment of pulmonary disease, PET showed higher specificity (92% vs. 70%) than CT for the detection of lung parenchyma lesions; however, the sensitivity was better for CT (93%) than for PET (57%).PET is better than CP in detecting locoregional disease and distant metastases in all sites except the lung, where it appears to be a useful adjunct to CT. The use of PET as a routine clinical tool can lead to a substantial change in the clinical management of suspected recurrent melanoma.

14603 Background: Emergence of targeted therapy for MRCC has been a turning point in improving outcomes. Evaluation of a tyrosine kinase inhibitor (TKI) plus an mTOR inhibitor to increase the magni...

14659 Background: Renal cell cancer (RCC) frequently overexpresses basic vascular endothelial growth factor, epithelial growth factor, and platelet derived growth factor. A phase I combination of p...

5107 Background: RAD001 is an oral mammalian target of Rapamycin (mTOR) inhibitor. Three mechanisms of anti-tumor activity; shuts down tumor response to nutrients and growth factors; cell cycle arrest at late G1 and anti-angiogenesis via VEGF. Molecular alterations in the mTOR modular pathway increase sensitivity in PTEN deficient tumors such as RCC. Endpoints: time-to-progression (TTP), response rate (RR), overall survival (OS), toxicity, and to assess changes in metabolic imaging utilizing CT-PET. Methods: Eligibility included; predominant clear cell, progressive measurable MRCC, adequate organ/marrow function, zubrod performance status (ZPS) = 2, no more than 1 prior therapy, and no active CNS involvement. RAD001 is given orally at a dose of 10mg daily without an interruption (28-day cycle), with dose modifications for toxicity. Re-evaluation was assessed every 2 cycles (8 weeks). RECIST criteria is utilized. TTP and OS are determined from entry into the study. Results: 41 pts have been enrolled. 37 pts are evaluable for response/toxicity. 2 pts toxicity only. 2 pts screened failures. 31 were male/8 female, median age 60 (38–80) years. 31 pts received prior therapy. 23 pts had a ZPS of 0, 13 /1 and 3/2. Sites of disease included; lung, nodal, liver, bone, adrenal, and kidney. 9 pts had 1 metastatic site, 17 pts/2 and 13 pts/3 or more. 15 pts continue to receive RAD001. 12 pts had partial responses, 19 pts were stable for 3+ months. Median duration of therapy is 8+ (range 01–20+) months. Treatment related adverse events; mucositis, skin rash, pneumonitis, hypophosphatemia, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, thrombocytopenia, anemia and elevated LFTs. PET scans have demonstrated decreased metabolic activity in responding or stable pts. Median overall survival is 11.5+ months (range 01–20+). Conclusion: RAD001 has promising anti-tumor activity in pts with MRCC demonstrated by partial response rate. Anti-tumor activity is further suggested by prolonged TTP =3 months. Anti-tumor activity, toxicity and metabolic imaging correlation will be presented. An additional 40 pts who failed prior sunitinib or sorafenib therapy are being enrolled. No significant financial relationships to disclose.

14572 Background: RCC is often regarded as a radio-resistant tumor. However, brain metastases from RCC have been successful treated with SRS. Therefore, metastases to extra-cranial sites may be treated with similar success using stereotactic body radiation therapy (SBRT), where image-guidance allows for the delivery of precise high dose radiation in a few fractions. We report our experience with SRS/SBRT in the management of primary and metastatic RCC. Methods: The image-guided Novalis radiation therapy system was used. Thirty patients with brain metastases were treated with SRS (16–22 Gy in a single fraction). Five of these patients underwent resection of their metastatic lesions after SRS and their pathology were reviewed. Twenty patients with extra-cranial metastatic lesions (orbits, head and neck, lung, mediatinum, sternum, clavicle, scapula, humerus, rib, spine, abdomen) and 2 patients with biopsy proven primary RCC (not surgical candidates), were treated with SBRT (24–32 Gy in 3–4 fractions over 1–2 weeks). All patients were immobilized in body cast and image-guidance was used for all fractions. 4D-CT was utilized in the treatment planning to assess tumor motion. Results: Of the 30 patients who received SRS to brain metastases, 25 showed decreasing or stable lesion size. Five patients showed an increase in size and underwent resection. Their pathology revealed necrosis in >99% of the specimen, with no viable RCC. Nineteen patients who received SBRT to extra-cranial metastases achieved symptom relief. One patient had local progression, yielding a local control rate of 95%. In the 2 patients with primary RCC, tumor size remained unchanged but their pain improved, and their renal function was unchanged post SBRT. There was no significant treatment related side-effect. Conclusions: Precise high dose radiation can cause significant tumor cell death in “radio-resistant” metastases from RCC. It also offers excellent local control and symptom palliation, without significant toxicity. Therefore, SBRT may represent a novel non-invasive, nephron-sparing option for the treatment of primary RCC as well as extra-cranial metastatic RCC. A prospective clinical trial using SBRT for primary and metastatic RCC is on-going. No significant financial relationships to disclose.