Memorial SloanKettering Cancer Center

New York City, NY, United States

Memorial SloanKettering Cancer Center

New York City, NY, United States
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Blazic I.M.,Memorial SloanKettering Cancer Center | Lilic G.B.,Center for Radiology and MRI | Gajic M.M.,Institute for Medical Statistics and Informatics
Radiology | Year: 2017

Purpose: To determine the impact of three different methods of region of interest (ROI) positioning for apparent diffusion coeffcient (ADC) measurements on the assessment of complete response (CR) to neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with rectal cancer. Materials and Methods: Institutional review board approval was obtained for this study; all patients gave written informed consent. ADCs were measured by two radiologists using three circular ROIs (three-ROIs), single-section (SS), and whole-tumor volume (WTV) methods in 62 patients with locally advanced rectal cancer on pre-and post-CRT images. Interobserver variability was analyzed by calculating intraclass correlation coeffcient (ICC). Descriptive statistics and areas under the receiver operating characteristic curves (AUCs) were calculated to evaluate performance in determining CR from pre-and post-CRT ADCs and ADC change. Histopathologic tumor regression grade was the reference standard. Results: SS and WTV methods yielded higher AUCs than did the three-ROIs method when determining CR from post-CRT ADC (0.874 [95% confdence interval {CI}: 0.778, 0.970] and 0.886 [95% CI: 0.781, 0.990] vs 0.731 [95% CI: 0.583, 0.878], respectively; P =.033 and P =.003) and numeric change (0.892 [95% CI: 0.812, 0.972] and 0.897 [95% CI: 0.801, 0.994] vs 0.740 [95% CI: 0.591, 0.890], respectively; P =.048 and P =.0021). Respective accuracies of SS, WTV, and three-ROIs methods were 79% (49 of 62), 77% (48 of 62), and 61% (38 of 62) for post-CRT, 79% (49 of 62), 86% (53 of 62), and 60% (37 of 62) for numeric ADC change, and 77% (48 of 62), 84% (52 of 62), and 57% (35 of 62) for percentage ADC change (ADC cut-offs: 1.21, 1.30, and 1.05 × 1023 mm2/sec, 0.33, 0.45, and 0.27 × 1023 mm2/sec increases, and 40%, 54%, and 27% increases, respectively). Post-CRT and ADC change measurements achieved negative predictive values of 96% (44 of 46) to 100% (39 of 39). Intraobserver agreement was highest for WTV-derived ADCs (ICC, 0.742 [95% CI: 0.316, 0.892] to 0.891 [95% CI: 0.615, 0.956]) and higher for all pretreatment than posttreatment measurements (ICC, 0.761 [95% CI: 0.209, 0.930] and 0.648 [95% CI: 0.164, 0.895] for three-ROIs method, 0.608 [95% CI: 0.287, 0.844] and 0.582 [95% CI: 0.176, 0.870] for SS method, 0.891 [95% CI: 0.615, 0.956] and 0.742 for WTV method [95% CI: 0.316, 0.892]). Conclusion: Tumor ADCs are highly dependent on the ROI positioning method used. Larger area measurements yield greater accuracy in response assessment. Post-CRT ADCs and values of ADC changes accurately identify noncomplete responders. WTV measurement of percentage ADC change provides the best results. © 2016 RSNA.


Rothenberg L.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2012

The introduction of new cross‐sectional imaging techniques in the 1970's and 1980's led to great improvements in the diagnosis and treatment of medical conditions. In this symposium, we will chronicle the development of three of these Methods: computed tomography (CT), magnetic resonance imaging (MRI), and ultrasonic imaging (US). Computed Tomography Early attempts to obtain trans‐axial radiographs employed unconventional mechanical motions of the x‐ray tube and screen‐film image receptor that produced images of limited utility. The introduction of the EMI Mk I computerized axial tomography (CAT) unit revolutionized imaging by providing electronic trans‐axial images of the brain that allowed clear separation of various tissues with very similar attenuation coefficients. The great success of this imaging process led to the Nobel Prize for Hounsfield and Cormack in 1979. Examples from the evolution of the x‐ray computed tomography technique, introduced initially by a large number of manufacturers over several “generations” of CT scanners will be presented. The changes include improvements in x‐ray detectors and detector arrays, image reconstruction algorithms, and body bolus/filters, as well as the introduction of slip ring technology. These upgrades led to shorter scanning and reconstruction times, greater body coverage per rotation, and reduced artifacts, along with increased spatial resolution and improved low contrast performance. A very brief overview of additional cross sectional x‐ray imaging devices and techniques that have been developed in recent years will conclude this section of the symposium. © 2012, American Association of Physicists in Medicine. All rights reserved.


Yorke E.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2012

The dose and dose‐volume metrics used in treatment planning are surrogates for the beneficial (tumor control) and adverse (normal tissue complications) biological effects of radiation therapy. It would be clearer to skip the surrogates and go directly to the effects. While this is not currently possible, or safe, planners and physicians are cautiously putting biologically related models into clinical use to assist them in evaluating treatment plan quality and in driving inverse planning algorithms. In this part of the session, we briefly review commonly used models that relate external beam radiation dose distributions to tumor control probability (TCP) or normal tissue complication probability (NTCP) for major complications Topics discussed include: 1. The common TCP and NTCP models 2. Current data supporting these and good sources of updates 3. Limitations of current models 4. Pitfalls ‐ why current models should be used with caution 5. Opportunities for future improvement Learning objectives: 1. Understand where to access NTCP model information and parameters and where to check for updates 2. Understand qualitative features of the dose‐volume dependence of three major dose‐limiting complications 3. Understand some of the pitfalls of taking current models too literally. © 2012, American Association of Physicists in Medicine. All rights reserved.


Xiong W.,Memorial SloanKettering Cancer Center | Huang D.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2013

Purpose: MRI image is most frequently used for target contouring and treatment planning in Gamma Knife stereotactic radiosurgery (SRS). This study is to compare geometric and dosimetric accuracy of CT and MRI‐based Monte Carlo (M.C.) simulation for Gamma Knife SRS. Methods: A cylindrical water phantom with scale for MRI QA was scanned and the MRI images were transferred to a planning system for geometric analysis. M.C. simulation was applied on patient geometries reconstructed from CT and MRI data for dosimetric comparison. In the M.C. simulation, Gamma Knife (Model C) unit geometry and material were reconstructed according to original unit. A heterogeneous patient MRI geometry was created by putting a 1.8 g/cc skull in the unity homogeneous MRI geometry based on MRI anatomy knowledge. The dose was calculated using M.C. simulation in both homogenous and inhomogeneous CT and MRI geometries with identical beam parameters. The dose distribution was compared by overlapping the isodose‐lines for each calculation. The DVH was derived by collecting dose on a small volume around isocenter. Results: In MR image, the maximum errors along all directions are within 0.5 mm in the volume of interest (VOI) which is about 15cm high and 20cm diameter in x and y plane. There is no observable difference of relative isodose lines in CT and MRI geometries. However, the absolute dose in heterogeneous CT geometry was 3.2% lower than the dose in homogeneous CT geometry from the DVH comparison. The absolute dose in homogeneous MRI phantom was 3.3% higher that dose in heterogeneous CT geometry. After applying heterogeneity correction to the skull for MRI, the difference was reduced to less than 2%. Conclusion: MRI image distortion is small with the maximum distortion within 0.5mm in VOI. MRI‐based Monte Carlo planning for Gamma Knife is feasible after applying proper skull heterogeneity correction. © 2013, American Association of Physicists in Medicine. All rights reserved.


Mageras G.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2011

This presentation reviews methods to manage respiratory motion during radiation delivery. Technological advances have made available new capabilities for measuring and reducing respiratory motion. Optical and spirometry devices, external to the patient, provide monitoring of patient voluntary motion and respiration. Radiographic detection of implanted fiducial markers has enabled internal motion monitoring at treatment. Methods that are currently used clinically or under investigation to actively mitigate respiratory motion include abdominal compression, breath hold, respiratory gating, breathing‐synchronized treatment, and real‐time motion tracking. Abdominal compression is the most commonly used technique with stereotactic body radiotherapy to reduce target respiratory motion. The organ deformations induced by the compression and residual target motion generally will vary with each patient setup, thus requiring image‐based evaluation and adjustment. Most widely used gating and breath‐hold systems infer tumor position from respiration monitors external to the patient. A large source of uncertainty stems from changes in the positional relationship between tumor and external signal, both between and within treatment fractions, thus requiring at least daily image guidance and recalibration. Real‐time motion tracking, involving image‐guided treatment delivery with automated motion correction, is challenging owing to temporal variations in breathing patterns. One such clinical system is based on a motion model that correlates real‐time external motion monitors with periodic x‐ray images of implanted fiducial markers. The accuracy of motion corrections depend on the x‐ray imaging system, tracking algorithm, and motion correlation model. Accuracy of implanted markers depends on their proximity and motion relative to the tumor. Learning Objectives: 1. Understand various radiation delivery practices to mitigate respiratory motion. 2. Understand the limitations, current expectations, and possible further improvements of motion mitigation systems. © 2011, American Association of Physicists in Medicine. All rights reserved.


Kirov A.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2011

Positron emission tomography (PET) brings to radiation therapy of cancer the critical advantage of defining the tumor based on its molecular properties. However, delineating the gross tumor volume (GTV) with PET is problematic due to the uncertainties in the biological and physiological processes governing the tracer uptake and to the instrumental inaccuracy of the PET images. Despite this, the delineation of tumors in PET images is used in radiation therapy for target definition, dose painting and treatment outcome assessment. The lecture will provide examples of the different tumor segmentation tasks and point to the different requirements they may present. It will further point to the segmentation challenges arising from the PET image specifics, inaccuracies and uncertainties. It will also propose a classification of the auto‐segmentation methods used in PET and provide examples of few auto‐segmentation methods representative of the different classes. Finally, the need of evaluation and validation of the segmentation techniques will be discussed. Learning objectives: 1. Understand the different requirements to PET segmentation set by the specific goal. 2. Be aware of the physical properties of PET images which affect segmentation accuracy. 3. Be able to provide a simple classification of the auto‐segmentation tools and explain the need for validation. © 2011, American Association of Physicists in Medicine. All rights reserved.


Humm J.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2010

This presentation will focus on methods to validate non‐invasive PET radiotracers for the quantification of loco‐regional hypoxia. MicroPET images will be shown of different hypoxia tracers and their uptake kinetics discussed. The use of compartmental analysis to define parametric images will be compared against single late time point imaging. Digital autoradiography will be used to determine the intra‐tumoral distributions of different hypoxia tracers, which will be compared against endogenous hypoxia‐related proteins, exogenous hypoxia markers and hypoxia reporter‐gene expression. Experiments to validate PET imaging of tumor hypoxia using image guided partial oxygen probes will be discussed. The lecture will conclude with efforts to clinical quantify the hypoxia distribution in head and neck patients. Learning Objectives: 1. Understand the different methods of detecting hypoxia (direct pO2 probe measurement, immunohistochemistry and surrogate imaging approaches). 2. Learn how potential hypoxia radiotracers are validated. 3. Understand the difference between static images of hypoxia radiotracer uptake versus parametric images of tumor hypoxia. 4. Understand the challenges of dose painting loco‐regional hypoxia. © 2010, American Association of Physicists in Medicine. All rights reserved.


Bernstein J.,Memorial SloanKettering Cancer Center
Medical Physics | Year: 2010

Background: Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation induces double strand breaks (DSB). Upon activation by DSB‐inducing agents ATM (for ataxia‐telangiectasia (A‐T) mutated) phosphorylates a large number of downstream targets including the products of several known breast cancer susceptibility genes (e.g. BRCA1 BRCA2 Chek2 p53). In this study we examine whether defects in these breast cancer susceptibility factors are associated with radiation‐induced induced breast cancers. Methods: The WECARE Study is a case‐control study nested within 5 population‐based cancer registries in the US and in Denmark. The 708 cases were women with asynchronous bilateral breast cancer (CBC) and the 1399 controls were women with unilateral breast cancer (UBC) individually matched to cases on year of birth race geographic region and date of diagnosis (interval). All participants were interviewed medical records were comprehensively reviewed and full genetic screening was conducted. For women who received radiation therapy (RT) absorbed radiation doses to quadrants of the (CB) were estimated using dosimetry reconstruction. Rate ratios (RR) and 95% confidence intervals were calculated using multivariable‐adjusted conditional logistic regression models. Results: The mean dose to the specific quadrant of the CB tumor was 1.1 Gy. Women <40 years of age who received >1.0Gy and with >5 year follow‐up had a 3‐fold increased risk of CBC (95% CI‐1.1–1.8). The RR of CBC associated with carrying a BRCA1/2 mutation was 4.2 (95% CI=2.8–6.1); however among carriers radiation was not associated with risk. Among women carrying rare ATM missense mutations the risk of developing CBC was slightly increased but was significantly elevated among women treated with RT and strongest for mutations selected on their likelihood to disrupt structure. Conclusions: Risk of radiation‐associated CBC was inversely related to age at exposure and dose dependent. A subgroup of rare mutations may increase risk of CBC among women with early onset breast cancer treated with RT. However the fraction of CBC attributed to this is quite small suggesting that radiation contributes little to the already high risk of CBC associated with carrying these breast cancer susceptibility factors. Learning Objectives: 1. Understand the role of DSB in CBC 2. Understand the basic study design of the WECARE Study 3. Understand the issues relating to genetic susceptibility and CBC risk. © 2010, American Association of Physicists in Medicine. All rights reserved.


Monson J.R.T.,University of Rochester | Probst C.P.,University of Rochester | Wexner S.D.,Cleveland Clinic | Remzi F.H.,Cleveland Clinic | And 4 more authors.
Annals of Surgery | Year: 2014

Objective: This study examines recent adherence to recommended neoadjuvant chemoradiotherapy guidelines for patients with rectal cancer across geographic regions and institution volume and assesses trends over time. CopyrightBackground: A recent report by the Institute of Medicine described US cancer care as chaotic. Cited deficiencies included wide variation in adherence to evidencebased guidelines even where clear consensus exists.Methods: Patients operated on for clinical stage II and III rectal cancer were selected from the 2006-2011 National Cancer Data Base.Multivariable logistic regressions were used to assess variation in chemotherapy and radiation use by cancer center type, geographical location, and hospital volume. The analysis controlled for patient age at diagnosis, sex, race/ethnicity, primary payer, average household income, average education, urban/rural classification of patient residence, comorbidity, and oncologic stage.Results: There were 30,994 patients who met the inclusion criteria. Use of neoadjuvant radiation therapy and chemotherapy varied significantly by type of cancer center. The highest rates of adherence were observed in highvolume centers compared with lowvolume centers (78% vs 69%; adjusted odds ratio =1.46; P0.001). This variation ismirrored by hospital geographic location. Primary payer and year of diagnosiswere not predictive of rates of neoadjuvant chemoradiotherapy.Conclusions: Adherence to evidencebased treatment guidelines in rectal cancer is suboptimal in the United States, with significant differences based on hospital volume and geographic regions. Little improvement has occurred in the last 5 years. These results support the implementation of standardized care pathways and a Centers of Excellence program for US patients with rectal cancer. © 2014 by Lippincott Williams & Wilkins.


Patent
Adaptive Biotechnologies Corporation and Memorial Sloankettering Cancer Center | Date: 2013-10-01

Disclosed are methods for determining the immunological status of the adaptive immune system of a subject by identifying and quantifying rearranged DNA (and/or subsequently transcribed RNA) sequences encoding T cell receptor (TCR) and/or immunoglobulin (IG) polypeptides, in a lymphoid DNA-containing sample from the subject. TCR and/or IG sequence diversity and sequence distribution permit immunocompetence and immune repertoire assessment and reflect the degree of T cell or B cell clonality and clonal expansion in the sample. Methods for stratifying patient populations on the basis of immunocompetence including likelihood of responding to immunotherapy are also described.

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