Medicine and Health Sciences Commons^™

Anthropometric Factors And Cutaneous Melanoma: Prospective Data From The Population-Based Janus Cohort, Jo S. Stenehjem, Marit B. Veierød, Lill Tove Nilsen, Reza Ghiasvand, Bjørn Johnsen, Tom K. Grimsrud, Ronnie Babigumira, Judy R. Rees, Trude E. Robsahm

Dartmouth Scholarship

The aim of the present study was to prospectively examine risk of cutaneous melanoma (CM) according to measured anthropometric factors, adjusted for exposure to ultraviolet radiation (UVR), in a large population-based cohort in Norway. The Janus Cohort, including 292,851 Norwegians recruited 1972–2003, was linked to the Cancer Registry of Norway and followed for CM through 2014. Cox regression was used to estimate hazard ratios (HRs) of CM with 95% confidence intervals (CIs). Restricted cubic splines were incorporated into the Cox models to assess possible non-linear relationships. All analyses were adjusted for attained age, indicators of UVR exposure, education, and smoking …

A Protocol For Prospective Studies" "5-Hydroxyvitamin D, Leptin And B Ass Index In Relation To Cutaneou Elanoma Incidence And Survival, Jo S. Stenehjem, Tom K. Grimsrud, Judy R. Rees, Linda Vos, Ronnie Babigumira, Marit B. Veierød, Trude E. Robsahm

Dartmouth Scholarship

Introduction The incidence and mortality rates of

cutaneous melanoma (CM) are increasing among fai skinned populations worldwide. Ultraviolet radiation s the principal risk factor for CM, but is also the mai source of 25-hydroxyvitamin D (25(OH)D), which has associated with reduced risk and better prognosis of cancer types. However, both low and high 25(OH)D l have been associated with increased risk of CM. Obe as measured by body mass index (BMI) is associated risk of several cancers and has also been suggested risk factor for CM, and may also be related to insuffi 25(OH)D and/or high leptin levels. Moreover, contract …

Diffusion Of Digital Breast Tomosynthesis Among Women In Primary Care: Associations With Insurance Type, Cheryl R. Clark, Tor Tosteson, Anna Tosteson, Tracy Onega, Julie Weiss, Kimberly A. Harris, Jennifer S. Haas

Dartmouth Scholarship

Digital breast tomosynthesis (DBT) has shown potential to improve breast cancer screening and diagnosis compared to digital mammography (DM). The FDA approved DBT use in conjunction with conventional DM in 2011, but coverage was approved by CMS recently in 2015. Given changes in coverage policies, it is important to monitor diffusion of DBT by insurance type. This study examined DBT trends and estimated associations with insurance type. From June 2011 to September 2014, DBT use in 22 primary care centers in the Dartmouth -Brigham and Women's Hospital Population-based Research Optimizing Screening through Personalized Regimens research center (PROSPR) was examined among …

The E2f4 Prognostic Signature Predicts Pathological Response To Neoadjuvant Chemotherapy In Breast Cancer Patients, Kenneth M. K. Mark, Frederick S. Varn, Matthew H. Ung, Feng Qian, Chao Cheng

Dartmouth Scholarship

Neoadjuvant chemotherapy is a key component of breast cancer treatment regimens and pathologic complete response to this therapy varies among patients. This is presumably due to differences in the molecular mechanisms that underlie each tumor’s disease pathology. Developing genomic clinical assays that accurately categorize responders from non-responders can provide patients with the most effective therapy for their individual disease. We applied our previously developed E2F4 genomic signature to predict neoadjuvant chemotherapy response in breast cancer. E2F4 individual regulatory activity scores were calculated for 1129 patient samples across 5 independent breast cancer neoadjuvant chemotherapy datasets. Accuracy of the E2F4 signature in …

Associations Between Genetic Variants In Mrna Splicing-Related Genes And Risk Of Lung Cancer: A Pathway-Based Analysis From Published Gwass, Yongchu Pan, Hongliang Liu, Yanru Wang, Xiaozheng Kang, Kouros Owzar, Younghun Han

Dartmouth Scholarship

mRNA splicing is an important mechanism to regulate mRNA expression. Abnormal regulation of thisprocess may lead to lung cancer. Here, we investigated the associations of 11,966 single-nucleotide polymorphisms (SNPs) in 206 mRNA splicing-related genes with lung cancer risk by using the summarydata from six published genome-wide association studies (GWASs) of Transdisciplinary Research in Cancerof the Lung (TRICL) (12,160 cases and 16,838 controls) and another two lung cancer GWASs of Harvard University (984 cases and 970 controls) and deCODE (1,319 cases and 26,380 controls). We found that a total of 12 significant SNPs with false discovery rate (FDR) ≤0.05 were mapped …

Transactivation Of The Estrogen Receptor Promoter By Brca1, William B. Archey, Bradley A. Arrick

Dartmouth Scholarship

Background: Absence of the estrogen receptor-α (ER) is perhaps the most distinctive pathological feature of breast cancers arising in women who inherit a mutation in BRCA1. Two hypotheses, not necessarily mutually exclusive, exist in the literature that describe mechanisms of ER transcriptional repression in breast cancer. One hypothesis suggests that methylation of cytosine–guanine dinucleotides (CpGs) primarily mediates repression, while the other maintains that transcriptional control is mediated by certain positive and negative promoter elements.

Methods: To determine if wild type BRCA1 could induce activity of the ER promoter, we performed a series of tran- sient transfections with ER promoter segments …

A Comparison Between Lynch Syndrome And Sporadic Colorectal Cancer Survivors’ Satisfaction With Their Healthcare Providers, Allison M. Burton-Chase, Wendy M. Parker, Katrina M. Polivka, Ellen R. Gritz

Dartmouth Scholarship

This study evaluated provider satisfaction in a sample of colorectal cancer (CRC) survivors with and without Lynch syndrome (LS). Participants were case–case-matched CRC survivors with (n=75) or without (n=75) LS (mean age of 55; range: 27–93). Participants completed a mailed questionnaire assessing demographics, clinical characteristics, healthcare utilization, psychosocial variables, and provider satisfaction. LS CRC survivors reported lower provider satisfaction scores on three subscales of the Primary Care Assessment Survey: communication (78.14 vs. 83.96; P<0.05), interpersonal treatment (78.58 vs. 85.30; P<0.05), and knowledge of the patient (60.34 vs. 69.86; P<0.01). Among LS CRC survivors, predictors for mean communication and trust subscale scores were location of treatment and socioeconomic status. Higher mean depression scores also were associated with trust, while social support predicted higher satisfaction with communication. Sporadic CRC survivor satisfaction is driven largely by age (communication, interpersonal treatment) and patient anxiety (communication), while seeing a provider more often was associated with increased satisfaction with knowledge of the patient. LS CRC survivors reported lower levels of provider satisfaction than sporadic CRC survivors. LS survivors who received care at The University of Texas MD Anderson Cancer Center, a comprehensive cancer center (CCC), reported higher satisfaction than those receiving care at other institutions. Depressive symptoms and socioeconomic status may impact provider satisfaction ratings. Exploration of other potential predictors of provider satisfaction should be examined in this population. Additionally, further research is needed to examine the potential impact of provider satisfaction on adherence to medical recommendations in LS CRC survivors, particularly those being treated outside of CCCs.

Does Travel Time To A Radiation Facility Impact Patient Decision-Making Regarding Treatment For Prostrate Cancer? A Study Of The New Hampshire State Cancer Registry, Fady Ghali, Maria Celaya, Michael Laviolette, Johann Ingimarsson, Heather Carlos, Judy R. Rees, Elias Hyams

Dartmouth Scholarship

Purpose: We sought to determine whether further distance from a radiation center is associated with lower utilization of external beam radiation therapy (XRT). Methods: We retrospectively identified patients with a new diagnosis of localized prostate cancer (CaP) within the New Hampshire State Cancer Registry from 2004 to 2011. Patients were categorized by age, D’Amico risk category, year of treatment, marital status, season of diagnosis, urban/rural residence, and driving time to the nearest radiation facility. Treatment decisions were stratified into those requiring multiple trips (XRT) or a single trip (surgery or brachytherapy). Multivariable regression analysis was performed. Results: A total of …

Constitutively Activated Pi3k Accelerates Tumor Initiation And Modifies Histopathology Of Breast Cancer, M. R. Sheen, J. D. Marotti, M. J. Allegrezza, M. Rutkowski, J. R. Conejo-Garcia, S. Fiering

Dartmouth Scholarship

The gene encoding phosphatidylinositol 3-kinase catalytic subunit α-isoform (PIK3CA, p110α) is frequently activated by mutation in human cancers. Based on detection in some breast cancer precursors, PIK3CA mutations have been proposed to have a role in tumor initiation. To investigate this hypothesis, we generated a novel mouse model with a Cre-recombinase regulated allele of p110α (myristoylated-p110α, myr-p110α) along with p53fl/fl deletion and KrasG12D also regulated by Cre-recombinase. After instillation of adenovirus-expressing Cre-recombinase into mammary ducts, we found that myr-p110α accelerated breast tumor initiation in a copy number-dependent manner. Breast tumors induced by p53fl/fl;KrasG12D with no or one copy of myr-p110α …

A Novel Genetic Variant In Long Non-Coding Rna Gene Nexn-As1 Is Associated With Risk Of Lung Cancer, Hua Yuan, Hongliang Liu, Zhensheng Liu, Kouros Owzar

Dartmouth Scholarship

Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wideassociation studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortiumin populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10−7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University anddeCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant(odds ratio = 1.17; 95% confidence interval = 1.11–1.24; P = 8.31 × 10−9). In further in silico analysis,rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

Elevated Mtss1 Expression Associated With Metastasis And Poor Prognosis Of Residual Hepatitis B-Related Hepatocellular Carcinoma, Xiu-Yan Huang, Zi-Li Huang, Bin Xu, Zi Chen

Dartmouth Scholarship

Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear.

Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed.

Human Polyomaviruses And Incidence Of Cutaneous Squamous Cell Carcinoma In The New Hampshire Skin Cancer Study, Anala Gossai, Tim Waterboer, Anne G. Hoen, Shohreh F. Farzan, Heather Nelson, Angelika Michel, Martina Willhauck-Fleckenstein, Brock Christensen, Ann Perry, Michael Pawlita, Margaret Karagas

Dartmouth Scholarship

Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epi- thelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population- based case–control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glu- tathione S-transferase capture assay of recombinantly expressed …

Associations Between Advanced Cancer Patients' Survival And Family Caregiver Presence And Burden, J. Nicholas Dionne-Odom, Jay G. Hull, Michelle Y. Martin, Kathleen D. Lyons

Dartmouth Scholarship

We conducted a randomized controlled trial (RCT) of an early palliative care intervention (ENABLE: Educate, Nurture, Advise, Before Life Ends) for persons with advanced cancer and their family caregivers. Not all patient participants had a caregiver coparticipant; hence, we explored whether there were relation- ships between patient survival, having an enrolled caregiver, and caregiver out- comes prior to death. One hundred and twenty-three patient-caregiver dyads and 84 patients without a caregiver coparticipant participated in the ENABLE early versus delayed (12 weeks later) RCT. We collected caregiver quality-of-life (QOL), depression, and burden (objective, stress, and demand) measures every 6 weeks for …

‘Much Clearer With Pictures’: Using Community-Based Participatory Research To Design And Test A Picture Option Grid For Underserved Patients With Breast Cancer, Marie-Anne Durand, Shama Alam, Stuart W. Grande, Glyn Elwyn

Dartmouth Scholarship

Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer.

Cyclin-Dependent Kinase Inhibitor P1446a Induces Apoptosis In A Jnk/P38 Mapk-Dependent Manner In Chronic Lymphocytic Leukemia B-Cells, Cody Paiva, J. Claire Godbersen, Ryan S. Soderquist, Taylor Rowland, Sumner Kilmarx

Dartmouth Scholarship

CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we conducted a pre-clinical study of a novel orally active kinase inhibitor P1446A in CLL B-cells. P1446A inhibited CDKs at nanomolar concentrations and induced rapid apoptosis of CLL cells in vitro, irrespective of chromosomal abnormalities or IGHV mutational status. Apoptosis preceded inactivation of RNA polymerase, and was accompanied by …

Microrna Molecular Profiling From Matched Tumor And Bio-Fluids In Bladder Cancer, David A. Armstrong, Benjamin B. Green, John D. Seigne, Alan R. Schned, Carmen Marsit

Dartmouth Scholarship

MicroRNAs have been identified as potential cancer biomarkers due to their presence and stability in many body fluids including urine and plasma, but the relationship of the pattern of expression of these messengers across various biological media has not been addressed and could provide important information in order to translate these biomarkers for epidemiologic or clinical use. We analyzed microRNA of matched FFPE-tumor tissue, plasma, urine exosomes (n = 16) and WBCs (n = 11) from patients with bladder cancer, using Nanostring miRNA assays and droplet digital PCR for validation. Pearson correlations were used to compare expression between …

Mice Null For The Deubiquitinase Usp18 Spontaneously Develop Leiomyosarcomas, Fadzai Chinyengetere, David J. Sekula, Yun Lu, Andrew J. Giustini, Aarti Sanglikar, Masanori Kawakami, Tian Ma

Dartmouth Scholarship

USP18 (ubiquitin-specific protease 18) removes ubiquitin-like modifier interferon stimulated gene 15 (ISG15) from conjugated proteins. USP18 null mice in a FVB/N background develop tumors as early as 2 months of age. These tumors are leiomyosarcomas and thus represent a new murine model for this disease.

Numerical Chromosomal Instability Mediates Susceptibility To Radiation Treatment, Samuel F. Bakhoum, Lilian Kabeche, Matthew D. Wood, Christopher D. Laucius

Dartmouth Scholarship

The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated radiation therapy. However, the mechanism for this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads to mitotic chromosome segregation errors in vivo and long-lasting aneuploidy in tumour-derived cell lines. These mitotic errors generate an abundance of micronuclei that predispose chromosomes to subsequent catastrophic pulverization thereby independently amplifying radiation-induced genome damage. Experimentally suppressing whole-chromosome missegregation reduces downstream chromosomal defects and significantly increases the viability of irradiated mitotic cells. Further, orthotopically transplanted human glioblastoma tumours in which …

Dna Methylation In Ductal Carcinoma In Situ Related With Future Development Of Invasive Breast Cancer, Kevin C. Johnson, Devin C. Koestler, Thomas Fleischer, Panpan Chen, Erik G. Jenson, Jonathan D. Marotti, Tracy Onega, Vessela N. Kristenen, Brock C. Christensen

Dartmouth Scholarship

Background: Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-invasive lesion associated with an increased risk for future invasive ductal carcinoma. However, accurate risk stratification for development of invasive disease and appropriate treatment decisions remain clinical challenges. DNA methylation alterations are early events in the progression of cancer and represent emerging molecular markers that may predict invasive recurrence more accurately than traditional measures of DCIS prognosis.

Results: We measured DNA methylation using the Illumina HumanMethylation450K array of estrogen-receptor positive DCIS (n = 40) and adjacent-normal (n = 15) tissues from subjects in the New Hampshire Mammography Network longitudinal breast imaging …

Trends In Initial Management Of Prostate Cancer In New Hampshire, Johann Ingimarsson, Maria Celaya, Michael Laviolette, Judy R. Rees, Elias Hyams

Dartmouth Scholarship

Purpose Prostate cancer management strategies are evolving with increased understanding of the disease. Specifically, there is emerging evidence that ‘‘low-risk’’ cancer is best treated with observation, while localized ‘‘high-risk’’ cancer requires aggressive curative therapy. In this study, we evaluated trends in management of prostate cancer in New Hampshire to determine adherence to evidence- based practice. Methods From the New Hampshire State Cancer Registry, cases of clinically localized prostate cancer diagnosed in 2004–2011 were identified and classified according to D’Amico criteria. Initial treatment modality was recorded as surgery, radiation therapy, expectant management, or hormone therapy. Temporal trends were assessed by Chi-square …

Role Of A Genetic Variant On The 15q25.1 Lung Cancer Susceptibility Locus In Smoking-Associated Nasopharyngeal Carcinoma, Xuemei Ji, Weidong Zhang, Jiang Gui, Xia Fan, Weiwei Zhang, Yafang Li, Guangyu An, Dakai Zhu, Qiang Hu

Dartmouth Scholarship

Background: The 15q25.1 lung cancer susceptibility locus, containing CHRNA5, could modify lung cancer susceptibility and multiple smoking related phenotypes. However, no studies have investigated the association between CHRNA5 rs3841324, which has been proven to have the highest association with CHRNA5 mRNA expression, and the risk of other smoking-associated cancers, except lung cancer. In the current study we examined the association between rs3841324 and susceptibility to smoking-associated nasopharyngeal carcinoma (NPC).

Methods: In this case-control study we genotyped the CHRNA5 rs3841324 polymorphism with 400 NPC cases and 491 healthy controls who were Han Chinese and frequency-matched by age (±5 years), gender, and …

The Influence Of Race/Ethnicity And Place Of Service On Breast Reconstruction For Medicare Beneficiaries With Mastectomy, Tracy Onega, Julie Weiss, Karla Kerlikowske, Karen Wernli

Dartmouth Scholarship

Racial disparities in breast reconstruction for breast cancer are documented. Place of service has contributed to disparities in cancer care; but the interaction of race/ethnicity and place of service has not been explicitly examined. We examined whether place of service modified the effect of race/ethnicity on receipt of reconstruction. We included women with a mastectomy for incident breast cancer in SEER-Medicare from 2005-2009. Using Medicare claims, we determined breast reconstruction within 6 months. Facility characteristics included: rural/urban location, teaching status, NCI Cancer Center designation, cooperative oncology group membership, Disproportionate Share Hospital (DSH) status, and breast surgery volume. Using multivariable logistic …

A Novel Curcumin Analog (H-4073) Enhances The Therapeutic Efficacy Of Cisplatin Treatment In Head And Neck Cancer, Bhavna Kumar, Arti Yadav, Kalman Hideg, Periannan Kuppusamy

Dartmouth Scholarship

Chemotherapy constitutes the standard modality of treatment for localized head and neck squamous cell carcinomas (HNSCC). However, many patients fail to respond and relapse after this treatments due to the acquisition of chemo- resistance. Therefore, there is an urgent need to develop novel drugs that could reverse the resistant phenotype. Curcumin, the constituent of the spice turmeric has been shown to have anti-inflammatory, anti-oxidant and anti-proliferative properties in several tumor types. However, use of curcumin has been limited due to its poor bio-absorption. Recently, a novel class of curcumin analogs, based on diarylidenylpiperidones (DAP), has been developed by incorporating a …

Influence Networks Based On Coexpression Improve Drug Target Discovery For The Development Of Novel Cancer Therapeutics, Nadia M. Penrod, Jason H. Moore

Dartmouth Scholarship

Background: Thedemandfornovelmolecularlytargeteddrugswillcontinuetoriseaswemoveforwardtowardthe goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. …

An Imaging-Based Platform For High-Content, Quantitative Evaluation Of Therapeutic Response In 3d Tumour Models, Jonathan P. Celli, Imran Rizvi, Adam R. Blanden, Iqbal Massodi, Iqbal Massodi, Michael D. Glidden, Brian Pogue, Tayyaba Hasan

Dartmouth Scholarship

While it is increasingly recognized that three-dimensional (3D) cell culture models recapitulate drug responses of human cancers with more fidelity than monolayer cultures, a lack of quantitative analysis methods limit their implementation for reliable and routine assessment of emerging therapies. Here, we introduce an approach based on computational analysis of fluorescence image data to provide high-content readouts of dose-dependent cytotoxicity, growth inhibition, treatment-induced architectural changes and size-dependent response in 3D tumour models. We demonstrate this approach in adherent 3D ovarian and pancreatic multiwell extracellular matrix tumour overlays subjected to a panel of clinically relevant cytotoxic modalities and appropriately designed controls …

Let-7 Microrna-Binding-Site Polymorphism In The 3′Utr Of Kras And Colorectal Cancer Outcome: A Systematic Review And Meta-Analysis, Scott M. Langevin, Brock C. Christensen

Dartmouth Scholarship

There is a small but growing body of literature regarding the predictive utility of a Let-7 microRNA-binding-site polymorphism in the 30 -untranslated region (UTR) of KRAS (KRAS-LCS6) for colorectal cancer outcome, although the results are conflicting. We performed a review and meta-analysis in an attempt to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on KRAS let-7 microRNA-binding site polymorphism (LCS6; rs61764370) and colorectal cancer outcome. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or estimated from each manuscript. Log HRs and log CIs were combined across studies using the inverse-variance …

Dynamic Dual-Tracer Mri-Guided Fluorescence Tomography To Quantify Receptor Density In Vivo, Scott C. Davis, Kimberley S. Samkoe, Kenneth M. Tichauer, Kristian J. Sexton, Jason R. Gunn, Sophie J. Deharvengt, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

The up-regulation of cell surface receptors has become a central focus in personalized cancer treatment; however, because of the complex nature of contrast agent pharmacokinetics in tumor tissue, methods to quantify receptor binding in vivo remain elusive. Here, we present a dual-tracer optical technique for noninvasive estimation of specific receptor binding in cancer. A multispectral MRI-coupled fluorescence molecular tomography system was used to image the uptake kinetics of two fluorescent tracers injected simultaneously, one tracer targeted to the receptor of interest and the other tracer a nontargeted reference. These dynamic tracer data were then fit to a dual-tracer compartmental model …

Feasibility Of Tomotherapy-Based Image-Guided Radiotherapy To Reduce Aspiration Risk In Patients With Non-Laryngeal And Non-Pharyngeal Head And Neck Cancer, Nam P. Nguyen, Lexie Smith-Raymond, Vincent Vinh-Hung, Paul Vos, Rick Davis, Anand Desai, Thomas Sroka

Dartmouth Scholarship

Purpose: The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk.

Building A Statistical Model For Predicting Cancer Genes, Ivan P. Gorlov, Christopher J. Logothetis, Shenying Fang, Olga Y. Gorlova, Christopher Amos

Dartmouth Scholarship

More than 400 cancer genes have been identified in the human genome. The list is not yet complete. Statistical models predicting cancer genes may help with identification of novel cancer gene candidates. We used known prostate cancer (PCa) genes (identified through KnowledgeNet) as a training set to build a binary logistic regression model identifying PCa genes. Internal and external validation of the model was conducted using a validation set (also from KnowledgeNet), permutations, and external data on genes with recurrent prostate tumor mutations. We evaluated a set of 33 gene characteristics as predictors. Sixteen of the original 33 predictors were …

Quantitative, Spectrally-Resolved Intraoperative Fluorescence Imaging, Pablo A. Valdés, Frederic Leblond, Valerie L. Jacobs, Brian C. Wilson, Keith D. Paulsen, David W. Roberts

Dartmouth Scholarship

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the …