Medical Genetics Commons^™

Cascade Testing After Exome Sequencing: Retrospective Analysis Of Linked Family Data At 2 Us Laboratories, Julie Stefka, Haley Streff, Pengfei Liu, Meghan Towne, Hadley Stevens Smith

Faculty, Staff and Students Publications

Purpose: Cascade testing, the process of testing a proband's at-risk relatives, is integral to realizing the full value of genomic sequencing. However, there is little empirical evidence on the uptake of cascade testing after a positive exome sequencing (ES) result in a population of probands with diverse clinical indications.

Methods: We retrospectively reviewed administrative data from 2 US clinical laboratories that perform ES. For each proband with a positive ES result, we used linked family data to describe the frequency of relatives' cascade testing performed at the same laboratory, variant detection yield of cascade tests, and characteristics of probands and …

Prevalence And Descriptive Epidemiology Of Turner Syndrome In The United States, 2000-2017: A Report From The National Birth Defects Prevention Network, Bailey A Martin-Giacalone, Angela E Lin, Sonja A Rasmussen, Russell S Kirby, Eirini Nestoridi, Rebecca F Liberman, A J Agopian, John C Carey, Janet D Cragan, Nina Forestieri, Vinita Leedom, Aubree Boyce, Wendy N Nembhard, Monika Piccardi, Theresa Sandidge, Xiaoyi Shan, Charles J Shumate, Erin B Stallings, Roger Stevenson, Philip J Lupo

Faculty, Staff and Students Publications

The lack of United States population-based data on Turner syndrome limits assessments of prevalence and associated characteristics for this sex chromosome abnormality. Therefore, we collated 2000-2017 data from seven birth defects surveillance programs within the National Birth Defects Prevention Network. We estimated the prevalence of karyotype-confirmed Turner syndrome diagnosed within the first year of life. We also calculated the proportion of cases with commonly ascertained birth defects, assessed associations with maternal and infant characteristics using prevalence ratios (PR) with 95% confidence intervals (CI), and estimated survival probability. The prevalence of Turner syndrome of any pregnancy outcome was 3.2 per 10,000 …

Late-Onset Cognitive Impairment And Modifiable Risk Factors In Adult Childhood Cancer Survivors, Nicholas S Phillips, Kayla L Stratton, Annalynn M Williams, Tim Ahles, Kirsten K Ness, Harvey Jay Cohen, Kim Edelstein, Yutaka Yasui, Kevin Oeffinger, Eric J Chow, Rebecca M Howell, Leslie L Robison, Gregory T Armstrong, Wendy M Leisenring, Kevin R Krull

Faculty, Staff and Student Publications

Importance: Long-term survivors of childhood cancer may be at elevated risk for new neurocognitive impairment and decline as they age into adulthood.

Objective: To determine whether aging adult childhood cancer survivors report more new-onset neurocognitive impairments compared with their siblings and to identify risk factors associated with such impairments.

Design, setting, and participants: Participants of this cohort study included adult survivors of childhood cancer from the Childhood Cancer Survivor Study and their siblings as a control group. The original cohort included survivors who received a diagnosis between January 1, 1970, and December 31, 1986, for whom longitudinal neurocognitive assessment was …

Secondary Validation Of An Ovarian Cancer-Specific Comorbidity Index In A Us Population, Chelsey Vranes, Hui Zhao, Mette Calundann Noer, Shuangshuang Fu, Charlotte C Sun, Ross Harrison, Pedro T Ramirez, Claus Kim Høgdall, Sharon H Giordano, Larissa A Meyer

Faculty, Staff and Student Publications

Objectives: The Ovarian Cancer Comorbidity Index (OCCI) is an age-specific index developed and previously found to be more predictive of overall and cancer-specific survival than the Charlson Comorbidity Index (CCI). The objective was to perform secondary validation of the OCCI in a US population.

Methods: A cohort of ovarian cancer patients undergoing primary or interval cytoreductive surgery from January 2005 to January 2012 was identified in SEER-Medicare. OCCI scores were calculated with the regression coefficients determined from the original developmental cohort for five comorbidities. Cox regression analyses were used to calculate associations between the OCCI risk groups and 5-year overall …

Outcomes Of The “Brca Quality Improvement Dissemination Program”: An Initiative To Improve Patient Receipt Of Cancer Genetics Services At Five Health Systems, Erica M Bednar, Minxing Chen, Michael T Walsh, Amanda L Eppolito, Molly H Klein, Kelly Teed, Brittany Hodge, Jordan Hunter, Han Gill Chao, Dillon Davis, Wilshauna Serchion, Cara Yobbi, Rebekah Krukenberg, Sandra B Jenkinson, Jennifer J Moore, Cassandra Garcia, Fatimaeliza Gonzalez, Towanna Murray, Linda D Nielsen, Brenda Ho, Megan Haas, Sarah B Greenzweig, Abby Anderson, Christina Johnson, Nichole A Morman, Elizabeth Bowdish, Emaline Wise, Julia N Cooper, Pauline Kefalas Russ, Katelyn Tondo-Steele, Buonarotti F De Gracia, Brooke Levin, Kristin Mattie, Kathryn Zarnawski, Molly Kalasinski, Jennifer Stone, Caitlin O'Brien, Alexa Bream, Aidan M Kennedy, Rachel A Paul, Michelle Bilbao, Maureen Romero, Rebecca L Carr, Jennifer M Siettmann, Anna K Vercruyssen, Kaycee Leon, Banu K Arun, Andrew V Grainger, David P Warshal, Erin Bowman, Timothy A Goedde, Deepa Halaharvi, Kellie Rath, Generosa Grana, Lida Mina, Karen H Lu

Faculty, Staff and Student Publications

OBJECTIVE: A quality improvement initiative (QII) was conducted with five community-based health systems' oncology care centers (sites A-E). The QII aimed to increase referrals, genetic counseling (GC), and germline genetic testing (GT) for patients with ovarian cancer (OC) and triple-negative breast cancer (TNBC).

METHODS: QII activities occurred at sites over several years, all concluding by December 2020. Medical records of patients with OC and TNBC were reviewed, and rates of referral, GC, and GT of patients diagnosed during the 2 years before the QII were compared to those diagnosed during the QII. Outcomes were analyzed using descriptive statistics, two-sample t-test, …

Pertuzumab, Trastuzumab, And An Aromatase Inhibitor For Her2-Positive And Hormone Receptor-Positive Metastatic Or Locally Advanced Breast Cancer: Pertain Final Analysis, Grazia Arpino, Juan De La Haba Rodríguez, Jean-Marc Ferrero, Sabino De Placido, C Kent Osborne, Dirk Klingbiel, Valentine Revelant, Christine Wohlfarth, Raf Poppe, Mothaffar F Rimawi

Faculty, Staff and Students Publications

PURPOSE: In PERTAIN's primary analysis (31 months' median follow-up), adding pertuzumab to trastuzumab and an aromatase inhibitor (AI) with/without chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated HER2-positive and hormone receptor-positive metastatic or locally advanced breast cancer (M/LABC). A potentially enhanced treatment effect was observed in patients with no induction chemotherapy. We present the final analysis (>6 years' median follow-up).

PATIENTS AND METHODS: Patients (N = 258) were randomized 1:1 to pertuzumab (loading/maintenance: 840/420 mg) plus trastuzumab (loading/maintenance: 8/6 mg/kg) every 3 weeks and an AI (1 mg anastrozole or 2.5 mg letrozole daily; Arm A), …

Bi-Allelic Snapc4 Variants Dysregulate Global Alternative Splicing And Lead To Neuroregression And Progressive Spastic Paraparesis, F Graeme Frost, Marie Morimoto, Prashant Sharma, Lyse Ruaud, Newell Belnap, Daniel G Calame, Yuri Uchiyama, Naomichi Matsumoto, Machteld M Oud, Elise A Ferreira, Vinodh Narayanan, Sampath Rangasamy, Matt Huentelman, Lisa T Emrick, Ikuko Sato-Shirai, Satoko Kumada, Nicole I Wolf, Peter J Steinbach, Yan Huang, Undiagnosed Diseases Network, Barbara N Pusey, Sandrine Passemard, Jonathan Levy, Séverine Drunat, Marie Vincent, Agnès Guet, Emanuele Agolini, Antonio Novelli, Maria Cristina Digilio, Jill A Rosenfeld, Jennifer L Murphy, James R Lupski, Gilbert Vezina, Ellen F Macnamara, David R Adams, Maria T Acosta, Cynthia J Tifft, William A Gahl, May Christine V Malicdan

Faculty, Staff and Students Publications

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development …

Renal-Hepatic-Pancreatic Dysplasia Type 2: Perinatal Lethal Condition Or A Multisystemic Disorder With Variable Expressivity, Kathryn Gunther, Essam M Imseis, Joyce P Samuel, Elizabeth A Hillman, Tiina H Ojala, Timo Jahnukainen, Paul R Hillman

Faculty, Staff and Student Publications

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data.

METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the …

Loss Of Neuron Navigator 2 Impairs Brain And Cerebellar Development, Andrea Accogli, Shenzhao Lu, Ilaria Musante, Paolo Scudieri, Jill A Rosenfeld, Mariasavina Severino, Simona Baldassari, Michele Iacomino, Antonella Riva, Ganna Balagura, Gianluca Piccolo, Carlo Minetti, Denis Roberto, Fan Xia, Razaali Razak, Emily Lawrence, Mohamed Hussein, Emmanuel Yih-Herng Chang, Michelle Holick, Elisa Calì, Emanuela Aliberto, Rosalba De-Sarro, Antonio Gambardella, Undiagnosed Diseases Network, Synaps Study Group, Lisa Emrick, Peter J A Mccaffery, Margaret Clagett-Dame, Paul C Marcogliese, Hugo J Bellen, Seema R Lalani, Federico Zara, Pasquale Striano, Vincenzo Salpietro

Faculty, Staff and Students Publications

Cerebellar hypoplasia and dysplasia encompass a group of clinically and genetically heterogeneous disorders frequently associated with neurodevelopmental impairment. The Neuron Navigator 2 (NAV2) gene (MIM: 607,026) encodes a member of the Neuron Navigator protein family, widely expressed within the central nervous system (CNS), and particularly abundant in the developing cerebellum. Evidence across different species supports a pivotal function of NAV2 in cytoskeletal dynamics and neurite outgrowth. Specifically, deficiency of Nav2 in mice leads to cerebellar hypoplasia with abnormal foliation due to impaired axonal outgrowth. However, little is known about the involvement of the NAV2 gene in human disease phenotypes. In …

Natural History Of Tango2 Deficiency Disorder: Baseline Assessment Of 73 Patients, Christina Y Miyake, Erica J Lay, Claudia Soler-Alfonso, Kevin E Glinton, Kimberly M Houck, Mustafa Tosur, Nancy E Moran, Sara B Stephens, Fernando Scaglia, Taylor S Howard, Jeffrey J Kim, Tam Dam Pham, Santiago O Valdes, Na Li, Chaya N Murali, Lilei Zhang, Maina Kava, Deane Yim, Cheyenne Beach, Gregory Webster, Leonardo Liberman, Christopher M Janson, Prince J Kannankeril, Samantha Baxter, Moriel Singer-Berk, Jordan Wood, Samuel J Mackenzie, Michael Sacher, Lina Ghaloul-Gonzalez, Claudia Pedroza, Shaine A Morris, Saad A Ehsan, Mahshid S Azamian, Seema R Lalani

Faculty, Staff and Students Publications

PURPOSE: TANGO2 deficiency disorder (TDD), an autosomal recessive disease first reported in 2016, is characterized by neurodevelopmental delay, seizures, intermittent ataxia, hypothyroidism, and life-threatening metabolic and cardiac crises. The purpose of this study was to define the natural history of TDD.

METHODS: Data were collected from an ongoing natural history study of patients with TDD enrolled between February 2019 and May 2022. Data were obtained through phone or video based parent interviews and medical record review.

RESULTS: Data were collected from 73 patients (59% male) from 57 unrelated families living in 16 different countries. The median age of participants at …

Artificial Intelligence-Based Ct Assessment Of Bronchiectasis: The Copdgene Study, Alejandro A Díaz, Pietro Nardelli, Wei Wang, Rubén San José Estépar, Andrew Yen, Seth Kligerman, Diego J Maselli, Wojciech R Dolliver, Andrew Tsao, José L Orejas, Stefano Aliberti, Timothy R Aksamit, Kendra A Young, Gregory L Kinney, George R Washko, Edwin K Silverman, Raúl San José Estépar

Faculty, Staff and Student Publications

Background

CT is the standard method used to assess bronchiectasis. A higher airway-to-artery diameter ratio (AAR) is typically used to identify enlarged bronchi and bronchiectasis; however, current imaging methods are limited in assessing the extent of this metric in CT scans.

Purpose

To determine the extent of AARs using an artificial intelligence–based chest CT and assess the association of AARs with exacerbations over time.

Materials and Methods

In a secondary analysis of ever-smokers from the prospective, observational, multicenter COPDGene study, AARs were quantified using an artificial intelligence tool. The percentage of airways with AAR greater than 1 (a measure of …

Rare Variant Enrichment Analysis Supports Greb1l As A Contributory Driver Gene In The Etiology Of Mayer-Rokitansky-Küster-Hauser Syndrome, Angad Jolly, Haowei Du, Christelle Borel, Na Chen, Sen Zhao, Christopher M Grochowski, Ruizhi Duan, Jawid M Fatih, Moez Dawood, Sejal Salvi, Shalini N Jhangiani, Donna M Muzny, André Koch, Konstantinos Rouskas, Stavros Glentis, Efthymios Deligeoroglou, Flora Bacopoulou, Carol A Wise, Jennifer E Dietrich, Ignatia B Van Den Veyver, Antigone S Dimas, Sara Brucker, V Reid Sutton, Richard A Gibbs, Stylianos E Antonarakis, Nan Wu, Zeynep H Coban-Akdemir, Lan Zhu, Jennifer E Posey, James R Lupski

Faculty, Staff and Student Publications

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by aplasia of the female reproductive tract; the syndrome can include renal anomalies, absence or dysgenesis, and skeletal anomalies. While functional models have elucidated several candidate genes, only WNT4 (MIM: 603490) variants have been definitively associated with a subtype of MRKH with hyperandrogenism (MIM: 158330). DNA from 148 clinically diagnosed MRKH probands across 144 unrelated families and available family members from North America, Europe, and South America were exome sequenced (ES) and by family-based genomics analyzed for rare likely deleterious variants. A replication cohort consisting of 442 Han Chinese individuals with MRKH was …

Large Scale Crowdsourced Radiotherapy Segmentations Across A Variety Of Cancer Anatomic Sites, Kareem A Wahid, Diana Lin, Onur Sahin, Michael Cislo, Benjamin E Nelms, Renjie He, Mohammed A Naser, Simon Duke, Michael V Sherer, John P Christodouleas, Abdallah S R Mohamed, James D Murphy, Clifton D Fuller, Erin F Gillespie

Faculty, Staff and Student Publications

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, …

The Evolution Of Acute Lymphoblastic Leukemia Research And Therapy At Md Anderson Over Four Decades, Elias Jabbour, Nicholas J Short, Nitin Jain, Fadi G Haddad, Mary Alma Welch, Farhad Ravandi, Hagop Kantarjian

Faculty, Staff and Student Publications

Progress in the research and therapy of adult acute lymphoblastic leukemia (ALL) is accelerating. This analysis summarizes the data derived from the clinical trials conducted at MD Anderson between 1985 and 2022 across ALL subtypes. In Philadelphia chromosome-positive ALL, the addition of BCR::ABL1 tyrosine kinase inhibitors (TKIs) to intensive chemotherapy since 2000, improved outcomes. More recently, a chemotherapy-free regimen with blinatumomab and ponatinib resulted in a complete molecular remission rate of 85% and an estimated 3-year survival rate of 90%, potentially reducing the role of, and need for allogeneic stem cell transplantation (SCT) in remission. In younger patients with pre-B …

Factors Associated With Open Access Publishing Costs In Oncology Journals: Cross-Sectional Observational Study, Alex Koong, Ulysses Grant Gardner, Jason Burton, Caleb Stewart, Petria Thompson, Clifton David Fuller, Ethan Bernard Ludmir, Michael Kevin Rooney

Faculty, Staff and Student Publications

Background: Open access (OA) publishing represents an exciting opportunity to facilitate the dissemination of scientific information to global audiences. However, OA publishing is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication.

Objective: In this observational cohort study, we aimed to characterize the landscape of OA publishing in oncology and, further, identify characteristics of oncology journals that are predictive of APCs.

Methods: We identified oncology journals using the SCImago Journal & Country Rank database. All journals with an OA publication option and APC data openly available were included. We searched …

Smad2/3 Signaling In The Uterine Epithelium Controls Endometrial Cell Homeostasis And Regeneration, Maya L Kriseman, Suni Tang, Zian Liao, Peixin Jiang, Sydney E Parks, Dominique I Cope, Fei Yuan, Fengju Chen, Ramya P Masand, Patricia D Castro, Michael M Ittmann, Chad J Creighton, Zhi Tan, Diana Monsivais

Faculty, Staff and Students Publications

The regenerative potential of the endometrium is attributed to endometrial stem cells; however, the signaling pathways controlling its regenerative potential remain obscure. In this study, genetic mouse models and endometrial organoids are used to demonstrate that SMAD2/3 signaling controls endometrial regeneration and differentiation. Mice with conditional deletion of SMAD2/3 in the uterine epithelium using Lactoferrin-iCre develop endometrial hyperplasia at 12-weeks and metastatic uterine tumors by 9-months of age. Mechanistic studies in endometrial organoids determine that genetic or pharmacological inhibition of SMAD2/3 signaling disrupts organoid morphology, increases the glandular and secretory cell markers, FOXA2 and MUC1, and alters the genome-wide distribution …

Epigenetic-Metabolic Interplay In The Dna Damage Response And Therapeutic Resistance Of Breast Cancer, Chandrima Das, Swagata Adhikari, Apoorva Bhattacharya, Sanjukta Chakraborty, Payel Mondal, Shalini S Yadav, Santanu Adhikary, Clayton R Hunt, Kamlesh K Yadav, Shruti Pandita, Siddhartha Roy, John A Tainer, Zamal Ahmed, Tej K Pandita

Faculty, Staff and Student Publications

Therapy resistance is imposing a daunting challenge on effective clinical management of breast cancer. Although the development of resistance to drugs is multifaceted, reprogramming of energy metabolism pathways is emerging as a central but heterogenous regulator of this therapeutic challenge. Metabolic heterogeneity in cancer cells is intricately associated with alterations of different signaling networks and activation of DNA damage response pathways. Here we consider how the dynamic metabolic milieu of cancer cells regulates their DNA damage repair ability to ultimately contribute to development of therapy resistance. Diverse epigenetic regulators are crucial in remodeling the metabolic landscape of cancer. This epigenetic-metabolic …

Patterns Of Co-Occurring Birth Defects In Children With Anotia And Microtia, Jeremy M Schraw, Renata H Benjamin, Charles J Shumate, Mark A Canfield, Daryl A Scott, Scott D Mclean, Hope Northrup, Angela E Scheuerle, Christian P Schaaf, Joseph W Ray, Han Chen, A J Agopian, Philip J Lupo

Faculty, Staff and Student Publications

Many infants with anotia or microtia (A/M) have co-occurring birth defects, although few receive syndromic diagnoses in the perinatal period. Evaluation of co-occurring birth defects in children with A/M could identify patterns indicative of undiagnosed/unrecognized syndromes. We obtained information on co-occurring birth defects among infants with A/M for delivery years 1999-2014 from the Texas Birth Defects Registry. We calculated observed-to-expected ratios (OER) to identify birth defect combinations that occurred more often than expected by chance. We excluded children diagnosed with genetic or chromosomal syndromes from analyses. Birth defects and syndromes/associations diagnosed ≤1 year of age were considered. We identified 1310 …

Crispr/Cas9 Screen Uncovers Functional Translation Of Cryptic Lncrna-Encoded Open Reading Frames In Human Cancer, Caishang Zheng, Yanjun Wei, Peng Zhang, Longyong Xu, Zhenzhen Zhang, Kangyu Lin, Jiakai Hou, Xiangdong Lv, Yao Ding, Yulun Chiu, Antrix Jain, Nelufa Islam, Anna Malovannaya, Yun Wu, Feng Ding, Han Xu, Ming Sun, Xi Chen, Yiwen Chen

Faculty, Staff and Students Publications

Emerging evidence suggests that cryptic translation within long noncoding RNAs (lncRNAs) may produce novel proteins with important developmental/physiological functions. However, the role of this cryptic translation in complex diseases (e.g., cancer) remains elusive. Here, we applied an integrative strategy combining ribosome profiling and CRISPR/Cas9 screening with large-scale analysis of molecular/clinical data for breast cancer (BC) and identified estrogen receptor α-positive (ER+) BC dependency on the cryptic ORFs encoded by lncRNA genes that were upregulated in luminal tumors. We confirmed the in vivo tumor-promoting function of an unannotated protein, GATA3-interacting cryptic protein (GT3-INCP) encoded by LINC00992, the expression of which was …

Systemic Lupus Erythematosus And Mortality In Elderly Patients With Early Breast Cancer, Sebastian Bruera, Xiudong Lei, Xerxes Pundole, Hui Zhao, Sharon H Giordano, Surabhi Vinod, Maria E Suarez-Almazor

Faculty, Staff and Student Publications

Objective: Patients with cancer and systemic lupus erythematosus (SLE) may have worse outcomes than those without SLE, given their comorbidities. We examined survival in elderly women with breast cancer (BC) and SLE and hypothesized that survival would be decreased compared with women with BC but without SLE.

Methods: We identified patients with BC and SLE and patients with BC without SLE in the Texas Cancer Registry and Surveillance, Epidemiology, and End Results, linked to Medicare claims. Overall survival (OS) was estimated after matching (age and cancer stage) and in multivariable Cox proportional hazards models adjusting for other cancer characteristics, treatment, …

Predictors Of Emergency Room Visits After Ambulatory Breast Cancer Surgery In The Medicare Population, Susie X Sun, Zhigang Duan, Henry M Kuerer, Sarah M Desnyder, Carrie Cunningham, Hui Zhao, Sharon H Giordano

Faculty, Staff and Student Publications

Background: Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery.

Patients and methods: Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well …

Surgical Results Of The Lung Cancer Mutation Consortium 3 Trial: A Phase Ii Multicenter Single-Arm Study To Investigate The Efficacy And Safety Of Atezolizumab As Neoadjuvant Therapy In Patients With Stages Ib-Select Iiib Resectable Non-Small Cell Lung Cancer, Valerie W Rusch, Alan Nicholas, G Alexander Patterson, Salama N Waqar, Eric M Toloza, Eric B Haura, Dan J Raz, Karen L Reckamp, Robert E Merritt, Dwight H Owen, David J Finley, Ciaran J Mcnamee, Justin D Blasberg, Edward B Garon, John D Mitchell, Robert C Doebele, Frank Baciewicz, Misako Nagasaka, Harvey I Pass, Katja Schulze, Ann Johnson, Paul A Bunn, Bruce E Johnson, Mark G Kris, David J Kwiatkowski, Ignacio I Wistuba, Jamie E Chaft, David P Carbone, Jay M Lee

Faculty, Staff and Student Publications

Objective: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery.

Methods: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was …

Treatment Of Cancer-Related-Fatigue In Acute Hematological Malignancies: Results Of A Feasibility Study Of Using Cognitive Behavioral Therapy, Sriram Yennurajalingam, Marina Konopleva, Cindy L Carmack, Courtney D Dinardo, Melissa Gaffney, Hayley Kristen Michener, Zhanni Lu, Penny Stanton, Jing Ning, Wei Qiao, Eduardo Bruera

Faculty, Staff and Student Publications

Background: Despite cancer related fatigue (CRF) being the most common, and debilitating symptom in patients with recently diagnosed acute hematological malignancies (HM), there are limited effective treatments for CRF in HM. The aim of this study was to determine the feasibility of cognitive behavioral therapy (CBT) for CRF in HM.

Methods: In this preliminary longitudinal prospective study, HM patients diagnosed a median of one month previously with moderate to severe fatigue were enrolled. Patients received CBT in seven weekly sessions for eight weeks. Change in Functional Assessment of Cancer Illness Therapy (FACIT) - Fatigue (primary), FACT-G, Pittsburg Sleep Quality Index …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

Objective: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

Summary of background data: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

Methods: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Prognostic Significance Of Acellular Mucin In Patients Undergoing Cytoreductive Surgery And Hyperthermic Intraperitoneal Chemotherapy (Crs/Hipec) For Appendiceal Neoplasms, Derek J Erstad, Kristen A Robinson, Karen Beaty, Safia Rafeeq, Yi-Ju Chiang, Kanwal Raghav, John P Shen, Michael J Overman, Wai Chin Foo, Melissa W Taggart, Paul F Mansfield, Richard E Royal, Keith F Fournier, Christopher P Scally

Faculty, Staff and Student Publications

Introduction: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients.

Methods: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed.

Results: Median age was 51 years, 70% were female, …

Rna Profiling Of Human Dorsal Root Ganglia Reveals Sex Differences In Mechanisms Promoting Neuropathic Pain, Pradipta R Ray, Stephanie Shiers, James P Caruso, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Megan L Uhelski, Yan Li, Robert Y North, Claudio Tatsui, Gregory Dussor, Michael D Burton, Patrick M Dougherty, Theodore J Price

Faculty, Staff and Student Publications

Neuropathic pain is a leading cause of high-impact pain, is often disabling and is poorly managed by current therapeutics. Here we focused on a unique group of neuropathic pain patients undergoing thoracic vertebrectomy where the dorsal root ganglia is removed as part of the surgery allowing for molecular characterization and identification of mechanistic drivers of neuropathic pain independently of preclinical models. Our goal was to quantify whole transcriptome RNA abundances using RNA-seq in pain-associated human dorsal root ganglia from these patients, allowing comprehensive identification of molecular changes in these samples by contrasting them with non-pain-associated dorsal root ganglia. We sequenced …

A Phase Ib/Ii Study Of Lenvatinib And Pembrolizumab In Advanced Endometrial Carcinoma (Study 111/Keynote-146): Long-Term Efficacy And Safety Update, Vicky Makker, Carol Aghajanian, Allen L Cohn, Margarita Romeo, Raquel Bratos, Marcia S Brose, Mark Messing, Lea Dutta, Corina E Dutcus, Jie Huang, Emmett V Schmidt, Robert Orlowski, Matthew H Taylor

Faculty, Staff and Student Publications

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff …

Health Benefits And Cost-Effectiveness Of Children's Oncology Group Breast Cancer Screening Guidelines For Chest-Irradiated Hodgkin Lymphoma Survivors, F Lennie Wong, Janie M Lee, Wendy M Leisenring, Joseph P Neglia, Rebecca M Howell, Susan A Smith, Kevin C Oeffinger, Chaya S Moskowitz, Tara O Henderson, Ann Mertens, Paul C Nathan, Yutaka Yasui, Wendy Landier, Gregory T Armstrong, Leslie L Robison, Smita Bhatia

Faculty, Staff and Student Publications

Purpose: To evaluate the outcomes and cost-effectiveness of the Children's Oncology Group Guideline recommendation for breast cancer (BC) screening using mammography (MAM) and breast magnetic resonance imaging (MRI) in female chest-irradiated childhood Hodgkin lymphoma (HL) survivors. Digital breast tomosynthesis (DBT), increasingly replacing MAM in practice, was also examined.

Methods: Life years (LYs), quality-adjusted LYs (QALYs), BC mortality, health care costs, and false-positive screen frequencies of undergoing annual MAM, DBT, MRI, MAM + MRI, and DBT + MRI from age 25 to 74 years were estimated by microsimulation. BC risks and non-BC mortality were estimated from female 5-year survivors of …

Incidence And Clearance Of Anal Human Papillomavirus Infection In 16 164 Individuals, According To Human Immunodeficiency Virus Status, Sex, And Male Sexuality: An International Pooled Analysis Of 34 Longitudinal Studies, Feixue Wei, Marc T Goodman, Ningshao Xia, Jun Zhang, Anna R Giuliano, Gypsyamber D'Souza, Nancy A Hessol, Maarten F Schim Van Der Loeff, Jianghong Dai, Karin Neukam, Alexandra De Pokomandy, I Mary Poynten, Ronald B Geskus, Joaquin Burgos, Isabelle Etienney, Anna-Barbara Moscicki, Maria Gabriella Donà, Maura L Gillison, Alan G Nyitray, Rebecca G Nowak, Evy Yunihastuti, Huachun Zou, Carmen Hidalgo-Tenorio, Nittaya Phanuphak, Jean-Michel Molina, Alice M Schofield, Stephen Kerr, Song Fan, Yong Lu, Jason J Ong, Admire T Chikandiwa, Sirinya Teeraananchai, Nicola Squillace, Dorothy J Wiley, Joel M Palefsky, Damien Georges, Catharina J Alberts, Gary M Clifford

Faculty, Staff and Student Publications

Background: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.

Methods: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their …

Patient-Reported Symptoms At Discharge And Risk Of Complications After Gynecologic Surgery, Xin Shelley Wang, Pedro T Ramirez, Qiuling Shi, Mona Kamal, Araceli Garcia-Gonzalez, Maria D Iniesta, Charles S Cleeland, Larissa A Meyer

Faculty, Staff and Student Publications

Objective: Current gaps in knowledge limit clinicians from fully implementing patient-reported outcomes in routine post-operative care.

Methods: This prospective study assessed symptoms via the gynecologic module of the MD Anderson Symptom Inventory (MDASI-PeriOp-GYN) in patients who underwent open laparotomy.

Results: At discharge, patient-reported moderate to severe (≥4 on a 0-10 scale) abdominal bloating or abdominal cramping, combined with length of stay of ≥4 days, were found to be associated with a higher risk of 30-day post-operative grade II-IV complications by the Clavien-Dindo system (all p values < 0.01). Also, length of stay of ≥4 days and moderate to severe urinary urgency at discharge were found to be associated with the need for re-admission (all p values < 0.01).

Conclusion: This study defined the clinically meaningful symptoms that related to the risk of …