tbuckley/cabot-search huggingface dataset:
Molecular profiling of ER+ metastatic breast cancers to reveal association of genomic alterations with acquired resistance to CDK4/6 inhibitors.
Authors: Pedram Razavi, Carlos Henrique dos Anjos, David N Brown, Li Qing, Christina Ping, Joshua Herbert, Jodecy Colon, Dazhi Liu, Maiya Mao, Larry Norton, Maurizio Scaltriti, David B. Solit, Mark E. Robson, Jorge S. Reis-Filho, Komal L. Jhaveri, Sarat Chandarlapaty
Journal: Journal of Clinical Oncology (2019)

1009 Background: Genomic profiling of ER+ metastatic breast cancer (MBC) has revealed highly prevalent genomic alterations (e.g. ESR1, NF1, ERBB2) associated with exposure to antiestrogen therapy and endocrine resistance. It is not known whether any such acquired genomic alterations are observed after exposure to now standard CDK4/6 inhibitors (CDK4/6i). Methods: To identify genomic alterations associated with acquired resistance to CDK4/6i + antiestrogen combinations, we prospectively performed tumor and matched normal sequencing on 1059 ER+ breast cancers from 845 MBC patients collected prior to (n = 838) or post-treatment with CDK4/6i (n = 221), including 110 pre- and post-treatment pairs. We performed gene enrichment analyses to identify the oncogenic mutations and copy number alterations that were more frequent in post-CDK4/6i samples compared to CDK4/6i-naïve samples and further compared these results to those of post-hormone alone therapy datasets. Results: The post-CDK4/6i samples were collected following exposure to CDK4/6i plus aromatase inhibitors (51%), plus fulvestrant (28%), or multiple/other (21%). Along with alterations previously associated with resistance to hormonal therapy alone, our analysis identified multiple genes to be specifically enriched in the post-CDK4/6i tumors. Among these, loss-of-function alterations in RB1 were significantly enriched in the post-CDK4/6i compared to CDK4/6i-naïve samples (7.9% vs. 2.7%, p-value = 1.5e-5). The majority of the RB1 mutations in the post-CDK4/6i tumors had loss of heterozygosity (LOH), while LOH was uncommon in the CDK4/6i-naive tumors. Additionally, multiple alterations in effectors of PI3K/AKT signaling (excluding PIK3CA), cell cycle (such as CDKN2A loss) and in Hippo signaling were more frequent in the post-CDK4/6i tumors. Conclusions: This large clinico-genomic analysis of the post- and pre-CDK4/6i MBCs reveals multiple genomic lesions to be enriched after exposure to CDK4/6i, highlighting therapy-related genomic evolution as a recurrent phenomenon and identifying unique genomic subsets that have strong potential to alter the benefit of subsequent lines of therapies.
Evaluation of combined biomarkers for tumor response to immunotherapy (I/O) in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Hayat Oum El Kheir Ramdani, Markus Falk, Stefanie Schatz, Markus Tiemann, Lukas Heukamp, Ed Schuuring, Harry J.M. Groen, Frank Griesinger
Journal: Journal of Clinical Oncology (2019)

e14269 Background: Immune checkpoint inhibitors have revolutionized NSCLC treatment. At present, the only established predictive biomarker for I/O-therapy stratification are PD-L1 expression and MSI status. However, the expression of PD-L1 is limited by heterogeneous expression and even high expressors not always respond to I/O therapy. The aim of the study is to evaluate the value of combinations of positive (Tumor Mutational Burden, PD-L1) and negative (a.o. CD73 expression and inactivating STK11 mutations) predictive markers in patients (pts) with advanced NSCLC on I/O therapy. Methods: A retrospective study was performed on a cohort of 54 pts with advanced NSCLC that have been treated with I/O between 2015 and 2017. Pts were selected by the availability of tumor tissue and based on tumor response evaluated by RECIST v1.1 criteria: only patients with durable tumor response (CR,PR ≥ 6 months) and patients with no tumor response (PD as best response) were analyzed for biomarkers: hybrid capture NGS assay for TMB (New Oncology) including STK11 mutations and IHC tests for PD-L1, CD73 and VISTA. Adjusted Cox regression and ROC analysis will be performed to evaluate the predictive value of the different biomarkers. Results: 43/54 pts received nivolumab, 11/54 pembrolizumab in different therapy lines (from 1st to 6th line). 24 pts were defined as having a durable tumor response (median PFS 20 months, median OS not reached) 30 pts as primary progressors (median PFS 2 months, p &gt; 0.0001), median OS 12 months, p &gt; 0.0001). In 30/54 pts enough material was available for TMB testing. The median TMB-value is 11.42 mutations/Mb. In 13 durable responders median TMB-value was 13.28 mutations/Mb versus 11.00 mutations/Mb in 17 primary non-responders. Additional analyses of PD-L1, CD73, STK11 and VISTA will be presented at the meeting as well as correlative data of the parameters analyzed. Conclusions: Our results suggest that integrating several biomarkers including positive and negative predictive markers may correlate better with responses to I/O than PD-L1 and TMB alone.
Acceptability of mobile health technology among cancer patients.
Authors: Rashmika Potdar, Arun Thomas, Matthew DiMeglio, Kamran Mohiuddin, Djeneba Audrey Djibo, Krzysztof Laudanski, Claudia M. Dourado, John Charles Leighton, Jean G Ford
Journal: Journal of Clinical Oncology (2019)

e18139 Background: Advances in wireless technology have led to the increasing use of mobile health platforms. This approach, tele-medicine, enables healthcare providers to communicate remotely with patients, thereby enhancing timeliness and quality of care, and patient engagement. However, few studies address barriers to its implementation, especially in medically under served populations. Methods: A cross-sectional survey of 151 cancer patients was conducted at an academic medical center in North Philadelphia, PA. A trained interviewer performed structured interviews regarding the barriers and facilitators of patients’ current and desired utilization of technology for healthcare services. Statistical significance was defined as p &lt; 0.05 on a two-tailed distribution. Chi-Square test was used for categorical variables. Odds ratios from logistic regression analysis were used to identify the relationship between demographic factors and willingness to utilize a mobile application for health surveillance. Results: Of the 151 patients who completed the survey, 35.8% were male; ages ranged from 21-104 years. Forty-two percent were married, 49.0% were single, and 9% were divorced at the time of the survey. No significant associations existed between the willingness to utilize a mobile health application and gender ( p = 0.73) or marital status ( p = 0.97). After controlling for other demographic variables, patients older than 70 were significantly less likely to utilize a mobile application. Conversely, patients with a college-level education or more were significantly more likely to utilize a mobile application [OR = 2.78, p = 0.01]. Conclusions: Age and education level represent potential barriers to mobile health applications for cancer patients in socioeconomically diverse community. Health networks should consider these factors when launching patient engagement platforms. [Table: see text]
Using tumor genomic profile testing and comorbidity level to personalize chemotherapy decisions among older patients with early-stage breast cancer.
Authors: Young Chandler, Claudine Isaacs, Jinani Jayasekera, Clyde B. Schechter, Christopher Cadham, Jeanne S. Mandelblatt
Journal: Journal of Clinical Oncology (2019)

e12055 Background: Under-representation of women ages 65+ (“older”) in the trials may limit clinical translation of results to this growing population. We used simulation modeling to estimate chemotherapy outcomes by age and comorbidity level among older women with early stage, estrogen-receptor+/HER2- breast cancers with an Oncotype DX score of 26+. Methods: A discrete-time stochastic state-transition model synthesized data from population studies and clinical trials to estimate outcomes over a 25-year horizon for subgroups of women based on age (65-69, 70-74, 75-79, and 80-89) and comorbidity levels (no/low, moderate, and severe). Age-, comorbidity-specific non-cancer survival was derived from a random 5% sample of women enrolled in the Medicare Part A and B program from 1992 to 2005 and included in the SEER areas. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer and other-cause mortality with chemoendocrine therapy or endocrine therapy alone. Sensitivity analysis tested the impact on outcomes of varying values of uncertain parameters. Results: Women with life expectancies of ≥ 7 years had net gains of 0.17 to 0.45 LYs (2.0-5.4 months) with chemotherapy; this group was mainly women aged 65-69 and 70-74 with no/low or moderate comorbidity. Women destined to develop distant recurrence gained between 4.2-10.4 months. LYs were reduced by chemotherapy toxicity. The majority of women died of other causes, ranging from 59% to 98% across all age groups and comorbidity levels, but chemotherapy reduced breast cancer mortality by 14.5% and 25.7% among women ages 65-69 and 70-74 with no/low comorbidity, respectively. Results were robust in sensitivity analyses, and chemotherapy improved all outcomes as treatment efficacy increased, assuming no change in toxicity. Conclusions: Older women with early stage, estrogen-receptor+/HER2- breast cancers with Oncotype DX scores of 26+ may benefit from chemotherapy, when both conditions of age &lt;75 and comorbidity at no/low or moderate level can be met. Personalized treatment decisions for older women will ultimately depend on comorbidity-specific lifespan and individual preferences for the balance of benefits and harms of chemotherapy.
Patient-reported disease burden in chronic lymphocytic leukemia, diffuse large B-cell lymphoma, and follicular lymphoma: Results from a national patient advocacy survey.
Authors: Mark Price, Arliene Ravelo, Maria Sae-Hau, Peggy Ann Torney, Victor Gonzalez, Elisa S Weiss, Carol Mansfield, Brennan Mange, Eydith Comenencia Ortiz, Anthony Masaquel, Keith Lamont Dawson
Journal: Journal of Clinical Oncology (2019)

e18198 Background: Evaluations of patients’ (pt) burden and priorities are increasingly important as novel treatments are developed. We aimed to better understand pt-reported disease burden in chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL). Methods: We developed a survey to understand pt disease burden, designed in consultation with medical experts, pt advocacy organizations, and survey scientists. Concept elicitation and cognitive pretesting were conducted. The survey was administered electronically to pts who had received either initial or subsequent treatment within the past year and consisted of categorical Likert options that quantified the impact of disease on physical function, sleep, cognition, work, emotional health, and quality of life (QoL). Results: The Leukemia &amp; Lymphoma Society and the Lymphoma Research Foundation recruited 424 pts: 309 with CLL, 59 with DLBCL, and 69 with FL; 51% were female. Mean age was 66 (range: 22–95). Results suggest that pts experience substantial disease burden across all surveyed subtypes. The most noteworthy results are highlighted in the following table that indicates the percentage of pts who agreed or strongly agreed to statements about disease burden. Additionally, large proportions of pts worried about their disease returning or getting worse (72% of pts with CLL, 83% of pts with DLBCL, and 79% of pts with FL), indicating high impact regardless of the indolent or aggressive nature of their disease. Most pts indicated that delaying disease progression was important to them (96% of pts with CLL, 96% of pts with DLBCL, and 92% of pts with FL). Employment status changed for 31% of pts who were working full or part time or on contract because of their diagnosis and treatment. Conclusions: Pts with CLL, DLBCL, and FL report experiencing substantial disease burden. Data from studies focusing on pt-reported disease burden can be used for education of the clinical community to address the key concerns of pts.[Table: see text]
Evaluating cancer outcomes of outpatient colonoscopies in elderly patients older than 85 years of age.
Authors: Joy A Lee, Xia Bi, Connie Y Huang, Walter Coyle
Journal: Journal of Clinical Oncology (2019)

e15079 Background: With increasing life expectancy, the incidence of colorectal cancer increases. Currently, there are few studies on cancer outcomes of outpatient colonoscopy in patients older than 85 years of age. Methods: The database at Scripps was queried for all outpatient colonoscopies performed under moderate sedation between April 1, 2012 to March 31, 2017 on patients aged 85 years and older. Patient demographics, indication for procedure, and endoscopic findings were obtained. Variables including location and stage of tumor, subsequent treatments, and overall mortality were analyzed. Results: 322 outpatient colonoscopies were reviewed. Median age was 86 years. 53% were females. Screening colonoscopies accounted for 2.1% of procedures. 40 (12.4%) colon cancers were detected. 38 (95%) were adenocarcinomas and 2 (5%) were neuroendocrine tumors. 26 (65%) were right sided colon cancers. Among those diagnosed with cancer, anemia was the most common indication followed by positive fecal occult blood test (FOBT). 20 (50%) of these patients had a FOBT within the past year. Of those FOBTs, 18 (90%) were positive. Median age of patients with colon cancer was 88 years. 70% were females. 12 (30%) patients had never had a colonoscopy. 19 (47.5%) were diagnosed at an advanced stage (stage III or IV). 32 (80%) pursued surgery, 10 (25%) received chemotherapy, and 5 (12.5%) received radiation. 3 (7.5%) patients received supportive care only. 1-year mortality was 22.5% and 3-year mortality was 40% from the time of diagnosis. Conclusions: To date, this is the first study in the United States that examines cancer outcomes in an elderly population undergoing an outpatient colonoscopy. Overall, patients over the age of 85 with colorectal cancer have good outcomes that are comparable to that of the general population and colonoscopies should be considered for appropriate candidates.
Case 40-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Kim A. Eagle, James F. Southern
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 62-year-old woman was admitted to the hospital because of increasing peripheral edema.There was a four-year history of Sjögren's syndrome, with a dry mouth and Raynaud's phenomenon. Two years before entry a test for antinuclear antibodies was positive in a titer of 1:1028, and a test for rheumatoid factor was negative. Microscopical examination of a lip-biopsy specimen was interpreted as consistent with Sjögren's syndrome. Seven months before admission a varicose vein in the right lower extremity was injected.One month later the patient experienced an abrupt onset of dysarthria, dysphasia, and a right facial droop and . . .
Racial and ethnic differences in the results of multigene panel testing of inherited cancer predisposition genes in breast cancer patients.
Authors: Siddhartha Yadav, Holly LaDuca, Eric Polley, Hermela Shimelis, Nancy Niguidula, Chunling Hu, Jenna Lilyquist, Jie Na, Kun Lee, Stephanie Gutierrez, Amal Yussuf, Steven Hart, Brigette Tippin Davis, Elizabeth Chao, Tina Pesaran, David Goldgar, Jill S. Dolinsky, Fergus Couch
Journal: Journal of Clinical Oncology (2019)

1514 Background: The prevalence of germline mutations in non-white patients with breast cancer and the germline genetic drivers of breast cancer risk in non-white populations are largely unknown. Methods: The study population included 77,900 women with breast cancer (Non-Hispanic white: 57,003; Black: 6,722; Asian: 4,183; Hispanic: 5,194; Ashkenazi-Jewish: 4,798) who underwent germline multigene panel testing of cancer predisposition genes from March 2012 to December 2016. The prevalence of predisposition gene mutations in racial and ethnic populations relative to non-Hispanic Whites was assessed while accounting for age at diagnosis of breast cancer, family history of breast and ovarian cancer, and estrogen receptor status of breast tumors. Associations between mutations in each gene and breast cancer risk were evaluated using reference controls. Results: The overall frequency of pathogenic mutations in known breast cancer predisposition genes was 9.1% for non-Hispanic Whites, 9.8% for African Americans, 10.2% for Hispanics, 7.6% for Ashkenazi-Jewish, and 7.5% for Asians. BRCA1 mutations were enriched (p &lt; 0.05) and CHEK2 mutations were under-represented in all racial and ethnic populations relative to non-Hispanic Whites. BRCA2 and BARD1 mutations were enriched in African Americans and Hispanics relative to non-Hispanic Whites, whereas PALB2 and RAD51C mutations were enriched in Hispanics. Among genes with mutation counts large enough for assessment, mutations in BARD1, BRCA1, BRCA2, PALB2 and TP53 were significantly associated with clinically relevant increased risks (odds ratio (OR) &gt; 2) of breast cancer across all ethnicities and races. Rates of variants of uncertain significance were highest among Asians (29%), followed by blacks (27%), Hispanics (21%), non-Hispanic whites (16%) and Ashkenazi-Jews (14%). Conclusions: While there is some similarity across ethnic groups, substantial heterogeneity exists in the prevalence of mutations in breast cancer predisposition genes across major racial and ethnic groups in the US population. These findings contribute to our understanding of breast cancer risk and have significant implications for genetic testing, screening, and management of patients with an inherited predisposition to breast cancer, with a need for continued analysis with increased cohort size in ethnic minority groups.
Annual Report to the Nation on the Status of Cancer, Featuring Cancer in Men and Women Age 20–49 Years
Authors: Elizabeth M Ward, Recinda L Sherman, S Jane Henley, Ahmedin Jemal, David A Siegel, Eric J Feuer, Albert U Firth, Betsy A Kohler, Susan Scott, Jiemin Ma, Robert N Anderson, Vicki Benard, Kathleen A Cronin
Journal: JNCI Journal of the National Cancer Institute (2019)

The American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and North American Association of Central Cancer Registries provide annual updates on cancer occurrence and trends by cancer type, sex, race, ethnicity, and age in the United States. This year's report highlights the cancer burden among men and women age 20-49 years.Incidence data for the years 1999 to 2015 from the Centers for Disease Control and Prevention- and National Cancer Institute-funded population-based cancer registry programs compiled by the North American Association of Central Cancer Registries and death data for the years 1999 to 2016 from the National Vital Statistics System were used. Trends in age-standardized incidence and death rates, estimated by joinpoint, were expressed as average annual percent change.Overall cancer incidence rates (per 100 000) for all ages during 2011-2015 were 494.3 among male patients and 420.5 among female patients; during the same time period, incidence rates decreased 2.1% (95% confidence interval [CI] = -2.6% to -1.6%) per year in men and were stable in females. Overall cancer death rates (per 100 000) for all ages during 2012-2016 were 193.1 among male patients and 137.7 among female patients. During 2012-2016, overall cancer death rates for all ages decreased 1.8% (95% CI = -1.8% to -1.8%) per year in male patients and 1.4% (95% CI = -1.4% to -1.4%) per year in females. Important changes in trends were stabilization of thyroid cancer incidence rates in women and rapid declines in death rates for melanoma of the skin (both sexes). Among adults age 20-49 years, overall cancer incidence rates were substantially lower among men (115.3 per 100 000) than among women (203.3 per 100 000); cancers with the highest incidence rates (per 100 000) among men were colon and rectum (13.1), testis (10.7), and melanoma of the skin (9.8), and among women were breast (73.2), thyroid (28.4), and melanoma of the skin (14.1). During 2011 to 2015, the incidence of all invasive cancers combined among adults age 20-49 years decreased -0.7% (95% CI = -1.0% to -0.4%) among men and increased among women (1.3%, 95% CI = 0.7% to 1.9%). The death rate for (per 100 000) adults age 20-49 years for all cancer sites combined during 2012 to 2016 was 22.8 among men and 27.1 among women; during the same time period, death rates decreased 2.3% (95% CI = -2.4% to -2.2%) per year among men and 1.7% (95% CI = -1.8% to -1.6%) per year among women.Among people of all ages and ages 20-49 years, favorable as well as unfavorable trends in site-specific cancer incidence were observed, whereas trends in death rates were generally favorable. Characterizing the cancer burden may inform research and cancer-control efforts.
Case 10-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Lucius F. Sinks, David L. Gang
Journal: New England Journal of Medicine (1984)

Presentation of CaseAn eight-year-old boy was admitted to the hospital because of proptosis.He was reported to be well until three weeks earlier, when proptosis of the right eye was noticed when he awoke one morning. During the few days before admission he complained of photophobia and a vague headache. One day before entry a computed tomographic (CT) scan of the orbits showed an orbital mass with intracranial involvement. He was referred to this hospital.The child's parents were divorced, and he had recently been taken into custody by his father, who recalled few details of his previous medical . . .