tbuckley/cabot-search huggingface dataset:
Case 6-1964
Authors: Victor Richards, Austin L. Vickery
Journal: New England Journal of Medicine (1964)

Presentation of Case*A seventy-six-year-old man entered the hospital because of pain in the abdomen and diarrhea.The patient had been well until six months previously, when he experienced the first of numerous attacks characterized by the sudden development of pallor and a shaking chill followed by the frequent passage of watery brown stools for several days. The episodes occurred fortnightly for five months and then increased in frequency to about once a week. A barium-enema examination and an upper gastrointestinal study, performed at another hospital, were negative except for a few colonic diverticula; a small-bowel study showed abrupt narrowing . . .
IGF-1 and IL-6 as predictors of sarcopenia in non-metastatic colorectal cancer patients.
Authors: Karam Khaddour, Karla Castellanos, Giamila Fantuzzi, Ece Mutlu, Sandra L Gomez-Perez
Journal: Journal of Clinical Oncology (2019)

e15150 Background: Insulin growth factor-1 (IGF1) and inflammatory biomarkers such as interleukin-6 (IL6) play a role in early carcinogenesis, predict prognosis and response to some therapies in colorectal cancer (CRC), and are altered in patients with sarcopenia. This study examines the association of IGF-1 and IL-6 with sarcopenia in patients with CRC. Methods: Fasting blood samples were collected at diagnosis of non-metastatic CRC (N = 59) and analyzed for serum IGF-1 and IL-6 by ELISA. Skeletal Muscle Index (SMI) was calculated from cross-sectional image at L3 from computed tomography. Sarcopenia was defined based on published cut points for adults with cancer stratified by body mass index (BMI) as: SMI &lt; 43 cm2/m2 for men and &lt; 41 cm2/m2 for women for normal and underweight; and SMI &lt; 53 cm2/m2 for men and &lt; 41 cm2/m2 for women for overweight and obese. Median and interquartile range (IQR) were reported for patients with sarcopenia versus those without sarcopenia. Spearman and logistic regression were used to examine associations between sarcopenia and serum biomarkers. Results: Median (IQR) age was 62 (49-85). Overall prevalence of sarcopenia was 44% (26/59). The prevalence of sarcopenia was 3% for males (2/59) and 5% for females (3/59) with a BMI &lt; 25 and 27% for males (16/59) and 8% for females (5/59) with a BMI≥25. Median and (IQR) for serum biomarkers in patients with CRC and sarcopenia versus those without sarcopenia were: IGF-1 43 (16) vs. 58.7(27.9) ng/mL (p = 0.007). Correlation between IGF-1 and sarcopenia was (r = -0.4, p = 0.004), but was not statistically significant for IL-6 (r = 0.02, p = 0.88). Both IGF-1 (OR = 0.82, 95% CI 0.69-0.98, p = 0.03) and IL-6 (OR = 0.83, 95% CI 0.70-0.98, p = 0.002) were significant predictors of sarcopenia after adjusting for race and BMI. Conclusions: In this sample of patients with CRC, IGF-1 and IL-6 levels were both lower in patients with sarcopenia compared to those without sarcopenia and levels of both markers predicted the presence sarcopenia.
Is the optimal biological dose of oncologic molecular-targeted therapies also clinically effective?
Authors: Pauline Corbaux, Mevidette El Madani, Michel Tod, Julien Peron, Denis Maillet, Jonathan Lopez, Gilles Freyer, Benoit You
Journal: Journal of Clinical Oncology (2019)

3060 Background: The determination of the optimal biological dose (OBD) defined as the lowest safe dose associated with biological efficacy, appears to be a promising endpoint for defining the recommended phase 2 trial dose (RP2D) of novel oncologic targeted therapies in early-phase clinical trials. However, the clinical relevance of OBD is still unknown. We conducted a review to assess if the OBDs of molecular targeted therapies defined during early phase trials were useful during subsequent drug development and for oncologic drug approvals. Methods: A systematic review was conducted to identify all the molecular targeted therapies approved by FDA in solid and hematological malignancies, and for which early phase trials defined OBDs. The publications of efficacy trials leading to the first FDA approvals were reviewed, as were the FDA approved doses and dosing schedules, which were compared to OBDs found in the early phase trials. Results: OBDs were reported in the early phase trial articles of 39.5% (32/81) FDA approved targeted therapies from 1999 to 2017 (19 small molecules and 13 monoclonal antibodies (mAbs)). The maximum tolerated doses (MTD) had not been reached for 59.4% (19/32) of these drugs. When both MTD and OBD had been defined, OBD were lower than MTD in 84.6% of cases, and equal for the others. The OBDs were chosen as the RP2Ds for 56.3% of the molecules. In that case, the final FDA approved doses were consistent with the OBDs for 83.3% of the drugs. These percentages did not differ in between small molecules and mAbs. OBDs mainly relied on indirect effects on the involved signaling pathway elements for small molecules (11/19, 57.9%), and on involved receptor occupancies for mAbs (6/13, 46.2%). In total, 23.5% of all FDA approved molecular targeted therapies were approved at their OBDs. Conclusions: Although still poorly investigated, OBD may represent a relevant complementary endpoint in in early phase trials of novel anti-cancer targeted therapies, as OBDs are selected as the final FDA approved doses in 83.3 % of cases when chosen as the RP2Ds, which is much higher than the previously reported 58.0 % when MTDs are chosen as the RP2Ds (Fontes-Jardim et al. JNCI 2015).
Use of ovarian suppression with endocrine therapy among premenopausal United States women with breast cancer, 2001-2016.
Authors: Sophie Emma Mayer, Jennifer Leigh Lund, Virginia Pate, Katherine Elizabeth Reeder-Hayes
Journal: Journal of Clinical Oncology (2019)

e12010 Background: Clinical trials indicate that adding ovarian suppression (OS) to endocrine therapy (ET) in premenopausal women with non-metastatic breast cancer improves disease-free and overall survival. However, injectable OS may add cost, potential side effect burden, and additional clinic visits to adjuvant therapy. It is not known to what extent OS is being used in contemporary community oncology settings. Methods: We identified women age 18-50 with incident breast cancer based on diagnosis codes from 2001-2016 in the commercial IBM MarketScan database. Eligible patients were continuously enrolled for a year prior to cancer diagnosis and filled at least 1 prescription for oral ET (i.e., tamoxifen, toremifene, anastrozole, letrozole, and/or exemestane) in the year after diagnosis. We classified use of OS as any prescription for a gonadotropin-releasing hormone agonist in outpatient pharmacy claims or procedure code for OS implant or injection 1) in the week prior to ET initiation or 2) following ET initiation and for up to 18 months after diagnosis. We estimated the proportion of women that were OS users in each diagnosis year using linear binomial regression, and examined associations between OS use, age at diagnosis, and geographic region. Results: A total of 26,114 women meeting all inclusion criteria were identified from the MarketScan database, of whom 1,452 (5.6%) were OS users. The most common OS drug was leuprolide or leuprorelin (55.2%), followed by goserelin (46.7%), and triptorelin (1.1%). Risk of OS use varied from 3.2% in 2001 to 9.3% in 2016, peaking at 11.4% in 2015. OS use varied by region (χ 2 p = 0.0003), with the highest use observed in the Northeast (6.5%) and the lowest in the South (5.0%). Younger patients were significantly more likely to use OS than older patients, with each additional year of age at diagnosis associated with a 0.57 percentage point lower risk (95% confidence interval [CI]: -0.63, -0.51). After controlling for age group (≤40, 41-44, 45-46, 47-48, 49-50) and region, each additional calendar year was associated with 0.25 percentage point greater risk of OS use (95% CI: 0.19, 0.31). Conclusions: OS use with ET appears to be increasing in US breast oncology practice among women under 50.
Abstract 3320: Graded Association Between Aortic Stiffness, Wave Reflections, and Duration of Vasculogenic Erectile Dysfunction: Linking Erectile Dysfunction With Generalized Vascular Disease
Authors: Charalambos Vlachopoulos, Nikolaos Ioakeimidis, Konstantinos Rokkas, Nikolaos Alexopoulos, Athanasios Tsokanis, Constadina Aggeli, George Roussakis, Christodoulos Stefanadis
Journal: Circulation (2007)

Objective: Aortic stiffness and wave reflections are markers of subclinical atherosclerosis and prognosticators of cardiovascular risk. Erectile dysfunction (ED) may be the early manifestation of a generalized vascular disease. We investigated the association between aortic stiffness, wave reflections and duration of ED. Methods: A total of 244 men with ED (detected with a validated questionnaire) were studied: 75 men (62±9 yrs, mean time interval of ED = 3 years) with coronary artery disease (ED-CAD) and 169 men (59±11 yrs) without CAD. Men without CAD were divided into three groups, according to ED duration: Group A ( 3 yrs, n=45). Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV) and wave reflections with augmentation index (AIx) of the aortic pressure waveform. Results: PWV and AIx values were comparable among ED-CAD patients and patients with time interval longer than 3 years (group C) and higher of those in men of groups...
Global burden of HPV-related cancers in men: A systematic literature review.
Authors: Stefan Varga, Xuan Wang, Karin Luttropp, Edith Morais, Anuj Walia, Laura Pimpin, Jennifer Eriksson, Smita Kothari
Journal: Journal of Clinical Oncology (2019)

e13108 Background: Human papillomavirus (HPV) causes about 5% of all cancer cases worldwide. Global male-specific incidence of HPV-related cancers, including anal (AC), penile (PC) and head and neck (HNC) cancer, is largely unknown. This study aims to summarize global incidence and HPV prevalence of these cancers in men. Methods: The systematic literature review was conducted following PRISMA guidelines. MEDLINE and EMBASE were searched for studies published in English between Jan 2008-Mar 2018 containing male-specific AC/PC/HNC incidence data, or HPV prevalence in AC/PC/HNC adult patients. Results: Fifty-six studies reported AC incidence in men between 1962-2014. The rate ranged between 0-1.5/100,000 persons in the general population. Globally, AC incidence increased over time. In the US, AC incidence in HIV-positive men increased from 10.5 to 20.7/100,000 person-years (PYs) from 1980-1989 to 1990-1995, and from 47 to 270/100,000 PYs between 1984 and 2013 in HIV-positive men who have sex with men (MSM). Prevalence of any HPV among men with AC ranged between 20-96%, HPV-16 and -18 being the most prevalent (14-100% vs 8-24%). PC incidence among men was reported in 14 studies between 1962-2015. The rate ranged between 0-10.2/100,000 persons (0-12.8/100,000 PY), with higher incidence rates in older men. Prevalence of any HPV among men with PC ranged between 6.3-100%, HPV-11 and -16 being the most prevalent (0.7-80% vs 18.1-79.2%). HNC incidence among men was reported in 66 studies between 1973-2014. Global cancer registry data reported a range of HNC incidence from 1.4-42.2/100,000, declining over time depending on the geographical location. The corresponding incidence range for oropharyngeal cancer (OPC) was 0.4-17.8/100,000, with higher incidence rates for men aged 55 and above and a rapid increase during the past decade in well-developed regions. Prevalence of any HPV ranged between 0-93.8%, HPV-16 and -18 being the most prevalent (1.2-86% vs 2.5-46.9%). Conclusions: This review demonstrates the existing burden of HPV-related cancers globally. Overall, the incidence of HPV-related AC and OPC appears to have increased among men between 1962 and 2015, highlighting a growing unmet medical need and the importance of preventing HPV infection.
Homologous recombination deficiency (HRD): A biomarker for first-line (1L) platinum in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Wungki Park, Winston Wong, Kenneth H. Yu, Anna M. Varghese, Nadeem Riaz, Vinod P. Balachandran, Imane H. El Dika, Nitya Prabhakar Raj, Danny Khalil, Geoffrey Yuyat Ku, Neil Howard Segal, Jia Li, Sree Bhavani Chalasani, Curtis Robert Chong, David Paul Kelsen, Ghassan K. Abou-Alfa, Michael F. Berger, Nikolaus Schultz, Christine A Iacobuzio-Donahue, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2019)

4132 Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway. [Table: see text]
Effectiveness and safety of ferric carboxymaltose to treat iron deficiency anemia in cancer patients.
Authors: Burak Yasin Aktas, Vildan Eda Kayku, Alma Aslan, Neyran Kertmen, Omer Dizdar, Şuayib Yalçin, Sercan Aksoy
Journal: Journal of Clinical Oncology (2019)

e23153 Background: Most cancer patients are faced with anemia during the disease course. Iron deficiency (ID) is one of the major causes of anemia in cancer patients.Bleeding, malabsorption and organ dysfunction may cause iron deficiency in cancer patients. Anemia may result in a decrease in the patient's performance and delayed chemotherapy. Administration of intravenous (IV) iron is a therapeutic option in cancer patients with iron-deficiency related anemia. In this study we analyzed effectiveness and tolerability of ferric carboxymaltose in cancer patients with iron deficiency anemia Methods: This is a retrospective analysis of 603 cancer patients who were treated with ferric carboxymaltose for anemia and iron-deficiency between October 2014 and April 2017 in a tertiary cancer clinic. Demographic data, cancer diagnoses, pre- and post-treatment hemoglobin levels, pre-treatment ferritin, serum iron, and transferrin saturation (TSA) levels were recorded. Results: The median age of the population was 55 (22-90) years, and 52% were male. Of 603 patients, 47.9% (n = 289) had gastrointestinal malignancies and 17% (n = 103) had breast cancer. A total of 331 patients (55%) received cytotoxic chemotherapy and 272 patients (45%) were not on anti-cancer treatment. Median dose of the ferric carboxymaltose is 1000 mg (500-2000). The median baseline hemoglobin, ferritin and TSA were 10.7 (7-13) g/dl, 28 (2.9-2200) ng/ml and 9.3 (1-19) %, respectively. The median hemoglobin level at the 12th week of treatment was 12.7 g/dl. The median increase in hemoglobin was 2.9 (-0.10-6.9) g/dl in patients whom received cytotoxic chemotherapy. Only 2 patients had allergic reaction during IV ferric carboxymaltose administration and treatment was discontinued. Conclusions: Intravenous-iron improved hemoglobin levels both in actively treated and not-actively treated cancer patients. The effect has been shown in the first 3 months after injection. This approach is safe and tolerable. However, the impact of tumor progression on IV iron replacement is unclear, further studies are required.
Prognostic factors for survival after relapsed acute lymphoblastic leukemia (ALL): A Children’s Oncology Group (COG) study.
Authors: Susan R. Rheingold, Lingyun Ji, Xinxin Xu, Meenakshi Devidas, Patrick A. Brown, Lia Gore, Naomi J. Winick, William L. Carroll, Stephen Hunger, Elizabeth A. Raetz, Mignon L. Loh, Deepa Bhojwani
Journal: Journal of Clinical Oncology (2019)

10008 Background: Survival of pediatric ALL patients (pts) now approaches 90%, but is historically poor for those who relapse. Methods: In the largest cohort assembled to date we analyzed overall survival (OS) rate post relapse, defined as duration between date of relapse and death, among pts diagnosed from 1996-2014 treated on 10 contemporary COG frontline trials. Comparisons of post-relapse OS were based on logrank tests, with two-sided p values reported. Results: Of 15,874 pts enrolled on frontline trials, 1,967(12%) relapsed. Relapse rates ranged from 35% in infant ALL to 9.7% in pts with NCI standard risk B-ALL. Rates were similar for T and B-ALL, 11% vs. 12%. Relapse patterns differed by phenotype: almost half of non-infant B-ALL relapses occurred late (≥36 mos), and at all time periods bone marrow (BM) relapse predominated. Conversely 65% of T-ALL relapses were early ( &lt; 18 mos) with similar number of isolated CNS (iCNS) and isolated BM (iBM) relapses. Median time to relapse was shorter for infant ALL and T-ALL (both 13.8 mos) compared to B-ALL (34.4 mos). The 5yr OS rates (±SE) after relapse for B, T, and infant ALL were 52±1%, 33±3% and 19±4%, respectively, with greater variability in OS by site in T vs. B-ALL. 5yr OS rates for pts with early BM relapse was similar for both B and T-ALL (28%), but pts with B-ALL who relapsed between 18-36 mos fared better than pts with T-ALL (OS 50±2% vs 34±8%, p = 0.014). The 5yr OS rates for pts with late relapses were 65±2% for B-ALL and 50±12% for T-ALL. In multivariable analysis, time to relapse, site of relapse, age &lt; 1 or &gt; 10 yrs at diagnosis, initial WBC &gt; 100K, and T-cell phenotype were associated with worse outcomes post relapse (all p &lt; 0.01). Sex, CNS status at diagnosis, or prior therapy on POG versus CCG/COG backbone did not influence OS. Compared to pts treated from 1988-2002 (Nguyen et al. Leukemia 2008), 5yr OS rate post relapse has improved over time for B-ALL from 37±2% to 52±1% (p &lt; 0.001) and T-ALL from 23±4% to 33±3% (p &lt; 0.05). 5-yr OS rates improved significantly for pts with iBM from 24±2% to 45±2% (p &lt; 0.001) and marginally for pts with iCNS from 59±3% to 65±3% (p = 0.15). Conclusions: In the modern era there are fewer relapses for B and T-ALL, however sites of recurrence and outcomes differ by phenotype. Infants continue to do poorly. Compared to prior analyses, survival after relapse is significantly improved.
Assessment of Leptomeningeal Carcinomatosis Diagnosis and Outcomes from 2005 to 2015 at Ohio State University.
Authors: Hannah Rinehardt, Evan Morgan, Mahmoud Kassem, Marilly Palettas, Abdul Miah, Iyad Alnahhas, Pilar Guillermo Prieto Eibl, Anupama Suresh, Akaansha Ganju, Nicole Olivia Williams, Vinay K. Puduvalli, Pierre Giglio, Maryam B. Lustberg, Robert Wesolowski, Sagar D. Sardesai, Daniel G. Stover, Jeffrey Vandeusen, Jose G. Bazan, Bhuvaneswari Ramaswamy, Anne M. Noonan
Journal: Journal of Clinical Oncology (2019)

e13554 Background: Leptomeningeal carcinomatosis (LMC) is a complication of advanced malignancies wherein primary tumors metastasize to the leptomeninges surrounding brain and spinal cord. LMC complicates 4-15% of malignant solid tumors with incidence increasing as survival of patients with advanced cancer improves. Diagnostic methods include magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) cytology. MRI findings may be nonspecific, and the gold standard of diagnosis is malignant cytology on CSF analysis. We assessed detection methods, incidence, and outcomes of LMC at The Ohio State University Comprehensive Cancer Center from 2005-2015. Methods: This was an IRB-approved single-institution retrospective study of 160 patients with confirmed diagnosis of LMC who were treated at the OSUCCC-James between Jan 1, 2005 and Dec 31, 2015. Patients with hematologic and central nervous system malignancies were excluded. Descriptive statistics were used to summarize demographic and clinical characteristics. Overall survival (OS) was defined as time from LMC diagnosis to death or last known follow-up, and was generated using Kaplan-Meier methods. Results: Median age of LMC diagnosis was 55.8 years (range: 48, 62.5). 69 (43%) patients had primary breast cancer, 41 (26%) had lung cancer, and 17 (11%) had melanoma. 73 patients (46%) presented with stage IV disease at initial diagnosis of the primary cancer, 41 (26%) with stage III disease, and 26 (16%) with stage II disease. Median time from diagnosis of primary cancer to diagnosis of LMC was 2 years (range: 0, 31.2). 158 (99%) patients had metastases at the time of LMC diagnosis, predominantly in bone (36%) or brain (36%). Median OS was 1.9 months (CI: 1.3, 2.5). 160 (100%) patients had an MRI of the brain or spine and 155 (97%) had MRI findings consistent with LMC. 75 (47%) patients underwent lumbar puncture, and 39 (52%) had CSF cytology positive for malignancy. Conclusions: Patients with LMC commonly presented with stage IV breast cancer, lung cancer, or melanoma with metastases to the brain or bone. Despite treatment, prognosis remains poor and confirmation of diagnosis can be challenging. Clinicians should have a low threshold for investigating LMC in high risk patients presenting with neurologic signs or symptoms.