tbuckley/cabot-search huggingface dataset:
Visceral fat and muscle changes during 6-week chemotherapy in pediatric Hodgkin lymphoma.
Authors: Wei Shen, Sneha Aidasani, Jun Chen, Roger Vaughan, Debra L. Friedman, Cindy L. Schwartz, Andrew Laine, Kara M. Kelly
Journal: Journal of Clinical Oncology (2016)

10532 Background: Obesity, as defined by elevated BMI, correlates with prognosis in some cancers but not Hodgkin lymphoma (HL). Potential explanations include 1) BMI cannot differentiate lean from fat tissue, especially visceral adipose tissue (VAT), a depot that is linked to cardiovascular diseases; 2) HL with B symptoms usually experience weight loss. In this study we use clinically collected PET-CT scans to measure VAT and muscle mass in HL. Methods: In a subsample (n = 101) of the COG AHOD0031 study cohort, we matched (same gender, age ±2yrs, height ±5cm, weight ±5kg) cases with controls for 13 out of 17 subjects with B symptoms, and 9 out of 14 with subsequent HL relapse. Multi-slice CT from head to mid-thigh were analyzed for VAT, subcutaneous adipose tissue (SAT) and muscle mass (sliceOmatic, Tomovision). Results: Among 13 patients with B symptoms at diagnosis (age, 15.7±2.7 yrs, muscle: 10.5±3.1 kg), borderline significantly less muscle (P = .08) was observed compared to the group without B symptoms (age 15.6±2.7 yrs, muscle 11.7±3.4 kg). We detected significant changes of VAT, SAT and borderline significant changes of muscle mass between baseline and after 6 weeks of chemotherapy (Table). Among 9 patients who subsequently developed a relapse, a non-significant trend towards more VAT was observed compared to the group who did not relapse (P = .17). The relapse group also showed a non-significant trend towards more VAT (P = .16) and SAT (P = .23) increases than the group w/o relapse. Conclusions: Significant increases in VAT and SAT and borderline significant decreases in muscle were noted after 6 weeks of chemotherapy in a small pediatric HL cohort using routine PET-CT. HL with B symptoms tends to have less muscle than those without B symptoms. Our small HL sample only shows a non-significant weak trend towards more VAT and SAT in the relapse group. Assessment of the full AHOD0031 cohort will allow further discrimination of the impact of body composition on relapse risk and toxicity in pediatric HL. Relapse (BL) Relapse Free (BL) Relapse (Δ 6wks) Relapse free (Δ 6wks) VAT, kg 1.9±1.2 1.4±1.9 0.5±0.4* 0.3±0.2* SAT, kg 8.8±6.5 7.6±6.1 1.1±1.1* 0.5±0.8† Muscle, kg 9.8±3.3 10.1±3.7 -0.3±0.5† -0.1±0.7 BL, baseline;*, P < .05; †, .05 < P < .10 for 6 wks vs. BL
HPV status and survival in non-oropharyngeal squamous cell carcinoma of the head and neck.
Authors: Vanessa Wookey, Adams Kusi Appiah, Avyakta Kallam, Vinicius Ernani, Lynette Smith, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2017)

6046 Background: HPV positive squamous cell carcinoma of the oropharynx and tonsil has been associated with increased survival. However, the prognostic value of HPV status for other primary sites is unclear. We assessed the effect of HPV status on survival in patients with non-oropharyngeal head and neck squamous cell carcinoma at all stages. Methods: Data was obtained from the National Cancer Database (NCDB) to determine the effect of HPV status on overall survival (OS) in adults with non-oropharyngeal head and neck squamous cell carcinoma (gum, lip, floor of mouth, tongue (excluding base), hypopharynx and nasopharynx) using SAS software. Pearson’s Chi square test was used for comparisons by HPV status. The Kaplan-Meier method was used to estimate OS and differences were compared using a log-rank test. A multivariate Cox proportional hazards regression model analysis was performed to determine effects of individual variables on outcomes. Results: Patients with all stages of squamous cell carcinoma of the gum, lip, floor of mouth, tongue (excluding base), hypopharynx and nasopharynx diagnosed from 2010 to 2013 with complete HPV data were included (n = 13,908). In univariate analysis, HPV positivity, female gender, Asian race, primary site (lip, tongue, nasopharynx and hypopharynx), private insurance and any treatment (except for chemotherapy alone) were associated with increased OS, whereas increased age, Black race, higher Charlson-Deyo comorbidity score, hypopharynx primary, and higher AJCC stage were associated with worse OS. After adjustment for covariates, HPV positivity was associated with improved OS (HR 0.83, 95% CI 0.74-0.93; p &lt; 0.001). Female gender, gum, lip, nasopharynx primaries, and private insurance on multivariate analysis predicted for improved OS, while age &gt; 70, higher Charlson-Deyo score and higher AJCC stage were associated with worse OS. Conclusions: HPV positivity and female gender are good prognostic factors in squamous cell carcinoma of the head and neck, independent of primary site. Trials evaluating de-escalation of treatment should be considered for HPV positive tumors from non-oropharyngeal sites in the head and neck region.
A phase 3, trial of gilteritinib, as maintenance therapy after allogeneic hematopoietic stem cell transplantation in patients with <i>FLT3-</i>ITD<sup>+</sup> AML.
Authors: Mark J. Levis, Mehdi Hamadani, Brent Logan, Matt Rosales, Alexander E. Perl, Steven Michael Devine, Erkut Bahceci, Yi-Bin Albert Chen
Journal: Journal of Clinical Oncology (2018)

TPS7075 Background: Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are a common indication for allogeneic hematopoietic stem cell transplant (HSCT) in first complete remission (CR1). Despite HSCT, relapses are common and cure rates are limited thereafter. The use of FLT3 inhibitors as post-HSCT maintenance therapy has not been prospectively evaluated. Gilteritinib is a highly selective, potent FLT3/AXL inhibitor with robust activity and favorable tolerability in relapsed/refractory AML. Several gilteritinib trials in AML include single arm post-HSCT gilteritinib maintenance therapy to establish the feasibility of this strategy. This trial will compare the safety and efficacy of 2-year maintenance therapy with gilteritinib versus placebo in patients with FLT3-ITD+ AML in CR1 after allogeneic HSCT. Methods: This Phase 3, randomized, double-blind, placebo-controlled multicenter trial (NCT02997202; Blood and Marrow Transplant Clinical Trials Network Protocol 1506), to be conducted at 149 sites worldwide, will enroll 532 adult subjects (aged ≥18 years) with FLT3-ITD+ AML in CR1 who are ≥30 days and ≤90 days from scheduled allogeneic HSCT. Of these 532 subjects, 346 subjects who have achieved successful engraftment without uncontrolled graft-versus-host disease (GVHD) or other serious toxicity will be randomized (1:1; stratified by conditioning regimen intensity, time from HSCT [Day 0] to randomization [30–60 days vs 61–90 days], and presence of minimal residual disease [MRD] in the pre-transplant bone marrow sample) to receive oral gilteritinib (120 mg) or matching placebo as maintenance therapy for 2 years. The primary endpoint is relapse-free survival (RFS) in the two treatment arms; RFS will be assessed from the time of randomization to the time of death or morphologic leukemia relapse (as defined by Revised IWG criteria). Overall survival is a key secondary endpoint. Other endpoints include safety/tolerability, non-relapse mortality, event-free survival, incidences of acute/chronic GVHD, and MRD. As of January 30, 2018, 47 patients have been enrolled and 11 have been randomized. Clinical trial information: NCT02997202.
Reticulocytic indices in assessing erythropoiesis effectiveness in multiple myeloma.
Authors: Irina B. Lysenko, Nailya Guskova, Ekaterina Guskova, Kristina Avanesova, Irina V. Tselishcheva, Viktoria Zakharchenko, Aliya K. Donskaya, Marina A. Gusareva, Izabella Torpudzhyan, Nadezhda Golomeeva, Svetlana V. Abakumova, Ekaterina Gornostaeva, Svetlana V. Belgova, Anastasia Nozdricheva
Journal: Journal of Clinical Oncology (2017)

e19510 Background: The purpose of the study was to analyze changes in reticulocytic indices and their role in assessing the effectiveness of erythropoiesis in patients with multiple myeloma. Methods: Thestudy included 10 patients with primary multiple myeloma (MM) and 16 patients with recurrent MM, stage II-III. Parameters of the peripheral blood were studied: Hb, RBC, MCV, MCH, RBC-He (red cell hemoglobin content), RET (number and percentage), IRF (immature reticulocyte fraction), high (HFR), median (MFR) and low (LFR) fluorescence reticulocytes, RET-He (reticulocyte hemoglobin content), RPI (reticulocyte production index). Results: Anemia was found in21 (80.8%) patients before treatment: grade I in 30.8%, II in 46.1%, III in 3.8%; normocytic hypochromic anemia – 6, normocytic normochromic – 15. Anemia detection rate in primary MM was 60.0%, recurrent – 93.7%. RET levels in grade I-II anemia were close to the norm, but IRF was increased due to MFR increase by 3.7 times and HFR – by 4.7 times. Grade III anemia: RET number decreased by 1.6 times due to IRF reduction by 2 times, in particular MFR and HFR fractions. As a result, RET-He was decreased to varying degrees in all cases. Patients with complete or partial remission showed no significant changes in erythrocyte parameters, but had RET level increased by 2.5 times, IRF – by 9 times due to MFR increase by 6.5 times and HFR by 30.8 times, RPI - by 2.0 times. The data showed the effectiveness of erythropoiesis during anticancer therapy. We did not observe signs of increasing anemia syndrome in patients with stabilization or patients resistant to treatment, as well as in patients with initial grade III anemia. Hb, RBC, RET and RPI were unchanged, but the ratio of fractions changed: the number of mature ones - LFR increased by 1.4 times and young ones - HFR decreased by 2.5 times, RBC-He were increased and RET-He doubled compared to the levels before treatment, which indicated the activation of processes of erythrokaryocyte hemoglobinization. Conclusions: RET, IRF, RET-He and RPI indices adequately reflect the process of recovery of erythropoiesis and its effectiveness in real time which is extremely important in tumor therapy monitoring.
Does screening for anxiety and depression efficiently identify patients who want help?
Authors: Linda A. Jacobs, Abigail N. Blauch, Donna A. Pucci, Angela DeMichele, Steven C Palmer
Journal: Journal of Clinical Oncology (2017)

e21604 Background: Screening cancer patients for psychosocial difficulties is recommended as a means of identifying individuals in need of assistance and improving outcomes. Although screening may identify individuals at risk for difficulties, it is unclear if screening a) identifies those willing to accept assistance or b) may have the consequence of rationing care away from those who want assistance but screen negatively. We examined these issues in a sample of breast cancer (BC) survivors. Methods: Consecutive non-metastatic BC survivors &gt; 1 year from end of treatment completed an online assessment including the Hospital Anxiety and Depression Scale and patients' desire for assistance with Anxiety and Depression prior to their survivorship visit. Results: Participants (N = 260) were predominately white (81.5%), college educated (81.2%), married/partnered (74.6%), and had an annual income of $60,000 or greater (69.3%). Most were diagnosed Stage I (48.3%) or Stage II (33.5%) BC, and underwent surgery (100%), chemotherapy (60.9%), and/or XRT (70.1%). Mean depression (M = 3.89; SD = 3.73) and anxiety (M = 6,63; SD = 4,47) scores were low and below the established cut point of 8 (all t &gt; -5.0; all p &lt; .001 ), although 20.7% and 42.3% screened positively for depression or anxiety, respectively. Screening positive for depression or anxiety was significantly associated with a desire for intervention (all X 2 &gt; 22.0; all p &lt; .001 ). However, only a minority of those screening positive for depression (32.1%) or anxiety (34.5%) desired intervention. The number of individuals screening negative but desiring intervention compared to those screening positive and desiring intervention was 76% for depression and 50% for anxiety. Conclusions: Most BC survivors screening positive for depression or anxiety do not desire intervention, at least within the cancer setting. In absolute numbers those screening negative, desire intervention relative to those screening positive at rates of 50-76%, representing a missed opportunity to improve outcomes. Screening without exploring desire for intervention may over identify individuals who do not desire help while missing a relatively large number of those who possibly may.
Diagnostic Testing for Elevated Cortisol in the Setting of an Adrenal Mass
Authors: Naykky Singh Ospina, William F. Young, Hans K. Ghayee
Journal: JAMA (2018)

An asymptomatic 66-year-old man had a 3.1-cm left adrenal mass detected on CT scan with normal vital signs, BMI of 37, normal physical examination, and an elevated cortisol level after an overnight 1-mg dexamethasone suppression test. What would you do next?
Adolescent and young adult (AYA) oncology patients: Disparities in access to specialized cancer centers.
Authors: Elysia Marie Alvarez, Theresa H.M. Keegan, Emily E. Johnston, Robert Haile, Lee Sanders, Olga Saynina, Lisa J Chamberlain
Journal: Journal of Clinical Oncology (2016)

e18020 Background: AYAs with cancer have had less improvement in survival compared to their younger counterparts. This may be partly due to differential access to specialized cancer centers (SCC), as treatment at SCCs has been associated with improved overall survival. This study examined social and clinical factors associated with AYA use of SCCs (defined as Children’s Oncology Group/National Cancer Institute-designated centers). Methods: We performed a retrospective, population-based analysis on all hospital discharges of AYA (ages 15-39) oncology patients in California during 1991-2012 (n = 118,558) using the private Office of Statewide Health Planning and Development database. Multivariable logistic regression analyses analyzed the contribution of age, race/ethnicity, health insurance, neighborhood-level income, distance from SCC, admission year, and diagnosis for those “always discharged from a cancer center.” A sensitivity analysis was performed that included patients with first discharge at a non-SCC. Results are presented as adjusted odds ratios (OR) and 95% confidence intervals (CIs). Results: Over the past 20 years, the percentage of AYAs discharged from SCCs has remained stable except for in the 15-18 (62% to 83%) and 19-21 (37% to 65%) age groups. In multivariable regression analyses, AYAs were less likely to always be discharged from a SCC if they had public insurance (OR 0.62, CI 0.60-0.64), were uninsured (OR 0.49, CI 0.44-0.54), were Hispanic (OR 0.86, CI 0.83-0.89), lived > 5 miles from a cancer center or had a diagnosis other than acute myeloblastic leukemia. AYAs were more likely to always use a SCC if they were younger than 32, female (OR 1.04, CI 1.01-1.07), black (OR 1.09, CI 1.03-1.15), Native-American (OR 1.35, 1.05-1.74) or living in a higher income neighborhood. The sensitivity analysis yielded similar results. Conclusions: Receiving care at a SCC is influenced by age, sex, health insurance, neighborhood income, race/ethnicity, geography, and diagnosis. Identifying the barriers associated with decreased utilization, especially in patients with public insurance, no insurance or of Hispanic race/ethnicity, is an important first step towards improving outcomes in this population.
Comprehensive echocardiographic assessment of cardiac function in patients with metastatic renal cell carcinoma newly initiated on sunitinib.
Authors: Le Wang, Vivek Narayan, Mary Putt, Stephen Michael Keefe, Naomi B. Haas, Daniel John Lenihan, Igor Puzanov, Anna Catino, James Fang, Steven M. Ewer, Karen Moncher, Chantal ElAmm, Guilherme Oliveira, Hari Narayan, Bonnie Ky
Journal: Journal of Clinical Oncology (2016)

e16072 Background: Sunitinib has been associated with several cardiovascular (CV) toxicities, including hypertension, left ventricular systolic dysfunction (LVSD), and symptomatic heart failure. However, our understanding of sunitinib-induced LVSD remains limited due to a lack of prospective studies with standardized CV assessments. In particular, the contribution of sunitinib-induced hypertension to subsequent LVSD is unknown. The objective of our study was to comprehensively define the changes in cardiac function in patients with metastatic renal cell carcinoma (mRCC) newly initiated on sunitinib. Methods: In this multicenter prospective cohort study, serial echocardiography was performed prior to the initiation of sunitinib and at standardized follow-up intervals during the course of therapy. Follow-up echocardiography occurred during cycles 1, 3, and 6 while on therapy. Measures of left ventricular ejection fraction (LVEF), strain, and strain rate were quantitated and summarized over time. Results: In total, 95 patients contributed 272 echocardiograms for analysis. Median increases in systolic and diastolic blood pressure were small, on the order of 0.5-2mmHg and 4-6mmHg, respectively. A large portion (41%) of patients had escalation of anti-hypertensive therapy while on sunitinib, including increased dosages or additional medications. As such, the median change in LVEF over time was only 1.2 to 3.9%. Furthermore, there was no significant longitudinal change in sensitive measures of cardiac function, including strain and strain rate through 6 cycles of therapy. Conclusions: In this prospective, non-clinical trial mRCC population newly initiated on sunitinib, the changes in BP, EF, and sensitive echocardiography measures of function were small. These findings may be related to the early initiation of anti-hypertensive therapy and resultant intensive BP control.
Clinical utility of molecular testing to select therapy in relapsed/refractory non-Hodgkin lymphoma: Mayo Clinic Center for Individualized Medicine experience.
Authors: Nabila Nora Bennani, Stephen Maxted Ansell, Thomas E. Witzig, Andew L. Feldman, Tammy M McAllister, Konstantinos N Lazaridis, Jan B. Egan, A. Keith Stewart, Grzegorz S. Nowakowski
Journal: Journal of Clinical Oncology (2017)

11571 Background: Relapsed/refractory (R/R) non-Hodgkin lymphomas (NHL) have a poor prognosis with limited treatment options. Our expanding knowledge of molecular alterations seen in R/R NHL allows identification of patients that potentially may benefit from a precision medicine approach. However, experience in routine clinical implementation of precision medicine has been limited. Here, we summarize our clinical experience in molecular characterization of RR NHL targeted therapy (TT) using next-generation sequencing (NGS), and selection of targeted therapy (TT) based on molecular profile. Methods: We conducted a prospective study in RR NHL through the Center for Individualized Medicine at Mayo Clinic. Consenting patients underwent NGS using FoundationOne Heme panel from biopsies done at time of relapse. Results of NGS were discussed at the Genomic Tumor Board and recommendations for TT were given based on matching specific molecular alteration(s) with potential agent(s) predicted to be active based on NGS. The agents could include FDA-approved, off-label use and clinical trial therapies. Results: 28 cases were enrolled: 18 aggressive NHL, 10 follicular lymphoma (FL). Molecular alterations were present in all cases. In aggressive B-cell NHL, CDKN2A/B gene cluster alterations were seen in 73% (8/11), while seen in only 1/7 T-cell lymphomas (TCL), and 1/10 FL. TP53 deletions were second most common genomic alterations in DLBCL (57%) and seen in 40% FL. JAK-STAT and ERBB pathways were altered in TCL (2/7 each). IGH-BCl-2 gene rearrangement were common in FL (70%), followed by MLL gene alterations (50%). Targetable mutations were present in 86% (24/28) of cases. A TT was recommended in all 24 cases, but received by 2 patients only. Remaining patients did not due to benefit from current therapy (10/24), ineligibility or lack of clinical trial (7/24) or interim clinical deterioration (5/24). Conclusions: Targetable mutations were identified in most cases of RR NHL with TT recommended for all cases. However, access to TT limits potential clinical benefit of molecular-based matching strategy. More studies are needed to assess impact on clinical outcomes.
Patient-reported outcomes in light of supportive medications in treatment-naïve lung cancer patients.
Authors: Johnny Hoang, Navneet Upadhyay, Dozie N Dike, Jaekyu Lee, Charles S. Cleeland, Hua Chen, Tito R. Mendoza, Meghana Trivedi
Journal: Journal of Clinical Oncology (2018)

10111 Background: Symptom burden of cancer patients is high and can be assessed using patient-reported outcomes (PROs). However, the impact of supportive medications on PROs has not been systematically assessed. We describe the supportive medications used by treatment-naïve lung cancer patients at hospital admission and assess the association between their use and PROs. Methods: Patients with a diagnosis of non-small cell or small cell lung cancer who had not received any form of cancer therapy at the initial visit and completed the MD Anderson Symptom Inventory (MDASI) survey within 45 days of diagnosis were included. Baseline patient and tumor characteristics and a complete medication list (categorized based on USP v7.0) were abstracted using the EPIC system. Symptoms were compared using Mann-Whitney U test in patients taking a supportive care medication. Results: Lung cancer patients (N = 459) with median age of 66 years (range: 23-90) were included in this study. About half (46%) of patients took any analgesics with 27% of patients taking opioid-containing regimen. One-third (31%) of patients with moderate to severe pain (5 or above on a 0 -10 scale) were not on any analgesics. Compared to patients not taking any analgesics, those on the opioid-containing regimen had significantly worse median pain scores (6 vs. 0), but not those on non-opioid analgesics (1 vs. 0). This was despite higher proportion of patients with moderate to severe pain taking opioid-containing regimen compared to those with mild pain (52% vs. 16%) . Patients on opioid-containing pain regimen also reported worse drowsiness, fatigue, disturbed sleep, shortness of breath, lack of appetite, general activity, mood, work, relations with others, walking, and enjoyment of life. Patients taking antidepressants did not significantly differ in any individual MDASI symptoms associated with depression compared to those not on the therapy. Conclusions: Treatment-naïve lung cancer patients presenting at MD Anderson had poorly managed pain and associated functional symptoms and interference. Since patients’ functional status may result in suboptimal cancer therapy, our results suggest a need for better pain and symptom management in these patients.