bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic immune-inflammation index to predict the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.
Authors: Lolli Cristian , Maruzzo Marco , Derosa Lisa , Sava Teodoro , Santoni Matteo , Massari Francesco , Wheater Matthew James , Aieta Michele , Scarpi Emanuela , La Russa Francesca , Crabb Simon J. , Cascinu Stefano , Galli Luca , Basso Umberto , De Giorgi Ugo 
Published: February 2017

547 Background: A systemic immune-inflammatory index (SII) based on lymphocyte (L), neutrophil (N), and platelet (P) counts has been recently developed. In this retrospective analysis, we explored its prognostic and predictive value at baseline and changes at week 6 during first-line sunitinib in patients (pts) with metastatic renal cell cancer (mRCC). Methods: We included 335 consecutive pts mRCC treated with first-line sunitinib for which P,N, and L data were available at start of therapy, and 6 weeks thereafter. The SII was defined as follows: SII = P x N/L. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the baseline data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion on PFS and OS was evaluated by Cox regression analyses. Results: An optimal cutoff point for the SII of 730 x 109stratified these pts into high (≥ 730) and low SII (<730) groups. Median age was 63 years (range, 27 to 88); histotype clear cell carcinoma was reported in 94% of cases; 29.6%, 59.4% and 11% were classified in the favorable, intermediate and poor Motzer prognostic groups, respectively. The median PFS was 6.2 months (mo) (95% CI=5.5-9.5) in pts with baseline SII ≥730 and 17.7 mo (14.3-21.8) in those with SII <730, P<0.0001. The median OS was 13.7 mo (95% CI=9.6-20.3) in pts with baseline SII ≥730 and 41.8 mo (95% CI=34.5-51.8) in those with baseline SII <730, P<0.0001. Data for SII at baseline and change in SII by week 6 using a cut-off of 730 are shown in the table. Conclusions: The SII is a powerful prognostic and predictive indicator of poor outcome in pts with mRCC. A validation study from prospective data is warranted. [Table: see text]
Correlation between findings from comprehensive genomic profiling and targeted therapy response in metastatic renal cell carcinoma.
Authors: Ho Thai Huu , Choueiri Toni K. , Wang Kai , Karam Jose A. , Chalmers Zachary Rockow , Frampton Garrett Michael , Elvin Julia Andrea , Johnson Adrienne , Liu Xueli , Lin Yulan , Joseph Richard Wayne , Stanton Melissa L. , Miller Vincent A. , Stephens Philip J. , Ross Jeffrey S. , Ali Siraj Mahamed , Pal Sumanta K. 
Published: February 2017

570 Background: Vascular endothelial growth factor- (VEGF-) and mammalian target of rapamycin- (mTOR-) directed therapies represent a standard of care in metastatic renal cell carcinoma (mRCC). However, these agents are not employed based on an assessment of predictive biomarkers such as genomic alterations (GA). We sought to determine if an association exists between GA detected by comprehensive genomic profiling (CGP) and the response to VEGFR and mTOR pathway targeted therapies in a cohort of mRCC treated in a clinical practice setting. Methods: The results of CGP performed in the course of clinical care on 31 consecutive mRCC obtained from patients who had received VEGFR- and/or mTOR-inhibitors were reviewed. Duration of treatment (DOT), extent and duration of clinical response was obtained from review of medical records. All classes of genomic alterations - base substitutions, short insertions, deletions, gene fusions, rearrangements and copy number - were assessed via CGP. Descriptive statistics were used to determine the frequency of GAs in groups segregated by the DOT with VEGF-directed agents. Results: The most common GAs detected in this series were in VHL (70%), PBRM1 (48%), SETD2 (32%), TSC1 (29%), MLL (19%), TERT (16%), ARID1B (16%) and KDM5C (16%). Across 61 administrations of VEGF-directed therapy in 27 patients, exceptional responses (DOT > 21 months) were more frequent amongst patients with GAs in KDM5C, PBRM1, and VHL. Conversely, these patients also featured a lower frequency of GA associated with response to mTOR-directed therapy, such as TSC1. Conclusions: Multiple GAs are more prevalent in exceptional responders to VEGF-directed therapy. Prospective validation of these findings may lead to use of CGP to optimize therapeutic selection.
Sunitinib to upregulate IFNg-STAT1 signaling and to increase indoleamine 2,3-dioxygenase (IDO) expression in renal cell carcinoma (RCC).
Authors: Jonasch Eric , Hoang Anh , Sun Mianen , Zhou Lijun , Ding Zhiyong , Zhang Xuesong , Bai Shanshan , Tannir Nizar M. , Liu Xiande 
Published: February 2017

614 Background: Recently we reported that antiangiogenic therapy-treated primary RCC demonstrated increased infiltration of CD4 and CD8 T cells and higher expression of the immune checkpoint ligand PD-L1, all of which were associated with therapy resistance. IFNg-STAT1 signaling pathway drives the expression of both immunosuppressive and immunostimulatory molecules that are involved in lymphocyte trafficking, antigen presentation and immune checkpoints. The purpose of this study was to assess the impact of antiangiogenic therapy on IFNg signaling and on a broader tumor specific immune profile. Methods: We performed immunohistochemical staining of tissue microarrays (TMAs) generated from 40 sunitinib treated primary RCC from patients treated on clinical trial and compared stains to untreated control tumors. We used Vectra imaging to spectrally unmix antibody signal and to quantitate expression levels. We used immunoblot and real-time PCR to investigate the changes in protein and mRNA, respectively. We assessed for statistical significance using an unpaired Student t test. Results: We found that sunitinib treated RCC tissues demonstrated STAT1 phosphorylation (1.2% vs. 4.8%; P<0.001) or nuclear localization (7.4% vs. 15.6%; P=0.005), which was inversely related to patient survival. Furthermore, sunitinib treatment magnified IFNg-induced STAT1 activity by increasing the activity of janus kinase 2 (JAK2) and decreasing the protein levels of inhibitors PIAS and SOCS. On the one hand, sunitinib increased the transcription of VCAM1, CCL4, HLA-B and CD80, which facilitate T cell infiltration or antigen presentation; on the other hand, sunitinib increased transcription of the T cell negative regulator IDO1 (1 vs. 3.2, P<0.001) and CTLA4 (1 vs. 3.1, P=0.01). Conclusions: These results indicate that sunitinib both positively and negatively regulates the tumor immune microenvironment via modulation of STAT1 mediated signaling. IDO upregulation is a key driver of T-cell nutrient deprivation and can be targeted therapeutically. These findings will help us devise precise interventions to overcome tumor cell specific immunosuppressive signaling.
Enhancing cancer survivorship through improved provider communication, care coordination, and professional education.
Authors: Daly John M. , Howald Alan G. , Filchner Kelly Ann , Miller Bonnie J. , Lyons Leanne , Denlinger Crystal Shereen , O'Brien Patrick , Schlueter Amanda , Gonzalez Evelyn , Seggev Jennifer 
Published: February 2017

104 Background: Care coordination among oncology and primary care physicians (PCPs) is an essential element of survivorship care. Providers at an NCI-designated comprehensive cancer center noted gaps in coordinating care with PCPs. We sought to develop a program that enhances communication and education between provider groups to ensure a seamless continuum of care thereby improving overall survivorship care. Methods: The Fox Chase Cancer Center (FCCC) Care Connect program was created to comprehensively connect PCPs in the regional service area with cancer center providers. Program participation requirements for PCP’s include attendance at 2 of 4 targeted professional education programs and participation in quality measures for breast, cervical, and colon cancer screening. Formalized processes to efficiently move patients between oncologists and PCP’s were established. Communication gaps were addressed by providing electronic access via a secure physician portal, access to FCCC disease navigation services, and establishment of designated referral navigators to coordinate clinical needs between provider groups. Results: FCCC initiated the Care Connect program with 5 PCP practices. During a 3 month pilot phase, FCCC directed 19 patients to Care Connect PCP’s to manage ongoing clinical needs and implement survivorship plans. Eight-six percent of referrals were classified as non-urgent. Median time from referral to PCP appointment was 16 days, 24% below regional average. One CME education program was conducted during the pilot phase. Of the attendees, 91% reported an intent to change current practice by implementing a new procedure, discussing new information or seek additional information. Attendees identified potential care barriers which will be included in future program development. Post-education, one practice referred 3 patients to the lung cancer screening program. Conclusions: A formal program that aligns PCPs and oncologists is an effective initiative to improve communication and awareness of cancer patient survivorship needs in oncology and primary care settings.
Reduction of paclitaxel neuropathy with cryotherapy.
Authors: Wilkinson Mary , Cocilovo Costanza , Vargas Hernan I. , Cohen Robert Alan , Bruce Sara , Edmiston Kirsten H. , Franco Claudia Yvette , Agra Maria Gracia , Bayer Suzanne , Khan Afifah , Le Lamvy , Saifollahi Parisa , Steimer Mary , Szeremeta Christopher , Deeken John F. 
Published: February 2017

124 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common and potentially debilitating side effect of taxanes. Prior studies indicate weekly paclitaxel results in grade 2 or higher neuropathy in 25% of patients. Patients may experience persistent pain that impacts quality of life. Currently, there is little data that exists on effective therapies for prevention of paclitaxel neuropathy. This study investigates the efficacy and safety of cryotherapy for the prevention of paclitaxel-induced peripheral neuropathy. Methods: This is a single arm, phase II study of the effects of cryotherapy for breast cancer patients undergoing 12 cycles of weekly paclitaxel. Cryotherapy was administered by hypothermia mitts and slippers to patients’ hands and feet during, and 15 minutes before and after paclitaxel treatments. Neurologic assessments and neuropathy questionnaires were evaluated at baseline, every 4 cycles during treatment, and every 6 months follow up for two years. The primary objective is to assess if cryotherapy can decrease the rate of peripheral neuropathy. The primary efficacy endpoint is the rate of neuropathy in patients undergoing weekly paclitaxel treatments. Results: Between November 2014 and June 2015, 41 patients were enrolled in the study. Of 39 evaluable patients, 19 (48.7%) were without neurologic toxicity. 19 (48.7%) had grade 1 toxicity, paresthesia but without pain. Only one patient (2.6%) had grade 2 toxicity. Cryotherapy treatment was well tolerated; one patient could not participate due to cold intolerance. Conclusions: Cryotherapy reduced the incidence of pain and grade 2 or higher sensory neuropathy in patients receiving weekly paclitaxel. Clinical trial information: NCT02230319. [Table: see text]
Comparison of physical function and falls among women with persistent symptoms of chemotherapy-induced peripheral neuropathy.
Authors: Winters-Stone Kerri M , Hilton Coleman , Luoh Shiuh-Wen , Jacobs Peter , Faithfull Sarah , Horak Fay B 
Published: February 2017

130 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment that may persist and impact physical function. Studies that quantify functional consequences associated with CIPN in post-treatment cancer survivors are rare, based on self-report, or use small samples. The purpose of this study was to compare objective and self-report measures of physical function, gait patterns, and falls between women cancer survivors with or without symptoms of CIPN. Methods: Baseline assessments from 678 women cancer survivors enrolled in exercise trials were available for analysis. Women who self-reported symptoms of CIPN (CIPN+) were compared to asymptomatic women (CIPN-) on the following: maximal leg press strength (LPmax); timed chair stand (CS), physical performance battery (PPB), gait patterns (speed (SP), step number (SN), stride length (SL), base of support (BOS), % time in double support (%DS)), self-report physical function (PF) and disability (DIS), and falls in the past year (% fallers). Group comparisons were made using analysis of covariance, adjusting for time since diagnosis and cancer site (breast or other). Results: After excluding women who had diabetes, were premenopausal at cancer diagnosis or had not received chemotherapy, 462 cases were analyzed (age: 62±6yrs; time since diagnosis: 5.8±4.1yrs). CIPN+ (N = 210) and CIPN- (N = 252) groups significantly differed on all measures (*p < 0.05; **p < 0.01), except maximal leg strength and base of support during a usual walk, with worse performance for CIPN+. Conclusions: In our sample of women cancer survivors, 45% had symptoms of CIPN an average of 6 years post treatment and significantly worse physical function, altered gait patterns and more falls than asymptomatic women. CIPN should be addressed early in treatment and strategies to improve function and mobility and prevent falls need to be tested. [Table: see text]
Grading financial toxicity based upon its impact on health-related quality of life (HRQol).
Authors: De Souza Jonas A. , Aschebrook-Kilfoy Brisa , Grogan Raymon , Yap Bonnie J. , Daugherty Christopher , Cella David 
Published: February 2017

16 Background: Financial toxicity (FTox) is an important symptom. We hypothesized that FTox can be graded based on statistically significant and clinically meaningful changes in HRQoL. Methods: FTox was assessed by the COST (COmprehensive Score for financial Toxicity) in 2 sets of cancer patients (pts). Set 1(S1): pts with Stage IV cancers on chemotherapy. Gradations of FTox were determined by ROC analyses based on conventions for clinically meaningful small (0.2), medium (0.5) and large (0.8) effect sizes (e.s.) for the FACT-G HRQoL instrument. Demographics, income, mood disorders (POMS), and symptoms (EORTC QLQ-C30) were collected. We computed η2 (Eta squared) to estimate the magnitude of the variability in HRQoL explained by specific symptoms. Set 2 (S2): pts and survivors with thyroid cancer within 3 years of diagnosis. In S2, HRQoL was assessed by the thyroid-specific City of Hope HRQoL measure. Results: A total of 600 cancer pts were assessed (233 in the S1 and 367 in the S2). S1: the median COST value was 23 (range 0-44). ROC curve analyses produced 4 COST grades (G): G0 ≥ 26 (99 pts, 42%); G1: ≥ 14-26 (71 pts, 31%); G2: > 0-14 (58 pts, 25%); and G3: = 0 (5 pts, 2%). Pts with G0 had no impact of FTox on their HRQoL. Absolute e.s. decreases in FACT-G by grade compared to G0 were: G1, 0.59 (95% CI: 0.27 – 0.90); G2, 0.92 (CI: 0.59 – 1.26); G3, 1.77 (CI: 0.83 – 2.70). In multivariate analyses, mood explained 22% (CI 13-31%) of the variability in FACT-G; FTox, 7.6% (CI 2.2-15%); fatigue, 5.6% (CI 1.1-12%); pain, 3.6% (CI 0.3-9.6%); and loss of appetite, 3.4%(CI 0.3-9.3%). VS: applying the COST thresholds to S2, we had: G0: 154 pts (42%); G1: 126 (34%); G2: 84 (23%); and G3: 3(1%). The decreases in HRQoL measured in e.s. were: G1: 0.84 (CI: 0.68 – 1.00); G2: 1.88 (CI: 1.67 – 2.09); G3: 2.99 (CI: 2.29 – 3.68). The association between HRQoL and FTox was significant in multivariate models in both sets (p < 0.001). Conclusions: We developed and validated a FTox grading system in 2 different set of patients. This grading was anchored on independent and clinically meaningful changes in HRQoL attributable to FTox. FTox is a meaningful event that can be objectively measured, and should be included in the assessment of patient-centered outcomes.
Determinants of adherence to physical activity guidelines among overweight and obese African American breast cancer survivors: Implications for intervention approach.
Authors: Smith Selina , Yoo Wonsuk , Ansa Benjamin E. , Coughlin Steven S. , Whitehead Mary S. 
Published: February 2017

178 Background: Public health agencies encourage breast cancer survivors (BCSs) to follow their physical activity guidelines (PAGs). However, adherence to these guidelines is low. African American (AA) BCSs are more often overweight or obese and less likely than women of other races to report adherence to physical activity (PA) recommendations. To address the research question, “what prevents AA BCSs from following PAGs,” we examined socioeconomic, clinical, and psychosocial correlates with PA levels. Methods: AA women diagnosed and treated for breast cancer participating in a breast cancer support group (n = 191) completed a lifestyle assessment tool (LAT) capturing demographic characteristics; breast cancer diagnosis and treatment history; health-related quality of life (HR-QoL); weight history, including body mass index and post-diagnosis weight gain; and physical activity. Logistic regression and analysis of variance were used to determine whether these covariates were associated with meeting ( > 17.5 MET h/wk); partially meeting (8.75-17.5 MET h/wk); or not meeting ( < 8.75 MET h/wk) PAGs. Results: Preliminary results indicate that 44.44% of AA BCSs met PAGs. This percent is below the national average for AA women (56.5%) and white women (67.5%). Conclusions: Identifying factors that influence adherence to physical activity behaviors is important in developing effective interventions. These findings may help generate hypotheses for future research to undergird efforts to increase PA among AA BCSs.
Post-traumatic stress disorder in young breast cancer survivors.
Authors: Vazquez Danny A. , Rosenberg Shoshana M. , Gelber Shari I. , Ruddy Kathryn Jean , Morgan Evan , Recklitis Christopher J. , Come Steven E. , Schapira Lidia , Partridge Ann H. 
Published: February 2017

202 Background: Posttraumatic stress disorder (PTSD) is associated with morbidity and mortality in affected populations. Cancer survivors experience PTSD at a rate higher than the general population, with young age and female gender identified as risk factors. While young women with breast cancer experience greater psychosocial distress in general following diagnosis (dx), little is known about PTSD in this population. Methods: Women dx’d with Stage I-III breast cancer at age ≤ 40 were surveyed as a part of a multi-site cohort study. Demographic, treatment, psychosocial characteristics (including self-reported psychiatric conditions and use of psychiatric medications prior to dx), anxiety and depression (Hospital Anxiety and Depression Scale), fear of recurrence (Lasry Scale), and social support (Medical Outcomes Study) were assessed within 1 year after dx. PTSD was measured at 30 months post-dx using the PTSD Checklist – Civilian Version; a score ≥ 50 was considered positive for PTSD. Univariable and stepwise multivariable logistic regression were used to evaluate factors associated with PTSD. Results: 572 women were eligible for this analysis; median age at dx was 37 (range: 17-40); 87% had Stage I or II cancer. 37/572 women (6.5%) met criteria for PTSD at 30 months. Lower educational attainment, less financial comfort, less social support, stage 2 (vs. 1) disease, receipt of chemotherapy, fear of recurrence, anxiety and depression, and psychiatric comorbidities were associated (p ≤ 0.05) with PTSD in univariable analyses. Chemotherapy (OR = 3.48, 95% CI = 1.09-11.06), anxiety by HADS (OR = 20.29, 95% CI = 7.83-52.53), and psychiatric comorbidities (OR = 4.22, 95% CI = 1.40-12.74) were associated with increased likelihood of PTSD, whereas college education (OR = 0.25, 95% CI = 0.10-0.59) and greater social support (OR = 0.41, 95% CI = 0.17-0.99) appeared to be protective in multivariable analyses. Conclusions: PTSD affects a minority of young breast cancer survivors, with the prevalence in our cohort similar to that seen in other breast cancer populations. Early identification of those at risk for developing PTSD is essential for the adequate treatment of affected women and for the improvement of health outcomes and quality of life in cancer survivors.
Sexual function of long-term rectal cancer survivors.
Authors: McMullen Carmit K. , Grant Marcia , Wendel Christopher , Bulkley Joanna E , Sun Virginia , Herrinton Lisa J. , Hornbrook Mark C. , Krouse Robert S. 
Published: February 2017

209 Background: Many rectal cancer survivors report problems with intimacy and sexual function after surgery. The extent of these problems is not well known. Methods: Long-term rectal cancer survivors (5+ years post-diagnosis) who were members of Kaiser Permanente with permanent ostomy (n = 183) or sphincter-sparing surgery (N = 394) completed a mailed survey. Participants were identified through tumor registries and health plan data. Items from the City of Hope Quality of Life Colorectal Cancer scale assessed disruption to intimate relationships due to the surgery on a scale of 0-10, with 10 indicating the least disruption. Other items assessed current experiences of and satisfaction with sexual function as well as comfort being undressed in front of a partner. Results: Survey response rate was 60.5% (N = 577). Respondents’ average age was 73 years, 41% were female, 63% were married or partnered at the time of survey, and 30% reported being sexually active. Fifteen percent of those who were not sexually active feared resuming sexual activity. Thirty-five percent of all respondents found their sexual activity unsatisfying. Of the 236 female respondents, 24% reported current problems with vaginal dryness, 12% with vaginal stricture, and 9% with vaginal pain. Of the 341 male respondents, 64% reported current problems getting an erection and 65% with maintaining one. Survivors with ostomy vs. sphincter-sparing surgery reported more interference with personal relationships (6.4 vs. 8.3, p < .001) and less ability to be intimate (5.1 vs. 7.0, p < .0001). A higher percentage with ostomy also reported discomfort being undressed in front of their partner (40.6% vs. 10.6%, p < .001). Conclusions: Many rectal cancer survivors were unsatisfied with their sexual activity. One in ten women reported vaginal stricture, which can be mitigated by early intervention. Nearly 1/4 reported problems (dryness, pain) that can be addressed at any phase of survivorship. Two thirds of men reported trouble with getting an erection and with maintaining one, indicating a significant opportunity for intervention in this cohort. Sexual function did not differ significantly between surgery groups. In line with previous reports, survivors with ostomy had more intimacy and body image problems.