tbuckley/cabot-search huggingface dataset:
Therapeutic imatinib monitoring in patients with gastrointestinal stromal tumours.
Authors: Pavlina Spiliopoulou, Dawn Currie, Caroline Haig, Fiona Cowie, Jeff D. White
Journal: Journal of Clinical Oncology (2016)

e22512 Background: Imatinib is the treatment of choice for GIST. Previous studies suggest that trough concentration (Cmin) of more than 1.1mg/L achieve better outcomes and that Cmin correlates with albumin and creatinine clearance (CrCl). Pharmacokinetics becomes steady after 3 months of therapy. We report imatinib Cmin values on patients treated for GIST outside a clinical trial, the pattern of their responses, as well as covariates affecting Cmin. Methods: Association wasexamined using Spearman correlation co-efficient (r), Mann-Whitney tests and linear models. Results: Imatinib Cmin was obtained from 38 patients with a mean age of 66 years (SD ± 10y). All but 3 patients received 400mg. Main reason for dose reduction was GI and skin toxicity. Response rates in 23 evaluable patients were SD 74%, PR 17% and CR 9%. Median duration of disease stabilisation in this highly selected cohort was 70 months (95%CI 51.8-88.3). Toxicities were grade 1 with rates of 42% GI, 55% oedema and 21% muscle cramps. Median treatment duration was 37 months (2-155); therefore Cmin had reached steady state for the majority of patients. Mean Cmin was 1.2mg/L(95% CI 1.02-1.38). There was a mildly negative correlation with CrCl (r = -0.29, p = 0.06) and this becomes more prominent when albumin is a covariate(p = 0.02). While overall there is a mild positive correlation with age (r = 0.33, p = 0.04), the association for females is stronger (0.636, p = 0.003) than for males (r = 0.189, p = 0.436). Patients reporting drug-induced toxicity and those on concomitant medications that increase Imatinib exposure had higher Cmin but this was not statistically significant (p = 0.29 and p = 0.88, respectively). Cmin was also not statistically significant between patients achieving CR/PR (n = 6) when compared to SD (n = 17) (p = 0.48) but their numbers were small. Conclusions: This small exploratory analysis is the first real data report for GIST patients in the West of Scotland. Toxicity profile of 400mg dose was comparable to that reported in the literature and mean Cmin was above the proposed cut-off level of 1.1mg/L. Age and CrCl seem to correlate with imatinib Cmin. The role of therapeutic monitoring of imatinib levels in GIST is unclear and more studies on patients on steady-state dose are needed.
Can serum IL-6 be a sentinel biomarker of cancer cachexia in gynecologic cancer patients?
Authors: Tomoyuki Yoshikwa, Masashi Takano, Hiroko Kouta, Miyuki Horikoshi, Takayoshi Asakawa, Kazuya Kudoh, Tsunekazu Kita, Kenichi Furuya, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2018)

e17544 Background: Cancer cachexia occurs in approximately 80% of cancer patients, and is the primary cause of death for 22–30% of all cancer patients. Cancer cachexia also diminishes quality of life in cancer survivors due to a severe loss of skeletal muscle mass. Although a multitude of cytokines have been implicated in facilitating a cachectic state, the correlation of serum IL-6 and cancer cachexia in gynecologic cancer patients has not been elucidated. Methods: The correlation between serum level of IL-6 and skeletal muscle volume in the patients with gynecologic cancers that received multiple lines of chemotherapy was retrospectively evaluated. We used the psoas index [PI (mm2/m2)], the psoas muscle major cross-sectional area divided by the height squared, measured using digital axial CT images, for the value of skeletal muscle volume. Serum level of IL-6 was dived into three categories: high ( > 12.0pg/mL), middle (4.0-12.0pg/mL), and low ( < 4.0pg/mL). PI value was also dived into three categories: high ( > 600mm2/m2), middle (500-600mm2/m2), and low ( < 500mm2/m2). Results: A total of 55 cases were assessed for the serum level of IL-6 and PI value: 26 cases with Mullerian cancers, 14 cases with endometrial cancers, 10 cases with cervical cancers, and 5 patients with others. In 22 cases with low IL-6, PI value was low in 9 cases (41%), middle in7 cases (32%), and high in 6 cases (27%). In 12 patients with middle IL-6, PI value was low in 3 cases (25%), middle in7 cases (58%), and high in 2 cases (17%). Among 21 cases with high IL-6, PI value was low in 14 cases (67%), middle in7 cases (33%), and high in no case (0%). High level of serum IL-6 was significantly associated with lower PI value in gynecologic cancer patients (p = 0.025). Conclusions: Serum level of IL-6 could be a sentinel biomarker for cancer cachexia in the patients with gynecologic cancers. Additionally, IL-6 could be a candidate for therapeutic target for the patients complicated with sarcopenia after multiple lines of chemotherapy.
Curative resection in digestive neuroendocrine neoplasms: Recurrence-free survival rate and definition of a risk score for recurrence.
Authors: Elettra Merola, Andreas Pascher, Timm Denecke, Ruza Arsenic, Bertram Wiedenmann, Gianfranco Delle Fave, Marianne E. Pavel
Journal: Journal of Clinical Oncology (2016)

4094 Background: Surgery with radical intent is the only curative option for digestive neuroendocrine neoplasms (DNENs), but clinical practice shows disease-free patients recurring even after years. Our aims were to determine, in a consecutive series of DNENs treated by radical surgery, the recurrence-free survival (RFS) rate (primary end point), and to define a risk score for recurrence (secondary end point). Methods: Retrospective analysis of sporadic pancreatic (PNEN) or small intestine NEN (SINENs) who were treated by R0/R1 surgery between 1993 and 2014, and had a minimum 12-month follow-up after resection. Patients were classified according to the ENETS TNM/grading system. Survival analysis was performed by Kaplan-Meier and comparisons with log-rank, while risk factor analysis was carried out by Cox-regression model; cut-off values were identified by ROC curves. Results: 215 patients (91 PNENs, 124 SINENs) were analyzed, with a median ki67 of 3% (range 1%-20%); 17.2% of them had a stage IV disease at diagnosis. Median RFS of the overall population was 61 months (5-yr rate: 49.5%). Four
Ethnic, racial and gender differences in presentation and outcomes of gastric cancer in a Michigan cohort.
Authors: Lilit Karapetyan, Ling Wang, Joseph Gardiner, Heather Laird-Fick
Journal: Journal of Clinical Oncology (2018)

e18656 Background: Studies have demonstrated inconsistent differences in the epidemiology and outcomes for gastric cancer (GC) based on race, ethnicity, and gender. We examined the association between these factors and diagnoses of GC in a cohort of patients in Michigan. Methods: We reviewed patients with GC diagnosed between 1990 and 2014 and enrolled in the Michigan Cancer Surveillance Program. Patients were followed up through 2016. Data extracted were age and stage at diagnosis, gender, race, and survival status at last follow-up. Statistical comparisons were assessed by chi-square tests in contingency tables and by the log-rank test for survival. Results: We identified 11,105 patients (66.5% male, 75.6% non-Hispanic White, 16.7% non-Hispanic black, 2.0% Hispanic, 1.5% Asian/Pacific Islanders, 3.9% other race) with complete data for analysis. Median age at time of diagnosis was 72 years (range 15 to 106 years). Males were diagnosed at younger age than females (median age: males = 70, females = 75, p < .0001). The distribution tumor stage was I (21.9%), II (30.2%), III (29.9%), IV (17.3%) and un-staged ( < 1%), and differed by sex (p < .003). Race was associated with stage (p = 0.036). There was a significant association of stage with survival (p < .0001), Stage I with the longest median survival.There was a significant association of race with survival (p < .018). Median survival time was lowest among non-Hispanic Black followed by non-Hispanic White, Asian/PI, Hispanic, Other race. There was a no significant association of sex with survival. Conclusions: Race, age at diagnosis and stage at diagnosis were associated with survival, but not sex. Future analyses will explore the effects of treatment modalities on survival.
TCT-658 Complex High and Indicated Percutaneous Coronary Indication: Does Operator Volume Influence Patient Outcome?
Authors: Tim Kinnaird, Sean Gallagher, James Spratt, Peter Ludman, Mark de Belder, Mark de Belder, Richard Anderson, Colm Hanratty, Colm Hanratty, Simon Walsh, Nick Curzen, Mamas Mamas
Journal: Journal of the American College of Cardiology (2018)
Prognostic value of minimal residual disease and polyclonal plasma cells in myeloma patients achieving a complete response to therapy.
Authors: Marcella Tschautscher, S. Vincent Rajkumar, Francis Buadi, Morie A. Gertz, Martha Lacy, Angela Dispenzieri, Suzanne R. Hayman, Yi Lisa Hwa, Amie L. Fonder, Miriam A. Hobbs, Steven R. Zeldenrust, John Anthony Lust, Nelson Leung, Prashant Kapoor, Taxiarchis Kourelis, Rahma M. Warsame, Ronald S. Go, Wilson I. Gonsalves, Robert A. Kyle, Shaji Kumar
Journal: Journal of Clinical Oncology (2018)

8030 Background: Achievement of a complete response (CR) to therapy has been associated with improved outcomes in patients with multiple myeloma (MM). More recently, increasing application of minimal residual disease (MRD) assessment following therapy has shown that MRD negativity is a powerful prognostic factor for survival outcomes. The presence of MRD, even among patients who have achieved a conventional CR, predicts inferior outcomes. Given this, we wanted to examine the impact of the polyclonal plasma cell (pPC) compartment among patients who achieved CR but still have MRD. Methods: This is a retrospective cohort study where 460 myeloma patients were identified who met criteria for CR per IMWG criteria and had application of multicolor flow cytometry to the bone marrow (BM) for the purpose of confirming CR. Mono and pPCs were estimated during MRD testing. A Kaplan-Meier model was used to determine OS and the 2-sided log-rank test to compare MRD+ and MRD- groups. TTNT was calculated as the difference from date of confirmed CR and date of next therapy. Results: The median duration from diagnosis to CR was 11.7 months. The median follow-up for the entire cohort was 33.5 months (95% CI; 31, 36) from CR; and the median OS was not reached (95% CI; 63 mos, NR). Median TTNT was 31 months (95% CI; 27,36). Among the 460 patients, 70% were MRD-, with a median TTNT of 37.6 months vs 23 months for MRD+ patients (p < 0.001); the median OS was not reached for either group, but there was a trend towards better survival for MRD- patients. The improved TTNT with MRD negativity was seen irrespective of prior treatment and SCT status. Among the 139 patients with residual disease, median percentage of pPCs was 65% (2.5 to 98.5), and those with > 95% pPCs had a significantly better TTNT (NR vs 23 months; p = 0.02) and a trend towards better OS. Conclusions: Achievement of MRD negativity predicts for better response durability and trend toward improved OS among patients in conventional CR treated with modern therapies. The impact seems independent of the type of therapy that results in achievement of CR and MRD negative status. Finally, an increased proportion of pPC predicts for better outcomes within those who have residual tumor cells.
Mcp1 Promotes Macrophage-Dependent Cyst Expansion in Autosomal Dominant Polycystic Kidney Disease
Authors: Marcelo F. Cassini, Vijayakumar R. Kakade, Elizabeth Kurtz, Parker Sulkowski, Peter Glazer, Richard Torres, Stefan Somlo, Lloyd G. Cantley
Journal: Journal of the American Society of Nephrology (2018)

Background In patients with autosomal dominant polycystic kidney disease (ADPKD), most of whom have a mutation in PKD1 or PKD2 , abnormally large numbers of macrophages accumulate around kidney cysts and promote their growth. Research by us and others has suggested that monocyte chemoattractant protein-1 (Mcp1) may be a signal for macrophage-mediated cyst growth. Methods To define the role of Mcp1 and macrophages in promoting cyst growth, we used mice with inducible knockout of Pkd1 alone (single knockout) or knockout of both Pkd1 and Mcp1 (double knockout) in the murine renal tubule. Levels of Mcp1 RNA expression were measured in single-knockout mice and controls. Results In single-knockout mice, upregulation of Mcp1 precedes macrophage infiltration. Macrophages accumulating around nascent cysts (0–2 weeks after induction) are initially proinflammatory and induce tubular cell injury with morphologic flattening, oxidative DNA damage, and proliferation-independent cystic dilation. At 2–6 weeks after induction, macrophages switch to an alternative activation phenotype and promote further cyst growth because of an additional three-fold increase in tubular cell proliferative rates. In double-knockout mice, there is a marked reduction in Mcp1 expression and macrophage numbers, resulting in less initial tubular cell injury, slower cyst growth, and improved renal function. Treatment of single-knockout mice with an inhibitor to the Mcp1 receptor Ccr2 partially reproduced the morphologic and functional improvement seen with Mcp1 knockout. Conclusions Mcp1 is upregulated after knockout of Pkd1 and promotes macrophage accumulation and cyst growth via both proliferation-independent and proliferation-dependent mechanisms in this orthologous mouse model of ADPKD.
Early changes in PSA and association with outcomes in mCRPC patients.
Authors: Pasquale Rescigno, David Dolling, Mattia Rediti, Vincenza Conteduca, Michael Ong, Haoran Li, Aurelius Gabriel Omlin, Sabine Schmid, Orazio Caffo, Andrea Zivi, Carmel Jo Pezaro, Courtney Morley, Nuria Romero-Laorden, Maria Isabel Saez, Niven Mehra, Spyridon Sideris, Shahneen Kaur Sandhu, Cora N. Sternberg, Ugo De Giorgi, Johann S. De Bono
Journal: Journal of Clinical Oncology (2018)

5063 Background: Declines in prostate specific antigen (PSA) levels at 12-weeks are currently used to evaluate treatments response in metastatic castration resistant prostate cancer (mCRPC). Early PSA fall by 30% at 4-weeks (PSA4w30) has been previously shown to be associated with better outcome in mCRPC in a small single-centre cohort. Methods: We identified mCRPC patients who had received Abiraterone Acetate (AA) between 06.01.06 and 08.09.17 in 13 cancer centres worldwide. Eligible patients had PSA levels assessed at baseline, after 4-weeks and/or 12-weeks of treatment. PSA response was defined as a ≥30% decline from baseline and PSA progression as a ≥25% increase from baseline. Association with overall survival (OS) was analysed using landmark multivariable Cox regression adjusting for previous chemotherapy, including cancer centre as a shared frailty term. Results: We identified 1057 patients who had received AA (447 pre-chemotherapy, 610 post-chemotherapy), with 835 patients having PSA values available at 4 and 12 weeks. Overall, 372/835 (44.5%) had PSA4w30; this associated with longer OS (mOS 22vs15 months; HR = 0.62; 95%CI 0.53–0.72; p < 0.001). A ≥30% PSA decline at 12-weeks (PSA12w30) associated with a lower mortality (mOS 22vs14; HR = 0.57; 95%CI = 0.48–0.67; p < 0.001). Sensitivity analyses confirmed the association between PSA4w30 and OS when pre- and post-chemotherapy cohorts were analysed separately. PSA4w30 strongly correlated with PSA12w30 (ρ = 0.92; p < 0.001). In total, 320/372 (86%) patients with a PSA decline at 4-weeks had a PSA decline at 12-weeks. Conversely, 11/835 (1.3%) patients progressed at 4-weeks and then met the criteria for PSA12w30. PSA4w30 remained correlated with OS (HR = 0.56; 95%CI = 0.48–0.65; p < 0.001) in multivariate analyses including other established prognostic factors in mCRPC (baseline ALP, LDH, Hb, M status and Gleason at diagnosis). Conclusions: PSA changes in the first 4-weeks of AA therapy are strongly associated with clinical outcome in mCRPC patients and should be prospectively evaluated in early treatment switch decision trials.
Utilization of KRAS mutation status testing in stage IV colorectal cancer (CRC) patients in the United States: National Cancer Data Base (NCDB) analysis.
Authors: Amila Orucevic, Natalie Bennett, Keith D Gray, John Lawrence Bell, Heidel Robert
Journal: Journal of Clinical Oncology (2017)

e15172 Background: KRAS mutation status is considered a predictive biomarker of personalized treatment in advanced stage CRC. Its testing is recommended by the National Comprehensive Cancer Network guidelines for stage IV CRC, since it determines the benefit of addition of anti-epidermal growth factor receptor therapy in wild-type KRAS CRC. Data on utilization of the test in the clinical practice across the US are lacking. Methods: Utilization of KRAS testing across the US is presented in a retrospective observational study of NCDB patients (pts) from 2010-2014. Demographics of stage IV CRC pts with recorded KRAS results were analyzed using frequency statistics and logistic regression analysis. Results: 479399 pts had CRC, 93514 (19.5%) were stage IV. 57208/93514 pts with known KRAS testing status entered our study. Mean age was 63.3 years; 51.2% were males. Only 33% (18867/57208) of stage IV CRC pts underwent KRAS testing. Testing was significantly ( p&lt;.001) influenced by pts age and socioeconomic status but not by race or facility type in which pts were treated (Table 1 - see adjusted odds ratio [AOR] and 95% CI). Conclusions: KRAS testing of stage IV CRC pts is underutilized in the US. Impact of its underutilization on outcomes of these pts requires further study. [Table: see text]
Diagnostic and prognostic roles of serum interleukin-32 (IL-32) levels in patients with pancreatic adenocarcinoma.
Authors: Senem Karabulut, Cigdem Usul Afsar, Vildan Yasasever, Mehmet Karabulut, Kayhan Erturk, Halil Alis, Meral Gunaldi, Kıvanc Derya Peker, Nergiz Dagoglu, Faruk Tas
Journal: Journal of Clinical Oncology (2016)

e15680 Background: This study was conducted to investigate the serum levels of interleukin-32 (IL-32) in patients with pancreatic adenocarcinoma (PA) and the relationship with tumor progression and known prognostic parameters. Methods: Thirty-three patients with PA were investigated. Blood samples were obtained from patients with PA at first admission, one month after surgery and two weeks before adjuvant or palliative treatment. Serum IL-32 levels were determined using enzyme-linked immunosorbent assay (ELISA). Age- and sex-matched 30 healthy controls were included in the analysis. Results: The median age at diagnosis was 59 years, range 32–84 years; 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (n = 19, 83%). The median follow-up time was 26.0 weeks (range: 1.0-184.0 weeks). At the end of the observation period, thirty-two patients (97%) were dead. Thirty-nine percent of 23 metastatic patients who received palliative chemotherapy (CTx) were CTx–responsive. Median overall survival (OS) of the whole group were 41.3±8.3 weeks [95% confidence interval (CI) = 25-58 weeks]. The baseline serum IL-32 levels were significantly higher in patients with PA than in the control group (p = 0.04). Serum IL-32 levels were significantly higher in the patients with liver metastatic disease (p = 0.05). Moreover, patients with elevated serum IL-32 concentrations had significantly favorable OS compared with those with lower levels (median 47.2 vs 32.7 weeks, respectively, p = 0.05). Conclusions: Serum levels of IL-32 may be a good diagnostic and prognostic marker for PA.
One way to shrink oncology patients’ emergency room length of stay.
Authors: Mohamed M. Hegazi, Phuong Ngo, Jugraj S. Dhanoa, Hugh W. Shoff, Goetz H. Kloecker
Journal: Journal of Clinical Oncology (2018)

e18850 Background: Oncology patients face multiple challenges during their treatment journey. One of the deterring factors for oncology patients to seek medical attention is the lengthy ER (Emergency Room) stay before admission to the hospital or discharge home. The goal of this project was to investigate the safety and utility of an early admission order as a way to shrink ER-LOS (Length of Stay). Methods: In this quality improvement project, we reviewed the ER-LOS of patients admitted to the medical oncology service overnight between September 2016 to January 2017 and September 2017 to January 2018. In August 2017, we implemented placement of an early admission order as soon as the patient was accepted for admission to general medical floor by the medical oncology team. We compared ER-LOS but focused on the duration between the call for admission to the time the patient was transferred to the floor. Our goal was to achieve less than 3hrs ER-LOS from the call for admission to floor arrival. We utilized Chi-Square for statistical significance. We monitored for any adverse events occurred with this process change. Results: We analyzed 70 cases that fit our criteria with 62 cases having the information needed. From September 2016 to January 2017, the average length of stay in the ER after admission acceptance in 25 cases was 5.05hrs compared to 3.6hrs in 37 cases from September 2017 and January 2018, a statistically significant decrease of 1.45hrs in ER-LOS (P value < 0.01). The average duration of ER-LOS was shortened from 9.02hrs to 7.52 in pre and post implementation respectively (P value > 0.05). The majority of admissions in both cohorts was for gastrointestinal and respiratory complaints. One patient in the post implementation cohort was transferred from the ER to the oncology floor without being seen by the admitting resident but had no complications. No significant adverse events were noted in the post implementation cohort. Conclusions: An early admission order can shorten the ER length of stay safely but close monitoring is still warranted for safety.