tbuckley/cabot-search huggingface dataset:
Response to induction chemotherapy for locally advanced nasopharyngeal cancer to predict prognostic impact of chemosensitivity.
Authors: Jiade J. Lu, Xiaoshuang Niu, Xiaoming Ou, Fei Liang, Chaosu Hu, Lin Kong
Journal: Journal of Clinical Oncology (2016)

6033 Background: Nasopharyngeal cancer (NPC) is highly sensitive to chemotherapy and radiotherapy, and concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced NPC (LA-NPC).The effectiveness of platinum-based induction chemotherapy (ICT) with novel agent(s)such as taxane on overall or disease-free survival has been suggested in prospective trials. The purpose of this study is to evaluate the clinical value of observed response to ICT in predicting treatment outcome in patients with LA-NPC. Methods: Between 4/2007 and 8/2014, 687 patients with LA-NPC(i.e., T3, T4, or N+) were treated with platinum-based ICT(100 patients with taxane +/-5FU or gemcitabine [TP/TPF/GP], and 17 with 5FU [PF]) and evaluated for response with MRI were identified. Among the 120 patients who had stable disease (SD) or progression (PD) after ICT (ICT-resistant), 117 were successfully matched for diagnosis/follow-up time, gender, TNM stage, ICT regimen, CRT regimen (none vs. low vs. high dose cisplatin vs. targeted agents), and adjuvant chemotherapy (none vs. TP/TPF/GP vs. PF) to 117of the remaining 567 patients who achieved complete or partial response (CR or PR) after ICT (ICT-sensitive) by propensity score analysis. Results: The median follow-up time was 34 months (range 3-97 months). The overall survival (OS), progression-free survival (PFS), and local/regional/distant-metastatic relaps free survival (LRFS/RRFS/DMFS) rates were significantly better in the ICT-sensitive group (Table). Conclusions: Response to ICT is a significant predictive factor not only for OS, PFS, and DMFS but also for locoregional disease control in patients with LA-NPC. Prospective study is needed to confirm such findings then evaluate whether more aggressive CRT and/or adjuvant chemotherapy regimens may improve the prognosis of the ICT-resistant LA-NPC patients. Treatment outcomes in ICT-sensitive vs ICT-resistant LA-NPC patients. 3-year (%) 5-year (%) P value ICT-resistant ICT-sensitive ICT-resistant ICT-sensitive OS 79.3 94.9 66.1 84.2 0.006 PFS 47.1 86.4 31.1 72.8 <0.001 LRFS 73.0 57.6 97.9 94.4 <0.001 RRFS 80.8 80.8 97.5 97.5 <0.001 DMFS 77.2 66.9 90.8 76.2 0.005
Thermal ablation for treatment of hepatic metastasis from thymic epithelial tumors (TETs).
Authors: Angela Chen, Nadine Abi-Jaoudeh, Min-Jung Lee, Jane B Trepel, Udayan Guha, Elliot B Levy, Venkatesh P Krishnasamy, Bradford J. Wood, Arun Rajan
Journal: Journal of Clinical Oncology (2017)

e20000 Background: Thermal ablation [radiofrequency ablation (RFA), cryoablation, microwave ablation (MWA)] has been used effectively for control of hepatic metastases from various solid tumors. However, these interventions have not been systematically evaluated in patients (pts) with TETs. We present our experience of the safety and clinical efficacy of thermal ablation in pts with advanced TETs and limited sites of disease progression. Methods: Pts with metastatic TETs followed at the National Cancer Institute were considered for thermal ablation if extrathoracic disease progression was limited to 3 or fewer anatomic sites amenable to percutaneous thermal ablative techniques. Appropriate imaging studies were used to evaluate for recurrence, and recurrence-free survival (RFS) was calculated. Biopsies were performed prior to ablation to study mutational and signaling events that may predispose to benefit. Results: From November 2012 to June 2016, 11 metastases (9 liver, 2 chest wall) in 4 pts (3 male, 1 female; median age 59.5 (range, 59-67); 3 thymic carcinoma, 1 WHO B2 thymoma; all Masaoka stage IVB) were treated with thermal ablation (6 MWA, 3 RFA, 2 cryoablation). Median size of metastasis was 1.5 cm (range, 1-4 cm). Local recurrence occurred at 2 (18%) of 11 treated sites, 11.5 months and 10 months after thermal ablation. All pts experienced distant recurrence (1 mesenteric/pelvic mass, 1 lung, 1 malignant pleural effusion, 1 liver) with a median RFS of 7 months (range, 2.5-14). Treatment was well tolerated with no serious adverse events. One pt died due to disease progression 9 months after thermal ablation; 3 pts are alive at the time of reporting (23.5, 37.5 and 38 months after treatment). Conclusions: Thermal ablation is well tolerated and largely successful in achieving local control in pts with advanced, unresectable TETs. Further studies are needed to assess the clinical benefit of thermal ablation compared with systemic therapy and surgery in specific pts with recurrent, oligometastatic TETs. The exact role of thermal ablation tools remains to be defined in this population. The potential for local thermally-induced cell death to induce or augment immunogenic tumor cell death will be assessed and reported.
Sub-lobar lung resections in patients with non-small cell lung cancer associated with positive nodes: Incidence, risk factors, and prognostic variables.
Authors: Kerri McKie, Malcolm M. DeCamp, John M. Varlotto, Thomas J. Fitzgerald, Paul Rava, William Vincent Walsh, Negar Rassaei, Lacey McIntosh, Karl Uy, Jennifer Baima, Akalin Ali, Debra Maddox, Isabel Emmerick, John Charles Flickinger
Journal: Journal of Clinical Oncology (2018)

e20507 Background: The incidence and prognosis associated with patients undergoing sub-lobar resections and having positive lymph nodes(PLN) has been rarely studied. Our investigation will retrospectively review this topic. Methods: The National Cancer Database(NCDB) was queried during the years 2004-2014 to assess patients undergoing sub-lobar resection (wedge, segmentectomy, and sub-lobar-NOS, N = 24,421) and specifically the patients with PLN (N = 3,220). Patients were excluded who had any pre-op chemotherapy and/or radiation, had follow-up of less than 3 months, had stage IV disease or > 1 tumor nodule. Multi-variable modeling(MVA) was used to determine factors for overall survival (OS). Propensity score matching(PSM) was used to determine pre-operative risk factors for PLN in patients having at least one node examined (matched by median number of nodes examined) and to assess the role of radiation in those patients with node positive disease (matched by age, sex, stage, chemotherapy, and number of nodes positive). Results: The incidence of PLN decreased progressively during our study from 17.9% in 2004 to 9.4% in 2014 (N1- 3.3-8.1% and N2 4.4 -9.6%). A lower risk of PLN was noted for squamous cell carcinomas, BAC cancers, and right upper lobe locations, but the risk increased with age, tumor size and clinical stage. In the node positive group, MVA demonstrated that OS was worse with males, older ages, non-Hispanic Whites (compared to Asian and White Hispanics), lowest income quartile, Charlson co-morbidity > 0, grade, tumor size, number of positive nodes, positive surgical margins, length of stay, and not receiving chemotherapy or radiation. PSM demonstrated that radiation increased OS in patients having PLN regardless of margin status or N level involvement. Conclusions: The incidence of node positive sub-lobar resections has decreased during the years of our study, but still can be found in nearly 10%. In both MVA and PSM, post-operative radiation improves OS.
Whole blood androgen receptor (AR) variant (ARV12, ARV14) expression and overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC).
Authors: Karthik Giridhar, Carlos Sosa, David W. Hillman, Cristobal T. Sanhueza, Liguo Wang, John C. Cheville, Scott Dehm, Manish Kohli
Journal: Journal of Clinical Oncology (2017)

5058 Background: The detection of full length AR (AR-FL) or AR variants (AR-Vs) in blood and association with outcomes in mCRPC is unknown. We compared whole blood mRNA expression of AR-FL and AR-Vs to circulating tumor cells (CTCs) for predicting OS and time to treatment failure (TTF). Methods: We isolated RNA from whole blood collected in PAXgene RNA tubes and concurrent metastatic tissue biopsy from 51 men with mCRPC prior to initiation of abiraterone acetate in a prospective clinical trial (NCT#01953640). Whole transcriptome sequencing (RNAseq) was performed on blood samples and paired biopsies to detect AR-FL, ARV1, ARV3, ARV7, ARV8, AR12, ARV14, and ARV45. Reads were aligned to the GRCh38 reference genome with the spliced-alignment TopHat2 package. The Pearson correlation coefficient was calculated between AR-FL in blood and matched bone biopsy. CTCs were determined using the CELLSEARCH assay. Cox proportional hazard regression analysis was performed on AR-FL, each AR-V, and CTCs for association with OS and TTF. We compared the area under the curve (AUC) using CTCs alone to a multivariable model that included AR-Vs for predicting OS. Results: The median follow up was 3.0 years, (range 0.3-3.5); the median CTC count was 3 (range 0-372); 34/53 men were deceased. Blood based AR-FL or AR-Vs were detected in 50/53 patients with following distribution: AR-FL (41/53), ARV3 (9/53), ARV45 (8/53), ARV12 (4/53), ARV14 (4/53), ARV7 (2/53), and ARV8 (2/53). Whole blood AR-FL transcripts were highly correlated to paired bone biopsy (r 2 = 0.76). Elevated transcripts of either ARV12 or ARV14 were associated with decreased OS [hazard ratio (HR) 3.46, p = 0.006]. CTC count ≥5 was associated with poorer OS [HR 3.42, p = 0.02] and shorter TTF [HR 3.52, p = &lt; 0.001]. Adjusting for CTC counts, in a multivariate model, blood AR12 expression was associated with poor OS [HR = 6.33, p = 0.009]. AR12 and CTCs trended toward improved AUC compared to CTC alone (0.78 vs 0.71, p = 0.07). Conclusions: AR-FL and AR-Vs are detectable in whole blood and are highly correlated with metastatic bone AR-FL expression. AR-Vs may add to prognostication in mCRPC and further validation is needed. Clinical trial information: NCT#01953640.
Prognostic impact of plasma CA 19-9, IL-6 and YKL-40 in patients with inoperable cholangiocarcinoma.
Authors: Dan Hogdall, Christian Dehlendorff, Mogens Karsboel Boisen, Ole Larsen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2016)

e15638 Background: Cholangiocarcinoma (CCA) is associated with chronic inflammation. We tested the hypothesis, that serum CA 19-9 in combination with the pro-inflammatory biomarkers IL-6 and YKL-40 (CHI3L1) have prognostic value. Methods: 56 patients with inoperable CCA were included in a prospective phase II study and treated with capecitabine, oxaliplatin, gemcitabine and cetuximab (GEMOXCAP+cet). Plasma samples were taken before first and second treatment and at evaluation every second month. Plasma CA 19-9 was determined using the Immulite 2000 GI-MA (Siemens) and plasma IL-6 and YKL-40 by ELISAs (IL-6: R&D Systems, UK; YKL-40: Quidel, USA). Results: Baseline plasma concentrations of CA 19-9, IL-6 and YKL-40 were elevated (compared to normal levels) in 80%, 63% and 41% of the patients, respectively. Patients with high (i.e. dichotomized according to normal levels) plasma YKL-40 or CA19-9 had shortest progression free survival (PFS) (YKL-40: HR = 1.99, 95% CI 1.10-3.61, p = 0.023; CA 19-9: HR = 2.38, 1.05-5.43, p = 0.039). Similar (non-significant) trend was found for IL-6 (HR = 1.68, 0.94-3.01, p = 0.0728). Patients with high levels of all 3 biomarkers had short PFS (HR = 7.9, 1.68-37.08, p = 0.0088). The changes (baseline log2-transformed level + log ratio for IL-6 and age-adjusted for YKL-40) in IL-6 and YKL-40 during treatment were also associated with PFS (IL-6: HR = 1.29, 1.06-1.59, p = 0.022; YKL-40: HR = 2.14, 1.15-3.98, p = 0.026). Patients with high plasma CA 19-9 (HR = 2.75, 1.15-6.58, p = 0.0225) or IL-6 (highest quartile; HR = 2.66, 1.20-5.91, p = 0.016) had shortest OS. Patients with high levels of all 3 biomarkers had short OS (HR = 7.01, 1.84-26.7, p = 0.0043). The changes (baseline log2-transformed level + log ratio for CA 19-9 and IL-6 and age-adjusted for YKL-40) in all 3 biomarkers were also associated with OS (CA 19-9: HR = 1.31, 1.15-1.50, p = 0.0002; IL-6: HR = 1.58, 1.29-1.94, p = 0.0001; YKL-40: HR = 2.68, 1.32-2.19, p = 0.0068). Conclusions: A combination of high plasma concentrations of CA 19-9, IL-6, and YKL-40 in patients with non-resectable CCA before and during treatment with (GEMOXCAP+cet) predicted poor prognosis. The number of patients is small and the results should be validated in a larger cohort.
Timing of initiation of adjuvant chemotherapy and the progression of breast cancer on a predominant hispanic population: A retrospective study.
Authors: Gerardo Cabanillas, Amandeep Singh Aujla, Andrea M. Popescu-Martinez
Journal: Journal of Clinical Oncology (2016)

10096 Background: The timing of adjuvant chemotherapy after the surgery has been suggested to have an important impact in the progression of the breast cancer. The aim of the study is to evaluate the association among the timing of the initiation of adjuvant chemotherapy and the progression of the breast cancer or metastasis in a predominant Hispanic population. Methods: Women diagnosed with breast cancer and enrolled in the oncology software at the New York Medical College Metropolitan Hospital Center from 2000 to 2014. Patients were classified into four group of 21 days each, from surgery to the beginning of adjuvant chemotherapy. They were grouped in cohorts of ethnicity, age at diagnosis, stage at diagnosis, hormonal status and metastasis. Statistical analysis was performed with Chi square and the Mantel-Haenszel-Chi square method with an established p value of < 0.05. Results: From a total of 354 patients, 148 were eligible. Hispanic population represented a total of 97 (65.5%), in whom 46 patients (47.5%) were from group B or ER/PR positive and Her2 negative. A total of 21% of patients in the Hispanic ethnic group, presented a triple negative hormonal type. The vast majority of patients have received adjuvant chemotherapy between 22 to 42 days after the surgery. The Chi square analysis result was 2.28 with a p-value of 0.51. A Mantel-Haenszel Chi square test was 0.392 with a p-value of 0.53. No statistical significant difference was found to establish the relationship of the timing to initiation of adjuvant chemotherapy and the progression of the breast cancer or metastasis. Conclusions: There was no relationship between the timing of the adjuvant therapy and the progression of the breast cancer. The predominant ethnic group in our study was Hispanic with an ER/PR positive and Her2 negative as the most common hormonal status. We obtained similar results as previous reports like in the Danish Breast Cancer Cooperative Group in 2005 by S Cold and the report by Colleoni and Gelber in 2014. Triple negative breast cancer is less common in the Hispanic population, leading us to expect a higher survival rates. We suggest further studies on Hispanic population and breast cancer.
Abstract 14833: National Trends in Complications and 30-day Re-hospitalization After Lead Removal/extraction: Analysis From a Cohort Of 42,878 Patients
Authors: Siva K Mulpuru, Peter A Noseworthy, Lindsey R Sangaralingham, Raphael Mawangi, Abhishek J Deshmukh, Nilay D Shah, Ammar M Killu, Samuel J Asirvatham, Yong-Mei Cha, Paul A Friedman
Journal: Circulation (2015)

Introduction: As the US population ages and indications for cardiac device implantation expand, there is a concomitant increase in patients undergoing lead removal/extraction (LR/E).. We sought to examine trends in outcomes and complications associated with LR/E. Methods: We conducted a retrospective analysis using data from a large U.S. commercial insurance database (privately insured and Medicare Advantage patients) identifying all patients undergoing LR/E between 2004 and 2013 with at least one year continuous medical plan enrollment prior to LR/E (to identify baseline comorbidities). Using ICD9 codes and CPT codes, major complications (hemorrhage requiring transfusion, vascular injury, pericardial complications, respiratory complications, cerebrovascular complications, and requirement for cardiac surgery) associated with LR/E and 30-day readmission rates were evaluated. Results: Among 42,878 patients who underwent LR/E (median age of 62 ( 54, 72) years, 70% male); approximately 1 in 40 experienced a major adverse event (2.4%) during the study period. Respiratory complications were the most common complication and 311 patients required cardiac surgery. 30-day readmission occurred in 11.1% of the total population. The most common reasons for readmission were heart failure exacerbation (18.7%) and device related complications (13.2%). Conclusion: The observed complication rates after LE/R in clinical practice are similar to those seen in recent clinical trials and have been relatively stable over the past 10 years.
Preclinical combination of radiation and fibroblast activation protein inhibition in pancreatic cancer.
Authors: Kristina Hoot Young, Kayla McCarty, David Friedman, Benjamin Cottam, Pippa Newell, Michael Gough, Marka R. Crittenden
Journal: Journal of Clinical Oncology (2016)

e23117 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma and poor immune infiltrate, in part driven by cancer-associated fibroblasts (CAFs). CAFs contribute to immune escape via sequestration of anti-tumor CD8 T cells, upregulation of immune checkpoint ligand expression, and immunosuppressive cytokine production and polarization of tumor infiltrating immune cells. Methods: We established syngeneic pancreatic tumors in immune competent C57BL/6 mice using Panc02 cells. From day 7-20, mice were treated with fibroblast activation protein (FAP) inhibitor UAMC-1110 or control. Radiation (RT) was delivered exclusively to the tumor using a 1cm collimator on the Small Animal Radiation Research Platform, 10Gy x 3 daily fractions on day 14, 15, and 16. Tumors were measured, and mice followed for survival. Using the same treatment groups above, tumors were harvested for flow cytometry and multiparameter immunofluorescence on day 14, 23 and 43. Results: UAMC-1110 alone had no effect on tumor growth or survival. RT caused a transient growth delay, resulting in a survival advantage. Combination treatment with radiation and UAMC-1110 resulted in two temporally distinct growth delays: an initial tumor growth delay significant over radiation alone at day 22, and a second late response at day 43; but did not translate to a survival advantage over RT. At day 14, UAMC-1110 treatment resulted in fewer intratumoral myeloid cells. At day 23, RT increased CD11b tumor infiltrate, MDSCs, and CD3 infiltrate. Tumors from combination treated mice had increased Gr1HI cells and CD4 T cells, including Tregs. Macrophages increased with UAMC-1110, RT, and combination therapy in an additive manner. While CD8 to CD11b ratio increased with UAMC-1110 treatment, only 3 CD8 T cells were present per 100 myeloid cells. Tumor immune infiltrate was equivalent at day 43. Conclusions: We tested a novel specific FAP inhibitor with radiation in a murine PDAC model. We found FAP inhibition altered tumor immune infiltrate and caused two temporally distinct decreases in tumor growth when combined with RT. Interrogation of tumor immune infiltrate demonstrates alterations in innate and adaptive immune populations.
Physician experience and understanding of clinical trial adverse event attribution.
Authors: Jennifer Le-Rademacher, Elizabeth M. Storrrick, Aminah Jatoi, Sumithra J. Mandrekar
Journal: Journal of Clinical Oncology (2018)

e14524 Background: The NCI and FDA mandate the collection of adverse events (AEs) in cancer clinical trials to ensure patient safety. Clinicians are also required to declare whether or not each AE is related to the cancer drug patients received (known as AE attribution). However, prior research from our group demonstrates that attribution is unreliable. An overhaul of the current system is thus needed to ensure new drugs are safe for patients and that the development of promising cancer drugs is not halted for unfounded safety concerns. Hence, we conducted a survey to understand the current AE attribution process and to help formulate recommendations for an improved system. Methods: An electronic survey was developed and conducted among 165 medical oncologists, hematologists, and cancer prevention specialists at the Mayo Clinic. It included 21 items that queried clinicians about their clinical practice and trial experience, their training in AE attribution assignment, and their recommendations for improving the current AE attribution system. Results: 61 (37%) clinicians responded to the survey. The median survey completion time was 3.7 minutes. 43% of responders were younger than 45 years of age and 28% were female. The median years of clinical practice experience was 15 (range: 1 – 64) and of trial experience was 12 (range: 2 – 45). 89% had served as a trial PI. 15% of responders received formal AE attribution training, 70% only received informal training, and 15% received none. Other AE attribution experience is summarized in Table 1. Conclusions: The majority (66%) of experienced clinicians/clinical trialists from a large academic institution suggest formal training as the most effective means to improve attribution accuracy. This highlights the need for formal attribution training considering investigators in multi-center trials are typically from smaller institutions with fewer colleagues to consult and who enroll only a few patients to each trial. Table 1. Consulted when assigning attribution colleagues 74% study PI 72% Information used baseline AEs 85% AEs from previous cycles 84% Confidence in attribution assessment self 80% literature 60% Suggested training formal 66% regulatory guidance 38% informal or mentoring 43%
Hospice use among Medicare fee-for-service (FFS) or managed-care organization (MCO) enrollees with leukemia and myeloma.
Authors: Adam J. Olszewski, Pamela Egan, Thomas William LeBlanc
Journal: Journal of Clinical Oncology (2018)

10025 Background: Hospice services are “carved out” of Medicare MCO contracts and covered by FFS Medicare. This financially incentivizes MCOs to enroll their patients (pts) in hospice early, and may affect survival outcomes. We compared the use of hospice at the end of life (EOL) and associated overall survival (OS) among MCO and FFS Medicare beneficiaries with hematologic cancers, who are known to underuse hospice and need effective strategies to improve their EOL care. Methods: From the linked Surveillance, Epidemiology, and End Results-Medicare database, we selected pts with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), or myeloma who died in 2007-2011. We identified their MCO/FFS status before death, hospice use at EOL, and disenrollment from hospice before death. We compared binary outcomes in multivariable robust Poisson models, reporting relative risk (RR) adjusted for multiple sociodemographic characteristics. OS from diagnosis was compared in Cox models, reporting adjusted hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 24,118 pts (median age 78 y, 43% women), 25% were enrolled in a MCO at EOL. MCO enrollees were 17% more likely to use hospice than pts with FFS Medicare (RR, 1.17; 95%CI, 1.14-1.21), consistent across histologies (Table). They were also less likely to use hospice services for < 3 days (RR, 0.82; 0.75-0.89). We found no difference in adjusted OS (HR, 0.98; 0.95-1.01), or in the rate of early hospice disenrollment (RR, 1.07; 0.91-1.27) between MCO and FFS enrollees. Conclusions: Compared with FFS enrollees, MCO enrollees with leukemia or myeloma use hospice more frequently and for longer, without any decrease in survival. Enhanced care coordination in MCO may contribute to more meaningful use of hospice among pts with these cancers, suggesting a novel strategy for improving quality of care at EOL in hematology. AML CLL Myeloma N 7,347 6,847 9,924 Hospice at EOL, MCO / FFS 54% / 47% 50% / 45% 55% / 48% RR (95%CI) 1.18 (1.12-1.24) 1.15 (1.08-1.22) 1.18 (1.12-1.23) < 3 days on hospice, MCO / FFS 19% / 25% 18% / 20% 17% / 21% RR (95%CI) 0.74 (0.64-0.87) 0.89 (0.74-1.06) 0.85 (0.74-0.98) HR for OS (95%CI) 1.01 (0.95-1.08) 0.94 (0.88-1.00) 0.98 (0.94-1.04)