tbuckley/cabot-search huggingface dataset:
Bronchial neuroendocrine neoplasms: A Surveillance Epidemiology and End Results (SEER) database review of treatment outcomes.
Authors: Mark Andrew Lewis, James C. Yao
Journal: Journal of Clinical Oncology (2015)

4098 Background: Bronchial neuroendocrine tumors (NENs) are a biologically heterogeneous group of malignancies with varied approaches to treatment. We queried the SEER database about outcomes of surgery and radiation. Methods: We identified 945331 cases in the SEER database with malignancies of the lung and extracted 187991 bronchial NENs – 130092 cases of small cell carcinoma, 44520 cases of large cell carcinoma, 3349 cases of neuroendocrine carcinoma (grades 3/4 [G3/4]), 9135 cases of typical bronchial carcinoid (grade 1 [G1]), and 895 cases of atypical bronchial carcinoid (grade 2 [G2]) – to examine clinical outcomes by treatment modality, including radiation in 82157 cases and surgery in 21352. Results: Surgical intervention on the primary NEN became less frequent as SEER stage become more extensive; operations were performed in 56.0% of cases of localized disease, 19.9% of regional disease, and 4.5% of distant disease. Proportionately more surgery was performed on lower-grade histologies (e.g. 84% of all-stage G1 NENs vs. 27% of large cell carcinomas). Significantly higher median survivals were seen across all SEER stages and histologies with surgical intervention vs. none (e.g. > 240 vs. 68 mos. for localized G1 NENs, p < .001). Across SEER stages, large cell carcinoma was the histology treated proportionately the most often with radiation, given to 52.3% of all cases, followed by 44.8% of small cell, 38.9% of G3/4 NENs, 15.3% of G2 NENs and 4.9 % of G1 NENs. Typical carcinoids did not benefit from radiation regardless of SEER stage, with the largest decrement in median survival in localized disease receiving radiation (37 mos.) vs. none (232 mos., p < .001). Conclusions: Patients undergoing surgery for bronchial NENs had longer survivals than those who did not undergo surgery, regardless of histology or SEER stage. G1 NENs treated with radiation had median survivals poorer than those who did not receive radiation. It is unclear if those patients receiving radiation had positive margins after surgery, initially inoperable disease, or other prognostic factors associated with worse outcomes. Nonetheless, there is no evidence of benefit for radiation administered to G1 NENs of any SEER stage.
Primary care physician continuity and end-of-life care intensity among Medicare cancer decedents.
Authors: Shi-Yi Wang, Laura D. Cramer, Craig Evan Pollack, Cary Philip Gross
Journal: Journal of Clinical Oncology (2017)

38 Background: While continuity with one’s primary care physician (PCP) care may be expected to reduce the intensity of end-of-life care, evidence to date has been inconclusive. Methods: Using the Surveillance, Epidemiology, and End Results–Medicare database, we identified 63,269 decedents who were diagnosed with cancer during the years 2004-2011, had at least 4 PCP visits within the year prior to cancer diagnosis, and died within 6-36 months of diagnosis. Care continuity was defined as having at least one outpatient visit within 6 months of cancer diagnosis by the PCP who saw the patient most frequently in the year before cancer diagnosis. Measures of intensive end-of-life care included chemotherapy received within 14 days of death, &gt; 1 emergency department (ED) visit, &gt; 1 hospitalization, ≥ 1 intensive care unit (ICU) admission or no hospice enrollment within 30 days of death. Using hierarchical generalized linear models, we examined the associations between care continuity and end-of-life care patterns, controlling for patient demographics, numbers of outpatient clinic visits prior to cancer diagnosis, clinical factors and survival duration. Results: Approximately 81.3% of our cohort (N = 51,462) had at least 1 visit with their PCP following their cancer diagnosis. Compared with those who did not have at least 1 visit, patients who saw their PCP after their cancer diagnosis were less likely to use hospice within 30 days of death (adjusted odds ratio [AOR] 0.86; 95% confidence interval [CI] 0.82-0.90). They were more likely to have repeated hospitalization (AOR 1.16; 95% CI 1.10-1.24), repeated ED visits (AOR 1.16; 95% CI 1.10-1.24), ICU admission (AOR 1.16; 95% CI 1.10-1.24), and in-hospital death (AOR 1.14; 95% CI 1.08-1.20). They also had higher expenditures within the last month of life. Results were virtually identical whether we further controlled for the Usual Provider Care index (UPC) or the Continuity of Care Index (COCI). Conclusions: Having a follow-up visit with one’s PCP is associated with an increase in end-of-life care intensity. Given potential confounding, the results should be interpreted with caution; however, this study indicates room for PCPs to improve end-of-life care quality for cancer decedents.
Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial.
Authors: Manish R. Patel, John Allan Ellerton, Jeffrey R. Infante, Manish Agrawal, Michael S. Gordon, Raid Aljumaliy, Carolyn D. Britten, Luc Dirix, Keun-Wook Lee, Matthew H. Taylor, Patrick Schöffski, Ding Wang, Alain Ravaud, Arnold Gelb, Junyuan Xiong, Galit Rosen, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2017)

330 Background: Avelumab is a fully human anti‒PD-L1 IgG1 antibody with promising efficacy and safety in patients (pts) with metastatic urothelial carcinoma (mUC). To further characterize the clinical activity of avelumab in mUC, we report a planned interim pooled analysis of 2 cohorts from a large phase 1b trial (NCT01772004). Methods: Pts with mUC progressed after platinum-based therapy or cisplatin-ineligible, and unselected for tumor PD-L1 expression, received avelumab 10 mg/kg (1 h IV) Q2W. Response was assessed every 6 wks by independent review per RECIST v1.1. Endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety (NCI CTCAE v4.0), and tumor PD-L1 expression (clone 73-10). Results: As of Mar 19, 2016, 241 pts received avelumab for a median of 8 wks (range 2-80); median follow-up was 7.3 mos (range 0-18.2). Primary tumor sites were upper tract (renal pelvis/ureter [23.7%]) and lower tract (bladder/urethra [76.3%]). 95.4% of pts had progressed on prior platinum therapy, and 63.4% had received ≥ 2 prior lines for advanced disease (range 0-6). In 153 pts with ≥ 6 mos follow-up, confirmed ORR was 17.6% (95% CI 12.0-24.6) with 9 complete responses and 18 partial responses; 24/27 (88.9%) were ongoing. Median DOR was not reached, and the 24-wk DOR rate was 92.0% (95% CI 71.6, 97.9). 36 pts had stable disease as best response (disease control rate 41.2%). Median PFS was 6.4 wks (95% CI 6.1-11.4), and median OS was 7.0 mos (95% CI 5.6-11.1). Based on a ≥ 5% PD-L1 staining cutoff in evaluable pts with PD-L1+ (n = 56) and PD-L1– (n = 75) tumors, ORR was 25.0% (95% CI 14.4-38.4) vs 14.7% (95% CI 7.6-24.7; p = 0.178). Treatment-related adverse events (TRAE) of any grade occurring in ≥ 10% of pts were infusion-related reaction (22.8%) and fatigue (12.0%). 7.5% had a grade ≥ 3 TRAE; fatigue (1.2%)/asthenia (0.8%) occurred in &gt; 1 pt. 28 pts (11.6%) had an immune-related TRAE (grade ≥ 3 in 2.5%). There was 1 treatment-related death (pneumonitis). Conclusions: Avelumab is well tolerated and shows promising clinical activity, including durable responses, in pts with mUC, regardless of tumor PD-L1 expression status. Follow-up is ongoing. Clinical trial information: NCT01772004.
Predictive value of Surgical Apgar Score for long-term outcome in patients with gastric cancer.
Authors: Masanori Tokunaga, Tomoyuki Irino, Rie Makuuchi, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2017)

178 Background: Recently, a simple and easy complication prediction system, the surgical Apgar score (SAS) calculated according to three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. We previously reported on the predictive power of SAS for severe complications after gastrectomy. However, the impact of SAS on long-term survival is still unclear. The aim of the present study was to clarify the relationship between SAS and survival outcome in patients with gastric cancer undergoing curative gastrectomy. Methods: This study included 302 patients who underwent curative gastrectomy at the Shizuoka Cancer Center in 2010. Clinical data, including intraoperative parameters, were collected retrospectively. When the SAS score was ≤ 6, patients were classified into an L-SAS group (n = 82), otherwise, they were classified into an H-SAS group (n = 220). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: There was no difference in demographic data including sex and age between the groups. Total gastrectomy was more frequently performed in the L-SAS group (43%) than in the H-SAS group (21%; P &lt; 0.001). The L-SAS group included patients with higher pT and pN stage. Five-year overall survival rate was worse in the L-SAS group (65.4%) than in the H-SAS group (82.7%; P &lt; 0.001). Multivariate analysis, which included age, sex, histology, pT, pN, type of surgery and SAS as covariates, identified lower SAS (HR, 1.71, 95% C.I., 1.04-2.80) as well as age (HR, 1.62, 95% C.I., 1.10-2.40) and pN (HR, 2.05, 95% C.I., 1.19-3.52) as independent prognostic factors. Conclusions: The SAS was found to be a predictive factor for survival. Intraoperative bleeding and vital signs may affect survival of patients, and therefore warrant special attention from surgeons and anesthesiologists.
Analytical Validation of the nCounter®-based Lymphoma Subtyping Test (LST) for Cell-of-Origin (COO) Identification in Formalin-Fixed Paraffin-Embedded (FFPE) Diffuse Large B-Cell Lymphoma (DLBCL) Specimens
Authors: Ning Chen, Shannon Dennis, Patrick Danaher, Brett Wallden, Tressa Hood, Xing Ren, Mingdong Liu, Naeem Dowidar, Amy Sullivan, Taryn Haffner, Alessandra Cesano, Sean Ferree, James Storhoff
Journal: Blood (2016)
Updated analysis of CALGB/ECOG/BMT CTN 100104: Lenalidomide (Len) vs. placebo (PBO) maintenance therapy after single autologous stem cell transplant (ASCT) for multiple myeloma (MM).
Authors: Sarah A. Holstein, Kouros Owzar, Paul G. Richardson, Chen Jiang, Craig C. Hofmeister, Hani Hassoun, David Duane Hurd, Edward Allen Stadtmauer, Sergio Giralt, Steven M Devine, Vera Hars, John R. Postiglione, Daniel Jordan Weisdorf, Ravi Vij, Jan S Moreb, Natalie Scott Callander, Thomas G. Martin, Thomas C. Shea, Kenneth Carl Anderson, Philip L. McCarthy
Journal: Journal of Clinical Oncology (2015)

8523 Background: CALGB 100104 studied Len vs. PBO maintenance following ASCT for newly diagnosed MM patients (pts), demonstrating improved time to progression (TTP), overall survival (OS) and increase in second primary malignancies (SPM) for Len at 34 months (mos) median follow-up. This is an updated intent-to-treat analysis of TTP, OS, and SPM at 65 mos median follow-up for OS. Methods: 460 pts age < 70 years with stable disease or better 100 days post ASCT were randomly assigned to Len (n = 231) vs. PBO (n = 229). Starting dose was 10 mg daily and was escalated to 15 mg daily after 3 mos. Primary endpoint was TTP (time of progressive disease (PD) or death from any cause). After several interim analyses, the study was unblinded at 18 mos median follow-up and 86/128 PBO pts without PD chose to cross over to Len. Results: SPMs diagnosed after randomization but before PD included 14 hematologic and 11 solid tumor SPMs in the Len arm vs. 3 hematologic and 7 solid tumor SPMs in the PBO arm (Table 1). Estimated median TTP is 53 mos for Len and 27 mos for PBO (hazard ratio (HR):0.54 (p < 0.001)). Median OS has not been reached for the Len arm and is 76 mos for PBO (HR: 0.60, p = 0.001). Cumulative incidence risk (CIR) of developing a SPM is higher for Len compared with PBO (p = 0.005) and the CIR of PD (p < 0.001) or death (p < 0.001) is higher for PBO. There was no difference in OS after PD between the Len or PBO arms. The TTP and OS benefit with Len was observed regardless of whether pts were in a complete response or not at randomization and for thalidomide vs. Len induction therapy. Conclusions: There is an increased incidence of SPMs for Len compared to PBO. Post ASCT Len maintenance continues to demonstrate significantly improved TTP and OS. Clinical trial information: NCT00114101. SPM Type Treatment Arm Hematologic (n) Solid tumor (n) Len MDS/AML (10) B-cell ALL (3) Hodgkin lymphoma (1) Breast (3) Prostate (2) Colon (1) Endometrial (1) Glioblastoma multiforme (1) Melanoma (1) Papillary thyroid (1) Salivary gland carcinoma (1) PBO Cross over to Len B-cell ALL(2) MDS (1) Endometrial (1) Melanoma (1) Renal cell (1) Invasive SCC (1) No cross over Melanoma (1) Ovarian/endometrial (1) Lung carcinoid (1)
Association of apolipoprotein-CIII (apoC-III), endothelium-dependent vasodilation and peripheral neuropathy in a multi-ethnic population with type 2 diabetes
Authors: Sharon Li Ting Pek, Chee Fang Sum, Lee Ying Yeoh, Simon Biing Ming Lee, Wern Ee Tang, Su Chi Lim, Subramaniam Tavintharan
Journal: Metabolism (2017)
Preliminary direct evidence of a dose-response relationship for [Y-90]-microsphere selective internal radionuclide therapy (SIRT) in hepatic malignancy.
Authors: Dale L Bailey, Kathy P Willowson, Elizabeth J Bernard, David Chan, Nick Pavlakis, Stephen John Clarke
Journal: Journal of Clinical Oncology (2015)

11064 Background: [Y-90]-SIRT has an established role in managing patients with primary and secondary hepatic neoplasia. Recently, imaging of the regional distribution of the implanted [Y-90]-microspheres with positron emission tomography (PET), usually imaged on a hybrid device incorporating X-ray CT (PET/CT), has been implemented. Aims: #1 - To determine SIRT dose (in Gy) to liver lesions identified on FDG PET/CT; #2 – to use early follow-up FDG PET/CT to examine metabolic response; and, #3 – to relate metabolic response to SIRT dose. Methods: Prospective data collection of baseline and early follow-up FDG PET/CT as well as Y-90 images within 24 hrs of SIRT (SIR-Spheres microspheres, Sirtex Medical, Sydney, AUS) between January 2013 and June 2014. Within a PET-defined volume of interest (VOI) we measured Total Lesion Glycolysis (TLG = lesion volume on FDG PET × average SUVVOI) for up to 5 target lesions. Fractional change (%) in TLG between baseline and follow-up was determined and compared to the average dose within the FDG-defined target lesion VOIs applied to the Y-90 PET images converted to dose maps. A positive change in TLG reflects a decrease in uptake (i.e., positive response). Results: Fifteen patients containing 32 measurable lesions (CRC = 18,HCC = 6,other = 8) were examined. Mean time from treatment to follow-up FDG PET/CT was 62±15 days. The data were fitted with a log function and showed a good correlation between dose and response (R2= 0.79). A significant metabolic response, defined as change in TLG of ≥ 50%, was seen in all lesions receiving a mean dose of ≥ 30 Gy. No relationship was observed between site of origin of the malignancy/pathology and response. Conclusions: Dose to tumour and normal tissue can be determined using Y-90 PET/CT imaging. The dose delivered correlates with the metabolic response seen. The dose maps can be used to immediately (with 24 hrs) determine if a therapeutic dose of Y-90 SIRT has been delivered on a lesion-by-lesion basis and, if sub-therapeutic, further action can be instigated.
A first-in-human phase I study of oral pan-CDK inhibitor BAY 1000394 in patients with advanced solid tumors: Dose escalation with an intermittent 3 days on/4 days off schedule.
Authors: Rastislav Bahleda, Anas Gazzah, Andrea Varga, Prabhu Rajagopalan, David Andrew Henderson, Martin Kornacker, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2012)

3012 Background: BAY 1000394 (BAY) is an oral pan-CDK inhibitor targeting CDKs 1,2,4, 7 and 9 in the low nanomolar range. A phase I dose escalation study was initiated to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics (PD) in patients (pts) with advanced solid tumors. Methods: BAY was administered twice daily in a 3 days on / 4 days off schedule (cycle length 21 days, 3+3 design). PK was evaluated on cycle 1 day 1 and day 10. Response rate was assessed according to RECIST 1.1. PD markers included CK18 fragments in plasma. Results: As of Jan 08 2011, 34 pts were treated at doses of 0.6 (3 pts), 1.2 (4), 2.4 (3), 4.8 (3), 9.6 (3), 19.2 (6) mg per day as oral solution and at doses of 10 (4), 15 (6) and 20 (2) mg per day as tablet. Tumor types included 10 colorectal, 4 mesothelioma and 20 others. Cohort 9 (20 mg tablet) is ongoing. Frequent CTCAEv4 grade 1/2 drug related AEs occurring in more than 25% of patients up to cohort 8 were asthenia, diarrhea, nausea, vomiting and anorexia. DLTs (grade 3, 1 pt each) were hyponatremia, aphtous stomatitis at 19.2 mg solution and arterial thrombosis at 15 mg tablet. Aphthous stomatitis (20%) has not been observed with the tablet formulation. Other grade 3 related AEs were asthenia in 2 and nausea and vomiting in one pt each. Nausea and vomiting on treatment days were observed despite antiemetic treatment (aprepitant +/- setron). PK was dose proportional up to 9.6 mg, T 1/2 was 10 hours, and relative bioavailability of tablet formulation was excellent; major metabolite levels were low (&lt;10%). Levels of CK18 fragments did not correlate with dose or tumor response. Stable disease (SD) lasting for 2-4 months was observed in 9 patients, among others in 4 of 4 mesothelioma and 2 of 2 ovarian pts. One additional pt with cholangiocarcinoma has ongoing SD lasting for 5 months. One of the ovarian pts had a significant decline of CA125 lasting for 3 months. Conclusions: The tablet formulation of BAY 1000394 was better tolerated than oral solution. So far, doses up to a 15 mg per day with concomitant antiemetic treatment showed an acceptable tolerability. SD was observed in 10 of 25 heavily pretreated pts across cohorts 3 – 8.
Phase III randomized trial of postoperative radiotherapy (RT) with or without carboplatin (Cb) in patients (pts) with head and neck squamous cell carcinoma (HNSCC)
Authors: J. T. Johnson, S. S. Agarwala, M. V. Karamouzis, D. E. Heron, D. E. Eibling, E. Cano, S. Urba, J. Gluckman, Y. Wang, A. Argiris
Journal: Journal of Clinical Oncology (2007)

6078 Background: Postoperative RT plus cisplatin is a standard treatment in high-risk resected HNSCC. However, the role of Cb in the same setting has not been established. Methods: Eligible were pts with macroscopically resected stage III/IV HNSCC with high-risk pathologic features (=3 nodes, extracapsular extension, perineural or angiolymphatic invasion, or involved margins), ECOG performance status 0–2, and adequate laboratory parameters. Pts were randomized to receive RT 59.4 Gy (1.8 Gy/day) versus the same RT plus Cb 100 mg/m 2 intravenously once weekly during RT. The primary endpoint was the 2-year disease-free survival (DFS); with a projected sample size 100 patients/arm, the power was 0.81 with alpha 0.1 to detect a 15% improvement (50% to 65%). Results: From 4/94 to 4/02, 76 pts were randomized, of whom 72 pts were eligible and analyzable (36/arm). The study was prematurely closed due to slow accrual. Median age 54 years (24–83); male/female: 60 pts/12 pts; primary sites: oral cavity (n=26), oropharynx (n=23), hypopharynx (n=8), larynx (n=15); stage III/IV: 6 pts/66 pts; ECOG performance status 0/1/2: 40 pts/30 pts/2 pts. Median follow-up was 5.3 years. The 2-, 3- and 5-year DFS with RT/Cb vs. RT was 70%, 60%, and 46% vs. 55% (p=0.21), 51% (p=0.48), and 43% (p=0.79) and the 2-, 3- and 5-year overall survival (OS) was 74%, 71%, and 47% vs. 51% (p=0.04), 51% (p=0.07) and 40% (p=0.59). There were no statistically significant differences in median DFS or OS. In the subset of pts with primary sites other than the oropharynx (n=49), RT/Cb resulted in better OS vs. RT (p=0.05, Wilcoxon; p=0.27, log-rank). RT/Cb was associated with infrequent grade III/IV toxicities, including leukopenia (RT/Cb 8% vs. RT 0%), stomatitis (11% vs. 3%), and dermatitis (6% vs. 3%). Gastrostomy tube was placed in 15 pts (RT/Cb 8 vs. RT 7). Conclusions: Our data do not show a statistically significant improvement in DFS with RT/Cb vs. RT but this may reflect insufficient sample size. The potential benefit of RT/Cb for a subset of pts merits further study. No significant financial relationships to disclose.
Factors affecting the risk of erroneous interpretation of online surgeon rating websites among the general population.
Authors: Christopher J. Weight, Brett Watson, Lucas Labine, Jacob Albersheim-Carter, Badrinath R. Konety
Journal: Journal of Clinical Oncology (2017)

121 Background: Several websites present estimated individual surgeon complication rates for surgeons in both the United States and Great Britain. Though some researchers have raised questions as to the validity and appropriateness of these publicly displayed outcome measures, there remains very little research into how the general public may interpret these data to make health care decisions. Methods: We invited attendees of the 2016 Minnesota State Fair who met entry criteria, (adults &gt; 18 years old, English speakers who were able to use a tablet computer) to complete our survey. Demographic data was presented along with various screen shots from online surgeon rating websites. Patients were then asked to interpret these graphics and report complication rates. Some graphics displayed complications rates for one surgeon alone, while others compared multiple surgeons side-by-side. Results: 392 participants completed the survey from a broad geographic distribution from the upper Midwest (179 unique zip codes). Median age was 49 (Interquartile range 28-61), the female:male ratio was 3:2, 57% had completed a college or graduate degree and 85% were Caucasian vs. 15% ethnic minorities. The majority of participants (76%) were able to correctly estimate complication rates when a single surgeon and his or her complication rates were shown, but when respondents were asked to compare/rank multiple surgeons, respondents overestimated complication rates by 5-7 fold, on average, for the lower ranking surgeons and only 15% of respondents could correctly identify the complication rate of the lowest performing surgeon. College graduates and those with a graduate degree were more likely to correctly estimate complication rates compared to participants with less education (odds ratio 1.98 95% CI 1.04-3.75, p = 0.035). Conclusions: Online surgeon rating websites that compare and rank surgeons may lead the general public to drastically overestimate the risk of postoperative complications. These errors in estimating complication rates appear to be reduced amongst those who are college educated and when viewing single surgeon outcomes in the absence of a comparison.