tbuckley/cabot-search huggingface dataset:
Recent changes in overall survival of real-life stage IV colorectal cancer patients.
Authors: Patricia Hamers, Amanda C.R.K. Bos, Anne Maria May, Cornelis J. A. Punt, Miriam Koopman, Geraldine R. Vink
Journal: Journal of Clinical Oncology (2019)

3522 Background: In the past decade, the reported median overall survival (mOS) in phase 3 trials of metastatic colorectal cancer (mCRC) patients increased from approximately 16 to over 36 months. However, only 2.5-20% of cancer patients participate in clinical studies and these are often patients with favourable prognostic factors. Therefore, we explored for which proportion of real-life stage IV CRC patients OS improved in recent years. Methods: Nationwide population-based data of all stage IV (synchronous metastatic) CRC patients diagnosed between 2008-2016 in the Netherlands who received local and/or systemic antitumor therapy were obtained from the Netherlands Cancer Registry (NCR). Initial treatment was registered in the NCR. Vital status was recorded until January 31 st 2018. OS per incidence year was determined for various percentiles, which represent the number of months after which 10-30-50-70-80-90% of the patients had died. For some percentiles survival time exceeded follow-up duration. Results: The total study population comprised 21,047 patients. mOS remained unchanged in the period 2008-2016 at around 15 months. OS of p10 and p30 increased by 1,5 months to 3,6 and 10,0 respectively. For the ‘best’ (longest-living) patients (p70-p80) OS improved in the period 2008-2016 by 4 and 6 months to 30 and 43 months, respectively. Follow-up duration is insufficient to analyse change over time for the 10% ‘best’ patients. mOS did not change for any of the treatment subgroups except for the patients who received exclusively non-systemic therapy (e.g. metastasectomy, radiotherapy) in which mOS improved by 11 months to almost 20 months. Conclusions: mOS of real-life stage IV CRC patients has not improved since 2008. We observed a clinically relevant survival improvement in only 30% of all treated patients and in all patients who received exclusively non-systemic therapy. These data illustrate the different outcomes between trial patients and total patient population, which emphasizes that trial patients represent a selection of patients with favourable prognosis. Our results highlight the value of real-life data to determine efficacy of innovations in daily clinical practice.
Can hormone receptors prevent metastatic spread of gastric cancer?
Authors: Irina V. Kaplieva, Oleg I. Kit, Elena M. Frantsiyants, Valeria A. Bandovkina, Yuriy A. Gevorkyan, Natalya V. Soldatkina, Nikolay S. Samoylenko, V. I. Aleynov, Irina S. Tishchenko, Maksim N. Duritskiy
Journal: Journal of Clinical Oncology (2019)

e15527 Background: The primary tumor and associated but distinct from it premetastatic niches include a number of important participants: immune cells, stromal cells, extracellular matrix and associated effectors, in particular hormone receptors. Cross-interaction between these components is key to tumor progression. The greater omentum and peritoneum are pre-metastatic niches for gastric cancer. The purpose of the study was to analyze levels of steroid hormone receptors in tissues of gastric cancer (GC) and its pre-metastatic niches: the peritoneum (P) and omentum (O). Methods: The main group included 21 patients with metastatic GC T 3-4 а N 0-3 M 1 ; the comparison group – 24 patients with non-metastatic GC T 3-4 а N 0-3 M 0 . Tissues of tumors, intact gastric tissues, omentum and peritoneum tissues were studied. The control group included 17 non-cancer patients; omental and peritoneal tissues were studied. Levels of receptors of estrogens (RE-α, RE-β), androgens (RA) and progesterone (RP4) were measured by ELISA. Results: Levels of RE-α in tissue of GC T 3-4 а N 0-3 M 1 were decreased by 1.7 times (P˂0.05) compared to controls, while in T 3-4 а N 0-3 M 0 they were increased by 1.2 times (P˂0.05). RE-β and RА did not change in both cases. RР4 in T 3-4 а N 0-3 M 1 was similar to control levels, and in T 3-4 а N 0-3 M 0 – was increased by 3.5 times. Levels of RE-α and β, RА and RР4 in O and P in T 3-4 а N 0-3 M 1 were similar to control levels, and in T 3-4 а N 0-3 M 0 they were higher: RE-α - by 3.9 and 2.4 times, RE-β – by 2.5 and 1.5 times (P˂0.05), RР4 – by 2.2 and 1.5 times (P˂0.05). RA in O and P in T 3-4 а N 0-3 M 0 was similar to control levels. Conclusions: Elevated levels of RE-α., RE-β and RR4 in peritoneal and omental tissues can be considered a factor associated with some characteristics of GC metastasis, and protective one at the same time. Obviously, levels of RE-α and RР in O and P correlate with the levels in tissues of GC T 3-4 а N 0-3 M 0 . However, this statement is disputable and requires further confirmation.
Reexamination of the UN10 Rule to Discontinue Resuscitation During In-Hospital Cardiac Arrest
Authors: Bradley J. Petek, Daniel N. Bennett, Christian Ngo, Paul S. Chan, Brahmajee K. Nallamothu, Steven M. Bradley, Yuanyuan Tang, Rodney A. Hayward, Carl van Walraven, Zachary D. Goldberger
Journal: JAMA Network Open (2019)

Several clinical decision rules (CDRs) have been developed to help practitioners know when to safely terminate resuscitative efforts after in-hospital cardiac arrest (IHCA). The UN10 rule, a CDR that uses 3 intra-arrest variables, has been shown to predict a poor chance of survival to discharge. However, its large-scale applicability in clinical settings remains unknown.To assess the performance of a parsimonious CDR in a national cohort of individuals with IHCA.This retrospective cohort study used a nationwide cohort from the American Heart Association Get With the Guidelines-Resuscitation IHCA registry to derive a sample of 96 509 patients from 716 US hospitals who experienced IHCA from January 1, 2000, to January 26, 2016. Data analysis began in January 2018 and concluded in June 2018.The UN10 rule uses 3 variables: (1) unwitnessed arrest, (2) nonshockable rhythm, and (3) no return of spontaneous circulation within 10 minutes of resuscitative efforts. The CDR indicates futility if all 3 criteria are met. This CDR was analyzed according to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline.The primary outcome was survival to hospital discharge following resuscitation. Favorable neurologic status at discharge was also assessed. Overall rates of survival and survival with favorable neurologic status (cerebral performance category score, 1 or 2) were compared with predicted values by the UN10 rule using 2 × 2 contingency tables.Of 96 509 patients, 55 761 (57.8%) were men, and the mean (SD) age was 67.1 (15.3) years. In total, 18 713 patients (19.4%) survived to discharge, and 16 134 patients (16.7%) were discharged with a favorable neurologic status. Overall, 15 838 patients (16.4%) met all 3 criteria for futility in the UN10 rule. A total of 1005 patients (6.3%) who met the UN10 rule survived to discharge, and 754 (4.8%) survived with favorable neurologic status. The percentage of patients meeting the UN10 rule (ie, predicting futile resuscitation) who actually survived in our study cohort was substantially higher than the initial derivation cohort (0%) and single-center validation cohort (1.1%). The positive predictive value of the UN10 rule was 93.7% (95% CI, 93.3%-94.0%), which was lower than the initial derivation cohort (100%; 95% CI, 97.5%-100%) and validation cohort (98.9%; 95% CI, 96.5%-99.7%).Patients who met the UN10 rule were associated with unfavorable neurologic status and low rates of survival after IHCA. Yet their survival rates are higher than reported in the initial validation study, raising the question of whether the UN10 rule may have limited utility as a definitive measure of futility during resuscitations in real-world clinical settings.
A multi-center phase Ib/II study of nal-irinotecan, 5-fluouracil and leucovorin in combination with nivolumab as second-line therapy for patients with advanced unresectable biliary tract cancer.
Authors: Vaibhav Sahai, Tyler Howard Buckley, Kent A. Griffith, Mark Zalupski
Journal: Journal of Clinical Oncology (2019)

TPS4154 Background: Patients (pts) with advanced biliary tract cancers (BTC) have poor prognosis despite systemic chemotherapy, and treatment beyond first-line platinum doublet remains investigational. The immunomodulatory properties of conventional cytotoxic therapy, particularly in regard to the upregulation of PD-L1 expression rendering tumor cells more sensitive to T cell-mediated lysis and neoantigen production, rapid emergence of chemotherapy resistance, and known modest efficacy of single agent PD-1 antibody in BTC provide a rationale for combining chemotherapy and immunotherapy. This multi-center, phase Ib/II, single-arm study is designed to investigate the role of nal-irinotecan, 5-FU and leucovorin in combination with nivolumab as second-line therapy in pts with advanced BTC. Methods: Key eligibility criteria include histologically confirmed advanced, unresectable biliary carcinoma (intra- or extra-hepatic and gallbladder) with progression or intolerance of first-line systemic therapy (excluding irinotecan and PD-1/PD-L1 antibody), measurable disease per RECIST v1.1, ECOG PS 0-1, Child Pugh A or B7, and absence of autoimmune disease or chronic steroid use. Primary objective of the phase Ib portion is to determine the recommended phase 2 dose, and of the phase II portion is to evaluate the median progression-free survival. Secondary objectives include evaluation of objective response rate per immune related (ir)RECIST, median OS and safety in this patient population. Exploratory objectives include identification of biomarker predictors of response and mechanisms of resistance through serial biopsies and blood collection (pre, on and post therapy), including sequential whole exome/transcriptomic analysis and immune cell subset analysis (tissue and blood). Therapy includes nal-irinotecan 70 mg/m 2 , leucovorin 200 (dose level -1) or 400 mg/m 2 (dose level 0), 5-fluouracil 2400 mg/m 2 IV over 46 hours, and nivolumab 240 mg on day 1 every 2 weeks for 6 months. In the absence of disease progression, pts may continue therapy for up to 2 years. Accrual goal is 30 evaluable pts. Using a null hypothesis value of median PFS of 2.9 months, and an alternative hypothesis of 5.0 months, this ongoing study has &gt; 80% power, with a two-sided alpha of 0.05 to identify treatment efficacy of study arm. Clinical trial information: NCT03785873.
Genomic testing and treatment landscape in patients with advanced non-small cell lung cancer (aNSCLC) using real-world data from community oncology practices.
Authors: Hinco Jasper Gierman, Seth Goldfarb, Monica Labrador, Caroline M. Weipert, Bill Getty, Stan M Skrzypczak, Casey Catasus, Steve Carbral, Mallika Singaraju, Nick Singleton, Nikhil Pai, Jose Sanchez, Jennifer Webster, Victoria M. Raymond, Richard B. Lanman, Ash Malik, Jeffrey A. Scott
Journal: Journal of Clinical Oncology (2019)

1585 Background: While aNSCLC is a leading cause of US cancer deaths, targeted therapies and immune checkpoint inhibitors (ICPi) have emerged as important new treatment options for these pts NCCN guidelines recommend testing of eight genes in aNSCLC patients at diagnosis. Targetable alterations (TA) in four genes, EGFR, ALK, ROS1, and BRAF, are associated with FDA-approved therapies. The labels for ICPis indicate that pts with TAs in EGFR and ALK are not candidates for first line treatment with ICPi. Methods: The Integra Connect database, which includes electronic medical record (EMR) and claims data on approximately 600,000 cancer patients, was queried across five community oncology practices (289 oncologists) to identify aNSCLC patients (stage 3B or 4) treated since January 2017. Manual review of charts was done to abstract tumor type/stage, drug regimens, and evidence of somatic genetic testing. A Wilcoxon rank sum test was used to test difference in time to results (TTR) for blood- vs tissue-based tests. Results: A total of 1,203 aNSCLC patients were identified. Testing rates varied from 54% for EGFR to 22% for all 4 genes (table). 163 patients had a TA in EGFR, ALK, ROS1 or BRAF, and 55% of these pts did not receive targeted therapy. 84 pts with TA’s in EGFR or ALK had no evidence of progression on targeted therapy, yet 31 (37%) received an ICPi; 24% had the TA test result prior to ICPi use and 13% received the TA result after starting ICPi. Median TTR for blood-based somatic tests was shorter than tissue-based tests (4 vs 14 days, p-value= 3.5-e07). Conclusions: Our analysis in the community oncology setting for aNSCLC pts finds evidence of underutilization of genomic testing, underutilization of targeted therapies, and ICPi use outside of label. Further research is needed to identify strategies to increase testing in aNSCLC pts to provide physicians with the information needed to make optimal treatment decisions. [Table: see text]
Impact of specialist palliative care delivered over three months prior to death on a colorectal cancer patient’s risk of experiencing aggressive end-of-life care.
Authors: Aynharan Sinnarajah, Madalene Earp, Pin Cai, Andrew Fong, Kelly Blacklaws, Safiya Karim, Winson Y. Cheung, Marc Kerba
Journal: Journal of Clinical Oncology (2019)

6614 Background: More patients are experiencing aggressive end-of-life (EOL) care. This is concerning as aggressive EOL care, on a population level, is associated with poor quality care. Specialist palliative care (PC) has been shown to help relieve EOL symptoms, improve patient quality of life, and reduce aggressive EOL care. This study aimed to estimate the impact of the timing of specialist PC, specifically PC delivered at least 3 months prior to death, on a colorectal cancer (CRC) patient’s risk experiencing aggressive care in the last 30 days of life. Methods: A population-based retrospective cohort study of adult patients who died from CRC in Alberta, Canada from 2011-2015. The Alberta Cancer Registry was used to identify the cohort, which was linked to healthcare resource use data in local, provincial, and national databases. Individuals who died &lt; 30 days from CRC diagnosis were excluded. Patients who accessed any of the provinces specialist PC services were deemed exposed to specialist PC (includes PC consult team, intensive PC unit, palliative home care, hospice). Aggressive EOL care was defined as having experienced at least one of: hospital death, &gt; 1 emergency department visit, &gt; 1 hospital admission, &gt; 14 days of hospitalization, ≥1 intensive care unit admission, ≥1 new chemotherapy program (or any treatment in the last 14 days of life). Logistic regression was used to model factors (specialist PC timing and clinical characteristics) associated with aggressive EOL care. Results: The cohort comprised 2979 patients. Most patients received specialist PC before death (58%); 60% had ≥1 indicator of aggressive EOL care. Relative to patients who received specialist PC &gt; 3 months before death, patients who received specialist PC &lt; 3 months before death were 1.5 times more likely to experience aggressive EOL care (CI: 1.2-1.9). Patients who received no specialist PC were 2.1 times more likely to experience aggressive EOL care (CI: 1.7-2.8). Short disease duration ( &lt; 1 year from diagnosis to death), younger age at death, living in a rural area, and male sex, were also associated with higher odds of experiencing aggressive EOL care. Conclusions: Specialist PC delivered &gt; 3 months before death reduces a CRC patient’s risk of experiencing aggressive EOL care over PC delivered &lt; 3 months before death.
Review of the treatment milestones for stage I non-small cell lung cancer at a regional rural cancer center.
Authors: Antoine Joseph Harb, G. Allen L'Italien, Sarah Sinclair, Adam Curtis
Journal: Journal of Clinical Oncology (2019)

e18305 Background: Treatment milestones were reviewed for all stage I non-small cell lung cancer (NSCLC) patients treated at Northern Light Cancer Institute (NLCI), from 2010 to 2017. Cases in which the initial time to treatment (TTT) exceeded 6 months and those not seeking treatment were considered non-typical and were excluded from analysis, resulting in 502 cases for this time period. Methods: Analysis demonstrated that patients primarily took one of three different pathways in the diagnostic process. This process typically involved a CT scan, PET scan, and a biopsy. The three primary diagnostic pathways were: CT-PET-Biopsy (29.7%), CT-Biopsy-PET (14.3%), or CT-PET (no biopsy) (39.8%), accounting for 83.9% of eligible patients. The primary mode of treatment for most patients was surgery (63.7%). Patients not eligible for surgery received stereotactic body radiation therapy (SBRT) (26.7%). Results: Patients undergoing surgery experienced a shorter average TTT compared to patients receiving SBRT for all years except 2016. (p &lt; 0.05). Time to treatment for surgical patients was stable at approximately 70 days from 2011-2014, at which time there was an average 27.9 day increase by 2016. TTT for SBRT patients increased from a mean of 67.4 days in 2010 to a high of 110.8 days in 2015 before decreasing to 90.0 in 2016. The different diagnostic pathways did not significantly differ from each other in terms of 3 year average TTT (2015-2017) for surgical patients (p = 0.59). SBRT patients who had a two-step diagnostic pathway (CT-PET) had TTT that was 22.7 days shorter than the three step pathway of CT-PET-Biopsy (p = 0.02). Patients receiving SBRT had a 1.56 points average higher Charlson Comorbidity Index, and were an average of 4.5 years older than those receiving surgery. Conclusions: Differences in TTT between treatment modalities are likely related to patient comorbidities and additional time needed for radiation planning and simulation. The changes seen since 2015 were thought to be secondary to the emergence of prior-authorization for procedures. This was a quality study aiming to identify the current treatment milestones and related wait times for each treatment modality in an effort to further optimize patient care.
Effect of mandatory research biopsy requirements on initiation of clinical trials.
Authors: Jonathan Hin Cheng, Justin Wayne Wong Tiulim, Anthony B. El-Khoueiry, Jorge J. Nieva
Journal: Journal of Clinical Oncology (2019)

e14057 Background: There has been an increasing requirement for fresh tumor tissue to enroll in clinical trials in order to look for specific biomarkers. This has been shown to increase screening duration and increase screen failure rates. It was important to corroborate these results in other centers. Methods: This study is a non-randomized retrospective analysis of patients in one subset of patients seen by research nurses who operated in the standard head/neck and lung team not including patients in the phase 1 program. All patients were enrolled in clinical trials from January 16, 2013 to May 28, 2018 at USC Norris Comprehensive Cancer Institute in Los Angeles. Patients who were required to give fresh research biopsies prior to intervention were part of the research biopsy group. Results: In total, 76 patients were analyzed in this study. 33 patients were in the research biopsy group and 43 patients were in the no biopsy group. Trials that required a fresh biopsy had a longer median screening duration (30 vs 14 days) than trials that did not require a biopsy (p &lt; .0001). Conclusions: Our study shows that requiring biopsies prior to clinical trial treatment results in a statistically significant delay in treatment. The informed consent forms that were part of clinical trials involving mandatory research biopsies did not reflect this delay in treatment. However, these delays did not result in a statistically significant decrease in number of days on trial or days until progression of disease.
Factors associated with breast cancer mortality-per-incident case in low-to-middle income countries (LMICs).
Authors: Anees B. Chagpar, Mario Coccia
Journal: Journal of Clinical Oncology (2019)

1566 Background: Reducing breast cancer mortality is a key healthcare challenge worldwide. We sought to determine the impact of macro-socioeconomic factors on breast cancer age-standardized incidence (ASI) and mortality-per-incident case (MPI) in LMICs. Methods: Data regarding breast cancer ASI and mortality in 78 LMICs were obtained from IARC/WHO. MPI was defined as the age standardized mortality divided by the ASI. Country-level socioeconomic data were obtained from World Bank, UN Development Project, and WHO data sources. Results: In 2018, the median ASI for breast cancer was 26.5 (range; 5-67.3) per 100,000 population in LMICs, with a median MPI of 50.6% (range 27-70%). ASI and MPI were inversely correlated (Spearman rho = -0.236, p = 0.044). Factors associated with ASI and MPI are shown in the table below. We found no factor could discriminate between the highest and lowest quartile in terms of ASI. However, all (except health expenditure as a % of GDP) were significantly different between the highest and lowest quartile in terms of MPI. Conclusions: Results suggest considerable variation in terms of breast cancer MPI within LMICs. Improved rates are seen with increasing GDP, literacy, contraceptive use, and provision of doctors and mammography, but overall % GDP expended on public health does not seem to significantly influence breast cancer MPI. [Table: see text]
Immunotherapy plus chemotherapy versus chemotherapy alone in metastatic non–small-cell lung cancer: A systematic review with meta-analysis.
Authors: Andre Deeke Sasse, Fernanda Proa Ferreira, Adolfo Jose de Oliveira Scherr, David Pinheiro Cunha, Vivian Castro Antunes Vasconcelos, Susana Oliveira Botelho Ramalho, Vinicius Correa Conceicao, Rafael Luis Moura Lima do Carmo
Journal: Journal of Clinical Oncology (2019)

e20700 Background: Palliative systemic therapy is the primary approach for stage IV non-small cell lung cancer(NSCLC). For patients with NSCLC that lacks targetable mutations, immunotherapy alone or in combination with chemotherapy has become a promising alternative, focusing survival and quality of life. Our objectives were to review, summarize and compare the evidence of immunotherapy plus chemotherapy in first-line treatment in comparison with chemotherapy alone in patients with metastatic NSCLC in terms of effectiveness. Methods: A systematic review of randomized controlled trials (RCTs) was planned. PubMed, Embase and Lilacs were searched for trials evaluating metastatic NSCLC patients, comparing chemotherapy alone versus chemotherapy plus anti-PD1, anti-PDL1 or anti-CTLA-4 agents. Four investigators independently extracted characteristics and results of identified studies and performed standardized quality ratings. Meta-analyses for overall survival (OS), progression-free-survival (PFS), overall response rates (ORR) and toxicities were performed. Results: Six RCTs met the inclusion criteria. One trial with anti-PD-L1 (Atezolizumab), three trials with anti-PD-1 (Pembrolizumab) and two trials with anti-CTLA-4 (Ipilimumab) were included. Three trials included non-squamous carcinomas, two trials included squamous cell carcinoma and one trial included all NSCLC. The combination of anti-PD-1 or anti-PDL1 to chemotherapy improved OS (Hazard Ratio [HR] for death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; p &lt; 0.0001). This combination also improved PFS (HR for progression or death, 0.57; 95% CI, 0.51 to 0.63; p &lt; 0.00001) and ORR (Odds Ratio [OR], 2.55; 95% CI, 1.80 to 3.61; p &lt; 0.00001). The combination of anti-CTLA-4 to chemotherapy slightly increased the PFS (HR 0.84; 95% CI, 0.73 to 0.96; p = 0.01), but not OS (HR 0.92; 95% CI, 0.80 to 1.05; p = 0.21) or ORR (OR 0.92; 95% CI, 0.71 to 1.19; p = 0.52). General and immune mediated adverse events were higher in all combination groups. Conclusions: In patients with previously untreated metastatic squamous and non-squamous NSCLC without EGFR or ALK mutations, the addition of anti-PD-1 or anti-PD-L1 to standard chemotherapy resulted in significantly longer overall survival and progression-free survival than chemotherapy alone.