tbuckley/cabot-search huggingface dataset:
Risk-adjusted margin positivity (RAMP) rate as a surgical quality metric for non-small-cell lung cancer (NSCLC).
Authors: Chun Chieh Lin, Matthew Smeltzer, Ahmedin Jemal, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2016)

8551 Background: The incidence of margin-positive (MP) NSCLC resection varies with patient demographics, clinical and institutional factors. We examined the utility of the RAMP rate in categorizing institutions into performance groups. Methods: Analyzing the National Cancer Data Base of stage I-IIIA NSCLC resections from 2004 – 2011, we used a multivariate logistic regression model to estimate the expected (E) number of MP cases in each facility by adjusting for patient risk-mix. We divided the number of observed (O) by the expected number of MP cases to obtain an O/E ratio for each facility. We categorized facilities as outperformers (ratio < 1, p < .05), non-outliers (p > .05), and underperformers (ratio > 1, p < .05). Facility characteristics across performance categories were compared by chi-square test. Adjusted 5-year survival rates were estimated by Kaplan-Meier analysis and compared across categories with the log-rank test. Results: A total of 100,235 eligible patients underwent surgery at 816 facilities. The overall O MP rate was 4.5%. Sixty-five facilities (8%) were outperformers (mean ratio = 0.39, CI: 0.35 – 0.43), 645 (79%) were non-outliers (mean ratio = 1.05, CI: 1.01 – 1.08), and 106 (13%) were underperformers (mean ratio = 2.4, CI: 2.25 – 2.55). Twenty-one percent, 67% and 13% of patients were treated in outperforming, non-outlier, and underperforming institutions, respectively. Sixty percent of outperforming institutions were Teaching/Research or NCI-designated programs vs. 0% Community Cancer Programs, and 34% Comprehensive Community Cancer Programs. However 21% of underperforming institutions were Teaching/Research or NCI-designated programs. All outperforming institutions were in the top 2 total cancer surgical volume quartiles, but so were 75% of underperformers and 76% of non-outliers. Adjusting for patient demographic and clinical characteristics, outperformers had a 5-year hazard ratio of 0.88 (CI: 0.85 – 0.9, p < .0001) compared to non-outliers; and 0.84 (CI: 0.81-0.88, p < .0001) compared to underperformers. Conclusions: Facility performance in NSCLC surgery can be captured by using the RAMP rate, potentially providing a valid quality improvement metric.
Pembrolizumab (pembro) in patients with advanced hepatocellular carcinoma (HCC): KEYNOTE-224 update.
Authors: Andrew X. Zhu, Richard S. Finn, Julien Edeline, Stéphane Cattan, Sadahisa Ogasawara, Daniel H. Palmer, Chris Verslype, Vittorina Zagonel, Laetitia Fartoux, Arndt Vogel, Debashis Sarker, Gontran Verset, Stephen Lam Chan, Jennifer J. Knox, Bruno Daniele, Scot Ebbinghaus, Junshui Ma, Abby B. Siegel, Ann-Lii Cheng, Masatoshi Kudo
Journal: Journal of Clinical Oncology (2018)

4020 Background: Initial results from KEYNOTE-224 (NCT02702414), an open label, phase 2 trial showed that pembro, an anti-PD-1 antibody, was active and safe in pts with advanced HCC previously treated with sorafenib. Here we report updated clinical results and biomarker studies. Methods: Eligible pts were age ≥18 y with histologically confirmed HCC, radiographic progression on/intolerance to sorafenib and disease not amenable to curative treatment, Child Pugh A, ECOG PS 0-1 and BCLC stage C or B. Pts received pembro 200 mg IV Q3W for 2 y or until disease progression, unacceptable toxicity, withdrawal of consent or investigator decision. Response was assessed every 9 wk. Primary endpoint was ORR (RECIST v1.1, central review). Secondary endpoints were DOR, DCR, PFS, OS and safety. Exploratory endpoint was relationship of PD-L1 IHC combined positive and tumor proportion scores (CPS and TPS; n = 52), and T cell inflamed gene expression profile (GEP; n = 42) with response. Data cutoff date was Nov 24, 2017. Results: Of 104 treated pts, 18 remained on therapy. Median age was 68 y (range 43-87), 21.2% were HBV+, 26% were HCV+, 94.2% were Child Pugh A, 79.8% had PD on sorafenib and 64.4% had extrahepatic disease. ORR was 16.3% (95% CI, 9.8 to 24.9, n = 17) and similar across differing etiologies; 66% of responders had duration ≥12 mo (Kaplan Meier) and median response duration was not reached (3.1 - 12.5+ mo). Best response was CR in 1 pt (1.0%), PR in 16 (15.4%), SD in 47 (45.2%) and PD in 34 (32.7%); DCR was 61.5%. Median PFS (95% CI) was 4.9 mo (3.4 to 7.0) and OS was 12.9 mo (9.7 to NA). PFS and OS 12 mo rates were 25.4% and 53.6%, respectively. Safety was similar to that observed for pembrolizumab in other indications. Immune-mediated hepatitis occurred in 3 (2.9%) pts; no cases of HBV/HCV flare were seen. Higher PD-L1 CPS in tumor and immune cells was associated with higher ORR and longer PFS, while PD-L1 TPS in tumor cells alone and GEP showed less robust associations with outcomes. Conclusions: These results confirm that pembro may be a promising treatment option for pts with advanced HCC. PD-L1 CPS was associated with clinical response to pembro while results for PD-L1 TPS and GEP were less robust; further study is needed to better define these relationships. Clinical trial information: NCT02702414.
A real-world observational study to explore clinical characteristics of Chinese patients with T1 non-small cell lung cancer complicated with lymph metastases.
Authors: Feng Jiang, Heng Zhao, Xiaofei Li, Lunxu Liu, Yang Liu, Jian HU, Xiangning Fu, Yin Li, Yijun Xu, Deruo Liu, Haiying Yang, Lin Xu
Journal: Journal of Clinical Oncology (2018)

e20523 Background: Clinical characteristics of lymph metastases are hetergeneous in the patients with T1 non-small cell lung cancer (NSCLC). Preoperative assessment of lymph metastases is essential to determine the appropriate treatment regimens. The study was designed to evaluate those potential factors that may influence lymph metastases. Methods: We conduct the study based on a national collaborative prospective lung cancer database (designed by LinkDoc Technology Co, Ltd.). The patients with pathologically diagnosed T1 non-small cell lung cancer who received surgical resection from 2014 to 2017 were enrolled. The univariate and multivariate logistic regression analyses were performed to analyze the risk factors that influnce lymph metastases. Results: A total of 10885 subjects were recruited in the study including 1808 patients with lymph metastases (16.6%) (N1: 640 patients/5.9%; N2: 1159 patients/10.6%). Of all the pN2 patients, 754(65.1%) patients were observed with N1 lymph nodes and 405 (34.9%) patients with skip metastases. The univariate and multivariate analyses showed the CEA levels before surgeries, tumor size, degree of differentiation, and tubular cancer embolus were potential risk factors of lymph metastases in the total population and in N2 population. The tuerculosis comorbidity was also found to be significantly related to lymph metastases. In the pN2 population, age and smoking history were predictive for N2 skip metastases. Conclusions: The relevance between clinical and tumor biological characteristics of the NSCLC patients, and lymph metastases were demonstrated in the Chinese real-world study that will offer clinical complementary guidance on management of T1 NSCLC patients in practice. Clinical trial information: NCT03413956.
Adjustments for confounding variables in observational population-based studies in oncology and comparison to results from randomized controlled trials.
Authors: Payal Dilip Soni, Ahmed Abugharib, Steven G Allen, Imran A Khan, Moazz Soliman, Robert Eric Simons, Robert Timothy Dess, Daniel Eidelberg Spratt
Journal: Journal of Clinical Oncology (2017)

e18135 Background: Observational population-based studies (OBS) allow large scale analyses to be done, and are increasingly used to compare cancer treatment modalities. Given the immense heterogeneity in these cohorts and the high potential for bias, we investigate how often appropriate statistical strategies are used to address confounding factors and the agreement of these studies with results from randomized controlled trials (RCT). Methods: A systematic literature search was conducted in MEDLINE using controlled vocabulary to identify OBS between 2000 and 2011, identifying 1814 studies. Studies reporting on survival that compare local therapies were included. Study details were extracted including survival outcomes, whether adjustments were made for age, stage, comorbidities, and if propensity score analyses or sensitivity analyses were performed. Studies with robust adjustments were compared to representative RCT results. Results: A total of 155 treatment comparisons met inclusion criteria. Median follow-up was available in 37% and median/mean age in 64% of comparisons. Age and stage were not adjusted for in 12% and 8% of studies, respectively. Only 10% adjusted for comorbidities, and 15% (n = 24) used either propensity adjustment (n = 21) or sensitivity analyses (n = 8). Of these 24, 11 had corresponding RCTs, and six had discordant findings. In five of the six studies, the RCT showed no survival difference while the corresponding OBS suggested more treatment was better than less, suggesting potentially unadjusted confounding. Greater degree of statistical adjustments correlated with year of publication, and all studies that used propensity adjustment and sensitivity analysis were after 2007. Conclusions: During the decade of OBS analyzed, the majority did not report the median follow-up or age, adjust for comorbidities, or perform robust statistical analyses to correct for potential bias. Even among studies with rigorous statistical adjustments, over half had discordant findings from RCTs. Given these findings, comparative OBS in oncology should be seen as hypothesis generating and caution should be used when interpreting the results.
P01.141 Different timing to use bevacizumab in patients with recurrent glioblastoma: early versus delayed administration
Authors: A Gonnelli, F Pasqualetti, A Molinari, M Cantarella, S Montrone, R Mattioni, D Baldaccini, M Fabrini, F Paiar
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is the most baleful malignant brain tumor in adults. After a diagnosis of relapsed GBM, multimodality salvage treatment are not incisive enough to improve overall survival (OS) beyond a few months, and their best use and the timing is not well established. Bevacizumab (BEV) seems to improve OS. The best timing for BEV administration requires further investigation. We report the results of a monocentric experience comparing the early use of BEV with delayed administration. Data was collected from September 2008 from pts who met the following criteria:0>18years, a pathologically-confirmed diagnosis of GBM, disease recurrence after up-front RT-CT or alone CT with TMZ, KPS >60, and administration of BEV with or without concomitant CT. Single agent BEV was administered at the time of the first recurrence (early administration) after standard up-front treatment, or at the time of disease progression following a second or even further advanced line of CT (late administration). BEV response and progression were assessed using RANO criteria. Disease assessment was performed every 2 months following the start of BEV, using MRI with a contrast agent, or at the onset of symptoms. This analysis includes 129 pts from September 2008 to July 2017 treated with BEV for recurrent GBM. 51 pts received early administration of BEV and 77 delayed administration. The median age at the beginning of BEV was 56.4 years, MGMT methylation status was assessed in 52 pts, and clinical benefit due to BEV in 47. Median KPS at the time of BEV first administration was 80 (range 60–100). At a median follow-up of 22.4 months (range 5.26–19.2), the median lapse from diagnosis of GBM to disease recurrence was 11.6 months; 13.1 for pts treated with deferred administration of BEV and 11.1 for pts with early administration (P=0.047). Median OS in pts treated with early BEV was 19.5 months, and in pts treated with delayed BEV it was 26.7 months (P=0.040). PFS with early and delayed use of BEV was 3.45 and 2.92 months, respectively (p=0.504). OS from the start of BEV were 6.18 months in pts with early administration, and 6.47 in the delayed administration group (p=0.318). Toxicity profiles were similar in the 2 groups. Clinical benefit was observed in 12 out of 49 pts treated with early BEV, and in 20 out of 47 treated with delayed BEV. According to univariate analysis, KPS, MGMT methylation and time from diagnosis to start of BEV were predictors of OS in all pts, regardless of the timing of administration of BEV The results obtained in this study suggest that the delayed administration of BEV can be considered in select pts with recurrent GBM. Further prospective studies are needed to better define the best time for BEV administration in pts with recurrent GBM
Cyclin-dependent kinases 4 and 6 inhibitors in HR+/HER2- advanced breast cancer.
Authors: Ying Wang, Yunfang Yu, Shengbo Liu, Qiyun Ou, Herui Yao
Journal: Journal of Clinical Oncology (2018)

e13048 Background: In a previous meta-analysis which published in 23rd NCCN Annual Conference, we reported that the addition of cyclin-dependent kinases 4 and 6 inhibitors (CDKi) to endocrine therapy (ET) improved progression-free survival (PFS) for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). This update aims to further confirm and compare the efficacy of different CDKi for HR+/HER2− ABC. Methods: We identify relevant randomized clinical trials (RCTs) published prior to February 2018. Direct and indirect evidence for PFS was calculated hazard ratios (HRs) and 95% credible intervals (CIs) using random-effects network meta-analysis. Quality of evidence was appraised with GRADE criteria. The PROSPERO registry number is 42018081105. Results: Seven RCTs including a total of 3,854 patients were identified. Combining direct effects showed that the addition of CDKi to ET significantly improved PFS for HR+/HER2− ABC (HR 0.54; 95% CI, 0.49 to 0.59; P< 0.0001; high certainty), with similar benefit for whom had not received prior treatment for advanced disease (HR 0.56; 95% CI, 0.49 to 0.63; P< 0.0001; high certainty) or progressed on previous endocrine therapy (HR 0.51; 95% CI, 0.43 to 0.61; P< 0.0001; moderate certainty). Overall indirect analysis showed no statistically significant difference of PFS existed among these three CDKi plus nonsteroidal aromatase inhibitor regimens as first-line therapy: palbociclib vs. ribociclib (HR 0.98; 95% CI, 0.52 to 1.80), palbociclib vs. abemaciclib (HR 1.00; 95% CI, 0.48 to 2.10), and ribociclib vs. abemaciclib (HR 1.00; 95% CI, 0.50 to 2.20). Besides, compared with palbociclib plus fulvestrant, abemaciclib plus fulvestrant provided similar PFS (HR 0.83; 95% CI, 0.20 to 3.50) in patients who had progressed on previous endocrine therapy. The risk of diarrhea was significantly greater with abemaciclib than with palbociclib or ribociclib. Conclusions: Our results confirmed that addition of CDKi to ET significantly improved PFS in patients with HR+/HER2− ABC. This is the first analysis compared different CDKi and indicated a clear advantage among different CDKi for HR+/HER2− ABC has not yet been established.
Analysis of water polo injuries during 8904 player matches at FINA World Championships and Olympic games to make the sport safer
Authors: Margo Mountjoy, Jim Miller, Astrid Junge
Journal: British Journal of Sports Medicine (2018)

Objective To analyse injuries of water polo players reported during four Summer Olympic Games (2004, 2008, 2012, 2016) and four Federation Internationale de Natation World Championships (2009, 2013, 2015, 2017). Methods Injuries during training and matches were reported daily by the team physicians and the local medical staff at the sports venues using an established surveillance system. Results A total of 381 injuries were reported, equivalent to 14.1 injuries per 100 players (95% CI ±1.42). The most frequent diagnoses were laceration (12.7%) and contusion (10.9%) of head, followed by (sub-)luxation/sprain of hand (9.5%) and contusion of trunk (6.5%) or hand (6.2%). More than half of the injuries (57.0%) occurred due to contact with another player. A quarter of the injuries (25.4%) were expected to result in absence from training or match; 10 (2.9%) resulted in an estimated time-loss of 3 or more weeks. About three-quarters of injuries (75.6%) occurred during matches, 86 during training. The incidence of match injuries was on average 56.2 injuries per 1000 match hours (95% CI ±6.74). The incidence of time-loss match injuries (14.7; 95% CI ±3.44) was significantly higher in men than in women. Conclusions A critical review of water polo in-competition rules and the implementation of a Fair Play programme may help to mitigate the high incidence of contact injuries incurred during matches. A water polo-specific concussion education programme including recognition, treatment and return to play is recommended. Finally, a prospective injury surveillance programme would help to better define water polo injuries outside of the competition period.
Neutrophil to lymphocyte ratio (NLR) as a useful prognostic marker for survival in patients with locally advanced (stage III) non-small cell lung cancer (NSCLC).
Authors: Ali Tahir, Wilma M Hopman, Andrew George Robinson
Journal: Journal of Clinical Oncology (2018)

e20511 Background: The aim of our study is to investigate the prognostic value of NLR in predicting outcomes in Stage III NSCLC patients, in both palliative and radically treated cohorts. Methods: A retrospective cohort diagnosed with Stage III NSCLC between January 1, 2008 and December 31, 2012 at the Cancer Centre of Southeastern Ontario was analyzed. Demographics, clinical and tumor characteristics, and hematological data at different time points were collected. A NLR ≥5 was used to define a high NLR and it was assessed at baseline and after radiation therapy. Associations of NLR level with well-established prognostic markers such as weight loss and performance status were assessed using chi-square tests and independent samples t-tests. Overall survival was compared using the Kaplan-Meier method and Multivariable Cox Proportional Hazards models. Results: A total of 233 patients with stage III NSCLC were included in the study. Median age at diagnosis was 68 years. One hundred patients (42.9%) were treated with radical-intent, and 133 patients (57.1%) with palliative-intent. Median survival was 16.7 months for patients with NLR < 5, and 7.7 months for NLR greater than ≥ 5 (p < 0.001). High NLR patients were significantly more likely to be treated with palliative intent (75.4% vs. 41.4%, p < 0.001). A high NLR was significantly associated with T stage, weight loss, and poor performance status. In multivariate analysis controlling for these known predictors within palliative and radically treated patients, NLR was no longer statistically significant. Conclusions: Elevated NLR (≥5) is a predictor of poor outcome and shorter survival in patients with stage III NSCLC as compared to patients with NLR < 5. The NLR is an inexpensive, verifiable test which can used, but clinically adds little to performance status, stage, and weight loss in stage III patients. Larger and prospective studies are needed to confirm the clinical utility of NLR.
Impact of health disparities on outcomes: Do black women with inflammatory breast cancer require individualized treatment intensification?
Authors: David Zaenger, Bryan M Rabatic, Nicholas A Madden, Joseph A Marascio, Edward M Marchan, Ke Huang, Sherif Shaaban, Feng Ming Kong, Catherine L Ferguson, Shou-Ching Tang, Ahmad M Albasheer, Alexander Green, Jed W Howington, Mahboubeh Pishgou, William D Martin, Maryam Aletan, Mohammed Firdos Ziauddin, John G Stewart, Byron G Dasher, Waleed F Mourad
Journal: Journal of Clinical Oncology (2016)

e18075 Background: Inflammatory breast cancer (IBC) is an aggressive breast cancer. The current treatment paradigm is trimodality therapy with neoadjuvant chemotherapy, modified radical mastectomy (MRM), and post-mastectomy radiation therapy (PMRT). Even with improving outcomes from systemic therapy, survival rates remain unsatisfactory prompting the need to identify patients that may benefit from treatment intensification. We hypothesized that oncologic outcomes of IBC differ between black and white women, contributing to possible health disparities. Methods: We searched the SEER database for women with non-metastatic [AJCC 6th (1988+)] IBC. All patients underwent MRM with the specified race, age, ER, PR, grade, nodal stage, and radiation data. Our primary endpoint was actuarial 5-year cause-specific survival (CSS). Results: We identified a cohort of 4841 women treated between 1998 and 2007. Black, white, and other races represented 13%, 81%, and 6% of the cohort respectively. The peak age at diagnosis was between 45-49 years in black women and 50-54 years in white women. The actuarial 5-year CSS for the whole cohort was 56%. Black, white, and other races had CSS of 42%, 58%, and 59% respectively. Black women had a statistically significant lower CSS than white women (Table 1). The CSS difference remained significant when controlling for receptor status, grade, nodal stage, age <70, and whether PMRT was utilized. The ER/PR+ rates in black and white women were 32% and 38% respectively while the ER/PR- rates were 50% and 44%. Black women had higher rates of high-grade disease than white women (79% v. 70%). Conclusions: Our study suggests a health disparity in black women with IBC. As such, select black women with IBC may be candidates for individualized treatment intensification such as additional adjuvant chemotherapy after standard neoadjuvant therapy and/or dose escalation of PMRT. Further prospective data, if feasible, is needed to confirm our findings and conclusions. 5-year actuarial cause-specific survival of inflammatory breast cancer by race. Race n= 5-year CSS (95% CI) All 4841 56% (54.0-57.2) Black 629 41% (37.3-46.0) White 3906 58% (55.8-59.3)