tbuckley/cabot-search huggingface dataset:
Efficacy of nivolumab (Nivo) as 2+ line treatment and quality of life (QoL) in advanced refractory non-small cell lung cancer (NSCLC) patients: Interim results of observational prospective study.
Authors: Konstantin K. Laktionov, Alla L. Arzumanyan, Larisa Bolotina, Valeriy Vladimirovich Breder, Natalia N. Buevich, Anastasia Danilova, Elena A Filippova, Anna Kornietskaya, Mikhail M Kramchaninov, Eugenia K Kushniruk, Dilorom H. Latipova, Fedor Vladimirovich Moiseenko, Tatiana P. Nikitina, Sergey V. Orlov, Rashida Orlova, Svetlana A. Protsenko, Ksenia A. Sarantseva, Daniil L. Stroyakovskiy, Anna V. Zinkovskaya, Tatyana I. Ionova
Journal: Journal of Clinical Oncology (2018)

e21126 Background: We aimed to evaluate quality of life (QoL) in advanced refractory NSCLC pts and clinical outcomes of nivolumab (Nivo) as ≥ 2nd line treatment within the expanded access program in RF. We report interim analysis on response rates, survival and QoL changes during Nivo treatment. Methods: Adult pts with advanced refractory NSCLC were enrolled in 7 centers. All the pts received Nivo 3 mg/kg q2w. Tumor response was assessed using RECIST v. 1.1., QoL – by RAND SF-36 at baseline, 4 and 12 weeks after treatment start. Overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meyer method. Cox regression was performed. For longitudinal QoL analysis GEE method was used. Results: The interim analysis was performed in the group of 176 pts with the median follow-up – 7.8 mos (64% – males; median age – 61.5 (29−80); ECOG PS 0-1/2-3 – 81%/19%; former/current smokers – 70%; non squamous NSCLC – 65%; ≥2 lines of previous systemic treatment – 52%, underweight – 30% pts). Efficacy was evaluated in 154 pts (median first evaluation – 2.1 mos): PR – 9.7%, SD – 48.7%, PD – 41.6% (21 pts had clinical PD). Median OS was 10.2 mos (95%CI 6.6–13.7), median PFS – 4.2 mos (95%CI 3.7–4.7). Univariate analysis revealed that poor pretreatment ECOG PS, disease progression at the first tumor evaluation as well as impaired pretreatment QoL were associated with shorter OS and PFS; pretreatment underweight – with shorter OS (log-rank, p < 0.05). In multivariate Cox regression analysis, disease progression (OS – HR, 95%CI 0,3 (0,1–0,6), PFS – HR, 95% CI 0,04 (0,01–0,9); p < 0.001) and impaired pretreatment QoL (OS – HR, 95%CI 2.2 (1.1–4.3); PFS – HR 95%CI 0,04 (0,01–0,9); p < 0.05) were associated with shorter OS and PFS. Before treatment QoL was significantly impaired in 45% pts. Upon GEE, improvement of QoL after 6 cycles was revealed (p < 0.001). Conclusions: Interim results from this study corroborate clinical benefit of Nivo treatment observed in clinical trials. Nivo treatment leads to meaningful QoL improvement in NSCLC pts. Satisfactory pretreatment QoL and disease control at first tumor evaluation predict better OS and PFS.
Whether preoperative enlarged lymph nodes affect long-term outcome following laparoscopic radical gastrectomy for gastric cancer? A propensity score-matched case control study.
Authors: Qiyue Chen, Changming Huang, Chaohui Zheng, Ping Li, Jianwei Xie, Jiabin Wang, Jian-Xian Lin, Jun Lu, Longlong Cao, Mi Lin
Journal: Journal of Clinical Oncology (2016)

e15542 Background: The aim of this study was to investigate the feasibility and oncologic efficacy of laparoscopic radical gastrectomy (LG) for gastric cancer with enlarged lymph nodes (LNs). Methods: We prospectively collected data from 855 patients who underwent LG between December 2009 and May 2012 due to gastric cancer and retrospectively analyzed these patients. According to a long-axis diameter of lymph node (LN) as measuredpreoperatively, patients were divided into large ( > 10 mm) and small ( ≤ 10 mm) lymph node groups (LG and SG). The long-term outcomes were compared in the matched groups using 1:1 propensity-score matching method. Results: Beforematching, most clinicopathologic characteristics including tumor size and tumor staging were significantly different between the LG and SG. After matching, only pN stage and neoadjuvant chemotherapy (NC) significantly differed between the two groups. Beforematching, the LG compared with the SG was associated with more LNs retrieved; while after matching, number of LNs retrieved were similar between the two groups, and it wouldn’t decrease as enlarged LNs area increases. 835 of 855 (94.2%) patients completed postoperative follow-up, and the median follow-up period was 41 (range 3-65) months. Beforematching, the LG demonstrated significantly lower 3-year overall survival rate (64.4% vs. 84.8%, P < 0.001); and in the LG, 3-year overall survival rates were similar among patients with different total number of enlarged LNs area. After matching, the 3-year overall survival rate of LG were comparable with that of SG(81.1% vs. 72.4%, P= 0.066). Multivariate Cox regression showed pTNM stage was the only independent prognostic factor. Stratified analysis according to pTNM stage demonstrated that 3-year overall survival rates of each stage were similar between the LG and SG. Conclusions: LG is also a safe and feasible procedure for gastric cancer with enlarged LNs compared to those without enlarged LNs. And the total number of enlarged LNs area has no impact onlong-term outcome of patients with the same tumor stage.
Phase I study of lurbinectedin (PM11083) in patients with advanced AML and MDS.
Authors: Christopher Brent Benton, Jose Rodriguez Diaz -Pavon, Abhishek Maiti, Naval Guastad Daver, Farhad Ravandi, Nitin Jain, Yesid Alvarado, Elias Jabbour, Sherry Pierce, Monica Kwari, Margarida A Santos, Sara Martinez, Mariano Siguero, Ayalew Tefferi, Jorge E. Cortes, Hagop M. Kantarjian, Animesh Dev Pardanani, Guillermo Garcia-Manero
Journal: Journal of Clinical Oncology (2017)

e18521 Background: The FDA-approved drug trabectedin is a DNA minor groove binder (MGB) with activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB, with activity against myeloid leukemia cells. A phase I clinical trial was initiated to determine recommended doses in MDS/AML. Further assessment of its safety, tolerability, and pharmacogenetics were studied. Methods: In total, 42 patients with relapsed/refractory MDS/AML received lurbinectedin, using a 3+3 study design. It was administered as a 1-hour IV infusion first at 3.5, 5, 6, and 7mg per dose on days 1 and 8. Subsequently, it was administered on days 1, 2, and 3, using 1, 1.5, 2, or 3mg per dose per patient. Results: Three patients had dose-limiting toxicities (DLTs), which were rhabdomyolysis (up to gr 4), hyperbilirubinemia (gr 3), and oral herpes (gr 3). All DLTs occurred in the 6 and 7mg cohorts. Adverse events included febrile neutropenia/infections (n = 3), GI (n = 6) and pulmonary (n = 2) toxicity, hyperhidrosis (n = 1), and QT prolongation (n = 1). Overall, 33 of 42 patients (79%) had reduction of blasts in peripheral blood (PB) or bone marrow (BM) at nadir, including 23 (55%) with &gt; 50% reduction in PB blasts alone (n = 18) or both BM and PB blasts (n = 5). One patient had PR, 2 patients had morphologic leukemia-free survival, and most (n = 30) were discontinued for progressive disease. Early deaths occurred from disease-related causes, not attributable to lurbinectedin. Thirty-two patients treated at MD Anderson were analyzed for clinical characteristics and responses. Notably, among patients with follow-up bone marrow biopsy, those with a cytogenetic abnormality at chromosome 11q21-23 had significantly greater bone marrow blast reduction than those without such abnormality (change in percentage blasts: -31±14% [n = 4] vs. 8±8% [n = 16], respectively; P= 0.04). Conclusions: Lurbinectedin is generally safe and tolerated at dose levels tested. While no sustained remissions &gt; 3 cycles were observed in these highest-risk patients, single-agent lurbinectedin was transiently leukemia suppressive for some patients, including some with abnormal chr11q or TP53 mutation. Rational combinations and situational uses of lurbinectedin are under consideration. Clinical trial information: NCT01314599.
Cancer survival in the context of growing hospital participation in Medicare ACOs.
Authors: Stephen Matthew Schleicher, Jessica A. Lavery, Brooke E. Barrow, David M. Rubin, Mark H. Radzyner, Elaine Duck, Peter Bach
Journal: Journal of Clinical Oncology (2018)

6543 Background: Accountable Care Organizations (ACOs) represent one of the main policy-level interventions to improve healthcare quality. We investigated the trend of 1) hospital participation in ACOs over time and 2) cancer survival rates at participating hospitals. Methods: We searched public reporting websites of all Pioneer and Medicare Shared Savings Program (MSSP) ACOs. We matched ACO participant lists with the Dartmouth Hospital Atlas to identify participating hospitals. Five year mortality rates of patients with cancer were captured in 100% Medicare fee-for-service claims data from 2011 assessed at the hospital level, as previously described.1 We calculated unadjusted cancer mortality rates for newly joining ACOs over time, and pooled estimates of survival comparing ACO to non-ACO control hospitals across hospital referral regions. Results: We identified 1,059 hospitals that participated in Medicare ACOs that joined through 2017. There was a trend towards increased hospital participation in ACOs, defined as the percentage of ACOs that included hospitals, over time (26.5% in 2012-2014 vs. 57.7% in 2015-2017). The five year overall survival rate for patients with cancer treated at new ACO hospitals was fairly stable over time (53.1% in 2012-2014 vs. 54.4% in 2015-2017). Similarly, there was no significant change in the odds of cancer survival for ACO vs. non-ACO hospitals over time. Conclusions: Despite growth in hospital participation within Medicare ACOs over time, the quality of cancer care at hospitals joining MSSP has remained stable. 20122 2013 2014 2015 2016 2017 New Medicare ACOs 146 106 119 89 100 99 Percent of ACOs including hospitals 22% 28% 28% 69% 59% 45% Survival rate in new ACO hospitals 52.8% 53.3% 53.5% 54.4% 54.8% 53.9% Odds ratio (95% confidence interval) for survival (ACO vs. non-ACO) 1.00 (0.98, 1.02) 0.97 (0.92, 1.02) 0.98 (0.94, 1.03) 1.01 (0.97, 1.05) 1.01 (0.98, 1.05) 1.01 (0.97, 1.05) 1Pfister DG, et al. JAMA Oncol, 2015; 2Includes the 32 initial Pioneer ACOs.
A breast cancer risk model as a predictor of interval cancer rate and tumor characteristics.
Authors: Nickolas Dreher, Irene Acerbi, Edward Kenji Hadeler, Yiwey Shieh, Michelle E. Melisko, Athena Investigators and Advocates, Laura Esserman, Laura van 't Veer
Journal: Journal of Clinical Oncology (2018)

1506 Background: The Breast Cancer Surveillance Consortium (BCSC) Risk Calculator is a validated and widely used risk model that predicts five- and ten-year risk of developing invasive breast cancer for women age 40-75. However, little research has been conducted to determine if women with high BCSC risk are also more likely to develop any particular type of cancer. These women may be at elevated risk to develop interval cancers, those that present symptomatically following a normal screening mammogram and are often faster-growing. If this were the case, women with high BCSC risk (defined here as the top 2.5% by age) may merit increased screening frequency. Methods: We calculated BCSC 5-year risk scores for female breast cancer patients who completed an online intake survey distributed by the Athena Breast Health Network before being seen at the UCSF Breast Care Center, and whose BI-RADS density category was available. We reviewed charts of patients who were in the top 2.5% of risk for their age according to national averages estimated by the BCSC, and we compared them to an equal number of female breast cancer patients from the lower 97.5%. We then compared the proportion of interval, ER-negative, node-positive, and high-grade cancers between each group using a Chi-squared test (two-sided alpha = .05). Results: Of 5253 female breast cancer patients who completed an intake survey, 1880 had BI-RADS data available. 131 of these patients fell in the top 2.5% of breast cancer risk for their age. Compared to 131 breast cancer patients from the lower 97.5% of risk, more high-risk patients developed an interval cancer within one year of a normal screening mammogram, with preliminary rates of 24.1% vs 4.1% respectively (p = 0.003). There was no significant difference between the rates of ER-negative, node-positive, or high-grade cancers between the two groups. Conclusions: Breast cancer patients in the top 2.5% of breast cancer risk according to the BCSC model are more likely to develop interval cancers, which may warrant tailored screening strategies.
Baseline peripheral blood biomarkers associated with clinical outcome of advanced lung cancer in patients treated with anti-PD-1 antibody.
Authors: Aixa Elena Soyano, Bhagirathbhai R. Dholaria, Julian A. Marin-Acevedo, Nancy N. Diehl, David Hodge, Yanyan Lou
Journal: Journal of Clinical Oncology (2017)

e20599 Background: The anti-PD-1 antibodies nivolumab and pembrolizumab have demonstrated improved overall survival (OS) and progression free survival (PFS) in a subset of patients with metastatic or locally advanced lung cancer (LC). To date, no blood biomarkers have been identified to predict clinical outcome to anti-PD-1 agents. Methods: A retrospective analysis of 52 patients with advanced LC and treated with anti-PD-1 antibodies in a single institution was performed. White blood cell count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute neutrophil to absolute lymphocyte count ratio (ANC/ALC), absolute eosinophil count (AEC), and platelet counts at baseline before start of anti-PD-1 antibody were assessed. Kaplan–Meier and Cox regression analysis were done. Results: 48 patients were treated with nivolumab (92.3%) and 4 patients with pembrolizumab (7.7%). Median follow up was 13.6 months and median OS was 26 months. Higher baseline ANC and ANC/ALC ratio significantly correlated with worse clinical outcomes. Patients with baseline ANC &gt; 6060/mm 3 had a significantly increased risk of death [hazard ratio (HR) = 2.46; 95% CI 1.12–5.42, P = 0.025] and of progression on anti-PD-1 antibody [HR = 2.41; 95% CI 1.25–4.64, P = 0.009] compared with patients with ANC ≤6060/mm 3 . Similarly, patients with baseline ANC/ALC ratio ≥ 4.59 had a significantly increased risk of death [HR = 2.41; 95% CI 1.11–5.24, P = 0.027] and of progression on anti-PD-1 antibody [HR = 2.08; 95% CI 1.10–3.95, P = 0.027] compared with patients with ANC/ALC &lt; 4.59. One year survival rate in patients who had ANC &lt; 3390/mm 3 , ANC 3390-6060/mm 3 and ANC &gt; 6060/mm 3 were 86.5%, 76.9% and 48.1% respectively. Conclusions: Increased baseline ANC and ANC/ALC were associated with poor PFS and OS in LC patients treated with anti-PD-1 antibodies. Although these findings need to be validated in a large sample size, our data suggested that baseline ANC and ANC/ALC ratio might help the risk stratification and assist treatment strategies. The potential predictive value of peripheral blood biomarkers for clinical outcomes to anti-PD-1 antibody should be further investigated in a prospective study.
Identification of osimertinib resistance mechanisms in Chinese NSCLC patients: Analysis from AURA17 trial.
Authors: Min Hu, Yi-Long Wu, Xuehua Zhu, Yun Sun, Xuesong Lu, Jia Wang, Mengzhao Wang, Ying Cheng, Yuan Chen, Yanqiu Zhao, Yuankai Shi, You Lu, Meiqi Shi, Helong Zhang, Xiangning Huang, Zhijie Ding, George Chen, Caicun Zhou
Journal: Journal of Clinical Oncology (2018)

9077 Background: Osimertinib is approved for metastatic NSCLC patients with EGFR T790M mutation after progression from EGFR-TKI therapy. Despite impressive tumor responses, drug resistance usually develops. Mechanisms of resistance to osimertinib are emerging, while resistance studies with large cohorts of Chinese patients are still lacking. Here we reported a resistance profile of osimertinib using plasma samples from 76 Chinese patients who had progressed by DCO2 (Nov. 4, 2016) of AURA17 study (NCT02442349), the pivotal trial for China market approval. Methods: Serial plasma cell-free DNA (cfDNA) were collected from baseline until progressive disease (PD) by investigator assessment. Capture-based 75-gene NGS panel was used to identify resistance mechanisms to osimertinib by comparing paired plasma cfDNA at baseline and PD. Droplet digital PCR was used to dynamically monitor EGFR mutation changes during treatment course. Association of cfDNA biomarkers with objective response rate (ORR) and progression-free survival (PFS) was analyzed. Results: 61 out of the 76 patients had detectable EGFR sensitizing mutations (L858R or Ex19Del) in their cfDNA samples at PD. Among them, 8 had acquired EGFR C797S, all in cis with T790M, with no enrichment for either L858R or Ex19Del (5:3). The median time of C797S detection from plasma was 2.8 (1.4-8.4) months prior to PD. EGFR amplification, L718Q, I744T, C775Y, G796S/D and T854I mutations were found in 13 patients. Aberrations in bypass tracks including ERBB2/3, FGFR3, HRAS, JAK1/2, MET, MTOR, NTRK1, PIK3CA, etc. were observed in 35 patients. Clearance of EGFR sensitizing mutations at weeks 3 or 6 of treatment was associated with favorable ORR (69.7% vs. 33.3% and 74.3% vs. 33.3%) and PFS (6.9 vs. 4.0 and 7.1 vs. 4.1 months, respectively). Presence of T790M at PD was correlated with longer PFS (8.2 vs. 4.2 months). Conclusions: Our study revealed diverse mechanisms of resistance to osimertinib in Chinese NSCLC patients. As the current subset has shorter PFS compared to the overall AURA17 population (6.2 vs. 9.7 months), analysis of plasma samples from patients who progressed by 24 months after last subject first dose (LSFD) is ongoing for a more comprehensive view. Clinical trial information: NCT02442349.
Rate of second malignant neoplasm in a cohort of early stage uveal melanoma followed at Instituto Oncológico Henry Moore (IOHM) in the last 15 years.
Authors: Gaston Martin Reinas, Ernesto Gil Deza, Eduardo L. Morgenfeld, Flavio Tognelli, Marcelo Muino, Edgardo G. J. Rivarola, Felipe G. Gercovich
Journal: Journal of Clinical Oncology (2016)

9587 Background: Uveal melanoma (UM) is a rare neoplasm with a 3.3% rate of second malignant neoplasm (SMN) according to the Collaborative Ocular Melanoma Study (COMS) (Diener-West m et al. Arch Ophthalmol 2005;123:601–604.). Two additional UM series confirmed these results (Chin K e al. Optometry 2007;78:396–401 and Kurli m et al. Am J Ophthalmol 2005;140:193–199). The objective of the present study is to show the incidence rate of SMN in a cohort of early stage UM followed at IOHM. Methods: Forty two Pt with early stage UM diagnosed between 1/12/2000 and 31/12/2015 were studied. Variables examined were: tumor size (small = less than 10mm; medium = 10-15mm; large = greater than 15mm), local treatment, distant recurrence and SMN. A survival analysis (Kaplan Meier - log rank test) comparing enucleation vs radiation as first line therapy was made. Results: Population characteristics (n = 42 Pt): Median age: 63 years (r 33-92y). Sex: male 17 Pt (40%) / female 25 Pt (60%). Stage (I = 17 Pt, II = 8 Pt, III = 17 Pt). Size of the tumor (small = 13 Pt, medium = 15 Pt, large = 14 Pt). Treatment: enucleation = 18 Pt (43%), radiotherapy 24 Pt (57). Local recurrence one Pt. Distant metastasis 6 Pt (Liver 4 Pt, Brain 1 Pt, Bone 1 Pt). Second Malignant Neoplasm: 9 Pt (Breast 3 Pt, Lung, Testis, Thyroid, Parotid, Meningioma and Skin basal cell carcinoma one each). One Pt had a third tumor (Endometrial carcinoma). The median follow up for the entire cohort was 36 months (r 1-187m). The comparison between enucleation and radiotherapy as first therapeutic approach did not show differences in overall survival (Log rank p = 0.274). The only predictive factor for survival was the size of the primary tumor (Log rank p = 0.02) with 100% survival in small tumors, 85% in medium tumors and 65% in large tumors. Conclusions: 1) In this cohort of 42 early UM followed at IOHM we find 9 Pt (21%) with SMN. It is between three to seven times higher than the expected rate according to international publications. 2) The next step in this research is to compare the genomic of the UM with the SPN in order to identify a mutational profile. 3) According to these results the screening for SMN in UM is mandatory.
Demography and survival of inflammatory breast cancer (IBC) based on histological subtypes: A hospital-based registry analysis.
Authors: Tithi Biswas, Tarun Kanti Podder, Charulata Jindal, Eric Chung, Jimmy T Efird
Journal: Journal of Clinical Oncology (2018)

e12587 Background: IBC is a rare but aggressive form of primary breast cancer characterized by rapid onset and progression with poor prognosis. Similar to non-inflammatory breast cancer, IBC can be separated based on histological expression of estrogen (ER), progesterone (PR) and human epidermal growth factor-2 (HER-2) receptors. Overall survival (OS) based on histologic subtypes of IBC is not well studied. This analysis aimed to study demography and OS outcome of IBC based on different histological subtypes. Methods: We utilized National Cancer Database to identify non-metastatic, pathology-confirmed IBC (N = 9,551) who underwent any form of surgery between 2004-2013. They were grouped into 4 different subtypes (HR+/HER2+, HR+/HER2-, HR-/HER2+, HR-/HER2-). Follow-up time was measured from the date of diagnosis to the date of death or censoring. Analyses were performed using SAS software (version 9.4; Cary, NC). Results: The median age at diagnosis was 55 years (IQR = 18 years). The median FU was 3.6 years (IQR = 3). Majority were white (80%), had private insurance (54%); 48% of tumors were > 5cm and 59% were poorly differentiated. Over 95% patients underwent mastectomy and 74% received radiotherapy (RT). Differences by hormone receptor type were observed for age, race, insurance, clinical stage, tumor size, lymph node invasion and grade (p < .0001) but not by treatment facility type/distance and co-morbidities. Neoadjuvant therapy (NAC) was administered to 33% of cases. HR-/HER2+ (66%) and HR+/HER2+ (61%) tumors had the highest pathologic complete response (pCR) rates, with corresponding 5-year survival probabilities of 81% (95%CI = 75-86%) and 71% (95%CI = 66-76%). Overall, survival was poor for triple-negative tumors (42%, 95%CI = 39-46%). On multivariable analysis, (MVA), TN subtype, positive margins, higher grade, lymph node invasion, not receiving systemic therapy and radiotherapy remained significantly adverse (p < .0001). Conclusions: This is a large observational study of IBC based on histologic subtypes showing differential tumor, patient and treatment characteristics, and overall survival.