tbuckley/cabot-search huggingface dataset:
Efficacy and safety of apatinib in extensive stage small cell lung cancer patients failed from two or more lines of chemotherapy.
Authors: Yutao Liu, Xingsheng Hu, Jiang Jun, Lin Yang, Shengyu Zhou, Peng Liu, Junling Li, Yan Wang, Xuezhi Hao, Yuankai Shi
Journal: Journal of Clinical Oncology (2019)

8553 Background: Information on the optimal therapy beyond the second-line treatment of small cell lung cancer (SCLC) is very limited and controversial. Inhibiting the components of the VEGF signaling pathway is an attractive treatment option for SCLC patients. Apatinib, a selective inhibitor of VEGF receptor-2 (VEGFR-2) tyrosine kinase, has been proven to be safe and effective for the treatment of a broad range of advanced solid tumors. In our prospective clinical study, we aim to evaluate the efficacy and safety of single-agent apatinib as treatment of extensive-stage (ES) SCLC patients after failure from at least two prior chemotherapy regimens. Methods: Twenty-two ES-SCLC patients treated with single-agent apatinib after failure from at least two prior chemotherapy regimens in our institution between November 2016 to August 2018 were enrolled in the clinical study. Apatinib mesylate was orally administered at a dose of 500 mg once daily on a 28-day cycle until evaluation of disease progression (PD) or the occurrence of unacceptable toxicity. Dosage reduction to either 425 mg or 250 mg once daily were permitted based on the evaluation of toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and adverse events (AE). Results: The median age was 56 years, ranging from 36 to 70 years. A majority (63.6%, 14/22) received apatinib as third-line treatment, while 22.7% (5/22) and 13.6% (3/22) received it as fourth or fifth-line treatment, respectively. Partial response (PR) was achieved by 3 (13.6%) patients and stable disease exhibited by 18 (81.8%) patients. The median PFS and OS were 5.4 and 10.0 months, respectively. Apatinib demonstrated a manageable toxicity profile, with grade I-III secondary hypertension and proteinuria as the most common AE. Grade III adverse events were only observed in 3 (13.6%) patients with either hypertension (1 patient) or proteinuria (2 patients). Except for these 3 patients, all the other patients experienced grade I-II adverse events. No grade IV and V AE were observed among the patients. Multivariate analysis revealed secondary hypertension as an independent predictor of OS ( p= 0.047). Conclusions: Apatinib is safe and effective in the management of ES-SCLC patients and can be considered as a treatment option after failure from at least two prior chemotherapy regimens. Secondary hypertension can be a potential prognostic factor for apatinib treatment. Clinical trial information: NCT02995187.
The tumor microenvironment in EGFR-driven loco-regional lung adenocarcinoma can predict higher risk of recurrence.
Authors: Maya Khalil, Ahmed Elkhanany, Yuanquan Yang, Sean Glenn, Antonios Papanicolau-Sengos, Carl Morrison, Grace K. Dy
Journal: Journal of Clinical Oncology (2019)

8521 Background: The role of EGFR tyrosine kinase inhibitors (TKIs) as adjuvant therapy in EGFR-mutated NSCLC is still controversial. Identifying biomarkers associated with increased risk of recurrence may help stratify pts &amp; guide adjuvant therapy. We hypothesized that tumor immune microenvironment (TME) alterations could predict disease-free survival (DFS) in these pts. Methods: The Cancer Genome Atlas (TCGA) lung Adenocarcinoma (LUAD) data at Genomic Data Common (GDC) was accessed for pt phenotype, updated outcome &amp; normalized gene expression profile (RNA seq). Immune landscape data was obtained from PANCAN. We chose to focus on 54 key TME genes, identified from a commercially available immune report card from OmniSeq (Inc.). Pt groups were divided via K-mean clustering. Group comparison was done via Likelihood Ratio (LR, categorical), Mann Whitney (continuous), log-rank (survival) &amp; Cox regression (outcome). Bonferroni correction was used to correct for multiple comparisons. Results: 877 pts with LUAD were identified, 32 of whom had EGFR mutations and were at stages I to III. The mutations were mostly in the TK domain, involving exons 18 (12%), 19 (27%), 20 (6%), &amp; 21 (33%). Only 3% harbored the T790M mutation. None of the pts received adjuvant TKI. Analysis of the impact of individual genes on DFS yielded a group of 8 genes whose high expression was associated with improved DFS: IL10 (HR 0.58, p 0.029), BTLA (HR 0.66, p 0.07), CD8A (HR 0.6252, p 0.099), CD39 (HR 0.454, p 0.037), CCR2 (HR 0.729, p 0.039), CSF1R (HR 0.70, p 0.087), ICOS (HR 0.66, p 0.062), &amp; CD4 (HR 0.67, p 0.059). K-mean clustering of the pts using these genes demonstrated 2 groups with distinct immune profiles. Group 1 was characterized by higher leukocyte and stromal fractions, lymphocyte infiltration score, macrophage regulation, TGF-ß response, &amp; T cell richness with less proliferation, pointing towards a more “inflamed” phenotype. Significant difference between the two groups in the immune subtypes was found (LR 10, p = 0.039). 90% of pts in the inflamed group had tumors with IFN-γ dominant, inflammatory, and TGF-ß dominant subtypes, while 45% of the “non-inflamed” group had lymphocyte depleted &amp; wound healing signatures. DFS was significantly longer in the inflamed group (median DFS 1480 vs 772 days, p = 0.002). Conclusions: In pts with resected EGFR-mutated LUAD, an inflamed TME is associated with prolonged DFS. Identifying these pts may help select those who would benefit from adjuvant therapy.
Urban/rural disparities in stage at presentation of colorectal cancer among young adults in the United States, 2007-2015.
Authors: Victoria Nguyen, David J. Delgado, Rachel Gray Denneny, Jay Subramoney, Brandon George, Edith P. Mitchell
Journal: Journal of Clinical Oncology (2019)

3598 Background: The overall incidence rate of colorectal cancer (CRC) has declined in recent decades but is rising in young adults (YA). Disparities also exist in CRC presentation and geographical residence. We examined associations between urban/rural residence and CRC stage at presentation among YA 18-50 years old, using the Surveillance, Epidemiology, and End Results (SEER) 1973-2015 registry. Methods: Retrospective cohort study using SEER patients (pts) diagnosed with CRC between 2007-2015, aged 18-50. Urban/rural status was defined at the county level as large metro, small metro, urban non-metro, and rural. Pts were grouped by age: 18-30, 31-40, and 41-50 years old. Stage was defined as in-situ/localized and regional/distant. We used multivariable logistic regression to describe associations between urban/rural status with stage at presentation, adjusting for tumor location, histology, grade, and patient attributes (e.g. insurance status). Results: 27,198 CRC pts were analyzed: 62.2% large metro, 27.4% small metro, 9.4% urban non-metro, and 67.1% regional/distant stage. In multivariable analysis, YA in urban non-metro counties had lower odds of regional/distant stage at presentation compared to YA in large metro counties (OR = 0.87, 95% CI = 0.79-0.97). Associations between small metro and rural status with stage at presentation were not significant (OR = 0.94, 95% CI = 0.89-1.01 and OR = 0.84, 95% CI = 0.64-1.10, respectively). YA with Medicaid or no insurance had higher odds of regional/distant CRC (OR = 1.28, 95% CI = 1.17-1.39 and OR = 1.34, 95% CI = 1.20-1.51, respectively) compared to YA privately insured. Other factors in YA associated with higher odds of regional/distant CRC included signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age (18-30 and 31-40 years old). Conclusions: YA in urban non-metro areas had lower odds of regional/distant CRC at presentation compared to YA in large metro areas. YA with Medicaid, no insurance, signet-ring histology, poorly-, moderately-, and undifferentiated grade, and younger age had higher odds of regional/distant CRC at presentation. Further research is needed to explore the etiology of these differences.
Single-arm, phase II study of pyrotinib in advanced non-small cell lung cancer (NSCLC) patients with HER2 exon 20 mutation.
Authors: Guanghui Gao, Xingya Li, Qiming Wang, Yiping Zhang, Jianhua Chen, Yongqian Shu, Yanping Hu, Yun Fan, Jian Fang, Gongyan Chen, Jun Zhao, Jianxing He, Fengying Wu, Jianjun Zou, Xiaoyu Zhu, Caicun Zhou
Journal: Journal of Clinical Oncology (2019)

9089 Background: HER2 exon 20 mutation is a well-known oncogenic driver in non-small cell lung cancer (NSCLC) and its testing is recommended by NCCN guidelines for NSCLC patients. However, up to now, there has been no approved targeted therapy for this patient population. Pyrotinib is an oral, irreversible pan-Her tyrosine kinase inhibitor (TKI) against HER1, HER2 and HER4, which, combined with chemotherapy, has recently been approved in China for HER2 positive advanced breast cancer. Methods: Stage IIIB or IV NSCLC patients with HER2 exon 20 mutation (confirmed in a central lab) and previously treated with at least one platinum-based chemotherapy were enrolled in this open-label, multi-center, single-arm phase II study. Patients with active brain metastases or prior use of HER2 TKI agents were excluded. Eligible patients received pyrotinib 400 mg once daily until disease progression, intolerable toxicity or withdrawal of consent. The primary endpoint was objective response rate (ORR) according to RECIST 1.1. Secondary endpoints included safety, progression-free survival (PFS), time to disease progression (TTP), duration of response (DOR) and overall survival (OS). This trial is registered on ClinicalTrials.gov (NCT02834936). Results: Between October 20, 2016 and December 10, 2018, 60 patients (33 female, 27 male) were enrolled. The median age was 57 years (range: 40, 72). A majority were stage IV patients (95%). Over 58% of patients have been treated with two or more prior chemotherapy regimens. As of Jan 21, 2019, the ORR as evaluated by investigators was 31.7% (95% CI 20.3%, 45.0%). Median DOR was 7.0 months (95% CI 5.5, 11.0) and median PFS was 6.8 months (95% CI 4.1, 8.3). 26.7% patients reported treatment-related grade 3 AEs. Diarrhea (20.0%) was the only treatment-related grade 3 AE that occurred in ≥ 2 patients. Treatment-related grade 4 AE was reported in 1 subject (elevated gamma-glutamyl transferase). The anti-tumor activities of pyrotinib was shown in various mutation types. Conclusions: Pyrotinib as a single agent demonstrated promising anti-tumor activity and acceptable safety profile in heavily pretreated HER2 mutant NSCLC patients. Clinical trial information: NCT02834936.
Abstract 12899: A New Prognostic Marker for Functional Deterioration in Heart Failure: Coronary Vascular Resistance
Authors: Mehmet S Cetin, Elif H Ozcan Cetin, Ugur Canpolat, Selahattin Aydin, Yesim Akin Guray, Dursun Aras, Ahmet Temizhan, Sinan Aydogdu
Journal: Circulation (2014)

Introduction: Heart failure (HF) is a challenging clinical syndrome with complex pathophysiology. Previous studies demonstrated that coronary flow reserve assessed by PET technique was impaired in HF. Transthoracic echocardiography (TTE) can provide reliable data for myocardial blood flow (MBF) which can be measured from coronary sinus (CS). In relation with MBF, coronary vascular resistance (CVR) can be evaluated. In this study, we aimed to evaluate the association of MBF and CVR with clinical data in HF. Methods: The MBF was measured in 100 patients (80 patients with HF (LVEF&lt;30%) and 20 healthy control subjects. MBF was measured from anterograde CS flow TVI at PLAX RV inflow view and CS diameter at A2C view (2Πr2*TVI*heart rate) and indexed to left ventricular mass index. Patient group was categorized based on NYHA functional classes (NYHA FCs). Results: There was an incremental trend for MBF with advancing NYHA FCs (β=0.253, p=0.015). MBF was similar among HF patients due to NYHA FCs. However, MBF was higher in NYHA FC 4 group compared to healthy subjects (p=0.029). Also, CVR was lower in HF patients than the control group (11.15±6.54 vs.24.84±7.29, p&lt;0.001). In the subgroup analysis, CVR was not statistically different between non-ischemic and ischemic etiology of HF (6.91±1.38 vs. 6.31±0.89, p=0.249). Additionally, CVR was significantly lower in NYHA FC 4 compared to other study groups. CVR was positively correlated with peak VO2 (β=0.596, p&lt;0.001), and Seattle Heart Failure Model derived life expectancy (β=0.476, p&lt;0.001) and negatively correlated with serum BNP level (β=-0.450, p=0.001), troponin I (β=-0.366, p=0.001) and serum uric acid level (β=-0.503, p&lt;0.001). In multivariate analysis, CVR is an independent predictor of mortality (HR:0.763 95%CI:0.624-0.933 P=0.008). In ROC analysis, a cut of value 6.73 for CVR has a 74% sensitivity and 66.7 % specifity for prediction of mortality in HF(AUC 0.825 P&lt;0.001). Conclusion: Our results showed that CVR was reduced with advancing FC in HF patients, despite MBF was similar among different FCs. In addition, CVR was significantly correlated with various prognostic markers in HF patients. Therefore, evaluation of MBF hemodynamics, particularly CVR, with TTE may utilize prognostic assessment of HF patients.
Tumor contact length used as a biomarker to predict extracapsular extension, lymph node involvement, and biochemical recurrence.
Authors: Públio Viana, Thiana Rodrigues, Davi alves martins Mota, Giuliano Guglielmetti, Diogo Assed Bastos, Arnaldo Fazoli, William Carlos Nahas, Rafael Coelho, Mauricio Cordeiro, Natally Horvat
Journal: Journal of Clinical Oncology (2019)

e16588 Background: Prostate cancer (PC) is the cancer most commonly diagnosed in men and the second leading cause of death. Multiparametric magnetic resonance imaging (mpMRI) is the benchmark imaging standard for local staging of PC. Patients with pathological extraprostatic tumor (pEPE) have a worse prognosis than those with confined organ disease with a higher risk of biochemical recurrence (BCR) after radical prostatectomy (RP). These factors, in addition to positive lymph nodes (PLN), are pivotal in the decision-making process regarding treatment. However, the subjective MRI analysis has low sensitivity in the detection of EPE and is plagued by the low interobserver agreement. Tumor contact length (TCL) is an objective parameter of mpMRI defined as the length of prostate cancer in contact with the prostate capsule, which may provide additional information about prostate cancer outcomes. We aimed to evaluate TCL as a predictor of pECE, PLN, and BCR in patients undergoing RP. Methods: In this Institutional Review Board approved single-institution prospective study, we update the follow-up of 148 patients and included 31 new patients, with prostate cancer who underwent prostate MRI before radical prostatectomy from March 2014 to november 2018. TCL was measured using T2-weighted magnetic resonance images.Postoperative prostate-specific antigen (PSA) values were obtained every 3 months in the first year, then biannually and annually thereafter. BCR was defined as PSA≥0.2ng/mL. The exclusion criterion was prior treatment. Results: The median follow-up was 44 months. 76/179 (42,4%) patients had pEPE, 12/179 (6,7%) had pLN, and 29/179 (16,2%) had BCR. TCL values were significantly higher in patients with pathological pECE ( 20,6 mm vs 9,9 mm, p &lt; 0.001). Using a cut-off of 11,9 mm we found area under curve (AUC) of 0,71 to predict pathological ECE, with sensitivity 72,5% and specificity 67,5% . Using a cut-off of 16,5 mm we found AUC of 0,64 to predict BCR, with sensitivity 54,2% and specificity 67,8% and with a cut-off of 21,7 mm the AUC to predict PLN was 0,77, with sensitivity 66,7% and specificity 83,6%. Conclusions: We prospectively demonstrated in our population that TCL values were significantly higher in patients with pEPE , PLN and BCR. If validated, this imaging biomarker may facilitate and inform patient counseling and decision-making.
Case 45-1983
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Barry J. Make, Richard L. Kradin
Journal: New England Journal of Medicine (1983)

Presentation of CaseA 31-year-old man was admitted to the hospital because of chest pain and a mass in the anterior thoracic wall.He was well until 3 1/2 months earlier, when he experienced left anterior chest pain. He was seen at another hospital, where a pleural friction rub was heard. An electrocardiogram and an x-ray film of the chest were normal. A diagnosis of pleurisy was made, and ibuprofen was prescribed. During the next few weeks he had a constant pressure sensation in the left anterior chest wall and began to have night sweats, chills, and a feverish sensation, . . .
Biomarker testing, treatment (Tx) and survival outcomes in Medicaid compared to commercially insured (CI) patients with advanced NSCLC (aNSCLC).
Authors: Yeun Mi Yim, Ning Wu, William Bruce Wong
Journal: Journal of Clinical Oncology (2019)

e18119 Background: Prior studies suggest cancer patients with Medicaid may have worse outcomes, however there is limited understanding on the drivers behind these observations. This study aimed to describe the association between insurance type with Tx patterns, biomarker testing, and survival outcomes in a real-world aNSCLC population. Methods: The Flatiron Health EHR-derived database was used to identify patients &lt; 65 years of age diagnosed with aNSCLC between 1/1/2011 to 10/31/2018. Logistic regression was used to assess the association between insurance type and (1) the likelihood of receiving first-line Tx of cancer immunotherapy (CIT)/other targeted therapy, or no Tx, and (2) the likelihood of receiving EGFR/ALK testing. Median OS, estimated by Kaplan Meier, was compared between patients with CI and Medicaid coverage, and hazard ratios were derived from Cox proportional hazard models adjusting for baseline characteristics. Results: 6639 aNSCLC patients were identified with CI (n = 6022) and Medicaid (n = 617). After adjusting for baseline characteristics, Medicaid patients were less likely to receive ALK or EGFR testing [OR 0.59, 95% CI (0.49, 0.72)]. Medicaid patients were also less likely to receive CIT or targeted therapy [OR 0.49, 95% CI (0.36,0.67)] and more likely to not receive any systemic Tx [OR 1.45, 95% CI (1.22, 1.73)]. Medicaid patients had a higher risk of death than commercially insured patients, however this difference varied by Tx group (table). Conclusions: Medicaid insured patients were associated with a higher risk of mortality compared to CI patients. Factors influencing this difference may be access to biomarker testing, subsequent receipt of CIT/targeted therapy and differences in care among untreated patients. [Table: see text]
Immune cell therapy for hepatocellular carcinoma
Authors: Eishiro Mizukoshi, Shuichi Kaneko
Journal: Journal of Hematology & Oncology (2019)

Given the success of immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cells in clinical settings, the host immune system plays an important role in the recognition and targeting of tumor cells in cancer immunotherapy. As a result, there have been numerous advancements in immune cell therapy using human immune cells. However, recent evidence suggests that one type of immunotherapy alone is not effective for the treatment of cancer, particularly solid tumors. Thus, effective immunotherapy combinations, such as the combination of checkpoint inhibitors and immune cell therapy, are needed. This review focuses on hepatocellular carcinoma among other solid tumors and discusses the current status and future of immune cell therapy in cancer immunotherapy.
Time matters: A retrospective study of cancer care in a Brazilian public university hospital.
Authors: Camila Brambilla Souza, José Tristão Neto, Tiago Costa de Padua, Hakaru Tadokoro, Michelle Almeida, Christian Ribas
Journal: Journal of Clinical Oncology (2019)

e18171 Background: The perception of symptoms, diagnosys, access to a cancer care institute and the first-line of therapy are milestones of cancer care. The success of an oncological treatment is directly relatable to these key-points and the time gaps between them. Growing research in developing countries points out the challenges of offering quality of care in this setting as social, cultural, economic and political factors are deeply intertwined. The objective of this study is to identify the key-points of cancer care, the time gaps between them and the time-related end-points of patients refered to a medical oncology department of a public university hospital in São Paulo, Brazil, in the period of one year. Methods: This is a observational retrospective study based on review of medical records of all cancer patients refered to the medical oncology department of a public university hospital in São Paulo, Brazil, from 01/01/17 to 12/31/17. The analysis was performed in January 2019. The data collected comprises the age at diagnosys, gender, primary tumor site, stage (AJCC 7th ed. staging system), onset of symptons, date of hystopathological diagnosys, the first therapeutic modality and when it was offered, intention of care (curative or palliative), outcomes and the following time-relations: symptoms-dyagnosis (SD), dyagnosis-treatment (DT) and symptoms-treatment (ST). Results: From 358 profiles, 275 were included. The average age at diagnosys was 58,7 years (15-88 years). Men were 147 (53,4%) and 128 (46,5%) were women. The most common primary tumor sites were gastrointestinal tract 22,9%, head and neck 20,3%, cutaneous melanoma 17,8% and genitourinary tract 16%. 160 (58,1%) patients were diagnosed at advanced/metastatic stages (III/IV). The median time-relations were: 5,5 months for SD; 2 months for DT and 8 months for ST. The first treatment offered was surgery at 63,2% of cases, radiotherapy 17,8%, systemic therapy 16,7% (endocrine therapy, targeted therapy or chemotherapy) or palliative care 1,8%. The intention of the initial treatment: 76,3% were curative and 23,2% palliative. At time of analysis, 63,6% of patients were alive, 19,2% deceased and 16,7% of unknown outcome. Conclusions: Our data endorses prevalent findings of developing countries epidemiological studies: late diagnosys, non-curative treatments and poor outcomes. Known causes are desfavorable social-economic conditions, symptom neglection, ineffective cancer screening and deficiency of public cancer care networks. We emphasize time goals as important quality indexes to guide new solutions.