tbuckley/cabot-search huggingface dataset:
Comprehensive genomic profiling of lung cancer cytologic specimens obtained by guided fine-needle aspirate biopsies.
Authors: Sugganth Daniel, Laurie M. Gay, Siraj Mahamed Ali, Charlotte Brown, Shakti Ramkissoon, James Suh, Eric Allan Severson, Keith Killian, Prasanth Reddy, Garrett Michael Frampton, Jo-Anne Vergilio, Julia Andrea Elvin, Vincent A. Miller, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2018)

e21002 Background: Fine-needle aspirate biopsies (FNAB) obtained under imaging and ultrasound guidance play a central role in the diagnosis and staging of lung cancer. These minimally-invasive procedures have facilitated a reduction in morbidity and in length of hospitalization and are often preferred strategies to obtain material for diagnosis and molecular testing. Methods: DNA was extracted from FFPE cytologic material prepared by various cell block protocols, from 234 patients with metastatic lung cancer received for clinical testing at a referral laboratory, comprehensive genomic profiling was performed using a hybrid-capture, adaptor ligation-based assay and analyzed for all classes of alterations. Results: The patients ranged in age from 33 to 95 years, males outnumbered females at a ratio of 1.25:1. Mediastinal, hilar and supraclavicular lymph nodes accounted for 136 metastatic sites, parenchymal lung in 57, a mediastinal or hilar mass in 20, liver in 11 and other sites in 8 patients. Endobronchial Ultrasound (EBUS) guided FNAB was used in 187 patients, CT guided FNAB in 24, esophageal Endoscopic Ultrasound (EUS) in 3, and direct US guided in 20 patients. The diagnosis was adenocarcinoma in 158 patients, squamous cell in 34, non-small cell in 25 patients, small cell in 11, neuroendocrine in 4 and carcinoma (NOS) in 2 patients. 201 cases passed review for adequacy and of these 181/234 (77.4 %) successfully completed sequencing and results were reported (95% CIs [71.4, 82.5]). Inadequate DNA was extracted in 10 cases (5%), 3 (1.5%) cases failed at library construction, 9 (4.5%) at hybrid capture and 2 (1%) at post-sequencing quality control. In 201 cases, a total of 550 substitution mutations, 152 indels, 404 copy number alterations and 41 rearrangement events were detected, including 24 activating mutations in EGFR, 3 MET splice-site alterations and 4 ALK, 3 ROS1 and 2 RET rearrangements. Conclusions: Guided FNAB provide a minimally invasive route to diagnosis, with reduction in morbidity associated with more invasive procedures and this data establishes the broad utility of complex genomic testing and identification of therapeutic targets on these limited cellularity lung cancer specimens.
Clinico-pathologic features and survival in elderly patients vs. older and younger adults with glioblastoma multiforme: An exploratory analysis of a series of consecutive patients.
Authors: Andrew Samir Iskandar, Wesley Kerr, Andrew Hwang, Stephanie Farrell, Michael Del Rosario, Steven C. Plaxe, Constantin Dasanu
Journal: Journal of Clinical Oncology (2018)

e14071 Background: Clinicopathologic characteristics and outcomes between older and younger glioblastoma multiforme (GBM) patients may differ. Methods: With approval of IRB, we conducted retrospective analysis in 156 consecutive patients (n = 156) with GBM treated at our insitution in 2007-2017. 79 patients were seventy years of age or younger (≤70) and 79 were older than seventy ( > 70). Clinicopathologic features, therapy and survival were compared between two cohorts. Statistical analysis: Significance of associations was assessed via Fishers' exact test. Survival analysis was performed via Cox proportional model with censoring to calculate hazard ratios (HR). Results: Compared to patients ≤70, the patients > 70 were less likely to undergo surgery (34% vs 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs 59%; p = 0.01) or radiation therapy (36% vs 56%; p = 0.03). Survival was worse in patients > 70 as opposed to patients ≤70 (average time to death 726 vs. 935 days; HR 0.53, p = 0.04). Patient gender, primary tumor size and use or radiation therapy did not correlate with survival. There was no significant difference in terms of primary brain tumor location between the two cohorts. Time to death correlated positively with surgical excision (1138 vs 733 days; HR 0.57, p = 0.004) and use of chemotherapy (935 vs 729 days; HR 0.59, p = 0.04). Conclusions: Older GBM patients displayed significantly shorter survival than their younger counterparts. They were less likely to receive surgery, adjuvant chemotherapy and/or radiation therapy. Our multivariate analysis suggests that both age groups derived benefit from surgical excision and chemotherapy. As our study is limited by sample size, larger studies are needed to confirm the significance of our findings.
Symptoms following TKI therapy discontinuation after achieving an adequate response in patients with chronic myeloid leukemia in chronic phase (CML-CP).
Authors: Ellen K. Ritchie, Islam Sadek, Irina Pivneva, Annie Guerin, Dominick Latremouille-Viau, Briana Ndife, George J. Joseph, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2018)

e19024 Background: This study assessed symptoms following TKI therapy discontinuation after achieving an adequate response among patients (pts) with CML-CP in the United States. Methods: The study was conducted among a variety of centers/institutions prior to NCCN treatment guideline update and FDA approval for inclusion of Treatment-free Remission data in the nilotinib US product label. Pt-level data were abstracted from chart records of adult pts with CML-CP who started first-line therapy TKI between 01/2006-03/2014 and who discontinued after achieving an adequate response per physician's assessment. Symptoms following discontinuation, severity, and treatments were characterized. Results: 146 pts (imatinib: 100; dasatinib: 30; nilotinib: 16) discontinued TKI therapy after achieving an adequate response. 25 (17%; imatinib: 20; dasatinib: 3; nilotinib: 2; mean TKI duration: 3.0 years) pts experienced symptoms following TKI therapy discontinuation. The most commonly reported symptom was musculoskeletal pain (11.6%; 41% grade 1, 35% grade 2, 24% grade 3). Other symptoms included gastrointestinal (GI; 6%) and neurologic/psychiatric symptoms (1%) with both 50% grade 1 and 50% grade 2. In most cases, symptoms were already present before TKI therapy discontinuation; musculoskeletal pain (7/17; 41%) and GI (5/8; 63%) and neurologic/psychiatric (2/2; 100%) symptoms. To treat musculoskeletal pain, 17 (100%) pts were recommended painkillers with 4 (24%) being prescribed opioid-containing medication; 8 (47%) were recommended NSAIDs; 2 (12%) were restarted on their initial TKI therapy; and 1 (6%) was prescribed steroids. For GI symptoms, 6 (75%) pts were prescribed proton pump inhibitors and 4 (50%) H2 blockers. For neurologic/psychiatric symptoms, 1 (50%) pt was prescribed antidepressants and 1 (50%) gabapentin. Treatment alleviated the symptoms for the majority of the pts (musculoskeletal pain: 94%; GI: 88%; neurologic/psychiatric: 100%). Conclusions: Symptoms following TKI therapy discontinuation after achieving an adequate response were observed in 17% of pts. Symptoms were largely of low severity and were alleviated by treatment.
Prognostic role of PD-L1 expressing tumor infiltrating lymphocytes in testicular germ cell tumors.
Authors: Michal Chovanec, Zuzana Cierna, Vera Miskovska, Katarina Machalekova, Katarina Kalavska, Katarina Rejlekova, Daniela Svetlovska, Dusan Macak, Stanislav Spanik, Karol Kajo, Pavel Babal, Jozef Mardiak, Michal Mego
Journal: Journal of Clinical Oncology (2016)

4544 Background: Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard chemotherapy is not curative in a small subgroup of patients. Previously we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. The aim of this study was to evaluate the prognostic value of PD-L1 expressing TILs in TGCTs. Methods: Surgical specimens from 223 patients with TGCTs (215 with primary testicular tumor, 8 with extragonadal GCT) were included into this translational study. TILs expressing PD-L1 were detected by immunohistochemistry using anti-PD-L1 monoclonal antibody and PD-L1 expression was scored semiquantitatively by multiplicative quickscore (QS) method. Assessments were performed in all histopathologic subtypes of TGCTs, germ cell neoplasia in situ (GCNIS) and results were correlated with clinical outcome. Results: PD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.6%), teratomas (35.7%) or GCNIS (79.7%) (all p < 0.05). Similarly, percentage of PD-L1 expressing TILs was highest in seminoma (62.0% of all TILs), followed by embryonal carcinoma (43.2%), yolk sac tumor (32.3%), teratoma (24.2%) and choriocarcinoma (21.4%). PD-L1 positive lymphocytes between tubules were present in 79.7% of GCNIS cases. Patients with seminoma with high infiltration of PD-L1 positive TILs (QS ≥ 10) had non-significantly better progression-free survival (HR = 2.07, 95% CI 0.6 – 7.16, p = 0.28) and significantly better overall survival (HR = 6.98, 95% CI (1.75 – 27.91, p = 0.047) opposite to patients with lower expresion of PD-L1 (QS < 10). In other histopathological subtypes, PD-L1 expressing TILs were not prognostic. Conclusions: In this translational study, we showed for the first time prognostic value of PD-L1 expressing TILs in seminoma. Our data imply that PD-L1 positive TILs could play a protective role in seminoma patients and we suppose, that presence of these TILs could be responsible for better prognosis of seminoma compared to non-seminoma.
Prognostication of older Hodgkin lymphoma (HL) patients (pts): Findings from a multicenter phase II study.
Authors: Andrew M. Evens, Ranjana H. Advani, Michelle A. Fanale, Sonali M. Smith, Irene B. Helenowski, Gregory Bociek, Andreas Kirschmer Klein, Jane N. Winter, Leo I. Gordon, Paul A. Hamlin
Journal: Journal of Clinical Oncology (2018)

7540 Background: Outcomes have been historically poor for older HL pts (ages ≥ 60 years (yr)). Furthermore, there are sparse data regarding prognostication. Methods: Untreated older HL pts received 2 initial doses of single agent brentuximab vedotin (Bv) 1.8 mg/kg q 3 weeks followed by 6 cycles of doxorubicin, vinblastine & dacarbazine (AVD); responding pts received 4 Bv consolidation doses. 48 pts enrolled (42 evaluable for response). Univariate (UVA) & multivariate (MVA) analyses were performed with Cox proportional hazard regression for survival. Results: Median age was 69 yrs (60-88); 63% male; ECOG PS 0: 40%, 1: 42%, 2: 20%; 82% stage III/IV; 60% IPS 3-7; median Cumulative Illness Rating Scale-Geriatric (CIRS-G) co-morbidity score 6 (52% grade 3/4); & 12% had baseline loss of instrumental activities of daily living (iADL). 52% of pts completed all intended cycles & 65% received at least 1 Bv consolidation; the median CIRS-G for pts who completed all intended therapy vs not was 4 vs 8, respectively (P= 0.03). ORR to initial Bv was 87% (CR 30%). After AVD, ORR & CR rates were 95% and 90%, respectively. Among all 48 pts, 2 yr PFS was 85% with 94% OS. Response to the initial 2 doses of Bv (CR/PR vs SD) was associated with 2 yr PFS rates of 100% vs 50%, respectively (P= 0.002). On UVA, increasing age and CIRS-G score & loss of iADLs were significant for PFS (Table). On MVA of all factors, only iADLs loss remained significant for inferior PFS (HR 8.19, 95%CI 1.2-57.6, P= 0.03). 2 yr PFS rates based on loss of iADLs vs not were 25% vs 94%, respectively (P< 0.0001) with 2 yr OS 67% vs 97%, respectively (P= 0.01). Pts with loss of iADLs received a median of 6.5 vs 12 intended cycles on study (P= 0.01); 67% vs 39% had a serious adverse event (P= 0.20); and CR rate was 60% vs 95% (P= 0.06). Conclusions: Outcomes for older HL pts treated with sequential Bv/AVD were overall excellent. The most dominant factor associated with divergent pt outcomes was baseline functionality, as assessed by iADLs. Clinical trial information: NCT01476410.UVA analyses. Variables* PFS HR 95% CI P Age 1.16 1.05-1.28 0.005 Female 4.97 0.96-25.7 0.06 ECOG PS 2.46 0.87-6.97 0.09 Loss iADLs 14.88 2.68-82.53 0.002 CIRS-G 1.21 1.06-1.38 0.005 *Non-significant factors: histology; EBV/EBER; albumin; stage; marrow involvement; IPS
Ratio of some fibrinolytic system components and biological aggressiveness of melanoma.
Authors: Valeria Bandovkina, Elena Mikhaylovna Frantsiyants, Irina V. Kaplieva, Lidia K. Trepitaki, Yulia A. Pogorelova, Natalia D. Cheryarina, Irina Valerevna Neskubina, Vyacheslav A. Sustretov, Maria I. Maksimova, Ludmila Rozenko, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e21069 Background: Melanomas of early stages in a horizontal growth phase can masquerade as a melanocytic nevus or other benign skin lesions. Activation of plasmin/plasminogen system is typical of both physiologic and pathologic processes. Cell remodeling and neoangiogenesis play critical role in melanoma invasion and metastasis. The purpose of the study was comparative analysis of plasmin/plasminogen system in tissues of nevi and melanomas of different sizes and extension. Methods: Activity of plasmin and plasminogen was studied and antigen and activity assays (ELISA) were performed for uPA, tPA and PAI-1 in tissues of nevi (n = 30) and melanomas pТ 1-2 N 0 M 0 (n = 17) and pТ 3-4 N 0-1 M 0 (n = 23). Intact tissue (n = 15) obtained in surgical treatment of patients without cancer was used for the control. Results: Plasminogen levels were decreased by 2 times in tissues of nevi and pТ 1-2 N 0 M 0 melanoma, while plasmin was unchanged. pТ 1-2 N 0 M 0 melanoma significantly differed from nevi by a marked activation of uPA without PAI-1 increase. Activation of plasminogen system in both рТ 1-2 N 0 M 0 melanoma and in nevi was not accompanied by plasmin accumulation. The main difference between tissues of nevi and pТ 1-2 N 0 M 0 melanoma was the uPA/PAI-1 ratio reduction by more than 40 times in nevi. pТ 3-4 N 0-1 M 0 melanoma was characterized by plasmin level increase by more than 19 times and uPA activity and content increase by 2.5 times, compared to pТ 1-2 N 0 M 0 , without an increase in PAI-1 activity. The uPA/PAI-1 ratio almost doubled. Conclusions: Normal plasmin levels in nevi and melanomas in a horizontal growth phase are probably the result of its inhibitors activity. Increased activity of fibrinolytic system, plasmin accumulation and uPA/PAI-1 increase in a vertical growth phase determine proliferative, invasive and metastatic potential of tumors.
Whole genome sequencing of <i>Mycobacterium tuberculosis</i>
Authors: Andrea M. Cabibbe, Timothy M. Walker, Stefan Niemann, Daniela M. Cirillo
Journal: European Respiratory Journal (2018)

<b>Next-generation sequencing approaches promise to become the future standard for drug-susceptibility testing and epidemiological investigation in tuberculosis and for other high-priority bacterial pathogens</b>http://ow.ly/kXsV30lLP78
A multidimensional view of racial differences in access to prostate cancer care.
Authors: Craig Evan Pollack, Katrina Armstrong, Nandita Mitra, Xinwei Chen, Katelyn R Ward, Archana Radhakrishnan, Michelle Elana Ross, Justin E. Bekelman, Charles C Branas, Karin Rhodes, David Grande
Journal: Journal of Clinical Oncology (2017)

e18048 Background: Racial differences in prostate cancer treatment and outcomes are widespread and poorly understood. We sought to determine whether access to care, measured across multiple dimensions, contribute to racial differences in prostate cancer. Methods: The Philadelphia Area Prostate Cancer Access Study (P2 Access) included 2374 men diagnosed with localized prostate cancer from 2012 to 2014. Patient survey data was used to determine experiences of accessing prostate cancer care (response rate 51.1%). An audit survey using simulated patient calls was used to determine appointment availability and wait times at 151 urology practices. Patient and practice addresses were geocoded to construct distance measures. We used multivariable logistic regression models to determine the association between five different domains of access—availability, accessibility, accommodation, affordability, and acceptability—and receipt of definitive treatment with radical prostatectomy or radiation, satisfaction with care, and doctor-patient communication. Results: There were 1907 non-Hispanic white and 394 black men in our cohort, the majority (71%) with stage 1 disease. Overall, 85% of men received definitive treatment with no differences by race. None of the access domains were significantly associated with definitive treatment overall or with radical prostatectomy in adjusted models. Black men were less likely to report good doctor-patient communication (60% vs 71%, p &lt; 0.001) and high satisfaction with their care (69% vs 81%, p &lt; 0.001). Communication ratings remained significantly lower among black men compared to white men in adjusted models (odds ratio = 1.49, 95% Confidence Interval 1.03, 2.16). Each domain of access was significantly associated with lower satisfaction with care and worse communication; however, differences in access did not mediate racial disparities for these measures. Conclusions: This study presents the first comprehensive assessment of access to prostate cancer care, showing that while access was related to overall satisfaction and better doctor-patient communication, it did not appear to explain racial differences in these measures of cancer care.
Cell surface GRP78 expression on T and NK cell sub-populations of breast cancer patients.
Authors: Rinat Yerushalmi, Ido Lubin, Julia Lipovettzky, Britta Hardy, Annat Raiter
Journal: Journal of Clinical Oncology (2017)

11561 Background: The targeting of unfolded protein response (UPR) in tumor cells has received much attention. However, data are sparse on the impact of UPR on T and NK cells. The master regulator of UPR is the glucose-regulated protein 78 (GRP78) that is expressed in some tumor cells or normal stressed cells. There are few studies concerning GRP78 expression on T and NK cells in cancer and its relationship to stress induction by chemotherapy. We aimed to reveal the effect of UPR activation on the peripheral T and NK cells of breast cancer patients by the evaluation of cell surface GRP78 expression on T and NK cells before and after neoadjuvant chemotherapy. Methods: Forty-seven patients with triple negative, ER positive/Her2 negative and Her2 positive breast cancer were included. FACS analysis of their blood specimens before and after neoadjuvant treatment was performed. For multicolor FACS analysis, anti-CD3, CD4, CD8, CD56, CD16, NKG2D, CD45RA, CD45RO, CCR7 CD62L and anti-GRP78 antibody (AF488) were added to one of the tubes. A second tube was incubated with IgG-AF488 as isotype control. Analysis of the different T and NK subpopulations that expressed cell surface GRP78 were analyzed with the Gallios Flow cytometer and Kaluza Flow Analysis Software (Beckman Coulter, Inc.). Results: The percentage of cell surface GRP78 baseline expression in CD3 (1.8±0.9), CD8 (2.9±1.5), NKG2D (4.8±2) and CD45RO/CD62L/CCR7 active T memory cells (2.1±0.5) in Her2 positive patients were significantly higher than in triple negative and ER positive/Her2 negative patients. GRP78 expression on CD56, CD16 and NKG2D cells measured after neoadjuvant treatment was significantly higher in patients with complete response (CR) compared to patients without CR. 89% of the CR patients presented with Her2+ subtype. The non-CR patients include triple negative and Her2 negative subtypes. Conclusions: GRP78 was found to be expressed in the different T and NK sub-populations. The level of expression changed with each breast cancer subtype and response to chemotherapy. These novel findings suggest that GRP78 may be used as a new predictive biomarker. It sets the stage for understanding the mechanism of UPR activation on the immune system in breast cancer.
P05.88 Radiomics analysis of brain metastases from non-small cell lung cancer brings relevant supplementary information to clinical scores
Authors: A Alentorn, C Philippe, A Grigis, M Ibañez-Julia, N Younan, A Duran-Peña, L Royer-Perron, J Goya-Outi, I Buvat, F Frouin, J Jacob, R Conforti, K Hoang-Xuan, V Frouin
Journal: Neuro-Oncology (2018)

Lung cancer, and more precisely, non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality due to its high prevalence. Likewise, brain metastases from lung cancer are the most frequent type of secondary brain tumors. Different prognostic scores have been proposed to better stratify the treatment of brain metastases. More recently, lung GPA has been updated considering two frequent molecular characteristics in lung adenocarcinoma: EGFR and ALK alterations. However, to the best of our knowledge, the crosstalk between imaging features and the currently used prognostic scores is unknown.We sought to analyze the clinical value of radiomics data in the prediction of survival in patients with brain mets from NSCLC. We have selected 29 patients with brain metastases of NSCLC treated during 2015–2016 at Pitié-Salpêtrière Hospital. We selected patients with neither previous history of brain mets nor brain surgery and high-quality structural MRI.We extracted 1428 radiomic features per patient, including: first-order statistics, volume, shape, texture and wavelet analysis using pyradiomics on Gadolinium enhanced T1 and FLAIR RM images. Using the plsRcox package, several Cox models were constructed with either clinical (GPA score, EGFR mutation and ALK fusion status) or radiomics features or both. The goodness of fit was assessed with the Harrell’s concordance index using 5 fold cross-validation. The performance of the radiomics model (mean Harrell’s C-index 0.88, SD 0.08) to predict OS was the best compared to the prediction using clinical data (mean Harrell’s C-index 0.77, SD 0.25). Surprisingly, the addition of clinical data to the radiomics model decreased the performance of OS prediction (mean Harrell’s C-index 0.83, SD 0.17). Radiomics analysis of brain mets from NSCLC may provide additional clinically relevant data on the survival, in a non-invasive way. The results of this small cohort are currently being validated in a larger dataset of patients.