tbuckley/cabot-search huggingface dataset:
Assessment of PD-L1 expression and oncogenic gene status in patients with small-cell lung cancer: Immuno-oncology biomarker study in LC-SCRUM-Japan.
Authors: Satoshi Oizumi, Kiyotaka Yoh, Shingo Matsumoto, Shingo Miyamoto, Naoki Furuya, Shinji Sasada, Norio Okamoto, Yuichiro Hayashi, Koji Tsuta, Noriko Motoi, Genichiro Ishii, Koichi Goto
Journal: Journal of Clinical Oncology (2019)

8558 Background: The clinical impact of PD-L1 expression and oncogenic gene status in patients with small cell lung cancer (SCLC) is not well characterized. We initiated this immuno-oncology biomarker study as part of nationwide genomic screening by LC-SCRUM-Japan (LC-SCRUM-IBIS). Methods: Tumor samples from lung cancer patients enrolled in LC-SCRUM-IBIS were primarily subjected to targeted next-generation sequencing (NGS) with Oncomine™ Comprehensive Assay. The PD-L1 expression was also analyzed by 4 immunohistochemistry (IHC) assays for 22C3, 28-8, SP263 and SP142. At this analysis, 22C3, 28-8, and SP263 were assessed in tumor cells (TC) as positive in &gt; 1%, and SP142 in both TC and tumor-infiltrating immune cells (IC) as positive in &gt; TC1/IC1, as previously reported. The association of PD-L1 expression, oncogenic gene status and clinical outcome was investigated in SCLC patients. Results: Between Feb 2017 and May 2018, 1017 lung cancer patients were enrolled in LC-SCRUM-IBIS. Among them, 933 patients had adequate tumor samples including 101 SCLC and 832 non-small cell lung cancer. Of 101 SCLC patients, the results of PD-L1 expression by 4 IHC assays were 18% in 22C3, 17% in 28-8, 11% in SP263 and 8% in SP142, respectively. Targeted NGS showed that 8 patients had at least one targetable oncogenic alterations, including 3 PIK3CA and 1 KRAS as mutations and 3 PTEN and 1 TSC2 as inactivating mutations. PD-L1 expression by 22C3 was associated with good performance status (P = 0.05) and the presence of oncogenic alterations (P = 0.004). PD-L1 status was not associated with response to cytotoxic chemotherapy and progression-free survival and overall survival in first-line treatment of SCLC patients. Conclusions: The frequency of PD-L1 expression in SCLC patients was relatively lower compared with that reported in other solid tumors. PD-L1 status by TC in 22C3 appears to be not correlated with clinical outcomes for cytotoxic chemotherapy of SCLC patients. Further investigation is needed to explore a predictive biomarker for immune checkpoint inhibitors. Updated results will be presented at the meeting.
Case 23-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Arlan F. Fuller, W. Dwayne Lawrence
Journal: New England Journal of Medicine (1985)

Presentation of CaseA 68-year-old woman was admitted to the hospital because of an abdominal mass.She was well until two months earlier, when she began to notice increasing pedal edema. One month before entry she was admitted to another hospital, where examination revealed edema of both legs and a large abdominal mass. Radiographic examinations, including excretory urograms (Fig. 1) and a computed tomographic study of the abdomen (Fig. 2), showed a large, multilocular mass that arose from the pelvis and contained calcifications. Eight days before admission a laparotomy revealed that a large, hard mass containing multiple cysts obliterated the . . .
The role of EGFR inhibitors as adjuvant therapy for EGFR mutation positive non-small cell lung cancer.
Authors: Peng Xie, Wenjie Tang, Xiaolin Li, Xindong Sun, Jinming Yu
Journal: Journal of Clinical Oncology (2019)

8508 Background: Cisplatin-based chemotherapy as adjuvant therapy for resected NSCLC has reached its plateau, and was limited by high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as adjuvant therapy for targeted patients. Methods: Studies were identified via an electronic search on Pubmed, EMBASE, ISI Web of Science, ScienceDirect, SpringerLink, The Cochrane library and so on. Pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis. Registration number: PROSPERO (CRD42018093144). Results: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. Results showed that adjuvant treatment with EGFR-TKIs can prolong both OS and DFS when compared to treatment without TKIs as adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I 2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P &lt; 0.00001; heterogeneity I 2 = 37%, P = 0.1). Results of predefined subgroup analyses in this meta-analysis suggested a greater DFS with EGFR-TKI mono compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.3). And we also find that treatment with EGFR-TKI plus chemotherapy was associated with significantly longer DFS as well as OS than chemotherapy mono in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95%CI, 0.34-0.68; P &lt; 0.00001; heterogeneity I 2 = 15%, P = 0.29; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I 2 = 57%, P = 0.05). And less grade 3 or higher AEs were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P &lt; 0.00001; heterogeneity I 2 = 22%, P = 0.28). Conclusions: Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completed resected patients with EGFR mutation-positive NSCLC. This project was supported by the National Natural Science Foundation of China (Grant No. 81502667), Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167).
Autonomy and dyspnea in palliative care: A case report
Authors: M. Martins, E. Campôa, M. Ferreira, P. Reis-Pina
Journal: Pulmonology (2019)

Abstract   The treatment of the symptom, dyspnea, involves pharmacological and non-pharmacological measures. Palliative care specialists use fewer common strategies for symptomatic control of dyspnea. Medical practice should always respect the autonomy of the patient and the proposed therapeutic plan should be compatible with his/her preferences.  The present case report illustrates the above-mentioned aspects in a patient with asthma-COPD overlap syndrome admitted to a Palliative Care Unit.
Tumor subtype and other prognostic factors in breast cancer patients with brain metastases: The updated graded prognostic assessment (Breast-GPA).
Authors: Paul W. Sperduto, Shane Mesko, Daniel Cagney, Eric Nesbit, Jason Chan, Jessica Lee, Will Breen, Diana Shi, Hany Soliman, Ryan Shanley, Ashlyn S. Everett, Laura Masucci, Jill Remick, Kristin Plichta, Supriya K. Jain, Cheng-Chia Wu, John Bryant, James B. Yu, Toshimichi Nakano, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2019)

1079 Background: Brain metastases (BM) are a common and fatal complication of breast cancer but survival varies widely based on various prognostic factors (PF). Hence, patient counseling and therapeutic decisions should be individualized. We previously published a prognostic index (Breast GPA) based on cohort A (1985-2007, n = 642), updated it with tumor subtype in cohort B (1993-2010, n = 400) and are now updating it with a larger contemporary cohort (C). Methods: A multi-institutional (19) multi-national (3) retrospective database of 2473 breast cancer patients with BM diagnosed from 1/1/2006-12/31/2017 was created and compared to our prior cohorts. Demographic, clinical, molecular factors, tumor subtype and treatment were correlated with survival. Kaplan-Meier survival estimates were calculated and compared with log-rank tests. Results: The median survival (MS) for cohorts A, B and C improved over time [12, 14 and 16 mo, respectively ( &lt; 0.01)] despite the subtype distribution becoming less favorable: Luminal B (ER/PR/HER2+) decreased from 26% to 21%; HER2 (HER2+/ER/PR-) decreased from 31% to 17%, Luminal A (ER/PR+/HER2-) increased from 20% to 31%; Basal (ER/PR/HER2-) was unchanged at 24%.MS by subtype improved from 21 to 27 mo in Luminal B, 18 to 25 mo in HER2, 10 to 14 mo in Luminal A and 6 to 9 mo in Basal tumors. The number of BM was 1 in 35%, ≤4 in 67% and &gt; 10 in 18%. PF significant for survival were tumor subtype, age, KPS, number of BM and extracranial metastases (ECM) (all &lt; 0.01). Surprisingly, Hispanic women (7%) showed improved survival (p &lt; 0.01). BRCA1 was mutated in 57/533 (11%) and those patients showed a trend (0.16) toward improved survival. Treatment patterns have changed: the use of whole brain radiation therapy decreased from 71% to 67% to 47% in cohorts A, B and C, respectively. Conclusions: Despite the shift to less favorable tumor subtypes, MS has improvedbut varies widely by diagnosis-specific PF. Compared to prior cohorts, number of BM and ECM were identified as new PF. Ethnic, genetic and treatment differences between the eras are apparent. The updated Breast GPA, based on these data, and the correlation between BRCA1 and tumor subtype will be presented.
Abstract 392: Increased Oxidative Stress and Apoptosis as Mechanisms for Adverse Effects of Chronic Pressure Overload and Catecholamine Stress in Mice with Cardiac Overexpression of Type 5 Adenylyl Cyclase
Authors: Lo Lai, Lin Yan, Che-Lin Hu, Shumin Gao, Chull Hong, Stephen F Vatner
Journal: Circulation (2008)

Studies with cardiac overexpression of type 6 adenylyl cyclase (AC6) suggest it protects against cardiac stress. Less is known about cardiac overexpression of AC5. We generated transgenic (Tg) mice with cardiac specific overexpression of AC5 and examined both the effects of pressure overload induced by 1 wk of transverse aortic banding (TAC) and 1 wk of chronic isoproterenol (ISO) delivered by osmotic mini-pump (n=8/group). TAC induced greater, p&lt;0.05, left ventricular (LV) hypertrophy, as assessed by LV/body weight, in AC5 Tg (4.9±0.2) compared with wild type (WT) (4.0±0.1) and exhibited a significant decrease, p&lt;0.05, in LV ejection fraction (LVEF) (58±4%) where LVEF was maintained in WT (75±1%). TUNEL analysis shows that apoptosis in AC5 Tg was twice that in WT, p&lt;0.05. This was confirmed by a 2-fold increase in activity of caspase 3 in AC5 Tg compared to WT mice, p&lt;0.05. The AC5 Tg began to develop heart failure as reflected by increased, p&lt;0.05, lung/body weight (10.2±1.6) vs WT (6.4±0.2). In the heart, the antioxidant manganese superoxide dismutase (MnSOD), quantified by western blotting, was decreased by 40% in AC5 Tg compared to WT mice, p&lt;0.05, after 1 wk of aortic banding. Chronic ISO also induced a greater, p&lt;0.05, decrease in LVEF (48±4%) compared to WT (60±2%). 100 microM of ISO stimulation increased cell viability by 36% and decreased apoptosis by 34% (p&lt;0.05 vs LacZ control). MnSOD was upregulated by 2.9-fold in AC5 knockdown myocytes after treatment with ISO for 48 hrs. These results demonstrate that cardiac overexpression of AC5 exerts adverse effects on oxidative stress and apoptosis in response to both chronic pressure overload and catecholamine stress.
Analysis of Chinese acral and mucosal melanoma patient genomic and neoantigen profiles in cancer vaccine development: A pilot study.
Authors: Xianling Guo, Song Gao, Li Yang, Juemin Fang, Guochao Wei, Xiaochun Ma, Zhikun Zhao, S Dilhan Weeraratne, Jane Snowdon, Sheng Wang, Xu Qing
Journal: Journal of Clinical Oncology (2019)

e14300 Background: Acral and mucosal melanoma are rare subtypes accounting for about 3% of all melanoma cases. The cutaneous melanoma genomic landscape is well defined; however, little is known about the acral and mucosal melanoma mutational spectrum. In this pilot study, we evaluated the genomic and neo-antigen profiles and tumor mutational burden (TMB) from acral and mucosal melanoma patients with the aim of designing personalized vaccines and longitudinally tracking patients’ clinical courses. Methods: Tumor whole exome sequencing and neo-antigen profiling of 5 acral and 3 mucosal melanoma patients at Shanghai Tenth Peoples Hospital, Tongji University, China between April 2018 and January 2019 was performed using YuceBio’s proprietary analytics platform. Watsonä for Genomics, an artificial intelligence decision-support system, was used for variant interpretation and annotation. A comparative analysis was performed on Chinese acral melanoma data with the published Caucasian acral cohort from the Translational Genomics Research Institute (TGen) and The Cancer Genome Atlas (TCGA) predominantly Caucasian cutaneous melanoma data set. Results: TMB in our acral/mucosal melanoma cohort was 2.26/Megabase (Mb) compared to over 20/Mb in published cutaneous melanoma studies. Tumor neo-antigen burden (TNAB) in our group was 1.03 neo-epitopes/Mb. Low TNAB levels were associated with low TMB levels in all tumors. Incidence of BRAF and NRAS mutant cases in our cohort was 0% (0/8) and 13% (1/8) respectively compared to 19% (5/27) and 7% (2/27) of the Caucasian acral population in the TGen dataset. Incidence of BRAF and NRAS mutations in the TCGA cutaneous melanoma dataset was 54% (237/440) and 28% (125/440), respectively. Conclusions: TMB was significantly lower in acral/mucosal than in cutaneous melanoma and may be a surrogate for TNAB. Detection of BRAF and NRAS mutations, the two most prevalent driver mutations in cutaneous melanoma, were significantly lower frequencies in both Chinese and Caucasian acral melanoma patients in this study, suggesting alternate cancer drivers may exist in this subtype. Strategies to address challenges of low TNAB in vaccine development are being explored.
Impact of mastectomy in women with stage IV HER2+ breast cancer.
Authors: Arslan Babar, Fahrettin Covut, Tariq Zuheir Kewan, Shafia Rahman, Stephen R. Grobmyer, Alberto J. Montero
Journal: Journal of Clinical Oncology (2019)

e12515 Background: Women with stage IV HER2+ breast cancer typically have longer overall survival (OS) compared to other breast cancer subsets due to the effectiveness of dual anti HER-2 antibody therapy. The role of mastectomy remains controversial. Methods: We reviewed patients who were diagnosed with stage IV HER2+ breast cancer between 2/2015 and 12/2017 at Cleveland Clinic. Overall survival (OS) was estimated by the Kaplan-Meier method, and compared by the log-rank test. Univariable and multivariable analysis were performed using Cox regression to identify predictors of OS. Results: We identified 47 patients, with a median age of 58 (range: 22 – 87). Twenty-eight (60%) and 14 (30%) patients had ER+ and PR+ disease, respectively. Four patients had brain metastasis at time of stage IV diagnosis. All patients received systemic therapy. 17 (36%) patients underwent mastectomy after diagnosis of stage IV breast cancer,. Of the 30 (64%) patients who did not undergo mastectomy, 24 (80%), 2 (7%), and 4 (13%) were treated with both chemotherapy and HER2-directed therapy, chemotherapy alone, and HER2-directed therapy alone, respectively. Breast radiotherapy was performed on 9 (53%) and 8 (27%) patients in mastectomy and no mastectomy cohorts, respectively. Median follow-up time was 22 months . The two-year OS for mastectomy and no mastectomy cohorts were 94% (95% CI: 83 – 100) and 50% (95% CI: 33 – 76), respectively (p=0.009). On univariable analysis, only mastectomy vs no mastectomy (HR: 0.18, 95% CI: 0.04 – 0.80, p=0.025) predicted OS. On multivariable analysis, mastectomy vs no mastectomy has remained to be statistically significant predictor of OS (HR: 0.08, 95% CI: 0.01 – 0.66, p=0.019), whereas age, chemotherapy, HER2-directed therapy, and breast radiation were not independent predictors of improved OS (p&gt;0.05). Conclusions: In our cohort, mastectomy was an independent predictor of longer OS in women with stage IV HER2+ breast cancer.
The whole genome landscape of adult metastatic sarcoma.
Authors: Eric Yang Zhao, Xiaolan Feng, Erin D. Pleasance, Tony L. Ng, Jasleen Grewal, Nissreen Mohammad, Sara Kristina Taylor, Christine E. Simmons, Amirrtha Srikanthan, Shahrad Rod Rassekh, Rebecca Deyell, Yaoqing Shen, Emma Titmuss, Howard John Lim, Daniel John Renouf, Karen A. Gelmon, Stephen Yip, Steven J. M. Jones, Marco A. Marra, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2019)

3137 Background: Metastatic sarcomas represent a heterogeneous, difficult to treat family of cancers with poor median overall survival of 18 months. While global sequencing initiatives have catalogued genomic variation among primary sarcomas, metastatic sarcoma is less well understood. Genome-guided targeted therapy has made promising advances but is difficult to study in sarcomas due to heterogeneity and low prevalence. Whole genome and transcriptome analysis (WGTA) can help elucidate sarcoma oncogenesis, metastasis, and potential therapeutic targets. Methods: Using whole genome (80X) and transcriptome (200M read) sequencing of 43 metastatic sarcomas across 19 subtypes, we analyzed structural variants (SV), copy-number variants (CNV), mutation signatures, gene expression, and the immune microenvironment. All prior treatments were retrieved through chart review. Results: 17 patients (40%) attempted WGTA-informed therapy, of which 8 (47%) were classified as responders. Metastatic sarcomas demonstrated recurrent CNVs, with 17p11-p12 amplification in 42% of cases. Some recurrent expression outliers were associated with potential targets (e.g. MYOCD, PMP22, COPS3) while others (e.g. ADORA2B) have not been previously observed in sarcoma. Discovery of oncogenic fusions refined diagnoses in two cases with atypical histology. Clustering by mutation signatures distinguished histological subtypes, and two signatures were novel in sarcoma: (1) a strong base excision repair signature associated with NTHL1 loss and (2) a cisplatin-associated signature exclusive to platinum-treated cases. Frequent homologous recombination deficiency was observed and was associated with response to ifosfamide in three leiomyosarcomas. Of four immunotherapy-treated cases, the only responder demonstrated outlier CIBERSORT immune infiltration score, which did not correlate with PD-L1 expression. Conclusions: This is the first in-depth WGTA of metastatic sarcoma. We found recurrent and potentially targetable CNVs, expression outliers, mutation signatures, and immune markers. Our results suggest that clinical translation is promising using actionable insights obtained through WGTA.
Low nationwide utilization of adjuvant chemotherapy (AC) in elderly patients with localized non-small cell lung cancer (NSCLC).
Authors: Kaushal Parikh, Urshila Durani, Jonathan Inselman, Shealeigh Funni, Gaurav Goyal, Ronald S. Go, Konstantinos Leventakos, Aaron Scott Mansfield
Journal: Journal of Clinical Oncology (2019)

6581 Background: While AC is recommended for all patients with stage IIA, IIB, and IIIA NSCLC, its use and benefit among the elderly population is unclear. Methods: We identified patients with stage IIA, IIB, or IIIA NSCLC using the National Cancer Database from 2006-2014. Patients were divided into age groups ≤65, 66-70, 71-75, 76-80, &gt; 80 years. Trends in AC use, factors influencing AC administration, and outcomes associated with AC were studied. Results: Out of 27368 patients, 13464 received AC and 13904 did not. 11% had stage IIA disease, 50% had stage IIB disease and 39% had stage IIIA disease. AC use was lower with increasing age (49% age ≤65 vs. 3% age &gt; 80 (P &lt; 0.0001)). Temporal use of chemotherapy for each age group was unchanged from 2006-2014. In multivariate logistic regression analysis, factors predictive of lower AC use were older age, Medicare or Medicaid insurance, academic center, and higher Charlson Comorbidity Index (CCI). Stage IIIA (OR 1.4, 95% CI 1.3-1.6) and Stage IIB (OR 1.3, 95% CI 1.2-1.4) had a higher chance of receiving AC than stage IIA. In a Cox proportional hazard model, younger age, female sex, academic center, private insurance, higher income, lower CCI, West coast center and AC were associated with better outcomes. When stratified by age and stage, AC was still associated with better survival (Table). Conclusions: AC utilization in stages IIA, IIB and IIIA NSCLC remains low, despite its association with improved survival in the elderly. Future clinical trials may be needed focused on elderly patients to establish the best regimen to optimize outcomes. [Table: see text]
Prognostic Value of Tumor Deposits for Disease-Free Survival in Patients With Stage III Colon Cancer: A Post Hoc Analysis of the IDEA France Phase III Trial (PRODIGE-GERCOR)
Authors: Jean-François Delattre, Romain Cohen, Julie Henriques, Antoine Falcoz, Jean-François Emile, Serge Fratte, Benoist Chibaudel, Jérôme Dauba, Olivier Dupuis, Yves Bécouarn, Frédéric Bibeau, Julien Taieb, Christophe Louvet, Dewi Vernerey, Thierry André, Magali Svrcek
Journal: Journal of Clinical Oncology (2020)

A post hoc analysis of all pathologic reports from patients with stage III CC included in the IDEA France phase III study (ClinicalTrials.gov identifier: NCT00958737) investigating the duration of adjuvant fluorouracil, leucovorin, and oxaliplatin or capecitabine and oxaliplatin therapy (3 v 6 months) was performed. The primary objective was to determine the prognostic impact of TD on disease-free survival (DFS). The effect of the addition of TD to LNM count on pN restaging was also evaluated. A multivariable analysis was performed to establish the association between TD and DFS.Of 1,942 patients, 184 (9.5%) had TDs. The pN1a/b and pN1c populations showed similar DFS. TD-positive patients had worse prognosis compared with TD-negative patients, with 3-year DFS rates of 65.6% (95% CI, 58.0% to 72.1%) and 74.7% (95% CI, 72.6% to 76.7%; P = .0079), respectively. On multivariable analysis, TDs were associated with a higher risk of recurrence or death (hazard ratio [HR], 1.36; P = .0201). Other adverse factors included pT4 and/or pN2 disease (HR, 2.21; P < .001), the 3 months of adjuvant treatment (HR, 1.29; P = .0029), tumor obstruction (HR, 1.28; P = .0233), and male sex (HR, 1.24; P = .0151). Patients restaged as having pN2 disease (n = 35, 2.3%) had similar DFS as patients initially classified as pN2.The presence of TDs is an independent prognostic factor for DFS in patients with stage III CC. The addition of TD to LNM may help to better define the duration of adjuvant therapy.