tbuckley/cabot-search huggingface dataset:
A signal-seeking trial of olaparib and durvalumab in homologous repair-deficient tumors: A sub-study of the cancer molecular screening and therapeutics (MoST) program.
Authors: Anthony M. Joshua, Amy Prawira, Subotheni Thavaneswaran, Rasha Cosman, Chee Khoon Lee, Katrin Marie Sjoquist, John Simes, David Morgan Thomas, David Espinoza, Lucille Sebastian, Mandy L. Ballinger, Wendy Hague, Sarah Chinchen, Emily Collignon, Maya Kansara, Talia Palacios, John Grady, Hayley Barker, Keith Thornton
Journal: Journal of Clinical Oncology (2020)

3073 Background: Data on the utility of a PARP inhibitor in combination with a checkpoint inhibitor remain limited, particularly in the histology agnostic setting with homologous recombination deficiency (HRD). This study evaluated the clinical activity of the combination of olaparib and durvalumab with the primary study endpoint of progression-free survival (PFS) at 6 months (PFS6m). Methods: This was a phase II, single-arm, signal-seeking study of the MoST program. Patients were recruited into two cohorts based on HRD genes, agnostic to histology: (1) BRCA 1/2 deficient tumours, excluding breast, prostate, ovarian cancers, and (2) other HRD related genes. Molecular testing was performed using in-house and commercial panels on archival tumour tissue centrally adjudicated by a molecular tumour board. All patients were treated with olaparib 300mg bid for 1 month, followed by combination with durvalumab 1500mg q4 weekly for 13 cycles. Olaparib treatment was then continued until disease progression. Results: Between Nov 2017-Feb 2019, 48 patients were enrolled (16 to BRCA 1/2 cohort 1 and 32 to HRD related genes cohort 2). Most common tumour sites were bone/soft tissue (15%, N=7), pancreas (13%, N=6) and stomach (8%, N=4). Overall best response in cohort 1 was PR (25%, N=4) and SD 4 (25%, N=4), and cohort 2 was PR (6%, N=2) and SD (56%, N=18). Median PFS was 3.65m (Cohort 1) and 3.56m (Cohort 2) respectively. PFS6m was 35% (Cohort 1) and 38% (Cohort 2) respectively. PDL1 status was not predictive of olaparib and durvalumab benefit. The most common grade 3/4 adverse events were anemia (11%%, N=4), abdominal pain (9%, N=3), increased lipase (9%,N=3), increased amylase (9%, N=3), dyspnea (6%, N=2), Hyperglycemia dyspnea (6%, N=2), Pancreatitis dyspnea (6%, N=2) and hematuria (6%, N=2). Conclusions: Olaparib and durvalumab show promising activity in a histology agnostic setting, particularly in BRCA deficient tumours. Further research is needed to identify biomarkers that correlate with treatment benefit. Results from longer clinical follow-up and additional biomarker analyses will be presented. Clinical trial information: ACTRN12617001000392 .
Deciphering molecular characters of multiple lung lesion using comprehensive genomic profiling and its association of histology.
Authors: Changbin Zhu, Yuan Qiu, Qiuhua Deng, Haihong Yang, Hanzhang Chen, Liping Liu, Dakai Xiao, Di Shao, Weiwei Li, Wenxi Jiang, Yongping Lin, Jianxing He
Journal: Journal of Clinical Oncology (2020)

e21051 Background: Differentiating multiple pulmonary lesions as multiple primary lung cancer (MLC) or intra-pulmonary metastasis (IPM) is critical for clinics. Radiological or histological (dis)concordance may be informative, while, genetic information may aid tracing lineage information on multiple lung lesions. This study aims to apply comprehensive genomic profiling deciphering intrinsic genetics of multiple lung lesions. Methods: 32 patients, 69 FFPE samples were applied to perform high-through put sequencing. 636 cancer-related genes were captured and sequenced by MGI-seq 2000. Raw data was processed via in-house developed pipeline. Unsupervised clustering was applied to cluster samples based on genetic characters after variant calling and annotation. Patients were categorized into “Genomic related” and “Genomic unrelated” groups. Another cohort consisting of 402 patients with mono-lesion was used as control cohort. Results: No difference of age of onset was found between 32 patients and 403 patients with mono lesion (60.5 versus 60 years). Male had relatively lower incidence of multiple lung lesions (RR:0.46,95%CI: 0.20-0.93, P = 0.04). Eight patients were classified as “Genomic related” by presenting same mutation in driver or tumor suppressor genes. Six of eight patients were characterized to carry EGFR L858R, in addition, two patients presented co-mutation of RB1(c.1814+1G &gt; T, p.E48Kfs*18) and TP53 mutations (p.H193R, p.R249S). Another two patients carried EGFR 19 Deletion. Two lesions from one patient with predefined diagnosis of intra-pulmonary metastasis showed biallelic loss of function mutations in same loci of NF1 gene (p.S2311*/ p.Q1360*) together with same KRAS mutation (p.G13C). Radiologically, no same lobe as well as left-right preference were revealed between “Genomic related” and “Genomic unrelated” groups. Histologically, there was no enrichment of patients with same histology subtype in “genomic related” group, verse visa. While, patients in “genomic related” group had higher ages at initial diagnosis (median age 69.5 vs 56.5 years, P = 0.04). Conclusions: Comprehensive genomic profiling should be applied to clinics distinguishing the nature of multiple lung lesion irrespective of radiological and histological diagnosis. [Table: see text]
The efficacy of anti-PD-1 combined with temozolomide in unresectable, advanced melanoma from one center.
Authors: Tu Hu, Wei Sun, Yu Xu, Zhi-Guo Luo, Yong Chen
Journal: Journal of Clinical Oncology (2020)

e22007 Background: Anti-PD1/PDL-1 immunotherapy has led to a new era of the unresectable, advanced melanoma treatment. However, there are still a significant part of patients suffer from primary or secondary drug resistance to immunotherapy. We sought to explore the efficacy and safety of anti-PD-1 plus Temozolomide in unresectable, advanced melanoma patients. Methods: Patients with unresectable, advanced melanoma were treated with anti-PD-1 plus Temozolomide, Temozolomide/DTIC based chemotherapy, or anti-PD-1 alone between 1 May, 2018 and 31 January, 2020. Data were retrospectively reviewed and statistically analyzed for best ORR and progression free survival, as well as toxicities. Results: Seventy-seven individuals were identified, including 37 (48.1%) with acral melanoma, 20 (26.0%) with cutaneous melanoma, 16 (20.8%) with mucosal melanoma and 4 (5.2%) with melanoma of unknown primary. Thirty-three (46.8%) patients had received postoperative adjuvant treatment before progression, and none of them had received anti-PD-1 treatment. The objective response rate of anti-PD-1 plus Temozolomide (n = 5, 41.7%) was higher than Temozolomide/DTIC (n = 1, 5%) or anti-PD-1 alone (n = 6, 20.7%) in the front-line therapy and second-line therapy (42.9%, 0%, 23.5%, respectively). Similar results were found in the third-line therapy. Although no significant difference was detected among these groups in the front-line therapy, the progression free survival of anti-PD-1 plus Temozolomide (median, 7 months) was higher than Temozolomide/DTIC (median, 2.5 months) (p = 0.009), while showing no significant difference with anti-PD-1 (median, 4.5 months) (p = 0.267) in the second-line therapy. The incidence of grade 3/4 toxicity was 8% (anti-PD-1 plus Temozolomide), 20.7% ( Temozolomide/DTIC) and 23.8% (anti-PD-1) respectively, mainly immunogenic pneumonia (0%, 0%, 10.3%) and hepatotoxicity (0%, 4.8%, 6.9%), and no significant difference was found among these groups. Conclusions: The efficacy of combination of anti-PD-1 and Temozolomide is better than Temozolomide/DTIC or anti-PD-1 alone in advanced melanoma and does not increase the toxicity. Therefore, Anti-PD-1 combined with Temozolomide may be used as front-line regimen in advanced melanoma.
食管上段异位胃黏膜15例分析及文献复习
Authors: 王永平, 丁夷峰, 蔡建庭, 陈向华, 叶挺
Journal: BMJ (2007)

食管上段异位胃黏膜(heterotopic gastric mucosa in the upper esophgus,HGMUE)是指胃黏膜出现在食管上段,表现为上段食管黏膜上的褐红色黏膜斑.临床并不少见,但在胃镜检查时易被遗漏或误诊为其他疾病.现将近2年来我们胃镜检查时发现的15例患者资料进行分析,并做相关的文献复习。
肾小球肾炎
Authors: 吴东, 蔡建芳, 陈嘉林
Journal: BMJ (2011)

一、血尿有没有,镜检很重要很多患者误认为只要尿色加深就是血尿，而血尿就是肾炎的代名词，这需要全科医师进行必要的评估和宣教。事实上尿液颜色受很多因素影响，如含色素的食物（例如樱桃、番茄）和某些药物（利福平、大黄）都可造成尿色加深，甚至状如血尿。因此，不能仅凭肉眼观察，须进行准确的尿液检验，方能明确有无血尿。首先要正确留取标本，尿常规以晨起第一次中段尿为佳，而尿沉渣镜检则以第二次尿更好。清晨留尿是为了避免白天各种因素（活动、进食等）对尿液的影响，中段尿是为了减少泌尿生殖道分泌物的干扰。
Profiling and prognostic implications of variants of unknown significance (VUS) in solid tumors.
Authors: Meena Sadaps, Bassam N. Estfan, Wei Wei, Davendra Sohal, Megan Lynn Kruse
Journal: Journal of Clinical Oncology (2020)

e19012 Background: While precision oncology is becoming increasingly integrated into standard of care for most incurable solid tumor malignancies, there is paucity of data regarding the clinical significance of VUS. In this study, we aim to evaluate whether the number of VUS is associated with overall survival (OS). We also analyze racial disparities pertaining to the number of VUS present and identify which, if any, genes possess prognostic implications. Methods: This is a retrospective review of 389 consecutive patients seen at Cleveland Clinic from 2014 to 2016 with incurable solid tumor malignancies, for whom next-generation sequencing (NGS) was ordered using Foundation One™ (Cambridge, MA). Demographics, number of VUS, genes involved, and race were summarized. OS was estimated by Kaplan-Meier and compared by log rank test. Results: Median age was 60 years, 202 (52%) patients were female, 338 (86.7%) were Caucasian, and 31 (8.0%) were African American. On NGS, 376 (97%) patients had VUS reported. The median number of VUS was 9 (range 1-116). When dichotomized at the median, the number of VUS did not affect OS. Genes most commonly implicated in reported VUS were LRP1B (88, 22.6%), MLL3 (83, 21.3%), MLL2 (73, 18.8%), ARID1B (70, 18.0%), PRKDC (60, 15.4%), PREX2 (58, 18.7%), and SPTA1 (56, 14.4%). Patients found to have a variant of unknown significance in MLL2 had worse median OS as compared to those who did not (2.61 vs 3.76 years respectively; p = 0.033). When profiled by race, Caucasians had lower numbers of VUS (p = 0.002; Table). Conclusions: We did not find a clear association between the number of VUS and OS. MLL2, a gene known to predict poor prognosis as a pathogenic variant, was seen in our study to have similarly poor prognostic implications as a variant of unknown significance. Racial disparities in genomics exist as African Americans are under-represented and have greater numbers of VUS as compared to Caucasians. Further research is warranted to elucidate these disparities. [Table: see text]
Multipeptide vaccine to prevent epithelial ovarian cancer relapse by microenvironment immunomodulation.
Authors: Juan Pablo Marquez-Manriquez, Alejandro Camacho-Hernandez, Pedro Alejandro Lucero-Diaz, Dolores Gallardo-Rincon, Martin Orlando Rosas-Delgado, Karla Ramirez Barron, Alberto Durazo, Jorge Alberto Cisneros Ruiz, Diana Karen Meneses-Velazquez, Alberto Durazo-Acuna
Journal: Journal of Clinical Oncology (2020)

e15268 Background: Typically cancer vaccines for relapse prevention in epithelial ovarian cancer (EOC) are administrated in distant anatomical sites away from the primary tumor location. Ideally for EOC relapse prevention vaccines we should explore different anatomical sites related with the original tumor location and nearby lymph nodes, in order to observe if the administration would have better clinical impact due to a potential access to the tumor microenvironment. Moreover most trials for EOC relapse prevention use one or few targets and is mainly unknown if they are relevant to promote EOC relapse. We treated EOC patients with a multi-peptide vaccine administered in lymph nodes (LN) and in the peritoneum area and were able to suppress cancer relapse with not significant adverse effects after eight years. Methods: We enrolled n = 25 EOC patients in our study and identified by systematic review and validated by siRNA six proteins involved in EOC relapse and fourteen peptides were predicted. Twelve peptides were immunogenic by Granzyme B ELISPOT, DTH and ELISA. Patients were immunized with the vaccine in axillary and inguinal LN subcutaneously every week for four weeks, every two-weeks four times and finally every month for a total of thirty-six months. Clinical and laboratory evaluations were performed every 2-months and at the end of the study. Results: 100% of the patients developed both antibodies against all the peptides by ELISA and CD8 specific cells. The peptides of the six proteins were able to induce T cell expansion in both peptides and purified protein (p = 0.0001) and (p = 0.05), respectively for Ape-1. The selected targets were all able to induce DTH and ELISA responses with statistical significance. Peptides predicted from Bcl-2, survivin, Ape-1, Sox2, EGFR and RCAS1/EBAG9 were able to increase and sustain the levels of Granzyme B ELISPOT. Bcl-2 A peptide (p = 0.001), Bcl-2 B (p = 0.005), Bcl-2 C (p.0002), survivin A (p = 0.001), Survivin C (0.05), Ape-1 A (0.0001), Ape-1 D (p = 0.001), Sox2 A (p = 0.003), Sox2 B (p = 0.0001), EGFR B (p = 0.0001) and EGFR D (p = 0.001). Conclusions: Treating EOC patients in remission in zones hardly explored previously in order to potentially improve the activation of antigen-specific Th1 and CD8 cells with specific peptides seems promising as a feasible and safe approach to prevent EOC relapse.
Novel mutations of <i>SYK</i> gene in solid tumors.
Authors: Jian Shi, Baoen Shan, Ningning Luo, Lihua Li, Xing Zhang, Rongfeng Liu, Chao Song, Yujie Shan, Yi Lu
Journal: Journal of Clinical Oncology (2020)

e13519 Background: Spleen tyrosine kinase ( SYK) is a non-receptor tyrosine kinase (NRTK) in cytoplasmic and plays a crucial role in multiple signaling pathways. The deletion of SYK gene expression will lead to the formation and metastasis of multiple solid tumors. Previous studies focus on the methylation of the SYK gene promoter and the protein isomers, including SYK (L) and SYK (S) which are differed by 23 amino acids in functional domains. Nevertheless, the knowledge of mutations in SYK remains poorly understood. Herein, next generation sequencing were performed to explore SYK mutations for further clinical research. Methods: We retrospectively analyzed the somatic mutations from a comprehensive genomic profiling in tumor tissue or blood ctDNA of 4,093 patients with pan-cancer, of which 2,213 patients using 528 genes panel and 1,880 patients using 539 genes panel, both of the panels contained all exon regions of SYK gene. SYK mutations analyzed by TCGA database was used as validation to our results. Results: In 4093 patients with pan-carcinoma, 36 patients were found mutations in SYK gene and the mutation frequency was 0.880%, of which 4 intron mutations and 32 cases of exon mutations were found in patients, respectively. A number of 9 mutations might affect protein function, which were stop-gained mutations and frameshift mutations and their proportion was 0.220%. The mutation frequency of SYK was consistent with TCGA. Among 9 mutations, 3 mutations were also found in TCGA, which were R574*, M34fs, E376*, respectively. And the rest 6 mutations were newly found, which were V395fs, N615fs, Y74*, G185*, Y74fs, Q145*, respectively. Colorectal cancer was the most common cancer type harboring SYK mutations, and TP53 was the most frequently co-mutated gene of SYK which was counted 5 both in our detected results and in TCGA database. Conclusions: Firstly report of 6 novel stop-gained and frame-shift mutations in SYK gene expanded the understanding of SYK in solid tumors. As a retrospective study in pan-cancer with a relatively small population and the mechanism is unclear, the conclusions of this study needed to be verified with a larger sample.
A phase II study of the selective MET kinase inhibitor INC280 in advanced papillary renal cell cancer.
Authors: Paul Denis Leger, Daniel da Motta Girardi, Munjid Al Harthy, Julia C. Friend, Lisa Mac, Erin Purcell, Cathy Vocke, Sandeep Gurram, Maria J. Merino, Peter Choyke, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Journal of Clinical Oncology (2020)

5075 Background: There are currently no approved systemic agents for patients with advanced type 1 papillary renal cell carcinoma (pRCC). Type 1 pRCC can occur in a hereditary form with germline alterations of MET (hereditary papillary RCC: HPRC) or in a sporadic form. Both hereditary and sporadic forms have similar histologic features and somatic MET alterations have been found in 15-20% of patients with sporadic pRCC. Furthermore, gain of chromosome 7, where MET and the gene for its ligand HGF are located, has been reported in a majority of patients with type 1 pRCC and may represent an alternative means of activating the MET pathway. This is a phase II study evaluating the activity of INC280, a highly selective and potent MET inhibitor, in patients with pRCC. Methods: Patients with advanced type 1 pRCC were treated with INC280 at a starting dose of 600mg PO twice daily (capsules). Later in the study course, the capsules were replaced with exposure-equivalent tablets (400mg PO twice daily). Eligible patients had an ECOG PS 0-2, no active brain metastases, and less than 4 prior lines of therapy. The primary endpoint was overall response rate (ORR) assessed by RECIST 1.1. Secondary endpoints included progression-free survival, disease control rate, and tolerability. Exploratory endpoints included the correlation between MET alteration/copy number gain and response to INC280. Results: Twenty subjects were enrolled from January 2014 to October 2019. Median age was 62 years, 60% of patients were classified as IMDC good risk and 40% as IMDC intermediate risk. Three patients (15%) achieved a confirmed partial response and seven (35%) had stable disease, including 4 (20%) who maintained stable disease for over 6 months. The most common treatment-related adverse events (AEs) were of grade 1-2 including nausea (85%), increased creatinine(70%) diarrhea(60%), fatigue(55%), limb edema(40%), increase in amylase(20%), triglycerides(20%), LFTs(20%), lipase(10%) and leukopenia(10%). INC280-related Grade 3-4 AEs included asymptomatic increased lipase (20%), increased LFTs (10%), increased amylase(5%), leukopenia (5%), lymphopenia (5%) and syncope (5%). Conclusions: INC280 demonstrated clinical activity in patients with advanced type 1 pRCC with an acceptable toxicity profile. The correlation between the presence of MET alteration and/or copy number gain and response to INC280 is under evaluation.
SNO 25th anniversary history series: Investing in the membership of the Society for Neuro-Oncology
Authors: Monica Venere, Gelareh Zadeh, Vinay Puduvalli, Chas Haynes
Journal: Neuro-Oncology (2020)

The Society for Neuro-Oncology (SNO) has long recognized that strategic investments back into the field pay significant dividends in terms of growing and broadening the reach of the organization and supporting the academic careers of our members.Over the years, SNO has created a number of committees, each tasked with addressing an unmet need in the field or increasing the participation and presence of an underrepresented group.This installment of the series of articles commemorating the 25 th Anniversary of the Society for Neuro-Oncology will focus on the work of the International Outreach Committee, the Young Investigators Committee, the Wellness Committee, and the recently established Women and Diversity Committee.Overall survival
A risk scoring system to predict overall survival for patients with liver cancer.
Authors: Haibei Xin, Guanxiong Zhang, Wei Zhou, Huan Chen, Dandan Liang, Henghui Zhang, Nan Li
Journal: Journal of Clinical Oncology (2020)

e16635 Background: Surgical resection is a common curative treatment for patients with primary hepatocellular carcinoma (HCC), and conventional strategies of assessing clinical and pathologic risk factors have been adopted to predict clinic outcomes in patients after curative surgery. We hypothesized that an ensemble learning approach which incorporates multidimensional features would enable effective prediction of patient survival. Methods: We analyzed data from 222 stage II-III HCC patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital (Shanghai, China). Baseline information for each patient includes clinical and pathologic risk factors, laboratory tests and in situ immunological profiles. Using machine learning, we developed CoxPH, GBS, CGBS, FSVM and NSVM models for patient overall survival (OS). Models were trained on 155 cases with 48 features. Thirteen-fold cross-validation (CV) was used to measure performance with area under the ROC curve (AUC) and C-Index (CI). The ensemble model was used to predict patient OS and validated on the subsequent 67 cases. Results: For all models tested, immune features, including the fraction of CD68+ and CD8+ cells in tumor, and CD8+ cells in stroma, play a crucial role in predicting patient OS. Using the ensemble CoxPH model (with superior value of AUC and CI), a risk scoring system for patient OS was developed. The scoring system could stratify patients into high-risk or low-risk groups, revealing different prognosis (validation cohort: HR, 6.5, 95% CI, 2.4-18, P = 3.4e-05). The CoxPH model was also predictive of the time to-recurrence (p &lt; 0.0001). In validation set, the scoring system predicted half-year mortality of patients with AUC of 0.9, and 1-year mortality of patients with AUC of 0.897. The scoring system could also predict half-year recurrence and 1-year recurrence with AUC more than 0.83. Conclusions: The machine learning-based risk scoring system offers a novel strategy for incorporating multidimensional risk factors to predict clinic outcome and may help medical practitioners to optimize clinical follow-up or therapeutic interventions. [Table: see text]