tbuckley/cabot-search huggingface dataset:
Adjuvant treatment for resected sub-centimeter T1 pancreatic cancer.
Authors: Walid Labib Shaib, Amit Sura Naranyan, Jeffrey M. Switchenko, Mehmet Akce, Juan Sarmiento, Shishir Maithel, David A. Kooby, Pretesh R Patel, Kenneth Cardona, Olatunji B. Alese, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2018)

4125 Background: The standard of care for pancreatic cancer (PC) patients with resected stage I to III is adjuvant chemotherapy. The role of adjuvant treatment for sub-centimeter T1 stage is unknown. This study evaluated treatment patterns and survival outcomes in T1 stage PC using National Cancer Database (NCDB). Methods: Retrospective review of the NCDB was conducted for T1 (tumor confined to the pancreas and 2 cm across or smaller), lymph node negative, surgically resected PC and no prior therapy. Patient demographics, tumor histology, treatment modalities, and survival trends were examined between 2004 and 2013. Adjuvant treatments were analyzed. Kaplan-Meier analysis and the log-rank tests were performed to determine the unadjusted association between overall survival (OS), size and treatment. Results: A total of 964 patients met criteria for inclusion. The median age was 66 (32-90). Majority were Caucasian (N = 807, 83.7%); 53.5% were female (N = 515), and moderately differentiated (N = 447, 46.4%). Tumors of 1-2cm constituted 71.2% (N = 686); 28.8% < 1cm (N = 178). Majority had negative surgical margins (N = 887, 93.3%). Patients who received surgery alone were 48.3% (N = 466); 27.5% received adjuvant chemotherapy (N = 265), and 22.6% had adjuvant chemotherapy and radiation (N = 218). Patients with < 1cm tumors who received adjuvant therapy had a median OS that was not reached v. 85.3 mo who received surgery alone (P = 0.41). In patients with 1-2 cm tumors, the median OS for patients who received adjuvant treatment was 70.7 mo v. 30.8 mo for patients who received surgery alone (P < 0.0001). The 12-mo, 24-mo, and 60-mo survival was 93.2%, 75.6% and 53.6% respectively, v. 72.5%, 61.0%, and 31.0%, respectively, for patients who received surgery alone. These results of adjuvant therapy for tumors < 1 cm v. 1-2 cm are paralleled for patients who received adjuvant chemotherapy (P = 0.08), and any adjuvant radiation (P = 0.15). Conclusions: This is the first report of adjuvant treatment analysis for resected PC patients with sub-centimeter stage I disease. Adjuvant treatment does not appear to improve survival in sub-centimeter T1, stage I PC.
Polymorphism in the circadian clock pathway to predict outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from TRIBE and FIRE-3 phase III trials.
Authors: Francesca Battaglin, Shu Cao, Joshua Millstein, Alberto Puccini, Ryuma Tokunaga, Madiha Naseem, Shivani Soni, Michelle McSkane, Martin D. Berger, Afsaneh Barzi, Wu Zhang, Vittorina Zagonel, Chiara Cremolini, Sebastian Stintzing, Fotios Loupakis, Alfredo Falcone, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2018)

3576 Background: The clock machinery comprises a complex network of transcription-translation feedback loops which regulates the circadian expression of target genes involved in key cellular functions. The disruption of the circadian clock has been associated with increased CRC risk, and the expression levels of core clock genes with clinicopathological features, survival and treatment response. We therefore hypothesized that genetic variants in clock genes may predict first-line treatment outcome in mCRC pts. Methods: Genomic DNA from blood samples of pts enrolled in two independent randomized phase III trials, TRIBE and FIRE-3, was genotyped through the OncoArray, a custom array manufactured by Illumina including approximately 530K SNP markers. The impact on outcome of 22 selected SNPs in 11 genes of the clock pathway (CLOCK, BMAL1, NPAS2, PER 1-2-3, CRY 1-2, RORa, hTIM, SIRT1) was analyzed. Results: A total of 451 pts were included in the analysis. TRIBE FOLFIRI/bevacizumab (bev) arm served as discovery cohort (n = 215, median PFS/OS: 9.7/26.2 mo), FIRE-3 FOLFIRI/bev arm as validation (n = 107, mPFS/OS: 11.5/31.4 mo) and FOLFIRI/cetuximab arm as control (n = 129, mPFS/OS: 12.8/49.8 mo). In the discovery cohort, the overall population carrying the 3’UTR CLOCKrs3749474 T/T variant showed a shorter mPFS (8.8 vs 10.4 mo) compared to pts with any C allele both in univariate (HR = 1.69; 95%CI 1.11-2.59; p = 0.012) and in multivariable analysis (HR = 2.06; 95%CI 1.26-3.37; p = 0.004). This effect was stronger in female pts (p < 0.001), and left-sided CRCs (p = 0.002). Significant interaction was found with gender (p = 0.005); however, no interaction was found with tumor location or RAS status. Findings were validated in overall pts in FIRE-3 bev cohort both in univariate (HR = 1.99; p = 0.027) and in multivariable analysis (HR = 2.45; p = 0.013). No significant association was observed in the control arm. Conclusions: Our results provide the first evidence that CLOCKrs3749474 polymorphism may have a predictive value in mCRC pts treated with first-line FOLFIRI/bev. This finding supports a possible role of clock genes in contributing to resistance to anti-VEGF treatment.
ニボルマブを受ける進行性黒色腫患者における生存率,持続的腫瘍寛解,長期的安全性
Authors: L Topalian Suzanne, Sznol Mario, F Mcdermott David, M Kluger Harriet, D Carvajal Richard, H Sharfman William, R Brahmer Julie, P Lawrence Donald, B Atkins Michael, D Powderly John, D Leming Philip, J Lipson Evan, Puzanov Igor, C Smith David, M Taube Janis, M Wigginton Jon, D Kollia Georgia, Gupta Ashok, M Pardoll Drew, A Sosman Jeffrey, Hodi F. Stephen
Journal: Journal of Clinical Oncology (2014)
Abstract 18164: Incidence and Risk Factors for Aki Pre-Cardiac Catherization in Patients Presenting With Stemi
Authors: Moses Ashukem, Jayshiv Badlani, Marian Calfa, Cesar Mendoza
Journal: Circulation (2016)

Background: The incidence of Acute Kidney injury (AKI) in patients with ST-Elevation Myocardial Infarction (STEMI) is between 10-30% post-PCI. It’s a marker of both significant inpatient and long term morbidity and mortality compared to non-AKI STEMI patients. They have a higher risk of future MI, strokes, heart failure, heart failure re-admissions, risk for long term CKD and Dialysis. All the current studies have looked at incidence and risk factors of AKI post-PCI. We aim to evaluate the incidence and risk factors for AKI pre- PCI in patients with STEMI. Methods: We retrospectively evaluated 636 patients who presented with STEMI between 2007 and 2013 in Jackson Memorial Hospital. Baseline characteristics, risk factors, echocardiographic and cardiac catheterization data were collected. AKI was defined based on AKIN network classification. I.e Cr > 0.3mg/dl from baseline - Stage 1, rise in Cr> 2x but   3x - stage 3. Results: PCI was conducted in 636 patients. Th...
Routine use of a modest next generation sequencing panel provides additional clinically useful data beyond single gene testing in non-small cell lung cancer and is fit for purpose as a clinical assay: Collated data from a single molecular diagnostic laboratory.
Authors: David Allan Moore, Kevin Balbi, Hendrik-Tobias Arkenau, Philip Bennett
Journal: Journal of Clinical Oncology (2018)

8540 Background: Testing of the EGFR gene for sensitising mutations is a critical part of patient stratification in non-small cell lung cancer. Analysis of a modest panel of relevant genes using a targeted Next Generation Sequencing (tNGS) has the potential to identify an extended range of actionable or trial-able alterations compared with more limited technologies. There are additional analytical and technological advantages to this approach. Sarah Cannon Molecular Diagnostics has been delivering somatic variant analysis through Oncomine solid tumour panel since 2014. This project involved the collation of data from 3 years’ worth of molecular diagnostic tNGS testing performed on non-small cell lung cancer specimens. Methods: The laboratory database was interrogated to identify all cases of non-small cell lung cancer submitted for testing from a 3 year period. Rate of rejection due to insufficient tumor, assay failure rate and turnaround time was calculated. For all cases successfully tested data was manually extracted for the relevant driver mutations and incidental evidence of gene amplification. Results: A total of 2796 NSCLC cases were submitted for multigene panel analysis over 3 years. 217 samples (7.8%) were rejected outright due to either low tumor content (189). Of 2579 accepted for testing, ‘analysis failed’ was reported in 131 (5.1%). Median turnaround time was 7 working days. 17% of cases reported were positive for a recognised EGFR driver mutation and 11% of EGFR-driven cancers also had a T790M mutation detected. 35% of those reported had evidence of a driver mutation in KRAS, 5.4% had other recognised driver mutations in BRAF, ERBB2, PIK3CA or NRAS and 3.5% of cases had no driver mutation but incidental evidence of amplification. Conclusions: A tNGS panel can be delivered as a diagnostic test for mutation analysis with an acceptable success rate and turnaround. Over 60% of patients have a driver event identified, providing additional relevant information beyond single gene testing.
Incidence of Progression of Persistent Nondysplastic Barrett’s Esophagus to Malignancy
Authors: Yonne Peters, Judith Honing, Wietske Kievit, Christine Kestens, Wiebe Pestman, Iris D. Nagtegaal, Rachel S. van der Post, Peter D. Siersema
Journal: Clinical Gastroenterology and Hepatology (2018)
An updated analysis of ICOGEN to demonstrate utility of a blood-based proteomic test to predict outcomes in EGFR TKI treated patients.
Authors: Yuankai Shi, Xiaohong Han, Li Zhang, Lieming Ding, Nicholas Dupuis, Alex Nickel, Lana Feng, Yishan Chuang, Gary Anthony Pestano, Xiaoqing Liu, Caicun Zhou, Li Zhang, Shucai Zhang, Dong Wang, Qiang Li, Shukui Qin, Chunhong Hu, Jianhua Chen, Fenlai Tan, Yan Sun
Journal: Journal of Clinical Oncology (2017)

e20655 Background: ICOGEN was a randomized Phase III clinical trial comparing two EGFR tyrosine kinase inhibitors (TKI), icotinib (I) and gefitinib (G), in EGFR gene mutation status unknown non-small-cell lung cancer (NSCLC) patients previously treated with platinum doublet chemotherapy. Plasma samples from study patients were retrospectively analyzed with a commercially-available blood-based proteomic test which has been shown to have prognostic and predictive properties in NSCLC. This study represents an updated analysis of ICOGEN to evaluate the ability of the test to predict outcome based on therapeutic regimen. Methods: Available pre-treatment plasma samples from ICOGEN were retrospectively analyzed with the proteomic test which classifies subjects as Good or Poor. Progression free survival (PFS ) and over-all survival (OS) were analyzed within treatment (TX) arms and test classification. Results: 352 subjects were evaluated, with 277(78.7%) classified as Good and 75(21.3%) classified as Poor. Among all patients evaluated with the proteomic test, the median PFS was 4.9 mo. and 2.3 mo. (HR [95% CI] 0.61 [0.46 – 0.81]; p = 0.0004) and median OS was 16.6 mo. and 5.5 mo. (HR [95% CI] 0.39 [0.29 – 0.50]; p &lt; 0.0001) for the Good and Poor sub-groups, respectively. Association between test result and PFS was significant in patients treated with I (6.0 mo vs. 1.9 mo, HR = 0.43, p &lt; 0.0001), but not significant in patients treated with G (3.7 mo vs. 2.5 mo, HR = 0.85, p = 0.429). Further evaluation demonstrated that the proteomic test predicted differential therapeutic benefit between icotinib and gefitinib for PFS (p int = 0.036). In OS, a significant association between test result and outcome was shown in both the I (16.3 mo vs. 4.0 mo, HR [95% CI] 0.27[0.19-0.39]; p &lt; 0.0001) and G (16.6 mo vs. 7.0 mo, HR [95% CI] 0.51[0.35-0.76; p = 0.0008) arms, which trended towards prediction of differential therapeutic benefit between icotinib and gefitinib for OS (p int = 0.086). Conclusions: For ICOGEN’s primary study endpoint, the proteomic test was predictive of differential therapeutic benefit between icotinib and gefitinib in EGFR mutations status unknown NSCLC patients.
Participation and response assessment of older adults with advanced cancer treated on phase I trials as compared to middle age and AYA patients: An analysis of 1489 patients.
Authors: Ishwaria Mohan Subbiah, Chad Tang, Arvind Rao, Gerald Steven Falchook, Vivek Subbiah, Razelle Kurzrock, Daniel D. Karp, David S. Hong
Journal: Journal of Clinical Oncology (2016)

10049 Background: Older adults (aged 65 and above) with advanced cancers are underrepresented in clinical trials particularly early phase clinical trials. To assess their participation and clinical response on phase I treatment, we analyzed the characteristics of such patients treated on phase I trials with an emphasis on comparison b/w middle age and adolescent/young adults (AYA). Methods: In total, 1489 consecutive patients treated on phase I trials b/w Dec 2004-July 2013 were separated into 3 age-based cohorts: AYA (15-39y), middle age (40-64y), elderly (65+y) and analyzed for clinical characteristics and response outcomes per RECIST. The clinical benefit (defined as a response of SD ≥ 6 months, PR, or CR, per RECIST) was determined for each cohort. We calculated the odds ratios of achieving a favorable clinical benefit for the 3 age cohorts, and for elderly and AYA in comparison to the middle age. Results: Of 1489 treated patients, 278 were elderly (18%, median age 68.9y), 220 AYA (15%, median age 32.6y), 991 middle age (67%, median age 53.8y). The median number of prior therapies was 3 in all three age groups and the most common malignancies were gastrointestinal (n = 438, 29%), gynecologic (n = 234, 16%), and thoracic/head/neck (n = 216, 15%). Median time on trial did not vary significantly between the 3 age cohorts (3 months in elderly, 3.5 months in middle age, 3.3 months in AYA). The odds ratio of achieving clinical benefit in elderly vs middle age is 1.10, p 0.19 (two-tailed), p 0.09 (one-tailed). Similarly the odds ratio of achieving clinical benefit in AYA vs middle age is 0.85, p 0.31 (proportions z-test, two tailed), p 0.15 (one-tailed). No significant differences were found in the odds ratio of response between the elderly, AYA and middle age cohorts. Analysis of the incidence of toxicities among the three age cohorts is in progress. Conclusions: Elderly patients accounted for less than 20% of patients on phase I clinical trials but those who participated were just as likely to achieve a clinical benefit as the AYA and middle age patients. Participation in phase I therapy may offer a reasonable therapeutic option for elderly patients with advanced cancers.
A phase 2, open-label study of the combination of spartalizumab (PDR001) and LAG525 for patients with advanced solid tumors and hematologic malignancies.
Authors: Sarina Anne Piha-Paul, Alpesh Amin, Christina Kovacs, Andrea Magley, D. Das Purkayastha, Ying Zhuo
Journal: Journal of Clinical Oncology (2018)

TPS2616 Background: Spartalizumab is an immunoglobulin G4 humanized monoclonal antibody that binds with subnanomolar affinity to PD-1. LAG525 is an immunoglobulin G4 humanized monoclonal antibody that binds LAG-3 with low nanomolar affinity, inhibiting the LAG-3 interaction with MHC class II and potentially restoring the activity of antitumor effector cells and enhancing anti–PD-1 antitumor activity. Preclinical studies demonstrated that simultaneous inhibition of PD-1 and LAG-3 resulted in synergistic antitumor activity (Woo SR. Cancer Res. 2012). PDR001XUS01 will evaluate the clinical benefit of combination checkpoint blockade (CPB) with LAG525 plus spartalizumab across multiple tumor types that are associated with low response rates (overall response rate [ORR] < 30%) to monotherapy CPB. Methods: This phase 2, open-label, parallel-cohort study will enroll patients aged ≥18 years with documented progression of small cell lung cancer, gastric/esophageal adenocarcinoma, castration-resistant prostate adenocarcinoma, soft tissue sarcoma, ovarian adenocarcinoma, advanced well-differentiated neuroendocrine tumors, or diffuse large B-cell lymphoma who received 1-5 prior lines of therapy, including ≥1 line of CPB monotherapy. A minimum of 5 patients and a maximum of 30 patients will be enrolled in each of the 7 tumor-type cohorts for a total planned enrollment between 35 to 210 patients. Patients will receive spartalizumab in combination with LAG525, administered intravenously every 3 weeks. The primary endpoint is the clinical benefit rate (CBR) at 24 weeks of treatment. CBR will be assessed by RECIST 1.1 for solid tumors and the Revised Response Criteria for Malignant Lymphoma for lymphoma (Cheson BD. J Clin Oncol. 2007). Secondary endpoints include ORR, time to response, duration of response, time to progression, and safety/tolerability. Accrual is ongoing. Clinical trial information: NCT03365791.
Assessing indicators of glioblastoma care quality in neuro-oncology centers: Baseline results of a pilot initiative.
Authors: Gabriel Zada, Jeffrey D Carter, Sandy Leong, Michelle Lin, Laurence Greene, Tariqa Ackbarali, Wendi Evanoff, Bicky Thapa, Tamar Sapir, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2018)

e18880 Background: Reports of quality improvement (QI) programs and metrics for care processes in glioblastoma (GBM) are lacking. We initiated a retrospective QI analysis for GBM teams at 2 major U.S. neuro-oncology centers. Methods: We plan to abstract 100 GBM patient charts to assess physicians’ performance of quality-based and guideline-directed diagnostic processes and outcomes, including time from diagnosis to pathology tests and reporting, surgery, chemotherapy, and radiotherapy; biomarker tests; tumor board reviews; clinical trial enrollment; and treatment practices. Results: Charts for 50 patients diagnosed between 2012-17 are included in this interim analysis. Mean age was 60 years (26-89) and median KPS was 80 (40-90); 42% were female; 68% were white; 34% were referred from community settings; and 14% were treated at a county/public hospital with an adjunctive treatment (chemotherapy, radiation). Baseline metrics for GBM care processes are presented. Conclusions: Addressing gaps in literature on QI metrics for GBM, these findings may inform the design of interventions across brain tumor centers for improving care processes and reducing delays in timely delivery of care for GBM patients. Barriers to quality care include inconsistent use of electronic records, treatment in a county or community hospital setting, fragmented care, and variable adaptation of newer diagnostic or clinical trial interventions. Measures for all 100 patients will be reported. Table. Metrics for GBM Care Processes Metrics (n = 50) Surgery 100% Postoperative MRI 78% Molecular test 80% Molecular test report Pathology report 70% 90% Chemotherapy 92% Radiotherapy 92% Tumor board review (TBR) Clinical trial considered (CTC) 54% 64% TBR + CTC 38% TBR + molecular test + CTC 26% Days from diagnosis to: Surgery 1 Postoperative MRI 4 Pathology report 8 Molecular test Molecular test report 8 19 Chemotherapy 25 Radiotherapy 33 Molecular Tests Ordered: MGMT promoter status 20% IDH1/2 mutation status 60% 1p19q codeletion 26% EGFR amplification 30% TERT promoter mutation 10% PD-L1 2% HLA-A2 2%
Contribution of interleukin-22, a T cell secreted cytokine, to renal cell carcinoma progression and association with poor outcome in RCC patients.
Authors: Marc Johannes Weidenbusch, Severin Rodler, Shangqing Song, Barbara Seliger, Manuel Ritter, Christian G. Stief, Hans-Joachim Anders, Philipp Nuhn, Michael D. Staehler
Journal: Journal of Clinical Oncology (2016)

4569 Background: Immunotherapy holds promise in RCC therapy. However, tumor-induced immune mechanisms add to resistance in RCC and little is known about how immunotherapy affects this. Interleukin-22 (IL-22) directly stimulates tumor cells, hence we examined the effect of IL-22 and its receptor (IL22R) on both RCC overall survival (OS) and progression free survival (PFS) and characterized the biological effect of IL-22 on RCC cells. Methods: RNA-seq data on 413 RCC cases from TCGA were analyzed by cbioportal. Intratumoral IL-22 and IL22R expression-stratified OS and PFS were calculated with Kaplan-Meier. Results were validated in an independent cohort of 40 RCC patients. FFPE-tissues were stained for IL-22 and IL22R. An array of eleven RCC cell lines was screened for IL22R expression and their biological behavior was characterized. Results: IL22R expression in RCC patients inversely correlates with median OS (46.12 vs. 85.45 mo; p < 0,01) and PFS (72.9 vs.91.33 mo; p < 0.05), and higher IL-22 expression is also associated with reduced median OS (47.04 vs. 85.45 mo; p = 0.0107mo). In the validation cohort, the association was confirmed for IL22R and IL-22 on the protein level. RCC cell lines have heterogeneous IL22R expression and IL22R+ cells increase their invasiveness, proliferation, hypoxic survival and resistance to RCC therapy in the presence of IL-22 in a dose-dependent manner. Conclusions: We show an effect of IL-22 on RCC outcomes in two independent patient cohorts. Both intratumoral IL-22 and IL22R are associated with worse prognosis and these findings are linked to RCC biology in vitro. We suggest IL22R as a prognostic marker and for the first time provide evidence for potential negative effects of immunotherapy by inducing T cell-derived IL-22 in RCC.
A pilot exploration of clinicopathologic features with solid papillary carcinoma of the breast.
Authors: Xu Yingchun, Fengchun Zhang, Xiaochun Fei, Hongmin Lu, Haiyan Xu
Journal: Journal of Clinical Oncology (2018)

e13056 Background: Solid papillary carcinoma of the breast (SPC) is classified as a special entity intraductal papillary tumor of breast tumors. Because of its rarity and specificity, its clinical behavior and its optimal treatment still remain controversial. The aim of this study is to analyze the clinicopathogical and immunophenotypic features of SPC, and to explore the choice of treatment options. Methods: A retrospective study of 56 cases of SPC was performed to analyze the clinicopathogical, immunophenotypic features and survival in these cases. All patients were followed up. Results: All cases were female with mean age of 65.36±14.06 years (range from 28 to 89 years), 85.7% of them were post-menopausal. There were 12 cases of in situ SPC, 9 cases of SPC with micro-invasion, 18 cases with invasive SPC, and 3 cases were accompanied by mucinous adenocarcinoma, 14 cases were accompanied with invasive ductal carcinoma. T1 accounted for 62.5% and the others were T2 (37.5%). 3 cases were found with lymph node metastasis. Approximately 62.5% of them were stage Ia, 33.9% were stage IIa, and 3.6% were stage IIb. Immunohistochemical analysis showed that most of the tumor cells expressed ER (96.4%) and PR (94.6%), all cases were CK5/6 negative. HER2 oncoprotein was positive in only 1 case. The average positive index of Ki-67 was 12.5%. About 78.6% of SPC were luminal A, and luminal B, HER-2 enriched and triple negative breast cancer were 17.9%,1.8% and 1.8%, respectively. The positive rates of Syn and CgA were 64.7% and 39.2%, respectively. The positive expression of P63, Calponin were 42.9% and 39.3% in the myoepithelial cells around tumor cell nests. All cases had follow-up data, the time of follow-up ranged from 6 to 61 months (average 18.6 months), 9 cases underwent chemotherapy, 7 cases underwent radiotherapy, 1 case underwent HER2 targeting therapy, and 47 cases underwent endocrine therapy (SERM,11; AI, 35; AI+OFS,1), all patients were disease-free so far. Conclusions: SPC of breast is a rare pathologic type of breast cancer, usually occurs in elderly females, with distinctive pathological features and immunophenotype. SPC often carries an indolent clinical behavior and its prognosis is better.