tbuckley/cabot-search huggingface dataset:
The largest sample size (2,200 cases) pooled analysis of LT-PCR achieving quantitative determination of folate receptor-positive CTCs for lung cancer in China.
Authors: Caicun Zhou, Jiatao Lou, Xiaoxia Chen, Xuefei Li, Jing Wu, Lihua Qiao, Xiaohui Liang, Xiaoqian Wang, Guohua Yang
Journal: Journal of Clinical Oncology (2016)

e23072 Background: As a novel biomarker of primary tumors, CTCs are well known to play an important role in cancer diagnosis, recurrence and metastasis, and disease monitoring. This study investigated the application of CTCs in lung cancer therapy by quantitative determination of folate receptor-positive CTCs. Methods: This study enrolled 2200 subjects (including 1586 lung cancer patients, 464 patients with benign lung diseases, 150 healthy subjects), and evaluated the existence of the CTC in peripheral blood and quantity in the patients with preliminary diagnosis by negative enrichment using immunomagnetic beads in combination with folate receptor-directed PCR. Results: Following ROC curve analyses of CTC levels in the patients with lung cancer, benign lung diseases and the healthy subjects, the cut-off of CTCs was 8.70 CTC Units/3mL with a specificity of 80.8% (496/614) and a sensitivity of 75.0% (1188/1584) as determined For stage II-IV lung cancer patients, the sensitivities were 66.0%(64/97), 77.0% (298/387), and 80.9% (581/718) respectively, and the sensitivity in stage I patients can reach up to 69.0% (147/213) as well. For patients with pulmonary nodules(1cm or less), the sensitivity can reach up to 85.0%(17/20). CTC levels appeared to have greater accuracy to diagnose lung cancer (AUC: 0.8004, P < 0.0001) than the combination of the other four lung cancer-specific serum tumor markers (CEA, NSE, CYFRA21-1 and SCC)(AUC: 0.7610, P < 0.0001);greater accuracy to diagnose squamous cell lung carcinoma than the model combining CYFRA211 with SCC(AUC:0.7685, P < 0.0001);In diagnosing SCLC, the area under ROC of CTC and NSE were 0.8004 and 0.6966,P<0.0001,respectively. CTCs were significantly related to tumor stage and tumor size other than pathological type. Conclusions: LT-PCR achieves quantitative determination of folate receptor-positive CTCs to diagnose lung cancer with high sensitivity and specificity, and significantly greater diagnosis accuracy than the model of combined lung cancer-specific serum tumor markers.
Clinical characterization and in silico drug sensitivity prediction model of rare EGFR mutations in non-small cell lung cancer.
Authors: Shinnosuke Ikemura, Hiroyuki Yasuda, Shingo Matsumoto, Mayumi Kamada, Junko Hamamoto, Tomoko Betsuyaku, Yasushi Okuno, Koichi Goto, Katsuya Tsuchihara, Kenzo Soejima
Journal: Journal of Clinical Oncology (2018)

e21221 Background: Recent genome scale characterization of cancers identified overwhelming numbers of novel, rare and uncharacterized somatic mutations, variance of unknown significance (VUS), in non-small cell lung cancer (NSCLC). In order to make these VUS information clinically worthy, further functional and biological characterization of each mutation is mandatory. In addition, development of novel strategy to overcome mutation diversity of lung cancer is anticipated. Methods: Using this largescale prospective cohort data of LC-SCRUM-Japan, nationwide lung cancer clinical and genomic characterization network in Japan, we characterized the frequency and distribution of rare EGFR mutations in NSCLC and clinical course of the patients harboring these mutations. In addition, to perform functional and biological characterization of each mutation, we created Ba/F3 EGFR minor mutation library. Furthermore, the in silico sensitivity prediction model has been developed to demonstrate binding affinity of protein and drug compound and applied to EGFR tyrosine kinase inhibitor with mutated EGFR. Results: Of the 2164 NSCLC patients examined by LC-SCRUM-Japan, 113 (5.2%) harbored the rare EGFR mutations. We found the diverse distribution of EGFR mutations throughout the gene, most major group included EGFR exon 20 insertion mutations (52 cases). We clarified the sensitivity profile of the VUS to EGFR tyrosine kinase inhibitors. Binding affinities calculated by the in silico sensitivity prediction model showed statistically significant correlation (R2: 0.7425, p value: < 0.05) with the experimentally observed IC50 values. Conclusions: These data may help choosing or predicting the appropriate inhibitor for lung cancer with VUS in EGFR, thereby contribute to the further development of precision medicine. Here, we clarified the diversity of VUS in EGFR and provide a novel insights, supercomputer utilized drug sensitivity prediction, to cancer field.
Duration of physician-industry relationships and prescribing changes in oncology.
Authors: Aaron Philip Mitchell, Aaron Winn, Jennifer Leigh Lund, Stacie Dusetzina
Journal: Journal of Clinical Oncology (2018)

6607 Background: Physicians who accept payments from a pharmaceutical company are more likely to prescribe that company’s cancer drug[s]. Whether long-term physician-industry relationships are more likely than intermittent relationships to result in practice changes is unknown. Methods: Open Payments data, containing industry-physician financial transactions, was linked to Medicare Part D prescription drug claims for 2013-2015. We identified physicians who treated each of 4 cancer types which had multiple orally-administered treatment options: renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (erlotinib, afatinib), CML (dasatinib, nilotinib), and prostate (abiraterone, enzalutamide). We used modified Poisson regression to test if the number of years (either 1, 2, or 3) in which a physician received payments was associated with increased prescribing of the paying company’s cancer drug in 2015. We also tested whether physicians at NCI-designated cancer centers were more likely to receive industry payments. Results: The physician cohort sizes were: RCC, 674; lung, 966; CML, 367; prostate, 1,483. Controlling for physician characteristics including practice size, prescribing volume, and total dollar amount received, physicians who received payments in all 3 years (vs. 1 year) were more likely to use the paying company’s drug within RCC (RR:1.69, 95%CI 1.32-2.17) and lung cancer (RR: 1.42, 95%CI 1.15-1.77), but not CML (RR:1.13, 95%CI 0.94-1.35) or prostate cancer (RR: 0.93, 95%CI 0.85-1.01). Results were similar comparing physicians who received payments in 3 years vs. 2 years: RCC RR:1.53, 95%CI:1.21–1.94; lung RR:1.12, 95%CI:0.93–1.35; CML RR:1.13, 95%CI 0.94–1.35; prostate RR:0.93, 95%CI:0.85–1.01. Physicians at NCI institutions were less likely to have received any industry payments during the study period (RR:0.70, 95%CI:0.61-0.80). Conclusions: Longer-term industry relationships may be associated with greater changes in drug prescribing than time-limited ones. Conflict-of-interest policies and disclosures may be more informative if specifying duration of industry relationships. This study was limited by a short time range, and lack of payment records prior to 2013.
Commonality and clinical, pathological, and prognostic characteristics of non-V600E BRAF mutations (BRAFMut) in metastatic colorectal cancers (mCRC) compared to V600 BRAFMut CRCs.
Authors: Jeremy Clifton Jones, Benjamin Kipp, Alexis Diane Leal, Jesse S Voss, Joleen Marie Hubbard, Robert R. McWilliams, Axel Grothey
Journal: Journal of Clinical Oncology (2016)

3529Background: BRAF mutations occur in approximately 10% of patients with CRC. Compared with patients with unmutated mCRC, V600 BRAFMutCRCs are associated with older age, female gender, right-side...
Survival endpoints with or without lymphadenectomy in women with stage I endometrial carcinoma: A matched-pair analysis.
Authors: Ahmed Ibrahim Ghanem, Nadia Khan, Meredith Mahan, Thomas Buekers, Mohamed A. Elshaikh
Journal: Journal of Clinical Oncology (2016)

e17105 Background: The role of regional lymphadenectomy (LA) in women with stage I endometrial carcinoma (EC) is controversial. The objective of the study is to determine the prognostic impact of LA on survival endpoints of women with stage I EC solely of endometrioid histology using match-pair analysis. Survival endpoints included recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). Methods: We identified 1257 patients with stage I EC who underwent hysterectomy between 1/1990 and 6/2015. Of those, 822 women underwent LA as part of their surgical staging while 435 did not (NLA). 435 women with NLA were matched to 435 women who had LA (1:1 match) based on 2009 FIGO stage, tumor grade and adjuvant management received (observation, vaginal brachytherapy or pelvic external beam radiation treatment). Univariate and multivariate modeling with Cox regression analysis was carried out for predictors of survival endpoints. Results: Median follow-up time for the study cohort was 48 months. The two groups were well balanced except for more peritoneal cytology performed and more lower uterine segment (LUS) involvement for LA group (p= 0.001 for both). 5-year survival endpoints between the two groups were similar. 5-year RFS for women in the LA group was 93.7% vs. 90% for NLA group (p= 0.081). Similarly, 5-year DSS was 97.7% vs. 98% (p= 0.536) and 5-year OS was 87.2% vs. 91.7% (p= 0.357). On multivariate analysis for the entire study cohort, older age, deep myometrial invasion and higher tumor grade were predictors of worse RFS (p= 0.031, p= 0.004 and p< 0.001), respectively. For DSS, higher tumor grade (p< 0.001), LUS involvement (p= 0.028) and FIGO stage IB (p= 0.022) were significant predictors of worse outcome. For OS, older age and LUS involvement were the only two independent predictors for shorter OS (p< 0.001). Conclusions: With this large study cohort, our study suggests that survival endpoints are not different between women with stage I endometrial carcinoma who underwent lymphadenectomy compared to those who did not. It appear that omitting lymphadenectomy for women with stage I disease is not associated with any worse survival outcome after matching for stage, grade and adjuvant management.
Impact of early FDG-PET directed intervention on preoperative therapy for locally advanced gastric cancer: A Cooperative Group random assignment phase II study (Alliance A021302) Impac.
Authors: Manish A. Shah, Qian Shi, Vivian E. Strong, Jon Strasser, David H. Ilson, Lawrence Kleinberg, Syma Iqbal, Evan John Wuthrick, Alexandra Levasseur, Nathan Hall, Jeffrey A. Meyerhardt, Eileen Mary O'Reilly
Journal: Journal of Clinical Oncology (2017)

TPS4135 Background: Gastric cancer is a prevalent and morbid illness for which new treatment strategies are needed. Peri-operative therapy is a standard approach that is associated with only a 15% improvement in overall survival. Early FDG-PET scanning, performed prior to cycle 2, can distinguish patients (pts) responding to chemotherapy from those who are not. FDG-PET non-responding pts have poorer survival. This study addresses the question of salvage therapy in pts who are PET non-responders. Specifically, does salvage chemotherapy with docetaxel /irinotecan improve pt survival in FDG-PET-nonresponding pts with locally advanced gastric cancer. Methods: This is a multicenter, cooperative group, NCI supported, randomized phase II study of salvage chemotherapy + surgery versus surgery and post-operative chemoradiotherapy in pts who are FDG-PET non-responders (defined as a decrease in SUV max of the primary tumor of less than 35%). A total of 176 pts with locally advanced, resectable gastric cancer who were FDG-PET non-responders to cycle 1 of platinum/capecitabine based chemotherapy will be randomized in a 1:1 manner to receive either (Arm A) surgery followed by fluoropyrimidine-sensitized radiotherapy (4500 cGy), or (Arm B) salvage chemotherapy with docetaxel / irinotecan (DI) for 2 cycles followed by standard resection and 3 cycles DI post-operatively. DI is administered as D 30 mg/m2, I 50 mg/m2 given on D1, D8 of a 21 day cycle. 416 pts will be screened to yield 162 non-responders (81 FDG-PET non-responders per treatment group). With expected 120 events, the study will have 80% power to detect a hazard ratio of 0.625 for improved survival at the one-sided significant level of 0.15. Pts will be required to provide tissue at the time of resection, as well as whole blood prior to resection for correlative studies associated with platinum sensitivity, FDG avidity, and prognostic markers. This study is available through all cooperative groups (SWOG, ACRIN/ECOG, Alliance, and NRG) and the National Clinical Trials Network. Enrollment began in November 2015. Support: U10CA180821, U10CA180882; Clinical Trial Information: NCT02485834 .
AB0156 Polysaccharides from dendrobium officinale ameliorate the development of murine sjögren’s syndrome via inducing il-10-producing b cells
Authors: F. Xiao, X. Lin, D. Liu, L. Lu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Primary Sjögren's syndrome (SS) is a chronic autoimmune disease with salivary gland (SG) hypofunction and inflammation. Currently, effective therapies for SS patients are still lacking. Polysaccharides derived from <i>Dendrobium officinale</i> (DOP) have been shown to possess immunomodulatory functions in various animal models. However, it remains unclear whether DOP can modulate immune responses and have potential therapeutic effects on SS. <h3>Objectives</h3> To investigate the immune modulatory and therapeutic effects of DOP on experimental SS (ESS) in mice. <h3>Methods</h3> Polysaccharides were extracted from <i>Dendrobium officinale</i> with removal of endotoxin. C57BL/6 mice were immunized with SG-derived proteins for ESS induction, followed by daily oral treatment of vehicle and different dosages of DOP. SG functions were assessed by monitoring saliva flow rates whereas lymphocytic infiltration and tissue destruction in SG were examined by histological analysis. Both T and B cell populations in peripheral lymphoid organs were analyzed by flow cytometry. The effects of DOP on IL-10-producing B cell (B10 cell) induction and Th17 cell differentiation were examined in culture. Moreover, TLR4 and TLR9 inhibitors were used to identify the function of TLR4/TLR9 in DOP-mediated effects. <h3>Results</h3> ESS mice with DOP treatment displayed significantly higher saliva flow rates than vehicle-treated ESS mice. DOP treatment ameliorated SG tissue destruction accompanied with profoundly reduced lymphocytic infiltration in ESS mice when compared with vehicle-treated counterparts. Moreover, DOP treatment markedly increased the numbers of B10 cells but decreased numbers of Th17 cells in peripheral lymphoid organs of ESS mice. Notably, DOP markedly increased frequencies and numbers of B10 cells but did not affect Th17 cells generation in culture. Moreover, TLR4 inhibitor, but not TLR9 inhibitor, significantly suppressed DOP-induced IL-10 production in B cells <h3>Conclusions</h3> The results show that DOP treatment ameliorates ESS disease development by inducing regulatory B10 cells, suggesting that DOP might be a promising candidate for treating SS. <h3>References</h3> [1] Ng TB, et al. Review of research on Dendrobium, a prized folk medicine. Appl. Microbiol. Biotechnol 2012;93:1795–1803. [2] Xiao F, et al. Proteasome inhibition suppresses Th17 cell generation and ameliorates autoimmune development in experimental Sjögren's syndrome. Cell. Mol. Immunol 2017. <h3>Disclosure of Interest</h3> None declared
Comparison of International Prognostic Scoring System (IPSS) and Revised IPSS (IPSS-R) in myelodysplastic syndromes (MDS).
Authors: Muhammad Umair Mushtaq, Abdullah Ali, Kiyomi Morita, Ronald Pinheiro, Muhammad Baig, Azra Raza
Journal: Journal of Clinical Oncology (2016)

e18549 Background: IPSS and IPSS-R stratifies MDS patients into low- to high-risk groups based on karyotype, bone marrow myeloblasts and cytopenias. We report the comparison of IPSS and IPSS-R in predicting overall survival (OS) in MDS patients. Methods: A retrospective review of 282 MDS patients, from Columbia University Medical Center Tissue Repository, was conducted. Karyotype and clinical factors were ascertained at the time of referral. Kaplan-Meier and cox regression analyses were conducted to correlate factors with OS. Median OS (mOS) and Hazard ratios (HR) with 95% confidence intervals (CI) were obtained. Results: Median age was 73 years with mOS of 105 months (95% CI 90.5-119.5). Median values for clinical factors were: myeloblasts 2%, hemoglobin (HGB) 9.6 g/dL, platelets (PLT) 109,000 cells/uL and neutrophils (ANC) 1895 cells/uL. Karyotype was good (65%), intermediate (20%) and poor (15%).As compared to ≤ 2% myeloblasts, 3-4% (HR 1.92, 95% CI 1.11-3.34, P = 0.021), 5-10% (HR 4.04, 95% CI 2.45-6.67, P &lt; 0.001) and 11-19% myeloblasts (HR 5.62, 95% CI 3.11-10.17, P &lt; 0.001) predicted poor OS.Poor karyotype vs. good karyotype (HR 2.87, 95% CI 1.81-4.55, P &lt; 0.001), HGB &lt; 10 g/dL (HR 1.84, 95% CI 1.18-2.85, P = 0.007), PLT &lt; 50,000 cells/uL (HR 2.09, 95% CI 1.38-3.15, P &lt; 0.001) and ANC &lt; 800 cells/uL (HR 1.74, 95% CI 1.13-2.67, P = 0.013) predicted poor OS. Median IPSS and IPSS-R scores were 0.5 (scale 0-3.0) and 3 (scale 0-9.5) respectively.As per IPSS, 79% patients had low- (low and intermediate-I) and 21% had high-risk disease (intermediate-II and high). IPSS high-risk (mOS 40 months, 95% CI 16-64) vs. low-risk patients (mOS 125 months, 95% CI 102-148) had poor OS (HR 2.92, 95% CI 1.94-4.38, P &lt; 0.001). As per IPSS-R, 57% patients were low- (very low and low), 18% were intermediate- and 24.5% were high-risk (high and very high). IPSS-R high- (mOS 40 months, 95% CI 19-61; HR 4.83, 95% CI 3.06-7.62, P &lt; 0.001) and intermediate-risk patients (mOS 67 months, 95% CI 5-129; HR 2.72, 95% CI 1.59-4.65, P &lt; 0.001) had poor prognosis vs. low-risk patients (mOS 165 months, 95% CI 109-221). Conclusions: IPSS-R low-, intermediate- and high-risk groups were better predictors of OS as compared to IPSS risk groups in MDS patients.
<i>HER2</i> positive rates are enriched amongst colorectal cancer brain metastases: A study amongst 1,920 consecutive patients.
Authors: Ryan Tan, Clarinda Wei Ling Chua, Si-Lin Koo, Su Pin Choo, Emile Tan, Simon Yew-Kuang Ong, Matthew C.H. Ng, David Wai-Meng Tai, Dominique Camat Macalinao, Choon Hua Thng, James Khoo, Kiat Hon Tony Lim, Tse Hui Lim, Alvin ST Lim, Iain B. Tan
Journal: Journal of Clinical Oncology (2018)

3612 Background: Brain metastases (BM) from colorectal cancer (CRC) are a rare but increasing event as patients survive longer. While human epidermal growth factor receptor 2 (HER2) gene amplification in breast cancer is well described and known to increase risk of brain metastases, information in CRC patients with brain metastases is lacking. Methods: A retrospective review of all radiologic imaging amongst 1920 consecutive CRC patients seen at National Cancer Centre Singapore identified 40 patients with radiological evidence of brain metastases. We retrieved resected primary tumour specimens or biopsies of metastatic sites from these 40 patients for fluorescence in situ hybridization (FISH) testing for HER2 gene amplification. HER2 amplification was defined as HER2/CEP17 ratio ≥2.0. Clinical characteristics were evaluated in relation to HER2 status. Results: The incidence of clinically evidence brain metastases in this cohort of CRC patients was 2% (40 of 1920). HER2 amplification was observed in 20% (8 of 40) of CRC patients who develop brain metastases. HER2 amplification was observed across most CRC primary sites (4 rectum, 3 right colon and 1 left colon) and was also seen in KRAS mutant CRC (2 of 8 patients). Mean HER2 copy number of HER2 positive (HER2+) patients was 10.7 (range 5.7 – 17.5). Brain metastases was preceded by metastases in either the lung or liver in 95% of patients (38 or 40) including all of the HER2+ patients. In 1 patient, HER2+ brain metastases was observed after Trastuzumab/Lapatinib therapy. Conclusions: Brain metastases in CRC is rare. However, compared to a reported HER2 positive rate of 5% amongst 912 KRAS wild-type metastatic CRC patients in the HERACLES study and 0% (0/44) amongst KRAS mutant patients reported in literature, HER2 amplification was observed in 20% (8 of 40) of all CRC patients in our study who develop brain metastases. This is one of the first studies to point to HER2+ disease being enriched amongst patients with brain metastases providing insight into a potential organotrophic site of metastases in HER2+ positive CRC.
Limitations of platform assays to measure serum 25OHD level impact on guidelines and practice decision making
Authors: Maya Rahme, Laila Al-Shaar, Ravinder Singh, Rafic Baddoura, Georges Halaby, Asma Arabi, Robert H. Habib, Rose Daher, Darina Bassil, Karim El-Ferkh, Maha Hoteit, Ghada El-Hajj Fuleihan
Journal: Metabolism (2018)
Impact and correlation of mutational load (ML) and specific mutations (mts) assessed by limited targeted profiling (LTP) with PD-L1 tumour expression (exp) in resected non-small cell lung carcinoma (NSCLC).
Authors: Jane Sze Yin Sui, MinYuen Teo, Sinead Toomey, Shereen Rafee, Julia McFadden, Kathy Gately, Martin P Barr, Steven G. Gray, Bryan Hennessy, Ken O'Byrne, Sinead Cuffe, Stephen P. Finn
Journal: Journal of Clinical Oncology (2017)

11587 Background: The advent of immunotherapy represents a paradigm shift in the treatment of NSCLC compared to conventional chemotherapy. Recent studies have shown higher mts burden assessed by exome sequencing are associated with improved objective response and clinical benefit. We performed this study to evaluate the impact of ML assessment by LTP, correlating with PD-L1 exp and clinicopathological variables in resected NSCLC. Methods: NSCLC patients(pts) who underwent curative resection between 1998 and 2006 at our institution were included. PD-L1 status was assessed using Ventana SP124 antibody on archival FFPE surgical tumour specimens cores. PD-L1 was scored positive if membranous staining was present in &gt;1% of tumour cells aggregated across the replicate cores to address heterogeneity. In collaboration with the Lung Cancer Genomics Ireland Study a targeted panel of 49 genes were assessed by Sequenom MassArray including genes in MAPK and PI3K pathways. Clinical data was obtained from hospital electronic database. Results: Ninety-one pts were included, of which 51 (56.0%) were males, with a median age of 65 years (range: 42 – 82). 51.6%, n=47 with squamous histological subtypes, 46.2%, n=42 were ex-smoker and 49.5%, n=45 had Stage I disease. 23.1%, n=21 had PD-L1 positivity. 149 mts were identified of which, 32(21.5%) with PHLPP2, 31(20.9%) with PIK3R1 and 21(14.1%) with TP53. The presence of PI3K and TP53 mts are associated with positive PD-L1 status (see table). An inverse correlation of PD-L1 positivity with ML of (1 vs 2 vs 3: 53.8% vs 30.8% vs 15.4%) was noted. Conclusions: We did not identify higher PD-L1 exp with higher ML assessed by a LTP widely used in clincial practice. However, positive PD-L1 exp was correlated with PIK3R1 and TP53 mts , warranting further investigation as potential modulators or surrogates of positve PD-L1 expression. [Table: see text]