tbuckley/cabot-search huggingface dataset:
Phase II study of preoperative chemotherapy with nab-paclitaxel and gemcitabine followed by chemoradiation for borderline resectable or node-positive pancreatic ductal adenocarcinoma.
Authors: Emerson Yu-sheng Chen, Garth William Tormoen, Adel Kardosh, Nima Nabavizadeh, Bryan Foster, Skye C. Mayo, Kevin G. Billingsley, Erin W. Gilbert, Christian Lanciault, Aaron Grossberg, Kenneth Gregory Bensch, Erin Maynard, Eric C. Anderson, Brett C. Sheppard, Charles R. Thomas, Charles D. Lopez, Gina M. Vaccaro
Journal: Journal of Clinical Oncology (2020)

697 Background: Pre-operative therapy for resectable pancreatic ductal adenocarcinoma (PDAC) may eliminate micro-metastatic disease early and help achieve negative surgical margins. The present study is based on the hypothesis that gemcitabine/nab-paclitaxel chemotherapy followed by chemo-radiation with fluoropyrimidine is a feasible and efficacious pre-operative treatment for borderline resectable or node-positive PDAC. Methods: This is a single-arm phase II trial to evaluate pre-operative treatment with 2 cycles of gemcitabine 1000 mg/m 2 and nab-paclitaxel 125 mg/m 2 on days 1, 8, 15 every 28 days followed by 50.4 Gy of intensity-modulated radiation therapy over 28 fractions with concurrent 5-fluorouracil or capecitabine prior to pancreatic resection. Patients were eligible if they met borderline resectable criteria or had abnormal regional nodes visible on contrast CT. After surgery, they were eligible to receive up to 4 additional cycles of gemcitabine/nab-paclitaxel. The primary endpoint was the R0 resection rate. Secondary endpoints included response to pre-operative therapy, overall toxicities, relapse-free survival, and overall survival. Results: Nineteen of 24 screened patients have been enrolled. Median age was 68, 10 (53%) were female, and 4 (21%) were non-Caucasian. Eleven (78%) had head of pancreas cancers, 13 (68%) exhibited both arterial and venous involvement, and 12 (63%) had positive clinical nodes. All 19 patients received 2 months of gemcitabine/nab-paclitaxel, of which 17 patients continued to chemo-radiation (1 developed metastatic disease and 1 moved out of state). In the interval between chemo-radiation and surgery, 3 developed metastatic disease, 1 became unresectable, 1 withdrew from study, and 1 was deemed too frail for surgery. Nine have undergone successful pancreatic resection, and 2 are pending resection. Conclusions: Pre-operative gemcitabine/nab-paclitaxel followed by chemo-radiation with fluoropyrimidine is feasible in patients with borderline resectable PDAC and represents another strategy to FOLFIRINOX-based therapy. A planned interim analysis is ongoing. Clinical trial information: NCT02427841.
Increased risk of hypothyroidism in patients with primary head and neck cancer compared to non-head and neck primary malignancies.
Authors: Omar A. Alaber, Apoorva K. Chander, Prantesh Jain, Aman Rajpal, Monaliben Patel, Christopher J. Hoimes, Prateek Mendiratta, Pierre Lavertu, Ankit Mangla
Journal: Journal of Clinical Oncology (2020)

37 Background: Immune related thyroiditis is a common adverse effect of Immune checkpoint inhibitors (ICI). We sought to determine if the incidence of hypothyroidism (HT) in patients with primary head and neck cancers (pHNC) who received ICI, is increased compared to other primary cancers (lung, gastrointestinal (GI), skin melanoma or urinary system(GU). Methods: Data were obtained from a commercial de-identified database (IBM Explorys Solutions, IBM, Inc.). Cases included patients ≥ 18 years with a diagnosis of pHNC and controls included patients with a diagnosis of lung, GI, skin melanoma or GU cancer. All patients received one of 5 ICI (Avelumab, Atezolizumab, Durvalumab, Nivolumab or Pembrolizumab). Incidence of HT was defined as patient with a new diagnosis of HT at least 1 day following initiation of ICI. All patients with diagnosed HT, thyroid cancer (previous/concurrent), lymphomas were excluded. Odds ratios (OR) and confidence intervals (CI) were calculated using chi-square test. Results: There were 238,490 patients with a diagnosis of pHNC, and 616,850 patients with a diagnosis of other cancers in the database. Out of 710 pHNC patients, 80 patients (18.6%) and out of 7420 patients with other primary cancers, 850 (12.57%) had a new diagnosis of HT. When compared to non-HNC patients, HNC cases had a 1.6 (CI = 1.23 - 2.05) times higher odds of developing HT. In subgroup analyses, HNC cases were significantly more likely to develop HT compared to patients with GI or lung cancer, but not with skin melanomas or GU cancers. Overall, male cases and adults aged 18 - 65 years were significantly more likely to develop HT. (Table). Conclusions: The risk of developing HT after ICI is higher in patients with HNC compared to other primary cancers. Men and patients between the ages 18-65 years with pHNC were more likely to become HT. [Table: see text]
Cobimetinib plus vemurafenib (C+V) in patients (Pts) with colorectal cancer (CRC) with <i>BRAF V600E</i> mutations: Results from the TAPUR Study.
Authors: Kelsey Klute, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Reza Nazemzadeh, Kathleen J Yost, Nicole L. Butler, Venu Perla, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2020)

122 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of CRC pts with BRAF V600E mutation treated with C+V are reported. Methods: Eligible pts had advanced CRC, no standard treatment (tx) options, measurable disease, ECOG PS 0-2, and adequate organ function. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts had BRAF V600E/D/K/R mutation and no MAP2K1/2, MEK1/2, NRAS mutations. Recommended dosing was C, 60 mg orally once daily for 21 days, 7 days off and V, 960 mg orally twice daily. Simon two-stage design was used to test the null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) according to RECIST (SD16+)), 18 more pts enrolled. If ≥7 of 28 pts have DC, the tx is worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Thirty pts enrolled from August 2016 to August 2018; 2 were not evaluable for efficacy. Demographics and outcomes are summarized in Table. All pts had BRAF V600E mutations. Eight PR and 8 SD16+ were observed for DC and OR rates of 57% (90% CI, 43% to 67%) and 29% (95% CI, 13% to 49%), respectively. Twelve pts had at least 1 grade 3 AE or SAE at least possibly related to C+V including elevated liver enzymes, decreased lymphocytes, dyspnea, diarrhea, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, upper GI hemorrhage, and vomiting. Conclusions: The combination of C+V showed anti-tumor activity in heavily pre-treated CRC pts with BRAF V600E mutations . Further study is warranted to confirm the efficacy of C+V in this population. Clinical trial information: NCT02693535. [Table: see text]
In vitro and in vivo efficacy and safety of tumor treating fields (TTFields) and sorafenib combination in hepatocellular carcinoma.
Authors: Shiri Davidi, Catherine Tempel-Brami, Mijal Munster, Karnit Gotlib, Einav Zeevi, Rosa S Schneiderman, Tali Voloshin, Moshe Giladi, Adrian Kinzel, Eilon D. Kirson, Uri Weinberg, Yoram Palti
Journal: Journal of Clinical Oncology (2020)

551 Background: Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. Sorafenib (oral multikinase inhibitor) is approved in patients with advanced HCC, yet survival benefit is limited. Tumor Treating Fields (TTFields) are an effective, anti-neoplastic treatment modality delivered via noninvasive, low intensity (1-3 V/cm), intermediate frequency (100-500 kHz), alternating electric fields. The study aim was to explore in vitro and in vivo effects of TTFields alone and combined with sorafenib for HCC treatment. Methods: HCC (HepG2 and Huh-7D12) cells were TTFields treated with at frequencies of 100-400 kHz for 72 hr using the inovitro system. Efficacy of TTFields and sorafenib combined treatment was tested at optimal frequency with various sorafenib concentrations. Cell counts, apoptosis induction, and clonogenic potential were determined. Healthy rats were used to assess safety of TTFields applied to the abdomen. N1S1 HCC cells were injected into the left hepatic lobe of Sprague Dawley rat; after 1 week, TTFields (1.2 V/cm) and sorafenib (10 mg/kg) were applied for 6 days. Tumor growth was evaluated using MRI. Results: The optimal TTFields frequency was 150 kHz in HepG2 and Huh-7D12 HCC cells. TTFields 150 kHz treatment (1.0 - 1.7 V/cm, 72 hr) led to cell count reductions (53-55%) and further decreases in clonogenic potential (65-69%). TTFields and sorafenib combination treatment led to a significant reduction in cell count (2-way ANOVA, P &lt; 0.05) vs either treatment alone. Also, tumor growth was significantly reduced in the combined treatment group vs the control group (student t test, P &lt; 0.01). Tumor volume (fold increase) in the combination treatment group (1.6) was significantly lower vs control (5.9, P &lt; 0.0001), TTFields alone (3.3, P &lt; 0.01), and sorafenib alone (2.3, P &lt; 0.05) groups. Safety studies did not reveal any TTFields related adverse events with delivery to the rat abdomen. Conclusions: In vitro and in vivo data demonstrated efficacy and safety of TTFields in HCC; and improved efficacy in combination with sorafenib. A phase 2 study (HEPANOVA; NCT03606590) will explore the clinical potential of TTFields 150 kHz plus sorafenib.
CD3+ tumor-infiltrating lymphocytes (TILs) as prognostic in patients (pts) with stage II colon cancer (CC) not treated with adjuvant chemotherapy (ADJ).
Authors: Edoardo Francini, Fang-Shu Ou, Stefano Lazzi, Roberto Petrioli, Andrea Giovanni Multari, Guido Pesola, Luciana Messuti, Elena Colombo, Virginia Livellara, Serena Bazzurri, Sara Cherri, Miano Salvatora, Eric Wolfe, Steven R Alberts, Joleen Marie Hubbard, Harry H. Yoon, Guido Francini
Journal: Journal of Clinical Oncology (2020)

167 Background: Previous studies have reported high TILs are a favorable prognostic factor in stage II CC. However, whether the impact of TILs on overall survival (OS) differs among pts who did or did not receive ADJ is still to be determined. We assessed the prognostic value of CD3+ TILs in pts with stage II CC according to whether they received ADJ or not (no-ADJ). Methods: Pts treated with curative surgery for stage II CC (2002-2013) were identified through the Santa Maria alle Scotte Hospital database. CD3+ TILs at the invasive front, center of tumor, and stroma, were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as &gt; 20%. Pts were classified as high or low TILs (L-TILs) and ADJ or no-ADJ. Cox models were used to assess OS with hazard ratio estimates (95% CI). Results: Of the 678 pts included (356 deaths), 137 (20%) received ADJ while 541 (80%) did not. ADJ comprised fluoropyrimidine +/- oxaliplatin. Median follow-up was 8.5 years. The distributions of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ pts had a significantly longer OS (P &lt; .0001) regardless of the TILS rate while L-TILs/no ADJ had significantly shorter OS and higher risk of death (HR = 1.41; 95% CI, 1.06-1.88; P &lt; .0001) [See table]. On multivariable analysis, adjusting for perforation, obstruction, T-stage, grade, &lt; 12 lymph nodes resected, lymphovascular and perineural invasion, the adverse prognostic impact of L-TILs (vs H-TILs) in no-ADJ pts was confirmed (HR = 1.36; 95% CI 1.02, 1.82; P = .0373). Conclusions: Low CD3+ TILs rate was independently associated with shorter OS in stage II CC pts who did not receive ADJ, but was not prognostic among pts who had ADJ. These data suggest a potentially different impact of TILs in chemo-treated vs -untreated stage II CC which could affect clinical decision making. [Table: see text]
Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma
Authors: Han-Ki Park, Youngwoo Choi, Dong-Hyun Lee, Sujeong Kim, Jong-Myung Lee, Sae Won Choi, Hee-Ra Lee, Mina Rho, Hae-Sim Park
Journal: Journal of Allergy and Clinical Immunology (2020)
Reverse CARTによりPCIに成功した右冠動脈慢性完全閉塞の1例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 山本明和, 落合正彦, 斎藤重男, 星本剛一, 御子柴幸, 磯村直栄, 芦田和博, 荒木浩, 小原千明
Journal: Circulation (2009)
KRAS status and survival in multicenter study of RAS mutations (MURAS) in patients with colorectal liver metastases receiving Y90 radioembolization treatment.
Authors: Meaghan Dendy Case, Anish Ghodadra, Paula M. Novelli, Vincent Wu, Suvranu Ganguli, Moritz Wildgruber, Michael Kohler, Charles Robinson, Charles Kim, David S. Wang, Daniel Y. Sze, Kenneth Kolbeck, Lori Russell, Johannes Uhlig, Johannes M. Ludwig, Hyun S. Kim
Journal: Journal of Clinical Oncology (2020)

239 Background: Assessment of the clinical outcome and prognostic factors of patients receiving Y90 radioembolization to treat colorectal liver metastases. Methods: Multi-institution retrospective study of patients with CRLM who received Y-90 radioembolization after undergoing molecular testing was performed. Patients treated between 2008 and 2019 were included from 7 institutions within the United States and Europe. Patient demographics, systemic therapy regimens, tumor characteristics, laboratory values and overall survival were analyzed between patients with differing histopathologic and genomic status. Genomic profiling was obtained for KRAS, BRAF, PIK3CA, AKT, MEK, NRAS and MMR genes. Kaplan-Meier survival estimation and multivariate Cox regression were analyzed. Results: 445 patients treated with Y90 radioembolization fulfilled the inclusion criteria. Of the total cohort, 430 patients were available who had documented KRAS mutation status. Average age at diagnosis was found to be 58.4 years for all patients (57.6% male, 42.4% female). Decreased survival post Y90 treatment was shown in those patients with mutant KRAS. The median survival in patients with mutated KRAS was 5.7 months, as compared to 8.0 months in those patients with wild-type KRAS (p&lt; 0.0001). Patient demographics including age, gender and race were not shown to be significant in overall survival post-Y90 treatment (p-values &gt;0.05). The average number of systemic chemotherapy treatments prior to Y90 was 2.15 and was similar between KRAS groups (mutant vs wild type.) KRAS status persisted as a significant predictor of survival on multivariate analysis (p&lt; 0.0001; HR 2.1 CI: 1.54-2.85). Conclusions: KRAS status is shown as a significant prognostic factor in patients with colorectal liver metastases receiving Y90 radioembolization.
Impact of intraoperative staging of gastric cancer on long-term survival.
Authors: Keisuke Koumori, Kazuki Kano, Hayato Watanabe, Yota Shimoda, Hirohito Fujikawa, Takanobu Yamada, Yasushi Rino, Munetaka Masuda, Takashi Oshima, Takashi Ogata
Journal: Journal of Clinical Oncology (2020)

302 Background: The preoperative stage and intraoperative stage of gastric cancer were unified as the clinical stage in the 8th edition of the TNM classification (UICC). Although there are some reports about the relationship between preoperative stage and prognosis, the relationship between intraoperative stage and prognosis remains unclear. The aim of this study was to clarify the impact of intraoperative diagnosis and staging on long-term survival. Methods: Overall survivals were examined in 915 patients who underwent curative resection for gastric adenocarcinoma between April 2011 and March 2019 in our hospital. Results: The median age of the patients was 69 years (27-90 years), including 585 male and 330 female. The median follow-up period was 33.6 months (0.1-86.7 months). The number of the patients according to intraoperative stage were 641(70.1 %) in stageI, 15(1.6%) in stageIIA, 135(14.8%) in stageIIB, 111(12.1%) in stageIII, 12(1.3%) in stageIVA and 1(0.1%) in stageIVB. The hazard ratios of intraoperative stage for overall survival were as follows (ref: StageI); StageIIA, 6.990 (95% CI: 2.473-19.760, p &lt; 0.001), StageIIB, 2.234 (95% CI: 1.220-4.092, p = 0.009), StageIII, 4.091 (95% CI: 2.416-6.928, p &lt; 0.001), StageIVA, 6.061 (95% CI: 2.150-17.080, p &lt; 0.001), StageIVB, 14.92 (95% CI: 2.035-109.3, p = 0.008). Conclusions: The survival of intraoperative StageIIA was poorer than StageIIB/III. Intraoperative positive lymph node metastasis could be negative impact of survival, even if tumor invasion was T1 or T2.
Exosomal markers (CD63 and CD9) expression and their prognostic significance using immunohistochemistry in right-sided and left-sided colon cancer.
Authors: Ben McCormick, Pranitha Prodduturvar, Wadad Mneimneh, Valeria Dal Zotto, Leander Grimm, Paul Rider, John Hunter, Greire Iliff, Clayton Smith, Girijesh Kumar Patel, Seema Singh, Ajay Singh, Moh'd M. Khushman
Journal: Journal of Clinical Oncology (2020)

182 Background: Exosomes play pivotal roles in cancer progression, metastasis and chemoresistance. CD63 and CD9 are widely accepted exosomal markers. Their pattern of expression and prognostic significance in patients with RSCC and LSCC is unknown. This study explored CD63 and CD9 expression and prognostic significance in patients with RSCC and LSCC using immunohistochemistry (IHC). Methods: Between 2015 and 2018, 63 patients underwent surgical resection of colon cancer for whom we had available tissues for CD63 and CD9 IHC staining. Two pathologists independently scored the CD63 and CD9 expression in the tumor and adjacent normal mucosa (ANM). Staining intensity was graded 1-3 and staining percentage was estimated in 10% increments. Mean Quick-score (Q-score) (intensity X percentage of staining) was calculated. Results: RSCC and LSCC represented 52% and 48% of the patients respectively. The ANM and Tumor CD63 Q-scores were 225 vs 191 (p = 0.009) in RSCC and 224 vs 154 (p = 0.0001) in LSCC, respectively. The ANM and Tumor CD9 Q-scores were 134 vs 152 (p = 0.142) in RSCC and 135 vs 154 (p = 0.137) in LSCC, respectively. In patients with RSCC and LSCC, the mean Tumor CD63 Q-score was 191 vs 154 (p = 0.024), while the mean ANM CD63 Q-score was 225 vs 224 (p = 0.920). The mean Tumor CD9 Q-score was 152 and 154 (p = 0.883), and the mean ANM CD9 Q-score was 134 vs 135 (p = 0.926). In our cohort, there was no difference in progression free survival (PFS) between patients with RSCC and LSCC (p = 0.2349). In all patients, there was no difference in PFS in patients with CD63 expression &lt; 100 and ≥100 (p = 0.8284). Among patients with RSCC, there was a significantly lower PFS in patients with CD63 expression &lt; 100 vs. ≥100 (p = 0.0259). However, among patients with LSCC, there was no difference in PFS in patients with CD63 expression &lt; 100 vs. ≥100 (p = 0.3494). Conclusions: To our knowledge, this is the first study to show a difference in exosomal marker (CD63) expression pattern and its prognostic significance in patients with RSCC and LSCC. There was a significant positive correlation between progression free survival in patients with RSCC and higher exosomal expression.
A pilot study of avelumab in Epstein-Barr virus-associated gastric cancer.
Authors: Ronan Andrew Mc Laughlin, John Aird, Orla McCormack, C. DeGascun, R. Hussein, B. Molloy, A. Malara, M. Galligan, Catherine Margaret Kelly, Peter Doran, Austin G. Duffy
Journal: Journal of Clinical Oncology (2020)

TPS473 Background: Gastric Cancer (GC) is the third most common cause of cancer related deaths worldwide. The median overall survival of patients with stage 4 disease is approximately 1 year. Current accepted treatment approach with chemotherapy is applied with little consideration for known genetic or biologic heterogeneity. Whilst immune-based approaches in GC look promising it is clear that single-agent PD1/PDL1 inhibition benefit a minority. We must clarify a means of identifying prospectively those patients who may benefit from this treatment. A recent landmark paper by The Cancer Genome Atlas (TCGA) proposed a classification of GC into four subtypes: Epstein-Barr-virus (EBV)-positive, microsatellite instable (MSI), chromosomal instable (CI), and genomically stable (GS). Two of the four – EBV and MSI subtypes – are likely to be immunogenic and amenable to PD1/PDL1 inhibition. Recent advances have shown EBV-positive tumors to be infiltrated by lymphocytes and be enriched for PDL1. Methods: This single centre single-arm pilot study in gastric or junctional adenocarcinoma will explore the hypothesis that administering anti-PDL1 therapy (Avelumab) in a prospectively identified population enriched for potential responders will result in improved outcomes. The anticipated frequency of EBV associated-GC (c10%) means that approximately N = 100 patients will be screened to identify N = 10 participants. If a positive signal for efficacy is seen this will provide a basis for a larger, multicentre study. Previously treated Patients with confirmation of stage 4 EBV- positive gastric or oesophago-gastric adenocarcinoma meeting eligibility criteria will be enrolled. Avelumab will be administered at a dose of 10mg/kg IV every 14days. Primary endpoint is to determine the 6-month progression free survival (PFS) of Avelumab in EBV-associated GC. Secondary endpoints include overall response rate, overall survival, median PFS time and feasibility/accrual rate at 12 months. Exploratory endpoints will be to evaluate changes in immune parameters in the peripheral blood over time. Kaplan-Meier methods for primary efficacy endpoint with two-tailed one-sample proportion test will be used to evaluate the evidence to reject the null hypothesis. Clinical trial information: 2018-002085-39.
Multiple primary cancers in patients with gastric cancer: A retrospective study in China National Cancer Center.
Authors: Qi Lei, Runfeng Zhang, Xi Zou, Aiping Zhou, Chun-Xia Du
Journal: Journal of Clinical Oncology (2020)

337 Background: Gastric cancer (GC) is common in China. With the total incidence of cancer keeping rising in China, the occurrence of multiple primary cancers with GC is growing. Early detection and diagnosis of second or more primary cancers are vital for patients’ survival. Methods: Patients with multiple primary cancers containing gastric adenocarcinoma treated in China National Cancer Center from January 2010 to December 2017 were included. A 6-month interval was used to separate synchronous and metachronous cancers (according to IARC/IACR criteria). Results: 479 patients met the criteria were included, with 452 (94.4%), 24 (5.0%), 3 (0.6%) patients having two, three or more primary cancer sites respectively, contributing a total of 510 cancer sites besides stomach (Table). Malignancies at 257 (50.4%) sites occurred with GC synchronously, while 253 (49.6%) occurred metachronously. The median age at the diagnosis of first cancer was 59 (interquartile range [IQR], 53-66) years. The median interval between the diagnosis of first primary cancer and metachronous second one was 50.3 (IQR, 23.7-97.0) months. Cancers outside gastrointestinal (GI) tract were more likely to occur with GC metachronously, while GI tract cancers were more likely to occur synchronously (χ²=55.36, p&lt;0.001). Out of 479 patients, there were 352 (73.6%) male and 127 (26.4%) female. The most common associated cancer was esophagus cancer (142, 40.3%) in male, and breast cancer (31, 25.4%) in female. 236 (49.8%) patients were current smokers or ex-smokers, and 190 (40.1%) were regular alcohol consumers. 110 (23.2%) had first-degree relative cancer family history, with 84 (17.7%) having GI tract cancer family history. Conclusions: GI tract including esophagus and colorectum should be carefully scrutinized during GC peri-operation period. Further genetic research is warranted to explore the potential pathogenesis of multiple primary cancers.[Table: see text]