tbuckley/cabot-search huggingface dataset:
The clinical significance of simple endoscopic scoring of patients with rectal cancer after concurrent chemoradiotherapy.
Authors: Jae Hyun Kim, Seun Ja Park
Journal: Journal of Clinical Oncology (2020)

109 Background: Neoadjuvant concurrent chemoradiotherapy (CCRT) is an effective treatment option for patients with rectal cancer. In this study, we investigated the clinical efficacy of simple endoscopic scoring of patients with rectal cancer after CCRT. Methods: Between July 2008 and October 2015, medical records including endoscopic imaging from 41 patients with rectal cancer who received CCRT were retrospectively reviewed. Two expert gastroenterologists reviewed the endoscopic images and assigned scores from 0–3 according to post-CCRT findings. The scoring criteria were as follows: 0 = scar without marginal elevation; 1 = clean-based ulcer without marginal elevation; 2 = clean-based ulcer with marginal elevation; 3 = non-clean-based ulcer. We evaluated image scores to predict long-term outcomes using Kaplan-Meier curves and Cox regression models. Results: The median follow-up duration was 55 months (interquartile range: 35–76). Patients with a low score (≤2) had a 17.2% recurrence rate, whereas patients with a high score (3) had a 50.0% recurrence rate. Patients with a low score had longer disease-free survival (DFS) than those with a high score in log-rank test (p = 0.026). In multivariate Cox regression analysis, a high score was a significant predictor of poor DFS in patients with rectal cancer after CCRT treatment (hazard ratio = 4.89, 95% confidence interval: 1.11–21.50, p = 0.036). Conclusions: This simple endoscopic scoring approach is helpful for predicting prognosis of patients with rectal cancer after treatment with CCRT.
Preclinical drug testing for clinical trial planning of novel combinative therapy with PI3K and MAPK inhibitors in colorectal cancer(CRC).
Authors: Cha Len Lee, Sinead Toomey, Mattia Cremona, Julie A. Workman, Bryan Hennessy
Journal: Journal of Clinical Oncology (2020)

179 Background: Combinative inhibitors with multiple actions to target downstream effectors are good strategy to reduce resistance occurrence. This is a preclinical study to evaluate efficacy of Palbociclib (P; CDK4/6 inhibitor) in combination with either Gedatolisib (G; P13K/mTOR dual inhibitors) or PD0325901 (PD; MEK 1/2 inhibitor) in CRC cell models. Methods: Five CRC cell lines with hot-spots mutations in PI3K and MAPK pathways genes are used. Cell growth assay is used to evaluate antiproliferative response to P, G and PD alone and in combination. RPPA is used to clarify the role actions of combinative drugs on resistance development and new druggable proteins. Paired t-test is used. Results: All cell lines except LS1034 (IC50=7.2µM) were sensitive to G. LS411N and SNUC4 were sensitive to P whereas Caco2, DLD1 and LS1034 were resistant (IC50&gt;15µM). All cells lines were sensitive to PD. When tested in combination, P+G has synergistic response in all cells lines, except for LS411N (CI=0.9; p=0.02). P+G is highly synergistic in LS1034 with KRAS mutation (CI=0.1; p=0.11). P+G is also synergistic in DLD1 with co-occurring PIK3CA and KRAS mutations (CI=0.6; p=0.04). P+PD is synergistic in all cells lines except for LS411N. In SNUC4 with PIK3CA mutation, both drug combinations have equal synergism (CI=0.5; p&lt;0.05). RPPA analysis is in progress and will be included in final abstract. Conclusions: This offers good rationale for further clinical development of P+G as beneficial therapy in treatment-resistant CRC patients. P+G offers better alternative to P+PD since MEK inhibitor resistance had been associated with tumours harbouring KRAS with(out) PIK3CA mutations. BRAFV600E and ERBB2 mutations are useful negative predictors in this cohort. [Table: see text]
心室細動を有する心原性ショック患者の治療のためのアミオダロンとニフェカラントの比較 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Takenaka Kotoe, Niki Shunnichro, Kurozumi Yuma, Yamamoto Takashi, Yamauchi Ryoko, Takenaka Hiroyuki, Haruna Yoshizumi, Ozaki Masaaki, Kitaguchi Shoji
Journal: Circulation (2013)
Analysis of early tumor shrinkage (ETS) and depth of response (DpR) in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line FOLFIRI plus panitumumab (Pani) or bevacizumab (Bev): Results from a randomized phase II WJOG6210G trial.
Authors: Naoki Izawa, Kohei Shitara, Toshiki Masuishi, Tadamichi Denda, Kentaro Yamazaki, Toshikazu Moriwaki, Hiroyuki Okuda, Chihiro Kondoh, Tomohiro Nishina, Akitaka Makiyama, Hideo Baba, Hironori Yamaguchi, Masato Nakamura, Akihito Tsuji, Taito Esaki, Yoshinori Miyata, Masahito Kotaka, Takeharu Yamanaka, Takako Eguchi Nakajima, Kei Muro
Journal: Journal of Clinical Oncology (2020)

201 Background: The WJOG 6210G trial demonstrated a similar efficacy between Pani and Bev arms at 2nd-line setting in pts with KRAS exon2 wild-type mCRC (Shitara K, et al, Cancer Sci 2016). The exploratory analyses of clinical trials evaluating 1st-line chemotherapy for mCRC have shown significant associations of ETS and DpR with prognosis; however, there is few data in 2nd-line treatment. We investigated whether ETS and DpR are associated with clinical outcomes in mCRC pts treated with 2nd-line treatment using the data of WJOG 6210G trial. Methods: ETS was defined as tumor reduction of 20% at week 8 compared to baseline in the sum of longest diameters of target lesions according to the RECIST criteria. DpR was defined as the percentage of maximum tumor shrinkage of target lesions. Fisher’s exact test and t-test were used to compare ETS and DpR between Pani and Bev arms. A Cox regression model was used to evaluate associations between ETS and progression-free survival (PFS), and overall survival (OS). The association of DpR with PFS and OS was analyzed using Spearman’s rank correlation coefficient. Results: Eighty-seven pts were evaluable for ETS and DpR (Pani, n = 41; Bev, n = 46) among 121 pts enrolled in the WJOG6210G. Pts in the Pani arm had a higher ETS rate (39.0 % vs. 8.7 %, p &lt; 0.001) and greater DpR [median: 23.7 % (range: -49.0 to 100) vs. 0 % (range: -40.7 to 61.5), p &lt; 0.001] than pts in the Bev arm. Pts with ETS achieved longer PFS [median: 10.5 vs. 5.4 m, HR: 0.40 (95% CI: 0.20-0.80), p = 0.009] and OS [median: 22.3 vs. 14.5 m, HR: 0.49 (95% CI: 0.23-0.98), p = 0.044] than pts without ETS in the Pani arm. Similarly, the Bev arm pts with ETS had longer PFS [median: 17.1 vs. 5.6 m, HR: 0.078 (95% CI: 0.004-0.38), p = 0.0002] and OS [median: 30.9 vs. 13.2 m, HR: 0.35 (95% CI: 0.083-0.99), p = 0.048]. There were moderately linear correlations of DpR with PFS and OS in both Pani (PFS: r = 0.75, p &lt; 0.001; OS: r = 0.60, p &lt; 0.001) and Bev arms (PFS: r = 0.68, p &lt; 0.001; OS: r = 0.44, p = 0.002). Conclusions: ETS and DpR were significantly associated with PFS and OS in mCRC pts treated with 2nd-line FOLFIRI in combination with Pani or Bev. Clinical trial information: UMIN000031621.
Gardenia Fruit–Related Blue-Gray Skin Pigmentation
Authors: Megumi Mizawa, Tsugunobu Andoh, Tadamichi Shimizu
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Efficacy of Divalproex vs Lithium and Placebo in Mania-Reply
Authors: Charles L. Bowden
Journal: JAMA (1994)

<h3>In Reply.</h3> —Drs Kravitz and Fawcett point out some of the design issues that arise in clinical research on bipolar disorder. We elected to include patients without consideration of their prior treatment response. One reason for this is that for purposes of inclusion/exclusion criteria, establishing prior response to treatment is confounded by numerous factors (eg, compliance, adequacy of dosing, and recency of prior treatment) that, taken in the aggregate, weaken prior treatment response as an explicit criterion. Also, the effectiveness of divalproex compared with placebo had been demonstrated in a sample of patients who were refractory to lithium, so it was important to determine the efficacy in a more generally representative sample.<sup>1</sup>The percentage assessed as having benefited from lithium is somewhat higher in this study than in the two other recent controlled clinical trials that reported this information; one study reported 46%<sup>2</sup>and the other 41%<sup>3</sup>
Anxiety among immunotherapy patients: Preliminary findings from <i>Immunotherapy &amp; Me</i>.
Authors: Alyssa Marie Jaisle, Nicholas James Power, Linda S. House, Tameka N. Jones, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2020)

104 Background: Immunotherapy is a relatively new method of cancer treatment which has seen little research into its psychosocial side effects. A clearer understanding of the source of anxiety for those undergoing immunotherapy is crucial as anxiety during cancer treatment can result in decreased treatment adherence, increased mortality rates, and other negative outcomes. This study surveyed 112 cancer patients undergoing immunotherapy to understand their top treatment-related concerns. Methods: RNs in twelve clinics across the U.S. recruited participants into Immunotherapy &amp; Me, a study run by the Cancer Support Community (CSC). Participants were given access to a selection of CSC’s world-class support resources designed to help them and their loved ones manage their treatment. While accessing these resources, participants were encouraged to complete a monthly survey online either at their clinic or at home for seven months. This survey included CancerSupportSource – CSC’s scientifically-validated distress screening tool – as well as some additional questions specifically tailored to immunotherapy patients. Results: The most frequent source of concern related to diagnosis and treatment was “feeling too tired to do things you want to need or do” ( M = 1.21, SD = 1.01), closely followed by “exercising and being physically active” ( M = 1.05, SD = .93). Other concerns included the future ( M = 1.03, SD = .99) and financial ( M = 1.02, SD = 1.16). There were significant differences between age groups in concerns about disruption to life F(4, 97) = 3.52, p &lt; .01; pain F(4,97) = p &lt; .05; finances F(4,97) = 2.86, p &lt; .05; and fatigue F(4, 96) = 2.47, p&lt; .05. Older participants were significantly less concerned about disruption to life as compared to younger participants while younger participants were more concerned about pain than older participants. Conclusions: Cancer patients undergoing immunotherapy do not have a single, outstanding concern. Instead, these patients have several concerns, the level of which varies significantly between age groups and gender. This suggests the need for a subsequent study that explores a more refined list of categories and probes which specific aspects of diagnosis and treatment generate these concerns. Clinical trial information: NCT03347058.
A phase II clinical trial of the phosphatidylserine targeting antibody, bavituximab, in combination with pembrolizumab in patients with advanced hepatocellular carcinoma.
Authors: Muhammad Shaalan Beg, Hao Zhu, David Hsieh, Syed Mohammad Ali Kazmi, Aravind Sanjeevaiah, Amit G. Singal, Radhika Kainthla, Leticia Khosama, Kimberli Crane, Rolf A. Brekken, Adam Charles Yopp
Journal: Journal of Clinical Oncology (2020)

TPS599 Background: Phosphatidylserine (PS) is an immunosuppressive lipid segregated to the inner leaflet of the plasma membrane of normal cells. PS is externalized to the outer leaflet of the plasma membrane on cells that line tumor blood vessels, tumor cells and exosomes in the tumor microenvironment creating a specific target for anticancer treatments. Bavituximab is a PS targeting antibody that binds to PS via β2 glycoprotein-1 (β2GP1), an abundant serum glycoprotein. Bavituximab can modulate the tumor immune microenvironment to promote anti-tumor immune activity. This clinical trial is evaluating the effect of combining bavituxumab and the checkpoint inhibitor pembrolizumab in patients with advanced hepatocellular carcinoma (HCC). Methods: This is a single arm phase 2 clinical trial for patients with histologically confirmed HCC which is not eligible for curative and/or loco-regional therapy. No prior systemic therapy for HCC is allowed. Patients should be &gt; 18 years, have Child-Pugh Score A, ECOG 0-1 and meet the following laboratory criteria: total bilirubin ≤ 2.0, INR ≤ 1.7; Hgb ≥ 8.5 g/dl; AST, ALT ≤5 times ULN; platelet ≥ 50,000/mm3; and albumin ≥ 2.5 g/dl. Major exclusion criteria include thromboembolic event within the last 6 months, clinically evident ascites, GI bleeding within 2 months, uncontrolled hypertension, HIV and autoimmune disease (except DM1, childhood allergies and thyroid abnormalities if adequately controlled. Dosing is as follows: Bavituximab: 3 mg/kg IV weekly, pembrolizumab: 200 mg IV every 3 weeks. The primary objective is to determine the overall response rate (ORR) of therapy. Secondary objectives are to determine the safety, tolerability and other measures of clinical efficacy (overall survival, 6 month PFS, and duration of response). Tumor and blood samples are being collected to assess for pharmacodynamic biomarkers. A minimax two-stage method will be used to analyze ORR after the first 15 patients are accrued. If 3 or more of the first 15 patients have either a complete or partial response, 13 additional patients will be enrolled. ORR will be analyzed by RECIST 1.1 criteria. Clinical trial information: NCT03519997.
Updated results from a phase Ib trial of regorafenib plus nivolumab in patients with advanced colorectal or gastric cancer (REGONIVO, EPOC1603).
Authors: Kohei Shitara, Hiroki Hara, Naoki Takahashi, Takashi Kojima, Akihito Kawazoe, Masako Asayama, Takako Yoshii, Daisuke Kotani, Hitomi Tamura, Yuichi Mikamoto, Nami Hirano, Masashi Wakabayashi, Shogo Nomura, Akihiro Sato, Hiroyoshi Nishikawa, Shota Fukuoka
Journal: Journal of Clinical Oncology (2020)

135 Background: In the phase 1 REGONIVO study, regorafenib of 80 mg/day plus nivolumab showed manageable safety profiles and encouraging anti-tumor activity for advanced colorectal cancer (CRC) or gastric cancer (GC) with objective response rate (ORR) of 36% in CRC and 44% in GC (Fukuoka, et al. ASCO 2019). Updated efficacy results are presented. Methods: Enrolled patients (pts) received regorafenib plus nivolumab in a dose-finding phase to estimate the maximum tolerated dose (MTD). Additional pts were enrolled in a dose-expansion phase. Regorafenib of 80 to 160 mg was administered once daily for 21 on 7 days off with nivolumab 3 mg/kg every 2 weeks. The primary endpoint was dose-limiting toxicity (DLT) during cycle one to estimate the MTD and the recommended dose. PD-L1 combined positive score (CPS) was assessed using the anti–PD-L1 28-8 antibody. Tumor mutation burden (TMB) was measured using Oncomine tumor mutation load assay. Results: Fifty pts were enrolled (25 CRC; 25 GC) until October 2018 with median prior treatment line of 3. Efficacy results were updated as of September 1st 2019. One CRC pt was with MSI-high but all other pts were with MSS or MMR-proficient. Among the 20 pts (9 CRC and 11 GC) with objective response (40%), responses are still ongoing in 13 pts (7 CRC and 6 GC) and the median duration of response was not reached (NR). Median progression free survival (PFS) was 7.8 months in CRC (95% CI, 2.8- NR) and 5.5 months (95% CI, 2.6-10.2 months) in GC. One-year PFS rate was 41.7% in CRC and 22.4% in GC. Median overall survival (OS) was not reached in CRC (95% CI, 9.7-NR) and 12.1 months (95% CI, 5.2-NR) in GC. One-year OS rate was 68% in CRC and 55.3% in GC. No significant difference of PFS and ORR was observed in CRC according to PD-L1 and TMB. Conclusions: Encouraging anti-tumor activity of the combination of regorafenib plus nivolumab had been maintained with long-term follow-up. A randomized study for MSS CRC is under planning. Clinical trial information: NCT03406871.
Immune modulation after Toca 511 and Toca FC treatment of colorectal cancer patients.
Authors: Gerald Steven Falchook, Jordi Rodon Ahnert, Shree Venkat, Arthur Donahue, Peder Horner, Amber Thomassen, William Accomando, Maria Rodriguez-Aguirre, Cornelia Bentley, Daniel Hogan, Derek Ostertag, Sharon Yavrom, Thian Kheoh, Douglas J. Jolly, Harry E. Gruber, Jolene Shorr, Jaime R. Merchan
Journal: Journal of Clinical Oncology (2020)

186 Background: Toca 511 (vocimagene amiretrorepvec) is a cancer-selective, retroviral replicating vector encoding yeast cytosine deaminase that converts 5-fluorocytosine (5-FC) into 5-fluorouracil in the tumor microenvironment (TME). In animal models, Toca 511 and 5-FC kill dividing cancer and nearby immunosuppressive cells, leading to antitumor immune activity. A Phase 1 study of Toca 511 &amp; Toca FC (extended-release 5-FC) in patients with recurrent high grade glioma revealed results consistent with this proposed mechanism. A Phase 3 trial is ongoing. Methods: Toca 6 (NCT02576665) is a Phase 1b, single-arm, multicenter study designed to investigate immunological changes after Toca 511 &amp; Toca FC treatment in patients with advanced solid tumors, including colorectal cancer (CRC). Patients received intravenous (IV) Toca 511 for 3 days, and underwent biopsy of metastatic tumor before and ~ 4 weeks after starting oral Toca FC. Toca FC was repeated every 4-6 weeks. Peripheral blood mononuclear cells and tumor biopsies were evaluated for treatment related immune responses. Results: 17 CRC patients with a median 5 lines of prior chemotherapy were enrolled. At last data cut-off, 9 patients were alive and the median overall survival was 9.4 months. A patient receiving concomitant panitumumab had a partial response. IV Toca 511 led to viral expression in tumor, which decreased post-Toca FC while maintaining a reservoir of virus in the remaining tumor. T cells shifted from naïve to effector phenotypes, CD4 memory T cells expanded, and/or B cells increased after Toca FC treatment in 36% of patients. Marked changes in tumor infiltrating cells (CD11b myeloid cells, Tregs, exhausted T cells and CD8 T cells) occurred after Toca FC treatment. Treatment has been generally well tolerated. We also plan to report insights gained from RNA analysis of TME and update on clinical finding. Conclusions: Clinical data suggest a signal of activity in these heavily pretreated CRC patients warranting further exploration. IV Toca 511 administration showed viral infection of CRC metastatic tumor. Toca 511 &amp; Toca FC may be associated with T cell mediated immune activity in peripheral blood and metastatic tumor, consistent with pre-clinical data in multiple tumor types. Clinical trial information: NCT02576665.
A phase II study investigating cabozantinib in patients with refractory metastatic colorectal cancer (AGICC 17CRC01).
Authors: Aaron James Scott, Steven J. Cohen, Atrayee Basu Mallick, Efrat Dotan, Philip Jordan Gold, Howard S. Hochster, Somasundaram Subramaniam, Afsaneh Barzi, Patrick Jud Blatchford, Wells A. Messersmith
Journal: Journal of Clinical Oncology (2020)

103 Background: Therapeutic resistance to antiangiogenics in metastatic colorectal cancer (mCRC) inevitably develops via multiple mechanisms including upregulation of the MET kinase pathway. Cabozantinib, an oral multityrosine kinase inhibitor targeting MET, AXL, and VEGFR, demonstrated significant anti-tumor activity in CRC xenograft and cell line models. Methods: A single-arm, two-stage phase II study was conducted at 7 AGICC centers nationwide. 44 patients (pts) with mCRC who had progressed on or were intolerant of standard of care agents were treated with cabozantinib 60 mg daily in q3 wk cycles. The primary endpoint was 12-wk PFS rate. Based on the control arm of phase III CORRECT study, the Kaplan-Meier 12-wk PFS rate estimate was 13% and served as the null hypothesis. This study was powered at 0.906 to detect the alternative hypothesis of 12-wk PFS rate of 33% with a type I error rate of 0.044. Secondary endpoints were safety, RR, OS, and retrospective analysis of PFS and RR based on RAS, BRAF, and PIK3CA mutation status. Results: 44 pts were enrolled and 34 pts were response-evaluable as having undergone at least the first 6-wk restaging scan. 10 pts discontinued treatment prior to the first 6-wk scan due to clinical disease progression. Median number of cycles was 4 and median follow-up was 2.5 months. As of data-cutoff 8/23/2019, 55 Grade 3/4 AEs were reported with the most common being hypertension, fatigue, diarrhea, pain, HFS, nausea, vomiting, and proteinuria. 32 SAEs occurred in 18 pts. 5 Grade 5 AEs were reported: disease progression (3), disseminated intravascular coagulopathy, and bowel perforation. 15 pts (34%) achieved ≥ 12-wk PFS and 8 patients remain on treatment. Best response was 1 PR and 31 SD with a DCR at 6 wks of 72.7%. Of the pts who achieved ≥ 12-wk PFS, 12 had left-sided primary tumors, 5 had a RAS mutation, 1 had a PIK3CA mutation, and all pts were BRAF WT and MSI stable. Conclusions: Cabozantinib was deemed safe and demonstrates encouraging efficacy in a heavily pretreated mCRC pt population. These results support further investigation of cabozantinib in mCRC. Clinical trial information: NCT03542877.
Potential Consequences of Changing Disease Classifications
Authors: Jenny A. Doust, Katy J. L. Bell, Paul P. Glasziou
Journal: JAMA (2020)

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