tbuckley/cabot-search huggingface dataset:
P01.142 Comparing Outcomes in Glioblastoma Multiforme patients undergoing Photodynamic Therapy with a Second-Generation Photosensitiser vs 5-Aminolevulinic Acid - A Single Site Retrospective Analysis
Authors: K Singh, O Kouli, A Kanodia, C Goodman, E Eadie, S Ibbotson, K Hossain-Ibrahim
Journal: Neuro-Oncology (2018)

Laser light in malignant brain tumours has been used in conjunction with photosensitizing drugs to both guide surgical resection (Photodynamic Diagnosis (PDD)) and to also enhance the extent of tumour destruction (Photodynamic Therapy (PDT)). Photosensitizing drugs given pre-operatively are taken up by rapidly dividing cells, resulting in fluorescence on exposure to low visible wavelength (blue) light (PDD) or generate cytotoxic singlet oxygen species upon exposure to high visible wavelength (red) light (PDT). PDT potentially offers benefit for patients with Glioblastoma Multiforme (GBM) where it’s highly invasive & heterogeneous nature makes complete resection impossible. As 5-ALA has European & US regulatory approval for PDD in GBM surgery, it is the most obvious candidate for PDT. A newer agent, Temoporfin, has demonstrated greater phototoxicity in animal models and enhances survival over matched pair (no PDT) controls in humans. This retrospective analysis aims to establish whether PDT with Temoporfin confers a greater degree of survival for GBM patients compared to using PDT with 5-ALA while undergoing a standard regime of care (surgical debulking, followed by Temozolomide with radiotherapy). Clinical data were gathered retrospectively from procedure and electronic medical records for patients undergoing PDT following surgical debulking of GBM from September 2009 to December 2012. Survival of those who underwent intra-operative treatment with Temoporfin was compared to those who were treated with 5-ALA, along with data on demographics, Karnofsky Performance Score, Charlson Co-Morbidity Index and lesion size. Median overall survival from point of surgery and PDT therapy for those treated with Temoporfin (n=6) was 4.2 mths (range, 1.2–32.3 mths), with 2-year survival rates of 16.7%. This was compared to those treated with 5-ALA (n=9) where median overall survival was 6.0 mths (range, 1.8–39.7 mths), with 2-year survival rates of 11.1%. No significant difference in survival was demonstrated between the two groups (log-rank test, p=0.835) and multivariate Cox regression analysis showed no statistically significant independent covariates. Despite evidence suggesting increased phototoxicity in animal models, these data demonstrate no difference in survival outcome between GBM patients treated with Temoporfin and those treated with 5-ALA. This may reflect inherent difficulties relating to laser light dispersion through brain tissue, even when using more penetrant red-light. However, the small number of patients in this retrospective analysis is a limitation to inferences that can be drawn. Nevertheless, given 5-ALA’s widespread regulatory approval, it remains the best opportunity for ongoing research into PDT for GBM.
Radiotherapy to bulky disease PET-negative after immunochemotherapy in elderly DLBCL patients: Results of a planned interim analysis of the first 187 patients with bulky disease treated in the OPTIMAL&gt;60 study of the DSHNHL.
Authors: Michael Pfreundschuh, Konstantinos Christofyllakis, Bettina Altmann, Marita Ziepert, Mathias Haenel, Andreas Viardot, Andreas Neubauer, Gerhard Held, Lorenz Truemper, Christian Schmidt, Lothar Kanz, Michael J. Hallek, Norbert Schmitz, Tobias Heintges, Christian Koelbel, Guenther Schneider, Christian Ruebe, Dirk Hellwig, Viola Poeschel, Niels Murawski
Journal: Journal of Clinical Oncology (2017)

7506 Background: RT to bulky sites improves outcome of elderly DLBCL patients [Lancet Oncol 2008; 9: 105-116; J Clin Oncol 2014; 32:112-1118]. Whether RT can be spared in PET-negative pts. after R-CHOP was prospectively addressed in OPTIMAL &gt;60. Methods: 61 to 80 y-old pts. were randomized in a 2x2 factorial design to 6xCHOP-14 or 6xCHLIP-14 (liposomal instead of conventional vincristine) plus 8 x rituximab 375 mg/m 2 (R) q 2 wks. or 12xR (days -4,-1,1,4,14,28,42,56,91,126,175, 238). Pts. with bulk (&gt;=7.5 cm) PET-positive after 6 cycles chemotherapy were assigned to RT (39.6 Gy), while PET-negative bulks were observed. Results: 187/505 (37%) had bulky disease and were compared to 117/306 (38%) RICOVER-60 pts. (38%) who had received 6xCHOP-14+8R. OPTIMAL&gt;60 pts. were older (70 vs. 68 years) and had more IPI=3 (33% vs. 29%) and IPI=4,5 (34% vs. 23%) compared to RICOVER-60. PET was performed in 166/187 OPTIMAL&gt;60 bulk pts. (reasons for no PET: early death: 5; excessive toxicity: 3; protocol violation: 1, non-compliance: 4, change of diagnosis: 6, others: 2). 80/166 (48%) bulks remained PET-positive after 6 cycles of chemotherapy and 62/80 (78%) were irradiated (reasons for no RT: progression: 8; medical reasons: 9; negative biopsy: 1), reducing RT from 67/117 (57%) in RICOVER-60 by 42% to 62/187 (33%) in OPTIMAL&gt;60. Despite the unfavorable demographics, outcome of the 187 bulk pts. in OPTIMAL&gt;60 was non-inferior to RICOVER-60, not even in the least intensive of the 4 OPTIMAL&gt;60 treatment arms consisting of 47 pts. who received 6xCHOP-14+8R as in RICOVER-60. 2-year PFS and OS in OPTIMAL&gt;60 was 79% and 88%, respectively, compared to 75% and 78% of the 117 RICOVER-60 pts. In a multivariable analysis adjusting for the IPI risk factors, the hazard ratio of the OPTIMAL&gt;60 compared to the RICOVER-60 bulk pts. was 0.7 (95% CI: 03.; 1.5; p=0.345) for PFS and 0.5 (95% CI: 02.; 1.3; p=0.154) for OS. Conclusions: RT can be spared in bulky disease PET-negative after chemotherapy. This strategy results in a 42% reduction of RT without compromising the outcome of these patients. Supported by Amgen, Roche, Spectrum. Clinical trial information: NCT01478542.
Impact of pre-diagnosis major depressive disorder and health-related quality of life on treatment choice for ductal carcinoma in situ in older women.
Authors: Daniela Lemos Buscariollo, Angel Cronin, Rinaa S. Punglia
Journal: Journal of Clinical Oncology (2016)

6526 Background: Limited data exists regarding how pre-diagnosis self-reported health-related quality of life (HRQOL) and mood disorders may impact treatment decisions for DCIS. Methods: We used the population-based SEER-MHOS linked dataset to assess impact of pre-diagnosis patient-reported HRQOL and major depressive disorder (MDD) on treatment decisions of older women with DCIS. Participants were women age ≥ 65 years who completed the MHOS ≤ 6 months before DCIS diagnosis. Predictor variables were MDD risk, Physical Component Summary (PCS), and Mental Component Summary (MCS) scores (measured by Short Form-36/Veterans RAND 12-item surveys). Presence of MDD risk was determined using a published algorithm based on response to four MHOS items. Associations between predictors and receipt of radiation therapy after breast conserving surgery (BCS+RT) versus surgery alone (BCS or mastectomy [MTX]) were assessed with univariate and multivariable logistic regression (MVA). Pre-specified covariates for MVA were age, number of comorbidities, diagnosis year, and marital status. Results: We identified 135 older women diagnosed with DCIS between 1998-2011 treated with BCS+RT (41%, n = 55), BCS (30%, n = 40), or MTX (30%, n = 40). Of these, 24% (n = 32) were at risk for MDD within 6 months before diagnosis. Among those at risk for MDD, 25% (n = 8) received BCS+RT, 34% (n = 11) BCS, and 41% (n = 13) MTX. Those at risk for MDD were less likely to receive BCT+RT relative to surgery alone (BCS/MTX; odds ratio [OR] 0.40, 95 % confidence interval [95% CI] 0.16 – 0.97, p = 0.04). After pre-specified covariate adjustment, women at risk for MDD remained less likely to receive BCS+RT (OR 0.30, 95% CI 0.12 – 0.80, p = 0.02). Backward selection MVA identified MDD risk and age as significant independent predictors for treatment. There were no significant associations between pre-diagnosis MCS or PCS and treatment. Conclusions: Older women at risk for MDD prior to DCIS diagnosis were less likely to receive RT after BCS compared to surgery alone. To our knowledge, this is the first study examining associations between DCIS treatment decisions and patient-reported HRQOL and MDD data collected prior to diagnosis.
Management of Liver Neuroendocrine Tumors in 2018
Authors: Deshka S. Foster, Robert Jensen, Jeffrey A. Norton
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in <i>EGFR</i>-Mutant NSCLC
Authors: Xiuning Le, Sonam Puri, Marcelo V. Negrao, Monique B. Nilsson, Jacqulyne Robichaux, Theresa Boyle, J. Kevin Hicks, Katherine L. Lovinger, Emily Roarty, Waree Rinsurongkawong, Ming Tang, Huiying Sun, Yasir Elamin, Lara C. Lacerda, Jeff Lewis, Jack A. Roth, Stephen G. Swisher, J. Jack Lee, William N. William, Bonnie S. Glisson, Jianjun Zhang, Vassiliki A. Papadimitrakopoulou, Jhanelle E. Gray, John V. Heymach
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Osimertinib was initially approved for T790M-positive non–small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients. Results: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as potential resistance drivers. Alterations of cell-cycle genes were associated with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P = 0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second PFS (PFS2) of 12.6 months; 21 patients received local consolidation radiation with a median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared with discontinuation (11.2 vs. 6.1 months, P = 0.02). Conclusions: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients. See related commentary by Devarakonda and Govindan, p. 6112.
Effect of ECOG PS on outcome of advanced or metastatic gastric patients treated with apatinib: Analysis from a post-marketing phase IV study.
Authors: Xiaoyan Lin, Jin Li, Shukui Qin, Lu Wen, Junsheng Wang, Wenying Deng, Tongfu Jia, Yi Ba, Haijun Zhong, Jianwei Yang, Yu-Xian Bai, Yifu He, Zhong Xie, Tienan Yi, Xiangyuan Wu, Feng Ye, Likun Liu, Yong Huang, Mei Wang, Guifang Zhang
Journal: Journal of Clinical Oncology (2018)

e16026 Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. The real benefits of apatinib for different patients (pts) with ECOG PS 0, 1, or ≥2 remain uncertain. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the effects of ECOG PS on clinical outcome. Methods: At the cutoff date of Dec. 21, 2017, Ahead-G201 study enrolled 1468 pts. 69 pts with missing data were excluded from this analysis. The adverse events (AEs) and clinical efficacy were evaluated for pts with ECOG PS 0, 1, and ≥2. Results: There were 229 pts with ECOG PS 0, 918 pts with ECOG PS 1, and 252 pts with ECOG PS ≥2. For baseline characteristics, statistical differences were observed in BMI. The mean daily dosage were respectively 514.3±98.5 mg, 518.2±101.5 mg, and 478.8±72.5 mg in pts with ECOG PS 0, 1, and ≥2. The data of safety and efficacy are listed in Table. For safety, the incidence of grade ≥3 drug related AEs (DRAEs) were respectively 26.6%, 30.9%, and 28.6% in pts with ECOG PS 0, 1, and ≥2. There was no significant difference among groups. For efficacy profile, no statistical difference was found in median progression-free survival (mPFS), but for median overall survival (mOS) the difference was significant (p< 0.001). The mOS were 7.8, 6.9 and 4.1 mos in pts with ECOG PS 0, 1, and ≥2. Multivariate regression analysis showed that ECOG PS was an independent prognostic factor for OS, after adjustment of baseline and treatment characteristics. Compared with ECOG PS ≥2, pts with ECOG PS 0 was significantly associated with longer OS (HR 2.63; 95%CI, 1.77-3.90). Conclusions: During apatinib treatment, the AEs were similar in pts with ECOG PS 0, 1, and ≥2. ECOG PS might be a prognostic factor for OS, and patients with ECOG PS 0 might benefit more. Clinical trial information: NCT02426034.Table ECOG PS-related safety and efficacy ECOG PS 0 (n = 229) ECOG PS 1 (n = 918) ECOG PS≥2 (n = 252) p DRAEs (%) 150 (65.5%) 602 (65.6%) 151 (59.9%) 0.242 DRAEs≥3 (%) 61 (26.6%) 284 (30.9%) 72 (28.6%) 0.408 ORR 12.4% 9.0% 12.7% 0.392 DCR 67.4% 68.4% 77.5% 0.274 PFS (mos, 95%CI) 4.0 (95%CI, 2.9-4.7) 4.5 (95%CI, 3.1-4.7) 3.4 (95%CI, 2.8-4.9) 0.746 OS (mos, 95%CI) 7.8 (95%CI, 6.6-12.2) 6.9 (95%CI, 6.1-7.7) 4.1 (95%CI, 3.4-4.7) < 0.001
P54 Case of Complex Tracheal Stenosis in Second Trimester Pregnant Woman: Idiopathic or Sequel of Endotracheal Tuberculosis?
Authors: N. Silva, W. Schmidt Aguiar, C. Amorim, D. Simões, K. Vasconcelos, R. Moreira, A. Vital, G. De Souto
Journal: Journal of Thoracic Oncology (2018)
Pathologic complete response (pCR) after neoadjuvant treatment in rectal cancer: Multi-institutional results in Spain.
Authors: Carles Pericay, Vicente Alonso, Mercedes Salgado Fernández, Ruth Vera, Maria Jose Safont, Carmen Guillen-Ponce, Ismael Macias Declara, Helena Asensio-Martínez, Jorge Adeva Alfonso, Javier Gallego Plazas
Journal: Journal of Clinical Oncology (2018)

e15690 Background: Standart treatment in locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NCRT). Of all treated patients (pts), less than 20% will achieve pCR. These pts have improved outcome, but neither prognostic nor predictive factors are described to define this group of patients. Aim: To describe clinical and pathologic characteristics of a series of pts in hospitals in Spain with pCR after NCRT in LARC. Methods: Patients treated with NCRT for LARC and pCR were included for analysis. Elegibility period: 2000 to 2016. Eight hospitals in Spain participated in the study. Clinical and pathological information was retrospectively collected, reviewed and followed-up. Informed consent was obtained. Statistical analyses was done based on SPSS v21. Results: 287 patients with pCR were recruited. Median age: 65.87 years (28.12-86.29) with 75% less than 72.52 years. Ratio male/female: 64,8%/35,2%. Stage pre-treatment: see table 1. Neoadjuvant Chemotherapy (CT): Fluoropyrimidine: 92.2%, Oxaliplatin combinations: 6.7%. Induction CT (36pt): Oxaliplatin combinations 100%. Surgery: High anterior resection 18.5%%, Low anterior resection 52.8%, Miles 22.4%, TEM: 5.9%. Median lymph nodes resected: 9 (0-30). Adjuvant CT: Yes/No 68.2%/31.8%. Delivey time since RTP to Surgery: 1.83 months (0.79-5,48). Time to relapse: since surgery: 12.52 month (2.89-58.36); since radiotherapy: 16.95 months (3.67-60.56). Follow-up: Relapse: 7.4% (21/287). At the end of the study, 11pt (3.9%) were dead of cancer and 25pt (8.8%) dead without cancer. OS: 11.97y (11.36-12.58). Relapse Free Survival: 12.61y (12.14-13.07). No differences between sex (p = 0.432), and administration of adjuvant CT (p = 0.446) were found. Performance of Miles surgery was statistically significant for progression (p = 0.015). Conclusions: pCR after NCRT in rectal cancer is feasible, but no prognostic o predictive characteristics could be concluded from our analysis. Table 1:. Ultrasonography and Magnetic Resonance Imaging pre-treatment results. TNM staging Ultrasonography Magnetic Resonance T1 1.9% 0.0% T2 13.5% 12.8% T3 78.8% 70.9% T4 5.8% 16.3% N- 49.0% 15.2% N+ 51.0% 84.8% Stage 1 5.8% 2.0% 2 43.2% 13.2% 3 51.0% 84.8%
Conditional Approximate Bayesian Computation: A New Approach for Across-Site Dependency in High-Dimensional Mutation–Selection Models
Authors: Simon Laurin-Lemay, Nicolas Rodrigue, Nicolas Lartillot, Hervé Philippe
Journal: Molecular Biology and Evolution (2018)

A key question in molecular evolutionary biology concerns the relative roles of mutation and selection in shaping genomic data. Moreover, features of mutation and selection are heterogeneous along the genome and over time. Mechanistic codon substitution models based on the mutation-selection framework are promising approaches to separating these effects. In practice, however, several complications arise, since accounting for such heterogeneities often implies handling models of high dimensionality (e.g., amino acid preferences), or leads to across-site dependence (e.g., CpG hypermutability), making the likelihood function intractable. Approximate Bayesian Computation (ABC) could address this latter issue. Here, we propose a new approach, named Conditional ABC (CABC), which combines the sampling efficiency of MCMC and the flexibility of ABC. To illustrate the potential of the CABC approach, we apply it to the study of mammalian CpG hypermutability based on a new mutation-level parameter implying dependence across adjacent sites, combined with site-specific purifying selection on amino-acids captured by a Dirichlet process. Our proof-of-concept of the CABC methodology opens new modeling perspectives. Our application of the method reveals a high level of heterogeneity of CpG hypermutability across loci and mild heterogeneity across taxonomic groups; and finally, we show that CpG hypermutability is an important evolutionary factor in rendering relative synonymous codon usage. All source code is available as a GitHub repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).
Co-amplification of <i>MET</i> and <i>PIK3CA</i> in NSCLC and data on a PDX mouse model.
Authors: Jin Kang, Xu-Chao Zhang, Jian Su, Zhi Xie, Wen-Feng Li, Yi-Long Wu, Jin-Ji Yang
Journal: Journal of Clinical Oncology (2017)

11591 Background: Amplification of the mesenchymal-epithelial transition ( MET) proto-oncogene or phosphatidylinositol3-kinase ( PI3K) is common in non-small-cell lung cancer (NSCLC) and represents a potential therapeutic target. NSCLC with coexisting driver mutations or amplifications is a cause of great concern. Methods: From 2013 until now, fluorescence in situ hybridization was used to screen for MET amplified NSCLC patients.The amplification of the MET was defined as centromere 7 ratio ≥ 2.0 and the criterion of Cappuzzi. The amplification of the PIK3CA was copy numbers ≥ 4.0. We established the patient-derived exnograft (PDX) mouse model from a dual MET/PIK3CA-amplified patient. Preclinical efficacy of single versus dual inhibition was evaluated in vivo. Six groups were allocated to receive the treatment of vehicle control, bozitinib,crizotinib, taselisib (PI3K inhibitor), bozitinib+taselisib, or crizotinib+taselisib, respectively. Results: Totally, 568 (568/2321, 24.47%) patients harbored positive MET amplification and 6 (6/568,1%) were comfirmed with dual MET/PI3K amplification. The two stageⅣ patients received MET inhibitor treatment.One trial (NCT02896231) patient was treated with bozitinib and achieved confirmed PR, but with 3 months PFS and 5 months OS. The best response was PR and PFS was 5.6 months for the other one receiving the study drug capmatinib (NCT02276027). In the PDX mouse model experiment, we found three single-anget inhibitors monotherapy to be active but only transiently effective in controlling the growth of PDX. The PDX models showed more sensitivity to taselisib among the three single-anget groups. In contrast, the combination of the two inhibitors caused a stronger and long-lasting growth inhibition in PDX models. The addition of taselisib to bozitinib or crizotinib monotherapy provided obvious enhanced activity. Regretfully, two mice died because of the toxicities in the crizotinib+taselisib group. Conclusions: Patients with dual MET/PIK3CA amplification represent a rare molecular subtype of NSCLC and have a relatively short duration of response to MET inhibitors.The combination of MET/PI3K inhibitors is synergistic preclinically.
Chloroquine as weekly chemoprophylaxis or intermittent treatment to prevent malaria in pregnancy in Malawi: a randomised controlled trial
Authors: Titus H Divala, Randy G Mungwira, Patricia M Mawindo, Osward M Nyirenda, Maxwell Kanjala, Masiye Ndaferankhande, Lufina E Tsirizani, Rhoda Masonga, Francis Muwalo, Sarah Boudová, Gail E Potter, Jessie Kennedy, Jaya Goswami, Blair J Wylie, Atis Muehlenbachs, Lughano Ndovie, Priscilla Mvula, Yamikani Mbilizi, Tamiwe Tomoka, Miriam K Laufer
Journal: The Lancet Infectious Diseases (2018)