tbuckley/cabot-search huggingface dataset:
Efficacy of gemcitabine in advanced unresectable biliary tract cancer
Authors: B. Mehrotra, S. Ahmed, A. Bhargava
Journal: Journal of Clinical Oncology (2004)

4259 Background: Gemcitabine is an active agent in pancreatic cancer.Limited data is available about its efficacy and tolerability in biliary tract cancers. Methods: We retrospectively evaluated gemcitabine efficacy in patients with advanced unresectable biliary tract cancer at Long Island Jewish Medical Center at New Hyde Park, New York from 1998 to 2002. The study protocol was approved by the hospital Institutional Review Board. Response was defined according to WHO criteria. Survival was calculated from initiation of gemcitabine therapy until death. Results: 12 patients with unresectable or recurrent biliary tract cancer were identified who received gemcitabine therapy. Median age at the time of diagnosis was 63 years (42–73) and Male: Female was 5:7. All patients had ECOG performance status of 0–1. Primary sites included: gallbladder cancer, n=3; intrahepatic cholangiocarcinoma, n=3; extra hepatic biliary duct cancer (including Klatskin tumors), n=6. Among 5 previously treated patients, 4 had received 5 fluorouracil and 3 were treated with local radiation therapy with concomitant 5 fluorouracil. Gemcitabine was administered once weekly infusion over 1 hour. Median delivered dose of gemcitabine was 750 mg/m2 (500–1000mg/m2) and median number of infusions administered were 9 (3–17). Adverse effects included grade 3 or 4 thrombocytopenia in 2 patients. Six patients required treatment interruption due to biliary tract infections. No objective responses were noted. Nine of 12 (75%) patients had stable disease, and 3 (25%) patients had disease progression. Median time to disease progression in patients with stable disease was 3 months (1–7+). Three of 9 patients with radiographic stable disease had greater than 50% reduction in serum CA 19–9 levels. Median survival of all patients was 6 months (2–15+). Conclusions: Gemcitabine therapy is well tolerated and has modest efficacy in biliary tract cancers.This agent merits further investigation as a single agent or as part of a combination therapy regimen. No significant financial relationships to disclose.
Methylations of NEUROG1, p16, and MLH1 and recurrence following adjuvant FOLFOX in colorectal cancer.
Authors: Hyun-Jung Lee, Sae-Won Han, Jeong Mo Bae, Nam-Yun Cho, Kyung-Hun Lee, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang, Seung-Yong Jeong, Kyu Joo Park, Jae-Gahb Park, Gyeong Hoon Kang, Tae-You Kim
Journal: Journal of Clinical Oncology (2012)

3624 Background: CpG island methylator phenotype (CIMP) is characterized by concurrent methylation of multiple CpG islands in tumor DNA, which can inactivate tumor suppressor genes or promote carcinogenesis. The prognostic impact of CIMP on treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP markers in colorectal cancer patients treated with adjuvant FOLFOX. Methods: Sporadic colorectal cancer patients treated with curative resection followed by adjuvant FOLFOX were included. DNA was extracted from formalin-fixed paraffin-embedded surgical specimen. 8 CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, P16, RUNX3 and SOCS1) were examined using MethyLight analysis. Disease-free survival (DFS) was evaluated according to each methylation loci. Results: A total of 322 patients were included. Methylation at 1 or more loci was observed in 150 patients (46.6%) and 6 or more loci in 15 (4.7%). During a median follow-up duration of 39.7 months, 55 recurrences were observed. Three year DFS in the patient cohort was 84%. CRABP1 (23.9%) was the most frequently methylated loci, followed by p16 (22.7%) and NEUROG1 (20.8%). Patients having methylation at NEUROG1 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.014) and p16 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.12) had worse DFS, whereas methylation at MLH1 had better DFS (3 year DFS 100% in (+) vs. 86% in (-), p = 0.19). In a combined analysis, patients with MLH1(-)/NEUROG1(+)/p16(+) had worst treatment outcome compared to MLH1(-)/NEUROG1(+) or p16(+), MLH1(-)/ NEUROG1(-) /p16(-), and MLH1(+) (3 year DFS 62%, 82%, 87%, and 100%, respectively; p = 0.002). In multivariate analysis, NEUROG1(+)/p16(+) was associated with significantly higher recurrence compared with other patients (adjusted hazard ratio (HR) 2.15 (95% confidence interval (CI) 1.08 - 4.27, p = 0.029). Conclusions: Methylation status of NEUROG1, p16, and MLH1 is associated with recurrence following adjuvant FOLFOX in stage II/III colorectal cancer. Further validation and translational studies to improve treatment outcome in the subset of patients are warranted in the future.
Association of pyrexia and durable response in advanced melanoma patients treated with the combination of dabrafenib and trametinib.
Authors: Edward Cha, Andrea Kantor, Alain Patrick Algazi, Jimmy Hwang, Jennifer Luan, Alan Paul Venook, Leslie Ziani, Shonda M Little, Kiran Patel, Adil Daud
Journal: Journal of Clinical Oncology (2012)

e19046 Background: Pyrexia (fever) is a common adverse event associated with combined BRAF and MEK inhibition (dabrafenib and trametinib). Although the mechanism of fever is unclear, we explore pyrexia as a pharmacodynamic marker for clinical response. Methods: A phase II international trial with dabrafenib and trametinib in metastatic melanoma (MM) and colorectal cancers (CRC) harboring BRAF mutations is ongoing. Twenty-nine patients (pts) were enrolled at UCSF between January 2011 and January 2012. Fevers were graded based on temperature and coinciding symptoms, and an episode of pyrexia was defined as a temperature of &gt;100 °F at least once a day for one or more consecutive days. Tumor assessments were performed every 8 weeks (wks). Results: To date, 13 pts with MM and 5 with CRC had tumor assessments up to 24 wks. In MM, pyrexia was reported 2 or more times in 7 pts; 5 had none, and 1 reported one episode of Grade 1 pyrexia. Episodes occurred 2-4 wks after starting treatment, and time between subsequent recurrences ranged from 1 to 25 wks. Neutrophil counts showed early fluctuations, but none had neutropenia. Of the 7 pts with recurring fevers, 5 had partial responses and 2 had stable disease at 8 wks. Of the 6 pts with nonrecurring or no fevers, 2 had partial responses at 8 wks, and 1 progressed. At 24 wks, all 7 pts with ≥ 2 fever episodes remained progression-free, whereas 0/6 pts with &lt; 2 fever episodes were progression-free (p &lt; 0.001). Pts without progression continued to have recurring fevers (median = 4). There were no differences by disease stage (12 of 13 with M1c) or mutation status (10 with V600E; 2 with V600K; 1 with V600E + V601I). While pts with CRC had pyrexia, no association between pyrexia and response was noted; however, only 5 pts are included in this analysis. Conclusions: In this limited analysis of pts with MM, recurrent fevers were associated with durable response (≥ 24 wks). These results suggest that pyrexia could be a marker for inflammation and antitumor activity. Further studies are underway to characterize cytokine profiles and immune responses. [Table: see text]
Incorporation of advanced image analysis in novel post-prostatectomy systems pathology models as an approach to replace the clinical Gleason and provide robust risk stratification.
Authors: Michael J. Donovan, Faisal M Khan, Richard Scott, Gerardo Fernandez, Carlos Cordon-Cardo
Journal: Journal of Clinical Oncology (2015)

e16134 Background: Quantitative analysis of formalin-fixed paraffin-embedded prostatectomy tissue can help guide management of post-operative prostate cancer (PCa) patients. We have previously published the results of our systems pathology (SP) based approach, which includes integration of clinical data (Gleason grade) with H&E morphology and biomarker multiplex immunofluorescence, to predict disease progression post treatment. We sought to remove the clinical histologic Gleason grade and problematic H&E metrics from our previous studies and construct new models which include IF prostate gland morphometry integrated with biological attributes. Methods: 373 patients with overall 5 year median follow up were analyzed to build a prostatectomy SP model for disease progression (including death-of-disease, metastasis or PSA rise post adjuvant therapy). Clinical metrics (without biopsy or prostatectomy Gleason) were combined with novel quantitative biometric features derived from computerized analysis of morphology and biomarker expression in immunofluorescent (IF) PCa images. This permitted differentiable analysis of PCa biomarkers such as androgen receptor (AR) in high and low Gleason grade glands of the patient. The concordance index (CI), sensitivity and specificity were used to assess performance of the model. Results: A multivariate model with a CI of 0.87, sensitivity of 81% and specificity of 86% was trained. The model consisted of 3 features including seminal vesicle invasion status and quantitative dispersion/spread of epithelial nuclei. The third and most important feature was a novel co-localization of AR in different glandular subtypes which separately assessed AR expression depending on the glandular sub-types within the tumor sample. Conclusions: A new SP model without clinical Gleason and H&E metrics has been trained to predict post-prostatectomy disease progression. Novel quantitative image analysis of morphology and IF biomarker expression yield robust and reproducible risk stratification. These models should add valuable information in constructing post-treatment paradigms for optimizing outcome.
The impact of pseudoprogression on the current treatment strategy of glioblastoma patients.
Authors: Edward A. Neuwelt, Prakash Ambady
Journal: Journal of Clinical Oncology (2015)

e13055 Background: Pseudoprogression is an inflammatory response to chemoradiotherapy (CRT) in high grade gliomas such as glioblastoma multiforme (GBM) that can be confused with true tumor progression on magnetic resonance imaging (MRI). Pseudoprogression is associated with improved survival. Current response assessment criteria do not adequately address important clinically relevant variables such as altered imaging findings due to vascular targeting agents, pseudoprogression that occurs beyond 3 months, or immune modulating agents that may enhance pseudoprogression. Our goal is to increase awareness in the neuro-oncology community of issues surrounding the diagnosis of pseudoprogression. Methods: This series consists of 68 patients previously reported with histologically-proven newly diagnosed GBM who received standard CRT consisting of radiation and temozolomide, as well as other study patients. Results: Median survival in 24 (35.3%) of the 68 previously reported patients with pseudoprogression was 34.7 months (95% CI 20.3-54.1), significantly longer than the 13.4 months (95% CI 11.1-19.5) in 44 (64.7%) patients without pseudoprogression (P < 0.0001). This report includes additional patients with pseudoprogression as determined using blood volume measures to correlate with survival. Conclusions: Improved detection of pseudoprogression and correct differentiation from true tumor progression is essential for optimal patient management and to evaluate outcomes in clinical trials, especially those including immunotherapy. The incidence of pseudoprogression was recently reported to be less than 10% using anatomical contrast enhanced imaging. However, this may be due to the limited sensitivity of anatomical contrast enhanced imaging in differentiating true progression from pseudoprogression. Additional quantitative measures like rCBV in the area of interest significantly minimizes false positive reading and better correlates with survival. rCBV should be a part of patient enrollment criteria in experimental studies to decrease the chance of enrolling patients with pseudoprogression, which could include as many as 50% of patients with glioblastoma.
Central nervous system involvement in T-cell lymphomas: A single center experience.
Authors: Ronit Gurion, Jocelyn Maragulia, Andrew David Zelenetz, Steven M. Horwitz
Journal: Journal of Clinical Oncology (2012)

8069 Background: Large experiences have reviewed the risk of central nervous system (CNS) involvement in diffuse large B-cell lymphoma (DLBCL), but there are limited data on CNS involvement by peripheral T cell lymphomas (PTCL). We characterized the incidence of CNS involvement, risk factors and outcome in a large single institution dataset of PTCL. Methods: Retrospective review of the T-cell lymphoma database at Memorial Sloan Kettering Cancer Center. We identified 232 patients with any subtype of PTCL between 1994-2011 with a minimum 6 months of follow-up or an event defined as relapse or death. We excluded indolent forms of cutaneous T cell lymphoma. Results: Histologies included PTCL-NOS (31%), angioimmunoblastic (16.8%), anaplastic (ALCL), ALK negative (12%), ALCL, ALK positive (6%), extranodal NK/T cell lymphoma (7.3%), adult T cell leukemia/lymphoma (ATLL) (7.3%), and transformed MF (8.6%). Median age was 58 years with 59.9% men. CNS disease was found in 17 patients (7.32%). 8 (47%) had pathologic confirmation and 7 (41.2%) were clinically diagnosed. Two had other diagnoses at biopsy: DLBCL and glioblastoma. Median time to CNS involvement was 2.33 months (range, 0.16 to 103.1). CNS prophylaxis was given to 24 (10.34%), primarily intrathecal methotrexate. There was no difference in CNS involvement in patients who received prophylaxis vs. those who did not: 3/24 (12.5%) vs. 12/208 (5.77%) (p=0.192) respectively. Univariate analysis identified: stage III-IV (p=0.03), bone marrow involvement (p=0.018), &gt;1 extranodal site (p&lt;0.001), and ATLL vs. all other subtypes, 23.5% vs. 6.4% (p=0.003) as risk factors for CNS disease. On multivariate analysis, &gt;1 extranodal site (p=0.004) and high intermediate (H-I) and high (H) IPI (IPI 3-5 &amp; 4-5) were predictive for CNS involvement (p&lt;0.05). The median survival of patients with CNS involvement was 2.628 months. Conclusions: Despite high relapse rates, PTCL carries a low risk of CNS involvement other than the ATLL subtype. As with other aggressive lymphomas, survival of patients with CNS involvement is poor and risk factors include: &gt;1 extra nodal site and H-I-H IPI. In this dataset, prophylactic intrathecal chemotherapy does not appear to reduce the risk of CNS disease.
Laparoscopic Hysterectomy for Endometrial Cancer
Authors: Jason D. Wright
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Food effect substudy of a phase 3 randomized double-blind trial of maintenance with niraparib (MK4827), a poly(ADP)ribose polymerase (PARP) inhibitor versus placebo in patients with platinum-sensitive ovarian cancer.
Authors: Kathleen N. Moore, Zhi-Yi Zhang, Shefali Agarwal, Manish R. Patel, Howard A. Burris, Robert E. Martell, Vikram Kansra
Journal: Journal of Clinical Oncology (2014)

e16531 Background: Niraparib is an oral, potent PARP1/2 inhibitor that induces synthetic lethality in BRCA1/2 deficient and platinum sensitive tumors. A recent study of oral agents approved by the US Food and Drug Administration in the last 10 years1 demonstrated that oral oncology drugs have generally been labeled to be taken fasting, despite food effects resulting in as large as a four to ten-fold increase in exposure for some drugs. Methods: The primary objective of the Food Effect Sub Study was to evaluate the effect of a high fat meal on the pharmacokinetics of a single 300 mg dose of niraparib in patients with ovarian cancer. A 2-treatment (fed versus fasting), 2-way crossover design was used to evaluate the effect of food on PK parameters. Sixteen subjects were enrolled in the food effect cohort, and each subject received 2 separate 300-mg doses of niraparib, 1 each in a fasting and a fed state. Results: Table below summarizes the key Pharmacokinetic Parameters Following 300 mg Oral Dose of Niraparib in the Absence Fasted (Ref) or Presence Fed (Test) of Food (N = 15). As shown in the table, the mean ratios of Cmax and AUC0-inf in the fed versus fasted state were 0.83 and 1.08, respectively. Plasma concentrations of niraparib declined in a similar manner under fed and fasted conditions with a mean t1/2 of 57 and 59 hours, respectively. The median Tmaxin the fed condition was approximately two times of that observed in the fasted condition and overall comparable for subjects under fasted and fed conditions. Conclusions: Administration of niraparib with food is expected to have a negligible effect on its pharmacokinetics. Clinical trial information: NCT01847274. Treatment Tmax (h) Cmax (ng/mL) AUC0-t (h*ng/mL) AUC0-inf (h*ng/mL) T1/2 (h) Fasted (ref) 3.5 ± 0.32 794 ± 107 28801 ± 4905 34565 ± 7602 59 ± 4.9 Fed (test) 8.1 ± 1.3 582 ± 59 29042 ± 3955 32514 ± 4738 57 ± 3.1 Ratio (fed/fasted) a 0.83 1.09 1.08 1.04 *Means of the individual ratios. 1 Geers HC, Bouvy ML, Heerdink ER (2011) Influence of therapeutic complexity on medication adherence in the Netherlands. Arch Intern Med 171:864–865.
Evaluation of the adjuvant radiation treatment-effect heterogeneity using genomic signature for locoregional relapse and long-term outcome.
Authors: Maggie Chon U Cheang, Charles M. Perou, Timothy Joseph Whelan, Cheng Fan, Tinne Laurberg, David Voduc, Scott Tyldesley, Torsten Nielsen, Karen A. Gelmon
Journal: Journal of Clinical Oncology (2014)

1031 Background: In a retrospective analysis of two similar randomized radiation therapy (RT) trials (i.e. British Columbia (BC) and DBCG 82b), we reported significant survival benefits for post-mastectomy RT in Luminal A. Here we examined the predictive value of additional genomic profiles in the BC trial for loco-regional recurrences (LRR) and breast cancer survival (BCSS) in node-positive, pre-menopausal breast cancer patients randomized to adjuvant chemoradiation or chemotherapy. Methods: In the BC trial, 318 patients received adjuvant cyclophosphamide, methotrexate, fluorouracil and were randomized to with or without postmastectomy RT. From 145 formalin fixed paraffin embedded tissues available, expression profiles of 66 genes were done with the Nanostring nCounter. Treatment effects on LRR and BCSS events were examined by subpopulation treatment effect pattern plots. The research-based PAM50 proliferation score, Risk of Recurrence score (ROR-T and ROR-PT), and genes related to basal-like (ie. 13-genes VEGF-signature (VEGF-s), RAD17, RAD50 and RB1) were calculated. Results: Overall, patients in the RT arm (n= 69) were significantly associated with better LRR and BCSS than the non-RT-treated arm (n = 76). No significant treatment-effect heterogeneity was detected for VEGF-s, RAD17 and RAD50 score. Patients with lower RB1 mRNA level, and higher proliferation score, had better LRR survival when they received RT (Table). The patterns of treatment efficacy on LRR and BCSS were the most significant for the varying levels of risk score (ROR-T, -PT), particularly for patients with higher scores (Table) who showed the poorest prognosis, but whom may still benefit from adjuvant RT. Conclusions: RB1, proliferation score and ROR-T predicted LRR and BCSS benefit for adjuvant RT. The clinical utility of these biomarkers as predictor requires confirmation in a second independent trial. STEPP analysis of the treatment effect of adjuvant RT at 10-years. Covariate Interaction test P LRR BCSS RB1 mRNA level KM 0.08 0.49 HR 0.03 0.41 Proliferation score KM 0.02 0.17 HR 0.06 0.24 ROR-T KM 0.01 < 0.001 HR 0.21 0.02 ROR-PT KM 0.02 0.09 HR 0.1 0.04 Abbreviations: KM, Kaplan–Meier; HR, hazard ratio.
Combined Treatment with Short Synthetic Anti-Lymphoma Peptide and CpG ODN; A Therapeutic Vaccine Which cures the A20 Lymphoma in Balb/C Mice.
Authors: Arne Kolstad, Roch Houot, Gerd Berge, Øystein Rekdal, Debra Czerwinski, Matthew Goldstein, Joshua Brody, R. Levy
Journal: Blood (2008)
Phase I clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 with green fluorescent protein imaging.
Authors: Jesus Corral Jaime, Anne Mary Young, Joaquin Mateo, Timothy Anthony Yap, Katie Ann Denholm, Krunal Jitendrakumar Shah, Nina Tunariu, Salem Sassi, Lena Karapanegiotou, David Mansfield, L Rhoda Molife, Kevin J. Harrington, Johann Sebastian De Bono
Journal: Journal of Clinical Oncology (2012)

2530 Background: GL-ONC1 is a genetically engineered vaccinia virus attenuated by insertion of the RUC-GFP (Renilla luciferase and Aequorea green fluorescent protein fusion gene), beta-galactosidase (lacZ) and beta-glucuronidase (gusA) reporter genes into the F14.5L, J2R (thymidine kinase) and A56R (hemaglutinin) loci. A phase I clinical trial of iv GL-ONC1 was pursued to evaluate safety, tolerability, tumour delivery, neutralizing antibody development and anti-tumour activity. Methods: GL-ONC1 was administered to patients with advanced solid tumours at escalating doses (1×10 5 , 1×10 6 , 1×10 7 , 1×10 8 , 1×10 9 , 3×10 9 plaque-forming units (pfu) on day 1; 1.667×10 7 and 1.667×10 8 pfu on day 1-3 of a 28-day cycle) using a 3+3 dose escalation design. Green fluorescent protein (GFP) imaging was performed on skin rash and mucosal tumour lesions at baseline and after each cycle. Optional tumour biopsies were obtained for pharmacodynamic and viral delivery evaluation. Results: 27 patients (21 males, median age 60 years) were treated. One of six patients at the 1x10 9 pfu dose level developed a dose-limiting, grade 3 rise in aspartate transaminase levels after a single infusion. Other reported adverse events (grade 1/2) included pyrexia (21), musculoskeletal pain (9), fatigue (8), nausea (7), and vomiting (4). Two patients developed skin rash during the first week of treatment, which appeared green by GFP and were positive to viral plaque assay (VPA). VPA of blood, urine, stool and sputum were negative for viral shedding in all but one patient who had positive shedding for 11 days. Increased neutralizing antibody titres were detected in all tested patients apart from one. Best response by RECIST was stable disease at 48 weeks (1), 24 weeks (3) and 8-12 weeks (5). A patient with squamous cell carcinoma of the tongue had a biopsy after 4 cycles which showed positive IHC staining of vaccinia virus. This is the first time that a virus is shown to be delivered to solid tumour after iv delivery. Conclusions: GL-ONC1 administered iv is well tolerated, with documented colonisation in patient tumour, and preliminary evidence of anti-tumour activity.
Dendritic Cells Display Subset and Tissue-Specific Maturation Dynamics over Human Life
Authors: Tomer Granot, Takashi Senda, Dustin J. Carpenter, Nobuhide Matsuoka, Joshua Weiner, Claire L. Gordon, Michelle Miron, Brahma V. Kumar, Adam Griesemer, Siu-Hong Ho, Harvey Lerner, Joseph J.C. Thome, Thomas Connors, Boris Reizis, Donna L. Farber
Journal: Immunity (2017)