tbuckley/cabot-search huggingface dataset:
A phase I trial of ublituximab (TG-1101), a novel glycoengineered anti-CD20 monoclonal antibody (mAb) in B-cell non-Hodgkin lymphoma patients with prior exposure to rituximab.
Authors: Owen A. O'Connor, Changchun Deng, Jennifer Effie Amengual, Mazen Y. Khalil, Marshall T. Schreeder, Daruka Mahadevan, Petros Nikolinakos, Ahmed Sawas, Jasmine M. Zain, Molly Patterson, Amber Moon, Emily K. Pauli, Kathy Cutter, Michelle Ann Mackenzie, Marnie Brotherton, Jamie Hodgson, Christen N Cooper, Peter Sportelli, Hari P. Miskin, Charles Michael Farber
Journal: Journal of Clinical Oncology (2014)

8524 Background: Ublituximab (UTX) is a novel mAb targeting a unique epitope on the CD20 antigen, glycoengineered for greater ADCC than rituximab (RTX). A prior Phase I/Ib trial with UTX monotherapy in patients (pts) with relapsed/refractory (R/R) CLL reported an ORR of 45%. Herein we report the results of a Phase I/Ib trial of UTX in pts with RTX R/R B-cell lymphoma (BCL). Methods: Eligible pts have R/R BCL that was previously treated with RTX containing regimens, with ECOG PS < 3. 3+3 dose-escalation evaluated cohorts of 450, 600, 900, and 1200 mg. Select expansion cohorts have included R/R NHL and CLL pts. UTX is administered weekly x 4 doses in Cycle 1 for NHL pts and on days 1, 8, 15 in Cycles 1 & 2 for CLL pts (cycle = 28 days), with maintenance for all pts. Primary endpoints: Maximum Tolerated Dose (MTD) and Dose Limiting Toxicities (DLT). Secondary endpoints: PK/PD and Efficacy. Results: 32 pts were enrolled. 17 M/15 F with: Median age 68 yr (range 45-88); ECOG 0/1/2: 12/18/2; Median prior Tx = 3 (range 1-9); 72% with > 2 prior RTX therapies; and 41% were RTX refractory. No DLTs have been observed. Gr 3/4 AE’s at least possibly related to UTX have been reported in 6/32 pts (19%) and include: neutropenia, anemia, weakness, and fatigue. Infusion related reactions requiring interruption occurred in 8/32 pts (25%); however, all pts received all planned infusions with an ave infusion time of ~90 min for dose 4 and later. PK/PD analysis is ongoing. As of Jan 2014, 29/32 pts are evaluable for response (Table). Median ALC depletion in CLL pts was 93% after 2 UTX infusions. Median PFS for all pts is 34 weeks (95% CI: 19, NA) with no observed progression in 16/29 pts (range 4 - 18 mo). Conclusions: Single agent UTX is well tolerated and active in RTX exposed patients. Responses were observed in 67% of CLL and 67% MZL pts with median PFS not reached for each group. 86% of pts achieved at least SD, including 100% of CLL, MZL and DLBCL pts. Studies are ongoing with UTX in combination with novel targeted agents (PI3K-δ and BTK inhibitors). Clinical trial information: NCT01647971. Type Pts (n) CR (n) PR (n) ORR (%) PD (n) % pts > SD for 12 wks FL 11 1 2 27% 2 82% CLL 6 - 4 67% - 100% MZL 6 2 2 67% - 100% MCL 5 - - - 2 60% DLBCL 1 - 1 100% - 100% Total 29 3 9 41% 4 86%
Developing a cardiac monitoring plan in at-risk cancer survivors.
Authors: Aubri Veneruso, Megan Rae Slocum, Sheetal Mehta Kircher, Nausheen Akhter, Gillian Murtagh, Jonathan Blake Strauss
Journal: Journal of Clinical Oncology (2017)

133 Background: Improvements in early detection, screening, and treatment of cancer translate into survivors living longer, highlighting the need for guidelines to address the late and long-term effects of cancer treatment. A particularly concerning effect is Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). Cancer treatments can result in a range of cardiovascular toxicity including left ventricular dysfunction, heart failure and radiation-induced heart disease (RIHD). Various consensus statements related to cardiovascular care for adult cancer survivors exist; however there are no globally accepted follow-up guidelines. Our purpose is to create a protocol to stratify a survivor’s cardiac risk and provide a basis for follow-up recommendations. Methods: We first evaluated existing resources within our institution and identified key stakeholders who were recruited to form a multidisciplinary workgroup (2 survivorship advanced practice providers, an oncologist, a radiation oncologist, and 2 cardio-oncologists). We then reviewed current research and literature on cardiotoxic cancer therapies and identified two consensus statements from the American Society of Echocardiography and the European Association of Cardiovascular Imaging which helped inform our protocol. Finally, we created a cardiac assessment that could be applied in the pre-treatment phase and extend into the post-treatment phase. Results: Two assessment tools were developed. The first is an algorithm initiated in the pre-treatment setting by an oncologist when a Type I or Type II cardiotoxic agent is planned. The second is a risk assessment tool that is initiated in the post-treatment setting to stratify cardiac risk and provide follow-up recommendations. Conclusions: Development of standardized guidelines for assessment and treatment of late and long-term effects of treatment is critical. This protocol has been developed to account for the many factors that contribute to overall cardiac risk after various anti-cancer therapies. Further data is needed to evaluate long-term cardiac and survival outcomes based on this protocol.
A randomized multicenter phase II trial on efficacy of a hydrocolloid dressing containing ceramide with a low-friction external surface for hand-foot skin reaction caused by sorafenib in patients with renal cell carcinoma.
Authors: Nobuo Shinohara, Norio Nonomura, Go Kimura, Masatoshi Eto, Hironobu Minami, Naoya Yamazaki, Seiji Naito
Journal: Journal of Clinical Oncology (2013)

9623 Background: Hand-foot skin reaction (HFSR) is the most clinically significant and dose-limiting dermatologic toxicity in metastatic renal cell carcinoma (mRCC) patients who receive sorafenib (SOR). At present, evidence-based management strategy is not completely established. Since HFSR may be attributed to keratinous disorders of the skin and tends to develop in areas on the soles of the feet subject to strong pressure, a hydrocolloid dressing containing ceramide (a protective dressing against pressure ulcer) may prevent the development and worsening of HFSR. The purpose of the study is to investigate the usefulness of this material for HFSR on the soles of the feet in mRCC patients treated with SOR. Methods: Patients with grade 1 HFSR on the soles of the feet were randomly assigned 1:1 to receive a hydrocolloid dressing containing ceramide (Arm A) or 10% urea cream (Arm B). The detailed protocol of this study was presented in ASCO 2011 (Trial in Progress; TPS 233). A hydrocolloid dressing containing ceramide was applied to affected sites on the soles of the feet, but not to the hands. The primary endpoint was the incidence of Grade 2 or 3 HFSR on the soles of the feet in the first 4 weeks. Results: Thirty-three patients were evaluated; 17 patients in Arm A and 16 patients in Arm B. There were no significant differences in baseline characteristics between two arms. Over the 4 weeks period of this study, the incidence of Grade 2 or 3 HFSR on the soles of the feet was significantly lower in Arm A than Arm B; 5 (29%) patients in Arm A versus 11 (69%) in Arm B, p=0.03. On the other hand, the incidence of HFSR on the hands was similar between two arms. The median time to Grade 2 or 3 HFSR on the soles of the feet was significant longer in Arm A compared with Arm B; not reach (95%CI 13-28+) in Arm A versus 22 days (95%CI 15-27), p=0.03. Regarding the pain levels on the soles, Arm A was superior to Arm B (p=0.05). Conclusions: These results indicate that a hydrocolloid dressing containing ceramide with a low-friction external surface is effective in preventing the worsening of HFSR caused by SOR in mRCC patients. Clinical trial information: UMIN000002016.
Handbook of Bacteriology for Students and Practitioners of Medicine.
Journal: JAMA (1925)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Prognostic factors for recurrence and reasonable operation method discussed of papillary thyroid carcinoma.
Authors: Rui Chen, Jingqiang Zhu, Tao Wei, Rixiang Gong, Zhihui Li, Hongling Peng, Feng Liu, Xiuhe Zou, Yu Ma
Journal: Journal of Clinical Oncology (2014)

e17021 Background: Papillary thyroid carcinoma(PTC) is the most common type of thyroid cancer. Up to 35% of patients with PTC develop locoregional recurrences and a third patients with local recurrences will eventually die of cancer. However, there is still controversy for PTC patients whether conventional undergo total thyroidectomy(TT)/ or neer total thyroidectomy(NTT). Through analyzing PTC patients with postoperative follow-up, look for the risk factors of recurrence of the disease, and then to propose a more reasonable operation method in the initial treatment. Methods: 694 PTC patients (143 males and 551 females) who underwent initial surgery to be enrolled between 2001-2010. The postoperative follow-up ranged from 24 to 124 months, and was 43.9±19.5 months on average. Results: 18 patients had temporary recurrent laryngeal nerve palsy, 8 patient had permanent recurrent laryngeal nerve palsy, 202 patients experienced temporary hypoparathyroidism and 18 patients experienced permanent hypoparathyroidism. 140 PTC patients of 332 patients have shown recurrence or metastasis. The mean duration of recurrence and metastasis is 34±11.5 months(range 8-72months). extrathyroidal extension (P<0.001), tumor-multifocal (P<0.001)and neck lymph node metastasis (P<0.001), extrathyroidal extension (P<0.001) and neck lymph node metastasis (P<0.001)were independent predictors of recurrence or metastasis with PTC. TT/NTT can reduce recurrence and metastasis rate in PTC patients with size > 1cm (P=0.013),Prophylactic CND can reduce and metastasis rate with PTC patients (P<0.001). Size of primary >4cm (P=0.003), extrathyroidal extension (P<0.001) were independent predictors for lateral lymph node metastasis with PTC. Conclusions: Size of primary >4cm, extrathyroidal extension and neck lymph node metastasis were predictors of recurrence or metastasis with PTC. For these PTC patients, a more extensive and thorough surgery should be adopt. TT/NTT can reduce recurrence and metastasis rate in PTC patients with size>1cm. PTC patients with size >1cm should be undergo TT/NTT in the initial treatment. Prophylactic CND can reduce postoperative recurrence and metastasis rate with PTC patients.
A three-gene expression signature model to predict neo-chemoradiotherapy response of esophageal squamous cell carcinomas.
Authors: Jing Wen, Hong Yang, Kongjia Luo, Yi Hu, Xu Zhang, Geng Wang, Yuping Chen, Zhijian Chen, Ting Lin, Huiyun Wang, Mengzhong Liu, Jianhua Fu
Journal: Journal of Clinical Oncology (2013)

e15135 Background: Preoperative chemoradiotherapy (CRT) followed by surgery has been proved to improve survival in comparison with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method could prediction CRT response. In this study, we aim to identify mRNA markers for ESCC CRT-response prediction. Methods: Gene expression analyses were performed on pretreatment cancer biopsies from 28 ESCCs who received neoadjuvant CRT and surgery. Surgical specimens were assessed for the pathological response to CRT. The identified differentially expressed genes were validated by real-time quantitative polymerase chain reaction (qPCR), based on which a classifying model was built up by Fisher’s linear discriminant analysis. The predictive power of this model was further assessed in another set of 32 ESCCs. Results: The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than 2-fold changes between pathological complete responsers (pCRs) and less than pCRs (&lt;pCRs), among which 6 genes (LIMCH1, SDPR, Clorf226, SLC9A9, GSTM3, and IGSF10) were down-regulated and 4 genes (MMP9, MMP1, MMP12 and OASL) up-regulated in pCRs versus &lt;pCRs. A prediction model based on qPCR values of 3 genes was built up, Y=-10.388 - 0.343 × MMP1 + 0.642 × LIMCH1 + 0.921 × Clorf226 with a cut-off value of 0.607. It provided a predictive accuracy of 85.7% with leave-one-out cross-validation. Further, the predictive power of this model was validated in another set of 32 ESCCs, among which a predictive accuracy of 81.3% was achieved. Conclusions: The combination of three genes by qPCR identified by microarrays in our study provides possibility for ESCC CRT prediction, which will facilitate individualization of ESCC treatment. Further perspective validation in larger independent cohorts is warranted to fully assess the predictive power of this prediction model.
Preliminary results from a phase Ib/II, open-label, dose-escalation study of the oral BRAF inhibitor LGX818 in combination with the oral MEK1/2 inhibitor MEK162 in <i>BRAF</i> V600-dependent advanced solid tumors.
Authors: Richard Kefford, Wilson H Miller, Daniel Shao-Weng Tan, Ryan J. Sullivan, Georgina Long, Rodrigo Dienstmann, Wai Meng David Tai, Keith Flaherty, Simone Stutvoet, Karl Maria Schumacher, Simon Wandel, Laure A. De Parseval, Josep Tabernero
Journal: Journal of Clinical Oncology (2013)

9029 Background: Clinical data indicate that combining a BRAF and a MEK inhibitor (BRAFi, MEKi) may be more effective than BRAFi monotherapy in BRAF-mutant metastatic melanoma and that a MEKi may overcome or delay resistance to a BRAFi. Methods: This ongoing phase 1b/2 study is evaluating the combination of LGX818, a potent, selective BRAF inhibitor, and MEK162, a selective MEK1/2 inhibitor, in BRAFi-naive and -pretreated patients with BRAF-mutant tumors. The objective of the phase 1b part is to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D) for oral, daily LGX818 + MEK162 in BRAF V600–mutant advanced solid tumors. A Bayesian logistic regression model with overdose control guides the treatment dose escalation. Results: As of January 8, 2013, 20 patients (7 BRAFi-naive melanoma; 9 BRAFi-pretreated melanoma; 2 BRAFi-naive thyroid cancer; 1 BRAFi-naive metastatic colorectal cancer; 1 BRAFi-pretreated colorectal cancer) were treated with LGX818 qd + MEK162 bid at the following dose levels (DLs): 50 mg + 45 mg, 100 mg + 45 mg, 200 mg + 45 mg, and 400 mg + 45 mg. No dose-limiting toxicity has been observed at these DLs. The next DL of 600 mg + 45 mg is under investigation. The single agent RP2Ds for LGX818 and MEK162 are 450 mg and 45 mg, respectively. The most common adverse events (≥ 20%, all grades) suspected to be treatment related were nausea, abdominal pain, and headache. No events of fever, hand-foot-skin reactions, hyperkeratosis, or squamous cell carcinoma were observed. In patients with at least 1 post-baseline CT scan available for investigator-determined response, a complete response was observed in 1/7 (14%) BRAFi-naïve melanoma patients and partial responses were observed in 5/7 (71%) BRAFi-naive melanoma patients, 2/9 (22%) BRAFi-pretreated melanoma patients (starting at 50 mg + 45 mg DL), and 1/2 thyroid cancer patients. Conclusions: Preliminary data from this study indicate that LGX818 + MEK162 can be safely combined with promising clinical benefit. No febrile events or photosensitivity were reported suggesting a distinct safety profile for this BRAFi/MEKi combination vs others. Clinical trial information: NCT01543698.
Effect of smoking on survival from non-small cell lung cancer.
Authors: Vijaya Raj Bhatt, Fausto R. Loberiza, Apar Kishor Ganti
Journal: Journal of Clinical Oncology (2013)

1570 Background: Although a well-established risk factor for lung cancer, the impact of smoking on the survival of non-small cell lung cancer (NSCLC) is not well-known. This study evaluated the effects of tobacco exposure on outcomes from NSCLC. Methods: We performed a retrospective analysis of Veteran’s Affairs Comprehensive Cancer Registry of NSCLC patients diagnosed between 1995 and 2009. Data abstracted included age, gender, family history, stage at diagnosis, histology, tumor grade, smoking history, other exposures, treatment received and overall survival (OS). Smoking status was categorized as never-smoker, past-smoker and current-smoker based on the self-reported history at diagnosis. Multivariate analysis was performed using SAS version 10.2. Results: The study population (n=61,440) comprised predominantly of males (98%), of which Caucasians (81%) formed the majority. The median age at diagnosis within this cohort was 68 years (range: 22-108 years) and median follow-up was 6 months (range: &lt;1 – 161 months). Squamous cell carcinoma (35%) and adenocarcinoma (30%) were the most common histologies. The majority (71%) presented with stage III or IV disease. Positive family history was identified in one-third. Current smokers were diagnosed with NSCLC at a younger age (65 yrs) compared to never-smokers (71 yrs) and past-smokers (72 yrs) (p&lt;0.001). After adjusting for age at diagnosis, grade, histology, family history and treatment, current-smokers (n=34613) [Hazard ratio (HR) 1.059; 95% CI, 1.012-1.108], but not past-smokers (n=23864) (HR 1.008; 95% CI, 0.962-1.056), had worse OS for Stage III and IV NSCLC, compared to never-smokers (n=2963). Smoking status was not prognostic in stage I and II NSCLC. Conclusions: Current smokers were 6 years younger than never-smokers at diagnosis of NSCLC. Although current smoking was associated with worse prognosis, especially in stages III and IV, the impact of smoking status on OS was modest, at least in males. Therefore, primary prevention of smoking cessation is more likely to be meaningful than efforts on smoking cessation after the diagnosis of NSCLC.
Use of an antibody-drug conjugate targeting tissue factor to induce complete tumor regression in xenograft models with heterogeneous target expression.
Authors: Esther CW Breij, David Satijn, Sandra Verploegen, Bart de Goeij, Danita Schuurhuis, Wim Bleeker, Mischa Houtkamp, Paul Parren
Journal: Journal of Clinical Oncology (2013)

3066 Background: Tissue factor (TF) is the main initiator of coagulation, that starts when circulating factor VII(a) (FVII(a)) binds membrane bound TF. In addition, the TF:FVIIa complex can initiate a pro-angiogenic signaling pathway by activation of PAR-2. TF is aberrantly expressed in many solid tumors, and expression has been associated with poor prognosis. TF-011-vcMMAE, an antibody-drug conjugate (ADC) under development for the treatment of solid tumors, is composed of a human TF specific antibody (TF-011), a proteaseEcleavable valine-citrulline (vc) linker and the microtubule disrupting agent monomethyl auristatin E (MMAE). Methods: TF-011 and TF-011-vcMMAE were functionally characterized using in vitro assays. In vivo anti-tumor activity of TF-011-vcMMAE was assessed in human biopsy derived xenograft models, which genetically and histologically resemble human tumors. TF expression in xenografts was assessed using immunohistochemistry. Results: TF-011 inhibited TF:FVIIa induced intracellular signaling and efficiently killed tumor cells by antibody dependent cell-mediated cytoxicity in vitro, but showed only minor inhibition of TF procoagulant activity. TF-011 was rapidly internalized and targeted to the lysosomes, a prerequisite for intracellular MMAE release and subsequent tumor cell killing by the ADC. Indeed, TF-011-vcMMAE efficiently and specifically killed TF-positive tumors in vitro and in vivo. Importantly, TF-011-vcMMAE showed excellent anti-tumor activity in human biopsyEderived xenograft models derived from bladder, lung, pancreas, prostate, ovarian and cervical cancer (n=7). TF expression in these models was heterogeneous, ranging from 25-100% of tumor cells. Complete tumor regression was observed in all models, including cervical and ovarian cancer xenografts that showed only 25-50% TF positive tumor cells. Conclusions: TF-011-vcMMAE is a promising new ADC with potent anti-tumor activity in xenograft models that represent the heterogeneity of human tumors, including heterogeneous TF expression. The functional characteristics of TF-011-vcMMAE allow efficient tumor targeting, with minimal impact on coagulation.
Index lesion tumor volume on MRI to predict adverse pathologic outcomes following radical prostatectomy.
Authors: Dordaneh Sugano, Abhinav Sidana, Brian P. Calio, Sonia Gaur, Amit L Jain, Mahir Maruf, Maria J Merino, Peter L. Choyke, Baris Turkbey, Bradford J. Wood, Peter A. Pinto
Journal: Journal of Clinical Oncology (2017)

43 Background: Tumor volume measured on postoperative pathology has been shown to be associated with adverse pathologic and oncologic outcomes. Advances in imaging technology may facilitate the prediction of these outcomes prior to surgery. In this study, we evaluated the predictive value of tumor volume of the index lesion (ILTV) calculated from prostate MRI in analyzing adverse pathologic outcomes following radical prostatectomy (RARP). Methods: Clinical and pathologic data from a prospectively maintained, single-institution database was analyzed for patients who underwent 3T MRI prior to RARP (without prior therapy) between 2007 and 2016. ILTV was calculated from T2W MRI by multiplying length by width by depth by 0.52. Adverse pathologic outcomes were determined on whole mount prostatectomy specimens, and defined as positive margins (PM), extracapsular extension (ECE), positive lymph nodes (LNI), and seminal vesicle invasion (SVI). Logistic regression was used to assess associations of clinical, imaging, and histopathological variables with adverse pathologic features. Results: From the 501 patients who underwent RARP, 490 received MRI prior to surgery. The median age of our cohort of was 60 years (IQR 10), and median PSA was 6.21 ng/ml (IQR 6). There were 74/480 patients (15.4%) with PM, 112/474 (23.6%) with ECE, 30/478 (6.4%) with LNI, and 32/482 (6.7%) with SVI. Patients with adverse outcomes had larger ILTV compared to those without (PM: 1.038cc vs 0.807cc, p=0.041; ECE: 1.388cc vs 0.765cc, p&lt;0.001; LNI: 2.970cc vs 0.797cc, p&lt;0.001; SVI: 2.269cc vs 0.798cc, p&lt;0.001). On multivariate analysis, ILTV was found to be an independent predictor of PM (OR: 1.149, p=0.036), ECE (OR: 1.269, p=0.001), LNI (OR: 1.387, p&lt;0.001), and SVI (OR: 1.341, p&lt;0.001). Conclusions: We demonstrate that Index Lesion Tumor Volume measured on T2W MRI is an independent predictor of PM, ECE, LNI, and SVI following RARP, and serves as a preoperative marker that may facilitate and inform patient counseling and decision making.