tbuckley/cabot-search huggingface dataset:
Update of a large single-institution series of first-line enhanced delivery of methotrexate with and without rituximab for primary central nervous system lymphoma.
Authors: Nancy Diane Doolittle, Rochelle Fu, Prakash Ambady, Edward A. Neuwelt
Journal: Journal of Clinical Oncology (2015)

e13013 Background: We previously reported outcomes in 101 primary central nervous system lymphoma (PCNSL) patients treated with first-line intra-arterial (IA) methotrexate (MTX)-based chemotherapy in conjunction with blood-brain barrier disruption (BBBD) without whole brain irradiation. Patients were treated at Oregon Health and Science University (OHSU) starting in 1982 through 2005, and were included in a multi-institutional efficacy and toxicity report of PCNSL patients treated with BBBD (Angelov et al, J Clin Oncol, 2009). To investigate the impact of a CD20+ antibody on response rate (RR) and survival in PCNSL, in 2005 first-line rituximab (IV) was added to monthly MTX-based BBBD. Herein we report updated outcomes of the 101 patients through 2014, with addition of 23 patients treated with first-line rituximab with BBBD. Methods: This retrospective review was IRB approved. We summarize overall patient characteristics and primary outcomes (RR, and proportions of patients alive at 3 years and 5 years from the date of first IA/BBBD) by whether or not treatment included rituximab. Results: At OHSU, 124 patients (63M/61F) were treated with first-line MTX-based IA/BBBD. Median age is 61.8 years (range, 5.7 to 82.7 years) and median KPS is 70 (range, 20 to 100), and are similar between patients with vs. without rituximab. There was one treatment-related mortality within 48 hours after BBBD; the RR is 80% (complete response [CR] 57%) with 48% (n = 60) patients alive at 3 years, and 36% (n = 45) alive 5 years after first treatment. Of 101 patients treated without rituximab, 46 (46%) are alive at 3 years whereas 14 of 23 patients (61%) treated with rituximab are alive at 3 years. The RR with first-line rituximab is 91% (CR 74%). Conclusions: The number of patients alive at 5 years is notable, though the length of follow up for patients treated with rituximab is too short for adequate evaluation of 5 year survival. As the next step, as suggested by Ney and Abrey (Leuk Lymphoma, 2009), we have developed a multi-institutional randomized trial to investigate if CD20+ maintenance immunotherapy may extend response duration after achieving CR from first-line MTX-based chemotherapy.
Effect of interferon-α/β on temozolomide activity against MGMT-positive glioma stem-like cells in vitro and in vivo.
Authors: Zhong-ping Chen, Dong Shen, Jie Wang, Qun-ying Yang
Journal: Journal of Clinical Oncology (2012)

e12503 Background: O6-methylguanine DNA methyltranferase (MGMT) is one of the main mechanisms of chemoresistance for alkylating agents in malignant gliomas. Recent studies have showed that glioma stem-like cells (GSCs) could be the main reason for tumor recurrence and chemoresistance. In this study, we aimed to explore the effects of interferon-α/β against MGMT-positive glioma stem-like cells, and to investigate whether interferon-α/β can enhance the efficiency of temozolomide (TMZ) and the possible mechanism Methods: The growth inhibition effect of TMZ, with interferon-α or interferon-β, against the MGMT-positive GSCs from human glioma cell lines U251 and SKMG-4 (U251G and SKMG-4G) was evaluated by using Cell Counting Kit-8 (CCK-8) assay in vitro, and in xenograft models. MGMT and NF-κB expression in the tumor samples were determined by RT-PCR and Western blot analysis. Results: Our results revealed that the anti-tumor activity of TMZ was significantly enhanced by combined using interferon-α/β in vitro. In xenograft models, the tumor growth inhibit rate (IR) of TMZ to SKMG-4G and U251G was 35.2%±2.28% and 16.7%±1.96%, respectively. When TMZ combined with interferon-α or interferon-β, the IR to SKMG-4G was 58.4%±4.34% and 63.4%±1.08%; and to U251G was 41.1%±8.66% and 44.5%±1.90%, respectively(P&lt;0.05). The expression of NF-κB and MGMT in MGMT-positive GSCs decreased significantly in both mRNA and protein levels after using interferon-α/β. Conclusions: Our results indicate that IFN-α/β can enhance the sensitivity of TMZ, possibly through down-regulate NF-κB expression resulting in lower MGMT transcription expression.
Predictors of patient-reported toxicities from endocrine therapy: Importance of illness perceptions, treatment beliefs, and fear of recurrence.
Authors: Xinni Song, Susan Faye Dent, Shailendra Verma, Mark J. Clemons, Nadine A. Graham, Marc Bedard, Lise Paquet
Journal: Journal of Clinical Oncology (2013)

542 Background: Numerous studies have documented the toxicities of endocrine therapy (ET) for early breast cancer (EBC) and their deleterious impact on quality of life and adherence. However, little is known about the factors that underlie patient's susceptibility to report toxicities. The identification of risk factors for toxicities from ET is important as it would allow early targeting of symptom management interventions for women more vulnerable to adverse effects of ET. This prospective study aims to examine the impact of pre-treatment perceptions of EBC, ET beliefs and fear of breast cancer (BC) recurrence (FBCR) on toxicities reported after 6 months of ET. Methods: Women diagnosed with EBC completed a survey prior to initiating endocrine therapy, then at 3, 6 and 12 months. Standardized self-report instruments were used to assess EBC perceptions, ET beliefs, FBCR and toxicities. Clinical and treatment variables were also evaluated. Univariate analyses and mulitivariate regression were conducted to identify factors associated (p&lt;0.1) with side effects at 6 months. Results: Since 9/2010, 173 patients have consented and 84 (mean age = 60 y) have completed the questionnaires at baseline and after 6 months of ET. Controlling for age, none of the clinical or treatment variables (stage of disease, type of surgery, receipt of chemotherapy and radiation therapy) were significant univariate predictors of toxicities. In multiple regression, stronger perceptions that BC has serious consequences on their lives (β=0.218, p&lt;0.05), greater concerns about the adverse effects of ET (β=0.215, p&lt;0.05) and higher levels of FBCR (β=0.316, p&lt;0.01) at baseline were associated with higher levels of reported toxicities. Conclusions: Baseline psychological factors predicted level of patient-reported toxicities to a larger extent than clinical/treatment factors. How patients perceived their illness, their beliefs about ET side effects and their fear of cancer recurrence are strongly associated with side effects experienced after 6 months of ET. These results could facilitate the identification of a subgroup of patients for early interventions to improve symptom management.
Searching for Neurodegeneration in the Blood of Patients With Alzheimer Disease
Authors: Douglas Galasko
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Maintenance therapy with bevacizumab with or without erlotinib in metastatic colorectal cancer (mCRC) according to KRAS: Results of the GERCOR DREAM phase III trial.
Authors: Christophe Tournigand, Benoist Chibaudel, Benoit Samson, Werner Scheithauer, Gérard Lledo, Frederic Viret, Thierry André, Jean François Ramée, Nicole Tubiana-Mathieu, Jérôme Dauba, Olivier Dupuis, Yves Rinaldi, May Mabro, Nathalie Aucoin, Ahmed Khalil, Jean Latreille, Christophe Louvet, David Brusquant, Franck Bonnetain, Aimery de Gramont
Journal: Journal of Clinical Oncology (2013)

3515 Background: The primary analysis of DREAM demonstrated that a maintenance therapy (MT) with bevacizumab (Bev) + EGFR TKI erlotinib (E) significantly improved progression-free survival (PFS) after a 1st-line Bev-based induction therapy (IT) in patients (pts) with unresectable mCRC. Methods: Pts were randomized to MT after an IT with FOLFOX-bev or XELOX-bev or FOLFIRI-bev between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (Bev 7.5 mg/kg q3w, E 150 mg/d ; arm B) until PD or unacceptable toxicity. Primary endpoint was PFS on MT. Secondary endpoints included PFS from inclusion, overall survival (OS) and safety. The impact of KRAS tumor status on treatment efficacy was evaluated in an exploratory analysis. Results: 700 pts were registered and 452 pts were randomized (228 in arm A, 224 in arm B). KRAS status was available for 413/452 (91%) pts. The median duration of MT was 3.6 m. Results for MT are presented below (Table). In the registered population, median OS was 24.9m (22.5 – 27.3). Conclusions: Maintenance treatment with bev + erlotinib increases PFS over maintenance with bev alone in pts with mCRC but does not prolong OS. Further follow-up will determine the impact of 2nd or 3rd line anti-EGFR Mabs in this study. Contrasting with anti-EGFR Mabs, KRAS tumor status is not mandatory to select pts with mCRC for treatment with erlotinib. Clinical trial information: NCT00265824. [Table: see text]
Chemotherapy (CTX) treatment patterns for early-stage breast cancer (ESBC): Changing use of anthracyclines (A).
Authors: Katherine M. Serrurier, Jimmy Hwang, Joseph P. McGuire, Daphne Lichtensztajn, Ann C. Griffin, Scarlett Lin Gomez, Allison W. Kurian, Michelle E. Melisko, Hope S. Rugo
Journal: Journal of Clinical Oncology (2013)

1083 Background: Anthracyclines (A), given in sequence or combination, have been the mainstay of adjuvant CTX for ESBC. Recent molecular studies have questioned the value of A for ESBC. Trials for ESBC, presented primarily in 2005, have demonstrated similar or improved efficacy with non-anthracycline (NA) CTX. We sought to understand changing use of A for ESBC from 2000-2010 as reported in the population-based 9-county Greater Bay Area Cancer Registry (GBACR). Methods: Using the GBACR database, we recorded use of A or NA based CTX regimens in women with ESBC and no prior CTX from 2000-2010, and correlated type of CTX with tumor stage, receptor status, and age. We evaluated the use of A vs. NA (80% taxane-based) CTX from 2000-2005 and 2006-2010. Results: 16,476 patients (pts) met criteria for inclusion; 2,032 (12%) were excluded (missing information, or CTX not given). Pt characteristics were: median age 52 (range 21-94), stage I (25%), II (56%), and III (19%), 69% HR+. From 2000-2010, 83% received A; overall use of A decreased (87% to 57%), and use of NA increased (13% to 43%). The Table compares use of NA CTX during the two time periods by clinical variables. With short follow-up there was no difference in survival based on use of A vs. NACTX. Conclusions: Use of NA CTX significantly increased during 2006-2010; this trend was independent of age or receptor status and was more pronounced in earlier stage disease. The timing of this change correlated with the presentation of two phase III trials, emphasizing the impact of early data from phase III trials on treatment practice, and confirming results from a large claims database (Giordano). Potential outcome differences will be evaluated in NSABP-B49 and with longer follow-up of this cohort. This study was supported by the UCSF Cancer Registry and CPIC. [Table: see text]
Palliative care doctors should be included in treatment discussions
Authors: Peter H Wise
Journal: BMJ (2017)

Murray and colleagues discuss early introduction of palliative care.1 This remains uncommon for metastatic cancer, unless poor physical performance contraindicates drug treatment. As the authors state, evidence shows that early palliative care—or best supportive care, my preferred term—benefits both quality and quantity of life, even if used alone in metastatic …
How is the current clinical management of endometrial cancer worldwide? An international survey by the North-Eastern German Society of Gynaecological Oncology (NOGGO).
Authors: Robert W. Kraetschell, Christina Fotopoulou, Sean Christopher Dowdy, Keiichi Fujiwara, Nobuo Yaegashi, Domenica Lorusso, Antonio Casado, Sven Mahner, Thomas J. Herzog, Ignace B. Vergote, David Scott Miller, Christian Marth, Marco Johannes Battista, Werner Lichtenegger, Jalid Sehouli
Journal: Journal of Clinical Oncology (2012)

5087 Background: Indication, technique and extent of lymph-node-dissection (LND) in endometrial cancer (EC) remains controversial and is strongly debated in cancer community. We conducted a national- and at a second step an international-survey evaluating the current status-quo of the surgical and medical management of EC. Methods: A validated 15-item-questionnaire regarding surgical and adjuvant procedures of EC was sent to all major gynaecological cancer societies and study groups worldwide. The questionnaire could also be answered online. Results: In a phase-I-national trial, the questionnaire was validated on basis of 316 German institutions. On the phase-II-international survey a total of 302 questionnaires were answered from 24 countries, mainly from Japan (38.7%), Spain (8.3%), Austria (7%), United-Kingdom (6.3%), Italy (6%), USA (4.3%) and Canada (4%). The vast majority of the participating clinics were academic (62.8%), while 75.2% of them belonged to gynaecology. Only 0.7% of the clinics internationally reported never performing LND in EC. 62.3% of the clinics perform both a pelvic and paraaortic lymph node dissection. 59.1% of the participants performed a systematic lymph node dissection with the intention of both adequate staging and for therapeutic value. 15.05% of the clinics perform LND up to the common-iliac-arteries, 9.03% up to the inferior-mesenteric-artery and 70.6% up to the renal-veins. The most common risk-factors to indicate LND were: high-grading (93%), non-endometrioid-histology (90.1%), lymphovascular-invasion (55.3%), blood-vessel invasion (45.4%) and tumor-diameter &gt;2cm (38.4%). For advanced stage III&amp;IV disease the vast majority (60% and 80%, respectively) of the physicians indicated systemic chemotherapy alone. Conclusions: This study presents the large variety in clinical management of EC worldwide, underlining so the high need of future prospective randomised trials which will establish standard and evidence based treatment guidelines for EC- disease.
Chronomodulated delivery schedule of oxaliplatin, 5 fluorouracil and folinic acid (FFL4/10) as first line treatment in metastatic colorectal cancer: Preliminary data of a phase II study
Authors: M. Pirovano, A. Quintè, S. Masseroni, A. Romanelli, A. Biffi, F. Scaglione, F. Fraschini, S. Sestini, R. Valsecchi, D. Tabiadon
Journal: Journal of Clinical Oncology (2004)

3738 Background: Oxaliplatin(OHP) and 5Fluorouracil(5FU) efficacy and toxicity strictly depend on circadian rhythms in cell cycle regulation, reduced glutathione content, dehydropyrimidine and thymidilate synthase activities, topoisomerase I activity, membrane permeability as well as liver and renal blood flow. Methods: From August 2002 to December 2003 (Tab.1) 27 untreated colorectal cancer patients(pt) were treated with OHP based chronomodulated delivery schedule using Melodie infusion system: OHP 25 mg / m2 /d1–4q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00pm); 5FU 900 mg/m2 and L-Folinic Acid (LFA) 150 mg/m2 d1–4,q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00am. Results: 147 cycles (6.11 average per pt.) were performed: average dose intensity was 48,21 mg/sqm/w, 319,28 mg/sqm/w 1630,41mg/sqm/w for OHP, LFA and 5FU respectively. Average dose according to body surface was 501mg/sqm, 3184,17mg/sqm, 16705,74mg/sqm respectively. No cycle was delayed due to toxicity. Haematological and hepatic toxicity weren't observed, neither was any gr. 4(WHO) toxicity. Radiological Objective Response evaluation has been performed in 23 pt (Tab.2). ORR was 65,22%. Median survival reached 13 months (only 3 pt died). Conclusions: These data seem confirm that FFL4/10 schedule has very interesting activity in metastatic colorectal cancer. Moreover, chronomodulated infusion is considerably less toxic than conventional flat or bolo infusion. No significant financial relationships to disclose.
PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma
Authors: Lakshmi Nayak, Fabio M. Iwamoto, Ann LaCasce, Srinivasan Mukundan, Margaretha G. M. Roemer, Bjoern Chapuy, Philippe Armand, Scott J. Rodig, Margaret A. Shipp
Journal: Blood (2017)
Post-orchiectomy adjuvant therapy versus surveillance for stage IS testicular cancer.
Authors: Sophia C. Kamran, Thomas Seisen, Sarah C. Markt, Mark A Preston, A. Lindsay Frazier, Christopher Sweeney, Clair Beard
Journal: Journal of Clinical Oncology (2017)

406 Background: To assess contemporary treatment patterns and survival for stage IS testicular cancer. Methods: Using the National Cancer Data Base, we identified 1,362 patients with AJCC stage IS testicular cancer (seminoma or non-seminoma) treated between 2004-2012 with either adjuvant therapy (AT) or initial surveillance. AT was defined as the receipt of chemotherapy, radiotherapy (RT), or retroperitoneal lymph node dissection (RPLND) as part of first line treatment after orchiectomy. Annual percent change (APC) in the use of AT was calculated and multivariable logistic regression analysis was performed to identify predictors of receiving AT. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and initial surveillance groups. All analyses were stratified according to histologic type. Results: Overall, there were 581 (43%) and 781 (57%) men with seminoma and non-seminoma, respectively. Among men with seminoma, 61% received AT (RT = 45%, chemo = 16%) while 39% received initial surveillance. The use of AT decreased over the study period (APC = -2.7; 95%CI: -4.4, 1.1; P = 0.001). Predictors of receiving AT included low income (OR = 1.63; 95%CI: 1.03, 2.56; P = 0.04), while year of diagnosis (OR = 0.89; 95%CI: 0.83, 0.96; P = 0.003) predicted the opposite. The 5-year IPTW-adjusted rates of OS were 99% and 97% in the AT and initial surveillance groups, respectively (HR = 0.36; 95%CI: 0.12, 1.14; P = 0.08). Among men with non-seminoma, 47% received AT (chemo = 38%, RPLND = 9%) while 53% received initial surveillance. The use of AT remained stable over the study period (APC = +0.8; 95%CI: -0.7, +2.2; P = 0.29). Predictors of receiving AT included stage ≥ pT2 (OR = 1.78; 95%CI: 1.06, 3.00; P = 0.03), and lymphovascular invasion (OR = 2.68; 95%CI: 1.88, 3.83; P &lt; 0.001). The 5-year IPTW-adjusted rates of OS were 97% and 95% in the AT and initial surveillance groups, respectively (HR = 0.66; 95%CI: 0.27, 1.61; P = 0.36). Conclusions: Trends in the use of AT for stage IS testicular cancer differed according to histologic type. Nonetheless, we report 5-year OS rates of ≥ 95% for seminoma and non-seminoma without any significant benefit with the use of AT.
ISO-005; An open-label, multiple-site, dose cohort, phase I/II study in patients with stage IV colorectal cancer.
Authors: Helena Anna Taflin, Yvonne Wettergren, Elisabeth Odin, Johan Haux, Bengt Gustavsson, Goran Ulf Carlsson
Journal: Journal of Clinical Oncology (2017)

TPS811 Background: Chemotherapy treatment of Colorectal Cancer, usually includes combinations with 5-Fluorouracil (5-FU). 5-FU is always combined with Leucovorin, (LV), which significantly enhances the therapeutic effect of 5-FU. The principal mechanisms of action are the same for Modufolin as for LV. However, in contrast to LV, Modufolin does not require metabolic activation to exert its effects - a clear advantage since the activation capacity shows great intra- and inter-individual variability leading to insufficient and unpredictable responses to LV in some patients. Methods: ISO-CC-005 is a multiple-site, international phase I/II study in patients with Stage IV Colorectal Cancer eligible for 5- FU/LV therapy alone or in combination with oxaliplatin or irinotecan. The study will investigate the tolerability of Modufolin at four dose levels and is designed as a safety study. Tolerability will be assessed by analysing the number and severity of DLTs associated with the chemotherapeutic agents, adversed events and the number of dose adjustments observed for each of the chemotherapeutic agents used in the different treatment arms. 39 valid patients are planned for inclusion, who will receive Modufolin twice every two weeks during four chemotherapy cycles. The study is on-going and still recruting eligible patients. Clinical trial information: NCT02244632.
Real-world economic outcomes among patients (pts) who initiated sunitinib or pazopanib as first targeted therapy (TT) for advanced renal cell carcinoma (aRCC): A retrospective analysis of Medicare data.
Authors: Nicholas J. Vogelzang, Sumanta K. Pal, Sameer Ghate, Nanxin Li, Elyse Swallow, Miranda Peeples, Miriam Zichlin, Mark Meiselbach, Jose Ricardo Perez, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

475 Background: Evidence on economic outcomes could provide insight on comparative economic benefit of TTs. This study assessed all-cause healthcare resource utilization (HRU) and costs among aRCC patients who initiated pazopanib and sunitinib, two commonly-used first TTs. Methods: Pts with aRCC who initiated sunitinib or pazopanib as first TT (index therapy/index date) were identified in this 100% Medicare data + Part D linkage (1/1/2006-12/31/2014). Characteristics were assessed during the 1 year prior to index date (baseline period) and pts were followed until death, end of eligibility, or end of data (study period), whichever was earliest. Pts were stratified by first TT initiated and 1:1 matched using propensity scores based on age, sex, race, year of RCC diagnosis, metastatic sites, comorbidities, and baseline inpatient, outpatient, emergency room, and pharmacy costs. Study period all-cause HRU and costs (2015 USD) were assessed on a per pt per month (PPPM) basis and compared between the matched cohorts. Results: Before matching, the cohorts were similar in baseline characteristics; however, the pazopanib cohort (n=526) was associated with higher outpatient visits and costs and lower pharmacy costs during the baseline period than the sunitinib cohort (n=1,185; all p&lt;0.05). After matching, all baseline characteristics were balanced (n=522 for both). First TT with pazopanib was associated with significantly lower total healthcare costs ($10,416 vs. $8,845, mean difference [MD]):$1,571, p&lt;0.01), total medical costs ($6,904 vs. $5,460, MD:$1,444, p&lt;0.01), inpatient costs ($4,035 vs. $2,914, MD:$1,120, p&lt;0.01), inpatient admissions (0.26 vs. 0.18, MD:0.08, p&lt;0.01), and inpatient days (1.9 vs. 1.4, MD:0.5, p&lt;0.01) compared with the sunitinib cohort. Conclusions: In this retrospective analysis of Medicare aRCC pts, treatment first line with pazopanib compared to sunitinib had lower follow-up all-cause healthcare costs and resource use, particularly with lower inpatient admissions and shorter length of stay.