tbuckley/cabot-search huggingface dataset:
Association of spiritual well-being pre- and post-radiotherapy for prostate cancer with health-related quality of life and psychological state.
Authors: Sara J Walker, Yiyi Chen, Amy Eiko Leatherwood, Kyungjeen Paik, Brandy Mirly, Charles R. Thomas, Arthur Hung
Journal: Journal of Clinical Oncology (2017)

214 Background: Cancer survivors often experience psychological stress, with impact on quality of life (QOL) and mortality. Religious/spiritual identity and well-being (WB) can also significantly relate to QOL among individuals with cancer. The specific aim of the current study investigates correlates of spiritual (WB), QOL, and psychological state before and after radiotherapy for prostate cancer (PC). We hypothesized that 1) positive correlations between pre-treatment spiritual WB and health-related QOL will be seen both time points and that 2) negative correlations between spiritual WB and depression and anxiety will be seen at both points. Methods: The PHQ-9 and GAD-7 assessed depression and anxiety, respectively. The FACT-P assessed physical, social, emotional, and functional WB. The FACIT-Sp-Ex assessed spiritual WB. Our sample ( N= 65) had mean age of 68 (range 52-81) and education of 16 years (range 10-20). Most participants (82%) identified as European-American. Associations were assessed by Pearson’s correlation coefficients. Results: Pre-treatment spiritual WB positively correlated with social, emotional, and functional well-being (all p &lt; .001). Spiritual and physical WB were not significantly related. Spiritual WB negatively correlated with depression and anxiety (both p &lt; .001). Among a smaller subsample ( N = 39) with pre-, mid-, and post-treatment assessment, spiritual WB significantly increased over time, p &lt; .001. Post-treatment spiritual WB again correlated with social, emotional, and functional WB (all p &lt; .001) and did not correlate with physical WB. Spiritual WB was again negatively correlated with anxiety ( p &lt; 0.05), but it was no longer associated with depression. Conclusions: Assessing and addressing spiritual WB can be helpful in itself, as well as in better understanding QOL and psychological state. Future directions include more fine-grained assessment of pre- and post-treatment spiritual WB in order to better understand which aspects of religious/spiritual identity relate more or less closely to post-treatment QOL for different stages of PC.
Rituximab maintenance Therapy in B-cell lymphoma: A meta-analysis.
Authors: Yucai Wang, Yan Shen, Fang Yang, Larysa Jessica Sanchez, Xiaoxiang Guan, Victor Tsu-Shih Chang, Michael Wang
Journal: Journal of Clinical Oncology (2015)

8551 Background: The role of rituximab (R) maintenance therapy (MT) in B-cell lymphoma is controversial. We reviewed data from clinical studies and conducted a meta-analysis to evaluate the efficacy and safety of R MT in follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Methods: PubMed, ASCO and ASH databases were searched for eligible clinical studies to date that investigated survival outcomes (OS, PFS, EFS and/or TTP) and adverse events of R MT in FL, DLBCL and MCL. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% CI were calculated using Comprehensive MetaAnalysis (v2). Results: 22 clinical studies of 6785 patients, including 15 randomized controlled trials (RCTs) enrolling 5029 patients, were included in this meta-analysis. In RCTs, R MT significantly prolonged PFS (HR = 0.60, 95% CI = 0.52-0.68, P < 0.001) and OS (HR = 0.79, 95% CI = 0.69-0.93, P = 0.005) in B-cell lymphoma. Improvement of PFS with R MT was demonstrated in all types of lymphoma studied. R MT increased OS in FL (HR = 0.76, 95% CI = 0.61-0.94, P = 0.010) but not DLBCL (HR = 0.88, 95% CI = 0.64-1.21, P = 0.425) or MCL (HR = 0.77, 95% CI = 0.47-1.27, P = 0.303) in RCTs. The survival benefits remained after including non-randomized clinical studies and retrospective studies. R MT increased the risks of neutropenia (RR = 1.82, 95% CI = 1.40-2.37, P < 0.001) and infection (RR = 2.49, 95% CI = 1.61-3.85, P < 0.001) but not cardiac dysfunction (RR = 1.61, 95% CI = 0.73-3.57, P = 0.242). Conclusions: R MT significantly improved PFS in FL, DLBCL and MCL as well as OS in FL. Whether R MT improves OS in DLBCL and MCL needs further study. Survival benefits of rituximab maintenance therapy in B-cell lymphoma. Study type Survival Type # of trials HR 95% CI P value RCT PFS FL 9 0.52 0.42-0.64 0.000 DLBCL 4 0.70 0.57-0.86 0.000 MCL 3 0.55 0.41-0.73 0.000 All 15 0.60 0.52-0.68 0.000 OS FL 7 0.76 0.61-0.94 0.010 DLBCL 2 0.88 0.64-1.21 0.425 MCL 1 0.77 0.47-1.27 0.303 All 10 0.79 0.69-0.93 0.005 All PFS FL 10 0.53 0.44-0.65 0.000 DLBCL 6 0.71 0.59-0.86 0.000 MCL 7 0.53 0.32-0.86 0.010 All 22 0.62 0.54-0.70 0.000 OS FL 8 0.77 0.64-0.92 0.005 DLBCL 3 0.85 0.63-1.15 0.284 MCL 4 0.62 0.42-0.91 0.015 All 15 0.76 0.66-0.88 0.000
The Lisboa Café
Authors: Shaurya Taran
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
Depersonalisation and derealisation: assessment and management
Authors: Elaine C M Hunter, Jane Charlton, Anthony S David
Journal: BMJ (2017)

#### What you need to know

- Depersonalisation and derealisation symptoms include having a sense of unreality and detachment; patients may describe using phrases such as “it is as if . . . ”

Patients who experience depersonalisation and derealisation often have difficulty in describing their symptoms. They experience a sense of unreality and detachment from their sense of themselves (depersonalisation: DP) or their perception of the world (derealisation: DR). In most cases these two symptoms co-occur. This article aims to help clinicians recognise depersonalisation and derealisation (DP DR) symptoms, diagnose the disorder, and discuss current treatment options.

Otherwise healthy people— Transient symptoms of depersonalisation and derealisation are very common in the general population, often during periods of stress or fatigue. One US phone study of more than 1000 people found that nearly a quarter reported a brief episode over the previous one year period.1

Those with a range of physical and mental health conditions— Such symptoms are also commonly associated with several medical conditions, such as migraine and temporal lobe epilepsy,2 and with psychiatric conditions, particularly anxiety disorders, such as panic, depression, or in those with complex post-traumatic stress or personality disorders who report a history of childhood abuse or trauma.3

Those with depersonalisation and derealisation disorder as a primary diagnosis —Less well known is that the symptoms of depersonalisation and derealisation can also occur as a chronic primary mental health disorder called depersonalisation derealisation …
Phase II study of everolimus monotherapy as first-line treatment in advanced biliary tract cancer: RADichol.
Authors: Yvonne H. Yeung, Fiona J.M. Chionh, Timothy Jay Price, Andrew Mark Scott, Hoanh Tran, Guangying Fang, Effie Skrinos, Carmel Murone, John M Mariadason, Niall C. Tebbutt
Journal: Journal of Clinical Oncology (2014)

4101 Background: Advanced biliary tract cancers (BTC) have a poor prognosis with limited standard chemotherapy options. The PI-3Kinase signalling pathway is frequently dysregulated in BTC and preclinical studies using mTOR inhibitors have shown activity in BTC cell lines. This exploratory phase II study aims to evaluate the clinical activity and safety of the mTOR inhibitor RAD001 (everolimus) in BTC, as well as to evaluate potential biomarkers of response in vivo and in vitro. Methods: Inclusion criteria included advanced BTC, no prior chemotherapy, adequate organ function and written informed consent. Treatment involved everolimus (10mg/d) and continued until tumour progression. The primary endpoint was disease control (DC) at 12 weeks (w). Secondary endpoints were response rate, progression free survival (PFS), overall survival (OS) and adverse events (AE). The two-stage study allowed progression to stage 2 when > 3 of 9 patients had DC at 12w and would be declared active when >13 of 27 had DC. Correlative in vitro studies evaluated biomarkers predictive of benefit to everolimus and exploratory endpoints include correlation with these biomarkers in vivo. Results: 27 eligible patients (median age 64 y) were enrolled between 2009 and 2011. At 12w, 48% had SD, 8% PR and 56% had DC. Median PFS was 6.0 months (95% CI, 2.1-11.2), median OS was 9.5 months (95% CI, 5.5-16.6) and DCR 76%. Treatment was well tolerated with stomatitis (63%) and rash (52%) being the most frequent AEs. The most common grade 3/4 AEs were infection (26%), pain (15%), hyperglycemia and hypercholesterolemia (11%). After progression, 26% received 2nd line chemotherapy. In vitro studies showed that k-ras mutation was associated with everolimus resistance (p=0.03). There was significant negative correlation between basal pAKT: tAKT and drug resistance regardless of k-ras status (r=-0.57, 95% CI -0.81 to -0.17, p=0.007). Mutation profiling for Ras and PIK3Ca mutations in tumour tissue from the trial is ongoing. Conclusions: Single agent everolimus demonstrates activity as monotherapy in advanced BTC, with an acceptable side effect profile. Two potential predictive biomarkers have been identified in vitro and are undergoing evaluation in vivo. Clinical trial information: NCT00973713.
A phase I food-effect study of the ribociclib (LEE011) drug-in-capsule (DiC) formulation in healthy subjects.
Authors: Shyeilla V. Dhuria, Ravi Siddani, Chelsea Marie Kosecki, Caroline Germa, Sabiha Mondal
Journal: Journal of Clinical Oncology (2015)

e13577 Background: Ribociclib, an oral, selective CDK4/6 inhibitor, is in clinical development as an anticancer agent. This randomized, two-sequence, crossover study assessed the effect of a high-fat, high-calorie meal on ribociclib exposure following a 600 mg dose. Methods: Healthy subjects (18–55 years; male or sterile/postmenopausal females; N = 24) received a single oral 600 mg DiC dose of ribociclib either on Day 1 under fasted conditions (no food or drink ~8–12 h prior to dose) and then on Day 13 under fed conditions (~800–1000 calories, ~50% from fat, ~35% from carbohydrates, ~15% from protein; sequence 1; n = 12), or on Day 1 under fed conditions and then on Day 13 under fasted conditions (sequence 2; n = 12). Blood draws for pharmacokinetic (PK) sampling were performed on Days 1 and 13 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 144, and 168 h post-dose. PK parameters were estimated from individual plasma concentration–time profiles using non-compartmental methods. Results: 23 of the 24 subjects (median age 33 years, 83% male) completed the study; 1 subject discontinued after the first dose in sequence 1 due to a ribociclib-unrelated adverse event (AE; nasopharyngitis). The geometric mean ratios for the fed versus the fasted state were 0.775 for Cmax (90% confidence interval [CI]: 0.700, 0.858), 0.993 for AUClast (90% CI: 0.924, 1.070), and 0.994 for AUCinf (90% CI: 0.925, 1.070). Median Tmax was delayed in the fed state (median difference in Tmax of 2 h). Similar trends were observed for LEQ803 (based on descriptive statistics of LEQ803 PK parameters), an active metabolite of ribociclib. 12 subjects experienced ≥ 1 AE (all Grade 1/2), most frequently headache (n = 4; 17%), dizziness (n = 3; 13%), and nausea (n = 3; 13%). Conclusions: Compared with the fasted state, oral administration of a 600 mg dose ofribociclib DiC with a high-fat, high-calorie meal decreased the rate of absorption of ribociclib resulting in a decrease in Cmax and a median difference in Tmax of 2 h. However, there was no effect on the extent of absorption of ribociclib as the overall exposure (AUClast and AUCinf) was unaffected. Overall, ribociclib was well tolerated and can be taken without regard to food.
A phase III randomised trial comparing the tolerability of dose-dense chemotherapy in older to that in younger breast cancer patients with four or more positive lymph nodes
Authors: S. Kuemmel, J. Krocker, A. Kohls, M. Budner, G.-P. Breitbach, K. Ruhland, U. Köhler, B. Reischauer, J.-U. Blohmer, D. Elling
Journal: Journal of Clinical Oncology (2004)

589 Background: Recently published data showed older patients to have similar dose-related benefits in reducing breast cancer-related relapse and mortality to those of younger women. This analysis was performed to assess the feasibility of a prospective randomised dose-dense regimen in the treatment of women over the age of 60. Methods: From June 1996 to November 2000, 211 primary breast cancer patients with four or more positive lymph nodes were prospectively randomised to either four cycles of epirubicin and paclitaxel (ET) at two-week intervals followed by three cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with G-CSF support (Group A) [age < 60 years (A1), n = 79; age ≥ 60 years (A2), n = 25] –or four cycles of epirubicin and cyclophosphamide (EC) at three-week intervals followed by three cycles of CMF (Group B) [age < 60 years (B1), n = 80; age ≥ 60 years (B2), n = 27]. Results: The median age was 52 years (range 26–59) in group A1, 64 years (range 60–71) in group A2, 48.5 years (range 32–59) in group B1 and 64 years (range 60–72) in group B2. All seven cycles were administered in 95% (A1), 100% (A2), 99% (B1) and 89% (B2) of patients. A dose reduction was made only in 1% (A1), 2% (A2), 1% (B1) and 1% (B2) of the cycles. In comparing these four groups, delays in administering cycles were more frequent in the dose-intensified group of older patients (6% in A1 vs. 17% in A2; 6% in B1 vs. 11% in B2). The hematological toxicity data are shown in Table 1. NCI-CTC grade 3–4 non-hematological toxicities were rare and revealed no differences between the groups. Conclusions: The administration of a dose-dense regimen with epirubicin and paclitaxel followed by CMF with G-CSF support is feasible in elderly patients with a tolerable safety profile. Referring to the analysed data, a decreased hematopoetic potency must be considered in older patients. No significant financial relationships to disclose.
A prospective evaluation of vascular endothelial growth factor (VEGF) and the immune system in stage III/IV melanoma.
Authors: Nicole Marie Agostino, Michael Weiss, Wenjing Shi, Wendy Kay Nevala, Stephen Hemperly, Svetomir Markovic, Suresh G Nair
Journal: Journal of Clinical Oncology (2013)

e20046 Background: The immune system and VEGF may play a role in melanoma behavior. We prospectively collected data in 10 stage III and 22 stage IV melanoma patients to observe factors influencing outcomes. Methods: We assessed median survival (MS), LDH, BRAF, VEGF, Th1/Th2 ratio, regulatory T cells (Tregs) and CD4/CD8 ratio, which were measured upon enrollment. LDH and BRAF were measured in standard commercial labs; VEGF via ELISA at LVHN; Th1/Th2 ratio and CD4/CD8 ratio via flow cytometry at Mayo Clinic. Stage III patients were treated with resection and interferon or observation. Stage IV patients were treated with some or all of the following: resection +/- GM-CSF, IL-2, ipilimumab, vemurafenib, carboplatin/paclitaxel/bevacizumab and temazolamide. Results: MS for stage IV patients was 48 months using a Kaplan-Meier survival curve. The only variable associated with survival was LDH, (HR=1.0017, 95%CI: 1.0003-1.0032, p=0.02). In stage IV patients, there was a positive correlation between VEGF and Tregs (r=.485, n=22 p=0.022) and a negative correlation between Tregs and Th1/Th2 (r=-.470, n=22, p=0.027). In stage III/IV patients who were alive at study completion, there was a positive correlation between CD4/CD8 and VEGF (r=.792, n=10, p=0.006). In patients who died, there was a negative correlation between Tregs and Th1/Th2 (r=-.660, n=12, p=0.02). 7 of the stage IV patients are currently disease free, including 5 of the 10 who received IL-2 +/- metastectomy. Conclusions: While a median survival of 48 months was provocative for stage IV patients, it may reflect referral selection at an IL-2 center. Recent advances such as ipilimumab (which lowers Tregs), BRAF inhibitors, and immunotherapy/aggressive resection as initial therapy may have impacted survival. The literature suggests that an elevated CD4/CD8 ratio predicts better outcomes. Higher VEGF levels have also been associated with lower overall survival in patients treated with IL-2. We found an association between higher VEGF levels and increased Tregs in deceased patients but not in living patients. In patients still alive, higher VEGF was balanced by a higher CD4/CD8 ratio. We did not find a correlation between baseline VEGF and survival.
Litmus test or destination systemic therapy? Trends in referral for surgery after initial systemic therapy in metastatic kidney cancer.
Authors: Liam Connor Macleod, Atreya Dash, George Schade, Scott S. Tykodi, John L. Gore
Journal: Journal of Clinical Oncology (2017)

502 Background: With nine new targeted and immunotherapeutic agents for metastatic kidney cancer (mRCC) since 2005, there is no randomized data supporting sequencing cytoreductive nephrectomy (CN) and newer systemic therapies (ST). Increased disease control with ST engenders concern that CN may shorten life or delay therapy. Thus, in all the best prognostic candidates, initial ST as a “litmus” test may be advocated prior to CN. We evaluated use of CN after initial ST, hypothesizing receipt of deferred CN to be associated with increased survival time, markers of increased performance status, less rapid disease, and socioeconomic status. Methods: The National Cancer Database was screened for adult patients with biopsy-proven mRCC treated with initial systemic therapy between 2006-2013. Covariates included demographic, oncologic, hospital-level, and geographic variables. Unadjusted and multivariable logistic regression was performed, identifying factors associated with CN after initial ST. Results: Of 14,651 patients treated with initial ST for mRCC, 709 (4.8%, median OS 19 months, IQR 9-35) underwent delayed CN compared with 13,942 (95.2%, median OS 5 months, IQR 2-13) treated with ST alone. On multivariable analysis, survival ≥3 months was highly associated with receipt of CN (OR 10.6, 95% CI 5.5, 20.5). However, of 9,796 surviving ≥3 months, only 689 (7%) underwent CN. Factors associated with lower odds of CN included older age, greater comorbidity, higher clinical stage (T and N), and unfavorable metastatic sites (i.e., brain, bone, liver) with all p&lt;0.001. Educational attainment was associated with receipt of CN, but hospital characteristics and travel burden were not. Conclusions: Effectiveness of CN in the modern mRCC era is uncertain. Initial ST is typically for those with poor prognosis. Yet, after an initial litmus test, re-evaluation of risk rarely leads to CN. Socioeconomic factors may affect CN decision-making, a potential disparity that merits further investigation.
Survival of patients (pts) treated with high-dose radiotherapy (RT) and concurrent chemotherapy for unresectable non-small cell lung cancer (NSCLC)
Authors: S. Schild, D. Graham, S. Hillman, S. Vora, G. Yolanda, J. Molina, H. Shahidi, J. Kugler, A. Adjei
Journal: Journal of Clinical Oncology (2009)

7544 Background: NCCTG N0028 was a trial that determined the MTD of RT that could be given with carboplatin &amp; paclitaxel was 74 Gy/34 fractions. This secondary analysis was performed to determine the survival of pts treated on this trial. Methods: Eligible pts had medically or surgically unresectable NSCLC, PS=0–1, weight loss &lt;10% in the prior 3 months(mo), no prior therapy, adequate laboratory &amp; pulmonary functions. Included were 25 pts with clinical stages I (4pts), II (1 pt), IIIa (12 pts), &amp; IIIb (8 pts). Treatment included: weekly I.V. paclitaxel (50mg/m2) &amp; carboplatin (AUC=2) during RT. The RT included 2 Gy daily to an initial dose of 70 Gy. The total dose was increased in 4 Gy increments until the MTD was determined. RT was delivered with 3-D treatment planning but no elective nodal RT. Three pts received 70 Gy, 18 pts received 74 Gy, &amp; 4 pts received 78Gy. Results: Pts were followed until death or from 10–67 mo (median: 28mo) in those alive at last evaluation. The median survival (MS) of the entire cohort was 42mo. The 5 stages I-II pts had a MS of 53 mo &amp; the 20 stage III pts had MS of 42mo. Conclusions: Standard dose RT is unable to sterilize disease in the majority of pts with unresectable NSCLC. While the addition of chemotherapy has significantly improved survival of these pts, the MS is generally 15–24 mo. These preliminary results suggest higher than standard doses of RT may improve disease control &amp; prolong survival. A phase III trial comparing standard-dose RT(60Gy) to high-dose RT (74Gy) is open and should more definitively address the issue of RT dose with concurrent chemotherapy for unresectable NSCLC. Future technological improvements in imaging &amp; targeting will provide methods to safely administer even greater RT doses which will likely further improve disease control. No significant financial relationships to disclose.