tbuckley/cabot-search huggingface dataset:
Tailoring end-of-life discussions to advanced cancer patients’ state of grief
Authors: H. G. Prigerson, A. A. Wright, S. D. Block, P. K. Maciejewski
Journal: Journal of Clinical Oncology (2009)

9500 Background: Prior research has shown end-of-life (EOL) discussions are not associated with significant psychological distress, but are associated with earlier referrals to hospice and lower rates of intensive care. Nevertheless, associations between EOL discussions and care received may vary depending on patients’ state of grief over their cancer diagnosis. The aim of this study was to determine how Kubler-Ross’ proposed 5 states of grief –numbness, anger, bargaining, depression, and acceptance –modify the effects of EOL discussions on EOL care received. We hypothesized that the early grief state of numbness would interfere with patients’ processing of an EOL discussion, thereby, reducing its association with care received. Methods: Coping with Cancer is an NCI/NIMH-funded, multi-site prospective, longitudinal cohort study of patients with advanced cancer, conducted from September 2002-February 2008. Analyses were based upon 316 deceased patients who were interviewed at baseline and followed until death 4.4 months later. Patients were assessed at baseline on 5 grief states in response to their cancer diagnosis (i.e., numbness, anger, bargaining, depression, and acceptance) and whether an EOL discussion with their physician had occurred. Information on medical care received in the last week of life was obtained from chart review, and regressed on the interaction between each of the 5 grief states and the patient's report of an EOL discussion. Results: Of the 5 grief states, only numbness significantly moderated the effect of EOL discussions on medical care received. For patients with higher than average numbness (i.e., ≥ 1 on the 0–4 numbness score continuum), the effect of EOL discussions on ventilation or resuscitation in the last week of life was significantly reduced by a factor of 10 [OR=9.96, 95% CI (1.21–82.2)]; the effect of EOL discussions on death in the ICU was significantly reduced by a factor of three [OR=2.98, 95% CI (1.01–8.78)]. Conclusions: Associations between EOL discussions and care received are much reduced among patients who are high on numbness (i.e., those who have not resolved the 1 st grief state). Physicians should consider their patients’ grief state (i.e., numbness) when deciding whether to engage in EOL discussions. No significant financial relationships to disclose.
Z antitrypsin polymerization is associated with enhanced pulmonary inflammation
Authors: Sam Alam, Zhenjun Li, Sabina Janciauskiene, Ravi Mahadeva
Journal: European Respiratory Journal (2012)

Severe antitrypsin (AT) deficiency due to polymerization of the Z variant is the commonest genetic cause of emphysema. There is variability in the development and progression of emphysema even in Z-AT homozygotes. We postulated that episodes of pulmonary inflammation could induce polymerization of Z-AT protein thereby further reducing the anti-proteinase protection. 8 Transgenic mice for human Z-AT (Z-mice) and M-AT (M-mice) received 10µg of intrapulmonary LPS. BALF and lung homogenates (LH) were assessed for lung injury and inflammation and AT conformations at day 1, d3 and d7. Z-mice had more lung injury than M-mice; Wet:dry lung ratio was higher in Z- than M-mice, d1, 6.5±0.42 vs. 4.5±0.24, p=0.001; d3, 7.1±0.51 vs. 5.7±0.29, p=0.03. Z-mice had more pulmonary PMNs d1, BALF 71±3x104cells (mean(SEM)) vs. 52±4, p=0.004; LH intracellular neutrophil elastase (NE), Z- vs. M-mice, median(IQR): d1, 418(490-391)ng/mg vs. 261(285-220), p<0.001. Z-mice had a higher concentration of 8-isoprostane (8-IP) and free NE in BALF compared with M-mice; 8-IP (Z vs. M), d1, 141±29ng/ml vs. 83±19; d3, 211±27 vs. 108±21, p<0.001; BALF, free NE, d1 (Z vs. M), median(IQR) 346(436-316)ng/ml vs. 213(245-113), p=0.001. ELISA and immunoblot revealed that LPS instillation in Z-AT mice led to the development of oxidized-polymers of Z-AT, which further reduces the anti-elastase protection and nullifies the anti-inflammatory effect of AT. This data suggests a molecular mechanism whereby infective exacerbations could further inactivate Z-AT and contribute to the faster decline in lung function in Pi ZZ individuals. This may explain some of the heterogeneity of the lung disease in these individuals.
A Randomized Controlled Clinical Trial of Dialogical Exposure Therapy versus Cognitive Processing Therapy for Adult Outpatients Suffering from PTSD after Type I Trauma in Adulthood
Authors: Willi Butollo, Regina Karl, Julia König, Rita Rosner
Journal: Psychotherapy and Psychosomatics (2015)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Although there are effective treatments for posttraumatic stress disorder (PTSD), there is little research on treatments with non-cognitive-behavioural backgrounds, such as gestalt therapy. We tested an integrative gestalt-derived intervention, dialogical exposure therapy (DET), against an established cognitive-behavioural treatment (cognitive processing therapy, CPT) for possible differential effects in terms of symptomatic outcome and drop-out rates. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We randomized 141 treatment-seeking individuals with a diagnosis of PTSD to receive either DET or CPT. Therapy length in both treatments was flexible with a maximum duration of 24 sessions. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Dropout rates were 12.2% in DET and 14.9% in CPT. Patients in both conditions achieved significant and large reductions in PTSD symptoms (Impact of Event Scale - Revised; Hedges' g = 1.14 for DET and &lt;i&gt;d&lt;/i&gt; = 1.57 for CPT) which were largely stable at the 6-month follow-up. At the posttreatment assessment, CPT performed statistically better than DET on symptom and cognition measures. For several outcome measures, younger patients profited better from CPT than older ones, while there was no age effect for DET. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Our results indicate that DET merits further research and may be an alternative to established treatments for PTSD. It remains to be seen whether DET confers advantages in areas of functioning beyond PTSD symptoms.
DEPDC5 variants increase fibrosis progression in Europeans with chronic hepatitis C virus infection
Authors: Maria Antonella Burza, Benedetta Maria Motta, Rosellina Margherita Mancina, Piero Pingitore, Carlo Pirazzi, Saverio Massimo Lepore, Rocco Spagnuolo, Patrizia Doldo, Cristina Russo, Veronica Lazzaro, Janett Fischer, Thomas Berg, Alessio Aghemo, Cristina Cheroni, Raffaele De Francesco, Silvia Fargion, Massimo Colombo, Christian Datz, Felix Stickel, Luca Valenti, Stefano Romeo
Journal: Hepatology (2015)

Chronic hepatitis C virus (HCV) infection may progress to cirrhosis and hepatocellular carcinoma (HCC). Recently, two genetic variants, DEPDC5 rs1012068 and MICA rs2596542, were associated with the onset of HCC in Asian subjects with chronic HCV infection. The aim of the present study was to analyze whether DEPDC5 and MICA genetic variants were associated with liver disease progression in European subjects with chronic HCV infection. In a Northern Italian discovery cohort (n = 477), neither DEPDC5 rs1012068 nor MICA rs2596542 were associated with HCC (n = 150). However, DEPDC5 rs1012068 was independently associated with cirrhosis (n = 300; P = 0.049). The association of rs1012068 with moderate to severe fibrosis was confirmed in an independent cross‐sectional German cohort (n = 415; P = 0.006). Furthermore, DEPDC5 rs1012068 predicted faster fibrosis progression in a prospective cohort (n = 247; P = 0.027). Next, we examined the distribution of nonsynonymous DEPDC5 variants in the overall cross‐sectional cohort (n = 912). The presence of at least one variant increased the risk of moderate/severe fibrosis by 54% ( P = 0.040). To understand the molecular mechanism underlying the genetic association of DEPDC5 variants with fibrosis progression, we performed in vitro studies on immortalized hepatic stellate cells (LX‐2). In these cells, down‐regulation of DEPDC5 resulted in increased expression of β‐catenin and production of its target matrix metallopeptidase 2 (MMP2), a secreted enzyme involved in fibrosis progression. Conclusion: DEPDC5 variants increase fibrosis progression in European subjects with chronic HCV infection. Our findings suggest that DEPDC5 down‐regulation may contribute to HCV‐related fibrosis by increasing MMP2 synthesis through the β‐catenin pathway. (H epatology 2016;63:418–427)
Biweekly cetuximab in combination with irinotecan as second-line treatment in patients with platinum-resistant gastroesophageal cancer (GEC).
Authors: Katrine Rahbek Schønnemann, Jon Kroll Bjerregaard, Mette K. N. Yilmaz, Helle Anita Jensen, Kirsten Marie Nielsen, Lene Weber Vestermark, Per Pfeiffer
Journal: Journal of Clinical Oncology (2012)

e14517 Background: Inspired by the promising results seen in patients (pts) with chemo-resistant metastatic colorectal cancer we evaluated a biweekly schedule of cetuximab (cet) and irinotecan (iri) - (Cetiri) (Pfeiffer et al. Ann Oncol 2008) in platinum resistant GEC. Methods: We treated and evaluated 111 consecutive pts with histological verified GEC adenocarcinoma and documented failure to first-line platinum-based treatment. Pts received cet 500 mg/m 2 and iri 180 mg/m 2 day 1 every 2nd week until progression or unacceptable toxicity. Toxicity was evaluated according to NCI-CTCAE v. 3.0. Response rate (RR) was evaluated according to RECIST v. 1.0 every 8th week. Clinical parameters and blood samples at baseline were analyzed in order to find prognostic and predictive values for prolonged overall survival (OS). Results: Pts were included from December 2007 to August 2010. Median age was 63 years (range 33-81). Performance status (PS) was 0-1 in 95 % of the pts. Thirty-six (46%) pts had more than two organs involved. Median number of courses were 5 (1-46). RR was 13% (13 PR) and 48 % had stable disease for at least 2 months. Median PFS and OS were 3.3 months (CI 2-4) and 5.6 months (CI: 5-7) respectively. Seventy six (68%) pts had treatment induced skin toxicity, rash. In a univariate analysis PS 0-1, normal baseline haematology and skin rash was associated with significantly increased survival. These parameters retained significance in a multivariate analysis. One patient had a curative intended resection after 28 courses and had an overall survival at 29.5 months. Two pts are still alive. Conclusions: Biweekly Cetiri is a convenient and well-tolerated second-line (SL) regimen in pts with GEC adenocarcinoma. Good PS, normal baseline haematology and development of skin rash indicate increased survival. Based on our findings biweekly Cetiri can be recommended as SL treatment to GEC pts in a good PS. Further studies into the role of rash are warranted.
Quality of life (QoL) impact of bevacizumab (BV) when combined with irinotecan + 5-FU/leucovorin (IFL) and 5-FU/leucovorin (FL) for metastatic colorectal cancer (mCRC)
Authors: A. Chawla, E. Holmgren, B. Nelson, D. Cella, K. Yost, H. Hurwitz, W. Novotny
Journal: Journal of Clinical Oncology (2005)

3564 Background: BV (Avastin) is a monoclonal antibody to VEGF. In the pivotal trial, 813 mCRC patients were randomized to IFL+placebo (411) or IFL+BV (402); BV added to first-line IFL significantly prolonged progression-free survival (PFS) and overall survival (OS). In a phase II study, BV added to FL significantly prolonged PFS. Evaluating changes in QOL was a secondary objective in both studies. Methods: Prespecified QOL endpoints were time to deterioration in QOL (TDQ), measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) colon cancer subscale (CCS), Trial Outcome Index (TOI-C) and FACT-C score. QOL deterioration was defined based on clinically meaningful decrease in scores: 3 points (CCS), 7 points (TOI-C), and 9 points (FACT-C). Median TDQ was evaluated for subjects with baseline and post-baseline assessments, using stratified log-rank test. Those who progressed or died before QOL declined were assigned TDQ of time to progression or death. Those who did not die or experience documented QOL deterioration or disease progression/death were censored at time of last QOL assessment. Those who discontinued without a post-baseline assessment or disease progression were censored at date of randomization. Results: In the pivotal trial, Arm1/Arm 2 baseline scores were available for 127/122 (CCS), 125/122 (TOI-C), and 124/121 (FACT-C) subjects. There was no statistically significant difference in TDQ (CCS, TOI-C, or FACT-C) between arms (Table 1). In the phase II study, baseline scores were available for 77/89 subjects. Median TDQ as measured by TOI-C (p=0.0477) and FACT-C score (p=0.0159) was significantly prolonged for FL+BV. Conclusions: When added to IFL, BV significantly prolonged OS and PFS without compromising QOL. Analyses of secondary measures of TDQ (TOI-C and FACT-C score) suggest a QOL gain with an increase in PFS for subjects receiving BV in addition to FL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, GlaxoSmithKline, Pfizer Genentech Genentech
Phase I evaluation of vandetanib with radiation therapy (RT) ± cisplatin in previously untreated advanced head and neck squamous cell carcinoma (HNSCC)
Authors: V. Papadimitrakopoulou, S. J. Frank, G. R. Blumenschein, C. Chen, M. Kane, E. E. Cohen, P. Langmuir, A. D. Krebs, S. M. Lippman, D. Raben
Journal: Journal of Clinical Oncology (2009)

6016 Background: Vandetanib is a once-daily oral anticancer agent that selectively targets VEGF, EGF and RET receptor tyrosine kinases. We report preliminary results from an ongoing open-label phase I study of vandetanib with RT ± cisplatin in patients (pts) with previously untreated, unresected, locally advanced (stage III-IV) HNSCC. Methods: Eligible pts received once-daily vandetanib for 14 days followed by either 1) concomitant vandetanib + RT (2 Gy/d, 5 d/wk; total 70 Gy) + cisplatin (30 mg/m 2 , 2 h iv infusion/wk) for 7 wks, or 2) concomitant vandetanib + RT (2.2 Gy/d accelerated fractionation, 5 d/wk; total 66 Gy) for 6 wks. The primary objective was to determine the safety, tolerability and maximum tolerated dose (MTD) of vandetanib in both regimens. The first pt cohort received vandetanib 100 mg/day; escalation to 200 mg and 300 mg in subsequent cohorts was permitted providing &lt;2/6 (33%) pts in the preceding cohort experienced a dose-limiting toxicity (DLT). Cohort expansion at the MTD of vandetanib was also planned. Results: As of Dec 1 2008, 24 pts (median age 53.5 yrs; 19 male; all M0) had received treatment with vandetanib + RT + cisplatin (n=18) or vandetanib + RT (n=6). In the triplet arm, no DLTs occurred in the initial vandetanib 100 mg cohort (n=6); an additional 6 pts were enrolled to receive vandetanib 200 mg but this dose was considered to exceed the MTD since DLTs were reported in 3/5 evaluable pts (Table). Vandetanib 100 mg was therefore declared the MTD with RT + cisplatin and cohort expansion at this dose continues. In regimen 2), 6 pts have received vandetanib 100 mg + RT and evaluation of this initial cohort is ongoing. Conclusions: This study, which continues to recruit, is the first to evaluate dual targeting of VEGFR/EGFR tyrosine kinases with chemoradiation or radiation alone in HNSCC pts. Among the 24 treated pts, 2 have completed the 2-year follow up, 1 death occurred that was causally related to cisplatin, and 21 remain in follow up or continue to receive treatment. [Table: see text] [Table: see text]
Hypertension in long-term survivors of childhood renal cancers.
Authors: A F Kantor, F P Li, A J Janov, N J Tarbell, S E Sallan
Journal: Journal of Clinical Oncology (1989)

The prevalence of hypertension was investigated in 119 adults who have survived for up to 53 years following the diagnosis of renal cancer in childhood (Wilms' tumor, 116 patients; renal carcinoma, three patients). Twenty-four (20%) have developed definite or borderline hypertension, as compared with 18.1 cases expected based on US population rates (relative risk [RR], 1.3; 95% confidence interval [CI], 0.9 to 2.0; P = .20). This nonsignificant excess is due to the heightened prevalence of definite hypertension among one subgroup of male patients. The findings are not explained by cigarette smoking, obesity, age, and stage at diagnosis of Wilms' tumor, or family history of hypertension. A case-comparison analysis within the cohort showed no consistent hypertensive effect associated with radiation therapy dose, radiotherapy concurrent with dactinomycin chemotherapy, or extent of renal surgery. Hypertension is not a common late complication of Wilms' tumor in our patients.
Combined therapy of locally advanced rectal adenocarcinoma with capecitabine and concurrent radiotherapy
Authors: I. Kocakova, M. Svoboda, K. Klocova, S. Spelda, I. Kocak, P. Slampa, I. Penka, R. Sefr, R. Vyzula
Journal: Journal of Clinical Oncology (2004)

3720 Background: Concomitant chemoradiotherapy with capecitabine could improve outcome in: patients with locoregionally advanced undisseminated rectal cancer. Methods: Since X/2001 to V/2003 capecitabine and concurrent radiotherapy was applied in locally advanced rectal cancer (cT3–4, and/or N+, M0). 43 patients, 31 men, 12 women, median age 59. Capecitabine 825 mg/m2 twice a daily was given concomitantly with pelvic radiotherapy 1,8 Gy daily up to 45 Gy followed by a boost up to 50,4 Gy. Results: Pathological complete response in 9(21%) pts, minimal microscopic residuum in 7(16%) pts and together 37% pts. with a substantial remission were diagnosed. Thymidylate synthase (TS), thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD) and TNFα mRNA/GAPDH mRNA relative levels from tumor and adjacent tissue has been measured by means of Real Time PCR. Before treatment TS mRNA median was higher in tumors (1.7x) than in adjacent mucosa. Changes in mRNA levels in the course of therapy were different in tumor and adjacent non affected mucosa. TS mRNA median level in tumors increased 1,3x in the course of therapy, but median in adjacent mucosa increased 2,3x. Tumor TS mRNA median in the course of therapy was 1.5x higher in responders (pT0,N0 or pR1,N0) than in non responders. Tumor TP mRNA median levels increased 3.09x in all pts, but only 2.63x in patients with remission. There was an 2.56x increase of mucosal TP mRNA in total, but negligible (1.004x) in patients with remissions in the course of therapy. Median tumor DPD mRNA level of non responders is 3.9x higher than in responders before therapy or 3.5x higher in the course of therapy respectively. Tumor TNFα mRNA median level is increased 2.8x in responders but 4.32x in non responders. Conclusions: The concurrent chemoradiotherapy proved to be effective for treatment of locally advanced rectal cancer. The analysis shows the increased level of TS mRNA in tumor tissue and elevation of TP mRNA in tumor during radiotherapy in all pts. But the evaluated markes of fluoropyrimidine metabolism don't correlate with therapeutic response. No significant financial relationships to disclose.
Impact of Adjuvant Endocrine Therapy on Quality of Life and Symptoms: Observational Data Over 12 Months From the Mind-Body Study
Authors: Patricia A. Ganz, Laura Petersen, Julienne E. Bower, Catherine M. Crespi
Journal: Journal of Clinical Oncology (2016)

To examine patterns of health and symptoms associated with the initiation of adjuvant endocrine therapy (ET) for primary breast cancer treatment.The mind-body study (MBS) observational cohort participants provided self-reported data on physical and mental health, ET-related symptoms, as well as depression, fatigue, and sleep obtained at enrollment (after primary treatment, prior to initiation of ET) and 6 and 12 months later. Longitudinal trajectories of outcome variables among three patient groups (no ET, aromatase inhibitor [AI], or tamoxifen) were compared by using linear mixed models.Two-thirds of the 186 women initiated ET, which was evenly split between AI and tamoxifen, and no significant differences were observed in self-reported measures among the groups at baseline or in covariate-adjusted analyses. Physical health scores were below normative levels initially and improved over time, but the AI group had a significantly lower score at 12 months (P = .05); mental health scores were within the normal range, were similar in each group, and did not change over time. The no-ET group showed either stable or declining symptom severity, whereas the ET groups often showed increased severity over time, and the AI group reported more severe musculoskeletal (P = .02), hot flash (P = .02), and cognitive problems (P = .006) at one or both of the follow-up time points compared with the no-ET group. The tamoxifen group had higher levels of hot flashes (P = .002), cognitive problems (P = .016), and bladder problems (P = .02) than the no-ET group.Attention should be given to the increased symptom burden associated with ET, and better efforts should be made to address patient-reported outcomes.
Phase I/II study of CPT-11 plus S-1 in patients with advanced gastric cancer
Authors: Y. Komatsu, S. Yuuki, N. Fuse, M. Takei, T. Miyagishima, M. Kudo, S. Hashino, M. Asaka, Y. Sakata
Journal: Journal of Clinical Oncology (2004)

4191 Background: We reported the results of phase I study part of the treatment with CPT-11 (irinotecan) and S-1, a new oral fluoropyrimidine, in gastric cancer patients at ASCO 2002. This paper reports Phase II study part using the previously defined recommended dose, including results of median survival time (MST). Methods: A combined treatment of CPT-11 and S-1 was performed in patients with inoperable advanced gastric cancer who had not received a prior chemotherapy. S-1 was orally administered twice a day for 14 consecutive days, and CPT-11 was administered as a 90-minute intravenous infusion on days 1 and 15. This schedule was repeated every 4 weeks. The patients received 80 mg/m2 /day dose of S-1 and 125 mg/m2 of CPT-11 recommended from phase I study. Results: Fifteen patients were registered in this Phase I study. And 9 patients were added in this Phase II study. Non-hematological toxicities were almost classified as grade 2 or lower, except for grade 3 nausea and grade 3 dermatitis at level 2. These adverse events were manageable by administering antiemetic drugs and drug rest. As for hematological toxicities, grade 4 neutropenia occurred in one patient at level 1 and level 2 at Phase I. And grade 4 neutropenia occurred in four patients at level 2 of Phase II. However, they recovered after the drug rest, and we could continue the administration based on the standard for dose modifications. These side effects were tolerable, and did not impede the schedule. An overall response rate was 54.2%. MST of this regimen is 581 days. Tissue typing MST was superior in significance in the well-differentiated type adenocarcinoma that was being undifferentiated type adenocarcinoma 450 days (95%CI 376 -936 day) for well-differentiated type adenocarcinoma 656 days (95%CI 227–673 days, P =0.04 logrank). Discussion: The results indicate that this combined treatment is applicable to outpatient treatments. MST of the therapy is 581 days meaningful results for this type of patients setting. The severities of adverse events differ individually, but manageable by carefully observing the patients and proper dose modifications. The updated analysis will be presented at the meeting. No significant financial relationships to disclose.
On behalf of the Scottish Gynaecological Cancer Trials Group. Phase III Randomized Trial of Docetaxel?Carboplatin Versus Paclitaxel?Carboplatin as First-line Chemotherapy for Ovarian Carcinoma
Authors: Vasey Pa, Jayson Gc, Gordon A, Gabra H, Coleman R, Atkinson R, Parkin D, Paul J, Hay A, Kaye Sb
Journal: JNCI Journal of the National Cancer Institute (2004)