bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of outpatient parenteral nutrition regimens of patients with GIT tumors with and without receiving simultaneous palliative systemic chemotherapy
Authors: Stuebs P. , Fahlke J. , Schmidt C. , Habermann P. , Hribaschek A. , Ridwelski K. , Lippert H.
Published: April 2020

18578

Background: The nutritional status of oncology patients significantly impacts the success of tumor-specific therapy.This study was designed to objectify the benefit of parenteral nutrition therapy (PN) administered in the ambulatory care setting and at home by evaluation of nutritional parameters in patients simultaneously undergoing palliative systemic chemotherapy. Methods: From 2003 through 2005 56 patients diagnosed with metastatic GIT tumors were included in the survey.43 patients received PN at home (hPN n=16) or in the ambulatory clinic (aPN n= 27) over a period of 8 weeks because of their poor nutritional status.Of 36 patients who underwent palliative systemic chemotherapy, 25 received PN (13 hPN/12 aPN).In aPN 600kcl were administered, while 1500 kcal where given in hPN.The therapy was administered 5 times a week.In all patients albumin and total protein were measured weekly along with body composition via bioelectric impedance analysis (BIA). Results: Over the course of 8 weeks a continuous decrease of albumin and total protein was found in patients not receiving PN.In aPN laboratory values decreased during the first 4 weeks and later stabilized at low levels.In hPN continuous increases in albumin and total protein were observed.BIA results were comparable.In patients receiving chemotherapy without PN there was an initial improvement of relevant BIA parameters followed by a noticeable decline, while in patients receiving chemotherapy and simultaneous PN a stabilization of values occurred after a slight initial decrease.Evaluation of the corresponding laboratory values showed no decline in the group receiving PN but a significant decline in patients receiving chemotherapy only. Conclusions: The nutritional status of patients with GIT tumors shows a continuous decline during chemotherapy without the addition of PN.This study’s data indicate an advantage of PN for patients with GIT tumors, when started early enough. When chemotherapy and PN are administered, there are limitations the use of BIA as a method of measurement.Verification of laboratory parameters specific to nutrition in the process of treatment is both adequate and necessary for assessment of nutritional status.

No significant financial relationships to disclose.
Early and late arrhythmogenic effects of doxorubicin
Authors: Kilickap S. , Barista I. , Akgul E. , Aytemir K. , Aksoy S. , Tekuzman G.
Published: April 2020

18587

Background: To determine the early and late arrhythmogenic effects of doxorubicin-containing chemotherapy regimens, and to identify associated risk. Methods: A prospective study including 29 patients who were treated with doxorubicin-containing regimens between September 2002 and September 2003. Cardiac evaluation was based on 24-hour electrocardiographic monitorization (Holter), which was performed during the first cycle of doxorubicin-containing regimens as well as after the last cycle of chemotherapy. Results: The mean age of the patients was 45.8 ± 15.1 (range 18–69) and the average dose of doxorubicin was 280.03 ± 113.50 mg/m2 (range 50–480). Holter records obtained during the first cycle of treatment revealed varying arrhythmias in 19 patients (65.5%). The most common arrhythmia was supraventricular extrasystole (n = 11, 37%). Holter records obtained after completion of therapy revealed a variety of rhythm abnormalities in 18 (62.1%) patients, with supraventricular extrasystole again being the most common arrhythmia (n = 13, 44.8%). Only 13 (44.8%) patients had arrhythmias documented in both Holter records. One patient presented with syncope during the first course of doxorubicin therapy and Mobitz type 2 atrioventricular block along with complete atrioventricular block lasting for 12 seconds were demonstrated after examination of Holter records. The patient subsequently underwent permanent pacemaker implantation. There was no correlation between the development of arrhythmia in the early and late period and sex, diagnosis, age, and previous radiotherapy history. Conclusion: Doxorubicin may result in arrhythmias both in early and late periods of treatment. These arrhythmias are rarely life threatening.

No significant financial relationships to disclose.
Outcomes and health status of patients undergoing usual care for highly emetogenic chemotherapy
Authors: Lewis C. R. , Olver I. N. , Walpole E. , Shannon C. , Pavlakis N. , Dalley D. , Van Hazel G. , Lybrand S.
Published: April 2020

18591

Background: Chemotherapy-induced nausea and vomiting (CINV) remains a significant issue for patients, especially management of delayed symptoms. The Perugia 2004 antiemetic guidelines recommended that anthracycline/cyclophosphamide (A/C) combination regimens be considered as high risk emetogenic potential. The aim of our study was to determine the extent of CINV, and effect on quality of life for chemotherapy-naïve patients in a practice-based environment. Methods: Eligible patients were receiving their 1st cycle of high risk emetogenic or carboplatin chemotherapy, administered with “standard care” (5HT3 antagonist + dexamethasone) antiemetics (use of NK1 antagonists excluded). Patients completed a daily diary for 5 days post chemotherapy, capturing data on CINV activity and rescue medications usage. Emesis and nausea-specific health status was measured by the Functional Living Index - Emesis (FLIE); general health status was assessed using a 100mm VAS (EQVAS). Results: Of 74 patients, 42 received an A/C regimen, 16 cisplatin and 16 carboplatin. Overall complete response (no vomiting, no use of rescue antiemetics during the study period) was 60% in patients receiving carboplatin, 24% A/C and 21% cisplatin. During the delayed phase, mean total emesis episodes for carboplatin was 0.6, A/C 2.21 and cisplatin 4.08. Patients receiving carboplatin reported less delayed nausea, and better outcomes for FLIE and EQVAS scores. Treatment with either A/C or cisplatin was associated with similar deterioration in nausea control across the study period, and similar impact on FLIE scores (see table ). Conclusions: Our results are consistent with the recommendation that A/C regimens be considered highly emetogenic, with similar impact on patient symptoms and quality of life compared with cisplatin. Delayed CINV remains a target for antiemetic intervention. Similar studies need to be repeated in patients receiving additional NK1 antagonists to assess their impact on CINV outside clinical trials.

[Table: see text]

[Table: see text]
A randomized phase II trial of gemcitabine plus treosulfan versus treosulfan alone in patients with metastatic uveal melanoma
Authors: Schmittel A. H. , Schmidt-Hieber M. , Bechrakis N. E. , Schuster R. , Siehl J. M. , Foerster M. H. , Thiel E. , Keilholz U.
Published: April 2020

8018

Background: In-vitro studies have suggested synergy of gemcitabine and treosulfan against uveal melanoma cells, and the combination of both drugs in the GeT regimen has shown activity in metastatic uveal melanoma patients. This first randomized phase II trial in this rare disease compared the efficacy of the gemcitabine/treosulfan (GeT) combination versus treosulfan alone. Methods: Chemotherapy-naïve patients with proven metastatic uveal melanoma were randomly assigned to receive 1000mg/m2 gemcitabine plus 3500mg/m2 of treosulfan (GeT) or 3500mg/m2 of treosulfan (T) alone. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. In the absence of disease progression a maximum of 6 cycles were administered. Results: Forty-eight patients were randomized. Seven confirmed stable diseases and one partial remission were observed in 24 patients (PR+SD=33%) treated with the GeT regimen, whereas no PR and only 3 SD (13%) were observed in the treosulfan alone arm (p=0.08). Median progression free survival was 3 months (95% CI 1.1–4.9) in the GeT arm and 2 months (95% CI interval 1.7–2.3) in the treosulfan arm (p=0.008, log-rank). Six and 12 months progression free survival was 34.8% and 17.9% and 16.7% and 0% always favouring the GeT arm. Conclusions: This first prospectively randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over treosulfan alone. Therefore GeT will further be investigated in randomized trials.

No significant financial relationships to disclose.
Correlation of molecular HLA typing and outcome in high-risk melanoma patients receiving adjuvant interferon
Authors: Gogas H. , Spyropoulou-Vlachou M. , Dafni U. , Tsoutsos D. , Markopoulos C. , Polyzos A. , Stratigos A. , Pectasides D. , Bafaloukos D. , Fountzilas G.
Published: April 2020

8029

Background: Serological typing for both HLA class I and class II antigen expression, has previously shown association of specific HLA antigen expression with clinical response and survival in patients with metastatic melanoma treated with IL-2 (e.g. HLA-DQ1). Purpose: To evaluate the impact of HLA class I (low-resolution) and class II (high-resolution) expression, on the outcome of high-risk melanoma patients receiving adjuvant high-dose interferon. Methods: 181 stage IIB, IIC and III melanoma patients (88 female and 93 male), median age 52.1 years and 246 healthy controls were included in this study. DNA was used for the determination of HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQB1 genotypes. Results: With a median follow-up of 37 months, 59 (group 1) patients have remained with no evidence of recurrence and 122 have recurred (group 2). Statistical significant differences between the two groups, were found in the following genotypes: HLA-A*02 (42% vs. 57.3%, p=0.08), HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 34.4%, p=0.01), HLA-B*57 (11.8% vs. 2.4%, p=0.02). Statistical significant differences between group 1 and healthy controls, were found in the following genotypes: HLA-A*33 (15.2% vs. 6.5%, p=0.05), HLA-B*51 (15.2% vs. 28.5%, p=0.05), HLA-B*57 (11.8% vs. 4.5%, p=0.05), HLA-Cw*03 (23.7% vs. 11%, p=0.01), HLA-Cw*06 (27.1% vs. 16.1%, p=0.06), HLA-DRB1*0701 (27.1% vs. 13.4%, p=0.01), HLA-DRB1*1601 (35.6% vs. 22.3%, p=0.01), HLA-DQB1*0202 (23.8% vs. 10.1%, p=0.09). Conclusions: Statistical significant differences were seen in HLA-A and HLA-B alleles between the patients with high-risk melanoma free of recurrence and those who recurred after treatment with adjuvant interferon. Additionally, differences were seen between healthy controls and melanoma patients free of recurrence.

No significant financial relationships to disclose.
Antigen-specific T cell responses in patients with melanoma treated with the CTLA4 blocking mAb ticilimumab
Authors: Ribas A. , Comin-Anduix B. , Bozon V. , Camacho L. H. , Bulanhagui C. A. , Jalil J. , Seja E. , Gualberto A. , Economou J. S. , Glaspy J. A. , Gomez-Navarro J.
Published: April 2020

8033

Background: We previously defined the magnitude of the minimum statistically significant change in value for the MHC tetramer and ELISPOT assays (Comin-Anduix, Clin Cancer Res 2006). We used those reference change values (RCV) to determine if the administration of ticilimumab to patients with melanoma expands the circulating populations of tumor antigen-specific T cells. Methods: HLA-A2.1+ pts with sIIIc or IV melanoma and baseline circulating MART-1-specific T cells above the low limit of detection by tetramer assay (LLD, 0.03% of CD8+ T cells) received ticilimumab at 10 mg/kg monthly. Two 40 ml blood samples were collected at baseline, and one at 1 and 2 weeks after each dose for 4 cycles. Primary endpoint was immune response for MART-1 by tetramer assay, for which the RCV is 80% (expressed as percent change from baseline). Results: Of 15 pts (2 sIIIc, 5 sIVa, 2 sIVb, 6 sIVc), 1 was not treated and 2 received only 1 dose due to rapid progression. The 12 remaining pts received 2–11 doses. Clinical immunologic response to ticilimumab was evidenced by immune-related toxicity (G3 diarrhea in 2 pts, G2 hypophysitis in 1 pt, G3 hepatitis in 2 pts) and by anti-tumor activity: CR in 1 pt (15+ mo), PR in 2 pts (9+, 8 mo), and SD in 3 pts (11, 8+ and 4 mo); the rest had PD at 4 mo or less. A mean of 2 baseline and 7 follow up (range 5–9) time points were tested by tetramer and ELISPOT assays. 4 pts had an increase in MART-1-specific T cells beyond the RCV on 1 or more occasions, but no pt had a consistent pattern of change over time. Indeed, there was no consistent pattern of change in any pt in circulating T cells specific for MART-1, gp100, tyrosinase, EBV, or CMV by tetramer or by ELISPOT assay. One pt had accessible regressing lesions which on biopsy showed heavy infiltration by CD8+/Granzyme B+ CTL and a 10-fold enrichment of gp100-specific T cells compared to his peripheral blood. Conclusion: Ticilimumab administered monthly induces immune-related phenomena and tumor responses in patients with melanoma without a demonstrable expansion of circulating melanoma antigen-specific T cells. Evaluation of melanoma antigen-specific T cells within the tumor may be a better way to study the mechanism of antitumor activity of CTLA4 blocking mAb.

[Table: see text]
Transdermal testosterone in female cancer survivors with decreased libido
Authors: Barton D. L. , Loprinzi C. , Wender D. , Dalton R. , Balcueva E. , Atherton P. , Bernath A. , Dekrey W. , Larson T. , Bearden J. , Sloan J.
Published: April 2020

8507

Background: Problems with sexual functioning are an issue negatively affecting the quality of life of female cancer survivors. Testosterone has been implicated as an important hormone in sexual functioning such as libido. Studies of transdermal testosterone have shown benefit in enhancing libido in women who have been diagnosed with hypoactive sexual desire disorder after bilateral oophorectomy. This phase III placebo-controlled clinical trial evaluated whether transdermal testosterone would increase libido in female cancer survivors. Methods: Women with a history of cancer, currently without evidence of disease, were eligible if they reported a decrease in sexual desire and had a sexual partner. Women must have been postmenopausal. Eligible women were randomized to receive 2% testosterone in Vanicream (10 mg daily) versus placebo Vanicream for four weeks, then crossed over to the opposite treatment. The primary endpoint, libido, was measured via the desire subscales of the Changes in Sexual Functioning Questionnaire (CSFQ), which were completed at baseline and at the end of 4 and 8 weeks of treatment. The primary endpoint was the average intra-patient change from baseline to four weeks in the CSFQ subscales between the two arms. A total of 64 patients per group were needed to provide 80% power to detect a difference of 8 units between the treatment means. Two-sided alternative hypothesis testing and a 5% Type I error rate were used. Results: One hundred fifty women were enrolled onto this study. Complete data were available for 132 women. For those on active testosterone cream, serum bioavailable testosterone levels increased significantly over placebo, with a mean change from baseline of 12 and 10 ng/dl for the first and second period, respectively (p<.0001). The average intra-patient change from baseline to week 4 in libido was 5.5 on testosterone and 4.4 on placebo (p=0.58). No carryover effect was detected. The difference in average intra-patient changes from baseline for the entire crossover design between the two arms was only 1.1 points (95% confidence interval of -1.2 to 3.4, p=0.35). Conclusion: Testosterone is not a panacea for libido troubles in women with a history of cancer. Further studies are needed to determine whether there is a role for transdermal testosterone in this population.

No significant financial relationships to disclose.
Double blind, placebo-controlled randomized study of chlorhexidine prophylaxis for chemotherapy-induced oral mucositis with nonblinded randomized comparison to oral cooling (cryotherapy)
Authors: Sorensen J. , Skovsgaard T. , Bork E. , Damstrup L. , Ingeberg S.
Published: April 2020

8508

Background: Oral mucositis is a frequent complication to many chemotherapy agents in conventional doses. Chlorhexidine prophylaxis has been beneficial in some studies and suggested detrimental in others, but never compared to cryotherapy. Methods: Previously untreatedpatients (pts) with colon or gastic cancer receiving the first course of bolus 5-FU 425 mg/m2 with leucovorine 20 mg/m2 daily in five days were randomized, pending informed consent, to either chlorhexidine 0.1% 15 ml mouthrinse one minut TID for 3 wks. (regimen A), or to doubble blind placebo (normal saline with same taste additive as in A) with same dose and frequency (reg. B), or to cryotherapy with crushed ice tips from 10 min. before to 35 min. after start of chemotherapy (reg. C). Pts self-reported on severity (CTC-grading, main end-point) and duration of oral mucositis and side effects on a questionnaire. 75 pts were planned in each arm to detect a 15% difference in grade 3–4 mucositis with a 5% type 1 error and a 20% power. Chi-square test and Mann-Whitney test were used. Results: Among 225 pts randomized, 206 answered the questionnaire (70, 64, and 63 pts in reg.A, reg.B, and reg.C) There were no differences between the regimens with respect to diagnoses, stage, age, gender, smoking habits, or performance status. Mucositis grade 3–4 (impaired oral nutrition/need of artificial nutrition) occurred in 13%, 33%, and 11% in regimens A, B, and C, respectively. Reg. B was significantly worse than A (p<0.01) and C (p<0.005). Median mucositis durations were A: 3 days (0–17), B: 5 (0–20), and C: 1 (0–20). Duration was significantly longer in B than in both A (p=0.035) and C (p=0.003). Pts <40 years had grade 3–4 mucositis in 36% compared to 18% among older pts (p=0.14). Conclusions: Oral mucositis is common with bolus 5-FU,but frequency and duration may be significantly improved by either prophylactic chlorhexidine or by cryotherapy, giving similar results. The latter is an easy and inexpensive treatment which however is drug- and schedule-dependent as it can not be used with infusional 5-FU or with chemotherapy with substantially longer half-lifes than 5-FU.

No significant financial relationships to disclose.
Effectiveness of intrathecal ziconotide in malignant pain: A combined analysis of two controlled trials
Authors: Burton A. W. , Lemus B. , Fletcher R. , Chandler S. , Marmon T.
Published: April 2020

8552

Background: Ziconotide is a nonopioid, N-type calcium channel blocker that inhibits neuronal calcium influx, thereby reducing neurotransmitter release at primary pain afferents. Clinical trials have shown ziconotide is useful in managing severe chronic pain, including nociceptive and neuropathic pain of malignant etiology. We reviewed the effectiveness of ziconotide using the Visual Analog Scale of Pain Intensity (VASPI: 100 mm=worst possible pain, 0 mm=no pain). Methods: Cancer patients from two double-blind, placebo-controlled trials (Studies 95–001 and 301) were analyzed. Study 95–001 used a fast titration scheme over 5 to 6 days, enrolling only patients with malignant pain due to cancer or AIDS. In Study 95–001, the initial dosing regimen was based on a pilot trial and was later modified due to the frequency of adverse events (AEs). The final slower titration, lower dosing regimen resulted in a reduced AE rate. Only patients from the final dosing regimen of Study 95–001 were included in this analysis. Study 301 used a slower titration scheme over 21 days, enrolling patients with malignant or nonmalignant pain. A two-sided, two-sample t-test was used to evaluate the null hypothesis that the mean percent change in VASPI score from baseline to end of titration for the ziconotide group was not significantly different from that of the placebo group (intent-to-treat population). Results: A total of 67 patients with malignant pain were treated in the trials; 51 (35 ziconotide, 16 placebo) had both baseline and end of titration VASPI scores. The ziconotide and placebo groups had similar mean baseline VASPI scores (75.5 and 75.8 mm, respectively). The mean percent improvement in VASPI score was 36.5% in the ziconotide group and 8.6% in the placebo group (p=0.0230). Conclusions: These results indicated that ziconotide was effective in relieving malignant pain.

[Table: see text]
Anticoagulation vs. vena caval filters in cancer patients with venous thromboembolism: Improved survival with anticoagulation
Authors: Barginear M. F. , Lesser M. L. , Strakhan M. , Khetarpal P. , Bradley T. , Budman D. R. , Shapira I.
Published: April 2020

8553

Background: Cancer patients (pts) have an increased incidence of venous thromboembolism (VTE). Inferior vena caval (IVC) filters are used extensively in the US; over 40,000 are inserted annually. The impact on survival of cancer pts receiving IVC filters has not been studied. Methods: A retrospective study examined 154 consecutive cancer pts with VTE in order to compare the effects of IVC filter placement with anticoagulation (AC) therapy on overall survival (OS), as measured from the time of VTE. Pts were classified into three treatment groups: AC (n=58), IVC filter (73), or combination IVC filter+AC (23). OS was analyzed using survival analysis methods (e.g., Kaplan-Meier Product-Limit Method, logrank test). Multivariate Cox regression was used to account for the possible confounders: ECOG performance status (PS) and type of thrombus. Results: Treatment groups did not differ with respect to age, gender, or albumin levels. Groups did differ for PS (P<0.033 chi-square test, better PS was associated with AC only) and for type of thrombus (P<0.007 chi-square, DVT was associated with AC, PE with IVC, and DVT/PE with AC+IVC). Median OS was significantly greater in pts treated with AC (11 mos) compared to IVC filters (3 mos) or IVC+AC (3.5 mos) (p<0.0046). IVC pts were 1.73 times more at risk of death than AC only (hazard ratio; 95%CI 1.18–2.52). Multivariate analysis revealed that PS and type of thrombus were not confounders and had no effect on OS. Conclusion: AC should be considered primary therapy for cancer pts with VTE. IVC filters should be considered a therapeutic option only when AC is strictly contraindicated. Prospective randomized trials are needed to address this issue.

No significant financial relationships to disclose.
Prospective validation of a risk model for first cycle neutropenic complications in patients receiving cancer chemotherapy
Authors: Lyman G. H. , Kuderer N. M. , Crawford J. , Wolff D. A. , Culakova E. , Poniewierski M. S.
Published: April 2020

8561

Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications (NC) in cancer patients receiving chemotherapy. Methods: 3,596 patients initiating a new chemotherapy regimen with solid tumors or lymphoma were registered at 115 randomly selected sites. Data on at least 1 cycle of chemotherapy were available on 3,468. A logistic regression model for cycle 1 NC was derived and then validated using a split sample random selection process. Results: The risk of cycle 1 NC ranged from 5.5%-30.2%, averaging 18.5% across tumor types. No significant differences in distribution of NC or predictive factors were observed between the derivation dataset (n=2,592) or the validation dataset (n=876). Major independent baseline clinical risk factors for cycle 1 NC in the derivation model include: prior chemotherapy (P=.044), number of myelosuppressive agents (P<.0001), anthracycline-based regimens (P<.0001), planned delivery >85% of standard (P<.0001), cancer type (P<.0001), concurrent antibiotics (P=.023) or phenothiazines (P=.006), abnormal alkaline phosphatase (P=.002), elevated bilirubin (P=.031), low platelets (P=.004), elevated glucose (P=.023) and reduced glomerular filtration rate (P=.013). Reduced risk of cycle 1 NC was associated with primary prophylaxis with a myeloid growth factor (P<.0001). Model R2 was 0.273 and c-statistic 0.80 [95% CI: 0.78–0.82; P<.0001]. At the median predicted risk of cycle 1 NC of 11%, model test performance consisted of: sensitivity 84%; specificity 57% and diagnostic odds ratio (DOR) 7.2 while cycle 1 NC risk was 31% and 6% among high risk and low risk half, respectively. The model performed well in the smaller validation dataset with a model R2 of 0.354 and c-statistic of 0.84 [95% CI: 0.81–0.87, P<.0001]. Test performance of the model in the validation sample included: sensitivity 90%; specificity 62%; DOR 14.1 and risks of 35% and 4% in high risk and low risk patients, respectively. Conclusions: Validation in a randomly selected patient sample suggests that this model has general applicability in identifying patients at increased risk for NC. Further validation in other independent cancer patient populations receiving chemotherapy is planned.

[Table: see text]
Predictors of fatigue and quality of life in a prospective palliative care cohort
Authors: Martin M. G. , Currow D. C. , Abernethy A. P.
Published: April 2020

8571

Background: Palliative care seeks to minimize distress at the end of life. Fatigue significantly diminishes quality of life (QOL) in this population. Are there potentially modifiable factors that influence fatigue and QOL? Methods: This analysis focuses on a subset of 198 patients from a larger 2×2×2 factorial randomized trial of pain education and care coordination conducted in South Australia. Selected participants were adults referred to a community palliative care service with pain in the preceding 3 months and a hemoglobin assessment within 14 days of enrollment. Pain, other symptoms, and Australia-modified Karnofsky Performance Status (AKPS) were recorded at enrollment. Predictors considered were anxiety, depression, dyspnea, constipation, pain, AKPS, hemoglobin, age, and gender. Dependent variables were global QOL from the McGill QOL Questionnaire and fatigue. Using forward stepwise linear regression, multivariate models predicting fatigue and QOL were constructed from significant univariate variables. Results: Mean age was 69 (standard deviation (SD) 13); 97% had cancer. Most frequent diagnoses were lung (18%), hematological (15%), and colorectal (15%) malignancies. Mean hemoglobin was 11.4 gm/dL (SD 1.9); median AKPS 60%; mean worst pain 4.0 (SD 3.4; 0–10 scale). Distressing symptoms (3–4 on 0–4 scales) included dyspnea (22%), constipation (13%), anxiety (11%), and depression (6%). Mean QOL was 5.9 (SD 2.0) on a 0–10 scale; mean fatigue was 2.3 (SD 1.0) on a 0–4 scale. The final multivariate model predicting fatigue included AKPS (p<0.01), constipation (p=0.02), and dyspnea (p=0.06). Hemoglobin was not predictive of fatigue (univariate p=0.7069). QOL was significantly influenced by fatigue (p=0.03), anxiety (p< 0.01), and AKPS (p= 0.01). Conclusions: Fatigue was driven by performance status, constipation, and dyspnea. In contrast to an oncology population, hemoglobin was not a significant contributor to fatigue in this population, consistent with other palliative care cohorts. QOL was driven by fatigue, anxiety, and performance status. This analysis of a prospectively collected population suggests that performance status, constipation, dyspnea, and anxiety are potentially modifiable variables impacting fatigue and QOL in the palliative care setting.

No significant financial relationships to disclose.
Prospective neurocognitive effects and quality of life (QOL) in patients with multiple brain metastases receiving whole brain radiation (WBRT) ± thalidomide on radiation therapy oncology group (RTOG) trial 0118
Authors: Fox S. , Berkey B. , Knisely J. , Chakravarti A. , Yung W. A. , Curran W. , Robins H. , Brachmen D. , Henderson R. , Mehta M. , Movas B.
Published: April 2020

8589

Background: RTOG 0118 was a randomized trial of WBRT (37.5 Gy/15 fractions) ± thalidomide in patients (pts) with brain metastases, which showed no effect on survival (Knisely et al, ASCO, 2005). This analysis examined the relationship between neurocognitive progression (NCP) and QOL in patients on both arms. Methods: NCP was assessed with the Folstein Mini-Mental Status Exam (MMSE) and QOL with the Spitzer QOL Index (SQLI). Pts with MMSE scores below age/education adjusted cutoff levels were considered to have NCP. T-test and Chi-Square statistics were used to determine significant differences in NCP and QOL between the two treatment arms over time. Results: Of 176 pts, 88 and 92% had SQLI and MMSE scores at baseline (43% were below the MMSE cutoff). Baseline SQLI (but not MMSE) was a significant predictor for OS (p=0.034). From baseline, SQLI and MMSE compliance rates were 74 and 60% at 1–2 months (mo), 37 and 29% at 4 mo, and 21 and 19% at 6 months, respectively. While QOL was stable, those who failed to meet MMSE cutoffs increased by 60% by 6 mo, on both study arms. Although a weak correlation (r=.23) existed at baseline between QOL and MMSE for both the WBRT (0.04) and WBRT/thalidomide (0.058) arms, there was no correlation beyond baseline. Conclusions: Baseline QOL is a significant predictor of OS. While QOL remained essentially stable, the degree of neurocognitive decline (60%) over time is concerning. These findings suggest the importance of these outcome measures in pts with brain metastases and the need for interventions to conserve cognitive status. RTOG is developing a trial to study the role of preventive strategies for NCP in brain metastases.

No significant financial relationships to disclose.
Symptom distress, quality of life and challenges of illness according to race and income in women with metastatic breast cancer
Authors: Rosenzweig M. , Wiehagen T. , Brufsky A. M. , Arnold R. M.
Published: April 2020

8609

Background: Response to a diagnosis of metastatic breast cancer (MBC) may vary according to race and income. The aims of this study were: 1) to identify quality of life, symptom distress and challenges of illness during MBC treatment and 2) to determine if these variables differ according to race and income. Methods: The study was a 2×2 prospective design conducted at an urban breast cancer center. Women with MBC were categorized into four groups based on race and income: white low (WL), white high (WH), African American high (AAH) and African American low (AAL). Instruments were 1) Symptom Distress Scale (SDS), (higher scores /worse distress) 2) Functional Assessment of Cancer Therapy (FACT), (higher scores/better QOL) and a 3) semi structured interview assessing patient perspectives of MBC. Interview analysis utilized grounded theory. Results: Preliminary results are for 51 women. Mean age was 58.2 years, with mean 24 months since MBC diagnosis. Quantitative data indicated worse quality of life in AA than white women. (P=0.06), with AALI women exhibiting worse symptom distress (P=0.03) as compared to white women. Qualitative data (n=48) corroborated quantitative data. The most prevalent themes among all sociodemographic groups were of hope (33/48 - 69%), faith (28/48 - 58%) and progressive loss (29/48, 60%). Each racial/economic delineation expressed unique themes: AALI talked about physical (7/7,100%)and social distress (6/7, 86%) as well as uncertainty regarding “whether treatment was worth it” (6/7 - 86%). WLI women verbalized an overall optimism, describing themselves as “lucky” (6/14 - 43%), with minimization of symptoms (10/14 - 71%). WHI women articulated a sense of betrayal at their progressive illness (9/20 - 45%) and fear of physical and economic dependence. Conclusion: Race and economic delineation brings unique symptom experience, quality of life and patient perspective to the metastatic breast cancer experience. These findings will advise tailored intervention.

[Table: see text]

No significant financial relationships to disclose.
Does one person provide it all? Defining the social support of women with cancer
Authors: Dizon D. S. , Gass J. , Bandera C. , Weitzen S. , Clark M.
Published: April 2020

8611

Background: Medical care encourages the appointment of a health care proxy in the event the patient cannot make decisions and it is assumed that this same person will serve other critical roles for the patient. Yet, this assumption that a patient truly relies on the same person for various supportive roles has never been formally evaluated. We hypothesized that there may be a large proportion of women with cancer who do not rely on the same person to be their primary support (PS), to participate in health care decision making as proxy (HCP), and serve as an emergency contact (EC). In order to evaluate this we conducted a questionnaire over a six-month period for women treated in the Program in Women’s Oncology (PWO). Methods: Patients seen at the PWO for a cancer diagnosis were invited to participate in a four part survey on social supports. Demographic data including age, race, cancer diagnosis, date of diagnosis, and current status were collected by chart review. Categorical variables were analyzed using Fisher’s Exact Test or Chi-square analysis. Results: Over 6 months, 224/228 women (98%) agreed to participate. The median age was 58 (range, 30–85). 138 (62%) had breast cancer, 78 (35%) had a gynecologic cancer, and 8 (3.5%) had a non-gyn/non-breast tumor (6/8 colorectal). 66% were married, 8% had a partner, and 26% did not identify a partner. In this sample, 43% did not name the same person as EC, PS, and HCP. 75% named the EC as HCP, 68% EC as PS, and 62% PS as HCP (p<0.05). Of married women (n=147) only 60% named their spouse to all three roles. Divorced women were not as likely to name a partner to one of these roles as were single women with partners. When asked to define primary support, women had diverse perspectives spanning the emotional, physical, intimate, and spiritual dimensions. Age did not appear to be a significant predictor of how these questions were answered. Conclusions: This study demonstrates the complex social support structures of women with cancer. Understanding these relationships may help to enable more effective patient-centered interventions designed to improve quality of care and ultimately the quality of life of cancer survivors.

No significant financial relationships to disclose.
A novel erythropoiesis-stimulating agent (AMG114) with 131-hour half-life effectively treats chemotherapy-induced anemia when administered as 200 mcg every 3 weeks
Authors: Österborg A. C. , De Boer R. , Clemens M. , Renczes G. , Kotasek D. , Prausova J. , Marschner N. , Hedenus M. , Hendricks L. , Amado R.
Published: April 2020

8626

Background: In treating chemotherapy-induced anemia (CIA), erythropoiesis-stimulating agents (ESAs) that can be administered every 3 wks (Q3W), a common chemotherapy schedule, are convenient for patients (pts) and minimize resource utilization. AMG114 is a hyperglycosylated analog of recombinant human erythropoietin, with 4 additional N-linked carbohydrates and 10-amino acid difference from human erythropoietin. In vitro and in vivo animal data for AMG114 predict increased biological activity and prolonged half-life compared with commercially available ESAs. Methods: This multicenter, randomized, double-blind, placebo-controlled, dose-finding, phase 1 study evaluated safety, pharmacokinetics (PK), and efficacy of AMG114 administered subcutaneously Q3W in anemic pts (hemoglobin [Hb] ≥ 8.5 and ≤ 10.5 g/dL) with nonmyeloid malignancies receiving nonplatinum chemotherapy. Patients received AMG114 or placebo for 6 wks (ie, 3 administrations), followed by 3 wks of observation. Efficacy was assessed by Hb change from baseline. Results: Three doses were tested in sequential dose escalation cohorts (including pts receiving placebo): 15 (n=10), 50 (n=18), and 200 (n=20) mcg. Tumor types were: breast (33.3%), non-Hodgkin’s lymphoma, pancreatic, and colorectal (12.5% each). Consistent with animal PK models, the 200-mcg cohort had adequate levels of AMG114 for evaluation of prespecified endpoints (Table). The safety profile of AMG114 was similar to placebo and expected for this population. Antibodies to AMG114 were not detected. Conclusions: AMG114, a novel ESA with an extended 131-hour half-life, appears to be safe and effective at stimulating erythropoiesis and raising Hb levels using 200 mcg Q3W. Although the need for new longer-acting ESAs in the CIA setting may be limited as it is possible to synchronize anemia therapy with most chemotherapy schedules using currently available ESAs, AMG114 may hold promise in other settings.

[Table: see text]

[Table: see text]
Incidence of deep venous thrombosis associated with central venous catheters (DVT-CVC) in cancer patients: A multicenter study
Authors: Feliu J. , Lecumberri R. , Jerez A. , Cantalapiedra A. , García T. , Gonzalez E. , García Frade J. , Vicente V. , Rocha E.
Published: April 2020

8627

Background: The reported incidence of DVT-CVC is extremely variable (0.3–28.3% for symptomatic thrombosis and 27–66% for asymptomatic thrombosis). Data in regarding new catheter materials and insertion techniques are very limited. Likewise, the use of antithrombotic prophylaxis in cancer patients with a CVC remains debatable. Methods: A prospective epidemiologic study was performed, which included adult patients with active cancer and no history of venous thromboembolism, in whom a long term CVC was inserted. Patients were followed-up for 90 days and a bilateral upper extremity Doppler-ultrasound was performed on days 45±5 and 90±5. Likewise, basal blood samples were taken and have been analyzed for hypercoagulability markers and prothrombotic factors. Results: Inclusion period lasted from July 2004 until May 2005. 141 patients have completed the follow up, with a mean age of 52.1±14.3 years (range 21–87). The cumulative incidence of DVT-CVC was 14.2% (20/141): 6.4% were symptomatic (9/141) and 8.9% were asymptomatic (11/123). All thrombotic events, excluding 4 cases, occurred before day 45. Neither age, gender, type of tumor (solid or haematological cancer), tumor stage, type of CVC (Port or tunnelled), number of lumens, side of insertion, platelet count or use of antithrombotic prophylaxis were significantly associated with the incidence of DVT-CVC, although only 1/8 patients with DVT-CVC receiving antithrombotic prophylaxis (12.5%) used high risk prophylaxis. Patients with prior central catheters tended to have a greater incidence of DVT-CVC (P=0.10). None of the basal plasma markers analyzed (fibrinogen, D dimer, F VIII, proteine C resistance, prothrombin fragments 1+2, thrombin-antithrombin complex) have been significantly associated with increased risk of DVT-CVC. Conclusions: DVT-CVC is a frequent complication in cancer patients, as with solid tumors so with haematologic malignancies. The incidence of DVT-CVC seems to be specially high the first few weeks following catheter placement. None of the basal plasma markers analyzed in this study have been associated with the incidence of DVT-CVC. New studies must be performed to allow identification of at risk patients who might benefit from antithrombotic prophylaxis.

No significant financial relationships to disclose.
Dose linearity of inhaled fentanyl (FT) with comparative pharmacokinetics to transmucosal fentanyl (A)
Authors: Jekunen A. P. , Cotterill-Jones C. , Dewlan P. , Tanner T. , Sikorska H. , Asking L. , Jouhikainen T.
Published: April 2020

8629

Background: Cancer patients frequently experience breakthrough pain which is a transitory flare of moderate or severe pain occurring on top of otherwise controlled, persistent pain. Fentanyl TAIFUN (FT), a novel breath-actuated dry powder inhaler is being developed for the treatment of breakthrough cancer pain in patients with ongoing opiate therapy. Methods: A randomized, open-label, crossover phase I study with 5 periods derived pharmacokinetics after fentanyl oromucosal (Actiq, A) and pulmonary (FT) administration in 30 healthy volunteers. Each single dose of study medication (200 mcg A; or 100, 200, 400 or 800 mcg FT) was administered following premedication with 50 mg of naltrexone with a minimum of 7 days between doses. Pharmacokinetic parameters were calculated from the plasma concentrations using a non-compartmental model. Results: The plasma concentrations of FT increased proportionally to the increasing dose and t1/2 was independent of the dose. FT had a linear elimination phase. FT had a substantially faster absorption and higher peak fentanyl concentration (Cmax) than A. Median Tmax was 1 and 60 min for FT and A, respectively. Moreover, there was an 8-fold increase in bioavailability of fentanyl during the first 20 min when 200 mcg FT is compared to 200 mcg A. Conclusions: The plasma concentrations from FT increases proportionally to the increasing dose while t1/2 is independent of the dose, and there is a linear elimination phase. Overall, FT is substantially more bioavailable than A during the important first 20–30 minutes after administration. Inhalation of FT allows an immediate and comparable availability of fentanyl suggesting potential for rapid pain relief.

[Table: see text]

[Table: see text]
Natural History of Adrenal Steroidogenesis in Autoimmune Addison’s Disease Following Diagnosis and Treatment
Authors: Napier Catherine , Allinson Kathleen , Gan Earn H , Mitchell Anna L , Gilligan Lorna C , Taylor Angela E , Arlt Wiebke , Pearce Simon H S
Published: April 2020

Context

The natural history of adrenal function in autoimmune Addison disease once diagnosed and treated has not been systematically studied, but several case reports of recovery from established adrenal failure suggest it may not be uniform.

Objective

To ascertain steroidogenic function in autoimmune Addison disease immediately following diagnosis and during prolonged treatment.

Design

We studied peak serum cortisol in response to ACTH1-24 in 20 newly diagnosed autoimmune Addison disease patients at first presentation and then again within a month. We also studied 37 patients with established Addison disease (for between 7 months and 44 years) in a medication-free state, measuring peak serum cortisol responses to ACTH1-24 and the urine LC-MS steroid metabolome.

Results

Adrenal steroidogenesis declined rapidly after steroid replacement treatment for newly diagnosed Addison disease was started, with a peak serum cortisol falling from 138 ± 19 nmol/L (SEM) at presentation to 63 ± 13 nmol/L over 4 weeks (P < 0.003).

Six of 37 participants (16%) with established Addison disease had detectable serum cortisol and urine glucocorticoid and mineralocorticoid metabolites during repeat testing, indicating variable degrees of residual adrenal function.

Conclusion

Autoimmune Addison disease is a heterogeneous condition, showing a rapid decline in adrenal steroidogenesis during the first few weeks following diagnosis, but low-level residual function in a minority of patients, which appears to persist for many years.
Plasma Trimethylamine N-Oxide and Risk of Cardiovascular Events in Patients With Type 2 Diabetes
Authors: Croyal Mikael , Saulnier Pierre-Jean , Aguesse Audrey , Gand Elise , Ragot Stéphanie , Roussel Ronan , Halimi Jean-Michel , Ducrocq Gregory , Cariou Bertrand , Montaigne David , Wargny Matthieu , Krempf Michel , Hadjadj Samy
Published: April 2020

Objective

Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D).

Research Design and Methods

We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D.

Results

The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P < 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514.

Conclusions

We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.
Is a Ridge Classification Helpful when Assessing Edentulous Patients?
Authors: Leyssen Wouter , Butt Kasim , Walmsley AD
Published: April 2020

The edentulous ridge classifications most commonly used have their limitations in treatment planning. They do not provide an indication of the complexities that may occur when constructing a new set of complete dentures. The new classification system suggested in this article helps with improved record-keeping, information exchange between colleagues, and communication between patient and clinician.

CPD/Clinical Relevance: The new edentulous ridge classification system links the various edentulous ridge shapes to possible complications that could arise during denture construction.
Conscious Sedation in Dentistry: Selecting the Right Patient
Authors: Hazara Roya
Published: April 2020

In recent years, conscious sedation has grown in popularity as an alternative to general anaesthesia in a primary setting due to its safety and efficiency. It is imperative to carry out a full patient assessment prior to treatment under conscious sedation. Conscious sedation is provided intravenously, by inhalation or oral route. Clinical and physical examination as well as medical, social and mental history play a fundamental role in selecting the right patient. In addition, to optimize safety of patients, it is necessary to follow available guidelines and standards, provide an appropriate environment and adequate staff training.

CPD/Clinical Relevance: This article highlights the importance of pre-assessment prior to treatment under conscious sedation. The vast majority of adverse events during sedation occur as a result of inadequate pre-assessment and preparation.
DESENVOLVIMENTO DE ELEMENTOS AERODINÂMICOS PARA VEÍCULOS DE COMPETIÇÃO TIPO BAJA SAE
Authors: Mafalda Rovilson
Published: April 2020

Neste artigo é apresentado o desenvolvimento de elementos aerodinâmicos paraum veículo de competição tipo Baja SAE. A competição Baja SAE envolveinstituições de ensino de todo Brasil, seus eventos já são tradicionais e envolvemuma grande quantidade de estudantes de diversas áreas de Engenharia. Em geralos projetos dos estudantes focam elementos essenciais nos carros como tração,suspensão, freios, porém se tem observado que elementos de aerodinâmica nãotêm despertado interesse das equipes. Buscando contribuir com o item deaerodinâmica descrito no regulamento da competição, este artigo aborda ospontos principais da aplicação de elementos aerodinâmicos em um protótipo BajaSAE típico. Espera-se com isso fomentar o interesse de estudantes para estedomínio e prover um método de incremento de desempenho destes veículos.