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1.
Potential of novel colchicine dosage schedule for the palliative treatment of advanced hepatocellular carcinoma.
Lin, ZY, Yeh, ML, Huang, CI, Chen, SC, Huang, CF, Huang, JF, Dai, CY, Yu, ML, Chuang, WL
The Kaohsiung journal of medical sciences. 2021;(7):616-623
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Abstract
Previous in vitro and in vivo experiments had demonstrated dose-dependent anti-cancer effects of clinical plasma colchicine concentrations on hepatocellular carcinoma (HCC) cells. This phase IIa trial was to evaluate the potential efficiency and safety of our novel colchicine dosage schedule for the palliative treatment of advanced HCC. The dosage schedule started from oral intake of 1 mg colchicine three times per day for 4 days and discontinuation in the following 3 days (one cycle). The treatment cycle was repeated and the dosage was adjusted ranging from 3 to 1.5 mg/day according to the condition of the participant. The control group was originated from chart review of 86 HCC patients treated by sorafenib for more than 2 months. Fifteen participants signed the inform consent. Two participants were excluded due to screening failure in one and less than four treatment cycles in another. For severe adverse events, the colchicine group demonstrated higher incidence of biliary tract obstruction (p = 0.0184) than the sorafenib group. Comparison grade 1 or 2 adverse events between two groups, the colchicine group had higher incidence of diarrhea (p = 0) and the sorafenib group had higher incidence of palmar-plantar erythrodysesthesia syndrome (p = 0.0045). There was no significant difference in mortality, median survival, and overall survival between two groups (all p > 0.2). In conclusion, our novel colchicine dosage schedule is clinically feasible and has the potential to be applied in the palliative treatment of advanced HCC especially based on the cost-effectiveness consideration.
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Interdisciplinary care of children with trisomy 13 and 18.
Weaver, MS, Anderson, V, Beck, J, Delaney, JW, Ellis, C, Fletcher, S, Hammel, J, Haney, S, Macfadyen, A, Norton, B, et al
American journal of medical genetics. Part A. 2021;(3):966-977
Abstract
Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and complex care needs. This Review Article provides a summation of the recent literature, informed by the study team's Interdisciplinary Trisomy Translational Program consisting of representatives from: cardiology, cardiothoracic surgery, neonatology, otolaryngology, intensive care, neurology, social work, chaplaincy, nursing, and palliative care. Medical interventions are discussed in the context of decisional-paradigms and whole-family considerations. The communication format, educational endeavors, and lessons learned from the study team's interdisciplinary care processes are shared with recognition of the potential for replication and implementation in other care settings.
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The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).
Lund, CM, Vistisen, KK, Olsen, AP, Bardal, P, Schultz, M, Dolin, TG, Rønholt, F, Johansen, JS, Nielsen, DL
British journal of cancer. 2021;(12):1949-1958
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Abstract
BACKGROUND Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. METHODS The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). RESULTS Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008). CONCLUSION Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. TRIAL REGISTRATION ClinicalTrials.gov ID: NCT02748811.
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Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases.
Zakaly, HMH, Mostafa, MYA, Deryabina, D, Zhukovsky, M
International journal of radiation biology. 2020;(6):779-789
Abstract
Purpose: In recent years, radionuclides like 177Lu have been considered promising material for the creation of therapeutic radiopharmaceuticals. With the therapeutic use of radiopharmaceuticals, the absorbed doses per tumor may exceed 10 Gy. It is extremely important that doses absorbed by healthy organs and tissues do not exceed the threshold for the incidence of deterministic effects.Materials and methods: The potential use of the radionuclide lutetium-177 for the palliative treatment of pain in bone metastases is analyzed. The radionuclide 177Lu is a beta-emitting nuclide with a maximal energy of 0.49 MeV and a half-life of 6.6 days (161 h). Two therapeutic agents were considered: methylene diphosphonate (MDP) and ethylenediamine tetramethylene phosphonic acid (EDTMP). Both drugs contain phosphorus compounds in their composition, which ensures high tropism in bone tissue. For both drugs, biokinetic models of 177Lu's behavior in the human body are created. A number of studies have shown that the radiochemical stability of these drugs is about 99%: these calculations took into account the presence of a free 177Lu radionuclide in each solution. The absorbed doses in organs and tissues when using the radiopharmaceuticals 177Lu-MDP and 177Lu-EDTMP, as well as the currently used drugs 153Sm-EDTMP and 89SrCl2, are compared. In order to assess the risk of the patient's exposure to a radiopharmaceutical, the absorbed doses are calculated for each organ where the radioactive label is mainly deposited: the kidneys, red bone marrow, liver and bone surface.Results: The intensity of dose accumulation when using different drugs on the pathological focus is different. The drug 177Lu-MDP is faster than other drugs when it comes to the full realization of the expected dose; therefore, a therapeutic effect is achieved faster when it is used. The slowest absorbed dose accumulates when strontium chloride is used. To compare the effectiveness of preparations based on the 177Lu radionuclide, an analysis of the radiopharmaceuticals currently used for the palliative therapy of bone metastases (89SrCl2 and 153Sm-EDTMP) was performed. For 89Sr, the most vulnerable organs are the kidneys, red bone marrow and liver, while for 153Sm-EDTMP, red marrow bone is most vulnerable. For radiopharmaceuticals based on the 177Lu radionuclide, the most vulnerable organs are the kidneys, liver and red bone marrow. This proves the effectiveness of the 177Lu-MDP and 177Lu-EDTMP radiopharmaceuticals.Conclusions: According to the results of the calculations, 177Lu-EDTMP and 177Lu-MDP demonstrate the best results for the palliative therapy of bone metastases.
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Clinical management patterns of advanced and metastatic gastro-oesophageal carcinoma after fluoropyrimidine/platinum treatment in France, Germany, Spain and the United Kingdom.
Brown, J, Liepa, AM, Bapat, B, Madhwani, S, Lorenzen, S, García-Foncillas, J, Candrilli, SD, Kaye, JA
European journal of cancer care. 2020;(2):e13213
Abstract
OBJECTIVE To describe treatment patterns and resource utilisation in France, Germany, Spain and the United Kingdom (UK) in patients with unresectable locally advanced and/or metastatic gastro-oesophageal adenocarcinoma (GEA), who failed first-line fluoropyrimidine/platinum treatment. METHODS Treating physicians completed a web-based chart review (2013-2015). Eligible patients were ≥ 18 years old; had unresectable locally advanced and/or metastatic gastric adenocarcinoma including the gastro-oesophageal junction; received first-line fluoropyrimidine/platinum-based therapy; and had ≥ 3 months of follow-up after first-line discontinuation. Data were summarised descriptively for each country. RESULTS There were n = 201 patients in France, n = 202 in Germany, n = 208 in Spain and n = 200 in the UK whose charts were reviewed. Percentages of patients receiving second-line therapy were 55% (France), 48% (Germany), 54% (Spain) and 29% (UK). At the start of second-line therapy, most patients had an ECOG performance status of 1 (range 0-3). Second-line therapy was primarily monotherapy, but agents used varied within and across countries. Supportive care use and resource utilisation were frequent whether receiving additional therapy or not; >60% patients had clinic visits unrelated to chemotherapy administration, and > 30% has ≥ 1 hospital admission. CONCLUSIONS For the time of study, established GEA treatment guidelines were generally followed. However, therapies varied widely in the second-line setting.
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Systemic Inflammation and Nutritional Status in Patients on Palliative Cancer Care: A Systematic Review of Observational Studies.
Cordeiro, LAF, Silva, TH, de Oliveira, LC, Neto, JFN
The American journal of hospice & palliative care. 2020;(7):565-571
Abstract
OBJECTIVE This systematic literature review explores the results of studies that have analyzed the association between inflammation and nutritional status in patients with cancer in palliative care. METHODS The bibliographic research was performed in May 2019, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Group guidelines. The inclusion criteria were papers that (1) had an online abstract available, (2) were original, (3) used a cohort or cross-sectional design, (4) involved patients with advanced cancer in palliative care, and (5) assessed the association between inflammation and nutritional status. The quality assessment was performed using the Newcastle-Ottawa Scale. RESULTS Nine studies were selected. Weight loss (WL; n = 7) was the most common nutritional marker employed and C-reactive protein (CRP; n = 6) was the most common inflammatory marker. There was considerable variability (39.0%-92.2%) in the proportion of patients who had WL in a 6-month period, while CRP >5 mg/dL was common in 45.3% to 73.9% of patients. Systemic inflammation was related to nutritional status, highlighting the relationship between CRP and WL and lean mass (LM). Patients with CRP >10 mg/L have been found to have a lower LM (P < .001) and a faster rate of loss of LM at a faster rate during the disease trajectory (P = .030). CONCLUSION Nutritional status is associated with systemic inflammatory response. Inflammatory markers should be considered an additional parameter for the nutritional diagnosis of patients with cancer in palliative care.
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Nutrition and gastroenterological support in end of life care.
Schütte, K, Middelberg-Bisping, K, Schulz, C
Best practice & research. Clinical gastroenterology. 2020;:101692
Abstract
Malnutrition and the broad spectrum of cancer cachexia frequently occur in patients with malignant disease of all tumour stages and impact on survival and quality of life of patients. Structured screening for the risk of malnutrition with validated tools and nutritional assessment are the prerequisite for adequate nutritional support in cancer patients. In patients receiving tumour directed therapy, the patients diet should meet the requirements to give optimal support, while later on comfort feeding is part of symptom focused palliation. The basis of nutritional support in a malnourished patient is nutritional counselling, and nutritional support can be offered within a step-up approach meeting the patient's needs. A combination of nutritional support with interventions targeting metabolic changes and physical exercise is suggested to treat cancer cachexia.
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The prognostic role of soluble TGF-beta and its dynamics in unresectable pancreatic cancer treated with chemotherapy.
Park, H, Bang, JH, Nam, AR, Park, JE, Jin, MH, Bang, YJ, Oh, DY
Cancer medicine. 2020;(1):43-51
Abstract
OBJECTIVES Transforming growth factor-beta (TGF-β) is a multifunctional regulatory factor. Here we measured serum soluble TGF-β (sTGF-β) levels and evaluated its dynamics and prognostic capabilities during chemotherapy in unresectable pancreatic cancer patients. METHODS We prospectively enrolled 60 patients treated with FOLFIRINOX as the first-line palliative chemotherapy. We collected blood samples at the time of diagnosis, first response assessment, and disease progression and measured serum sTGF-β using an enzyme-linked immunosorbent assay. RESULTS The patients' median overall survival (OS) and progression-free survival (PFS) were 10.3 (95% confidence interval [CI], 8.5-12.1) and 6.5 (95% CI, 4.9-8.1) months, respectively. Patients with low sTGF-β at diagnosis (<31.2 ng/mL) had better OS and PFS than patients with high sTGF-β, respectively, (OS, 13.7 vs 9.2 months; hazard ratio [HR], 2.602; P = .004; PFS, 9.0 vs 5.8 months; HR, 2.010; P = .034). At the time of disease progression, sTGF-β was increased compared with that of diagnosis (mean, 26.4 vs 23.9 ng/mL). In particular, sTGF-β was significantly increased at disease progression in patients with a partial response (mean, 25.7 vs 31.0 ng/mL; P = .049). CONCLUSIONS Pretreatment sTGF-β levels can serve as a prognostic indicator in unresectable pancreatic cancer patients treated with FOLFIRINOX chemotherapy. Likewise, the dynamics of sTGF-β during chemotherapy have prognostic value.
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The Impact of Palliative Care Team Consultation on Quality of Life of Patients with Advanced Cancer in Dutch Hospitals: An Observational Study.
Brinkman-Stoppelenburg, A, Vergouwe, Y, Booms, M, Hendriks, MP, Peters, LA, Quarles van Ufford-Mannesse, P, Terheggen, F, Verhage, S, van der Vorst, MJDL, Willemen, I, et al
Oncology research and treatment. 2020;(9):405-413
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INTRODUCTION Experimental studies have shown that palliative care team (PCT) involvement can improve quality of life (QoL) and symptom burden of patients with advanced cancer. It is unclear to what extent this effect is sustained in daily practice of hospital care. OBJECTIVE This observational study aims to investigate the effect of PCT consultation on QoL and symptom burden of hospitalized patients with advanced cancer in daily practice. METHODS After admission to 1 of 9 participating hospitals, patients with advanced cancer for whom the attending physician answered "no" to the Surprise Question were invited to complete a questionnaire, including the EORTC QLQ-C15-PAL, at 6 points in time, until 3 months after admission. Outcomes were compared between patients who received PCT consultation and patients who did not, taking into account differences in baseline characteristics. RESULTS A total of 164 patients consented to participate, of whom 32 received PCT consultation. Of these patients, 108 were able to complete a questionnaire at day 14, of whom 19 after receiving PCT consultation. After adjusting for baseline differences, EORTC QLQ-C15-PAL scores for pain, appetite, and emotional functioning at day 14 were more favorable for patients who received a PCT consultation. CONCLUSION PCT consultation decreased patients' symptom burden and tends to have a positive effect on QoL of hospitalized patients with advanced cancer, even if the PCT is consulted late in the patient's disease trajectory.
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Home artificial nutrition in palliative care cancer patients: Impact on survival and performance status.
Ruggeri, E, Giannantonio, M, Agostini, F, Ostan, R, Pironi, L, Pannuti, R
Clinical nutrition (Edinburgh, Scotland). 2020;(11):3346-3353
Abstract
BACKGROUND AND AIMS The prevalence of malnutrition is over 70% in advanced cancer patients and impacts negatively on survival and quality of life. Artificial nutrition can be integrated into a home palliative care program. This observational study aims to describe the criteria for identifying the cancer patients that could benefit from home artificial nutrition (HAN) and to evaluate its impact on survival and performance status. METHODS The selection criteria for patient's eligibility to HAN were: Karnofsky Performance Status (KPS) ≥40, life expectancy ≥6 weeks, inadequate caloric intake ± malnutrition, suitable psycho-physical conditions and informed consent. The access route for nutritional therapy (home parenteral nutrition, HPN; home enteral nutrition, HEN) was chosen according to the ESPEN Guidelines. The parameters considered were: primary site of the tumor; oral food intake; nutritional status; stage of cachexia; fluid, energy and protein supplied by HAN; survival. RESULTS From 1990 to 2019, 43,474 cancer patients were assisted at home in Bologna (Italy). HAN started in 969 patients (2.2% of total patients, 571 men and 398 women, mean age 65.7 ± 12.7 years): HPN in 629 patients (64.9%), with gastrointestinal obstruction as the main indication; HEN in 340 patients (35.1%), with dysphagia as the main indication. Considering the 890 deceased patients, the mean survival after the start of HAN was 18.3 weeks and 649 patients (72.9%) survived more than 6 weeks. The mean survival was higher in HEN (22.1 weeks) compared to HPN patients (16.1 weeks) (p < .001). After one month, KPS was unchanged in 649 (67.0%), increased in 232 (23.9%) and decreased in 88 patients (9.1%). The mean KPS increased in patients starting HAN in pre-cachexia and cachexia (p < .001). Cachexia and refractory cachexia at the entry were associated with a reduced survival [odds ratio: 1.5 and 2.3 respectively, p < .001 for both condition] respect to pre-cachexia. CONCLUSIONS The selection criteria allow the identification of the patient who can take advantage of HAN. HAN can be effective in avoiding death from malnutrition in 73% of patients, and in maintaining or improving the KPS at one month in 90% of cases. The benefits provided by HAN on survival and performance status depend on the cachexia degree at the entry.