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Purpose: Despite the increasing popularity of supplement use among the cancer community, the current evidence on its effect on mortality in large studies is inconclusive. This study examined the association of dietary supplement use with mortality risk in a large population-based cohort. Methods: This prospective cohort study analyzed data from the UK Biobank on participants who were diagnosed with cancer before July 31, 2019 and self-reported whether they had regular intake of dietary supplements (vitamins, minerals, or non-vitamin non-mineral [NVNM] supplements) after cancer diagnosis. The associations between the use of supplements with mortality were analyzed using Cox proportional hazards models, adjusting for confounders (sociodemographic factors, lifestyle and comorbidities). Results: This analysis included 30,239 participants (mean age: 60.0 years; 61.9% female). Over half (57.8%) were supplement users. At a median follow-up of 11.9 years, 5577 all-cause deaths were registered. A marginal protective effect of supplement use on the risk of all-cause (adjusted hazard ratio [aHR] = 0.95, 95% CI = 0.90–0.99) and cancer (aHR = 0.89, 95% CI = 0.83–0.95) mortality were found, but not the risk of mortality due to other causes. In subgroup analyses, only NVNM dietary supplements were significantly associated with a lower risk of all-cause mortality (aHR = 0.88, 95% CI = 0.83–0.93). Both vitamins (aHR = 0.93, 95% CI = 0.87–0.99) and NVNM dietary supplements (aHR = 0.88, 95% CI = 0.82–0.94) were associated with a modest decrease in cancer mortality which were marginally significant. Conclusions: This is one of the largest cohort studies that identified the associations of dietary supplements with survival in the cancer population. However, the associations are small and should be interpreted cautiously due to the variations among different supplements and the small effect size. Future studies should investigate the effect of individual supplements, particularly NVNM supplements, on improving other cancer-related outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to test the influence of vaccination characteristics and gain/loss-framing of information, on parental acceptance of the coronavirus disease 2019 (COVID-19) vaccination for their minor children. A discrete choice experiment was conducted among parents of children aged 0-17 years from September to October 2021 in Hong Kong. Respondents were randomly assigned to four groups with different framing of information and asked to choose hypothetical vaccination alternatives, described by seven attributes that were derived from prior qualitative interviews. A mixed logit model was adopted to analyze the effect of attributes and information framing on parental vaccination acceptance. The vaccine acceptance rates under different scenarios were also estimated. A total of 298 valid responses were obtained. It was found that the BioNTech brand, higher efficacy, less serious adverse events and more vaccination coverage in children significantly improved parental acceptance. Additionally, loss-framing increased parental acceptance compared with gain-framing, while the presentation of mortality information did not make a difference. Acceptance was also associated with parental uptake of the COVID-19 vaccine and the children's age.Conclusion: The findings imply that factors including gain/loss information framing, importance of vaccine characteristics, and peer influence have a significant effect on parents' decisions to get their children vaccinated. Parents with younger children had greater vaccine hesitancy, and information framing techniques should be considered in vaccination promotion for combating such vaccine hesitancy. Future studies could be conducted to identify the moderators and mediators of information framing to facilitate its implementation.What Is Known: • Parental acceptance of COVID-19 vaccine was found to be associated with various socio-economic and psychosocial factors, while the evidence on impact of vaccination characteristics was limited. • Behavioral interventions, including information framing, have been used to promote various health behaviors.What Is New: • Loss-framing of information on vaccine effectiveness improves vaccine acceptance, while additional information on how the vaccine reduces death does not make a difference, which can be used to inform communication with the public in vaccination promotion. • The social norm (i.e., the vaccine uptake amongst other people) is important for increasing the parental vaccine acceptance rate. [ABSTRACT FROM AUTHOR]

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by "Cochrane risk of bias 2" tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: − 0.76; 95% CI − 1.19 to − 0.32, I2 = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections. Protocol registration at PROSPERO: CRD42020214305. [ABSTRACT FROM AUTHOR]

Background: In the USA, colorectal cancer is among the top diagnosed cancers. The current study specifically targets the US adult population that have a history of colorectal cancer. Methods: We used the 2017 National Health Interview Survey (NHIS) to investigate the prevalence and predictors of colorectal cancer survivors using complementary medicine in the past 12 months in a representative sample of the US population (N = 26,742). We descriptively analyzed the 12-month prevalence of any complementary medicine use separately for individuals with a prior diagnosis of colorectal cancer and those without. Using chi-squared tests and backward stepwise multiple logistic regression analyses, we identified predictors of complementary medicine use in the past 12 months. Results: A weighted total of 1,501,481 US adults (0.6%) had a history of colorectal cancer. More individuals without (weighted n = 76,550,503; 31.2%) than those with a history of colorectal cancer (weighted n = 410,086; 27.3%) had used complementary medicine. The most commonly used complementary medicine among colorectal cancer patients was mind-body medicine, followed by chiropractic. A higher prevalence of complementary medicine use was associated with being female, higher educated and/or living in the US Midwest or South. Conclusions: In this study, over one fourth of the US colorectal cancer survivors had used complementary medicine. Mind-body medicine was found to be the most commonly used. With evidence supporting the effectiveness and safety of mind-body medicine use among colorectal cancer patients, promoting the use of evidence-based mind-body medicine for colorectal cancer management could be considered. [ABSTRACT FROM AUTHOR]

Background: Molecular profiling is increasingly used to match patients with metastatic cancer to targeted therapies, but obtaining a high-quality biopsy specimen from metastatic sites can be difficult.Methods: Patient samples were received by Perthera to coordinate genomic, proteomic and/or phosphoproteomic testing, using a specimen from either the primary tumour or a metastatic site. The relative frequencies were compared across specimen sites to assess the potential limitations of using a primary tumour sample for clinical decision support.Results: No significant differences were identified at the gene or pathway level when comparing genomic alterations between primary and metastatic lesions. Site-specific trends towards enrichment of MYC amplification in liver lesions, STK11 mutations in lung lesions and ATM and ARID2 mutations in abdominal lesions were seen, but were not statistically significant after false-discovery rate correction. Comparative analyses of proteomic results revealed significantly elevated expression of ERCC1 and TOP1 in metastatic lesions.Conclusions: Tumour tissue limitations remain a barrier to precision oncology efforts, and these real-world data suggest that performing molecular testing on a primary tumour specimen could be considered in patients with pancreatic adenocarcinoma who do not have adequate tissue readily available from a metastatic site. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial.Methods: Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35-175 mg/m2/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined.Results: There were no dose-limiting toxicities (DLTs) in cohorts 1-3. There was a DLT in one of six patients in cohort 4 (112.5 mg/m2) (grade 3 neutropenia causing treatment delay > 15 days) and a DLT in one of three patients in cohort 6 (175 mg/m2) (grade 4 neutropenia and grade 3 abdominal pain). A second patient in cohort 6 experienced a serious adverse event (cycle 1, grade 4 ANC ≤ 7 days, cycle 4, grade 2 left ventricular dysfunction). This dose level was determined to be above the MTD. No DLTs were seen in seven patients treated in cohort 5 (140 mg/m2). The MTD of IP nab-paclitaxel was established at 140 mg/m2 on days 1, 8, and 15 of a 28-day cycle. There was a PK advantage for IP nab-paclitaxel, with an IP plasma area under the concentration-time curve (AUC) ratio of 147-fold (range 50-403) and therapeutic range systemic drug levels. Eight of 27 enrolled patients had progression-free survival ≥ 6 months. One patient experienced complete response, and one patient experienced partial response. Six patients had stable disease.Conclusions: Weekly IP nab-paclitaxel has a favorable toxicity profile, a significant pharmacologic advantage, and promising clinical activity.Clinical Trial Registration: NCT00825201. [ABSTRACT FROM AUTHOR]

Background: Trastuzumab with cisplatin and fluoropyrimidine is the standard treatment in metastatic HER2-positive gastric or gastroesophageal (GE) junction adenocarcinoma; however, there is limited data on the efficacy of trastuzumab in combination with a three-drug regimen in this setting. We examined the efficacy and safety of modified docetaxel, cisplatin and 5 fluorouracil (mDCF) plus trastuzumab in a single-arm multicenter phase II trial.Methods: Previously untreated patients with HER2-positive metastatic gastric or GE junction adenocarcinoma were treated with mDCF and trastuzumab every 2 weeks. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included objective response rate, overall survival (OS), and toxicity.Results: We enrolled 26 patients with metastatic HER2-positive gastric or GE junction adenocarcinoma between February 2011 and June 2015. The median age of patients was 62 years; 96% had a Karnofsky performance status equal to or greater than 80%. With a median follow-up of 25.4 months, the 6-month PFS was 73% (95% CI 51-86%). The objective response rate was 65%, the median PFS was 13 months (95% CI 6.4-20.7) and the median OS was 24.9 months (95% CI 14.4-42.5). Grade 3/4 toxicities included neutropenia (42%), fatigue (23%), and hypophosphatemia (15%). There were no episodes of febrile neutropenia.Conclusion: The combination of mDCF and trastuzumab is effective and safe in patients with metastatic HER2-positive gastric or GE junction adenocarcinoma and can be considered as an option for selected patients. This trial is registered at ClinicalTrials.gov, number NCT00515411. [ABSTRACT FROM AUTHOR]

Approximately 5-10% of all pancreatic cancer patients carry a predisposing mutation in a known susceptibility gene. Since >90% of patients present with late stage disease, it is crucial to identify high risk individuals who may be amenable to early detection or other prevention. To explore the spectrum of hereditary pancreatic cancer susceptibility, we evaluated germline DNA from pancreatic cancer participants (n = 53) from a large hereditary cancer registry. For those without a known predisposition mutation gene (n = 49), germline next generation sequencing was completed using targeted capture for 706 candidate genes. We identified 16 of 53 participants (30%) with a pathogenic (P) or likely pathogenic (LP) variant that may be related to their hereditary pancreatic cancer predisposition; seven had mutations in genes associated with well-known cancer syndromes (13%) [ATM (2), BRCA2 (3), MSH2 (1), MSH6 (1)]. Many had mutations in Fanconi anemia complex genes [BRCA2 (3 participants), FANCF, FANCM]. Eight participants had rare protein truncating variants of uncertain significance with no other P or LP variants. Earlier age of pancreatic cancer diagnosis (57.5 vs 64.8 years) was indicative of possessing a P or LP variant, as was cancer family history (p values <0.0001). Our multigene panel approach for identifying known cancer predisposing genetic susceptibility in those at risk for hereditary pancreatic cancer may have direct applicability to clinical practice in cases with mutations in actionable genes. Future pancreatic cancer predisposition studies should include evaluation of the Fanconi anemia genes. [ABSTRACT FROM AUTHOR]

Purpose: A capsule formulation of the tyrosine kinase inhibitor dovitinib (TKI258) was recently studied in a phase 3 renal cell carcinoma trial; however, tablets are the planned commercial formulation. Therefore, this randomized 2-way crossover study evaluated the bioequivalence of dovitinib tablet and capsule formulations in pretreated patients with advanced solid tumors, excluding breast cancer.Methods: In this 2-part study, eligible patients received dovitinib 500 mg once daily on a 5-days-on/2-days-off schedule. During the 2-period bioequivalence phase, patients received their initial formulation (capsule or tablet) for 3 weeks before being switched to the alternative formulation in the second period. Patients could continue to receive dovitinib capsules on the same dosing schedule during the post-bioequivalence phase.Results: A total of 173 patients were enrolled into the bioequivalence phase of the study (capsule → tablet, n = 88; tablet → capsule, n = 85), and 69 patients had evaluable pharmacokinetics (PK) for both periods. PK analyses showed similar exposure and PK profiles for the dovitinib capsule and tablet formulations and supported bioequivalence [geometric mean ratios: AUClast, 0.95 (90 % CI 0.88-1.01); C max, 0.98 (90 % CI 0.91-1.05)]. The most common adverse events, suspected to be study drug related, included diarrhea (60 %), nausea (53 %), fatigue (45 %), and vomiting (43 %). Of 168 patients evaluable for response, 1 achieved a partial response, and stable disease was observed in 32 % of patients.Conclusions: Dovitinib capsules and tablets were bioequivalent, with a safety profile similar to that observed in other dovitinib studies of patients with heavily pretreated advanced solid tumors. [ABSTRACT FROM AUTHOR]

Purpose: A diagnosis of pancreatic cancer is often associated with higher symptom burden, lower functional status, and worse quality of life (QOL). To date, few interventions have focused on the unique QOL needs of patients with pancreatic cancer. The purpose of this pilot study is to determine the feasibility of an interdisciplinary supportive care planning intervention in patients with pancreatic cancer during disease-focused treatments.Methods: Patients enrolled in this prospective, pre- and post-intervention pilot study received a supportive care intervention that included the following three components: comprehensive QOL assessment, case presentation at interdisciplinary care meetings, and two nurse-administered educational sessions on QOL concerns. Patients completed outcome measures that included the FACT-Hep, FACIT-Sp-12, and self-report of finances and out-of-pocket costs since diagnosis. Measures were completed at baseline prior to receiving the intervention, and follow-up occurred at 1 and 2 months post-intervention.Results: A total of 10 patients were enrolled during a 4-month period who provided informed consent, received the intervention, and completed the study (58 % accrual). Examination of pre- and post-intervention QOL outcomes revealed changes across the three evaluation time points that were not statistically significant. Patients were highly satisfied with the intervention, with 80 % reporting that the intervention was "excellent." Discussions during the interdisciplinary care meetings and educational sessions were largely focused on physical and psychosocial needs.Conclusions: An interdisciplinary supportive care planning intervention was potentially feasible and acceptable for pancreatic cancer patients in an ambulatory care setting. [ABSTRACT FROM AUTHOR]

Background: While surgical resection of pancreatic adenocarcinoma provides the only chance of cure, long-term survival remains poor. Immunotherapy may improve outcomes, especially as adjuvant to local therapies. Gene-mediated cytotoxic immunotherapy (GMCI) generates a systemic anti-tumor response through local delivery of an adenoviral vector expressing the HSV-tk gene (aglatimagene besadenovec, AdV-tk) followed by anti-herpetic prodrug. GMCI has demonstrated synergy with standard of care (SOC) in other tumor types. This is the first application in pancreatic cancer. Methods: Four dose levels (3 × 10 to 1 × 10 vector particles) were evaluated as adjuvant to surgery for resectable disease (Arm A) or to 5-FU chemoradiation for locally advanced disease (Arm B). Each patient received two cycles of AdV-tk + prodrug. Results: Twenty-four patients completed therapy, 12 per arm, with no dose-limiting toxicities. All Arm A patients were explored, eight were resected, one was locally advanced and three had distant metastases. CD8 T cell infiltration increased an average of 22-fold (range sixfold to 75-fold) compared with baseline ( p = 0.0021). PD-L1 expression increased in 5/7 samples analyzed. One node-positive resected patient is alive >66 months without recurrence. Arm B RECIST response rate was 25 % with a median OS of 12 months and 1-year survival of 50 %. Patient-reported quality of life showed no evidence of deterioration. Conclusions: AdV-tk can be safely combined with pancreatic cancer SOC without added toxicity. Response and survival compare favorably to expected outcomes and immune activity increased. These results support further evaluation of GMCI with more modern chemoradiation and surgery as well as PD-1/PD-L1 inhibitors in pancreatic cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Meta-analysis (MA) of randomised trials is considered to be one of the best approaches for summarising high-quality evidence on the efficacy and safety of treatments. However, methodological flaws in MAs can reduce the validity of conclusions, subsequently impairing the quality of decision making. AIMS: To assess the methodological quality of MAs on COPD treatments. METHODS: A cross-sectional study on MAs of COPD trials. MAs published during 2000-2013 were sampled from the Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effect. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. RESULTS: Seventy-nine MAs were sampled. Only 18% considered the scientific quality of primary studies when formulating conclusions and 49% used appropriate meta-analytic methods to combine findings. The problems were particularly acute among MAs on pharmacological treatments. In 48% of MAs the authors did not report conflict of interest. Fifty-eight percent reported harmful effects of treatment. Publication bias was not assessed in 65% of MAs, and only 10% had searched non-English databases. CONCLUSIONS: The methodological quality of the included MAs was disappointing. Consideration of scientific quality when formulating conclusions should be made explicit. Future MAs should improve on reporting conflict of interest and harm, assessment of publication bias, prevention of language bias and use of appropriate meta-analytic methods. [ABSTRACT FROM AUTHOR]

Purpose: Everolimus, an oral inhibitor of mammalian target of rapamycin, can augment the efficacy of HER inhibitors in preclinical studies. This study was conducted to determine the safety and pharmacokinetics (PK) of the combination of lapatinib, a Her1 and 2 inhibitor, and everolimus and to describe its anti-tumor activity in the Phase I setting. Methods: In Part I, dose escalation to define the maximum tolerated dose (MTD) was performed. In Part II, PK of both drugs were analyzed to assess drug-drug interaction. Results: Twenty-three evaluable patients with advanced cancers were treated on six different dose levels in Part I of the study. The dose-limiting toxicities were diarrhea, rash, mucositis, and fatigue. The MTD of the combination was 1,250 mg of lapatinib and 5 mg of everolimus once daily. In Part II of the study, 54 patients were treated with the combination at the MTD. The mean everolimus time to maximum concentration was increased by 44 %, and mean clearance was decreased by 25 % when co-administered with lapatinib, though these differences were not statistically significant. There was no significant influence on the PK of lapatinib by everolimus. Two patients achieved a partial response [thymic cancer (45+ months) and breast cancer (unconfirmed PR; 7 months)]; 11 patients attained stable disease of at least 4 months. Conclusions: Lapatinib and everolimus are well tolerated at doses of 1,250 and 5 mg po daily, respectively. Stable disease ≥4 months/PR was achieved in 13 of 78 patients (17 %). [ABSTRACT FROM AUTHOR]

Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m and later bi-weekly at 12, 15, and 18 mg/m. The maximum tolerated dose (MTD) was determined at 15 mg/m bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39-79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD ( n = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT T values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing. [ABSTRACT FROM AUTHOR]

Objective: To examine the Eastern-Western difference in the interpretation of Integrative Medicine Attitude Questionnaire (IMAQ) by assessing the psychometric properties of a revised Chinese medicine (CM)-specific version of IMAQ (CM-IMAQ). Methods: Factor and Rasch analysis were performed with data collected from a mail survey of 165 Hong Kong Western medical doctors (WMD) randomly sampled from the official registry. The structural validity, unidimensionality, item fit, and differential item functioning (DIF) of the Hong Kong CM-IMAQ were evaluated. Results: Confirmatory factor analysis (CFA) demonstrated that the original IMAQ factor structure was not concordant with our data on Chinese WMD, and subsequent explanatory factor analysis (EFA) validated a new three-factor model for CM-IMAQ: (1) attitude towards 'tonification', (2) attitude towards the effectiveness of CM, and (3) attitude towards CM knowledge. The original IMAQ factor on holism and doctor-patient relationship disappeared. Rasch analysis confirmed the unidimensionality of 'tonification' and the effectiveness domains, but further refinement of the knowledge domain is needed. Conclusions: Cultural adaptation of the IMAQ has demonstrated differences between Eastern and Western doctors trained in allopathic medicine in their interpretations of holism in healthcare. For Chinese WMD, the emphasis of holistic care is placed on 'tonifying' the body rather than on nurturing the mind and spirit. Confucian and Taoist conceptualizations of mental health as well as the persistent stigma towards mental illness within modern Chinese culture may explain why Chinese WMD do not regard mental health promotion as part of routine healthcare. [ABSTRACT FROM AUTHOR]

Purpose: GSK923295 is an inhibitor of CENP-E, a key cellular protein important in the alignment of chromosomes during mitosis. This was a Phase I, open-label, first-time-in-human, dose-escalation study, to determine the maximum-tolerated dose (MTD), safety, and pharmacokinetics of GSK923295. Patients and methods: Adult patients with previously treated solid tumors were enrolled in successive cohorts at GSK923295 doses ranging from 10 to 250 mg/m. GSK923295 was administered by a 1-h intravenous infusion, once weekly for three consecutive weeks, with treatment cycles repeated every 4 weeks. Results: A total of 39 patients were enrolled. The MTD for GSK923295 was determined to be 190 mg/m. Observed dose-limiting toxicities (all grade 3) were as follows: fatigue ( n = 2, 5%), increased AST ( n = 1, 2.5%), hypokalemia ( n = 1, 2.5%), and hypoxia ( n = 1, 2.5%). Across all doses, fatigue was the most commonly reported drug-related adverse event ( n = 13; 33%). Gastrointestinal toxicities of diarrhea ( n = 12, 31%), nausea ( n = 8, 21%), and vomiting ( n = 7, 18%) were generally mild. Frequency of neutropenia was low (13%). There were two reports of neuropathy and no reports of mucositis or alopecia. GSK923295 exhibited dose-proportional pharmacokinetics from 10 to 250 mg/m and did not accumulate upon weekly administration. The mean terminal elimination half-life of GSK923295 was 9-11 h. One patient with urothelial carcinoma experienced a durable partial response at the 250 mg/m dose level. Conclusions: The novel CENP-E inhibitor, GSK923295, had dose-proportional pharmacokinetics and a low number of grade 3 or 4 adverse events. The observed incidence of myelosuppression and neuropathy was low. Further investigations may provide a more complete understanding of the potential for GSK923295 as an antiproliferative agent. [ABSTRACT FROM AUTHOR]

Background: 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors. Methods: Twenty patients received one dose of intravenous and subsequent cycles of oral 3-AP following a 3 + 3 patient dose escalation. Intravenous 3-AP was administered to every patient at a fixed dose of 100 mg over a 2-h infusion 1 week prior to the first oral cycle. Oral 3-AP was administered every 12 h for 5 consecutive doses on days 1-3, days 8-10, and days 15-17 of every 28-day cycle. 3-AP was started at 50 mg with a planned dose escalation to 100, 150, and 200 mg. Dose-limiting toxicities (DLT) and bioavailability were evaluated. Results: Twenty patients were enrolled. For dose level 1 (50 mg), the second of three treated patients had a DLT of grade 3 hypertension. In the dose level 1 expansion cohort, three patients had no DLTs. No further DLTs were encountered during escalation until the 200-mg dose was reached. At the 200 mg 3-AP dose level, two treated patients had DLTs of grade 3 hypoxia. One additional DLT of grade 4 febrile neutropenia was subsequently observed at the de-escalated 150 mg dose. One DLT in 6 evaluable patients established the MTD as 150 mg per dose on this dosing schedule. Responses in the form of stable disease occurred in 5 (25%) of 20 patients. The oral bioavailability of 3-AP was 67 ± 29% and was consistent with the finding that the MTD by the oral route was 33% higher than by the intravenous route. Conclusions: Oral 3-AP is well tolerated and has an MTD similar to its intravenous form after accounting for the oral bioavailability. Oral 3-AP is associated with a modest clinical benefit rate of 25% in our treated patient population with advanced solid tumors. [ABSTRACT FROM AUTHOR]

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83-1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58-1.03; for dominant model: OR = 1.04, 95% CI = 0.82-1.31; for recessive model: OR = 0.87, 95% CI = 0.69-1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38-3.47; for dominant model: OR = 2.15, 95% CI = 1.37-3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background: In the USA, colorectal cancer is among the top diagnosed cancers. The current study specifically targets the US adult population that have a history of colorectal cancer.Methods: We used the 2017 National Health Interview Survey (NHIS) to investigate the prevalence and predictors of colorectal cancer survivors using complementary medicine in the past 12 months in a representative sample of the US population (N = 26,742). We descriptively analyzed the 12-month prevalence of any complementary medicine use separately for individuals with a prior diagnosis of colorectal cancer and those without. Using chi-squared tests and backward stepwise multiple logistic regression analyses, we identified predictors of complementary medicine use in the past 12 months.Results: A weighted total of 1,501,481 US adults (0.6%) had a history of colorectal cancer. More individuals without (weighted n = 76,550,503; 31.2%) than those with a history of colorectal cancer (weighted n = 410,086; 27.3%) had used complementary medicine. The most commonly used complementary medicine among colorectal cancer patients was mind-body medicine, followed by chiropractic. A higher prevalence of complementary medicine use was associated with being female, higher educated and/or living in the US Midwest or South.Conclusions: In this study, over one fourth of the US colorectal cancer survivors had used complementary medicine. Mind-body medicine was found to be the most commonly used. With evidence supporting the effectiveness and safety of mind-body medicine use among colorectal cancer patients, promoting the use of evidence-based mind-body medicine for colorectal cancer management could be considered. [ABSTRACT FROM AUTHOR]

Objective Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are frequently used in the management of cancer-related symptoms. Their effectiveness and safety of acupuncture and related therapies are discussed controversial. The authors aim was to provide an overview to summarise the evidence on acupuncture for palliative care of cancer. Methods A systematic review of 23 systematic reviews was conducted. The systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews was assessed using the Methodological Quality of Systematic Reviews Instrument. Results The methodological quality of the 23 systematic reviews was regarded satisfactory. Evidence was found for acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. For the treatment of cancer-related pain, hot flashes and hiccups, and improving patients' quality of life there are conflicting results. There is currently insufficient evidence to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Conclusion The results of the study suggest that there is evidence for the use of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. As acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer patients. [ABSTRACT FROM AUTHOR]

Acupuncture and related therapies such as moxibustion and transcutaneous electrical nerve stimulation are often used to manage cancer-related symptoms, but their effectiveness and safety are controversial. We conducted this overview to summarise the evidence on acupuncture for palliative care of cancer. Our systematic review synthesised the results from clinical trials of patients with any type of cancer. The methodological quality of the 23 systematic reviews in this overview, assessed using the Methodological Quality of Systematic Reviews Instrument, was found to be satisfactory. There is evidence for the therapeutic effects of acupuncture for the management of cancer-related fatigue, chemotherapy-induced nausea and vomiting and leucopenia in patients with cancer. There is conflicting evidence regarding the treatment of cancer-related pain, hot flashes and hiccups, and improving patients' quality of life. The available evidence is currently insufficient to support or refute the potential of acupuncture and related therapies in the management of xerostomia, dyspnea and lymphedema and in the improvement of psychological well-being. No serious adverse effects were reported in any study. Because acupuncture appears to be relatively safe, it could be considered as a complementary form of palliative care for cancer, especially for clinical problems for which conventional care options are limited. [ABSTRACT FROM AUTHOR]