Genetic polymorphisms of insulin-like growth factor 1 and insulin-like growth factor binding protein 3, xenoestrogen,phytoestrogen, and premenopausal breast cancer

BackgroundPrevious studies suggest a combined effect of insulin-like growth factor 1 (igf-1) and igf binding protein 3 (igfbp-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the igf-1 signalling pathway and serum concentrations in the igf system, which are associated with premenopausal breast cancer (bca) risk.MethodsBetween 2010 and 2012, our study recruited 140 premenopausal bca patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (oc) use, dietary habits, and other bca risk factors. TaqMan assays were used to determine igf-1 rs1520220 and igfbp-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (easis) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ors) and 95% confidence intervals (cis) of the igf-1 rs1520220 and igfbp-3 rs2854744 genotypes, oc use, and intake of easis. Stratified analyses were performed to detect the gene–environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (iors) by the multiplicative model, with 95% cis. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (reri), attributable proportions of interaction (apis)] and 95% cis.ResultsThe igf-1 and igfbp-3 genotypes, oc use, and easis were not found to be associated with bca risk (p > 0.05). Stratified analysis showed that the risk of bca was markedly increased in women carrying the igfbp-3C allele and using ocs compared with women either carrying the igfbp-3C allele or using ocs (or: 3.02; 95% ci: 1.04 to 8.79). The interaction coefficients ior, reri, and api were 4.89 (95% ci: 1.09 to 21.90), 2.42 (95% ci: −0.76 to 5.61), and 0.80 (95% ci: 0.46 to 1.67) respectively.ConclusionsThe igfbp-3 rs2854744 polymorphism and oc use might synergistically increase premenopausal bca risk.     

Cancer incidence,mortality, and stage at diagnosis in First Nations living in Manitoba

BackgroundIn the present study, we examined breast (bca) and colorectal cancer (crc) incidence and mortality and stage at diagnosis for First Nations (fn) individuals and all other Manitobans (aoms).MethodsSeveral population-based databases were linked to determine ethnicity and to calculate age-standardized incidence and mortality rates. Logistic regression was used to compare bca and crc stage at diagnosis.ResultsFrom 1984–1988 to 2004–2008, the incidence of bca increased for fn and aom women. Breast cancer mortality increased for fn women and decreased for aom women. First Nations women were significantly more likely than aom women to be diagnosed at stages iii–iv than at stage i [odds ratio (or) for women ≤50 years of age: 3.11; 95% confidence limits (cl): 1.20, 8.06; or for women 50–69 years of age: 1.72; 95% cl: 1.03, 2.88). The incidence and mortality of crc increased for fn individuals, but decreased for aoms. First Nations status was not significantly associated with crc stage at diagnosis (or for stages i–ii compared with stages iii–iv: 0.98; 95% cl: 0.68, 1.41; or for stages i–iii compared with stage iv: 0.91; 95% cl: 0.59, 1.40).ConclusionsOur results underscore the need for improved cancer screening participation and targeted initiatives that emphasis collaboration with fn communities to reduce barriers to screening and to promote healthy lifestyles.     

Population-based home care services in breast cancer: utilization and costs

Objective

To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc).

Methods

Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005–2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis.

Results

Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient–year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient–year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased.

Interpretation

Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population.     

Treatment outcomes for male breast cancer: a single-centre retrospective case–control study

Background

Male breast cancer (bc) is a rare disease, and the availability of information on treatment outcomes is limited compared with that for female bc. The objective of the present study was to compare disease-free (dfs) and overall survival (os) for men compared with women having early-stage bc.

Methods

This retrospective case–control study compared men and women treated for stage 0–iiib bc at a single institution between 1981 and 2009. Matching was based on age at diagnosis, year of diagnosis, and stage. Treatment, recurrence, and survival data were collected. Kaplan–Meier analysis was used to calculate os and dfs.

Results

For the 144 eligible patients (72 men, 72 women), median age at diagnosis was 66.5 years. Treatments included mastectomy (72 men, 38 women), radiation (29 men, 44 women), chemotherapy (23 men, 20 women), and endocrine therapy (57 men, 57 women). Mean dfs was 127 months for women compared with 93 months for men (p = 0.62). Mean os was 117 months for women compared with 124 months for men (p = 0.35). In multivariate analysis, the only parameter that affected both dfs and os was stage at diagnosis.

Conclusions

This case–control study is one of the largest to report treatment outcomes in early-stage male bc patients treated in a non-trial setting. Male patients received systemic therapy that was comparable to that received by their female counterparts, and they had similar os and dfs. These results add to current evidence from population studies that male sex is not a poor prognostic factor in early-stage breast cancer.     

Prognostic value of pretreatment circulating neutrophils,monocytes, and lymphocytes on outcomes in lung stereotactic body radiotherapy

PurposeIn the present study, we determined the association of pretreatment circulating neutrophils, monocytes, and lymphocytes with clinical outcomes after lung stereotactic body radiotherapy (sbrt).MethodsAll patients with primary lung cancer and with a complete blood count within 3 months of lung sbrt from 2005 to 2012 were included. Overall survival (os) was calculated using the Kaplan–Meier method. Factors associated with os were investigated using univariable and multivariable Cox proportional hazards regression. Fine–Gray competing risk regression was performed to test the association of the neutrophil:lymphocyte (nlr) and monocyte:lymphocyte (mlr) ratios with two types of failure: disease-related failure and death, and death unrelated to disease.ResultsOf the 299 sbrt patients identified, 122 were eligible for analysis. The median and range of the nlr and mlr were 3.0 (0.3–22.0) and 0.4 (0.1–1.9) respectively. On multivariable analysis, sex (p = 0.02), T stage (p = 0.04), and nlr (p < 0.01) were associated with os. On multivariable analysis, T stage (p < 0.01) and mlr (p < 0.01) were associated with disease-related failure; mlr (p = 0.03), nlr (p < 0.01), and sbrt dose of 48 Gy in 4 fractions (p = 0.03) and 54 Gy or 60 Gy in 3 fractions (p = 0.02) were associated with disease-unrelated death. Median survival was 4.3 years in the nlr≤3 group (95% confidence interval: 3.5 to not reached) and 2.5 years in the nlr>3 group (95% confidence interval: 1.7 to 4.8; p < 0.01).ConclusionsIn lung sbrt patients, nlr and mlr are independently associated with os and disease-unrelated death. If validated, nlr and mlr could help to identify patients who would benefit most from sbrt.     

Effects of dna-dependent protein kinase inhibition by NU7026 on dna repair and cell survival in irradiated gastric cancer cell line N87

Repair of radiation-induced dna double-strand breaks is a key mechanism in cancer cell radio-resistance. The synthesized compound NU7026 specifically inhibits dna-dependent protein kinase (dna-pk) within the non-homologous end-joining repair mechanism. Earlier studies demonstrated increased radiosensitivity in dna-pk deficient cells compared with wild-type cells. In chronic leukemia cells, NU7026 appears to enhance the cytotoxic effect of chlorambucil. The radio-modifying effects of NU7026 on cell survival, cell cycle, apoptosis, and dna double-strand break repair have yet to be studied in gastric cancer cells.

Methods

The gastric cancer cell line N87 was treated with 0 Gy or 4 Gy in the presence of NU7026 at a dose range of 0–20 μmol/L. Clonogenic assays were used to assess cell survival after treatment. Cell-cycle distribution was analyzed using propidium iodide with fluorescence-activated cell sorting. Apoptosis was detected using annexin-V and propidium iodide with fluorescence-activated cell sorting. The γH2AX assay was used to measure dna double-strand breaks.

Results

Statistically significant increases in G2/M arrest were observed in N87 cells treated with radiation and NU7026 compared with those treated with radiation alone (p = 0.0004). Combined treatment also led to an increase in apoptosis (p = 0.01). At 24 hours, the γH2AX analysis revealed more dna double-strand breaks in N87 cells treated with radiation and NU7026 than in those treated with radiation alone (p = 0.04). Clonogenic assays demonstrated declining cell survival as both the radiation and the NU7026 dose increased. The dose enhancement factor at 0.1 survival fraction was 1.28 when N87 cells were treated with 4 Gy radiation and 5 μmol/L NU7026.

Conclusions

In gastric cancer cells, NU7026 appears to enhance the cytotoxic effect of irradiation as assessed by clonogenic assays. This increased cytotoxicity might be the result of an increase in dna double-strand breaks resulting in G2/M cell arrest and possibly higher levels of apoptosis.     

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma

Background

Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy.

Methods

In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child–Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt.

Results

Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8–8.5 cm), which decreased with tace to 5.0 cm (range: 3.3–7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival.

Conclusions

The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.     

Population-based utilization of radiation therapy by a Canadian breast cancer cohort

We examined trends in radiation therapy (rt) utilization by a population-based breast cancer cohort in Ontario. The provincial cancer registry provided a breast cancer cohort based on diagnosis dates from April 1, 2005, to March 31, 2010. Staging information was also available. The cohort was then linked, by encrypted health card number, to linkable administrative datasets, including rt utilization.The average age in the identified female breast cancer cohort (n = 39,656) was 61.6 ± 14.0 years. Almost two thirds of the patients (n = 25,225) received rt, and staging information was available for 22,988 patients (9541 stage i, 8516 stage ii, 4050 stage iii, and 881 stage iv). The average number of rt courses received by the patients was 1.4 ± 0.7 for stage i, 1.8 ± 1.1 for stage ii, 2.5 ± 1.3 for stage iii, and 2.8 ± 2.4 for stage iv. The ratio of conventional rt to intensity-modulated rt was 70.9%:16.6% for stage i, 71.6%:11.3% for stage ii, 74.6%:4.6% for stage iii, and 89.6%:2.2% for stage iv.From 2005 to 2010, almost two thirds of a Canadian female breast cancer cohort received rt, and the average number of courses increased with disease severity. A similar trend was observed with the type of rt (use of conventional rt increased with disease severity). The next step is to apply unit costs to the number of fractions and to obtain rt planning and radiation therapist times.     

Health system costs for stage-specific breast cancer: a population-based approach

Objective

The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage.

Methods

Incident cases of female invasive bca (2005–2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars.

Results

This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations.

Conclusions

Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.     

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors,potentiate the anti-angiogenic effects of bevacizumab by suppressing angiopoietin2, BiP,and Hsp90α in human colorectal cancer

Background:

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are commonly prescribed because of their therapeutic and preventive effects on cardiovascular diseases. Even though they have been occasionally reported to have antitumour activity, it is unknown whether statins have anti-angiogenic effect in human colorectal cancer (CRC).

Methods:

A total of 11 human CRC cell lines were used to test the effects of bevacizumab, statins, and bevacizumab plus statins on human umbilical vein endothelial cell (HUVEC) viability and invasion in vitro. To determine the molecular mechanism of statins as anti-angiogenic agents, we performed an angiogenesis antibody array and proteomics analysis and confirmed the results using immunoblot assay, HUVEC invasion rescue assay, and siRNA assay. The antitumoural effects of bevacizumab and statins were evaluated in xenograft models.

Results:

A conventional dose of statins (simvastatin 0.2 μM, lovastatin 0.4 μM, atorvastatin 0.1 μM, and pravastatin 0.4 μM) in combination with bevacizumab directly reduced the cell viability, migration, invasion, and tube formation of HUVECs. The culture media of the CRC cells treated with bevacizumab or statins were also found to inhibit HUVEC invasion by suppressing angiogenic mediators, such as angiopoietin2, binding immunoglobulin protein (BiP), and Hsp90α. The combined treatment with bevacizumab and simvastatin significantly reduced the growth and metastases of xenograft tumours compared with treatment with bevacizumab alone.

Conclusions:

The addition of simvastatin at a dose used in patients with cardiovascular diseases (40–80 mg once daily) may potentiate the anti-angiogenic effects of bevacizumab on CRC by suppressing angiopoietin2, BiP, and Hsp90α in cancer cells. A clinical trial of simvastatin in combination with bevacizumab in patients with CRC is needed.     

In vitro and in vivo studies on the inhibitory effects of myocardial cell culture medium on growth of a human lung adenocarcinoma cell line,A549

BackgroundAlthough the heart is one of the body’s vital organs, with an abundant blood supply, metastasis to the heart is considered rare. In a previous study, we found that the myocardial microenvironment might contain a low molecular weight natural tumour suppressor. The present study was designed to investigate the inhibitory effect of cardiac myocyte–conditioned medium (cmcm) on the growth of A549 human lung adenocarcinoma cells in vitro and in vivo.MethodsAn mtt assay was used to detect the inhibition ratio with respect to A549 proliferation. Human lung adenocarcinoma cells (A549 cell strain) were transplanted subcutaneously into nude mice to produce tumours. The xenograft tumour growth in mice was observed after selected drug administration.ResultsAfter treatment with cmcm and cisplatin (Cis), A549 cell viability significantly declined (p < 0.001). The cell viability in the cmcm and Cis groups were 53.42% ± 3.45% and 58.45% ± 6.39% respectively. Growth of implanted tumour cells in vivo was significantly inhibited in the cmcm group, the group treated with recombinant human adenovirus–p53, and the Cis-treated group compared with a control group. The inhibition rates were 41.44% in the cmcm group, 41.34% in the p53 group, and 64.50% in the Cis group. Lung metastasis capacity was significantly reduced in the presence of cmcm (p < 0.05). Lung metastasis inhibition rates in mice were 56.52% in the cmcm group, 47.83% in the p53 group, and 82.61% in the Cis group. With cmcm, the lives of A549-tumour-bearing mice could be significantly prolonged without any effect on weight loss.ConclusionsUse of cmcm has the effect of reducing A549 cell viability, tumour volume, and lung metastasis rate, while prolonging survival duration without severe toxicity.     

Plerixafor for autologous stem-cell mobilization and transplantation for patients in Ontario

BackgroundHigh-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony–stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0.24 mg/kg, provides a sustained increase in circulating CD34+ cells for 10–18 hours. The main purpose of the present report was to evaluate the most current evidence on the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct for patients in Ontario so as to make recommendations for clinical practice and to assist Cancer Care Ontario in decision-making with respect to this intervention.MethodsThe medline and embase databases were systematically searched for evidence from January 1996 to March 2015, and the best available evidence was used to draft recommendations relevant to the efficacy of plerixafor in enhancing hematopoietic stem-cell mobilization and collection before asct. Final approval of this practice guideline report was obtained from both the Stem Cell Transplant Steering Committee and the Report Approval Panel of the Program in Evidence-Based Care.RecommendationsThese recommendations apply to adult patients considered for asct:

• ■ Adding plerixafor to g-csf is an option for initial mobilization in patients with non-Hodgkin lymphoma or multiple myeloma who are eligible for asct when chemotherapy cannot be used and only g-csf mobilization is available.
• ■ For patients with a low peripheral blood CD34+ cell count (for example, <10/μL) at the time of anticipated stem-cell harvesting, or with an inadequate first-day apheresis collection, it is recommended that plerixafor be added to the mobilization regimen to maximize stem-cell collection and to prevent the need for remobilization.
• ■ It is recommended that patients who have failed a previous mobilization attempt undergo remobilization with g-csf and plerixafor, with or without chemotherapy.

     

Quality of life of nasopharyngeal cancer survivors in China

Purpose

We assessed the quality of life (qol) of nasopharyngeal carcinoma (npc) survivors with a survival time of more than 2 years in Fujian, China, and we analyzed factors influencing qol.

Methods

We calculated the prevalence of psychological distress and radiotherapy (rt)–induced symptoms in 216 npc survivors who participated in a cross-sectional survey. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (version 3.0) was used to assess the qol of npc survivors. Multiple linear regression was applied to analyze the factors influencing qol.

Results

The prevalence rates of rt-induced symptoms and psychological problems were 11.58% (95% ci: 7.21% to 15.58%) for difficulty in swallowing, 17.59% (95% ci: 12.51% to 22.67%) for mouth dryness or sores, 13.89% (95% ci: 9.28% to 18.50%) for nasal dryness or congestion, 18.52% (95% ci: 13.34% to 23.70%) for fatigue, 11.11% (95% ci: 6.92% to 15.30%) for frequent dizziness, 18.06% (95% ci: 12.93% to 23.19%) for decline in hearing, 14.81% (95% ci: 10.07% to 19.55%) for poor sleep quality, 18.52% (95% ci: 13.34% to 23.70%) for worry about disease recurrence, 18.98% (95% ci: 13.75% to 24.21%) for anxiety, and 25.00% (95% ci: 19.23% to 30.77%) for depression. Mean survival times were 4.32 ± 2.63 years in patients with mouth dryness or sores, 4.26 ± 2.90 years in patients with fatigue, and 5.60 ± 2.94 years in patients with a decline in hearing. The mean global qol score was 74.21 (95% ci: 72.22 to 76.20). At a significance level of α = 0.05, the factors influencing qol were age (p = 0.032), education level (p = 0.001), anxiety score (p < 0.001), depression score (p < 0.001), mouth dryness or sores (p < 0.001), fatigue (p = 0.027), and disease stage (p = 0.044).

Conclusions

The prevalence rates of mouth dryness or sores, fatigue, decline in hearing, depression, and anxiety were high in npc survivors with a survival time of more than 2 years. These rt-induced symptoms and psychological problems can last for many years after rt. The qol of the npc survivors was good. Factors influencing qol were age, education level, anxiety, depression, mouth dryness or sores, fatigue, and disease stage. Our results suggest that during clinical treatment, doctors should minimize the radiation dose to the ears of patients. In addition, our results emphasize the importance of providing oral and ear nursing and psychological care to npc survivors.     

Wellness Beyond Cancer Program: building an effective survivorship program

BackgroundThe Wellness Beyond Cancer Program (wbcp) was launched in 2012, first accepting patients with colorectal cancer (crc) and, subsequently, those with breast cancer (bca), with the aim of standardizing and streamlining the discharge process from our cancer centre. Patients are discharged either to the wbcp nurse practitioner or to their primary care provider (pcp). The program incorporates survivorship care plans (scps) and education classes; it also has a rapid re-entry system in case of recurrence. The objective of this paper is to describe the process by which a cancer survivorship program was developed at our institution and to present preliminary evaluation results.MethodsQualitative surveys were mailed to patients and pcps 1 year after patients had been referred to the wbcp. The surveys addressed knowledge of the program content, satisfaction on the part of patients and providers, and whether scp recommendations were followed. Questions were scored on the level of agreement with each of a list of statements (1 = strongly disagree to 5 = strongly agree).ResultsFrom March 2012 to November 2014, 2630 patients were referred to the wbcp (809 with crc, 1821 with bca). Surveys were received from 289 patients and 412 pcps. Patients and pcps gave similar scores (average: 4) to statements about satisfaction; pcps gave scores below 4 to statements about communication with the wbcp.ConclusionsAt 1 year after discharge, patients and pcps were satisfied with program content, but there is an opportunity to improve on communication and provision of cancer-specific information to the pcps. Using the wbcp to ensure a safe transition to the most appropriate health care provider, we have standardized the discharge process for crc and bca patients.     

Purinergic regulation of vascular endothelial growth factor signaling in angiogenesis

P2Y purine nucleotide receptors (P2YRs) promote endothelial cell tubulogenesis through breast cancer cell-secreted nucleoside diphosphate kinase (NDPK). We tested the hypothesis that activated P2Y₁ receptors transactivate vascular endothelial growth factor receptor (VEGFR-2) in angiogenic signaling. P2Y₁R stimulation (10 μM 2-methyl-thio-ATP (2MS-ATP)) of angiogenesis is suppressed by the VEGFR-2 tyrosine kinase inhibitor, SU1498 (1 μM). Phosphorylation of VEGFR-2 by 0.0262 or 2.62 nM VEGF was comparable with 0.01 or 10 μM 2MS-ATP stimulation of the P2Y₁R. 2MS-ATP, and VEGF stimulation increased tyrosine phosphorylation at tyr1175. 2MS-ATP (0.1–10 μM) also stimulated EC tubulogenesis in a dose-dependent manner. The addition of sub-maximal VEGF (70 pM) in the presence of increasing concentrations of 2MS-ATP yielded additive effects at 2MS-ATP concentrations <3 μM, whereas producing saturated and less than additive effects at ⩾3 μM. We propose that the VEGF receptor can be activated in the absence of VEGF, and that the P2YR–VEGFR2 interaction and resulting signal transduction is a critical determinant of vascular homoeostasis and tumour-mediated angiogenesis.     

Radiation costing methods: a systematic review

ObjectiveCosts for radiation therapy (rt) and the methods used to cost rt are highly diverse across the literature. To date, no study has compared various costing methods in detail. Our objective was to perform a thorough review of the radiation costing literature to identify sources of costs and methods used.MethodsA systematic review of Ovid medline, Ovid oldmedline, embase, Ovid HealthStar, and EconLit from 2005 to 23 March 2015 used search terms such as “radiation,” “radiotherapy,” “neoplasm,” “cost,” “ cost analysis,” and “cost benefit analysis” to locate relevant articles. Original papers were reviewed for detailed costing methods. Cost sources and methods were extracted for papers investigating rt modalities, including three-dimensional conformal rt (3D-crt), intensity-modulated rt (imrt), stereotactic body rt (sbrt), and brachytherapy (bt). All costs were translated into 2014 U.S. dollars.ResultsMost of the studies (91%) reported in the 33 articles retrieved provided rt costs from the health system perspective. The cost of rt ranged from US$2,687.87 to US$111,900.60 per treatment for imrt, followed by US$5,583.28 to US$90,055 for 3D-crt, US$10,544.22 to US$78,667.40 for bt, and US$6,520.58 to US$19,602.68 for sbrt. Cost drivers were professional or personnel costs and the cost of rt treatment. Most studies did not address the cost of rt equipment (85%) and institutional or facility costs (66%).ConclusionsCosting methods and sources were widely variable across studies, highlighting the need for consistency in the reporting of rt costs. More work to promote comparability and consistency across studies is needed.     

Selected abstracts submitted to the 2nd International Cancer Fatigue Symposium: Putting the Pieces Together: Hyatt Regency,Montreal, Quebec; October 3–4, 2010

Objectives:

In this study, we used the European Organisation for Research and Treatment of Cancer (eortc) Quality of Life Questionnaire-30 (qlq-C30) to investigate cancer-related fatigue symptoms in digestive cancer patients.

Methods:

Between June 2007 and June 2009, the study enrolled 262 inpatients with cancer of digestive system from 4 Guangzhou hospitals: 50 patients with pancreatic cancer (pc), 60 with liver cancer (lc), 50 with esophageal cancer (ec), 50 with gastric cancer (gc), and 52 with colorectal cancer (cc). Fatigue in these patients was evaluated using 3 items from the eortc qlq-C30 assessing fatigue symptoms (total possible score: 3–12).

Results:

Fatigue scores were significantly higher in female patients than in male patients (6.34 ± 2.72 vs. 5.56 ± 2.47, p = 0.022). Patients staged iii or iv by TNM experienced more severe fatigue than did those staged i or ii (6.39 ± 2.70 vs. 5.24 ± 2.34, p = 0.001). Fatigue symptoms were more severe in patients who received chemotherapy than in those who underwent surgery (6.92 ± 2.75 vs. 5.13 ± 2.15, p = 0.000). In each digestive cancer group, scores by TNM stage and treatment were similarly significantly different, but the differences between male and female patients were nonsignificant. Fatigue scores were sharply higher in the pc group (9.74 ± 2.28) than in the other 4 groups (lc: 6.03 ± 1.62; ec: 4.12 ± 1.32; gc: 4.76 ± 1.30, cc: 4.44 ± 1.29; all p = 0.000). In addition, scores were higher in the lc group than in the ec group, the gc group, and the cc group (all p = 0.000). Differences between the ec group, the gc group, and the cc group were nonsignificant (all p > 0.05).

Conclusions:

Symptoms of fatigue are an obstacle for digestive cancer patients, especially at advanced stages or when being treated with chemotherapy. Pancreatic cancer patients experience more severe fatigue.

• Curr Oncol. 2010 Oct; 17(5): 78–83.
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• P002 Liver Cancer–Related Fatigue: Its Correlations with Quality of Life and Social Support of Patients

Curr Oncol. 2010 Oct; 17(5): 78.

P002 Liver Cancer–Related Fatigue: Its Correlations with Quality of Life and Social Support of Patients

L. Jia,^*† S.M. Jiang,^*† and Y.H. Liu^*†

L. Jia

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by L. Jia

S.M. Jiang

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by S.M. Jiang

Y.H. Liu

^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaFind articles by Y.H. LiuAuthor information Copyright and License information Disclaimer^*Guangzhou First Municipal People’s Hospital and^†Guangzhou Medical College, Guangzhou, Guangdong, ChinaCopyright 2010 Multimed Inc.     

Risk perception and psychological morbidity in men at elevated risk for prostate cancer

ObjectiveAs prostate-specific antigen (psa) makes prostate cancer (pca) screening more accessible, more men are being identified with conditions that indicate high risk for developing pca, such as elevated psa and high-grade intraepithelial neoplasia (hgpin). In the present study, we assessed psychological well-being and risk perception in individuals with those high-risk conditions.MethodsA questionnaire consisting of a psychological symptom survey, a trait risk-aversion survey, and a cancer-specific risk perception survey was administered to 168 patients with early-stage localized pca and 69 patients at high risk for pca (n = 16 hgpin, n = 53 psa > 4 ng/mL). Analysis of variance was used to examine differences in psychological well-being and appraisal of risk between the groups.ResultsCompared with the pca group, the high-risk group perceived their risk of dying from something other than pca to be significantly lower (p = 0.007). However, pca patients reported significantly more clinically important psychological symptoms.ConclusionsThe identification of prostate conditions that predict progression to cancer might not result in the psychological symptoms commonly experienced by pca patients, but does appear to be related to a distorted perception of the disease’s mortal risk. Patients with pca experience reduced psychological well-being, but better understand the risks of pca recurrence and death. Education on the risks and outcomes of pca can help at-risk men to view health assessments with reduced worry.     

Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Background

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Methods

We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.

Results

During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.

Conclusions

Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.     

Negative predictive value of preoperative computed tomography in determining pathologic local invasion,nodal disease,and abdominal metastases in gastric cancer

BackgroundBefore undergoing curative-intent resection of gastric adenocarcinoma (ga), most patients undergo abdominal computed tomography (ct) imaging to determine contraindications to resection (local invasion, distant metastases). However, the ability to detect contraindications is variable, and the literature is limited to single-institution studies. We sought to assess, on a population level, the clinical relevance of preoperative ct in evaluating the resectability of ga tumours in patients undergoing surgery.MethodsIn a provincial cancer registry, 2414 patients with ga diagnosed during 2005–2008 at 116 institutions were identified, and a primary chart review of radiology, operative, and pathology reports was performed for all patients. Preoperative abdominal ct reports were compared with intraoperative findings and final pathology reports (reference standard) to determine the negative predictive value (npv) of ct in assessing local invasion, nodal involvement, and intra-abdominal metastases.ResultsAmong patients undergoing gastrectomy, the npv of ct imaging in detecting local invasion was 86.9% (n = 536). For nodal metastasis, the npv of ct was 43.3% (n = 450). Among patients undergoing surgical exploration, the npv of ct for intra-abdominal metastases was 52.3% (n = 407).ConclusionsPreoperative abdominal ct imaging reported as negative is most accurate in determining local invasion and least accurate in nodal assessment. The poor npv of ct should be taken into account when selecting patients for staging laparoscopy.