Characteristics of clinically node negative breast cancer patients needing preoperative MRI.

BACKGROUND: International guidelines do not recommend magnetic resonance imaging (MRI) for all breast cancer patients at primary diagnostics. This study aimed to understand which patient or tumor characteristics are associated with the use of MRI. The role of MRI among other preoperative imaging methods in clinically node negative breast cancer was studied. MATERIAL AND METHODS: Patient and tumor characteristics were analyzed in association with the use of MRI by multivariable logistic regression analysis in 461 patients. Primary tumor size was compared between MRI, mammography (MGR), ultrasound (US) and histopathology by Spearman correlation. The delays in surgery and diagnosis were analyzed among patients with or without MRI, and axillary reoperations were evaluated. RESULTS: Age (p < 0.0001), primary operation method (p < 0.0001), tumor histology (p < 0.0001) and HER2 status (p = 0.0064) were associated with the use of MRI. Spearman correlations between tumor size in histopathology and the difference in tumor size between histopathology and imaging methods were 0.52 in MGR, 0.66 in US and 0.36 in MRI (p < 0.0001 for all). A seven-day delay in surgical treatment was observed among patients with MRI compared to patients without MRI (p < 0.0001). Axillary reoperation rates were similar in patients with or without MRI (p = 0.57). CONCLUSION: Patient selection through prearranged characterization is important in deciding on optimal candidates for preoperative MRI among breast cancer patients. MRI causes moderate delays in primary breast cancer surgery. Preoperative MRI is useful in the evaluation of tumor size but might be insufficient in detecting lymph node metastases.

Can a machine-learning model improve the prediction of nodal stage after a positive sentinel lymph node biopsy in breast cancer?

Background: The current standard for evaluating axillary nodal burden in clinically node negative breast cancer is sentinel lymph node biopsy (SLNB). However, the accuracy of SLNB to detect nodal stage N2-3 remains debatable. Nomograms can help the decision-making process between axillary treatment options. The aim of this study was to create a new model to predict the nodal stage N2-3 after a positive SLNB using machine learning methods that are rarely seen in nomogram development.Material and methods: Primary breast cancer patients who underwent SLNB and axillary lymph node dissection (ALND) between 2012 and 2017 formed cohorts for nomogram development (training cohort, N = 460) and for nomogram validation (validation cohort, N = 70). A machine learning method known as the gradient boosted trees model (XGBoost) was used to determine the variables associated with nodal stage N2-3 and to create a predictive model. Multivariate logistic regression analysis was used for comparison.Results: The best combination of variables associated with nodal stage N2-3 in XGBoost modeling included tumor size, histological type, multifocality, lymphovascular invasion, percentage of ER positive cells, number of positive sentinel lymph nodes (SLN) and number of positive SLNs multiplied by tumor size. Indicating discrimination, AUC values for the training cohort and the validation cohort were 0.80 (95%CI 0.71-0.89) and 0.80 (95%CI 0.65-0.92) in the XGBoost model and 0.85 (95%CI 0.77-0.93) and 0.75 (95%CI 0.58-0.89) in the logistic regression model, respectively.Conclusions: This machine learning model was able to maintain its discrimination in the validation cohort better than the logistic regression model. This indicates advantages in employing modern artificial intelligence techniques into nomogram development. The nomogram could be used to help identify nodal stage N2-3 in early breast cancer and to select appropriate treatments for patients.

Radiation dose estimation in computed tomography examinations using NRPB-SR250 software in aretrospective analysis of a patient population.

Computed tomography (CT) imaging contributes to a major part of medical radiation exposure. With regard to patients safety, frequent CT examinations (CTEs) performed on the same patient are of particular concern. Tools for tracking the individual patient radiation exposure history and cumulative dose assessment may become important. Here, the applicability of the NRPB-SR250 software was assessed in a retrospective analysis of radiation doses from CTE made consecutively in male patients. Most of the examinations focused on the abdomen or the whole body. The mean number of CTs per patient was 6.8. Significant cumulative effective doses were observed: 76 (66 %) patients received an effective dose higher than 50 mSv, while the maximum was ∼280 mSv. A more than 3-fold effective dose difference was observed between scanners, depending on the scanning protocols. The NRPB-SR250 software proved to be a robust tool for the assessment of organ doses and the effective radiation dose from CT, while challenges were encountered in finding the precise imaging data in retrospective protocols.

Physicians' self-assessment of cancer pain treatment skills--more training required.

PURPOSE: Adequate pain control is essential in cancer treatment. We surveyed Finnish physicians' perception on their skills and training needs on palliative pain management. METHODS: A structured questionnaire with multiple choices and open ended questions was used for collecting data in 2006-2008. Of 720 physicians participating, 59 were working in oncology and 661 physicians in internal medicine, geriatrics, and primary health care. RESULTS: The principles of the WHO guidelines of cancer pain management were not well known. Forty-six percent of oncologists and 32% of other physicians (P < 0.0001) knew the analgesic ladder consisting of three steps. Forty-seven percent of oncologists and 61% of other physicians considered pain treatment of cancer patients being well managed in Finland. Only 24% of oncologists and 5% of other physicians considered the education in palliative care being currently at a satisfactory level. Oncologists reported a need of training in interaction and communication skills, ethical questions, and palliative home care. The other physicians expressed the strongest need for training in pain management and palliative care. CONCLUSIONS: To have more confidence in treating cancer, pain physicians would benefit in training and education in palliative care. It should be systematically included both in general and specialist training and continuous medical education.

Detection of human papillomavirus genotypes in bronchial cancer using sensitive multimetrix assay.

BACKGROUND: Since first suggested in 1979, evidence on the involvement of human papillomavirus (HPV) in bronchial carcinogenesis has been accumulated through several lines of research. The causal role of HPV in lung cancer still remains controversial, however, and more data are needed particularly on genotype distribution and cofactors of HPV regarding this disease. MATERIALS AND METHODS: The present series consists of 77 patients diagnosed and treated for lung cancer at the Department of Respiratory Medicine, Turku University Hospital, (Finland) during 2008-2010. All available histological samples (n=77) were subjected to HPV genotyping with the Luminex-based Multimetrix kit, detecting 24 low-risk (LR) and high-risk (HR) HPV types. Pertinent clinical data were collected and subjected to univariate and multivariate regression analysis to disclose the covariates associated with HPV detection in lung cancer. RESULTS: Out of 77 histological samples analyzed, four (5.2%) (three squamous cell and one adenocarcinoma) were found to be HPV-positive, out of which three were HPV16 infections and one a double-infection with HPV6 and HPV16. All four patients were males, and all but one reported no asbestos exposure. Three of them had refrained from smoking for a period >22 years. Disease-specific survival was twice as long for individuals with HPV+ than those with HPV- tumors (25.5 vs. 12.8 months), but confounding by treatment cannot be excluded. In univariate analysis, four covariates were significantly associated with HPV detection: i) older age (p=0.003) ii) older age at smoking initiation (p=0.027), iii) fewer years of active smoking (p=0.036), and iv) fewer total pack years (p=0.002). In a multivariate regression model adjusted to all significant covariates, only absolute age was significantly associated with testing as HPV-positive (odds ratio=1.16, 95% confidence interval 1.04-1.39, p=0.008). CONCLUSION: Given the fact that initiation of smoking at an older age, fewer pack years and long smoking abstinence were associated with HPV, it is tempting to speculate that oncogenic HPV can substitute smoking as a risk factor, leading to lung cancer in these patients despite >22 years elapsing since their smoking cessation. In the era of prophylactic HPV vaccination, there is an urgent need to provide more data on the global HPV burden and covariates of the virus associated to lung cancer.

Clinicopathological significance of cyclooxygenase-2 and cell cycle-regulatory proteins expression in patients with esophageal squamous cell carcinoma.

The aim of this study was to examine the expression of the molecular markers cyclooxygenase-2 (COX-2), Ki-67, cyclin A, and p27 in patients with esophageal squamous cell carcinoma (ESCC), to ascertain the relationship of these makers with the clinicopathological significance of the patients, and to assess the additional prognostic value of the expression profile of these proteins for ESCC patients. The expression levels of COX-2, Ki-67, cyclin A, and p27 proteins of a series of primarily resected ESCC samples were determined by immunohistochemistry method. Clinicopathological and molecular factors affecting survival were analyzed by multivariate analysis. A total of 78 specimens were included in this study. Expression of COX-2 was observed in 43 (55.1%) cases, and high levels of expression of Ki-67, p27, and cyclin A were observed in 57 (73.0%), 33 (42.3%), 43 (55.1%) cases, respectively. The results of univariate survival analysis indicated that more advanced tumor stage, lymph node involvement, systemic dissemination, the levels of expression of COX-2, Ki-67, cyclin A, and p27 were associated with survival (all P-value < 0.05). Multifactorial survival analysis revealed that only lymph node involvement, over-expression of cyclin A, and low p27 expression were associated with the survival of the patients (hazard ratios = 2.83, 4.7, 2.9, respectively; P= 0.025, 0.042, 0.005, respectively). Among the molecular markers assessed, the expression of cell proliferation markers cyclin A and p27 are independent prognostic factors in patients with ESCC, whereas neither COX-2 nor Ki-67 is of independent prognostic value.

Anaemia and other predictors of fatigue among patients on palliative therapy for advanced cancer.

The association of anaemia and other predictors of fatigue was studied in cancer patients on palliative treatment. A cohort of 128 consecutive patients (61 men and 67 women, mean age 63.6 years; range 36-85) was interviewed using the Edmonton Symptom Assessment System (ESAS) questionnaire, with 11 items describing cancer-related symptoms in visual analogue scale (VAS). Routine haematological samples were analysed at the time of interview. Both univariate and multivariate analyses were used to assess the independent predictors of fatigue. Out of the 10 symptoms recorded, fatigue was the single most frequent, reported by 91.3% of the patients, followed by pain (74.8%), sleeplessness (78.0%) and depression (74.2%). Anaemia was a significant determinant of fatigue (p=0.040)(OR=5.09; 95% CI 1.013-25.647). Out of the symptoms recorded, fatigue was significantly associated with depression (p=0.035), loss of appetite (p=0.016), anxiety (p=0.050), and sleeplessness (p=0.016). Total wellbeing was negatively associated with fatigue (OR=0.48, 95% CI 0.011-0.020)(p=0.0001). In multivariate analysis, anaemia was the most powerful independent predictor of fatigue, with OR=38.27 (95% CI 2.62-559.19)(p=0.008), followed by sleeplessness (OR=14.06 95% CI 1.44-137.02 p=0.023) and loss of appetite (OR=10.30 95% CI 1.04-101.10, p=0.045). Fatigue was unrelated to sex or age, or to the type of cancer, or the treatment category. Fatigue was common among cancer patients on palliative care. The single most powerful independent explanatory factor of fatigue was anaemia, implicating a need for interventional studies.

Effects of sea buckthorn berries on infections and inflammation: a double-blind, randomized, placebo-controlled trial.

OBJECTIVE: To study the effect of sea buckthorn berries on the number and duration of common cold (CC) infections. As secondary objectives the effects on digestive and urinary tract infections (DTI, UTI), and serum C-reactive protein (CRP) concentrations were also investigated. SUBJECTS: A total of 254 healthy volunteers were randomly assigned to receive sea buckthorn or placebo product during the study, which 233 of them completed. RESULTS: There were no significant differences in the number or duration of CC or DTI between groups (CC: relative risks (sea buckthorn vs placebo) for the number and duration were 1.15 (95% CI 0.90-1.48) and 1.05 (95% CI 0.87-1.27), respectively). In the sea buckthorn group, as compared to the placebo, the serum CRP concentrations decreased significantly (difference in median change -0.059 mg/l, P=0.039). The number of UTI was too small to draw solid conclusions, but the results indicate the subject merits further investigation. CONCLUSION: Sea buckthorn berries did not prevent CC or DTI. However, a reductive effect on CRP, a marker of inflammation, and a risk factor for cardiovascular diseases, was detected.

Needs of developing the skills of palliative care at the oncology ward: an audit of symptoms among 203 consecutive cancer patients in Finland.

BACKGROUND: To clarify the prevalence and severity of the symptoms, 203 consecutive patients with breast, prostate and other cancers treated mainly for palliation were surveyed. MATERIALS AND METHODS: The series includes 116 men and 87 women with the mean age of 65 years (range 27-86 years). The patients filled-up the Edmonton Symptom Assessment System (ESAS) questionnaire with 11 items describing cancer-related symptoms in the visual analogue scale (VAS). RESULTS: Altogether, 98% of the patients reported at least 1 of the 10 symptoms. There was a significant difference in the score frequencies between the 10 symptoms (p = 0.0001), fatigue receiving the highest frequency (50.8%) of the high scores. Fatigue was also the single most frequent symptom reported by 86.3% of the patients, followed by pain at effort (71.5%), sleeplessness (71.1%) and depression (59.0%). The most disturbing syndrome was pain (n = 48, 23.9%), followed by fatigue (n = 28, 13.9%), depression (9.5%) and dyspnoea (6.0%). Altogether, 75% had more than 5 symptoms and 10% reported all 10 symptoms. The total number of symptoms was not significantly associated with sex (p = 0.781) or age (p = 0.062), but it was associated with the diagnostic group; patients with breast cancer (n = 41) and those with prostate cancer (n = 44) reported fewer symptoms than the patients with other cancers (n = 116)(p = 0.023, Kruskal-Wallis). CONCLUSIONS: Symptoms related to cancer are common among patients treated with palliative indication, but if not specifically surveyed, may remain un-detected and un-treated. ESAS as a clinical tool brings more symptoms to the attention of the physicians and helps in getting a comprehensive insight into the patient's problems.

Cost-effectiveness of intensive adjuvant chemotherapy for high-risk breast cancer: is tailored and dose-escalated chemotherapy with growth factor support (GFS) more costly and less effective than marrow-supported high-dose chemotherapy - results from a randomized study.

Based on randomized studies bone-marrow supported (BMS) high-dose chemotherapy (HDCT) is not superior to conventional CT as adjuvant treatment for high-risk breast cancer. To compare the cost-effectiveness of these treatments we examined the data of Finnish patients in the SBG9401 trial 1. Patients were randomized to receive either dose-escalated (de FEC) (group A, n =59) or FEC and HDCT+BMS (group B, n =70). They received adjuvant radiotherapy (RT) + tamoxifen. All direct health care costs of first line treatment at the oncology units were considered as well as productivity costs within the first 3 years of follow-up. Effectiveness was measured by the number of survival days during 5 years of follow-up. The mean direct health care costs were significantly higher in group B (25829 euro in group A vs. 36605 euro in group B, p <0.001), mainly due to a higher number of hospital days. Half of the costs in group A was due to the use of filgrastim (15335 euro in A and 2969 euro in B, p <0.001). The costs of RT were only 5% of total costs. There was no statistically significant difference between the groups in the number of survival days, but sensitivity analysis based on bootstrapping suggested that treatment A would be a less costly and more effective alternative in a great majority of cases.

Long-term follow-up of the SBG 9401 study comparing tailored FEC-based therapy versus marrow-supported high-dose therapy.

BACKGROUND: The purpose was to investigate adjuvant marrow-supportive high-dose chemotherapy compared with an equitoxicity-tailored comparator arm. PATIENTS AND METHODS: Five hundred and twenty-five women below the age of 60 years with operated high-risk primary breast cancer were randomised to nine cycles of granulocyte colony-stimulating factor supported and individually tailored FEC (5-fluorouracil, epirubicin, cyclophosphamide), (n = 251) or standard FEC followed by marrow-supported high-dose therapy with CTCb (cyclophosphamide, thiotepa, carboplatin) therapy (n = 274), followed by locoregional radiotherapy and tamoxifen for 5 years. RESULTS: There were 104 breast cancer relapses in the tailored FEC group versus 139 in the CTCb group (double triangular method by Whitehead, P = 0.046), with a median follow-up of all included patients of 60.8 months. The event-free survival demonstrated 121 and 150 events in the tailored FEC- and CTCb group, respectively [P = 0.074, hazard ratio (HR) 0.804, 95% confidence interval (CI) 0.633-1.022]. Ten patients in the tailored FEC regimen developed acute myeloid leukaemia (AML)/myelodysplasia (MDS). One hundred deaths occurred in the tailored FEC group and 121 in the CTCb group (P = 0.287, HR 0.866, 95% CI 0.665-1.129). CONCLUSION: The update of this study shows an improved outcome linked to the tailored FEC treatment in relation to breast cancer relapse, but also an increased incidence of AML/MDS.

The effect of beta-glucan on the glycemic and insulin index.

OBJECTIVE: To determine the effects of oat products with increasing beta-glucan content on the glycemic (GI) and insulin indexes (II) of oat products, and to establish the effect of physical properties of beta-glucan on these physiological responses. DESIGN: Test group (n=10) randomly attended to three glucose tolerance tests and glycemic response tests for four oat bran products. SETTINGS: Functional Foods Forum and the Department of Food Chemistry, University of Turku, and the Department of Food Technology, University of Helsinki. SUBJECTS: One male and nine female volunteers were recruited from university students and staff, and all completed the study. INTERVENTIONS: GI and II of different products were calculated for each subject using the average of parallel glucose tolerance tests and the subsequent glycemic/insulinemic responses for each product. Average indexes for products were calculated according to the individual data. RESULTS: The glycemic responses to oat products with increasing amounts of beta-glucan had lower peak values than the reference glucose load. The amount of extractable beta-glucan had a high correlation between the glycemic and insulinemic response. CONCLUSION: In addition to the total amount of beta-glucan in oat products, the amount of extractable beta-glucan in oat products explains the magnitude of the decrease in glycemic responses to carbohydrate products.

Serum TRACP 5b and ICTP as markers of bone metastases in breast cancer.

BACKGROUND: The purpose of this cross-sectional study was to evaluate the value of serum tartrate-resistant acid phosphatase 5b (TRACP 5b) and carboxyterminal telopeptide of type I collagen (ICTP) separately and in combination as markers of bone metastases compared to total alkaline phosphatase (tALP) in breast cancer. MATERIALS AND METHODS: Two groups of patients were studied, one with verfied bone metastases (N=46) and one without bone metastases (N=141). Bone marker levels were correlated with the presence or absence of bone metastases. RESULTS: Serum TRACP 5b concentrations exhibited the largest area under the receiver-operating characteristics (ROC) curve (AUC=0.845), followed by ICTP (0.818) and tALP (0.814) when all patients were included in the analysis. With the combination of TRACP 5b and ICTP, the AUC increased to 0.881. In multivariate regression analysis, all three markers were significant predictors of bone metastases. CONCLUSION: Serum TRACP 5b, ICTP and tALP exhibited equal performances in the detection of bone metastases. The combination of TRACP with ICTP did not significantly improve the detection of bone metastases over tALP.

Palliative chemotherapy with trofosfamide in advanced prostate cancer.

BACKGROUND: A phase II study with trofosfamide in hormone-refractory prostate cancer was conducted to test the palliative efficacy. PATIENTS AND METHODS: Twenty patients suffering from advanced prostate cancer were treated with per os trofosfamide after progression on androgen ablation and/or estramustine. The mean age was 72 years. The patients were treated with 150 mg/day as continuous treatment. The treatment was continued until progressive disease or severe toxicity. RESULTS: A decline in the prostate specific antigen (PSA) level was observed in 5 patients (27%) with a 0-25% decline in 2 patients and a >50% decline in 3 patients (16%, 95% confidence interval 3.4-39.6). There were no clinical or radiological complete (CR) or partial (PR) responses in 19 evaluable patients. Some toxicity was observed: 15 patients developed anaemia and grade 2-4 adverse effects were observed in 16 patients. One patient died of cardiac event. CONCLUSION: Trofosfamide has some activity in hormone-refractory advanced prostate cancer. When used in fragile or heavily pre-treated patients, careful monitoring for haematological and cardiac effects is recommended.

Survival markers related to bone metastases in prostate cancer.

Prognostic value of a bone resorption marker, tartrate-resistant acid phosphatase isoform 5b (TRACP 5b), and two matrix metalloproteinases (MMP-2 and MMP-9) was compared with the standard clinical analyses of total alkaline phosphatase (tALP) and prostate-specific antigen (PSA), in prostate cancer (PC) patients with (BM+) or without (BM-) bone metastases. Diagnostic accuracy evaluation showed the highest area under the curve for tALP (AUC=0.98), followed by PSA (AUC=0.87), TRACP 5b (AUC=0.82), MMP-9 (AUC=0.62) and MMP-2 (AUC=0.53). Significantly shorter survival was observed for patients with tALP (p<0.001), TRACP 5b (p=0.002) and PSA (p<0.001) levels, above the determined cut-off values compared with lower marker levels. In multivariate Cox regression analysis, only tALP and PSA, in addition to Gleason score were independent prognostic factors for survival. Of the three novel markers tested, only TRACP 5b proved to be predictive of survival in PC with bone metastases. MMP-2 and -9 are thus not recommended for further studies in this context.

Unmet needs in information flow between breast cancer patients, their spouses, and physicians.

This study focused on the needs and sources of disease information of breast cancer patients and their spouses during early disease in two settings: at the department of oncology (AD) and on a rehabilitation course (RC). The aim was to characterize those patients and spouses who are not content with average information. Eighty percent of AD and 31% of RC patients were content with the available information (p < 0.001) and 75% of AD spouses and 43% of RC spouses reported similarly (p = 0.008). Higher education, younger age, and shorter time (<1 year) since diagnosis indicated a greater need for information among patients, whereas among spouses, only education level was associated with it. More information was needed on prognosis, cancer as a disease, its influence on daily life, and treatment effects. In both groups, the same proportion of patients reported to have felt involved in decision making sufficiently (60%), inadequately (27%), and 19% versus 16% did not want to be actively participating in decision making. The patients were mostly satisfied with participation in decision making, but they expressed unsatisfactory needs on information during early years of breast cancer. Similarly, their spouses were not content with available information.

Effect of adjuvant androgen deprivation on thyroid function tests in prostate cancer patients.

Androgen deprivation (AD) used in the treatment of prostate cancer is known to alter concentrations of sex hormones and their binding globulins. Less is known as to its effect on thyroid hormones. In this prospective study the effects of AD on thyroid function were clarified. Levels of serum thyroid stimulating hormone (TSH), free thyroxine (FT4) and thyroid binding globulin concentrations were measured in prostate cancer patients treated with either radical radiotherapy and androgen deprivation for 12 months (AD) or radical radiotherapy alone (RT). Measurements were made at baseline, and at 3, 6 and 12 months. At baseline and at 3 months the results of thyroid function tests did not differ significantly between groups. A significant decline in serum testosterone in the AD group was accompanied by a significant decline in FT4 at 6 and 12 months, while no significant changes in thyroid function were observed in the RT group. The decline in FT4 among AD patients did not evoke a normal TSH response. Prolonged use of AD hampers the interpretation of thyroid test results. This finding has substantial implications for the follow-up of patients in hormonally treated prostate cancer.

Dietary attitudes and changes as well as use of supplements and complementary therapies by Australian and Finnish women following the diagnosis of breast cancer.

OBJECTIVE: This study investigated self-reported dietary attitudes and changes, and use of complementary approaches among breast cancer patients in relation to age, education and time since diagnosis. DESIGN AND SETTING: Australian (ABC, N=215) and Finnish (FBC, N=139) breast cancer patients were surveyed at the university cancer centres with voluntary participation. Logistic regression models were used to adjust for differences in demographic patient characteristics between the groups. The influence of demographic variables was further studied separately or combined. RESULTS: In all, 30% of FBC patients and 39% of ABC patients reported having changed their diet (P=0.033). Higher education, younger age and longer time from diagnosis were significantly associated with the probability of changes. The main changes reported included reduced consumption of animal fat, sugar and red meat, and increased consumption of fruits and vegetables. In all, 6% of ABC and 4% of FBC patients had stopped smoking and 24% of ABC and 27% of FBC patients reported to have increased their level of physical exercise. Choices were associated with age (P<0.007), length of the disease history (P <0.01) and level of education (P <0.002). CONCLUSION: One-third of breast cancer patients surveyed reported to have changed their dietary habits. Both populations reported a need for dietary and lifestyle counselling. This need was experienced as poorly recognised by the physicians at present, and warrants future studies in dietary behaviour of breast cancer patients.