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Objectives: Treatment decisions in ethically complex situations are known to depend on a physician's personal characteristics and medical experience. We sought to study variability in decisions to withdraw or withhold specific life-supporting treatments in terminal care and to evaluate the association between decisions and such background factors.Design: Readiness to withdraw or withhold treatment options was studied using a terminal cancer patient scenario with alternatives. Physicians were asked about their attitudes, life values, experience, and training; sociodemographic data were also collected.Setting: Finnish physicians, postal survey.Survey Sample: Five hundred general practitioners, 300 surgeons, 300 internists, and 82 oncologists.Results: Treatments most often forgone were blood transfusion (82%) and thrombosis prophylaxis (81%). Least willingly abandoned were intravenous (i.v.) hydration (29%) and supplementary oxygen (13%). Female doctors were less likely to discontinue thrombosis prophylaxis (p=0.022) and supplementary oxygen (p<0.001), but more readily x ray (p=0.039) and laboratory (p=0.057) examinations. Young doctors were more likely to continue antibiotics (p=0.025), thrombosis prophylaxis (p=0.006), supplementary oxygen (p=0.004) and laboratory tests (p=0.041). Oncologists comprised the specialty most ready to forgo all studied treatments except antibiotics and blood transfusion. The family's wishes (alternative 1) significantly increased treatment activity. Young and female practitioners and oncologists were most influenced by family appeal. Advance directives (alternative 2) made decisions significantly more reserved and uniform. Different factors in the physician's background were found to predict decisions to withdraw antibiotics or i.v. hydration.Conclusion: The considerable variation observed in doctors' decisions to forgo specific life-sustaining treatments (LST) was seen to depend on their personal background factors. Experience, supervision, and postgraduate education seemed to be associated with more reserved treatment decisions. To increase the objectivity of end of life decisions, training, and research are of prime significance in this ethically complex area of medicine. [ABSTRACT FROM AUTHOR]

Background: Presence of immune cell infiltrates in tumor may influence outcome of patients with node negative breast cancer (BC) (Schmidt et al 2008). High expression of CXCL13 (B lymphocyte chemoattractant chemokine) was strongly associated with favorable survival in one recent series consisting of BC patients treated with adjuvant chemotherapy (Razis et al. 2012). Here we examined the clinical significance of breast tumor CXCL13 mRNA levels within the context of the FinHer trial, where patients were randomly assigned to receive 3 cycles of either docetaxel or vinorelbine followed by 3 cycles of FEC. Patients with HER2-positive BC had a second randomization for trastuzumab vs. control. Since intratumoral B cells are of particular importance for obtaining response to chemotherapy in triple negative BC (TNBC) and of limited value in luminal BC (Schmidt et al. 2012), and trastuzumab treatment is a confounding factor in HER2+ BC, we focused on TNBC. Methods: RNA was extracted from FFPE tumor tissue of 917 (90.8%) out of the 1010 patients who participated in the FinHer trial. CXCL13 mRNA expression was measured using RTqPCR. The molecular subtypes (luminal, HER2-enriched and triple-negative) were determined using IHC and central chromogenic in situ hybridization (CISH) testing. Prognostic significance of factors was assessed using univariate and multivariate analyses. Distant disease-free survival (DDFS) between groups was compared using the log-rank test. Results: Tumor CXCL13 mRNA expression showed a bimodal distribution and correlated negatively with tumor ESR1 mRNA levels (r = -0,31; p < 0.0001). 146 (15.9%) out of the 917cancers were classified as TNBC. High tumor CXCL13 mRNA levels above the median were strongly associated with favorable 5-yr DDFS in TNBC compared to low levels (85% vs. 60%; p < 0.0001). The prognostic value of tumor CXCL13 was evident in the subset of women with TNBC treated with vinorelbine (5-year DDFS 90% vs. 40%; p < 0.0001), whereas no significant association was found in the docetaxel arm (5-year DDFS 80% vs. 80%; p = 0.76). When only patients with TNBC and low CXCL13 mRNA levels were assessed, patients treated with docetaxel had better DDFS compared to those treated with vinorelbine (5-year DDFS 80% versus 40%; p < 0.0064). There was no DDFS difference between treatment arms in patients exhibiting high CXCL13 expression. Conclusions: Tumor CXCL13 mRNA expression is a favorable prognostic factor for women with TNBC treated with adjuvant chemotherapy providing further evidence that the host immune response may influence outcome of patients with early BC. The clinical significance of the host B cell immune response may vary substantially pending on the type of chemotherapy administered. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of multi-parametric magnetic resonance imaging (MP-MRI), including dynamic contrast-enhanced MRI and diffusion-weighted MRI, for monitoring tumor tissue changes after volumetric-modulated arc radiotherapy in localized prostate cancer (PCa), and to compare the radiotherapy induced tumor tissue changes between conventional, moderate and extreme hypofractionated groups. Furthermore, we aimed to evaluate if follow-up by MRI has an incremental value compared to the standard care by prostate-specific antigen (PSA) serum level measurement., Materials and Methods: Fifty-five men (mean age: 70±5 [SD] years; range: 60-79 years) with biopsy-proven PCa underwent MRI examination before radiotherapy, and at 3 and 12 months after radiotherapy. Pharmacokinetic analysis post-processing platform with dedicated software (Tissue 4D) was used to generate colorized parametric maps of enhancing tumors. The volume transfer constant (K trans ), reflux constant (K ep ), and initial area under curve (iAUC) were calculated from the tumors. Tumor apparent diffusion coefficient (ADC) value was measured on the ADC map. The patients were allocated into three radiotherapy groups: 17 conventional (39×2Gy), 16 moderate (20×3Gy) and 22 extreme hypofractionated (5×7.25Gy) regimen., Results: Sixty lesions were detected in the prostates of the 55 patients. Follow-up MRI showed decreases in tumor size and degree of enhancement. K trans , K ep , and iAUC all decreased at 3 months (P<0.001, respectively) and decreased further at 12 months (P<0.001, respectively). ADC increased at 3 months (P<0.001) and increased further at 12 months (P<0.001). There were no significant differences in the percentage changes of the measured MP-MRI parameters of the tumors from baseline to 12 months between the conventional, moderate and extreme hypofractionated regimen groups., Conclusion: MP-MRI is a reliable tool for lesion detection and follow-up, providing both qualitative and quantitative data., (Copyright © 2019 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The constructs evaluated in investigating association between psychosocial factors and cancer survival has varied between studies, and factors related to quality of life (QOL) have shown contradictory results. We investigated the effect of socioeconomic and early QOL and psychological factors on disease-free time and survival in localized prostate cancer., Methods: A consecutive sample of patients with localized prostate cancer (T1-3, N0, M0) treated with external beam radiotherapy completed validated questionnaires on coping with cancer (the Ways of Coping Questionnaire WOC-CA), anger expression (the Anger Expression Scale), life events (the Life Experience Survey), and various aspects of QOL (the Rotterdam Symptom Checklist, the Depression Scale DEPS, the EORTC QLQ-C30, the LENT-SOMA outcome measure) approximately 4.5 months after diagnosis. Cox regression analyses were used to determine the predictors of the disease-free and overall survival times measured from the date of diagnosis to the date of a PSA-relapse and date of death., Results: After controlling for biological prognostic factors, age, and adjuvant hormonal therapies, moderate and high socioeconomic status and an increased level of pain predicted longer survival, whereas an increased level of prostate-area symptoms and fatigue and, especially, reports of no/few physical symptoms were predictors of a shorter survival time. A longer PSA-relapse-free time was predicted by Cognitive Avoidance/Denial coping, whereas problems in social functioning, hopelessness, and an excellent self-reported QOL predicted a shorter PSA-relapse-free time., Conclusions: Higher socioeconomic status was prognostic for longer survival, as previously reported. Patients with a seemingly good QOL (few physical complaints, excellent self-reported QOL) had poorer prognoses. This association may due to the survival decreasing effect of emotional non-expression; patients with high emotional non-expression may over-report their wellbeing in simple measures, and thus actually be in need of extra attention and care.

Background: Nivolumab-ipilimumab demonstrated a survival benefit over sunitinib in first-line setting for metastatic renal cell carcinomas (mRCCs) and is becoming a new standard of care for naïve patients with intermediate or poor risk prognosis (International mRCC Database Consortium). The efficacy of subsequent vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs) after nivolumab-ipilimumab failure remains unclear., Methods: Medical records of mRCC patients treated with nivolumab-ipilimumab, who received subsequent TKI, as part of Checkmate 214 study were reviewed in 13 institutions. Baseline characteristics, outcome data including progression-free survival (PFS), response, overall survival (OS) and toxicities were retrospectively collected., Results: Overall 33 patients received subsequent TKI after nivolumab-ipilimumab failure. Median follow-up from start of subsequent TKI is 22 months (19-NR). Best response was assessed in 30 patients: 12 partial responses (36%), 13 stable diseases (39%) and five progressive diseases (15%). Median PFS from start of TKI was 8 months [5-13]. Median PFS with first-generation (sunitinib/pazopanib) and second-generation TKI (axitinib/cabozantinib) was 8 months [5-16] and 7 months (5-NA), respectively. PFS in second line was significantly longer in patients with a long first-line duration of response to the double immune checkpoint blockade (≥6 months) with 8 versus 5 months for short responder (<6 months) (p = 0.03). OS rate was 54% at 12 months. Toxicity was as expected: 42% developed at least one toxicity grade ≥3., Conclusion: This is the first report of outcomes with TKI, after first-line nivolumab-ipilimumab failure. Median PFS suggests a sustained benefit of TKI and supports trials investigating the optimal sequence., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but to date has not proven effective in prostate cancer., Objective: o evaluate whether six cycles of docetaxel alone improve biochemical disease-free survival after radical prostatectomy for high-risk prostate cancer., Design, Setting, and Participants: Open-label, randomised multinational phase 3 trial. Enrolment of 459 patients after prostatectomy., Inclusion Criteria: high-risk pT2 margin positive or pT3a Gleason score ≥4+3, pT3b, or lymph node positive disease Gleason score ≥3+4. Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m 2 every 3 wk without daily prednisone (Arm A) or surveillance (Arm B) until endpoint was reached. Primary endpoint was prostate-specific antigen progression ≥0.5 ng/ml., Intervention: Docetaxel treatment after prostatectomy., Results and Limitations: Median time to progression, death, or last follow-up was 56.8 mo. Primary endpoint was reached in 190/459 patients-the risk of progression at 5 yr being 41% (45% in Arm A and 38% in Arm B). There was evidence of nonproportional hazards in Kaplan-Meier analysis, so we used the difference in restricted mean survival time as the primary estimate of effect. Restricted mean survival time to endpoint was 43 mo in Arm A versus 46 mo in Arm B (p=0.06), a nonsignificant difference of 3.2 mo (95% confidence interval: 6.7 to -1.5 mo). A total of 116 serious adverse events were recorded in Arm A and 41 in Arm B with no treatment-related deaths. Not all patients received docetaxel by protocol. The endpoint is biochemical progression and some patients received radiation treatment before the endpoint., Conclusions: Docetaxel without hormonal therapy did not significantly improve biochemical disease-free survival after radical prostatectomy., Patient Summary: In this randomised trial, we tested whether chemotherapy after surgery for high-risk prostate cancer decreases the risk of a rising prostate-specific antigen. We found no benefit from docetaxel given after radical prostatectomy., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate whether diffusion-weighted imaging (DWI) apparent diffusion coefficient (ADC) correlates with prostate cancer aggressiveness and further to compare the diagnostic performance of ADC and normalized ADC (nADC: normalized to non-tumor tissue)., Patients and Methods: Thirty pre-treatment patients (mean age, 69years; range: 59-78years) with prostate cancer underwent magnetic resonance imaging (MRI) examination, including DWI with three b values: 50, 400, and 800s/mm 2 . Both ADC and nADC were correlated with the Gleason score obtained through transrectal ultrasound-guided biopsy., Results: The tumor minimum ADC (ADC min : the lowest ADC value within tumor) had an inverse correlation with the Gleason score (r=-0.43, P<0.05), and it was lower in patients with Gleason score 3+4 than in those with Gleason score 3+3 (0.54±0.11×10 3 mm 2 /s vs. 0.64±0.12×10 -3 mm 2 /s, P<0.05). Both the nADC min and nADC mean correlated with the Gleason score (r=-0.52 and r=-0.55, P<0.01; respectively), and they were lower in patients with Gleason score 3+4 than those with Gleason score 3+3 (P<0.01; respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.765, 0.818, or 0.833 for the ADC min , nADC min , or nADC mean ; respectively, in differentiating between Gleason score 3+4 and 3+3 tumors., Conclusion: Tumor ADC min , nADC min , and nADC mean are useful markers to predict the aggressiveness of prostate cancer., (Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Aim: Weekly paclitaxel is widely used in the treatment of metastatic breast cancer (MBC). Our aim was to test its efficacy and tolerability as a second-line therapy for MBC in daily oncology practice., Patients and Methods: Paclitaxel (90 mg/m(2)) was given intravenously three times weekly in a 4-week cycle to 91 patients with disease progression after hormonal (42%) or cytostatic therapy (57%). The median age was 54 years; metastatic sites were the lung (39%), liver (52%) and bone (47%). 64% of patients had more than one site of metastasis., Results: Median time-to-progression was 7.5 months (range=6.5-8.5 months) and median overall survival time was 20.1 months (range=13.7-26.5 months). We observed 10 complete (12%) and 37 partial (43%) responses (an overall response rate of 55%). Severe side-effects were rare (grade 3-4 neutropenia 13% and septic episodes in three cases)., Conclusion: Weekly paclitaxel was shown to be an effective and well-tolerated treatment for advanced breast cancer.

Aim: The aim of the present study was to examine the impact of obesity and physical activity on the health and wellbeing of patients with breast cancer shortly after the adjuvant treatments., Patients and Methods: A total of 537 women aged 35 to 68 years with newly-diagnosed breast cancer were enrolled into the exercise intervention study. The physical activity, physical performance (2-km walking test), cardiovascular risk factors, quality of life (EORTC-QoL-C30), co-morbidities and body-mass index (BMI) were measured after the adjuvant treatments., Results: Overall, 191 (39%) patients were overweight (BMI=25-30) and 85 (17%) obese (BMI ≥ 30). Physical activity and performance (p<0.001 and p<0.001), QoL (p<0.001) and high density lipoprotein (HDL)-cholesterol decreased (p<0.001) whereas age (p=0.009), co-morbidities (p<0.001), hypertension (p=0.011), metabolic syndrome (p<0.001), low density lipoprotein (LDL)-cholesterol (p=0.0043), triglycerides (p<0.001), glucose (p<0.001) and insulin (p<0.001) increased linearly with BMI. Higher waist circumference (p=0.0011), triglyceride (p=0.020), insulin (p=0.0098), rate of metabolic syndrome (p=0.028), and lower HDL-cholesterol (p=0.012) and QoL (p<0.001) were associated with low physical activity. Physical activity and BMI were the most important determinants of physical performance (p<0.001 and p<0.001, respectively)., Conclusion: Obesity and a sedentary lifestyle are related to poor physical performance, increased risk of cardiovascular diseases and impaired QoL, leading to a vicious circle, which impairs patients' physical health and QoL.

Several effective drugs have become available for prostate cancer therapy, which are being used after the development of castration resistance and studied already at an earlier stage of prostate cancer therapy. Novel hormonally acting drugs include degarelix, enzalutamide and abiraterone. Cytotoxic agents that have proven effective in studies include the docetaxel derivative cabazitaxel, denosumab in the prevention of complications caused by bone metastases, and radium-233 chloride as treatment for bone metastases. The optimal sequence of administration of the novel drugs as well as combining them are subject to intensive research.

In this 12-month RCT, we examined whether aerobic impact exercise training (3x/week) could facilitate breast cancer survivors' recovery by enhancing their bone structural strength, physical performance and body composition. After the adjuvant chemo- and/ or radiotherapy, 86 patients were randomly assigned into the training or control group. Structural bone traits were assessed with pQCT at the tibia and with DXA at the femoral neck. Agility (figure-8 running), jump force and power (force platform), grip strength and cardiovascular fitness (2-km walk test) were also assessed. Training effects on outcome variables were estimated by two-way factorial ANCOVA using the study group and menopausal status as fixed factors. Bone structural strength was better maintained among the trainees. At the femoral neck, there was a small but significant 2% training effect in the bone mass distribution (p=0.05). At the tibial diaphysis, slight 1% to 2% training effects (p=0.03) in total cross-sectional area and bone structural strength were observed (p=0.03) among the postmenopausal trainees. Also, 3% to 4% training effects were observed in the figure-8 running time (p=0.03) and grip strength (p=0.01). In conclusion, vigorous aerobic impact exercise training has potential to maintain bone structural strength and improve physical performance among breast cancer survivors.

Background: Radical radiotherapy (RT) combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13)., Methods: The inclusion criteria are the following: men >18 and ≤75 years of age, WHO/ECOG performance status 0--1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4+3), PSA >10; T2, Gleason 8--10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mgm(-2) d 1. cycle 21 d) or no docetaxel after radical RT (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org)., Results: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3--4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3--4 toxicities at 12 weeks after the randomization., Conclusions: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.

Background: In the treatment of many types of cancer, combination chemotherapy has been shown to be better than single-agent chemotherapy. The aim of our phase I-II clinical trial was to assess the efficacy and toxicity of docetaxel-ifosfamide combination chemotherapy in patients with castration-resistant metastatic prostate cancer (CRPC)., Patients and Methods: A total of 31 patients were enrolled to receive first-line chemotherapy consisting of 40-60 mg/m(2) docetaxel followed by 3.0 g/m(2) ifosfamide with mesna. All drugs were administered intravenously. The maximum duration of the chemotherapy was six cycles. The median age of the patients was 70 (range 58-82) years. Prostate specific antigen (PSA) responses were determined according to the PSA working group guidelines and all toxicities, time-to-progression and overall survival were determined according to the WHO criteria., Results: The objective PSA response rate was 32% in 11/31 patients. The mean PSA value at baseline was 300 (range 2.5-1577) μg/l. The overall median survival was 14.1 months; 15 patients were alive at a median follow-up time of 18 months. The observed side-effects were as expected, with grade 3-4 neutropenia developing in 38% of the cycles, whereas febrile neutropenia occurred in only 12% of the patients. The median number of administered cycles was 4.8. No acute hypersensitivity reactions were observed. Transient renal insufficiency developed in two patients, thus necessitating dose reductions., Conclusion: The combination of docetaxel and ifosfamide seems to be well-tolerated and has some activity in patients with CRPC. However, newer docetaxel-based combination chemotherapy regimens need to be further developed in other to provide more efficacious and well-tolerated treatment options for earlier phases of CRPC.

Unlabelled: Information on detailed treatment costs and the economic burden of renal cell carcinoma (RCC) is rare. The current study provides treatment costs and outcomes of patients with metastatic RCC (mRCC), as well as estimates of the future burden from the perspective of Finnish health care. These results offer a baseline against which the impact of emerging treatments may be evaluated., Materials and Methods: Information on treatment modalities, survival, and the cost of treatment was retrospectively gathered from mRCC patients (n = 83) receiving first-line interferon-alpha (IFN). Predictions of the number of new cases, premature deaths, and productivity losses were made using local epidemiological data, which were projected to the future using population growth forecasts. The future costs of mRCC treatment and the budget impact of sunitinib were estimated through modeling., Results: Patients survived 11.9 months (median; 95% CI 9.2-14.7) after initiation of active IFN treatment, accruing an average total treatment cost of 951 euros. Most of the treatment costs were due to hospitalization and active IFN treatment. The aging of the population leads to nearly a 2% increase in the absolute number of new diagnoses annually, while at the same time it results in declining productivity losses. The estimated five-year population cost of IFN-based treatment was 16M euros-26M euros. Adding sunitinib to the first-line treatment protocol increased this cost by 13M eruos-41M euros., Conclusions: Despite the limited number of patients, metastatic renal cell carcinoma places a considerable economic burden on Finnish society. Treatment costs are likely to increase substantially due to the adoption of new and more expensive medications, the aging population, and enhanced survival times.

Radiotherapy (RT) produces oxidative stress and local inflammation. This study aimed at clarifying the role of different cytokines (VEGF, TNFalpha, IL-1beta, IL-6, IL-8, IL-12 and IL-18) in bronchoalveolar lavage (BAL) fluid and in the serum of lung cancer patients at baseline and during RT. Bronchoscopy and BAL were performed on 36 lung cancer patients and 36 controls for diagnosis; patients receiving RT had a second bronchoscopy during RT. Serum samples were obtained during RT and three months after RT. In this study lung cancer patients had higher levels of serum and BAL fluid IL-6 and serum IL-8 compared to controls (p<0.001, p=0.039 and p=0.030, respectively). RT caused a significant increase of BAL fluid IL-6 (p=0.037). There were no significant associations between baseline cytokine levels and adverse events or response to treatment. Higher baseline serum and BAL fluid IL-8 and serum VEGF levels (p=0.036, p=0.027 and p=0.014, respectively) were associated with shorter survival. This study shows that lung cancer is associated with upregulation of IL-6 and IL-8. The increase of BAL fluid IL-6 during RT might be attributed to enhanced RT-related oxidative stress or increased cell death. Serum and BAL fluid IL-8 and serum VEGF might have a prognostic role in survival of lung cancer., (2009 Elsevier Ltd. All rights reserved.)

To examine lipid peroxidation during radiotherapy (RT), exhaled pentane samples were collected from 11 lung cancer patients before RT and 30 and 120 min after the start of RT on days 1, 4 and 5 and at 30 and 40 Grays, if possible. Exhaled pentane samples were collected once from 30 healthy controls. Serum thiobarbituric-acid-reactive substances (TBARS) and conjugated dienes (CD) were obtained from patients on each exhaled air collection day. Lung cancer patients had higher exhaled pentane levels than controls (1.73 ng/L vs 0.83 ng/L, p=0.017). Exhaled pentane levels tended to decrease during the first RT day (p=0.075) and levels of CD decreased during the first week of RT (p=0.014). Higher pre-treatment pentane levels predicted better survival (p=0.003). Elevated exhaled pentane levels before RT may be due to the lipid peroxidation burden associated with cancer. The decrease of lipid peroxidation markers during RT may be attributable to enhanced antioxidant defense mechanisms.

Objectives: To investigate the oxidant effects of adriamycin-containing chemotherapy (CT), we evaluated various antioxidants, total antioxidant capacity (TRAP) and different parameters of oxidative and nitrosative stress during combination CT., Design and Methods: Blood samples were obtained from 16 small cell lung cancer patients at baseline and several times during the first, second and sixth CT cycles., Results: There were significant decreases in serum urate and serum proteins during all cycles, serum TRAP during the first two cycles, plasma ascorbic acid and serum TBARS during the first cycle, and serum conjugated dienes and plasma alphatocopherol during the last cycle. The baseline levels of tocopherols increased significantly between the first and sixth CT cycles. Higher levels of baseline plasma thiols were associated with better overall survival (p=0.008)., Conclusions: Adriamycin-containing CT causes significant oxidative stress as implied by reduced levels of protective antioxidants. Long-term CT treatment seems to enhance lipid peroxidation.

Objectives: To assess oxidative damage to DNA during lung cancer (LC) treatments., Design and Methods: Urinary levels of 8-oxoguanine (8-oxoGua) and levels of 8-oxo-2'-deoxyguanosine (8-oxodG) from urine and whole blood were determined in 36 non-cancer controls and 65 LC patients before any treatments. Samples were also obtained of LC patients during and after radiotherapy (RT, n=33) and chemotherapy (CT, n=16)., Results: Stage IV LC patients had higher urinary 8-oxoGua and 8-oxodG levels than patients with stage I-III disease (p=0.044 and p=0.034, respectively). Urinary 8-oxodG levels increased during the first week of RT (p<0.001). Nuclear 8-oxodG increased during RT and 3 months after start of RT. Nuclear 8-oxodG levels also rose between the first two CT cycles (p=0.043), and urinary 8-oxodG levels during the sixth CT cycle (p=0.009)., Conclusions: Urinary DNA damage biomarker levels may be associated with LC stage. Both RT and CT increase the parameters of DNA oxidation.

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p=0.016, p<0.001 and p=0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p=0.044, p=0.034 and p=0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively.

Background: The treatment results of metastatic melanoma are miserable if the tumor has spread beyond the soft tissue and lung, in particular, if dacarbazine (DTIC)-based therapy has failed. Platinum analogs and vinca alkaloids have shown some activity in melanoma. Interleukin-2 (IL-2) may augment the efficacy of chemotherapy., Patients and Methods: A prospective phase II pilot study was conducted to evaluate the efficacy and tolerability of a regimen which contained carboplatin (450 mg/m(2) on day 1), vinorelbine (30 mg/m(2) on day 1) and IL-2 (9 MU subcutaneously once daily on days 2-5 and 9-12) in metastatic melanoma. Twenty-two patients (11 men, 11 women; median age 56 years) were eligible, of whom 13 had cutaneous, 6 ocular and 3 unknown primary melanoma. Seventeen patients (77%) had liver metastases and an equal number had received prior chemotherapy and/or interferon-alfa for recurrent disease., Results: One partial response was recorded, yielding a response rate of 4.5% . Nine patients had stable disease for a median of 6.0 months (range 3.0-8.6 months). The median time to progression for all patients was 1.8 months (range 0.7-8.6 months) and the median survival was 7.2 months (range 1.4-42.0 months). Toxicity was moderate but manageable. Myelosuppression was the most significant adverse event., Conclusion: This regimen may offer clinical benefit for melanoma patients with poor prognosis as second-line therapy after DTIC has failed.

Objective: There is no certainty about the contributing factors or the psychological processes involved in cancer progression. Many studies have suffered from poor theoretical basis, methodological flaws, and only one or few psychosocial factors investigated at a time. We examined the simultaneous contribution of several theory-based psychosocial elements to survival time in melanoma., Methods: A consecutive sample of patients with localized (Clarke II-IV) melanoma (N=59) were evaluated with validated questionnaires on coping with cancer, anger expression, perceived social support, noncancer life stresses, and domains of quality of life (QOL) 3-4 months after diagnosis. Cox regression analyses were used to determine the predictors of survival time from the date of diagnosis to the date of death or the last follow-up., Results: After controlling for age, gender, and Breslow depth for the tumor, the baseline psychological variables related to the cancer-prone Type C response pattern, namely, anger nonexpression (repression), hopelessness, and better single-item self-reported QOL predicted shorter survival. Before hopelessness was added to the model, the amount of depressive symptoms and heavy perceived impact of diagnosis were also predictive. In addition, longer survival was strongly predicted by Cognitive Escape-Avoidance coping, which included items close to the concept of denial/minimizing., Conclusion: Anger nonexpression, hopelessness, and overpositive reporting of QOL--all proposed to include in the Type C response style or reflect emotional nonexpression--seem to comprise a set of factors that reduce survival, whereas denial/minimizing response to the diagnosis as such predicts longer survival.

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.

Purpose: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the "basal phenotype" tumor group may comprise more than one biological entity., Experimental Design: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival., Results: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type ("basal") and a partially positive type ("basoluminal") often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P < 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification., Conclusions: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.

Objective: To explore whether genetic polymorphisms in platelet receptors known to be associated with platelet activity have any association with haematogenous metastases in renal cell carcinoma (RCC), as platelets and their fibrinogen receptors may be central to haematogenous cancer spread, in addition to various adhesive proteins on both platelets and tumour cells on themselves., Patients and Methods: The glycoprotein alpha(IIb)beta3 (GPIIb/IIIa) is the main fibrinogen receptor on platelets, with GPIb-IX-V and GPIa/IIa being the von Willebrand Factor and collagen receptors, respectively. In a cross-sectional survey of 128 men treated for RCC (55 with disseminated disease and 73 with a local disease), they were genotyped using DNA extracted from freshly drawn blood, and central clinical data were recorded., Results: The frequency of possessing the GPIIIaPl(A2) allele among patients with metastatic RCC was 43.6%, and with local disease was 24.7% (P = 0.024). The frequencies of the different alleles of the GIB-IX-V, C3550T and GPIa/IIa C807T polymorphisms did not differ between the groups. In a stepwise logistic regression (metastatic vs local RCC) the Pl(A2) allele remained a significant risk factor, with an odds ratio of 2.7 (95% confidence interval, 1.1-6.5; P = 0.02)., Conclusion: The prothrombotic Pl(A2) allele of platelet fibrinogen receptor GPIIb/IIIa increased the risk of metastases in RCC in men.

Purpose: Amplification of the HER-2/neu and topoisomerase IIalpha (TOP2A) genes has been linked to the effects of anthracyclines. Their role in predicting the outcome of anthracycline-based adjuvant chemotherapy for breast cancer patients has remained controversial., Patients and Methods: The present substudy of the Scandinavian Breast Group trial 9401, in which an epirubicin-based regimen (nine courses of tailored and dose-escalated fluorouracil, epirubicin, and cyclophosphamide [FEC]) was compared with three or four courses of standard FEC followed by bone marrow-supported high-dose chemotherapy (cyclophosphamide, thiotepa, and carboplatin), included high-risk breast cancer patients (with eight or more positive axillary lymph nodes or at least five nodes with additional poor prognostic indicators). Amplification of HER-2/neu was determined retrospectively in paraffin-embedded tumor tissue sections by chromogenic in situ hybridization. TOP2A was tested only in HER-2/neu-amplified tumors., Results: HER-2/neu amplification alone, which was present in 32.7% of the tumors, was a strong prognostic factor for short relapse-free (P = .0034) and overall survival (P = .0008) but showed no direct association with treatment assignment. TOP2A coamplification, which was present in 37% of HER-2/neu-amplified tumors, was associated with better relapse-free survival in patients treated with tailored and dose-escalated FEC (hazard ratio [HR] = 0.45; P = .049). A statistical multivariate Cox's regression analysis confirmed the predictive significance of TOP2A coamplification (HR = 0.30; P = .020) in HER-2/neu-amplified tumors. There was no such association in patients with HER-2/neu-amplified tumors without TOP2A gene amplification., Conclusion: Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines.

The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors.

This randomized phase II study was designed to compare the efficacy and tolerability of dacarbazine (DTIC) and bleomycin, vincristine, lomustine and DTIC (BOLD) combined with natural interferon-alpha (nIFN-alpha) or recombinant interferon-alpha2b (rIFN-alpha2b) in patients with advanced melanoma. The treatment arms were: A, DTIC plus nIFN-alpha; B, BOLD plus nIFN-alpha; C, DTIC plus rIFN-alpha2b; D, BOLD plus rIFN-alpha2b. One hundred and eight patients were randomized, of whom 106 were eligible to be analysed for efficacy. Overall, 56% of patients had abdominal visceral and/or bone involvement. The response rates were 8% (2/25) in arm A, 13% (4/31) in arm B, 12% (3/25) in arm C and 24% (6/25) in arm D. The differences were not statistically significant by the usual chi-squared test. However, when analysed using the Cochran-Armitage trend test, the one-sided P values were close to significant (0.085 and 0.033). All of the eight complete responses occurred in patients with soft tissue and/or lung metastases and the BOLD regimens produced six of them. There were no significant differences in survival (arm A, 11.1 months; arm B, 9.8 months; arm C, 9.1 months; arm D, 7.5 months; P=0.62). BOLD was more toxic than DTIC. With the present sample size, there were no statistically significant differences in efficacy between the arms, but there was a trend towards a higher response rate with BOLD plus rIFN-alpha2b. Patients with soft tissue or lung metastases may achieve more complete responses with BOLD regimens.

Purpose: Matrix metalloproteinases (MMP) are proteolytic enzymes that play an important role in various aspects of cancer progression. In the present work, we have studied the prognostic significance of serum levels of gelatinase B (MMP-9), collagenase-1 (MMP-1), and collagenase-3 (MMP-13) in patients with advanced melanoma., Experimental Design: Total pretreatment serum levels of MMP-9 in 71 patients and MMP-1 and MMP-13 in 48 patients were determined by an assay system based on ELISA. Total MMP levels were also assessed in eight healthy controls. The active and latent forms of MMPs were defined by using Western blot analysis and gelatin zymography., Results: Patients with high serum levels of MMP-9 (> or = 376.6 ng/mL; n = 19) had significantly poorer overall survival (OS) than patients with lower serum MMP-9 levels (n = 52; median OS, 29.1 versus 45.2 months; P = 0.033). High MMP-9 levels were also associated with visceral or bone metastasis (P = 0.027), elevated serum alkaline phosphatase level (P = 0.0009), and presence of liver metastases (P = 0.032). Serum levels of MMP-1 and MMP-13 did not correlate with OS. MMP-1 and MMP-9 were found mainly in latent forms in serum, whereas the majority of MMP-13 in serum was active (48 kDa) form. MMP-13 was found more often in active form in patients (mean, 99% of the total MMP-13 level) than in controls (mean, 84% of the total MMP-13 level; P < 0.0001). After initiating the therapy, patients with elevated levels of MMP-1 (> or = 29.8 ng/mL, n = 10) progressed more rapidly than patients with lower levels (median, 1.9 versus 3.5 months; P = 0.023). Serum levels of MMP-9 and MMP-13 did not correlate with the time to progression (TTP). In multivariate analysis with age and gender, MMP-9 or MMP-1 turned out to be independent prognostic factors for OS [P = 0.039; hazard ratio (HR), 1.8; 95% confidence interval (95% CI), 1.03-3.3] or TTP (P = 0.023; HR, 2.7; 95% CI, 1.15-6.4), respectively., Conclusions: Our findings provide evidence that MMP-1, MMP-9, and MMP-13 play important roles at different phases of metastatic melanoma spread and that serum MMP-9, in particular, could have clinical value in identifying patients at high risk for melanoma progression.

Background: Quality of life (QoL) is a multidimensional construct, and several psychosocial and medical factors can predict a patient's QoL. We investigated the impact of factors in the psychological stress processes on QoL 3 months after diagnosis of melanoma or breast cancer., Patients and Methods: In consecutive melanoma and breast cancer patients with localized disease, cancer-specific social support, coping with cancer, personality trait anger expression, non-cancer stress, sociodemographic variables, cancer and treatment variables, and QoL (evaluated as self-reported psychological and physical symptoms, self-perceived QoL, and depression) were assessed with validated quantitative questionnaires. The associations between QoL and the other factors were investigated with multivariate methods., Results: Only a few factors differed between melanoma and breast cancer, in terms of treatment modalities and gender. The amount of received social support was higher among breast cancer patients. The predicting power of psychological stress factors on all the QoL measures was strong, but differed between the treatment groups (surgery only versus adjuvant treatment). Psychosocial factors were the strongest predictors of QoL, not cancer type or treatment. Behavioral Escape-Avoidance coping was associated with worse QoL. However, non-cancer life stresses showed the strongest QoL-decreasing influence. QoL-enhancing factors, including social support, were seen clearly only within the breast cancer patients receiving adjuvant treatment., Conclusions: QoL of newly diagnosed cancer patients is highly associated with psychosocial factors. Non-cancer life stresses seem to be very important in the QoL of newly diagnosed cancer patients. Adjuvant treatment may comprise supportive psychosocial factors that enhance QoL in cancer.

Goals of Work: To investigate potentially health-enhancing domains of cancer patients' social relationships we evaluated various dimensions of social support as experienced in early cancer., Patients and Methods: In consecutive samples of 72 melanoma and 103 breast cancer patients diagnosed 3-4 months earlier, we evaluated the cancer-specific social network and received social support by the Structural-Functional Social Support Scale (SFSS) validated within the study. In addition, social support was measured by the MOS Social Support Survey as perceived support, and by Seeking Social Support items from the Ways of Coping Questionnaire as coping activity. SFSS measures the number of people who have been aware of the patient's cancer and the amount of social support the patients have received from them., Main Results: A large number of people from various potential support-providing sources had been aware of the patients' cancer, and the patients had received support through these interactions. A greater number of support providers did not mean an increase in the support received. Social support was distinguished into subgroups according to its source, but the division into functional support types was weak. Support assessed as perceived support or as a coping activity did not cover the received disease-specific support of several sources., Conclusions: With the SFSS, it was possible to obtain detailed information on the disease-specific social network and social support. It may be beneficial to distinguish support according to the sources and to also measure support beyond the closest relationships. We hope that our measure and the results obtained will assist in identifying the targets for psychosocial interventions.

We carried out a postal survey of a sample of Finnish doctors ( n=1182) concerning their attitudes and ethical decisions in end-of-life care. A scenario was presented in which a patient with terminal cancer wished to obtain unorthodox treatment. Factors possibly influencing decision making such as general attitudes, life values and demographics were investigated. The response rate was 62%. The patient's plan to use unorthodox treatment was accepted by 54% of doctors. Gender or speciality did not influence the decision, but doctor's age was a significant factor ( P=0.0005). Doctors aged 35-49 years were more accepting; younger and older ones less accepting. Doctors who had clinical experience in terminal care were more compliant to the patient's plan ( P=0.034). A stepwise logistic regression analysis was used to create a model for explaining not accepting versus accepting the treatment with the background variables. Altogether eight independent significant variables were included in the final model of explaining a doctor's choice in the presented scenario. According to the model the patient's wish was more frequently accepted if the doctor was middle-aged, had clinical experience in terminal care, valued a high standard of living, considered terminal care satisfying, was less critical of health economics, considered advance directives helpful, had a high fear-of-death index score, and valued professional status less.

This phase I study was designed to evaluate the activity toxicity and pharmacokinetics of docetaxel combined with ifosfamide in the treatment of hormone-refractory prostate cancer. Ten patients received a median of 4.6 treatment cycles. Docetaxel was administered at a dose of 40 mg/m2 in a 1-hour infusion followed by ifosfamide 3,000 mg/m2 in a 24-hour infusion every 3 weeks. The optimal sequence of chemotherapeutic agents was investigated by reversing the order of administration in the second cycle and by collecting a total of six pharmacokinetic blood samples per cycle from all patients during the first and second cycles. The sequence of administration did not influence the pharmacokinetics of docetaxel. Prostate-specific antigen (PSA) responses were observed in four out of nine patients, with a PSA response rate of 44.4% (complete response + partial response). The treatment was well tolerated. No grade IV toxicities were recorded and grade III leucopenia resulted in dose-reductions in 6 cycles (13.3%). The pharmacokinetic parameters of docetaxel were similar in both sequences. Our recommendation for further phase II studies is ifosfamide followed by low-dose docetaxel. Further phase II efficacy studies are warranted.

The palliative efficacy and toxicity of single-ifosfamide chemotherapy were investigated in patients with progressive metastatic hormone-refractory prostate cancer (HRPC). Thirty patients were randomised to receive ifosfamide by a 24-hour infusion on day 1 or a 3-hour infusion on days 1-4 at three week intervals until renewed disease progression or a total of six chemotherapy cycles. Response was analyzed according to the guidelines of the Prostate-Specific Antigen Working Group (1999). All 30 patients were included in the final analysis. 1 (3%) PSA normalization, 8 (27%) partial responses, 3 (10%) stabile diseases and 18 (60%) progressive diseases. The mean time to progression was 2.4 months, (range 0 -17) months and the median survival time was 13.6+ months, (range 2 -52). The treatment was well tolerated. No severe gr III-IV hematotoxicities were observed. In conclusion ifosfamide is effective and well tolerated as a single-agent in the treatment of HRPC. Further studies including ifosfamide in combination chemotherapy of HRPC are in progress.

Thirty-one patients with advanced breast cancer either resistant to anthracycline-based regimens or relapsing after anthracycline-based adjuvant chemotherapy received a combination of a 3-h infusion of paclitaxel 135 mg/m2 on day 1 and a 4-h infusion of ifosfamide 1.7 g/m2 on days 2 to 4 of a 22-day cycle. For inclusion in the study, patients had to have measurable or evaluable progressive metastasis or local disease, and to have received only one prior regimen for metastatic disease; 31 patients with a median age of 49 years (range: 30-69) entered the study. Nine patients (29%) had lung metastasis, while 17 (55%) had liver metastasis, and 19 (61%) had bone metastasis. Only seven patients (23%) had lymph node metastasis and four (13%) had skin metastasis. A median of seven cycles of treatment was delivered. Responses were evaluated according to World Health Organization (WHO) guidelines and side effects according to National Cancer Institute (NCI) criteria. A panel of oncologists and one radiologist reviewed all responses. At baseline, only three patients (10%) were free from the adverse effects of the prior therapy; severe nonhematological toxicity occurred in less than 8% of patients. However neutropenia grade 3-4 occurred in 88%, while only 3% had severe infections. Severe thrombocytopenia and anemia were rare (4% and 8%, respectively). The overall response rate was 42% (13% complete response). Median survival and progression-free survival rates after initiation of treatment were 19.3 months and 6.1 months, respectively. With an objective response rate of 42% and median survival of 19 months, the combination of paclitaxel and ifosfamide seems to offer a promising regimen with acceptable side effects in advanced breast cancer patients relapsing after anthracycline-based adjuvant treatment or resistant to anthracycline treatment.

In local or metastatic cancer, a prognostic tumour marker could be a valuable tool in the selection of different treatments. In renal cell cancer (RCC) no such markers have been available. We therefore evaluated the association between several pretreatment serum markers, tumour classification and short term survival in RCC patients. Serum samples were collected before surgery and three months thereafter from 24 RCC patients. Interleukin-6 (IL-6), IL- 12, soluble IL-2 receptor (sIL-2R) and intercellular adhesion molecule-1 (sICAM-1) were measured in serum samples using specific commercial enzyme immunoassay kits. Serum IL-6, sIL-2R and sICAM-1 levels before nephrectomy were significantly higher in non-local tumours than in local ones (mean IL-6 53 pg/ml versus 6.3 pg/ml, and sICAM-1 443 ng/ml versus 290 ng/ml, sIL-2R 3779 pg/ml versus 1796 pg/ml). In contrast, IL-12 levels were higher in local tumours (148 versus 102 pg/ml) and the levels increased significantly (P < 0.005) after removal of the primary tumour in patients with local disease. All patients with local tumours had normal IL-6 values, while only one with a non-local tumour had IL-6 levels below 10 pg/ml. In addition, IL-6 and sICAM-1 levels before operation were significantly higher in patients with short (less than one year) survival (p=0.007 to IL-6 and p=0.006 to sICAM-1). In contrast, patients with shorter survival had significantly lower IL-12 (p=0.03) levels. Our findings suggest that RCC induces changes in several immunological parameters. These soluble immunological factors, IL-6, IL-12, sIL-2R and sICAM-1, might have a role as prognostic factors in RCC.

Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an immunological marker that may also serve as an indicator of tumour progression. Normal and neoplastic cells are capable of releasing these molecules into circulation. We evaluated the association between pretreatment serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with advanced melanoma. The patients with liver and/or bone metastases had significantly higher sICAM-1 levels than those with soft tissue and/or lung involvement (P=0.002). In addition, there was a trend towards higher sIL-2R levels in patients with more metastatic sites (P=0.07). In univariate analysis, the number of metastatic sites (P=0.0001, odds ratio (OR) 3.0, 95% confidence interval (CI): 1.7-5.3), the metastatic site (P=0.01, OR 2.3, 95% CI: 1.2-4.4) and the levels of sICAM-1 (P=0.011, OR 2.5, 95% CI: 1.2-5.0), sVCAM-1 (P=0.036, OR 2.1, 95% CI: 1.0-4.3) and sIL-2R (P=0.0016, OR 3.0, 95% CI: 1.5-6.0) were found to be statistically significant prognostic factors for survival. In multivariate analysis, the number of metastatic sites was the dominant prognostic indicator. After it was excluded from the analysis, the sIL-2R level and the metastatic site were found to be significant. It can be concluded, that high sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add to clinical data predicting the patient's outcome.

The aim of this prospective study was to assess the quality of cancer pain control during the last week of life in two different types of units for terminal cancer patients in Finland: on health centre wards (N=20) and in a hospice (N=30). Pain scores (VAS), defined daily doses (DDD), routes of administration and costs of pain medication were analysed for each patient. On the 7th-last day before death and during the very last day of life (24 h), respectively, the following results were seen: proportions of patients using strong opioids 64% and 84%, mean equivalent parenteral morphine doses of strong opioids 42 mg and 57 mg, mean pain scores (VAS 0-10) 3.11 and 3.05, mean daily cost of pain medication 2.22 and 2.90 euros. Pain control was thus found to be good with low costs. On the 7th day before death strong opioids were used for a greater proportion of patients on the health centre wards. Differences were also seen in the routes of administration used for strong opioids. Weak opioids were used more in the hospice and NSAIDs, more on the health centre wards. However, no differences were found either in the mean doses of strong opioids or in the quality or the costs of pain control between the health centre wards and the hospice.

This study evaluates palliative treatment of inpatient cancer patients in two health centres and in one hospice in Finland. Apart from outpatient clinics, health centres in Finland also have inpatient wards where patients are treated by GPs. The hospice provides a home-like environment for terminal patients, who are cared for by a specialist in internal medicine. Our patient population comprised 36 health centre patients and 36 hospice patients enrolled in 1998. A structured questionnaire was used containing information on diagnosis, duration of the illness, current medication, daily activities, and socioeconomic background. The nurses assessed their patients' emotional needs. We found that the two groups of patients were similar in terms of gender, marital status and social situation. The hospice patients were significantly younger (P < 0.05) and better educated than the health centre patients (P = 0.001), and their disease had lasted longer (P < 0.05). Upon admission, 12 (33%) of the hospice patients were using opioids, as were 6 patients (17%) in the health centre group. During the treatment period in the hospice the nurses reported more anxiety and depression in their patients (P < 0.05); staff in the health centres were more often unable to report on their patients' feelings. Hospice patients (20/35) were significantly (P < 0.001) more concerned about the wellbeing of their relatives than patients in the health centres (2/35). In the hospice 18 patients (50%) showed significantly (P < 0.001) more spiritual needs than health centre patients (4/34). We conclude that more education is needed to improve the awareness of the multidimensional needs of terminally ill cancer patients in primary health care.