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Purpose. The aim of this paper was to investigate whether cancer genetic counseling could be considered as a stressful event and associated with more anxiety and/or depression compared to other cancer-related events for instance attending mammography screening or receiving a cancer diagnosis. Methods. A total of 4911 individuals from three Scandinavian countries were included in the study. Data was collected from individuals who had attended either cancer genetic counseling (self-referred and physician-referred) or routine mammography screening, were recalled for a second mammograpy due to a suspicious mammogram, had received a cancer diagnosis or had received medical follow-up after a breast cancer-surgery. Data from the genetic counseling group was also compared to normative data. Participants filled in the Hospital Anxiety and Depression Scale twice: prior to a potentially stressful event and 14 days after the event. Results. Pre-counseling cancer genetic counselees reported significant lower level of anxiety compared to the cancer-related group, but higher levels of anxiety compared to the general population. Furthermore, the level of depression observed within the genetic counseling group was lower compared to other participants. Post-event there was no significant difference in anxiety levels between the cancer genetic counselees and all other groups; however, the level of depression reported in the self-referred group was significantly lower than observed in all other groups. Notably, the level of anxiety and depression had decreased significantly from pre-to post-events within the genetic counseling group. In the cancer-related group only the level of anxiety had decreased significantly post-event. Conclusion. Individuals who attend cancer genetic counseling do not suffer more anxiety or depression compared to all other cancer-related groups. However, some counselees might need additional sessions and extended support. Thus, identifying extremely worried individuals who need more support, and allocating further resources to their care, seems to be more sufficient. [ABSTRACT FROM AUTHOR]

Background. From March 1994 to March 1998, breast cancer patients (an estimated relapse risk with 70% or more within five years with standard therapy) were randomised to treatment with tailored fluorouracil, epirubicin, and cyclophosphamide (FEC) therapy or FEC followed by marrow-supported high dose therapy in the Scandinavian Breast Group 9401 study. The aim of the present paper was to investigate differences in toxicity and eight health-related quality of life (HRQoL) variables (physical functioning, role functioning, emotional functioning, social functioning, cognitive functioning, fatigue, nausea-vomiting, and global quality of life) between women in the six dose steps used in the tailored and granulocyte colony stimulating factor supported FEC-arm at the assessment point 16 weeks after random assignment to treatment. Methods. The European Organization and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30 were mailed to the patients. Results. A total of 157 (87%) in the tailored FEC-group responded to the questionnaire within the time frame 16 weeks after inclusion in the study. Overall, toxicity was low, reaching grade 1--2 also in the higher dose steps. There were no overall differences between the dose steps on any of the tested HRQoL variables. Patients at dose step 4 scored statistically significantly higher on physical functioning than patients at dose step 1 (p == 0.022) and compared to those at dose step 2 (p == 0.014). Patients at dose steps −−2 and −−1 (combined to one group) reported statistically significantly higher mean scores on cognitive functioning than patients at dose step 1 (p == 0.022). Conclusion. Patients who received higher doses, based on the tailored dosing strategy, did not seem to have worse HRQoL than those who had lower doses. [ABSTRACT FROM AUTHOR]

Symptoms of posttraumatic stress disorder (PTSD) and adjustment disorder (AjD) are common in hematological cancer patients as they face severe stressors during their serious disease and often intensive treatment, such as stem cell transplantation (SCT). Aims of the present study were to provide frequency and risk factors for PTSD and AjD based on updated diagnostic criteria that are lacking to date. In a cross-sectional study, hematological cancer patients were assessed for stressor-related symptoms via validated self-report questionnaires based on updated criteria for PTSD (PCL-5) and AjD (ADMN-20). Frequency and symptom severity were estimated among the total sample and SCT subgroups (allogeneic, autologous, no SCT). SCT subgroups were compared using Chi-squared-tests and ANOVAs. Linear regression models investigated sociodemographic and medical factors associated with symptomatology. In total, 291 patients were included (response rate: 58%). 26 (9.3%), 66 (23.7%) and 40 (14.2%) patients met criteria for cancer-related PTSD, subthreshold PTSD and AjD, respectively. Symptom severity and frequency of criteria-based PTSD and AjD did not differ between SCT subgroups (all p > 0.05). Factors associated with elevated symptomatology were younger age (PTSD: p < 0.001; AjD: p = 0.02), physical comorbidity (PTSD: p < 0.001; AjD: p < 0.001) and active disease (PTSD: p = 0.12; AjD: p = 0.03). Based on new criteria, a considerable part of hematological cancer patients reports PTSD and AjD symptoms. Younger patients and patients with physical symptom burden might be particularly at risk and need to be monitored closely to enable effective treatment at an early stage. [ABSTRACT FROM AUTHOR]

Stereotactic body radiotherapy (SBRT) is an effective therapeutic approach in patients with liver metastases. However, long-term changes in hepatic normal tissue have to be taken into account in multimodal treatment regimes. Magnetic-resonance-imaging (MRI) based morphologic liver alterations (MMA) after liver SBRT have been analyzed longitudinally. 57 patients treated with gantry-based or robotic-based SBRT of 69 treatment volumes of liver metastases, who had long-term follow-up (FU) ≥6 months were included in this retrospective analysis. Post-SBRT MMAs were contoured on each contrast-enhanced-T1-weighted (T1w) MRI-sequence. Morphologic/volumetric data of the liver and MMAs were evaluated longitudinally, including the dependency on treatment-related factors of the planning target volume (PTV) and liver. The median FU time was 1 year [6–48 months]. 66 of 69 treatment volumes developed MMAs (mean 143.8 ± 135.1 ccm at first appearance). 31.8% of MMAs resolved completely during FU. Of the persisting MMAs 82.2%/13.3% decreased/increased in size until last available FU. Morphological characterization of the MMAs at first appearance included 75% hypointense and 25% hyperintense T1w-MRI-based appearances. Hypointense as compared to hyperintense appearance was significantly associated with a higher mean liver dose EQD2α/β=3 Gy (p = 0.0212) and non-significantly greater MMA size. Variance analysis demonstrated a significant reduction of MMA and total liver volume after SBRT (p < 0.0001). The volume reduction decelerated longitudinally for both MMA (p < 0.0001) and liver size (p = 0.0033). Radiation doses (PTV-BEDα/β=3 Gy and 10 Gy) were not significantly associated with MMA volume reduction. SBRT of liver metastases with mean liver dose EQD2α/β=3 Gy > 18 Gy were characterized by greater MMA volumes (p = 0.0826) and steeper MMA reduction gradients during FU than those with EQD2α/β=3 Gy ≤ 18 Gy (p < 0.0001). Radiogenic MMAs either completely resolve or usually decrease in volume with pronounced reduction during short-term FU. This course was independent of the MMA's morphological appearance. Further, increased mean liver dose was associated with greater MMA size and a greater gradient of MMA size reduction during FU. [ABSTRACT FROM AUTHOR]

Background: We previously developed and psychometrically validated a self-reported memory problem (SRMP) measure using principal component analysis. In the present study, we applied item response theory (IRT) analysis to further examined the construct validity and determine item-level psychometric properties for the SRMP. Methods: The sample included 530 female breast cancer survivors (61% non-Hispanic White, mean age = 57 years) who were recruited from community-based organizations and large health care systems. We examined the construct validity, item-level psychometric properties, and differential item functioning (DIF) of the SRMP using confirmatory factor analysis (CFA), IRT and logistic regression analysis models. Results: The CFA confirmed a one-factor structure for the SRMP (comparative fit index [CFI] = 0.996, root-mean-square-error-approximation [RMSEA] = 0.059). As expected, SRMP scores correlated significantly with pain, mood, and fatigue; but not spiritual health locus of control (SPR). DIF analysis showed no measurement differences based on race/ethnicity and age groups. Conclusion: The CFA and DIF analysis supported the construct validity of the SRMP and its use in an ethnically diverse breast cancer population. These findings provide further evidence of the generalizability for the SRMP, and support its utilization as a psychometrically valid and reliable screening measure of cancer and treatment-related memory difficulties. [ABSTRACT FROM AUTHOR]

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p <.05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria. [ABSTRACT FROM AUTHOR]

Background. Gastrointestinal stromal tumors (GIST) are rare and before 2000, patients had a dismal prognosis with a median survival of less than a year after tumor metastasis. However, the median overall survival has increased to more than five years following the introduction of imatinib and other tyrosine kinase inhibitors (TKI). Little is known about the psychosocial consequences of treatment of GIST, but this is important because patients now are treated and live for longer. This cross-sectional study assessed quality of life, distress, and fear of cancer recurrence or progression in patients with GIST. Material and methods. Eighty-six patients with localized or metastatic GIST were asked to participate. Patients completed self-report questionnaires including the EORTC-Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, Impact of Event Scale, Cancer Worry Scale, and Fear of Cancer Recurrence Inventory. Results. Fifty-four patients (median age 63.3 years) completed the questionnaires, 33 (61%) of whom were receiving TKI treatment at the time of the study. Overall, the GIST patients had a good global quality of life, but 28 patients had high levels of fear of cancer recurrence/progression. This high level of fear was not related to patient- or treatment-related variables. These patients experienced significantly higher levels of psychological distress, functional impairments, and difficulty making plans for the future than did patients with lower levels of fear. Conclusions. More attention should be paid to specific cancer-related problems, such as fear of cancer recurrence/progression, in addition to general quality of life issues in patients with GIST. [ABSTRACT FROM AUTHOR]

Purpose. To report results from the five-year follow-up on a previously reported study using image-guided radiotherapy (IGRT) of localized or locally advanced prostate cancer (PC) and a removable prostate stent as fiducial. Material and methods. Patients with local or locally advanced PC were treated using five-field 3D conformal radiotherapy (3DRT). The clinical target volumes (CTV) were treated to 78 Gy in 39 fractions using daily on-line image guidance (IG). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were scored using the radiotherapy oncology group (RTOG) score and the common toxicity score of adverse events (CTC) score. Urinary symptoms were also scored using the international prostate symptom score (IPSS). Results. Median observation time was 5.4 year. Sixty-two of the 90 patients from the original study cohort were eligible for toxicity assessment. Overall survival, cancer-specific survival and biochemical freedom from failure were 85%, 96% and 80%, respectively at five years after radiotherapy. Late toxicity GU and GI RTOG scores ≥ 2 were 5% and 0%. Comparing pre- and post-radiotherapy IPSS scores indicate that development in urinary symptoms after radiotherapy may be complex. Conclusions. Prostate image-guided radiotherapy using a prostate stent demonstrated survival data comparable with recently published data. GU and GI toxicities at five-year follow-up were low and comparable to the lowest toxicity rates reported. These findings support that the precision of the prostate stent technique is at least as good as other techniques. IPSS revealed a complex development in urinary symptoms after radiotherapy. [ABSTRACT FROM AUTHOR]

Background. Treatment of localized prostate cancer (PC) is controversial. This is the first randomized study comparing an open surgery procedure (radical prostatectomy) with a combination of high-dose rate brachytherapy (2 × 10 Gy) and external beam radiotherapy (25 × 2 Gy) in PC patients in Sweden 1996-2001. The two randomization arms were compared regarding differences in patients-reported outcomes, such as complications and health-related quality of life (HRQoL). Material and methods. The patients had localized/locally advanced PC, clinical category T1b-T3a, N0, M0 and PSA ≤ 50 ng/ml. All underwent total androgen blockade (six months). Self-reported HRQoL and symptoms including urinary, bowel, and sexual side effects were investigated prospectively before randomization and 12 and 24 months after randomization. A total of 89 patients were randomized and completed the EORTC QLQ C-33 and EORTC PR-25 questionnaires. Results. Over the study period, there were no discernible differences in HRQoL, or complications between the two groups. Emotional functioning, however, improved statistically significantly over time, whereas Social functioning decreased, and financial difficulties increased. No statistically significant differences in group-by-time interactions were found. The survival rate was 76%. Only eight patients (9%) died of PC. Conclusion. Open radical prostatectomy and the combined high-dose rate brachytherapy with external beam radiation appeared to be comparable in the measured outcomes. It was not possible to draw any conclusion on the efficacy of the two treatments due to insufficient power of the study. [ABSTRACT FROM AUTHOR]

Background. The precise etiology of fecal incontinence (FI), which occurs frequently following external beam radiotherapy (EBRT) for prostate carcinoma is unknown. It is possibly related to pelvic nerve injury. The aim of this study was to assess the incidence of pudendal nerve dysfunction in men with FI after EBRT for prostate cancer compared to men with FI but no history of EBRT. Material and methods. Data were evaluated from 74 men with intact anal sphincters on endo-anal ultrasound (17 post-EBRT) who had been investigated for FI at a tertiary center. Wexner incontinence scores, pudendal nerve function, anorectal manometry, and rectal sensitivity were compared between the two patient groups. Results. Post-radiotherapy patients were older (77 ± 6 vs. 62 ± 17 years, p < 0.005) and had worse incontinence than those with no history of radiotherapy (Wexner score; 13 ± 3 vs. 8 ± 4; p < 0.005). Bilateral pudendal nerve terminal motor latency (PNTML) was abnormal in 87% of radiotherapy versus 22% of non-radiotherapy patients (p < 0.001) and the significant difference persisted even after correction for age differences. Anal sphincter pressures and rectal sensitivity for both groups were similar. Conclusion. There is a markedly higher incidence of pudendal nerve dysfunction in men with FI after EBRT for prostate cancer compared with men with FI from other etiologies. The increased severity of incontinence in radiotherapy patients is not matched by alterations in either anal sphincter pressures or rectal sensitivity compared to FI in non-ERBT patients. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was: 1) to compare health-related quality of life (HRQoL) scores of breast cancer survivors to matched controls; and 2) to examine the relative impact (explained variance) of the type and number of co-morbidities on HRQoL. Material and methods. Data from the KARMA project was used in this cross-sectional study. For each woman diagnosed with breast cancer (n = 2552) there were two healthy age- and geographically matched females (n = 5104). Breast cancer survivors were categorized according to time since diagnosis: recently diagnosed (0-1 year), short- (2-5 years), mid- (6-10 years), and long-term survivors (> 10 years). Women completed a questionnaire addressing demographics (age, educational level, and geographical location), lifestyle factors (body mass index (BMI) and smoking), co-morbidities, and HRQoL. The difference in explained variance in six HRQoL-domains between demographics, lifestyle factors, and co-morbidity in women with breast cancer and matched controls was examined by hierarchical regression analyses. Results and conclusion. Women recently diagnosed (n = 63), reported the worst HRQoL followed by short-term survivors (2-5 years, n = 863). Thereafter, HRQoL scores further improved (6-10 years, n = 726), and were comparable to healthy females after 10 years (n = 893). Co-morbidity has a negative impact on HRQoL, which increased with time after diagnosis. Cardiovascular disease and depression were the strongest associates. Breast cancer survivors report clinically significant improvement in HRQoL scores six years after diagnosis. Co-morbidity has a negative impact on HRQoL, which increases with time after diagnosis, even though the number of co-morbidities remains stable. In long-term survivors there should be increasing awareness of co-morbidity and its impact on HRQoL. [ABSTRACT FROM AUTHOR]

Background. Studies show a cross-sectional association between physical activity (PA) and fatigue among lymphoma cancer patients. However, few longitudinal studies have examined whether PA has a sustained effect on fatigue over time. Purpose. To examine the longitudinal relationship between PA and fatigue. Methods. All living individuals diagnosed with lymphoma between 1999 and 2010 as registered by the Dutch population-based Eindhoven Cancer Registry received a questionnaire on three time points. Generalized linear mixed models were used to estimate the independent effects of PA on fatigue. Results. PA and fatigue levels did not differ between patients short-term (< 1 year) and long-term after diagnosis (1-5 years or > 5 years). PA behavior was relatively constant over time with 84% of the patients meeting the Dutch PA guidelines at all assessment periods. Fatigue scores also remained fairly stable over time with 46% of the patients never being fatigued and 29% always being fatigued. Multivariate analyses showed that patients who met the PA guidelines scored 6.2 (95% CI 3.1-9.2) points lower on total fatigue over time (between subject effect; p < 0.01), compared to patients not meeting PA guidelines. Conclusion. During a period of two years, PA and fatigue levels were rather stable within lymphoma patients. Patients who met the PA guidelines reported lower levels of fatigue compared to those not meeting the guidelines, which appeared to be a constant association over time. The observed association between PA and fatigue underlines the importance to focus upon physical training in the care of cancer patients. [ABSTRACT FROM AUTHOR]

The article discusses research which examines the association of cranio-spinal irradiation (CSI) for medulloblastoma with the development of diabetes mellitus (DM) in long-term survivors. It indicates the potential of proton beam therapy (PBT) and helical tomotherapy (HT) to reduce total dose to pancreas and pancreatic tail in the setting of CSI for medulloblastoma. It reveals that patients receiving central nervous system (CNS) irradiation are at risk for the development of late effects.

Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of oxaliplatin which can negatively influence quality of life. We aimed to study the influence of cumulative dose, dose schedule and dose reductions of adjuvant oxaliplatin on long-term severity and prevalence of CIPN among colorectal cancer (CRC) survivors. Material and methods. In total 207 patients, diagnosed with CRC between 2000 and 2009 who underwent adjuvant treatment with oxaliplatin, were included. They completed the EORTC QLQ-CIPN20 2-11 years after diagnosis. Data on oxaliplatin administration and acute neuropathy during treatment were extracted from the medical files. Subscales were analyzed with analysis of covariance and neuropathy symptoms with logistic regression analysis. Results. Patients who received cumulative oxaliplatin dose of ≥ 842 mg/m2 had a significantly worse EORTC QLQ-CIPN20 sensory score compared to those who received a low cumulative dose of < 421 mg/m2 (mean 19 vs. 8; p = 0.02). They more often reported tingling toes/feet (13% vs. 2%, respectively; p = 0.01). Dose intensity and time delay did not influence the occurrence of CIPN. Patients receiving a dose reduction because of neuropathy (N = 50) reported a significantly worse sensory score at very similar cumulative doses, than those who did not receive a dose reduction because of neuropathy (N = 96) (mean 21 vs. 15; p = 0.01). Conclusion. Cumulative dose of oxaliplatin is associated with long-term CIPN. The risk of developing long-term CIPN could only be reduced by decreasing the cumulative dose, whereas delay probably is not beneficial. Patients receiving a dose reduction because of acute neuropathy are still at risk of developing long-term CIPN. Future studies should focus on identifying patients who are at risk of developing CIPN. [ABSTRACT FROM AUTHOR]

Background. Electrochemotherapy describes the use of electric pulses to enhance chemotherapy uptake, and has proven highly efficient in treating cutaneous metastases. Patients referred for electrochemotherapy present with diverse clinical pictures, from multiple small lesions to large, ulcerated lesions. Post-electrochemotherapy pain has been observed in some patients. The objectives of this study were to evaluate pain scores before and after electrochemotherapy, and to investigate if patients at risk of post-procedure pain could be identified. Methods. Seven cancer centres in the International Network for Sharing Practices on Electrochemotherapy (INSPECT) consecutively and prospectively reported to a common database. Electrochemotherapy consisted of intratumoural or intravenous injection of bleomycin, followed by delivery of electric pulses in local or general anesthesia. Results. Of 121 patients 39% had metastatic melanoma, 18% squamous cell carcinoma, 16% breast cancer, 13% basal-cell carcinoma, and 14% other malignancies. Median size of the largest nodules was 2.3 cm (range 0.3-40 cm). A majority of patients presented with low pain scores, and this continued through follow-up (74%). A subset of patients had moderate (13%) or severe pain (13%) after treatment. Post-procedure pain was statistically significantly associated with: 1) moderate or severe pain before treatment (p < 0.0001); 2) size of the largest treated lesion (p < 0.01); 3) previous irradiation (p < 0.02); and 4) high treatment current value (p < 0.0001). Conclusion. The majority of patients had no or mild pain after electrochemotherapy. Patients at risk for post-procedure pain could be identified at the pre-treatment visit, and/or at the time of treatment, enabling a pain management strategy for this group. [ABSTRACT FROM AUTHOR]

Background. Few studies have explored fatigue in different groups of lymphoma survivors and the association with hormonal dysfunctions. The aims were to analyze associations between fatigue and thyroid and gonadal function in male lymphoma survivors. In addition, the impact of chronic fatigue on work situation and daily functioning were explored. Patients and methods. This cross-sectional study included male lymphoma survivors diagnosed in 1980-2002, aged ≤ 50 years at diagnosis and > 18 years at survey in 2007. The participants (n = 233, median age at survey: 48 years, median observation time: 15 years) completed questionnaires assessing levels of fatigue, chronic fatigue (duration ≥ 6 months), mental distress, daily functioning and work situation. Levels of thyroid and gonadal hormones were assessed. The participants were grouped according to diagnosis: Hodgkin lymphoma (HL, n = 131), aggressive/very aggressive non-Hodgkin lymphoma (NHL) (n = 67) and indolent NHL (n = 35). Thyroid hormones were categorized as normal (n = 174) or latent hypothyroidism (elevated thyroid stimulating hormone, n = 59). Gonadal hormones were categorized as normal (n = 111), elevated follicle stimulating hormone only (n = 45), primary (n = 35) or secondary hypogonadism (n = 42). Uni- and multivariate regression analyses were performed. A p value < 0.05 indicated the level of significance. Results. The survivors of HL and aggressive/very aggressive NHL had similar fatigue levels and similar prevalence of chronic fatigue (HL: 31%, aggressive/very aggressive; NHL: 27%). Survivors of indolent NHL had lower fatigue levels and prevalence of chronic fatigue (11%). Latent hypothyroidism was associated with increased fatigue levels (p = 0.042). Gonadal function was not associated with levels of fatigue or chronic fatigue. Mental distress was associated with increasing fatigue levels and chronic fatigue (p < 0.001). We found negative associations between chronic fatigue, daily functioning and work status. Conclusions. Fatigued lymphoma survivors should be investigated for thyroid function. The negative impact of chronic fatigue on daily functioning and work status emphasizes the importance of maintaining the effort in understanding the mechanisms behind fatigue. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this work was to investigate cardiorespiratory fitness in breast cancer patients at different time points of anti-cancer treatment. Patients and methods. Non-metastatic breast cancer patients (n = 222, mean age 55 years) were categorized into four subgroups according to their treatment status. Cardiopulmonary exercise testing (CPET) was used to measure patients' cardiorespiratory fitness, including oxygen delivery and metabolic muscle function. Testing was performed by bicycle ergometry, and maximal oxygen uptake (VO2peak) was measured. Heart rate during exercise at 50 watts (HR50) was assessed as a cardiocirculatory parameter and ventilatory threshold (VT) was used as an indicator of the O2 supply to muscle. Analysis of covariance was used to estimate the impact of different cancer treatments on cardiorespiratory fitness with adjustment for clinical factors. Results. Submaximal measures were successfully assessed in 220 (99%) and 200 (90%) patients for HR50 and VT, while criteria for maximal exercise testing were met by 176 patients (79%), respectively. The mean VO2peak was 20.6 ± 6.7 ml/kg/min, mean VT 10.7 ± 2.9 ml/min/kg and mean HR50 112 ± 16 beats/min. Chemotherapy was significantly associated with decreased VO2peak, with significantly lower adjusted mean VO2peak among patients post adjuvant chemotherapy compared to patients with no chemotherapy or those who just started chemotherapy regime (all p < 0.01). Patients post adjuvant chemotherapy reached only 63% of the VO2peak level expected for their age- and BMI-category (mean VO2peak 15.5 ± 4.8 ml/kg/min). Similarly, HR50 was significantly associated with treatment. However, VT was not associated with treatment. Conclusion. Breast cancer patients have marked and significantly impaired cardiopulmonary function during and after chemotherapy. Hereby, chemotherapy appears to impair cardiorespiratory fitness by influencing the oxygen delivery system rather than impacting metabolic muscle function. Our findings underline the need of exercise training in breast cancer patients to counteract the loss of cardiorespiratory fitness during the anti-cancer treatment. [ABSTRACT FROM AUTHOR]

Background. Patients treated with external beam radiotherapy (EBRT) may suffer from long-term anorectal adverse effects. The purpose of the present study was to assess long-term functional and structural anorectal changes in patients previously treated with EBRT for prostate cancer and to suggest the mechanism behind the development of the adverse effects. Material and methods. Our previously proposed RT-induced anorectal dysfunction (RT-ARD) score, developed with the intention to survey anorectal dysfunction was used to identify patients with and without anorectal symptoms. Among 309 patients surveyed with the questionnaire, we chose 23 patients with the highest RT-ARD score and 19 patients with the lowest RT-ARD score. They were investigated by multimodal rectal sensory stimulation, standard anal physiological tests. Changes of the rectal mucosa were assessed by flexible sigmoidoscopy and graded by the Vienna Rectoscopy Score (VRS). Results. The mean follow-up time was 3.8 (range, 2.8; 8.6) years in patients with high RT-ARD and 3.8 (range, 2.6; 5.9) in patients with low RT-ARD. Endoscopic evaluation revealed higher VRS scores in patients with high RT-ARD compared to patients with low RT-ARD (p = 0.002). Patients with high RT-ARD had increased rectal sensory response to distension manifested both as volume (p = 0.006) and cross-sectional area (p = 0.04), and they had reduced maximum anal resting pressure assessed by anal manometri (p = 0.02). Conclusions. Long-term anorectal symptoms correlate to changes in anorectal biomechanical properties and rectal mucosal injury. Our data suggests that RT-induced long-term anorectal dysfunction is multifactorial caused by injury of the rectal mucosa and the internal anal sphincter combined with increased rectal sensitivity and reduced rectal functional capacity. [ABSTRACT FROM AUTHOR]

Background. Fatigue and emotional reactivity are common among women suffering from breast cancer and might detrimentally affect these women's quality of life. This study evaluates if the stress management delivered either in a group or individual setting would improve fatigue and emotional reactivity among women with a newly diagnosed breast cancer. Material and methods. Participants (n = 304) who reported elevated levels of distress at three-month post-inclusion were randomised between stress management in a group (GSM) (n = 77) or individual (ISM) (n = 78) setting. Participation was declined by 149 women. Participants completed the Multidimensional Fatigue Inventory (MFI-20) and the Everyday Life Stress Scale (ELSS) at the time of inclusion, 3- and 12-month post-inclusion. Analyses were made according to intention to treat and per-protocol principles. Mann-Whitney tests were used to examine differences between the two intervention groups. Results. No significant differences were detected between the GSM and ISM groups on fatigue or emotional reactivity. In addition, there were no changes over time for these outcomes. Conclusions. There were no differences between the two intervention arms with reference to fatigue or emotional reactivity; however, a clinically interesting finding was the low number of women who were interested in participating in a psychosocial intervention. This finding may have clinical implications when psychosocial support is offered to women with a newly diagnosed breast cancer and also in the planning of future studies. [ABSTRACT FROM AUTHOR]

While the detrimental effects of cranial radiotherapy on the developing brain are well known, the effects on cognitive performance of low doses of ionizing radiation is less studied. We performed a population-based cohort study to determine whether low doses of ionizing radiation to the brain in infancy affects cognitive function later in life. Further we hypothesized that the dose to the hippocampus predicts cognitive late side effects better than the anterior or the posterior brain doses. Material and methods. During 1950-1960 3860 boys were treated with radiation in Sweden for cutaneous hemangiomas before the age of 18 months. Of these, 3030 were analyzed for military test scores at the age of 18 years and 2559 for the highest obtained educational level. Results. Logical, spatial and technical test scores were not affected by increasing irradiation doses. The verbal test scores displayed a significant trend for decreasing scores with increasing doses to the hippocampus (p = 0.005). However, the absolute mean difference between the zero dose and the highest dose category (median 680 mGy) was very small, only 0.64 stanine points, and the significance was dependent on the highest dose category, containing few subjects. The educational level was not affected by brain irradiation. Overall, the hippocampal dose was a better predictor of late cognitive side effects than the doses to the anterior or the posterior brain. In conclusion, there was no decrease in logical, spatial and technical verbal or global test scores after ionizing radiation doses up to 250 mGy, but a subtle decrease in verbal test scores if the highest dose category was included (median 680 mGy). However, the clinical relevance of this decline in the highest dose group is questionable, since we could not find any effect on the highest obtained educational level. [ABSTRACT FROM AUTHOR]

Background. Geometrical distortion is a major obstacle for the use of echo planar diffusion-weighted magnetic resonance imaging (DW-MRI) in planning of radiotherapy. This study compares geometrical distortion correction methods of DW-MRI at time of brachytherapy (BT) in locally advanced cervical cancer patients. Material and methods. In total 21 examinations comprising DW-MRI, dual gradient echo (GRE) for B0 field map calculation and T2-weighted (T2W) fat-saturated MRI of eight patients with locally advanced cervical cancer were acquired during BT with a plastic tandem and ring applicator in situ. The ability of B0 field map correction (B0M) and deformable image registration (DIR) to correct DW-MRI geometric image distortion was compared to the non-corrected DW-MRI including evaluation of apparent diffusion coefficient (ADC) for the gross tumor volume (GTV). Results. Geometrical distortion correction decreased tandem displacement from 3.3 ± 0.9 mm (non-corrected) to 2.9 ± 1.0 mm (B0M) and 1.9 ± 0.6 mm (DIR), increased mean normalized cross-correlation from 0.69 ± 0.1 (non- corrected) to 0.70 ± 0.10 (B0M) and 0.77 ± 0.1 (DIR), and increased the Jaccard similarity coefficient from 0.72 ± 0.1 (non-corrected) to 0.73 ± 0.06 (B0M) and 0.77 ± 0.1 (DIR). For all parameters only DIR corrections were significant (p < 0.05). ADC of the GTV did not change significantly with either correction method. Conclusion. DIR significantly improved geometrical accuracy of DW-MRI, with remaining residual uncertainties of less than 2 mm, while no significant improvement was seen using B0 field map correction [ABSTRACT FROM AUTHOR]

Background. Breast carcinomas (BC) can have abnormal choline (Cho) metabolism. Earlier studies indicated that Cho uptake can differ between different subtypes of BC. The purpose of this study was to investigate uptake of 2-[18F]-fluoroethyl-choline ([18F]FECh) in three different patient-derived breast cancer xenografts (BCXs) using dynamic positron emission tomography (dPET). Material and methods. Nine athymic nude mice bearing bilateral MAS98.12 (basal-like), HBCx34 or MAS98.06 (both luminal B) BCXs were subjected to a 90-minute dPET scan following a bolus injection of 10 MBq of [18F]FECh. A Patlak Plot analysis and a well-established two-tissue compartment model were fitted to the uptake curves of the whole tumors, providing estimates of transfer rates between the vascular, non-metabolized and metabolized compartments. Patlak slope KP and intercept V, the rate constants k1, k2, k3, the intravascular fraction vb and MR[18F]FECh were estimated. Additionally, analyses of terminal blood samples and tumor cell suspension incubated with [18F]FECh were performed. Results. [18F]FECh uptake in all BCXs was similar to surrounding normal tissue, thus creating no image contrast. The average liver uptake was 10 times higher than the tumor uptake. The uptake in MAS98.12 was higher than in the other two BCXs during the whole course of the acquisition, and was significantly higher than in HBCx34 at 10-30 minutes after injection. No significant differences were found for k1, MR[18F]FECh and intravascular fraction vb. Patlak slope KP, k2 and k3 were significantly lower for the MAS98.12 xenograft, in line with in vitro results. KP was correlated with both MR[18F]FECh and k3. Conclusions. dPET demonstrated that different subtypes of breast cancer have different uptake of [18F]FECh. Differences in rate constants and KP were in line with in vitro uptake in cell suspensions and earlier spectroscopy and gene expression analysis. [ABSTRACT FROM AUTHOR]

Background. Appropriate information provision is an important determinant of patient satisfaction and might also affect health-related quality of life (HRQoL) of cancer patients. The aim of this study was to examine the relationship between perceived information provision at baseline and HRQoL, anxiety and depression among lymphoma patients two years later. Material and methods. This study is part of a longitudinal, population-based survey among all lymphoma patients diagnosed between 1999 and 2009 as registered in the Eindhoven Cancer Registry (southern part of The Netherlands). Patients between six months and 10 years after diagnoses received the first questionnaire including the EORTC QLQ-INFO25, EORTC QLQ-C30 and HADS at baseline (T1) and the second two years later (T2). All analyses are stratified for time since diagnosis (< 2 and ≥ 2 years since diagnosis). Results. At baseline 69% of the patients (n = 1186) responded, at T2 355 (30%) patients responded. For patients < 2 years since diagnosis, receiving more medical test information was associated with higher levels of cognitive functioning (ß = 0.46; p = 0.04) and lower levels of anxiety (ß = −0.41; p = 0.04) at baseline, no prospective relationships were found. For patients ≥ 2 years since diagnosis, receiving more medical test information (ß = 0.20; p = 0.03) was associated with better emotional functioning, while receiving more treatment information was associated with worse emotional functioning (ß = −0.21; p = 0.04). Among this group, satisfaction with the received information was associated with better functioning (ß ranging from −0.15 to −0.33; all p < 0.05) at baseline, and these relationships remained significant prospectively for physical (ß = −0.13; p = 0.02) and emotional functioning (ß = −0.13; p = 0.04) only. Stability of satisfaction with received information over time was associated with better emotional (ß = −0.13) and better cognitive functioning (ß = −0.09; p < 0.05) at T2. Conclusion. The present study showed that satisfaction with received information among lymphoma patients was associated with better HRQoL at baseline (only for patients ≥ 2 years since diagnosis), but not at follow−up when corrected for baseline HRQoL. [ABSTRACT FROM AUTHOR]

The article presents a study on lung injury caused by radiation after concurrent neoadjuvant chemoradiotherapy for treatment of locally advanced breast cancer (LABC). It mentions that attaining a pathological complete response (pCR) to the therapy is considered a significant factor. It also notes its representation of a regimen based on anthracycline.

Background. Physical activity during chemotherapy has been shown in several studies to reduce fatigue, improve symptoms and impact positively on health-related quality of life (HRQoL). Challenges associated with intervention studies on physical activity during cancer treatment relate to consistent adherence. The primary objective was to study feasibility and adherence of physical activity intervention among patients with cancer during adjuvant chemotherapy treatment. The secondary objective was to investigate the effects of physical activity on health aspects, including HRQoL, symptoms and surrogate markers for cardiovascular disease. Material and methods. This randomized controlled trial included patients with breast cancer (BRCA) and colorectal cancer (CRC) during adjuvant chemotherapy. The intervention continued for 10 weeks and included daily walks of 10 000 steps and a weekly supervised group walk. Adherence was assessed by a pedometer and the number of participants who reported step counts every week and percentage of participants who achieved the target steps every week. Results. Adherence average reached 91% during the intervention period; in total 74% completed the exercise intervention. The majority of the participants achieved an average of 83% of the target of 10 000 steps per day for 10 weeks. There was a significant increase in daily physical activity (p = 0.016) in the intervention group. Significant differences were also found for some breast cancer-specific symptoms [swelling, mobility and pain (p = 0.045)]. The study showed a relatively small weight gain an average of 0.9 kg in the intervention group and 1.3 kg in the control group. Conclusion. Physical activity in the form of walking is feasible during adjuvant chemotherapy treatment despite increasing symptoms. The physical activity increased in the intervention group during the study time and had a positive impact on breast symptoms and the weight gain was lower in comparison to previous studies. [ABSTRACT FROM AUTHOR]

Background. Concurrent chemo-radiotherapy (CON-CRT) is recommended for selected patients with stage III non-small cell lung cancer (NSCLC), but utilization varies. We assessed the response to national guidelines introduced in 2004 and the impact on outcomes. Material and methods. Retrospective study of stage III NSCLC patients treated with radical intent non-surgical treatment during 2003-2010 in a university medical center characterized by multidisciplinary assessment, routine use of four-dimensional computed tomography for radiotherapy planning, and rapid implementation of radiotherapy advances. Results. Between 2003 and 2010, 319/435 (73%) patients with stage III NSCLC received (chemo) radiotherapy. The number receiving CON-CRT in successive two-year periods increased from 13/48 (27%) - 40/80 (50%) - 63/90 (70%), to 74/101 (73%). Median overall survival (OS) from start of radiotherapy was 18.6 months for CON-CRT (190/319) and 17.4 months for sequential (SEQ), typically hypofractionated, CRT (90/319) (p = 0.78). Eleven months OS with radiotherapy alone (39/319) was significantly shorter (p = 0.006). OS did not differ between the four periods (p = 0.87). CON-CRT was not over-represented in the 16% of patients dying within five months of starting radiotherapy. Conclusions. Between 2003 and 2010, CON-CRT for stage III NSCLC was rapidly and safely increased. However, OS did not increase and, as practiced, did not differ between CON- or SEQ-CRT. [ABSTRACT FROM AUTHOR]

Background. Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. Material and methods. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Results. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m2 (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Conclusion. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development of metabolic syndrome and CVD years later in individual testicular cancer survivors. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the impact of intercellular contact during radiation exposure on cell survival in regions of reduced dose. Methods. The PC3 human prostate adenocarcinoma cell line was irradiated using a 6 MV x-ray beam to assess clonogenic cell deaths with the specific aim to investigate cell survival in a dose cold spot. Radiation-induced cell survival in a 20% lower dose region, compared to that of cells receiving 100% of the prescribed dose (2 Gy), was assessed for experimental set-ups when under-irradiated cells were either in direct contact with cells receiving 2 Gy or irradiated separately. In addition, the results were compared against non-irradiated controls. Results. A significant (p < 0.001) decrease in cell survival was found when cells, collocated in the same flask, received either 100% or 80% of the prescribed dose (the dose distribution contained a cold spot of 20% lower dose) compared to non-irradiated cells. However, in the experiment in which the entire flask was exposed to only 80% of the prescribed dose, the mean difference in cell survival compared to non-irradiated control was not significant (p > 0.05). This was contrary to a significant decrease (p < 0.001) in survival of cells receiving 100% of the prescribed dose versus the control. Additionally, significant reduction (p < 0.05) in cell survival was observed for cells which were under-irradiated by 20% but collocated in the same flask with cells receiving 100% dose compared to cells where the entire flask was irradiated with 80% of the prescribed dose. Conclusion. For the given cell line, under existing growing and treatment conditions, the cell survival in the dose cold spot region was significantly lower when under-irradiated cells were in contact with the cells receiving 100% of the prescribed dose compared to survival of cells under-irradiated by the same amount of radiation but treated separately to cells receiving 100% dose. [ABSTRACT FROM AUTHOR]

Gliomas are characterized by high invasiveness and poor prognosis. Better understanding of the mechanism of invasion in glioma cells is essential to the design of effective therapy. Recently Grb2-associated binder 2 (Gab2), a member of the DOS/Gab family of scaffolding adapters, has been reported to play important roles in the development and progression of human cancers. However, it is not known whether Gab2 has any role in the migration and invasion of gliomas. This study attempts to investigate the association between Gab2 expression and progression of gliomas and the molecular mechanism of Gab2 in the glioma cell invasion. Methods. The expression of Gab2 in pairs of matched glioma tissues and their normal brain tissues was detected by Western blot. Immunohistochemistry was applied to evaluate the expression of Gab2 in 163 cases of histologically diagnosed gliomas. The invasive character of Gab2 decreased glioma cells and control glioma cells were investigated in vitro and in vivo in SCID mice brain. Results. Gab2 is found to be high expressed in gliomas and a subset of cancer cell lines. Statistical analysis suggested that the up-regulation of Gab2 correlated with the WHO grade of gliomas (p < 0.01) and that patients with high Gab2 expression levels exhibited shorter survival time (p < 0.01). In an animal experiment, knockdown of Gab2 through siRNA inhibited invasive ability of glioma cells into the brain of SCID mice. In cell research, reduction of Gab2 by siRNA inhibits the migration and invasion of glioma cells by mediating cytoskeleton rearrangement and MMPs expression. Additionally, IGF-1-induced pAkt and pmTOR phosphorylation was suppressed by the knockdown of Gab2. Conclusion. Gab2 may be a useful prognostic marker for gliomas and a novel therapeutic target for glioma invasion intervention. [ABSTRACT FROM AUTHOR]

Background. The interactions between cancer-associated fibroblasts (CAFs) and cancer cells or tumor-infiltrating lymphocytes (TILs) and cancer cells play important roles in cancer progression and metastasis. However, studies related to the crosstalk between CAFs and TILs in tumor microenvironment (TME) are still lacking. In this study, we mainly investigated the interactions between CAFs and TILs. Material and methods. The distribution of TILs rich in regulatory T cells (Tregs) in breast cancer tissues was evaluated using hematoxylin-eosin staining and immunohistochemistry with anti-CD3, anti-Foxp3, and anti-α-smooth muscle actin antibodies. Homologous CAFs/normal fibroblasts (NFs) and TILs cultured in vitro were identified and detected using immunocytochemistry and flow cytometry (FCM). The direct interaction among these cell types was studied via a factorial design in a co-cultured system. Their indirect interaction was assayed using Transwell plates. The cell cycle and apoptosis of CAFs/NFs co-cultured with TILs was analyzed using propidium iodide staining. Results. Histochemistry demonstrated most of the TILs including Tregs, were distributed in the cancer stroma, adjoining to CAFs. This finding implies that both cell types interact closely in the TME. Identification of the cultured cells showed that CAFs maintained their activated phenotype within limited passages in vitro, and that the TILs population contained a high percentage of Tregs. Data analysis of the factorial design suggests significant interactions among CAFs, NFs, and TILs in both direct and indirect contact ways. The CAFs and NFs were suppressed signally by TILs, which are probably induced by the secretory cytokines derived from TILs or Tregs. Although apoptosis was not detected in CAFs/NFs, the cell cycle assay suggested that the CAFs/NFs were arrested in the G2/M phase by the TILs and their secretory cytokines. Conclusion. CAFs and NFs were dramatically suppressed by Tregs-rich TILs. This suggests the interaction between TILs and CAFs might modify the TME in an unknown manner. [ABSTRACT FROM AUTHOR]

Background. To characterize the stage-specific prognostic relevance of preoperative systemic inflammatory response, defined by C-reactive protein (CRP), in colon cancer (CC) patients. Material and methods. Data from CC patients operated on from 1998 to 2007 at three hospitals from three different Nordic countries were collected retrospectively from national registries, local databases and/or patient records. Patients with emergency surgery, infection or auto-immune disease were excluded. Associations between clinical or histopathological variables and CRP were assessed. Patients were followed from the date of surgery to death or end of follow-up. Disease-specific survival (DSS) was the main endpoint. Results. In total, 525 patients with age and stage distributions which were representative for CC patients were included. None of the patients was lost to follow-up. Age, TNM Stage, WHO differentiation grade and right-sided tumor location significantly associated with elevated CRP values, in contrast to postoperative morbidity, which did not. CRP levels were found to be a strong prognostic factor for DSS in CC. The risk of death due to CC was augmented with increasing levels of CRP in every stage of operated CC. Both short- and long-term DSS were impaired. The sub-hazard ratios for CRP-levels above 60 mg/L were 7.37 (CI 2.65-20.5) for stage I+ II, compared to 3.29 (CI 1.30-8.29) for stage III and 2.24 (CI 1.16-4.35) for stage IV. Conclusion. Increase of CRP concentrations correlate with clinically relevant poorer disease-specific survival in each stage of CC. [ABSTRACT FROM AUTHOR]

Purpose. Besides basic measurements as maximum standardized uptake value (SUV)max or SUVmean derived from 18F-FDG positron emission tomography (PET) scans, more advanced quantitative imaging features (i.e. 'Radiomics' features) are increasingly investigated for treatment monitoring, outcome prediction, or as potential biomarkers. With these prospected applications of Radiomics features, it is a requisite that they provide robust and reliable measurements. The aim of our study was therefore to perform an integrated stability analysis of a large number of PET-derived features in non-small cell lung carcinoma (NSCLC), based on both a test-retest and an inter-observer setup. Methods. Eleven NSCLC patients were included in the test-retest cohort. Patients underwent repeated PET imaging within a one day interval, before any treatment was delivered. Lesions were delineated by applying a threshold of 50% of the maximum uptake value within the tumor. Twenty-three NSCLC patients were included in the inter-observer cohort. Patients underwent a diagnostic whole body PET-computed tomography (CT). Lesions were manually delineated based on fused PET-CT, using a standardized clinical delineation protocol. Delineation was performed independently by five observers, blinded to each other. Fifteen first order statistics, 39 descriptors of intensity volume histograms, eight geometric features and 44 textural features were extracted. For every feature, test-retest and inter-observer stability was assessed with the intra-class correlation coefficient (ICC) and the coefficient of variability, normalized to mean and range. Similarity between test-retest and inter-observer stability rankings of features was assessed with Spearman's rank correlation coefficient. Results. Results showed that the majority of assessed features had both a high test-retest (71%) and inter-observer (91%) stability in terms of their ICC. Overall, features more stable in repeated PET imaging were also found to be more robust against inter-observer variability. Conclusion. Results suggest that further research of quantitative imaging features is warranted with respect to more advanced applications of PET imaging as being used for treatment monitoring, outcome prediction or imaging biomarkers. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related with computed tomography (CBCT) systems for radiotherapy.

Introduction. The cure rate of early stage Hodgkin's lymphoma (HL) is excellent; investigating the late effects of treatment is thus important. Esophageal toxicity is a known side effect in patients receiving radiotherapy (RT) to the mediastinum, although little is known of this in HL survivors. This study investigates the dose to the esophagus in the treatment of early stage HL using different RT techniques. Estimated risks of early esophagitis, esophageal stricture and cancer are compared between treatments. Material and methods. We included 46 patients ≥ 15 years with supradiaphragmatic, clinical stage I-II HL, who received chemotherapy followed by involved node RT (INRT) to 30.6 Gy at our institution. INRT was planned with three-dimensional conformal RT (3DCRT). For each patient a volumetric modulated arc therapy (VMAT), proton therapy (PT) and mantle field (MF) treatment plan was simulated. Mean, maximum and minimum dose to the esophagus were extracted from the treatment plans. Risk estimates were based on dose-response models from clinical series with long-term follow-up. Statistical analyses were performed with repeated measures ANOVA using Bonferroni corrections. Results. Mean dose to the esophagus was 16.4, 16.4, 14.7 and 34.2 Gy (p < 0.001) with 3DCRT, VMAT, PT and MF treatment, respectively. No differences were seen in the estimated risk of developing esophagitis, stricture or cancer with 3DCRT compared to VMAT (p = 1.000, p = 1.000, p = 0.356). PT performed significantly better with the lowest risk estimates on all parameters compared to the photon treatments, except compared to 3DCRT for stricture (p = 0.066). On all parameters the modern techniques were superior to MF treatment (p < 0.001). Conclusions. The estimated dose to the esophagus and the corresponding estimated risks of esophageal complications are decreased significantly with highly conformal RT compared to MF treatment. The number of patients presenting with late esophageal side effects will, thus, likely be minimal in the future. [ABSTRACT FROM AUTHOR]

Introduction. Dynamic 18F-FDG PET allows the study of glucose distribution in tissues as a function of time and space. Using pharmacokinetics, the temporal uptake pattern of 18F-FDG may be separated into components reflecting perfusion and metabolism. Bevacizumab is an angiogenesis inhibitor which prevents the growth of new blood vessels, and may potentially lead to normalization of the blood circulation in the tumor. The purpose of the study was to explore the use of dynamic PET as a tool for monitoring treatment effect, reflected by changes in perfusion and metabolism. Materials and Methods. Twelve athymic nude mice, bearing the bilateral triple-negative human breast cancer xenograft MAS98.12 were treated with bevacizumab (5 mg/kg i.p.). Dynamic PET data was acquired prior to and 24 and 72 hours after treatment for 1 hour after injection of 10 MBq 18F-FDG and fitted with a FDG two-tissue compartment model. The changes in the rate constants k1, k3, MRFDG and the vascular fraction ν B were assessed. To evaluate the effect of treatment regimes, 30 mice, randomized in 5 groups, received either vehicle (0.9% NaCl), bevacizumab (5 mg/kg i.p.), doxorubicin (8 mg/kg i.v.) or bevacizumab and doxorubicin either together, or doxorubicin 24 hours after bevacizumab treatment. Tumor volume was measured twice a week. Results. The perfusion-related rate parameter k1 and the metabolic rate constant k3 decreased significantly 24 hours after treatment. This decrease was followed by an increase, albeit non-significant, at 72 hours post treatment. Doxorubicin given 24 hours after bevacizumab showed less antitumor effect compared to concomitant treatment. Conclusions. Dynamic PET can detect changes in tumor perfusion and metabolism following anti-angiogenic therapy in mouse xenograft models. Longitudinal dynamic PET, used to assess the efficacy of anti-angiogenic treatment, can identify the time frame of potential tumor vasculature re-normalization and allow optimal timing of supplementary therapy (radiation or chemotherapy). [ABSTRACT FROM AUTHOR]

Background. Breast cancer survivors may experience adverse effects of cancer and/or treatment years after completion of therapy, which can considerably decrease quality of life (QoL). Little is known about the time course of QoL in breast cancer survivors beyond the fifth year post-diagnosis, when routine follow-up care has usually terminated. We therefore explored in detail whether and to what extent restrictions in breast cancer survivors persist and whether changes or aggravations in QoL occurred over time. Material and methods. QoL was assessed 1, 3, 5, and 10 years post-diagnosis in a population-based cohort of initially 387 female breast cancer patients from Saarland (Germany), using the EORTC QLQ-C30 and QLQ-BR23. Time course of QoL over 10 years post-diagnosis was assessed for survivors and survivors' QoL was compared cross-sectionally to the German general population after adjustment for age. Results. A total of 182 out of 238 patients alive (76.5%) responded in the 10-year, 160 patients (67.2%) participated in all follow-ups. Although breast cancer survivors and controls reported comparable general health and overall QoL, survivors reported significantly more restrictions on most functioning and symptom scales at each follow-up. Detriments in various QoL dimensions (e.g. physical and social functioning; pain, financial difficulties) aggravated from year 5 to 10. Generally, restrictions were largest for the youngest survivors. Conclusion. Relevant restrictions in QoL persist over years in breast cancer survivors and affect predominantly younger women. The aggravation of restrictions in QoL beyond the fifth year may indicate deficits in health care and psychosocial support of breast cancer patients after completion of routine follow-up care. [ABSTRACT FROM AUTHOR]

Background. Fear of cancer recurrence (FCR) or cancer progression is one of the most frequent distressing psychological symptoms in cancer patients. In contrast to anxiety disorders according to the ICD-10 or DSM-IV, FCR describes an emotional response to the real threat of a life-threatening illness. Elevated levels of FCR can become dysfunctional, causing considerable disruption in social functioning, and affect well-being and quality of life (QoL). We examined the prevalence and course of FCR in cancer patients during and after a rehabilitation program, and investigated associations between demographic, medical and psychosocial factors. We further aimed to identify predictors of FCR one year after cancer rehabilitation. Methods. A total of eligible N = 1281 patients (77.5% participation rate) were consecutively recruited on average 11 months post-diagnosis and assessed at the beginning (t1) (1148), at the end (t2) (1060) and 12 months after rehabilitation (t3) (n = 883). Participants completed validated measures assessing FCR, anxiety, depression, QoL, social support, and a range of cancer- and treatment-related characteristics. Results. At t1, 18.1% of our sample was classified as having high levels of FCR and 66.6% showed moderate levels of FCR. Fear of recurrence decreased over time (p < 0.001) (η² = .095), however, at follow-up 17.2% of our sample showed high levels of FCR and 67.6% had moderate levels of FCR. Linear regression analysis (stepwise backward) including demographic, medical and psychosocial factors, revealed that lower social class, having skin cancer, colon cancer or hematological cancer, palliative treatment intention, pain and a higher number of physical symptoms, depression, lower social support and adverse social interactions predicted FCR one year after rehabilitation (R² adjusted = 0.34) (p < 0.001). Conclusion. Our data provide evidence that elevated levels of FCR represent a continuing problem in cancer patients. The need to enhance cancer rehabilitation and survivorship programs including interventions tailored to specific problems such as FCR is emphasized. [ABSTRACT FROM AUTHOR]

Background. Successful cell therapy relies on the identification and mass expansion of functional cells for infusion. Cryopreservation of cells is an inevitable step in most cell therapies which also entails consequences for the frozen cells. Material and methods. This study assessed the impact of cryopreservation and the widely used protocol for rapid expansion of T lymphocytes. The effects on cell viability, immunocompetence and the impact on apoptotic and immunosuppressive marker expression were analyzed using validated assays. Results and conclusion. Cryopreservation of lymphocytes during the rapid expansion protocol did not affect cell viability. Lymphocytes that underwent mass expansion or culture in high dose IL-2 were unable to respond to PHA stimulation by intracellular ATP production immediately after thawing (ATP = 16 ± 11 ng/ml). However, their reactivity to PHA was regained within 48 hours of recovery (ATP = 356 ± 61 ng/ml). Analysis of mRNA levels revealed downregulation of TGF-β and IL-10 at all time points. Culture in high dose IL-2 led to upregulation of p73 and BCL-2 mRNA levels while FoxP3 expression was elevated after culture in IL-2 and artificial TCR stimuli. FoxP3 levels decreased after short-term recovery without IL-2 or stimulation. Antigen specificity, as determined by IFNγ secretion, was unaffected by cryopreservation but was completely lost after addition of high dose IL-2 and artificial TCR stimuli. In conclusion, allowing short-time recovery of mass expanded and cryopreserved cells before reinfusion could enhance the outcome of adoptive cell therapy as the cells regain immune competence and specificity. [ABSTRACT FROM AUTHOR]

Background. We investigated the radiographic and pathologic response rate of esophageal adenocarcinoma treated with neoadjuvant chemoradiation in patients taking metformin. Material and methods. Two hundred eighty-five patients with esophageal adenocarcinoma treated with concurrent chemoradiation (CRT) followed by esophagectomy from 1997 to 2012 were included in the study, including 29 diabetics taking metformin, 21 diabetics not taking metformin and 235 non-diabetics. Pre- and post-treatment positron emission tomography (PET) scans were available for 204 patients. Pathologic response was graded at the time of surgery. Response rates were compared using both the χ2 statistic as well as ANOVA with post-hoc LSD analysis. Multivariate logistic regression analysis was performed to control for predictors of pathologic complete response (CR) after CRT. Results. The overall rate of pathologic CR for the study population was 20%. The pathologic CR rate was higher in patients taking metformin (34.5%), compared to diabetic patients not taking metformin (4.8%, p = 0.01) and non-diabetic patients (19.6%, p = 0.05). Pathologic CR was related to metformin dose, with ≥1500 mg/d associated with a higher CR rate. No significant difference seen in pre-CRT maximum tumor SUV (p = 0.93), however post-CRT maximum SUV was significantly decreased in patients taking metformin (p = 0.05). On multivariate logistic regression, metformin use was independently associated with pathologic CR (p = 0.04). Metformin use was also associated with decreased in field loco-regional failure following radiation (p = 0.05). Conclusion. Metformin use is associated with a dose-dependent increased response to CRT in esophageal cancer and may be a sensitizer to this therapy. [ABSTRACT FROM AUTHOR]

Background. Weight loss is common among patients with squamous cell carcinoma of the head and neck (SCCHN) and is mainly due to tumor and treatment related factors. The aim of the present study was to evaluate weight loss in patients with SCCHN undergoing two different radiotherapy (RT) schedules. Material and methods. Nutritional data were analyzed from the ARTSCAN study, a controlled randomized prospective Swedish multicenter study conducted with the aim of comparing conventional fractionation (2.0 Gy per day, total 68 Gy during 7 weeks) and accelerated fractionation (1.1 + 2.0 Gy per day, total 68 Gy during 4.5 weeks). Seven hundred and fifty patients were randomized and 712 patients were followed from the start of RT in the present nutritional study. Results. The patients had a weight loss of 11.3% (± 8.6%) during the acute phase (start of RT up to five months after the termination of RT). No difference in weight loss was seen between the two RT fractionation schedules (p = 0.839). Three factors were significantly predictive for weight loss during the acute phase, i.e. tumor site, overweight/obesity or lack of tube feeding at the start of RT. Moreover, the nadir point of weight loss occurred at five months after the termination of RT. Conclusion. The results of the present study showed no difference in weight loss between the two RT fractionation schedules and also highlight that weight loss in SCCHN is a multifactorial problem. Moreover, the nadir of weight loss occurred at five months after the termination of treatment which calls for more intense nutritional interventions during the period after treatment. [ABSTRACT FROM AUTHOR]

Background. As previously demonstrated, tumor associated macrophages (TAMs) infiltration is associated with some cancers invasion and metastasis. However, the role of TAMs in the gastric cancer remains unclear. Methods Three- dimensional dynamic migration imaging system and real time RT-PCR were used to quantitatively investigate the effect of macrophages on the cancer cell mobility and gene expression related to cancer invasion and metastasis, including ADAM8, ADAM9, MMP9, TIMP3, VEGF-A and IL8 genes, in AGS, HGC-27, Hs-746T and NCI-N87 gastric cancer cell lines under normal or hypoxic conditions. Results. Under normal conditions, the cancer cell invasion rate was increased significantly and all six gene expressions were upregulated in all four cancer cell lines by macrophages. Under hypoxia the changes in the cancer cell invasion rate induced by macrophages was negatively correlated to the TIMP3 expression. In non- metastatic cell line AGS, the increase in migration rate induced by macrophages was further elevated under hypoxia with increased ADAM8 and ADAM9 expression and decreased MMP9 and TIMP3 expressions. Under hypoxia, the induction by macrophages for IL-8 expression was increased significantly in distant metastatic cell lines NCI-N87 and HS-746T, VEGF-A was increased in HGC-27 cell line. Conclusions. Both macrophages and hypoxia play an indispensable role in regulating the invasion of gastric cancer cells in vitro; ADAMs, MMP9 and TIMP3 might be involved in TAM induced invasive power of gastric cancer cells. [ABSTRACT FROM AUTHOR]

Background. Carcinosarcomas are a highly malignant type of endometrial carcinomas where extra uterine spread and recurrences are frequent. There is no consensus regarding the best treatment of this group of malignancies. Material and methods. In a complete geographic series of 322 cases of primary uterine carcinosarcomas prophylactic pelvic irradiation and/or chemotherapy was used as postoperative treatment in the majority of the cases. Vaginal brachytherapy was also added as a boost. The primary surgery was extended hysterectomy in 23 cases (10%), and simple hysterectomy in 220 cases (90%). In 46 cases (14%) no major surgery was possible. Results. In the complete series 123 recurrences (38%) were recorded. Locoregional recurrences (11%) and distant recurrences (28%) were most frequent. Type and extent of surgery was not associated with the risk of tumor recurrence. Extended surgery did not reduce the risk of local and regional recurrences. In the complete series, the five-year overall survival rate was 30% and the recurrence-free survival (RFS) rate was 27%. The five-year pelvic disease control was 82% in stage I, 68% in stage II, and 76% for more advanced stages. The five-year locoregional RFS rate was 63% for patients treated with surgery alone, 68% after addition of adjuvant chemotherapy, 86% after adjuvant radiotherapy, and 95% after combined chemotherapy and radiotherapy. Conclusion. Radiotherapy seems to be the most important constituent of the adjuvant therapy. Serious late tissue reactions, requiring surgery, from the bladder and intestine occurred in 2.5% of the irradiated cases. The death of three patients could be related to radiotherapy and of four patients due to the cytotoxic treatment. This population-based series may serve as a baseline for improvements by, e.g. standard care programs and referral to a few specialist centers for this rare and serious disease. [ABSTRACT FROM AUTHOR]

Background. Patients with head and neck squamous cell carcinoma (HNSCC) often lose a considerable amount of muscle mass following the disease and treatment. This is an independent mortality predictor, lowering muscle strength and functional performance. Progressive resistance training (PRT) increases muscle mass among healthy individuals and groups of cancer patients, but it has not been investigated in HNSCC patients. Furthermore, studies in healthy subjects show an additive effect of protein and creatine supplementation following PRT. Objectives. Firstly, to investigate the feasibility of 12 weeks of PRT ± protein and creatine supplementation among HNSCC patients. Secondly, to investigate group changes over time and group differences regarding lean body mass (LBM), muscle strength and functional performance following PRT ± dietary supplementation. Material and methods. Thirty patients were randomized into two groups: a PROCR group undergoing a seven-day pre-trial creatine loading protocol followed by 12 weeks of PRT with creatine and protein supplementation and a PLA group undergoing a seven-day pre-trial placebo ingestion protocol followed by an identical PRT protocol with placebo supplementation. Before the pre-trial and pre- and post-PRT evaluation of LBM, maximal isometric and isokinetic muscle strength and functional performance were performed. Results. Seventy percent of the patients completed the intervention and the PRT adherence rate was 97%. No significant group differences were found in any endpoints. From pre- to post-PRT, LBM increased significantly in the PROCR group by 2.6 ± 2.2 kg (p < 0.0001) and increased in the PLA group (1.3 ± 1.1 kg, p = 0.07). Maximal isometric and isokinetic muscle strength as well as functional performance increased significantly in both groups. Conclusion. PRT is feasible in radiotherapy treated HNSCC patients. Following PRT, lean body mass, muscle strength and functional performance increased significantly in both groups (LBM only borderline significant in PLA group) with no significant group difference in any endpoint. [ABSTRACT FROM AUTHOR]

Background. Given the longevity of thyroid cancer patients, any impairment in health-related quality of life (HRQoL) during the follow-up period is of considerable concern. Therefore, the first aim of this study was to assess (thyroid cancer specific) HRQoL among long-term thyroid cancer survivors and to compare this with the HRQoL of an age- and sex-matched normative population. Secondly, our aim was to investigate which clinical and socio-demographic characteristics and thyroid cancer specific problems were associated with HRQoL. Material and methods. All patients diagnosed with thyroid cancer between 1990 and 2008, as registered in the Eindhoven Cancer Registry, received a survey on HRQoL (EORTC QLQ-C30) and disease-specific symptoms (THYCA-QoL). The scores were compared with age- and sex-matched cancer free controls (n = 800). A series of multiple linear regression analyses were conducted to investigate the independent associations between clinical, socio-demographic and thyroid cancer specific factors with HRQoL. Results. A total of 306 patients (86%) responded to the invitation. Thyroid cancer survivors had significantly lower scores on physical, role, emotional, cognitive and social functioning (p < 0.001) compared to the normative population after adjusting for comorbidities. Sympathetic problems [feeling chilly (52%), hot flushes (40%)], neuromuscular problems [cramp legs (43%) and pain joints/muscles (64%)] and abrupt attacks of fatigue (50%) were the most often reported thyroid cancer specific complaints. Thyroid cancer specific neuromuscular, concentration, sympathetic and psychological problems explained 41-58% of the variance in HRQoL. Clinical and socio-demographic factors explained a small part of the variance in (thyroid cancer specific) HRQoL (1-27%). Conclusion. Long-term thyroid cancer survivors experience more symptoms and deteriorated HRQoL compared to the normative population. Thyroid cancer specific neuromuscular, sympathetic, concentration and psychological symptoms are stronger associated with HRQoL than clinical and socio-demographic factors alone. Awareness of these specific determinants of HRQoL could help health care practitioners to provide better supportive care. [ABSTRACT FROM AUTHOR]

Background. Anxiety and depression in cancer patients are associated with poor health-related quality of life (HRQOL). Clinical interventions to detect and support patients with these symptoms need to be developed and evaluated. We investigated the feasibility of screening with the Hospital Anxiety and Depression Scale (HADS) in a clinical oncology setting. In patients with anxiety or depression symptoms (HADS >7) we explored the use of clinical assessment and psychosocial support and described the development of anxiety, depression and HRQOL during a six-month period. Material and methods. Four hundred and ninety-five consecutive patients were screened for anxiety and depression at the time of their first visit at an oncology department (baseline). Half of the patients with HADS >7 on any of the two HADS subscales were referred to clinical assessment and psychosocial support (intervention group, IG) and half received standard care (SCG) using a historical control group design. HADS and EORTC QLQ-C30 were completed at baseline and after one, three and six months. Results. One hundred and seventy-six (36%) of 495 patients had anxiety or depression symptoms at screening, HRQOL at baseline was clearly impaired for them. Thirty-six (43%) of 84 IG patients attended clinical assessment, resulting in subsequent psychosocial support for 20 (24%) of them. In the SCG, only five (5%) patients attended clinical assessment after self referral, two received subsequent psychosocial support. Anxiety and depression decreased and HRQOL increased statistically significantly over time although anxiety was frequent and HRQOL impaired during the entire six month period. There were no differences between the SCG and IG regarding anxiety, depression or HRQOL at any time point. Conclusion. Systematic screening with HADS is feasible for oncology patients in clinical settings; it identifies patients with persistent symptoms and increases referral to clinical assessment and utilisation of psychosocial support. [ABSTRACT FROM AUTHOR]

Background. The degree of trust in and satisfaction with the physician has been shown to have important implications for treatment outcomes. This study aims to examine individual differences in patients' trust, satisfaction and general distress from an attachment theoretical perspective. Material and methods. One hundred and thirty recently diagnosed cancer patients of three medical hospitals were extensively interviewed by trained psychologists to assess attachment style. Patients completed standardized questionnaires three and nine months after diagnosis to assess trust, satisfaction and distress. t-tests and repeated measures ANOVAs were used to examine differences between securely and insecurely attached patients and changes over time. A mediation model based on a bootstrapping method was used to examine whether trust mediated between attachment and satisfaction, and attachment and distress. Results. Insecurely attached patients (N = 45, 35%) reported less trust in and satisfaction with their physician, and reported more general distress than securely attached patients three and nine months after diagnosis (p < 0.05). Trust and distress levels did not change over time. Trust mediated between attachment and satisfaction, but not between attachment and distress. Conclusion. Insecurely attached patients trusted their physician less than securely attached patients, and in turn were less satisfied with their physician. Their higher levels of general distress were not related to their lower levels of trust. Attachment theory provides a framework to interpret differences in patients' trust, satisfaction and distress, and may help physicians respond in such a way that their patients feel secure, which in turn is expected to result in better health outcomes. [ABSTRACT FROM AUTHOR]

Introduction. Evidence exists that exposure of non-irradiated cells to Irradiated Cell Conditioned Medium (ICCM) can cause effects similar to those resulting from direct radiation damage. This study attempts to validate the stochastic model, relating absorbed dose to the emission and processing of cell death signals by non-irradiated cells, in vitro in PC3 human prostate cancer cell line. Methods. The recipient cell survival was measured after exposure of cells to ICMM derived from donor cells: a) exposed to radiation doses from 2 Gy to 8 Gy and b) of concentrations varying from 2 × 102 to 6 × 106 irradiated with 2 Gy. Results. Exposure to ICCM, irradiated with doses between 2-8 Gy, resulted in a significant (p < 0.001) decrease in clonogenic survival of non-irradiated recipient cells compared to the control group. However, dose dependency above 2 Gy was not observed, indicating that any dose threshold was below 2 Gy. A significant (p < 0.001) decrease in survival was found in recipient cells exposed to the ICCM, derived from different concentrations of donor cells exposed to 2 Gy, compared to the control group. The recipient cell survival following exposure to ICCM derived from 2 × 102 cells was significantly higher (p < 0.5) compared to the rest of donor cell concentrations, indicating that the toxicity of ICCM depends on the cellular concentration of donor cells. Non-linear regression data fitting provided reasonable agreement with the microdosimetric model for the induction of cell killing through medium-borne signals. Conclusion. For the given cell line and given experimental conditions, significant decreases in cell survival were observed in non-irradiated cells exposed to ICCM derived from donor cells of various concentrations and irradiated with different doses. [ABSTRACT FROM AUTHOR]

Background and purpose. To evaluate the patterns of locoregional relapse and survival following submandibular gland (SMG)-sparing intensity modulated radiotherapy (IMRT). Patients and methods. Eighty patients with laryngeal (n = 15), oropharyngeal (n = 50), hypopharyngeal (n = 11) or nasopharyngeal cancer (n = 4) were treated by submandibular gland-sparing IMRT for head and neck squamous cell cancer between July 2000 and December 2008. All patients were treated by bilateral IMRT. Thirty-nine (49%) received definitive radiotherapy (RT) and 41 (51%) postoperative RT. The contralateral parotid gland (PG) and SMG were included in the dose optimization planning program with intent to keep the mean doses for PG and SMG below 23 Gy and 28-30 Gy, respectively. The ipsilateral glands were also spared when considered feasible. Results. During a median follow-up time of 51 months (range, 24-117 months) nine local recurrent tumors were observed. Four of these nine patients were salvaged by surgery with no further recurrence. All local recurrences were located within the high-dose CTVs. None of the locally recurrent cancers were located at the vicinity of the spared PGs or SMGs. No recurrent tumors were observed in the contralateral neck. The Kaplan-Meier estimate for local control at five years following IMRT was 88% for the whole cohort and the corresponding figure for local control following salvage surgery was 94%. The estimates for five-year overall survival and disease-specific survival were 85% and 90%, respectively. Conclusion. In selected head and neck cancer patients who are estimated to have a low risk of cancer recurrence at the nodal levels I-II and who are treated with SMG-sparing IMRT the risk of cancer recurrence at the vicinity of the spared salivary glands is low. [ABSTRACT FROM AUTHOR]

Background. While effective treatment of prostate cancer with radiotherapy and hormones increase survival, adverse effects may reduce quality of life (QoL). The aim of this study was to investigate frequency and severity of self-assessed late adverse effects, and identify the patients most exposed. Material and methods. QoL of 317 cancer survivors with primary stage T1-T3 prostate cancer treated with conformal radiotherapy (70-78 Gy) and androgen deprivation therapy was analyzed by using SF-12 and EPIC-26 questionnaires. Patients were stratified into three groups, filling out the questionnaires 1-2, 2-3, and 3-4 years after radiotherapy. Differences between groups were tested with ANOVA and the χ2 test. The influence of marital status, severe obesity, smoking, stage of disease, and applied dose of radiotherapy on QoL was evaluated with multiple linear and logistic regression analyses. Results. Of 337 patients, 317 (94%) answered the questionnaire. The sexual and hormonal summary scores in the EPIC significantly improved during time since radiotherapy (p < 0.001). Current smoking had a negative effect on SF-12 Physical Component Summary (PCS) and the Mental Component Summary (MCS) scores, on EPIC bowel overall bother (OR 7.8; p = 0.003), on EPIC mean urinary incontinence scores, and on the sexual domain. Severe obesity had a negative influence on SF-12 PCS and vitality. Severe obesity also was a negative predictor for moderate-to-severe problems in the EPIC urinary incontinence, and in the hormonal domain. Living alone was associated with lower SF-12 PCS, MCS scores, and SF-12 general health, social functioning, and the EPIC hormonal domain. The stage of disease or the radiation dose had no statistically significant impact on QoL. Conclusion. Results showed significant negative associations between smoking, severe obesity and living alone on self-assessed late adverse effects after radiotherapy for prostate cancer. This information may guide rehabilitation. [ABSTRACT FROM AUTHOR]

Background. The influence of pregnancy on survival in melanoma has been a controversial issue. Objective. In this retrospective study we investigated whether pregnancy (overall or temporally melanoma-related) has any effect on melanoma progression or patient outcome. Methods. Patient data were collected from Turku University Hospital records concerning all women in fertile age (15-45 years) and diagnosed with melanoma between January 1, 1990 and December 31, 2009. We collected data on melanoma characteristics, treatment, pregnancies and patient outcomes. Results. Of the 334 patients, 248 (74%) had been pregnant in some point during their life while 55 (17%) were nulliparous. The history of pregnancies could not be verified in 31 women (9%). Progression of melanoma to advanced stage was found in 58 (17%) of these women. Altogether, 35 women (14%) with at least one pregnancy had disease progression in contrast to 14 women (26%) with no pregnancies (p =0.049). Women with at least one pregnancy had a 94% probability to survive from melanoma compared to nulliparous women of whom only 83% survived (p =0.041). In Multivariate (COX) analysis pregnancy was a favourable factor for disease-specific survival (DSS) (HR 3.75; 95% CI 1.24-11.34; p =0.019) when adjusted for age (HR 1.064; 95% CI 1.00-1.13; p =0.50), localisation and stage (p =0.040), and Breslow (HR 1.32; 95% CI 1.10-1.58; p =0.002). However, when ulceration of the primary tumour was included in the multivariate model, Breslow remained as the only independent predictor of DSS (HR 1.58; 95% CI 1.34-1.86; p =0.0001) and pregnancy was dropped from the stepwise backward model in the step preceding the last one (p =0.081). Conclusion. Pregnancy is not a risk factor for disease recurrence or progression in melanoma patients, but instead can exert some favourable influence on prognosis. [ABSTRACT FROM AUTHOR]