Stress beliefs moderate the impact of COVID-19 related work stress on depressive, anxiety and distress symptoms in health care workers.

Health care workers are at increased risk for mental health issues due to high psychological and physical job demands. According to a recent study, stress beliefs (i.e., believing stress to be detrimental to one's health) might influence physicians' mental health in response to a naturalistic stressor (COVID-19 hospital working conditions). Due to a small sample size and high alpha error inflation, the suggested association needs to be interpreted with caution. The current study aims to replicate those findings in a larger sample. A cross-sectional survey among N = 418 (64.1% female; Median age = 30-39 years) physicians and nurses of a large German medical centre was conducted during the COVID-19 pandemic (May/June 2021). Perception of pandemic related increase of work stress was assessed via self-report. Stress beliefs were assessed with the Beliefs About Stress Scale, and mental health symptoms were assessed with the 21-item Depression Anxiety Stress Scale. Stress beliefs moderated the association between increased work stress and mental health symptoms. Increased work stress was associated with increased depressive, anxiety and distress symptoms only in health care workers with medium (simple slope = 2.22, p < .001; simple slope = 1.27, p < .001; simple slope = 3.19, p < .001) and high (simple slope = 3.13; p < .001; simple slope = 1.66, p < .05; simple slope = 4.33, p < .001) negative stress beliefs. Among health care workers with low negative stress beliefs increased work stress was not associated with increased depressive, anxiety and distress symptoms. This confirms negative stress beliefs as variable of interest in research on the impact of stress on mental health in health care workers.

Reduced Psychosocial Well-Being among the Children of Women with Early-Onset Breast Cancer.

BACKGROUND: Approximately 27% of female breast cancer patients are diagnosed before the age of 55, a group often comprising mothers with young children. Maternal psychosocial well-being significantly impacts these children's psychosocial well-being. This study assesses the well-being of children with mothers who have early-onset breast cancer. METHODS: We examined the eldest child (up to 15 years old) of women with nonmetastatic breast cancer (<55 years old, mean age: 40) enrolled in the mother-child rehab program 'get well together'. Using maternal reports on children's well-being (the Strengths and Difficulties Questionnaire; SDQ), we describe the prevalence of abnormally high SDQ scores and identify protective and risk factors via linear regression. RESULTS: The mean SDQ scores of 496 children (4-15 years old, mean age: 8) fell below the thresholds, indicating psychosocial deficits. However, most SDQ scores deviated negatively from the general population, especially for emotional problems, with one in ten children displaying high and one in five displaying very high deficits. Female sex, more siblings, a positive family environment and maternal psychosocial well-being were protective factors for children's psychosocial well-being. CONCLUSIONS: Children of mothers with breast cancer may benefit from improved maternal well-being and family support. Further research is needed to identify appropriate interventions.

Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) in Locally Advanced or Metastatic Breast Cancer: Prospective Cohort Study.

BACKGROUND: Eribulin, a halichondrin-class microtubule dynamics inhibitor, is a preferred treatment option for patients with advanced breast cancer who have been pretreated with an anthracycline and a taxane. Peripheral neuropathy (PN) is a common side effect of chemotherapies for breast cancer and other tumors. The Incidence and Resolution of Eribulin-Induced Peripheral Neuropathy (IRENE) noninterventional postauthorization safety study assessed the incidence and severity of PN in patients with breast cancer treated with eribulin. PATIENTS AND METHODS: IRENE is an ongoing observational, single-arm, prospective, multicenter, cohort study. Adult patients (≥18 years of age) with locally advanced or metastatic breast cancer and disease progression after 1-2 prior chemotherapeutic regimen(s) for advanced disease were treated with eribulin. Patients with eribulin-induced PN (new-onset PN or worsening of preexisting PN) were monitored until death or resolution of PN. Primary endpoints included the incidence, severity, and time to resolution of eribulin-induced PN. Secondary endpoints included time to disease progression and safety. RESULTS: In this interim analysis (data cutoff date: July 1, 2019), 67 (32.4%) patients experienced any grade eribulin-induced PN, and 12 (5.8%) patients experienced grade ≥3 eribulin-induced PN. Median time to resolution of eribulin-induced PN was not reached. Median time to disease progression was 4.6 months (95% CI, 4.0-6.5). Treatment-emergent adverse events (TEAEs) occurred in 195 (93.8%) patients and serious TEAEs occurred in 107 (51.4%) patients. CONCLUSION: The rates of any grade and grade ≥3 eribulin-induced PN observed in this real-world study were consistent with those observed in phase III randomized clinical trials. No new safety findings were observed.

Immune response of heterologous versus homologous prime-boost regimens with adenoviral vectored and mRNA COVID-19 vaccines in immunocompromised patients.

Due to rare but major adverse reactions to the AstraZeneca adenoviral ChAdOx1-S-nCoV-19 vaccine (ChAd), German health authorities recommended adults under 60 who received one dose of ChAd, to receive a second dose of the BioNTech mRNA BNT162b2 vaccine (BNT) as a booster. Studies in the general population suggest an enhanced efficacy of the heterologous (ChAd-BNT) compared to the homologous (BNT-BNT) vaccination regimen. However, an analysis of the efficacy in patient populations with a high risk of severe COVID-19 due to acquired immunodeficiency is still missing. We therefore compared both vaccination regimens in healthy controls, patients with gynecological tumors after chemotherapy, patients on dialysis and patients with rheumatic diseases concerning the humoral and cellular immune response. The humoral and cellular immune response differed substantially in healthy controls compared to patients with acquired immunodeficiency. Overall, the most significant differences between the two immunization regimens were found in neutralizing antibodies. These were always higher after a heterologous immunization. Healthy controls responded well to both vaccination regimens. However, the formation of neutralizing antibodies was more pronounced after a heterologous immunization. Dialysis patients, on the other hand, only developed an adequate humoral and particularly cellular immune response after a heterologous immunization. Tumor and rheumatic patients also - to a weaker extent compared to dialysis patients - benefited from a heterologous immunization. In conclusion, the heterologous COVID-19 vaccination regimens (ChAd-BNT) seem to have an advantage over the homologous vaccination regimens, especially in immunocompromised patients such as patients with end-stage kidney disease treated with hemodialysis.

Young Adult German Breast Cancer Patients Participating in a Three-Week Inpatient Mother-Child Rehab Program Have High Needs for Supportive Care.

A known cut-off problem hampers the interpretation of quality of life (QOL) scores. The purpose of this study was to apply a novel approach for the EORTC QLQ-C30 instrument to identify the proportion of breast cancer (BC) patients in need of supportive care. Changes in QOL during the COVID-19 pandemic were evaluated, as well as changes over time (after treatment termination and up to 4 years later). Data were obtained from a cohort study on young adult BC patients with minor children participating in a mother-child rehab program. Cross-sectional QOL data were collected from 2015 to 2021 (baseline). Follow-up data were available for up to 4 years after diagnosis for a subgroup. The baseline cohort included 853 women (mean age 35 years). More than 50% had a need for supportive care. In the subgroup with follow-up, this proportion remained at a high level up to several years after diagnosis. During the COVID-19 pandemic, changes regarding the proportion with this need were not as high as expected-with the exception of changes on the QLQ-C30 scale 'role functioning' (+15%). Even several years after diagnosis, every second BC patient with minor children had a need for supportive care, which is much higher than previously found. Healthcare staff should be aware of this potential need and should address this issue.

Novel approach of desensitization in allergic reaction to Olaparib.

INTRODUCTION: PARP (Poly ADP Ribose Polymerase) inhibitors are an effective maintenance therapy for various entities, such as BRCA (breast cancer gene) mutated or HRD (homologous recombination deficiency) positive primary platin-sensitive advanced ovarian cancer after platin induction therapy and in relapse after responding to carboplatin reinduction. Other entities are metastatic BRCA mutated pancreas, prostate and Her2-negative breast cancer. Therefore, patients with allergic reactions to PARP inhibitors should undergo a desensitization procedure to be able to receive this efficient therapy. CASE REPORT: We conducted a two-day desensitization on a 45-year-s old patient with advanced ovarian cancer who displayed symptoms of an allergic reaction to Olaparib. MANAGEMENT AND OUTCOME: Using an Olaparib tablet suspension, we orally administered increasing Olaparib doses, starting with 12.5 mg and reaching a cumulative dose of 387.5 mg on the first day and starting with 100 mg and reaching a cumulative dose of 600 mg on the second day, without concomitant antiallergic medication.Except for mild erythema on day one receding within the hour, no further allergic reactions appeared during desensitization. The patient has since received 300 mg of Olaparib twice a day without further complications or interruptions. CONCLUSION: Desensitization in a two-day suspension protocol is a safe method that ensures effective maintenance therapy for patients with allergic reactions to PARP inhibitors.

Conditional Disease-Free and Overall Survival of 1,858 Young Women with Non-Metastatic Breast Cancer and with Participation in a Post-Therapeutic Rehab Programme according to Clinical Subtypes.

BACKGROUND: Breast cancer in young women is associated with unfavourable tumour biology and is the main cause of death in this group. Conditional survival analysis estimates survival rates under the pre-condition of already having survived a certain time. OBJECTIVES: To describe conditional disease-free and overall survival of female breast cancer patients according to clinical subtypes and age. METHODS: This study analyses information from 1,858 breast cancer patients aged between 21 and 54 years, who were taking part in a post-therapeutic rehab programme (time between diagnosis and rehab start: maximum 24, median 11 months). Mean follow-up time was 3.6 years. We describe biological, clinical and pathological features in regard to different age groups (<40 and ≥40 years) and report conditional 5-year survival rates for overall and disease-free survival, and Cox proportional hazard models. RESULTS: Very young and young patients differed in regard to hormone receptor negativity, tumour grade, lymphovascular invasion, and molecular subtypes. Young women bore triple-negative and HER2-like disease more frequently. Conditional 5-year overall survival did not differ substantially between women <40 and 40-54 years of age (95 vs. 96%). It was highest for women with cancer of the luminal A subtype (98%) and lowest for the triple-negative subtype (91%). Lymphangiosis was a significant predictor of death. Results for disease-free survival were comparable. CONCLUSIONS: Conditional 5-year overall survival after non-metastatic breast cancer was as high as 95.5%, and disease-free survival was 85.2%. When controlling for time between diagnosis and rehab start, molecular subtypes influenced overall and disease-free survival prospects. When additionally controlling for clinical characteristics, this effect only remained stable for disease-free survival.

Maintaining an Adult Hematology/Oncology Service at a Tertiary Care Center during the SARS-CoV-2 Pandemic: An Eight-Week-Experience with a Newly Implemented Procedural Plan.

Treatment of cancer patients has become challenging when large parts of hospital services need to be shut down as a consequence of a local COVID-19 outbreak that requires rapid containment measures, in conjunction with the shifting of priorities to vital services. Reports providing conceptual frameworks and first experiences on how to maintain a clinical hematology/oncology service during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are scarce. Here, we report our first 8 weeks of experience after implementing a procedural plan at a hematology/oncology unit with its associated cancer center at a large academic teaching hospital in Germany. By strictly separating team workflows and implementing vigorous testing for SARS-CoV-2 infections for all patients and staff members irrespective of clinical symptoms, we were successful in maintaining a comprehensive hematology/oncology service to allow for the continuation of treatment for our patients. Notably, this was achieved without introducing or further transmitting SARS-CoV-2 infections within the unit and the entire center. Although challenging, our approach appears safe and feasible and may help others to set up or optimize their procedures for cancer treatment or for other exceedingly vulnerable patient cohorts.

Psychosocial and family-centered support among breast cancer patients with dependent children.

OBJECTIVE: To evaluate the psychosocial situation of breast cancer (BC) patients with dependent children, with regard to who used family-centered psychosocial support (PS) services, reasons against using it, as well as existing, unmet needs, and current PS need. METHODS: Data were collected via survey and patient files during an inpatient rehabilitation program for mothers with BC, who were accompanied by a child <12 years. Descriptive statistics and tests for statistical significance were used. RESULTS: Out of the total of 561 patients, 23.0% had used family-centered PS services before. Common reasons against it were enough support, no anticipated need and organizational issues. Patients stated a high number of unmet needs. The most urgent ones related to their children. About 59.3% of mothers stated a current PS need (PSN) and 33.3% a need for their children. Little social support and a worse maternal HRQOL, but not time since diagnosis, were related to a higher PSN in mothers and children (bivariate association). CONCLUSION: Among BC patients with dependent children, clinicians need to take the whole family and their support needs into account. They should know about the existing organizational barriers, which need to be overcome with the help of tailored offers. Patients with low HRQOL, little social support and single-mothers (with regard to children's PSN) need special attention as these can be indicators of high PSN.

Use of Complementary and Alternative Medicine among Young Patients with Breast Cancer.

BACKGROUND: Complementary and alternative medicine (CAM) has received increasing attention in Western countries and is especially common among breast cancer (BC) patients. So far, its effectiveness has not been well studied, which is in part due to the contextuality of CAM along with a lack of information of why patients use it. OBJECTIVES: Young BC patients constitute a special patient group regarding clinical characteristics, QOL, and their role in society. Since little is known about their CAM use, this study aimed at exploring it as well as their reasons for CAM use. METHODS: Data on CAM and sociodemographics were collected via questionnaire in the context of a rehabilitation program for young mothers with BC. Initial BC diagnoses were between 2009 and 2014 (recruitment period 2012-2015). Clinical characteristics were derived from the patient files. Descriptive statistics were used to describe frequencies and statistically significant differences were tested. RESULTS: Among the 827 patients, with an average age of 39.6 years, 62.5% had used CAM with regard to their cancer. CAM use was significantly higher in women with higher educational level, higher employment status, and statutory health insurance, respectively. The average monthly expenses on CAM were EUR 50. Every 5th woman used CAM without her physician's knowledge. The types most often used were dietary supplements with vitamins or minerals. The most frequent reasons for CAM use were to strengthen the immune system, support conventional medicine, and combat side effects. CONCLUSIONS: CAM plays an important role for young BC patients with regard to prevalence and monthly expenses, and was used for a wide range of reasons. Certain subgroups with more frequent CAM use could be identified. Physicians should therefore proactively talk about CAM with their young BC patients, so that patients do not need to rely on information sources on CAM outside the medical system.

Blood Flow Suppresses Vascular Anomalies in a Zebrafish Model of Cerebral Cavernous Malformations.

RATIONALE: Pathological biomechanical signaling induces vascular anomalies including cerebral cavernous malformations (CCM), which are caused by a clonal loss of CCM1/KRIT1 (Krev interaction trapped protein 1), CCM2/MGC4607, or CCM3/PDCD10. Why patients typically experience lesions only in lowly perfused venous capillaries of the cerebrovasculature is completely unknown. OBJECTIVE: In contrast, animal models with a complete loss of CCM proteins lack a functional heart and blood flow and exhibit vascular anomalies within major blood vessels as well. This finding raises the possibility that hemodynamics may play a role in the context of this vascular pathology. METHODS AND RESULTS: Here, we used a genetic approach to restore cardiac function and blood flow in a zebrafish model of CCM1. We find that blood flow prevents cardiovascular anomalies including a hyperplastic expansion within a large Ccm1-deficient vascular bed, the lateral dorsal aorta. CONCLUSIONS: This study identifies blood flow as an important physiological factor that is protective in the cause of this devastating vascular pathology.

Early-Onset Breast Cancer: Effect of Diagnosis and Therapy on Fertility Concerns, Endocrine System, and Sexuality of Young Mothers in Germany.

BACKGROUND: The purpose of this study was to analyze the effect of breast cancer therapy on fertility concerns and sexuality of young mothers with breast cancer in Germany. METHODS: During a mother-child rehabilitation program, 1,191 young mothers with locoregional primary breast cancer, treated between 2006 and 2014, were recruited. Data included sociodemographic data, TNM stage, tumor biology, therapies, and patient-reported outcomes such as sexuality and fertility concerns. RESULTS: The mean age at diagnosis was 40 years. Approximately a quarter of the patients stated that family planning had not been completed at the time of diagnosis. Nearly half of all patients had been informed as to how treatment could affect fertility, but counseling at a specialized fertility center was offered to only 13%. Of all patients, 4% took a consultation and 2% underwent fertility preservation procedures. CONCLUSION: Our study indicates that only a minority of patients is referred to fertility centers although family planning is incomplete at the time of diagnosis in about 25% of young women with breast cancer. Thus, these patients should not only be informed about the effects of treatment on fertility and sexuality, but should be referred to a fertility center.

[Signs of social inequality in information seeking and evaluation of information among young women with breast cancer - results of a cohort study]. / Hinweise auf soziale Ungleichheit im Informationsverhalten und in der Informationsbewertung junger Frauen mit Brustkrebs ­ Ergebnisse der Kohortenstudie "gemeinsam gesund werden".

OBJECTIVE: The extent to which cancer patients are well-informed can have manifold effects. The aim of this study was to explore both the sources of information that young breast cancer patients with children use and how they evaluate the information obtained. METHODS: Participants were recruited within a rehabilitation program for young mothers with non-metastatic breast cancer (the Groemitz project "gemeinsam gesund werden"). Data on information seeking, the level of information, socio-demographic data and clinical characteristics were collected using a questionnaire. RESULTS: The patients (n=827) used several additional sources of information - most frequently the internet (69.5%; n=767). The majority felt well informed about their disease and found the information provided easy to understand. A social gradient was observed in relation to media use, information evaluation and obtaining a second opinion. CONCLUSION: To young breast cancer patients, the internet is crucial for obtaining further information. The indication of a social gradient underlines the importance of addressing the information needs of patients with a lower socioeconomic status.

Effects of Combined Treatment with Vitamin D and COX2 Inhibitors on Breast Cancer Cell Lines.

BACKGROUND: Vitamin D is known for its anticancer potential. Prostaglandin E2 (PGE2) is a proliferative and inflammation-activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX2). A link between vitamin D and PGE2 metabolism was shown recently. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines, we investigated the influence of calcitriol and the COX2 inhibitor celecoxib on cell growth via the MTT test, as well as on the protein and mRNA expression of COX2 using western blot and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX2 inhibitor celecoxib and even more strongly by their combination. Moreover, calcitriol inhibited COX2 protein expression in MDA-MB-231 cells, as well as COX2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a synergistic growth-inhibitory effect in breast cancer cell lines.

Gynecologic oncologists' attitudes and practices relating to integrative medicine: results of a nationwide AGO survey.

PURPOSE: The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals' knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. METHODS: Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. RESULTS: Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. CONCLUSION: There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

A New Scoring Tool to Assess Overall Survival in Patients With Intracerebral Metastases From Gynecological Cancers.

OBJECTIVE: This study aimed to facilitate individualized treatment strategies for intracerebral metastases from gynecological cancers by creating a specific overall survival (OS) score. METHODS/MATERIALS: Fifty-six patients irradiated for cerebral metastases from gynecological cancers were included. Eleven factors were retrospectively analyzed for OS: age, Eastern Cooperative Oncology Group (ECOG) performance score, cancer type, histology, histologic grading, initial stage, number of lesions, extracerebral metastases, time between cancer diagnosis and brain metastases treatment, recursive partitioning analysis class, and type of treatment. Independent predictors of OS were incorporated in the score (better OS, 1 point; worse OS, 0 points). RESULTS: On Cox proportional hazards analysis, performance score (hazards ratio, 1.98; 95% confidence interval, 1.30-3.23; P = 0.001), no extracerebral metastases (3.34; 1.46-8.96; P = 0.003), and recursive partitioning analysis class 1 (3.27; 1.97-5.65; P < 0.001) were significant. The following points were assigned: ECOG score 1 to 2 = 1 point, ECOG score 3 to 4 = 0 points, no extracerebral metastases = 1 point, extracerebral metastases = 0 points. Sum scores were 0 (n = 32), 1 (n = 15), or 2 points (n = 9). Six-month OS rates were 6%, 67%, and 100%, respectively (P < 0.001). CONCLUSIONS: A predictive tool including 3 groups with significantly different OS probabilities was designed for patients with cerebral metastases from gynecological cancers. This tool will aid in choosing individual treatments.

Routine Clinical Practice for Patients With Recurrent Ovarian Carcinoma: Results From the TROCADERO Study.

OBJECTIVE: Treatment options for patients with recurrent ovarian carcinoma are diverse, and different therapies are recommended based on platinum-free interval (PFI). Data examining the association between platinum sensitivity, treatment strategy, and outcomes are limited, particularly for partially platinum-sensitive (PPS) patients. This study characterized clinical features and outcomes in patients with recurrent ovarian carcinoma in the context of sensitivity to platinum-based therapy. METHODS: Anonymized case records were obtained from eligible European medical sites. Eligible patients were 18 years or older with epithelial ovarian carcinoma who had received 1 or more platinum-based therapies and had 1 or more subsequent relapses. Patient records were categorized by PFI and analyzed based on demographic and clinical data using descriptive statistics. RESULTS: There was no difference between PFI in PPS patients receiving platinum versus nonplatinum therapy (8.9 [range, 6.0-12.0] and 8.3 [range, 6.0-11.3] months, respectively). Overall survival in patients with platinum-sensitive, PPS, platinum-resistant, and platinum-refractory disease was 43.0 (95% confidence interval [95% CI], 25.1-42.3), 20.5 (95% CI, 17.7-24.8), 12.7 (95% CI, 10.4-14.2), and 9.8 (95% CI, 6.6-14.9) months, respectively. Among PPS patients, overall survival was 23.5 (95% CI, 18.4-37.3) and 18.7 (95% CI, 11.0-23.5) months for those who received platinum and nonplatinum-based therapy, respectively. No demographic or clinical characteristics were identified that indicated a difference between PPS patients who received platinum-based therapy versus those who did not. CONCLUSIONS: Partially platinum-sensitive patients with recurrent ovarian carcinoma who received platinum-based therapy had improved outcomes compared with those who did not. No clear demographic criteria for choosing platinum- versus nonplatinum-based therapy for PPS patients were identified from patient records.

Combined treatment of breast cancer cell lines with vitamin D and COX-2 inhibitors.

BACKGROUND: Vitamin D is known for its anti-cancerogenous potential. Prostaglandin E2 (PGE2) is a proliferation and inflammation activating agent. The production of PGE2 is dependent on the activity of cyclooxygenase-2 (COX-2). A link between vitamin D and PGE2 metabolism was recently shown. MATERIALS AND METHODS: In MDA-MB-231 and MCF-7 breast cancer cell lines we investigated the influence of calcitriol and the COX-2 inhibitor celecoxib regarding cell growth via MTT test, as well as on the protein and mRNA expression of COX-2 using western blot and qRT-PCR. RESULTS: The proliferation of MCF-7 and MDA-MB-231 was inhibited by both calcitriol and the COX-2 inhibitor celecoxib and even stronger by their combination. Moreover, calcitriol inhibited the COX-2 protein expression in MDA-MB-231, as well as the COX-2 mRNA expression in both cell lines. CONCLUSION: The combination of calcitriol and celecoxib demonstrated a cooperative growth-inhibiting effect in breast cancer cell lines.

Vitamin D inhibits ovarian cancer cell line proliferation in combination with celecoxib and suppresses cyclooxygenase-2 expression.

BACKGROUND: Vitamin D exhibits multiple anti-proliferative and pro-differentiating actions. Prostaglandin-(PG)E2 is a tumor-promoting tissue hormone anabolized by cyclooxygenase-2 (COX-2). Recently, a link between the PG and vitamin D metabolism was reported. MATERIALS AND METHODS: The influence of calcitriol and celecoxib on the proliferation of ovarian cancer cell lines was measured and the impact of calcitriol on the protein and mRNA expression of COX-2 was quantified by western blot and qRT-PCR, respectively. RESULTS: After COX-2 induction with interleukin (IL)-1ß, 10 µM celecoxib did not significantly inhibit the proliferation of OVCAR-3 cells, whereas calcitriol showed such an effect; however, the combination of the two substances had an additive influence. After induction by IL-1ß, calcitriol inhibited the COX-2 protein, as well as its mRNA expression significantly in OVCAR-3 and SKOV-3 cells. CONCLUSION: These data suggest a correlation between PG and vitamin D metabolism in their anti-tumorigenic activity in ovarian carcinomas.

Radiosurgery with 20 Gy provides better local contol of 1-3 brain metastases from breast cancer than with lower doses.

AIM: To determine the optimal dose of radiosurgery-alone for patients with 1-3 cerebral metastases from breast cancer. PATIENTS AND METHODS: Patients receiving 20 Gy (n=20) were compared to those receiving 16-18.5 Gy (n=10) for local control, distant brain control and overall survival. Seven other variables were also evaluated. RESULTS: Radiosurgery dose achieved significance on univariate (p=0.002; log-rank and Wilcoxon test) and multivariate analysis (p=0.004) of local control. Twelve-month local control rates were 94% after 20 Gy and 48% after 16-18.5 Gy. On univariate analysis of distant brain control, radiosurgery dose was not a significant factor, with 12-month rates of 73% and 60%, respectively. Regarding overall survival, radiosurgery dose was of borderline significance (p=0.059; Wilcoxon test). Twelve-month overall survival rates were 75% and 40%, respectively. On Cox regression analysis, radiosurgery dose exhibited a trend for improving survival (p=0.10). CONCLUSION: Radiosurgery with 20 Gy resulted in significantly better local control and led to a trend towards improved overall survival compared to treatment with 16-18.5 Gy.