Ralph Muecke

Selenium in Oncology: From Chemistry to Clinics

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more and more the attention of both laypersons and expert groups. The interest of oncologists mainly focuses in the following clinical aspects: radioprotection of normal tissues, radiosensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that Se has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas, as well as in the head and neck region, including endolaryngeal edema. Another randomized phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. The aim was to evaluate whether sodium selenite is able to compensate a preexisting selenium deficiency and to prevent radiation induced diarrhea in adjuvant radiotherapy for pelvic gynecologic malignancies. Through this study, the significant benefits of sodium selenite supplementation with regards to selenium deficiency and radiotherapy induced diarrhea in patients with cervical and uterine cancer has been shown for the first time in a prospective randomized trial. Survival data imply that supplementation with selenium does not interfere with the positive biological effects of radiation treatment and might constitute a valuable adjuvant therapy option especially in marginally supplied individuals. More recently there were emerging concerns coming up from two large clinical prevention trials (NPC, SELECT), that selenium increases the possible risk of developing diabetes type II. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantage and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, even if further research is needed.

Multicenter, Phase 3 Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology

PURPOSE We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. METHODS AND MATERIALS Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84μg/L were randomized before RT either to receive 500 μg of selenium (in the form of sodium selenite [selenase, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 μg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. RESULTS A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. CONCLUSIONS Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea.

Selenium or No Selenium— That Is the Question in Tumor Patients: A New Controversy

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more attention from both laypersons and expert groups. The interest of oncologists mainly focuses on the following clinical aspects: protection of normal tissues, sensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that it has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism, and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. In 2009, a significant benefit of sodium selenite supplementation—with no protection of tumor cells, which is often suspected by oncologists— was shown in a prospective randomized trial in gynecologic cancer patients undergoing radiation therapy. More recently, concerns arose from 2 large clinical prevention trials (NPC, SELECT) that selenium may increase the risk of developing type 2 diabetes. Despite obvious flaws in both studies and good counterarguments, controversy remains on the possible advantages and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are becoming obvious, even though further research is needed.

Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs – a retrospective multicenter study of 502 patients

A total of 502 patients treated between 1990 and 2002 with low-dose radiotherapy (RT) for painful heel spurs were analysed for prognostic factors for long-term treatment success. The median follow-up was 26 months, ranging from 1 to 103 months. Events were defined as (1) slightly improved or unchanged pain after therapy, or (2) recurrent pain sensations during the follow-up period. Overall 8-year event-free probability was 60.9%. Event-free probabilities of patients with one/two series (414/88) were 69.7%/32.2% (p <0.001); >58/ ≤58 years (236/266), 81.3%/47.9% (p =0.001); high voltage/orthovoltage (341/161), 67.9%/60.6% (p =0.019); pain anamnesis ≤6 months/ >6 months (308/194), 76.3%/43.9% (p =0.001); single dose 0.5/1.0 Gy (100/401), 86.2%/55.1% (p =0.009); without/with prior treatment (121/381), 83.1%/54.9% (p =0.023); men/women (165/337), 61.2%/61.5% (p =0.059). The multivariate Cox regression analysis with inclusion of the number of treatment series, age, photon energy, pain history, single-dose and prior treatments revealed patients with only one treatment series (p <0.001), an age >58 years (p =0.011) and therapy with high voltage photons (p =0.050) to be significant prognostic factors for pain relief. Overall low-dose RT is a very effective treatment in painful heel spurs.

Online survey of patients with breast cancer on complementary and alternative medicine.

About 50% of cancer patients use complementary and alternative medicine (CAM). Women with breast cancer use CAM more frequently than others. We linked a questionnaire to the largest internet portal for cancer patients in Germany. The questionnaire addresses attitude towards CAM, disclosure to the oncologist, source of information, and objectives for use of CAM. 80 patients with breast cancer took part in our study, 61 currently using CAM. Most frequently used CAM methods were selenium, relaxation techniques, prayer, vitamin C, and meditation. Satisfaction was highest with relaxation techniques, vitamin C, homeopathy, yoga and Chinese herbs, lowest with mistletoe and acupuncture. 70% of participants did not think their oncologist took time to discuss CAM. Only 16% believed that their oncologist was well-informed about CAM. 46% relied on naturopaths and non-medical practitioners concerning CAM. Objectives for the use of CAM were to reduce side effects, boost the immune system, and become active.

Attitude of employees of a university clinic to complementary and alternative medicine in oncology

BACKGROUND Cancer patients often use complementary and alternative medicine (CAM), yet discussion with the oncologist is often missing and oncologists lack knowledge in CAM. PATIENTS AND METHODS In order to learn more about the attitude of professionals in oncology toward CAM, a survey was conducted on employees of a German university clinic using a structured questionnaire. RESULTS In total, 547 employees took part in the survey. One-third would definitely use CAM on cancer patients. Female employees are more interested in CAM than males (80% versus 20%; P = 0.001); physicians are less interested than nurses (57% versus 72%; P = 0.008). 2.5% of physicians and 9% of nurses are convinced that CAM is as effective as conventional therapy in cancer. Fifty-two percent of physicians and 12% of nurses agree that adverse effects due to CAM may be possible. Seventy-three percent did not consider themselves adequately informed on CAM for their professional work. CONCLUSIONS As a substantial part of participants would use CAM on cancer patients and most are interested in but not trained on this topic, there is a need for training of professionals from different professions working in oncology.

Multicenter, Phase III Trial Comparing Selenium Supplementation With Observation in Gynecologic Radiation Oncology: Follow-Up Analysis of the Survival Data 6 Years After Cessation of Randomization

Purpose. In 2010, we reported that selenium (Se) supplementation during radiation therapy (RT) is effective for increasing blood Se levels in Se-deficient cervical and uterine cancer patients, and reduced the number of episodes and severity of RT-induced diarrhea. In the current study, we examine whether of Se supplementation during adjuvant RT affects long-term survival of these patients. Patients and Methods. Former patients were identified and questioned with respect to their health and well-being. Results. A total of 81 patients were randomized in the initial supplementation study, 39 of whom received Se (selenium group, SeG) and 42 of whom served as controls (control group, CG). When former patients were reidentified after a median follow-up of 70 months (range = 0-136), the actuarial 10-year disease-free survival rate in the SeG was 80.1% compared to 83.2% in the CG (P = .65), and the actuarial 10-year overall survival rate of patients in the SeG was 55.3% compared to 42.7% in the CG (P = .09). Conclusions. Our extended follow-up analysis demonstrates that Se supplementation had no influence on the effectiveness of the anticancer irradiation therapy and did not negatively affect patients’ long-term survival. In view of its positive effects on RT-induced diarrhea, we consider Se supplementation to be a meaningful and beneficial adjuvant treatment in Se-deficient cervical and uterine cancer patients while undergoing pelvic radiation therapy.

Survey of German Non-Medical Practitioners Regarding Complementary and Alternative Medicine in Oncology

Background: In total, 40-70% of cancer patients use complementary or alternative medicine (CAM). Many of them ask for advice from non-medical practitioners (NMPs). Our aim was to investigate the attitude of NMPs regarding their treatments for cancer patients. Methods: A survey was performed on members of NMP associations, using an online questionnaire on diagnosis and treatment, goals for using CAM, communication with the oncologist, and sources of information. Results: Of the 1,500 members of the NMP associations, 299 took part. The treatments were found to be heterogeneous. Homeopathy is used by 45% of the NMPs; 10% believe it to be a treatment directly against cancer. Herbal therapy, vitamins, orthomolecular medicine, ordinal therapy, mistletoe preparations, acupuncture, and cancer diets are used by more than 10% of the NMPs. None of the treatments is discussed with the respective physician on a regular basis. Conclusions: Many therapies provided by NMPs are biologically based and therefore may interfere with conventional cancer therapy. Thus, patients are at risk of interactions, especially as most NMPs do not adjust their therapies to those of the oncologist. Moreover, risks may arise from these CAM methods as NMPs partly believe them to be useful anticancer treatments. This may lead to the delay or even omission of effective therapies.

Attitude of oncology/hematology nurses from German speaking countries towards complementary and alternative medicine

Objective: 40 – 50% of cancer patients use complementary or alternative medicine (CAM). While oncologists are skeptical regarding CAM, no data has been published with respect to nurses. The objective of our study was to learn about the attitude of nurses with a specialization in cancer care towards CAM. Subjects and methods: A survey was performed on nurses in Germany, Switzerland and Austria using an online questionnaire, which addressed attitude towards, and experiences with CAM. Results: 877 participants filled in the questionnaire. 61% have a very positive or positive attitude towards complementary (CM) and 20% towards alternative medicine (AM). 71% rate their knowledge as high to moderate regarding CM. 43% use some source of information on CAM and 48% would like more training on CAM. The most important reason to use CM is the patient becoming active (50%). CM is a means for reducing side effects (46%), increasing coping (42%), or quality of life (47%). For AM, less than 20% give positive statements. Risks as a result of interactions and side effects are anticipated by 40 (CM) and 50% (AM). Conclusion: In sum, many but not all participants are aware of the pros and cons of CAM. In general, they have a positive attitude towards CM. In order to make CM safer, a structured training should be offered.

Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH

Background. The aim of this exploratory study was to evaluate whether significant differences exist between whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH), healthy male inhabitants (HMI) in northern Bavaria and the normal value. Furthermore, we investigated whether differences exist between prostatic tissue selenium levels (PTSL) in patients with PC, BPH and the benign tissue surrounding the PC. Material and methods. We prospectively evaluated WBSL in 24 patients with PC, 21 patients with BPH, and 21 HMI. Measurements of PTSL were performed in 17 patients with PC and 22 patients with BPH. In 9 cases with PC, measurements were also done in the benign tissue surrounding the carcinoma. Measurements were performed using automated graphite furnace atomic absorption spectrophotometry. Results. In patients with PC, there is a significantly lower WBSL in comparison to HMI (p=0.04). There is no significant difference in WBSL between BPH-patients and HMI (p=0.13) and between PC- and BPH-patients (p=0.67). In all patients and the HMI, there is a significantly lower WBSL in comparison to the recommended normal value of 85 – 162 µg/l (p<0.01). There is no significant difference in PTSL between PC and BPH (p=0.49), and between PC and the tissue compartment surrounding the PC (p=0.56). PTSL seemed to be reduced in the compartment surrounding the PC in comparison to BPH (p=0.03). In PC-patients, there is no significant correlation between WBSL and prostate specific antigen (PSA) (?=−0.20; p=0.36), Gleason score (?=0.32, p=0.13), and T-stage (?=0.22; p=0.23). Conclusion. Since the WBSL measured in all men with PC and BPH, and in HMI participating in our study were significantly lower than the recommended normal range, our findings may support the recommendation of selenium supplementation.