Büntzel et al. (2010): Selenium Substitution During Radiotherapy of Solid Tumours - Laboratory Data from Two Observation Studies in Gynaecological and Head and Neck Cancer Patients

Reference ↗
Title	Selenium Substitution During Radiotherapy of Solid Tumours Laboratory Data from Two Observation Studies in Gynaecological and Head and Neck Cancer Patients
Topic	Selenium
Author	Buentzel, J, Micke, O, Kisters, K, Bruns, F, Glatzel, M, Schoenekaes, K, Kundt, G, Schaefer, U, Muecke, R
Year	2010
Journal	Anticancer Research
DOI	https://ar.iiarjournals.org/content/30/5/1783.short

Study Note

This study includes the samples of 2 studies (Büntzel et al. (2010): Limited effects of selenium in the prevention of radiation-associated toxicities - results of a randomized study in head neck cancer patients, Muecke et al. (2010): Multicenter, phase 3 trial comparing selenium supplementation with observation in gynecologic radiation oncology), reporting the outcome of change in selenium concentration in the blood as a result of selenium administration.

Brief summary

This study includes the samples of two studies, each with a sample of head and neck patients Büntzel et al. (2010): Limited effects of selenium in the prevention of radiation-associated toxicities - results of a randomized study in head neck cancer patients or gynecological cancer patients Muecke et al. (2010): Multicenter, phase three trial comparing selenium supplementation with observation in gynecologic radiation oncology who were randomly divided into two arms and received or did not receive additional selenium during the period of radiotherapy. All subjects had a proven selenium deficiency. This study served only to demonstrate the change in selenium concentration in the blood as a result of selenium administration. Both arms had comparable selenium levels at the beginning of the study. There was a significantly higher selenium concentration in the blood of the arm that received selenium halfway through radiotherapy (around week four) and at the end of radiotherapy. This difference was no longer significant six weeks after radiotherapy. This study can be seen more as an addition to the two studies by Büntzel et al. (2008) and Mücke et al. (2008) than as an independent study. Very little marginal information is given here about the patients or the course of treatment and no details are given about the drop-outs that obviously took place.

Diese Studie umfasst die Stichproben von zwei Studien mit jeweils einer Stichprobe von Hals-Nasen-Kopf Tumorpatienten Büntzel et al. (2010): Limited effects of selenium in the prevention of radiation-associated toxicities - results of a randomized study in head neck cancer patients oder gynäkologischen Krebspatienten Muecke et al. (2010): Multicenter, phase three trial comparing selenium supplementation with observation in gynecologic radiation oncology, welche zufällig in zwei Gruppen eingeteilt wurden und während der Zeit der Radiotherapie zusätzlich Selen erhielten oder nicht. Alle Probanden hatten ein nachgewiesenes Selendefizit. Diese Studie diente nur zur Darstellung der Veränderung der Selenkonzentration im Blut durch die Selengabe. Beide Gruppen hatten zu Beginn der Studie einen vergleichbaren Selenspiegel. Es zeigte sich jeweils zur Hälfte der Radiotherapie (etwa vierte Woche) und zu dessen Ende eine bedeutsam höhere Selenkonzentration im Blut der Gruppe welche Selen erhalten hatten. Dieser Unterschied war sechs Wochen nach der Radiotherapie nicht mehr bedeutsam. Diese Studie kann eher als Zusatz zu den beiden Studien von Büntzel et al. (2008) und Mücke et al. (2008) gesehen werden, als eine eigenständige Studie. Es wird hier sehr wenig Randinformation zu den Patienten oder den Ablauf der Behandlung gegeben und es werden keine Angaben zu den offensichtlich stattgefundenen Drop-Outs gemacht.

Study Design

Prospective / Retrospective Prospective: forward-looking, examples include clinical trials, cohort studies, and long-term observational studies;</br>Retrospective: backward-looking, relying on existing data, examples include case-control studies and retrospective cohort studies	Prospective
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	Multicentric
Blinding No: Open, all parties are aware of group assignments;</br>Single: one party is unaware of group assignments (generally participants);</br>Double: two parties are unaware of group assignments (generally the participants and the researchers); </br>Triple: concealing group assignment from additional parties	No
Is randomized	Yes
Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control	No
Number of arms	2

Study characteristics

Inclusion criteria	Patients suffering from gynaecological or head and neck cancer who were irradiated because of their disease
Exclusion criteria	NI
N randomized	128
Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment.	PP Analysis
Specifications on analyses	NA
Countries of data collection	Germany
LoE Level of evidence	2b Oxford 2009
Outcome timeline Data collection times	Selenium concentration measured at baseline, after 4 weeks, after the end of radiotherapy and 6 weeks after the end of radiotherapy Overall duration: 7 weeks of radiotherapy

Characteristics of participants

Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors.	Curative, Adjuvant
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	Gynecologic Cancers, Head and Neck Cancers
Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis	Early Stage, Advanced Stage
Specifications on cancer stages	Head and Neck cancer - Advanced Stage Gynecologic cancer - FIGO Stadium I-IV
Comorbidities	NI
Current cancer therapies	Radiation therapy
Specifications on cancer therapies	NI
Previous cancer therapies	Surgery
Gender	Mixed
Gender specifications	NI
Age groups	Adults (18+)
Age groups specification	Mean(SD) Intervention arm: 63.83(9.2) years Control arm: 63.03(10.5) years

Arms

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Intervention
Number of participants (arm) N randomized	63
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Not seperated by arm n=7
Drop-out reasons	NI
Intervention	Sodium selenite
Dosage and regime	500µg sodium selenite 2 days before the start of radiotherapy and on days with radiotherapy; and 300 µg sodium selenite on days without radiotherapy (weekends and vacations), orally as a liquid 1 hour before radiotherapy
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	49
Side effects / Interactions	NI

Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment	Passive control
Number of participants (arm) N randomized	-999
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	Not seperated by arm n=7
Drop-out reasons	NI
Intervention	Usual Care
Dosage and regime	NA
One-time application	No
Duration in days For long-term interventions, the number of days is an estimation.</br>A value of -999 indicates that the exact duration cannot be extracted from the study due to ambiguous or incomplete information. See Outcome timeline or Dosage and regime for further information.	49
Side effects / Interactions	NA

Outcomes

Selenium level

Outcome type As specificed by the authors	Primary
Outcome specification	Serum concentration and whole blood concentration
Type of measurement	GFAAS (Graphite Furnace Atomic Absorption Spectrometry)
Results during intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	At baseline no significant differences; Significant differences in selenium concentrations (serum and blood) at half of radiotherapy (p<0.0001)
Results after intervention - Results during intervention means that the time of data collection is during or shortly after the period of the intervention (e.g. on the last day or a few days after). The results therefore still relate to the direct effects of the intervention.</br>- Results after intervention means there is a longer break between the time of data collection and the end of the intervention, e.g. more than a week. The results relate more to long-term effects.</br>- If a categorization in Results during vs. after intervention is not possible (e.g. survival data), the results are summarized under Results after intervention under the headline "Overall".	At 6 weeks after irradiation no significant differences; Significant differences in selenium concentrations (serum and blood) at the end of radiotherapy (p<0.0001)

Risk of Bias Assessment: Cochrane RoB tool 2.0
Bias arising from the randomization process	NA
Bias due to deviation from intended intervention (assignment to intervention)	NA
Bias due to deviation from intended intervention (adhering to intervention)	NA
Bias due to missing outcome data	NA
Bias in measurement of the outcome	NA
Bias in selection of the reported result	NA
Other sources of bias	NA
Overall RoB judgment	NA

Funding and Conflicts of Interest

Funding	NI
Conflicts of Interest	NI

Further points for assessing the study

Sample

Power analysis performed	?
- Sample size corresponds to power analysis	?
- Reasons for insufficient sample size based on power analysis	?
If no power analysis performed: at least moderate sample size (n >= 30 per arm)	?
Ethnicity mentioned	?

Alternative Explanation

Other explanations for an effect besides the investigated intervention	?
- Possibility of attention effects	?
- Possibility of placebo effects	?
- Other reasons	?

Statistics

Correct use of parametric and non-parametric tests Testing for normal distribution only necessary if parametric tests are used, NI: use of parametric tests without report of normal distribution testing	?
Correction for multiple testing	?
Measurement of compliance	?
Consistent reporting in numbers (figures, flowchart, abstract, results)	?
Comprehensive and coherent reporting	?
Cross-over	?
- Sufficient washout period	?
- Tested for carry-over effects	?
- Tested for sequence effects	?

Interpretation of results

Effect sizes reported (clinical vs. statistical significance)	?
Side effects systematically recorded	?
Side effects considered in result interpretation	?
Ethics votum	?

Additional Notes

PRO:

• Ethics approval obtained.

CONTRA:

• Arm comparability tested only for age.
• No demographic information provided.
• No information on the dropout of 7 participants.
• Few conditions given.