Mix et al. (2015): Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck: Difference between revisions
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|Reference=Publication: Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck | |Reference=Publication: Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck | ||
}} | }} | ||
=Brief summary= | =Brief summary= | ||
In this study, 18 patients with squamous cell carcinoma of the head and neck who were undergoing chemotherapy and radiotherapy were randomly assigned to two arms in which they either received selenium | In this study, 18 patients with squamous cell carcinoma of the head and neck who were undergoing chemotherapy and radiotherapy were randomly assigned to two arms in which they either received selenium seven days before, during and three weeks after treatment or a placebo. The results after seven weeks showed no differences between the arms in the development of oral mucosal inflammation or tumor response to treatment. There were also no differences in overall survival, progression-free survival or quality of life at twelve months. There were a number of side effects of chemotherapy and radiotherapy in both arms. However, no direct comparison was carried out here. Overall, the sample is very small, which may well mean that differences were not significant, but as described, comparisons were not always made. Overall, the reporting is very superficial in view of the general study descriptions/framework conditions and in particular the description of the results. | ||
In dieser Studie wurden 18 Patienten mit Plattenepithelkarzinom des Kopf-Hals-Bereiches, welche sich einer Chemo- und Radiotherapie unterzogen zufällig zwei Gruppen zugeordnet, in der sie entweder Selen | |||
In dieser Studie wurden 18 Patienten mit Plattenepithelkarzinom des Kopf-Hals-Bereiches, welche sich einer Chemo- und Radiotherapie unterzogen zufällig zwei Gruppen zugeordnet, in der sie entweder Selen sieben Tage vor, während der Behandlung und drei Wochen danach bekamen oder ein Placebo. Die Ergebnisse nach sieben Wochen zeigen keine Unterschiede zwischen den Gruppen bezüglich der Entwicklung von Mundschleimhautentzündung, oder der Tumorantwort auf die Behandlung. Es zeigen sich auch keine Unterschiede im Gesamtüberleben oder dem Progressionsfreien-Überleben, sowie der Lebensqualität nach zwölf Monaten. Es zeigten sich eine Reihe von Nebenwirkungen der Chemo- und Radiotherapie in beiden Gruppen. Hier wurde allerdings kein Gruppenvergleich durchgeführt. Insgesamt ist die Stichprobe sehr klein, dies kann durchaus dazu führen, dass Unterschiede nicht signifikant geworden sind, allerdings wurden wie beschrieben auch nicht immer Vergleiche durchgeführt. Insgesamt ist die Berichterstattung sehr oberflächlich in Anbetracht der allgemeinen Studienbeschreibungen/ Rahmenbedingungen und insbesondere der Ergebnisbeschreibung. | |||
=Study Design= | =Study Design= | ||
| Line 21: | Line 21: | ||
{{RCT study general properties | {{RCT study general properties | ||
|Inclusion criteria=Patients with stage III or IV | |Inclusion criteria=Patients with stage III or IV Head and Neck Squamous Cell Carcinoma scheduled for 7 weeks of concurrent cisplatin and radiation, biopsy-proven locally advanced Head and Neck Squamous Cell Carcinoma, in oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or paranasal sinuses, Eastern Cooperative Oncology Group performance status of 0-2 | ||
|Exclusion criteria=Patients who underwent definitive surgery (anything beyond excisional biopsy), those with Stage IVc disease (nonregional metastatic disease), those with malignancy within the previous five years, prior radiotherapy, HIV or hepatitis C positivity, platinum hypersensitivity, inability to tolerate oral medications (in absence of feeding tube), symptomatic peripheral neuropathy, planned use of amifostine, and significant comorbidity | |Exclusion criteria=Patients who underwent definitive surgery (anything beyond excisional biopsy), those with Stage IVc disease (nonregional metastatic disease), those with malignancy within the previous five years, prior radiotherapy, HIV or hepatitis C positivity, platinum hypersensitivity, inability to tolerate oral medications (in absence of feeding tube), symptomatic peripheral neuropathy, planned use of amifostine, and significant comorbidity | ||
|N randomized=18 | |N randomized=18 | ||
| Line 29: | Line 29: | ||
|LoE=2b Oxford 2009 | |LoE=2b Oxford 2009 | ||
|Outcome timeline=T0: Baseline | |Outcome timeline=T0: Baseline | ||
T1: Week 4 | T1: Week 4 | ||
T2: Week 7 during treatment | T2: Week 7 during treatment | ||
T3: Week 6-8 post-treatment | T3: Week 6-8 post-treatment | ||
T4: Follow-up 3 months after completion of the study | T4: Follow-up 3 months after completion of the study | ||
| Line 43: | Line 47: | ||
|Stage cancer=Advanced Stage | |Stage cancer=Advanced Stage | ||
|Cancer stage specification=Head and Neck region; stage III or IV | |Cancer stage specification=Head and Neck region; stage III or IV | ||
|Comorbidity= | |Comorbidity=No selenium deficit at baseline | ||
|Current cancer therapy=Chemotherapy, Radiation therapy | |Current cancer therapy=Chemotherapy, Radiation therapy | ||
|Specifications on cancer therapies=Radiotherapy: 70 Gy at 2 Gy per fraction in 35 daily treatments, 5 days a week for 7 weeks, chemotherapy: Cisplatin dosed at 100 mg/m² intravenously over 3h in 1000mL saline on days 1, 22, and 43 of radiotherapy | |Specifications on cancer therapies=Radiotherapy: 70 Gy at 2 Gy per fraction in 35 daily treatments, 5 days a week for 7 weeks, chemotherapy: Cisplatin dosed at 100 mg/m² intravenously over 3h in 1000mL saline on days 1, 22, and 43 of radiotherapy | ||
| Line 65: | Line 69: | ||
|Side Effects / Interactions=NI | |Side Effects / Interactions=NI | ||
|Order number=1 | |Order number=1 | ||
|Arm topic=Selenium | |||
}} | }} | ||
{{Arm | {{Arm | ||
| Line 77: | Line 82: | ||
|Side Effects / Interactions=NI | |Side Effects / Interactions=NI | ||
|Order number=2 | |Order number=2 | ||
|Arm topic=Selenium | |||
}} | }} | ||
{{Arm Overview}} | {{Arm Overview}} | ||
| Line 88: | Line 94: | ||
|Results during intervention=NA | |Results during intervention=NA | ||
|Results after intervention=Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4) | |Results after intervention=Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4) | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=1 | |Order number=1 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 105: | Line 112: | ||
|Results during intervention=NA | |Results during intervention=NA | ||
|Results after intervention=Only one patient from the intervention arm did not reach CR and died | |Results after intervention=Only one patient from the intervention arm did not reach CR and died | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=low risk | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=low risk | ||
|Order number=2 | |Order number=2 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 122: | Line 130: | ||
|Results during intervention=NA | |Results during intervention=NA | ||
|Results after intervention=After 12 months: No significant differences between arms | |Results after intervention=After 12 months: No significant differences between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=low risk | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=low risk | ||
|Order number=3 | |Order number=3 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 139: | Line 148: | ||
|Results during intervention=NA | |Results during intervention=NA | ||
|Results after intervention=After 12 months: No significant differences between arms | |Results after intervention=After 12 months: No significant differences between arms | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=low risk | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=low risk | ||
|Order number=4 | |Order number=4 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 156: | Line 166: | ||
|Results during intervention=No significant difference for the 7 weeks of intervention | |Results during intervention=No significant difference for the 7 weeks of intervention | ||
|Results after intervention=No significant difference for week 6-8 post-treatment and Follow-up within a year | |Results after intervention=No significant difference for week 6-8 post-treatment and Follow-up within a year | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=low risk | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=low risk | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=5 | |Order number=5 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 173: | Line 184: | ||
|Results during intervention=NA | |Results during intervention=NA | ||
|Results after intervention=Overall: | |Results after intervention=Overall: | ||
Hearing dysfunction n=1 each in the intervention arm and placebo arm; | * Hearing dysfunction n=1 each in the intervention arm and placebo arm; | ||
elevated creatinine n=1 in the placebo arm; | |||
myelosuppression: anemia in the placebo arm n=1; | * elevated creatinine n=1 in the placebo arm; | ||
leukopenia in the intervention arm n=3 and placebo arm n=2; | |||
dermatitis in the intervention arm n=2; | * myelosuppression: anemia in the placebo arm n=1; | ||
dry mouth in the placebo arm n=2; | |||
dysgeusia in the intervention arm n=2, placebo arm n=1; | * leukopenia in the intervention arm n=3 and placebo arm n=2; | ||
odyno-/dysphagia in the intervention arm n=1, placebo arm n=2; | |||
oral/throat pain in the placebo arm n=2; | * dermatitis in the intervention arm n=2; | ||
mucus/sputum intervention arm n=3, placebo arm n=1 | |||
|Bias arising from the randomization process= | * dry mouth in the placebo arm n=2; | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |||
* dysgeusia in the intervention arm n=2, placebo arm n=1; | |||
* odyno-/dysphagia in the intervention arm n=1, placebo arm n=2; | |||
* oral/throat pain in the placebo arm n=2; | |||
* mucus/sputum intervention arm n=3, placebo arm n=1 | |||
|Bias arising from the randomization process=low risk | |||
|Bias due to deviation from intended intervention (assignment to intervention)=low risk | |||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to deviation from intended intervention (adhering to intervention)=NA | ||
|Bias due to missing outcome data= | |Bias due to missing outcome data=low risk | ||
|Bias in measurement of the outcome= | |Bias in measurement of the outcome=some concerns | ||
|Bias in selection of the reported result= | |Bias in selection of the reported result=low risk | ||
|Other sources of bias= | |Other sources of bias=some concerns | ||
|Overall RoB judgment= | |Overall RoB judgment=some concerns | ||
|Order number=6 | |Order number=6 | ||
|Outcome topic=Selenium | |||
}} | }} | ||
{{Outcome Overview}} | {{Outcome Overview}} | ||
| Line 204: | Line 225: | ||
{{Further points for assessing the study | {{Further points for assessing the study | ||
|power analysis performed= | |power analysis performed=Yes | ||
|Sample size corresponds to power analysis= | |Sample size corresponds to power analysis=No | ||
|Reasons given for samples being too small according to power analysis= | |Reasons given for samples being too small according to power analysis="The trial was planned to recruit 80 patients but, due to funding constraints, recruitment was suspended after 18 patients and an interim analysis was performed to see if a sufficiently promising effect could be discerned to warrant further funding." | ||
|Samples sufficiently large= | |Samples sufficiently large=No | ||
|Ethnicity mentioned= | |Ethnicity mentioned=Yes | ||
|Other explanations for an effect besides the investigated intervention= | |Other explanations for an effect besides the investigated intervention=Yes | ||
|Possibility of attention effects= | |Possibility of attention effects=NA | ||
|Possibility of placebo effects= | |Possibility of placebo effects=NA | ||
|Other reasons= | |Other reasons=* Small sample size, possibility of beta error | ||
|Correct use of parametric and non-parametric tests= | |Correct use of parametric and non-parametric tests=NI | ||
|Correction for multiple testing= | |Correction for multiple testing=No | ||
|Measurement of compliance= | |Measurement of compliance=Yes | ||
|Consistent reporting in numbers= | |Consistent reporting in numbers=Yes | ||
|Comprehensive and coherent reporting= | |Comprehensive and coherent reporting=Yes | ||
|Cross-over= | |Cross-over=No | ||
|sufficient washout period= | |sufficient washout period=NA | ||
|Tested for carry-over effects= | |Tested for carry-over effects=NA | ||
|Were sequence effects tested= | |Were sequence effects tested=NA | ||
|Effect sizes reported= | |Effect sizes reported=No | ||
|Were side effects systematically recorded= | |Were side effects systematically recorded=No | ||
|Side effects taken into account in the interpretation of the results= | |Side effects taken into account in the interpretation of the results=NA | ||
|Ethics / CoI / Funding= | |Ethics / CoI / Funding=Yes | ||
|reasons given for samples being too small according to power analysis=? | |reasons given for samples being too small according to power analysis=? | ||
|Testing for normal distribution=? | |Testing for normal distribution=? | ||
| Line 235: | Line 256: | ||
{{Additional Notes | {{Additional Notes | ||
|Additional Notes=Note: Chemotherapy compliance: 8x every 3 cycles of cisplatin, 6x 2 cycles, 2x 1 cycle, 1x, 1x no chemotherapy | |Additional Notes=Note: Chemotherapy compliance: 8x every 3 cycles of cisplatin, 6x 2 cycles, 2x 1 cycle, 1x, 1x no chemotherapy | ||
PRO: | PRO: | ||
| Line 243: | Line 265: | ||
* Measurement of selenium concentration at baseline (no group difference). | * Measurement of selenium concentration at baseline (no group difference). | ||
* Comparability of groups at baseline established. | * Comparability of groups at baseline established. | ||
CONTRA: | CONTRA: | ||
Latest revision as of 14:34, 25 November 2024
| Reference ↗ | |
|---|---|
| Title | Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck |
| Topic | Selenium |
| Author | Mix, M, Singh, AK, Tills, M, Dibaj, S, Groman, A, Jaggernauth, W, Rustum, Y, Jameson, MB |
| Year | 2015 |
| Journal | World journal of clinical oncology |
| DOI | https://doi.org/10.5306/wjco.v6.i5.166 |
Brief summary
In this study, 18 patients with squamous cell carcinoma of the head and neck who were undergoing chemotherapy and radiotherapy were randomly assigned to two arms in which they either received selenium seven days before, during and three weeks after treatment or a placebo. The results after seven weeks showed no differences between the arms in the development of oral mucosal inflammation or tumor response to treatment. There were also no differences in overall survival, progression-free survival or quality of life at twelve months. There were a number of side effects of chemotherapy and radiotherapy in both arms. However, no direct comparison was carried out here. Overall, the sample is very small, which may well mean that differences were not significant, but as described, comparisons were not always made. Overall, the reporting is very superficial in view of the general study descriptions/framework conditions and in particular the description of the results.
In dieser Studie wurden 18 Patienten mit Plattenepithelkarzinom des Kopf-Hals-Bereiches, welche sich einer Chemo- und Radiotherapie unterzogen zufällig zwei Gruppen zugeordnet, in der sie entweder Selen sieben Tage vor, während der Behandlung und drei Wochen danach bekamen oder ein Placebo. Die Ergebnisse nach sieben Wochen zeigen keine Unterschiede zwischen den Gruppen bezüglich der Entwicklung von Mundschleimhautentzündung, oder der Tumorantwort auf die Behandlung. Es zeigen sich auch keine Unterschiede im Gesamtüberleben oder dem Progressionsfreien-Überleben, sowie der Lebensqualität nach zwölf Monaten. Es zeigten sich eine Reihe von Nebenwirkungen der Chemo- und Radiotherapie in beiden Gruppen. Hier wurde allerdings kein Gruppenvergleich durchgeführt. Insgesamt ist die Stichprobe sehr klein, dies kann durchaus dazu führen, dass Unterschiede nicht signifikant geworden sind, allerdings wurden wie beschrieben auch nicht immer Vergleiche durchgeführt. Insgesamt ist die Berichterstattung sehr oberflächlich in Anbetracht der allgemeinen Studienbeschreibungen/ Rahmenbedingungen und insbesondere der Ergebnisbeschreibung.
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 | Double |
| 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 with stage III or IV Head and Neck Squamous Cell Carcinoma scheduled for 7 weeks of concurrent cisplatin and radiation, biopsy-proven locally advanced Head and Neck Squamous Cell Carcinoma, in oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or paranasal sinuses, Eastern Cooperative Oncology Group performance status of 0-2 |
|---|---|
| Exclusion criteria | Patients who underwent definitive surgery (anything beyond excisional biopsy), those with Stage IVc disease (nonregional metastatic disease), those with malignancy within the previous five years, prior radiotherapy, HIV or hepatitis C positivity, platinum hypersensitivity, inability to tolerate oral medications (in absence of feeding tube), symptomatic peripheral neuropathy, planned use of amifostine, and significant comorbidity |
| N randomized | 18 |
| 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. | ITT Analysis |
| Specifications on analyses | Three interim analyses were planned: the first after 20 patients have completed Chemo-Radiotherapy to ensure toxicity in the selenium arm was not unacceptably high and the second and third after one third and two thirds of the patients had been followed for at least 18 months |
| Countries of data collection | NI |
| LoE Level of evidence | 2b Oxford 2009 |
| Outcome timeline Data collection times | T0: Baseline
T1: Week 4 T2: Week 7 during treatment T3: Week 6-8 post-treatment T4: Follow-up 3 months after completion of the study and then at further 3-month intervals over 2 years, then every 6 months until 5 years thereafter |
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 |
|---|---|
| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included | Skin Cancer - Squamous Cell Carcinoma |
| 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 | Advanced Stage |
| Specifications on cancer stages | Head and Neck region; stage III or IV |
| Comorbidities | No selenium deficit at baseline |
| Current cancer therapies | Chemotherapy, Radiation therapy |
| Specifications on cancer therapies | Radiotherapy: 70 Gy at 2 Gy per fraction in 35 daily treatments, 5 days a week for 7 weeks, chemotherapy: Cisplatin dosed at 100 mg/m² intravenously over 3h in 1000mL saline on days 1, 22, and 43 of radiotherapy |
| Previous cancer therapies | NI |
| Gender | Mixed |
| Gender specifications | 17/18 male |
| Age groups | Adults (18+) |
| Age groups specification | Median: 57 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 | 10 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 1 |
| Drop-out reasons | Patient complained of "bad taste" and withdrew from the trial |
| Intervention | Selenomethionine |
| Dosage and regime | Selenomethionine 3600 µg/m²(in 800 µg tablets) 2x daily 7 days before chemotherapy, during chemotherapy 1x daily, and daily for 3 weeks after chemotherapy |
| 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 | Placebo |
|---|---|
| Number of participants (arm) N randomized | 8 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 0 |
| Drop-out reasons | NA |
| Intervention | Placebo |
| Dosage and regime | 2x daily 7 days before chemotherapy, during chemotherapy 1x daily, and daily for 3 weeks after chemotherapy |
| 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 |
Outcomes
Mucositis
| Outcome type As specificed by the authors | Primary |
|---|---|
| Outcome specification | Grade 3 or 4 |
| Type of measurement | NI |
| 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". | NA |
| 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". | Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4) |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | some concerns |
Tumor response
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Complete response rate (CR) |
| Type of measurement | RECIST 1.0 Criteria (Response Evaluation Criteria in Solid Tumors) |
| 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". | NA |
| 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". | Only one patient from the intervention arm did not reach CR and died |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | low risk |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | low risk |
PFS (Progression-Free Survival)
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | NA |
| Type of measurement | Observation |
| 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". | NA |
| 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". | After 12 months: No significant differences between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | low risk |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | low risk |
OS (Overall Survival)
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | NA |
| Type of measurement | Observation |
| 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". | NA |
| 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". | After 12 months: No significant differences between arms |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | low risk |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | low risk |
Quality of life
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Measured with EORTC C-30 Version 3 and EORTC QLQ - H&N35 |
| Type of measurement | EORTC QLQ (European Organisation for Research and Treatment of Cancer Core/ Quality of Life questionnaire) |
| 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". | No significant difference for the 7 weeks of intervention |
| 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". | No significant difference for week 6-8 post-treatment and Follow-up within a year |
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | some concerns |
Toxicity
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Other treatment-associated side effects such as xerostomia, renal impairment, hearing dysfunction, and myelosuppression |
| Type of measurement | NI |
| 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". | NA |
| 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". | Overall:
|
| Risk of Bias Assessment: Cochrane RoB tool 2.0 | |
|---|---|
| Bias arising from the randomization process | low risk |
| Bias due to deviation from intended intervention (assignment to intervention) | low risk |
| Bias due to deviation from intended intervention (adhering to intervention) | NA |
| Bias due to missing outcome data | low risk |
| Bias in measurement of the outcome | some concerns |
| Bias in selection of the reported result | low risk |
| Other sources of bias | some concerns |
| Overall RoB judgment | some concerns |
Funding and Conflicts of Interest
| Funding | “Supported by A grant from the Health Research Council of
New Zealand (in part).“ |
|---|---|
| Conflicts of Interest | Authors declare no conflict of interest. |
Further points for assessing the study
Sample
| Power analysis performed | Yes |
|---|---|
| - Sample size corresponds to power analysis | No |
| - Reasons for insufficient sample size based on power analysis | "The trial was planned to recruit 80 patients but, due to funding constraints, recruitment was suspended after 18 patients and an interim analysis was performed to see if a sufficiently promising effect could be discerned to warrant further funding." |
| If no power analysis performed: at least moderate sample size (n >= 30 per arm) | No |
| Ethnicity mentioned | Yes |
Alternative Explanation
| Other explanations for an effect besides the investigated intervention | Yes |
|---|---|
| - Possibility of attention effects | NA |
| - Possibility of placebo effects | NA |
| - 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 | NI |
|---|---|
| Correction for multiple testing | No |
| Measurement of compliance | Yes |
| Consistent reporting in numbers (figures, flowchart, abstract, results) | Yes |
| Comprehensive and coherent reporting | Yes |
| Cross-over | No |
| - Sufficient washout period | NA |
| - Tested for carry-over effects | NA |
| - Tested for sequence effects | NA |
Interpretation of results
| Effect sizes reported (clinical vs. statistical significance) | No |
|---|---|
| Side effects systematically recorded | No |
| Side effects considered in result interpretation | NA |
| Ethics votum | Yes |
Additional Notes
Note: Chemotherapy compliance: 8x every 3 cycles of cisplatin, 6x 2 cycles, 2x 1 cycle, 1x, 1x no chemotherapy
PRO:
- Ethics approval obtained.
- Participants were instructed to keep a diary of tablet intake.
- Intent-to-treat analysis conducted.
- Sample size calculation performed.
- Measurement of selenium concentration at baseline (no group difference).
- Comparability of groups at baseline established.
CONTRA:
- Very small sample size.
- No indication of selenium deficiencies present.
- Very superficial reporting, particularly in the results section, with little information on blinding.
- No group comparison for number of chemotherapy/radiotherapy side effects or selenium concentration.