Brief summary
In this study, patients with head and neck tumors were examined during radiotherapy. The patients were instructed to apply a gel to the entire oral cavity 3 times a day, with half receiving a curcumin gel and the other half a placebo gel. There were more cases of severe mucositis (an inflammation of the mucous membrane, a common adverse side effect of radiotherapy) in the curcumin arm than in the placebo arm. In addition, patients in the curcumin arm reported less burning in the mouth and had less redness of the oral mucosa and minor mouth ulcers. There are some criticisms of this study. Only a very small sample was examined and it cannot be ruled out that the two arms differed at the beginning of the study because very few characteristics of the patients were reported at the beginning of the study. In addition, the quality of reporting in the study was generally poor; for example, there was no information on the extent to which the patients used the gels as instructed.
In dieser Studie wurden Patienten mit Kopf-Hals-Tumor während der Radiotherapie untersucht. Die Patienten bekamen die Anweisung 3 Mal täglich den gesamten Mundraum mit einem Gel zu bestreichen, wobei die eine Hälfte ein Curcumin-Gel bekam und die andere Hälfte ein Placebo-Gel. In der Curcumin-Gruppe gab es mehr Fälle von schwerer Mukositis (eine Entzündung der Schleimhaut, eine häufige unerwünschte Nebenwirkung von Radiotherapie) als in der Placebo-Gruppe. Zudem berichteten die Patienten der Curcumin-Gruppe geringeres Brennen im Mund und hatten kleinere Hautrötungen der Mundschleimhaut und kleinere Geschwüre im Mund. An dieser Studie gibt es einige Kritikpunkte. Es wurde nur eine sehr kleine Stichprobe untersucht und es ist nicht ausgeschlossen, dass sich die beiden Gruppen zur Beginn der Studie unterschieden haben, weil nur sehr wenige Charakteristiken der Patienten zu Beginn der Studie berichtet wurden. Zudem hat die Studie allgemein eine schlechte Berichtqualität, es fehlt zum Beispiel die Angabe, inwiefern die Patienten die Gels so verwendet haben, wie es vorgegeben war.
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
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Prospective
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| Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals
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Monocentric
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| 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
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Double
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| Is randomized
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Yes
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| Cross-over Participants alternate between different treatment groups or conditions over a specified period, allowing each participant to serve as their own control
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No
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| Number of arms
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2
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Study characteristics
| Inclusion criteria
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Minimum age of 18 years, presence of head and neck cancer, minimum radiation dose of 50 Gy (the least dose resulting in mucositis), the ability of patient to use topical gel (by his/her or examiner’s report), minimally 50% of patient’s oral cavity in radiation field (according to the radiotherapist’s opinion)
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| Exclusion criteria
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History of radiation therapy or chemotherapy in previous year, chemotherapy protocol in addition to radiotherapy, any allergy to condiments, especially "Turmeric root", any complications due to the use of topical gel during the study, suffering from any kind of oral disease such as active oral infection, ulcer, having any systemic disease or taking any medication
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| N randomized
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37
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| 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.
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ITT Analysis
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| Specifications on analyses
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ITT not specified, but no drop-out reported.
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| Countries of data collection
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Iran
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| LoE Level of evidence
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2b Oxford 2009
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| Outcome timeline Data collection times
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T0: Baseline
T1-T3: Tag 7, 14, 21
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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.
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Curative
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| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included
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Head and Neck Cancers
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| 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
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NI
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| Specifications on cancer stages
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NI
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| Comorbidities
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NI
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| Current cancer therapies
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Radiation therapy
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| Specifications on cancer therapies
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NI
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| Previous cancer therapies
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NI
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| Gender
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Mixed
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| Gender specifications
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16% female
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| Age groups
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Adults (18+)
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| Age groups specification
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Mean (SD): 51.34 (12.08) years
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Arms
| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Intervention
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| Number of participants (arm) N randomized
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19
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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0
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| Drop-out reasons
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NA
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| Intervention
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Curcumin
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| Dosage and regime
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Topical turmeric gel (0.5%); Coat entire mouth with gel 3 times a day
Start: day 0 radiotherapy
Duration: entire radiotherapy (21 days)
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| One-time application
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No
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| 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.
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21
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| Side effects / Interactions
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NI
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| Arm type Active control: group receives active treatment; </br>Passive control: for example treatment as usual, waiting control, no treatment
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Placebo
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| Number of participants (arm) N randomized
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18
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| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date
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0
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| Drop-out reasons
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NA
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| Intervention
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Placebo Gel
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| Dosage and regime
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Coat entire mouth with gel 3 times a day
Start: day 0 radiotherapy
Duration: entire radiotherapy (21 days)
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| One-time application
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No
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| 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.
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21
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| Side effects / Interactions
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NI
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Outcomes
Mucositis
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
|
Max. degree of mucositis
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| Type of measurement
|
Observation, WHO-Scale (World Health Organisation)
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| 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".
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Max. degree of mucositis (number (%) of patients):
- Grade 1: Intervention arm: 15 (78.9%), Placebo arm: 3 (16.7%)
- Grade 2: Intervention arm: 4 (21.1%), Placebo arm: 8 (44.4%)
- Grade 3: Intervention arm: 0 (0%), Placebo arm: 7 (38.9%)
- Grade 4: Intervention arm and Placebo arm: 0
- Difference between arms in distribution of grades: p < 0.001
- Time between T0 and onset of max. mucositis: no numbers given; p = 0.315
Incidence of max. mucositis (number (%)):
- 7 days: Intervention arm: 4 (21.1%), Placebo arm: 8 (44.4%)
- 14 days: Intervention arm: 6 (31.6%), Placebo arm: 4 (22.2%)
- 21 days: Intervention arm: 9 (47.4%), Placebo arm: 6 (33.3%)
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| 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".
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NA
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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some concerns
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| Bias due to deviation from intended intervention (assignment to intervention)
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low risk
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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low risk
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| Bias in measurement of the outcome
|
some concerns
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| Bias in selection of the reported result
|
some concerns
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| Other sources of bias
|
some concerns
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| Overall RoB judgment
|
some concerns
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Mucositis
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Burning Sensation in the mouth
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| Type of measurement
|
VAS (Visual Analogue Scale)
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| 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".
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Significant difference between intervention vs. placebo arm in mean (SD):
intervention 3.7 (2.1) vs. placebo 7.9 (2.0); p < 0.001
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| 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".
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NA
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
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some concerns
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| Bias due to deviation from intended intervention (assignment to intervention)
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low risk
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
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low risk
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| Bias in measurement of the outcome
|
some concerns
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| Bias in selection of the reported result
|
some concerns
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| Other sources of bias
|
some concerns
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| Overall RoB judgment
|
some concerns
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Erythema
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Oral mucosal erythema
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| Type of measurement
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Observation
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| 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".
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Significant difference between intervention vs. placebo arm for max. size in mm (mean (SD)):
intervention 4.9 (2.2) vs. placebo 8.9 (2.7); p < 0.001
|
| 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".
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NA
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
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| Bias arising from the randomization process
|
some concerns
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| Bias due to deviation from intended intervention (assignment to intervention)
|
low risk
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| Bias due to deviation from intended intervention (adhering to intervention)
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NA
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| Bias due to missing outcome data
|
low risk
|
| Bias in measurement of the outcome
|
some concerns
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| Bias in selection of the reported result
|
some concerns
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| Other sources of bias
|
some concerns
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| Overall RoB judgment
|
some concerns
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Oral ulcus
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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NA
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| Type of measurement
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Observation
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| 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".
|
Significant difference between intervention vs. placebo arm for max. size in mm (mean (SD)):
intervention 1.3 (2.7) vs. placebo 6.4 (4.2); p < 0.001
|
| 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".
|
NA
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| Risk of Bias Assessment: Cochrane RoB tool 2.0
|
| Bias arising from the randomization process
|
some concerns
|
| Bias due to deviation from intended intervention (assignment to intervention)
|
low risk
|
| Bias due to deviation from intended intervention (adhering to intervention)
|
NA
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| Bias due to missing outcome data
|
low risk
|
| Bias in measurement of the outcome
|
some concerns
|
| Bias in selection of the reported result
|
some concerns
|
| Other sources of bias
|
some concerns
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| Overall RoB judgment
|
some concerns
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Funding and Conflicts of Interest
| Funding
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NI
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| Conflicts of Interest
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According to authors no conflict of interest.
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Further points for assessing the study
Sample
| Power analysis performed
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No
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| - Sample size corresponds to power analysis
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NA
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| - Reasons for insufficient sample size based on power analysis
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NA
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
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No
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| Ethnicity mentioned
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No
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Alternative Explanation
| Other explanations for an effect besides the investigated intervention
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Yes
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| - Possibility of attention effects
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NA
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| - Possibility of placebo effects
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NA
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| - Other reasons
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- Possible baseline differences cannot be excluded, hardly any information on baseline characteristics (only gender, age and radiotherapy dose)
- Poor report quality (e.g. no information on how cancer types are distributed between the arms, no information on dropout and compliance)
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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
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Yes
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| Correction for multiple testing
|
NA
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| Measurement of compliance
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NI
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| Consistent reporting in numbers (figures, flowchart, abstract, results)
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Yes
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| Comprehensive and coherent reporting
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No
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| Cross-over
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No
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| - Sufficient washout period
|
NA
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| - Tested for carry-over effects
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NA
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| - Tested for sequence effects
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NA
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Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
No
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| Side effects systematically recorded
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NA
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| Side effects considered in result interpretation
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NA
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| Ethics votum
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Yes
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Additional Notes
PRO:
- Ethics approval obtained
- Double-blinding
CONTRA:
- Small sample size
- No power analysis
- Possible baseline differences cannot be ruled out
- Limited information on baseline characteristics (only gender, age, and radiotherapy dose)
- Poor reporting quality (e.g., no information on cancer types distribution between arms, no data on dropout and compliance)
