Study Note
Brief summary
Radiotherapy is a common cancer treatment. Many patients experience skin reactions due to radiotherapy. In this study, researchers examined the efficacy of a cream containing Boswellia serrata. Women scheduled to receive radiotherapy for postoperative breast cancer treatment were divided into two arms. One arm received a base cream (ingredients not defined) and the other a skin cream with Boswellia serrata. Women who applied the Boswellia cream to their skin reported their skin reactions as less intense compared to women who applied the base cream. Additionally, it was less necessary for them to apply hydrocortisone cream to treat their skin during radiotherapy.
Die Strahlentherapie ist eine häufige Krebsbehandlung. Bei vielen Patienten kommt es durch die Strahlentherapie zu Hautreaktionen. In dieser Studie untersuchten Forscher die Wirksamkeit einer Creme, die Boswellia serrata enthält. Frauen, die eine Strahlentherapie zur postoperativen Behandlung von Brustkrebs erhalten sollten, wurden in zwei Gruppen eingeteilt. Eine Gruppe erhielt eine Basiscreme (Inhaltsstoffe nicht definiert) und die andere eine Hautcreme mit Boswellia serrata. Frauen, die die Boswellia-Creme auf ihre Haut auftrugen, bewerteten ihre Hautreaktionen weniger häufig als intensiv, als Frauen, die die Basiscreme auftrugen. Außerdem war es weniger nötig, dass sie während der Strahlentherapie eine Hydrokortisoncreme zur Behandlung ihrer Haut auftragen mussten
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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NI
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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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NI
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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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Breast cancer patients undergoing adjuvant radiotherapy after surgery
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| Exclusion criteria
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Radical mastectomy
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| N randomized
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114
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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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NI
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| Specifications on analyses
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Student´s t and Mann-Whitney U test for arms comparison
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| Countries of data collection
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Italy
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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, after surgery
T1: After 5 weeks
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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, Adjuvant
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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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Breast Cancer
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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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Radiation therapy with 2 tangential fields with a photonbeam energy of 6 Mv
50 Gy, 5 doses weekly about 5 weeks
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| Previous cancer therapies
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Surgery
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| Gender
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Female
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| Gender specifications
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100 % 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 age: 58.2 years, min = 32, max = 78,
Median = 58.5 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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57
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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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NI
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| Drop-out reasons
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NI
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| Intervention
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Boswellia cream 2% in Phytosome® (Bosexil®)
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| Dosage and regime
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Applied directly after radiotherapy and in the evening or on treatment-free days in the morning and evening
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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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25
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| Side effects / Interactions
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Patients report non-absorption of residues; typical and characteristic odor of the cream was reported as pleasant or too intense.
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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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57
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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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NI
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| Drop-out reasons
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NI
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| Intervention
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Base cream
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| Dosage and regime
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Applied directly after radiotherapy and in the evening or on treatment-free days in the morning and evening
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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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25
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| Side effects / Interactions
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itching, burning and epidermal changes: 49,2 %
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Outcomes
Wound healing
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Intensity of erythema upon radiation therapy at the 50 Gy dose
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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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NA
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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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Significant distribution differences between the arms
Boswellia arm: more often with mild or moderate erythema (78% compared to 51% in base cream arm)
Placebo arm: more often with intense erythema (49% compared to 22% in boswellia arm)
Differences in grades of visual intensity of erythema were statistically significant
Objective assessment, Computerized photo analysis:
Significantly lower magenta color percentage in the boswellia arm (10.1%) compared to the placebo arm (13.3%)
Higher proportion of patients treated with boswellia cream scored slight intensity of erythema compared to those of base cream arm (50.0% vs 23.0%)
A lower fraction of boswellia cream arm patients scored visual intensity of erythema as intense compared to patients of the base cream arm (19.0% vs 48.6%)
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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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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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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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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
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?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Dermatitis
| Outcome type As specificed by the authors
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Primary
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| Outcome specification
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Usage of Hydrocortison
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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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NA
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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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Significantly lower use of hydrocortisone in the boswellia arm (25%) compared to the placebo arm (63%), p < 0.0001
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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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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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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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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
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?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Wound healing
| Outcome type As specificed by the authors
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Secondary
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| Outcome specification
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Toxicity
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| Type of measurement
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RTOG Acute Radiation Morbidity Scoring Criteria (Radiation Therapy Oncology Group)
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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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NA
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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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Tendency towards lower incidence/expression of superficial skin symptoms in the boswellia group compared to the placebo group, p=0.066
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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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?
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| Bias due to deviation from intended intervention (assignment to intervention)
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?
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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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?
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| Bias in measurement of the outcome
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?
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| Bias in selection of the reported result
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?
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| Other sources of bias
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?
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| Overall RoB judgment
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?
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Funding and Conflicts of Interest
| Funding
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Two authors are employees of Indena SpA (manufacturer of pharmaceuticals, natural foods and personal care).
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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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?
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| - Sample size corresponds to power analysis
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?
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| - Reasons for insufficient sample size based on power analysis
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?
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| If no power analysis performed: at least moderate sample size (n >= 30 per arm)
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?
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| Ethnicity mentioned
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?
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Alternative Explanation
| Other explanations for an effect besides the investigated intervention
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?
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| - Possibility of attention effects
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?
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| - Possibility of placebo effects
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?
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| - Other reasons
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?
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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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?
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| Correction for multiple testing
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?
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| Measurement of compliance
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?
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| Consistent reporting in numbers (figures, flowchart, abstract, results)
|
?
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| Comprehensive and coherent reporting
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?
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| Cross-over
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?
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| - Sufficient washout period
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?
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| - Tested for carry-over effects
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?
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| - Tested for sequence effects
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?
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Interpretation of results
| Effect sizes reported (clinical vs. statistical significance)
|
?
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| Side effects systematically recorded
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?
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| Side effects considered in result interpretation
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?
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| Ethics votum
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?
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Additional Notes
