Heggie et al. (2002): A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue

Reference ↗
Title	A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue
Topic	Aloe vera
Author	Heggie, S, Bryant, GP, Tripcony, L, Keller, J, Rose, P, Glendenning, M, Heath, J
Year	2002
Journal	Cancer Nursing
DOI	https://doi.org/10.1097/00002820-200212000-00007

Brief summary

Radiotherapy is a common cancer treatment. Many patients experience skin reactions as a result of radiotherapy. In this study, researchers investigated the effect of an aloe vera gel on skin reactions from radiotherapy for the postoperative treatment of breast cancer. From the start of radiotherapy until two weeks after the end of radiotherapy, 101 women applied an aqueous cream and 107 women applied an aloe vera gel to the irradiated skin area. Women who applied the aloe vera gel were more prone to mild desquamation in the irradiated skin area and moderate pain, otherwise no differences between the groups were detectable.

Die Strahlentherapie ist eine häufige Krebsbehandlung. Bei vielen Patienten kommt es durch die Strahlentherapie zu Hautreaktionen. In dieser Studie untersuchten Forscher die Wirkung eines Aloe Vera Gels auf Hautreaktionen aus der Strahlentherapie zur postoperativen Behandlung von Brustkrebs. Vom Beginn der Strahlentherapie bis zwei Wochen nach Abschluss der Bestrahlung trugen 101 Frauen eine wässrige Creme und 107 Frauen ein Aloe Vera Gel auf den bestrahlten Hautbereich auf. Frauen, die das Aloe Vera Gel auftrugen, waren anfälliger für leichte Hautabschuppungen im bestrahlten Hautbereich und mittelstarke Schmerzen, ansonsten waren keine Unterschiede zwischen den Gruppen nachweisbar.

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	?
Monocentric / Multicentric Monocentric: conducted in one center/ hospital; </br>Multicentric: conducted in multiple centers/ hospitals	?
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	?
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	-999

Study characteristics

Inclusion criteria	?
Exclusion criteria	?
N randomized	-999
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.	?
Specifications on analyses	?
Countries of data collection	?
LoE Level of evidence	?
Outcome timeline Data collection times	?

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.	?
Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included	?
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	?
Specifications on cancer stages	?
Comorbidities	?
Current cancer therapies	?
Specifications on cancer therapies	?
Previous cancer therapies	?
Gender	?
Gender specifications	?
Age groups
Age groups specification	?

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	115
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	8
Drop-out reasons	Not arm-specified: 17 2 subjects refused to continue participation 5 received a reduced radiation dose 2 had a total mastectomy 3 had infection on commencement of treatment 1 had extra treatment fields 1 was randomized twice 3 developed an allergic reaction to the assigned topical preparation
Intervention	Aloe vera
Dosage and regime	3x daily (including immediately after treatment on treatment days) topical 98% aloe vera gel on the irradiated breast during and for 2 weeks after radiation therapy + all patients: routine skin care recommendations: using only mild baby soap on the treatment site, airing skin twice daily, and wearing loose cotton clothing next to treated skin + all patients: radiation therapy
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.	60
Side effects / Interactions	2 subjects developed an allergic reaction to the assigned topical preparation.

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	110
Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date	9
Drop-out reasons	Not arm-specified: 17 2 subjects refused to continue participation 5 received a reduced radiation dose 2 had a total mastectomy 3 had infection on commencement of treatment 1 had extra treatment fields 1 was randomized twice 3 developed an allergic reaction to the assigned topical preparation
Intervention	Placebo
Dosage and regime	3x daily (including immediately after treatment on treatment days) topical aqueous cream on the irradiated breast during and for 2 weeks after radiation therapy + all patients: routine skin care recommendations: using only mild baby soap on the treatment site, airing skin twice daily, and wearing loose cotton clothing next to treated skin + all patients: radiation therapy
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.	60
Side effects / Interactions	1 subject developed an allergic reaction to the assigned topical preparation.

Outcomes

Toxicity

Outcome type As specificed by the authors	Primary
Outcome specification	Erythema Weekly skin assessments were completed and recorded by a research nurse. Erythema was rated as 0 = none, 1 = mild, 2 = moderate, 3 = severe.
Type of measurement	Morbidity rating scale (by Dische)
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".	There was no significant difference between the two treatment arms in terms of cumulative probability, prevalence, or duration of erythema. For subjects who did not have chemotherapy, those in the placebo arm had a significantly greater incidence of grade 2 or more erythema than those in the aloe vera arm (71% vs. 51%) (p = 0.02).

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

Toxicity

Outcome type As specificed by the authors	Primary
Outcome specification	Dry desquamation/Moist desquamation Weekly skin assessments were completed and recorded by a research nurse. Extent of treatment area affected by dry desquamation and/or moist desquamation was recorded as 0-100% and was divided into the following intervals (>1%, >25%, >50%). Areas affected by moist desquamation were also identified according to site, ie, sternum, axilla, inframammary fold, upper inner quadrant, upper outer quadrant, lower inner quadrant, or lower outer quadrant.
Type of measurement	Morbidity rating scale (by Dische)
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".	The cumulative probability for any dry desquamation (>1%) was greater in the aloe vera arm compared with the placebo arm (70% vs. 41%) (p<0.001) There was no difference in the duration of reaction between the two treatment arms. There was no significant difference between the two treatment arms in terms of cumulative probability, prevalence, or duration of moist desquamation.

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

Toxicity

Outcome type As specificed by the authors	Primary
Outcome specification	Pain Subjective ratings for pain were recorded as 0 = none, 1 = mild, 2 = moderate, 3 = severe.
Type of measurement	Morbidity rating scale (by Dische)
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".	For the subjects the cumulative probability of grade 2 or more pain was greater in the aloe vera arm than in the placebo arm (26% vs. 17%) (p = 0.03). For subjects who had drainage, those in the aloe vera arm had a significantly greater incidence of grade 2 or more pain compared with those in the placebo arm (40% vs. 20%) (p = 0.01). For subjects who received chemotherapy, there was no difference in pain levels between the two treatment arms. For subjects, who did not have chemotherapy, those in the aloe vera arm had a significantly greater incidence of grade 2 or more pain compared with those in the placebo arm (26% vs. 12%) (p = 0.02).

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

Toxicity

Outcome type As specificed by the authors	Primary
Outcome specification	Itching Subjective ratings for itching were recorded as 0 = none, 1 = mild, 2 = moderate, 3 = severe
Type of measurement	Morbidity rating scale (by Dische)
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 between the arms at each assessed time point (p = 0.15-0.94); this was also the case with the duration of the reaction.
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".	The cumulative probability for itching toxicity (grades 1 or more, grades 2 or more, grades 3 or more) was greater in the aloe vera arm than in the placebo arm, but the difference was not significant. There was no significant difference between the treatment arms for grade 2 or more itching according to whether or not a subject had undergone chemotherapy. Drainage: The proportion of subjects who had lymphocele drainage was similar in both arms. Within the aloe vera arm, subjects who had lymphocele drainage experienced a significantly greater incidence of grade 2 or more itching compared with subjects who did not have lymphocele drainage (46% vs. 23%) (p = 0.01).There was no significant difference within the placebo arm for drainage versus no drainage.

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

Funding and Conflicts of Interest

Funding	?
Conflicts of Interest	?

Further points for assessing the study

Sample

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

Alternative Explanation

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

Statistics

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

Interpretation of results

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

Additional Notes

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