Ryan et al. (2013): Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients: Difference between revisions
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|Reference=Publication: Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients | |Reference=Publication: Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients | ||
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=Brief summary= | =Brief summary= | ||
In this study, breast cancer patients were examined during radiotherapy, with one half taking curcumin alongside radiotherapy and the other half taking a placebo. In the curcumin | In this study, breast cancer patients were examined during radiotherapy, with one half taking curcumin alongside radiotherapy and the other half taking a placebo. In the curcumin arm, the severity of radiodermatitis (a common skin disease associated with radiotherapy) was found to be significantly lower at the end of radiotherapy than in the placebo arm. The two arms showed different courses of radiodermatitis severity. From the fourth week onwards, the intensity in the curcumin arm increased less steeply than in the placebo arm and even decreased slightly from week six to seven. In addition, there were fewer cases of moist skin peeling in the curcumin arm. With regard to the redness of the dermatitis, the pain experienced and other adverse symptoms such as nausea and vomiting, there were virtually no differences between the curcumin and placebo patients. A positive aspect of this study was the double blinding (investigators/patients did not know which arm they belonged to). On the negative side, however, only a very small sample was examined and a large number of individual tests were carried out. This increases the probability that a significant difference will be calculated by chance, even though there is actually no difference. | ||
In dieser Studie wurden Brustkrebspatientinnen während der Radiotherapie untersucht, wobei eine Hälfte parallel zur Radiotherapie Curcumin einnahm und die andere Hälfte ein Placebo. In der Curcumin-Gruppe wurde die Schwere von Radiodermatitis (eine häufige Hautkrankheit, die mit Radiotherapie assoziiert ist) am Ende der Radiotherapie deutlich geringer eingeschätzt als in der Placebo-Gruppe. Die beiden Gruppen wiesen unterschiedlicher Verläufe der Radiodermatitis-Schwere auf. Ab der vierten Woche stieg die Intensität in der Curcumin-Gruppe weniger steil an als in der Placebo-Gruppe und nahm von Woche sechs bis sieben sogar leicht ab. Zudem traten in der Curcumin-Gruppe weniger Fälle von feuchter Hautablösung auf. Hinsichtlich der Röte der Dermatitis, des erlebten Schmerzes und weiterer unerwünschter Symptome wie z.B. Übelkeit und Erbrechen fanden sich so gut wie keine Unterschiede zwischen den Curcumin- und den Placebo-Patienten. Positiv an dieser Studie war die doppelte Verblindung (Untersuchter/Patienten wissen nicht, welcher Gruppe sie angehören). Negativ war jedoch, dass nur eine sehr kleine Stichprobe untersucht wurde und dass sehr viele Einzeltests durchgeführt wurden. Das erhöht die Wahrscheinlichkeit, dass man zufällig einen bedeutsamen Unterschied berechnet, obwohl eigentlich kein Gruppenunterschied vorhanden ist. | In dieser Studie wurden Brustkrebspatientinnen während der Radiotherapie untersucht, wobei eine Hälfte parallel zur Radiotherapie Curcumin einnahm und die andere Hälfte ein Placebo. In der Curcumin-Gruppe wurde die Schwere von Radiodermatitis (eine häufige Hautkrankheit, die mit Radiotherapie assoziiert ist) am Ende der Radiotherapie deutlich geringer eingeschätzt als in der Placebo-Gruppe. Die beiden Gruppen wiesen unterschiedlicher Verläufe der Radiodermatitis-Schwere auf. Ab der vierten Woche stieg die Intensität in der Curcumin-Gruppe weniger steil an als in der Placebo-Gruppe und nahm von Woche sechs bis sieben sogar leicht ab. Zudem traten in der Curcumin-Gruppe weniger Fälle von feuchter Hautablösung auf. Hinsichtlich der Röte der Dermatitis, des erlebten Schmerzes und weiterer unerwünschter Symptome wie z.B. Übelkeit und Erbrechen fanden sich so gut wie keine Unterschiede zwischen den Curcumin- und den Placebo-Patienten. Positiv an dieser Studie war die doppelte Verblindung (Untersuchter/Patienten wissen nicht, welcher Gruppe sie angehören). Negativ war jedoch, dass nur eine sehr kleine Stichprobe untersucht wurde und dass sehr viele Einzeltests durchgeführt wurden. Das erhöht die Wahrscheinlichkeit, dass man zufällig einen bedeutsamen Unterschied berechnet, obwohl eigentlich kein Gruppenunterschied vorhanden ist. | ||
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{{Characteristics of participants | {{Characteristics of participants | ||
|Setting=Adjuvant | |Setting=Curative, Adjuvant | ||
|Types of cancer=Breast Cancer | |Types of cancer=Breast Cancer | ||
|Stage cancer=Early Stage, Advanced Stage | |Stage cancer=Early Stage, Advanced Stage | ||
| Line 40: | Line 40: | ||
|Current cancer therapy=Radiation therapy | |Current cancer therapy=Radiation therapy | ||
|Specifications on cancer therapies=Standard fractionated RT (~1.8–2.4 Gy per session) for four to seven weeks with or without boost for a total radiation dose of ≥ 42 Gy | |Specifications on cancer therapies=Standard fractionated RT (~1.8–2.4 Gy per session) for four to seven weeks with or without boost for a total radiation dose of ≥ 42 Gy | ||
Prior (n(%)): | Prior (n(%)): | ||
Lumpectomy 27 (90%) | |||
Chemotherapy before radiation 13 (43.3%) | * Lumpectomy 27 (90%) | ||
* Mastectomy 3 (10%) | |||
* Chemotherapy before radiation 13 (43.3%) | |||
|Previous cancer therapies=Surgery, Chemotherapy | |Previous cancer therapies=Surgery, Chemotherapy | ||
|Gender=Female | |Gender=Female | ||
| Line 58: | Line 63: | ||
|Drop-out reasons=Patient-initiated n=1, Ineligibility n=1, Non-compliance n=1 | |Drop-out reasons=Patient-initiated n=1, Ineligibility n=1, Non-compliance n=1 | ||
Overall reasons for n=5: patient-reported hot flashes (1/5) | Overall reasons for n=5: | ||
* patient-reported hot flashes (1/5) | |||
* undisclosed personal reasons (1/5) | |||
* ineligibility due to concurrent participation in another RT intervention trial (1/5) | |||
* and noncompliance with study procedures (2/5) | |||
|Intervention=Curcumin (Curcumin C3 Complex®) | |Intervention=Curcumin (Curcumin C3 Complex®) | ||
+ “Standard care” topical agents for radiation dermatitis (i.e., Radiaplex® gel, silvadine, hydrocortisone cream) were allowed | + “Standard care” topical agents for radiation dermatitis (i.e., Radiaplex® gel, silvadine, hydrocortisone cream) were allowed | ||
|Dosage and regime=500mg capsules (≥95% curcuminoids), 3 times daily, 4 capsules each time | |Dosage and regime=500mg capsules (≥95% curcuminoids), 3 times daily, 4 capsules each time | ||
Duration: 7 weeks (entire | |||
Duration: 7 weeks (entire radiationtherapy) | |||
|One-time application=No | |One-time application=No | ||
|Duration in days=49 | |Duration in days=49 | ||
| Line 75: | Line 89: | ||
|Drop-out reasons=Patient-initiated n=1, Non-compliance n=1 | |Drop-out reasons=Patient-initiated n=1, Non-compliance n=1 | ||
Overall reasons for n=5: patient-reported hot flashes (1/5) | Overall reasons for n=5: | ||
* patient-reported hot flashes (1/5) | |||
* undisclosed personal reasons (1/5) | |||
* ineligibility due to concurrent participation in another RT intervention trial (1/5) | |||
* and noncompliance with study procedures (2/5) | |||
|Intervention=Placebo (500 mg calcium hydrogen phosphate and yellow food coloring) | |Intervention=Placebo (500 mg calcium hydrogen phosphate and yellow food coloring) | ||
+ “Standard care” topical agents for radiation dermatitis (i.e., Radiaplex® gel, silvadine, hydrocortisone cream) were allowed | + “Standard care” topical agents for radiation dermatitis (i.e., Radiaplex® gel, silvadine, hydrocortisone cream) were allowed | ||
|Dosage and regime=3 times daily, 4 capsules each time | |Dosage and regime=3 times daily, 4 capsules each time | ||
Duration: 7 weeks (entire | |||
Duration: 7 weeks (entire radiationtherapy) | |||
|One-time application=No | |One-time application=No | ||
|Duration in days=49 | |Duration in days=49 | ||
| Line 92: | Line 116: | ||
|Outcome type=Primary | |Outcome type=Primary | ||
|Outcome name=Dermatitis | |Outcome name=Dermatitis | ||
|Outcome specification=Severity of radiodermatitis (skin measurements weekly after the 5th | |Outcome specification=Severity of radiodermatitis (skin measurements weekly after the 5th radiationtherapy session) | ||
|Type of measurement=RDS (Radiation Dermatitis Severity) | |Type of measurement=RDS (Radiation Dermatitis Severity) | ||
|Results during intervention=Mean difference | |Results during intervention=Mean difference: | ||
* Intervention arm – Placebo arm (SD; 95% CI) = -0.8 (0.8, -1.4; -0.2); p = 0.008 | |||
Model over time: | Model over time: | ||
Intervention vs. | |||
* Intervention vs. Placebo (without considering time): p = 0.963, but significant arm/week interaction p = 0.007, i.e., the trend over time is different | |||
* According to the graph, Intervention and Placebo follow a similar trend until week 4, after which the values in the Intervention arm increase less sharply and even decrease slightly in week 7, while the Placebo arm continues to increase | |||
|Results after intervention=NA | |Results after intervention=NA | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=some concerns | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=high 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=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=high risk | ||
|Order number=1 | |Order number=1 | ||
|Outcome topic=Curcumin | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 114: | Line 144: | ||
|Outcome specification=Moist desquamation | |Outcome specification=Moist desquamation | ||
|Type of measurement=Observation | |Type of measurement=Observation | ||
|Results during intervention=Number in % | |Results during intervention=Number in %: | ||
Intervention arm: 28.6%, Placebo arm: 87.5%; p = 0.002 | * Intervention arm: 28.6%, Placebo arm: 87.5%; p = 0.002 | ||
|Results after intervention=NA | |Results after intervention=NA | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=some concerns | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=high 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=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=high risk | ||
|Order number=2 | |Order number=2 | ||
|Outcome topic=Curcumin | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 132: | Line 163: | ||
|Outcome specification=Redness of skin | |Outcome specification=Redness of skin | ||
|Type of measurement=Observation | |Type of measurement=Observation | ||
|Results during intervention=Intervention vs. placebo (without considering time): p = 0.328 | |Results during intervention=Intervention vs. placebo (without considering time): p = 0.328 | ||
Arm/week interaction: p = 0.588, i.e., no significant differences in the redness trend | Arm/week interaction: p = 0.588, i.e., no significant differences in the redness trend | ||
|Results after intervention=NA | |Results after intervention=NA | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=some concerns | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=NA | ||
|Bias due to deviation from intended intervention (adhering to intervention)=NA | |Bias due to 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=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=high risk | ||
|Order number=3 | |Order number=3 | ||
|Outcome topic=Curcumin | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 150: | Line 184: | ||
|Outcome specification=NA | |Outcome specification=NA | ||
|Type of measurement=MPQ-SF (McGill Pain Questionnaire - Short Form), SI (Symptom Inventory questionnaire) | |Type of measurement=MPQ-SF (McGill Pain Questionnaire - Short Form), SI (Symptom Inventory questionnaire) | ||
|Results during intervention=Mean change from baseline to end of | |Results during intervention=Mean change from baseline to end of radiotherapy (95% CI): | ||
Pain at | * Pain at radiotherapy site: Intervention arm: 1.929 (0.855, 3.002), Placebo arm: 1.313 (0.365, 2.260); p = 0.504 | ||
Other pain: Intervention arm: –0.286 (-1.309, 0.738), Placebo arm: –0.563 (-1.432, 0.307); p = 0.967 | |||
* Other pain: Intervention arm: –0.286 (-1.309, 0.738), Placebo arm: –0.563 (-1.432, 0.307); p = 0.967 | |||
MPQ-SF: | MPQ-SF: | ||
Considering types of pain: gnawing, aching, splitting (Intervention arm > Placebo arm, p < 0.021), otherwise no significant differences | * MPQ - total: Intervention arm: 4.643 (2.045, 7.241), Placebo arm: 2.875 (1.543, 4.207); p = 0.144 | ||
* Perceived pain: Intervention arm: 0.857 (0.358, 1.356), Placebo arm: 0.813 (0.523, 1.102); p = 0.644 | |||
* Sensory pain: Intervention arm: 3.286 (1.217, 5.354), Placebo arm: 1.750 (0.827, 2.673); p = 0.081 | |||
* Affective pain: Intervention arm: 0.500 (0.061, 0.939), Placebo arm: 0.375 (-0.008, 0.758); p = 0.550 | |||
* No significant differences between intervention and placebo arms | |||
* Considering types of pain: gnawing, aching, splitting (Intervention arm > Placebo arm, p < 0.021), otherwise no significant differences | |||
|Results after intervention=NA | |Results after intervention=NA | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=some concerns | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=high 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=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=high risk | ||
|Order number=4 | |Order number=4 | ||
|Outcome topic=Curcumin | |||
}} | }} | ||
{{Outcome | {{Outcome | ||
| Line 180: | Line 222: | ||
|Results during intervention=No significant differences (nausea, vomiting, depression, shortness of breath, memory, appetite, diarrhea, urination, skin, sleep, fatigue, activity, mood, work, relationships, walking, quality of life) | |Results during intervention=No significant differences (nausea, vomiting, depression, shortness of breath, memory, appetite, diarrhea, urination, skin, sleep, fatigue, activity, mood, work, relationships, walking, quality of life) | ||
|Results after intervention=NA | |Results after intervention=NA | ||
|Bias arising from the randomization process= | |Bias arising from the randomization process=some concerns | ||
|Bias due to deviation from intended intervention (assignment to intervention)= | |Bias due to deviation from intended intervention (assignment to intervention)=high 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=NA | ||
|Overall RoB judgment= | |Overall RoB judgment=high risk | ||
|Order number=5 | |Order number=5 | ||
|Outcome topic=Curcumin | |||
}} | }} | ||
{{Outcome Overview}} | {{Outcome Overview}} | ||
| Line 200: | Line 243: | ||
{{Further points for assessing the study | {{Further points for assessing the study | ||
|Samples sufficiently large=? | |power analysis performed=NI | ||
| | |Sample size corresponds to power analysis=NI | ||
|Reasons given for samples being too small according to power analysis=NA | |||
|Samples sufficiently large=No | |||
|Ethnicity mentioned=Yes | |||
|Other explanations for an effect besides the investigated intervention=No | |||
|Possibility of attention effects=NA | |||
|Possibility of placebo effects=NA | |||
|Other reasons=NA | |||
|Correct use of parametric and non-parametric tests=Yes | |||
|Correction for multiple testing=No | |||
|Measurement of compliance=Yes | |||
|Consistent reporting in numbers=Yes | |||
|Comprehensive and coherent reporting=Yes | |||
|Cross-over=No | |||
|sufficient washout period=NA | |||
|Tested for carry-over effects=NA | |||
|Were sequence effects tested=NA | |||
|Effect sizes reported=No | |||
|Were side effects systematically recorded=NA | |||
|Side effects taken into account in the interpretation of the results=NA | |||
|Ethics / CoI / Funding=Yes | |||
|Blinding reliable=? | |||
|Check whether blinding was successful=? | |||
|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=? | ||
|Correct application of statistical tests=? | |Correct application of statistical tests=? | ||
|mono- or multicentric=? | |mono- or multicentric=? | ||
}} | }} | ||
{{Additional Notes | {{Additional Notes | ||
|Additional Notes=PRO: | |Additional Notes=PRO: | ||
* Ethical approval obtained | * Ethical approval obtained | ||
* Double-blind with control (Intervention arm: 5/14 (35.7%) of patients think they are in the curcumin arm, | * Double-blind with control (Intervention arm: 5/14 (35.7%) of patients think they are in the curcumin arm, placebo arm: 2/16 (12.5%) of patients think they are in the placebo arm). | ||
* High comparable compliance rates (Mean (SD): Intervention arm: 96.6% (6.6%), Placebo arm: 98.4% (3.2%); p = 0.344) | * High comparable compliance rates (Mean (SD): Intervention arm: 96.6% (6.6%), Placebo arm: 98.4% (3.2%); p = 0.344) | ||
* Assessment of expected and actual pain at baseline | * Assessment of expected and actual pain at baseline | ||
CONTRA: | CONTRA: | ||
* Very small sample size | * Very small sample size | ||
* Dropout rate: Intervention arm: 18%, Placebo arm: 11% | * Dropout rate: Intervention arm: 18%, Placebo arm: 11% | ||
* No intention-to-treat analysis | * No intention-to-treat analysis | ||
* No control for multiple testing | * No control for multiple testing | ||
}} | }} | ||
Latest revision as of 14:25, 21 November 2024
| Reference ↗ | |
|---|---|
| Title | Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients |
| Topic | Curcumin |
| Author | Ryan, JL, Heckler, CE, Ling, M, Katz, A, Williams, JP, Pentland, AP, Morrow, GR |
| Year | 2013 |
| Journal | Journal of Radiation Research |
| DOI | https://doi.org/10.1667/RR3255.1 |
Brief summary
In this study, breast cancer patients were examined during radiotherapy, with one half taking curcumin alongside radiotherapy and the other half taking a placebo. In the curcumin arm, the severity of radiodermatitis (a common skin disease associated with radiotherapy) was found to be significantly lower at the end of radiotherapy than in the placebo arm. The two arms showed different courses of radiodermatitis severity. From the fourth week onwards, the intensity in the curcumin arm increased less steeply than in the placebo arm and even decreased slightly from week six to seven. In addition, there were fewer cases of moist skin peeling in the curcumin arm. With regard to the redness of the dermatitis, the pain experienced and other adverse symptoms such as nausea and vomiting, there were virtually no differences between the curcumin and placebo patients. A positive aspect of this study was the double blinding (investigators/patients did not know which arm they belonged to). On the negative side, however, only a very small sample was examined and a large number of individual tests were carried out. This increases the probability that a significant difference will be calculated by chance, even though there is actually no difference.
In dieser Studie wurden Brustkrebspatientinnen während der Radiotherapie untersucht, wobei eine Hälfte parallel zur Radiotherapie Curcumin einnahm und die andere Hälfte ein Placebo. In der Curcumin-Gruppe wurde die Schwere von Radiodermatitis (eine häufige Hautkrankheit, die mit Radiotherapie assoziiert ist) am Ende der Radiotherapie deutlich geringer eingeschätzt als in der Placebo-Gruppe. Die beiden Gruppen wiesen unterschiedlicher Verläufe der Radiodermatitis-Schwere auf. Ab der vierten Woche stieg die Intensität in der Curcumin-Gruppe weniger steil an als in der Placebo-Gruppe und nahm von Woche sechs bis sieben sogar leicht ab. Zudem traten in der Curcumin-Gruppe weniger Fälle von feuchter Hautablösung auf. Hinsichtlich der Röte der Dermatitis, des erlebten Schmerzes und weiterer unerwünschter Symptome wie z.B. Übelkeit und Erbrechen fanden sich so gut wie keine Unterschiede zwischen den Curcumin- und den Placebo-Patienten. Positiv an dieser Studie war die doppelte Verblindung (Untersuchter/Patienten wissen nicht, welcher Gruppe sie angehören). Negativ war jedoch, dass nur eine sehr kleine Stichprobe untersucht wurde und dass sehr viele Einzeltests durchgeführt wurden. Das erhöht die Wahrscheinlichkeit, dass man zufällig einen bedeutsamen Unterschied berechnet, obwohl eigentlich kein Gruppenunterschied vorhanden ist.
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 | Monocentric |
| 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 | Diagnosed with noninflammatory breast cancer or carcinoma in situ and prescribed radiotherapy without concurrent chemotherapy at the University of Rochester Cancer Center |
|---|---|
| Exclusion criteria | Patients who: had bilateral breast cancer; previous radiation to the chest or breast area; diagnosis of inflammatory breast cancer; breast reconstruction and/or expanders prior to RT; were taking anti-coagulant therapy (warfarin, coumadin or heparin) or antiepidermal growth factor receptor (EGFR) therapy or were receiving partial breast irradiations |
| N randomized | 35 |
| Analysis PP: Per Protocol analysis, i.e. only participants included who adhered to the study protocol.</br>ITT: Intention-to-treat analysis, i.e. all randomized participants included regardless of any drop-outs or changes in assignment.</br>mITT: modified Intention-to-treat analysis can refer to analyses in which participants with missing outcome data are excluded or it can refer to analyses in which only participants who received at least one treatment dose are included. In this case, participants dropped out of the study prematurely for reasons unrelated to the treatment. | PP Analysis |
| Specifications on analyses | NA |
| Countries of data collection | United States |
| LoE Level of evidence | 1b Oxford 2009 |
| Outcome timeline Data collection times | Assessed at baseline, weekly after every fifth radiotherapy session, at the end of radiotherapy, and at 2 post-radiotherapy appointments (1-month and 6-months post-radiotherapy) |
Characteristics of participants
| Setting Refers to cancer therapy setting.</br>- Curative therapy: aims to completely eradicate a disease and achieve a full recovery; </br>- Neo-adjuvant therapy: form of curative therapy, given before the primary treatment for cancer (usually surgery); </br>- Adjuvant therapy: form of curative therapy, given after the primary treatment for cancer (usually surgery); </br>- Palliative therapy: focuses on providing relief from symptoms and improving the quality of life for patients, without necessarily targeting the underlying disease; </br>- Active surveillance: involves close monitoring of disease progression without any intervention (typically used for prostate cancer);</br>- No therapy setting: Patients who completed therapy/are currently not in cancer treatment, cancer survivors. | Curative, Adjuvant |
|---|---|
| Types of cancer "Other Cancers" means that only a subpopulation was specified, but further unspecified cancer types were included | Breast Cancer |
| Cancer stages Early Stage: generally refers to cancer that is localized to the area where it started, mostly stages I and II;</br>Advanced Stage: cancer that has spread beyond its original site, mostly stages III and IV, with stage IV indicating distant metastasis | Early Stage, Advanced Stage |
| Specifications on cancer stages | 0 – IV |
| Comorbidities | NI |
| Current cancer therapies | Radiation therapy |
| Specifications on cancer therapies | Standard fractionated RT (~1.8–2.4 Gy per session) for four to seven weeks with or without boost for a total radiation dose of ≥ 42 Gy
|
| Previous cancer therapies | Surgery, Chemotherapy |
| Gender | Female |
| Gender specifications | 100% female |
| Age groups | Adults (18+) |
| Age groups specification | Mean (SD) = 58.1 (2.2) 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 | 17 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 3 |
| Drop-out reasons | Patient-initiated n=1, Ineligibility n=1, Non-compliance n=1
Overall reasons for n=5:
|
| Intervention | Curcumin (Curcumin C3 Complex®)
|
| Dosage and regime | 500mg capsules (≥95% curcuminoids), 3 times daily, 4 capsules each time
Duration: 7 weeks (entire radiationtherapy) |
| 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 | According to information no side effects. |
| 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 | 18 |
| Drop-out Number of participants who left the study for any reason or did not provide information on every data collection date | 2 |
| Drop-out reasons | Patient-initiated n=1, Non-compliance n=1
Overall reasons for n=5:
|
| Intervention | Placebo (500 mg calcium hydrogen phosphate and yellow food coloring)
|
| Dosage and regime | 3 times daily, 4 capsules each time
Duration: 7 weeks (entire radiationtherapy) |
| 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 | According to information no side effects. |
Outcomes
Dermatitis
| Outcome type As specificed by the authors | Primary |
|---|---|
| Outcome specification | Severity of radiodermatitis (skin measurements weekly after the 5th radiationtherapy session) |
| Type of measurement | RDS (Radiation Dermatitis Severity) |
| 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". | Mean difference:
|
| 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 |
| 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) | high 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 | NA |
| Overall RoB judgment | high risk |
Dermatitis
| Outcome type As specificed by the authors | Primary |
|---|---|
| Outcome specification | Moist desquamation |
| 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". | Number in %:
|
| 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 |
| 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) | high 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 | NA |
| Overall RoB judgment | high risk |
Dermatitis
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Redness of skin |
| 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". | Intervention vs. placebo (without considering time): p = 0.328
|
| 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 |
| 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) | NA |
| 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 | NA |
| Overall RoB judgment | high risk |
Pain
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | NA |
| Type of measurement | MPQ-SF (McGill Pain Questionnaire - Short Form), SI (Symptom Inventory 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". | Mean change from baseline to end of radiotherapy (95% CI):
|
| 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 |
| 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) | high 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 | NA |
| Overall RoB judgment | high risk |
Toxicity
| Outcome type As specificed by the authors | Secondary |
|---|---|
| Outcome specification | Further symptoms of the Symptom Inventory |
| Type of measurement | SI (Symptom Inventory 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 differences (nausea, vomiting, depression, shortness of breath, memory, appetite, diarrhea, urination, skin, sleep, fatigue, activity, mood, work, relationships, walking, quality of life) |
| 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 |
| 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) | high 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 | NA |
| Overall RoB judgment | high risk |
Funding and Conflicts of Interest
| Funding | "This study was supported by the FDA IND no. 75,444; NCI PHS grant 1R25CA10618; Dermatology Foundation Research Career Development Award; and URMC CTSI KL2-RR024136. A special thanks to all of the patients with breast cancer who participated in this clinical trial. We thank the Radiation Oncology Red and Yellow Service team members and the Departments of Radiation Oncology and Dermatology for assistance and support of this study." |
|---|---|
| Conflicts of Interest | See Funding. |
Further points for assessing the study
Sample
| Power analysis performed | NI |
|---|---|
| - Sample size corresponds to power analysis | NI |
| - Reasons for insufficient sample size based on power analysis | NA |
| 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 | No |
|---|---|
| - Possibility of attention effects | NA |
| - Possibility of placebo effects | NA |
| - Other reasons | NA |
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 | Yes |
|---|---|
| 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 | NA |
| Side effects considered in result interpretation | NA |
| Ethics votum | Yes |
Additional Notes
PRO:
- Ethical approval obtained
- Double-blind with control (Intervention arm: 5/14 (35.7%) of patients think they are in the curcumin arm, placebo arm: 2/16 (12.5%) of patients think they are in the placebo arm).
- High comparable compliance rates (Mean (SD): Intervention arm: 96.6% (6.6%), Placebo arm: 98.4% (3.2%); p = 0.344)
- Assessment of expected and actual pain at baseline
CONTRA:
- Very small sample size
- Dropout rate: Intervention arm: 18%, Placebo arm: 11%
- No intention-to-treat analysis
- No control for multiple testing