We will use the Population, Concepts and Context framework to implement eligibility criteria for included studies.37

Participants with cancer who are receiving chemotherapy, radiotherapy or other biological therapy for treatment of cancer will be sought. There will be no restrictions by population characteristics (eg, sex, age, comorbidities, geographic location), or type or stage of cancer.

The core intervention of interest is antioxidant dietary supplements concomitant with chemotherapy, radiotherapy or other biological therapy for cancer. We are defining antioxidant dietary supplements as orally consumed products with known ability to prevent cellular damage by reacting with oxidising free radicals.40 Antioxidant dietary supplements cover a wide range of substances, including vitamins (eg, vitamin C), minerals (eg, selenium), amino acids (eg, n-acetylcysteine), carotenoids (eg, lycopene), botanicals (eg, polyphenols), and hormones (eg, melatonin). Studies involving intravenous administration of antioxidants in a medical setting (eg, intravenous vitamin C) will be excluded from this scoping review. Oral and intravenous antioxidants are not only processed differently by the body but oral supplements may be taken by patients without direct assistance of medical professionals, and thus, have different clinical and public health implications. Studies involving mushrooms and mushroom products will be excluded because their mechanism is primarily through immunomodulation.41 Studies involving compound herbal formulas will also be excluded due to the potential for multiple mechanisms of activity that confound the research question. Finally, although many foods such as fruits and vegetables are good sources of antioxidants, whole food dietary interventions (eg, changes in food habits) will also be excluded from this scoping review due to the potential for confounding by non-antioxidant dietary components with known activity against cancer (eg, histone deacetylase-inhibition, DNA methylation).42 43

The core outcomes of interest will consist of (1) therapeutic response to treatment with chemotherapy, radiotherapy or other biological therapy, (2) improvements in chemotherapy-related side effects and quality of life and (3) increases in adverse effects potentially related to antioxidant supplementation. Response to treatment may be measured as mortality or with indicators of morbidity (eg, cancer progression, recurrence). Because it may not be possible to establish whether side effects and other adverse events are more likely related to the cancer treatment or to the supplement use, we will document when adverse events are presented within the reviews as side effects due to either cancer treatment or supplement use, but we will discuss the findings both separately and jointly. We will include outcomes measured at any time point.

The context is cancer treatment with curative intent. The palliative use of chemotherapy, radiotherapy, or other biological therapies will be excluded because a core aspect of this scoping review is the evaluation of the evidence on antioxidant supplements with regard to possible interference with the curative objectives of treatment. We will not restrict context by date, healthcare setting or country.

Citations for retrieved records will be downloaded into EndNote X8 and deduplicated. Citations will then be uploaded to Covidence and screened for inclusion in two stages.44 At the first stage, two team members will independently screen all records for relevance on the basis of record title and abstract. Prior to title and abstract screening, the team members will carry out a pilot screening of randomly selected records, to ensure that they understand and agree on the initial inclusion criteria. During the title and abstract screening, discrepancies between screeners will regularly be resolved, to prevent development and continuation of differing interpretations of the inclusion criteria.45 All records that are deemed to be potentially relevant to the scoping review will progress to full-text screening. Once records are ready for full-text screening, a calibration exercise will be performed in which all team members screen a set of the same randomly selected 25 records against the inclusion and exclusion criteria for the review. The results of this screening will be compared between team members, and any necessary clarifications to the inclusion and exclusion criteria, or modifications of those criteria, will be made and documented in the completed scoping review. After any clarification or modification of the selection criteria, and agreement among the team on the results of the calibration exercise, two team members will independently screen each full text record for inclusion. Discrepancies between screeners will be resolved by discussion or involvement of a third team member. The study citation and brief reason for exclusion will be provided for each excluded record and a flow chart of the screening process will be provided in accordance with PRISMA-ScR.

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