Methods

A systematic literature search was conducted in accordance with PRISMA guidelines. The search strategy was based on the approved list of anticancer drugs available at data.tp53.org.uk/cancerdrugs.php.⁵ Both drug classes and individual agents were included. To determine the inclusion of abbreviations, abbreviations were searched independently of their full terms (e.g., ADC NOT antibody drug conjugate). If screening of the first 50 results yielded no relevant studies, the abbreviation was excluded.

The most recent search was performed on 2 April 2026. Publications were limited to those published from 1 January 2000 onwards. Studies in languages other than English, Dutch, French, or German were excluded, as were systematic and narrative reviews. Only studies reporting original patient data (e.g., retrospective cohort studies and prospective studies) were included.

Studies were eligible if they included cancer patients treated for primary or metastatic disease with SRT within 30 days of a novel systemic therapy. Studies involving hormonal therapy, chemotherapy or radioligand therapy were excluded, as were studies combining SRT with both novel systemic agents and chemotherapy administered within one week of SRT.

SRT was defined as treatment with fraction doses ≥5 Gy delivered in a maximum of 12 fractions. Both intracranial and extracranial SRT were included. Systemic therapy had to be administered within 30 days before or after radiotherapy.

Studies that did not clearly report AE outcomes or treatment timing are excluded, as were studies pooling AEs across drug classes without stratification, or selecting patients by prior AEs. AEs had to be graded according to the CTCAE, or described in sufficient detail to allow grading by the authors.

Titles and abstracts were independently screened by two reviewers. Discrepancies were resolved by a third reviewer. Full-text screening, data extraction, and risk-of-bias assessment were performed by one reviewer, with consultation from additional reviewers when needed.

Data extracted included publication year, study design, patient and tumour characteristics, radiation dose and fractionation, type and timing of systemic therapy, and toxicity outcomes, with a focus on high-grade adverse events. Only grade ≥3 adverse events (CTCAE) were included in the analysis.

Risk of bias was assessed using the JBI case series tool (for studies without a control group), the JBI case report tool (for case reports), the RoB 2 tool (for randomised controlled trials), and the ROBINS-I v2 tool (for non-randomised studies with a control group).

Studies assessed with RoB 2 or ROBINS-I v2 were excluded if the overall risk of bias was rated as high. For the JBI tools, studies were excluded if any item related to the outcome of interest was rated as "unclear" or "no" (e.g., poorly described adverse events), or if three or more items overall were rated as "unclear" or "no."

The current analysis sums up grade ≥3 AE rates across studies, separately per AE category. Only studies reporting sufficient data to calculate these rates are included. AEs are categorized as follows:

• Overall AEs (OAEs): possibly, probably, or definitely attributable to either systemic therapy or SRT.
• RT-related AEs (RTAEs): possibly, probably, or definitely attributable specifically to SRT.

The table below compares the total number of study arms and patients extracted from the literature with the subset shown in the interactive charts. Arms are displayed when: (1) the drug group has been assigned unambiguously, and (2) the toxicity reporting type is treatment-related (SBRT + drug) or RT-only (the two categories shown in the patient infographics). Arms with other toxicity coding (e.g. all AEs, drug-only) are extracted but not yet included in the visualisations.

Coverage is updated automatically as new extractions are completed and drug group assignments are finalised. The goal is to reach 100% visualisation as the extraction process is completed.

Expected grade ≥3 AE rates for drugs in monotherapy were derived from published literature and can be reviewed in the drug reference table .

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