Radiation Oncology · Reference

Timing Radiation Around Systemic Therapy and Surgery

Published holds for systemic therapy around radiosurgery and fractionated radiation, and intervals between radiation and surgery

Updated November 2026

This page collects published statements on holding systemic therapy around stereotactic radiosurgery (SRS), stereotactic radiotherapy (SRT) and fractionated radiation, and on intervals between radiation and surgery. It is written for teaching. The drug holds come from the cited sources, and each statement names its source and evidence type. For patient care, follow institutional protocols and the treating oncology team.

Timoteo Almeida, MD, MSc, PhD, FCNS | Departments of Neurological Surgery and Radiation Oncology

How to read this page

Orientation

Before means the interval between the last dose of the drug and the start of radiation; after means the interval between the end of radiation and the next dose. A statement applies before and after unless it is marked Before or After. The SRS/SRT column is about brain radiosurgery; statements from the EORTC-ESTRO OligoCare consensus, which covers extracranial SBRT only, stay in that column with the label “Extracranial SBRT”. DEGRO notes that the OligoCare recommendations “should not be uncritically applied to SRS/SRT for BCBM, since pathomechanisms of toxicity may differ” (Borm 2024 (DEGRO)).

Markers: Reported in secondary source the primary text was not accessible, and the statement is taken from named papers that cite it. From public-comment draft read from the society’s public-comment draft; the final wording was not checked. No published recommendation found the searches for this page found none; this does not prove that none exists. Sources disagree both positions are shown side by side. Not verified against the original the figure or wording could not be checked against the original or final text. Not checked a detail that was not checked in the primary source. Protocol window a window written into a trial protocol (a trial rule, not a recommendation), shown apart from recommendations.

Half-lives are from current US prescribing information (DailyMed). Brand names are US brands confirmed on DailyMed. PMIDs and DOIs were checked in November 2026.

Part I. Drug lookup
Part II. Drug table by class
Part III. Timing around surgery
Where the evidence is thin or sources disagree
References

Part I

Drug lookup

41 drugs in 12 classes. Search by generic name, US brand or class to see one drug’s holds around brain SRS or SRT and fractionated RT, surgery intervals from the label, toxicity signals, evidence type and sources. The same rows are in the tables in Part II, which can be read, printed and searched without the lookup.

Statements that apply to all drug classes

Statements that are not specific to one drug class. They apply to the class tables below unless a class or drug row says otherwise.
Scope	Statement	Evidence type
Brain SRS	“Currently, it appears most studies support concurrent systemic therapy + SRS with no need for a washout period.” The guideline also notes that “there is difficulty in defining concurrent treatment due to differences in half-life.” (Ladbury 2024 (RSS))	Guideline (case-based)
Brain SRS with chemotherapy, targeted therapy or ICI	77 studies, 6,384 patients: “no skin toxicities, no clearly increased rate of bleeding, or radiation necrosis with significant clinical impact”; “SRS combined with systemic therapy appears to be safe, allowing the continuation of treatment.” (Borius 2021)	Systematic review
Cranial and extracranial SRT	SRS with targeted therapy or ICI was mostly well tolerated cranially; severe toxicity was high with BRAF inhibitors. Extracranially, a possible increase with EGFR TKIs and bevacizumab. The review included SRT given during or within 30 days of the drug. It reports what each study did and gives no hold recommendation by drug. (Kroeze 2017)	Systematic review
Cranial and extracranial SRT	Prospective registry (TOaSTT): 514 SRTs (271 cranial) with biological cancer therapy given within 30 days or less. Severe acute adverse events 5.3%, severe late 6.3%. Uninterrupted therapy was “not associated with increased severe acute or late adverse events (OR 2.32; 95% CI 0.87–6.22)”. Interrupting therapy was not associated with worse PFS or OS. (Looman 2026 (TOaSTT))	Prospective cohort
SRT with targeted therapy	TOaSTT database (2009–2018), retrospective analysis, 454 SRTs: targeted therapy was interrupted in 44% (median 7 days, range 1–42). Any-grade toxicity was higher when EGFR inhibitors (p=0.016) or BRAF/MEK inhibitors (p=0.009) were continued. Severe toxicity did not differ by interruption. (Kroeze 2021)	Retrospective cohort
Stereotactic RT, all drugs	French preliminary recommendations: a “sufficient therapeutic window (in the order of at least 5 half-lives) between the systemic and local modalities must be left in routine practice” for stereotactic combinations other than cetuximab in head and neck cancer. (Thariat 2014)	Consensus or review
Brain metastases	Rec 2.1: upfront local therapy for symptomatic brain metastases “regardless of the systemic therapy” (evidence-based, high, strong). Rec 2.2: for asymptomatic patients, local therapy “should not be deferred unless” Recs 2.3–2.7 apply (high, strong). The guideline gives no guidance on holding systemic therapy around SRS. (Vogelbaum 2022 (ASCO-SNO-ASTRO))	Guideline
Brain SRS	“Caution is advised in combining SRS with systemic therapy and immunotherapy.” Certain combinations “(TKIs, T-DM1)” may carry a radionecrosis risk “(30%-40%)” higher than SRS alone. No hold intervals are set. From public-comment draft Not verified against the original (Gondi 2022 (ASTRO))	Guideline (draft)
Spine SBRT	“Together with the treating medical oncologist a decision can be made whether to continue or temporarily stop the targeted/immune therapy at/around the time of the SBRT, and if the latter then for how long.” No interval is given. (Guckenberger 2024 (ESTRO))	Guideline
OligoCare and brain SRS/SRT	The OligoCare recommendations “should not be uncritically applied to SRS/SRT for BCBM, since pathomechanisms of toxicity may differ” (BCBM: breast cancer brain metastases). (Borm 2024 (DEGRO))	Guideline
Breast cancer brain metastases	“Due to the lack of reliable data, the decision on whether systemic therapy needs to be interrupted during radiotherapy should be made individually on a case-by-case basis within an interdisciplinary board.” (Borm 2024 (DEGRO))	Guideline
Postoperative SRS or WBRT (trial rule)	N107C: “Cytotoxic chemotherapy was not allowed during SRS or WBRT, but could start immediately afterwards.” (Brown 2017 (N107C))	RCT
Any RT, then ICI	RT within 90 days before starting an ICI was not associated with more serious adverse events: 16,835 patients from 68 trials (1,733 with RT in the 90 days before ICI), “No difference in grade 3 to 4 AEs”; findings persisted after 1:1 propensity matching. Not CNS-specific; concurrent use was not studied. (Anscher 2022 (FDA))	Pooled trial data

Part II

Drug table by class

One table per class. Where a class row is present, it holds statements that apply to every drug in the class, and the drug rows add what is specific to each drug. “See class row” means the drug has no separate statement for that column.

Immune checkpoint inhibitors

Immune checkpoint inhibitors: 3 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All immune checkpoint inhibitorsClass statements	Extracranial SBRT (OligoCare consensus; covers extracranial SBRT only): Reported in secondary source Sources disagree As reported by Liu 2023 and Vandaele 2025 Most experts advised against an ICI and SBRT on the same day. For anti-CTLA-4, alone or with anti-PD-(L)1, allow “at least one week” between drug and SBRT. No 1-week pause is reported for anti-PD-(L)1 alone. (Kroeze 2023 (OligoCare); via Liu 2023, Vandaele 2025) As reported by Zayed 2023 and Kepka 2024 Avoid the same day, with “a minimum ICI interruption of 1 week” before or after SBRT for all ICIs. (Shirai 2025 reports instead that no interruption beyond the SBRT days is needed.) (Kroeze 2023 (OligoCare); via Zayed 2023, Kepka 2024, Shirai 2025) Brain SRS, drug-specific hold: No published recommendation found	WBRT or conventional RT: No published recommendation found OligoCare covers SBRT only.	Not addressed in the sources used here	Radiation necrosis (RN): Symptomatic RN after SRS with ICI: HR 2.56 (95% CI 1.35–4.86, P=.004); melanoma HR 4.02 (1.17–13.82, P=.03). n=480, 115 on ICI. (Martin 2018) RN, pooled: Melanoma: treatment-related necrosis 16.0% with SRS plus ICI vs 6.5% with SRS alone (OR 2.35, p=0.065). NSCLC: 2.9–3.4% vs 0–2.9%. Risk rises most in the first 12 months. (Kim 2021) RN, pooled: PD-1/PD-L1 with SRS: grade 3 radiation-induced brain necrosis 5% (95% CI 3–8); grade 3 or higher neurologic events 7%. 34 studies, 2,587 patients. (Alswaiti 2026) Outcomes by timing: Concurrent vs non-concurrent SRS plus ICI: 1-year OS 64.6% vs 51.6% (p<0.001); overall RN 5.3%. Concurrent ICI 12-month OS OR 1.74. Hypothesis-generating. (Lehrer 2019, Lu 2019) Single series: Lung cancer, single center: concurrent immunotherapy during SRS was associated with RN (16.2% RN overall). (Du 2026) RT before ICI: RT within 90 days before starting an ICI: no difference in grade 3 to 4 adverse events (16,835 patients from 68 trials, 1,733 with RT in the 90 days before ICI); findings persisted after 1:1 propensity matching. Not CNS-specific; concurrent use not studied. (Anscher 2022 (FDA))	Consensus (secondary source)Retrospective cohortMeta-analysisMeta-analysis (individual patient data)Pooled trial data
PembrolizumabKeytrudaHalf-life 22 days label	See class row	See class row	Not addressed in the sources used here	See class row	US label
NivolumabOpdivoHalf-life 25 days label	Sequencing (ASCO-SNO-ASTRO): Rec 2.6: asymptomatic melanoma brain metastases on ipilimumab plus nivolumab, or on dabrafenib plus trametinib (BRAF-V600E): “local therapy may be delayed until there is evidence of intracranial progression” (informal consensus, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO))	See class row	Not addressed in the sources used here	Combination with ipilimumab: Thoracic SBRT (extracranial): in-field severe toxicity 26% with anti-PD-(L)1 plus anti-CTLA-4. Reported in secondary source (Kroeze 2023 (OligoCare); via Liu 2023)	GuidelineConsensus (secondary source)US label
IpilimumabYervoyHalf-life 15.4 days label	Sequencing (ASCO-SNO-ASTRO): Rec 2.6: asymptomatic melanoma brain metastases on ipilimumab plus nivolumab, or on dabrafenib plus trametinib (BRAF-V600E): “local therapy may be delayed until there is evidence of intracranial progression” (informal consensus, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO))	See class row	Not addressed in the sources used here	Extracranial: Thoracic SBRT (extracranial): in-field severe toxicity 12% with anti-CTLA-4 and 26% with anti-PD-(L)1 plus anti-CTLA-4. Reported in secondary source (Kroeze 2023 (OligoCare); via Liu 2023)	GuidelineConsensus (secondary source)US label

BRAF and MEK inhibitors

BRAF and MEK inhibitors: 5 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All BRAF and MEK inhibitorsClass statements	ECOG consensus: Hold “≥1 day before and after SRS”; resume after the same interval. “Time off systemic treatment should be minimized.” Applied to all BRAF and MEK inhibitors “for the sake of consistency and simplicity” despite the half-life difference (dabrafenib 8 h, vemurafenib 57 h). (Anker 2016 (ECOG))	ECOG consensus: Hold “≥3 days before and after fractionated RT”; resume after the same interval. “Consider dose per fraction <4 Gy unless using a stereotactic approach.” (Anker 2016 (ECOG))	Not addressed in the sources used here	ECOG consensus: Almost all grade 3 dermatitis occurred with concurrent use. Deaths possibly related to bowel perforation, liver hemorrhage and pulmonary hemorrhage. Intracranial RN and hemorrhage “do not appear increased”. (Anker 2016 (ECOG)) Systematic review: Cranial: 20 severe events in 75 patients (27%), including grade 3/4 cerebral edema in 15%; the authors advise caution because of a risk of cerebral edema and hemorrhage. Ly et al.: hemorrhage 61% vs 23%, without statistical testing. (Kroeze 2017) Registry: Any-grade toxicity was higher when BRAF/MEK inhibitors were continued during SRT (p=0.009); severe toxicity did not differ by interruption. (Kroeze 2021) RSS guideline: BRAF inhibitor use concurrently with SRS “was associated with a significantly increased rate of intratumoral bleeding” (in the same paragraph that supports no washout in general). (Ladbury 2024 (RSS))	ConsensusSystematic reviewRetrospective cohortGuideline (case-based)
VemurafenibZelborafHalf-life 57 h label	Study practice: Ahmed et al. paused vemurafenib 2–3 days before and after SRT (what one study did, as reported in the review; not a recommendation). (Kroeze 2017)	See class row	Not addressed in the sources used here	Label: “Radiation sensitization and recall... have been reported in patients treated with radiation prior to, during, or subsequent to vemurafenib treatment. Monitor patients closely when vemurafenib is administered concomitantly or sequentially with radiation treatment.” (W&P 5.10) (Zelboraf label)	Systematic reviewUS label
DabrafenibTafinlarHalf-life 8 h label	Sequencing (ASCO-SNO-ASTRO): Rec 2.6: asymptomatic melanoma brain metastases on ipilimumab plus nivolumab, or on dabrafenib plus trametinib (BRAF-V600E): “local therapy may be delayed until there is evidence of intracranial progression” (informal consensus, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO))	See class row	Not addressed in the sources used here	Label: No radiation warning found in a text search of the label. (Tafinlar label)	GuidelineUS label
EncorafenibBraftoviHalf-life 3.5 h label	See class row	See class row	Not addressed in the sources used here	Label: No radiation warning found in a text search of the label. (Braftovi label)	US label
TrametinibMekinistHalf-life 3.9–4.8 days label	Sequencing (ASCO-SNO-ASTRO): Rec 2.6: asymptomatic melanoma brain metastases on ipilimumab plus nivolumab, or on dabrafenib plus trametinib (BRAF-V600E): “local therapy may be delayed until there is evidence of intracranial progression” (informal consensus, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO)) Extracranial SBRT (OligoCare): MEK inhibitors: not on the same day as SBRT; interrupt “for up to two weeks”. Reported in secondary source (Kroeze 2023 (OligoCare); via Vandaele 2025)	See class row	Not addressed in the sources used here	Label: No radiation warning found in a text search of the label. (Mekinist label)	GuidelineConsensus (secondary source)US label
CobimetinibCotellicHalf-life 44 h label	Extracranial SBRT (OligoCare): MEK inhibitors: not on the same day as SBRT; interrupt “for up to two weeks”. Reported in secondary source (Kroeze 2023 (OligoCare); via Vandaele 2025)	See class row	Not addressed in the sources used here	Label: No radiation warning found in a text search of the label. (Cotellic label)	Consensus (secondary source)US label

EGFR and ALK tyrosine kinase inhibitors

EGFR and ALK tyrosine kinase inhibitors: 6 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All EGFR and ALK tyrosine kinase inhibitorsClass statements	Extracranial SBRT (OligoCare): EGFR TKI: SBRT dose and fractionation “need not change”, but no consensus on taking the TKI on RT days or on the length of any interruption. The consensus also reports no increased toxicity with EGFR, ALK and mTOR inhibitors. Reported in secondary source (Kroeze 2023 (OligoCare); via Uehara 2026, Vandaele 2025, Konnerth 2024) Sequencing (ASCO-SNO-ASTRO): Recs 2.3 and 2.4: asymptomatic EGFR-mutant patients on osimertinib or icotinib, or ALK-positive patients on alectinib, brigatinib or ceritinib: “local therapy may be delayed until there is evidence of intracranial progression” (informal consensus, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO)) Sequencing (ARS AUC): SRS followed by TKI was “usually appropriate” in several scenarios, for example 2–4 brain metastases. (Nagpal 2024 (ARS AUC)) Brain SRS, drug-specific hold: No published recommendation found	WBRT (ARS AUC): WBRT with concurrent TKI: “broad disagreement”, defaulting to “may be appropriate”. “Published data demonstrate the safety of concurrent TKI and WBRT, but do not demonstrate a consistent advantage.” (Nagpal 2024 (ARS AUC))	Not addressed in the sources used here	Systematic review: Cranial: no increased severe toxicity (Schwer, Kim, Weickhardt). Extracranial: a possible increase with EGFR TKIs. (Kroeze 2017) Registry: Any-grade toxicity was higher when EGFR inhibitors were continued during SRT (p=0.016); severe toxicity did not differ by interruption. (Kroeze 2021)	Consensus (secondary source)GuidelineAppropriate-use criteriaSystematic reviewRetrospective cohort
OsimertinibTagrissoHalf-life 48 h label	See class row	See class row	Not addressed in the sources used here	Label: No hold language around RT in the label, except interstitial lung disease (ILD) management after chemoradiation. LAURA (after definitive chemoradiation): ILD or pneumonitis, including radiation pneumonitis, 56% vs 38% with placebo. (Tagrisso label)	US label
Erlotinib	See class row	See class row	Not addressed in the sources used here	RSS guideline: “Concurrent erlotinib showed an increased incidence of radionecrosis, though this was in patients who received both WBRT and SRS” (citing Borius). (Ladbury 2024 (RSS))	Guideline (case-based)
Icotinib	See class row	See class row	Not addressed in the sources used here	See class row	See class row
AlectinibAlecensaHalf-life 33 h label	See class row	See class row	Not addressed in the sources used here	See class row	US label
BrigatinibAlunbrigHalf-life 25 h label	See class row	See class row	Not addressed in the sources used here	See class row	US label
CeritinibZykadiaHalf-life 41 h (geometric mean, single dose) label	See class row	See class row	Not addressed in the sources used here	See class row	US label

Anti-EGFR antibodies

Anti-EGFR antibodies: 1 drug.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
CetuximabErbitux	Extracranial SBRT (OligoCare): Anti-EGFR antibodies: not on the same day as SBRT; pause “at least one week before or after SBRT”. Reported in secondary source (Kroeze 2023 (OligoCare); via Uehara 2026, Vandaele 2025, Konnerth 2024) Stereotactic RT with cetuximab: Reported in secondary source Sources disagree Thariat 2014 (French preliminary recommendations) Combined stereotactic ablative radiation therapy and cetuximab “can be recommended” in head and neck tumors; cetuximab is the exception to the rule of at least 5 half-lives. (Thariat 2014) OligoCare (extracranial SBRT), as reported by Vandaele 2025 Anti-EGFR antibodies: not on the same day as SBRT; pause at least one week before or after SBRT. (Kroeze 2023 (OligoCare); via Vandaele 2025)	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	Consensus (secondary source)Consensus or review

HER2-directed drugs

HER2-directed drugs: 5 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All HER2-directed drugsClass statements	Extracranial SBRT (OligoCare, as reported by DEGRO): Trastuzumab and pertuzumab “can be administered on the same day as SBRT without a treatment break or dose reduction”. For T-DM1, no consensus on interruption, though SBRT without dose reduction was agreed; the same applies to CDK4/6, HER2 and PARP inhibitors. Reported in secondary source (Kroeze 2023 (OligoCare), Borm 2024 (DEGRO))	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	Consensus (secondary source)Guideline
TrastuzumabHerceptin	See class row	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	See class row
PertuzumabPerjeta	See class row	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	See class row
Trastuzumab emtansine (T-DM1)ado-trastuzumab emtansineKadcylaHalf-life about 4 days label	Brain SRS: No published recommendation found No consensus defines a safe T-DM1 interval around SRS. Meta-analysis: “Caution is advised when irradiating intracranial sites concurrently with T-DM1.” (Salvestrini 2023) Meta-analysis: “Intracranial stereotactic RT remains the setting in which caution is warranted, particularly in patients receiving T-DM1.” (Visani 2026) Definition used in one study: Lebow 2023 defined “concurrent” as SRT given ≤7 days before or ≤21 days after the ADC. (Lebow 2023)	Meta-analysis: Grade 3 or higher pneumonitis under 1% and skin 1%; the combination was considered acceptable for locoregional RT in non-metastatic disease. (Salvestrini 2023) Meta-analysis: “Supports the use of conventional extracranial RT during treatment with T-DM1, T-DXd, and SG.” (Visani 2026) Label: Adjuvant breast RT given concurrently with the drug is described in the label. (Kadcyla label)	Not addressed in the sources used here	RN with SRS: Geraud 2017 (n=12; 4 concurrent, 8 sequential; with or without WBRT): RN 50% with concurrent vs 28.6% with sequential use. Stumpf 2019 (n=45): clinically significant RN 39.1% with T-DM1 vs 4.5% without, a 13.5-fold increase (p=0.02); the authors “advise caution in the combination”; proposed mechanism: astrocytic swelling through AQP4. Id Said 2022 (67 patients, 223 brain metastases): T-DM1 after SRS HR 2.5 (1.2–5.3); RN probability 29.9%; median time to RN 4.8 months. (Geraud 2017, Stumpf 2019, Id Said 2022) RN, pooled: Grade 3 or higher RN 17% (pooled). (Salvestrini 2023) ADCs, pooled: Intracranial RT with ADCs: grade 3 or higher treatment-related adverse events 8% overall, highest with T-DM1 at 13% (95% CI 1–34%). 29 studies, 3,817 patients. (Visani 2026) ADCs with SRT: Concurrent ADC SHR 4.31 (1.95–9.50) for symptomatic RN (n=98; concurrent = SRT ≤7 days before or ≤21 days after the ADC). Grade 4–5 RN 7.1% vs 0.7% of lesions. In previously irradiated lesions, 24-month symptomatic RN 42.0% vs 9.4%. No difference by agent among concurrent lesions (P = .74). (Lebow 2023) ADCs with SRT, by agent: By agent (univariable, from the authors' published reply): T-DM1 SHR 3.90, T-DXd 3.97 (1.14–13.81), sacituzumab govitecan 5.18 (0.64–42.11). Not verified against the original (Lebow 2023) ASTRO guideline: Certain combinations “(TKIs, T-DM1)” may carry a radionecrosis risk “(30%-40%)” higher than SRS alone. From public-comment draft Not verified against the original (Gondi 2022 (ASTRO)) Regional consensus: “Trastuzumab emtansine combined with stereotactic radiosurgery shows elevated radionecrosis risk.” (Debbi 2026) Label: In the adjuvant setting, radiation pneumonitis: discontinue for grade 2 not responding to standard treatment, and for grade 3 or higher. KATHERINE: radiation pneumonitis 1.8% (11/623 with adjuvant RT), 2 cases grade 3. (Kadcyla label)	Meta-analysisRetrospective cohortUS labelGuideline (draft)Consensus (regional expert panel)
Trastuzumab deruxtecan (T-DXd)fam-trastuzumab deruxtecanEnhertuHalf-life 5.4–5.7 days label	Brain SRS: No published recommendation found No consensus defines a safe T-DXd interval around SRS. Definition used in one study: Lebow 2023 defined “concurrent” as SRT given ≤7 days before or ≤21 days after the ADC. (Lebow 2023)	Meta-analysis: “Supports the use of conventional extracranial RT during treatment with T-DM1, T-DXd, and SG.” (Visani 2026) Regional consensus: T-DXd is “favorable” with whole-breast and palliative RT. (Debbi 2026) Label: Adjuvant breast RT given concurrently with the drug is described in the label. (Enhertu label)	Not addressed in the sources used here	RN with SRS: Sources disagree Lebow 2023 (n=98) Concurrent ADC SHR 4.31 (1.95–9.50) for symptomatic RN; no difference by agent among concurrent lesions (P = .74). T-DXd univariable SHR 3.97 (1.14–13.81), from the authors' published reply (not verified against the original). (Lebow 2023) Chun 2026 (113 patients); Visani 2026 meta-analysis No RN with T-DXd (0/29 patients) vs 11 cases without it; T-DXd associated with better RN-free survival (HR 0.31). Visani: “Current data does not suggest a similar risk signal for T-DXd or SG.” (Chun 2026, Visani 2026) Steele 2026: Symptomatic RN in 3/15 (20%) patients exposed to anti-HER2 ADCs (agents not separated). For anti-HER2 therapy overall (6/28, 21%), adjusted OR 2.49 (0.66–9.41), not significant. (Steele 2026) Label: In the adjuvant setting, if only RT pneumonitis is suspected, “consider interruption... for Grade 2 and permanently discontinue... for Grade ≥3”. DESTINY-Breast05 (adjuvant RT): radiation pneumonitis 31% (29% with concurrent RT, 34% sequential; all grade 1–2); radiation skin injury 20%. (Enhertu label)	Retrospective cohortMeta-analysisConsensus (regional expert panel)US label
TucatinibTukysaHalf-life 11.9 h label	Sequencing (ASCO-SNO-ASTRO): Rec 2.7: local therapy may be deferred on tucatinib, capecitabine and trastuzumab (evidence-based, low, weak). (Vogelbaum 2022 (ASCO-SNO-ASTRO))	No published recommendation found	Not addressed in the sources used here	Retrospective: Symptomatic RN in 4% of lesions with SRS plus tucatinib, capecitabine and trastuzumab. (Khatri 2023)	GuidelineRetrospective cohortUS label

Other antibody-drug conjugates

Other antibody-drug conjugates: 3 drugs.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
Sacituzumab govitecanTrodelvyHalf-life 6.5–6.7 days (SN-38 22–24 h) label	Brain SRS: No published recommendation found No consensus interval found.	Meta-analysis: “Supports the use of conventional extracranial RT during treatment with T-DM1, T-DXd, and SG.” (Visani 2026)	Not addressed in the sources used here	ADCs with SRT: Symptomatic RN: a trend only, univariable SHR 5.18 (0.64–42.11), from the authors' published reply and also reported by DEGRO. No difference by agent among concurrent lesions (P = .74). (Lebow 2023, Borm 2024 (DEGRO)) ADCs, pooled: Intracranial RT pooled across ADCs: grade 3 or higher treatment-related adverse events 8% overall. (Visani 2026)	Meta-analysisRetrospective cohortGuidelineUS label
Datopotamab deruxtecanDatroway	No published recommendation found	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	None
Enfortumab vedotinPadcev	No published recommendation found	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	None

Anti-VEGF agents

Anti-VEGF agents: 3 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All anti-VEGF agentsClass statements	Before Extracranial SBRT (OligoCare): Anti-VEGF antibodies: not on the same day as SBRT. To limit severe GI toxicity, give SBRT “≥1 week after drug administration”. Reported in secondary source (Kroeze 2023 (OligoCare); via Shirai 2025, Vandaele 2025) After Extracranial SBRT (OligoCare): “With a treatment break during SBRT and for ≥one additional treatment cycle afterward”; resume after at least one skipped cycle. Reported in secondary source (Kroeze 2023 (OligoCare); via Shirai 2025, Vandaele 2025)	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	Consensus (secondary source)
BevacizumabAvastinHalf-life 20 days (11–50) label	See class row	See class row	Label: “Withhold for at least 28 days prior to elective surgery. Do not administer Avastin until at least 28 days following major surgery and until adequate wound healing.” (Avastin label)	Systematic review: Cranial SRT: severe local toxicity in 12/192 (6%). The added risk “appears to be small or non-existing” and the drug “could possibly even be protective” against RN. Extracranial: a possible increase in toxicity. (Kroeze 2017) Label: No RT-specific hold in the label. (Avastin label)	US labelSystematic review
RamucirumabCyramzaHalf-life 14 days label	See class row	See class row	Label: Withhold 28 days before elective surgery. Do not give for at least 2 weeks after major surgery and until adequate healing. (Cyramza label)	Not addressed in the sources used here	US label
Ziv-afliberceptZaltrapHalf-life about 6 days label	See class row	See class row	Label: At least 4 weeks before elective surgery and at least 4 weeks after major surgery. (Zaltrap label)	Not addressed in the sources used here	US label

Multikinase inhibitors

Multikinase inhibitors: 2 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All multikinase inhibitorsClass statements	Extracranial SBRT (OligoCare): Multikinase inhibitors as a class: not on the same day as SBRT; interrupt “up to two weeks”. Reported in secondary source (Kroeze 2023 (OligoCare); via Uehara 2026, Vandaele 2025, Konnerth 2024)	No published recommendation found	Not addressed in the sources used here	Not addressed in the sources used here	Consensus (secondary source)
CabozantinibCabometyxHalf-life about 99 h label	See class row	See class row	Label: Stop at least 3 weeks before surgery, including dental surgery. Do not give for at least 2 weeks after surgery. (Cabometyx label)	Not addressed in the sources used here	US label
LenvatinibLenvimaHalf-life about 28 h label	See class row	See class row	Label: Withhold at least 1 week before surgery and for at least 2 weeks after. (Lenvima label)	Not addressed in the sources used here	US label

CDK4/6 inhibitors

CDK4/6 inhibitors: 3 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All CDK4/6 inhibitorsClass statements	Extracranial SBRT (OligoCare): “No consensus was reached on whether or not CDK4/6 inhibitors can be administered on the same days as SABR”; there is “no clear recommendation regarding a minimum time interval”. DEGRO reports the same consensus as SBRT without dose reduction, with no consensus on interruption. Reported in secondary source (Kroeze 2023 (OligoCare), Borm 2024 (DEGRO); via Kubeczko 2024, Kubeczko 2026) Breast consensus (ESTRO-endorsed): “Did not recommend concomitant RT-CDK4/6 inhibitors in the adjuvant setting due to insufficient evidence, but supported case-by-case use in the metastatic setting.” Reported in secondary source (Meattini 2024 (ESTRO-endorsed); via Kubeczko 2026)	Breast consensus (ESTRO-endorsed): “Did not recommend concomitant RT-CDK4/6 inhibitors in the adjuvant setting due to insufficient evidence, but supported case-by-case use in the metastatic setting.” Reported in secondary source (Meattini 2024 (ESTRO-endorsed); via Kubeczko 2026)	Not addressed in the sources used here	Retrospective: Brain SRS series: 15 patients, 42 lesions (palbociclib or abemaciclib); 43% concurrent. RN in 2 lesions (5%), both after 4 prior RT courses. (Figura 2019)	Consensus (secondary source)GuidelineRetrospective cohort
PalbociclibIbranceHalf-life 29 h label	See class row	See class row	Not addressed in the sources used here	Label: No RT language in the label. (Ibrance label)	US label
RibociclibKisqaliHalf-life 32 h label	See class row	See class row	Not addressed in the sources used here	Label: No RT language in the label. (Kisqali label)	US label
AbemaciclibVerzenioHalf-life 18.3 h label	See class row	See class row	Not addressed in the sources used here	See class row	US label

PARP inhibitors

PARP inhibitors: 1 drug.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
OlaparibLynparzaHalf-life 14.9 h label	Extracranial SBRT (OligoCare): SBRT without dose reduction; no consensus on interruption. Reported in secondary source (Kroeze 2023 (OligoCare), Borm 2024 (DEGRO)) Brain SRS: No published recommendation found	Brain RT: No published recommendation found	Not addressed in the sources used here	Label: The label mentions MDS/AML after prior RT. (Lynparza label)	Consensus (secondary source)GuidelineUS label

mTOR inhibitors

mTOR inhibitors: 1 drug.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
EverolimusAfinitorHalf-life about 30 h label	Brain SRS: No published recommendation found	No published recommendation found	Label: Withhold at least 1 week before surgery and for at least 2 weeks after. (Afinitor label)	Extracranial SBRT (OligoCare): SBRT with mTOR inhibitors “did not show increased toxicity rates”. Reported in secondary source (Kroeze 2023 (OligoCare); via Konnerth 2024) Label: “Radiation sensitization and recall can occur in patients treated with radiation prior to, during, or subsequent to” everolimus (W&P 5.12). (Afinitor label)	US labelConsensus (secondary source)

Cytotoxic chemotherapy

Cytotoxic chemotherapy: 8 drugs. The first row applies to every drug in the class.
Drug	SRS/SRT (brain) hold	Fractionated RT hold	Surgery and wound healing	Toxicity signals	Evidence type
All cytotoxic chemotherapyClass statements	Brain SRS: washout: Sources disagree No washout (RSS 2024; Borius 2021) No washout needed per the RSS guideline; Borius found no clinically significant increase in toxicity. (Ladbury 2024 (RSS), Borius 2021) Interval (Thariat 2014) At least 5 half-lives between the drug and stereotactic RT (French preliminary recommendations). (Thariat 2014) Trial eligibility rule (brain metastasis RCT), not a recommendation: N107C: no cytotoxic chemotherapy during SRS or WBRT; it could start “immediately afterwards”. (Brown 2017 (N107C))	Trial eligibility rule (brain metastasis RCT), not a recommendation: N107C: no cytotoxic chemotherapy during SRS or WBRT; it could start “immediately afterwards”. (Brown 2017 (N107C))	Not addressed in the sources used here	Radiation recall review: Most commonly reported radiation recall agents: doxorubicin, docetaxel, paclitaxel, gemcitabine and capecitabine. “It is not possible to predict which patients will react.” It also states that “it seems likely that risks can be minimized by prolonging the interval between completion of radiotherapy and initiation of chemotherapy”; no specific interval is given. (Burris 2010)	Guideline (case-based)Systematic reviewConsensus or reviewRCTReview
CapecitabineXelodaHalf-life about 0.75 h (capecitabine and the 5-FU formed from it) label	SRS series: 31 stereotactic sessions (90 lesions); 71% within 1 month of capecitabine. “No increased toxicity... no cases of radionecrosis.” (Mills 2021) Brain-specific hold: No published recommendation found	Label (conventional RT): Rectal cancer: 825 mg/m² twice daily with concomitant RT (1,250 mg/m² without RT). Concurrent use is the labeled standard. (Xeloda label)	Not addressed in the sources used here	Review: Radiation recall reported. (Burris 2010)	Retrospective cohortUS labelReview
Fluorouracil (5-FU)Half-life 8–20 min after IV bolus; 5-FU formed from oral capecitabine about 0.75 h (Xeloda label) label	See class row	See class row	Not addressed in the sources used here	See class row	US label
TemozolomideTemodarHalf-life 1.8 h label	SRS with temozolomide: No published recommendation found	Before Concurrent, no hold: Glioblastoma: continue concurrently, 75 mg/m² daily, 7 days a week, “from the first to the last day of radiotherapy” (60 Gy in 30 fractions). Label: 42–49 days concurrent. (Stupp 2005, Temodar label) After Maintenance: Glioblastoma: maintenance begins “4 weeks after concomitant use phase completion” (label), at 150–200 mg/m² on days 1–5 every 28 days for 6 cycles (Stupp 2005; label). Adjuvant anaplastic astrocytoma: begin “4 weeks after the end of radiotherapy”, for 12 cycles (label). (Stupp 2005, Temodar label)	Not addressed in the sources used here	Grade 3–4 hematologic toxicity 7% during the concurrent phase. Label: weekly CBC during the concurrent phase. (Stupp 2005, Temodar label)	RCTUS label
Gemcitabine	Label (applies to radiation therapy in general; no SRS-specific data): “Not recommended for use in combination with radiation therapy.” “May cause severe and life-threatening toxicity when administered during or within 7 days of radiation therapy.” The supporting data are from thoracic conventional RT. (Gemcitabine for Injection label)	Label: More than 7 days apart. “Not recommended for use in combination with radiation therapy.” “May cause severe and life-threatening toxicity when administered during or within 7 days of radiation therapy.” “Excessive toxicity has not been observed when [gemcitabine] is administered more than 7 days before or after radiation.” (Gemcitabine for Injection label)	Not addressed in the sources used here	Label: Radiation recall reported. (Gemcitabine for Injection label)	US label
PaclitaxelHalf-life 13.1–52.7 h (mean values by dose and infusion length) label	Brain-specific hold: No published recommendation found	Brain-specific hold: No published recommendation found	Not addressed in the sources used here	Label and review: “Radiation pneumonitis has been reported in patients receiving concurrent radiotherapy.” Taxanes are among the most commonly reported recall agents. (Paclitaxel injection (Teva) label, Burris 2010)	US labelReview
DocetaxelHalf-life 116 h label	Brain-specific hold: No published recommendation found	Brain-specific hold: No published recommendation found	Not addressed in the sources used here	Label and review: “Radiation pneumonitis in patients receiving concomitant radiotherapy” and “radiation recall phenomenon” (postmarketing). (Docetaxel (Beizray) label, Burris 2010)	US labelReview
DoxorubicinAdriamycinHalf-life 20–48 h label	See class row	No published recommendation found No specific interval given. The recall review notes that risks may be minimized by a longer interval between RT completion and chemotherapy. (Burris 2010)	Not addressed in the sources used here	Label: “Can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver.” “Radiation recall... can occur in patients who receive doxorubicin hydrochloride after prior radiation therapy.” Additive cardiomyopathy risk with mediastinal RT. (Doxorubicin hydrochloride injection (Pfizer) label)	ReviewUS label
Methotrexate	See class row	Interval: No published recommendation found No published numeric interval found between high-dose methotrexate and WBRT. Standard regimens give HD-MTX induction followed by consolidation. Label: “The risk of leukoencephalopathy is increased with prior cranial radiation.” “Concomitant radiation therapy increases the risk of soft tissue necrosis and osteonecrosis.” (Methotrexate injection (Hospira) label) PCNSL guideline (EHA-ESMO): Consolidation WBRT 36–40 Gy “should be avoided or deferred in elderly patients because of the high risk of disabling neurocognitive impairment [I, D]”. Combined chemoradiotherapy is associated with disabling neurotoxicity, cumulative 5-year incidence 25%-35%. (Ferreri 2024 (EHA-ESMO))	Not addressed in the sources used here	Label: Methotrexate “can cause radiation recall”. (Methotrexate injection (Hospira) label)	US labelGuideline

Part III

Timing around surgery

Six scenarios: preoperative SRS to resection; postoperative cavity SRS or SRT; postoperative cranial RT, definitive and palliative; postoperative spine RT, with hardware and imaging; proton therapy and skull base; and re-operation after RT, with drug holds around surgery. Protocol windows from trials are shown apart from recommendations.

Preoperative SRS to resection

Preoperative SRS to resection. Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Published series and guidance
Asher 2014	“A median of 1 day elapsed between NaSRS and resection.” Dose reduction: median 14 Gy (range 11.6–18 Gy) prescribed to the 80% isodose. A published erratum (2014;89:696) was not checked. Not checked (Asher 2014)	Prospective and retrospective cohort
Patel 2016 (retrospective)	“Planned resection within 48 hours.” Preoperative vs postoperative SRS: median PTV margin 0 mm vs 2 mm; peripheral dose 14.5 Gy vs 18 Gy; preoperative SRS “used a dose-reduction strategy based on tumor size”. Retrospective comparison: lower leptomeningeal disease (3.2% vs 16.6%) and symptomatic RN (4.9% vs 16.4%) with preoperative SRS, both p=.010. (Patel 2016)	Retrospective cohort (2 institutions)
Prabhu 2019 (n=117)	“Surgery generally followed within 48 hours”; median 2 days. Dose “reduced approximately 10–20% from standard dosing”. Listed advantage: “reduced risk of RN due to smaller irradiated volume without need for cavity margin expansion”. No reason is given in the abstract. (Prabhu 2019)	Retrospective cohort
PROPS-BM cohorts	PROPS-BM (n=242): most patients single fraction, median 15 Gy; interval not given in the abstract. PROPS-BM (n=404): “median (IQR) of 2 (1–4) days before resection”; median 15 Gy in 1 fraction or 24 Gy in 3 fractions; “target margin expansion greater than 1 mm” was associated with ARE risk. (Prabhu 2021 (PROPS-BM), Prabhu 2023 (PROPS-BM))	Multicenter cohort
PROPS-BM, fractionation	Single fraction (median 15 Gy) vs 3–5 fractions (median 24 Gy in 3): 2-year cavity local recurrence 16.3% vs 2.9% (p=.004); propensity-matched 19.8% vs 3.3% (p=.003); no difference in adverse radiation effect, meningeal disease or survival. (Prabhu 2024 (PROPS-BM))	Multicenter cohort
PROPS-BM, dose	Historical “10% to 20% dose reduction”. Standard dose defined as ≥20 Gy for lesions ≤2 cm, ≥17 Gy for >2–3 cm and ≥14 Gy for >3–4 cm. No difference in 2-year local recurrence (16% vs 15%) or ARE (8% vs 6%) between standard and reduced dose (n=307); meningeal disease 2% (standard) vs 8% (reduced), p=.07. (Prabhu 2025 (PROPS-BM))	Multicenter cohort
Palmer 2022	Fractionated preoperative SRT, 24–25 Gy in 3–5 fractions; interval not given in the abstract. (Palmer 2022)	Retrospective cohort (multi-institutional)
ASTRO 2022 guideline	Preoperative SRS is “conditionally recommended as a potential alternative to postoperative SRS” (low quality). No interval given. From public-comment draft (Gondi 2022 (ASTRO))	Guideline (draft)
ASCO-SNO-ASTRO	Rec 4.1: “No recommendation regarding the specific sequence of therapy can be made” (order of surgery and RT); no interval given. (Vogelbaum 2022 (ASCO-SNO-ASTRO))	Guideline
Consensus or guideline interval	No published recommendation found No published consensus interval found. Published windows range from a median of 1–2 days (series) to the trial windows below. None of the sources read gives a reason for the interval.
Protocol windows (trial rules, not recommendations)
NRG-BN012 (phase III)	Arm II: “Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction.” Exclusion: “Planned administration of” cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors within the 3 days prior to, the day of, or within 3 days after the completion of SRS; “chemotherapy and immunotherapy outside of this window are allowed”. Protocol window (NRG-BN012 (NCT05438212))	Trial protocol (registry)
MD Anderson (phase III)	Arm description: “SRS within 30 days of randomization followed by surgery within 30 days.” The registry's detailed description gives 15 days for the first step (Group I: SRS within 15 days, then surgery within 15 days). Eligibility ≤4 cm for single fraction and ≤7 cm for multifraction. Protocol window (MD Anderson (NCT03741673))	Trial protocol (registry)
Mayo MC167C (randomized)	Arm B: SRS on day 1, then “Within 4 weeks, patients undergo surgery”. Protocol window (Mayo MC167C (NCT03750227))	Trial protocol (registry)
Canadian phase III	Surgery “within one week of SRS”; more than 1 week between preoperative SRS and resection is a minor deviation and more than 3 weeks a major one. More than 2 weeks between planning MRI and SRS is a major deviation. The trial was terminated. Protocol window (Das 2022, Canadian phase III (NCT04474925))	Trial protocolTrial protocol (registry)

Postoperative cavity SRS or SRT

Postoperative cavity SRS or SRT. Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Recommendations and published data
Review	“There is a general consensus to perform postoperative SRS/HSRT to the resection cavity within maximum four weeks after surgery with planning MRI acquired < 7 days before treatment.” The statement covers both SRS and HSRT. (Minniti 2021)	Review
RSS guideline	“The general consensus is to perform SRS within 4 weeks after surgery, with target planning MRI performed 7 days or fewer before SRS.” (Ladbury 2024 (RSS))	Guideline (case-based)
Guideline	ASCO-SNO-ASTRO: RT “shortly after surgery”; “No recommendation regarding the specific sequence of therapy can be made” (Rec 4.1); no day window given. (Vogelbaum 2022 (ASCO-SNO-ASTRO))	Guideline
Guideline	ASTRO 2022: no window given. From public-comment draft (Gondi 2022 (ASTRO))	Guideline (draft)
Fractionated SRT	No published recommendation found Fractionated cavity SRT: no fractionation-specific window found.
Single series	Longer surgery-to-SRS delay predicted recurrence (HR 1.625, p=0.003); “ideally within 3 weeks”. 12-month control fell from 87% to 61% beyond 3 weeks (as quoted in Minniti). (Iorio-Morin 2014, Minniti 2021)	Retrospective cohortReview
Single series	A delay over 30 days: local failure HR 4.525 (1.239–16.527); ROC threshold 30.5 days (AUC 0.637). The cohort included single-fraction SRS and fractionated SRT. (Yusuf 2018)	Retrospective cohort
Single series	Local recurrence 2.3% at ≤4 weeks, 14.5% at >4–8 weeks and 48.5% at >8 weeks; after 8 weeks local recurrence did not differ from patients who never received SRS (48.5% vs 50.0%, p=0.91). (Roth O'Brien 2021)	Retrospective cohort
Single series and meta-analysis	Sources disagree Single series (Iorio-Morin 2014, Yusuf 2018, Roth O'Brien 2021) Earlier SRS, within about 3–4 weeks, was associated with better local control. (Iorio-Morin 2014, Yusuf 2018, Roth O'Brien 2021) Meta-analysis (Nwankwo 2023) 22 studies, 1,338 patients (median timing 14.5–41 days), study-level meta-regression: median time to SRS was not associated with local failure (p=0.16) or survival (p=0.54). Longer median time was associated with lower regional failure (p=0.043; borderline, p=0.05, after adjusting for sex). Heterogeneity was significant. (Nwankwo 2023)	Retrospective cohortMeta-analysis
Cavity volume over time
Atalar 2013	Greatest volume change on postoperative days 0–3; no significant change up to 33 days. “No benefit of cavity shrinkage in waiting longer than the first 1 to 2 weeks” (68 cavities). (Atalar 2013)	Retrospective cohort
Jarvis 2012	Between surgery and SRS, 46.5% of cavities were stable, 23.3% collapsed by >2 cm³ and 30.2% grew by >2 cm³; 5 cavities showed local progression before SRS (43 cavities). Planning imaging “as close to SRS delivery as possible”; “delaying SRS after surgery does not offer the benefit of cavity collapse in most patients”. (Jarvis 2012)	Retrospective cohort
Shah 2016	Volume reduction 13% when the pre-SRS MRI was <1 month after the postoperative MRI vs 61% at ≥1 month (p=0.0003); 52% showed progression in the cavity wall in the interval; local recurrence not different at <1 vs ≥1 month (p=0.46, n=21; the full text's p=0.46 is for interval vs wall progression). (Shah 2016)	Retrospective cohort
Alghamdi 2018	Compared planning-MRI cavity with preoperative tumor volume (61 cavities). For tumors ≥3 cm, cavities imaged at 22–42 days were 28% smaller than the preoperative tumor (p=0.0007); cavities imaged before 21 days were on average larger than the tumor, most of all for small tumors. “Caution must be taken when treating cavities in the early (<21 days) interval after surgery as it may lead to irradiating more normal tissue especially in small tumors.” No early postoperative cavity baseline was measured. (Alghamdi 2018)	Retrospective cohort
Does waiting shrink the cavity	Sources disagree No volume benefit from waiting (Atalar 2013; Jarvis 2012) Most volume change in the first days; no benefit from waiting beyond the first 1 to 2 weeks; cavities as likely to grow as to collapse. (Atalar 2013, Jarvis 2012) Shrinkage with time (Shah 2016; Alghamdi 2018) Larger reduction with a longer interval, and early treatment may irradiate more normal tissue; Shah also found progression in the cavity wall before SRS in 52%, at similar rates with shorter and longer intervals. (Shah 2016, Alghamdi 2018)	Retrospective cohort
Protocol windows (trial rules, not recommendations)
NRG-BN012 (phase III)	Arm I: “Within 10–30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.” Protocol window (NRG-BN012 (NCT05438212))	Trial protocol (registry)
MD Anderson (phase III, preoperative vs postoperative)	Surgery, then SRS “within 30 days”. Protocol window (MD Anderson (NCT03741673))	Trial protocol (registry)
Mayo MC167C (randomized)	Arm A: SRS “within 2 weeks” of surgery. Protocol window (Mayo MC167C (NCT03750227))	Trial protocol (registry)
Canadian phase III	Postoperative SRS “within 3 weeks of surgery”; over 3 weeks is a minor deviation and over 6 weeks a major one. Protocol window (Das 2022)	Trial protocol
MD Anderson phase III (published)	SRS “within 30 days of surgery” (postoperative SRS vs observation). Protocol window (Mahajan 2017)	RCT

Postoperative cranial RT

Postoperative cranial RT. Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Definitive RT: adult glioma
EANO guideline	“Radiotherapy should start within 3–5 weeks after surgery” (citing Press 2020). Extent of resection: MRI “within 24–48 hours of surgery”. (Weller 2021 (EANO))	Guideline
ASTRO 2025 guideline	Expert opinion: “approximately 3 to 6 weeks after surgery may be most appropriate.” Some data favor starting <4 weeks after surgery, but a meta-analysis found no benefit in that range. After needle biopsy only, start <3 weeks from final pathology is preferred. A planning or diagnostic MRI within 3 weeks of starting RT is preferred. (Yeboa 2025 (ASTRO))	Guideline (expert opinion)
Registry	NCDB (n=30,414): no time point after week 5 changed OS. Starting at weeks 0–1, >1–2 and >2–3 was slightly worse (HR 1.18, 1.23 and 1.11). “Early initiation before 3 weeks may be detrimental.” (Press 2020)	Registry analysis
Trial	Stupp trial: the start window was not checked in the primary (only the abstract was read). Regimen as in the temozolomide row. Not checked (Stupp 2005)	RCT
Definitive RT: pediatric medulloblastoma and other tumors
Pediatric medulloblastoma	NCDB (n=1,338; ages 3–21, RT within 90 days): RT ≤3 weeks after surgery was associated with worse 5-year OS (72.5% vs 77.8–80.5%; aHR 1.72 vs 3.1–4 weeks). “>5 weeks but within 90 days... did not adversely impact OS.” Reason given: “Postoperative RT timing should allow for healing and the development of an optimal treatment plan.” Caveats: early-RT patients were younger, more often M1–3 and subtotally resected, and extent of resection was unknown in 63%. (Chin 2018)	Registry analysis
Meningioma	No published recommendation found Meningioma (EANO 2021, full text read): no surgery-to-RT interval given. The guideline notes “controversies” about timing, and says the value of early adjuvant RT after gross total resection of WHO grade 2 meningioma is unresolved. (Goldbrunner 2021 (EANO))	Guideline
Ependymoma	No published recommendation found Ependymoma (EANO 2018, full text read): no numeric interval; the pediatric recommendations table gives RT timing as “Postoperatively”. (Rudà 2018 (EANO))	Guideline
Adult medulloblastoma	Adult medulloblastoma (EANO-EURACAN 2019): full text not accessible; timing not verified. Not verified against the original (Franceschi 2019 (EANO-EURACAN))	Guideline
Palliative RT: WBRT after resection of brain metastases
Guideline window	No published recommendation found No numeric guideline window found.
ASCO-SNO-ASTRO	ASCO-SNO-ASTRO, clinical interpretation of Rec 4.1: local control requires RT (WBRT or SRS) to be “provided shortly after surgery”; no day window given. (Vogelbaum 2022 (ASCO-SNO-ASTRO))	Guideline
N107C	No published recommendation found N107C: start window not found in the main text or registry; the registry scan windows are in the N107C row below. (Brown 2017 (N107C))	RCT
Protocol windows (trial rules, not recommendations)
COG ACNS0331 (pediatric medulloblastoma)	“Within 31 days after definitive surgery, all patients begin therapy.” Protocol window (COG ACNS0331 (NCT00085735), Michalski 2021 (COG ACNS0331))	Trial protocol (registry)RCT (results of the registered protocol)
Patchell 1998 (RCT, surgery then WBRT vs surgery alone)	Protocol: radiotherapy “was started within 28 days after surgery”. Postoperative MRI 2–5 days after surgery, before randomization. Protocol window (Patchell 1998)	RCT
EORTC 22952 (WBRT)	Surgical patients were randomized within 4 weeks after surgery; the protocol allowed a maximum of 6 weeks between surgery (or radiosurgery) and WBRT (Kocher 2011, Methods). The registry phrase “adjuvant WBRT within 4 weeks after surgery” sits in the radiosurgery arm (Arm III). Protocol window (Kocher 2011 (EORTC 22952), EORTC 22952 (NCT00002899))	RCTTrial protocol (registry)
N107C (registry)	Postoperative scan ≤35 days before pre-registration and ≤28 days before randomization. Protocol window (N107C (NCT01372774))	Trial protocol (registry)

Postoperative spine RT

Postoperative spine RT. Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Palliative conventional RT after decompression
Patchell 2005 (RCT)	30 Gy in 10 fractions in both arms; surgery “followed by RT within 14 days”. The 14-day figure comes from the SCIRE evidence table (full table read); it is not in the abstract, and the trial full text was not read. Reported in secondary source (Patchell 2005; via SCIRE table)	RCT (secondary source)
Rades 2010	Matched pairs: RT “applied a median of 2 wk postoperatively” (SCIRE evidence table, full table read; the paper itself was not read). Reported in secondary source (Rades 2010; via SCIRE table)	Retrospective cohort (matched pairs) (secondary source)
Kumar 2020 (systematic review, expert opinion)	“An interval of 2 weeks, the minimum being 7 days, is optimum between RT-surgery or vice versa; this can be reduced further by postop-stereotactic body RT.” “Postop-RT has fewer wound complications versus preop-RT.” Of 20 studies reporting the interval, one found more complications at ≤7 days. Based on “published literature and expert opinions”; the evidence is called “insufficient”, so these are the review's expert-opinion conclusions. (Kumar 2020)	Systematic review
Itshayek 2010 (systematic review)	Only one retrospective study addressed it; it “suggested” that surgery within seven days of radiation increases the rate of postoperative wound complications. The interval “should be at least one week” in either direction. The reported RT-surgery interval in 9 studies was 5–21 days. (Itshayek 2010)	Systematic review
Wound complications by sequence	Sources disagree Ghogawala 2001 Major wound complications 32% with RT before surgery vs 12% with surgery first (p<0.05). (Ghogawala 2001) Ahluwalia 2024 No difference: 6.9% with preoperative RT, 4.4% with postoperative RT and 6.2% with none (p=0.802). Postoperative SBRT 5.6% vs EBRT 4.1%. (Ahluwalia 2024)	Retrospective cohort
Ahluwalia 2024, timing	Postoperative RT at a median of 28.7 days; time to RT did not differ between patients with and without wound complications (32.9 vs 29.0 days, p=0.391). (Ahluwalia 2024)	Retrospective cohort
SBRT after separation surgery
MSKCC series	“Within two to four weeks of separation surgery either single-fraction (24 Gy) or hypofractionated SRS was administered” (n=186). (Laufer 2013)	Retrospective cohort
Itshayek 2014 (systematic review and expert opinion)	“Animal studies and limited evidence in humans suggest that at least 1 week is indicated between SRS and surgery or surgery and SRS.” (Itshayek 2014)	Systematic review and expert opinion
Consensus survey	No published recommendation found Postoperative spine SBRT consensus (19 centers): no surgery-to-SBRT interval in the consensus items. (Redmond 2017)	Consensus survey
Contouring consensus	No published recommendation found Contouring consensus: no interval. It co-registers preoperative MRI, postoperative MRI, CT simulation and “CT myelogram when necessary”. No later (“2020”) postoperative contouring consensus was found. (Redmond 2017 (contouring))	Consensus
Guideline	No published recommendation found ESTRO 2024 spine SBRT guideline: no interval stated for postoperative SBRT. (Guckenberger 2024 (ESTRO))	Guideline
Society statements	No published recommendation found No ISRC or ISRS statement with a postoperative spine SBRT interval was found.
Hardware and planning imaging
ESTRO 2024	“CT myelogram may be used for delineation of the spinal cord and cauda equina in circumstances where metallic artifacts are interfering with the visualization.” (Guckenberger 2024 (ESTRO))	Guideline
Consensus survey	Hardware and scar “do not need to be included in CTV unless believed to be specifically at risk due to the surgical approach or direct involvement by tumor”. Cord delineation on T2 MRI “or a CT myelogram in cases of significant hardware artifact”. (Redmond 2017)	Consensus survey
Meta-analysis	Carbon fiber (CFR-PEEK) vs titanium, pooled: similar hardware failure (OR 1.73, p=0.47) and deep infection (OR 1.62, p=0.43); significantly lower artifact volume (SMD -1.36, p<0.001); local recurrence (OR 0.58) and mortality (OR 0.52) non-significantly lower. (Zhang 2026)	Meta-analysis
Phantom study	Titanium caused the largest error (Acuros XB underestimated the mean spinal canal dose by 7.2% at 6 MV); carbon fixation was comparable to no fixation. (Prochazka 2026)	Phantom study
Review	Review of artifact, contouring, dose calculation, IGRT and robustness with titanium and CFR-PEEK implants, for photons and protons. (Suda 2026)	Review

Proton therapy and skull base (chordoma, chondrosarcoma)

Proton therapy and skull base (chordoma, chondrosarcoma). Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Interval and planning imaging
Interval	No published recommendation found Surgery-to-RT interval: no published recommended interval found, including the PTCOG chordoma delineation consensus abstract, the 2026 global chordoma consensus abstract, the 2017 recurrent-chordoma consensus (full text read) and the PSI series. The 2015 chordoma consensus full text was not accessed. The PSI series (spinal) recommends “prompt adjuvant proton therapy”, without a number. (McDonald 2026 (PTCOG), Radaelli 2026, Stacchiotti 2017, Stacchiotti 2015, Murray 2020)	ConsensusRetrospective cohort (spinal)
PTCOG skull base chordoma	Delineation uses preoperative and postoperative imaging. CTV_High covers the “bone and mucosa of the entire primary tumor bed and any residual disease with median 5 mm margin”; CTV_Intermediate the “entire tumor bed with median 5 mm margin, the remainder of the clivus”, modified for decompressed “pushing” tumor. No postoperative MRI or CT timing is given in the abstract. (McDonald 2026 (PTCOG))	Consensus
Recurrent chordoma consensus	“CT may be a useful ancillary imaging modality, particularly to assess the bone involvement and when surgical implants or hardware limit MRI reliability.” (Stacchiotti 2017)	Consensus
Postoperative imaging timing	No published recommendation found No skull base postoperative imaging timing found.
Hardware and proton range (no skull base data found; the two studies are spinal)
PSI series (spinal)	Spinal chordoma or chondrosarcoma with pencil-beam protons (PSI, n=155): surgical stabilization in 39% remained significant on multivariate analysis for worse outcome, with gross residual disease and treatment before 2008. This is an association; stabilized patients may have had more extensive disease. The authors recommend “prompt adjuvant proton therapy”. (Murray 2020)	Retrospective cohort (spinal)
Phantom study (spinal)	Chordoma target phantom (3 mm setup, 3.5% range uncertainty): CFR-PEEK behaved like a normal spine for protons; titanium gave a larger difference in proton plan quality under uncertainty. (Shi 2022)	Phantom study (spinal)
Consensus (recurrent chordoma, all sites; spine given as the example)	Metal implants cause CT/MRI artifacts and add uncertainty to particle range; their presence “may be a key factor in deciding not to deliver curative RT or in deciding to deliver it with photons ... instead of particles” (level IV-B). Before debulking or separation surgery, consider modifying, removing or replacing metal implants with carbon fiber devices, in well-selected cases. No skull-base-specific statement was found. (Stacchiotti 2017)	Consensus

Re-operation after RT

Re-operation after RT. Rows are listed by source, not ranked. Protocol windows are trial rules, not recommendations.
Source	Recommendation, finding or window	Evidence type
Surgery in a previously irradiated field
Spine	Kumar 2020, expert-opinion conclusion: “If RT-surgery window is > 12 months, wound-complications rise.” Kumar also concludes that preoperative RT has more wound complications than postoperative RT (sources disagree; see Wound complications by sequence in Postoperative spine RT). Itshayek 2010: one retrospective study suggested more wound complications when surgery follows RT within 7 days. (Kumar 2020, Itshayek 2010)	Systematic review
Cranial	No published recommendation found Re-craniotomy after RT or SRS (for example, for necrosis): no published recommended interval found. Early salvage surgery straight after chemoradiation for glioblastoma: 2 wound complications in 17 patients (single series, no interval rule). (Yamaguchi 2026)	Retrospective cohort
Drug holds around any surgery (US labels)
Bevacizumab	“Withhold for at least 28 days prior to elective surgery. Do not administer Avastin until at least 28 days following major surgery and until adequate wound healing.” (Avastin label)	US label
Ramucirumab	Withhold 28 days before elective surgery. Do not give for at least 2 weeks after major surgery and until adequate healing. (Cyramza label)	US label
Ziv-aflibercept	At least 4 weeks before elective surgery and at least 4 weeks after major surgery. (Zaltrap label)	US label
Cabozantinib	Stop at least 3 weeks before surgery, including dental surgery. Do not give for at least 2 weeks after. (Cabometyx label)	US label
Lenvatinib	At least 1 week before and at least 2 weeks after. (Lenvima label)	US label
Everolimus (mTOR)	At least 1 week before and at least 2 weeks after. (Afinitor label)	US label

Summary

Where the evidence is thin or sources disagree

Where sources disagree

Each pair is shown side by side as published. The page does not choose between them.

Conflicting statements, side by side.
Question	One position	Other position
OligoCare and checkpoint inhibitors (extracranial SBRT)	Avoid the same day; at least 1 week only for anti-CTLA-4, alone or with anti-PD-(L)1. No 1-week pause reported for anti-PD-(L)1 alone. (via Liu 2023, Vandaele 2025)	Avoid the same day, with a minimum 1-week interruption before or after SBRT for all ICIs. (Shirai 2025: no interruption beyond the SBRT days.) (via Zayed 2023, Kepka 2024, Shirai 2025)
Brain SRS: washout	No washout (RSS 2024; Borius 2021). (Ladbury 2024 (RSS), Borius 2021)	Hold BRAF and MEK inhibitors at least 1 day around SRS (ECOG); at least 5 half-lives (Thariat 2014). ASTRO advises caution without numbers. (Anker 2016 (ECOG), Thariat 2014, Gondi 2022 (ASTRO))
Checkpoint inhibitors and radionecrosisDifferent measures: Martin (HR) and Kim (OR) compare ICI with no ICI; the 5% figures (Lehrer overall RN, Alswaiti grade 3 necrosis) are pooled rates without a non-ICI comparator, and Lehrer's OS benefit is not an RN outcome.	Higher RN with ICI (Martin 2018; Kim 2021, melanoma OR 2.35, not significant). (Martin 2018, Kim 2021)	Low pooled RN, about 5%, and an OS benefit with concurrent use (Lehrer 2019; Alswaiti 2026). (Lehrer 2019, Alswaiti 2026)
T-DXd and radionecrosis	More symptomatic RN with concurrent ADCs, SHR 4.31 (1.95–9.50), with no difference by agent (P = .74) (Lebow 2023). (Lebow 2023)	No RN with T-DXd, 0/29 (Chun 2026). Visani 2026 meta-analysis: “Current data does not suggest a similar risk signal for T-DXd or SG.” (Chun 2026, Visani 2026)
Postoperative SRS timingDifferent measures: Nwankwo is a study-level analysis of median timings (14.5–41 days), so it does not test delays beyond about 6 weeks; the single series compare individual patients by delay, including >8 weeks.	Single series favor 3–4 weeks or less (Iorio-Morin 2014; Yusuf 2018; Roth O'Brien 2021). (Iorio-Morin 2014, Yusuf 2018, Roth O'Brien 2021)	The 2023 meta-analysis found no association with local failure; longer median time was associated with lower regional failure (Nwankwo 2023). (Nwankwo 2023)
Spine RT before surgery and wound complicationsDifferent settings: Ghogawala used conventional RT in 1970–1996; Ahluwalia had 29 patients with preoperative RT, of whom 2 had events.	32% vs 12% major wound complications with RT first (Ghogawala 2001). (Ghogawala 2001)	No difference by sequence (Ahluwalia 2024). (Ahluwalia 2024)
Cetuximab with stereotactic RT	Combined stereotactic RT and cetuximab “can be recommended” in head and neck tumors (Thariat 2014). (Thariat 2014)	OligoCare, extracranial SBRT: pause anti-EGFR antibodies at least 1 week before or after SBRT (as reported by Vandaele 2025). (Kroeze 2023 (OligoCare); via Vandaele 2025)
Cavity volume between surgery and SRSDifferent measures: Atalar measured volume change by postoperative day (68 cavities) and Jarvis the share that grew or collapsed (43 cavities); Shah compared imaging intervals of <1 vs ≥1 month; Alghamdi compared the planning cavity with the preoperative tumor, not with an early postoperative cavity.	No volume benefit from waiting beyond the first 1 to 2 weeks; cavities as likely to grow as to collapse (Atalar 2013; Jarvis 2012). (Atalar 2013, Jarvis 2012)	Larger shrinkage with a longer interval (Shah 2016; Alghamdi 2018, against the preoperative tumor); Shah found progression in the cavity wall before SRS in 52%, at similar rates with shorter and longer intervals. (Shah 2016, Alghamdi 2018)

Where the evidence is thin

OligoCare primary text was not read. All drug-specific SBRT hold rules on this page are reported in secondary sources, and the secondary papers disagree on checkpoint inhibitors. OligoCare covers extracranial SBRT only; no equivalent intracranial consensus with drug-by-drug intervals was found. (Kroeze 2023 (OligoCare))
“Concurrent” is defined differently across studies. Often within 4 weeks; Lebow 2023 used SRT ≤7 days before or ≤21 days after the ADC, and the RSS guideline notes the difficulty of defining concurrent treatment because half-lives differ. (Ladbury 2024 (RSS), Lebow 2023)
T-DM1 is consistently reported as higher-risk with SRS: pooled grade ≥3 RN 17% (Salvestrini); clinically significant RN 39% (Stumpf); RN probability 30% (Id Said); 2 of 4 concurrent patients (Geraud). No consensus defines a safe T-DM1 or T-DXd interval around SRS. (Salvestrini 2023, Stumpf 2019, Id Said 2022, Geraud 2017)
CDK4/6, PARP, mTOR and other ADCs with brain RT. No consensus intervals; only small series or extracranial consensus.
Cytotoxic drugs with SRS. The gemcitabine label's >7-day rule is written for radiation therapy in general, but its data come from conventional thoracic RT. No other label gives an interval, and no brain-SRS-specific interval exists for capecitabine, taxanes, gemcitabine or anthracyclines. Radiation recall cannot be predicted, and no interval is defined. (Gemcitabine for Injection label, Burris 2010)
Methotrexate and WBRT. The label and guideline confirm greater neurotoxicity with cranial RT, but no numeric sequencing interval is published. (Ferreri 2024 (EHA-ESMO))
Postoperative SRS timing. The “within 4 weeks” consensus is review-level, not a graded guideline recommendation. (Minniti 2021)
Preoperative SRS to resection: no consensus interval exists. Series report medians of 1–2 days; trial windows range from within 7 days (NRG-BN012) to within 4 weeks (Mayo) and within 30 days (MD Anderson). None of the sources read gives a reason for the interval.
Meningioma, ependymoma and adult medulloblastoma: the meningioma and ependymoma guidelines (full text read) give no numeric interval; the adult medulloblastoma guideline full text was not accessible. Pediatric medulloblastoma: the COG protocol starts within 31 days, and NCDB data show worse OS when RT starts within 3 weeks. (Chin 2018)
WBRT after resection: no numeric guideline window. Trial windows: Patchell 1998 started RT within 28 days; EORTC 22952 allowed up to 6 weeks; the N107C start window was not found. (Patchell 1998, Kocher 2011 (EORTC 22952))
Spine: the Patchell 2005 “within 14 days” figure is second-hand; systematic reviews give at least 7 days (optimum 2 weeks); the MSKCC separation-surgery series used 2–4 weeks; no consensus body states a postoperative SBRT interval. (Kumar 2020, Laufer 2013)
Skull base protons: no surgery-to-RT interval and no skull-base-specific hardware statement found. The recurrent-chordoma consensus addresses metal implants and particle range for all sites; the other hardware evidence is spinal (a phantom study and one PSI series). (Stacchiotti 2017, Shi 2022, Murray 2020)
No published recommendation found: craniotomy after SRS; a steroid taper schedule tied to SRS timing; steroid dose before starting an ICI with SRS; a WBRT start window after metastasis resection.
Check before teaching: the ASTRO 2022 brain metastases statements were read from the public-comment draft on astro.org, and the “caution” sentence and the 30%-40% figure were not verified against the final guideline; the Lebow 2023 per-drug figures come from the authors' published reply, which was not located for this page; the Stupp start window was not checked in the primary; the NCCN CNS guideline was not publicly accessible and was not used. (Gondi 2022 (ASTRO), Lebow 2023)

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