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Prof. Dr. Mustafa Özdoğan · Medical Oncologist

Radionecrosis or Tumor Recurrence in Brain Metastases? How to Tell the Difference

Radionecrosis or Tumor Recurrence in Brain Metastases? How to Tell the Difference
In this article

A Growing Lesion on MRI After Radiosurgery: Radionecrosis or Tumor Recurrence?

After stereotactic radiosurgery (SRS) for brain metastases, an MRI months or years later can show an enhancing, swollen, growing lesion. It is either tumor recurrence or radionecrosis, damage to the irradiated brain tissue, and on imaging the two often look very similar. This article summarizes the place of MRI features, perfusion imaging, spectroscopy, amino acid PET, and biopsy in telling them apart; how radionecrosis risk rises with dose and volume; and the evidence on bevacizumab, surgery, and laser interstitial thermal therapy (LITT). For some primary tumors that can spread to the brain, see our articles on stomach cancer (in Turkish), colon and rectal cancer, and liver cancer; for the general picture, see stage 4 and metastasis. Key sources: Galldiks et al., Neuro Oncol 2019 (doi:10.1093/neuonc/noz003) and Minniti et al., Radiat Oncol 2011 (doi:10.1186/1748-717X-6-48).

24% / 10%share of lesions with radionecrosis after SRS: all / symptomatic (Minniti 2011, 310 lesions)
51% / 0%1-year radionecrosis risk: V12 above 10.9 cm³ / below 3.3 cm³ (Minniti 2011)
86% / 88%FET PET sensitivity / specificity (Ceccon 2017, 62 patients; mean TBR threshold 2.0)
77.5%neurological improvement with bevacizumab (Türkiye, 10 centers, 40 patients; mostly second line)
Quick Answer · Physician Summary
  • What was found: In a series of 310 metastases treated with SRS alone, radionecrosis occurred in 24% of lesions (10% symptomatic); the 1-year risk rose from 0% to 51% with the volume of brain receiving 12 Gy (V12).
  • Basis: Imaging accuracy rests on small, retrospective, mostly single-center studies. The RANO/PET report found amino acid PET consistently accurate, while FDG PET was highly variable (level 2 evidence).
  • Caution: No single test separates the two with certainty, and cut-offs such as perfusion thresholds vary between studies. MRI clues, time since SRS, and dose-volume are read together; if doubt remains, biopsy or surgery is considered.
  • In practice: Do not expect a growing lesion to be labeled “recurrence” or “necrosis” right away; ask about MRI features, time since SRS, V12, and systemic therapy. The decision belongs to the tumor board.

Why is this distinction hard, and why does it matter?

SRS delivers a high dose to a small target; besides tumor cells, nearby blood vessels and brain tissue can be affected. Radionecrosis is tissue damage that can appear months or years later in the irradiated area; on MRI it enhances like a recurrence, causes swelling, and can grow. That is why no single visual or numeric sign can separate the two with certainty.

It matters because the treatments differ: recurrence usually calls for repeat SRS, surgery, or a change in systemic therapy, whereas radionecrosis is managed with steroids and, if needed, bevacizumab or surgery. A wrong label can lead to an unnecessary operation or a delayed treatment.

The key questions are: how long after SRS did the lesion grow, what do MRI and advanced imaging show, did dose and volume raise the risk, and where does systemic therapy (for example immunotherapy) stand? No single test answers these; reading the findings together does.

Is this a new problem?

No; it has been debated for years as radiosurgery became widespread. What has changed is the testing of advanced MRI methods and amino acid PET, the quantification of dose-volume risk, and the publication of a standard PET response framework:

2009
Perfusion MRI study
The power of perfusion MRI to separate necrosis from recurrence in lesions growing after SRS was tested in a series of 34 lesions (Hoefnagels et al.).
2011
V12 and radionecrosis risk
In a series of 310 lesions treated with SRS, radionecrosis risk rose markedly with the volume of brain receiving 12 Gy (Minniti et al.).
2019
RANO/PET report
The report stated that amino acid PET should be preferred over FDG PET, while noting that the evidence is limited (Galldiks et al.).
2024
Bevacizumab series from Türkiye
A multicenter series of 40 patients from 10 centers reported clinical improvement after bevacizumab (Zoto Mustafayev et al.).
2025
PET RANO BM 1.0 and a current review
The first standard response criteria for brain metastases based on amino acid PET were published (Albert et al.); methods for telling the two apart were reviewed again (Lasocki et al.).

How can radionecrosis be told apart from tumor recurrence in brain metastases?

No single test does it: the distinction comes from reading MRI features (thin rim or nodular enhancement, diffusion, susceptibility sequences), time since SRS, and dose-volume together. When doubt remains, perfusion MRI, MR spectroscopy, and especially amino acid PET add confidence; if it persists, biopsy or surgery is considered. The tumor board decides.

How do radionecrosis and recurrence differ on MRI?

On contrast-enhanced T1 images both often look like a lesion with an enhancing rim. The table below summarizes tendencies described in a 2025 review and other sources; none of them diagnoses on its own.

Feature Leans toward radionecrosis Leans toward tumor
Contrast enhancement Thin rim-shaped enhancement Distinct nodular enhancement
Spread and shape Enhancement crossing anatomical boundaries, clustered lesions, change in shape —
Diffusion Central restriction matching the necrotic core* —
Susceptibility sequences Small, clustered susceptibility foci Absence of these foci raises concern for tumor
Perfusion (rCBV) Low High
MR spectroscopy Low NAA, choline, and creatine High choline and choline/NAA; raised lipid and lactate
Amino acid PET Low uptake (below threshold) High uptake (above threshold)

A dash means the source describes only one direction. *Cell-rich tumors, coagulative necrosis from bevacizumab, and intralesional hemorrhage can mimic central restriction. Perfusion and spectroscopy results depend on the analysis method and threshold. The figure below shows how these inputs combine.

Figure 1 · Four inputs read together

Simplified schematic; not to scale

MRI pattern rim or nodule Perfusion / spectroscopy rCBV, choline Amino acid PET FET, FDOPA, MET Timing and dose months after SRS, V12 Likelihood of radionecrosis / recurrence a combination of findings, not one test if unclear, tumor board and possibly biopsy
How to read it: The four boxes at the top show the inputs read together: MRI pattern, perfusion and spectroscopy, amino acid PET, and the time and dose since SRS. The arrow means they are weighed together, and the bottom box shows that the result is a likelihood, not a definite label; if doubt remains, the tumor board and, if needed, biopsy come in. The schematic is derived from the text and contains no new data.

How common is radionecrosis, and at what dose?

The Minniti series: risk rises with volume

Among 310 metastases in 206 patients treated with SRS alone (Minniti et al. 2011), radionecrosis developed in 24% of lesions (75/310); 10% were symptomatic and 14% asymptomatic. In symptomatic radionecrosis the median onset was about 11 months (range 2–32). Risk rose markedly with the volume of brain receiving 12 Gy (V12): the 1-year risk was 0% below 3.3 cm³, 16% at 3.3–5.9 cm³, 24% at 6.0–10.9 cm³, and 51% above 10.9 cm³. The authors noted that a V12 above about 8.5 cm³ corresponded to a 1-year risk above 10%. Severe neurological complications (RTOG grade 3–4) occurred in 12 patients (5.8%).

Minniti 2011: 1-year radionecrosis risk by V12

Percent. Each bar is one of four slices of the SRS-treated metastases, split by V12.

V12 below 3.3 cm³
0%
V12 3.3–5.9 cm³
16%
V12 6.0–10.9 cm³
24%
V12 above 10.9 cm³
51%

Single-center retrospective series; lower is better. There is a small numerical inconsistency between the abstract and the results section of the paper (the 51% from the results was used instead of the 47% in the abstract).

Does immunotherapy raise the risk of radionecrosis?

Immune checkpoint inhibitors (ICI) are increasingly combined with SRS, and the question is whether risk goes up. In a multicenter retrospective series of 2,540 brain metastases in 395 patients with non-small cell lung cancer (Lehrer et al. 2023; single-fraction SRS, median margin dose 19 Gy), the 1-year cumulative incidence of radionecrosis was 4.8% overall (3.8% symptomatic); it was 3.8% with concurrent ICI and 5.3% with nonconcurrent ICI. In multivariable analysis the significant predictor was a V12 of 10 cm³ or more; the authors concluded that ICI did not increase radionecrosis risk and that ICI can be continued even if radionecrosis develops. This series had no comparison group without ICI.

1-year cumulative radionecrosis incidence after ICI + SRS

Lehrer 2023, 395 patients; any grade. Values are percent.

All patients

95.2%

Concurrent ICI

96.2%

Nonconcurrent ICI

94.7%
radionecrosis (any grade)no radionecrosis

The “no radionecrosis” share is calculated as the remainder to 100. There is no comparison group without ICI; the series is retrospective. Symptomatic radionecrosis: 3.8% in all patients, 3.8% with concurrent and 3.6% with nonconcurrent ICI.

How well does advanced imaging separate them?

According to the RANO/PET working group report (Galldiks et al. 2019), amino acid PET shows consistently high accuracy in separating treatment-related change from recurrence (level 2 evidence), whereas the accuracy of FDG PET varies widely between studies (sensitivity 40–95%, specificity 50–100%). For amino acid PET, individual studies in the report had sensitivity of 74–90% and specificity of 73–100%; thresholds depend on the tracer (for example a mean TBR of 2.0 for FET). The evidence is mostly retrospective, single-center, and not confirmed by histology in every case.

Two amino acid PET studies from the RANO/PET report

Percent. Light bars are FET PET (62 patients), dark bars FDOPA PET (42 patients).

FET · sensitivity
86%
FET · specificity
88%
FDOPA · sensitivity
90%
FDOPA · specificity
92%

Single-center retrospective studies (Ceccon 2017; Cicone 2015); thresholds were a mean TBR of 2.0 for FET and a maximum TBR of 1.6 for FDOPA. Higher is better. Because the patient groups and tracers differ, the bars do not answer which tracer is better. In some studies the report’s text and table disagree; table values were used.

There is no single firm threshold for perfusion MRI. In a series of 34 lesions growing after SRS (Hoefnagels et al. 2009; 20 recurrences, 14 necroses; histology in only 6 lesions), a relative cerebral blood volume (rCBV) above 1.85 relative to gray matter gave a sensitivity of 70.0% and a specificity of 100%; above 2.00 relative to white matter it gave 85.0% and 71.4%. In other words, sensitivity and specificity shift with the reference tissue and threshold.

Hoefnagels 2009: rCBV for recurrence vs necrosis

Percent. Light bars use gray-matter-referenced rCBV, dark bars white-matter-referenced rCBV.

rCBV (gray matter, >1.85) · sensitivity
70.0%
rCBV (gray matter, >1.85) · specificity
100%
rCBV (white matter, >2.00) · sensitivity
85.0%
rCBV (white matter, >2.00) · specificity
71.4%

Single center, 34 lesions; the reference diagnosis was mostly clinical and radiological follow-up (histology in 6 lesions). Higher is better. These thresholds cannot be transferred directly to other centers.

On MR spectroscopy, choline and the choline/NAA ratio rise in tumor, whereas NAA, choline, and creatine fall in irradiated tissue; these methods also depend on the analysis and the threshold. FDG PET is limited by the high uptake of normal brain; for general information on PET-CT see our article. The new PET RANO BM 1.0 criteria (Albert et al. 2025), the first standard response framework based on amino acid PET, may help separate treatment effect from true progression.

The decision path when doubt remains, and how radionecrosis is treated

The first step in symptomatic radionecrosis is a corticosteroid. For patients who do not respond to steroids or cannot take them because of side effects, the Dutch national guideline suggests discussing bevacizumab (7.5 mg/kg every 2–3 weeks, 4 cycles) in a multidisciplinary board; surgery and LITT are also options. Figure 2 summarizes a path to follow when MRI remains unclear.

Figure 2 · Decision path when MRI is unclear

Simplified schematic; the decision is made with the team for each patient

Is MRI alone distinctive enough? rim/nodule, diffusion, susceptibility Yes: picture is clear treat accordingly; close MRI follow-up continues No: unclear perfusion MRI or amino acid PET; repeat MRI Still unclear or worsening biopsy or resection is considered; the tumor board decides
How to read it: First ask whether MRI alone is distinctive enough (top box). If yes (right), treatment is planned accordingly and followed with MRI. If no (left), perfusion MRI or amino acid PET is requested and MRI is repeated at a short interval. The bottom box shows that if doubt persists or the lesion worsens, biopsy or resection is considered and the tumor board decides. The schematic is derived from the text and contains no new data.

Biopsy, surgery, and laser interstitial thermal therapy (LITT)

If imaging stays unclear and the lesion keeps growing or causing symptoms, biopsy or resection is considered for pathological confirmation; surgery can also relieve mass effect. For the general logic of biopsy and, as an example, stomach biopsy, see those articles; for the wording of reports see terms in pathology reports. In a retrospective single-center comparison of LITT (Sujijantarat et al. 2020; 25 LITT and 13 bevacizumab patients with radionecrosis), median overall survival was 24.8 months with LITT and 15.2 months with bevacizumab (p = 0.003); at 1 year, lesion volume fell by a median of 64.7% with LITT, whereas with bevacizumab it rose by a median of more than 100% (p = 0.010). The authors note it is unclear whether this reflects treatment effect or selection bias.

Bevacizumab: what does the evidence say?

Randomized evidence for bevacizumab in radionecrosis is very limited, and two of the studies include no patients with brain metastases; a multicenter series from Türkiye is also shown below. Placing different patient groups side by side directly would not be correct.

Study Comparison and patients Finding Comment
Levin 2011 (randomized) Bevacizumab vs placebo; 14 patients (head-and-neck tumors, meningioma, glioma; no brain metastases) All 7 patients on bevacizumab improved neurologically, none on placebo did; 5 of the 7 on placebo worsened Very small sample; serious adverse events in 2 of 12 in the bevacizumab arm
Xu 2018 (randomized) Bevacizumab vs methylprednisolone; 112 patients with nasopharyngeal carcinoma (no brain metastases); open-label Clinical improvement 62% vs 43%; at least 25% edema reduction at month 2 in 66% vs 32% Serious adverse events in 1 patient per arm (2%)
Zoto Mustafayev 2024 (Türkiye) 10 centers, retrospective; symptomatic radionecrosis after SRT, 40 patients Neurological improvement 77.5% (complete 45%, partial 32.5%) No control arm; given as second line in 72.5% of patients

The Dutch guideline group notes that two randomized studies showed bevacizumab reduces radiological radionecrosis, but because these studies included no patients with brain metastases, had small samples, and had crossover or randomization problems, they were not taken into the formal evidence synthesis. Superiority over steroids for symptom control has not been shown. In non-randomized series, clinical improvement ranged from 50–100%, the share of patients whose steroid dose could be reduced from 76–100%; recurrence after stopping bevacizumab from 6–100% (median 19%), and grade 3–4 adverse events from 0–24%.

Xu 2018: bevacizumab vs methylprednisolone (radionecrosis after nasopharyngeal cancer)

Percent. Colored bars are bevacizumab, gray bars methylprednisolone (comparison arm).

Clinical improvement · bevacizumab
62%
Clinical improvement · methylprednisolone
43%
At least 25% edema reduction (month 2) · bevacizumab
66%
At least 25% edema reduction (month 2) · methylprednisolone
32%

Arms of the same study; 112 patients, open-label randomized trial; no patients with brain metastases. Higher is better. Values are taken from the summary in the Dutch national guideline.

In a multicenter retrospective series from Türkiye (Zoto Mustafayev et al. 2024), clinical response in 40 patients with symptomatic radionecrosis was distributed as follows:

Türkiye 2024: clinical response after bevacizumab

Percent; 40 patients. The “no response” share is patients outside complete and partial response.

Any improvement
77.5%
Complete response (no further treatment needed)
45%
Partial response (steroids or repeat bevacizumab needed)
32.5%
No response (surgery needed)
22.5%

Single-arm retrospective series; no control group. The “no response” share is calculated by subtracting from 100. For the improvement bars higher is better, for no response lower is better. Bevacizumab was first-line in 27.5% and second-line in 72.5% of patients.

In 10 patients of the same series with serial MRI, median edema volume was 75.9 cc at radionecrosis, rose to 113.65 cc after steroids (39.8% increase, p = 0.074), and fell to 19.5 cc after bevacizumab (p = 0.041). The number of patients is very small; the authors call for a prospective study. Bevacizumab carries bleeding and thromboembolism risks: if a serious sign of bleeding appears (for example blood in the stool), seek care immediately.

Steroids and side effects: what to expect

In the Minniti series 34 patients became steroid-dependent and 16 took high-dose dexamethasone for more than 4 months, so the burden of long-term steroids is also weighed. During steroid treatment side effects such as fatigue can appear; for drug and food interactions, an interactions guide is useful.

The state of disease outside the brain also shapes the decision: if systemic therapy is ongoing, radionecrosis management is planned together with the oncology team. For targeted therapy, see next-generation sequencing (NGS) and why the location of a mutation matters; for access to new drugs, the access map of FDA-approved new cancer drugs in Türkiye; and, where suitable, clinical trials.

Can radionecrosis and recurrence coexist?

In practice the two are not always cleanly separated: one lesion can contain both necrosis and tumor tissue, and “one or the other” can be misleading. In such cases, rather than relying on one test, MRI, PET, and the clinical course are followed together; in difficult cases a second opinion is reasonable.

Limits of the current evidence

Most imaging-accuracy studies are small, retrospective, and single-center, and the reference diagnosis is often clinical follow-up rather than histology. Thresholds vary with the scanner, analysis method, and tracer, so a threshold from one publication may not give the same result elsewhere. Criteria such as PET RANO BM 1.0 are a step toward standardization; access to amino acid PET in Türkiye could not be verified for this article.

How to read the results

Strengths

  • The rise of radionecrosis risk with dose and volume (V12) was seen in the same direction in both the Minniti and Lehrer series.
  • The RANO/PET report finds consistently high accuracy for amino acid PET and recommends amino acid tracers over FDG PET.
  • MRI clues (thin rim, nodular enhancement, susceptibility foci) can be obtained from standard MRI in daily practice.
  • For bevacizumab there are randomized studies and a multicenter series from Türkiye; the side-effect profile is defined.

Points to watch

  • No single test: MRI, perfusion, spectroscopy, and PET each fail to separate the two with certainty on their own.
  • Thresholds do not transfer: rCBV and TBR thresholds vary with the study, scanner, and tracer.
  • Weak evidence: Most accuracy data are retrospective and single-center; not every case has histology.
  • Indirect bevacizumab evidence: The randomized studies include no patients with brain metastases; shrinkage under bevacizumab can be pseudoresponse and complicates response assessment on imaging.
  • Limited immunotherapy data: The Lehrer series has no control group without ICI.

Practical suggestions for patients and families

If an MRI after SRS reports a growing lesion, these steps may help:

  • Ask how many months after SRS the lesion grew, how it changed from earlier MRIs, and for the dose-volume information (for example V12).
  • Ask which findings the radiologist assessed (rim or nodular enhancement, diffusion, susceptibility foci).
  • If there is doubt, ask whether perfusion MRI, MR spectroscopy, or amino acid PET is appropriate and at which center it can be done.
  • Ask whether the decision is made at a tumor board (radiation oncology, neurosurgery, medical oncology, neuroradiology); request a second opinion if needed.
  • Clarify the state of disease outside the brain too; for example, if the source is stomach or colon, endoscopic follow-up and how stomach cancer looks on endoscopy complete the picture. For systemic treatment side effects see diarrhea and easing side effects with nutrition.
  • Seek care without delay for a new or worsening headache, a seizure, weakness in an arm or leg, or speech difficulty.
Common misconceptions
  • “An enhancing lesion that grows must be recurrence.” No. Radionecrosis can look exactly like this; telling them apart requires reading the findings together.
  • “PET or perfusion gives the final answer.” No. Accuracy can be high but it is not absolute; thresholds vary with center and method.
  • “Radionecrosis always causes symptoms.” No. In the Minniti series more than half of the lesions with radionecrosis (44 of 75) were asymptomatic.
  • “Bevacizumab suits everyone.” No. Because of bleeding and thromboembolism risk, the Dutch guideline advises against starting it in patients with bleeding risk, uncontrolled hypertension, or significant cardiovascular history.
The situation in Türkiye
  • There is a multicenter series from Türkiye (Zoto Mustafayev et al., BMC Cancer 2024; 10 centers, 40 patients): bevacizumab was mostly given as second line and neurological improvement of 77.5% was reported. Being retrospective and uncontrolled, it cannot show the true effect.
  • We could not verify for this article whether the (off-label) use of bevacizumab for radionecrosis is reimbursed by SGK. For general rules see SGK cancer drug reimbursement conditions, and for unreimbursed drugs cancer drugs licensed in Türkiye but not paid by SGK.
  • We could not verify how access to amino acid PET (FET, FDOPA, MET) and MR spectroscopy varies between centers in Türkiye; ask your treating team and the nuclear medicine center.
  • We could not verify which centers in Türkiye perform LITT; the LITT data above reflect the experience of a single center abroad.

Frequently asked questions

What is radionecrosis and when does it appear?
Radionecrosis is late damage to irradiated brain tissue; on MRI it can form an enhancing, swollen, growing lesion that looks like recurrence. In the Minniti series it occurred in 24% of lesions after SRS; in symptomatic cases the median onset was about 11 months. Risk rises as the volume of brain receiving 12 Gy grows.
Can MRI alone separate radionecrosis from recurrence?
Often it is not enough on its own. Thin rim enhancement, enhancement crossing anatomical boundaries, and small clustered susceptibility foci lean toward radionecrosis; distinct nodular enhancement and the absence of those foci lean toward recurrence. When doubt remains, perfusion MRI and amino acid PET add confidence.
How accurate is amino acid PET?
In the RANO/PET report, amino acid PET accuracy was consistently high (level 2 evidence); individual studies had sensitivity of 74–90% and specificity of 73–100%. The evidence is mostly retrospective and single-center; FDG PET accuracy is far more variable.
How is radionecrosis treated?
The first step in symptomatic radionecrosis is a corticosteroid. If there is no response or steroids cannot be used, bevacizumab (7.5 mg/kg every 2–3 weeks, 4 cycles) is discussed in a multidisciplinary board; surgery and LITT are options too. Bleeding and thromboembolism risks of bevacizumab are taken into account.

Glossary

Radionecrosis
Damage to irradiated brain tissue that develops months or years later; on MRI it can look like recurrence.
SRS (stereotactic radiosurgery)
Precise radiation in which a high dose is delivered to a small target in one or a few sessions.
V12
The volume of brain (cm³) receiving 12 Gy or more; associated with radionecrosis risk.
Perfusion MRI (rCBV)
MRI that measures blood flow in tissue; relative cerebral blood volume is usually high in recurrence.
MR spectroscopy
An MRI method that measures tissue chemistry (choline, NAA, lipid, lactate).
Amino acid PET
PET that shows tumor metabolism using amino acid tracers (FET, FDOPA, MET).
TBR
The ratio of lesion uptake to normal brain uptake; the threshold varies with the tracer.
Bevacizumab
A drug that blocks blood vessel formation (VEGF); used to reduce edema in radionecrosis.
LITT
A minimally invasive surgical method that treats a lesion by heating it with a laser.

DROZDOGAN Academy Commentary

Reading “lesion has grown” on a post-SRS scan can be frightening. It does not always mean recurrence; radionecrosis can give the same picture, and telling them apart requires several findings to be read together.

⚡ Why it matters

Recurrence and radionecrosis need different treatments; a wrong label can lead to an unnecessary operation or a delayed treatment. Because the images look alike, this distinction is a clinically important uncertainty.

✅ Strengths

There are consistent findings on the dose-volume relationship (V12), MRI clues, and amino acid PET; the new PET RANO BM 1.0 criteria bring standardization.

⚠️ Limitations

Accuracy data come from small, retrospective, single-center studies; thresholds do not transfer; randomized evidence for bevacizumab includes no patients with brain metastases; the immunotherapy data have no control group; access to advanced imaging in Türkiye was not verified.

🩺 In practice

For a growing lesion we first look at timing (months since SRS), dose-volume information, and MRI clues, and request perfusion or amino acid PET when needed. The decision comes not from one scan but from weighing the findings together at the tumor board. For the idea of monitoring recurrence with a blood test after surgery, see our article on post-operative ctDNA testing; we could not verify a standard use for telling radionecrosis apart.

❓ Open questions

Can shared, transferable thresholds be set for perfusion and amino acid PET? How will PET RANO BM 1.0 change recurrence-versus-necrosis decisions in daily practice? How will the link between immunotherapy and radionecrosis look in controlled studies?

Bottom line: No single test answers whether it is radionecrosis or recurrence; MRI clues, timing, dose-volume, and, when needed, perfusion or amino acid PET are read together, and with persistent doubt biopsy and the tumor board step in.

Transparency Note
  • This article was prepared in November 2026.
  • It is based on abstracts of the publications listed in the references, open-access pages, and secondary summaries; because full texts (especially on PubMed and some journal sites) could not be accessed, some details were taken from abstracts.
  • The “no radionecrosis” shares were calculated as the remainder to 100 and the “no response” share by subtraction from 100; the bar widths are ours. The statements that “radionecrosis and recurrence can coexist” and that “biopsy/resection is considered when unclear” are general clinical knowledge not stated directly in the sources. The Academy commentary is our own.
  • In the Minniti paper there is a small inconsistency between the abstract (47%) and the results section (51%); the results section was used. In some studies the text and table of the RANO/PET report disagree; table values were used. Levin 2011 and Xu 2018 data come from the summary in the Dutch national guideline. Information about Türkiye (SGK, PET and LITT access) should be confirmed before publication.
  • The comparisons in the charts are arms of the same study or within one study; patient groups, tracers, and thresholds from different studies cannot be compared directly. The schematics are derived from the text and contain no new data.
  • This article is not medical advice; consult your physician for diagnosis and treatment decisions.

References

  1. Minniti G, Clarke E, Lanzetta G, et al. Stereotactic radiosurgery for brain metastases: analysis of outcome and risk of brain radionecrosis. Radiat Oncol 2011;6:48. doi:10.1186/1748-717X-6-48
  2. Galldiks N, Langen KJ, Albert NL, et al. PET imaging in patients with brain metastasis: report of the RANO/PET group. Neuro Oncol 2019;21:585-595. doi:10.1093/neuonc/noz003
  3. Albert NL, Galldiks N, Berghoff AS, et al. RANO criteria for response assessment of brain metastases based on amino acid PET imaging (PET RANO BM 1.0). Nat Med 2025. doi:10.1038/s41591-025-03633-7
  4. Lasocki A, Sia J, Stuckey SL. Differentiation between radiation necrosis and true tumour progression after radiotherapy to intracranial metastases. J Med Imaging Radiat Oncol 2025;69:414-424. doi:10.1111/1754-9485.13847
  5. Hoefnagels FWA, Lagerwaard FJ, Sanchez E, et al. Radiological progression of cerebral metastases after radiosurgery: assessment of perfusion MRI for differentiating between necrosis and recurrence. J Neurol 2009;256:878-887. doi:10.1007/s00415-009-5034-5
  6. Madhugiri VS, Almeida ND, Goulenko V, et al. Neuroimaging after brain radiotherapy and radiosurgery. Practical Neurology, March 2026. practicalneurology.com
  7. Lehrer EJ, et al. (senior author Ahluwalia MS). Immune checkpoint inhibition with single-fraction stereotactic radiosurgery in non-small cell lung cancer brain metastases (395 patients, 2,540 metastases). J Neurooncol 2023. doi:10.1007/s11060-023-04413-4 ; summarised by The ASCO Post
  8. Dutch national guideline, brain metastases: bevacizumab for radionecrosis (summarises Levin 2011 and Xu 2018 randomized trials). richtlijnendatabase.nl
  9. Levin VA, Bidaut L, Hou P, et al. Randomized double-blind placebo-controlled trial of bevacizumab therapy for radiation necrosis of the central nervous system. Int J Radiat Oncol Biol Phys 2011;79:1487-1495.
  10. Sujijantarat N, Hong CS, Owusu KA, et al. Laser interstitial thermal therapy (LITT) vs. bevacizumab for radiation necrosis in previously irradiated brain metastases. J Neurooncol 2020;148. doi:10.1007/s11060-020-03570-0
  11. Zoto Mustafayev T, Turna M, Bolukbasi Y, et al. Clinical and radiological effects of bevacizumab for the treatment of radionecrosis after stereotactic brain radiotherapy. BMC Cancer 2024;24. doi:10.1186/s12885-024-12643-6
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