What the Study Found
- A whole-body PET (positron emission tomography) scan detected 98% of the bone marrow disease that biopsies also found.
- When the scan came back clear, it was right 100% of the time, so about three-quarters of the group could safely skip the biopsy.
- A positive scan was less certain: it was right only about 90% of the time, so suspicious results still need confirmation.
- Children whose marrow disease showed up on both tests fared worse than those flagged by the scan alone, hinting at more advanced disease.
The needle goes in at an angle through skin and muscle, into the hip bone, until it reaches the marrow inside, and children with a rare cancer called rhabdomyosarcoma have often had to endure it twice, once on each side, just to find out whether the disease has spread there. A scan already used to find the tumor itself, it turns out, can often replace that needle. A clear image, a large international study found, is trustworthy enough on its own to close the question, but a suspicious one still needs a second look, because bruised or inflamed marrow can light up almost exactly the way cancer does. That asymmetry, more than any single number in the results, is the discovery a research team spent years gathering enough patients to prove.
Rhabdomyosarcoma is rare, but it is the most common soft-tissue cancer in children and teenagers, arising from tissue that would otherwise go on to become muscle. Whether the disease has reached the bone marrow changes everything about staging and treatment: three-year, event-free survival runs just 14% to 17% for children with marrow or bone involvement, compared with 34% to 37% for those whose metastases spare it.
The historical standard has been the bone marrow aspirate and biopsy, sampled from both hip bones on the assumption that a needle anywhere in the marrow will catch any cells that have spread there. Rhabdomyosarcoma doesn’t always infiltrate marrow evenly, though, and a biopsy only tests the two spots where the needle actually goes in, so patchy disease elsewhere in the skeleton can be missed. The scan works differently: patients get a small dose of a radioactive sugar tracer called FDG (short for fluorodeoxyglucose), and because cancer cells are hungry for fuel, they soak up more of it than healthy tissue does and light up on the resulting image, the same principle behind PET imaging described in the National Cancer Institute’s own patient guide to rhabdomyosarcoma. The same PET scan, in other words, that first spots the tumor can in principle survey the entire skeleton for the same telltale glow, without a needle anywhere near the hip.
Getting a biopsy in a child usually means general anesthesia, plus the ordinary risks of bleeding or infection that come with any needle procedure, and a study tracking repeated bone marrow procedures under anesthesia in children with cancer found real, if usually minor, complications along the way, so doctors have wanted a less invasive alternative for years. Nobody had tested the swap in a large enough group of children with this specific cancer, though, until an international team pooled records from patients treated across Europe and North America.
Putting the Scan to the Test
The researchers, working through a consortium called INSTRuCT, gathered records on 313 children and young adults with rhabdomyosarcoma from 18 hospitals, everyone of whom had both a bone marrow biopsy and a PET scan done before starting chemotherapy. Of those, 301 had tumors that lit up clearly enough on the scan to be usable for the main comparison, called FDG-avid tumors in the paper’s own terms. Because every patient in the group had both tests, the team could compare them head to head rather than relying on separate studies with different patients.
Simone Hettmer, a pediatric oncologist at University Medicine Halle in Germany and the study’s senior author, has watched the limits of the needle approach up close. “Bone marrow sampling has, until now, been considered the gold standard for determining whether the tumor has spread to a patient’s bone marrow. However, this procedure is painful and only provides information about the situation at the site of the puncture. Patchy bone marrow involvement may therefore be missed,” she says.
Across the 301 patients with FDG-avid tumors, the scan and the biopsy agreed almost every time: both flagged marrow disease in 54 patients, and both came back clear in 222, for an overall match rate that left the scan looking almost as trustworthy as the needle it might replace. The scan caught marrow disease in another 24 patients whose biopsy missed it, and it detected 98% of every case biopsy itself confirmed, a sensitivity high enough that a clear PET result carried a 100% chance of truly being clear, at least in this group. The needle still won exactly once: a single patient had tumor cells on biopsy that the scan never picked up. The tradeoff sits on the other side of the ledger, where the scan was less disciplined about calling something abnormal that was not: specificity came in at 90%, meaning a meaningful share of positive results reflected something other than cancer, most likely inflammation, injury, or ordinary marrow activation rather than tumor itself. Even genuine marrow disease was not always straightforward to picture, since about a third of the FDG-avid cases involved only a handful of scattered spots, one to five foci, rather than a single obvious mass.
Where the Needle Still Wins
The two positive groups were not clinically identical, either: children whose marrow disease was confirmed by both the scan and biopsy had a hazard of death nearly seven times higher than children with no marrow disease at all, while children flagged by the scan alone carried a hazard roughly two and a half times higher, a gap the researchers link to more extensive disease rather than to the test itself. It is an association, not a randomized comparison, and the study cannot say why concordant cases trend more severe, only that they do.
Timing mattered too: when the scan was performed after chemotherapy had already started, sensitivity for marrow disease fell to 86%, and when it was done only after the tumor itself had already been surgically removed, sensitivity dropped further, to 60%, though both of those subgroups were small enough that the estimates carry wide uncertainty. The biopsy side of the comparison had its own weak spot: sampling was frequently inadequate by published standards, with a share of specimens either one-sided or too short a core to trust fully, which raises a separate question about how solid the historical gold standard really was to begin with.
What Changes at Diagnosis
The practical upshot, the authors argue, is a reordering of the diagnostic sequence rather than the end of the biopsy altogether: scan first, and only reach for the needle, or an MRI, when the scan itself raises a flag. That flag still needs following up, since a positive image alone was accurate only 90% of the time in this cohort, but a negative one, done correctly and covering the whole body before treatment starts, appears to be close enough to conclusive. Reineke Schoot, a pediatric oncologist at the Princess Mรกxima Center in Utrecht and the study’s co-senior author, frames it as a shift rather than a shortcut. “A positive FDG-PET scan is a strong indication of bone marrow involvement but still requires confirmation. Conversely, patients with a negative FDG-PET scan can likely avoid a painful bone marrow biopsy in about three-quarters of cases,” she says. “Our study suggests that this approach is truly practice-changing,” Schoot adds.
Rhabdomyosarcoma is a small enough disease that a single retrospective study rarely settles anything for good, and prospective confirmation, testing the scan-first approach as it happens rather than after the fact, is the obvious next step before it becomes routine practice everywhere. For now, the more immediate change is smaller and more concrete: the next child who needs staging for this cancer may walk out of the imaging suite already done, with no second procedure and no second dose of anesthesia, unless the picture on the screen says otherwise.
Reference
Mercolini, F., Just, M., Shulkin, B. L., Collins, N. B., Crane, J., Harrison, D., Affinita, M. C., Allen-Rhoades, W., Alessi, A., Asaftei, S. D., Arnold, M. A., Chen, S., Chiaravalli, S., FitzGerald, F., Freitag, M. T., Iftner, J. L., Khalatbari, H., de Keizer, B., von Luettichau, I., โฆ Zucchetta, P. (2026). Omitting Bone Marrow Sampling in FDG-Avid Rhabdomyosarcoma With 2-[
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F]FDG PET-Negative Marrow: Results From an International Retrospective Study. Journal of Clinical Oncology. https://doi.org/10.1200/jco-25-03080
- Study type: Multicenter international retrospective study (peer reviewed, Journal of Clinical Oncology), a paired diagnostic comparison of FDG-PET/CT or FDG-PET/MRI against bone marrow aspirate/biopsy in the same patients.
- Sample size: 313 patients in the main cohort; 301 with FDG-avid primary tumors formed the primary diagnostic-accuracy analysis group.
- Exposure: FDG-PET/CT or FDG-PET/MRI imaging, performed before chemotherapy and tumor removal.
- Comparison group: Bilateral bone marrow aspirate/biopsy (BMAB) from the iliac crests, the historical diagnostic gold standard.
- Follow-up: Not reported in the material reviewed for this article.
- Funding / conflicts of interest: Individual author disclosures include consulting, honoraria, research funding, stock, and patent relationships with a range of pharmaceutical and biotech companies. The two corresponding/senior authors, Hettmer and Schoot, reported no conflicts. No single study funding source is specified in the material reviewed; the work was coordinated through the INSTRuCT consortium.
- Data availability: Not reported in the material reviewed for this article.
- Main limitation: Retrospective design with a skew toward patients who had more advanced (metastatic and/or FOXO1-rearranged) disease, and PET-positive marrow lesions were not routinely biopsied to confirm they were true tumor rather than injury or inflammation.
FAQ
Is a PET scan alone enough to skip a bone marrow biopsy for every child with this cancer?
Not for every child. A PET scan alone was enough to rule out marrow disease in the large majority of children whose tumor was FDG-avid, provided the scan covered the whole body and was done before any treatment began. Children whose tumors were not FDG-avid, or whose scan came back positive, still need a biopsy or an MRI to confirm what is happening.
Why does a positive PET scan still need to be confirmed if the test works so well?
A positive PET scan still needs confirmation because things other than cancer, such as a bruise, an infection, or ordinary marrow activity, can light up on the scan in a similar way to tumor. The study found the scan correctly ruled out marrow disease essentially every time it came back clear, but a positive result was accurate only about 90% of the time, so doctors still confirm it before changing a treatment plan.
What happens if a child’s tumor does not light up on the PET scan in the first place?
If a tumor is not FDG-avid, meaning it does not take up the radioactive sugar tracer used for PET imaging, the scan cannot reliably rule marrow disease in or out, and a bone marrow biopsy is still needed. Most of the rhabdomyosarcoma tumors in this study did take up the tracer strongly, but a small share did not, and those children were not part of the group who could safely skip the biopsy.
Could this approach change biopsy practice for other children’s cancers, too?
The study only tested this approach in rhabdomyosarcoma, so it does not directly answer that question for other pediatric cancers. PET imaging is already used to stage several other cancer types, though. A multicenter trial found FDG-PET could reliably help stage several kinds of pediatric sarcoma, not just rhabdomyosarcoma, and a study published in 2024 asked the identical question in Ewing sarcoma, a different childhood bone cancer, reaching a similar conclusion about skipping the biopsy when the scan is clear. The same logic, that a clean whole-body scan can rule out marrow spread without a needle, may eventually be tested more broadly.
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