Simple Blood Ratio Predicts Survival in Young Bone Cancer Patients

A routine blood test that costs only a few dollars may help doctors predict which teenagers with bone cancer are most likely to survive, according to new research from Vietnam. The study, published in the journal iScience, found that the ratio of two types of white blood cells measured after chemotherapy but before surgery was a powerful indicator of long-term survival in patients with localized osteosarcoma, the most common bone malignancy of adolescence. The finding is striking precisely because the test is so ordinary: a complete blood count, available in nearly every clinic on Earth, may carry prognostic information that expensive imaging scans cannot easily provide.

Osteosarcoma is rare, affecting roughly three to four people per million each year, but it is devastating for the young patients it strikes. Treatment typically involves months of chemotherapy to shrink the tumor, followed by surgery to remove it, and then further chemotherapy to mop up any remaining disease. Survival depends heavily on whether the cancer is still localized at diagnosis: patients with localized disease have five-year survival rates of 70 to 77 percent, while those whose tumors have already spread to distant organs fare far worse, with survival dropping to between 24 and 36 percent. Because follow-up care is costly and burdensome, the researchers were interested in whether cheap, routinely collected blood values could help stratify risk without adding financial strain on families.

The research team, led by scientists at VinUniversity and the Vinmec Healthcare System, focused on a cohort of 100 Vietnamese patients with localized osteosarcoma treated between 2022 and 2024. The group was predominantly adolescent, with 72 percent under 18 years old and a mean age at diagnosis of just under 16 years. Notably, 62 percent of the patients were female, a higher proportion than typically reported in osteosarcoma studies, which the authors attribute to the referral patterns of their institution. Nearly all patients received neoadjuvant chemotherapy before surgery, and 90 percent received adjuvant chemotherapy afterward, reflecting standard treatment protocols for this aggressive malignancy.

The central innovation of the study lies in its timing. Most previous biomarker research in osteosarcoma has measured inflammatory blood markers before any treatment begins, capturing the biology of the untreated tumor. This team instead examined blood drawn in the window after neoadjuvant chemotherapy but before the operation, a period the authors describe as an underappreciated stress test of the patient’s body. Chemotherapy profoundly suppresses the bone marrow, and how quickly and completely the immune system rebounds during this interval may reveal something fundamental about a patient’s physiological resilience, their capacity to tolerate treatment, and their ability to keep residual disease in check.

The researchers calculated three ratios from the complete blood counts: the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the lymphocyte-to-monocyte ratio (LMR). Each ratio pits a different arm of the immune and inflammatory system against another. Lymphocytes are the immune cells responsible for recognizing and killing tumor cells, while monocytes can be recruited by tumors to support their growth and spread. Neutrophils and platelets, meanwhile, are associated with inflammation, angiogenesis, and metastasis. A low LMR, therefore, could signal both weakened antitumor immunity and heightened tumor-promoting inflammation at the same time.

The results were clear for one marker and ambiguous for the rest. Using receiver operating characteristic analysis, the team determined that an LMR cutoff of 1.615 best separated survivors from non-survivors, achieving an area under the curve of 0.72, which was statistically significant. Patients whose LMR was at or above this threshold had significantly better overall survival than those below it. In a multivariable Cox proportional hazards model adjusting for age, sex, and chemotherapy status, an LMR below 1.615 remained an independent predictor of death, carrying a hazard ratio of 4.19. In other words, patients with low post-chemotherapy LMR faced roughly four times the risk of dying compared with those whose immune profiles had recovered more robustly.

Equally interesting was what the LMR did not predict. When the researchers analyzed progression-free survival at 24 months, a window chosen because most osteosarcoma relapses occur within the first two years, none of the biomarkers, including LMR, showed a significant association. This dissociation suggests that the LMR is not simply a proxy for tumor aggressiveness. Instead, the authors argue, it reflects host factors: immune recovery, physiological reserve, and the body’s capacity to withstand the cumulative assault of cytotoxic therapy. Early progression, by contrast, is likely governed by the intrinsic molecular biology of the tumor itself, including its metastatic potential and treatment resistance, which peripheral blood counts cannot capture.

The other markers told a more complicated story. The NLR, which has been reported as a prognostic factor in French, Chinese, and Turkish osteosarcoma cohorts, showed no significant association with survival in this Vietnamese population, in either univariable or multivariable analysis. The PLR was initially associated with poorer survival in univariable analysis, but this signal vanished after adjustment for other variables. Hemoglobin levels also failed to predict outcomes, even though 72 percent of patients were anemic before surgery. In sensitivity analyses treating the biomarkers as continuous variables, LMR retained the direction and approximate magnitude of its protective effect, with each unit increase in LMR associated with a 51 percent reduction in the hazard of death in univariable modeling, and it achieved the highest discriminative accuracy of the three indices, with a C-index of 0.729.

The team also subjected their findings to bootstrap internal validation using 1,000 resamples, an honest accounting of the uncertainty inherent in a small retrospective cohort. After optimism correction, the model’s C-index fell from 0.729 to 0.628, confirming moderate overfitting and modest real-world discrimination. Crucially, however, the bootstrap confidence interval for LMR remained entirely below the null threshold, indicating that its protective association was stable despite the sample size, whereas the interval for PLR crossed 1.0, marking its prognostic value as unreliable in this cohort. The authors also compared their data-derived cutoffs with those from 16 previous studies encompassing 2,762 patients, mostly from China, and found that cutoff values varied enormously across populations, and none of the external thresholds produced statistically significant survival differences in their own cohort.

The study has real limitations that the authors acknowledge candidly. It was retrospective, single-center, and small, with only 10 deaths among 100 patients, which limits statistical power. Missing clinical data on tumor site, size, surgical margins, and histological response prevented more extensive adjustment, even though large registry studies and the intercontinental EURAMOS-1 trial have established these conventional factors as the true pillars of osteosarcoma prognosis. Blood was sampled at only a single time point, and chronic inflammatory conditions, infections, transfusions, and nutritional status were not systematically documented. Still, the core message stands: a simple, nearly free blood ratio, measured at the moment when a young patient’s body is recovering from chemotherapy’s hardest blow, may identify those who need closer surveillance and more intensive support. In resource-limited settings like Vietnam, where the cost of follow-up imaging can determine whether a patient returns to the clinic at all, such an accessible biomarker could make a genuine difference, provided the findings are confirmed in larger, prospective, and more diverse populations.

Subject of Research: Prognostic value of post-chemotherapy blood inflammatory ratios in localized osteosarcoma

Article Title: Lymphocyte-to-monocyte ratio predicts survival in localized osteosarcoma in Vietnamese patients

Article References: Thu Hien, T. T., Quoc, D. N., Thanh, T. D., Thanh Hai, T. T., Quang Sang, N. T., Dung, T. T., Nguyen, X.-H., & Vu, S. H. (2026). Lymphocyte-to-monocyte ratio predicts survival in localized osteosarcoma in Vietnamese patients. iScience, 29(10), Article 117676. https://doi.org/10.1016/j.isci.2026.117676

Image Credits: AI Generated

DOI: 10.1016/j.isci.2026.117676

Keywords: osteosarcoma, lymphocyte-to-monocyte ratio, biomarker, survival, neoadjuvant chemotherapy, inflammation, immune recovery, Vietnam, pediatric cancer, blood test, prognosis, oncology