Recently, our comprehension of DMG/K27M has advanced, albeit with ongoing revisions in the current classification [1, 5]. However, the natural history, molecular characteristics, response to treatment, and clinical outcomes of the disease still lack clarity. Consequently, there's a pressing need to delve into the characteristics and prognosis of this aggressive condition. In this study, based on outpatient and post-admission data from DMG/K27M patients, we extensively investigated their clinical attributes concerning age and tumor location. Our exploration extended to a comprehensive evaluation of patient prognoses, identifying potential factors that clinicians could employ to assess patient survival rates.
DMG/K27M stands as a rare and gravely prognostic disease. Currently, relevant studies focusing on the spinal cord or comparing the clinical characteristics and prognosis of adults and pediatric patients have been reported [23, 24]. However, comprehensive exploration of this particular subtype remains limited, and its clinical characteristics remain unclear. Identified as a new subtype in 2016, it amalgamates previous entities of DIPG and infiltrating midline glial neoplasms [1, 4]. DIPG is a pediatric biased disease with tumors located in the brainstem, which accounts for the majority of DMG/K27M diseases [27]. Nonetheless, the tumors of the 64 patients included in this study were mostly located in the thalamus, and the majority of them were adults. While this age-tumor site correlation aligns with prior findings [26], the varying age distributions and tumor locations may, to some extent, account for the disparities in results. In our study, we found differences in clinical symptoms and MRI findings among the three groups of patients (thalamus, brainstem, and spinal cord), notably highlighting better prognosis among those who presented with dizziness. Based on these findings, our results suggest that ages and tumor sites should be considered comprehensively to explore and evaluate potential factors affecting patient prognosis.
In previous studies, Hu et al. and Wang et al. demonstrated that p53 mutation and 1p19q co-deletion were autonomous predictors for OS in patients [19, 28]. Nonetheless, there were no significant molecular features in this cohort that suggested a correlation with patient outcomes, possibly because most patients in our cohort had genotypes with good prognosis, which may result in longer survival time. Notably, an interesting clinical manifestation of these patients is the so-called "dizziness,” which complained of vertigo or ataxia in patients. Shu et al. reported a rare adult patient with an atypical symptom, dizziness as the chief complaint, and finally diagnosed as medulloblastoma by biopsy, which is an enlightening case [29]. Drawing from our extensive clinical observations and follow-up, we've uncovered a trend indicating that patients presenting with this symptom tend to exhibit improved outcomes, which has not been reported before. Therefore, we speculate that this clinical symptom may contribute to the early diagnosis and treatment of DMG/K27M. This deserves the attention of researchers and clinicians, but more clinical evidence is also needed to support this hypothesis.
Presently, an established optimal regimen for DMG/K27M remains elusive, and previous treatments for high-grade glioma are often applied. Wang et al. showed that high KPS and radiotherapy may significantly prolong survival in tumor patients [28, 30]. However, this study found that patients who underwent at least conventional treatment (such as maximal safe surgical resection with radiotherapy and chemotherapy) had relatively better prognosis. This suggests that this regimen may still be the most effective therapeutic modality for DMG/K27M. Although the patients in our study who received further targeted or immunotherapy did not have a satisfactory treatment effect, based on the available data, we can observe that only a small proportion of patients with a better prognosis did not adhere to the complete stage treatment regimen. This implies that encouraging DMG/K27M patients to adhere to the standard treatment regimen as much as possible, particularly those presenting with dizziness as a chief complaint, could potentially yield favorable prognostic benefits. Nonetheless, this argument needs to be supported by a larger sample size and better long-term follow-up. It's essential to recognize that there are limitations to the current clinical treatments for patients with DMG/K27M. Apart from the high cost associated with treatment, the determination of the optimal treatment regimen remains a challenge.
In summary, DMG/K27M is a rare disease that is characterized by difficult surgical resection, insufficient evidence-based basis for radiotherapy and chemotherapy, lack of therapies with specific drugs, and lack of optimal treatment regimens. Significantly, our study is the first to propose that DMG/K27M patients presenting with dizziness as their initial symptom may exhibit a more favorable prognosis. We've identified four factors—tumor location, dizziness, KPS, and treatment—as potential prognostic indicators in DMG/K27M patients.