====== Brain metastases prognosis ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1Jqs22NP9Nc1NFv8jraMfgwQaVf0nKbd3VIhzyD67_GDKFFcaF/?limit=15&utm_campaign=pubmed-2&fc=20240227073113}} {{ ::brain_metastases_outcome.jpg?250|}} In a systematic review and meta-analysis of patients with Intracranial metastatic disease in the setting of limited or stable extracranial disease, the limited systemic disease was associated with improved OS and intracranial PFS. Future prospective trials should aim to collect granular information on the extent of extracranial disease to identify drivers of mortality and optimal treatment strategies in patients with brain metastases ((Li AY, Gaebe K, Zulfiqar A, Lee G, Jerzak KJ, Sahgal A, Habbous S, Erickson AW, Das S. Association of Brain Metastases With Survival in Patients With Limited or Stable Extracranial Disease: A Systematic Review and Meta-analysis. JAMA Netw Open. 2023 Feb 1;6(2):e230475. doi: 10.1001/jamanetworkopen.2023.0475. PMID: 36821113.)). ---- Overall [[prognosis]] depends on [[age]], [[extent]] and activity of the [[systemic disease]], number of [[brain metastases]] and [[performance status]]. In about half of the patients, especially those with widespread and uncontrolled systemic malignancy, [[death]] is heavily related to extra-neural lesions, and treatment of cerebral disease doesn't significantly improve survival. In such patients the aim is to improve or stabilize the [[neurological deficit]] and maintain [[quality of life]]. [[Corticosteroid]]s and [[whole brain radiotherapy]] usually fulfill this purpose. By contrast, patients with a limited number of brain metastases, good [[performance status]] and controlled or limited systemic disease may benefit from aggressive treatment as both qualities of life and survival are primarily related to the treatment of brain lesions. Strong positive prognostic factors include good functional status, age <65 years, no sites of metastases outside of the central nervous system (CNS), and controlled primary tumor ((Gaspar L, et al. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997;37:745–751.)), the presence of single metastasis in the brain, long interval from primary diagnosis to brain relapse, and certain cancer subtypes such as [[HER2-positive brain metastases]] and [[EGFR]] [[Non-Small cell lung cancer intracranial metastases]] ((Melisko ME, Moore DH, Sneed PK, De Franco J, Rugo HS. Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival. J Neurooncol. 2008;88:359–365.)) ((Eichler AF, et al. Survival in patients with brain metastases from breast cancer: the importance of HER-2 status. Cancer. 2008;112:2359–2367.)) ((Eichler AF, et al. EGFR mutation status and survival after diagnosis of brain metastases in nonSmall-cell lung cancer. Neuro Oncol. 2010;12:1193–1199.)). ===== Recursive partitioning analysis class ===== [[Recursive partitioning analysis class]] http://rcalc.ccf.org, under the category “Brain Cancer” ((Barnholtz-Sloan JS, Yu C, Sloan AE, Vengoechea J, Wang M, Dignam JJ, Vogelbaum MA, Sperduto PW, Mehta MP, Machtay M, Kattan MW. A nomogram for individualized estimation of survival among patients with brain metastases. Neuro Oncol. 2012 Jul;14(7):910-8. doi: 10.1093/neuonc/nos087. Epub 2012 Apr 27. PubMed PMID: 22544733; PubMed Central PMCID: PMC3379797.)). In a study of the [[Royal North Shore Hospital]], on [[univariate]] [[analysis]], number of [[metastases]] (P = 0.04), symptomatic extracranial disease (P = 0.04) and early CNS relapse within 6 months (P < 0.01) had worse [[survival]]. No grade 3-4 [[toxicity]] events were noted in 129 patients undergoing [[RT]] ((Or M, Jayamanne D, Guo L, Stevens M, Parkinson J, Cook R, Little N, Back M. Focal radiation therapy for limited brain metastases is associated with high rates of local control and low subsequent whole brain radiation therapy. ANZ J Surg. 2019 Mar 5. doi: 10.1111/ans.15040. [Epub ahead of print] PubMed PMID: 30836451. )). ---- It is presently unknown whether patients with brain metastases from heavily pre-treated cancers have a significantly different prognosis than those with less pre-treatment ((Lanier CM, McTyre E, LeCompte M, Cramer CK, Hughes R, Watabe K, Lo HW, O'Neill S, Munley MT, Laxton AW, Tatter SB, Ruiz J, Chan MD. The number of prior lines of systemic therapy as a prognostic factor for patients with brain metastases treated with stereotactic radiosurgery: Results of a large single institution retrospective analysis. Clin Neurol Neurosurg. 2017 Dec 27;165:24-28. doi: 10.1016/j.clineuro.2017.12.021. [Epub ahead of print] PubMed PMID: 29289917. )). ===== Recurrence ===== [[Intracranial metastases recurrence]]. ===== Hyperglycemia ===== High blood sugar levels (like in [[diabetes]]) are linked with shorter [[survival]] in people who have [[cancer]] that has spread to the brain. Keeping blood sugar in a healthy range is advisable, especially during cancer treatment, though it's not yet proven to change outcomes. In a [[retrospective]] [[observational cohort study]] Poudyal et al. ((Poudyal S, Rothe F, Jeong S, Gleim N, Hambsch P, Nägler F, Papsdorf K, Kuhnt T, Barrantes-Freer A, Güresir E, Klagges S, Nicolay NH, Seidel C. Hyperglycemia is associated with poor survival in patients with brain metastases treated with radiotherapy. Strahlenther Onkol. 2025 Jun 16. doi: 10.1007/s00066-025-02414-y. Epub ahead of print. PMID: 40522460.)) aimed to determine if hyperglycemia itself, independent of a diabetes diagnosis, could be a negative prognostic factor in patients undergoing radiotherapy for brain metastases. ---- ==== 1. Poor Study Design and Underpowered Sample ==== This is a severely underpowered retrospective analysis with only 62 patients. Dividing such a small cohort into quartiles and running multivariate Cox regressions is statistically irresponsible. The use of arbitrary cut-off points (e.g., >7.8 mmol/L) suggests data dredging rather than hypothesis-driven science. ==== 2. Confounding Bias: Steroids, Disease Burden, and Reverse Causality ==== The study fails to control for key confounders, most notably **[[dexamethasone]]**, a known hyperglycemic agent commonly used in these patients. No data on dosage, duration, or timing are provided. Worse [[prognosis]] may reflect more aggressive disease requiring higher [[steroid]] doses — making [[hyperglycemia]] a *marker*, not a cause, of poor outcome. ==== 3. Misleading Statistics and Weak Significance ==== The [[hazard ratio]]s (2.05 and 1.95) have wide [[confidence interval]]s and borderline [[p-value]]s (0.021 and 0.035), which in oncology are hardly compelling. The so-called “trend” in non-diabetics (HR = 2.54, p = 0.099) is not statistically significant, and no correction for multiple comparisons was performed — raising the risk of false positives. ==== 4. Clinical Overreach Without Causality ==== Despite being a purely observational study, the authors hint at clinical implications. This is dangerous. There is no intervention, no glucose control strategy, and no evidence that modifying glycemia alters outcomes in this population. Such suggestions are speculative and potentially misleading. ==== 5. Redundancy in Literature ==== It is already well known that diabetes and poor metabolic control are associated with worse outcomes in cancer. This study adds little beyond reinforcing that uncontrolled glucose levels are **associated** with worse prognosis — without clarifying whether this is biologically or clinically relevant. ===== Conclusion ===== This paper typifies the [[overinterpretation]] of weak retrospective associations. With a small [[sample]], unadjusted confounding, questionable statistical rigor, and inflated conclusions, it falls short of providing actionable evidence. Until [[prospective]], controlled studies are conducted, this finding should remain **hypothesis-generating only**, not practice-changing. ===== References =====