Show pageBacklinksCite current pageExport to PDFBack to top This page is read only. You can view the source, but not change it. Ask your administrator if you think this is wrong. ====== Recurrent high-grade glioma treatment ====== {{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1Zorz_P_0HTCaroJyfrWC0RjNTrBRWZB_2QJN4QgXJDvoNgM3e/?limit=15&utm_campaign=pubmed-2&fc=20250618151541}} ---- ---- see [[Recurrent Glioblastoma treatment]]. ---- Recurrent high-grade glioma, especially [[glioblastoma]], remains one of the greatest challenges in neuro-oncology due to inevitable recurrence and limited therapeutic options. ===== General Principles ===== * Treatment must be individualized based on: * Age and functional status (KPS) * Time to recurrence (>6 months = better prognosis) * Tumor location and volume * Molecular markers (MGMT methylation, IDH status, etc.) ===== Treatment Options ===== ==== 1. Surgical Re-resection ==== * Recommended in patients with good KPS and accessible lesions * Goals: reduce mass effect, obtain updated histology/molecular profile * May improve overall survival in selected patients ==== 2. Re-irradiation (re-RT) ==== * Techniques: hypofractionated RT, SRS, pulsed RT, proton therapy * Indicated when recurrence occurs >6 months after initial RT and is focal * Risk of radiation necrosis; may be reduced by adding bevacizumab ==== 3. Systemic Therapy ==== === Bevacizumab (BEV) === * Anti-VEGF monoclonal antibody * Palliative effect: reduces edema and steroid need * No proven OS benefit; improves PFS and symptoms === Chemotherapy === * Temozolomide rechallenge (if MGMT-methylated, long interval) * Lomustine (CCNU) — modest benefit * Combinations: BEV + lomustine (better PFS) * Others: PCV, irinotecan, regorafenib (REGOMA trial) === Targeted Therapy === * Applicable in specific mutations (EGFR, BRAF, etc.) ==== 4. Clinical Trials / Experimental Therapies ==== * Tumor Treating Fields (TTFields) * Immunotherapy (PD-1 inhibitors – limited efficacy) * Oncolytic viruses, CAR-T cells, vaccines * Always consider clinical trial enrollment when available ===== Expected Outcomes ===== ^ Treatment ^ Median OS (recurrence) ^ Comments ^ | Surgery | 9–12 months | Only for selected, high-functioning patients | | Re-irradiation | 6–10 months | Best if >6 months since initial RT | | Bevacizumab alone | 4–6 months | Improves symptoms, not OS | | Lomustine | 6–8 months | Modest benefit | | BEV + lomustine | ~9 months | ↑PFS, unclear OS benefit | | Clinical trial | Variable | Best option in qualified centers | ===== Simplified Algorithm ===== - **KPS ≥70, accessible lesion** → consider **surgical re-resection** - **Focal recurrence, >6 months from RT** → consider **re-RT ± BEV** - **Symptomatic edema or rapid progression** → consider **BEV ± chemo** - **Actionable mutations** → consider trials or targeted therapy - **Poor KPS, multiple recurrences** → palliative care, steroids ===== Systematic review and meta-analysis ===== In a [[systematic review]] and [[meta-analysis]] published in [[Therapeutic advances in neurological disorders]] of non-randomized, two-arm clinical trials comparing re-irradiation + bevacizumab versus bevacizumab alone in patients with recurrent [[high-grade glioma]]s (rHGG), aiming to demonstrate [[superiority]] in [[survival]] outcomes. Hammed et al. claim that the combination therapy improves overall survival (OS) and progression-free survival (PFS) without increasing grade ≥3 toxicity, and propose it as a potentially standard salvage approach ((Hammed A, Al-Qiami A, Hasan A, Richter G, Zakria Alnajjar A, Rosenbauer J, Kostev K, Ismail O, Braun V, Tanislav C. Efficacy and safety of combining re-irradiation with bevacizumab compared to bevacizumab alone in the management of recurrent high-grade gliomas: a meta-analysis and systematic review. Ther Adv Neurol Disord. 2025 Jun 14;18:17562864251343574. doi: 10.1177/17562864251343574. PMID: 40529988; PMCID: PMC12171250.)). ---- 💣 Critical Appraisal 1. Low-Level Evidence in Disguise This is a meta-analysis based entirely on retrospective, non-randomized studies, with all the biases and heterogeneity that come with them. The use of ROBINS-I and II to "evaluate" these studies does not mitigate the inherent confounding by indication, selection bias, and lack of treatment standardization. The authors repeatedly conflate association with causation, ignoring the fact that hazard ratios in observational cohorts are not treatment effects. 2. Pooling Apples and Oranges The methodology pools data across studies with wildly heterogeneous re-irradiation protocols (doses, volumes, pulsed vs. non-pulsed), variable use of BEV (dose, schedule), and differing baseline characteristics. Combining such studies and then reporting pooled HRs is statistical theater with no clinical applicability. Worse yet, subgroup analysis by age, gender, and performance status in this context becomes [[data dredging]], not hypothesis testing. 3. Toxicity Reporting = Wishful Thinking The authors claim no increase in grade 3 toxicity — without acknowledging that toxicity data are the weakest part of retrospective trials, often underreported and inconsistently graded. The meta-analysis fails to stratify by radiation volume or cumulative dose, which are critical in assessing toxicity in re-irradiation contexts. 4. Clinical Relevance? Minimal at Best While the paper reports a statistically significant HR for OS (0.69), the absolute median survival gains are not reported. No mention is made of quality of life, neurocognitive outcomes, or steroid dependence, which are central in rHGG salvage treatment. Improving OS by a few weeks while ignoring the trade-offs is misleading at best and harmful at worst. 5. Prospective Trials? Good Luck The authors end by calling for prospective trials — a noble gesture, but an empty one given that they have already drawn definitive therapeutic conclusions. This dual messaging — “Here is the answer, but someone else should prove it” — is the hallmark of pseudo-precision medicine built on methodological sand. 🧯 Final Verdict This study offers an [[illusion]] of progress in [[recurrent high-grade glioma treatment]]. It recycles weak retrospective data through the statistical blender of [[meta-analysis]] and pours out [[hazard ratio]]s that look impressive but mean very little. It is a classic case of [[overconfident conclusion]]s from underpowered, heterogenous data. Until proper randomized evidence emerges, clinicians should resist the temptation to treat these results as [[practice-changing]]. The paper is more [[editorial decoration]] than solid [[evidence]]. ===== References ===== recurrent_high-grade_glioma_treatment.txt Last modified: 2025/06/18 19:32by administrador