Neurooncology

Comparison of survival benefit and safety profile between lenvatinib and donafenib as conversion therapy in patients with hepatocellular carcinoma 

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In a retrospective comparative cohort study, Hou et al. 1) published in the American Journal of Translational Research, the authors—affiliated with the Department of Oncology, Department of Gynaecology and Obstetrics, and Department of Neurosurgery at Shijiazhuang People’s Hospital (Hebei, China), as well as Beijing Water Conservancy Hospital—compared the survival benefit and safety profile of lenvatinib versus donafenib as conversion therapy in patients with hepatocellular carcinoma (HCC) at China National Liver Cancer (CNLC) stages I–III.

Lenvatinib demonstrated significantly superior survival outcomes—both in overall survival and progression-free survival—compared to donafenib. It also showed better tolerability, with fewer grade ≥3 adverse events.

❌ 1. Study Design: Retrospective = Weak Evidence

This is yet another retrospective single-center analysis, plagued by inherent biases—selection, reporting, and confounding—that no amount of statistical massaging can resolve. No randomization, no blinding, and no control for treatment timing or physician discretion. In oncology, where treatment nuances matter, such designs should be considered hypothesis-generating at best, not guidance for clinical practice.

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Temporal trends and risk factors associated with stroke mortality among cancer patients

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In a retrospective cohort study published in the Journal of Clinical Neuroscience, Ahmed et al. with Cleveland Clinic Cerebrovascular Center, West Virginia University participation 1) analyzed data from over 5.9 million patients diagnosed with a first primary cancer, based on the SEER database (2000–2020). The study aimed to quantify the risk of stroke-related death (SD) in cancer patients and to identify temporal trends and associated clinical and demographic risk factors. Stroke-related mortality (SD) among cancer patients has significantly declined over the past two decades across all cancer types and both sexes. However, older age, non-white race, male sex, and specific cancer types—notably nervous system, respiratory, and head and neck cancers—are associated with a higher risk of stroke death. Conversely, patients receiving chemotherapy or radiotherapy had a lower risk of SD compared to those who received no treatment.

⚠️ Fatal Methodological Flaws

No Clinical Stroke Classification

The authors report on “stroke mortality” without differentiating ischemic vs. hemorrhagic strokes, nor providing stroke etiology or timing relative to cancer diagnosis or cancer treatment—rendering any mechanistic or preventative inference purely speculative.

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Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery.

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In a preclinical experimental study, Obuchi et al. (2025)—with contributions from the Department of Neurosurgery at Leiden University Medical Center—engineered extracellular vesicles for selective cargo loading and enhanced functional delivery, using a modified CD63 scaffold and VSV-G fusion, with in vivo validation in mouse brain models. 1)

🚫 1. Rebranding Complexity as Innovation The authors tout a modular EV engineering system using CD63, mCherry, FLAG-tags, nanobody fusions, and VSV-G. But this is not scientific ingenuity—it’s molecular bricolage. Each component is repurposed from older literature and glued together without real conceptual novelty. The result? A bloated acronym soup with more moving parts than scientific value.

⚠️ What’s pitched as a breakthrough is closer to a tech demo in search of a clinical rationale.

❌ 2. Absence of Disease-Relevant Application Despite name-dropping CRISPR, Cre, and Cas9, no disease context is addressed. No glioma model. No neurodegenerative target. No proof that the cargo accomplishes anything biologically meaningful in the recipient tissue. The mouse brain “validation” is just a fluorescent readout, not a therapeutic outcome.

The cargo arrives, but so what? This is payload delivery without a payload purpose.

🧪 3. Methodological Blind Spots No quantification of EV heterogeneity or functional subpopulations.

No rigorous comparison with alternative delivery systems (e.g., AAVs, lipid nanoparticles).

No evidence of endosomal escape for actual cytoplasmic/nuclear action.

No dose-response curves, toxicity profiling, or repeatability metrics.

This is a biotech prototype, not a therapy-in-the-making.

🔥 4. VSV-G: The Short-Term High, Long-Term Problem The use of VSV-G, a viral fusogen with broad tropism and high immunogenicity, is particularly careless. While it boosts in vitro uptake and helps “sell” delivery efficiency, it introduces a critical translational liability: poor specificity, potential immune activation, and unsuitability for clinical use.

❝Putting VSV-G on EVs is like installing a rocket engine on a paper boat—it moves faster, but it’s doomed to burn out or sink.❞

🧱 5. Structural Inefficiency and Complexity The system requires:

Engineering CD63 with dual tags

Fusing cargo to a nanobody

FLAG-based purification

VSV-G pseudotyping

TEV protease cleavage

This is logistically unscalable for clinical or industrial production and riddled with points of failure. The more components you bolt on, the more it resembles a lab curiosity, not a deliverable platform.

📉 6. Journal Inflation and Institutional Complacency The publication in J Extracell Vesicles is not a mark of impact, but rather a reflection of how EV journals have drifted into translational cosplay, applauding synthetic elegance over clinical relevance. The heavyweight affiliations (MGH, Harvard, etc.) likely ensured acceptance despite the absence of therapeutic depth or mechanistic rigor.

🧠 Conclusion: A study more interested in showing what’s technically possible than what’s biologically meaningful. It trades therapeutic relevance for engineering flair, while ignoring the hard questions of targeting, safety, scalability, and necessity.

This is not a step toward Evidence-based medicine—it’s a flashy side road to nowhere.

1)

Obuchi W, Zargani-Piccardi A, Leandro K, Rufino-Ramos D, Di Lanni E, Frederick DM, Maalouf K, Nieland L, Xiao T, Repiton P, Vaine CA, Kleinstiver BP, Bragg DC, Lee H, Miller MA, Breakefield XO, Breyne K. Engineering of CD63 Enables Selective Extracellular Vesicle Cargo Loading and Enhanced Payload Delivery. J Extracell Vesicles. 2025 Jun;14(6):e70094. doi: 10.1002/jev2.70094. PMID: 40527733.

Epithelioid angiosarcoma of the cervical spine: A case report.

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Nan et al. 1) describe a rare case of epithelioid angiosarcoma (EA) involving the cervical spine, presenting with pathological fracture and kyphotic deformity, and document the surgical and adjuvant management as well as the clinical outcome in the World Journal of Clinical Cases.

1. Predictable Yet Pointless

The authors claim novelty by describing a rare anatomical presentation of EA. However, this degenerates into a predictable narrative with no new pathophysiological insights, no hypothesis generated, and no clinical paradigm challenged. It is the kind of “rare case” that proliferates in low-barrier journals precisely *because* it demands no intellectual risk.

2. Zero Diagnostic Value

The authors bypass the opportunity to deepen our understanding of the radiological-morphological signature of EA in the spine. No comparative imaging, no differential diagnostic flowchart, no histopathological discussion beyond standard CD31/CD34 immunostaining. If this case had been published in 1995, it would be equally uninformative.

3. Therapeutic Confusion Disguised as Aggressiveness

Two major spine surgeries (posterior decompression + anterior corpectomy) followed by immediate radiotherapy in a moribund patient demonstrate therapeutic overreach without oncological strategy. There is no discussion on multidisciplinary planning, palliative thresholds, or whether delaying surgery or avoiding the second procedure might have prevented ARDS. The reader is left with the impression of a surgical reflex, not an evidence-based decision.

4. No Discussion of Differential Diagnosis or Biomarkers

In a tumor type notorious for being misdiagnosed as metastasis, chordoma, or sarcoma NOS, the absence of a differential diagnostic framework or advanced markers (ERG, FLI1, HHV-8, etc.) is alarming. Histological laziness cloaked in “rare disease” rhetoric.

5. Outcome Reporting: Conveniently Truncated

The patient dies 3 weeks after surgery, yet the discussion fails to draw any causal or cautionary link between the interventions and the fatal ARDS. No autopsy data, no postmortem imaging, no pulmonary workup. This omission sterilizes the clinical narrative, reducing it to anecdote.

6. Ethically Murky

The case implicitly raises an ethical dilemma—should maximal surgery be performed in aggressive, terminal tumors without demonstrated systemic control? Yet the authors shy away from even mentioning this, let alone framing it for academic discussion.

7. Journal Choice Reflects the Paper’s Weakness

Published in a journal known for minimal peer review stringency, the article offers no citations of recent molecular or targeted therapy advances, no engagement with broader oncological guidelines, and no rationale for the treatment decisions beyond procedural listing.

Definitions (for Teaching Purposes)

  • Histological laziness: Failing to provide in-depth pathology discussion beyond CD31/CD34 and H&E staining in vascular tumors.
  • Surgical reflex: The tendency to operate based on mechanical findings (compression, fracture) without integrating prognosis or systemic disease behavior.
  • Ethical sterilization: Avoiding uncomfortable questions about futility, risk-benefit tradeoffs, and overtreatment in end-stage patients.
  • Postmortem evasion: Reporting a perioperative death without diagnostic closure (autopsy, imaging, or medical reflection).

Conclusion

This case report is an example of procedural reporting devoid of scientific merit, clinical reflection, or ethical introspection. It contributes nothing to the understanding of EA, its diagnosis, biology, or management—beyond reiterating its rarity. In its current form, it is neither hypothesis-generating nor practice-changing, and serves as a cautionary tale on how not to write a case report.

Suggested Revisions

  • Include comparative radiology with metastatic disease and primary bone tumors.
  • Provide autopsy findings or detailed explanation of respiratory decline.
  • Discuss therapeutic alternatives (e.g., single-stage surgery, biopsy + RT, palliative care).
  • Frame the case within an oncological decision-making algorithm.
1)

Nan YH, Chiu CD, Chen WL, Chen LC, Chen CC, Cho DY, Guo JH. Epithelioid angiosarcoma of the cervical spine: A case report. World J Clin Cases. 2025 Jun 16;13(17):101593. doi: 10.12998/wjcc.v13.i17.101593. PMID: 40524767; PMCID: PMC11866273.