Beyond Resection: Surgery as an Evolutionary Bottleneck Shaping Tumor Evolution and Treatment Response in Diffuse...

Area of Science:

• Neuro-oncology
• Cancer Biology
• Surgical Oncology

Background:

• Surgical resection is a primary treatment for central nervous system (CNS) tumors, especially diffuse gliomas.
• Traditional evaluation focuses on quantitative metrics like extent of resection and survival.
• Despite complete resection, malignant CNS tumors frequently recur, indicating incomplete understanding of post-surgical dynamics.

Purpose of the Study:

• To propose a framework redefining surgery as a biological driver in CNS tumor progression.
• To synthesize evidence on how surgical trauma impacts the tumor microenvironment and evolution.
• To challenge anatomy-based surgical completeness paradigms with a biological perspective.

Main Methods:

• Literature review synthesizing evidence on surgery-induced biological changes.
• Conceptual framework development reframing surgery's role.
• Analysis of molecular and evolutionary perspectives on tumor recurrence.

Main Results:

• Surgical trauma induces inflammation, hypoxia, and immune modulation, reprogramming the tumor microenvironment.
• These changes promote the survival of adaptive, invasive tumor cell subpopulations.
• Surgery acts as a selective bottleneck, driving clonal selection and molecular divergence.
• Discrepancy between anatomical and biological margins explains recurrence patterns.

Conclusions:

• Surgery is a biologically active event influencing CNS tumor progression and recurrence.
• Surgery-induced changes impact the effectiveness of adjuvant therapies like radiotherapy and systemic treatments.
• Future neuro-oncology requires integrating biological insights into surgical planning and postoperative care for improved disease control.